DIP Episode 625 - The 5 USMLE “Gaps” (Step 1-3)

Welcome. My name is Divine. This is episode 625 of the Divine Intervention Podcast. In today's podcast we're going to be addressing gaps. We're going to be addressing what? Gaps. I'm going to call this podcast literally gaps and the USML Es. Gaps and the USML Es. The USML Es they love to test gaps and the thing is I've noticed in my experience. Many students struggle with these gaps. So my goal is to really help you understand them. So you can crush your exams. Alright. So the very first one I'm going to start off with is the anion gap. It's the anion gap. So the thing is we know that there are two anion gaps that are commonly tested on the USMLE exams. There is high anion gaps and there's normal anion gaps. So the first thing we should try to figure out is what's the anion gap formula. We know that many times we use this in reference to metabolic acid doses. An anion gap is pretty much your sodium minus your chloride plus bicarb. So your sodium minus your chloride plus bicarb. So let's look at this. Sodium is a carion. It's positively charged. Chloride is an anion. It's negatively charged. Bicarb is an anion. It's negatively charged. But I want to say something to you. There are other anions in the body that are not considered in this formula. There are other carions in the body that are not considered in this formula. So let's conceptually try to understand. And I guess before I jump in there. So what's a normal anion gap? A normal anion gap is 12 or lower.

So the spread between the amount of sodium you have in your body and the combination of your chloride and bicarb, the spread between those numbers should be 12 or lower. If that spread is higher than 12, then you have a higher anion gap. So think about it. If that spread is higher than 12, it means that there must be something that is reducing how much chloride or how much bicarb you have. But for purposes of this discussion, we're going to focus on the things that deeply how much bicarb you have. Let me ask you this. What is bicarb? Bicarb is a base. What do bases do? Bases can help us neutralize acids. So if there is a lot of acid in your blood, right? So say for example, there is a lot of lactate acid in your blood or you have diabetic ketoacidosis or you have whatever. If there is so much acid in your blood, your body is going to be working really hard to neutralize all that acid. Because if your blood becomes too acidic, there are many enzymes that will not work. There are many enzymes that are pH dependent. And if they stop working, that's bad. That's really, really bad. Because the person could die. That's why I see doses is dangerous. Your bicarb is working over time to try to clobber clobber clobber clobber clobber down that acid. So that's why we have this concept of a high anion gap in a bicarb acidosis. It means that there is something that is just eating up your bicarb, eating up your bicarb, eating up your bicarb.

And again, the thing that is most likely to eat up your bicarb is a lot of acid. So if a person has like lactate acidosis, or if a person has, basically if you have lactate acidosis, that bicarb acidosis, you have urea. Remember urea indicates that your kidneys don't work. And your kidneys are one of the most important organs for getting rid of acid. So if your kidneys are not working, you are not getting rid of acid. You are holding onto acid, you are neutralizing bicarb. And that's going to put you in trouble. And also, if your kidneys are not working, you will not be generating bicarb. And if you can generate bicarb, then that bicarb part of your formula will also go down. And that's going to cause a high anion gap. So you really, you really cause the high anion gap in a bicarb acidosis by two mechanisms. Number one, your kidneys are not generating bicarb. So it's almost like you're generating less of the neutralizer of acid. And then two, the acid you have you're not excreting it. That's a problem. That's a problem. So that's what's going to cause a high anion gap. Something depleting your bicarb. So the sodium part of your formula then just becomes the spread between it and the chloride and bicarb just widened. Because the bicarb part is going down a lot because something is eating it up. And then the concept of a normal anion gap, right? Normal, normal, normal anion gap. A normal anion gap means that, oh, that spread is not changing. That spread is not changing.

It's like, hey, the difference between sodium minus chloride plus bicarb is not changing. Hmm. Hmm. So that means that what may be happening is that you may be swapping out your body may be losing a lot of bicarb and replacing it with a ton of chloride. Or your body may be losing a ton of chloride and replacing it with a ton of bicarb. Right? And many times when you see a normal anion gap metabolic acidosis and I've made podcasts where I go into detail on these. It means that, hey, your body is like almost like playing you, you with chloride and bicarb. Is it like, wow, okay. I'm getting a lot of chloride back as I'm losing all my bicarb or, hmm, I'm getting all my bicarb back as I'm losing a lot of chloride. But most of the time, most of the time. So let's get to real talk. Most of the time, what's happening is that you're losing a lot of bicarb and you're replacing it with a ton of chloride. You're losing a lot of bicarb, right? So you're like, hmm, I'm losing a lot of bicarb. But if you're up in the amount of chloride you have, then that spread is not going to change. Right? Because remember the anion contributors. Bicarb is a contributor. Chloride is a contributor. If you're losing bicarb, let's say you lose like three units of bicarb, but you're replacing with three units of chloride. That's going to balance things out, right? That's literally going to balance things out. So just something I want to keep at the back of your mind.

