DIP Episode 635 - USMLE Step 2/3 Rapid Review Series 133 (Some HY Basic Science Mechanisms)

All right, welcome. My name is divine. This is episode 635 of the divine intervention podcast and into this podcast I'm gonna be Continue our rapid review series for the US Emily step 2 ck and step 3 exams This is going to be series 600 series 133 and into this podcast I'm gonna be focusing a lot on some mechanisms. I just decided to kind of collate some kind of strange mechanisms that People do not be attention to what actually end up showing up a lot on the US Emily exams They tend to be a little kind of basic sciencey, but again very important Although also just this cross some classic vignettes as we go So what if they give you a question about a 24-year-old female and they tell you that for the past four days she has been having a lot of joint pain and Detailed that on physical exam she has this Vesicular rash that's kind of diffuse and that she also has tenderness like her wrists and in her fingers and things like that What should you be thinking about here? Well, I really hope you're saying that oh divine this person has gonna coccol Thritis right this person has an septic arthritis caused by Nasir gonorrhea, right? So what is the classic presentation of that septic arthritis gonna be well? It's gonna be a person that is sexually active, right? A person that is sexually active although on the US Emily exams They can also give it to a person that has a terminal complement protein defect, right?

So remember when people have a C5 or C6 or C7 or C8 or C9 defects It does increase the risk of Nasir olinfections either Nasir olingitis or Nasir gonorrhea, right? So for presence of terminal complement protein defect a C5 to C9 defect is gonna increase the risk of Nasir olinfections both gonna coccol or Manin go coccol, okay, so the person has Septic arthritis in this case caused by Nasir gonorrhea, right? And remember typically the way is gonna present is is gonna affect more than one joint This is not a mono-athritis like you see in most cases of septic arthritis It's gonna be a polyathritis is gonna affect many many joints, right? And then they will also typically have some kind of rush on the skin, right? The rash can be vesicular, it can be postures, it can be poppules, it can be echinocys, right? And then typically they will also have this phenomenon known as tenocino-vitis In fact, let me give you a trick here if you see on the US Emily exams a young person and you see the term tenocino-vitis You really want to think about gonococcal arthritis, right? What in the world do I mean by tenocino-vitis? Well tenocino-vitis literally means that Synovium that bays the synovium that basically showers tendons, you know, it's like inflamed, right? So it hurts, right? That's very classic in people that have gonococcal arthritis, right? So it's something I want to keep at the back of your mind on exams, right?

And typically, you know, you're gonna treat this person with something like septic arthritis, right? You're gonna give septic arthritis, although if you've not ruled out chlamydia, you also need to add in some Doxycycline or is it through my腐? Right? And then what if they give you a question about a patient? And they tell you that this patient is a 24-year-old male, right? Or let's say female 24-year-old female and that for the past, you know 24 hours she has been noticing this a pure lint cervical discharge, right? And then we're told that You know, gram stain of the discharge the reveal so gram negative deep low. Gram negative cox gram negative organisms, right? So let's let's put it that way. Discloses gram negative organisms, right? gram negative cox I and then they tell you that without treatment which of the following complications would most likely arise from this person's representation? Well, if you see this, I would really hope you're thinking of the answer that talks about pelvic inflammatory disease, right? In fact, our friends at the MBM is they like to do this thing with complications of disease or presentations of disease or prognosis of disease these days, right? So this person what is the original thing the person has? Well the person has something called a mucopyral lint serviceitis, right? mucopyral lint serviceitis serviceitis is something that can be caused by chlamydia It can also be caused by chlamydia tracomitus or gonorrhea, right? Nice.

They're gonorrhea, right? Now the thing is if you treat it again, the treatment is the same as what you used to treat you know, so you give like septraxomplos doxycycline or septraxomplos is ethyromycin but if you don't treat it it can actually progress to pelvic inflammatory disease, right? pelvic inflammatory disease. I remember PID how's that gonna present? Well, you're gonna see purulent, you know vaginal discharge and then you're gonna see cervical motion tenderness and then you're gonna see bilateral and next-alternus, right? So that's something you're gonna see on your exams So you just want to keep at the back of your mind and then what if they give you a question about a patient and they tell you that this patient, you know, has this history, you know, for this second vignette I mentioned and that the person has been having trouble with fertility, right? This person, you told that the person has had unprotected intercourse with her husband for, for you know, like 15 months and the person has not been able to conceive and then they ask you about the mechanism behind the patient's symptoms I really hope you're thinking about the answer that talks about a fallopian tube scarring fallopian tube scarring. I'm again one of these strange things our friends at the MBM is love to test, right? So what's the deal here? Well, the thing is people that have had PID, this is why PID is kind of worrisome, right?

