DIP Episode 52 - Comprehensive USMLE Step 1 Renal Review (Session 1 of 3)

Okay, welcome. My name is divine. I'm a PGY one transitional year resident. I'm in today's podcast. I'm going to be talking about some stuff relating to Reno. This is basically going to be a complete Reno review for the USMLE step one. This is going to be in two parts. This will be the first of two parts. So let's begin. So slide number one. A patient taking a diabetes medication presents with a chief complaint of flank pain and dysuria. Right. So what's the diagnosis here? Right. So if a patient has flank pain and dysuria and let's assume they have fever I would really hope you're thinking about pylon a fritis. Remember pylon a fritis causes flank pain versus cystitis that causes a suprapubic pain and the pathophysiology here. Right. So the diabetes medication, right, and pylon a fritis, right? That makes you think of a UTI. So hopefully that gets you thinking about the SGLT2 inhibitors like a canagly flosen, the pagly flosen and empagly flosen. Okay. They basically inhibit the sodium glucose linked transporter that you find at the level of the proximal convoluted tubium. So you basically whisk the glucose in the urine. Those drugs work really well. The lawyer blog gluteus really well. But they also cause a lot of glucose urea, right? Which can basically create a wonderful like buffet for bacteria and fungi, right? And it can basically cause a lot of problems in your in your nephron. So they can cause UT Is.

Now the apical surface modification shared by the PCT in relation to the small bowel, that's microv lie. Remember the proximal tubule has a simple cuboidal epithelium, but it has microv lie. Remember microv lie constitutes the brush border that's also found in your GI tract. And the driving force for reabsorption in the nephron is essentially the sodium potassium ETP pump. Remember that this pump basically makes sodium and extracellular ion and potassium and intracellular ion, right? So it pumps three sodiums out of the cell and two potassiums in. And then a PTH, that's parathyroid hormone. Also think of it as the phosphate trashing hormone. It's effect of the proximal convoluted tubule that PTH essentially, so the way phosphid is reabsorbed in the proximal tubule is that phosphid is reabsorbed concurrently right in a same border with sodium. So again remember sodium is primarily an extracellular ion, so as sodium flows down its gradient into the cell, phosphate can follow alongside, okay, in a same port, that's a kind of secondary active transport if you may. That transportor, the endosythosis of that transportor is actually increased by parathyroid hormone, okay? And then with regards to reclaiming bicarb at the level of the proximal tubule, basically if you filter bicarb from the glomerulus into a woman's space and then into the proximal tubule, that bicarb will combine with hydrogen ions, okay? And then it will form a carbonic acid.

And then an enzyme known as carbonic anhydrase will split of that carbonic acid into water and carbon dioxide. Those diffuse across the membrane of the proximal convoluted tubule cell, okay? And then they are converted back by, I guess, a more intracellular isoform of carbonic anhydrase into bicarb which goes to the blood side through the basalateral side of the PCT cell and then the hydrogen ions are extruded back into the urine side to keep the cycle going. As those hydrogen ions are extruded, remember to maintain electronic trality, sodium ions are truly brought in, right? So there's like a sodium hydrogen anti-porter, as hydrogen comes out, sodium comes in and that transportor specifically its activities increased by angeotencing 2. So that's why if you're in a volume depleted state, right? So if you're in a volume contracted state, if you may, as angeotencing 2 does its job more and more because remember if your volume down, you'll increase the activity of your urine and geotencing our dosterone system. As hydrogen ions are coming out, okay? As hydrogen ions are coming out, you're basically causing an alkalosis, right? That's why it is said that angeotencing 2 maintains a contraction alkalosis. Now potassium and acid-based balance with dorsolamide administration, right? So dorsolamide is a carbonic anhydrase inhibitor, right? So because it kind of sounds like acid-dorsolamide, right? So because it inhibits acid-dors, uh, carbonic anhydrase, right?

You basically waste by carbine your urine, right? So you basically get a metabolic acidosis with taking dorsolamide. In fact, if you want to be a little more specific, you get a non-anion gap metabolic acidosis and if you actually want to be a little super-more specific, right? You actually get a type 2-in-autoblacidosis, right? A proximal RTA from taking a carbonic anhydrase inhibitor. And then, uh, because dorsolamide is a diuretic, right? It makes your volume down. So if it makes you the volume down, that should increase the activity of your urine and geotencing our dose-turne system. And if your RAS system is up-regulated, right? Your levels of our dose-turing will increase. And if you think about the principal cell, right? That will essentially make sodium be, uh, that will increase the activity of that inactional of the principal cell. Sodium will get into the lumen of your, I mean, I guess, going to cellular for the principal cell of your collecting duct and that will create a negative charge on the urine side that will draw potassium, okay? So you get a hypochylinea because it's a diuretic. Now, um, if you compare the beginning and the end of the proximal tubule, right? So at the beginning of the proximal tubule, basically, across the proximal, uh, convoluted tubule, you reabsorb sodium and water, basically at the same rate. So the sodium concentration really doesn't change.

Contrast that we chloride, where at the early part of the proximal convoluted tubule, you reabsorb more water than chloride. So the concentration of chloride actually goes up. And then towards the end of the proximal convoluted tubule, you actually reabsorb more chloride than water. So the chloride concentration ultimately goes down. So there's an initial uptick in the concentration of chloride and then a downtick. And, um, I've talked about the PCT-mediated acid-based response in the setting of volume depletion. I also mentioned, uh, yeah. So I've talked about that that's the contraction, alkalosis, angiotensin-2 business. And then at what plasma glucose level does glucose begin to shop in the urine? That will be at a plasma glucose of about 200, okay? It's actually kind of higher to know that. So remember, at the proximal tubule, right? It's again, sodium glucose, link transport, and SGLT2 transporter that helps make that happen. Contrast that with SGLT1, that you find more in the GI tract. So, uh, at a plasma glucose level of like 200 mixed predestinator, you'll begin to find a glucose showing up in the urine, okay? And then the next question says at what plasma glucose level are all, all SGLT2 transporters are treated, right? That will actually be at a much higher level at a level of 375, okay? So you can see, we define, that doesn't make any sense. How would you begin to see glucose in the urine at a plasma glucose level of 200?

When all the SGLT2 transporters are not such aether. The reasoning behind that is, the SGLT2 transporters have different properties. Some get saturated at much lower plasma glucose levels than others, okay? So each of those transporters have different mechanics. So because they have different mechanics, you can sort of imagine that, um, you may begin to see glucose in the urine at different plasma glucose levels. In fact, that phenomenon, right? So basically the thing that's responsible for the phenomenon, I'm discussing with these last two questions is the concept known as SPLEY, okay? And then the last question here says there are three higher conditions that, higher conditions that have an association with, um, with, um, pelagra, right? So pelagra, right? So pelagra is a vitamin B3 or an ISN deficiency. I discussed that in the biochem reviews. Um, so there are three higher things that can cause this, right? One is you're just not consuming enough ISN in the diet, right? So that can give you pelagra. Another thing that would happen is you could have carcinoid syndrome. So remember, in carcinoid syndrome, you essentially have a tumor that's making a ton of serotonin. Um, if you remember from a previous podcast, I mentioned that another name for serotonin is 5 HT, 5 hydroxy-triptofem.

So if you're diverting all your triptofem towards the synthesis of serotonin, if a person has like carcinoid syndrome, you can already begin to imagine that, um, uh, you have less triptofem available for the synthesis of ISN, and then you can run into trouble with pelagra. Another thing that could also happen is if a patient has like heart-nob disease, so heart-nob disease, I discussed this in the biochem reviews, right? But as a quick review again, heart-nob disease, you essentially have, um, uh, problem with the transporter that brings in, um, neutral amino acids at the level of the proximal tubio. Uh, it's also a defect in the GI tract because that transporter is also found in the GI tract, but if you have a deficiency of that transporter, you cannot reabsorb neutral amino acids like triptofem, and if you cannot bring in triptofem, you basically have no feet stuck for the synthesis of NISN, so that can also cause a pelagra like presentation. And I mean, generally, for those things, you want to go ahead and just replace like NISN in the diet. You can give like nicotinic acid or whatever it's called, okay, and please don't forget the four days of pelagra, um, is like diarrhea, right? dermatitis, right? So you have like skin findings, they also have dementia, so they're like forgetting things or acting crazy, and then death is the fourth deep. So next slide.