And again, I believe I have made podcasts in the past where I really went into detail on normal anion gap metabolic acidosis. So, and one thing I think I want to clarify that will be helpful for the audiences. People are like, oh, divine. I've heard this concept a lot of on measured anions on measured anions and high anion gap metabolic acidosis on measured anions on measured anions. See, those on measured anions are the things that are clobbering your bicarb in high anion gap metabolic acidosis. Like for example, let me ask you this. Lactic acid is lactate part of the formula for anion gap. It's not. Right? But if you build up a lot of lactate, it means you're building up a ton of lactate acid. And that lactate acid, your body is going to have to neutralize you with bicarb. Right? So the bicarb is being taken away and it's not like there's some chloride that's replacing it. That's why the anion gap becomes high. But again, in the case of a normal anion gap metabolic acidosis, you have stuff that's happening like diarrhea, one RTA. That's eating up your bicarb but somehow your body is replenishing the chloride. So that's why the spread between the sodium and the combination of the chloride and bicarb does not change. All right? So that's the first gap I want to describe the serum anion gap. Okay? Well, I'd be remiss if I don't go to the second gap, which is the urinary anion gap, the urinary anion gap. Okay, so what's the urinary anion gap?

The urinary anion gap, what's the formula? It's your sodium plus your potassium. So your urinary sodium plus your urinary potassium minus your urinary chloride. Okay? That's the urinary anion gap. What is the USMLE purpose for the urinary anion gap? The USMLE purpose for the urinary anion gap is to help you figure out if diarrhea is the cause of your normal anion gap metabolic acidosis or if a distal RTA, a type 1 RTA is the cause of your normal anion gap metabolic acidosis. Remember, a distal RTA is a type 1 RTA. That's a problem at the level of the alpha-intercalated cell. If the alpha-intercalated cell does not work, you're not able to acidify your urine. That's going to cause a normal anion gap metabolic acidosis. Right? Because that alpha-intercalated cell lets job is to excrete acid. If you're not able to excrete acid, then you're going to hold onto a lot of hydrogen ions in your bloodstream. As you hold onto all those hydrogen ions in your bloodstream, that's going to deplete your bicarb. That's going to cause a metabolic acidosis, but typically that process is accompanied by a lot of chloride generation. That's a different discussion. I believe I've had that in a different part of the world, so I'm not going to go into the weeds on that. What's the purpose of the urinary anion gap? Sodium plus potassium minus chloride. What's the purpose? Literally, what's the purpose? The purpose of the urinary anion gap is this.

It literally is a barometer for how your kidney is responding with chloride. It's a barometer for how your kidney is responding with chloride. Let me break it down for you. Let's look at the normal situation. If you're acidic, because again the goal is, I told you that again, it's a barometer for how your kidneys are responding with chloride. So how should your kidneys respond with chloride if you're acidic? Because again, the purpose of urinary anion gap is to help you delineate. I gave the purpose. See, if you want to learn a concept, the smart thing to do first is to understand. Okay, before I start learning this concept, what's my purpose? What's my purpose? If you understand the purpose, then it doesn't seem like you're just mindlessly memorizing stuff. The purpose of the urinary anion gap, just repeated again for people that were not being attention is, hey, is my normal anion gap metabolic acidosis being caused by diarrhea? Or is it caused by a distal RTA, a type 1 RTA? So the thing is, if you have an extra renal cause of acidosis, like diarrhea, like diarrhea, because the thing is your colonic fluid is rich in bicarb, very rich in bicarb. So if you're spending a lot of time in the bathroom, you're pooping, pooping, pooping, pooping, pooping a lot, guess what? You're dumping a ton of bicarb away from your body. As you're losing bicarb, your body is becoming acidotic, because you're losing a buffer. You're losing something that offers acid, so you become acidotic.

