DIP Episode 83 - USMLE Step 1 Hematology Review (Part 5)

Okay, welcome. My name is Divine. I am a PGY1 transitional year resident, a win-intor ideology. This is the third episode of the Divine Intervention podcast and in today's episode we'll be continuing a discussion of HIMONC as a review for the USM Lista.com exam. I'm almost certain that we'll have one more podcast and after that actually I'm not all I'm certain we'll have one more podcast and that'll be the final one. So part six will be the final conclusion of HIMONC for for the USM Lista.com exam and I apologize I haven't made podcast in a while. I'm on a busy medicine rotation and I've had a ton of patients the last few weeks so just kind of hard right. So but let's go ahead and begin. So and they are actually attached slides for this because I want that to employ certain like testing strategies with this particular episode because I feel it's particularly important to be able to differentiate certain things I'm going to discuss today and this podcast is floridly high yield for the USM Lista.com one. I can almost promise you you probably get like six seven questions just from this podcast alone. So question one we have a twin three-year-old male being treated for resistance schizophrenia that becomes February okay. His white count is 750% neutrophilus detected on CBC and then I have a closely related vignette here. There about a 34-year-old female has proptosis on physical exam and she has new onset a fib.

So I really hope that for the first person right so you're like oh they've got schizophrenia if you've got resistance schizophrenia is not responsive to treatment I really really hope you're thinking about okay you've tried how to pair it or not work in you've tried many of the other it's typical is not working so you're jumping into the land of a clasapin. Remember clasapin is one of two psychiatric medications that has been shown to decrease the risk of suicide that is actually very high yield to know for the USM Lista.com one it decreases the risk of suicide the other one is lithium that's used for bipolar disorder. So clasapin right to remember one high yield side effect is a granulose itosis right so this person basically has a neutropinic fever because of the white count is 700 and the half 50% neutrophils 50% of 700 is 350.

So they have a neutrophil count less than 500 right you're worried about an intra-pinic fever so the next thing you want to do is basically this is more for step 2ck you want to start them on a drug that covers pseudomonas right so you're likely to use paparacillin and tizobactam or you can use an amino glycoside or like gentamysen or you can use a seftazidim that's a third genersion sephilosporin that covers pseudomonas or sefepim that's a fourth genersion sephilosporin that covers pseudomonas or you can use your your command divine think you can use your monobactams like astrayonam or you can use your carbapenem like meropenem, eropenem, imipenem, doropenem those all covers pseudomonas so that's I guess a nice review of us pseudomonas so I mean pseudomonal coverage right so again if a patient has a neutropinic fever you want to cover pseudomonas and then the other thing and I'm giving you is basically a person that likely has greas disease right they have hyperthyroidism I remember hyperthyroidism one of the most common causes in the US is greas disease remember that's where you have like thyroid stimolitis and monoglobulins that attack the TSH receptor on the follicular cells of the thyroid gland right so they have the proptosis and you've probably seen those scary pictures in textbooks and then they also have like new anserifib remember it's actually very high you to notice the most common arrhythmia in patients with hyperthyroidism is is a fib that's actually a very high-yield concept that's tested on the USML is right so why would they have a neutropinic fever I really hope you're thinking about the anti thyroid medications like p2y or methamazone remember that both of those medications actually can cause a granolocyteosis as a side effect so you basically need to watch white blood cell counts when patients are on those drugs now so those patients have neutropin

