DIP Episode 149 - Comprehensive USMLE Renal Pharmacology 2

Okay, welcome. My name is Devine, I'm a resident. This is episode 149 of the Divine Intervention Podcasts. And in this podcast, I will really be focusing on Reno from Ecology. This will be the second part in the series. So let's just jump right into it, right? So let's, again, if you look at the nephron, right, you know that we have the glomerulus and besides the glomerulus, we have the tubular cells. The first big one, I guess I'll go ahead and talk about, is the proximal convoluted tubular. Right? So for the proximal convoluted tubular for the most part, if you're looking in terms of like cell structure, right on the blood side, we actually have the sodium potassium, ATP is pump, okay? That moves three sodium out into the blood and brings two potassium into the cell. And then on the urine side, we have protons that go into the urine, right? And then we have sodium that comes into the cell. There's like a sodium hydrogen anti-pointer. And the thing is that hydrogen in the urine will pair up with a bicarb to form carbonic acid, okay? And then that carbonic acid is broken down by an enzyme known as carbonic anhydrase into carbon dioxide and water. And then this carbon dioxide and water can diffuse back into the proximal convoluted tubular cell and then it's converted back to carbonic acid again by carbonic acid and hydrase just a different iso-form of carbonic anhydrase. And then the bicarb, right? It can then leave, it can then leave to go into the blood, right?

So the basal side, the blood side, the bicarb can leave the PCT cell and then chloride will come in in exchange. Remember, you always want to try to maintain an electron neutrality where possible cell. If bicarb is living in a cell, that's a negative charge. You want a negative charge chloride to come into the cell. So on the blood side, there is a chloride bicarb anti-pointer and again on the blood side, you also have the sodium potassium, ATP is pump. And then the urine side as I described, there is a sodium hydrogen anti-pointer and there is also there is also there are also the transporters that help with reabsorbing stuff. But yes, the big thing you want to remember is that sodium, a hydrogen anti-pointer. It so happens, there is also like the SGLT two receptor. It's a transporter actually on the urine side in the proximal converted tubule. That transporter helps you reabsorbed sodium and glucose at the same time. Remember, sodium uses this thing called basically use like gradient energy because there are high concentrations of sodium outside the cell. So with those high concentrations of sodium outside the cell, as that sodium flows down, it's concentration gradient into the cell, glucose can go alongside. So it so happens that that is the LT2 transporter. You can actually block it with one of the diabetes drug classes. They are called the SGLT2 inhibitors drugs like the ending glyphlose drugs like canaglyphlosein, diapaglyphlosein, and paglyphlosein.

They all work for that purpose. And just again, kind of like relating this to something you've seen when you're learning G-I, the thing is, if you notice, when people are digesting food, when people are digesting a ton of food, those people tend to become hypochlorimic. The reason people become hypochlorimic is that. The transporter is in the stomach, who release a ton of chloride into the lumen of the stomach, because obviously they'll maintain the low pH environment of the stomach, so they'll help with food digestion. And essentially, if you really think about this sodium hydrogen antipotor, I talked about, I just mentioned on the urine side, that if you have increased the activity of that transporter, you will actually have something called a bicarbaryclemation. And you'll ultimately get a metabolic alkylosis, because if you think about it, if that sodium hydrogen antipotor is working really hard, then that means that you'll be getting more hydrogen ions into the urine. So you're losing hydrogen ions in a sense, so you get a metabolic alkylosis. But in the process of doing that, you're getting bicarb, because by dumping those hydrogen ions in, you're binding with bicarb, and then carbonic and hydrogen is those, it's magic, and you get that bicarb back into the proximal convoluted tubule cell. Again, these are all high-yields to understand, and it so happens that that sodium hydrogen antipotor, its activity is actually increased by angiotensin too.

