Understanding Glomerulofiltration and Its Processes

All right Ninja Nerds, in this video we're going to specifically start talking about glomerulofiltration. All right, before we do that, before we even get into glomerulofiltration, we have to look at the structure of something specific. What is that structure that we have to talk about? We have to talk about what's called a renal corpuscle. Okay, so first off, what is a renal corpuscle? Let's actually define what a renal corpuscle is. So, renal corpuscle is two things. Okay? The first thing is actually the glomerulus. Okay? Which is capillaries, which is a tuft of capillaries. The other thing is the Bowman's capsule. Or sometimes they even call it the glomerular capsule. We're just going to call it the Bowman's capsule. Okay, so two components of the renal corpuscle. Again, what are those two components of the renal corpuscle? The two components of the renal corpuscle is specifically the glomerular capsule. glomerulus, which is the tuft of capillaries, and the Bowman's capsule. Let's first talk about the glomerulus and the filtration membrane, which is a part of it, and then we'll talk about the Bowman's capsule. Let's first focus on the glomerulus. notice here this right here is the glomerulus because this is the tuft of capillaries right here so a glomerulus is like a tuft of capillaries and here's what's interesting if you notice let's say that this is the vessel coming into the glomerulus so this is feeding into the glomerulus when it goes into the glomerulus it's actually called afferent arteriole Okay, so if there's a vessel that's feeding the glomerulus, it's called the afferent arteriole. And again, this is the glomerulus right here. Right here is the glomerulus. Okay, so we'll put that right above it. This is our glomerulus, which is our tuft of capillaries. Oh, what type of capillaries is there within the glomerulus? That's really, really important. You know what type of capillaries are here in the glomerulus? They're actually called fenestrated. Capillaries. You know what fenestrated capillaries means? Okay, so let's say I take one of these endothelial cells and I zoom in on them. So let's say here's an endothelial cell. Okay, here's the nucleus of the endothelial cell. In this endothelial cell, it has little holes. Look at this. You see this little hole right there? Little channel basically. That's a fenestration. There's another one over here too. They have them all around these things. There's hundreds upon hundreds, even thousands of these little fenestration pores on this endothelial cell. Now, these fenestration pores, what are they for? Let me explain. explain to you what they're for. Well first off how big are these little things? You know these little things right here these fenestrations are approximately about 50 to 100 nanometers in diameter. That's really freaking small. So about how much? 50 to 100 nanometers in diameter. So really what can actually filter through this? Okay you know within the blood you have your plasma which is consisting of a lot of water and different types of solute molecules right? And then also you have formed elements. like your white blood cells, your red blood cells, your platelets. Any type of formed elements cannot fit through these fenestrations, okay? So any type of formed elements cannot fit through these actual fenestration pores. So formed elements are, again, what? What are those components of formed elements? Red blood cells, white blood cells, platelets, none of those can get in. Okay? What can pass through? The different components of the plasma. So you know like small proteins? Small proteins can pass through this. What else can pass through this? Water. What else can pass through this? Electrolytes. Like sodium and potassium and calcium and chloride and a whole bunch of other different types of molecules. A lot of different things. Okay, and even nutrients. Waste products, all different types of molecules can pass through these actual fenestration pores. Okay, so these fenestration pores are basically riddled against all these little endothelial cells within the glomerulus. That's one important point. Okay, what is this structure draining the glomerulus? Here's a really, really interesting. Watch this. Usually it's a vein, right, or a venule. This is actually called the efferent. arterial. This is one of the only examples in the body in which a capillary bed is being fed by an arterial and then drained by an arterial. Okay, so we have apharein arterial feeding the glomerulus, we have an epharein arterial draining the glomerulus, and the glomerulus is again fenestrated capillaries. What does it mean to be fenestrated? It's these little pores In the endothelial cell, right, there are about 50 to 100 nanometers in diameter. And what do they allow for things for it to pass through? Electrolytes, nutrients, small proteins, water molecules, and even maybe some large molecular weight proteins that are less than 100 nanometers in diameter. Because if they're less than 100 nanometers in diameter, they can pass through the actual fenestration pores. So let's even say, not only small proteins, but like we'll say moderate size proteins. And again, any proteins or any molecules that are about less than 100 nanometers in diameter can fit through these fenestration pores. Now look at this little nice blue, baby blue thing that we have right here. You see this blue membrane right here? This is one of the most critical parts of the actual glomerulus. One of the most important points of the glomerulus. You know what this thing is actually called? This blue membrane structure? Let's actually show it over here. This blue membrane structure right here that I'm kind of showing here, that I'm zooming in on right here. This is actually called the glomerular basement membrane. So again, what is it called? The glomerular basement membrane. Now some of you might be thinking, okay, it's just a basement membrane. What significance does that have? Oh my goodness, so much significance. Okay. This glomerular basement membrane is extremely interesting because if I were to, let's say I actually zoomed in on even more. Let's say I even zoomed in on this layer even more. You know the glomerular basement membrane is actually three sub-layers? Look at this. Let's say I zoom in on it for a second. So here's the glomerular basement membrane. In the glomerular basement membrane, there's three layers. Let's say here I make a black layer right there. A real, real thick black layer. This thick black layer is actually going to be specifically... Consisting of type 4 collagen. So what is this layer right here consisting of? It's specifically consisting of type 4 collagen and laminins, these different types of proteins. Okay, so one is actually going to be type 4 collagen and if you notice it's really dense. You know what they call this actual layer? They call this the lamina densa. Okay. So one layer right smack dab in the middle which is consisting of type 4 collagen and laminins is called the laminidensa. Then let's say that this is the endothelial side. And what do I mean by endothelial side? I mean that here's your endothelial cells. This part of the membrane closest to the endothelial cells is this side. Then you have these black cells which I'm going to talk about called the podocytes. That's going to be on this side. So the podocyte, I'm going to put podocyte layer. Okay, on this side here, towards the endothelial cells, it's a thinner like tissue, okay? It's a thinner layer. This layer right here is actually made up of specific types of molecules like proteoglycans, okay, or glycosaminoglycans, particularly heparin sulfate. And guess what else you're going to find on the other side? The same thing, heparin sulfate. These are the different types of glycosaminoglycans. Now, here's the next part that's really interesting. Heparin sulfate is extremely negatively. charged. Okay? So it's very, very negatively charged. So if I were to show that here, let's say I show it here in orange. On this side, what are you gonna have? A lot of negative charges. What would you have on this side? A lot of negative charges. That's important. I'm going to talk about that, why that is. Now, if I were to be particular, this side is closest to the endothelial cell. We call this side lamina rara. interna and then we call this side, so that's lamina rara interna, the one towards the endothelial lining. The one on the opposite side towards the podocyte lining is actually called the lamina rara. externa. Okay, so the glomerular base membrane has actually three different sub layers. One in the middle is actually the lamina denso with type 4 collagen laminins. Lamina rara interna and lamina rara externa are consisting of heparin sulfate. Okay, so a different type of glycosaminoglycan which has a lot of negative charges on it. Why is this important? Okay. You know inside of our blood we have these things called plasma proteins. Let's say I represent a plasma protein here as like albumin. You know what albumin charges inside of the blood generally are most plasma proteins? It's negatively charged. Let's say I draw another plasma protein just for the heck of it. I put in here Let's say I put in here specifically different types of immunoglobulins. So I'm going to put IgG and we'll just be for the heck of it, we'll put IgG. Immunoglobulins, these are also negatively charged. I could even put fibrinogen or different types of transport, other types of transport proteins. The whole point is proteins inside of our actual plasma are negatively charged. What's the charge on this glomerular basement membrane? Negative charge. So it's very, very negatively. Now if you know a little bit about biology, you know that same charges repel one another. So for example, if I have albumin, I represent albumin here as this circle, and then all around him I have negative charges. If he tries to come through this membrane, or any type of molecule that's negatively charged, tries to come through that membrane, what's going to happen to it? It's going to repel it. So can