ic fevers and again they essentially have like you know like basically just think of them as having like like some kind of a destruct don't think think of it as like a bone marrow suppression a sort of deal right so the big concept I'm sort of talking about with these two things right so I talked about two situations where people have like low white counts the thing is people that actually have like clasping toxicity or p2y methamazone toxicity because actually occasionally have scenarios where you actually suppress the entire like all their like hematopoietic cells right so they may have like low white cells low playclats low red cells that is rare but that is certainly possible right so basically the big concept I sort of want to talk about here is like a plastic anemia right so remember a plastic anemia can be caused by many many many many things right so it can be caused by drugs right so you're thinking about like your anti thyroid medications you're thinking about your your clasping right remember those things can cause a plastic anemia also don't forget like certain viruses remember your poster child in fact it's probably the only single stranded DNA virus you need to know for the USML is step one but that happens to be a powerful virus being 19 remember it can cause like the slapped cheek rash in kids and remember that it's classically on the USML is it can show up as like a lady that works in a dick here that has that has like weird like joint complaints and remember that it can also cause like hydroxpitalis if kid has like congenital like parvo b19 infection and also don't forget right people with hemoglobin opathies right so like sickle cell disease and whatnot they can get like an aplastic crisis in the setting of in the setting of a parvo b19 infection or it so that's another thing that can cause a plastic anemia if you look at the second vignette where I

talk about like a 12-year-old male that has over the last few is developed like massive generalis lymphatic anapathy and hypytospelano-megaly and then a flow cytometric studies reveal a 15-17 translocation so obviously notice a cute pro myocytic leukemia because you've listened to the previous podcast that I just gave and then I say that you know he's been trans trans-transition dependent on his life and physical exam is notable for the absence of the right thumb that's kind of weird okay and his head circumference has always been in the second percentile right so this person basically has a microcephaly right so what's your diagnosis right so this patient has developed aml right that's why it's called acute leukemia it develops over a relatively short period of time and actually for these things you want to treat them relatively quickly because they actually acute leukemias especially when a person has like a blast crisis they actually like rapidly fatal so you don't want to sort of like mess around and sort of stew around with acute leukemias for the most part so this person has aml right and he develops this aml in the setting of basically the way set of this question is they've had like a chronic condition and then somehow they've gotten aml as a result right so this question I'm referring to I'm essentially talking about um fanconi anemia right so remember fanconi anemia right can the classic we will present on mbm is is kids may have like coffee or less spots right so remember coffee or less spots not always cost by endocrine disorders they can also be caused by hematologic disorders and the key one you want to know is fanconi anemia right so fanconi anemia can cost coffee or less spots usually those kids tend to have like thumb abnormalities and then in addition to that those kids tend to have like very tiny heads right so like microcephaly and they add increa

sed risk of like many hematologic malignancies right so those are kind of like high your fins you want to keep at the back of your mind so this child has this child has fanconi anemia right and remember that fanconi anemia right the pathophysiology arises because or let's put it this way it basically arises because people have issues with like double-stranded DNA repair right so I believe I may have talked about this or I will talk about this in one of the cell biology podcasts where I talk about like how you can use like homologous recombination is one of like these high-yield mechanisms behind like double-stranded DNA repair and if you have problems with those that's how fanconi anemia presents in fact in general the patient has fanconi anemia if you expose them to something that like an agent that sort of puts a lot of stress on DNA the classic one is like mitomycin so let's say you're trying to like grow lymphocytes in the presence of mitomycin that places a lot of like stress on DNA you notice that these people have a ton of like chromosome breaks right if you're doing those specific studies in the presence of mitomycin that's one of the ways that a fanconi anemia is actually diagnosed so don't forget skin problems thumb problems small head increase risk of hematologic malignancies think about fanconi anemia please don't confuse fanconi anemia with fanconi syndrome I'll talk about that in a in a bit right so again this first like basically is just talking about the plastic anemia so just so to keep all these things at the back of your mind and again remember when I talked about like primary mylofibrosis right in one of the earlier hemon podcasts I said that primary mylofibrosis those people also have like a dry type when you do a bone marrow aspiration and they have like those tear drop sheep to red blood cells symphen arises with with a plastic anemia you'll als

