all right Ninja nerds in this video we're going to talk specifically about the distal convoluted tubal so if you guys haven't already seen it go and watch the loop of Henley all right and even the proxil convoluted Tu before that because now what we're going to do is we're going to goe and start here so if you guys remember if you guys have already caught up to this point you'll remember that we talked about what's happening here remember that we actually had the proximal convoluted tubal and then we had the here the loop of Henley and again the loop of Henley was consisting of this descending portion here and this ascending portion here and now we're going into the distal convoluta tubal and if you guys remember we said that there was a specifically tubular reabsorption here so whenever we're moving substances from the actual uh kidney tubules to the actual blood and we talked about many of the mechanisms there and then we also talked about how these mechanisms could also be going in the reverse Direction so how we can move specific types of solute molecules from the blood into the kidney tubules through tubular secretion so this is tubular secretion and this event right here was tubular reabsorption we had many many things that were going on here all right and if you guys also remember what was happening here in the loop of Henley well if you guys remember you can recall there was on the ascending limb there was these specialized Transporters right and these specialized Transporters were pumping in sodium pottassium and two chloride ions into the actual cells here of the actual ascending Loom of loop of Henley and then here on the basil lateral membrane you had these channels to pump the sodium out here you had the channels to pump the actual two chloride ions out here and you even had some channels that were actually pumping some of the potassium on but not as many and the same thing was going on here on this channel same thing sodium pottassium two chloride ions are being pumped out here and then again there's a channel here here channel here and a channel here and the sodium ions are being pumped out sodium and then the potassium ions are being pumped out and the two chloride ions were being pumped out if you guys remember what was this doing they was concentrating the sodium and the chloride out here the pottassium ions out here and what was the whole purpose that wasn't it making the meary interstitium very very salty because if you remember what was the actual gradient as we moved down we said it was approximately 300 Milli osmol here as we mooved down let's say it went down to about 500 m OS moles as we kept going down we said it could get down to about 700 milliosmoles it got dropped down to 900 milliosmoles and then it can get up to 1200 at the deepest parts of the renal medulla and again this was Milli Osmos per liter Milli Osmos Milli Osmos and milliosmoles and milliosmoles and again what was contributing to this actual as you're moving downwards the medul interstitial gradient is is actually increasing it's getting saltier it's because of these sodium potassium 2 chloride Co Transporters also if you remember some of this actual potassium ion was leaking out here remember some of the pottassium I were actually being pushed out here and whenever the potassiums were actually accumulating out here it was generating a little bit of an actual charge across these actual inner cell membrane of the ascending tubules and what did that do that charge actually caused some of the calcium ions and the Magnesium ions to bounce up against these charges and be repelled and then move out here right so then the Magnesium was accumulating out here as well as the calcium was accumulating out here and these were also contributing to the medular inal gradient right and as I was making this really really salty what was happening it was pulling what molecules out remember it was pulling molecules of water out so water was being pulled out here all right cool now why did I mention all this because if you guys remember 65% of the sodium was absorbed here 65% of the water was absorbed here then if you go to the remaining parts here here in the actual descending limb of loop of Henley about how much water was actually absorbed okay we get 65 then if I add on another about 15% about 15% what does that leave me with okay so 15 plus 65 70 80% right so what does that mean how much water I have going into this distal convoluted tubal then so going up here to the distal convoluted tubal I might only have about 20% water going over here that's why I'm mentioning all this stuff 65% sodium was reabsorbed here how much sodium was actually reabsorbed here approximately 35% so 35% of that sodium that was actually coming out here 35% of it was actually being in this reabsorb process okay so how much does that leave okay 65 Plus plus 35 okay it's going to be 70 okay uh whoopsie I made a mistake this should not be 35 this should be 25 that is my I'm sorry so 25% so 65% plus this 25% that leaves you with a remaining 10% okay so this would leave you with a remaining 10% of the sodium ions okay so you have about 10% of the sodium ions remaining 20% of the water ions remaining and again this was called that countercurrent multiplier mechanism right and then this was also the Vasa Rector which was helping to be able to Main maintain that by preventing the rapid removal of salts all right so that's good enough I just wanted to get you guys up to this point of why I had 10% sodium left and why I had 20% water left also what is the actual um osmolality here because if you remember it was approximately here inside of the PCT it was actually 300 milliosmoles and then as it left here from the actual what as you go down the descending Loop of Henley had actually become very very salty and it was 1200 milliosmoles right because it was losing a lot of the water then as it ascended it went up here and we said it was about to anywhere around 100 to 200 Milli Osmos but generally it's right around 100 okay so 125 okay now that is what we have now what we need to figure out is how is some of these molecules being reabsorbed here in the distal convoluted tubal and how are molecules being secreted that's what we're going to do now okay so in the early part so this whole part here is the distal convoluted tubal right here okay this whole top part here but we can divide it into two parts we can say coming about right here let's