7.11 Anatomy Transcript PDF

The external steeper is 1 that you're going to have, some control over, and it's the 1 that inhibition of is what allows the vitreousion reflux. So if you get this vitreousion reflux and, again, that stretch of the bladder, causing this reflex to occur. And once it becomes powerful enough, it's gonn...

The external steeper is 1 that you're going to have, some control over, and it's the 1 that inhibition of is what allows the vitreousion reflux. So if you get this vitreousion reflux and, again, that stretch of the bladder, causing this reflex to occur. And once it becomes powerful enough, it's gonna pass through the pedendal nerves. This is gonna be important, pedendal nerve you need to understand is what is going to allow for nutrition to occur to the external sphincter and inhibits it. So the external sphincter is contracted and by con by inhibiting that contraction, you are allowing for urination to occur. So if you have inhibition more potent in the brain than the voluntary constrictor signals to the external sphincter, you're gonna have urination. So what does this mean? Daddy, daddy, I need to pee. Hold it. When you say hold it or when daddy says hold it, what you're doing is you're contracting your external sphincter trying to overcome the inhibition of that external sphincter. So the inhibition of the external sphincter is based on the micturition reflex. If your bladder just like babies. If their bladders get big enough, they're gonna get so many of these reflexes occurring, they're just gonna urinate on themselves. When you, potty train a baby or a a toddler, what are you doing? You're teaching them to control their external sphincters so they do not urinate on themselves or in a diaper. They can hold it hold it, hold the bladder in the urine until they can go to a a place that is socially acceptable and relieve themselves. That's what we're talking about here. You guys already knew that. Alright? So you have areas in the brain that are, can either inhibit this vitreousine reflex or, can facilitate the vitreousum reflex. You have areas in the brainstem, mainly in the pons, our old friend the pons, and you have centers in the cerebral cortex that are mainly inhibitory that can become excitatory. So the high centers are in people that have been potty trained. The high centers of the brain are the ones that are exhibiting spinal control. In other words, toddlers that have not yet been potty trained, what do they they are just going by spinal cord reflexes. But once you've been body trained and figured out, I don't have to urinate as soon as I get a micturition reflex, I can quote unquote hold it, then you have parts of your brain that are essentially over overcoming this response to to urinate, and you're attracting that sphincter until it's a socially acceptable time for you to urinate. Hang on. Got my dropped it. Can you guys still hear me? So much stronger. I lost £7, I would. Go ahead, Jay. So by strong facilitative, it's gonna cause the contraction of the shrinkage so you don't pee in inhibition of the for instance, it's gonna be gonna cause relaxation of the shrinkage so you do urinate. So it's, like, kinda backwards. Yes. In that particular sentence where they yes. I I do know what you're talking about. They did switch it around. Facilitated to urinate. Yeah. Alright. So voluntary urination, you are contracting the abdominal muscles. When you contract the abdominal muscles, what you're doing is increasing pressure and stretching the walls of the bladder. So you, and again, we're all, nurses here, and so I think we can talk about pee pee without too much embarrassment. Whenever you're, trying to urinate and you contract your abdominal muscles, you're making your bladder stretch a little bit. You're pushing you're pushing against the bladder just a little bit. That is facilitating stretch, which is facilitating another micturition reflex. Because remember, this is all stretch. It's stretch feedback. So you're stretching, getting that response to your neck. There you go. That's, 0.3 there. So you're gonna it by stretching, it's gonna stimulate those stretch receptors, excite the nutrition reflex, and simultaneously inhibit the external neutrals sphincter. You'll empty the bladder with rarely more than 5 to 10 milliliters left in the bladder. Alright. Now we're kinda off, nutrition. We're gonna talk specifically about absorption, secretion, but more specifically or, more poignantly, we're gonna talk about filtration. So this common theme that we keep talking about over and over is we are filtering filtration, lots and lots and lots of ultra filtrate through the nephron on a daily basis. Way more than we urinate. We urinate about a liter a day, and we are filtering a lot, lot more than that liter. And it's almost like it's very nonspecific how we're filtering this stuff out. We're filtering and filtering and filtering, and then through the loop, you'll fill the approximate convoluted tubule, then loop the discol convoluted tubule. You're you're now you're fine tuning what's made in that urine and reabsorbing or secreting from the blood back into the urine or reabsorbing from that ultrafiltration back into the blood. So it's like you it's like you're really non