So your body is going to be like, oh no, I don't like having all this acid around. So your body is going to be like, hey, acid excretion organ, I need your help. Well, what is the acid excretion organ? I said this earlier in the spot, guess what I was talking about? The sermoneion gap. It's the kidney, right? The kidney is your acid excretion organ. So your kidneys is going to be like, okay, I know we have an excess of acid, I know we have an excess of hydrogen ions, and we'll help you get rid of it. But there's a cost to the kidney. The kidney can not just peel hydrogen ions, right? You purely like explode or something like that. You can just peel hydrogen ions. You have to peel out in a complex. What's that complex? That complex is as ammonium chloride. Is that what? Ammonium chloride. So those hydrogen ions, your kidneys bind those hydrogen ions to ammonia, to form ammonium. But again, there is this renal professor when I was in medical school that always said you cannot peel the electricity. Yeah, you literally cannot peel the electricity. So those hydrogen ions that your body has in excess because you have diarrhea and you've lost so much by carber. Those hydrogen ions, your body will complex it to ammonia to form ammonium. And then that ammonium is still a carer ion. Your body is going to be like, hey, let's slap some chloride on this ammonium, right? Ammonium and chloride they love each other very deeply.

So you bind chloride to that ammonium and boom, ammonium chloride goes out to your urine. Okay, so if you have an extra in all problems like diarrhea causing your nagma, your normal anion cap and apolic acidoses, your body has an excess of hydrogen ions, your kidneys are working. So it's going to bind those excess hydrogen ions to ammonia to me, ammonium. And just repeating myself here, you'll slap some chloride on that so you don't peel out electricity. So the amount of chloride in your urine should be high, right? Because there's a lot of ammonium chloride in your urine, right? So let's go back to the urin anion cap formula. If there's a lot of chloride in your urine, sodium plus potassium minus chloride. If there is more chloride, then that chloride part can overwhelm the sodium and the potassium part. The anion part will be more than the cadaion part. So you're going to get a negative urine anion cap. This is why when you have diarrhea, you have a negative urine anion cap. There is this numonic out there that, oh, negative, you know, like your diarrhea, like your gut, negative. But again, why memorize when you can just understand the mechanism? Okay, so why is it that because many of you have probably memorized from some onky deck that if you have a distal RTA, a type 1 RTA. You will have a positive urine anion cap. Well, why is that the case? Well, the reason there is that again, let's look at the pathophysiology.

It always goes back to those delicious pathophysiology, right? If a person has a distal RTA, your offer intercalated cell is not working. You cannot acidify the urine. So that kidney that you're banking on, oh, Mr. Kidney, please help me get rid of this excess hydrogen ions I have. Well, you can do that if the thing that does the urine acidification is not working. So guess what? You put his going to hold on to a lot of hydrogen ions. So that that hydrogen ion ammonia business is not happening. You're not making any ammonia. If you're not making any ammonia, you're not making any ammonium chloride. So what's going to happen to the amount of chloride in your urine? It's not going to be much because you're not even generating it in the first place. You're not. You're not generating the chloride in the first place. You're just not. You're just not. Right? So the sodium and the potassium part of the urine anion cap formula is going to overwhelm the chloride part of the urine anion cap formula. That's why you're going to have a positive urine anion cap. Okay? So that's the second gap I am going to discuss in this podcast. Right? So if don't gap number one, ceremony on gap hopefully makes sense to you now. Gap number two urine anion gap. All right. Gap number three is going to be the osmolo gap. We're going to talk about the osmolo gap, the osmolo gap. All right. So what is the deal with the osmolo gap? Okay.

Well, first, before we talk about the osmolo gap, let's talk about how to measure like what's the formula for serimosmolarity osmolarity. And the measurement is in mille osm per kilograms of water. M osm per kilograms of water. Right? So we know that formula serimosmolarity was the formula really out. Okay. It's the two. These two times your sodium plus glucose divided by 18 plus B. You end divided by 2.8. Right? Sodium times two plus glucose divided by 18 plus B. You end divided by 2.8. That's the formula. You use a formula when you want to when you want to calculate stuff, right? That's right. We want to calculate stuff. So if you want to calculate the serimosmolarity, that's what you do. But the good thing is we have labs that can help us literally measure the serimosmolarity. You can literally do a blood test. You grab some blood from somebody and measure the osmolarity from it. Okay. And in a perfect world, in an ideal world, what you measure in the blood stream should match up with what you calculate from the formula. Okay. What you measure in the blood stream should match up with what you calculate from the formula. In fact, the spread between those two numbers should never be greater than 10. Should be less than 10, right? Should be like less than 10.

