five ensnared in this video we're going to continue on with a discussion and we're going to finish up with the late distal tubules right and then we're getting ready to talk about the intercalated a cells and B cells and then the collecting car so that's what we're going to talk about now we're going to finish off and we're going to discuss the activity of the intercalated a cells intercalated B cells and the actual antidiuretic hormone acting on the principal cells and even this would also be remember I told you this is a special type of cell this cell right here is actually called a principal cell let's actually write this down this is called a principal so principal cells are just basically cells that maintain your actual mineral balance your mineral balance and your water balance whereas these intercalated a cells and B cells are maintaining your acid-base balance but again if you guys remember where we left off we talked about sodium chloride reabsorption with an early distal to distal tubules BIA the sodium chloride send quarters we talked about calcium reabsorption which is dependent upon the parathyroid hormone and we talked about in the late distal tubules our dosterone that can actually cause increased sodium reabsorption in cost potassium ion secretion and then also we said if the anti directed hormones present it can actually increase the expression of aquaporins aquaporin too specifically right and then that will actually allow for water to flow in and follow the sodium ions into the blood which would not only increase sodium and decrease potassium levels but it would increase the water which would increase your blood volume increase your blood pressure okay so now that we've done that let's go ahead and see how these suckers are working here okay so let's do the first one which is the intercalated we'll do this one we'll say this is the intercalated a cell and i'm going to kind of underline that a cell because this is really going to be easy to remember why the end way i intercalated a cells and B cells thanks thank goodness whoever named these darn things they were kind to us and helped us to make make it a lot easier started giving someone's name to it you know thank goodness for that okay so intercalated a silent recliner b-cells these are the two ones that were going to talk about quickly intercalated a cell remember this is for acidosis so a is for the acidosis type of conditions so respiratory acidosis metabolic acidosis and then the B is for basic conditions so basic conditions what do I mean alkalosis so alkalosis okay so whether this be metabolic alkalosis or whether this be respiratory alkalosis this is how our body can compensate for that acid-base balance it helps to be able to keep them within the homeostatic range let's see how it does it's really cool okay so let's do the a cell first so let's say that you actually have high co2 levels within the blood so if the co2 levels that actually kind of move out of the blood and they'll go into our actual intercalated a cells when they come into the intercalated a cells this co2 will combine with what's called water and in the presence of this enzyme here it will form so what's this enzyme here called this enzyme is actually really important let's write this in sign down this enzyme is called carbonic anhydrase and carbonic anhydrase is actually stimulating this step and what it's doing is it's activating it's confusing the water in the co2 and converting it into it's called carbonic acid so h2 co3 this is called carbonic acid then what happens is carbonic acid disassociate into two things one of the things is protons the other thing is going to be bicarbonate okay so two things it disassociates into one is going to be the protons and the other one is going to be bicarbonate okay well think about what the problem was if it's acidosis what does that mean that the pH is that means that an acidosis you have a low pH that means that there's a lot of protons okay a lot of protons what's in the blood okay cool that means that there's very little basis to be able to counteract these protons all right well this is a base this is bicarbonate bicarbonate is a good base he's a weak base but he'll be able to tie up some of those protons that means I want to get a lot of this base into the blood to tie up those protons I don't want any important protons in the blood because it's making the pH acidic let me get rid of these protons so that's what our body does and look what it does here's this channel here which is channel protein right here so look here's this nice channel protein and this channel protein what it's going to be doing is remember there were some of these potassium ions that were being excreted here these potassium ions are sneaky they're like hey man you want to get rid of me you can't get rid of me I'm coming back at you so what happens some of these potassium lines are going to try to come into the cell and what happens is some of these actual protons are going to try to go out of the cell here too and because you're moving protons from actually low concentration to high concentration and you're moving potassium ions from low concentration to high concentration what do you think this requires this requires ATP so this will require ATP so this is actually going to be a ATP dependent pathway okay now you know what else you can actually happen here to whenever you're in acidosis sometimes in certain situations your body wants to be able to secrete certain substances that it doesn't really like what are some of those substances that it doesn't really like it can actually deal with one of them is ammonia so you see here nh3 this is called ammonia this stuff is toxic man super neurotoxic can cause a lot of problems cerebral edema a lot of different things so what can happen is ammonia has specialized transporters here with on the luminal membrane and whenever ammonia is actually brought in look what can happen to this ammonia this ammonia can actually be excreted out if this ammonia is excreted out into the urine look what can happen here these actual protons that you pumped out can combine which the actual ammonia so now this proton can actually combine with this actual ammonia here and when these two combine you're going to get what's called ammonium which is a weak acid okay and this is one of our actual buffer systems within the earring okay cool so that's one mechanism right