DIP Episode 476 - USMLE Step 2/3 Rapid Review Series 100

All right welcome my name is divine this is episode 476 of the divine intervention podcast into this podcast we're going to be continuing the rapid review series for the USM list step two CK and step three exams this is going to be series 100 that's a big milestone series 100 let's just get right into it now what if they give you a question about a 20-year-old female they tell you that she has never had men sees before they tell you that her breasts are Turner stage five but are axillary and pubic here are Turner stage two what should you be thinking about what's your diagnosis well I would hope you're saying that divine this sounds an awful lot like androgenic sensitivity syndrome a yes I remember our friends at the USM list sometimes call this a different name they call it testicle feminization syndrome just be careful of that remember our friends at the USM list and this whole business with derivatives ready take what you know just give it a bunch of different names so just be careful right androgenic sensitivity syndrome is the same thing as testicle feminization syndrome so what are the key details of this the solder well the critical detail here is that these people genotypically right at the genetic level they're really male they're really 46y but phenotypically at the I am looking at your level they are they they look female so what's the pathophys behind this the solder well the pathophys behind this the solder is that the testosterone receptor is not working great if your testosterone receptor does not work great then you won't respond to testosterone so on the outside you're not gonna look male you're not gonna look male on the outside you're gonna look female because remember testosterone doing its job is what causes the wolfian dot to develop many of the male internal structures and you know DHT also kind of makes you look male on the outside and stuff li

ke that so for the most part these people just really struggle with the testosterone receptor so again genotypically they're males but phenotypically they're females and one common cause of concern on step two step the wine how do I tease this apart from molarian egenesis you know many people know about molarian egenesis where you know sometimes it's called Meyer Rokitanski Kosterhouser syndrome MRK H syndrome you should learn molarian egenesis that's the kind of like the big big said but if you notice here the critical thing with molarian egenesis is that these people are molarian dots just does not form for whatever reason right but one critical thing that people forget and you see this as a very critical point of differentiation is that molarian egenesis when you have molarian egenesis you still have intact ovaries you still have intact ovaries right so these people on the genetic level right they actually women and phenotypically they're also women so they're 46x x and phenotypically they're also women right so the molarian dot does not develop but they still have ovaries because the ovaries are not derived from the molarian dot so because the ovaries are still intact this will not be making good amounts of estrogen from the granulosa cells and they're going to be making good amounts of testosterone from their thicker cells so honestly these people they have good breasts so let's say the person is like in their 20s and they have primary men or rare they're going to have good breasts so they are a tanner stage for their breasts will be pretty advanced but also the tanner stage for the pubic and axillary hair will also be advanced you'll be like tanner stage 405 because again estrogen controls your breasts and your genes control your pubic and your axillary hair people that have a is androgen sensitivity syndrome they don't have any estrogen problem so their breasts

look great but the pubic and axillary hair does not look good because they have an androgen issue on the flip side people that have molarian egenesis their breasts are great because estrogen is not a problem and the axillary and pubic hair is also great because androgen is also not a problem that's a very critical difference between these two things and again another critical difference which I've mentioned already is that people that have a is the aginotypically 46xy but phenotypically females but people that have molarian egenesis their aginotypically 46xx and phenotypically they're going to be females as well right and again you know people that have androgen sensitivity syndrome you may wonder okay divine so why do they not have mancies well the thing is if you remember one of the things that are produced by the testis is this thing called molarian inhibiting factor sometimes it's called anti-molarian hormone or molarian inhibiting hormone all different things for the same things gonna basically milk your molarian duct right so because he nukes the molarian duct you'll not produce those molarian structures and what are the things that are derived from the molarian duct but it's gonna be your fallopian tubes your your uterus your cervix and your upper vagina all those things do not develop when you have AIS because those testis those that go not because the presence 46xy is producing AMH or MIA for MIA whichever name you you know the floats your boat and that's gonna basically milk the molarian duct and you won't produce any derivative of the molarian duct right so why do people that have molarian egenesis also because think about these it's kind of hard to have kids if you don't have a uterus right but if you also look at it from the flip side in molarian egenesis again molarian duct does not develop so they don't have fallopian tubes no uterus no cervix no upper