You don't sleep on PID, you try to actually like treat it because it can become problematic on long term, right? So how can it become problematic? Well, the thing is that infection and inflammation can lead to scarring of the fallopian tubes and when the fallopian tubes scar that can increase your risk of things like ectopic pregnancy, right? It can also make things infertile because if it's scarred then all those are cilia that line the fallopian tubes they cannot beat the eggs and if the eggs cannot be beat then how is it going to find sperm to fertilize it? That's going to be hard, right? That's going to be hard. So keep that at the back of your mind for for exams. All right, now what if they give you a question about a patient and tell you that the patient, you know, three weeks ago was placed on an oral hypoglycemic medication and then the patient presents, you know, was found by his wife, you know, 30 minutes ago that he was passed out, he was unresponsive and then they tell you that blood glucose measurement, you know, when emergency medical services were called was like 45, right? And then the ask which of the following is the most likely etiology of this patient's representation, right? I'd really hope you're picking the answer that talks about a sulfonyl urea toxicity, right? I'd really hope you're picking the answer that talks about sulfonyl urea toxicity, right?

The thing is of all the oral hypoglycemic drugs, the classic one that tends to have the strongest association with hypoglycemia that our friends at the end beam is love to test are your sulfonyl ureas, are your sulfonyl ureas, right? So how exactly do sulfonyl ureas cause this problem? Well, the thing is if you think about it, if you understand the way insulin is secreted normally, then you're going to understand how sulfonyl ureas can cause hypoglycemia, right? So remember insulin comes from the pancreatic beta cells. So if glucose enters through the glute two transporters to the pancreatic beta cells, it then gets phosphorylated to glucose six phosphid by glucose kinase, right? And then that glucose six phosphid is going to be metabolized obviously in, you know, glycolysis, TCA cyclanol, those things into ATP, right? And then that ATP blocks a potassium channel that we find in the pancreatic beta cell blocks the potassium channel. When you block that potassium channel, potassium will not be able to leak out of the cell because remember potassium is primarily an intracellular ion. So potassium cannot leak out of the cell. If you cannot leak out of the cell, the cell is going to depolarize because you're retaining more of a positive charge within the cell. The cell is going to depolarize. Then that's going to cause, right? That's going to cause a voltage-gated calcium channel to open.

Calcium is going to rush into the pancreatic beta cell and then you're going to shoot out insulin, okay? So again, ATP produced from the metabolism of glucose is going to block a potassium channel in the pancreatic beta cell. That is going to cause the cell to depolarize. A voltage-gated calcium channel is going to open and then calcium comes in and then that causes insulin to be released together with CPAP type. That's how insulin is released. So how do sulfonyl ureas work? Well, sulfonyl ureas, that potassium channel that I said is blocked by ATP is also blocked by sulfonyl ureas. In fact, sulfonyl ureas literally trigger the secretion of insulin, okay? They literally trigger the secretion of insulin, right? So they block that ATP-dependent potassium channel insulin is secreted and think about it if you're a thing that causes more insulin to be secreted, more insulin to be secreted. Well, what do you think is going to happen to your blood glucose levels? That can actually lead to a tanking of your blood glucose, right? So again, that's how sulfonyl ureas work. And remember, of all the oral hypo glycemic agents, the one that probably has that is not probably on the USMLA exams, the one that has the strongest association with hypo glycemia are going to be a sulfonyl ureas. And then one thing I just want to say here, you know, just to kind of tie in another pathology or another concept is your meglith night.

Your meglith night are another group of diabetes medications that include drugs like repaglinite and nataglinite. Those drugs also work just like the sulfonyl ureas. They actually blocked that ATP-dependent potassium channel, but there are some two, there are two key differences between those drugs and the sulfonyl ureas. They have less risk of hypo glycemia compared to the sulfonyl ureas. Number two, they are not associated with sulfur allergy. So if a person has a sulfur allergy, and you don't want to give them a sulfonyl urea, a very good idea in those circumstances is to strongly consider a meglith night like repaglinite or nataglinite, right? And then one other thing I want to tie in is I said that hey, if you want to make ATP in a pancreatic beta cell, right? Glucose enters through glucose 2 and then is converted to glucose 6-phosphate by glucose right? And then that glucose 6-phosphate is metabolized, you make ATP and block that potassium channel. Well, the thing is what if glucose kinase does not work? Or what if glucose kinase is not as sensitive? What kind of disease will that increase your risk of? So let's say for whatever reason glucose kinase is just not very sensitive to glucose because again literally what does glucose kinase do? It converts glucose to glucose 6-phosphate. That conversion needs to happen for ATP to be made in the pancreatic beta cell.