So if there is a big spread between what you're measuring in the blood and what you calculate from your formula, it means that, wow, there's a lot of stuff in this person's blood that is not being accounted for in the formula. Right? Because again, this formula shows us like, hey, what does this formula account for? Sodium glucose and B1. You're here. Right? So if you notice that, hmm, man, okay, what I'm calculating, I'm getting this number. But chi, what I'm measuring from the blood from doing a blood test on the patient is much higher. It means that, ooh, there must be some other thing that is not in this formula that is accounting for how high these numbers are. So what could that something be? Well, it could be things that are not in that formula like alcohols, like methanol, right? Or ethanol, right? Or ethylene glycol or Manitol, right? Those things are very powerful osmos. They are very powerful osmos, very, very powerful osmos. Right? They are very osmoticly active, like Manitol. There's a reason you use Manitol as a diuretic because it's like a sugar that can hold onto so much water. Right? So all these sugars, all these oils, if you go back to organic chemistry, alcohols are very good at complexing with water. Right? So they can really contribute to that ceremony of molality. Right?

So if you see a high, a big gap between your measured, what you measure in the blood, you know, join a person's blood, and what you calculate with your two times sodium plus glucose over 18 plus BUN over 2.0 formula, you know that there must be something else contributing to osmolality that normally does not contribute to osmolality, like alcohols. Typically it's going to be alcohols or Manitol on the USMEL exams. All right. So that's gap number three. So we've done the seramonion gap, we've done the urine anion gap, we've done the osmologap. All right. The next gap we're going to talk about is the sag. There's one many people just mightily struggle with, but by the end of this explanation is going to make great, great, great sense to you. Right? So what a sag stand for S.A.A.G. sag stands for the serum, albuming, a side is gradient serum albuming, a side is gradient. So basically like let's use a simpler language. What is this exactly? Well, we have serum and we have a side is what's a side is a side is is when you have fluid that kind of completes in your belly, you know, for many different reasons, you can have a side is for many different reasons, you can have a side is because you know, you've been a big time alcoholic, cirrhosis is eating up your liver or you have other things like heritthryhemochromatosis that crushes the liver or non-acoholic fatty liver disease or whatever that's messes up your liver, right? That causes you to have a side is right or cancer.

Overein cancer is a cancer that loss to cause a side is right or inflammation infection, right? So what carries syndrome many different things, right? So there are many causes of a side is so you're like, gee, is there a convenient elegant way I can tease apart these different causes? Yeah, yeah, right? Yeah, and we use to do that. So sag is the serum albumin, a side is gradient, right? So it's like you take the amount of albumin in the serum as your first number and then take the amount of albumin in your acidic fluid, that's the second number and you take the difference between them, okay? You take the difference between them ideally, ideally, ideally, the amount of albumin within your side is can tell you something, right? Because normally, right? Like, oh, most of the albumin should be tied up in your serum, right? Your acidic fluid should not have a ton of albumin in it, right? Should have a ton of albumin in it, right? But again, that's the whole reason why we're like, hey, let's take the difference between the albumin in the serum and the albumin in the acidic fluid. So let's look at this logically, right? Many of us remember the cut off 1.1 that hey, if your sag gradient is 1.1 or greater, oh, poor, all hypertension is the cause of your a side is, but hmm, if your sag gradient is less than 1.1, right?

So 1.1 does not count if it's less than 1.1, then oh, cancer, infection, nephrodix syndrome is the likely cause of your a side is, okay, hey, let's make that mix sense instead of just blindly memorizing things. Okay, so let's look at a high sag gradient, right? So what will cause the spread between the amount of albumin in your serum to be, oh, cause it to be a much higher number than the amount of albumin in your acidic fluid? Well, the big classic cause, I think you should file a way in your mind for the exam is portal hypertension, but why is that the case? Well, if you have portal hypertension, if you have portal hypertension, is almost like you're causing a traffic jam within your portal system. If you cause a traffic jam within your portal system, what happens to the hydrostatic pressure within your portal system? The hydrostatic pressure is going to rise, and if that hydrostatic pressure rises, you're going to have a lot of fluid extroversition out of your portal system. You're going to have a lot of fluid extroversition, right? So it's just fluid that is extravaceted. It's like a pressure thing. A lot of fluid is extravaceted and a lot of fluid is extravaceted. Notice what I said, I said it's fluid that is extravaceted, right? Fluid can easily pass very small holes, can easily pass very small membranes, right? Like your blood vessels, your portal system, right, can let fluid out. So that fluid that is coming out is like clean and clear.