vagina they don't have any of those things again kind of hard to have mancies when you have no no uterus right but again if you notice the gonad in people that have AIS is like a test is a testis the gonad in people that have molarian egenesis is an over again these things I feel like people over complicate them they're just like two or three things that help you differentiate them and the USML is many times they'll include adequate information for each of you to differentiate these two these two things okay now what if they give you a question on in fact let's maybe do a few vignettes related to the anemias right so what if they give you anemia in a person that has lost weight and the person is over age 50 right and let's say the person they tell you that a hemocult testis positive well we want to think about some kind of GI malignancy right in that case you probably want to think about some kind of iron deficiency anemia remember iron deficiency anemia causes a microcytic anemia right and again your stores are depleted so your furtions gonna be low your furtions low then you're gonna be hungry for iron TIBC your you know total ion binding capacity is gonna be pretty pretty high right and your transfer insaturation again transference literally shuffles iron around your blood you don't have enough iron so it's not gonna be it's not gonna be for it so you're gonna have a decrease transfer insaturation now what if they give you a question about a person you know that's from like Vietnam and this person has a microcytic anemia and they tell you that you know many family members are kind of like transfusion dependent um then you know and they give you like a um a blood smear you'll see target cells although many times you don't do that anymore in exams but they can also just say that oh they perform hemoglobin electrophoresis and you notice that well the hemoglobin A2 is

elevated if you see that then obviously this person has beta thal major right remember beta thalassemia is another cause of microcytic anemia and again you're gonna see target cells on a blood smear now beta thalassemia for this person to be transfusion dependent it pretty much tells you that the person likely has a beta thal major right it's just highly unusual to have beta thal minor and be transfusion dependent because those beta gloving genes we have two genes that quote for those right so if you have beta thal minor one gene is kind of screwed up so you you know you still have one gene that's kind of helping out right but beta thal major is where both are messed up so you essentially don't have any beta gloving if you don't have any beta gloving you're gonna have a few problems right like number one uh you won't be able to make adult hemoglobin because that ultimate gloving is alpha 2 beta 2 well it's kind of hard to make alpha 2 beta 2 if you don't have beta gloving genes right but these people have an increase in hemoglobin A2 hemoglobin A2 is alpha 2 delta 2 alpha 2 delta 2 clearly that does not involve beta gloving genes so the person is gonna be fine right I'm telling you this there are causes there are many causes of increase hemoglobin A2 but on the USMD step two step three exams if you see an increase in hemoglobin A2 they pretty much testing some variant of beta thalassemia if the person has like very significant same thalves their transfusion dependent it's probably beta thal major that they have they probably do not have beta thal minor and one thing I also want to say here is between the two because obviously there are two kinds of thalassemias this is the alpha thalassemias and it's the beta thalassemias the thing is when people think of hemoglobin apathes they always think that oh every kind of hemoglobin apathes is diagnosed with hemoglobin electr

ophoresis that is absolutely not true okay sickle cell disease is in fact diagnosed with hemoglobin electrophoresis beta thalassemia is in fact diagnosed with hemoglobin electrophoresis but it is floridae high you to know that you should not do hemoglobin electrophoresis for alpha thalassemia because hemoglobin electrophoresis may distort basically it may be normal you may notice actually is normal in many people that have alpha thalassemia well why is that because the thing is I kind of think of the alpha globin gene the alpha globin chain as almost like a wrickly meeting step of every kind of hemoglobin right I mean think of any notable hemoglobin you know contains alpha chains right like hemoglobin f is alpha 2 gamma 2 adult hemoglobin is alpha 2 beta 2 that which is hemoglobin a hemoglobin a 2 is alpha 2 delta 2 right so the thing is hemoglobin electrophoresis is almost like a test of proportions so because like pretty much all your major hemoglobin have alpha chains in them if you have a deficiency of alpha chains then everything will be proportionately decreased so you will not see any proportional differences in the kinds of hemoglobin for most kinds of alpha thalassemia right but if you look at beta thalassemia for example the thing is beta he's only found in one kind of hemoglobin adult hemoglobin alpha 2 beta 2 that's hemoglobin a right so if you do hemoglobin electrophoresis you notice that man this presents hemoglobin is pretty low but the others are kind of going through the roof because again these ones do not include the beta globin chain so again it's very very high you to know that beta thalassemia can be diagnosed with hemoglobin electrophoresis alpha thalassemia absolutely cannot be diagnosed right so we've talked about like the two big causes of micrositic anemia we've talked about iron deficiency anemia we've talked about thalassemia the other one

