DIP Episode 289 - The Ultra HY Alcoholic Podcast for the USMLE Step 1-3

Okay, welcome. My name is Devine. This is episode 289 of the Divine Intervention podcast. And in this podcast I'm going to be talking about an important topic. This is a topic that shows up on step one, step two CK, and on step three. And the topic is going to be alcoholism and the USM Ls, right? So we'll be like Devine, are you trying to teach yourself to be alcoholics? No, that's certainly not my goal here. But I just want to discuss alcoholism in the context of every possible way for the most part that you can show up on a step one exam, on a step two CK exam, on a step three exam. It'd be surprising how many questions on issue SME comes from alcohol. It can come from a biochem perspective. It can come from a clinical perspective. It can come from a SQLI perspective. So we hit all those things. And then at the very end, I will talk about the comprehensive step to CK course that I've been advertising for a while. So the thing is so alcohol, right? We all know what alcohol is. Alcohol is ethanol, right? You know, people drink a ton. And you know, for many different reasons, I'm not going to judge anyone here. But basically, like, you know, people get people, you know, people drink alcohol for many different reasons. And when you consume alcohol, you know, you can have a lot of deleterious effects in the body. And, you know, in general, for purposes of MBM exams, you want to know that if a person has alcohol withdrawal, you have to treat it.

Alcohol withdrawal is fatal, right? You can go into delirium tremens. They can have all these visual hallucinations that you've probably heard of as alcoholic hallucinosis. So for those people, you usually want to give them a benzodiazepine, right? And if you want to give like a long actin like prophylactic benzodia, you want to use something like a chlorides epoxide, chlorides epoxide is what's known as lebrio. It's a long actin, a benzodiazepine that can be used to prevent the sequelae over alcohol withdrawal, right? And classically, on MBM exams, when they give you alcohol withdrawal questions, it'd be a person that after surgery, they start having visual hallucinations, they start to be weird, they start to have incisions, right? And it's usually like going to be surgery that they had to have because they were in some kind of trauma accident. Obviously, the thing that put them in the trauma accident in the first place was that they were drunk, right? So that's the way that usually presents. And then remember, for a person who has alcohol used the sort of NBM Es, you want to consider putting them on an outtrek soon or e-compersit. Those are the classic drugs that I used on NBM Es to treat alcohol used the sort. And you know, you should also recommend that those people get into alcoholics anonymous. So the thing is alcohol, so how those alcohol works.

So really, like this podcast, again, I want to take it from a path of physiology all the way to clinical presentations and all those things because again, it's just something I want that if a person that's taking step one listens to, they'll get all the alcohol is in questions, right? If a person's taking step to CK step three is listening to this, they'll get all the alcohol is in questions, right? You should expect a few alcohol-related questions on you exam, right? So let's look at it from a metabolic perspective first, right? So the thing is where do, you know, after a person drinks alcohol, what happens to it? Well, the thing is, alcohol is actually reabsorbed in the stomach and in the small intestine, especially in the do partner, right? So many people for some reason think that the stomach has no ability to reabsorb certain things that is just not true, right? The stomach is actually able to reabsorb not just alcohol, right? But you can absorb some other things, but alcohol is reabsorbed not just in the stomach, but also like in the small intestine. And one thing that happens after it's been reabsorbed is that it then goes to the liver to be metabolized, right? I remember from studying this, right? That first, you know, alcohol dehydrogen is walked on the alcohol and converted to acetaldehyde. And then, as a acetaldehyde dehydrogen is, we then act on that as a acetaldehyde and converted to to acetic acid, right? So those are the two big enzymes.

And then there are also some liver, cytokromem enzymes like C2 E1. That's especially useful for those studying for step one that metabolize alcohol. And remember that alcohol has zero-order elimination, right? Alcohol has zero-order elimination. Remember, there are three things in general that have zero-order elimination. You need to know for endemic exams, right? Phenetone is one of them. Ethymol or alcohol is another, they're an aspirin, right? So remember the P, P in the morning, PEA, right? So Phenetone ethanol and alcohol, right? So you get rid of a fixed amount per unit of time, right? Not a fixed fraction per unit of time. That's an important distinction to keep at the back of your mind, right? So the liver does a lot of metabolism of alcohol. But again, even the stomach, the thing is the stomach will really please a huge role. As you'll see, when we get to talking about wanky carcacin syndrome, the stomach also plays a huge role in the metabolism of alcohol, right? And the thing is, it's not just in the liver. You don't just find alcohol dehydrogen is only in the liver. You can also find alcohol dehydrogen is in the stomach, right? And the thing is in women in general, they tend to have very low levels of alcohol dehydrogenics in the gastric lining, right? So because they have lower levels of alcohol dehydrogenics, they reabsorb a lot of just straight up alcohol, they just consumed.

