DIP Episode 456 - USMLE Step 2/3 Rapid Review Series 95

Alright, welcome. My name is Divine. This is episode 456 of the Divine Intervention Podcast. Until these podcasts will continue to be rapid review for the USMLE. Step 2, see can step 3, it's going to be series 95. So what if they give you a question about a patient and they tell you that this patient, she has a history of muscle weakness and that many of her kids have the exact same problem. In fact, all of her kids have the exact same problem. If you see that, I would really hope you're thinking about some kind of mitochondrial disorder. I remember our friends at the USMLE exams, they like to test mitochondrial disorders and sometimes they can even show you a family tree. They can show you like an inheritance diagram where you basically see like, okay, dad, mom, their kids and all those things. Remember mitochondrial disorders will only be passed on from from moms to all her kids. If you see any transmission from dad, it cannot be a mitochondrial disorder by definition. Because mitochondrial disorders, they only hear it from mom. All the mitochondria in your human body is not a herithic from mom. One thing that's pretty important to know is that many times those people are going to have muscle problems. They can have muscle problems. I mean, there are many kinds of mitochondrial disorders. Like me last, the other one is a lot of people with lactic acidosis and stroke-like episodes. There's the liver, hereditary optic neuropathy.

And again, typically, if you were to perform some kind of muscle biopsy, you're going to see those ragged red fibers. That's something that's kind of important to keep in mind, for example. You're going to see those ragged red fibers, ragged red fibers, ragged red fibers. Now, one thing that's also important to keep in mind with mitochondrial disorders is that it's not everyone that has the same symptom severity, or even the same kinds of symptoms. I mean, notice me, maybe like, wait, you all got the same stuff from mom. Why you haven't differences in your symptom severity, why you have any differences in the kinds of symptoms you have. When you see stuff like that, I would strongly, strongly, strongly encourage you to think in terms of this concept known as heteroplasmic. heteroplasmic is something that is very common with mitochondrial disorders. Basically, the thing that's going to happen is you're going to notice that the number of mitochondria that each child of that affected mom gets is not the same. So even within different cells, you'll notice that they may get like dissimilar numbers of mitochondria. So, since, so obviously, maybe if you have like more muted mitochondria within a particular cell type, you're going to get more symptoms there. But if you have less muted mitochondria, then you'll have fewer symptoms. So that's something that's kind of important to keep in the back of your mind for, for example.

Now, what if they give you a question about a 35-year-old male? They tell you that, although many times they like to meet this up in your question, but the telly-dewish person has difficulty seeing at night. The person has a lot of epistaxis, a lot of bleeding, bloodied area. And then they show you blood smear. And you'll notice that you see red blood cells, they seem to have all these spiky edges to say, candle sites. And then they give you a bunch of labs. And notice that, you know, their cholesterol is extremely low. The kind of microbes are really, really low. When you see something like, and they tell you that it's the person has an issue of seagulls. When you see something like this, I really hope you're thinking about EBITDA lipoproteinemia. EBITDA lipoproteinemia. They love to test EBITDA lipoproteinemia. That's just a truth. It's one of these disorders where you have a mutation in a protein known as a micro-somal transfer protein, MTP. But you have a mutation in MTP. You're going to have a lot of problems with generating. It will be 100. And if you're going to not make it, it will be 100. Then you're basically going to be incapable of absorbing fats and fat related derivatives from your GI tract. So, because it will be 100 is how you're pretty much pachy like a lot of triglycerides, kind of microns, fat soluble vitamins, and get them reabsorbed into the body. But if, again, you cannot assemble it will be 100. Then yes, don't get me wrong.

The enterocytes can absorb fats and fat soluble vitamins, but they will literally be stuck within the enterocytes. They will literally have no place to go. They literally have no place to go. And if they literally have no place to go, then you're going to be in some very, very, very big trouble. Because basically you're going to be able to reabsorb those things. So those people's cholesterol is low. But again, there's many issues they're going to have, right? There's cholesterol. People look at it as all bad. It's when it's in excess that it's bad. But we need cholesterol for many processes in the body, including like just making most of your plasma membranes, an cholesterol for that. But these people are also going to have a lot of fat soluble vitamin deficiencies, right? Remember, fat soluble vitamins are the, what is AD and K. When people have issues with vitamin A, they're going to have vision problems. They're going to have like micrpline-ness. When they have vitamin D, they're going to have rickets in a child or osteomal lesion and an adult. You're going to notice not lots and lots and lots and lots of heinous things, right? Like they can have like fractures with minimal trauma. You'll notice that you'll have like an incidence of secondary hyper-prout thyroid. Secondary hyper-prout thyroid is in, right? So since they don't have an ovative in D, they can have a vitamin D deficiency. The calcium is going to be very low. That's going to trigger the release of PTH.

