 Our next topic is gonna be on acute tubular necrosis. Well, before we move forward, I want to explain to you that this is just another subset of a tubular interstitial disease, the beautiful story behind this. Now, what is acute tubular necrosis? Let's take a look at it. Acute a very short amount of time. Tubules, here the tubule, remember those renal tubules cells I told you about? Yep, that's one of them. We're gonna talk about them in a minute. But now necrosis, man, they're dead. Oh, yeah, they died. But what caused them to die? Yeah, that's what I need to talk about. Well, the definition of acute tubular necrosis is due to kidney severe hyper-profusion to the kidneys. Also with toxicity, which we're gonna talk about in a minute. But if you have severe hyper-profusion to the kidney plus a toxic compound, you develop ischemia, ischemia's decreased blood flow, no nutrients, no oxygen to the tubules. These tubules, they want to be fed. Eventually, it will lead to what? Infarction, infarction and eventually developing necrosis and they start to slouch off. So here's the story. Acute looking renal tubule cell. It's always getting its nutrients. Every day, food is coming in, it's eating up, it's got the oxygen, it's got the nutrients, it's feeling good, it's undergoing oxidative phosphorylation, it's got ATP and it's cranking up and it's also working. That's a typical day for a renal tubule cell. However, one day, they cut off the supply. There was a hyper-profusion state that happened in the body and all of a sudden, yeah, initially, these patients are gonna develop some acute renal failure. But if this becomes persistent and become what? Severe and they're still not getting any perfusion to the kidneys, guess what's going to happen? It doesn't can't really hang in there for so long and then you get a toxic compound? Oh, that is some bad news. If you get some toxicity to it with it, eventually, they're gonna become necrotic and they're gonna slouch off. Now, I've drawn a diagram to illustrate the simple thing telling you how normal blood flow goes to the renal tubules. It's a sample of a tubule. However, if we cut off the perfusion, if we cut off the perfusion to the kidneys, guess what, this tubule cells are gonna start to slouch off and guess what's gonna foam? We got from this brown, yuckish stuff we call muddy brown cast. Well, what can cause severe hyper-profusion to the kidneys? Well, number one. If you use a heart cardiac surgery or you have sepsis, sepsis or you have cardiac surgery or even what, aortic surgery, what kind of aortic surgery are we talking about? If you had a big aortic anus ruptured and they had to replace this, what eventually happens is during the surgery, they have to clamp off this top of the aorta and also clamp up the bottom so they can fix this area during that period of time. You might get decreased perfusion to your kidneys. Oh, that is some bad news. If you keep getting persistence hyper-profusion, you're gonna become ischemia to the kidneys, you're gonna renal its efficiency, eventually necrosis. If you become septic, you get systemic work. Vesodilatations, all the blood vessels are so dilated, it decreases the perfusion to your kidneys because they're just rushing down, they're all floating down, nothing is getting perfused to the beautiful kidneys. Well, aside from sepsis, what about things that cause, this is called hypertension, right? This will cause you to become hypotension. Well, you might say to me, wait a minute, I really get it, yeah. If that's just hypertension, if I have like heart failure or if I have a hemorrhage, I can develop the same thing, but in this case, it's persistent, it's constant, it's constant, it's not going away. If I have hyper-profusion and I replace back the fluid in your vasculature when you're hypotensive, oh, guess what? It reverses. Drugs, oh, what drugs are we talking about? Oh, well, aminoglycosides. Aminoglycosides, like what? They're the mean glass, right? The gentle mycine, neomycine, amikicine, Tobra mycine. These drugs, aminoglycosides, they're very nephrotoxic. Guess who else? Cisplatin, the guy that makes you deaf and also damages your kidneys, yeah, it's nephrotoxic. What about the drug we use for patients with fungal infection? Amphotaricine B, the B is gonna blow up your kidneys. Remember, amphotaricine B, Cisplatin, aminoglycosides are toxic to your kidneys. So if you have toxicity from a drug to your tubules, right, it's like you've got the drug squishing up and damaging your tubules and on top of that, we're not getting any blood flow. All the blood supply has been cut off due to ischemia, right? Because you have hypertension and you're having decreased blood flow, right? Decrease blood flow and decrease proficiency of the kidneys. This is gonna cause your renal tubule cells to die and when they die, they're gonna slouch off. It has nothing to do with your glomerulus. The glomerulus defines only the tubules. Now, there's three phases for this renal tubule cells to develop and die and become necrotic. See what happens, become toxic and you die. Well, so, since there are three phases, what do you think is the first phase is gonna be? Well, they have hyper-profusion to the kidneys, right? So this is very acute onset. This is just a new injury that's been happened. So this is called the prodromal phase and this is basically at the acute phase of injury. Now, this is when the new onset of renal failure is start to develop. Now, the second phase, since I'm having hyper-profusion to the kidneys, will I be able to pee? No, so if I don't pee, we call that what? Oligoruria, by definition, is usually less than what? 400 mLs in 24 hours. If you're not peeing up to 400 mLs in 24 hours, you're Oligoruria. Guess what? It gets worse. Now, if you're not making any urine at all, we call that anuric. At that point, you even make less than 100 mLs in 24 hours. That means, what does this mean? That means initially you had renal injury so you had an acute renal failure, right? From hyper-profusion, but because it becomes more persistent, if I keep decreasing the amount of food going to my kidneys through the glomerules, I can't filter anything through the tubules. If nothing's getting to the tubules, nothing is coming out. That's how I develop Oligoruria. The