Renal | Proximal Convoluted Tubule

what's up ninja nerds alright in this video we're going to continue we're going to talk about the proximal convoluted tubules if you haven't seen our video so far on the glomerular filtration go up click on that alright alright so we started off right you know where we were filtering right so we were over here in the actual meritless right and when we were in the glomerulus if you remember this was where we had that filtering process that glomerular filtration right so we filtering again do you guys remember we were filtering water that was a very important component we were filtering like electrolytes like sodium and potassium and chloride and what else calcium magnesium tons of different chemicals right you're filtering filtering nutrients like glucose and amino acids and vitamins and just keeps going on lipids a whole bunch of different types of chemicals and maybe even very very small proteins very small proteins like insulin right or maybe even a little bit of hemoglobin all right so these that think that you're filtering you're filtering tons of different substances in now when they're filtered now generally the blood we have to talk about a term called osmolality okay so I want to get this term a belay now ozmo leti now osmolality is referred to is that usually the volume of particles so the volume of particles per kilogram of solvent so usually you can use it as like like moles usually heard five heard of all what's called molality molality is divided as moles of solute over kilograms of solvent well this is kind of a similar concept it's just a number of particles within one kilogram of that actual solvent right so that's our odd molality now generally inside of the actual blood this glomerulus it's normally about 300 milliosmoles per liter okay that's what it normally is now when we're filtering across this actual blue merula filtration membrane and into this actual Bowman's capsule into the PCT it's generated about the same so about again 300 milliosmoles I'm just going to use 300 milliosmoles right now so it's coming into the proximal convoluted tubule at what at 300 milliosmoles now we have to start seeing how we can get substances from this kidney tubules and into the blood or how we can get substance from the blood into the kidney tubules that called so just by definition here let's say that I have just a generic structure here let's say here's my actual glomerulus and here's my proximal convoluted tubule and again here's my actual capillary here and here's the part of the capillary if I have substances that are moving from the blood and into the kidney tubules so this process here where you're moving substances from the blood into the kidney tubules is called tubular secretion now tubular secretion is an active process meaning it requires ATP and we'll talk about substances that we secrete in here now there's another one let's say that I'm moving substances from the actual kidney tubules so from the kidney tubules and into the blood that process is called tubular reabsorption in depending upon what kind of chemicals you're reabsorbing it could be active or passive it just depends and we're going to discuss that okay so now that we've got that basic concept let's go ahead and talk about the things that are undergoing tubular reabsorption first and we'll mix in their times of tubular secretion all right so let's start here at these channels here because we have to develop this concept here with these channels you see these pink channels here these pink channels are called sodium and potassium ATP ASE's so what they're doing is they're pumping three sodium's out of the cell and two potassium into the cell same thing I guess on three sodium out of the cell two potassium into the cell three sodium's out and two potassium in what's significant about all of that the significance about that is that all this process were here requires a TP adenosine triphosphate right so ATP is required all of these steps because what's happening you're pumping sodium from areas of low concentration outside of the cell where there is high concentration you're pumping it against its concentration gradient same thing with potassium you're pumping potassium into the cell ninety seven ninety seven percent of the potassium in our body is found inside of ourselves so if you pump it from low to high concentration that's also active transport so here these are all around the actual basolateral cell membrane so over here what else would I have I'd also have three sodium ions pumping this out and two potassium ions pumping in and same thing three sodium ions out and then these two potassium ions and and again what would this require this step would require a TP primary active transport okay what is that doing then what is that doing to the concentration here inside of the cell what's pushing sodium out so the concentration of sodium inside of the cell is low okay while the concentration of potassium inside of the cell is actually going to be high okay that's good now we're going to talk about why on the cell membrane here there's these specialized transporters look at this transporter here this transporter right here he can transport two things at once one of the substances that he transports is sodium the other substance that it can transport is glucose so look at this I'm going to draw a glucose here which is GU LC right there's my glucose and here's my sodium this guy can transport sodium into the cell from the kidney tubules into the cell which isn't a problem because sodium is really high out here and really low in here so when it's moving from high to low concentration what is that that's passive diffusion doesn't require ATP but glucose is actually very low out here as compared to in here it's higher so if you try to pump glucose into the cell you're pumping it against its concentration gradient but because sodium is go down his concentration