And really, the proximal convoluted tubule of the nephron is the workhorse of the nephron, so you kind of make sense that most renal cell carcinomas actually are raised from the proximal convoluted tubule, and you should hopefully also remember that renal cell carcinomas tend to secret a ton of irithropoetin, like ipo, in a primary or plastic fashion. Other cancers, I guess, that can produce an ipo, will be things like hepatocelular carcinoma, that also secrets ipo-hemanjioblastoma. It's a brain tumor type that's classically associated with VHL, one ipo-landal, and that also secrets ipo, right? So these people tend to have very high hematocrit because they are producing a crap ton of hemoglobin. And then the proximal convoluted tubule, some other high-yield things you want to remember, I would want you to remember this condition where people have like a cola, like COLA, transporter defect. Basically, there's a transporter on the urine side of the proximal convoluted tubule that helps with reabsorbing the amino acids, cysteine, or nithen, lysine, and arginine. Okay? So the thing is, if people have a defect in this transporter, they are not able to reabsorb cysteine, and that cysteine can form polymers, they're kind of shaped like benzene rings. The easy way to remember that is that cysteine sounds an awful lot like 16, okay? I remember a benzene ring is a six-membered ring, so that's kind of like a nice way to remember that.

So, under those circumstances, those people tend to get like a lot of kidney stones, so that's a high-yield thing to keep at the back of your mind. And then the thing is, you can actually treat this cola-transporter defect with acetyzolomide. Acetyzolomide is a carbonic and hydrate inhibitor, right? Because by inhibiting carbonic and hydrate, that carbonic, that bicarbaryclemation process is impaired. And if that process is impaired, you'll keep a lot of bicarbary urine, right? So by keeping all that bicarbary urine, you can solubilize acetyl, because remember, a bicarbaryclemation solubilize is acid really well. You can solubilize an acetyl-carb based kidney stone like a cysteine stone, okay? So again, you inhibit carbonic and hydrates, you all colonize the urine, right? You all colonize the urine, and by doing that, you'll solubilize those as cysteine stones. That's a very high-yield means of testing acetyzolomide on the USMLA exams. And I remember, acetyzolomide, you can also use it for like acute mountain sickness. I believe I've talked about that in prior podcasts, because again, it helps you sort of like encourage the kidney and lung in dumping bicarbaryclemation in the urine, because if you have mountain sickness, right? You're going to higher elevations, when you go to higher elevations, you become hypoxic because the oxygen tension in the atmosphere decreases, right? Because the atmospheric pressure is going down as you go to higher elevations.

So if you have that happening, you become hypoxic, right? When you become hypoxic, the way your body responds to try to get oxygen on board is to cause hyperventilation. Well, if you hyperventilate, you'll create a respiratory alkalosis, right? And the way your body tries to, the way your body tries to compensate for that respiratory alkalosis is with metabolic acidosis, right? And for your body to create that metabolic acidosis, you will have to get rid of as many bicarb as possible in the urine. So by giving acetyzolomide, you can sort of encourage that process along. And again, because many people memorize this, oh, oh, diuretics cause hypochylemia and metabolic alkalosis. Hypochylemia and metabolic alkalosis, or oh, if something has a hypochylemia as a side effect, it must also have metabolic alkalosis, that is not always true. That could not be further from the truth. Remember, acetyzolomide, by being a carbonych and hydrism inhibitor, it makes you dump bicarb in your urine. When you dump bicarb in your urine, right, you actually develop a metabolic acidosis because you're literally losing base, you develop a metabolic acidosis, but because acetyzolomide is a diuretic, right, it makes you volume down. And if you have volume down, you will increase the activity of the reneinendrotensin adosterone system because you're hypochyl, profusing the afrin arterial.

If you increase the activity of your reneinendrotensin adosterone system, right, if you go back to the principal cell, you will increase the activity of that inek channel that you'll find on the surface of the principal cell of the collecting duct. Now bring sodium in because it's been activated by ourosterone, that will create negative charges in the urine that will draw out potassium, right, so you get hypochylemia. So if you see a diuretic question on the USMLA exams where a person has a combination of a metabolic acidosis, but they have a concomitant hypochylemia, I really want you to think about acetyzolomide. Okay, acetyzolomide is a carbonych and hydrism inhibitor. And remember, in addition to acetyzolomide, there's another drug known as dorsolomide, dorsolomide is also a carbonych and hydrism inhibitor. And please don't forget, right, essentially because acetyzolomide makes your dump, it causes a metabolic acidosis because it makes your dump by carbs in your urine. Acetyzolomide is actually a high yield cause of a renal tubular acidosis. If you want to be a little more specific, type 2 renal tubular acidosis. That is something that your friends at the MBM love to test, but it's something that whatever bizarre reason people don't think about, okay? So acetyzolomide and your carbonych and hydrism inhibitors, because are type 2 or proximal renal tubular acidosis. That's something I described in great detail in my in my renal podcasts.