o have a dry type when you do like a bone marrow aspiration but in general I'll say for the USML is do not associate a plastic anemia with tear drop sheep to red blood cells so I think that's all I want to say for this slide and I mean obviously right because if a person has a plastic anemia and they're not making enough red blood cells you would imagine that the aratical side count should be low right it should be pretty low and in addition right because the anomic in red blood cells how do you think the period to be the endothelial cells that constitute the period to be like a pillars of the kidneys would respond I would really hope that you're saying they're like oh wait there's no red blood cells here let's spike up a production of a retropeweaten okay so you sort of keep those things at the back of your mind so I think yeah I feel pretty good about the slide so let's go ahead and move on to the next question so the next question says a 13 year old immigrant from Athens right so it's a pleasing grease or if you're an MBA fan remember the Greek freak right Yannis Antito Combo so pretty great basketball player probably be the successor to LeBron James but that's a different story let's come back to the real world so 13 year old immigrant from Athens is brought to a pediatrician to establish care basic labs obtained and notable for him who glubing of nine he's asymptomatic a blood smeared consistent with the findings from below so my question what is your diagnosis and what is the pathophysiology right so I am really really hoping that you recognize on this image that we are looking at target cells right and if we're looking at target cells that means we are very likely referring to a thalacemia although remember target cells can be found in like liver disease they can even be found in many other diseases right but usually for the US MLE's you want to think about tha

lacemia's first you want to think about liver disease second okay if you see target cells so but one thing right that you've probably heard me mention is that in general for the US MLE exams the pictures are not absolutely necessary for you to get a question right right so basically if they give you geography and I in an MBA me question you're trying to tell you something right if you if they mention like Greece right you're like this person probably has like some kind of like thalacemia likely like a beta thalacemia right because beta thalacemia is a very common in people of Greek ancestry I'm trying to see if there's any other like Greek association for the US MLE's yeah the G6 PD deficiency right so it's also associated with with with Greece right but that's besides the point but again if you did not have the picture and I just said Greek person anemia microcetic first thing that really should come to your mind is a beta thalacemia okay like a beta thalacemia minor for example right so and the classic finding right on imaging on on microscopy right if you do a blood smear at these are target cells right so you see like like red like pink in the center a white rim around it and then pink on the edges of the red blood cell right that's classic for for target cell kind of looks like a bullseye so the thalacemias right so obviously right you should hopefully know that your thalacemias right there are two kinds of thalacemias right so there's like alpha thalacemias there is beta thalacemias and the alpha guess let's maybe spend some time talking about some nice pathophys here right so let's talk about the the beta thalacemias first right so the beta thalacemias basically the rises when you have issues with making globin right remember him all globin is made of him and globin right so if you have troubles with making globin then you have troubles making him all globin an

d if you're not making him all globin right you have an anemia right you have like a microcytic anemia sort of picture okay so in general right you get like beta globin gene the beta globin gene I believe if I'm not mistaken is on chromosome is on chromosome 11 so and usually you get like one chromosome 11 from that and one chromosome 11 from mom right so if you have mutations in one gene right you have something called beta thal minor if you have mutations in both genes you have something called beta thal major okay and for the USML is actually high you to know that the most common mutation that causes beta thalacemia for the most part is a mutation with like the process of alternative splicing okay just one of those weird high-year things you want to keep at the back of your mind and the thing is there are actually like a crap ton of mutations that cause beta thalacemia right it's like there's probably like I don't know like 70 80 90 different mutations that can call beta thalacemia so if you really think about it because this is one very nice way they can tie this with with cell biology on step one right it's like multiple different kinds of mutations that can give rise to one phenotype that's something known as like especially like at the same gene right so it's like it's like all like little mutations here and there but they're all in the same gene but they can cause the same like phenotypic presentation that's something known as like a lillic heterogeneity okay so it's like oh their leals their their because remember right two copies of the same gene are known as alleles right but those alleles you can have like multiple different mutations in them that can cause a lot of that can cause basically the same the same troubling presentation think about that concept a lillic heterogeneity that's a very nice way they can actually test that on the usm only step one exa

