DIP Episode 513 - USMLE Step 2/3 Rapid Review Series 112

Welcome, this is Divine. This is episode 513 of the Divine Intervention Podcast. In today's podcast we're going to be continuing the Rapid Review series for step 2 and step 3. So let's get right to it. So what if they give you a question about a 16 year old male? And you're told that a specimen from this 16 year old male was being analyzed at autopsy and that he had a history of recurring respiratory infections. And we're told that he had low levels of some of his immunoglobulins. But some of his immunoglobulins were also elevated. And then we're told that a biopsy of the brain, like for analysis of a brain specimen, shows the absence of percangy cells in the cerebellum. If you see that combination, what should you be thinking about? I hope you're saying, oh Divine, this sounds a lot like ataxia telangeptasia. It's just one of these weird things that they love to test on the USMLA exams. And it's not just for step 1, it's also for step 2 and for step 3. But generally you're going to see these are going to be kids that they're going to have a lot of infections. And you're going to notice that as they grow in life, they're going to start having ataxia. Many times he's going to start in the middle of their bodies and then he's going to proceed peripherally. That's something you want to keep at the back of your mind. And one thing to also keep in mind with it, ataxia telangeptasia, is that many times in the Q-stem. So they'll give you the progressive difficulty with walking.

They'll give you the respiratory infections. They'll give you the movement and the malities that are slowly progressive, right? Because again, you're damaging your cerebellum and I'll explain the pathophys here in a bit. But not just that as well. You'll also notice that you have some kind of eye finding. You'll have some kind of eye finding. Either they'll have taryngeptasia in the eye, they'll have conjunctivitis, something like that. If you see that combination, you really want to think about itaxia telangeptasia. And remember, this is obviously a genetic disease, a rosomal recessive disease. And what's the pathophys? Well, the thing is you have a mutation in a gene that controls DNA repair. You have a mutation in a gene called an ATM gene, you know, like an ATM machine that controls a DNA repair. So these kids, they have issues dealing with DNA repair. So you may wonder why would an issue with DNA repair cause me to start having problems with infections? Well, here's one thing that people do not realize. See me wondering like, man, how does this cause issues with the immune system? Well, one thing you need to remember is that your immune system, many of us not at least for the adaptive immune system, you would have generated so much diversity. You would have made all these antibodies, you get exposed to an infection and it's almost like you're on transform your immune system to recognize this thing you couldn't recognize before.

Well, one of the ways your body does that is that it does these double-stranded DNA breaks in many of our white blood cells, especially in the lymphocytes. And then so they can generate that diversity. And then after it's done, the double-stranded DNA breaks and, you know, it's going to fix them. So basically it's almost like your immune system routinely goes through this process of double-stranded DNA breaks, fix them, double-stranded DNA breaks fix them. But if the gene, the ATM gene doesn't work, yeah, you can generate those double-stranded DNA breaks, but you'll be able to fix them. So if you can fix them, you're going to be in a lot of trouble. So these kids, they tend to have recurring infections, right, because the immune system doesn't work well. And one thing people don't give the immune system credit for is that your immune system has the ability to deal with cancer cells. So these people, because the cancer cells, because the immune system doesn't work well, they actually produce post-allot of malignancy. And remember for these kids, you really want to try to avoid x-rays in them because x-rays have this wonderful ability to induce double-stranded DNA breaks. And that can certainly cause problems for these people. Sometimes when you examine, they can ask you that, what are you going to find on imaging? Brain imaging? Well, you want to pay the answer to this serabella trophy.