gradient it helps for glucose to go against his concentration grading this is an example of secondary active transport okay so what's happening here one more time sodium is going down its concentration gradient glucose is going up his concentration gradient so this is an example of secondary active transport why not direct because remember that sodium that we were pushing out and pushing potassium in we were directly using ATP right why to decrease the sodium concentration in the cell so that when sodium comes into the cell that's moving passively and it can help to bring the glucose with it okay I guess what else is happening that same mechanism is happening but over here on this cell look what happens on this cell over here I have another transporter and this transporter can transport two substances at the same time also this one is going to transport sodium and it's going to transport it into the cell what do we say again what was the concentration of sodium in these cells it's actually going to be low and again just to continuously keep applying that concept why what was here at that actual basolateral membrane here now all of these kidney tubules cells there was three sodium ions being pumped out and two potassium ions being pumped in which was keeping the sodium concentration low you know what else is transporting it and with it it's also transporting in with it amino acids so any types of amino acids they're actually low out here and high inside of our cells so when if you have to move this from areas of low to high doesn't require ATP it does but because sodium is going down his concentration gradient he helps transport the amino acid into the cell by what type of process this is again another example of secondary active transport okay so this is going to happen with sodium and glucose and sodium amino acid it can also happen with lactate so lactic acid also so this could also happen if I were to just include over here this could also happen with lactate okay which is this is a conjugate base form of lactic acid okay so we're getting these things in so where are these things going now let's say that the glucose gets into the cell when it gets into the cell there's specific transporters on the basolateral membrane so look at this transporter here here's a transporter here and what's it going to do it's going to transport this glucose from the cell and out to the bloodstream and so now we completely reabsorb the glucose into the bloodstream so now the glucose is in the blood what about this amino acid let's call these amino acids over there they have specific types of transporters so they have transporters that will facilitate their diffusion right and look where they're going to go they're going to move out of this tbo cell and into the blood and now what's in the blood amino acids that's again two of the reabsorption what else was going to be able to come with sodium two we also said that there would be lactate reabsorption so you're also going to have over here lactate okay so lactate will also come here also now here's one concept I need to get straight with you guys if we assume that we're not taking in too much glucose I'm not housing a pizza alright I'm eating normally generally all of the glucose that we filter all of the lactate that we filter all of the amino acids that we filter really important concept 100% of this is reabsorbed super super super important concept to get across if we're assuming normal physiological conditions all of the glucose all of the amino acid is not the vitamins all the glucose all the amino acids and all the lactate 100% of that will be reabsorbed from the kidney tubules and into the blood okay that takes care of that let's move on and let's see what's happening also with this sodium let's keep going with the sodium here so we reabsorbed a lot of sodium and we're all I'm going to talk about what else he's good for so now let's actually move on to another transport protein let's do this one in orange this is a pretty intense mechanism but we're going to try to make very a lot of sense of it okay so first off let's say you know what else is really filtered also pretty heavily bicarb so bicarbonate which is hco3 negative is very very filtered in this area watch what happens here okay so I'm going to take this bicarb right and it's going to start moving down over here and I want to get that bicarb into the cell but it does in a weird way okay in our blood we have co2 right and see you two can actually move into our cells when co2 is in our cells he combines and reacts with water now there's an enzyme that catalyzes this reaction this conversion of co2 and water to this next molecule which is called h2 co3 which is called carbonic acid there's an enzyme that catalyzes this step right here this enzyme is called carbonic anhydrase so what does this enzyme doing he's catalyzing the conversion of co2 and water to carbonic acid then look what happens to carbonic acid he's very unstable and he disassociates into two different chemicals one is protons the other component is bicarbonate so two components are actually broken down as a form of this one is bicarbonate and the other component is a proton look what happens here remember that sodium that we had in here that sodium is going to move through this channel okay it's going to move through this channel as it moves through this channel it helps to be able to push this proton out so this is an example of a sodium hi antiporter and again this is another example of secondary active transport okay this proton is going to combine with that bicarbonate so let's share the bicarb right here watch this it's a really weird mechanism but you know that's the way the body works right look what happens if i take bicarb and protons i disiike read it out and I combine them I'm going to get h2 co3 which is carbonic acid guess who else is out here kind of like on the membrane look you've