DIP Episode 382 - USMLE Step 2CK/3 Rapid Review Series 73

Okay, welcome. My name is Divine. This is episode 382 of the Divine Intervention Podcasts. And into this podcast, I'm going to be continuing the rapid review series for the US Emily step two, CK step three exams. This is going to be series 73. If you're taking step two, CK step three, anytime within the next, I would say, four to six weeks, I do have one of two classes that you may be interested in. So one is the MBME Test Ticking Strategies class. That's going to be taking place on the 22nd of this month. And then I'm going to be having the 20 hour step two, CK slash step three. Obviously, it also applies to complex level two and third review courses to help people schedules that have to be on rotations is going to be on the 23rd and the 30th of this month. It's going to be from 80m to 6pm, Pacific time on each of those days. It's going to be 10 hours each day. And then for a more comprehensive review, I am having a divine intervention step two CK school. This is going to be taking place early, it's going to be taking place from the 2nd to the 13th of May. It's going to be from one day to Friday for those two weeks. And there is a limited number of spots for the class because the class is a high level class, very detailed review class. It's something that I'm going to invest very deeply in everyone that's attending. And I have a podcast that I meet specifically that highlights what we're going to be achieving during that class.

There's going to be an adaptive learning session. There's actually going to be adaptive learning sessions that take place every day where we use like a multi-modal or push to review material. And then we'll have also regular sessions every day where we use a lot of scenarios. I mean, there is like tons of scenarios we're going to be using to review a lot of the material that's classically tested on the exam. And then we're also going to have like a foundation section where we heat on just foundational things from step one, where the understanding is necessary and helpful to succeed in on step two. So we're going to have that. And then we're also going to have an expanded testing strategy scores that's going to be a part of it. It's going to be about five hours total. So again, if that one has a much more limited number of spots. So if you're interested in any of those courses, ship me an email through the website and I'll give you some more information on cost registration and everything. The courses are going to be held over Zoom. Each of these courses are going to have course packets that you get every day. And you're going to be able to take very good notes. There's going to be a lot of time devoted to answering people's questions. So you're going to get a lot from if you register for these classes. Okay, so let's begin. One thing I want to start off by saying is I want to talk about some key enzymes that are classically tested on the USMLSTEP2 CK, step three exams. Right?

These are things that people routinely ignore, right? But they're things that are high or to know. So let's jump into it. First one, what if they give you a question about an immigrant from Greece? And they tell you that this person was admitted for a CHF exacerbation. And then the I mean, the person sorry was admitted for a hypertensive crisis. And then the person got a proper therapy. And then he was noticed like two days after admission to the hospital. This person started having a lot of cyanosis, right? And you'll notice that this person, they will give you the bicarb will be normal, right? So the person doesn't have any acidosis. But you notice that this person's hemoglobin has dropped. And then they tell you that the LDH, the lactated dehydrogen is has been increased. And then they also tell you that the HAPTO Globin is decreased. And then they tell you that the COMPS test is negative. When you see this permutation of things, what should you be thinking about? I'll really hope you're saying, hmm, divine, I kind of know where you're coming from here. This sounds an awful lot like G6 PD deficiency. So what is G6 PD deficiency? Remember G6 PD deficiency is glucose 6.4.2 dehydrogen is deficiency. So what happened here? Well, this person came in for a hypertensive crisis. Okay, well, we know that many times, when a person has a hypertensive crisis, my trope side is a pretty good drug to give to those people.