So a 70-year-old male with a two-year history of urinary dribbling presents with, uh, one day he's sure of severe flank pain and cost of vertebrae lungo tenderness, right? So if you see flank pain and CV tenderness, and hopefully you can decipher that this patient has a BPH, uh, hopefully you're thinking about pylonofritus, right? And again, the risk factor for this specific patient, right? So old guy with urinary dribbling, that's a benign per static hyperplegia, okay? Um, the classic pediatric risk factor for pylonofritus is something known as a VUR vesico-irritere reflux, where you essentially have a reflux of, um, of urine from the bladder to the uriners, right? So because you're having that reflux, you're introducing a, uh, uh, bugs into the urinary system and that can cause a lot of trouble, right? And the most likely bug, if you're thinking about a UTI is equal, I equalize the most common cause of UT Is. Um, if you see a person that has these symptoms and the urinary pH is 8, that's super basic. Uh, I hope you're thinking about a URI-spositive bug, right? Potentially like proteus-mirabilis. Um, another one that is also URI-spositive that could also cause those kinds of problems is, uh, is a staff's approfitticus, but for proteus-mirabilis, that's the most common answer in exams, on NVME exams. Uh, the classic culture finding, right, is like swarming motility on eager, okay? That's just a buzzword you want to try to remember.

And then the most likely bug in a sexually active young female, this is actually the second most common cause of UT Is. That'll be staff's approfitticus, okay? And, um, next question says the histologic finding in the chronic form of pylonofritus, right? So chronic pylonofritus, classically, if you do like, uh, let's say you do a kidney biopsy and you look at the tissue on the microscope, you actually have a finding known as thyroidization of the kidney. So you may wonder like, huh, define, does it mean that thyroid follicles literally go to the, literally go to the, uh, to the kidney, no, that's not what happens, right? That kind of be, uh, magic. That doesn't really happen. The thing that actually happens is remember the thyroid gland has simple cuboidal epithelium. The convoluted tubules also have simple cuboidal epithelium, right? So in chronic pylon, right? All that inflammation, you can sort of have like a highline deposit in the lumen and the lumen, I guess, of those are convoluted tubules, but because they're all surrounded by cuboidal epithelium, just kind of like your thyroid gland, right? You can have that thyroid, thyroidization appearance of the nephron. And, uh, on your analysis, you'll actually see something known as an eosynophilic cast, okay? Please do not confuse an eosynophilic cast with actual eosynophils. Actual eosynophils in the urine should get you thinking about, um, uh, acute intestine and arthritis, right?

Remember that has a triad of fever, russian eosynophilia, okay? But if you see eosynophilic casts, think more about chronic pylonofritis. And basically, the way you manage pylonofritis from a colloquial USML is you give sephiraxial, that's a third generation cephalosporine, okay? Another thing you can do is you can give like an IV fluoroquino lump, okay? Those are two higher things you want to keep in mind for pylonofritis. And then the classic demographic for UT Is, right? It's females, females have a short a urethra, so that's why there's an increased incidence of UT Is in females. But in pregnant women, right? So pregnancy is a hyper-progesteroneic state if you may, right? So they're very high levels of progesterone impregnancy. The thing is progesterone is a smooth muscle relaxant, right? So if you relax the smooth muscles, like in the urethers, for example, that can cause like urinary steases, right? And that can increase the presence risk of, uh, of UT Is. Now the next slide, right? So says, uh, to differentiate pylonofritis from a cystitis, right? So pylonofritis is more severe than cystitis, okay? In a cystitis, you're in, I mean in pylonofritis, you actually see why blood cell cares, very high, you know that? Why blood cell cares in the urine? Contrast that with a cystitis where you see no casts in the urine, okay? And the pain in pylonofritis, right? It's like flank pain, flank pain, CV tenderness versus cystitis. That is more um, supropubic pain, okay?

And fever is pathonomonic force pylonofritis. Uh, many times on MDM is you mean not necessarily sees fever, in the setting of a cystitis. So then the next question says, uh, hematuria in a recent Egyptian immigrant who was previously like a swim instructor, right? So hopefully you're thinking about a hemorrhagic cystitis and hopefully you're thinking about a she's to somahematobia with that, okay? And then a same presentation, but this is a patient on chemotherapy. Uh, hope you're thinking about again, hemorrhagic cystitis, but that's more with cyclophosphamide. Uh, cyclophosphamide, right? Remember, it's an alkaliate in the agent that's used as an anti-cancer medication, although it's also used to treat many of the nephritic and nephritic syndroms. So cyclophosphamide can cause hemorrhagic cystitis, remember? I'm a double-light of a cyclophosphamide, is a acrolym, that acrolym is a vesicant. It can basically scrub away your blood epithelium and cause a hemorrhagic cystitis. So you can kind of prevent that by giving a drug known as mesna. Mesna binds up our crulines so that you don't have the destruction of the bladder. Okay, remember, cyclophosphamide can actually increase the presence risk of a bladder cancer. And then the next part says, again, hemorrhagic cystitis on the patient with pink eye and sore throat. This is more viral infection, right? So hopefully you're thinking about, um, adnovirus. Remember, adnoviral infection is known as firingoconjunctivitis, right?

So firingoconjunctivitis. The firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, the firingoconjunctivitis, you can also give a fluoroquinolone, right? So like superfluxusin works great for UT Is, alternatively you can also give like trimethypermysol from ethoxazole, okay? Backtrep. Those things work pretty well for cystitis. And then, and just real quick, nitroferentoin can be used for cystitis, you do not use nitroferentoin for pylon, I just thought I should sort of throw that out there. Okay, and then this last question is kind of something you need to know, right? So like 48 female history of rheumatoid arthritis presents with a one year history of recurring episodes of flank pain and the theory that I've not responded to appropriate antibiotics, okay? And the renaul biopsy reveals granulomas, diffuse granulomatos inflammation of the left kidney.

This is just something you want to know, it's known as a zanthogranolomeras, so zanthoride, so Xan, THO, and then granolomeras, pylonophritis, it's a pretty severe form of pylonophritis. Really, the only way you can treat is to get rid of the kidney. That's like the definitive treatment, you basically do an effectomy and the patient is cured, but so it's a pretty bad form of a pylonophritis. And the your analysis findings in UT Is, right? So like your your leukocyte esterides will be positive, you'll see bacteria in the urine, you'll see positive nitrites, right? You'll see white blood cells in the urine, so you have a pyuria. If you see a sterile pyuria, right? So like you see white cells in the urine, but you're not seeing any bugs. Think about appendicitis, that's one thing that could classically cause that, and the thing that could cause that is a chlamydia. If chlamydia is what's causing the UTI, that can actually cause a sterile pyurgy. So sort of keep that at the back of your mind. And then the biggest risk factor associated with UT Is in hospitalized patients, that's basically the use of indwelling catheters, okay? Easy question there. Now next to an patient with a history of well-controlled CHF is rushed to the ED from a movie theater, after it began to complain of severe eye pain, okay? So let's assume it has glaucoma. He's given an IV formulation emergency while awaiting transfer to a tertiary care center.

Three hours after the patient, three hours later, the patient begins to complain of difficulty breathing, chest or scotation reveals bilateral crackles which will not present an initial exam. So let's assume this patient has glaucoma, right? To elevated intracular pressures, right? We could potentially give monitor for that, right? And remember, monitor, right? Yeah, it's good for glaucoma, right? And it's also a good diuretic, right? But it's not like if you want to use it as a diuretic, you inject it directly into the kidneys, no. You inject it into the bloodstream first, right? So initially, because monitor is a non-reabsorbable sugar, right? It doesn't really cross membranes very well. Manitalk can increase your intravascular volume. And if you have like CHF, like congestive heart failure, you cannot handle that extra volume, that can sort of tip you over the edge and you get into trouble pretty quickly. So this patient got monitor for glaucoma, okay? That expanded is intravascular volume and let's say his heart could not handle that extra volume. So he went into a congestive heart failure or exacerbation, okay? And again, monitor is a non-reabsorbable sugar, it basically stays in the lumen of the of the nephron, okay? And pulls water alongside and then you basically pee that. But classically, if you look at text, you see that, oh, monitor works at the proximal tube, blah, blah, blah, okay?