That is why if a man drinks a certain amount of alcohol and a woman drinks the exact same amount of alcohol, the woman who will in general have higher levels of alcohol, like just straight up alcohol in her blood compared to the man, right? And remember, in general, women just generally have like a lower blood volume, right? Or you can see like all the fluids in their bodies just less somewhat than men, right? So that alcohol is being distributed over a smaller amount of fluid. So it's just a lot more concentrated, right? So again, this is precisely why women did tend to have higher blood alcohol levels for the same level of alcohol consumed compared to men, right? So this is particularly why again women, they can have a lot of really bad sequelae from alcoholism because it's almost like alcohol has like an increased bioavili, I guess if we really wanted to summarize this and make it a, you know, pretty easy to remember. Essentially, women have a higher bioaviliability of alcohol compared to men, right? Women have a higher bioaviliability of alcohol compared to men, right? So again, very high you to know the enzymes that metabolize alcohol and notice men versus women differences, right? So what are some things that happen with alcoholism from a biochemical perspective? Well, if you really think about it, alcohol dehydrogen is, right? And as a touti-hydrogynees because these are dehydrogenes enzymes, these enzymes lead to the formation of a lot of NEDH, right?

They need to lead to the formation of NEDH. So that means any reaction that uses NEDH as a reactant is going to work better, right? So what are some examples of those reactions? Well, the first one is going from pyruvate to lactate, right? Because remember, normally in glycolysis, that pyruvate to lactate step happens at the end so that you can regenerate NED plus for that glycerol, the high three-phosphide dehydrogeny step in glycolysis so you can keep going. So when a person is a big-time alcoholic, in going from pyruvate to lactate, you convert NEDH to NED. So that's why lactica builds up in people that are alcoholic, right? So again, they can give you a question about like some chronic alcoholic or a person that's acutely intoxicated and give you a bunch of acybase values. You want to pick the one ready a bicarbase law, right? Because alcoholics, they tend to have like a big-time lactica sedoses, right? And then also going from acydoacety to beta hydroxybutyrate, that's also done by that also that reaction also makes NEDH get converted to NED, right? So again, alcoholics, they tend to have high levels of beta hydroxybutyrate, which again is an example of a of a ketone body, right? So if you don't come to you as a surprise that alcoholics, they tend to have acydoacidosis as well, right? And then the thing is if you remember from glycolysis, right?

So you know, you have fructose, your fructose, you know, one six-base phosphate and then that fructose, once this phosphate is split by aldolase, at least one of its isophorms, right? And then you form a dihydroxyacetone phosphate. Well, the thing is that dihydroxyacetone phosphate can be converted to glycerol three-phosphate, right? Again, and in this reaction, NEDH is also converted to NED, you can remember alcoholics the half-high levels of NEDH. And the thing is for those of you that are taking step two, CK step three, I know this basic science part may be boring you a bit, but the thing is if you understand it, it'll make the step two, CK step three stop just like extremely easy, like it won't seem like I'm trying to force you to memorize something. That's the thing I always tell people, one of the best ways of learning, even as a resident, even as a senior med student, like a third, fourth year, is just to understand pathophysiology. If you understand pathophysiology, you can see clinical problems for what they are and solve them, just not more predominantly, but anyhow, right? So, this glycerol three-phosphate that's made from DHCP, right? Dihydroxyacetone phosphate, you can actually use it to make triglycerides. Remember triglycerides, right? Literally contain glycerol and three-phary fatty acids, right? So glycerol or three-phosphate, right? It leads to the formation of fatty acids, right?

So this is one of the reasons why alcoholics be thin to get hepatic steatosis, right? They get a lot of fatty liver because, again, just all that, like really many of the metabolic things you see in alcoholism, you can trace it back to having elevated levels of any DH, right? The elevated levels of any DH. So again, that's really high autonore. So again, alcoholics, they'll have a low-bicarb, they'll have a high anion gap metabolic acidosis, right? And remember, I said that, alcohol dehydrogen is converted alcohol to acetaldehyde. Remember alcohol dehydrogen is, is actually the recline-itine enzyme of alcohol metabolism, right? And then that acetaldehyde dehydrogen is, right? Converts acetaldehyde to acetic acid or acetyl-toe whatever, right? Guess what that acetyl, you know what? It can actually be converted down the line to acetyl-coe, right? It can be converted to acetyl-coe. It can be converted to acetyl-coe. And again, remember acetyl-coe is one of those big feet stocks that I necessary for the synthesis of triglycerides, right? So again, that also explains why people that are alcoholics, right? Again, they tend to have high levels of fat in their liver. They tend to have a lot of fat in their liver, right? So and this pyruvita that is being converted to lactate, you can already begin to see that because if you think back to gluconeogenesis pyruvita is actually one of the key agents used in gluconeogenesis, right?

Remember, like pyruvates to oxaloacetate and then oxaloacetate, it's being converted to phosphorynopyrovate, right? So the thing is when people are alcoholics, right? Again, they are depleting their pyruvita, putting all in lactic acid. And as they keep putting all in lactic acid, right? There's less pyruvita available. And that pyruvita is not available. They are not going to be able to do gluconeogenesis, so people that have alcoholism, they tend to be hypoglycymic, right? They tend to be hypoglycymic. It's very important to know that they tend to be hypoglycymic. And one thing that they love to test on imbiimis are like, okay, what are some labs you may find in a present that's an alcoholic? Well, the thing is people that alcoholics remember, they tend to have this asd to ALT ratio that's usually greater than 2 to 1, right? Although to be honest with you, I would not stick with that heart and fast-reloin imbiimis. As long as the EST is appreciably higher than the ALT, even if it's not in a 2 to 1 ratio, the person is likely an alcoholic of some sort, right? And again, you may wonder, okay, why is the EST much higher than the ALT? Well, it makes sense. The thing is alcohol directly is like directly toxic to the mitochondria, right? So it basically destroys the mitochondria. So when you destroy the mitochondria, you can already begin to see that there will potentially be some problems, right? Like one, you're going to have a lot of issues with ATP production.