come to about right here if I come about right here anything in front of this actual uh purple line here is the early distal tubal so again this is the early distal tubal I'm going to put DT there and over here on this side is going to be the late distal tubal so over from here is going to be the late distal tubal all right in the early distal convoluted tubal there's some specialized Transporters here look at this this is pretty cool let's do this in this color here so there's some specialized Transporters here on the actual luminal membrane closest to the actual urine right on this there's going to be this specialized channel before we talk about that channel there's another channel in the basolateral membrane so back here you know they're on almost every single cell within our body right these channels are sodium potassium ATP so they're pumping what they're pumping sodium ions out and they're pumping potassium ions in and if we really should be picky we should say that it's actually pumping three sodium ions out and two potassium ions in same thing here pumping three sodium ions out into the actual extracellular fluid and pumping two potassium ions into the cell and the intracellular fluid but what do we say because they're pumping them against their concentration gradients what does these two steps here require they require the presence of ATP so this will require ATP and this step will also require ATP because you're pumping them against their concentration gradients but here's what's really cool you know you know what other ions actually we're going to be present here too so we said there's about 10% of the sodium uh left you know what else is a little bit left here too besides that chloride ions so there's even going to be some chloride ions there's even going to be other ions here too there's going to be calcium that we're going to talk about here in a second so there can even be other different LS but for for right now we're going to talk about about chloride sodium and we'll talk here about calcium in a second okay now sodium concentration right here in the actual specifically what this actual luminal fluid they actually filtrate which is in getting ready to make urine this concentration out here is actually going to be higher because we're pumping sodium ions out here so the sodium concentration inside the cell here is actually going to be very low so that means that sodium ions are going from high concentration to low concentration via this trans transporter well guess what else can happen we can take chloride ions with us so because of that we can take these chloride ions with us and this is going to be through this sorter so this is a sodium chloride so that's a sodium chloride sorter because it's moving in the same direction and if we take this sodium and this chloride into the cell what can happen then you have these actual pumps here and what can happen you can actually have that sodium be pushed out what can happen to the chloride chloride has spe uh special channels let's draw these channels here let's do it in this purple color here and these chloride ions have a special Channel and what can happen is we can take this actual chloride and pump it out into the blood and that is what can happen so look at that we can get the chloride ion into the blood and we can get some of these sodium ions into the blood right so it's a pretty cool mechanism right there okay so again what can happen in the early distal tubal some of this sodium there's 10% remaining out of this 10% only five to six% of it is going through this process with the early distal tubal so again out of this 10% only five to 6% of it is being reabsorbed here in the early distal tubu okay so that means there's only about about 3 to 4% remaining okay all right I'm sorry uh four to 5% remaining okay so now 10% out of that 10% 5 to 6% it was actually being reabsorbed here within the early distal tubal via the sodium chloride importers which are going to be helping to get them in and the sodium potassium pumps are basically helping to decrease the sodium concentration in the cell so it can move down its concentration gradient all right boom done so we talked about the sodium and we talked about the chloride ions now let's talk about this calcium you know there's a hormone that our parathyroid gland produces whenever our actual calcium levels within the blood are low so let's say here up here at the top by I actually have low blood calcium levels right so let's say here in the blood I actually have low blood calcium levels right what this low blood calcium levels can actually do is you have here let's say here's your thyroid gland in the back of the thyroid gland you have these little uh glands here in the back and they're called your what is this structure called par thyroid glands when you have low blood calcium levels these low blood calcium levels can stimulate these Para thid glands to produce a hormone called parathyroid hormone so depending upon the the demands of the body this calcium will they get reabsorbed or will just get go out in the urine it all depends upon the demands of the body so what happens is this parathyroid hormone it has a receptor present here on this actual cell of the distal convoluted tubal look at this and here it actually can bind on so look this parathyroid hormone can be circulating in the blood and it can come and actually bind onto this receptor and stimulate this receptor if it stimulates this receptor it'll activate a second messenger system so what can it do it can activate a g stimulatory protein that g stimulatory combine GTP that can come over here and bind onto a aor enzyme what is that aor enzyme called This enzy is called ad denate cyclas what does he do he takes ATP and converts it into cyclicamp what does p cyclicamp do activates protein cyas a and then if you guys have seen this mechanism so many times you already know what's going to happen what does protein kyes a do well here on the actual cell membrane the luminal membrane there's these actual calcium modulated channels so there's these calcium modulated channels here and these channels are going to be very very sensitive to the actual changing levels of parathyroid hormone so if the parathyroid hormone is present it's going to activate this protein cyas a and guess what this protein cyas a is going to do it's going to come over here and it's going to stimulate these channels if it stimulates these