But if glucose kinase does not respond very well to glucose, if it's not very sensitive to glucose, or let's say there's some kind of genetic mutation in glucose kinase, are you going to make glucose 6-phosphate? No, if you don't make glucose 6-phosphate, are you going to make ATP in a pancreatic beta cell? No, if you don't make ATP in a pancreatic beta cell, are you going to close that potassium channel and release insulin? No, you won't. So those people are going to have high pool in solenemia and that can lead to them developing diabetes. That is very, very high you to know for your exams. In fact, our friends at the MBM is they like to test a Modi, M-O-D-Y, maturity onset diabetes of the young, maturity onset diabetes of the young. One of the classic pathophysiologies, our friends at the USME Ls love to test, is they love to test it from the perspective of a glucose kinase mutation. So you can have a glucose kinase mutation where it takes a very high amount of glucose for it to start working or the glucose kinase doesn't just even work at all, right? That can absolutely positively lead to hypoinsulinemia, which can also lead to diabetes. Again, you may think that, oh, this is too basic science-y. There is no way I would ever see it on my exams until you then see it on your exams and you're like, hmm, that's strange, right? So please keep that in the back of your mind on your test. All right.

Now, what if they give you a question about a patient and they tell you that this is a 42-year old male and his BMI is 31 and you're told that is hymo globin A1 C is 7.3, right? And you're told that this person has not visited the physician within the last 10 years and you're told that his blood pressure is like 149 over 85 and you know, you're told that his total cholesterol is like 267. And then they ask you without treatment, which of the fully represents the most likely cause of mortality in this patient? Well, if you see that, I really hope you can pick the answer that talks about coronary artery disease. This is super high you to know for your test. Again, if you notice, I'm talking about the most common cause of mortality. I'm hitting prognosis prognosis prognosis in this podcast. This person has diabetes, right? The A1 C is pretty high. What is the most common cause of death in a diabetic on your exams? The most common cause of death in a diabetic on your exams is going to be coronary artery disease. Guys, this is super, super high you to know for your test. What is the most common cause of death in a diabetic on the USML exams? The most common cause of death in a diabetic on the USML exams is going to be coronary artery disease. It's going to be coronary artery disease. Okay? Coronary artery disease. All right. Now, what if they give you a question about, they give you an arrow question on your exams? And they want you to use that arrow.

They want you to use a series of arrows to differentiate type 1 diabetes from type 2 diabetes. They want you to differentiate literally type 1 diabetes from type 2 diabetes. And they give you, you know, your arrows include insulin, your arrows include CPAP type, right? And then your, so how do you differentiate type 1 diabetes from type 2 diabetes that way? Well, I really hope that you're saying that for type 1 diabetes, the person is going to have decreased insulin and decreased CPAP type. But for type 2 diabetes, the person is going to have increased insulin and increased CPAP type. You're like, with what? Hey, I thought in diabetes, you have an insulin deficiency. Right. Right. So let's talk about it, right? To make sure it makes sense in your head, right? So what happens in type 1 diabetes? Well, remember, type 1 diabetes is an autoimmune insolidus. You literally make autoantibodies against your pancreatic beta cells against insulin, right? So your beta cells basically die. If your beta cells die, you're literally not going to make insulin. If you're not making insulin, you'll also not make CPAP type. So your insulin is going to be low and your CPAP type is going to be low as well. Okay. But contrast this with a person that has type 2 diabetes, right? Where they have more of an insulin resistance. So these people are actually making tons and tons of insulin. It's just that the body is very resistant to it.