selective. You're just filtering out a bunch of stuff. Right? And then as it goes along that loop, it's like you're fine tuning it to make it exactly what you need so that your electrolytes and your acid base balance and bicarb and all of that, water, sodium, potassium, chloride, all of that is exactly what you need. And then you draw a BMP, and you're like, oh, look. There's sodium, potassium, chloride, c02. All of that is perfect. Why is it perfect? Because you you reabsorbed what you needed, maybe secreted a little bit more because you had a little bit too much as it went down the neck bone. Right? So we're gonna talk specifically about each step. You have the merino filtration, very non selective. You're just filtering out everything but large protein molecules, really. You're filtering out a whole bunch of stuff. Not everything, but you're filtering out a lot. Reabsorption of, substances from the renal tubules back into the blood. So it's like but that is passing down along the proximal convoluted tubule and and the, descending limb of the loop, and you're like, give me some of that. I gave you too much. Now give me some of that back. Or I've got too much here. That's a crucial. We'll give you that. Get rid of this too for me. Alright? Alright. So a large amount of fluid, virtually free of protein. And you're gonna see that the fenestrations in the glomerulus are not necessarily too small for this protein, but they're electrically charged. The fenestrations are electrically charged to prevent protein molecules large protein molecules, from exiting out into the pill tray. So substance in the plasma except for proteins most substances, excuse me, in plasma except for proteins, were gonna be filtered so the concentration of the glomerular filtrate in the Ohlins capsule is almost the same as the plasma. So it's almost like you're getting rid of everything. Right? And then you're being selective as it goes down the electron. It's gonna be modified by reabsorption of water and specific solutes back into the blood or by secretion, from the peritubular capillaries into the tubules. So give me just a second. We're on slide 57. I'll go back to 57 in a minute. So as this is coming off the afferent arterio let's say we have a little bit, of, constriction of the efferent arteriole. We have an increased filtration pressure, and we have adequate filtration flow. We're gonna talk about that in the next lecture. You're getting rid of so much so much of this, what is in the plasma is coming out in the Bowman's capsule and starting to go down these tubules. Okay? So you have almost the same concentration of electrolytes as what's into the plasma coming out and coming around here. This vasorectal or peritubular capillaries, whichever depending on which 1 we're talking about. Remember this just to medullary nephron, this is for concentration of urine. This is for, more getting rid of the certain, electrolytes. But as it's going down through here, they're going to start to get fine tuning of this. And so now it's like, you know what? You got way too much sodium. Give me some of that sodium back. I need some more sodium back. So now all of a sudden you're reabsorbing sodium back into the bloodstream, and now my sodium concentration in this filtrate has decreased. And it's gonna go down here, and there's gonna be we're gonna talk about each leg of this. You're gonna have different transporters, aquaporins. You're gonna have hydrogen, sodium hydrogen transporters. You're gonna have all of these things that are gonna be specific as we go down this, loop of Henle or proximal convoluted tubules, loop of Henle, thick ascending loop, distal convoluted tubule. Each 1 of these are gonna have specific transporters that are in the basolateral wall of that loop that are going to allow for that fine tuning to occur. This is why diuretics work at different parts of the nephron because they're affecting either sodium or they're affecting chloride or they're affecting, like, carbonic and hydrates. And so they're they're mitigating sodium hydrogen co transporters, aquaporins, Aldactone, spironolactone. All of these things are working at different parts, You know, we all know that, furosemide or Lasix is a loop diuretic. Well, it's working on the thick ascending limb of that loop because of the transporter that are in that part of the loop. Why doesn't life 6 works on the floor from the proximal convoluted tube? Because it's it's that's not the the transporters that is affecting the amount of volume that comes out into this substrate. It works here because that's the type of transporter that LASA works on. There are no sodium, or excuse me. There are very few sodium, and chloride transporters that would LASIK would work on kind of a 2. Does that make sense? Okay. So let's go back to 57. Alright. So let's go through each type, filtration only. You have a byproduct of, muscle metabolism called creatine excuse me, not creatine. Creatinine. And creatinine you don't need creatinine. You don't need not 1 molecule of creatinine. Your body's making plenty of creatinine. You wanna get rid of all the creatinine. In fact, we test urine function by doing what? A creatinine clearance. Right? So you don't need any creatinine. So it would make sense