And then two, that cells soup all those enzymes that you find in the mitochondria are going to be released, right? Like, AST, aspartate transaminase, is actually a mitochondrial enzyme, right? So when the mitochondria is destroyed, all its contents will leak out into the bloodstream, right? And that's going to cause an increase in AST, right? Not just basically like releasing AST from the bag of AST, which in this case is the mitochondria, right? And the thing is, if you remember, whenever a person has a lot of lipid metabolism going on, they need a ton of smooth endoplasmic reticulum to make that happen, right? This is something you probably learned in cell biology in your first year or something like that, right? If you're dealing with lipid metabolism, you need a lot of smooth endoplasmic reticulum, right? So the thing is, again, I already talked about how people that are alcoholics, they have high NEDH, and because of that high NEDH, they have a lot of glycerol 3-4-feet. So because they have a lot of glycerol 3-4-feet, they are making a ton of lipid, right? All that lipid metabolism, you need smooth endoplasmic reticulum to make that happen, right? Well, for all that smooth endoplasmic reticulum to come on board, you basically need to make a ton of them, right? So you need to make a ton of them.

So people that have, that are big time alcoholics, they actually have, again, they can easily make this a cell biology question on step one, they have a higher number of smooth endoplasmic reticulum like in the hepatocytes and things like that. And the thing is, one enzyme that is very useful in the smooth endoplasmic reticulum is gamma glutamol transferase, GGT, right? So as you're making most smooth endoplasmic reticulum, you should have a commensurate increase in your GGT levels. So this is why an increase in GGT is a relatively specific finding on embankment exams and alcoholism, right? So that's actually higher to know for exams. Although GGT is not just elevated for those reasons, right? GGT is also elevated when a person has obstructive liver disease of some sort, right? He has obstructive liver disease. So many times, you know, give you these questions on embankment, where the out force is elevated and the GGT is elevated. That localizes the out force elevation to an obstructive liver disease. But if you notice that while the out force is elevated, but the GGT is normal, then that out force elevation is almost invariably going to be from metabolic bone disease on an embankment exam. So again, that's one way they can integrate those things on tests. And then remember, people that are alcoholics, they also tend to have a pretty high, pretty high incidence of a like gout, right? Or even nephrolathiasis. So you may wonder why?

Again, all this lactic acid, all this bit of hydroxybutyric acid, that's increasing because they have high levels of any DH. Well, those things, the body is going to try to get rid of them, right? It's going to use a transporter to try to get rid of these things. Only problem is those transporters that your body uses to get rid of lactic acid, to get rid of beta hydroxybutyric acid, those are the same transporters that I used to get rid of uric acid, right? So there's more competition. Right? So if there's more competition, you have less excretion of uric acid, right? To be like an under excreter of uric acid. So that's going to cause hyper-uricemia, and that can increase the presence risk of gout, right? That can increase the presence risk of gout. And again, if you have a ton of uric acid, again, that could potentially lead to crystalline the frappathy, right? Like uric acid, uric acid, stones, right? So with us, all the ways your friends at the MIME can go after alcoholism. Well, the thing is alcoholism can cause many problems, right? It can cause many problems. It can cause like a megaloblastic anemia, right? Because the thing is alcohol directly inhibits the reabsorption of folate in the gut, right? In fact, many people that are alcoholics tend to have big time folate deficiency, right? Because again, there is an enzyme that helps you reabsorb folate in the GI tract. That enzyme is directly inhibited by alcohol, right?

So people that have alcoholism, they'll have low folate because they're not reabsorbing adequate amounts of it. If you're not reabsorbing adequate amounts of it, you know, they're going to have a lot of problems with DNA synthesis, right? So because they have DNA synthesis problems, they'll have a megaloblastic anemia. So the MCV will be greater than 100 and the greater than 100 on an MIME exams, right? And then many times, right, they can give you a question on MIME is about an alcoholic that was found down, right? And then you'll see that OMS brings the alcoholic to the hospital and this alcoholic has like red urine and elevated creatinine. Well, you want to think about our abdominal analysis, right? So remember again, you drink, drink, drink a ton, right? You pass out for like 18, 24 hours, whatever, however long it takes. The thing is when your muscles are not being used, right? They're they're going to be destroyed. They're going to start breaking down. An alcohol is also again directly toxic to muscle. So that myoglobin is going to be released into the circulation. It's going to go torch the presence kidneys cause an acute tubular necrosis, right? So you'll have like an acute kidney injury. You'll basically have an injury or an acute kidney injury, right? And as you'll see, right? Those people's urine will be red. And again, when you do your analysis, you'll see a ton of blood, it'll be like three plus four plus blood.