Now my trope side and many of those nitrates derivatives, they are very powerful oxidizing agents, right? So they can put a red blood cell under just astronomical amounts of oxidative stress. Those astronomical amounts of oxidative stress can cause lots of problems, right? They can literally cause lots of problems. They can cause, you know, you to have your red blood cells humanizing, right? Because again, all these free radicals and all these things are eating them up, right? Because remember, glucose 6.4.2 dehydrogen is that pathway helps you produce any DPH. That any DPH helps you replenish your glutathione. So if that system doesn't work very well, your red blood cells even have a lot of problems dealing with the oxidative stress. And that's going to cause the molasses of your red blood cells, right? And remember, lactity hydrogen is an intracellular enzyme. So whenever you humanize things, right? It doesn't just have to be red blood cells. It can be like cells that are being killed, like lymphocytes because you're trading some leukemia lymphoma. You're going to have an increase in your LDH, right? And because the person is having red blood cell, he molasses, you can already begin to imagine that your HAP2 globin is going to go down. Remember, most times you have a hemolytic anemia, your HAP2 globin is going to go down. That's very high you to know for purposes of exams. And then that's not all of it as well.

Remember, these people, because they're having so much emolasses, what kind of bilirubin will be elevated? Well, I really hope you're saying, oh, divine. It's going to be an indirect hyperbibiliarubinemia. So these people are going to have an increase in their indirect bilirubin, right? So they're going to have an increase in their indirect bilirubin, right? And remember, on a blood smear, these people that have glucose 6-phosphate dehydrogen is deficiency, right? You're going to find these high-end bodies, you're going to find bite cells, right? And again, please don't pick g-sixptideficiency as an answer. If you see a presentation like this in a female, right, that would not be prudent. Knowing as g-sixptideficiency has ex-linked recessive inheritance, right? So since he has ex-linked recessive inheritance, it's going to be a boy, it's going to be a male disorder on the exam. And I think one thing that may be helpful here is to recognize that again, it's not just my traits that cause this oxidative stress. They can give you this question with father beans, they can give you this question with um, prima quen, that malaria drug that helps with killing those hypnosis-like forms, that you find in the liver, they can give you this with tremethoprimsulfrimethoxysol, they can give you with just many different drugs that are very powerful oxidizing agents, right? They can give you a mitrofuran toin, right? Remember, nitrofuran toin, nitro contains nitrates, right?

It's a drug that is commonly used in women to treat cystitis, right? These are all different ways they can test glucose 6-phosphate dehydrogenies on your exams, right? And you may say why is the cumstest negative? Well, remember, this immolacy is not immune-mediated, it's not being mediated by antibodies, it's being mediated by oxidative stress, right? So that's something you want to keep at the back of your mind on exams, right? Now, the thing is our friends at the MBM is really smart, right? So this presentation I gave at the beginning, obviously they're going to put glucose 6-phosphate dehydrogenies deficiency as an answer because that's the correct answer. But what are some key distractors our friends at the MBM is want to slot into these kinds of situations on exams? Well, one thing that they would love to obviously slot in is they will put cyanide poisoning, right? They'll put cyanide poisoning because cyanide poisoning can absolutely cause hypoxia, right? They're going to put cyanide poisoning because remember cyanide, right? Basically, when the patient has cyanide poisoning, right? That cyanide is very toxic to oxidative phosphorylation, right? It messes up one of the complexes of the electron transport chain. If you mess up that complex, well oxidative phosphorylation is not going to be working anymore. So surprise, surprise, you're going to be dependent on glycolysis as your exclusive source of energy.

Well, we know that there's only so much glycolysis can do, right? So those people, because glycolysis is now running at full steam, right? And there's no recourse with the TCE cycle or the electron transport chain. Lactin dehydrogenine is going to be working over time, right? So those people, they're going to be having a buildup of lactic acid, right? Because they need to keep glycolysis going, right? So that's very high yield to keep at the back of your mind for, for example, right? That's very, very high yield to keep at the back of your mind, for example, they can give you a cyanide poisoning case. But people that have cyanide poisoning, they will almost invariably have a high anion gap metabolic acid doses, right? Because cyanide poisoning can cause a lactic acid doses, right? They can tell you that they have like a special smell to their breath, right? They can give you stuff like that, right? And remember, people that have cyanide poisoning, the hemoglobin is going to be normal, right? Because cyanide poisoning does not cause you to have hemolicycin, so anything that will decrease your hemoglobin. And they also not have that indirect type of lyrabinemia that we have come to see with glucose 6-4-3 D hydrogenine deficiency, right? Another classic thing our friends at the MBM is can do, right? Is the compute methemoglobinemia as an answer? Remember, methemoglobinemia is very different, right?