Right, because again, this inability to fix double-stranded DNA breaks is lethal to the cell, so over time, those cells are going to die. And one other thing I will see is you can kind of throw at the back of your mind with people that have a tangle of telangetages that their AFP is high. Their alpha-fiddle protein is going to be elevated. I'm going to say that again, their alpha-fiddle protein is going to be elevated. So maybe as a small quick segue, let's just look at the causes of increased alpha-fiddle protein range. It acts as telangetages, it's a classic one. You love to test an example. I ask yourself, what kind of a variant malignancy can cause it in your AFP? It's going to be a yolk sac tumor. Remember, sometimes we call those endodermal sinus tumors. What kind of malignancy can also raise AFP? Don't forget, AFP can also be elevated in hepatocellula carcinoma. And also one of those extra-tibial throwing. If you see elevated AFP in a child that has one side of the body being bigger than the other, or they tell you something about the child having macrophilosia, or they tell you something about the child having hypoglycemic seizures as a newborn. All these things come together to make you think of Beckwith Whitman syndrome. Remember, hemi hypertrophy? It's a classic find it. Beckwith Whitman syndrome is associated with hepatoblastoma. Hepatoblastoma is a benign liver mass. That can also raise the AFP.

So let's just summarize again, you need to know the causes of elevated AFP on your exams. Himandublastoma, I mean, sorry, hepatoblastomas, right? He pato, not himandu. He patoblastomas, hepatocellula carcinomas, endodermal sinus and yolk sac tumors, and etaxia telangetages. Make sure you know these things I just, this dimension for your exams. And again, just in general, etaxia telangetages, I'll see maybe let me make your lives a little simpler. Essentially, these people, all their immunoglobulins are low for the most part, especially the ones that are like big time, your IgAs, your IgGs, your IgEs. For the most part, those ones tend to be decreased, just kind of take it like that. That's more than adequate for your exams. Now, what if they give you a question about a, let's see, how do we put this? What if they give you a question about a 15-year-old male? And you're told that it was brought in by his parents because he's had a lot of respiratory infections. And he tell you that, you know, his tools are very far smelling, and that they tend to float in the toilet after he's pooped. And then they ask you, which of the following vitamins should be replaced on a regular basis in this patient? I really hope that you're going to look for the answer that says one of these fat soluble vitamins and pick that, right? So, let's kind of break this down. So, what's going on here? This person clearly has 65 process, right?

As 65 process, remember, something that they love to test on exams is another more recessive disorder, basically in the CFTR gene. If that happens, then the chloride channel that's associated with the CFTR gene is not going to work. And if it doesn't work, that's a problem because that chloride channel does a bunch of stuff. One thing he does is that he puts chloride ions in the lumen of your GI tract and water can follow. So, that makes your GI tract secretions a little more liquid, which is helpful, right? So, they don't have constipation. Remember, my conium ilias can actually be a pretty classic presentation in cystic fibrosis on the exams, because those people's tools are too thick. So, it's just hard. So, within the first 40 days of life, those kids don't poop. Remember, you're supposed to poop within the first 40 days of life, simple as that. Number two, those transporters also help your ribs work right from your sweat. They help your ribs work chloride from your sweat. Well, if those transporters don't work, you'll not be able to reabsorbed chloride from your sweat. So, you're going to have more chloride in your sweat. So, that's the basis of the sweat chloride testing for cystic fibrosis. You're going to see an increase in your sweat chloride. Now, those CFTR transporters are also necessary for bringing out your pancreatic exocrine pancreatic secretions. Remember, the pancreatic secretions are divided into two kinds. There's the exocrine secretions.

Those are for the most part of your pancreatic enzymes. And your endocrine secretions, things like insulin and glucagon. Remember, glucagon is made in the pancreas. Something people can forget with step one, but glucagon is made in the pancreas. glucagon is made in the alpha cells of the pancreas. Insulin is made in the beta cells in the eyelids of a longer horns. So, the thing that happens here is that you cannot release your exocrine pancreatic secretions if those CFTR transporters don't work. And if those things don't work, then you're going to have a lot of trouble. Think about it. If your pancreatic enzymes cannot make you switch to your small intestine, you're going to have a lot of malabsorption. Especially like lipids. You have fat malabsorption. So, if you have fat malabsorption, you're going to be able to reabsorb fat. So, you're going to notice that, wow, this person has these false-melene stools, false-melons when he goes rotten. Believe it or not. So, they're going to have false-melene stools. They're going to have fatty stools, floating stools, mal. Sometimes, these are the reason the word false-melons, they'll use the word malodorous. But also, if you cannot reabsorb fat, think about it. You're also going to have a lot of issues with reabsorbing fat-soluble vitamins, like vitamin A, vitamin D, vitamin E, and vitamin K. Let me ask you this. Of those four vitamins, which one do you think our friends at the MBA Meas will really, really focus on?

