hello and this is where we dropped off uh for the end of uh part two on the chapter on the kidneys so this is chapter 12 kidneys and we're starting part three we had just gone through the different parts of the renal tubal the proximal tubal the loop of Henley the distal tubal and the collecting duct we talked about um the different processes that occur in each of those places now we're going to take a closer look at some of the specifics so there's a lot of text um there's a lot of information here but I'm going to try to put it in terms that will be easier to understand and you can carry this with you as you move forward from this class you know from before um we have sodium potassium pumps in all of our cells and the cells of the renal tubal are no no different there's a strong uh gradient there's a lot more sodium on the outside of the cells than there is on the inside of the cells we maintain a resting membrane potential all of that stuff the cells of the renal tubal use that fact to their advantage to move other things across the membrane it's so clever I can hardly stand it um so the sodium gradient is used for what's called secondary active transport um meaning that we pumped some sodium out so that we had to put some energy into that um but then the sodium could sneak back in if it wanted to there's some pressure to push the sodium back in because there's so much of it out of the cell and so little of it inside the cell um but this the sodium is going to travel down its concentration gradient but it brings a buddy with it so it crosses bringing another solute against that solute concentration gradient so I'm going to give you a way to think about it um if you've ever been to a nightclub or have seen one on in a movie um you know sometimes there's a line of people waiting outside the nightclub to get in they want to get in and yet you'll see like some really super foxy chick comes up in a very skimpy dress big bosoms showing off and the bouncer lets that person in wants plenty of females to come in um because that will attract more males and that will attract more males to spend more money on buying drinks uh so it's a business decision um this is the sodium trying to get back into the nightclub the the sodium is hotly desired want they want the sodium to come in but the sodium says oh can I bring my friend and then the sodium brings you know a glucose molecule or brings an amino acid with it that's so clever okay so that's what we mean by secondary active transport um because of the usual sodium gradient we have more on the outside than on the inside and we worked at that we we pumped a bunch of sodium out now the sodium we get to use that to our advantage to pull something else across the membrane and so it's things like glucose and amino acids that move by secondary active transport um there's some other details about other things moving through oh this is an important point water does not get pumped all water needs is to put some tubes for it put that into the cell membrane and water will move through those channels that the channels are referred to as aqua porins water holes um it's just a way for the water to pass through and so the water just moves according to the osmotic gradient all right as you're reading about this you will see things about the apical membrane and the basolateral membrane and I kept getting these things mixed up in my head and so I finally had to come up with a way that I could remember um which one's which so apical is on is is facing the the tubular fluid all right so I know it's not elegant but this is how I remembered APLE has a p in it it's on the P side where the filtrate is that's that side and then what's referred to as the basolateral starts with a B so does blood that's on the blood side of things and why this matters is you're basically trying to move things across um from the inside of the renal tubule out so that it can get pulled in back back into the peritubular capillary well it's a cell here um so it's going to have to go through the cell membrane twice it's going to have to go once it's going to have to go through once on the on the filtrate side and then it has to go through the second time on the side where it's closer to the blood so that's how you get things across uh so apical is the P side all right um in the proximal tubule that's when the glucose is being recollected remember uh had about 20% of all the stuff that's in the plasma about 20% of all that little stuff comes out including the glucose and ordinarily the glucose is is quite valuable to us and under under circumstances of normal blood sugar levels we pull back all of that glucose if the patient's glucose is so elevated that these transport mechanisms fail that's how you know and then we don't get all the glucose back into the bloodstream stream that's how some of the urine that's how some of the glucose ends up in the urine uh that's where diabet the name for diabetes melus comes from it means sweet urine because there's glucose in the urine that's not where it's supposed to be but um some pharmacology folks said you know what we should use this to our advantage and there is a drug there there's a class of drugs sglt uh transport Inhibitors um and the way those drugs work is they say look um we're going to pull some of the glucose back into the bloodstream but if you have a diabetic patient who you're trying to manage with other medications also but on top of everything else let's see if we can get rid of some of the glucose that's in the blood by letting it leave in the urine so these sg2 Inhibitors um the suffix I'm sure say it wrong G glyph gphin so I just think G like glycogen and then flow like urine flow so glucose in the urine um basically it blocks these uh transport proteins so that we don't pull the glucose back in of course it has some side effects like you know urinary tract infections and so on um so that's not great but it is the way one of these medications works is by um working on a transporter here in the kidney of all places um that that's how we help control somebody's blood glucose okay there's more information on this slide but I'm not going to go into it that was the thing that I wanted to point out was uh glucose transporter