channels by phosphor right so it can put some phosphates on this channel some phosphates here it's going to activate these channels and guess what they're going to do any calcium that's actually present here in the urine the filtrate that's getting ready to make urine will be sucked in okay so this calcium will be sucked in here now some of this calcium can be bound a small percentage of it can be bound to a protein inside of it called calbindin but most that we want to get onto the blood because we want to increase the blood calcium levels well how do we do that okay calcium is going to be in specifically calcium is in a lower concentration inside the cell right now it's in a higher concentration out in the blood and remember this is comp I know that the calcium levels are low don't get confused here yes the blood calcium levels are low but still the amount of calcium present within the cell is much lower than that okay so this gradient is it have to go against its concentration gradient well we have a way of dealing with that our body is so clever we have these proteins here on the actual basolateral membrane and look what they can do they can help to pump some of this calcium out here into this actual blood and then what it can do with it is it can bring sodium ions in because sodium again will be moving from it's usually always in higher concentration outside the cell so if it's in higher concentration outside the cell it's going to move from High concentration to low concentrations in the cell this is an example of a secondary active transport so again this is a secondary active transport there is another mechanism too and all it's doing is let's say here I put another pump I put another pump and I put this one in green say I make this one a green pump this green pump here all it's doing is it's taking the calcium and it's pumping it out here against its concentration gradient and it's bringing protons in so this would would directly utilize ATP this process would directly utilize ATP so this is an ATP dependent process okay so that's how this mechanism is working all right so let's quickly review the early distal tubal what's happening as the urine is coming up it's coming up with an actual hypo what would you call this hypotonic right because the actual uh osmolality is very very low because there's going to be a decent amount of water in this case very little solutes right about 100 to 120 milliosmoles but again it could range up to 200 just depends upon the situation there's about 10% of the sodium remaining about 20% of the water remaining there's a little bit of chloride there's a little bit of calcium there's other ions here too but we said in the early distal tubal there's these specialized sodium chloride sorters that are bringing the sodium and the chloride into the actual cell by secondary active transport how because these sodium potassium pumps are pumping the sodium out con concentrating it outside the cell and causing the concentration inside the cell to be lower so sodium moves down its concentration gradient which helps to pull chloride with him then the other part is that calcium is also here present within our actual filtrate if we want to get the calcium into the blood what would need to be the stimulus we would need to have hypocalcemia low blood calcium levels which would stimulate the parathyroid gland to make parathyroid hormone which would stimulate these actual cells within the distal convoluted tubal to activate protein KY a which will phosphorate these modulated calcium channels on the luminal membrane and pull calcium in some of the calcium combin to calind in but most of the calcium will actually go out into the blood to increase the blood calcium levels and bring it back to normal values okay now why did I mention that sodium chloride importer because you know there's drugs that can actually inhibit this that's the whole point is knowing why you know sometimes we're mentioning all these darn things there's what's called thide th iide is basically a diuretic it basically inhibits this actual sodium chloride Sorter and if it inhibits the sodium chloride sorter 5 to 6% of the actual sodium that you're going to reabsorb and also water can follow you know dependent upon whether the actual ADH hormone is present that would affect the actual salt reabsorption and the water reabsorption so instead of actually allowing for it to reabsorb you lose the salt and the water and the urine right called diuresis so you lose the blood volume a little bit all right that's that part now let's come to the late distal tubal the later part of the distal tubal has these specialized cells that are responsible for responding to aldosterone okay so let's see here what hormone where was that hormone actually going to be produced the aldosterone if you guys remember if you come over here to this right corner we had the adrenal gland so here's our adrenal gland right here sits on top of the kidneys right and there was this one part of the adrenal gland which was up at the top part consist of these actual globulars like cells right and these globular cells were responding to different types of stimuli and they were producing a hormone called aldosterone and then aldosterone would do what it would actually circulate to this actual cell what were some of the stimuli for aldosterone production if you guys remember one of the stimuli was actually going to be a very powerful stimulus due to Angiotensin 2 and the other stimulus was actually going to be what whenever the actual sod iium levels within the blood are decreasing and whenever the potassium levels within the blood are increasing okay so whenever you have hyponatremia and hyperemia that can stimulate the actual adrenal gland produce aldosterone okay so now now that we know that and there is other stimula they even believe that CR a little bit of the corticotropin releasing hormone small amounts of the corticotropin releasing hormone can also stimulate this too okay anyway what is aldosterone doing okay well we got to remember something aldosterone is actually a steroid hormone right so look here let's see here's our aldosterone we'll do know with this a aldosterone is a steroid hormone so it can actually pass right through the actual lipid bilayer of the cell as it passes through the lipid by layer of the cell do you guys remember that it stimulates specific genes activates transcription factors when it activates