I get through this actual glomerular basement membrane? No. That's good at helping to act as a good filter. So now it's acting as a very good filter. So any type of negatively charged particles that actually try to move through the glomerular basement membrane is repelled. But, if you know again about biology, what actually is going to want to come to the negative charge? Positively charged particles, right? So anything that's positively charged is going to want to come to the negative charges. So any type of positively charged particles that we might have with inside of the plasma is going to want to what? Pass through here. What are positively charged molecules usually? Different types of electrolytes like sodium and potassium and calcium and magnesium. So that's really really interesting. Any type of positively charged substances are going to pass through the glomerular basement membrane easily. Anything that's neutral, it's going to be a little bit harder than positively charged species to pass through, but it can still pass through. any negatively charged species or different types of molecules are going to be repelled and prevented from entering into this actual glomerulin capsule here. Okay? So, if it's big enough, like large molecular weight proteins or large different solute molecules and they move through the fenestration pores, usually protein molecules are negatively charged so they'll be repelled by the glomerular basement membrane. So we have two barriers so far apart of this filtration membrane. So now we've developed what our glomerulus is really made up of. So let's actually write those two things out. What are the two components? One is actually the, specifically, the endothelial lining. which is what? Finistrated, guys. Remember that. With the finistration pores, which are approximately about 50 to 100 nanometers in diameter, which allow for certain things to pass through. What's the other component of the glomerulus? The other component of the glomerulus is the, I'm just going to put glomerular basement membrane, GBM, right? And this is important because he has negatively charged surface, which repels negatively charged particles. So if you think about it like this, negatively charged particles are repelled. Positively charged particles move through. Any neutral charge will also move through, but not as readily as positively charged particles. Okay? Those are the two components of the glomerulus. Now, what about the Bowman's capsule? Okay, for the Bowman's capsule, there's actually two different components. One, one is actually the parietal and the other one is the visceral layer. but specifically these are your podocytes. Okay so now let's look at this. Okay so we talked about the finished rate of capillary endothelium, we talked about the glomerular basement membrane, now we're going to talk about the visceral layer of the Bowman's capsule, specifically the podocytes. These podocytes, you know what podo actually means foot, so it's foot cells. So if you see at the end part it has these little little different foot processes. Okay these have in between the podocytes, let's say here's a podocyte, so let's say this is podocyte one. And this is podocyte 2, podocyte 3, podocyte 4, podocyte 5. In between podocyte 1 and 2, there is a specific type of protein molecule. Look at this. You see this? It's kind of like interconnecting here. So here's another one. Here's another one interconnecting. Here's another one between four and three interconnecting. And here's one between four and five interconnecting. You see what these little orange molecules are that are interconnecting our podocytes? This is actually called a very important protein. I wouldn't be mentioning if it's not. This molecule here is actually this orange molecule is called nephrin. Now, nephrin is important because there are certain types of conditions in glomerulonephritis where you can actually have mutations within this nephrin protein. Why is that significant? Because you know nephrin is really, really important for being able to To control what's actually making it through what? What's so far of what they have to go through to get to this point? They'd have to go through the fenestration pores. They'd have to make it through the negatively charged glomerular basement membrane. And then they have to get between these little things here. What's this space right here called? Between the podocytes here called. What's that space there called? That space between the podocytes is actually called the filtration slit. And the filtration slit is approximately 25 to 30 nanometers in diameter. So now, if it's made it through the fenestration pores, if it's made it through the negatively charged glomerular basement membrane, and if it's less than 25 nanometers, approximately 25 to 30 nanometers in diameter, it'll make it through. But then guess what? This nephrin proteins only allow for molecules, anything that's actually 7 to 9 nanometers in diameter or less, to pass through. Okay, nephrin is this protein molecule and he's actually forming this structure around the, so this space is the filtration slit. But nephrin is kind of like a thin protein structure that's spanning that filtration slit. And because it's spanning the filtration slit, they call this the slit diaphragm. Okay, so it's called the slit diaphragm and a slit diaphragm is composed of nephrine and nephrine is only allowing for molecules that are less than 7 to 9 nanometers to be able to pass through this area. Okay. Then, what do we have on the outside edges here? We have the parietal layer of the Bowman's capsule. So it's continuous with the visceral layer of Bowman's capsule. So the podocytes cling to the capillaries and it goes continuous with the parietal layer. layer of the Bowman's capsule to make a nice space so that anything that's filtering out isn't just lost. It's collected into this nice little Bowman's space here. Okay, so what are the two components of the Bowman's capsule? Ready? The podocyte layer and it has spaces in between the podocytes which are called filtration slits and they're approximately 25 to 30 nanometers in diameter. And then it has this protein molecule that are in between the podocytes linked together, right? And nephrin is the component of it. It's making this. slit diaphragm which is only allowing for molecules that are about less than seven to nine nanometers to make it through this area. Okay so now let's go ahead and just kind of recap what can actually move through here because we kind of got a basic component of everything that's making up this renal corpuscle. Let's cover what can make it through now. Okay so we can have plasma proteins let's just represent A as albumin, IgG antibodies is another different type of protein. Let's represent our electrolytes like sodium, potassium. calcium, chloride, what else would you have? You'd have calcium, you'd have magnesium, you could have bicarbonate, tons of different molecules, different types of actual electrolyte molecules, right? What else would you have over here? You'd have glucose, you'd have amino acids, you'd have different types of lipids, you'd have urea, different types of waste products, right? Like even creatinine or creatinine, which is a breakdown product of the muscles, skeletal muscles from creatine phosphate. you'd have vitamins, tons of different molecules in here, right? And what's one of the more important ones that we should definitely mention? Water. All these are different molecules which are running through our plasma, right? And this isn't even all of them, we could even have other things in there. But again, the basic component is that you have electrolytes flowing through the plasma, you have different types of nutrient sources and waste products flowing through the plasma, you have water which is making up like 93% of the plasma, and you have different types of plasma proteins, okay? Albumin, fibrinogen, I could even even put in there I could put in the F for fibrinogen if I needed to okay so there's fibrinogen and if I bring it it would also have negatively charged particles on it right different types of amino acids that make it negatively charged now out of these things what did I tell you can actually fit through the fenestration pores anything that's actually less than 50 to 100 nanometers in diameter can pass right through so most of these substances can actually pass through But, what did I tell you the glomerular basement membrane has on it? Negatively charged particles. So anything that's negatively charged, like these actual, what? Any of these plasma proteins are repelled. This is repelled and this is repelled. From what? The glomerular basement membrane. What else did I tell you about the glomerular basement membrane? Any type of positively charged particles are going to move through faster and easier than negatively charged. charged particles. So if you had to compare here, bicarbonate would be a little bit harder to filter, right, as compared to sodium, potassium, calcium, magnesium. And chloride would be harder to filter as compared to potassium. But nonetheless, these substances are filtered. So what would be filtered out here? You would have, it would actually move through the fenestration pores, through the glomerular basement membrane, and these particles, as long as they're less than what? At least 25 to 30 nanometers in diameter, as well as if they're less than 7 to 9 nanometers in diameter, what's going to come out here? You're going to have bicarb, you're going to have sodium, you're going to have potassium, chloride, calcium, magnesium, water's even going to be out here. What else would be out here? Glucose, amino acids, lipids, urea, creatinine, all these different types of molecules are being filtered out. Look at all of these things. All of these are being filtered out and again what are they running through? As a quick recap, running through the fenestration pores as long as they're less than 50 to 100 nanometers in diameter. Anything that's negatively charged is repelled by the glomerular basement membrane. They pass through