ordinarily will pull back all the glucose that got filtered out um but it can be a target for an a diabetes drug okay um other points here about the proximal tubu this is where um the the cells actively excrete uh certain drugs and so they're taken from the blood side across um into the filtrate summary of the proximal tubal part of this um by the end of the proximal tubal under normal circumstances 100% of the nutrients that is the glucose and the amino acids will have been reabsorbed those are the small nutrients that fit through the glomerulus and they get filtered out but we want them back usually we want them back and I talked about the the one medication or the one type of medication that blocks the glucose transporter to let more of the glucose go out in the urine um most of the bicarbon it's been reabsorbed and many of the uh electrolytes have been reabsorbed drugs and toxins get secreted here um the rest of the time the like for the loop uh the loop of Henley and the distal convoluted tubal it's mostly going to be water and electrolytes that we're going to deal with from now on so now we are in the loop of Henley um and what I want to point out is there is something called a sodium pottassium 2 chloride or nkcc transporter it's going to bring a bunch of electrolytes from the filtrate and bring those back into the bloodstream try to get them back um reclaim those electrolytes when we bring electrolytes over remember we said the water's going to move along Aqua porins the water follows a lot of those electrolytes and so where the these electrics get hold the water will follow and if we want to get rid of some of the water there are medications like furosemide um and other so-called Loop Diuretics when we say loop di it's not like Loop diuretic it's the loop of Henley that's where they that's where they work is on this transporter the nkcc secondary transporter sodium potassium to Chloride um transporter that's what getting blocked and so let's follow the logic so if we leave instead of transporting the electrolytes in over here we leave them here in the filtrate that's going to leave um the water in the filtrate so that gets peed out right so the person's blood volume will decrease their blood pressure will decrease but they're losing electrolytes and most notably people have side effects when they their their potassium levels drop and let's see now we're um a little bit further along we're out of the loop of Henley now we're in the distal convoluted tubal and now we get to see um some other Transporters also with electrolytes there is um reabsorption of sodium and chloride it's a secondary active transporter so again like the nightclub thing with the Sodium wanted to come across um the sodium comes across welcome you and your Slinky dress um oh chloride is your friend and has to come with you so all right come on in and so that's that's the way these two ions come across well that's another Target because once again when you move those electrolytes across um water comes through aqua porins and wants to come in and that's being blocked if we want to block it with a thide diuretic um this is where the thide diuretics act as in the distal tubal and so we block the uptake of the sodium we block the uptake of the chloride less of the water comes across more of the water is going to stay in the tubule and will get peed out like all the diuretics this one um interferes with sodium uptake um but it has less of an impact than the the Loop Diuretics did because remember the loop the Loop diuretics are directly acting on a transporter that moves potassium in addition to the sodium and the and the chloride um all right and I'm GNA skip that and finally we get to the final stretch um of the Nephron this is the collecting duct um resorption of reabsorption of sodium happens here happens in a lot of places but here's one of them them and this my friends is where a hormone that we've talked about before the hormone aldosterone that's that final hormone in the renin Angiotensin aldosterone system aldosterone remember aldosterone that was the Italian guy making the nice sauce um that's the one that's going to pull back some some sodium bring reabsorb more sodium so bring more sodium in so Al Stone directly impacts the bringing in of the sodium indirectly because of the sodium being brought in water will follow that but we've said before there are there are at least two hormones that affect uh water balance aldosterone was one of them and then the other one was what I typically refer to as anti-diuretic hormone or ADH um because I think of it in terms of part of the endocrine system um but it's also known it's exactly the same molecule it's also known as Arginine baso pressin or AVP so whenever I use one name I try to use the other one in case some of you learned it the way I did um which was as ADH um so this one water reabsorption depends on as we've said the aquaporin channels well what anti-diuretic hormone does for us or um Arginine vasopressin what that does for us with respect to the water and the kidneys is it puts more of these aquaporins in the in the membrane it already had them kind of waiting around and then it puts them in to the membrane and that allows water um to come across from the filtrate from the pide um into the cell and then across to the blood side you know the action of anti-diuretic hormon it's ongoing all the time and you've experienced when it's uh when it's being messed with when it's being inhibited um caffeine inhibits it the release of it and so does alcohol and this is the explanation for why when we consume if we consume CA caffeine and alcohol um the ADH is being blocked or or inhibited so we don't get as many aquaporin so that means we don't reabsorb as much water and we pee our brains out um we just we release a lot of water and so that's how important uh the role of anti-diuretic hormone or AV ADH or ABP um that's the role of those it's telling um the the cell to put more aquaporin here on the P side on the apical side and get some of that water in and get it back into the blood and that's happening again in the collecting duct I think there was one more thing um oh this is going over that in a little bit more detail um the nephron water movements