I think that's like a episode of 52 to 54. And then you should also not forget that acetyzolomide is used to treat oponangoglokoma. So you may ask, why is it being used to treat oponangoglokoma? Well, the reason there is that carbonych and hydrism is actually used in the production of acous humor. So if you give a carbonych and hydrism inhibitor, you will decrease the production of acous humor. And that will ultimately relieve intracular pressures in the setting of glaucoma. It also so happens that carbonych and hydrism is also used in the is also one of the big enzymes involved in the synthesis of CSF. So cerebrospinal fluid. So you can actually treat idiopathic intracranial hypertension. Some people know it as a pseudo-tomor cerebride with acetyzolomide, because again by inhibiting carbonych and hydrism, that will decrease the production of CSF and that will help with lowering those intracranial pressures. And then the thing is acetyzolomide can also be used to treat central sleep apnea. So the thing is, I've done a ton of searching in the literature, I've not exactly found why this is the case. But here is my teleological, so teleological is something that makes sense. But I mean, I don't necessarily have a scientific basis, but I promise you like this explanation actually is pretty legit. So think about it, if a person has central sleep apnea, they have decreased the respiratory drive.

Well, if you think about it, if you give those people acetyzolomide, we know that by virtue of its role as a carbonych and hydrism inhibitor, acetyzolomide will cause a metabolic acidosis. Well, the way a body responds or tries to compensate for a metabolic acidosis is with a respiratory alkylosis. And to achieve a respiratory alkylosis, you essentially have to increase your, increase your respiratory drive. You essentially have to hyperventilite, right? So I kind of think of it as using pharmacology to induce an acybase disorder that would cause the body to hyperventilite. In so doing, you're improving the person's respiratory drive. So that's my theological explanation for why acetyzolomide may be used in the setting of a central sleep apnea. And with this whole business with carbonych and hydrism, I guess one thing I'll also go ahead and say is if a person has like a deficiency of carbonych and hydrism too, that can actually cause an endocrine, the soder known as osteopetrosis. That is something that you'll likely learn as you're studying endocrine for the USMN step one. Well, that's your patrosis. Basically, it's a problem where you have like trouble reserving bone appropriately because it so happens that you actually need an acetic environment to be able to resort bone. So if you have a deficiency of carbonych and hydrism too, you would have issues creating that acetic environment that's necessary for bone resorption. Okay? So that's something very high you'll do.

Want to make sure you know, you want to make sure you know for exams. And I mean, I guess if you're looking at the proximal convoluted tubular game, you see divine. You've been spending so much time on the PCT again, all these like anything you hear me say today, I promise you they are all high you to know for USMN exams. So these are just things again. You definitely want to keep at the back of your mind. If you're looking at the proximal convoluted tubular, right? Remember that you were absorbed about like 67% like two thirds of the water from your earring. You reabsorbed two thirds of that in the proximal convoluted tubular. That's also where you reabsorb like two thirds of your sodium chloride, right? 100% of your glucose is also reabsorbed in the PCT. In your lane is actually not reabsorbed in the PCT. And also this compound known as a paraminohypuric acid pH, it's also not reabsorbed in the PCT. The thing that actually happens to pH at the level of the PCT is that it's actually secreted at this level. And the thing is your friends, the MBMI, or I guess your USMLE friends, they kind of expect you to know the concentrations of stuff as those things are, like you know, sort of traverse the PCT. And remember the right concentration if your chemistry person concentration is mass over volume, right? That's like the one big thing you want to keep at the back of your mind, right?