the filtration slits, which is about 25 to 30 nanometers in diameter. Then there's the nephrine, which is making up that slit diaphragm, and as long as any particle is less than 7 to 9 nanometers in diameter, it'll get freely filtered. And what are those molecules that are most commonly freely filtered? They are glucose, amino acids, lipids, urea, creatinine, different types of electrolytes, even lactic acid and vitamins. Different types of molecules are filtered out and then where will they go? They'll move out here into the actual what? Proximal convoluted tubule. Now one more thing before we go into these pressures. Okay, let's say by some chance some type of macromolecule gets through the fenestration pores, gets through this actual glomerular basement membrane, and gets hung up in this filtration slit by the slit. diaphragm. What are we gonna do with that? It's just, let's say it's actually dangling. Let's say here it is. Let's say out somehow albumin is just freaking dangling from this thing. Okay, like a monkey. Look what happens. You see these cells right here? These little like piranha looking cells. They're getting ready to frick something up. You know what these cells are called? They're called mesangial cells. So what are these cells here called? These little piranha looking cells. They're called mesangial cells. Now mesangial cells are very very important to the glomerular structure right because they have a couple different properties. One is they'll actually phagocytose any type of molecules that get hung up in that actual slit diaphragm. which is composed of nephrin. So that guy right there, he's gonna come over and he's gonna phagocytose any macromolecules that get stuck and hung up in that slit diaphragm. You know what else he can do? He also has contractile activity. So he can contract, contract what? He can contract and control the amount of blood flow that's coming in through the 8th baron arteriole and into the glomerular capillaries. We'll discuss that. Also, he has gap junctions. Gap junctions that connect him to these cells from other cells which are called the maculodensis cells. What are these cells here called? These little violet or maroon cells, they're called JG cells. Specifically, juxta. glomerular cells. If you remember these, these are the ones that are producing renin. And renin was important for our blood pressure, right? So they're actually baroreceptors, so pressure receptors. They pick up different types of changes in pressure. When the pressure is low, they'll secrete renin. And if you remember, renin was important for being able to maintain our blood pressure. Okay? And he can get signals from who? Pretend here was that mesangial cell. The mesangial cell, has little gap junctions that connect him to these actual JG cells. And he can allow for different types of positively charged ions to come over here and stimulate him to release renin. We'll talk about that in the tubulo glomerular feedback mechanism. Okay, so we've covered a lot about the actual glomerulus in the Bowman's capsule and everything it can filter, what allows for it to filter. I think we've done pretty good on this. Now let's come over here and let's cover all the pressures that are involved in this. What's actually allowing for this net filtration? So what did I say? Net filtration. So what are we going to talk about now? We need to talk about the net filtration. But you know nothing likes to move on its own. It has to get a little bit of a push. So you have to apply some pressure. Okay? What is that called then? We're going to talk about net. Filtration pressure. Because you know when we're talking about things that are being filtered, it happens over a given period of time. When something is being filtered over a given period of time, and where is it occurring? It's occurring in the glomerulus. So there's what's called a glomerular filtration rate. So there's a glomerular filtration rate and generally we describe this as the amount of fluid that's actually being, you know, plasma volume that's actually being filtered out of the glomerulus and into the Bowman's capsule for every one minute. So we refer to this as the volume of plasma that's being filtered from the glomerulus for every one minute. On average, that's about 125 milliliters per minute. Now some of you might be like, where the frick did that come from? Let me explain to you. About every one minute, okay, there is approximately 1,200 milliliters of plasma flowing through the glomerulus. So for every one minute, 1,200 milliliters is flowing through this area. Now, out of that 1,200 milliliters, only 625 milliliters per minute. are going to be used in this filtration process. So, 1200 milliliters per minute are passing through here. But out of that 1200 milliliters, 625 are being used in the filtration process. The remaining amount is passing by. So now, what's actually leaving then? So, 1200 is coming in, 625 is going to be used in this filtration process. But, 575 milliliters per minute is actually going to be leaving out. Now, here's what's the interesting part. Out of that 625 milliliters per minute that you're actually going to be coming out of this, here's what's crazy. Only 20% of it is actually going to be filtered. Okay? So 1,200 milliliters is passing through here. 625 milliliters we're going to use for this filtration process. But out of that 625 mils, we're only going to really filter 20% of it. What is 20% of 625? That is actually 125 milliliters per minute. Okay? That's where we get that glomerular filtration rate. Okay. Now that we've done that, we know specifically how we get the glomerular filtration rate. But now we got to talk about factors that are affecting the glomerular filtration rate. What's actually affecting the glomerular filtration rate? So in other words, what can increase it, what can decrease it, so on and so forth. Okay, so the first part of it is the net filtration pressure. Now net filtration pressure is consisting of the forces that are trying to push things out. So pressures... Trying to push things, so I'm going to put pressures, forcing out. Okay, so let's take a look at those pressures. But then it's also dependent upon the difference of the pressures forcing things out minus the pressures pulling things in. So pressures pulling. In. Okay, let's look at these two different components here because glomerular filtration rate is dependent upon this and something else that we'll talk about in a second. Okay, so look at this first pressure. This first pressure here is actually going to be called glomerular hydrostatic pressure. Now glomerular hydrostatic pressure is actually trying to push things out of this capillary. So he's trying to push things out of the capillary. That's what glomerular hydrostatic pressure is. Now generally, as blood is flowing through here, so let's say blood is flowing through the afferent arteriole, because this is the afferent arteriole and this is the efferent arteriole. When the blood is flowing through here, the glomerular hydrostatic pressure is defined as the pressure that's trying to push the plasma components out of the capillary and into this actual... Bowman space. So that's what glomerular hydrostatic pressure is. It's defined as the actual forces that are trying to push the plasma, a specific volume of the plasma out of the glomerular capillaries into the Bowman space. This number on average is about 55 millimeters of mercury. Okay, that's the average glomerular hydrostatic pressure. Now, there's another pressure. There's a pressure that's exerted by specific types of plasma proteins, like albumin. Albumin is trying to be able to keep things into the blood. He doesn't want things to leave the blood. Okay? So this is actually going to be a specific pressure, and this pressure we're going to call colloid osmotic pressure. And colloid osmotic pressure is exerted by Plasma proteins that are being able to try to keep the water into the bloodstream. So where is the arrow pointing? It's trying to keep the actual water and prevent the water from leaving out into the space. So keep it into the blood. This colloid osmotic pressure is on average, okay, on average about specifically 30 millimeters of mercury. So about 30 millimeters of mercury, okay? So 30 millimeters of mercury for the colloid osmotic pressure and that's exerted by who? Albumin. Now there's one more. As fluid is being filtered out here, right? Think about it like a funnel. So here's the fluid, and it's trying to filter down into this little funnel right there. As the fluid is trying to filter in through this area, what happens? If you try to pour a lot of fluid into a funnel at once, what happens? It overflows, right? Same thing is happening here. As you start trying to push fluid out into this actual Bowman's capsule, there's a narrow filtering process here. So some of the fluid can start backing up and backing up and backing up and exert a pressure that wants to push things. back into the actual capillary. What is this pressure called? It's trying to push things back into this capillary bed. This right here is called capsular hydrostatic pressure. This is called capsular hydrostatic pressure. So the capsular hydrostatic pressure is the pressure that's being exerted by the actual pressure built up within the Bowman's capsule. And as it's trying to drain, there's a back pressure that tries to push fluid back into the actual glomerular capillaries. And this on average is approximately 15 millimeters of mercury. Okay, so now we have all of our, basically all these pressures that are pushing things out and all the pressures that are trying to pull or push things in. Technically, there is one more pressure that I could mention here, and it's zero though. So it's not really necessary to mention it. But, and the reason why is there's a pressure that you can technically consider out here. And then let's say there's a pressure trying to pull things into this actual... Bowman's capsule. That pressure would technically be called the capsular osmotic pressure. But what do we say as long as the filtration