Of course, they're really going to focus on this whole vitamin D business, because there's one that has so many clinical symptoms, and it's readily apparent. So, that's why, on your exams, they could easily just write a question. If you notice, I'm giving you many different cystic fibrosis vignettes. They could easily write a question where a CF patient, you're just like, oh, I got to give this person a vitamin D. I mean, I guess they could test the other one. So, if they give you a question about like, CF patient, and the person is having trouble reading at night, then you probably want to think about some kind of vitamin A deficiency. So, that presents, essentially, develop like some kind of night blindness. Or they tell you that, well, this person is having movement abnormalities. That's going to be a vitamin E problem. Remember, vitamin E maintains your spinal cerebellar tract. So, if you have a vitamin E deficiency, you have an improperly maintained spinal cerebellar tract. And if that doesn't work well, then you're going to have issues with, um, etaxia on your exams. I remember the spinal cerebellar tract goes from the spinal cord to the cerebellum. That's what's called spinal cerebellar. And let me ask you this. If a person has a vitamin E deficiency, what may you find on a blood smear? Well, I really hope you're saying, oh, divine. I'm going to find e-cantocytes. It's one of those weird bizarre things that you may think is going with step one, but it's really not.

And actually, it's heavily furnished these days on step two and step three. So, you're going to see e-cantocytes. Because remember, vitamin E is necessary for membrane integrity. It really helps you properly build and stabilize many of the membranes that you're having in your body, especially your rib blood cell membrane. So, if you have a vitamin E deficiency, you will not have appropriate rib blood cell membrane integrity. And you'll have an e-cantocyte. Those are those rib blood cells that basically have like spiky edges. I would encourage you to maybe look up a picture of that on your, on your exams. Whenever you see a can of the site, many times they're testing either fat malabsorption. Well, one other please, they love to test this with is with EBITDA lipoproteinemia. EBITDA lipoproteinemia, where these people, because they have a micro-sumotransfer protein defect, they're not able to assemble chylo-microns. And if you're not assemble chylo-microns, then you have no way of bringing fat soluble vitamins from your enterocytes. So, these people, they don't have a rib absorption defect. They're able to reabsorb, because remember when you reabsorb something from your GI tract, it goes into your enterocytes first. Those are the cells that align, the lumen of your GI tract, and then from the enterocytes, it goes into your lymphatic system, right?

So, the thing is, they are able to get those things into their enterocytes, but those things cannot go beyond the enterocytes, because they cannot assemble these April lipoproteins. So, if you cannot assemble those, yes, your reabsorb, your fat soluble vitamin is fine, but you can just, you can not just get to the body, because you have this micro-sumotransfer protein defect, right? Whenever you see can of the site, I'm telling you that that's probably like a big, big, big pathology, you want to kind of keep at the back of your mind. Now, what toward vitamin K deficiencies since we're talking about the fat soluble vitamins, what vitamin K deficiencies present us? Simple, simple, simple, it's going to be bleeding, bleeding, bleeding, bleeding. Why? Because remember, vitamin K is necessary for activation of your clotting factors. I'm just trying to use this to bring in some more vignettes, because again, step two, step three, these days, they're beginning to become more pharmacology, focus, believe it or not, right? But if you remember studying from step one, there's this process known as gamma-capoxylation. Gamma-capoxylation is something that is done by an enzyme. It's something that is necessary for the activation of certain clotting factors, like factors two, seven, nine, and ten. And also protein CNS, so they'll remember protein CNS are more anti-cwaugulant proteins. But that gamma-capoxylation is an activation step for those things.