last but not the least is the poly-oligurics phase. Now, after these cells have not received any blood flow for so long and toxicity has been damaging the tubules, now when there's perfusion to the kidneys, we're gonna develop something called polyuria, which is vigorous because at that point, water that hasn't been excreted, now it's just gonna pour down the drain and you're gonna have vigorous polyuria. But it's gonna come with what? Some yucky stuff called muddy brown cast. Just think about it. When all these cells die off and all the filtration go through, you're just gonna wash all of them down and it's just gonna come out and you're gonna peel this yucky-looking brown, muddy cast. That's necrotic tubules that have died. Oh, I'm sorry. Society lost. How are we gonna make the diagnosis? Well, the way we're gonna diagnose this issue of pathology, making the diagnosis, is what we're gonna order what? I'll get your renal function test, right? And check your BUN creatinine. It's usually 10 to one at the initial onset of renal failure. And it might sound like, wait a minute, initially you might get a ratio of 20 to one because when we have pre-renal azotemia, that's what we get, right? When you have pre-renal azotemia, your BUN to creatinine ratio is usually 20 to one. It could be 40 to two. That's usually what? The ratio, but as it gets persistently worse and the cells start to die off, what happens is the ratio becomes 10 to one. Now, there are all the key factors we need to know, like what will be your urine osmolilatine. What about phenol? Remember phenol, fractional excretion of sodium. What percentage would that be? And last but not the least is the what? The urine sediment. What are we gonna see in the urine sediment? Well, let's think of this, let's think it's true. If I'm damaging your renal tubules, if something is dead, it can't perform its function, right? If I can perform my function, will I be able to reabsorb how much fractional excretion of sodium will be? Wouldn't it be very high? Because now sodium can be reabsorbed back into the body, so it's gonna do what? Sodium is gonna come out. When sodium come out, what's gonna happen? A urine sodium, check the amount of sodium in the urine, it's gonna be greater than 40. That's gonna be very high. That's telling you the tubules are dead, the sodium is what? It's escaping, normally what? We reabsorb it back into the body. Well, if I'm losing all the sodium, what's gonna be the fractional excretion of my sodium? It's gonna be greater than 1%. Why? Because I'm excreting all this what? Sodium, because the tubules are not working, they're usually what? Reabsorb it, if they reabsorb it, it should be less than one, but because they're losing and they're dying, they're like, oh, they just look at the sodium, hi, sodium, and the sodium just walks past them and they don't touch it, they don't touch it. Fraction excretion of sodium is what? Greater than 1%, and urine sodium is what? Greater than 40. Well, if the cells are dead, when water is straddling, you know, Mr. Water, H2O is walking down the street, he sees Mr. Sodium running down the street, he's like, oh, hold on, Sodium, let me catch up. It catches up with the water and the sodium, and guess, since the tubules are, I'm pretty much dead, we'll meet you guys outside also. Well, guess what? The urinal's more likely, it's gonna be what? It's gonna be really, really low, it's gonna be less than 350. Because the urinal tubules normally concentrate your urine, now they can't, because they're dead, they're like, hmm, guess what? I'm dead, I'm gonna meet you guys outside, and when the urinal tubules start to break off, they're gonna form something we call muddy brown cast. Muddy brown cast. So this makes absolute sense. Cells are dead, everything walking by them, they're following their ancestors, they're like, you know what, we're gonna just move out, we're moving out, well, muddy brown cast comes out, sodium, that's not supposed to be reabsorbed, it's like, well, if that's the guy that's supposed to reabsorb me, and he's not doing this job, I'm just gonna follow wherever he's going. Water said, hmm, wait a minute, oh, sodium is going, I'm gonna follow sodium too. We'll follow sodium, and then your urinal smell is so dilute, because it's not concentrated, because the cell that's supposed to be doing the job basically is already dead, and they're walking out. All right, so usually, what are those? Those are the epithelial cells, don't forget, the epithelial cells are the tubular cells inside your tubules. Well, how do we fix this? Now that we know the cells are dead, and everything is what, slouching off, the beating in the creatinine was elevated, and all of this explaining what the diagnosis is, what do we do? The cells are dead. I mean, if the cells are dead, how am I going to treat it? Treatment. So, if our Q tubular necrosis, well, got some bad news, there's no therapy for our Q tubular necrosis, because the tissues are dead. Because we can't really reverse the urinal failure at this point because the tissues we're trying to solve, it's like having myocardic ischemia to myocardic infarction. If you're still ischemic, we might be able to save the tissue, but once the tissue is dead, can't bring them back from the grave. So there's really not much we can do, we can fix the underlying problem by doing what? If you're on amino glycoside, stop the amino glycoside. Right? Because that's what's toxic to your kidneys. Right? If you're taking amphotericin B, stop, don't take it anymore. Well, if you're still what? Hyper-profusing your kidney, we can give you hydration, but at this point in the game, you know what? It's not really gonna do much good other than maybe salvage the rest of the tissues that's not dead yet. So, if they've lost all the tubules in that inside the kidneys, guess what? We just lost the entire sink. We can't filter anything anymore. You're gonna have to go on dialysis. If they go into what? Severe renal failure. If they go into severe renal failure at that point, they're gonna have to go to dialysis. Since your sink doesn't work anymore, we're gonna have to bring in a new sink, which is a machine. All right? And that's the end of acute tubular necrosis. Thank you very much for watching. Have a great day. Bye-bye.