So if you sort of think in terms of these numbers that I just mentioned, the concentration of sodium should stay the same across the PCT, right? Because it's like if you're looking at it as a mass over volume measure, the volume is going down by 67% because your reabsorbing water. But the mass of sodium is also going down by 67% because you're reabsorbing sodium. So overall that ratio should not change. So the concentration of sodium should stay the same across the proximal coveleutubial. The thing is for glucose, right? The mass of glucose decreases to zero, right? So the concentration of glucose at the end of the proximal coveleutubial should also be zero, right? The thing is if you're looking at inulin, right? In inulin, there is no change in mass, right? Because you do not reabsorb it, you do not secret any extra amounts across the level, across the PCT, right? So the mass of inulin, there is no change. But guess what? The volume of water decreases, right? So the numerator is not changing. If you're looking at that mass over volume measure, the numerator is not changing, but the denominator is decreasing. So overall the concentration of inulin increases as you go across the proximal coveleutubial. Now, PAH paraminol-hyperic acid is different. The thing is the mass actually increases across the proximal coveleutubial, right? Because paraminol-hyperic acid, guess what? You're secreting even extra into the proximal coveleutubial. But also think about it, right?

So the numerator is going up. But the denominator again, like I said, is coming down because you are reabsorbing water across that proximal coveleutubial. So the thing is the concentration of PAH actually increases a ton across the PCT, okay? Because the numerator is going up and the denominator is going down, right? Compare and contrast this with what is it called with inulin where the numerator is not changing whether the denominator is decreasing. So if you're comparing all these things, they can give you this classic example question where they give you a graph and on the x-axis they show you like distance along the proximal coveleutubial. And then on the y-axis they show you concentration and then they show you different compounds and then you're supposed to be able to pick out all the concentration of this compound decreases or stays the same or goes up or goes up by a ton. They usually give you those four options on the exam and you want to be able to map those to different compounds, right? So again, to summarize, as I've mentioned, the glucose concentration decreases as it traverses the proximal coveleutubial. The sodium chloride concentration does not change. The inulin concentration goes up but it doesn't go up as much as the paraminol-hyperic acid or concentration. Again, let me see to find this stuff must be low yield. Well, I wish you all the best if you're thinking with that.

I promise you again, like I said, of 200,000s and thousands of people for these USMLE exams. These things shop a ton on the test, right? Then again, people don't pay attention to them and then they end up getting holed on the test. I don't want you listening to this podcast to get holed. Okay. Now, another high-yield thing you want to keep at the back of your mind is with the proximal coveleutubial is this disease known as a heart-nob disease. Okay? Heart-nob disease. Basically, here's my go right. So this is a renal from a collagey podcast. But the honest truth is, I want you to learn these transporters from every possible USMLE angle. That is ultimately my go with this because again, the thing is, the USMLE very rarely tests like one to one knowledge where it's like, oh, what works at the level of the proximal coveleutubial acid or zolomide? It inhibits carbonic and hydrae is EA. No, right? That's not, that's, that's really unfortunate. You know what happens on the USML Es? The thing your friends at the MVMA love to do is they love to integrate pieces of information. Okay? So that's, that's a, that's a big thing you, I guess, you need to keep, you need to keep at the back of your mind with this, right?

So you want to not just learn things from the perspective of, oh, let me learn in the context of renal, but you want to know about the proximal coveleutubial from the context of genetics, from the context of endoprenology, from the context of GI because that's how the integrate things on the test. So the thing is, another high-yield proximal coveleutubial related pathology is something called heart-nove disease, okay? Heart-nove disease, it's a disease where you have trouble reabsorbing neutral amino acids and the big one you probably care about here is tryptophan. The thing is tryptophan is super high yield to no, for example, right? Because if you're not, if you don't reabsorb tryptophan, you've got a real problem on your hands, right? Because tryptophan is used to make vitamin B, come on the vine, think it used to make vitamin B3, right? Vitamin B3, vitamin B3 is a nice thing, I have to think about that for a second. And the thing is, if you have that nice in deficiency because you're not able to reabsorb tryptophan, well, you're in a lot of trouble. You get into a lot of trouble like having like pelagra, right? And remember, pelagra has four D's, right? Like diarrhea, dermatitis, dementia, and death, right? That's obviously not a good outcome. One other thing that can actually also cause pelagra on MDM Es is if a person has serotonin syndrome. So serotonin syndrome arises when a person has a mass, it's usually in the appendix that produces a ton of serotonin.

