急性肾损伤：BUN、肌酐与Nephron (Video 1)
Welcome to another MedCram lecture. We’re going to talk about acute renal failure, and for that we’re going to sort of bring up our Chem 7 again. We talked about this before. You remember you’ll see this a lot. It’s standard. We have sodium. You’ve got potassium. You’ve got chloride. You’ve got the bicarb, and we can talk about the BUN and the creatinine.
So that’s this third column BUN, which should be referred to as the B-U-N; never call it the BUN; it stands for the blood urea nitrogen. Okay, blood urea nitrogen and the Cr is simply creatinine. Okay, so blood urea nitrogen and creatinine. So these things have to do with acute renal failure, but let’s get into a little bit about what they are and where they came from.
As you know, when you’re talking about energy, you remember something from biochemistry called the Krebs cycle, and it goes around and around and you remember what went into it first? There’s this thing called acetyl CoA. It was basically two carbons. What came out of Krebs cycle? ATP, you had these reducing agents nadh and fadh2. They went into electron transport chain … the electron transport chain, and you got ATP. So basically you need to have two carbon units to get into this Krebs cycle.
Well, let’s talk about what are the three different types of energy sources in the body. There are three types. We know that there’s carbs, and carbs are usually six-carbon chains, and six-carbon chains get broken down into 2 X 3 carbon chains and then remember one of these carbons comes off in the form of CO2 during glycolysis. Then you’ve got a two-carbon chain and boom you’re ready to enter the Krebs cycle.
好吧，让我们谈谈人体中三种不同类型的能源。有三种类型。我们知道有碳水化合物，而碳水化合物通常是六个碳链，六个碳链分解为2 X 3碳链，然后记住其中的一个碳在糖酵解过程中以CO2的形式脱落。然后，您已经有了一条由两条碳组成的链，并且您已经准备好进入克雷布斯循环。
The other one is fats or lipids. Okay, you remember that? It had the carboxylic end on it, and you had a bunch of these carbons that went off. It was 16 carbons then it’s promotu CoA. And then remember beta-oxidation, it chops these things up into two-carbon units; you’re able to enter into Krebs cycle.
Well, the last energy group is proteins. Proteins, if you recall, are a collection or a string of amino acids, which have the backbone of N-C-C, many of another N-C-C. Well, we have proteases that are chopping up these proteins. They’re chopping them up into these NCC units. These are amino acids. How do you get these C-Cs into C-Cs? While you basically chop off this N group, and then boom, you’ve got C-Cs going in, and you can make ATP.
The problem is that there are these Ns that are left behind. So what are these Ns? These Ns are something called ammonia or NH3. Okay, so we got to get rid of these NH 3 groups. Well these NH 3 groups ammonia as what it’s known as. Ammonia is toxic to the body. It’s toxic to the brain. If you have too much of it, it can cause hepatic encephalopathy. So the body’s got to do something about it, somehow to get rid of it. And that’s why we talked about the BUN. okay. So clear the screen here.
问题在于有这些N被遗忘了。那么这些Ns是什么？这些Ns称为氨或NH3。好的，所以我们必须摆脱这些NH 3基团。这些NH 3将氨称为氨。氨对身体有毒。对大脑有毒。如果摄入过多，可能会引起肝性脑病。因此，人体必须对此采取某种措施，以某种方式摆脱它。这就是我们谈论BUN的原因。好的。因此，请清除此处的屏幕。
We’ve got NH3, which is ammonia, and NH3 goes to the liver. Okay, here’s my picture of the liver. So it goes into the liver. And what comes out is something that looks like this: C double bond O; with NH3 or NH2 on one side and an NH2 on the other. This is urea (U-R-E-A). It goes into the blood, and then you get blood urea nitrogen.
So the nitrogen is now compounded; this is not toxic. So this is really nice to have because you can excrete this through the kidney. So again ammonia goes to the liver and then gets made into urea through something called the urea cycle, which we won’t get into. Then you get this BUN; now BUN (blood urea nitrogen) goes to the kidney. Okay, there’s my little picture of the kidney, and it goes out and that’s how you get rid of BUN.
So we know how that happens. Let’s talk a little bit about the BUN. Remember the first point is it’s made in the liver. Okay, and there are a couple of things that have absolutely nothing to do with the kidneys that could increase the amount of BUN that you measure in the blood.
First of all, let’s talk about Burns. So Burns is a catabolic state. What do you think’s going to happen when you have Burns. Burns is going to cause you to have more protein breakdown. As we already know, more protein breakdown is going to give you more ammonia.
All right, what about steroids? Again steroids induce a catabolic state. A catabolic state is going to give you more breakdown of proteins. That’s going to give you more ammonia. The liver is going to make more urea. What about certain antibiotics, tetracycline? Okay. So here are tetracycline, BURNS, steroids, catabolic state. Okay, all of these things can do it.
Let’s talk about something else. Let’s say you’ve got liver problems. Now in liver problems, or liver failure, or cirrhosis. You can get esophageal varices. Esophageal varices is basic the situation where blood is trying to get back to the heart through the liver. The liver is dysfunctional, and because of that, the blood has to find an alternative route back to the heart. One of those ways is through the esophagus. So these tiny veins which are normally built only to take so much blood becomes engorged, and so these veins can burst and high mortality associated with this.