I'm going to talk about is it's going to be lead poisoning right so usually on the exam they'll give you some question about a person you know that's maybe like an immigrant or they deal with like old pottery or the person works with car batteries stuff like that when you see something like this think of lead poisoning and many times they're going to have paraphrony or apathy and abdominal pain that's very high you to know paraphrony or apathy and abdominal pain right because why do you think lead poisoning causes a micrositic anemia well here's the thing here's the thing in general if you have any problem with the synthesis of hemoglobin you will get micrositic anemia right literally if you have any problem with the synthesis of hemoglobin you will in fact have a micrositic anemia well why is that or think about it um the thing is hemoglobin look at the name hemoglobin it's made of hemoglobin well a globin we've talked about it at the genetic level right globin is is made from a gene you know transcribe said gene make mRNA translate said mRNA make protein right fine so that's the globin part we've talked about that part right because again the thing is if you're able to organize things in your head it's just a lot easier to remember these these things right but if you have a globin problem well you're gonna have a hemoglobin problem so you're gonna have micrositic anemia if you have a hem problem then you will not be able to make hemoglobin and that's also gonna cause micrositic anemia right and I'll explain why that micrositis is a thing because many people just kind of memorize it but there's actually some pathophase there I'll give you like a pretty pretty good description of of what why that happens but if you look at the him so we said that hemoglobin is hem plus talked about the globin part the hem part he is made of iron plus proto-poffering iron plus proto-p

offering right that iron if you have a deficiency of iron you have iron deficiency anemia you're gonna have a reduced uh you're gonna have a micrositic anemia from that so we'll talk about that part right but the other part is the proto-poffering part where proto-poffering is made in the hemsynthesis pathway right and the thing is led it just so happens that it kind of crosses two key enzymes in that pathway it crosses a-li dehydrate a-li dehydrate dehydrates amino levolinic acid dehydrates and it also shuts down a ferro-killities ferro-killities actually is what combines iron and proto-poffering to make him right so because led inhibits those processes it's going to cause people to have it's gonna cause people to have a uh micrositic anemia right so uh why do why do these problems with hemoglobin synthesis specifically cause a micrositic anemia well the reason that these specifically cause micrositic anemia is that typically red blood cells like the thing is there is let me introduce a concept and we have talked about in this in previous podcast but it's a concept that Ashura talked about here it's actually very important many things in the body are not controlled necessarily by just a mount they are controlled by concentrations i'm gonna say that again many things in the body are not controlled necessarily just by a mount they are oftentimes controlled by concentrations right so the thing is we know that concentration is mass over volume many of you remember this from general chemistry you know c-course m-over-v concentration is mass over volume well the thing is mass in a red blood cell many times is constituted by hemoglobin volume right is you know the dimensions of the cell so the thing is your body wants to keep your hemoglobin concentration fairly constant right your body wants to keep hemoglobin concentration fairly constant that's at least this is the way i

love to think about it so if the mass of hemoglobin is going down for any cause either you have phallacemia or you have iron deficiency or you have lead poisoning then if you want to keep everything if you want to keep that concentration fairly constant as the numerator is going down right because if you think about it the numerator going down is causing the concentration to dip well if you want to bring that concentration back almost like a state of homostasis the denominator of that fraction has to go down as well right because if you think about it if you decrease volume then you can bring concentration back up because again by having phallacemia or iron deficiency or lead poisoning your mass of hemoglobin is going down that's bringing down your concentration you don't want that you want to bring that concentration back to like homostasis so what are you going to do you're going to crush the volume of the cell make the cell smaller so that even that smaller amount of hemoglobin will still give you a decent amount of concentration because you may wonder divine why does concentration matter concentration matters because many things in the body work with the gradient many things with the body working with the gradient things have to go from an area of high concentration to an area of low concentration right that's how things flow right and again you know you may think the riboset is just like some tiny cell no one cares well you should care because here's the thing if your riboset don't work great you're going to have tissue hypoxia and tissue hypoxia carried over time can lead to heart failure you can just cause many things to not work right it can cause many many things to not work right so the this stuff is kind of kind of important to keep at the back of your mind okay so the riboset basically reduces in size almost like a compensation for the reduced amount of he