It technically works all through the nephron, but if you want to go with semantics, oh, it works well in the PCT. The other drug that works well in the PCT is the eocabonic and hydrism inhibitors, right? So like acetyzolomide or dorsolomide, okay? And again, that works by inhibiting carbonych and hydrism, right? Then the electrolyte, the arrangement is associated with carbonych and hydrism inhibitors. Remember, carbonych and hydrism inhibitors help you waste by carbonych in the urine. So if you waste that by carbonych in the urine, right? That will cause a metabolic acidosis. Remember I said it's an magma and on an ion gap metabolic acidosis, if you want to be a little more specific, it's a type 2 RTA. And because your carbonych and hydrism inhibitors are diuretics, they make you volume down. If you volume down, you will, if you volume down, you will essentially rev up your reading and jotesin out those current systems. So if you remember that principle, cell business I discussed earlier, you basically waste potassium in your urine. So you get a hypochylemia. So it's a unique cluster of findings because usually hypochylemia is associated with a metabolic alkalosis. But if you see the unique combo of hypochylemia and a metabolic acidosis, okay? Think about a carbonych and hydrism inhibitor, okay? And carbonych and hydrism, right? It's a, it's a pretty important enzyme in the synthesis of ekeosumor.

So if a patient has glaucoma, you can actually give them a carbonych and hydrism inhibitor. And that will decrease the synthesis of ekeosumor. And that can sort of decrease in chocolate pressures. Another thing your acidosolomy can be used for is with central sleep apnea, right? So, it really knows the mechanism why, right? But I mean, I have a teleologic mechanism if you may, that I can propose, right? So if you sort of think about it this way, if a patient takes acidosolomyte, right? Because of its role as a diuretic and because of its mechanism of action, you get a metabolic acidosis, right? So if you sort of think about it, the way your body compensates for metabolic acidosis is with respiratory alkalosis, right? And how do you cause a respiratory alkalosis in a human being? You make them hyperventilite, right? So hyperventilite is sort of raises your respiratory rate. So that can potentially help with a central sleep apnea. Where the problem you have is a decrease the, decrease the, decrease the, what do I mean? A decrease the respiratory drive, okay? And mounting sickness, right? If you go to higher elevations, you kind of have hypoxic, right? So your respiratory rate goes up, right? So you get like a respiratory alkalosis if you may. Your body sort of tries to compensate for that by creating a metabolic acidosis. So the kidney tries to dump a bicarbonate in the urine. You can sort of speed that process along with acid and zolomide, okay?

And cola-transporter defect, right? So cola-transporter defect, am I talked about this in the biochem review? Well this is basically where you have issues with a transporter that helps you reabsorb basic amino acids at the level of the proximal tubule. If you have trouble reabsorbing those basic amino acids, right? So like cysteine, or methane, lysine, and arginine, right? One particular problem you can get is cysteineuria, right? So you can form like cysteine stones in the urine, right? Remember the acid as soap, shaped as hexagons, like benzene rings if you may. So those cysteine stones, you can actually solubilize them pretty well in a basic environment. So an unusual use of acidosolomide is actually for the treatment of, for the treatment of a cysteinuria, okay? It just basically solubilizes those cysteine stones and then you don't get into trouble. And remember cysteine sounds a lot like cysteine. So that should help you remember that it's those stones that sort of ship like hexagons. But you can also give sodium bicarbon, that can help with that, okay? And then you only diegetic that's free for soft allergies. It's a lube diegetic, that's a thachrinic acid, it's a pretty safer. No, it does not cause soft allergies, but it actually has a pretty high risk of auto toxicity actually compared to the other lube dieetics. Okay, next question. Himoglobin of 8 at mcv of 85 in a patient with a history of chronic kidney disease, right? So this is an homocytic anemia, right?

So hopefully you know that if you have a chronic kidney disease, well bipyparitubalocapyleris and if you're saying bipyparitubalocapyleris, you're not making ipo. If you're not making ipo, you will not stimulate your red blood cell precursors, right? You basically stop making red blood cells. So you can get a homocytic anemia in the setting of a chronic kidney disease. Now the mechanism behind the production, or I guess the Christian of, let's call it more production of ipo. It's kind of like a super high-year basic science thingy that I think is probably useful to know for exams, right? Because it's a nice way for denting, you know, and self-hesiology, or self-alogy, if you may. Right? So the thing is, there is something known as hef 1 alpha, heif 1 alpha, it's a transcription factor for ipo, okay? If heif 1 alpha is doing its job, you make a ton of ipo, and then your ipo can go do what ipo does, right? So the thing is, when you're under, when you're under conditions where there's enough oxygen around, right? You don't need to make more red blood cells necessary, right? So you should potentially downregulate your production of ipo, right? So the thing is, when you're under like normal oxygen tension conditions, heif 1 alpha is actually hydroxylated, remember, hydroxyl groups kind of contain oxygen, right? So a good oxygen tension will promote more hydroxylation of heif 1 alpha. If you hydroxylate heif 1 alpha, that actually targets it for degradation, right?

And this is why I see that this is a nice, a cell biology time for step one. There is a ubiquitin, you need to basically pully ubiquitinate heif 1 alpha, the hydroxylated form to have it destroyed. And the ubiquitin ligase that makes that happen is VHL from hipo lendout. So if heif 1 alpha is hydroxylated, VHL recognizes it, that target that you pully ubiquitinate it, and that sends it to the proteism for degradation. But contrast that with a patient that is hypoxic, right? If you're hypoxic, you obviously want more red blood cells, right? Because if you think about the oxygen carrying capacity equation, if you have more hemoglobin, right? Which you can get from having more red blood cells, that would increase your oxygen carrying capacity, right? So when you own the hypoxic conditions, heif 1 alpha is not hydroxylated, because it's not hydroxylated, it cannot be recognized by the ubiquitin ligase, VHL. And if that recognition does not happen, so if you're again, if you own the hypoxic conditions, you're not hydroxylating heif 1 alpha, it's not recognized by VHL, right? So heif 1 alpha then does his job by acta as a transcription factor for hipo, and that hipo goes and promotes the synthesis of red blood cells if you may. Okay, next question. Capupeidospasm explores a prolonged QT interval in a patient with a histrochronic kidney disease. That's hypoxic, I'll see me.

Remember, if you have a kidney disease, you essentially have no activity of one alpha hydroxylates, and if you have no activity of one alpha hydroxylates, you don't convert 25 hydroxy vitamin D, right? That's calcium diol, to 125 dihydroxy vitamin D, okay? That's calcium trial. So if you cannot make a calcium trial from calcium diol, you don't have active vitamin D, and you do not absorb calcium and phosphate in the gut, okay? So you get a hypo calcium, that's actually a cause of a secondary hyperparthyroidism, we're going to talk about this in a little slide. Okay, now, rising creatinine in the patient with a prolonged histrovostero-thritis, who takes large amounts of dichrofenin, that's an end set on a daily basis. Hopefully you're thinking about like, like, renal failure from chronic end-set use, end-set can cause a lot of bad, bad, bad, bad problems for the kidneys, right? So they can cause like a renal-popularynecrosis, okay? That classically presents us like immaturia and like rising creatinine in the patient that just takes pretty high doses of end-sets on a pretty routine basis. Remember, there are other things that can cause renal artery, I mean renal-popularynecrosis, right? So like, end-sets can, that's like the classic thing that causes them on exams. Sickle cell disease is actually another high-alt cause of renal-popularynecrosis, and then one other thing that can do the trick is diabetes. Yep, diabetes can also cause renal-popularynecrosis.