Remember, methemoglobin is when iron is not in the 2-plus form because if you look at no hemoglobin, the iron that is in the 2-plus form is not in the 3-plus form. The 2-plus form is the ferrous iron, 3-plus form is the ferric iron. Ferric iron has no ability to carry oxygen. Ferrous iron can carry oxygen, every 2-plus, right? So the thing is when you have methemoglobinemia, right? Again, you're going to be powerfully hypoxic, right? Because you have the iron in your hemoglobin being in the 3-plus state, can carry oxygen, so you're going to have a lot of problems, right? You're going to have lots and lots and lots of problems, right? So they're going to be hypoxic, but again, remember, these people are going to have normal hemoglobin. That's very high-youturnal. They're going to have normal hemoglobin, right? They're not going to be in an emic territory. You're going to be in anemic territory if you have G6 PD deficiency, but if methemoglobinemia, you're not going to be in anemic territory. It's almost more like a qualitative problem with hemoglobin than a quantitative problem with hemoglobin. But hemoglobin just has the wrong charge. When it has the wrong charge, it cannot hold oxygen very well, right? Remember, for person has methemoglobinemia, you're going to treat them with methylene blue, right? You're going to treat them with methylene blue. You're going to treat them with methylene blue.

Okay, and again, a good reason why you put methemoglobinemia as an answer is because they know that methemoglobinemia has an association with taking drugs that are powerful oxidizing agents, right? So again, just keep things you want to keep at the back of your mind. They will usually be some key differentiating factors that will help you tease one thing apart from the other, right? They'll help you tease one thing apart from the other, right? And to even add to the confusion a little further, we know that if you want to treat cyanide poisoning, you're going to treat it by inducing a methemoglobinemia, right? Because cyanide, again, it has a very strong affinity for ironing the 3 plus form, right? So many times when a person has cyanide poisoning, right? We're going to treat them with an emol nitrate. Emol nitrate, again, it's an nitrate, patholoxidizing agents is going to switch the iron in your ribloids cells from the 2 plus form to iron in the 3 plus form, right? And then that 3 plus iron is very good at binding cyanide. You're also going to give cyanide, you're going to form cyanide, and then that's something that can be safely excreted from the body. Alternatively, for cyanide poisoning, you can just give cyanocobalamin, right? Cyanocobalamin is like a vitamin B 12 derivative, right? So it's pretty easy on exams. Again, you've heard me talk about derivative answers at nauseam, right? They may not put cyanocobalamin as an answer.

They just would be 12 derivative as an answer, right? And you know, you're going to use that to again go ahead and excrete the cyanide, right? So again, these are just all high-yield things to know for the purposes of your exams, right? And then what if they give you a question about a patient and tell you that, you know, these are three-year-old boy or less than six-month-old boy, and the mom tells you that she has been having this sweet, she's been using the sweet smell to his diapers, that his ears smell sweet, he smells, has the sweet smell, right? If you see something like this, right? This person obviously has MSUD, right? Has maple syrup urine disease, right? Has maple syrup urine disease? Now, what's the key enzyme that's defective in maple syrup urine disease? Remember the key enzyme that's defective, right? It's an enzyme that we know as branched chain ketoacid dehydrogenase, right? Branching ketoacid dehydrogenase, it's an enzyme that helps you break down branched chain amino acids, right? So it's going to be things like, it's going to be things like leucine, isolucine, veiling, things of that nature, right? We're able to break down those, if you can't break down those branch amino acids, they're going to build up in your serum, and that's going to be a huge problem, right? So the thing is how do we treat these people? Well, if you think about it, branching ketoacid dehydrogenase is an enzyme that is heavily expressed in the liver, right?