The thing is serotonin, I mean, if you've studied psychiatry serotonin is also known as 5 HT, right? 5 hydroxyptophan. So that means serotonin comes from triptophan. So if you have a tumor that's overproducing serotonin, you're going to use up all your triptophan. So that would divert that triptophan away from the production of niacin. And that can also cause a pelagra-style symptoms. And again, remember, if you have problems at the level of the proximal convoluted tubule, that will essentially cause a type 2 renal tubula sedosis. That will cause a type 2 RTA, right? The type 2 RTA in general is associated with hypochylemia. The thing is RTA is like the renal tubula sedosis tends to mess people up on tests. People always like freak out like, oh, divine. I have no clue what to do. How do I learn this? Learn that, learn this, learn that. The thing is RTA is to be honest, I can probably give like a 1 R electron RT As. I find them like incredibly fascinating. But I really don't want to give a 1 R podcast. So I'm searching. You probably don't want to listen to a 1 R podcast. So let me just give you this trick that should help you resolve pretty much most of the RTA questions you see. So the way an RTA pops up on NV Me exam says, you'll give your question about a person that has a metabolic acid doses. Whenever you see a person that has a metabolic acid dose, the first thing you always want to do is to calculate something called the anion gap. You always want to calculate the anion gap.

And the anion gap is sodium minus chloride plus bicarb. Now, if you have high anion gap metabolic acid doses, you know, you're dealing with those mod pals, whatever. So like like a methanol, poisoning, uremia, DKA, parodahide, or propelling glyco, isoniazide, lactic acid doses, ethylene glyco, poisoning and salicylics. Those things all cause a high anion gap metabolic acid doses. But if you calculate the anion gap, you're like, hmm, this thing is like less than 12. Then you know you're thinking about a normal anion gap metabolic acid doses. The thing is the RTA is the Reynoldsy-Rylacidosis. Yeah, all examples of normal anion gap metabolic acid doses. So if you see a magma question, so a normal anion gap metabolic acid doses question on your test. One of the things you want to think about is an RTA, right? So there are three types actually. There's more than three types of RTA. But for purposes of the USML exams, there's only three you need to know. And those three, again, they are kind of confusing. But again, let me give you some tricks and make your life a profoundly easy. Right? So the thing is there are three types of RT As you need to know. There's a type two RTA. There's a type one RTA and there's a type four RTA. In fact, let me say it again, there's a type two RTA. There's a type four RTA and there's a type one RTA. Okay? Those RT As, I mentioned it like in the order two four one. So I hope you remember like the order in which those RT As pop up.

Like a type two RTA is a problem where you have issues at the proximal tubule. A type four RTA is a problem where you have issues at the principal cell of the collectin, though, where you have like a high-poil of student's state. And then a type one RTA is a distal RTA. It's the one that operates where you have issues at the alpha intercalate cell of the distal net front. So to figure out the type of RTA you have, the first thing you should do is look at the person's urine peach. Okay? Look at the person's urine peach. If a person has a higher-in peach, your job is done. They have a type one RTA. The end, right? You don't have to think beyond that. But if and the magic number you want to remember is 5.5, for persons urine peach is more than 5.5. That means they have a type one RTA. End of story, right? Now, if a person has a normal urine peach, so let's say the urine peach is like less than 5.5, then the only other options you have is either a type two RTA or a type four RTA. And the way you differentiate between those two is look at the person's potassium. If the person has hyperkalemia, so hyperkalemia, that's a type four RTA, right? Because a type four RTA for the most part is associated with hypodosterone states. And if you remember from the first renal pharmacology podcast I made, I said whenever you have an aldosterone excess, you tend to have hyperni-tremia and hypokillemia and metabolic alkalosis, right?