moglobin so that's why you're going to get a microcetic anemia also you're going to get a microcetic anemia you know if you know anemia of chronic disease kind of straddles both both ages of things you know it's kind of like how do I put it sometimes it can be neuromocytic sometimes it can be microcetic usually we're going to find it in people that have like chronic inflammatory diseases right like Croz disease or stradile colitis, scleroderma, you see a person has like some kind of vasculitis right or you see a person has like rheumatoid arthritis all these chronic inflammatory diseases they can all cause that that problem right an emia of chronic disease right even anemia of chronic disease believe it or not can again it can be normal cellic but it can also be microcetic right the big agent there obviously is hep side in right hep side in pretty much those two things to you want you don't reabsorb ironier got and two it pretty much prevents your bone marrow microphygis from releasing the iron you have so your iron stores are good your phyridine is actually pretty pretty high but your TIB Cs low right because again when your body sees inflammation it thinks that wow bacteria around and the thing is bacteria they do actually need iron to survive so if you keep the iron in the bone marrow microphagis the bacteria will clearly what bacteria wants to go inside the microphage that sounds like a death wish right so the bacteria will know when you know you know if you keep that iron away from bacteria they will not reproduce and that would help right so anemia of chronic disease right caused by hep side in the side of kind of those those things so the phyridine is going to be high your TIBC is going to be low and again transferring again like I said is the protein that shuffles iron around in your bloodstream if the iron is stuck in your bone marrow in those bone marrow micr

ophagis and not in your bloodstream then that's going to cause you to have a decrease of transferring saturation if you're thinking about my moscetic anemia as many people just memorize all this lesson less and less but honestly moscetic anemia is the easier to categorize them as is as follows one is the anemia hemolytic if a person has some kind of hemolytic anemia or if they have anemia from chronic kidney disease all those things are going to be your normal acidic anemia so any kind of hemolytic anemia right like hereditary psoriasitis that's a hemolytic anemia a hereditary lymphocytosis that's a hemolytic anemia although immune hemolytic anemia does go to me on normal acidic anemia right if a person has kidney disease if you have CKD well you're not going to be making epoch because epoch literally is making your kidneys if you don't make epoch then you may have to stimulate your red loss cell precursors or you're going to get in a lot of trouble right you're going to get in a lot of trouble with with anemia right you're going to get in a lot of trouble with anemia remember heidic chisers like tosesis, muvacurusumodaminin, the solder you know spectrum anchoring those band proteins are you notice that those are red lossel membrane proteins so these people there's no problem with their hemolytic anemia right the problem is with a red lossel membrane in fact that's why the mchc is up the hemoglobin is fine but the size of the membrane of the red cell is diminished right so going back to that concentration business I discussed the mchc is going to go up right and again because the hemoglobin is so concentrated if you don't be in hypotonic solution that's that red lossel literally will explode that's essentially the basis of the osmotic fragility test that we see with a hereditary sphero cytosis although these days we also love this eocene 5 malaymide acid right and the

n if you're thinking about macrosidic anemias if you're thinking about macrosidic anemias right you want to think about B12 deficiency fully deficiency right those things in hebit DNA and again you may wonder okay why will inhibiting DNA synthesis cause me to have macrosidosis well let me explain if you think about it when your DNA synthesis happens you know like during the s phase right you know of the cell cycle right I know who who surprise surprise you're starting for step two step three you're like oh gee divine s phase wait what yeah yeah yeah those things you learn back in the day our first step one are kind of important or you know maybe back in undergrad actually so here you know so the thing is as DNA is being synthesized if you notice when you know my toses is about to happen for example the cell actually does increase in size because if you think about it the cell when my toses happens the cell is basically going to be splitting into parts well if you want to split into parts and you want the parts that you're making to be the same size as the ancestor then you better believe that that cell is going to get bigger right but the thing is the way think of B12 or fully deficiencies that these people kind of hit a roadblock of some sort right they're like man okay she like okay the cell is getting bigger and bigger this was getting bigger and bigger gee the cell is getting bigger and bigger but man what is the DNA that we can use to separate you know make DNA material for this new cell DNA material for this new cell so you kind of have a bottle neck there because the cell is getting bigger but the DNA synthesis is not catching up with that size of the cell you end up having a macrosidic anemia that's actually an advice way to kind of think think about it right that's a very nice way to think about it so just kind of categorize these things in your mind you know