membrane is nice and actual kept intact and it's not going to have any type of fluctuation. in its activity, there shouldn't be any type of plasma proteins out in this area. So if there's no plasma proteins into this area, can there really be any osmotic pressure out here? No. So normally the colloid osmotic pressure in this area is zero millimeters of mercury. we don't even really consider this one into the equation. Okay, so now let's come over here and let's look and see what we got now. So if we take the pressures trying to force things out or even if you technically think about it the cholerosmotic pressure trying to pull things out, what is the pressures associated here? So technically we could say the first pressure is the glomerular hydrostatic pressure plus the capsular osmotic pressure technically, right? What was the glomerular hydrostatic pressure? It was approximately 55 millimeters per second. of mercury and then what was the colloid osmotic pressure? It was approximately zero millimeters of mercury right assuming normal activity. What were the pressures that were trying to pull things in? It was the colloid osmotic pressure right and that was actually trying to pull things in via the albumin. Then there was actually going to be the back pressure of the capsule trying to push things in which is called the capsular hydrostatic pressure. What's the colloid osmotic pressure? pressure on average is about 30 millimeters of mercury plus the capsular hydrostatic pressure which is about 15 millimeters of mercury. If you do 55 minus approximately 45, what's your net filtration pressure? 10 millimeters of mercury. Okay, now from this we can derive a specific concept that due to these pressures any fluctuations in your net filtration pressure directly affects your glomerular filtration rate. So then other words your net filtration pressure is proportional to your glomerular filtration rate. So in other words, any increase in net filtration pressure increases your GFR. Any decrease in net filtration pressure decreases your GFR. Wow, you developed a heck of a concept. there right okay so there's two components here that are affecting this one is the surface area of the glomerulus okay so surface area of the glomerulus that's one thing the other thing that's going to determine this is also going to be Specifically, the permeability. So the permeability of glomerulus. Okay, so let's say I take two different types of glomeruli. One like this. Alright, so there's the afferent arteriole that's actually taking the blood in. Here's the efferent arteriole. Let's draw another one though. Okay, now look at this puppy. Whoa! A-Ferran arterial, E-Ferran arterial. What's the difference that you notice between these two? This one has a very small surface area. So he has a very small surface area. There's not much surface area to actually upon to filter. So this will have a lower glomerular filtration rate, right? Because it has a smaller surface area. But if you have a large surface area, you have much more surface area for filtration. So this would result in a greater glomerular filtration rate. That should be almost intuitive, right? That should make complete sense. Smaller the surface area, the smaller the GFR. The greater the surface area, the greater the GFR. Simple as that. What could change the surface area? Certain types of conditions could actually make it a little thicker. You know there's actually a condition and you've probably heard of it called diabetes, but specifically it's called diabetic nephropathy. And with diabetic nephropathy, there's actually protein and actual specific deposits in this actual glomerulus that make it thicker. And as you make it thicker, it actually decreases the surface area, which can affect the glomerular filtration rate. But I'm just giving you a clinical correlation to surface area and how important it is for glomerular filtration rate. Okay? So let's say I take two different types of glomeruli here. Let's say I take this one, same surface area for both of them. So look, here's another one, same surface area for this guy also. But look at the difference here. Watch this. Let's say that this one only has one, two, three channels here to filter things out. Okay, three channels. While this one over here has one, two, three, four, five. five channels on the same surface area, what's going to happen to this guy's filtration rate? This one will have a greater glomerulofiltration rate, right? Because he has a lot more permeability. This one will have a lower glomerulofiltration rate because he has less permeability. What kind of diseases could affect this? You ever heard of glomerulonephritis? So there's a condition called glomerulo. nephritis and whenever there's damage to the glomerulus it actually can affect the basement membrane and make the basement membrane very very uh it can actually destroy the basement membrane and make it very porous what happens to the glomerulus filtration rate if the actual glomerular basement membrane was affected and very poor so you would have a higher glomerular filtration rate and you would lose a lot of proteins into the urine okay okay so now as an overall concept here if I were to take surface area and permeability of the actual capillaries and combine them together, this actually gives me a specific term. This term is called KF. And KF stands for filtration coefficient. Okay, so now I can actually derive one last formula that we need here. We can say that glomerular filtration rate technically is equal to the net filtration pressure times the filtration coefficient. Because before we said that net filtration... pressure is directly proportional to GFR. Increase in NFP increases GFR. Filtration coefficient is dependent upon surface area and permeability of the glomerulus. Any fluctuations in the filtration coefficient also directly affects the glomerular filtration rate. One last thing here guys. Let's apply a clinical correlation to these actual net filtration pressure because I think that's significant. Okay so let's say that I take these three different pressures here the most important ones the glomerular hydrostatic pressure, the colloid osmotic pressure here, and then the capsular hydrostatic pressure. What could be certain situations that could affect these things? Well, I told you before that glomerular hydrostatic pressure is directly dependent upon your systemic blood pressure. So if your BP is really high, if your systemic blood pressure is high, what happens to your glomerular hydrostatic pressure? It increases your glomerular hydrostatic pressure. What happens if your BP goes down? So what happens if you're having hypotension? Your glomerular hydrostatic pressure, hydrostatic pressure goes down. It's that simple. Okay. So glomerular hydrostatic pressure is directly dependent upon your systemic blood pressure and increase. Increase in blood pressure increases the glomerular hydrostatic pressure, whereas a decrease decreases the glomerular hydrostatic pressure. What about colloid osmotic pressure? Let's say that you actually have too many different types of proteins in the blood, like there's a condition called multiple myeloma. Where you have too many different types of proteins in the blood. If that happens, what happens to the amount of proteins in the blood? They go up. If the amount of proteins in the blood go up, you start holding on to more water in the blood. If you hold on to a lot of water, what happens? The colloid osmotic pressure is going to increase, right? So this increases colloid osmotic pressure. What happens if you have hypoproteinemia, so low proteins in the blood? So this could be due to maybe someone who's gluten sensitive and they decide to like take and eat house of pizza. And what happens? They don't feel good and they have the Hershey squirts, right? So they start losing a lot of substances, right? Or maybe they have some type of actual disease. Maybe they have been infected by the giardia and they lose a lot of proteins into their actual feces, right? So what happens then? You lose proteins. If you lose proteins, can you hold on to as much water inside of the bloodstream? No. So what happens to your colloid osmotic pressure if you lose proteins? This decreases colloid osmotic pressure. And then what happens then? You start losing fluids a lot more than normal into the actual Bowman space. Okay, what about capsular hydrostatic pressure? Well, let's say that you get like a freaking massive kidney stone stuck in your nephron loop or something like that, right? So you get what's called a renal calcule that's greater than five millimeters in diameter and it gets stuck. So a renal calcule, right? So just a kidney stone. greater than 5 millimeters in diameter, so greater than 5 millimeters in diameter, and it gets stuck in one of the actual nephron loops. Let's say here's your nephron loop, and here's your actual Bowman's capsule. If you have a stone stuck there, what's going to happen to the pressure? It's going to start backing up and it's going to start increasing and trying to push things back into the glomerulus. So what would that do to your capsular hydrostatic pressure if you had like a kidney stone? It's going to increase. your capsular hydrostatic pressure. There's other conditions too like renal ptosis when individuals are really really emaciated they don't they lose a lot of weight rapid weight loss their kidneys drop and it kinks up and fluid flows back into their kidneys it's called hydronephrosis. That also can cause this problem too. So not only can renal calcule do this but also hydronephrosis due to renal ptosis. Okay, this can also increase capsular hydrostatic pressure. And then what would be the result of an increase in capsular hydrostatic pressure? You would have more fluid being pushed back into the glomeruli and not as much net filtration. Alright Ninja Nerds, we covered a lot in this video about glomerular filtration. Thank you guys for sticking with us and watching this. We really appreciate it. I hope you guys enjoyed it. I hope it all made sense. Until next time Ninja Nerds.