got like a big nose so here's this guy here and here's his head let's say I put his head here and like there's this little eye right and he's got a couple hairs on his head okay and he's smiling but he's got like a huge his look as his faces his nose is below his chin he's all frakked-up but look what happens this h2 co3 reacts with that enzyme what's that enzyme called again that enzyme right there is called carbonic anhydrase that same enzyme that converted co2 in water to carbonic acid this is him also look what he does he converts this h2 co3 and to co2 and water okay now as a result I'm going to get that co2 in water that's actually going to leave okay but do you see how I secrete these protons out now what is the relevance of that I still didn't get my bicarb in what's what's what's going on with the bicarb that bicarb is actually going to get pushed into the blood I see this bicarb right here that we made as a result that's getting pushed into the bloodstream how much of it is actually getting pushed into the blood approximately about 90% okay so do you see here look what happens here this is really really cool here's the bicarb that you wanted to reabsorb but you just actually see-cret this proton out right so co2 and water makes carbonic acid breaks down to H+ and bicarb that H+ gets secreted while sodium comes in the antiporter combines with the bicarb out here in forms carbonic acid and then the carbonic anhydrase converts it into co2 and water now bicarb didn't get into the cell but you made the bicarb indirectly and then put it into the blood that's amazing so now we got that bicarb into the blood 90% of is actually getting reabsorbed okay that helps also for the sodium reabsorption also so we have sodium reabsorption here also you see how a critical sodium is in this process all right what else here's another interesting thing you know have sodium is moving in with the amino acid that's moving in with the glucose it's moving in with the lactate it's moving in as the protons are coming out water feels obliged to follow him so as the sodium is moving in so let's actually show over here let's say here is actually going to be just for the sake of it let's say I put another one of those sodium channels over here that sodium glucose channel right so over here was that sodium channel and it was chant transporting with a glucose now when the sodium is coming in and it's coming with the glucose guess who loves to fall off water water feels obliged to follow the sodium so water moves by the process of osmosis right where it actually moves from the kidney tubules and into the blood and who is it following as a result it's following this sodium ions because these sodium ions are actually going to be reabsorbed also now about how much sodium is being reabsorbed here in the proximal convoluted tubule about 65% sodium how much water is actually getting reabsorbed also 65% it's almost exactly equal and again the water is following the sodium because he feels obliged you know that's call whenever the water falls the salt into the blood when actually it follows it this is a specific name let's actually write this name up here it is called obligatory water reabsorption okay so what is obligatory water reabsorption obligatory water reabsorption is when the water is following the actual salt into the blood because it feels obliged and it's moving by this actual diffusion process or osmosis right from areas of high to low concentration following the salt okay so now we've got rid of the water so we've got our water about 65% of him we've got 65% of the sodium we've gotten almost all hundred percent of our organic nutrients what about this potassium and this calcium and and this magnesium what about those guys they move you see these little Issa how you have these two cells these are approximate convoluted tubules cells you see this little space in here these are the blue molecules or your tight junctions they love to move through that space they love to move through that space so watch what's happening here let's say I take with me calcium I take with me magnesium and I take with me potassium and these guys can move in between the cells what's that call when you move in between the cells and you get moved into the blood right what is this process here called when they move between the cells so this is called para cellular transport okay so para cellular transport is when it's actually calcium magnesium potassium even a little bit of chloride ions to I could even include chloride in there too if I want right just a little bit of it move in between the cells right so they move in between the cells and into the bloodstream and that's how we get these substances into the blood now in general very little calcium and magnesium are actually reabsorbed in this area but potassium approximately about generally fifty-five percent of the potassium and about 50 percent of the chloride ions are also going to be reabsorbed in this area okay so chloride is actually going to move by this mechanism but there's also another mechanism to get chloride in let's say I put another transport protein on the membrane here's another transporter and this transporter is moving sodium and it's moving chloride ions it's a symporter it's moving sodium and chloride ions into the cell and then where's the sodium and the chloride going the sodium and the chloride are actually get pushed into the blood okay and that's another way that we can get chloride into the blood one is by para cellular route very very little of it but most of it is actually going to be by the sodium and chloride code transport mechanism and again about 50% of the chloride ions are going to be reabsorbed and about 55% of the potassium ions are going to be reabsorbed here okay now we have to talk about these lipids okay now lipids this should be the easiest one to remember guys why because lipid soluble substances can pass through the