that when you get to the glomerulus, you just filter out all the all the creatinine. You filter all of it out. Do I need to reabsorb some creatinine back into the bloodstream? No. I have no functional use for creatinine. It is a waste product. So it's filtration only. Am I gonna secrete any more creatinine from the, vasorecta or the peritibular capillaries into the ultrafiltrate? No. Because it all filtered out at the glomerulus. Filters freely, filters easily. You'll see that in just a minute. So I'm not reabsorbing or secreting. I'm just filtering it because I don't need any of it. That makes sense. K? Am I going too slow? Can you speed it up? Note to self. If you ever have an opportunity to lecture on phentermine, pass. Alright. Substance b is freely filtered, but also partially reabsorbed. This is going to be an example of an electrolyte. Like, an an electrolyte would be an example of this. I'm gonna filter out some sodium, but maybe I filtered out too much sodium. And I've changed my osmolality. And as that is going through the body's life, you got too much. Give me some of that back. I I need some of that back in my bloodstream. You I gave you too much. Because I gave you a whole bunch of water and I gave you a whole bunch of salt. And you know what? I gave you too much water. Now my osmolality is too high. Give me some of that back. Right? And that's that's, bridge junction. Substance c is freely filtered, but is not excreted into the urine because all of the filtered substance is reabsorbed from the petitioles back into the blood. This would be an amino acid and glucose. So what does this mean? It's the same thing I just said. Instead of a little bit of sodium and chloride, I'm gonna redo a bottle. Why would unless I have diabetes if I'm not a diabetic, why would I want glucose in my urine? I don't. Glucose is an energy substrate for me. So, like, I need glucose. Right? I need amino acids. Those are good things for me. So I'm gonna reabsorb all. Even though recent filter in the glomerulus, I'm reabsorbing all of it back. I gave it to you for a minute. You were repeating for a minute, but now I need all of it back. Substance d, freely filtered and is not reabsorbed. And in fact, additional subs, quantities of this are gonna be, secreted, into the renal tubules. K? This is gonna be something that's dangerous, like, something that's toxic. If I have an, an organic acid, I'm gonna filter all that out, but I can't possibly filter out all of it because I've got a lot of organic acid. Like, let's say, salicylic acid or acetylsalicylic acid, aspirin. Right? And I'm trying to get rid of the salicylic acid, salicylate, and, glomerulus. And I've got a bunch of it out, but there's still some in my bloodstream. Now I have the opportunity to secrete more into the urine to get rid of even more. That's what they're talking about. Hey, Ethan. Is, secretion active transport? Some of it is. Yes. Yeah. We're gonna talk specifically about the secretion, and most of it is active transport. It's not based on concentration gradients. K. So it says, for for each substance in the plasma, you're gonna have a combination of filtration, reabsorption, and secretion. Reabsorption is going to be more important than tubular secretion. Secretion is gonna play an important role in determining, potassium and hydrogen ions. So certain foreign substances of drugs are poorly reabsorbed and are secreted from the blood into the tubules so that and this is this is basically what we just said about acetylsalicylic acid. You're filtering a bunch and you're gonna secrete even more because it's bad for you. You don't need it. This is talking about sodium and chloride and bicarbonate are gonna be reabsorbed. Excuse me. Says, for both substances, you're gonna have a rate of filtration and reabsorption, and that's gonna be extremely large relative to rate to the rates of excretion. And this is just saying you are filtering out a lot. You're also reabsorbing a lot. You you would imagine if your concentration is the same as plasma, your urine concentration of electrolytes is not anywhere near your plasma concentration, you don't have, you know, a sodium concentration in your urine as high as your plasma concentration, a 135. You're not gonna have that. But when it's that high up in the proximal convoluted tubule, it is that high. And you're dependent upon that entire nephron to reabsorb it back. So why do you filter out, so much? Why do you make it seems like it's a waste. Right? I have to reabsorb all of this stuff back. And the whole the whole point behind this is getting rid of waste products, getting rid of things that are toxic to your body. So the the kidneys are basically, like, let's get rid of everything and just keep and reabsorb the things that we need. Versus if we didn't get rid of everything and we've depended upon that entire loop to try and get rid of things, then it would be active transport secretion, a lot of energy production trying to get rid of toxic things to us. So we filter out everything. Very nondescript, non selective, just filter it all out. It all goes through the penetration of the glomerias, and then we reabsorb it as we need it, the things we need. The entire plasma can be filtered and processed about 60 times