That's going to trigger a secondary hyper-prout thyroid is in. Although in this case of secondary hyper-prout thyroid is in, their phosphate is going to be low. Because remember, when you have a bit of lipoprotein, it's a GI tract problem. It's not a kidney problem. It's when you have a kidney issue as your cause of secondary hyper-prout thyroid is in that. Even in the presence of that IPTH, you will not be able to trash the phosphate. So you hold onto that phosphate. So, but if a presiding secondary hyper-prout thyroid is in, for a non-kidney related cause, typically the phosphate is going to be low. And then these people, e-beta-lipoprotein, you can also have vitamin E deficiency. Remember, vitamin E deficiency, typically will be associated with acanthocytosis on a blood smear. So you're going to have ribloids with this spiky membrane. And then many times, though, they have vitamin E deficiency, they also will have a lot of itaxia because they have dysfunction of the spinal cerebellar tract, the dysfunction of the spinal cerebellar tract. These are all things they can test on your exams. And then the vitamin K problem, again, you're going to have a lot of bleeding. Because vitamin K is very important. I mean, how is it important in your cognition cascade? Well, it is because if you think about it, there's this female senzheim that you've probably heard of known as vitamin K, Poxyreductase. Where have you heard of that before? I don't know, maybe with Warfarin.

Because we know that Warfarin works by inhibiting vitamin K, Poxyreductase. So let's maybe look at the function of vitamin K, Poxyreductase. Obviously, it tells you that that enzyme probably uses vitamin K. And what does it do? It basically is used for the gamma-cavoxylation of some critical chlorine factors, like factors 27, 9, and 10. And also protein CNS. Although remember that protein CNS are anti-quagulan proteins 279 antenna-quagulation proteins. Okay, so again, that's going to be the classic presentation of ebidolipoproteinemia on your exams. They can just be physically like throwing a bunch of vitamin deficiencies. When you see a bunch of fat-soluble vitamin deficiencies, low cholesterol, think of ebidolipoproteinemia. In fact, many times when you see a handful of sites on a bloodstream, or the ulyssamine exams, they are almost certainly going to be testing ebidolipoproteinemia. Okay, now, what if they give you a question about a patient? And to tell you that this patient presents with one artist from severe chest pain that began while he was arguing with his spouse or whatever. And then the else, you're like, what's the most likely mechanism behind the patient's chest pain? You know, the person is maybe like 30-something years old or whatever. And you don't have many risk factors for having a minor carcinofarction. But if you see that, I want you to think of alpha-1 medicated viso-constriction of the coronary vessels.

Alpha-1 medicated viso-constriction of the coronary vessels. Now, what's causing that? Well, again, if you're getting in a very intense state, you get all worked up. Then you're going to release calycola means, no epinephrine is probably the big one to worry about here. And no epinephrine can do a lot of things, right? You can activate alpha-1 receptors. And alpha-1 receptors will find them on blood vessels. So it's going to cause constriction of your blood vessels. If you constrict your blood vessels, right? Like let's say, a coronary artery, for example, that there'll be diminished blood flow. You can get in trouble. There'll be diminished blood flow. You'll get in trouble. You'll get in trouble. Now, what if they give you a question about a patient that has... How do I frame this? What if they give you a question about a patient? And they tell you that this patient has... You know, flung pain that is related to the growing. And they tell you that it's an African-American female. And they tell you that she has a long history of like, you know, dry cough. You see something like this. I really hope you're thinking about sarcoidosis. I really hope you're thinking about sarcoidosis. The thing is, for whatever reason, the US and the US... We just like to go after hypercalcemia mechanisms on exams. And many people tend to screw those on. The thing is, hypercalcemia mechanisms are pretty, pretty, pretty high yield. Again, there are many routes to hypercalcemia.