phospholipid bilayer okay because they can move right through so let's say here I have any type of lipid material any type of lipids any lipid soluble solutes you know what's one of them which is really really interesting I'm going to put it up underneath it you're real you're really pad soluble solute these guys can pass through the membrane and get right into the bloodstream okay so any type of lipid soluble subs solutes or urea can get pulled into the blood so now I have my lipids in the blood I have urea in the blood okay now out of the urea not all of it gets reabsorbed only a small percentage of it is getting reabsorbed okay lipids technically you want to try to get as much as your lipids in there all right so lipids are getting reabsorbed in your Riyaz getting reabsorbed now one last thing and we're going to finish this off small proteins remember I told you there were these two small proteins that I mentioned there or those two small proteins that I mentioned I mentioned insulin and hemoglobin right now generally proteins aren't filtered but if there is very very tiny small proteins that are filtered in this process sometimes that can happen right so now let's show that right here okay actually now let's put it right here guys because now we know that this that this happens right here right with the calcium and the actual chloride ions now on the membrane you're going to have these specific types of receptors here kind of like these little like protein receptors okay let's say these small proteins actually get filtered by some chance as these small proteins are filtered they can get caught on to these little receptors as they're caught on to these receptors so let's say that this one is insulin and let's say if this one is hemoglobin why would you have hemoglobin in the urine maybe you could have because of some type of hemolytic anemia or some type of transfusion reaction whatever it might be there could be many reasons but neck technically you don't want there to be very much hemoglobin an all filter but it can't it is possible if that hemoglobin our insulin is filtered look what happens we take and we endocytosed this whole thing here so we're actually gonna bring this another that's called clathrin-coated molecules and they create this little pit and they pull it in by endocytosis so i just pulled in by receptor mediated endocytosis with these clathrin-coated molecules let's say here's your receptors they're disassociated away from the insulin the hemoglobin what happens to that insulin and what happens to that hemoglobin well you combine it inside of the cell with lysosomes so now you have these little hydrolytic enzymes and guess what these hydrolytic enzymes do they break down the actual protein the insulin and the hemoglobin so this is insulin and this is hemoglobin after guess what's going to look like afterwards so now let's draw the vesicle your receptors actually get recycled through an endosome processing pathway but then look what happens to this influence in this hemoglobin they get broken down into their constituent amino acids and then look what i'm going to do with this look what i'm going to do with this i'm going to take this and I'm going to bring it in this vesicle is going to fuse with that cell membrane when that vesicle fuses with the cell membrane what happens look at this I can put those amino acids out here into the blood okay so now I have all of these amino acid out in the blood okay so that's another way of this whole reabsorption process okay so that's the way of beating insulin and hemoglobin is two receptor mediated endocytosis and then digesting those proteins into small amino acid and then reabsorbing them okay one last pathway here that we have to talk about for this entire process here is with respect to parathyroid hormone we're not going to talk too much about it we're going to a little brief little thing on it let's say I come over here and I have on this cell membrane right here I have a specific channel let's make this channel Orange so let's say here's this orange channel this channel normally wants to be able to bring sodium in and it wants to bring in phosphate ions okay that's normally what this channel wants to be able to do but let's say here on the cell of this proximal convoluted tubule I have a receptor here and this receptor here is for the parathyroid hormone so let's say this is the parathyroid hormone so P T H what the parathyroid hormone does is it binds onto this receptor and activates a G stimulatory protein that G stimulatory protein then gets and goes and activates adenylate cyclase a dentally cyclase does what it converts ATP into cyclic a and P and then cyclic a and P gets converted into protein kinase a guess what protein kinase a does he comes over here and he puts phosphates onto this transporting that normally you would think all that's going to activate it no it does not this transporter is inhibited if this transporter is inhibited what happens to these phosphates they don't get reabsorbed what happens to them they get excreted okay that is another way of this whole process occurring here okay so parathyroid hormone can activate this intracellular pathway to cause phosphate excretion okay now we've done that we have to talk about a couple secretion mechanisms okay now generally you have inside of your cells you have a molecule called glutamine okay that's an amino it's actually a specific type of amino acid now glutamine can undergo this process of what's called deamination now there's actually two amine groups on glutamine so when you remove both of them you're actually going to get two amine groups nh3 right but not only you're going to deaminate it meaning that you remove the amine group you're going to acidify it too so you're going to acidify those actual specifically as ammonia so you're going to add h plus is on to it so what do you get whenever you have nh3 plus and that extra