B12 deficiency many times they'll have peripheral neuropathy they can have so-bad kid combine the generation of the spinal cord where the cortical spinal tract and the brussel columns those not works they're going to have upper motor nearer on symptoms and they're also going to notice that they're going to have problems with fine touch and proper perception right fine touch and and proper perception right and also vibratory sensation so they're going to have all those all those problems they're going to have all those all those problems you know you're they're going to have like an increase in their homocysteine and they're also going to have an increase in their methanol malonic acid levels because remember methanol maloneux cohe mutates right it's an enzyme that converts methanol maloneux cohe to succino cohe uses vitamin B12 as a cofactor right it doesn't use folate at all right so that's why folate deficiency the only thing it does is that it raises your homocysteine folate doesn't do anything to your methanol maloneux acid levels okay so these are happy to review go ahead and stop here if you're taking step two or step three or step one anytime soon I have classes that literally start tomorrow right I literally have a biostatistics class it's a four hour class it's for step one to step three tomorrow it's a four hour class if you're interested it's in the evening should be an email I'll give you some more information and then I have a social sciences ethics quality improvement healthcare systems communications professionalism class so five hour class that one is actually going to be taking place on Friday so five hour class is going to be taking place on Friday evening again if you're interested it's for step one to step three should be an email and then I have a test taking strategy class also for step one to step three that's on Saturday it's also in the eveni

ngs from like five to seven thirty p.m.

Pacific time all these classes over Zoom if you're interested you should be an email I'll give you some more information and then if you take a step towards step three you're trying to get in your scores before you know the ira's deadline or whatever I have a class that starts next week it's going to be next week Monday Tuesday Thursday and Friday next week Monday Tuesday Thursday and Friday um it's 20 hour class for step two step three and also if you're taking your shelf exams I want like a very good road overview that class is exactly what you need again there are many people that have taking these classes done extremely well and these classes are not lectures they are pretty much all based on scenarios pretty much all based on scenarios um many people have taking these classes again like literally I've got it emails I get emails almost every day wow definitely I go into two 60s two 70s or whatever after taking these classes uh these classes are all scenarios lots of integration lots of explanation of pathophase so I think it's something I'm going to find to be helpful and then finally I do uh offer these podcasts on the major apps Apple Google Spotify have a You Tube channel divine intervention usm.ly podcast and videos that's where I post the videos that I make and then I also have I also offer one I want you to learn for all the usm.ly exams you know like med school exams as well as shelf exams and I help with ira's applications right you know personal statements rec letters um editing your ira's applications supplemental applications do more interviews um and then I also have another website called divineinterventional life lessons.com many people have been like wow divine I love your life lessons um so I said off from a separate website it's bible based many of you know the Christian so bible based website and right now we have like I think almost 210 podcasts

I post like two podcasts every week just check out divineinterventionalife lessons.com there's actually an Apple podcast as we share with that called the divine intervention life lessons podcast okay so thank you for listening to me today I hope you find the stuff to be helpful I promise you this episode 100 is actually pretty high I mean this rapid reviews you know series 100 is actually pretty pretty high yield so we'll see you in a piece of 477 God bless you have a wonderful rest of your weekend bye for now thank you

AIS is 46,XY; MRKH is 46,XX.

Anti-Müllerian Hormone (AMH).

Low ferritin, high Total Iron Binding Capacity (TIBC), and low transferrin saturation.

Because most major hemoglobins contain alpha chains; a deficiency in alpha chains causes proportional decreases across all measured hemoglobins, making the test appear normal.

ALA dehydratase and Ferrochelatase.

Peripheral neuropathy, difficulty with fine touch/proprioception, and potential upper motor neuron signs (e.g., spasticity).

Defective androgen receptor leading to inability to respond to testosterone.

Androgen Insensitivity Syndrome (AIS).

In AIS, breasts are good (estrogen fine), but pubic/axillary hair is poor (androgen issue); in MRKH, both breasts and pubic/axillary hair are typically advanced.

Elevated Hemoglobin A2 (HbA2).

Anemia of Chronic Disease (ACD), due to hepcidin trapping iron in macrophages.

The cell size increases during preparation for mitosis, but DNA synthesis cannot keep up with the increasing cell volume, creating a bottleneck.

Methionine synthase/Methanolmalonic acid pathway; Methylmalonic Acid (MMA) and Homocysteine accumulate.

Defective androgen receptor leading to inability to respond to testosterone.

Androgen Insensitivity Syndrome (AIS).

In AIS, breasts are good (estrogen fine), but pubic/axillary hair is poor (androgen issue); in MRKH, both breasts and pubic/axillary hair are typically advanced.

Elevated Hemoglobin A2 (HbA2).

Anemia of Chronic Disease (ACD), due to hepcidin trapping iron in macrophages.

The cell size increases during preparation for mitosis, but DNA synthesis cannot keep up with the increasing cell volume, creating a bottleneck.

Methionine synthase/Methanolmalonic acid pathway; Methylmalonic Acid (MMA) and Homocysteine accumulate.