those transcription factors it leads to the production of different types of proteins let's look at those proteins so let's say here's one Protein that's actually being produced and let's say that there's going to be another Protein that's going to be produced we'll make this in green back here and then there's going to be another protein we'll make this one let's just make this one black and here's this other protein so three proteins are being made so now let's draw each one of these proteins so here's one protein which is going to be in here in the actual basolateral membrane you guys probably already know what this protein is then there's going to be another protein protein which is embedded into the luminal membrane so here's this protein here in the actual luminal membrane and then there's going to be another protein which is embedded here in the actual luminal membrane as well okay these the this late part of the distal tubal you need to understand is very very um specific so when we look at the distal tubal in general it's impermeable to water it's generally impermeable to water it depends upon hormones to make it permeable and also you noticed here that the in the early disto tubio the solutes could actually be reabsorbed independent of hormones but in this part here calcium is dependent upon hormones this right here the lay distal tubul is also dependent upon hormones okay now aldosterone can stimulate this actual cell and what it does it leads this proteins here the development of this protein and this protein can actually lead to the actual allowing of sodium ions to come into the cell so now we can have sodium ions coming into the cell and why can sodium ions come into the cell I got you look sodium ions here it makes this other protein guess what this protein is doing it's pumping out three sodium it's pumping in what two potassium ions so this is pumping out three sodium ions and pumping into the cell two pottassium ions two potassium ions and then over here two potassium ions why is this important okay so what's happening to the sodium concentration in the cell well sodium is leaving so the sodium concentration inside the cell is going to decrease okay what's happening to potassium well we're concentrating the potassium into the cell right more than we normally are because normally pottassium is always high in the cell so the potassium concentration inside the cell is actually going to increase so now sodium is going to want to go from low concentrations to high concentrations and then it's going to get reabsorbed so then where can it go from here as it gets it's going to go and get reabsorbed out into the blood and bring more sodium ions into the blood so the sodium ions within the blood are going to go up but then the problem was that we had a lot of potassium in the blood the problem was also that we had a lot of potassium in the blood we had this hyperemia right well now we're going to pull potassiums out of the blood put it into this cell through the sodium potassium pumps and guess what else is going to happen that potassium right there look where it's going it's going right out here let's Chuck that sucker out in the urine so now potassium ions are getting excreted out into the urine but again it's moving from high concentration to low concentration and the same thing here the sodium ions are going from high concentration to low concentration so it's not requiring any energy the only one that requires energy is this structure back here which is the sodium potassium pumps and they can require the utilization of ATP to make ADP and inorganic phosphate right okay so now if the sodium ions are being reabsorbed into the blood what's happening to the sodium ions within the blood they're going up if the potassium ions are getting yanked out of the blood and then secreted what's happening to the pottassium levels with in the blood it is going down okay so now the potass so the potassiums within the blood are going down and what was the problem originally well the problem one of the problems originally was that there was low sodium levels within the blood and that there was high potassium levels we fixed that we brought the sodium levels up and we brought the potassium levels down angot tensin 2 is a stimulus because it wants to increase blood pressure and I'll explain why here in just a second why that can happen okay now what is really important here is there's another hormone that can be present here within this area and it's called the anttic hormone so if the anti- dtic hormone is present we're going to go into his mechanism in another video but I just want you to understand something here the anttic hormone also called vasopressin can act on these cells as well and what it'll do is it'll help to make these little pores inside of the membrane because remember I told you that generally the distal convoluted tubal and even the collecting duct is impermeable to water it depends upon hormones if ADH is present ADH can actually act on these cells and open up these aquaporn and pull water in and the water will love to follow the salt and if the water is following the salt what will happen to the amount of water getting pulled into the bloodstream the water volume will go up and if the water volume goes up what happens to your actual blood pressure the blood pressure goes up which helps to be able to take care of that issue with Angiotensin too right and we again we'll go over this mechanism with the ADH because it's more important that we understand how it's working within the collecting duct but it can be acting in the distal convoluted tubal the late part of the distal tubal but again if ADH is not present you're not going to be able to pull a lot of water with it but again remember that the water will love to follow the actual sodium ions and it will go into the blood increase the actual blood volume which will increase the blood pressure okay now what we're going to do is we're going to go over these intercalated a cells and intercalated B cells but we actually should couple this with the actual uh collecting duct cells so what we're going to do is we're going to stop this video here and we're going to go into the next part where we're actually going to talk about specifically the collecting duct uh cells specifically with ADH and we'll talk about the interated a cells and the intercalated B cells all right Engineers I'll see you guys in that video all right