hydrogen you get ammonium ions so you get NH 4 plus then you're also going to oxidize that glutamine so you're going to oxidize him meaning that you remove electrons right or you remove the hydrogen's and that's going to convert it into two bicarbonate ions now if you are in metabolic acidosis meaning that your actual ph and the blood is very low so let's say here is your ph normally peach is 7.35 to 7.45 right let's say that it's starting to go down says this the pH is actually below 7.35 and what happens is your body has to be able to compensate for that so what it does is it starts deaminated in the glutamine and producing - ammonium x' and - by carps why look what happens to this bicarb I'm going to take this by carbon I'm going to put it into the blood but anytime bicarb is actually leaving we have to prevent this cell from undergoing any change in its its electoral electronegativity right so I have to bring something in as a result so as the bicarb is getting put into the blood chloride ions are coming into the cell but what did I just do - the blood what did I put into the blood stream I put two bicarbonate ions what's that going to do to the pH if you put in this bicarbonate it's going to praying the pH back up so it's going to try to fix the pH bringing the pH back up to about 7.35 to 7.45 again it's going to attempt to what happens with these ammonium x' you're going to have some type of active transporter here what I mean by active transporter that means in order for me to pump this ammonium out I have to utilize ATP for this to occur and then where's this ammonium going to go it's going to get pushed into the actual kidney tubules and as a result what am I going to have out here in the kidney tubules in h4 positive which can disassociate into ammonia NH plusses but again this could be in dynamic equilibrium right so now I produce this what was the other mechanism that we talked about just to quick recap that one remember we had the co2 that was coming in here and that co2 is combining with water and then with the presence of carbonic anhydrase it was making carbonic acid and then carbonic acid was disassociated into bicarb and protons were happening those protons you were excreting them but how did you get the protons out they don't just naturally excrete on their own right you had to bring sodium ions in which is an example of a secondary active transport so you're secreting the protons out but where's that bicarb going that bicarb is going into the bloodstream and if you get bicarb into the bloodstream what happens to the pH again the pH will try to rise back up to alkaline levels all right so you know there's other things that can also be secreted besides you know this actual protons and this ammonium you know inside of the actual blood there's certain things that we just can't get rid of because maybe it actually got reabsorbed because it was little bit soluble or because we couldn't filter it right so substances like that what I'm saying is could usually be like drugs so certain drugs maybe not maybe not get filtered completely what kind of drugs am i talking about ah main ones that I'm talking about it's like penicillin so penicillin actually gets us accreting this part are also uh certain types of cephalosporins even methotrexate okay even methotrexate a lot of different chemicals are secreted a lot of different drugs are actually excreted at this point but if these drugs are secreted into the kidney tubules here's what you have to remember that this process by which the drugs are being excreted into this actual proximal convoluted tubule requires ATP it's an active process because I told you that remember that tubular secretion is an active process what else can also be secreted other different types of organic bases and organic acids so like organic acids could be like uric acid you know uric acid is a breakdown product of specifically our nucleotides or you've probably even heard of bile salts so bile salts or bile acid there are also other components and there's even other things too you've heard of morphine right so morphine opioid drug right they actually use it for pain relief right so morphine can also be excreted bile salts can be excreted uric acid can be excreted even through certain things like oxalate ions so oxley ions all of these substances organic bases and organic acids can be excreted into the actual kidney tubules but once again in order for them to be excreted over here into the kidney tubules what does it require it requires ATP it's an active process no free lunch here okay so again one more time a drug such as penicillin or cephalosporins and methotrexate or tonne of tons of different types of drugs are actively secreted into the actual proximal convoluted tubule utilizing ATP or certain types of organic acids like uric acid may be certain types of bile salts or certain types of organic bases like oxalate and morphine those things are going to be pushed out through certain types of transporters which require ATP into the proximal convoluted tubule and they'll be lost in the urine hopefully right so again tubular reabsorption could be passive or active right depends upon which molecules they are in tubular secretion is generally an active process okay so require a teepee and the reason why we would do tubular secretion is because you might not be able to get rid of that substance because it got reabsorbed too much or because it couldn't filter or maybe because it was lipid soluble of some form right or because you need to rid the body of excess potassium or protons in general I hope all of this made sense I hope you guys really enjoyed it in the next video we're going to talk about the loop of Henle until next time Engineers

Channel: Ninja Nerd

Views: 432,401

Keywords: proximal convoluted tubule, tubular secretion, tubular reabsorption

Id: ISpVjQSlml4

Length: 33min 42sec (2022 seconds)

Published: Wed Jun 21 2017