So if you want to fix that problem, you have to kind of swap out the current liver and put it a new one, right? You need a liver transplant to treat that. But in the interim, because you don't just go out on the street and get livers, what you're going to be doing is you're going to put them on a diet that is high, I mean, that is low, sorry, that is low in leucine, isolucine and veiling, right? That's very high autonome. Now, what if they give you a question about, and that this disease by the way has autosomal recessive inheritance, right? Again, knowing the inheritance pattern of certain key diseases is pretty high autonome for the NV Me exams. Okay, let's go to another enzyme. What if they give you a question about a six-year-old boy? They tell you that over the course of his life, he has had many, many infections, right? Many, many infections, they tell you that he has had all these, that he has had to come to the emergency room, like four times over the last year, with a floctrine masses in his groin, in his axilla, right around his neck, and that each time they've drained these floctrine masses, right? They found gram-positive coxine clusters, right? So we see them, gram-positive coxine clusters. Floctrine mass sounds a lot like an abscess, and then you're like, she, can I have positive coxine clusters? Staphoreus, abscesses, boy, recurrent infections, that's an immunodeficiency disease, right? This person I'm just describing in this question has CGD.

Well, what causes CGD? Well, remember, CGD is associated with the deficiency of NADPH oxidase, right? Remember, NADPH oxidase is used in your oxidative burst pathway, right? That oxidative burst pathway is extremely important in neutrophils, right? So these people's neutrophils are pretty important, right? Again, it's a problem with NADPH oxidase, right? With NADPH oxidase. And I'm going to make a tie-in real quick with G6 PD deficiency in a bit towards the end here. But it's a primary NADPH oxidase, right? So they're not able to generate these oxygen-free radicals, that helps you kill organisms, right? Especially catalys positive organisms, so it's going to be things like Staphoreus, Seresia, right? Aspergilos, Candida, they're going to have recurrent infections, Bocodiria, with these particular organisms, right? So again, very high yield to keep these things at the back of your mind, for example, right? So again, it's a neutral field problem. So how do we treat this problem? Well, the way we treat this problem is we're going to give interferon gamma. Well, what in the world does interferon gamma do? Well, remember, it probably learns this back in the day from like the phoma, which is an awesome guy, by the way, right? From Pithoma or Gullian, again, these are both great in the field of medical education, I respect these people a lot, right? But you go back, so I guess shout out to them.

So if you kind of go back in time, you probably remember learning some reading the first three chapters of Pithoma that when you have acute inflammation, the first cells that show up are your neutral fields. And then, hmm, after the first like 24, 48 hours, the people that are going to come in next are your macrophages, right? Your macrophages come in, right? So the thing is, since your neutral fields are pretty important, right? Because they don't have any deep age oxidies working well. It would make sense that you want to bring in someone to kind of pick up the slack. You want those macrophages to not chill for 24 to 48 hours before they show up. So you give an agent that has the ability to activate macrophages like interferon gamma. Interferon gamma is a very powerful stimulating factor for macrophages. So the thing that's going to happen in those circumstances is you're going to spruce up the activity of your macrophages and you're going to calm and you're going to help you with that infection. And remember, CGD should not be in a girl on exams, right? It's an ex-linked recessive disorder. It's an ex-intercessive disorder, right? So you can only get that on exams for the most part if you're a guy, right? It's going to be a boy, right? It's going to be a boy, right? So the time with G6 P did efficiency because again, I like keeping these rapid review series on their 20 minutes. But so I'm going to just see this and then I'm going to wrap up here, right?