a day this way. And that's why you have such a high filtration rate so that you can get rid of those, those toxic things just based on filtration, not based on secretion. That make sense to everybody? Alrighty. Let's move on to the next lecture. I'll tell you what, let's take, let's take a 5 minute break and let everybody get, the PowerPoint pulled up. See you in a minute. Are we back? Alright. Now we're gonna talk about, specifically about the glomericos. So what we're doing is we're gonna break down each part of this nephron into its component parts and talk about each 1, individually. So, as we talked about, you're gonna have, the glomerulus filtering this as the first start as the first phase of urine production. And this is gonna filter through we're gonna talk about the anatomy that of that into Bowman's capsule. Almost it says a 180 liters per day. That's a lot. A 180 liters per day. Most of it is gonna be reabsorbed, and thank God, right, that it's gonna be reabsorbed or thank goodness it's gonna be reabsorbed, leaving only about a liter of fluid. I said that earlier, to be treated each day. Rate of glomerular filtration, as you're gonna see here in just a minute, is gonna be dependent upon blood flow and special properties of glomerular capillary membranes. Just like we talked about capillary, permeability in the past, we're gonna have AKF for this too. We're gonna have a filtration coefficient. That's gonna be dependent upon how large are the fenestrations at in the glomerular capillary to allow for things to transfer across, just like we talked about with the water hose. We have a water hose. Somebody told me on my on the course evaluations, by the way, that they wish I would draw more. Sorry. So here we go. We're gonna draw more. No. I'm sorry that you have to look at my drawing. So if we have a water hose and we have holes in here, right here, and we have flow going this way, if I have larger holes, I'm gonna get more filtration out. That's pretty easy. How can I increase the amount of water that comes out here versus how much goes out this way? Yeah. Exactly. Jake and Ethan are are both doing this. Yeah. So what you're gonna do is you're gonna squeeze this down, and when you squeeze this down, this doesn't have anywhere to go, but now it's gonna squirt out your face. Right? It's coming out this way. And the larger the holes, the more filtration is gonna occur. The larger the holes is gonna be considered oh, sorry. It's gonna be considered to be your kf. K? Would it be protein 3, this ultrafiltrator or deliridylor filtrate? When I was, studying, I used to hold the lantern for Florence Nightingale. And when I would, when we were studying all this, the, glomerular filtrate was called vulture filtrate. But it's essentially protein free and devoid of cells, including red blood cells. If you've got blood urine, everybody would agree that's a bad thing. Right? That's not good? Alright. Other constituents, like electrolytes, are gonna be similar to the concentration in the plasma in this ultrafiltrate. Again, very non selective. Low molecular weight substance such as calcium and fatty acids are not gonna be filtered because they're gonna be partially bound to plasma proteins. Okay? So things like citrate and calcium, some fatty acids are gonna be bound to plasma proteins. So half of the plasma calcium and most of the plasma, fatty acids are gonna be bound proteins, and so they're not gonna be filtered. So remember, if it's attached to protein and proteins, resistant, to filtration. So the glomerular capillaries filter fluid at a rate determined by, and this should look really familiar to you, The balance of hydrostatic and colon osmotic forces across the capillary membrane. So if you have atrial atrial atrial all of the blood Marius and you have Bowman's capsule like this, and then we're starting the proximal convoluted tubule right here. So if I have a lot of plasma, this yellow is going to be a capillary. It's I probably should have drawn that in red. This is all capillary. If I have a lot of plasma in here that can't be filtered out excuse me, protein in here that can't be filtered out, if I have a lot of albumin that can't be filtered out, am I gonna have a high osmotic pressure in the capillary? Yes. Yes. So are things going that are attracted to that albumin going to want to escape the capillary? No. Right. Exactly. If I have a lot let's say I have a a problem. I have diabetes or I have proteinuria for some reason, like hypertension that has destroyed the fenestrations and the basement, membrane of the glomerulus. We'll talk about that in just a second. If I've destroyed all that and now I'm leaking protein into the glomerulus, have I increased the colloid automatic pressure inside Bowman's capsule? Is that gonna draw more fluid out? Yes. You with me? So just like in the capillaries, it's the exact same concept. Depending on where your proteins are, it's going to determine, your rate of filtration. So, you're gonna have can you guys can you hear me okay now? Can you hear okay. Sorry. I I heard a beep. So you're gonna have 3 layers. Instead of 2 for a normal systemic capillary off somewhere in the body, this is gonna have 3 layers. You're gonna have an endothelium, a basement membrane, which