Let's maybe walk through some of them in this review. So this person that has sarcoidosis, obviously we know that they're going to have a lot of vitamin D. Because again, it's a granuloma that's disease. Well, granuloma is that associated with epithelial macrophages. Those macrophages were today to produce a little one alpha hydroxylase. That's going to convert 25 hydroxyl vitamin D, which we call calcium dial, to 125 dihydroxyl vitamin D, which is called calcium trial. That vitamin D is going to cause increased calcium reabsorption for the gut from the gut. So you're going to have hypercalcemia. They can give you a question about a person that has nephrodix syndrome, restrictive cardiomyopathy, and hypercalcemia. And they have like bone pain. And again, that should make you think about multiple my lower. Again, the hypercalcemia mechanism, there's a little difference. Remember, multiple my lower is a plasma cell discrecha. Sometimes it's literally putting multiple my lower is an answer. They'll put plasma cell discrecha as an answer. That's a very good derivative answer right there. But they multiple my lower, remember you're making a lot of interlocking one from those plasma cells. Interlocking one, they're very powerful activator of osteoclasts. When you activate osteoclasts, you're going to reserve bone. And that's going to cause you to have hypercalcemia. That's going to cause you to have hypercalcemia.

Now, what if they give you a question about a patient that is, has been a smoker for a long period of time. And then again, you notice that you have hypercalcemia symptoms. Well, again, think about a pharmacome relief peptide from the scone cell long cancer. And PTHRP literally works just like PTH. And when you have high levels of PTHRP, you're going to make a lot of calcium. And that can cause a hypercalcemia crisis. And remember when people have hypercalcemia, one of the first things you need to do for those people is to give them fluids. Is to give them fluids. Volume expansion is the first treatment for symptomatic hypercalcemia. Volume expansion is the first treatment for symptomatic hypercalcemia. And one of these other weird because honestly, there are quite a number of tidbits that people learn on the wards. That just end up either one being flat or wrong, or two, not being particularly useful on the USML exams. But there's a tidbit from the wards with hypercalcemia that typically is actually quite helpful on the USML exams. So if they give you a question about a person that has hypercalcemia, and those people are commenting for a primary care visit, the most likely cause of hypercalcemia in those people. It's going to be primary hyperparthyroidism, probably from some kind of parathoid at the moment.

But if you notice a person is admitted to the hospital in a USML question, and they have hypercalcemia, the most likely cause in those people is going to be some kind of malignancy. And again, it's not only a small long cancer that's associated with hypercalcemia. It is not only multiple myeloma that's associated with hypercalcemia. Another classic malignancy on USML exams that tends to be associated with hypercalcemia, is actually a renal cell course inoma. Many people kind of play off renal cell course inoma, but it's actually one of these cancers that are pretty high to know about. It can cause hypercalcemia. It's associated with hypercalcemia. But remember, it's also associated with a person having police-like femial, because again, many times renal cell course inomas can be carried through poising. And we know what ipos capable of. ipos is going to stimulate your renal cell precursors. You're going to make a lot of renal cells. You're going to make a lot of renal cells. So again, just going to keep these major things in mind with regards to hypercalcemia. I mean, there are drugs that can literally cause hypercalcemia. For example, if a person is taking a thazide diuretic, that can cause them to have hypercalcemia. Because remember, thazide is the block that sodium chloride, the same powder, that we find at the level of the distal-convular tubule. When you do that, that's going to decrease the amount of intracellular calcium.

I mean, intracellular sodium in the distal-convular tubule cell. And if you decrease the amount of intracellular sodium in those cells, then your sodium calcium exchanger that is on the blood side, on the basal surface of the DCT cell, will have increased activity. That sodium calcium exchanger that brings in sodium and extrude calcium into the bloodstream. So extrude more calcium into the bloodstream. So that will, in turn, lower the amount of intracellular calcium that we find in the DCT cell. If that happens, then your DCT literally has a calcium channel that is actually controlled by DTH. That makes you bring in calcium, bring in calcium, bring in calcium. So you're going to bring in more of that calcium through the urine surface, through that calcium-idated channel. And that's going to cause you to reabsorb more calcium from your urine. So basically, when you take a thiazide erratic, you're going to have hypercalcemia because your reabsorb more calcium. But you're going to have hypocalcyuria. And again, you can already see how you can begin to take advantage of these things. That hypocalcyuria is going to be helpful in people that have kidney stones, or have a history of kidney stones. If you have a history of kidney stones, look at the erratic stuff, maybe not the smartest idea, because many kidney stones contain calcium in some way, shape or form.