there okay well we still didn't take care of the issue we got rid of those some of the protons that's outstanding but what about this by car all right let me fix this carbonic any hydration let's just denote it for right now since we know that enzyme let's send out at sea a since we can make some room here so CA is carbonic anhydrase now look what happens this bicarbonate has channels here in this actual basolateral membrane and on this basolateral membrane i'm going to pump the actual bicarb out and then work in this bicarb go I can take this bicarb and I can put this by carve into the bloodstream and as I increase the bicarb in the blood stream what happens to the pH of the blood stream what eventually happens to the pH the pH will go back up to normal levels because some of those bicarbonate ions will tie up some of those protons but you know like anything we have to have things being transported with it so there's a specialized transporter right here because you're losing negative ions right so we have to bring negative ions in so we bring chloral ions to prevent that excessive negative ion shift okay so that's how the intercalated a cells are working what about the intercalated b-cells take this pathway and flip it now instead of getting rid of the protons get rid of the bicarb and instead of actually putting the by carbon to the bump of the protons on someone that's all we're going to do let's see how that works and we're going to move through it fast because we already know how it's going to work so again if there's co2 here and there's water what can happen these two guys can fuse if these two guys fuse you're form carbonic acid carbonic acid can actually disassociate into protons and into bicarbonate and again what was this enzyme here that was controlling this step here between co2 - carbonic acid with the water here this was the carbonic anhydrase he was catalyzing this step here and then what was happening okay well now we have this channel here let's have this channel here and now what's going to happen is we're going to take this bicarb and we're going to get rid of that bicarb but again we're losing negative ions so what ions what I want to come into the cell I want there to be a negative ions coming into itself to a compensate for this negative ion loss so guess who comes to the rescue chloride and chloride can come into the cell and then there's special or ID channels here on the basolateral membrane that the chloride will actually exit through okay we'll leave out of the cell okay that's cool so I got rid of some of this bicarb I'm urinating out a lot of the bicarb and this situation okay so I'm losing a lot of my base alright cool and again why would I be doing this why would I be activating this pathway if the exact opposite of this one so what does that mean for the pH okay well this pH must be really high I must have a high pH that must mean that I actually have what a lot of bicarb in the blood and I have not a lot of protons in the blood okay where in this situation a high lots of protons and very little bicarbonate and we fix that by increasing the bicarb in the blood and get ring or the protons now we're just going to do the exact opposite we're going to reabsorb the protons and get rid of the bicarb so that's how we do it through this pathway so that will get rid of the bicarb this way but then we have to bring these actual protons in so now there's going to be channels to bring protons in and whenever you're pushing the protons against that gradient you're going to want to bring the actual potassium ions in here and so some of these potassium ions can be brought into the cell and because both of these guys are going against their concentration gradient this path will require the presence of a T P the ATP independent process then if these protons that you're actually bringing into the actual blood come into the blood what happens to the pH the pH goes back down to homeostatic range okay so that's how the intercalated a cells will work and that's how the intercalated B cells are working you know another thing that your actual distance re of your collecting duct could actually do besides that you also have other cells that can be secreting certain types of substances like drugs and toxins so drugs toxins and even another a breakdown product called creatinine create our creatinine and actually I should say like that creatinine so it can secrete toxins can secrete drugs can see creatinine and what else did we secrete we also secreted ammonia and we can also secrete protons and we can also secrete by car so that's actually showing us some of the secretory processes and some of the actual reabsorb the process but now we have one more thing like left to do okay now let's say that we have to release this other hormone we talked about a little bit we said that there was this ADH right let's go over here to this structure and again this is not the testicles I know it looks like it but this again this is the actual hypothalamus and this the pituitary gland now in the pituitary gland remember here in the hypothalamus before we say that remember in the hypothalamus we had the collection of these neurons here and these neurons were actually coming specifically from the super optic nucleus so these actual cell bodies up here in the hypothalamus what is this again Supra optic nucleus and then they had these axons that actually what move through from the hypothalamus to the posterior pituitary and whenever it was stimulated will release the hormone antidiuretic hormone and again what else do we call it vaso pressin now the question is why are we releasing vasopressin what's the stimulus why are we doing this because that's what we want to ask ourselves rather than ask ourselves why is this happening not just knowing all this just happens why okay so ADH is going to be released whenever the plasma osmolality is changing okay so what do I mean by that before I do that let me explain what he's doing because that's also gonna help us so osmolality Osmo leti okay so before I even explain whether it's high or low let me explain what aah does real quickly ADH pulls water from the kidney tubules into the blood if it pulls water into the blood remember the terms I want you guys to remember the term hypertonic hypotonic and isotonic hypotonic means that there's more solutes in there is water hypotonic means that there's more water than solutes