And that gamma-capoxylation is done by an enzyme known as vitamin K epoxide reductives. Look at the name vitamin K epoxide reductives. So it's an epoxide reductives that literally depends on vitamin K. So if vitamin K does not work, then that epoxide, if if we have a vitamin K deficiency, then that epoxide reductives will not work. If the epoxide reductives does not work, then you will not be able to gamma-capoxylation activity those clotting factors. But if you have no activity those clotting factors, the secondary hemostasis is going to be terrible. So you're going to have a lot of bleeding. But again, I'm telling you this, if you're testing CST fibrosis and you're testing a vitamin D deficiency, then you're going to go after a vitamin D deficiency. And again, if they give you a question about a person that has CST fibrosis, they can see which of the following is most commonly associated with CST fibrosis. They will put an answer choice in their great wisdom that says endocrine pancreatic insufficiency, or they will put an answer choice that says exocrine pancreatic insufficiency. What answer should you pick? Again, I pretty much answer this, when it's exocrine pancreatic insufficiency. People that have CST fibrosis, they are endocrine pancreas for the most part works fine. Okay? Is there exocrine pancreas that is problematic? I may wonder, but divine.

If I have the CFTR transporter business, why is it that my endocrine pancreatic secretions, at least early in disease, can still be released into the bloodstream? So remember, your pancreas is like two organs smashed into one in a sense. Is that endocrine pancreas? Remember endocrine organs? Where do you secret hormones into? Remind me again. Like what does endocrine called note? It means you're secreting things into the bloodstream. That's like a hard and fast rule with endocrine organs. They secret their stuff into the bloodstream, so you can travel elsewhere and do something learnt in college. But don't talk about divine, it's a college experience. But that says a lot about the phonopolecology experience. I'm just kidding. I had a phonoclegic experience, but anyway. But basically, the endocrine pancreas is going to secret things into the bloodstream. It does in secret things into the pancreatic ducts. Please don't make this mistake on your exam. The exocrine pancreas, which are your pancreatic enzymes for the most part, secret things into the pancreatic duct. Your endocrine pancreas secrets things into the bloodstream. I can almost pronounce you there's probably no resource that I will say this. But this actually something that's very, very high you to know for your exams. So again, just kind of keep these things in mind. This vitamin supplementation questions with some diseases. They just love to test them. Because they'll give vitamin D as an answer.

They'll give you these B vitamins. Obviously, those are not fat soluble. They'll give you this vitamin C. Those are not fat soluble. But honestly, the USMEL is one to be very devious for assistive fibresist questions. They'll say, oh, which of the following ends? It's actually supplemented. They'll give it a vitamin D as an answer. They'll give vitamin E as an answer. Peak vitamin D. That's probably just a more life-important vitamin for these people. Most of the vitamin E, like no one cares, but you should probably care about vitamin D more. Vitamin D does a ton of stuff in your body. It helps your nerves up, calcium and phosphating in your gut. It helps you maintain a good solubility product so that you can mineralize your bone. There are just so many problems you're running into in life if you have a vitamin D deficiency. So, what if they give you a question about a person that, you know, they tell you that this person has been having a lot of malnourished tools and floating tools. Well, that this person, and what in the question, they tell you that the person has a history of recurrent respiratory infections. If you see something like this, what should you be thinking about? I really hope you're saying, oh, divine. This sounds like celiac disease. Celiac disease is a malabsorbed tip disorder. I'm not going to spend much time on this. I've talked about this in many other podcasts, but remember, you've pretty much, I literally discussed this in detail.