But if you have a low aldosterone state, so like a hypo aldosterone state, for example, if a person has like an adicence disease, where they've had an autoimmune destruction of the adrenal cortex, then that will cause a type four RTA, right? And because they have low levels of aldosterone, they'll have like hyponitremia, right? They'll have hyperkalemia, and they'll have a metabolic acidosis, okay? They'll have a non-anion gap metabolic acidosis, most specifically they have a type four RTA, causing that non-anion gap metabolic acidosis. Really if you want more on RT As, I can talk about those in a pretty great detail as well in my renal, like mainstream renal podcasts. Again, I believe that's between episodes 52 and 54. But a type two RTA, the proximal RTA, it's a hypochylemia RTA, okay? So again, that's how you do your RT As. Look at the urine pH, it's in more than 5.5. If it is, that's a type one RTA done. And that type one RTA actually tends to be a sort of hypochylemia. But if you notice the urine pH is normal, right? So less than five and a half, then you'll see you're like, okay, see that type two RTA or type four RTA. Well, so the way you pick those two up are to look at the potassium. The patient is hyperchylemic, so if the potassium is greater than like 5.5, right? Then your job is done. That patient has a type four RTA, right? But if a person, if a person has hypochylemia, right?

And they have a urine pH that's less than five and a half then that's a type two or proximal RTA. And then also please do not forget that in the proximal tubule, 25 hydroxy vitamin D is also converted by one alpha hydroxylase to 125 dihydroxy vitamin D, okay? The thing is, PTH parathiric hormone actually increases the activity of one alpha hydroxylase. That's again, something high yield you again, hopefully you want to keep at the back of your mind for example. That's why if a person has kidney disease, right? If a person has chronic kidney disease, those people tend to have those people tend to have a hypochylemia, right? Because if you think about it, if you have CKD, then you have no activity of one alpha hydroxylase. So you do not convert calcium dial, which is again 25 hydroxy vitamin D to calcium trial, which is also known as 125 dihydroxy vitamin D, right? So you don't have any of those things. So if you don't have 125 dihydroxy vitamin D, well you lose the ability to reabsorb calcium and phosphide in the gut, right? So those people have a hypochylemia, again, all high yield things to keep at the back of your mind for example. And then I think, because I really would do want to keep the podcast at like around like 30 minutes. So let me say some, let me say something about this non-anion gap and abolic acid doses business, right? So I said that RT As are a cause of a non-anion gap and abolic acid doses.

And again, I discussed this in very great detail in episodes of 52 to 54. The thing is, RT As are not the only cause of a normal anion gap and abolic acid doses. The thing is diarrhea can also cause a nagma. So your Cime say nagma to stand for normal anion gap and abolic acid doses. So you may then say, divine on exams, how will I be able to differentiate a nagma from an RTA from a nagma that's caused by diarrhea? Well, the thing you can use is actually something called a urine anion gap. So there is a serum anion gap that's calculated by doing like sodium minus chloride plus bicarb. But there is also something called a urine anion gap that you can calculate by doing sodium plus potassium minus chloride. Okay? The thing is the urine anion gap is can help you differentiate between diarrhea as the cause of a nagma versus an RTA as the cause of that nagma, right? So how would you differentiate between those states? The thing is the urine anion gap in diarrhea tends to be negative. And there's this nice mnemonic I used to remember that negative, right? So in diarrhea, right? The urine anion gap is negative, right? So gods like your GI tract. So it's negative. So let me see. Okay, divine fine. I love your mnemonic, but how, how, why is that the case? Well, if you think about it, if you have a diarrhea, you get them at a Bollykha sedoses, right? Because if you have diarrhea, the thing is, I guess let me back track here for a second.

Whenever you vomit, you tend to lose a ton of acid. Whenever you have diarrhea, you tend to lose a lot of base. The reason behind that is for the most part, your GI secretions distal to the stomach are very rich in bicarb. On the other, especially like your colon, but your GI secretions proximal to the pyloric sphincter are very rich in acid. So the thing is if you have diarrhea, you're going to, you know, put a ton, you know, spend your time, uh, fed it to the, to the restroom. Um, so you're going to, you know, get rid of all that bicarb. So the thing is by getting rid of all that bicarb, you get them at a Bollykha sedoses. So your body is like, oh crap, this is made of Bollykha sedoses, not good, not good, not good. So let me try to get rid of as much protons, as many protons as possible. Well, to get rid of those protons, right? Your kidneys will help with in that process. The thing is, as your kidneys are dumping those protons in the urine, well, your body is smart. You don't want to pee electricity, right? I mean, that's obviously another good thing. I kind of think of it as, oh, you don't want to electrocute your kidneys or something, right? So the thing is your body does not get rid of protons like, oh, as pure protons, that is just not possible. That would damage the kidneys severely. So the thing is your body gets rid of protons as ammonium ions. So it binds that hydrogen ion.