isotonic means that there's actually equal amounts of solute and water ADH what's to pull water into the bloodstream so wants to have more water in the blood what does that mean that must mean that the actual blood was hypertonic originally there wasn't a lot of water so the plasma osmolality must be high okay and that's why he must be being stimulated what's another reason why you can be stimulated another reason why is because it is soccer angiotensin 2 he just loves to stimulate everybody so angiotensin 2 can also stimulate ADH so angiotensin q to consuming ADH as well as a high plasma osmolality and even certain drugs and other stimuli can stimulate the ADH production but we're going to stick with these two main ones increased plasma osmolality which means there's very little water and high amounts of solutes and the second one is that there is angiotensin 2 production meaning that you want to increase your blood pressure okay well how is it going to do all this crap let's see okay so ADH is released ADH comes over here and he sees his receptor and he's like oh yeah what is he going to do to this receptor okay let's actually show this receptor right here here's this receptor here's our vasopressin receptor right this is our basal press and receptor and whenever it actually binds on to this vaso pressin receptor what happens ADH binds on to this receptor on the actual kidney specifically in the collecting duct because now we're talking about the collecting duct so again intercalated a cell integral A to B cell they can be found not just in the collecting duct but they can also be found in the late distal tubule okay so nucleated a cells intercalated B cells are found in the actual lay distal tubules and in the collecting duct in this last one here what is this type of cell this is another principal cell because he's controlling our water and ion balance this is the one that ADH is acting on when the acts on this vasopressin receptor he'll activate the G stimulatory protein he's bound to who binds the gtp becomes active as he becomes active he comes and activates another effector enzyme this effector enzyme is called adenylate cyclase when it activates adenylate cyclase adenylate cyclase converts ATP into cyclic and B which then goes in activates protein kinase hey what is protein kinase a do I'm so glad you asked so here inside of this cell you're going to have a special vesicles these pre synthesized vesicles look at these vesicles they're so cool because they have on them these specialized channels these blue protein channels here these blue protein channels are aquaporins but there's special type of Locka form these aqua points are called aquaporin - why am I telling you that because if you guys have watched our endocrinology videos you'll know that there's actually aquaporins 3 and 4 on the basolateral member so what are these ones aquaporin 3 or aquaporin 4 so you guys would know that now right now another thing is that there's actually going to be these proteins that are present on this vesicle they're like basically snare proteins and what protein kinase a does is is he comes over here and he puts some phosphates on these different proteins by phosphorylating this it causes this sucker to start fusing with the actual membrane when this thing fuses with the cell membrane then what happens well now let's actually show you here look there's going to be protein channel under all three protein channels here and again what are these protein channels alright so these protein channels here are going to be aquaporin - this is aquaporin - right here originally there was no channel there there was no channel there but then when ADH came to this area what happened it activated this whole second messenger system and did what led to the fusion of these vesicles with exact 0.2 s to the membrane now water is going to start flowing through these channels from areas of high concentration to low concentration where will this water go it'll go through here and then out through these aquaporin 3 & 4 then through the aqua point 3 & 4 work in that water go they can go into the bloodstream as water goes into the bloodstream what happens to the blood vol the blood volume goes up so as water comes into the blood an increasing amount of water our blood volume goes up what happens to the blood pressure that goes up so that takes care of the initial stimulus which was the angiotensin 2 but what about more water well if I have more water I'm going to have my water increase to where it can become equal to about where my actual solutes is so that takes care of my plasma osmolality so it brings the plasma osmolality down to it reaches a normal point so it actually reaches a normal plasma osmolality it tries it tries to make it isotonic right so about 300 milliosmoles okay that takes care of that issue and again if you remember I just want you guys to make sure that you understand this we talked about this guy here ADH he can work in the collecting duct and he can work within the late part of the distal tubules ok so if the ADH in the aldosterone is present it can reabsorb some sodium and water and that is actually variable so remember I said here 10% of the sodium was remaining right out of that 10% 5 to 6 percent of it was actually reabsorbed here what about that remaining 4 to 5% the remaining 4 to 5% is right here this is the remaining 4 to 5% so the remaining 4 to 5% is actually going to be dependent upon the presence of aldosterone calcium was also getting reabsorbed here but it was dependent upon the presence of PTH then what did we say 20% of the water was being reabsorbed ok what is the water depend upon all we said water is depend upon these aquaporin tubes well again what was this one here aquaporin 2 this would be aquaporin - right and this is dependent upon 88 right ADH has to stimulate the aquaporin 2 formation right on the luminal membrane and it's not just happening here within the again you can call this like the late distal tubular or the cortical collecting duct and then this is actually going to be you know more of your actual later part of the collecting duct so again answer the right a corpsman can act at the lay distal tubule all the way down throughout the collecting duct so if ADH is present it can pull water but the amount of water that's being reabsorbed that percentage of water is variable because it depends upon the body's demands and it depends