But the time with G6 P did efficiency, if you notice, most people that have G6 P did efficiency, they tend to become symptomatic when they have a lot of infections, right? So you may be like, hmm, define. Why do people with G6 P did efficiency become more symptomatic when they have a lot of infections? Well, let me explain. Here's the thing that happens. The thing is, look at the name of the enzyme that's deficiency in CGD, NADPH oxidase, okay? So that means it's an enzyme in an oxidase that uses NADPH. Well, what is that fancy thing you are not able to produce if you have G6 P did efficiency? It's going to be NADPH. You're not going to be able to make NADPH. So if you cannot make NADPH when an infection happens, NADPH is like, okay, we're in the world, is my, where the world is my NADPH, right? You're going to become more symptomatic because sickness, illness, places are big metabolic demand on your body for more NADPH that you cannot feel. You can't feel those orders, right? Because you, you don't have a glucose-6-phosphidia hydrogen is working well, right? So times of sickness are very hot, strong hot spots for people to become symptomatic in glucose-6-phosphidia hydrogen is deficiency. So I'm going to go ahead and stop here. Again, as I do at the end of every podcast, I do a four-one-one-todayne for all the USMLE exams. Step one, step two, CK step three, complex level two and three, pre-clean, coma, school exams, 30-ish-elf exams.

The only thing I don't do here is OMM, I'm not very, does something I've just never studied. So I don't do here to OMM. And then I have these review courses that I offer, right? I have the disk school, right? It's a 75-hour school, taking place in the first two weeks of May for step two, step three, complex level two and three. And then I have my 20-hour review course, Testikinplees on the 23rd and 23rd and 30th of this month, April. And there might be any Testikin-Strategy course, Testikinplees on the 22nd of April. Again, if you're just listening to those podcasts, you have an idea of how I teach. I don't like giving lectures. Giving lectures is not my strong suit. My strong suit is making integrations. And then using those integrations and clinical contexts and scenarios with a deep explanation of pathophysiology to really help you understand things. So that's exactly how I teach. And then I have these podcasts on the major podcast apps, right? On Apple podcasts, Google podcasts, Spotify, other You Tube channel, Divine Intervention, USMLE Podcasts and videos. So if you go on that You Tube channel, you're going to find the videos that I make. And then I have a new Life Lessons podcast that I just started, right? If you go on my website, there's a new website called Divine Intervention Lifelessens.com. That's a Bible-based website. I just go over like 10 to 15 minutes, very quick snapshot life lessons on common problems faced by humanity.

You can also find that podcast, associated with the website on Apple Podcasts. It's called The Divine Intervention Life Lessons Podcast. So thank you for listening to me. I wish you all the best, have a wonderful rest of your day. God bless you. Thank you. Bye for now.

G6 PD (Glucose-6-phosphate dehydrogenase), NADPH oxidase, Branched chain ketoacid dehydrogenase.

Hemolytic anemia with decreased haptoglobin, increased LDH, and indirect hyperbilirubinemia; bite cells on smear.

Both are X-linked recessive disorders (sex-linked).

Methemoglobinemia causes hypoxia with normal total hemoglobin; G6 PD deficiency causes hemolysis/anemia.

It causes lactic acidosis (high anion gap metabolic acidosis) because it inhibits oxidative phosphorylation, forcing reliance on anaerobic glycolysis. Hemoglobin is typically normal.

Deficiency of NADPH oxidase, impairing the oxidative burst necessary to kill catalase-positive organisms.

Exposure to powerful oxidizing agents (e.g., nitrates, primaquine).

Inhibition of oxidative phosphorylation in the mitochondria, leading to excessive anaerobic glycolysis and lactic acid buildup.

Branched chain ketoacid dehydrogenase (MSUD).

Methylene blue (a reducing agent that converts Fe³⁺ back to functional Fe²⁺).

Interferon gamma; it activates macrophages, helping compensate for defective neutrophil oxidative burst.

Bite cells (due to oxidative damage).

Exposure to powerful oxidizing agents (e.g., nitrates, primaquine).

Inhibition of oxidative phosphorylation in the mitochondria, leading to excessive anaerobic glycolysis and lactic acid buildup.

Branched chain ketoacid dehydrogenase (MSUD).

Methylene blue (a reducing agent that converts Fe³⁺ back to functional Fe²⁺).

Interferon gamma; it activates macrophages, helping compensate for defective neutrophil oxidative burst.

Bite cells (due to oxidative damage).