But then you do your urine microscopy, you don't see any red blood cells. That tells you that you're dealing with your dealing with myoglobin, right? And then remember, alcohol in and of itself, right? As I said, it's metabolized by this cytochrome P450 system, right? Like, like, like C2 E1, for example, in fact, I think I may have mentioned this in prior podcasts before. Remember, alcoholism can actually modulate the cytochrome P450 system, right? For persons with chronic alcoholic, the cytochrome P450 system will be revved up, right? So they can give you a question about a person that gets pregnant. On while taking OC Ps, that's an alcoholic. Well, that's what happened. She took a ton of alcohol, you know, big time alcoholic. Whenever you're a chronic alcoholic, Cp450 is revved up, right? Because again, you got to metabolize the alcohol somehow, right? It can just chill in your body, right? So as that Cp450 has been metabolized, I mean, as the alcohol has been metabolized by Cp450, you know, Cp450 is revved up. So you're going to start metabolizing all the drugs very quickly, like OC Ps, for example. So the person can get pregnant. What remember, when a person acutally drinks a large amount of alcohol, right? When you drink a very large amount of alcohol, that actually causes an inhibition of the cytochrome P450 system, right? So the P450 system is inhibited when a person is acutally alcoholic, the P450 system is revved up when a person is a chronic alcoholic, right?

So going back to this whole liver business, right? So because if a person is a chronic alcoholic, we drink a ton of alcohol, right? Over time. And the Cp450 system is revved up whenever a person has like a hympathway problem, that's going to, that's going to be exacerbated by consuming alcohol, right? Because those hympathway problems, the thing, the last thing you want to do is to cause more flux through the hympathway, right? So the disorders I'm talking about here are things like perfuricutinia tarda, or you know, which is a uroid deficiency, right? Europe of urology in decarboxylase, or acutin to methane perfuric, which is, which is, what's the sense? I'm command divine. Pinalboda and jelly diamines, right? So buffalb, bilinogen diamines, deficiency, right? So if you increase flux through those pathways, those profiling will begin to accumulate and the person will start having like an exacerbation of symptoms, right? So again, whenever you give any Cp450 activator, like alcohol, right? Or you know, things like barbiturates or, who cares, you're full of carbamazepine, phenetoin, rifampine, St. John's word, so that could be a hub of supplement question. You can always exacerbate the presence symptoms of perfuricutinia tarda, or acutin to methane tarda, perfuric, right? So that's why you don't, again, that's why alcoholism is not great. And I think one thing I forgot to mention, when I was mentioning the alcoholic enzymes, right? Remember this drug, disulfurum, right?

I think the treating is anti abuse. It inhibits as a toutohydi hydrogenase. It's a drug that you can use for people that are very motivated to stop drinking, right? Because when you inhibit as a toutohydi hydrogenase, you're going to have very high levels of as a toutohydi. You're going to have a very serious hangover, tomobomidine, stuff like that. But again, on NBM is, though, your first line agents that you want to use to treat alcohol, use the solder, things like naltrexone and naltrexone and e-comperseed, right? Naltrexone e-comperseed. And don't forget that disulfurum is a side effect, right? So like, if a person is being treated for like, ganearella vaginalis, so like bacterial vaginosis, or giargia, or entamibahistolereca, right? Stuff like that, right? Again, if you're taking metronidazone, metronidazone has the ability to inhibit as a toutohydi hydrogenase, right? That's why people can have this disulfurum effect. We're taking metronidazone, fragile, basically, right? So you need to be careful in that regard. Again, you can just see the different ways, you can integrate alcoholism on NB Ms, right? So just something you want to be mindful of. Something you want to be mindful of, right? So we've talked about again how alcoholics can get fully deficiency and get them a globalistic anemia as a result of that, right? Remember, in fully deficiency, your homocysteine levels will be elevated, but your metronidazone levels will be normal, right?

And the thing is alcoholism can cause infertility, right? That's a classic thing, the test on NBM exams to talk about a person that's having trouble, you know, having an erection, having trouble, uh, procreating with their spouses, right? And alcoholism is the cause, right? Because especially in men, alcohol, actually, um, uh, mix the test, like again, alcohol is a cytotoxic agent, basically, because if you really think about it, right? You probably remember some of the stuff I don't know, like your first year or whatever, how when the mitochondria is porous, when is destroyed, certain agents are released from it, that trigger a boptosis, right? We know that alcohol is a mitochondrial toxin, right? So if you damage mitochondria, that's going to be a problem. It's just simple as that, right? That's going to be a huge problem. So the thing is many times over, if a person keeps taking alcohol over time, especially cells that have a lot of mitochondria, that have a lot of the, you know, very dangerous stuff that can be released, that can trigger eboptosis. Um, when a person is an alcoholic, over time, cells will begin to die. They just, like, cells can begin to die in the, in the testicles, right? That's why people that have, that are big time alcoholics, they tend to have, um, very small testicles, right?

And if you have small testicles, because you've killed of many of the cells in there, and I'm going to be making as much testosterone, testosterone is the primary control of libido, is the primary control of sex drive, right? And you're also not going to be making adequate amounts of sperm if you're a big time alcoholic, right? And obviously there's this whole thing with fetal alcohol syndrome, right? Remember the key thing there is the philtrum, right? Is the philtrum? Uh, they will have some kind of philtrum anomaly, right? Because the envy me, they do this party trick where they'll mix and match all these, uh, uh, findings you see in other genetic disorders, and then you'll throw in philtrum there. Basically, if you ever see any envy me question, and the philtrum is abnormal, it's going to be fetal alcohol syndrome, right? So they can call it like a small philtrum, they can call it an indistinct philtrum, uh, they can call it a barely perceptible philtrum. Basically, if you see any philtral abnormality, right? That's going to be fetal alcohol syndrome, right? Remember, those keys, they tend to have intellectual disability, they tend to have all these cardiac defects, especially VS Ds, right? If you see like a cardiac defect question in a fetal alcohol syndrome, always speak VSD, always be VSD, that's kind of like the big one there, right? And then if you're looking at like the esophagus, for example, right?