upon the presence of ADH if you have a lot of ADH more watery absorption less ADH less watery appropriate symbols that right okay now one more thing here you guys remember here within the vase erecta within the days erect what was this again let's go back down or actual imaginary gradient okay this was 300 milliosmoles 500 million walls 700 million walls 900 million walls 1200 milliosmoles right so it's getting saltier as you move down why remember it was because of this counter-current multiplier mechanism as the ascending limb was going up its pumping sodium potassium chloride calcium magnesium out which is pulling water out of the descending limb the vases are wrecked again what is this structure here called the structure is called the Vasa recta and the base erect is just basically a pair tubular capillary network present within the deep part of the medulla and what it's doing is as you're going down it's getting saltier who would want to come out water water wants to come out to where it's salty right because it loves to go out to where the salty area is being honored obligatory water movement right okay well in the same time as you're going down salt is actually going to move from high concentration to low concentration so some of the sodium chloride is actually going to move in here and then as I have some of the sodium chloride moving in why am I doing this okay well hold on before I explain why I'm doing in a second as we turn back around the process reverses so now water is going to want to go back into this actual capillary network and as water tries to go back into the capillary network that's kind of interesting all right what happens if sodium quart the sodium chloride gets pushed out as it's going back up why in is it doing this if you guys remember what did we call the vases erecta we called this a specialized thing we call it at the counter-current exchanger right and we've said that the counter-current exchange of the BAE's erecta had two functions one is prevented the rapid removal of salt that was one of the big things we said that it actually did two things right one is it prevented rapid sodium chloride removal that was one of the big things because as it's going down it's actually pulling in some of the sodium chloride from the medullary interstitial space and providing a little bit of water onto the area but if this is actually happening so much if we actually have so much water absorption it can wash away a lot of the salt so we don't want to lose a lot of that salt from the watery absorption so what do we do we pull some of the salt into this veins erecta because it's coming in at 300 milliosmoles but when it leaves the actual really Osmo of the osmolarity of the blood coming out of the base erecta is approximately 325 nearly osmoles so it actually takes a little bit more sodium chloride with it to prevent the rapid removal of the salt from the medullary interstitial space what else thing to do it also provides oxygen to the nearby tissue cells right but it's a very sluggish blood flow we said why am I telling you this because I remember we said that this was contributing to the medullary interstitial gradient which was trying to pull the water out make make very very concentrated during that sole purpose there's another thing that's contributing to this it's also helping in this process his name is urea so urea is also contributing to this process look here so urea is right here urea actually gets reabsorbed in the last part of the actual collecting duct so in the last part of the collecting duct after a lot of the water is being reabsorbed the urea concentration here starts really increasing and by facilitated diffusion it moves out of the collecting duct and here into this medullary interstitial space as it's going down look what actually happens it actually gets reabsorbed back here into the actual ascending limb but as its doing that your real actual e accumulates out here and urea is a solute if urea is accumulating out here for a little bit before it actually gets reabsorbed what is it helping to do it's helping to make the module even more salty so this process here is called urea or cycling because it just keeps going you'll actually go back in here and then go back and get reabsorbed now some of it will actually get lost in the urine let's not confuse that a lot of it will get lost in the urine but some of it will actually get recycled this is called urea recycling and again this is important because why Adachi is helping to maintain it's actually helping to do two things two things make concentrated urine that's what it wants to do it wants to make concentrated urine and it wants to contribute to the actual medullary interstitial gradient so it wants to contribute to maj Allari gradients alright to be able to make concentrated here in other words okay so we covered what have we covered before we actually in this whole video guys we covered within this video we talked about indicated a cells and how they work in acidosis we talked about the intercalated B cells and how they work in alkalosis we talked about the principle cells responding to the antibiotic or mone and how that actually helps to increase water reabsorption we talked about how the collecting duct and the distal tubular are also playing a role in secreting drugs and toxins and creatinine and protons and even ammonia we discussed a little bit about here about the counter-current exchanger and how that's helping to prevent the rapid removal of salt and provide oxygen to the tissue cells nearby and we talked about how this urea recycling is helping to contribute to the medullary interstitial gradient and it's helping to make concentrated urine Messner's I hope all of this made sense I really hope you guys enjoyed I really hope it did in the next video we're going to try to do is we actually take everything and put it all together and see how all the reabsorb different secretory mechanisms are actually occurring so you guys can see everything in a nice one action flow because that's what we really want to do we want to make everything make sense iron engine so we're going to have one more video and that's going to be the entire overview of the entire reabsorption and secret secretory process all right insurance I hope it made sense if it did please hit the like button subscribe put some comments down the comment section as always engineers until next time