In fact, diabetes is the most common cause of renal-popularynecrosis in the, in the US. And another thing is, so what do I mean by the capopidospasim? Let me just sort of backtrack a little here. Capopidospasim, that's kind of like the, the trussosine in a patient that has a hypocalcemia. Basically, if you're tight, if you put a blood pressure curve and sort of make it tight, around the arms of a patient that's a hypocalcemia. You sort of have like these twitching movements of the, of your couple, basically like movements around your couple, made a couple of joints, okay? So that can basically present as a capopidospasim. That's the trussosine of hypocalcemia. Another classic physical exam finding in the hypocalcemia is the schwo-stech sign. So you tap the cheek and you basically have like spasim of your, I think it's your mastodomusose if I'm not mistaken, right? But you basically have like spasim of the cheek, that's the schwo-stech sign, right? So cheek, CH, schwo- schwo-stech, CH as well. It's like CH, V-O-S-T-E-K, okay? Those are signs of, of hypocalcemia. And remember that hypocalcemia actually prolongs the Q-T interval. In fact, as a general rule, any notable electrolyte imbalance that has hypocalcemia, prolongs the Q-T interval, right? So like hypocalcemia, hypocalemia, hypomagnesemia, those things are prolong the Q-T interval. And then this is, the Rhinon-Ajutezinal Dosterone system, right?

It's a pretty, it's a system every medicine should know about, basically, right? Rhinon is released from your Jocso-Glomerular cells, okay? Your GG cells. And that converts Androtensinogen to Androtensin One, okay? And then that Androtensin One goes to the lungs, basically, and it's converted by the endothelial cells of pulmonary capillaries to Androtensin Two. And then Androtensin Two does a ton of stuff, right? Like you can go to the brain, increase your thirst response, you can go to the super optic nucleus of the hypothalamus, and that helps you make a ton of ADHD, okay? Another thing that would happen with Androtensin Two is that you can go to the Zonaglu merulosa of the adrenal cortex, okay? And you can increase the synthesis of our Dosterone, which is a mineral And then Androtensin Two is also a powerful visual constrictor, okay? Axon type 1 receptors, so you can constrict the blood vessels, and that can raise your blood pressure, because you're essentially increasing your systemic vascular resistance. And then don't forget that Androtensin Two also has activity at that sodium hydrogen anti-pointer at the level of the proximal convoluted tubule. And then finally, I know there's one more thing I'm forgetting. Yeah, one of the Thenrotensin Two does is if you look at the e-frame material, it actually causes a selective visual constriction of the e-frame material. So that sort of raises your GFR, okay?

And then don't forget that your kidneys can also do gluconeogenesis, right? So if a patient's liver is shot, you can basically keep making enough, not a great amount, but a decent amount of blood glucose with the kidneys. Now, next question says what happens to the osmolarity of tubular fluid, relative to plasma fluid during the following events, right? So the first one is traversing the thin, descendant limb of the loop of Henley, okay? I remember the thin descendant limb of the loop of Henley, right? It's kind of like around the medulla, right? And the medulla has a very high salt concentration, right? So the thin descendant limb of the loop of Henley is actually just permeable to water. It's not permeable to salt, okay? So your tubular fluid actually becomes hypertonic, relative to your plasma fluid. But if you're traversing the thick ascended limb of the loop of Henley, right? The thick ascended limb of the loop of Henley actually has, like the sodium potassium to chloride a same powder, right? So that part of the nephrine is permeable only to, to what is it called? It's permeable only to salt, okay? So it's not permeable to water. So because it's not permeable to water, right? Your tubular fluid actually becomes hypotonic relative to your plasma fluid. And don't forget that the thin descendant limb of the loop of Henley has a simple squamous epithelium versus your thick ascended limb of the loop of Henley that actually has a simple cuboidal epithelium.

Or remember, unlike the proximal convoluted tubular, the simple cuboidal epithelium that constitutes your thick ascended limb of the loop of Henley does not have microvillage, okay? And the key transportors that are prey to the level of the thick ascended limb, I'll just say that you have that sodium potassium to chloride. It's called like the NKCC transporter that basically brings in one sodium, one potassium and two chlorides, right? So that sort of maintains electron neutrality. You're bringing in two cations total and two anions total, okay? But the thing is there is actually a potassium channel as well on the, on the urine side, right? So the apical side that basically pulls out potassium from the lumen, I mean from the intracellular environment of a thick ascended limb of the loop of Henley cell. And that potassium as it comes into the urine side, it sort of creates a positive charge. And then that positive charge actually causes paracelola or absorption of calcium and magnesium, okay? So those are the high yield transporters that sort of prey to the level of the thick ascended limb of the loop of Henley. So again, calcium and magnesium are absorbed in a paracelola fashion, very high yield to know that specific terminology. That potassium channel that actually helps you extract potassium to create the positive charge is actually known as a romky channel. And remember that a thick ascended limb of the loop of Henley, that's where your loop diuretics work.

And that's where basically butter syndrome operates. We'll talk about that in a later slide. Now the next question says, expect that urinary lapse, so be sure to create an urinary sodium phenant, urinary similarity in a 65-year-old meal with a six-month history of our urinary dribbling. So, for potassium has a six-month history of urinary dribbling. And again, it's an old guy, hopefully that gets you thinking of BPH, right? So, basically this is an AKI slide, a kidney injury slide, right? So you sort of think about it. For potassium has prolonged, I mean, AKI, in fact let me sort of backtrack a little, so there are three kinds of AKI, so there's like pre-renol, intrarino, post-renol, right? The most common kind is actually intrarino. So, if a patient has like BPH, they have like a chronic or prolonged post-renol obstructive nephropathy, if you may, right? So, the thing is if you have a prolonged post-renol obstructive nephropathy, the thing that happens is that your B-renol to creatinine is actually less than 15, your urinary sodium is actually greater than 40, your phenyl will be greater than 2%, and your urinary similarity is really less than 350. I don't want this podcast to be super long, so I'm going to keep moving. The mechanism is not super, super high-o for step one. The mechanism of a pre-renol, like the values are kind of high, also I'll talk about those.

But if you have a prolonged post-renol AKI, if you may, that you can get with like the urinary retention of BPH, you'll have like B-ren creatinine less than 15, urinary sodium greater than 40, phenyl be greater than 2% of your urinary similarity will be less than 350. Okay? And the thing is the next one question sort of says expected urinary labs in a patient with an increase in creatinine from 1 to 2.5, 36 hours after undergoing a study for the evolution of a possible PE, right? So, for patient is being evaluated for PE, right? So, you should probably know at this point that you get a CT angiogram, right? That requires some kind of contrast, right? And contrast can cause contrast nephropathy if you may, right? So, it can cause like acute tubulinacrosis. And remember that acute tubulinacrosis is the most common cause of intra-renol acute kidney injury, right? So, the higher you think you sort of want to commit to memory there is that. The urinary labs you observe in acute tubulinacrosis is the exact same thing as what you observe in a prolonged post-renol acute kidney injury. So, the labs like the B-end creatinine being less than 15 urinary sodium being greater than 40, phenyl being greater than 2% of urinary similarity being less than 350 is sort of the same thing that obtains in ATN, okay? But the way you differentiate between a prolonged post-renol AKI and ATN is that in ATN you find like the modibrown cast, right?

So, like those granola epithelial cast in the urine, you find those in ATN where you actually don't find any cast at least in general in a post-renol prolonged AKI. Now, the expected urinalysis and urine microscopy findings in an alcoholic that is found down with an ecagiure of illimpyc T-waves, hopefully this gets you thinking about um um um rhodomyolysis, okay? Rhodomyolysis? Rhodomyolysis, right? It can uh basically if you're like in one spot for a long period of time, that can cause like muscle cell death, okay? That can cause muscle cell death and if your muscle cells are dying, remember potassium is an primarily an intracellular ion, right? So, that potassium sort of spills into the circulation and if the potassium spills into the circulation, that can cause a hyperkalemia, right? So, that can cause like a picked T-waves, right? On uh on an ecagi, but some other high-yield things you want to remember is that uh how do you treat hyperkalemia? And then I'll talk about the urinary findings. The thing is hyperkalemia can be treated in many ways, right? So, the first thing you do is you give calcium gluconate, right? Um that sort of stabilizes the myocardial, right? You can also give calcium chloride, that also does the same thing. And nothing you can do is you can basically try to increase the activity of the sodium potassium ATP spump, okay? The sodium potassium ATP spump, remember that pumps sodium out of the three sodiums out of the cell and two potassiums in, right?