People that have alcoholism, they can have like malaria-wise tear, right? You can have malaria-wise tear. Um, although remember, who they have malaria-wise tear, they'll just have like blood in their in their in their in the stuff they expect to reach and the stuff they cough up, but they will not be human dynamicly unstable, they will not have the subcutaneous infezima or anything like that, right? Because obviously for persons who have a dynamicly unstable, or they have high fever or the apietoxic, or you see the subcutaneous infezima, or you see like nummideastinum, um, or neuropericardium, right? Then you're beginning to worry about those people potentially rupturing their esophagus. In that case, right? That's bear-half syndrome, right? Bear-half syndrome. Remember, if you ever suspect that the esophagus has ruptured and you're asking you for a diagnostic test on your exam, remember, you don't want to use barium. You want to use gastrographic, right? Remember, another name for gastrographic in on NBM Es is water-sunable contrasta, Nema, right? And again, alcoholism again, if a person has hepatic stia-tosis over time again, from this elevated levels of any of the age leading to increase synthesis of glycerol, three-phosphate, then over time the presence liver can begin to fail, right? And the presence liver fails, they can develop portal hypertension, right? And that can cause us of adiovericides, right? And so adiovericides again, it's a huge problem, right?

It's a huge problem. It's a huge problem. And again, with all these direct toxic effects of alcohol on cells, right? It can damage the asinar cells that make up like your pancreas, your pancreatic dots. So you can begin to release all these pancreatic enzymes prematurely and then destroy the pancreas, right? That's how people get acupuncturitis. That's how people get chronic pancreatitis. Remember, chronic pancreatitis on imaging. You'll notice that these people's pancreas, they are all, they're all calcified, right? So they have like a calcified pancreas. I mean, essentially, that pancreas is dead. And that pancreas is dead again. That's going to be a huge problem, right? Because I'm not going to be able to make insulin, right? So those people are going to be automatic diabetics. But then in addition to being a diabetic, they also not making pancreatic enzymes, right? So those people are going to have an absorption, especially like a fat, an absorption, they're going to have like oily stores, they're going to have floating stores, right? So for those people, usually on inbimies, you'd have to give them pancrea lipes, right? Pancrea lipes. You need to give them pancrea lipes on inbimic enzymes, right? And if I'm saying I was chronic pancreatitis, please don't pick the answer that involves resetting the pancreas. I can almost guarantee you get the question wrong, right? And remember that alcoholism, like alcohol has like an additive effect on many malignancies, right?

On many malignancies, especially like scrimmosell cancers of like their suffigals, of the oral tract of the, you know, firing geotracking on all those things, right? So just stuff to be aware of with alcoholism, right? Again, alcohol, mitochondrial, I think there are just some key things I've kind of hit on today. Again, I'm not done with this podcast, sorry. I want this again to be really comprehensive to alcohol. I want you to listen to this podcast and after you listen to this, any alcohol question, you see you just, you just, you'll just be like an auto-click question, hopefully for you on the exam. Again, big theme I think I've discussed a lot of today is alcoholism, mitochondrial toxin. If you damage the mitochondria, you release things that cause cells to undergo hipoptosis, right? That's a pathway, maybe I'll talk about it like in a future podcast, but I don't want to go down that route right now because I have quite a bit, I still need to discuss, right? So, again, if cells begin to undergo hipoptosis, you begin to lose cells that, again, especially that have a lot of mitochondria, because the cell that has a lot of mitochondria, if it's exposed to a big time mitochondrial toxin like alcohol, then that cell is more pretty exposed to hipoptosis. So without the cells that have a lot of mitochondria in the body, well, the cells in your cerebellum, right? So as they begin to die, as the prison begins to lose the perkinji cells, right?

They have like atrophy of the cerebellum, or your cerebral cortex, again, as those cells begin to die, right? The cerebral cortex gets smaller and smaller, right? It gets smaller and smaller. So that's why people that have that alcoholics, they tend to have a very like cerebral atrophy, right? And again, whenever you have cerebral atrophy, you can already begin to see that, it's almost like your skull is not like your skull gets smaller, your skull is a box, right? It's a bone. So the thing is, that skull, if you have a smaller brain inside it, then that brain begins to dance around, in the present skull. If that brain begins to dance around in the present skull, you'll begin to have a sharing of your bridging veins, right? That's why subdurolycema tumor. So if you get a question about an alcoholic, where did you notice that man? Well, the last two weeks, this person has become more somnolent, no very responsive, has signs of increase in entrepreneurial pressure. You want to think about a subdurolycema tumor, right? Sharing of those bridging veins, that's a very common finding in people that are alcoholics. Just again, the pathophysic mix sense, they have cerebral atrophy, right? So they have a smaller brain dancing around in a fixed size box, aka the skull, right? So they can share those bridging veins and get a subduro, they can get a subdurolycema tumor, right? They can get a subdurolycema tumor.