So you’ve got bleeding. What is bleeding? Bleeding is that (blood gets) into the digestive tract? Well, when that happens, you’ve got these red blood cells. Red blood cells are full of globin. Globin is a protein. You digest down all this protein. Guess what you’re going to get? You’re going to get ammonia. Well, you already have liver failure, so you’re not making this urea, and so what’s going to skyrocket? Your ammonia levels going to skyrocket. That’s why we see in patients with liver failure who have bleeding esophageal bleeding. They get hepatic encephalopathy. And in fact, that’s how you can tell they’re having a paddock encephalopathy.
Now, let’s say that they have GI bleeding, and it’s not due to liver failure. If their livers are working just fine, you won’t see a buildup of ammonia, but in fact the liver will take that ammonia, and guess what? You’re going to have an increase in BUN, so you can have an increase in your BUN if you have GI bleeding, and your liver is working.
What are some things that could cause your BUN to decrease? So all of these things cause your BUN to go up. What are some things that could cause your BUN to go down? Well, the obvious thing is that your liver is not working. Because if your liver is not working, you’re not going to make BUN: liver failure. I see this all the time; patients come in with liver failure, and I’ll look on the Chem Seven. And their BUN is pretty low, sometimes it’s really even undetectable.
Okay, so we’ve talked about BUN. Let’s review that again. It’s synthesized in the liver. Things that increase, it that has nothing to do with the kidney, would be fever, catabolic State, bleeding tetracyclines, all sorts of things. Things that decrease it would be liver failure because it can’t make the BUN.
Okay, with all those things in mind, let’s talk about what we’re talking about today, which is kidney failure. So I’m going to draw a nephron. Here is my little stylized nephron. Remember the kidney works kind of like you should clean out your closet; you take everything out of the closet, and then you put back just the stuff that you want to keep, and everything else gets thrown away.
So here’s the nephron, and here is the blood supply. So you have the afferent arteriole going in, and this is a bunch of capillaries. And what you have is you’ve got flow of fluid into Bowman’s capsule, or the glomerulus, and things go down. Basically, everything that you want to keep gets reabsorbed, and what is left gets dumped out into the toilet.
Okay, but remember stuff that you want to keep gets reabsorbed, and most of the stuff that gets reabsorbed gets reabsorbed right here at something we call the proximal convoluted tubule (PCT). Probably 70% of the stuff that gets reabsorbed gets reabsorbed here at the proximal convoluted tubule. So about 70% of stuff here in the proximal convoluted tubule gets reabsorbed.
So really there are two things that you’ve got to be aware of that affect the serum concentration of things in the serum. So if things here are being reabsorbed back into the serum, and those two things are is the GFR (glomerular filtration rate).
What is the rate at which stuff is being filtered into Bowman’s capsule? If you’ve got acute renal failure, this is going to be reduced, and therefore, for instance, if less BUN is being filtered into Bowman’s capsule, you’re going to have an increase in your BUN outside. That goes for just about anything that’s being filtered. The less filtration rate, the greater that accumulation is going to be in the serum because it’s just not being filtered.
But there’s an extra added thing here with BUN, and that is that once it gets filtered, if this GFR or this glomerular filtration rate, is low, it’s going to go along here more slowly. If it goes along here more slowly, it’s more likely to be reabsorbed because BUN is specifically reabsorbed here at the proximal convoluted tubule.
So there are in fact two reasons why the BUN would go up in a low GFR situation. Number one: it’s because it’s not being filtered at the same rate, and the stuff that is being filtered is more likely to be reabsorbed. That’s going to become very important later on.
Now. This is in contradistinction to something called creatinine. We talked about creatinine. Creatinine basically comes from muscle, but specifically, creatinine is also filtered here at Bowman’s capsule, but it is not reabsorbed. It just keeps going through and right on out.
In fact, there are areas here where creatinine is actually actively secreted. So what does that mean? That means that if there is a low glomerular filtration rate, that’s a reason why creatinine is going to go up. But it’s not going to have the other reason to go up because it’s not being actively reabsorbed. In fact, it’s being secreted, and so creatinine only goes up for one reason in a low GFR. That’s the major difference between creatinine and the BUN.
let’s talk a little bit about creatinine. What is creatinine?
Okay, creatinine again and the chem 7 is this area down here? And where does it come from? It comes from muscles so muscle breakdown is going to give you creatinine. It’s just a natural byproduct. So the more muscle you have the higher your correct name is going to be normally and the less muscle you have the less you’re creating this going to be and typically you need to see a reduction in your GFR by a least 50% before you see an
In you’re creating. So what are some non renal things that could increase creatinine things that have absolutely nothing to do with the GFR. Well as we talked about remember there are areas here in the nephron specifically where creatinine is secreted. If you could take a inhibitor of that and block it you would block the secretion of creating that would increase your serum concentration of creatinine and there are a couple of drugs that do.
That one of them is called cimetidine.
Tagamet it’s an H2 blocker. And the other one is an antibiotic called trimethoprim.
Okay, so you’ll see an increase in creating for that. What about decreased creatinine? What could cause a decrease in creatinine? We talked about profound muscle-wasting solo muscles. So if you don’t have any muscles that would cause you’re creating to go down and that would be a reason for your crafting to be low. Okay. So to review remember be un is synthesized in the liver. It is both reabsorbed. It is filtered and reabsorbed the
Creatinine is filtered and secreted. It is not reabsorbed. So if there is a Slowdown in filtration The Bu n is going to be increased because of lack of filtration and also because reabsorption the creatinine is only going to be increased because of lack of filtration. Therefore, you’re going to see a larger be un increase then you would create an in in the low Flow State. Alright that does it for part 1 join me for part 2