So, um you can basically redistribute potassium from the extracellular environment to the intracellular environment by increasing the activity of the sodium potassium ATP spump, right? So, how do you do that? There are two main ways you can do that, right? Actually, the fastest, we are probably the preferred way of doing that is to give insulin. So, insulin increases the activity of that pump, okay? Well, you also give insulin with glucose, right? Because you don't want to make your patient hypo glycine can die, right? That's not usually like, that's not ideal, that's never ideal, right? So, you give insulin plus glucose, the insulin will increase the activity of the sodium potassium ATP spump. And the thing you can also do is to give a beta-2 agonist, right? Like, I'll be it or all, that increases the activity of the pump, that basically redistributes the potassium to the intracellular environment. Another thing you can do for hyper-kilinear is to sort of take advantage of the proton potassium anti-pointer that's found on the surface of pretty much every cell, right? So, if you give sodium bicarp, you will create like metabolic alkalosis in the blood, that alkalosis will draw hydrogen ions out of cells. As hydrogen ions have been drawn out of cells, potassium goes in the reverse direction. So, again, that redistributes the potassium to the intracellular environment.

And then a drug you could actually give, actually drugs you could give to help you like physically get rid of potassium. One is you can give a diuretic like a loop, like a few or some, now help you get rid of potassium in the urine because remember, loop diuretics make your volume down, right? So, that increases the activity of urine in anodotron system, right? So, you basically waste that potassium in the urine. And then one other thing you can do is you can give Kexelate. Kexelate, they call it like sodium polystyrene sulfonite, if I'm not mistaken. So, that Kexelate, remember, it makes Kexelate out of your body, okay? Kexelate makes Kexelate out of your body. Although, it's not used much anymore. It basically binds up potassium and you get rid of it in your poop, but no one releases it anymore because it can cause a like boundary crosses, okay? So, the urinary labs in the patient with Rhabdomiolis is the big thing you want to remember is that your urine will be positive for blood, right? But it will be negative for Rx cells when urine microscopy, okay? Because it's primarily myoglobin that you're seeing on your urine dipstick. And again, no right thinking question writer will say, oh, a patient was found down alcoholic blah, blah, blah. The urine was positive for blood on dipstick, but negative for Rx cells, right? No one is going to do that. If not, everyone will across step one, if the root question is like that.

The way they'll probably present that is they'll give you like a urinalysis on step one and you'll see that the blood will be like three plus or four plus, right? So then it's like, oh, this patient has a lot of like hematuria if you may. But then they will see that you do like urine microscopy and you see like zero to two red blood cells per high power field. That's pathonomonic for Rhabdomiolis, right? Because it's like, you're seeing four plus blood on dipstick, but you're like wait, zero to two red cells per high power field. That's literally like no hematuria at all, okay? So that's a classic way that Rhabdomiolis may present with labs on exams. Okay. Now patient, recently in a motor vehicle accident, systolic blood pressure in the 60s, right? So this patient potentially has a pre-renal AKI, okay? Because they have volume down. So in a pre-renal AKI, the thing is you have volume down, right? So that will increase the activity of urine and juteins in our dose-turing system, right? So because angiotensin two goes up, remember I said that the super optic nucleus of the hypothalamus responds to that angiotensin two, so it makes a lot of EDH. EDH helps you reabsorb urea, right? It basically inserts like some urea transporters in the distal nephra, so you reabsorb a ton of urea. So because you reabsorb in more like BUN and you're not necessarily reabsorb in creatinine, your BUN to creatinine will actually go up. So it's more than 20 in periodically Ki.

Because our dose-turing is elevated because you're running angiotensin our dose-turing system is revved up. You reabsorb a lot of sodium, right? At the level of like the distal convoluted tubule with that sodium chloride simporter and also at the level of the principle cell, right? With that in echannel, right? So that can basically reduce your urinary sodium, right? So urinary sodium will be less than 20 in a periodically Ki. And then again, because you reabsorb in a ton of sodium, your phenyl will be less than 1%, and because again, you reabsorb in a ton of sodium to try to conserve volume, right? Water sort of follows the long side, right? So your urinary osmolarity will be really high, it will be like greater than 500. You have a concentrated urea. Okay? Now, the thing is the urinary labs in a patient with pre-rinolique Ki is actually the same as the urinary labs in a patient that has kind like any kind of like glomerulon arthritis, right? So that's sort of like a leading to the next part, last part of this question that says, oh, how will these urinary labs be differentiated from the urinary labs expected from an individual with hematuria? Two weeks after a recent upper respiratory infection. The thing is if you're two weeks out from a, if you have hematuria, two weeks after a recent URI, hopefully you're thinking about post-triptococcal or glomerulon arthritis, okay? So PSG and PSGN is a kind of nephritic syndrome, okay?

So acute glomerulon arthritis actually has like the B-ane creatinine being like greater than 20 urinary sodium being like less than 20, the phenyl being like less than 1% of the urinary modality being like greater than 500. But the thing is you have like red blood cell cast in the urine, if you have a glomerulon arthritis versus a pre-rinolique ki that usually has nothing in the urine or if you see something you see like chialin cast, right? Basically you find chialin cast in any person that has a concentrated urine if you have volume down, okay? Those chialin cast are really made of like something known as a tamar hospital protein and again to sort of round out this slide, the most common kind of aka is acute tubular necrosis, right? So like intra-rinol aka. And one last thing I would just say is acute tubular necrosis can be caused by like the amino glycoside, right? So your 30s bacterial cytolinimeters and then comisin, okay? So let's move on to the next slide. So the erectus, so she had the combination of hypochylemia, hypochalcemia, hypomagnesemia, metabolic alkalosis, soft allergies and auto toxicity, right? They'll be your lube diuretic, right? So remember your lube diuretic, the micivolium down, so that increases the activity of your rainy nitrogen and our dust urine system. So our dust urine, right? Through the mechanism I've discussed many times already, right? You basically whisper potassium in your urine so you get a hypochylemia with that.

Remember that lube diuretics, right? The inhibit that sodium potassium chloride, I mean sodium potassium-2 chloride are a simple at the level of the thickest in the limb of the lube of Henley. So if the inhibit that transporter, right? You basically do not reabsorb potassium. So again, that can cause hypochylemia, but another thing that can happen is because you are not reabsorbing that potassium, remember that rom-cage channel I talked about? You basically don't have that coupled release of potassium into the lumen or the urine side basically of the thickest end in the limb of the lube of Henley. So you never really create that positive charge that helps you paraselulally. We absorb magnesium and calcium, okay? So you can get a hypochylemia and hypochylminesemia with lube diuretic, right? And remember again, lube diuretics make you volume down. That reabs of your reabs of your rainy nitrogen and our dust urine system, right? So if you sort of think about our dust urine at the level of the alpha-intercalated cell, you increase the activity of that proton pop, okay? So you're basically dumping a lot of protons in the urine, so that can also cause a metabolic alkalosis, okay? And basically your lube diuretics are auto-toxic and you have a soft allergies with the exception of a ethycrinic acid.

Now the alternative therapy from the same drug class that avoids the associated soft allergy, again, that's ethycrinic acid, the limiting side effect with ethycrinic acid is that it's super-super-auto toxic, right? So it's something you don't use if you don't have to, okay? And really one sort of thing I guess I want to mention here is that your lube diuretics and also your thiozyze, they actually increase the production of Prosteglandents, okay? So that's actually one mechanism behind the blood pressure lowering effect of your thiozytes and your lubs, but you're, yeah, both of them, right? Is one, they make your volume down, right? So you decrease your blood volume, decrease your blood pressure that way, but another thing they also do is they increase the synthesis of Prosteglandents, right? So that dilutes your vasculature, so that essentially decreases your systemic vascula resistance, right? So that's why in general, for, if a patient is taking these diuretics like a lube or a thiozide, right? You kind of want to avoid taking insides alongside because that's sort of blunts the blood pressure lowering effects of your, of your lube diuretics and your thiozides, right? And the genetic disease that's like taking a lube diuretic, right? That's a, that's a better syndrome. Remember it's called a zomorecessiva inheritance, okay? And then if a patient taking a lube diuretic, right?