We have to talk about what's called a renal corpuscle. Okay, so first off, what is a renal corpuscle? Let's actually define what a renal corpuscle is.

So, renal corpuscle is two things. Okay? The first thing is actually the glomerulus. Okay? Which is capillaries, which is a tuft of capillaries.

The other thing is the Bowman's capsule. Or sometimes they even call it the glomerular capsule. We're just going to call it the Bowman's capsule. Okay, so two components of the renal corpuscle.

Again, what are those two components of the renal corpuscle? The two components of the renal corpuscle is specifically the glomerular capsule. glomerulus, which is the tuft of capillaries, and the Bowman's capsule. Let's first talk about the glomerulus and the filtration membrane, which is a part of it, and then we'll talk about the Bowman's capsule.

Let's first focus on the glomerulus. notice here this right here is the glomerulus because this is the tuft of capillaries right here so a glomerulus is like a tuft of capillaries and here's what's interesting if you notice let's say that this is the vessel coming into the glomerulus so this is feeding into the glomerulus when it goes into the glomerulus it's actually called afferent arteriole Okay, so if there's a vessel that's feeding the glomerulus, it's called the afferent arteriole. And again, this is the glomerulus right here. Right here is the glomerulus. Okay, so we'll put that right above it.

This is our glomerulus, which is our tuft of capillaries. Oh, what type of capillaries is there within the glomerulus? That's really, really important.

You know what type of capillaries are here in the glomerulus? They're actually called fenestrated. Capillaries.

You know what fenestrated capillaries means? Okay, so let's say I take one of these endothelial cells and I zoom in on them. So let's say here's an endothelial cell.

Okay, here's the nucleus of the endothelial cell. In this endothelial cell, it has little holes. Look at this. You see this little hole right there? Little channel basically.

That's a fenestration. There's another one over here too. They have them all around these things.

There's hundreds upon hundreds, even thousands of these little fenestration pores on this endothelial cell. Now, these fenestration pores, what are they for? Let me explain.

explain to you what they're for. Well first off how big are these little things? You know these little things right here these fenestrations are approximately about 50 to 100 nanometers in diameter. That's really freaking small. So about how much?

50 to 100 nanometers in diameter. So really what can actually filter through this? Okay you know within the blood you have your plasma which is consisting of a lot of water and different types of solute molecules right?

And then also you have formed elements. like your white blood cells, your red blood cells, your platelets. Any type of formed elements cannot fit through these fenestrations, okay? So any type of formed elements cannot fit through these actual fenestration pores.

So formed elements are, again, what? What are those components of formed elements? Red blood cells, white blood cells, platelets, none of those can get in. Okay? What can pass through?

The different components of the plasma. So you know like small proteins? Small proteins can pass through this. What else can pass through this? Water.

What else can pass through this? Electrolytes. Like sodium and potassium and calcium and chloride and a whole bunch of other different types of molecules.

A lot of different things. Okay, and even nutrients. Waste products, all different types of molecules can pass through these actual fenestration pores. Okay, so these fenestration pores are basically riddled against all these little endothelial cells within the glomerulus.

That's one important point. Okay, what is this structure draining the glomerulus? Here's a really, really interesting. Watch this.

Usually it's a vein, right, or a venule. This is actually called the efferent. arterial. This is one of the only examples in the body in which a capillary bed is being fed by an arterial and then drained by an arterial.

Okay, so we have apharein arterial feeding the glomerulus, we have an epharein arterial draining the glomerulus, and the glomerulus is again fenestrated capillaries. What does it mean to be fenestrated? It's these little pores In the endothelial cell, right, there are about 50 to 100 nanometers in diameter. And what do they allow for things for it to pass through?

Electrolytes, nutrients, small proteins, water molecules, and even maybe some large molecular weight proteins that are less than 100 nanometers in diameter. Because if they're less than 100 nanometers in diameter, they can pass through the actual fenestration pores. So let's even say, not only small proteins, but like we'll say moderate size proteins.

And again, any proteins or any molecules that are about less than 100 nanometers in diameter can fit through these fenestration pores. Now look at this little nice blue, baby blue thing that we have right here. You see this blue membrane right here? This is one of the most critical parts of the actual glomerulus.

One of the most important points of the glomerulus. You know what this thing is actually called? This blue membrane structure? Let's actually show it over here. This blue membrane structure right here that I'm kind of showing here, that I'm zooming in on right here.

This is actually called the glomerular basement membrane. So again, what is it called? The glomerular basement membrane.

Now some of you might be thinking, okay, it's just a basement membrane. What significance does that have? Oh my goodness, so much significance.

Okay. This glomerular basement membrane is extremely interesting because if I were to, let's say I actually zoomed in on even more. Let's say I even zoomed in on this layer even more.

You know the glomerular basement membrane is actually three sub-layers? Look at this. Let's say I zoom in on it for a second. So here's the glomerular basement membrane.

In the glomerular basement membrane, there's three layers. Let's say here I make a black layer right there. A real, real thick black layer. This thick black layer is actually going to be specifically... Consisting of type 4 collagen.

So what is this layer right here consisting of? It's specifically consisting of type 4 collagen and laminins, these different types of proteins. Okay, so one is actually going to be type 4 collagen and if you notice it's really dense.

You know what they call this actual layer? They call this the lamina densa. Okay.

So one layer right smack dab in the middle which is consisting of type 4 collagen and laminins is called the laminidensa. Then let's say that this is the endothelial side. And what do I mean by endothelial side? I mean that here's your endothelial cells.

This part of the membrane closest to the endothelial cells is this side. Then you have these black cells which I'm going to talk about called the podocytes. That's going to be on this side. So the podocyte, I'm going to put podocyte layer. Okay, on this side here, towards the endothelial cells, it's a thinner like tissue, okay?

It's a thinner layer. This layer right here is actually made up of specific types of molecules like proteoglycans, okay, or glycosaminoglycans, particularly heparin sulfate. And guess what else you're going to find on the other side?

The same thing, heparin sulfate. These are the different types of glycosaminoglycans. Now, here's the next part that's really interesting. Heparin sulfate is extremely negatively.

charged. Okay? So it's very, very negatively charged.

So if I were to show that here, let's say I show it here in orange. On this side, what are you gonna have? A lot of negative charges.

What would you have on this side? A lot of negative charges. That's important.

I'm going to talk about that, why that is. Now, if I were to be particular, this side is closest to the endothelial cell. We call this side lamina rara. interna and then we call this side, so that's lamina rara interna, the one towards the endothelial lining. The one on the opposite side towards the podocyte lining is actually called the lamina rara.

externa. Okay, so the glomerular base membrane has actually three different sub layers. One in the middle is actually the lamina denso with type 4 collagen laminins. Lamina rara interna and lamina rara externa are consisting of heparin sulfate.

Okay, so a different type of glycosaminoglycan which has a lot of negative charges on it. Why is this important? Okay.

You know inside of our blood we have these things called plasma proteins. Let's say I represent a plasma protein here as like albumin. You know what albumin charges inside of the blood generally are most plasma proteins?

It's negatively charged. Let's say I draw another plasma protein just for the heck of it. I put in here Let's say I put in here specifically different types of immunoglobulins.

So I'm going to put IgG and we'll just be for the heck of it, we'll put IgG. Immunoglobulins, these are also negatively charged. I could even put fibrinogen or different types of transport, other types of transport proteins. The whole point is proteins inside of our actual plasma are negatively charged.

What's the charge on this glomerular basement membrane? Negative charge. So it's very, very negatively. Now if you know a little bit about biology, you know that same charges repel one another. So for example, if I have albumin, I represent albumin here as this circle, and then all around him I have negative charges.

If he tries to come through this membrane, or any type of molecule that's negatively charged, tries to come through that membrane, what's going to happen to it? It's going to repel it. So can I get through this actual glomerular basement membrane?

No. That's good at helping to act as a good filter. So now it's acting as a very good filter.