we just mentioned, and you're gonna have a layer of podocytes, epithelial podocytes surrounding the outer surface of the basement membrane. Okay? So you have endothelium out here. Let me blow this up so that you can see. So you're gonna have an endothelium here. They're gonna have a basement membrane here. This is full of fibers and mesh lattice work. And they're gonna have these podocytes out here that are kinda coming off of these fenestrations. And so these fenestrations the size of these fenestrations is going to help us determine our KF, our filtration coefficient. This is just repeating what we've already said. The capillary endothelium is perforated by, fenestrate or fenestrations similar to those found in the fenestrated capillaries found in the liver. The cup for cells in the liver, I believe, is what they're referring to here. The fenestrations are relatively large, And the endothelial cell proteins so in this endothelium, think back to our cell membrane. The proteins that are in this endothelium are going to be endowed with fixed fixed, not moving, in hernia, negative charges. So if I have a big hunkin' negative, charged albumin molecule, do opposites attract or opposites opposites repel. Right? No. I mean, like charges repel. Right? So if I had negative coming to something that's surrounded by negative, it's gonna repel them. Yeah. Does that make sense? Okay. Then you're gonna have the basement membrane. This is gonna be a meshwork of collagen and proteoglycan fibrillate. They're gonna have large spaces, and you're gonna have a large amount of water and small solutes that's filtering freely through that. Also, not allowing for plasma proteins to go through, but they are also negatively charged. So you have negative charges around the fenestrate. You have negative charges in the basement membrane, and you're gonna have polo sites. And, the foot processes are gonna be separated by slit pores through which this glomerulotrophiltrate moves. The epithelial cells, also negatively charged. That's gonna prevent filtration of plasma proteins. So all 3 of these layers are gonna have negative charges that are repelling albumin or other plasma proteins from being able to go through. That's why proteinuria should be a negative finding on your analysis. If you're looking at your analysis, they got protein in your urine. They've got a problem, most likely in the basement membrane. The basement membrane kind of is the 1 you're thinking of, like chronic hypertension, hypertensive crisis, you know, something like that. The capillary is gonna be thicker than most other capillaries, but it's more porous and filters fluid at a higher rate. Okay. Despite this, you're gonna have reasonably selective. And I know we've said it's gonna be non selective, non selective filtration. What they're talking about is specific to large molecules that are negatively charged. It's gonna be selected to those. For everything else, it's gonna be reasonably non selective. So here's a list of things that are filterable through the glomerular capillaries. Water, sodium, glucose, indolent, all have to filter straight through the glomerulus with no difficulty absorbing. Myoglobin, You've heard of myoglobin urea? Like rhabdomyolysis, myoglobin urea. Point 75 filterability. So if you have a lot of myoglobin, you are you can filter some myoglobin. Albumin, look at the filtration filterability excuse me, the filterability of albumin. Very, very, very, very well. Glucose is going to be freely filtered, but also rapidly reabsorbed. Remember, we're filtering it, but that's not the end of the story. We're gonna reabsorb that glucose, unless they have diabetes. And then you have glucose urine. You have glucose in your urine. Right? Remember when we said diabetes colitis was urine that tasted mallow like honey. Right? And so that glucose in the urine is how you diagnose that. It used to be how you would diagnose if somebody has diabetes back when I was holding the lantern for Florence. Okay. And believe me, after the 4th or 5th test, you got really sick of being the 1 that was testing urine that day. Yeah. It's just so nasty. Alright. We'll blame that on Feinergy. Y'all wanna blame that 1 on Feinergy? We'll say it was Feinergy's fault. Okay. I'm gonna get fired. Alright. The diameter of the plasma protein of albumin is, about 6 nanometers. The pores are thought to be 8 nanometers. So the pores are large enough for the albumin to go through. But why doesn't the albumin go through the pores? Because they are surrounded by negative charges. Remember we said albumin is this big old hunk and negatively charged molecule? Remember we said that? A negative going into a negative is gonna be repelled, just like marriage. Hi, Jay. So then why does increasing the size of the Fenestrae, if they're already large enough to fit out human cause proteinuria even though there's negative charges in the 3 membrane? Yeah. Because you're increasing the diameter, which is pulling the negative charges away from the center to allow for the albumin now to go through. So, basically, you're decreasing the electrostatic forces of the negative charge. Alright. This figure is showing the electrical charge affecting the filtration of different molecular weight dextrans, And