Actually, the previous podcast is episode 512. But you've literally destroyed your microbiology with these anti-glyadins, anti-domicial anti-tissue transgotuminis antibodies. So, if you kill your microbiology, you can already absorb stuff. So, you're going to get in trouble. You're going to get in trouble. That's actually pretty high yield to know for, for example, pretty high yield to know for exams. So, it causes a malabsorbed tip disorder. But let me see something here that I think is kind of important. Not emphasizing many resources. Well, actually pretty high yield to know for your exams. If you see a person that has celiac disease, and they tell you that, or this person has recurrent respiratory infections, what is going to be the most likely cause of recurrent respiratory infections in a person that has celiac disease? I'm going to tell you it's Ig deficiency. You're like, what? Yes. Ig deficiency has a very strong association with celiac disease. So, how can they test this? And again, to be honest with you, I'm not surprised that that association exists, because I just kind of think of it this way. Like, man, if IgA, which guards your mucus or surfaces, is not working as well as in short, or you don't have enough of it, then you can already begin to see that man. You may begin to have all these aberrant inflammation and all these problems in your, your, your mucus or surfaces that may lead to trouble.

So, again, I'm not saying every person that has celiac disease has Ig deficiency, but I kid you not. I will say probably like the most common immunodeficiency disease in people that have celiac disease is Ig deficiency. So, how is this exam relevant? Well, I've already talked about one purview that you can test this with. To give you a question about a person that has celiac disease, they have recurrent respiratory infections, what's the most likely cause? Pick Ig deficiency. Okay. What's another way they can test this? One thing that people do not realize is that many times when we're testing people for celiac disease, you know, many people have memorized anti-glareden, anti-indomisial, anti-tichotransitrutamines antibodies. But those are the auto-antibodies in celiac disease, but many times we check for the IgA forms of those antibodies. Right? So, when we're testing people for celiac disease, we check IgA against glaredin against the endomisial antigen and against tissue transprotaminis. You may wonder, why do we check those instead of the IgGs? Well, think about it. People that have celiac disease, they have a lot of inflammation, they make auto-antibodies against the amuletical surfaces. What do you think those auto-antibodies are going to look more like? It's probably going to be more like an IgA. Why? Because IgA is the guardian of your mucosa. IgA is literally the guardian of your mucosa.

So those auto-antibodies, you're probably going to see much better titers of IgA against glaredin against the endomisial antigen and against tissue transprotaminis than other antibodies. So when we're testing people for celiac disease, we check the IgAs of those antibodies. Again, I'm sure many of you listening to this podcast you've never heard this before. But I promise you this, this is very, very high-yout for the USMLE exam. But think about it. If a person has Ig deficiency, are those antibodies going to be positive? Probably not. So that may make you falsely believe that a person does not have celiac disease. So if people that have celiac disease, would have... And people that have celiac disease, you suspect celiac disease and you know they have Ig deficiency, what is going to be your next step in diagnosis of their celiac disease? I really hope you're saying that, ooh, divine, we're going to check IgG against the endomisial antigen, against the glaredin antigen and against the tissue transprotaminis antigen. And it's just pretty high-yout to know for your exams, right? So having a negative IgA against those antigens does not mean that you do not have celiac disease. And remember, people that have Ig deficiency, they also tend to get an aphilactic trans reactions with blood transfusions. So just kind of make sure you keep these things at the back of your mind for your exams, make sure you know this stuff, like literally make sure you know this stuff.

And since we kind of talked about cystic fibrosis, I think one thing I should mention is, remember, cystic fibrosis, they tend to get a lot of pneumonia. Under age 20, you're thinking more about stuff, over age 20, you're thinking more about pseudomonas. And remember, those pseudomonas pneumonia, we tend to treat them in people that have cystic fibrosis with amino glycosides, we can use cephapym, you can use cephazidine. Remember, you've got to know some generations of your cephalosporines for step two, step three. And also if you are like, ah, divine, come on, please don't make me memorize this, sorry. But there are certain generations you need to know. And there are certain critical drugs in each generation that you need to know. For example, cephalzolin, you need to know that generation. And I'll get back to this cystic fibrosis story in a bit. But cephalzolin is a first generation cephalosporine you need to know. We tend to use it as prophylaxis before we start most surgeries, antibody prophylaxis. Third generation, probably the biggest group you need to know about, cephalaxolin is a big one there. cephalaxolin is used to treat meningococcal infections, is used to treat a lot of GI infections, is used to treat those spontaneous bacteria to nitase. Another one to know in the third generation for step two, step three, cephotoxin. cephotoxin is almost like baby cephalaxol. So you can use it in kits. So if you see me, you need to see if cephotoxin is not a bad idea.