Now, to, I guess maybe your upper conversation today, the thing I'm really going to hit on from an alcohol perspective is wernicicorsoca. These are some of those things you can almost guarantee, you're going to see in some way shape of form on your exam, right? On your exam. So what is this whole deal with wernicicorsoca syndrome? The deal with wernicicorsoca syndrome is, these people get it because of a thiamine deficiency, right? These people get it because of a thiamine deficiency, right? Remember thiamine is vitamin B1, right? And wernicicorsoca syndrome, right? I mean wernicis, you probably should separate this. And again, I'll talk pathophysiology in a bit, right? So you need to understand, okay, what are the findings in wernicis? Well, it's a triad, right? So the triad is confusion, right? The other second part of the triad is of thymoplesia. So the thymoplesia can be like a person having nice stagmus or something like that. And then the third part of the triad is etaxia, right? So these people have like problems with geats, problems with movement, right? But the thing is, usually people get wernicis first. Wernicis is like an acute event to get the wernicis first. And then after they get the wernicis, if it's not treated and it keeps going, going, going, deal with them with a corsocaf. Wernicis is reversible. Corsicaf is not. Corsicaf is irreversible, right? And corsocaf happens when a person has amnesia.

The amnesia can be antigrid, it can be retrograde, doesn't matter, right? And then they also begin to have a confabulations. So they begin to mix stuff up, right? So the thing is, people that have wernicic corsocaf, they have problems with like their memory sources, right? So the thing is, they may see something that is not true or you may tell them something that is not true and they'll just agree with it, right? So those are classic ways that wernicic corsocaf syndrome arises on the exams, right? So the thing is, what are some things that can cause wernicic corsocaf? Well, obviously the big one, right, is alcoholism, right? Alcoholism. So you may wonder, hmm, define, why does alcoholism cause wernicic corsocaf syndrome? Well, alcoholism causes wernicic corsocaf syndrome because for many reasons, right? Basically, you can maybe think of this as, okay, define, how does alcoholism cause a b1 deficiency? Or let me explain. Well, the first thing is, again, alcohol directly impairs the reabsorption of vitamin b1 in the GI tract, right? Again, vitamin b1 is reabsorbed quite heavily in the GI tract, right? So the thing is, when people have, whenever people are big time alcoholics, they're going to impair the reabsorption of b1 in the GI tract. So they're going to have a thymine deficiency as a result of that. That's one. The other thing with alcohol is thymine that you reabsorbed is not just the thymine you use, right?

The thing is thymine has to be converted to other enzymes, you know, you can, like for it's to work for it to be a cofactor, you know, which it is for many reactions. It needs to be activated, it needs to be phosphorylated, right? Into like either thymine, diphosphate or thymine, pyrophosphate. The thing is thymine diphosphate, thymine pyrophosphate, the enzymes that lead to the affirmation are actually inhibited by alcohol. So even if you have thymine in the body, it can work when the presence of an alcoholic because you're killing all those enzymes that are needed for its activation, right? And then the thing is one of the primary places where you store thymine in the body is the lever, right? But again, we know how alcohol messes up a presence lever. Well, if you mess up a presence lever, right? Because the thing is when a person has fat a lever, your hepatocytes is almost like their work in life becomes to store fat, which is not the unnatural duty. It does the natural duty of your diphocytes, right? So if most of their life's work is now to store fat, well, they're going to have a lot of problem storing all the things like thymine, right? So those are all the different mechanisms behind an alcoholic thing. Developing thymine in deficiency, right? And when you develop thymine deficiency, again, it's going to cause problems, right? Like there are certain enzymes like if you remember pyrovidia hydrogenase, right?

Remember pyrovidia hydrogenase uses a tender loving care for lancine, you know, like thymine, like boicacid, quinzyme, FEDH, and NEEDH, right? So that thymine is not available, right? So pyrovidia hydrogenase doesn't work. Then if you go down to the TCE cycle, right? There's this enzyme that also uses thymine, alpha-ketogluidorydehydrogenase. It doesn't work, right? Because again, the person is deficient in thymine, right? Remember, alpha-ketogluidorydehydrogenase also uses this tender loving care for lancine business, right? And then if you go down to the breakdown of branching amino acids, there's this enzyme known as branching amino acid dehydrogenase, right? It also uses tender loving care for lancine. Remember, that's the enzyme that's defective in a person that has me posterior in disease, right? So those people that have a thymine deficiency, right? Again, they are going to have problems breaking down, leucine, isoleucine, and veiling, right? And then remember, an enzyme in the, in fact, this is the reclimiting enzyme of the nonoxidative phase of the pentosephosphate pathway, transkytolis. Transkytolis uses thymine as a cofactor, but remember transkytolis though, doesn't use every other thing in the, it doesn't use the loving care for nancypox, it just uses thymine, right? As it's cofactor.