the blue arrows so in general water's moving out of the nephrons we recollecting water um the maximum um water that we can recollect happens so these don't get changed too much um but here in the collecting duct this is when we can really ramp up those aquaporins and put a bunch of them into the the cell membrane and um that's going to suck a lot of the water out of the collecting duct if we do that that doesn't suck all the waste out of the collecting n that's just drying it out it's just pulling the the water out of the collecting duct and so what we end up with is a smaller volume of urine that's much more concentrated so the urine becomes darker and and just more concentrated in contrast so look here at the collecting duct everything else is going to stay the same look at that we still reabsorb some water so that you know this isn't the only place that we reabsorb water but this is where we're going to get maximum diuresis um where all the water that was reabsorbed is reabsorbed everything that's already in the collecting duct we're going to leave it in the collecting duct and that's why the very large volume of very dilute urine um when there is um when we have not put the the the aquaporin in place to recollect this water um some of you may know this disorder um it's called diabetes incipit uh diabetes in the sense so diabetes means that which passes through a vessel um so urine um and insipidus means insipid or um dilute um and so diabetes inp insipidus is this disorder in which we are not making um a lot of ADH not making a lot of ADP same thing anti-diuretic hormone Arginine vasopressin um that's being released think I may have mentioned it um hopefully it this comes up again where where it's released from um but it causes us to not put a bunch of aquaporin in and just leave the the the fluid in the collecting duct and so enormous amounts of of fluid are released total body fluid and electrolyte balance the kidneys um they have to release some they have to get rid of some waste and has to be dissolved in some water there's no way around that however um the kidneys can excrete all the waste that we need to have excreted in as little as 300 milliliters for in a day typically we release more water than that we release 08 to 1.2 liters um per day and that just goes to show that the kidneys are really maintaining homeostasis by um releasing water or holding on to water uh depending on what the the body needs and yeah okay so this is where it is and so so summarize transport um after the proximal tubule by this time most of the sodium and chloride have been reabsorbed so it's here in the loop and in the um distal convoluted tubal that the diuretics act um they interfere with sodium reabsorption and therefore they interfere with water reabsorption and they do that by blocking those membrane transport proteins um as we said the Loop Diuretics because of the membrane transport protein that it blocks the nkcc um that one is going to have a bigger impact on potassium levels the other diuretics have a bigger impact um on on sodium and less on on pottassium um what else um water's been reabsorbed um under normal conditions of antidiuresis due to the actions of ADH also known as ABP and I keep looking for something is it here okay so uh apparently I failed to tell you this but um the where anti-diuretic hormone comes from um it's in the head it's from the posterior pituitary I'm almost certain I have this written somewhere I'm going to show it to you but I'm going to say it now um as a student I couldn't keep track of what's coming out of the anterior pituitary there's a ton of stuff coming out of there and what's coming out of the posterior pituitary until I finally hit upon posterior pituitary the abbreviation in my head was p p posterior pituitary so PP this is the hormone that affects the amount of urine that's being produced so that's coming from PP posterior pituitary so the body the kidneys um maintain the acid base balance and clear out toxic compounds from the body and so what consequences does that have when these tubules stop working right um when there is acute disrup ruption uh due to blockage of glomular filtration because maybe limited the blood supply or or you know the we constricted blood flow through the area um or the cells of the tubal died um that collapses and then that blocks the flow um through those if all of if we have th that kind of dysfunction well all of the things we said that had to leave the body aren't going to leave the body we're going to end up retaining sodium chloride and water and I didn't mention it here um there should actually be potassium here as well um that's one of the side effects of side effects that's one of the problems with having kidney dysfunction is having hyperemia it's having potassium levels too elevated so if you could add that in your in your notes sodium chloride and pottassium that's going to cause us to hold on to more water this is going to lead to hypertension because we have more liquid in the tubes in the blood vessels and since we're increasing the pressure we're going to get more leaking in the capillaries and that's where with the systemic edema comes from um there's also an interference with this maintenance of metabol of pH balance and so because we're going to not be peeing out the extra hydrogen ions we end up with metabolic acidosis metabolic um this was a confusing term but it's in contrast to respiratory acidosis it's so the two categories are respiratory acidosis and everything else acidosis so this is one of the everything else so we refer to it as metabolic acidosis um obviously the other uh waste products uh the other things that we need to get rid of like the Ura and the creatinine those are going to build up because we don't have a way out any drugs that are supposed to get out through the kidneys aren't getting out so those can build up to toxic levels um and this is so bad that uh the patient may need renal replacement therapy or dialysis as it is also known um and that needs to be continued until normal kidney function recovers and if it doesn't recover then the the person and because of um more chronic problems developing than the person's on dialysis longer term that's the end of part three