So in type 2 diabetes, your insulin is going to be very, very high and your CPAP type is going to be very, very high as well. Okay. Remember, type 2 diabetes is not an autoimmune disease. Type 1 diabetes is. Okay. Type 1 diabetes is, right? And one evil, let me not call it an evil question, but one strange, bizarre thing, our friends at the MVM is going to do to you on the exams. You do know what they can do to you. They can literally give you a question about a person that's a diabetic, right? And the person is not on any medication. And then they also give you other things like the person's smokes and the person has like high blood pressure and all these things. And then they ask which of the following interventions would cause the greatest decrease in mortality over the next 10 years in this patient. And they will give you an answer that says blood sugar control. They will give you an answer that says blood pressure reduction. They will give you an answer that says smoking cessation. Which answer choice should you pick? I really hope you're picking the answer that says smoking cessation, right? Again, it will be a diabetic that smokes, but stopping smoking is going to help that diabetic a lot more than targeting their blood sugars. You're like, wow, yes, that is a very high-yield thing to know for you exams, right? Because the thing is smoking causes so many problems.

Smoking causes high blood pressure, smoking causes lung cancer, smoking causes bladder cancer, smoking causes renon cell carcinoma, smoking causes pancreatic cancer, smoking causes a triple A, smoking causes PAD, smoking causes a lot of problems, right? So the thing is, even if you have blood sugars that are out of control and you're diabetic, if you smoke, smoking cessation is going to reduce your risk, is going to reduce your mortality by more than controlling the person's blood sugar. That is very, very, very high yield to know for purposes of the USML exams. That is extremely high yield to know for the purposes of the USML exams. All right, now what if they give you a question about a patient and they tell you that this patient is a 55-year-old female and you're told that she has a remote histral breast cancer, you know, and that over the last three months she has been having a profancialness of breath and you're told that profancialness of breath and on physical exam, you can hear crackles in her lungs and then you're told that on echocardiographic evaluation, there's biventricular dilation. If you see this, what is the most likely cause of the patient's presentation? Well, I hope you're saying divine, this person likely has drug toxicity. You will just put an answer that says drug toxicity. Remember, when a person has breast cancer, right, you can treat it with, you know, chemo, you know, radiation, surgery and all those things, right?

But you're seeing this person has a diluted cardiomyopathy, right? So what's going to be the likely cause of the diluted cardiomyopathy? Well, it can be caused by transduziumab, although transduziumab is going to cause a reversible diluted cardiomyopathy, but your anthrocycline, right? Your doxorubicin, your donorubicin, right? In the chemo world, they call those as red devils. Those can also cause a diluted cardiomyopathy, but in this case, it's going to be an irreversible diluted cardiomyopathy, it's going to be an irreversible dose-dependent diluted cardiomyopathy. So what's the mechanism behind the diluted cardiomyopathy, the irreversible diluted cardiomyopathy that we see with doxorubicin? They love to test this a lot on the exams. So actually, that rises from a series of reasons, right? So number one is that we know that these anthrocyclines are topoisomerase two inhibitors, right? They literally inhibit topoisomerase two. Well, the thing is they don't just inhibit topoisomerase two in cancer cells. They can also inhibit topoisomerase two in many cells of the body, right? So like, for example, they can inhibit topoisomerase two in your cardiac myocytes, right? And as they inhibit topoisomerase two in your cardiac myocytes, that's going to cause death of those cardiac myocytes, right? Because, you know, you pretty much stop cell division, so that is going to trigger a poptosis, and that's going to cause death of the cardiac myocytes. So that's one mechanism, right?

And the thing is these drugs, they also vary toxic to the mitochondria. How do you toxic to the mitochondria? Well, the thing is they all accumulate intracellularly, and then they bind iron. And when they bind iron, they cause the generation of lots of reactive oxygen species. And those reactive oxygen species are very toxic to the mitochondria. And when you damage the mitochondria, that's going to cause the release of a lot of pro-epoptotic substances like caspases from the mitochondria. And that can cause program cell death of that cardiomyocyte, right? So that's why those people are going to have a diluted cardiomyopathy. And one of the ways you can prevent this is number one, give a smaller dose because it's dose-dependent. But number two, another thing that's very high you to know here is that you can also use the drug dexrazoxin, dexrazoxin. Dexrazoxin is an ion key later, right? By binding up the iron that is around, then you won't be able to do the fainting reaction that your anthracyclins like doxone donor obesity use to cause a diluted cardiomyopathy. Okay. And then the last thing I think I want to address here, and then we'll go ahead and wrap this up. This is a rapid review podcast. Is what if they give you a question about a patient? And they tell you that this patient is a 25 year old female and she goes for a pap smear.