So you can already begin to see that they are minim metabolic pathways, especially metabolic pathways that handle glucose that will be impaired when a person has a thymine deficiency, right? So what's the deal with that? So when that happens, you can already begin to see that, this is potentially a big, big, big, big problem, right? So this is why when a person comes into the emergency room on the hypoglycemic, you typically want to give them IV thymine first, at least on NBM Es before you give glucose, right? You give them IV thymine first before you give glucose. If you give them the glucose, then you'll please more for metabolic demand for thymine that you're already deficient in, right? And that can begin to cause problems, that can trigger rainy keys, that can trigger course cofs, right? And again, alcoholism, right? Again, I've kind of talked about how we can cause how we can cause these, how we can cause these B1 problems, right? But remember, there are other people that can get rainy key course coforn NBME exams. If a person's stomach has been ticking out, right? If a person's stomach has been ticking out, so let's see, they give you a question about a person that has had a gastrectomy. Those people can also have wienicic or so cof syndrome over time. Because again, thymine is also reabsorbed in the, although this one is not as clearly elucidated, but if a moment's ticking, thymine is also reabsorbed in the stomach, right?

So when a person has a gastrectomy, they're going to develop a thymine deficiency, right? If a person has just been chronically malnourished for some reason, if a person has chronically malnourished for some reason, so let's see, for example, a person has like a classic one, they love these days on NBM Es, is a person having mostly so big guy in the sorter, hypermysiose-gravidarum. Those people, they have like a very high risk of developing wienicic or so cof syndrome, right? Or if they give you a question about like an immigrant, and they tell you that, oh, there's immigrant, you know, it's a lot of polished rice, right? That race is basically not 45, the person can, so if you see an immigrant with like wienicic or so cof syndrome, the person is not an alcoholic, it's probably from a dietary deficiency, right? The person just eating a ton of polished rice. Remember, polished rice is rice that has essentially is not 45, with thymine, right? At least in general, polished rice is not well 45 with thymine, so those people can develop a thymine deficiency as a result of that, right? They can develop a thymine deficiency as a result of that. So again, thymine deficiency alcoholism is a very, very, very high yield, it's a very high yield topic, right? It's a very high yield topic. So again, and we've talked about how alcohol can really messes up thymine metabolism in many different ways, right? And again, as we said, when the person is an alcoholic, right?

Again, you're going to have a lot of problems with energy generation, right? Because again, the power of it is depleted. So again, things that depend on energy, depend on ATP, you don't work as well, right? And again, thymine is a key enzyme for energy generation. We use thymine for the power of it, hydrogen is complex, we use thymine for the citric acid cycle, right? We use thymine for the pentose-hot-fit pathway. So if those pathways are not working, you're going to have a lot of ATP generation problems, right? A lot of ATP generation problems. So organs that use ATP like the brain begin to fail. That's how people get a lot of like against their bilatrophy, cerebral atrophy with alcoholism, right? But also remember, a part of the brain that is very metabolically active is the mammillary bodies, right? So those mammillary bodies, they undergo atrophy, they undergo infarction in people that have a thymine deficiency, right? Or again, like the heart, the heart uses a ton of ATP, right? Use a ton of ATP. If the heart is not able to make adequate amounts of ATP because again, it's a presence in alcoholics or they have a thymine deficiency, the heart becomes almost developed, they almost develop like an ischemic cardiomyopathy, which is diluted, right? So over time, people that are alcoholics, right? People that have thymine deficiency, B1 deficiency, the developer diluted cardiomyopathy, right?

That's basically, and you know, when the person's heart stops working, it's a systolic heart failure from the diluted cardiomyopathy. Fluid will begin to back up in the blood, in their blood vessels, right? So they'll have a lot of extravaciation, right? So they become it demadas, right? That's essentially why the heart failure that's associated with B1 deficiency, thymine deficiency is called weight berry, berry. When the naming sounds. So again, just these are all things to, these are all things to keep at the back of your mind with regards to alcoholism, and again, this whole thymine business. And one other thing I also want to say is, remember that people that are alcoholics, they tend to have hypomagnesemia, right? They tend to have hypomagnesemia, just in general people that are alcoholics, they tend to be hypomagnesemic, and when they are hypomagnesemic, that can cause a lot of problems, right? hypomagnesemia can make a pressing hypokalcemic, right? Because they will not respond to calcium repatient, it can also make them hypokillemic, right? And those people will not respond to potassium repatient, right? And then in addition to that, right? hypomagnesemia can cause a prolongation of the acute interval, right? In cause of prolongation, it can cause a prolongation of the of the of the acute interval, right? And the thing is, even for thymine to work, thymine requires magnesium for appropriate function, right?

So the thing is like it's almost like for enzymes that use thymine inside the cell. For them to bind thymine, magnesium is required to activate that process of thymine binding to an enzyme that uses thymine. So again, you can already see how an alcoholic just has many problems, right? Like your hypomagnesemic at this line, you already have a thymine deficiency, but whatever little thymine is available, it's not even going to be able to bind to the enzymes that need it as a cofactor, right? They need it as a cofactor. So again, just all, all high yield things to kind of keep out the back of your mind without cohalicin. So I think I've pretty much mentioned the realtor thing I want to say. Yeah, I think I've pretty much mentioned everything I want to say. And I guess maybe the last thing I'll see that I didn't mention, remember alcohol, dehydrogenase, I'm using inhibited by formapisol, right? So like if a pressing has methanol, poison, then you can give them formapisol. They only inhibited alcohol, or what dehydrogenase, so that they don't form, formic acid, which can cause a slash form out. I just can cause a lot of problems for them. So I think I'm going to go ahead and pause here. Again, this podcast is, I think as I finish it up now and begin to realize that it's probably one of the highest yield podcasts I've ever made. I would definitely encourage you to really listen to this, really know this and know this code so that you don't bungalow your exams.