It has a flunkpin and hematuria, that should get you thinking about nephrodisiases, a kidney stone, okay? Remember, lube diuretics, right? They cause a high bucalsemia, but it causes hypercalcyria, so the increase your risk of having a calcium kidney stones, okay? Now next question, I've talked about the Renin and Jutansin of Dostroin System already, talked about the functions of adjutants in two, the stimuli for the operation of that pathway ready is, if for example, your activity beta one receptors, activation of beta one receptors, increases the activity of your Renin and Jutansin of Dostroin System, so that makes you release more if you hypoperfuse your afferent aturo for any reason, right? So let's assume you have Renin and Adristinosis, a fibromuscular dysplasia, or you're taking an NSAID, right? Remember, NSAID's decrease of the synthesis of persta-glundance, so that causes a constriction of the afferent aturo, right? So that sends less blood to the, the GG cells basically see less blood, those can not increase the activity of your Renin and Jutansin of Dostroin System, and you secret more Renin that way, okay? And next part of this question says, what happens to the constriction of adjutants in two? If an experiment is done comparing the blood in pulmonary arteries and pulmonary veins, right? So remember, this can be a nice experimental question on the USML Es. Remember, your pulmonary capillaries contain an- and Jutansin convert in enzyme A's, okay?

So really, if you compare the concentration of adjutants in two between your pulmonary vein and your pulmonary artery, the angiotensin two, concentration should be a lot higher in the pulmonary veins, right? Because basically, angiotensin one goes through the endothelial cells of the pulmonary capillaries, the express A's, that converts angiotensin one to angiotensin two, okay? So your angiotensin two levels should be much higher in the pulmonary veins compared with the pulmonary arteries, okay? And really, the two hormones that inquiry the irises in the setting of CHF, those are ENPM, BMP, AMP, HR, natuytic peptide should come from the HR, right? And then BMP, that name is kind of a misnomer. Brain, natuytic peptide does not come from the brain, it actually comes from the ventricles. So sort of think about it as VMP in your mind. So ventricular natuytic peptide, it means that's not what it's termed, okay? So those are hormones, right? So if you're half CHF, let's assume blood is sort of collecting in your heart, that distance the heart, that increases the synthesis of AMP and BMP, okay? Those things actually dilates the afran arterial, okay? And constrict the effran arterial, right? So if you do that, that should raise your GFR, right? And basically encourage a diuresis. And the thing these hormones do is that they actually inhibit the synthesis of renein. So they effectively dial down your renein and your tensin out of the sterine system.

So they basically like encourage diuresis, right? They prevent you from reabsorbing like sodium and water and all that stuff in the nephra. So they make you on like angiotensin too, that increases GFR, but makes you reabsorb most stuff. AMP and BMP, increase GFR, but they actually blunt the activity of the renein and your tensin system. So they actually make you waste a lot of your time. And the thing that happens with these drugs is that they work through cyclic GMP, right? So they actually bring in good viso dilators. So because they're very good viso dilators, the decreased systemic vascular resistance that way, right? So they can lower blood pressure. And the one thing I will just say is that these hormones AMP and BMP, they're actually broken down by an enzyme known as neprilizing, okay? Neprilizing breaks down AMP and BMP to inactive stuff. So if you were to give a drug that's neprilizing inhibitor like Sacubitro, for example, they'll prevent the breakdown of AMP, BMP so you can potentially affect. Those drugs actually been investigated as treatments for CHF. In fact, there's this drug known as entresto. It's a combination of an AMP, Val-Sarten and Sacubitro, which is a neprilizing inhibitor. It's actually being used right now actually in the treatment of CHF. Okay, good. So next question, PTH in relation to the kidney. So PTH, right? Remember, I said that it's also known as the phosphate trashing hormone.

Earlier in this podcast, I said that at the level of the PCT, right? It effectively causes you to endocytosis, those are sodium phosphate simporters that you find at the level of the proximal tubule. Okay? So that decreases the reabsorption of phosphate, so PTH should lower your blood phosphate levels, right? For calcium, if you go to the distal convoluted tubule, in fact, let me just real quick talk about the distal convoluted tubule. So the distal convoluted tubule has simple cuboidal epithelium. So I established that fact. Next thing is, if you look at the urine side, so the epical side of the distal convoluted tubule, you have a couple of transporters, right? So the first one is like a sodium chloride simporter, okay? That simporter basically lets in sodium, lets in chloride. And that makes sense, right? Because you're maintaining the electron, you try to keep by having one positive charge and one negative charge. Another thing you find on the epical side is you actually have a channel that helps you reabsorb magnesium. I'll just throw that out there, though. That's kind of low yield for step one. And then another transporter you'll find is a calcium transporter. That calcium transporter is actually found on the epical side as well. And its activity is actually increased by PTH. So that's actually how PTH helps you reabsorb calcium. It helps you reabsorb calcium at the level of the distal convoluted tubule, okay? And then on the blood side, right?

You obviously have the sodium potassium ETP spumps, so the basalateral side, you have the sodium potassium ETP spumps. But in addition, you have sodium calcium exchanger that brings in sodium into the cell. Again, that kind of makes sense, right? That's a kind of like anti-port, but it's a secondary active transport mechanism. You bring in sodium into the cell and then you extrude calcium into the bloodstream, okay? So that's kind of like a high-youthee you want to keep in mind. Okay. And so the genetic syndrome, that's a similar phenotype to taking the thiazide, that's a gyromancin syndrome, that's also a Zomor recessiva inheritance, okay? And again, I've said that the distal tubule has a simple cuboidal epithelium, but it has no microv-light unlike the proximal tubule. Now, the osmolarity of the tubular fluid compared to the blood of the osmolarity, right? Remember the distal tubule is permeable only to salt, it's not permeable to water. So your tubular fluid actually becomes hypotonic relative to your plasma fluid, okay? And then the other hormone that operates at the DCT, that will be your, let's see, sorry, again, I apologize for all the arms, I give these lectures mostly from memory. Our dose during, right? So our dose increases the activity of that sodium chloride sympoder, then I just mentioned that you find on the apical side, so that's the other hormone, besides PTH, that acts at the level of the DCT.

And then of the different diuretics, which is most appropriately used for calcium nephrolithyasis perphylaxis, it's actually your thiazide, you actually do not want to use loops for this. Remember loops, the waste calcium in the urine, right? So they cause hypercalcyria, that's bad for a person that has a history of a calcium archidney stones. So what's the mechanism behind thiazides being useful for perphylaxis against the calcium nephrolithyasis, right? So the mechanism is kind of complicated, but it's actually kind of cool and actually makes perfect sense. So the thing is, I said that thiazides inhibit the sodium chloride sympoder that you find on the apical side of the distal convoluted tuber, right? So the DCT, if inhibits that sodium chloride sympoder, right? What happens to the intracellular concentration of sodium in the DCT? It should go down, right? If it goes down, so if the intracellular concentration of sodium goes down, and we know that sodium already is primarily an extracellular ion, what happens to the gradient of flow of sodium into the cell? So like from the basal lateral side to the intracellular environment of a DCT cell, what should happen to that gradient of flow? It should increase, right? Because if you're lowering the intracellular concentration of sodium by blocking that sodium chloride sympoder, and you're keeping the amount of sodium on the outside of the cell fixed, that should make the gradient like steeper, right?