It's like clean and clear, right? So because that fluid is clean and clear, it doesn't have much if any argument in it. It doesn't. So that acidic fluid you are generating from the increased hydrostatic pressure, it's clean and clear. There's no argument inside it, but your serum still has all that argument in it. So guess what? If we measure the amount of argument in that acidic fluid and we measure the amount of argument in your serum, there's going to be a big spread because that argument in your serum did not move. It stayed, the only thing that moved was fluid. The thing that's going to cause that is portal hypertension, right? And again, just be careful on your exams. It's not only cirrhosis that can cause portal hypertension. Again, all of this you don't have to memorize if you just do some simple reasoning, for example, if you have a portal vein thrombosis, if your portal vein is blocked for whatever reason, that's going to risk pressures within your portal system, right? So it's almost like a, if you mess up your portal vein, that's like a pre portal cause of a side. If you have cirrhosis where your liver is like messed up because of alcohol or fatty liver disease or hemochromatosis or whatever, then that's like an intra hepatic cause, right? So sorry. So the portal vein thrombosis issue is a pre hepatic cause of a side. Cirrhosis is an intra hepatic cause of a side. What do we think of as a post hepatic cause of portal hypertension that can lead to a side.

What if you have a hepatic vein thrombosis, but carry syndrome with stuff like paroxysmonectrinoma hemoglobinuria or polycythemia vera, right? Or let's say you have a blockade within your IVC, okay? Or let's say you have heart failure and fluid is just backing up, right? All those things are going to risk portal pressures, right? Those things are going to be as really with a high sat, right? Honestly, the way I think of a high sat, I think of it as like a trans-unit, is like a trans-unit as side. Because it's clean, it doesn't have a lot of stuff, you can mix some parallels to the lungs with trans-unit, plural effusions, trans-unit, plural effusions arise because you have increased hydrostatic pressures. Let's say you have CHF, your left heart is not pumping blood, right? So fluid is just going to back up into your pulmonary vessels, especially your pulmonary capillaries. There's going to be fluid extraversation, that fluid that is extraversating is clean, right? It's clean, it's going to be a trans-unit. That's why if you notice, light criteria, hey, ratio of serum protein to, I mean, ratio of plural fluid protein to serum proteins less than 0.5. It means that weight, that plural fluid, that plural fluid doesn't contain a lot of protein because it's clean compared to the serum. Or hey, ratio of serum, plural fluid, LDH to serum LDH less than 0.6. Again, intuitively, it means that weight, that plural fluid is clean, it doesn't have a ton of LDH in it, right?

So again, there is almost like an analog between a trans-udidifluorol of fusion and porol hypertension causing a high suck, right? A big spread, right? When you have a trans-udidifluorol of fusion, there's a big spread in the amount of protein when you're comparing the serum to the plural fluid. Why? Because the plural fluid, the stuff that extraversated out is pretty clean. Hopefully, making those parallels can really help you. So what can cause a low-sacridian? Again, you can think of this intuitively, that if I have a low-sacridian, it means that the spread between the amount of albuming in my acidic fluid and the amount of albuming in my serum, the spread is small. So that means for that spread to be small, albuming must have leaked out. albuming must have leaked out from your serum into that acidic fluid to boost the amount of albuming within that acidic fluid. So that means membranes must have been disrupted. So now you just need to ask yourself, what is something that can displace membranes? What can displace membranes? Well, there's a lot of stuff that can displace membranes, typically inflammation, right? Because when you have inflammation, remember, you produce things like histamine. Histamine increases vascular permeability, right? Breedy-kindness, those things increase vascular permeability. When you increase vascular permeability, surprise, surprise. The stuff inside your vascular, inside your vessels, we're going to leak out like albuming, right?

So your acidic fluid is going to be rich in albuming. Your serum is going to be rich in albuming too. So that's going to cause you to have a low-saggredient. How about cancer? Cancer? Why does cancer cause a low-saggredient? Well, number one, cancer causes inflammation. Your body is going to be inflamed to try to deal with that cancer, right? So you're making all these histamines and Breedy-kindness, right? So that's going to increase vascular permeability and that's going to cause some albuming to leak out. But also remember, what's one thing with cancer? All these cancers, man, they make all these things like cut here. They don't regularly things like cut hearings. When you don't regularly cut hearings, cut hearings, hold cells together, they hold the integrity of things together. If that integrity is lost because they are downregulated, things are going to get leaked here, right? So all that albuming inside your serum is going to leak into your acidic fluid. So the spread between the albuming and your acidic fluid and your serum, that spread is going to be very small, right? So you're going to get a low-saggredient, right? But then there's one curious case I want to visit here and that's nephrodix syndrome. Many people are like, oh, divine! Nephrodix syndrome, why does it cause a low-saggredient? Well, again, look at the formula for saggredient. A amount of albuming in your serum minus a amount of albuming in your acidic fluid. Okay.