So for these people in general, what you just need to do is give them something like a thiazide erratic, is going to reduce the amount of calcium in their urine. It's going to decrease the risk of kidney stones. But also, that hypercalcemia side effects that we see with thiazides will be ideally in a person that has a history of hypertension, but in addition to that, they can come in time to have osteoporosis, where they have like decreased bone marrow density for whatever reason. So, say for example, you know, a person is on a rexect, and they have hypertension. They want to put them on a medication for hypertension. Again, it's not a bad idea to put those people on thiazides. Again, it's going to be helpful in those folks, again, why? Because, well, that on a rexect, your body is going to be like, man, you're not eating enough for me. If you're not eating enough for me, I'm not going to be raising a little human being inside you. So, those people, you're pretty much going to shut down. Their HPG axis is shut down. They will essentially not make G&RH, so they will not make FSH or LH, they will not make a stretching. They essentially have a hypo-gonadotropic hypo-gonadism. It's hypo-gonadotropic because they're going to have a trapping, their FSHLH is low. And it's a hypo-gonadism because, again, the estrogen is low. So, because they have that low estrogen, their bone marrow density is not good.

And again, you may ask yourself, divide what's the mechanism behind that low bone marrow density if you don't have a low estrogen? The thinnest way estrogen increases the synthesis of a protein known as osteoportagrin. Osteoportagrin. So, osteoportagrin, if it's diminished because you have a low estrogen, then you're going to have more interaction between osteoclasts and osteoblasts. You're going to have that kind of interaction that you don't want if you're trying to prevent your bones from being reserved. And that interaction you don't want is that interaction between a rank and a rank ligand. When that interaction happens, your osteoclasts are going to be stimulated. They're going to reserve your bone. And you're going to get in some trouble. That's kind of like the big thing there. So, again, I'm going to encourage you to kind of keep that at the back of your mind. So, when you have low estrogen, you're going to have a decreased bone marrow density. So, those people, it will be helpful for them to have adequate serum calcium. That's why, again, phycydioretics is not necessarily about idea in those folks. Not necessarily about idea in those folks. If you notice in this podcast, I'm going over a lot of basic science-related things because many people just when you're taking a step to step three, they just believe that the USML is the size to take a high-cortico walk from basic science. You could not be more mistaken than that.

You literally could not be more mistaken than that. Just be very careful. Don't ignore the importance of understanding mechanisms. You'll be quite surprised at how frequently those things are tested on the USML exams. You'll be quite surprised at how frequently those things are tested on the USML exams. Let's me go over one last thing and then we'll call it for today. Let's see. So, what if they give you a question about a patient? The tell you that this patient is 25-year-old female. The tell you that she had very poor prenatal care. The tell you that she's at 32-weeks just a day and feet-of-heart tones are no longer heard. And they tell you that she delivers a markedly hydropic, still-born infant. And they tell you that in the process of delivery, there was a very false smell to her amniotic fluid. And then they tell you that the took a sample of the amniotic fluid and the found gram-positive bacilli. When you see something like this, you want to think about the stereosis. Sometimes they can ask, what is the most likely cause of the biggest risk factor for this presentation? Well, you want to think about exposure to delimits. You don't think about exposure to delimits. At least that's the classic picture of a leisterian fetch on the USML exams. Leisteria is a pretty high-yield bug to know for USML exams because they are mainly wazely contested. That's why again they recommend be careful with delimits if you're pregnant woman because if you do.

And then most of them are probably okay. But again, you could also have leisteria stuck with them. But leisteria is very good at surviving in cold environments. So it loves delimits. So when it comes after that delimit, you consume it, then you can transfer the leisteria to the child. Leisteria causes a particular syndrome in kids known as granulomatosis and phantissepticum. So that can cause, basically like a very hydropic infant that will not be born alive. Not a good situation there. And for USML purposes, what is the drug of choice for treating leisteria? The drug of choice for treating leisteria is ampeicillin. In fact, because leisteria is a potential cause of an amniotic fluid infection, which we call coramionitis, that's one of the reasons why ampeicillin is part of the standard drug regimen for coramionitis. In general, we treat coramionitis with ampeicillin and gentamysin. And also, leisteria can cause meningitis in little kids in like neonates. So that's why when you see a meningitis question for a newborn, typically on exams, we're going to give them safe triax, I mean, safe autoaxing. We try not to give safe triaxing to little kids because it's a social and intraeparicolisthesis. So we don't have them having like binary issues, you know, direct type of inhibitor. We need all that jazz. But basically, you know, little kids can get leisteria infections.