To bring more sodium into the cell. If you make that gradient steeper, you basically increase that secondary active transport around the sodium calcium exchanger, right? So a lot of sodium comes in because the gradient is stronger, so more calcium gets pumped out into the blood side, right? So the basal lateral side, okay? And if you're pumping out more calcium through that sodium calcium exchanger, that should also lower the intracellular concentration of calcium at the distal convoluted tubule. So again, walk with me some more. If the intracellular concentration of calcium goes down some more in the DCT, right? That calcium transporter that's on the epical side, you have increased activity of that transporter, right? Because it's like a vastly faded diffusion transporter if you may, right? So because there are lower amounts of calcium inside the cell, you just reabsorb even more calcium through that epical calcium channel, okay? So that's how thazide diuretics can cause high par calcium, so the increase the amount of calcium in your urine, I mean in your blood, but because high porcal seury, the decrease the amount of calcium in your urine, right? So that is why your thazide diuretics are pretty good for perphylaxis against the calcium on epithylithiasis. So again, it cause hypercalcemia and hypocalcyria, so that's the mechanism behind those two findings.

Now the next question says that 25-year-old male is rushed to the ED by ambulance after passing out in his friends apartment, he started, he started, so let me correct that, he started complaining of severe flank pain about 30 minutes before he passed out, he's blood pressure in the root to the ED 65 of a papoble, that's bad news obviously. Fast ultrasound conducted in the ED reveals an oblique, reveals an oblique structural ecogenic masses around the left kidney, a similar lesion is also found in the right kidney, the patient has a history of intellectual disability and has multiple high porpigmented marcus on his skin. Three years ago, the patient on the went the neurosurgical procedure for the removal of several benign tumors, so what's your diagnosis, right? So hopefully you're thinking about tuberous sclerosis, right? So if you see a renal mass in tuberous sclerosis, right? Hopefully you're thinking about a renal angiomyelipoma, right? So if you sort of do a biopsy of that, you'll see like angiol, right? So blood vessels, mayo, you'll see a muscle and lipoma, right? So you'll see fat cells, right? So a renal angiomyelipoma is associated with tuberous sclerosis, right? Multiple high porpigmented marcus on the skin, right? Those are your ashtif spots. Please don't forget that tuberous sclerosis is inherited in a rosomal dominant fashion, okay?

Now next slide, I've talked about the thazardiretic mechanism of action in hebisusodium chloride, a simple or other level of the DCT. The representative examples, right? So there's like HCTZ hydrochlorothiazide, there is a clothalidone, right? There is metolazone and then there's one known as endopamined. Those last three are actually more commonly tested because hydrochlorothiazide, if they put it on an NVME exam, everyone get the question correct, right? Because it already has thazard in the name. And then calcium balance with thazardiruse, right? So again, thazardine causes hypercouncymia and hypocalceria, already it's caused the mechanism in the previous slide. If you compare thazardsides to loops, right? So which is as either a hyersic of hyponych, so many people erroneously think that loops have a hyersic of hyponych, that's not necessarily true, and actually more with thazardides. So let me just cause the mechanism behind that. The thing is, if you're thinking about your sodium concentration in the body, that's basically like sodium over water, right? That's one fact that only establish. Second fact that I want to establish is that loop diuretics, we already said that they work at the level of the thickest end of the loop of Henley. They essentially inhibit the sodium potassium to chloride as importer, okay? Now, that sodium potassium to chloride's importer is actually heavily responsible for the ions that create that medallary concentration gradient.

So the thing is, if you take a loop diuretic, because of its mechanism of action, first thing's first you're losing sodium in the urine, that's the first thing, but the second thing that also happens is that you are destroying your medallary concentration gradient. So because you're destroying your medallary concentration gradient, you will not be able to reabsorb water at the medulla of the nephra. So you're losing a lot of sodium, but you're also losing a lot of water, right? So you're proportionally losing sodium and water, so you actually don't get that bad of a hypo nitramia with a loop diuretic contrast that with a thiazide. A thiazide blocks the sodium chloride sympota at the DCT, makes you lose sodium in the urine, right? But the thing is your thiazides actually do not really make you lose water, okay? That's why thiazides are not very strong diuretics. Loop diuretics actually the most powerful kind of diuretic, right? So thiazides, because the sodium chloride sympota at the DCT is not primarily responsible for the medallary concentration gradient, you actually retain water quite well. I mean, you don't lose as much water, let's put it that way. You don't lose as much water if you're thinking of thiazides, right? So we're losing all this sodium, but you're not losing as much water. You can see how that sort of sets you up for a hypo nitramia because the numerator in that sodium of a water fraction, right?

It's going down a lot, but the denominator is not going down proportionally, unlike what you have with loops, okay? So actually thiazides have a higher risk of a hypo nitramia. Now, how is an effrogenic di secondary to lithium-use treated, right? So an effrogenic di is treated with, is treated with inech channel blockers. If it's being caused by lithium, you just remember, lithium, right, is if you go back to sodium, like general chemistry from college, lithium and sodium is the sodium in the same group, lithium, I think is like element three, sodium is like element 11, but they all have just one election in the optimal shell, right? So they kind of have similar properties. In fact, lithium is a little smaller than sodium, right? So if you sort of think about it, the principal cell of the collecting duct, right? Sodium uses that inech channel. Lithium being smaller, having a similar charge could potentially also use that same channel, right? So, can you sort of see where I'm going with this? Lithium can go through that inech channel, and by going through that inech channel, it can sort of scrub the signaling cascade of ADH. Remember, ADH works on the blood side, right? So the visolateral side, on visopressin vitro receptors, which are GS-Copold, okay? So lithium uses that inech channel to gain access to the principal cell to cause an effrogenic diabetes inseparatus, right?

So if you give an inech channel blocker, like amyloidotriamterine, you could potentially reverse or prevent lithium-induced nephrogenic diabetes inseparatus. And why am I making such a fuss about this? I'm making fuss about this because in general, for nephrogenic diabetes inseparatus, you can give a thiazide diuretic works pretty well for nephrogenic GI, right? But the thing is nephrogenic GI that is specifically caused by lithium, you do not use thiazides, and here's why. I don't necessarily have the time to go into the mechanism. If you're interested, just send me a message or something and I'll try to break it down for you. But basically, the rule you want to remember is that anything that makes you volume down or anything that increases the activity of the renein-indretensin aldosterone system will increase lithium toxicity. That's just kind of a rule you want to remember, right? So think about it, if you think a thiazide, that will decrease the activity of your renein-indretensin, that will make you volume down. So that will increase the activity of your renein-indretensin aldosterone system. So that will make you more lithium toxic. And I guess I'll sort of give you throw you a bone here. The thing is, if your RAS system increases its activity, right? Our dust run will be doing a lot. And one of the things our dust run does is to increase the activity of that inek channel that we absorb sodium.

Well, I just told you that lithium also uses that channel to gain access to the principal cell. So if a patient takes a thiazide diuretic for an effiginate DI from lithium, they'll make them volume down. They'll increase the activity of the RAS system. They'll make more aldosterone available. They'll increase the activity of the inek channel at the level of the principal cell. And that will make you basically absorb more lithium. So you can, basically your lithium levels rise much and that can cause a more lithium toxicity, right? So that's not generally preferable. And then the metabolic arrangements as you know ferside use, right? So they cause like hypercalcemia already talked about the mechanism, it cause hypocoucure already talked about the mechanism. But you probably memorize this thing, like hyperglook with thiazides, right? So they cause hyperglycemia, hyperlipedemia, hyperglycemia, hypercalcemia. Let me talk about the mechanisms behind the first two, right? So hyperglycemia, hyperlipedemia. The jury is still kind of out on this, but if you sort of read the literature, there is some thinking on why this may be the case, right? So the proposed thinking, if you may, is that if you sort of backtrack to some endocrinology, right, to how insulin is released, right? So insulin is obviously released from the beta cells in the pancreatic eye legs. So the thing that happens is the way insulin is released is that glucose, right?