Let's assume you have nephrodix syndrome. What are you pin-off through your kidneys? You're pin-off the ton of albuming. Okay. As you peel out all that albuming, what happens to the amount of albuming in your serum? I promise you it's not a trick question. It's going to go down. If the amount of albuming in your serum goes down, then the spread between what is in your serum and what is in your acidic fluid. Even if your acidic fluid is clean, that spread is going to be lower. So that's why nephrodix syndrome causes a low sagg. That's why it causes a low sagg. That's the mechanism. That's the pathophysiology behind that. Okay. So again, that's the whole point behind the serum albuming a side-is-gredient. Right? It just tells you, hey, are your vessels permeable to albuming or not? What's going to cause versoprimability, cancer infection? Well, in the case of photohypertension from botquyari syndrome, of cirrhosis, or pothovin thrombosis, or whatever, your vessels are not permeable to albuming. They're just permeable to fluid. Hopefully that's a good summary of that. So what's the last gap we're going to discuss in this podcast? The last gap we're going to discuss in this podcast is the AA-gredient. If you notice, I'm just trying to discuss things where there's something in one compartment, there's something in another compartment, and there's a spread between them. Right? So the AA-gredient. So what is the AA-gredient? The AA-gredient is the viola at your gradient.

And again, what does he do? What's the purpose? Basically, he's like, hey, what's the partial pressure of oxygen in the alveoli? That's the big A. Hey, what's the partial pressure of oxygen in my arteries? That's the little A, right? And then you take the spread between those two numbers, and that's your AA-gredient. Right? That's literally your AA-gredient. So again, partial pressure of oxygen in your alveoli, that's the big A. partial pressure of oxygen in your blood vessels, that's the little A in your arteries. You take the spread between those two numbers, and that is your AA-gredient. So what is the ideal situation? The ideal situation is that, hey, every oxygen that gets deposited in your alveoli, gets into your arteries. That's like, whoa, that's ideal. That's ideal. Well, the world is not ideal. Sorry. Sorry. Sorry. The world is sadly not ideal. The world is sadly not ideal. Right? The world is sadly not ideal. Right? So, you know, your lungs, there's some slippage, there's some losses, and I'm not going to go into those details. Right? But normally, the spread between your arterial, I mean, your vial oxygen, partial pressure, your arterial oxygen, partial pressure, that spread is usually, there's usually some spread, it's physiologic, not a big deal. But why would you have a high AA-gredient versus a normal AA-gredient? See, let me give you a simple way to understand this. Because it's like, hey, what's the purpose of the AA-gredient formula?

We use this formula to determine, do I have a cause of hypoxemia that is outside the lung? Do I have a cause of hypoxemia that is inside the lungs? Right? Because think about this. If the cause of the hypoxemia is outside the lungs, let's just think about this very, very logically. If I have a cause of hypoxemia that's outside the lungs, then the problem is, hey, I'm just not bringing in enough oxygen into the lungs. If you don't bring enough oxygen into the lungs, you're not bringing in enough oxygen into the alveoli. Do you know what's going to happen? Then, the alveoli is not going to have enough oxygen to deliver to your pulmonary vessels. Right? So it's like garbage in, garbage to arteries. Right? So garbage into an alveoli, garbage into arteries. You didn't bring in enough oxygen into your alveoli. The alveoli cannot make oxygen out of thin air. It literally has nothing to give to your arteries. So the spread between those two numbers will be normal. That'll be a normal ingredient. If a non-oxygen is not coming into your alveoli, then your alveoli cannot manufacture oxygen of its own out of the blue to magically give to your arteries. Right? You give garbage to your alveoli. So your alveoli is going to give garbage to your arteries. So there's garbage in your alveoli. There's garbage in your arteries. So the spread between those numbers is completely fine. Right? So whenever you have an extra pulmonary cause of hypoxemia, that's going to be a pseudo-dynamal ingredient.