Remember, ammonia is a very powerful base, sort of going back to a general chemistry and college ammonia, right? It has like, you know, like all these lone electrons on its nitrogen. So that's a very good electron donor. I'm just seeing that out there for the organic chemistry, I inclined folks that are listening to this. Really, renown is a chemistry science, believe it or not. So you form ammonium ions and then that ammonium combines with chloride, right? That ammonium combines with chloride to form ammonium chloride and then you pee that out, you know, safe and sound. Now, the thing is because you are peeing out ammonium chloride, that means a lot of chloride is showing up in your urine, okay? A lot of chloride is showing up in your urine. So because you are putting more chloride in your urine, if you look at that urine ion gap equation, that is sodium plus potassium minus chloride, right? That chloride part is getting bigger and bigger and bigger, right? That's why the urine anion gap is negative in diarrhea. The thing is in RT As, the urine anion gap tends to be like zero or like positive, okay? The thing is there are mechanisms behind that, but to be perfectly honest, it's more trouble than it's worth. If it's something you're interested in, reach out to me, I'll be more than happy to explain. It's just one of those things that demands like a solid 30 minute explanation for you to really understand that. So I think I'm going to go ahead and pause here again.

I know I couldn't finish renown farm here, but again, I'm going to, I promise I'm going to finish it, I'm going to finish it this week. That's mine, that's my game plan. But again, I want to, I want to essentially make you like masters of the nephron and masters of renown from ecology. And as I do at the end of every podcast, right? So I do offer one on one tutoring for a ton of exams, all the USMLA exams, step one, two CK, two CSTEP three, pre-clinical med school exams, third year clerkship self exams, and then I do this thing I call like longitudinal tutoring right where I work with like a first or second year med student like all through the pre-clinical coursework. And at the same time, I will concurrently tutor them for step one so that when they hit the dedicated peers, they're like super, super ready. Same thing for third years, I tutor you for your shelf exams, but at the same time, I concurrently tutor you for the step two CK exam. These people tend to have like very short dedicated periods and everyone I've done this with has been wildly successful in the USMLA exams. And then if you have a college buddy that needs tutoring for like Gen CAM, O-CAM, physics, bio-CAM, histology, physiology, offer tutoring for all those things. And then if you're a med student applying to residency, so like an era's application or a college student applying to med school, so an AMCA's application, I do offer like one-on-one like advising consulting for that.

So like personal statement writing, literature of recommendation, mocking interviews, editing your applications, I do all those things. I mean I've worked with like literally like tons and tons of people on those things. And again, the vast majority of people have worked with have been successful. So I do hope you get something from this podcast and I hope to see you in the next one. Have a wonderful rest of your day. God bless you. Thank you.

SGLT2 (Sodium-Glucose Linked Transporter 2).

Acetylcysteine (or other CA Is like acetazolamide).

Urine pH greater than 5.5.

A negative UAG (Urine Anion Gap).

Defective tryptophan reabsorption leads to Niacin ($\text{B}_3$) deficiency.

Type 4 RTA (due to hypoaldosteronism).

$1-\alpha$-hydroxylase.

Type 1 RTA, Type 2 RTA, and Type 4 RTA.

It inhibits carbonic anhydrase, causing increased urinary bicarbonate excretion ($\text{HCO}_3^-$), which raises urine pH and increases stone solubility.

Significant loss of base/bicarbonate in the GI tract, leading to compensatory kidney excretion of $\text{NH}_4\text{Cl}$.

Tryptophan.

$1-\alpha$-hydroxylase.

Type 1 RTA, Type 2 RTA, and Type 4 RTA.

It inhibits carbonic anhydrase, causing increased urinary bicarbonate excretion ($\text{HCO}_3^-$), which raises urine pH and increases stone solubility.

Significant loss of base/bicarbonate in the GI tract, leading to compensatory kidney excretion of $\text{NH}_4\text{Cl}$.

Tryptophan.