So any type of negatively charged particles that actually try to move through the glomerular basement membrane is repelled. But, if you know again about biology, what actually is going to want to come to the negative charge? Positively charged particles, right? So anything that's positively charged is going to want to come to the negative charges.

So any type of positively charged particles that we might have with inside of the plasma is going to want to what? Pass through here. What are positively charged molecules usually?

Different types of electrolytes like sodium and potassium and calcium and magnesium. So that's really really interesting. Any type of positively charged substances are going to pass through the glomerular basement membrane easily.

Anything that's neutral, it's going to be a little bit harder than positively charged species to pass through, but it can still pass through. any negatively charged species or different types of molecules are going to be repelled and prevented from entering into this actual glomerulin capsule here. Okay? So, if it's big enough, like large molecular weight proteins or large different solute molecules and they move through the fenestration pores, usually protein molecules are negatively charged so they'll be repelled by the glomerular basement membrane. So we have two barriers so far apart of this filtration membrane.

So now we've developed what our glomerulus is really made up of. So let's actually write those two things out. What are the two components? One is actually the, specifically, the endothelial lining. which is what?

Finistrated, guys. Remember that. With the finistration pores, which are approximately about 50 to 100 nanometers in diameter, which allow for certain things to pass through. What's the other component of the glomerulus? The other component of the glomerulus is the, I'm just going to put glomerular basement membrane, GBM, right?

And this is important because he has negatively charged surface, which repels negatively charged particles. So if you think about it like this, negatively charged particles are repelled. Positively charged particles move through. Any neutral charge will also move through, but not as readily as positively charged particles.

Okay? Those are the two components of the glomerulus. Now, what about the Bowman's capsule?

Okay, for the Bowman's capsule, there's actually two different components. One, one is actually the parietal and the other one is the visceral layer. but specifically these are your podocytes.

Okay so now let's look at this. Okay so we talked about the finished rate of capillary endothelium, we talked about the glomerular basement membrane, now we're going to talk about the visceral layer of the Bowman's capsule, specifically the podocytes. These podocytes, you know what podo actually means foot, so it's foot cells. So if you see at the end part it has these little little different foot processes. Okay these have in between the podocytes, let's say here's a podocyte, so let's say this is podocyte one.

And this is podocyte 2, podocyte 3, podocyte 4, podocyte 5. In between podocyte 1 and 2, there is a specific type of protein molecule. Look at this. You see this? It's kind of like interconnecting here. So here's another one.

Here's another one interconnecting. Here's another one between four and three interconnecting. And here's one between four and five interconnecting. You see what these little orange molecules are that are interconnecting our podocytes?

This is actually called a very important protein. I wouldn't be mentioning if it's not. This molecule here is actually this orange molecule is called nephrin. Now, nephrin is important because there are certain types of conditions in glomerulonephritis where you can actually have mutations within this nephrin protein.

Why is that significant? Because you know nephrin is really, really important for being able to To control what's actually making it through what? What's so far of what they have to go through to get to this point? They'd have to go through the fenestration pores. They'd have to make it through the negatively charged glomerular basement membrane.

And then they have to get between these little things here. What's this space right here called? Between the podocytes here called.

What's that space there called? That space between the podocytes is actually called the filtration slit. And the filtration slit is approximately 25 to 30 nanometers in diameter. So now, if it's made it through the fenestration pores, if it's made it through the negatively charged glomerular basement membrane, and if it's less than 25 nanometers, approximately 25 to 30 nanometers in diameter, it'll make it through.

But then guess what? This nephrin proteins only allow for molecules, anything that's actually 7 to 9 nanometers in diameter or less, to pass through. Okay, nephrin is this protein molecule and he's actually forming this structure around the, so this space is the filtration slit.

But nephrin is kind of like a thin protein structure that's spanning that filtration slit. And because it's spanning the filtration slit, they call this the slit diaphragm. Okay, so it's called the slit diaphragm and a slit diaphragm is composed of nephrine and nephrine is only allowing for molecules that are less than 7 to 9 nanometers to be able to pass through this area. Okay.

Then, what do we have on the outside edges here? We have the parietal layer of the Bowman's capsule. So it's continuous with the visceral layer of Bowman's capsule.

So the podocytes cling to the capillaries and it goes continuous with the parietal layer. layer of the Bowman's capsule to make a nice space so that anything that's filtering out isn't just lost. It's collected into this nice little Bowman's space here.

Okay, so what are the two components of the Bowman's capsule? Ready? The podocyte layer and it has spaces in between the podocytes which are called filtration slits and they're approximately 25 to 30 nanometers in diameter.

And then it has this protein molecule that are in between the podocytes linked together, right? And nephrin is the component of it. It's making this.

slit diaphragm which is only allowing for molecules that are about less than seven to nine nanometers to make it through this area. Okay so now let's go ahead and just kind of recap what can actually move through here because we kind of got a basic component of everything that's making up this renal corpuscle. Let's cover what can make it through now. Okay so we can have plasma proteins let's just represent A as albumin, IgG antibodies is another different type of protein. Let's represent our electrolytes like sodium, potassium.

calcium, chloride, what else would you have? You'd have calcium, you'd have magnesium, you could have bicarbonate, tons of different molecules, different types of actual electrolyte molecules, right? What else would you have over here?

You'd have glucose, you'd have amino acids, you'd have different types of lipids, you'd have urea, different types of waste products, right? Like even creatinine or creatinine, which is a breakdown product of the muscles, skeletal muscles from creatine phosphate. you'd have vitamins, tons of different molecules in here, right?

And what's one of the more important ones that we should definitely mention? Water. All these are different molecules which are running through our plasma, right? And this isn't even all of them, we could even have other things in there. But again, the basic component is that you have electrolytes flowing through the plasma, you have different types of nutrient sources and waste products flowing through the plasma, you have water which is making up like 93% of the plasma, and you have different types of plasma proteins, okay?

Albumin, fibrinogen, I could even even put in there I could put in the F for fibrinogen if I needed to okay so there's fibrinogen and if I bring it it would also have negatively charged particles on it right different types of amino acids that make it negatively charged now out of these things what did I tell you can actually fit through the fenestration pores anything that's actually less than 50 to 100 nanometers in diameter can pass right through so most of these substances can actually pass through But, what did I tell you the glomerular basement membrane has on it? Negatively charged particles. So anything that's negatively charged, like these actual, what? Any of these plasma proteins are repelled.

This is repelled and this is repelled. From what? The glomerular basement membrane.

What else did I tell you about the glomerular basement membrane? Any type of positively charged particles are going to move through faster and easier than negatively charged. charged particles.

So if you had to compare here, bicarbonate would be a little bit harder to filter, right, as compared to sodium, potassium, calcium, magnesium. And chloride would be harder to filter as compared to potassium. But nonetheless, these substances are filtered.

So what would be filtered out here? You would have, it would actually move through the fenestration pores, through the glomerular basement membrane, and these particles, as long as they're less than what? At least 25 to 30 nanometers in diameter, as well as if they're less than 7 to 9 nanometers in diameter, what's going to come out here? You're going to have bicarb, you're going to have sodium, you're going to have potassium, chloride, calcium, magnesium, water's even going to be out here. What else would be out here?

Glucose, amino acids, lipids, urea, creatinine, all these different types of molecules are being filtered out. Look at all of these things. All of these are being filtered out and again what are they running through? As a quick recap, running through the fenestration pores as long as they're less than 50 to 100 nanometers in diameter. Anything that's negatively charged is repelled by the glomerular basement membrane.

They pass through the filtration slits, which is about 25 to 30 nanometers in diameter. Then there's the nephrine, which is making up that slit diaphragm, and as long as any particle is less than 7 to 9 nanometers in diameter, it'll get freely filtered. And what are those molecules that are most commonly freely filtered?

They are glucose, amino acids, lipids, urea, creatinine, different types of electrolytes, even lactic acid and vitamins. Different types of molecules are filtered out and then where will they go? They'll move out here into the actual what?