Hmm? What are those extra pulmonary causes? What will cause you to put garbage amounts of oxygen in your alveoli? Well, easy. If you take a ton of opioid, you hypoventilate, right? Or you're like, hmm, I want to climb out Everest without preparing. Well, that's going to put you in trouble. Right? Remember, as you go to a higher elevation, the atmospheric pressure goes down. So there's still 21% of oxygen in the atmosphere, but you have 21% of a smaller number. Right? So let's say, hey, at sea level, atmospheric pressure is 760. But you go to the top of the Everest. I don't know what atmospheric pressure is there. Let's make up a number. Let's say 600. 21% of 760 is like 152-ish, more like 159.0 something, but different discussion. But if you go to the top of Everest, let's say it's 600. 21% of 600 is like 126, I think. 152 is not 126. When you go to the top of Everest, you're sending less to the alveoli. Since you're sending less to the alveoli, the alveoli is just going to send less to your arteries. So the spread between those numbers is not going to be the same. Right? There's just garbage in our VOLI, garbage in. So it's going to deliver garbage to arteries. Garbage minus garbage is normal. Right? So you're going to have a normal AA gradient when you have an extra pulmonary cause, an extra pulmonary cause of hypoxemia. But you're going to have a high AA gradient if you have an intra pulmonary cause, an intra pulmonary cause of hypoxemia. Right?

So that means that there is somebody that is serving as a barrier. There is something that is making your VOLI not contact your arteries very well. Right? There's something in your... There's something making your VOLI, the oxygen inside your VOLI, not contact your arteries. Right? So because they cannot establish contact, they cannot establish contact. The spread between those partial pressures of oxygen is going to widen. Right? So like for example, if a person has pulmonary fibrosis, you're making the alveolar walls thick. You're building a wall, literally, between the alveolar loomand and your arterial loomand. If that wall is too thick, then it's like, oof, the oxygen is going to be stuck in the alveolar. It's not going to be able to get to your arteries. So the spread between those things are going to widen. Right? You're going to have a high, an ingredient. Right? Or if you have some kind of VQ mismatch. Right? Ventilation proficient mismatch. Let's see you have a PE. Let's say you have like the worst, terrible PE. Right? Your pulmonary arteries are occluded. If your pulmonary arteries are occluded, is blood able to get to the lungs? No. If blood doesn't get to the lungs, is it going to get oxygenated? No. If it doesn't get oxygenated, what happens to the amount of oxygen in your blood? It's going to dip. Right? Well, there's oxygen in your alveolar. It's just waiting. It's like, I guess we'll see when blood will show up. But the blood never shows up.

The blood never shows up because the pulmonary arteries have been occluded. So guess what? That's going to cause a high, an ingredient. Right? Or if you have like a right to a left shunt, let's say you have like some like icing mängers or something bad. Where like blood flows directly from the right side of your heart to the left side of your heart. Did that blood, that's a shunt, by the way. That's a shunt, by the way. Did that blood ever get to your lungs to get oxygenated? No. The alveolar is working just fine. It's like, hey, I brought oxygen, but I don't see any blood customers to pick up this oxygen. Right? So guess what? That's going to cause problems as well. That's going to cause a high, an ingredient. In fact, there is one crazy question our friends at the MBM is going to really shake you up. That's an EV malformation. What happens to the AEG radiance when you have an EV malformation? Let's say for example, you have a Hereditary Hemorrhagic Telangectesia, which many people know as Osler, Weber, and Dulcendrum. The thing that's going to happen is you have EV Ms. What's an EVM? What's an EVM? An EVM is a direct connection between an artery and an vein. Hmm. Direct connection between an artery and an vein. Is that a normal situation? No, it's not. It's not a normal situation. The normal situation of life is that blood goes from arteries and then goes into capillaries and then goes into veins. That's how things are supposed to happen.

So an EVM, you skip the whole capillary part and the thing is capillaries are important. Why are capillaries important? Capillaries are important because that's where gas exchange happens. So if you have a HHT Osler, Weber, and Dulcendrum, you have a lot of pulmonary EV Ms. Blood is flowing through your lungs, blood is not flowing through capillaries in the lungs. So even if blood is flowing through your lungs, it's not flowing through capillaries. So that blood is flowing through your lungs, but it's not getting oxygenated. Hmm. So if it doesn't get oxygenated, what will happen to the partial pressure of oxygen in your blood? It's going to be low. Hmm. Okay. But by having those pulmonary EV Ms, it's not doing anything to the amount of oxygen inside your eye. So the spread between those numbers is going to widen. Okay. So a killer USM-Lq question, which can really shake a lot of people is that, hey, what happens to the AA gradient? In people that have Osler, Weber, and Dulcendrum, it's high. And again, it's not something you have to memorize. It makes perfect sense if you think about it. All right. So that's all those are all the gaps I have for you. Serum anion gap. We talked about that. You're an anion gap. We talked about that. Osmolo gap. We talked about that. Serum, Albumina, Cytis gradient. We talked about that. AA gradient. We talked about that. This is one of my more usual lectures, but honestly, the stuff is pretty high yield.