But honestly, another area you may see cephotoxin being used is for SBP. Adults can literally also take cephotoxin. Another third generation of cephalosporine to know is cephotoxidine. Cephotoxidine is the only third generation of cephalosporine that you need to know for the USML Es that covers pseudomonas. In general, essentially for USMLE purposes, third gen cephalosporine do not cover pseudomonas. The exception to that is what? Cephotoxidine. And then, fourth generation cephopim also covers pseudomonas. You should know that. A very big side effect of cephopim we need to know for your exams are GI-obsets. So again, maybe wondering divine, you're focusing so much on farming this podcast. I'm doing that because again, the USML Es these days, they care a lot about pharmacology. Especially for step two and even more so for step three. Okay, so let's go back to our CF story. So again, we say that people over 20, the FCC fibrosis, they tend to get a little pseudomonas. So how are we going to treat that? Again, we can use that amino glycoside as the very common answer on exams. But if you don't see that, think of cephotoxidine covers pseudomonas. Think of cephopim and covers pseudomonas. Think of fluoroquino loans, like livo-floxicin, for example, covers pseudomonas. Don't forget your carbopenem, like imi-penem, with silas-tatin or meropenem. Those also cover pseudomonas. And then don't forget astrayonam. Astrayonam is one of those monobactams.

It also has the ability to cover pseudomonas. Okay, so I think I'm going to go ahead and stop here since the repiter review podcast. But again, hopefully you've seen that I've integrated a lot of stuff. I offer review courses for the USMLE exams. I have a 20 hours take just a three course starting today. I made a separate podcast on that. Or if you want more information, just shoot me an email through the website. And then the first week in March, I have a step one class. And I have a bunch of other classes as well offer bio stats, social sciences, and ethics, testikings, strategies. Just shoot me an email. They all over Zoom, I'll give you some more information. And they're not lectures. They're pretty much all question-based. They all vignette-based. Because that's more realistic for your exams. And then I offer one or one two-terrain for all the USMLE and complex exams. I have this podcast on Apple Google and Spotify. I have a You Tube channel you can check out. I've on the website called divining intervention life lessons.com. Every week I post two podcasts, biblical perspective, addressing a life lesson. And there's actually an Apple podcast associated with that. Call the divining intervention life lessons podcast. So thank you for listening to me today. Have a wonderful rest of your day. God bless you and bye for now. Thank you.

Recurrent respiratory infections + progressive ataxia + telangiectasias (skin/eye).

Mutation in the ATM gene.

IgA deficiency.

Vitamin A deficiency.

Cefepime (4th generation) or Cephotoxidine (3rd generation).

Exocrine secretions go into the pancreatic ducts; Endocrine secretions go directly into the bloodstream.

Hepatoblastoma, Hepatocellular Carcinoma (HCC), Yolk Sac Tumor/Endodermal Sinus Tumor, and Ataxia Telangiectasia.

Necessary for gamma-carboxylation and activation of clotting factors II, VII, IX, and X.

IgG antibodies against tTG (or endomysial/gliadin antigens).

Acanthocytes (spiky red blood cells).

Any fat-soluble vitamin deficiency (A, D, E, K), but the underlying cause is usually CFTR defect/pancreatic insufficiency.

Cerebellar atrophy/trophic changes (loss of Purkinje cells).

Hepatoblastoma, Hepatocellular Carcinoma (HCC), Yolk Sac Tumor/Endodermal Sinus Tumor, and Ataxia Telangiectasia.

Necessary for gamma-carboxylation and activation of clotting factors II, VII, IX, and X.

IgG antibodies against tTG (or endomysial/gliadin antigens).

Acanthocytes (spiky red blood cells).

Any fat-soluble vitamin deficiency (A, D, E, K), but the underlying cause is usually CFTR defect/pancreatic insufficiency.

Cerebellar atrophy/trophic changes (loss of Purkinje cells).