mple so so that's it with the beta thalacemia right but there's a few more things we should discuss here right so I said that you get one chromosome 11 from mom one chromosome 11 from that the one chromosome 11 if the one chromosome 11 from mom and the one from that basically tells you that you have two genes total right so that's why you know one gene you have beta thal minor you know two genes you have beta thal major right and the thing is classically to diagnose these hemoglobin operatis like beta thalacemia right the thing you want to go ahead and do is something called a hemoglobin electrophoresis and the thing is if you're dealing with beta thal minor on hemoglobin electrophoresis you have an increase in hemoglobin F right but that is actually not diagnostic I'll say the thing that's more diagnostic for beta thalacemia is an increase in hemoglobin A2 okay in fact let me tell you this this is floridly high to know for the usm please if a person okay has an increase in hemoglobin A2 on a usm on any usm exam doesn't matter step one step two step three you should have a very good reason for not picking beta thalacemia minor okay you should have a very very good reason for not picking beta thal minor so so remember your different hemoglobin right so hemoglobin A is like alpha 2 beta 2 hemoglobin A2 is alpha 2 delta 2 hemoglobin F is alpha 2 gamma 2 right so the reason why your hemoglobin A2 will increase in the setting of beta thal minor is that you don't have as much in the way of beta globing gene change right so other kinds of hemoglobin that do not depend on the presence of a beta globing chain will begin to spurs up right so you have more hemoglobin A2 so alpha 2 delta 2 you will actually have more hemoglobin F alpha 2 gamma 2 right but the big thing you want to look for in exams is an increase in alpha 2 delta 2 right hemoglobin A2 and let me ask you a quick q

uestion do you think a person will have hemoglobin A detected on hemoglobin electrophoresis if they have beta thal minor I really hope you're saying yes right because remember if you have beta thal minor one of your beta globing gene change like genes is still working so you're still making some beta globing okay so you still make some hemoglobin A so you have like you still from your alpha 2 beta to some hemoglobin A right and the reason I'm asking this question is that if you notice if hemoglobin electrophoresis shows you increasing hemoglobin A2 increasing hemoglobin F and you still detect hemoglobin A so that's not how hemoglobin that tells you you're dealing with beta thal minor however what if you see an increase in hemoglobin A2 and increase in hemoglobin F and you are not detecting hemoglobin A if you see those hemoglobin electrophoresis results I am really really really hoping that you are thinking about beta thal major right because in beta thal major you're two beta globing gene change are screwed up so if they are both screwed up you're not making any more beta globing so if you're not making any more beta globing you will not be able to make any kind of hemoglobin that depends on the presence of a beta globing chain basically hemoglobin A so no hemoglobin A but your hemoglobin A2 will go up because hemoglobin A2 does not contain beta globing and your hemoglobin F will go up because your hemoglobin F does not contain a beta globing right so again you need to be able to interpret these hemoglobin electrophoresis results for your exam they are very very high yo to no and then your alpha thalacymias right so your alpha thalacymias so the thing is think more about chromosome 16 versus the chromosome 11 we talked about for the beta thalacymias so think more about chromosome 16 and the thing is you actually get two genes from each parent for your two like alpha

globing genes from each parent right so it's like two from that two from mom both on chromosome 16 right so you basically have like four alpha globing genes right so again keeping with a theme of a thalacymia as where is like oh you're not making enough of a globing gene chains if one of the four genes is screwed up you have some malonymia no one really cares not clinically significant but if you lose two you begin to care right that's like alpha thal many people call it like alpha thalacymia trait right so those people have like so malonymia you can detect it on labs but there are not things that there are not things that people you know classically get like super symptomatic from however there is one high-yield key thing you want to know for your exams the thing is right so I say that there are four total alpha globing genes and I said if you lose one no one really cares if you lose two they actually two different ways you could lose two right so you could lose both genes from one chromosome or you could lose one gene from one chromosome so one gene from like that chromosome 16 that you have and one gene from mom's chromosome 16 that you have right so if you're losing both genes from the same chromosome so let's say oh both of the alpha globing genes on that's chromosome 16 and knocked out that is the cis kind of alpha thalacymia trait but if you're losing one alpha globing gene from that's chromosome 16 and one alpha globing gene from mom's chromosome 16 that is the trans alpha thalacymia trait and it so happens that's the trans alpha thalacymia trait is actually the clinical presentation is usually not a severe as the cis alpha thalacymia trait right so remember your cis and trans right from organic chemistry like you'll see South Keens and your trans alkenes let's shut down that organic chemistry discussion I don't give some people nightmares but basically the ci