In fact, it's probably like one of the third most common causes of, is one of the top five at least, in terms of causes of meningitis and little kids. So that's why we give safe autoaxing. That's a third gen safe loss sparring. Honestly, that's going to be covering the gram negatives of ampeicillin. It's going to be covering the gram positives. They will give ampeicillin to cover specifically leisteria. The thing is, again, there is really not many drugs as good as ampeicillin for the treatment of leisteria. And then also, if you see meningitis in a person over at each 50, then you also want to add ampeicillin to their meningitis regimen. Many times, if you're over at 50, we're going to give you safe triaxone. You know, now we're orders or like, you can take safe triaxone, you'll be fine. Then we give bank, we also give ampeicillin, we also give ampeicillin. We also give ampeicillin. Again, to cover the leisteria. So again, many times meningitis, they love to go after it with little kids, like neonidol, period. And then also with adults over at age 50. It's very rare for adults that are under age 50 and you know, like teenage years or higher to get leisteria based meningitis. But again, you've got to treat the ampeicillin. Now, the final thing I'm going to say about ampeicillin actually is that, I mean, about leisteria, the initial exams is that it's actually a fairly common cause of opportunistic infections in people that are taking TNF inhibitors.

One of these red factoids kind of pops up out of the blown exams when you've got to know that stuff. The thing is again, TNF is necessary for granuloma maintenance. So, and we know that leisteria is a granuloma dos infection. So, if a person is on a TNF inhibitor, they don't have anything basically to deal with granulomas properly. So, those people can have really, really nasty leisteria infections. People that are on TNF inhibitors, they have really, really nasty leisteria infections. Okay, so I'm going to go ahead and stop here. Again, I do offer review courses for all the USMN exams. Step one, step two, step three. And then I have a 500 multiple choice questions review course for step two, step three, that's coming up next month in June from June 1st to June 11th. And then I have an MBA me testing strategy scores. Many people have taken me funded to be helpful. That's for step one, to step three. I've a biostatistics bootcamp that really teaches you how to raise in through bio stats. That's also for step one, to step three. Then I have a five hour social sciences and ethics quality improvement and communications review. So, if you have any of those classes, just shoot me an email and I'll give you some information through the website. And then I also have these podcasts on the major apps, Apple, Google and Spotify, Apple Podcast, Google Podcasts, Spotify, other You Tube channel called Divine Intervention, USMN podcasts and videos.

That's where I post the videos that I make. And if you have a Word Press account and you subscribe to my website, Divine Intervention Podcast.com, you will get an email notification whenever I make a new podcast. Finally, I have this new website called Divine Intervention Lifelessens.com. I post two podcasts every week. That from a biblical perspective addresses a life lesson. Many people have listened to those podcasts and found them to be massively helpful. I actually do, again, roughly two podcasts every week and there's an Apple Podcast associated with it. It's called the Divine 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.

Maternal only; mitochondria are passed exclusively from mother to all children.

Ragged red fibers (RR Fs).

Heteroplasmy—the varying number of mutant mitochondria between cells or individuals.

Low cholesterol/triglycerides, acanthocytosis on blood smear, and fat-soluble vitamin deficiencies (especially E).

1-$\alpha$-hydroxylase, converting calcidiol to active calcitriol.

Volume expansion (IV fluids).

Listeria monocytogenes.

Plasma cell dyscrasia leading to increased osteoclast activity (via Interlocking one), causing excessive bone resorption.

Renal cell carcinoma (RCC).

Ampicillin (often combined with Gentamicin and Ceftriaxone).

It increases intracellular sodium in the DCT, stimulating the Na+/Ca2+ exchanger, leading to increased calcium reabsorption.

It facilitates the gamma-carboxylation of clotting factors II, VII, IX, and X, making them functional.

Squamous cell lung cancer (or other tumors producing PT HrP).

Plasma cell dyscrasia leading to increased osteoclast activity (via Interlocking one), causing excessive bone resorption.

Renal cell carcinoma (RCC).

Ampicillin (often combined with Gentamicin and Ceftriaxone).

It increases intracellular sodium in the DCT, stimulating the Na+/Ca2+ exchanger, leading to increased calcium reabsorption.

It facilitates the gamma-carboxylation of clotting factors II, VII, IX, and X, making them functional.

Squamous cell lung cancer (or other tumors producing PT HrP).