And then again, as I do at the end of every podcast, there is a step two CK comprehensive step two CK slash step three. Basically, the course will be extremely helpful for anyone taking step two CK or step three. It's coming up from the 25th to the 27th of March. Again, I don't have unlimited spaces available. So once the number of spots available is full, then the course will be closed. So if you want to sign up, just shoot me an email through the website. It's 16 and a half hours. It's 5 and a half hours each day from 11 a.m. to 4.30 p.m. Pacific time on the 25th, 26th and 27. So 5 and a half hours each day. Now we cover like neuro, Pied surgery, psychoby-guine, internal medicine, bio-stats, ethics and all those things that the MBMI introduced in November of 2020 like professionalism, communications and all those things, right? Again, had the first iteration of the course. It's basically an expanded version of the 10-hour course, but again, the people that attended the course that was last week, I got extremely good feedback from them. And I also have the MBMI Testikin Strategies course. That's on the 24th of March, for 2 and a half hours. But again, we'll go through like really step to seek is step 3 is those are exams that depend very heavily on how good you are taking tests in addition to the knowledge of acolytid.

So most people take both courses together, they take the test against strategy's course the first day and then the next three days they take the comprehensive review. Again, the review is very comprehensive. We go over like 1100, very likely even close to 1200 concepts over those three days, right? So again, it's a very high-yield course and again, I go at a reasonable speed. So the vast majority of people I go to take pretty good notes. And then please subscribe to the podcast. So it's on Google Podcast, it's on Apple Podcasts, it's on Spotify. The most recent 150 podcasts will be on those apps. If you want the earlier podcasts, then I'd encourage you to go to the website. Every podcast I've made from episode one all the way down is on the website. You can download it on the website, you can listen to it from the website. And the website, just in case, is divineinterventionpodcast.com. If you subscribe to that website, then whenever I make a new podcast, you'll get a notification. And then I also have a You Tube channel, Divine Intervention, USMLE podcast and videos. So please subscribe to that. That's where I post my videos. So again, any little bit of support helps. So thank you for listening. Please listen to this podcast, me good notes. This is going to, I can almost promise you, this will be the source of many correct answers on your step one, your step two, secure your step three exams.

So today I'm not going to be sharing a life lesson, but you know, just encourage you. And I guess I want to reach out to those people in Texas. And in parts of the country where you know, they're kind of out of power. And just had a lot of problems in recent times with the weather. I print out, you know, God's grace speaks with you and you know, God's grace is with you. And you don't suffer any losses and you know, things come back to normal. At least that's my prayer. So thank you for listening. I'll see you next time. God bless you. Thank you.

Alcohol dehydrogenase ($\text{ADH}$) converts ethanol to acetaldehyde, which is then converted by acetaldehyde dehydrogenase to acetate.

Phenetone, Ethanol (alcohol), and Acetaminophen (or Aspirin).

Women generally have lower total body water volume and gastric $\text{ADH}$ levels, leading to a smaller distribution volume and thus higher concentration.

Confusion/Encephalopathy, Ataxia, and Ophthalmoplegia.

Myoglobinuria, resulting from muscle breakdown (rhabdomyolysis) due to alcohol toxicity.

Chronic alcoholism causes $\text{CYP450}$ induction (upregulation), while acute intoxication causes $\text{CYP450}$ inhibition.

IV Thiamine. It must be given first because glucose metabolism increases the demand for thiamine ($\text{B}_1$), potentially precipitating or worsening the deficiency if administered alone.

Any philtral abnormality (e.g., small, indistinct, or barely perceptible philtrum).

Alcohol is a mitochondrial toxin; damage releases mitochondrial enzymes ($\text{AST}$) into the bloodstream.

Gastrectomy (due to impaired B1 reabsorption) or chronic malnutrition/dietary deficiency (e.g., polished rice diet).

High levels of $\text{NADH}$ lead to lactic acid buildup, increasing uric acid precursors. The body's transporters for lactate and $\beta$-hydroxybutyrate compete with those used for uric acid excretion, leading to under-excretion.

Subdural hematoma (or subdural collection). This occurs because the brain shrinks and moves within the fixed skull size.

IV Thiamine. It must be given first because glucose metabolism increases the demand for thiamine ($\text{B}_1$), potentially precipitating or worsening the deficiency if administered alone.

Any philtral abnormality (e.g., small, indistinct, or barely perceptible philtrum).

Alcohol is a mitochondrial toxin; damage releases mitochondrial enzymes ($\text{AST}$) into the bloodstream.

Gastrectomy (due to impaired B1 reabsorption) or chronic malnutrition/dietary deficiency (e.g., polished rice diet).

High levels of $\text{NADH}$ lead to lactic acid buildup, increasing uric acid precursors. The body's transporters for lactate and $\beta$-hydroxybutyrate compete with those used for uric acid excretion, leading to under-excretion.

Subdural hematoma (or subdural collection). This occurs because the brain shrinks and moves within the fixed skull size.