And then they tell you that all that examination of the pap smear by a pathologist reveals, you know, like a densely, reveals abnormal squamous cells with a densely packed nucleus with a surrounding perinuclear halo, right? So they tell you you see abnormal squamous cells with a densely packed nucleus with a surrounding perinuclear halo. And then they ask you which of the following is the most likely diagnosis? Well, I really hope you're picking the answer that talks about HPV, right? The thing is many of you know that, hey, of course, the vine is talking about a pap smear and we're seeing abnormal findings. Of course, it's got to be HPV, right? I can promise you our friends at the NVME exams, they will test this thing in an indirect fashion to throw you off, right? So they may tell you things like, hey, abnormal squamous cells with a densely packed nucleus and surrounding a surrounding perinuclear halo, right? What cell type am I describing here? Well, I'm describing a coilo site. I'm describing a coilo site. If you look at this thing, histologically, I'm actually encouraged to be able to identify this histologically, they look like fried eggs, they look like fried eggs, right? So whenever you see coilo site doses on your exams, think about HPV infection. In fact, think about the HPV 16s and 18s, right? The ones that tend to be associated with cancer, the ones that tend to be associated with cancer, right? The ones that tend to be associated with cancer.

So I would imagine that that person, at some point, is going to need some kind of co-poscopy with biopsy, okay? Some kind of co-poscopy with biopsy. Now, just to wrap this up, what are the pathologies that have that fried egg appearance that we see on the US Emily exam? So what we've talked about the HPV coilo sites, right? Don't forget your testicular seminomins and also don't forget the brain tumor, that brain tumor that likes to bring the frontal lobe, the oligodangeru glioma, the oligodangeru glioma. It's also associated with that fried egg appearance. All right, so we're going to go ahead and stop here. Again, if you love the way I teach, you're going to love my classes, you're going to love one or one children with me. I offer a bunch of review classes for the US Emily exams. I actually have a bunch that's starting the month of March, right? So I have a two and a half hour testicking class. I have a four hour biostatistics class. I have a five hour social science ethics, quality improvement, and the hospital medicine class. These first three classes are first step one or the way to step three. They're all held over Zoom. Oh my, classes actually are held over Zoom. And then I have a 20 hour step two, step three class, and I have a three hour last mini review. That's just exclusively first step two and step three. And then I have a 50 hour class taking place in the month of June, held only once a year, very limited spots available.

That is for step two, CK and step three. And then I also have a 25 hour step one class. So if you're interested in any of these classes, just shoot me an email. I can give you some more information. I'm the one that teaches all these classes. I teach them through Zoom. I also offer one on one tutoring, and I also help with Eras applications, mock interviews, personal statements, and things like that. And remember, I have this podcast on Apple Google and Spotify, so check those out. And I also have another website called divineinterventionlifelessons.com. Divineinterventionlifelessons.com. Many of you know I'm a Christ follower. So every week, I post like one or two podcasts where from a biblical perspective, I address a life lesson. There's actually an Apple podcast associated with that called the Divine Intervention Life Lessons podcast. So thank you for listening to me today. I will see you God willing episode 636. Again, pay attention to these mechanisms. They're very high yield. They're very testable. So have a wonderful day. God bless you and bye for now. Thank you.

Purulent vaginal discharge, cervical motion tenderness (CMT), and bilateral/adnexa tenderness.

C5 through C9 defects increase the risk of septic arthritis caused by Neisseria species.

Coronary artery disease (CAD).

Sulfonylureas.

They have a lower risk of hypoglycemia, and they are not associated with sulfur allergy.

HPV infection, Testicular seminomas, and Oligodendroglioma (brain tumor).

Coilocytosis (abnormal squamous cells with perinuclear halo).

Polyarthritis, vesicular rash, and tenosynovitis.

1) Smaller dosing/dose reduction; 2) Dexrazoxane (an iron chelator).

Blocking ATP-sensitive potassium channels in pancreatic beta cells, leading to depolarization and massive insulin release.

Mutation in glucose kinase.

Untreated mucopurulent cervicitis caused by Chlamydia or Gonorrhea.

Coilocytosis (abnormal squamous cells with perinuclear halo).

Polyarthritis, vesicular rash, and tenosynovitis.

1) Smaller dosing/dose reduction; 2) Dexrazoxane (an iron chelator).

Blocking ATP-sensitive potassium channels in pancreatic beta cells, leading to depolarization and massive insulin release.

Mutation in glucose kinase.

Untreated mucopurulent cervicitis caused by Chlamydia or Gonorrhea.