Proximal convoluted tubule. Now one more thing before we go into these pressures. Okay, let's say by some chance some type of macromolecule gets through the fenestration pores, gets through this actual glomerular basement membrane, and gets hung up in this filtration slit by the slit. diaphragm. What are we gonna do with that?

It's just, let's say it's actually dangling. Let's say here it is. Let's say out somehow albumin is just freaking dangling from this thing. Okay, like a monkey.

Look what happens. You see these cells right here? These little like piranha looking cells. They're getting ready to frick something up. You know what these cells are called?

They're called mesangial cells. So what are these cells here called? These little piranha looking cells.

They're called mesangial cells. Now mesangial cells are very very important to the glomerular structure right because they have a couple different properties. One is they'll actually phagocytose any type of molecules that get hung up in that actual slit diaphragm.

which is composed of nephrin. So that guy right there, he's gonna come over and he's gonna phagocytose any macromolecules that get stuck and hung up in that slit diaphragm. You know what else he can do? He also has contractile activity.

So he can contract, contract what? He can contract and control the amount of blood flow that's coming in through the 8th baron arteriole and into the glomerular capillaries. We'll discuss that.

Also, he has gap junctions. Gap junctions that connect him to these cells from other cells which are called the maculodensis cells. What are these cells here called?

These little violet or maroon cells, they're called JG cells. Specifically, juxta. glomerular cells.

If you remember these, these are the ones that are producing renin. And renin was important for our blood pressure, right? So they're actually baroreceptors, so pressure receptors.

They pick up different types of changes in pressure. When the pressure is low, they'll secrete renin. And if you remember, renin was important for being able to maintain our blood pressure. Okay?

And he can get signals from who? Pretend here was that mesangial cell. The mesangial cell, has little gap junctions that connect him to these actual JG cells.

And he can allow for different types of positively charged ions to come over here and stimulate him to release renin. We'll talk about that in the tubulo glomerular feedback mechanism. Okay, so we've covered a lot about the actual glomerulus in the Bowman's capsule and everything it can filter, what allows for it to filter. I think we've done pretty good on this. Now let's come over here and let's cover all the pressures that are involved in this.

What's actually allowing for this net filtration? So what did I say? Net filtration.

So what are we going to talk about now? We need to talk about the net filtration. But you know nothing likes to move on its own. It has to get a little bit of a push. So you have to apply some pressure.

Okay? What is that called then? We're going to talk about net.

Filtration pressure. Because you know when we're talking about things that are being filtered, it happens over a given period of time. When something is being filtered over a given period of time, and where is it occurring?

It's occurring in the glomerulus. So there's what's called a glomerular filtration rate. So there's a glomerular filtration rate and generally we describe this as the amount of fluid that's actually being, you know, plasma volume that's actually being filtered out of the glomerulus and into the Bowman's capsule for every one minute.

So we refer to this as the volume of plasma that's being filtered from the glomerulus for every one minute. On average, that's about 125 milliliters per minute. Now some of you might be like, where the frick did that come from? Let me explain to you. About every one minute, okay, there is approximately 1,200 milliliters of plasma flowing through the glomerulus.

So for every one minute, 1,200 milliliters is flowing through this area. Now, out of that 1,200 milliliters, only 625 milliliters per minute. are going to be used in this filtration process. So, 1200 milliliters per minute are passing through here.

But out of that 1200 milliliters, 625 are being used in the filtration process. The remaining amount is passing by. So now, what's actually leaving then? So, 1200 is coming in, 625 is going to be used in this filtration process.

But, 575 milliliters per minute is actually going to be leaving out. Now, here's what's the interesting part. Out of that 625 milliliters per minute that you're actually going to be coming out of this, here's what's crazy.

Only 20% of it is actually going to be filtered. Okay? So 1,200 milliliters is passing through here.

625 milliliters we're going to use for this filtration process. But out of that 625 mils, we're only going to really filter 20% of it. What is 20% of 625?

That is actually 125 milliliters per minute. Okay? That's where we get that glomerular filtration rate. Okay. Now that we've done that, we know specifically how we get the glomerular filtration rate.

But now we got to talk about factors that are affecting the glomerular filtration rate. What's actually affecting the glomerular filtration rate? So in other words, what can increase it, what can decrease it, so on and so forth. Okay, so the first part of it is the net filtration pressure.

Now net filtration pressure is consisting of the forces that are trying to push things out. So pressures... Trying to push things, so I'm going to put pressures, forcing out.

Okay, so let's take a look at those pressures. But then it's also dependent upon the difference of the pressures forcing things out minus the pressures pulling things in. So pressures pulling.

In. Okay, let's look at these two different components here because glomerular filtration rate is dependent upon this and something else that we'll talk about in a second. Okay, so look at this first pressure. This first pressure here is actually going to be called glomerular hydrostatic pressure.

Now glomerular hydrostatic pressure is actually trying to push things out of this capillary. So he's trying to push things out of the capillary. That's what glomerular hydrostatic pressure is.

Now generally, as blood is flowing through here, so let's say blood is flowing through the afferent arteriole, because this is the afferent arteriole and this is the efferent arteriole. When the blood is flowing through here, the glomerular hydrostatic pressure is defined as the pressure that's trying to push the plasma components out of the capillary and into this actual... Bowman space. So that's what glomerular hydrostatic pressure is.

It's defined as the actual forces that are trying to push the plasma, a specific volume of the plasma out of the glomerular capillaries into the Bowman space. This number on average is about 55 millimeters of mercury. Okay, that's the average glomerular hydrostatic pressure.

Now, there's another pressure. There's a pressure that's exerted by specific types of plasma proteins, like albumin. Albumin is trying to be able to keep things into the blood.

He doesn't want things to leave the blood. Okay? So this is actually going to be a specific pressure, and this pressure we're going to call colloid osmotic pressure.

And colloid osmotic pressure is exerted by Plasma proteins that are being able to try to keep the water into the bloodstream. So where is the arrow pointing? It's trying to keep the actual water and prevent the water from leaving out into the space. So keep it into the blood. This colloid osmotic pressure is on average, okay, on average about specifically 30 millimeters of mercury.

So about 30 millimeters of mercury, okay? So 30 millimeters of mercury for the colloid osmotic pressure and that's exerted by who? Albumin.

Now there's one more. As fluid is being filtered out here, right? Think about it like a funnel.

So here's the fluid, and it's trying to filter down into this little funnel right there. As the fluid is trying to filter in through this area, what happens? If you try to pour a lot of fluid into a funnel at once, what happens?

It overflows, right? Same thing is happening here. As you start trying to push fluid out into this actual Bowman's capsule, there's a narrow filtering process here. So some of the fluid can start backing up and backing up and backing up and exert a pressure that wants to push things. back into the actual capillary.

What is this pressure called? It's trying to push things back into this capillary bed. This right here is called capsular hydrostatic pressure. This is called capsular hydrostatic pressure.

So the capsular hydrostatic pressure is the pressure that's being exerted by the actual pressure built up within the Bowman's capsule. And as it's trying to drain, there's a back pressure that tries to push fluid back into the actual glomerular capillaries. And this on average is approximately 15 millimeters of mercury. Okay, so now we have all of our, basically all these pressures that are pushing things out and all the pressures that are trying to pull or push things in.

Technically, there is one more pressure that I could mention here, and it's zero though. So it's not really necessary to mention it. But, and the reason why is there's a pressure that you can technically consider out here. And then let's say there's a pressure trying to pull things into this actual... Bowman's capsule.

That pressure would technically be called the capsular osmotic pressure. But what do we say as long as the filtration membrane is nice and actual kept intact and it's not going to have any type of fluctuation. in its activity, there shouldn't be any type of plasma proteins out in this area.