Comes in through gluteus transporters for the, for the, for the pancreatic beta cells, right? And then by some magic of biochemistry from ATP, that ATP blocks ATP blocks potassium channels in the pancreatic beta cells, okay? And then by blocking potassium channels, you leak less potassium out of the pancreatic beta cell. That makes the cell depolarize and you squared out insulin, okay? The thing is, so you need to block that potassium channel, make that cell depolarize and then you make insulin. If you opened up that potassium channel for some bizarre reason, that cell will not depolarize and you will not make insulin in that case. So the thinking is that thiazides directs actually open up those potassium channels at the level of the pancreatic beta cells, okay? So if you open up those potassium channels, your pancreatic beta cells never depolarize, you never secret insulin, right? Insulin's job is to lower your blood glucose levels, right? So if you cannot make insulin, your blood glucose levels will be high, hyperglycemia. If you do not release insulin, right, you do not upregulate fatty acid synthesis, right? So you do not store your fatty acids in adipocytes, so you could potentially get a hyperglycemia with that. Another thing with insulin, right, is that, I mean, another thing with thiazides is that they can cause a hyperglycemia because they actually increase the reabsorption of euric acid at the level of the nephron.

They're mechanisms behind that, but I don't have time to go into that right now, so I'm going to skip that, but remember that thiazides can cause a hyperglycemia and the thing they do is they actually increase the reabsorption of euric acid, okay? And then to sort of round out this slide, so the preferred agent for the management of hypertension with the following comorbidities, right? So like hypertension and osteoporosis, you want your blood calcium to be as high as possible if you also have osteoporosis, right? So thiazides are probably a good, good choice there. Phypertension and BPH, right? BPH, you want to try to open up the bladder next so that you can drain your brain better. So think about an alpha one blocker like Prasocin or thiazocin for that purpose. It will lower your blood pressure but also open up the bladder neck. Remember for BPH, you can also use a five-hour ferriductase inhibitor like a finasteride and do tasteride because DHT promotes the growth of the prostate. And then another thing you could do is if you have hypertension and diabetes, right, you can give an acinhibitor, right? So an ERB. Remember in diabetes, you have known it's zymatic like a constellation of the of the e-frame material. So that increases GFR and that causes like intraglomerular hypertension which can cause like hyperfiltration injury. So you can sort of slow down the death of person's kidneys. A person, a diabetic person's kidneys might give an acinhibitor, right?

Because by blocking the synthesis of angeotensin 2, you effectively, you effectively, so by giving an acinhibitor, you make less angeotensin 2, if you make less angeotensin 2, you cause less construction of the e-frame material, right? So that basically delies the e-frame material that decreases GFR, right? It decreases intraglomerular hypertension and that sort of decreases the risk of hyperfiltration injury. So that sort of slows down damage of the kidneys in diabetes, in diabetic kidney disease. Okay? And then if a patient has hypertension and hyperthyroidism, you can give a beta blocker for that purpose. Remember that hyperthyroidism, right? If you're going back to endocrine, the thing that helps you convert T4 to T3 is a 5-prem Dioid Nees in the periphery. I'm not 5-prem Dioid Nees coming inhibited by beta blockers like proprenolone. Okay? So hyperthyroidism plus hypertension, give a beta blocker for that. Okay? And again, I've talked about the electrolyte imbalance with astrocytes, the cause hypochylemia, the cause metabolic alkalosis, because the revopy or reneinendotensin are a dust-rune system because they make you volume down. Okay? And all diuretics cause half-sophere allergies with the exception of ethycrinic acid. Okay? So next slide. The three constituents of the glomerular filtration barrier, they're three things, right? So we have the endothelial cells that constitute the glomerular capillaries. Okay?

Remember, those are simple squamous cells, but they have finis freechants. And then the second thing is the glomerular basement membrane. Remember it has a negative charge. Okay? And that's created by a heparan sulfate. Okay? Remember that the GBM contains typhal collagen, right? You actually make all the antibodies against that typhal collagen in a good pastoral syndrome. And then the third part of the glomerular filtration barrier, the podocyte food processes. Okay? Remember, the podocyte constitutes the visceral layer of a woman's capsule. Okay? The visceral woman's, or whatever. Okay? And the capillary network of the glomerulus, again, simple squamous has finisrations. And a venous portal system, let me just sort of break this down, right? So sort of think about the liver, for example, right? So the liver has the sinusoidal capillaries. That's what I actually kind of did my research on in Mexico, but back to the real world, right? So you have sinusoidal capillaries in the liver. Those capillaries are fed by portal veins, and then they are drained by the hepatic vein, right? So usually a set of capillaries are fed by arterios and drained by venials, right? Yeah, fed by arterios drained by venials, right? But the thing is in the kidneys, specifically, you have something known as an arterial portal system. So your glomerular capillaries are fed by the afren arterios and drained by the effren arterios. That's kind of an arterial portal system.

The reason why you may want to have stuff like that is, if you want to regularly things, because think about it, right? If you have like a capillary system, you can, if you're sending things to a venial from a capillary, right? It goes all the way back to the heart and then you distribute it all around the body. But if you wanted to keep the local concentrations of things really high, right? You can just sort of say like, oh, from arterial to capillary to arterial, as obtains in the kidney, or from like venial to capillary to venial, as obtains in the liver, and also in the hypo thalamic hypophysila portal system. And then last week, then I'll talk about here, pathway of blood flow from the other. This is just unfortunately something you have to memorize. But basically, right? So from the abdominal leotere, the renal arteries sort of comes off at the L1 L2. And then from the abdominal abdominal leotere, you form like the renal arteries, and then from the renal arteries, you form like mental arteries, and then from segmental arteries, you form the lower arteries, from lower arteries, you form interlobar arteries. And then from those interlobar arteries, you form your arqueoid arteries, right? It's called arqueoid because it sort of takes a 90 degree turn.

If you look at those histologically, and then after that, you have your interlobular arteries, which then form your afrin arterials, you then have your glomerular capillaries, and then you have your effrin arterials, and then you form your peritubular capillaries, and then by some magic, you form the renal vein, and then you go the way back to the IVC, okay? So that is how blood basically flows from the aorta all the way back to the heart through the kidneys, okay? So that's where I'm going to stop today. This podcast is kind of running long. I will continue this in the future, and we will go through that. So thank you for listening. I'll see you next time. God bless.

Swarming motility on agar plate.

Sodium-phosphate symporter; Parathyroid Hormone ($\text{PTH}$).

Diarrhea, Dermatitis, Dementia (and Death).

Thyroidization of the kidney; Eosinophilic casts in the urine.

Pre-renal AKI (e.g., volume depletion); due to increased aldosterone activity leading to maximal urea reabsorption by the collecting duct.

They increase $\text{Ca}^{2+}$ reabsorption in the distal convoluted tubule (DCT) by increasing the gradient, thereby decreasing urinary calcium excretion.

Endothelial cells (with fenestrations), Glomerular Basement Membrane ($\text{GBM}$), and Podocyte foot processes.

The kidney has an "arterial portal system" (fed by afferent arteriole, drained by efferent arteriole); the liver uses a true portal vein system.

Angiotensin II; it causes a metabolic alkalosis (contraction alkalosis).

1. Dietary $\text{Niacin}$ deficiency. 2. Carcinoid syndrome (due to $\text{5 HT}$ diversion). 3. Hartnoblstein disease (defect in neutral amino acid transport).

NSAID use (classic exam answer); others include Sickle Cell Disease or Diabetes Mellitus.

Loop diuretics; they cause hypercalciuria, increasing the risk of stones.

Zero to two red blood cells per high power field (indicating myoglobinuria rather than true hematuria).

Endothelial cells (with fenestrations), Glomerular Basement Membrane ($\text{GBM}$), and Podocyte foot processes.

The kidney has an "arterial portal system" (fed by afferent arteriole, drained by efferent arteriole); the liver uses a true portal vein system.

Angiotensin II; it causes a metabolic alkalosis (contraction alkalosis).

1. Dietary $\text{Niacin}$ deficiency. 2. Carcinoid syndrome (due to $\text{5 HT}$ diversion). 3. Hartnoblstein disease (defect in neutral amino acid transport).

NSAID use (classic exam answer); others include Sickle Cell Disease or Diabetes Mellitus.

Loop diuretics; they cause hypercalciuria, increasing the risk of stones.

Zero to two red blood cells per high power field (indicating myoglobinuria rather than true hematuria).