this is just an experiment, is all this is. So, basically, they took a dextrans, and they can make this dextrans as negatively charged as they want and as big as they want. Okay? What they were able to show is that negatively charged deck strands are going to so, excuse me, negatively charged, so that would be a poly and ionic dextrans. Negatively charged dextrans are going to be poorly filtered even though they are really small. Excuse me. Yeah. Even though that next strand molecule is small, it's polyanionic. It's negatively charged. It's gonna be poorly filtered. Larger positive polycationic cat hold this. Positive cationic is a positive. The opposites attract? Yes. And so even with larger molecular size, we're getting a high filterability coefficient. And what this all this is showing is it's not the size of the molecule. It's the fact that it's negatively charged. It's a little bit precise, but that's not the main factor. Alright. Negative change, nephropathy, the glomeruli doc. Glomeruli will become more permeable to plasma proteins, and they look normal under a standard light microscope. You look at it under an electron microscope and you get flattened polo sites, so minimal change. There wasn't much change that we could see with a microscope. But you look at it under an electron microscope They think this is a t cell secretion of cytokine cytokines that are injuring the phytonocytes and are increasing permeability of molecular proteins, specifically albumin. This is gonna allow for, increased glomerular capillary, filtration, and you get protein area or albuter albuterin area. Hey, Jokic. Yeah. That was fine. So it's damage to the podocytes that causes increase in the filtration of albumin. Is that what is this my understanding? Okay. That's exactly right. So, normally, you're you're filtering very little plasma proteins, albumin being the number 1 plasma protein that we think of. So you shouldn't have much in there at all, but the podocytes are negatively charged. That was the third layer. Right? You destroy the podocytes, they're negatively charged. Well, if you're destroying the podocytes, you no longer have that last barrier to filtration. Now you're getting rid of more more, protein into the urine. Most common in young children, that can also occur in adults. Well, mercury filtration is going to be determined by the sum of the hydrostatic and colloid alphonic forces. All of that stuff that we talked about. Where's the colloid? Do we have a lot of colloid on the inside of the capillary or in the base in the, Bowman's capsule? You know, where's where's the colloid? What's the pressure? What's the hydrostatic pressure? Do I have a squeeze down of the efferent arterial and increasing pressure through those capillary membranes. And then the glomerular k f, and that's gonna be your, filtration coefficient. So, again, this should look very, very, very, very familiar to you. Yeah. Glomerular hydrostatic pressure. What is that? If I squeeze down the epidermal arterial, I'm increasing the pressure inside of here. K? The glomerular colloid osmotic pressure that's pulling back. Bowman's capsule pressure. This is how full is this with fluid and how much is it wanting to push back. Notice I do not have a Bowman's capsule osmotic pressure. Why? Thea? Because you're not filtering out, proteins into into perfect. Right. You should not, unless you have an a pathology, have much protein in here at all. So this would be 0. Hey. Real quick. These are essentially, like, the stalling forces. Right? The what now? Stalling forces? Yes. But yes. But we're not calling them that. It's similar to capillary, pressures, but we're not calling them that. Yeah. Yeah. I've never thought of it that way. So under normal conditions, that's what we're talking about. Protein, remember to filtrate, considered to be 0. And now we, everybody knows why it should be 0. So the k f is gonna be a measure of the product of a hydraulic conductivity, that this means ability to move water. Hydraulic, hydro, water, conductivity, and the surface area of the glomerular cathlex. In other words, the more finished array I have, the higher the k s, and the, bigger the diameter of those, the higher the k Alright. So increased KF raises glomerular filtration and decreased KF. It reduces glomerular filtration changes in KF are not providing primary mechanism for the normal daily regulation of gFR. We okay? Everybody okay? I see people smiling. I haven't seen anything funny. I just wanna make sure it's not a conversation offline that I don't know about. Are we good? Nothing? Okay. Cool. You know, I get paranoid. I'm paranoid. I'm just kidding. Not really. Okay. So some disease processes that are lowering kf are reducing the number, by reducing the number of functional glomerular capillaries or by increasing the thickness of the glomerular capillary membrane and reduce its hydraulic conductivity. And this is what we're talking about hypertension. Chronic uncontrolled hypertension is destroying or increasing not destroying, but increasing the thickness of the basement membrane. That's that middle layer. Right? With cardioglycans that were freely filtering water. There is a loss of capillary function from the destruction of the basement