So if there's no plasma proteins into this area, can there really be any osmotic pressure out here? No. So normally the colloid osmotic pressure in this area is zero millimeters of mercury.

we don't even really consider this one into the equation. Okay, so now let's come over here and let's look and see what we got now. So if we take the pressures trying to force things out or even if you technically think about it the cholerosmotic pressure trying to pull things out, what is the pressures associated here?

So technically we could say the first pressure is the glomerular hydrostatic pressure plus the capsular osmotic pressure technically, right? What was the glomerular hydrostatic pressure? It was approximately 55 millimeters per second. of mercury and then what was the colloid osmotic pressure?

It was approximately zero millimeters of mercury right assuming normal activity. What were the pressures that were trying to pull things in? It was the colloid osmotic pressure right and that was actually trying to pull things in via the albumin. Then there was actually going to be the back pressure of the capsule trying to push things in which is called the capsular hydrostatic pressure.

What's the colloid osmotic pressure? pressure on average is about 30 millimeters of mercury plus the capsular hydrostatic pressure which is about 15 millimeters of mercury. If you do 55 minus approximately 45, what's your net filtration pressure?

10 millimeters of mercury. Okay, now from this we can derive a specific concept that due to these pressures any fluctuations in your net filtration pressure directly affects your glomerular filtration rate. So then other words your net filtration pressure is proportional to your glomerular filtration rate. So in other words, any increase in net filtration pressure increases your GFR.

Any decrease in net filtration pressure decreases your GFR. Wow, you developed a heck of a concept. there right okay so there's two components here that are affecting this one is the surface area of the glomerulus okay so surface area of the glomerulus that's one thing the other thing that's going to determine this is also going to be Specifically, the permeability.

So the permeability of glomerulus. Okay, so let's say I take two different types of glomeruli. One like this.

Alright, so there's the afferent arteriole that's actually taking the blood in. Here's the efferent arteriole. Let's draw another one though. Okay, now look at this puppy. Whoa!

A-Ferran arterial, E-Ferran arterial. What's the difference that you notice between these two? This one has a very small surface area.

So he has a very small surface area. There's not much surface area to actually upon to filter. So this will have a lower glomerular filtration rate, right?

Because it has a smaller surface area. But if you have a large surface area, you have much more surface area for filtration. So this would result in a greater glomerular filtration rate.

That should be almost intuitive, right? That should make complete sense. Smaller the surface area, the smaller the GFR.

The greater the surface area, the greater the GFR. Simple as that. What could change the surface area? Certain types of conditions could actually make it a little thicker. You know there's actually a condition and you've probably heard of it called diabetes, but specifically it's called diabetic nephropathy.

And with diabetic nephropathy, there's actually protein and actual specific deposits in this actual glomerulus that make it thicker. And as you make it thicker, it actually decreases the surface area, which can affect the glomerular filtration rate. But I'm just giving you a clinical correlation to surface area and how important it is for glomerular filtration rate. Okay?

So let's say I take two different types of glomeruli here. Let's say I take this one, same surface area for both of them. So look, here's another one, same surface area for this guy also. But look at the difference here. Watch this.

Let's say that this one only has one, two, three channels here to filter things out. Okay, three channels. While this one over here has one, two, three, four, five.

five channels on the same surface area, what's going to happen to this guy's filtration rate? This one will have a greater glomerulofiltration rate, right? Because he has a lot more permeability.

This one will have a lower glomerulofiltration rate because he has less permeability. What kind of diseases could affect this? You ever heard of glomerulonephritis?

So there's a condition called glomerulo. nephritis and whenever there's damage to the glomerulus it actually can affect the basement membrane and make the basement membrane very very uh it can actually destroy the basement membrane and make it very porous what happens to the glomerulus filtration rate if the actual glomerular basement membrane was affected and very poor so you would have a higher glomerular filtration rate and you would lose a lot of proteins into the urine okay okay so now as an overall concept here if I were to take surface area and permeability of the actual capillaries and combine them together, this actually gives me a specific term. This term is called KF. And KF stands for filtration coefficient. Okay, so now I can actually derive one last formula that we need here.

We can say that glomerular filtration rate technically is equal to the net filtration pressure times the filtration coefficient. Because before we said that net filtration... pressure is directly proportional to GFR.

Increase in NFP increases GFR. Filtration coefficient is dependent upon surface area and permeability of the glomerulus. Any fluctuations in the filtration coefficient also directly affects the glomerular filtration rate.

One last thing here guys. Let's apply a clinical correlation to these actual net filtration pressure because I think that's significant. Okay so let's say that I take these three different pressures here the most important ones the glomerular hydrostatic pressure, the colloid osmotic pressure here, and then the capsular hydrostatic pressure.

What could be certain situations that could affect these things? Well, I told you before that glomerular hydrostatic pressure is directly dependent upon your systemic blood pressure. So if your BP is really high, if your systemic blood pressure is high, what happens to your glomerular hydrostatic pressure? It increases your glomerular hydrostatic pressure.

What happens if your BP goes down? So what happens if you're having hypotension? Your glomerular hydrostatic pressure, hydrostatic pressure goes down.

It's that simple. Okay. So glomerular hydrostatic pressure is directly dependent upon your systemic blood pressure and increase. Increase in blood pressure increases the glomerular hydrostatic pressure, whereas a decrease decreases the glomerular hydrostatic pressure. What about colloid osmotic pressure?

Let's say that you actually have too many different types of proteins in the blood, like there's a condition called multiple myeloma. Where you have too many different types of proteins in the blood. If that happens, what happens to the amount of proteins in the blood?

They go up. If the amount of proteins in the blood go up, you start holding on to more water in the blood. If you hold on to a lot of water, what happens? The colloid osmotic pressure is going to increase, right? So this increases colloid osmotic pressure.

What happens if you have hypoproteinemia, so low proteins in the blood? So this could be due to maybe someone who's gluten sensitive and they decide to like take and eat house of pizza. And what happens?

They don't feel good and they have the Hershey squirts, right? So they start losing a lot of substances, right? Or maybe they have some type of actual disease. Maybe they have been infected by the giardia and they lose a lot of proteins into their actual feces, right?

So what happens then? You lose proteins. If you lose proteins, can you hold on to as much water inside of the bloodstream? No. So what happens to your colloid osmotic pressure if you lose proteins?

This decreases colloid osmotic pressure. And then what happens then? You start losing fluids a lot more than normal into the actual Bowman space.

Okay, what about capsular hydrostatic pressure? Well, let's say that you get like a freaking massive kidney stone stuck in your nephron loop or something like that, right? So you get what's called a renal calcule that's greater than five millimeters in diameter and it gets stuck. So a renal calcule, right?

So just a kidney stone. greater than 5 millimeters in diameter, so greater than 5 millimeters in diameter, and it gets stuck in one of the actual nephron loops. Let's say here's your nephron loop, and here's your actual Bowman's capsule. If you have a stone stuck there, what's going to happen to the pressure? It's going to start backing up and it's going to start increasing and trying to push things back into the glomerulus.

So what would that do to your capsular hydrostatic pressure if you had like a kidney stone? It's going to increase. your capsular hydrostatic pressure.

There's other conditions too like renal ptosis when individuals are really really emaciated they don't they lose a lot of weight rapid weight loss their kidneys drop and it kinks up and fluid flows back into their kidneys it's called hydronephrosis. That also can cause this problem too. So not only can renal calcule do this but also hydronephrosis due to renal ptosis.

Okay, this can also increase capsular hydrostatic pressure. And then what would be the result of an increase in capsular hydrostatic pressure? You would have more fluid being pushed back into the glomeruli and not as much net filtration. Alright Ninja Nerds, we covered a lot in this video about glomerular filtration.

Thank you guys for sticking with us and watching this. We really appreciate it. I hope you guys enjoyed it. I hope it all made sense. Until next time Ninja Nerds.

Transcript for:Understanding Glomerulofiltration and Its Processes

Transcript for:
Understanding Glomerulofiltration and Its Processes