It will break open your understanding for so many concepts that people just blindly memorize. You don't have to blindly memorize things if you're just kind of putting the time out attention to try to understand stuff. So do you like the way I teach? If you do, then you're going to love my classes. I have a bunch of classes coming up starting next week. Actually starts next Monday and rolls all the way to the Monday after that. Right before things give it. Right. So I have a test taking strategies class. It's one and a half hours long. It's for step one to three. I have a biostatistics class. It's a four hour classes for step one to three. I have a social sciences and ethics class. It's a five hour classes for step one to step three. It's all taking place next week. I made a podcast where I highlight those classes. Again, I think you can really benefit a lot from them. So if you're interested, shoot me an email. I can give you some more information. So those are step one to three classes. How about step two and three classes specifically? Well, I have a 20 hour class for step two and step three. That's coming up next week as well. It's going to be taking place next week Saturday, Sunday and the Monday after that. It's compressing to three days. It's a 20 hour class. Eight hours one day, eight hours the two, four is the three. So 20 hours total. It's for step two and step three specifically level two, level three.

And then if you're studying for step one, if you're studying for step one or level one, I have a killer class that is coming up the first five days of December, December first to December fifth. So 25 hour class, five hours every single day. And the class is for who? For people taking step one or level one or for people taking step two or step three or level two or three. I have poor basic science foundations because the truth is these exams, these exams are hitting the basic sciences hard. Step two, step three, level two, level three. They're hitting the basic sciences hard these days. So I recommend the step one review to many people. Many people actually benefit from it. And the thing is, it's very clinically focused just like step one has become these days. Right? For those of you that have not taken step one from any years, go back and look at the step one practice questions these days. They're like extremely clinical. Right? So you want that extremely clinical focus? You're going to really like the class. And again, I break down path of physiology. I don't just give you stuff to memorize. There is some stuff you'll have to memorize. But I really try to explain things. Right? I really try to explain things, make integrations, show you how they're going to test those things on exams. So you're going to benefit a lot from those classes. I also for one or one tutoring, although that's limited. But I do offer one or one tutoring sketches pretty busy.

And then I have these podcasts again on the different apps Apple Google Spotify. I have a You Tube channel, Divine Intervention, USM.ly podcast and videos where I post the videos that I make. And then don't forget, I also help with era's applications, mock interviews, personal steaming editing, recommendation letter editing, era's application editing. I do all those things. And finally, I have another website called Divine Intervention Lifelessens.com. Divine Intervention Lifelessens.com. Every week, I post like one to two podcasts where from a biblical perspective, many of you know I'm a Christ follower, from a biblical perspective, I post a life lesson. Many people listen to that and they find that to be helpful. Divine Intervention Lifelessens.com. There's actually an Apple podcast associated with that called the Divine Intervention Life Lessons Podcast. So thank you for listening to me today. This is one of my longer podcasts, but it's pretty high yield. I'll see you in the next podcast. God bless you and bye for now. Thank you.

$\text{Anion Gap} = \text{Na} - (\text{Cl} + \text{HCO}_3)$.

The body is compensating by losing bicarb and replacing it with chloride, keeping the overall electrical balance stable.

Lactate consumes serum bicarbonate ($\text{HCO}_3^-$) for neutralization, depleting the base component of the formula.

To differentiate between diarrhea-induced NAGMA and distal Renal Tubular Acidosis (RTA).

Significant bicarb loss from the gut (e.g., severe diarrhea), leading to high urinary chloride excretion.

The cause of hypoxemia is an intra-pulmonary problem, such as V/Q mismatch or fibrosis, where gas exchange surfaces are impaired.

8 to 12 mEq/L (or $\le 12$).

Portal hypertension (e.g., cirrhosis, portal vein thrombosis).

Negative UAG (due to massive $\text{HCO}_3^-$ loss and compensatory high urinary chloride excretion).

Distal RTA (Type 1 RTA), because the kidney fails to acidify urine, leading to low urinary chloride.

Inflammation or cancer (due to increased vascular permeability) OR Nephrotic Syndrome (due to hypoalbuminemia).

Methanol and Mannitol (or other alcohols/polyols).

8 to 12 mEq/L (or $\le 12$).

Portal hypertension (e.g., cirrhosis, portal vein thrombosis).

Negative UAG (due to massive $\text{HCO}_3^-$ loss and compensatory high urinary chloride excretion).

Distal RTA (Type 1 RTA), because the kidney fails to acidify urine, leading to low urinary chloride.

Inflammation or cancer (due to increased vascular permeability) OR Nephrotic Syndrome (due to hypoalbuminemia).

Methanol and Mannitol (or other alcohols/polyols).