membrane. And, again, that's gonna be this 1 with the proteo black hands. So you're thickening this, making it harder for water to transport through. And these are gonna be your people with, like, stage 2 chronic kidney disease, stage 3 chronic kidney disease, from chronic hypertension. You talk to people and you're like, I have stage 3 chronic kidney disease. Did your nephrologist tell you what happened? Yeah. I had high blood pressure and I didn't know it. I kept getting headaches taking the BC powders, but it didn't help. But I had high blood pressure, never knew that. DCP powders didn't help the kidneys either, did they? The aspirin in there? Changes in Bowman's capsule pressure are not normally going to serve as a primary means for regulating glomerular filtration. Bowman's capsular pressure can, though, cause significant reductions in gonorrhea infiltration. And the biggest example that you can think of is a postrenal disease such as a kidney stone. You have a a urine stone that is blocking the ability for the kidneys to get rid of, urine, and that pressure is gonna build up and cause hydronephrosis, and that is going to increase Bowman's capsule pressure. By increasing Bowman's capsule pressure from, say, 18 to 72 by increasing all of this pressure in here with backward flow of urine, urine not being able to escape, is that going to decrease my glomerular, filtration? Yes. So blood in this glomerular capillary. So you have The a third arterial, you've got plasma proteins in the blood. Everybody agree you have plasma proteins in the blood? In the blood. In the blood. Not in Bowman's capsule, but in the blood. Yes. We have plasma proteins, and it comes in here, and life is good. Life is good. And I'm filtering out water as I'm going in through here. What am I doing to the plasma concentration of protein if I'm filtering out water? I'm increasing plasma protein concentration, but because I'm filtering out water. So as I'm going through this, what am I doing to the colloid osmotic pressure in the capillary? Increasing it. What am I doing to filtration the further along this I go? I'm decreasing glomerular filtration. So it starts out life is good, life is good, then all of a sudden, I've got a whole lot of negatively charged, big honking plasma protein molecules in the blood that are doing the what? Resisting things being moved out. So the the, glomerulus starts out freely filtering water, but then as we go, we are decreasing the amount of filtration we can have because we're increasing the concentration of plasma protein. That makes sense? So the normal colloid osmotic pressure of plasma entering the glomerular capillaries is 28. It's gonna rise to 36 by the time the blood reaches the ether end of the capillary. So here we have a an average of 32. Okay? So as this is going from afferent to efferent, the further we go in here, more fluid is being filtered out freely. The higher the concentration of plasma proteins, the higher the folioid osmotic pressure becomes. Y'all with me? That's pretty easy. So 2 factors influencing the glomerular colloid osmotic pressure is the arterial plasma colloid osmotic pressure. That makes sense? It's in the atrium arterial. How much plasma protein do you have? And the fraction of plasma filtered by the glomerular capillaries the fraction of plasma filtered by the glomerular capillaries. Increasing the arterial plasma of choloid osmotic pressure raises the glomerular capillary osmotic pressure, which decreases the glomerular filtration. Does everybody understand that? If you don't understand that, raise your emoji hand. Let's see. Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid and allsponic pressure. So if I have larger, fenestrating, if I'm getting rid of more fluid faster, then I'm increasing my concentration of plasma proteins in the capillary. Got it? Yeah. Got it. That's very easy. Okay. Changes in renal blood flow is going to also influence glomerular filtration rate. When you increase renal blood flow, you're gonna have a lower fraction of plasma initially filtered out of the glomerular capillaries. That's gonna cause a low a slower rise in that up colonosmotic pressure, and you're gonna have less of an inhibitory effect. The merrier hydrostatic pressure has been estimated about 60, and that's what it's saying here under normal conditions. Increasing glomerular hydrostatic pressure is increasing glomerular filtration rate. That makes sense. And you can increase the hydrostatic pressure by increasing arterial pressure. We would call that pressure diuresis. Okay. Either arterial resistance and ether arterial resistance. I mean, this is not necessarily things that increase. These are factors that increase. So in other words, hyperarcturnal resistance and hyperarcturnal resistance and arterial pressure are affecting glomerular filtration. Or excuse me. Glomerular hydrostatic pressure, which is affecting glomerular filtration. Alright. If you increase afferent arterial resistance, does it make sense that you are decreasing, the marital filtration? So let's go back to our example with the water hose. We're gonna use a, a green water hose. So if we have a water hose and we have holes here, and this is, connected to the house. Big water hose. Right? If we have a hose here, this is connected, and I have the ability to turn that water hose and and constrict that water hose, am I going to increase or decrease flow in this wander nodes? I'm decreasing flow. And if I'm decreasing flow, this is, by the way, the a parent arterial, and this would be the e parent, and this would be the glomerular capillaries. If I'm decreasing flow here, I'm decreasing blood flow through the entire nephron, the vasorectal, the pericuteal capillaries, all of it. If I decrease it here, everything downstream is gonna be affected by that. Alright? K? Consequently, if I decrease flow on the efferent arteriole, what am I going to do to filtration? I'm increasing filtration, but if I decrease flow significantly enough like this, really decreased flow where it can barely go through, what am I doing to flow through the peritubular capillaries? I'm decreasing flow through the peritubular capillaries, but at the same time, I've increased flow excuse me, increased filtration. Does that make sense? K. K. So what we're saying? Increasing resistance decreases rate of blood flow, increasing resistance, increases glomerular filtration. K? So as long as the increase of a efferent resistance does not reduce renal blood flow too much. This is what we're talking about. Remember? That really like, you have hardly had any space in there? As long as it doesn't affect renal blood flow too much, will myrioliter filtration increases slightly. Because epirt constriction is reducing renal blood flow. So in other words, this is all of this is represented by the, glomerular capillary. So it's showing this as a big light ballooned out area. But if we're really gonna look at it, it'll look like this. Right? It's capillary, capillary, capillary, like this. So if I decrease this, am I also decreasing what can come in over here? If you've got this constricted, it's also going to constrict, renal blood flow on the afferent side or renal blood flow in, altogether. So if you have constriction of the uterine arterials being severe, the rise in colloid osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure caused by efferent arterial construction. So the net force for filtration is decreasing causing reduction of GFR. Let let's explain that. If I if I constrict this and I have increased filtration occurring but less blood flow going through, I'm getting rid of more water, less blood, increasing plasma proteins here, which is pulling water back out or preventing water from being able to leak. Now I've decreased my GFR. Does that make sense to everybody? I won't go on any further unless you got this. Okay. We're almost done, guys, for the day. But my higher levels of constriction, there's a slight increase in GFR, severe constriction, a decrease in GFR. So if we have, let's look at afferent first. If we have increase in arterial resistance, renal blood flow is going to drop. Okay? And the filtration is going to drop. What are we saying? If we have an increase in ouch. Apron oh, not stay in my ear. If we have a increase in arterial resistance on the apron side, what does this makes sense. Does renal blood flow decrease? Yes. Because it it's stopping right here at the beginning. K? Does glomerular filtration decreased. Yes. Why? I can't even get it here because we've done that. K? So you look at that, and then you compare it to this. What happens when I have ether arterial resistance to glomerular filtration rate? Just like the water hose, I'm squeezing down on this side of the water hose, making more water shoot out the fenestrations. I'm increasing until I've decreased I've, caused such an increase in resistance that now I'm increasing the concentration of plasma proteins. And now all of a sudden I have an opposing force pulling water back in. Now I have a decrease in glomerular filtration. Does that make sense? What happens to efferent when I increase efferent arterial resistance to renal blood flow? Same curve almost exactly as aPIR. Here. Here. It's almost the exact same curve. Why? Because it's all of 1 vessel. You're just squeezing it here versus squeezing it here. Yes. K. Is that why low dose dopamine causes increased urine output and high dose dopamine decreases urine output, or is that something completely different? It's because you have dopaminergic receptors and, dopaminergic, agonists in low dose dopamine. They call that a renal tonic dopamine that is actually causing, apron arterial vasodilation and increasing glomerular filtration rate and renal, blood flow with low dose dopamine. You and that's up to 10 mics per kid per minute. You get greater than 10 mics per kid per minute, and you have renal toxic dopamine dosing. So renal tonic helps renal perfusion. Renotoxic decreases renal perfusion. And it all depends on do you have more alpha than you do dopaminergic effects. Makes sense? K. Alright. Alright. It's slide 37. It's about as much as I got today, guys. Probably need to go sit down because I'm feeling a little peckish, little little tired. And I'm afraid I'm gonna start making mistakes. We will pick up with this, on Tuesday, and expect your lecture, from last Tuesday, to drop this week. And we will talk about exam and exam review at the beginning of class next week. Sound good? See you. Feel better. Thank you.