s alpha thalacymia trait tends to be more severe than the trans alpha thalacymia trait and if any is the trans alpha thalacymia trait is usually far more in like Africans right so if you see like a Ghanian or Nigerian with alpha thalain you examine you really want to think about the trans alpha thalatrate right so if they have alpha thalatrate and they're Ghanian or Nigerian think about the trans kind of the alpha thalatrate right versus a person that's like from Vietnam or like some kind of like South Asian population you want to think more about the cis alpha thalacymia trait and that tends to be a little more severe and the thing is if you really think about it what do you think would potentially happen if two people with cis alpha thalatrate get married right so let's assume you have like two people they get married and let's assume that on luckily the deformed chromosome 16 from mom that is missing both alpha globin genes is transmitted to the to the fetus and then did the formed chromosome 16 with both alpha globin genes knocked out from that is also unfortunately translated to the fetus basically that fetus will have a defective chromosome 16 from that with the cis alpha thalatrate issues and a defective chromosome 16 from mom with the cis alpha thalatrate issues so guess what that fetus will not have any alpha globin genes and guess what that fetus will not be born why is that because that fetus has something known as hemoglobin hemoglobin barks right so that's basically where you've lost all four alpha globin genes change right so basically those kids will have like gamma four hemoglobin that's called hemoglobin barks it's not compatible with life those kids would likely die in your right so contrast that with a kid that loses three of the four alpha globin genes change that's called hemoglobin H disease they tend to have like very severe anemia okay and that

severe anemia basically arises from birth and that's where you want to be careful right because people may be like divine why is that important for exams here's why it's important the thing is beta thal minor right I said that oh beta thal minor arises when one of your so remember I said when I told him about beta thal minor I said like okay one beta globin gene is screwed up right so they'll have like anemia right but the thing is they're and then in beta thal major they lose both beta globin genes right so people beta thal major they actually get severe anemones right and they sort of become like transfusion dependent but it's actually high yield to know that their symptoms do not start until after six months because remember you have a crap on a hemoglobin if at birth and it's sort of processed for about six months so you don't really get symptoms right that birth with beta thal major because you are not heavily dependent on hemoglobin that needs beta globin genes okay but if a person has like hemoglobin H disease where they've lost three alpha globin genes right those people have severe symptoms from birth because hemoglobin F itself requires alpha globin genes right remember hemoglobin F is alpha 2 gamma 2 so patients with hemoglobin H disease have problems from birth patients with beta thal major have problems from from after six months of delivery okay so it's again one of those rare things you want to know so I feel like I've talked about some hair stuff so let me just summarize this real quick if you lose one alpha globin gene known really cares not clinically relevant I mean you have some anemia but known really cares if you lose two you can lose it in one of two is you can lose it the cis way think about agents with that and that's more severe and you can lose it the trans way think about where staffer can't that's less severe right and then if you lose al

l three if you lose three of four you have something called hemoglobin H disease severe anemia from birth okay if you lose all four never born right that's hemoglobin births because they are forming gamma for hemoglobin right that's hemoglobin births hemoglobin H is actually hemoglobin that is a beta 4 tetramer right because again if you have very limited alpha you the bitters will begin to congregate amongst themselves right so you have a beta 4 tetramer and then for beta thalcemia I said that and I'll say this in general hemoglobin electrophoresis is not useful for alpha thalcemias okay there's reasoning behind that but I don't really have the time because I don't want this podcast to be too long so I'm gonna move on because there's other important things I need to cover but hemoglobin electrophoresis is awesome for beta thalcemia and I said in beta thal minor they'll have an increase in hemoglobin A2 and increase in hemoglobin F and hemoglobin A will still be detectable on hemoglobin electrophoresis contrast out a beta thal major where they have an increase in hemoglobin A2 and increase in hemoglobin F and hemoglobin A will not be detectable on hemoglobin electrophoresis and the reasoning behind that is because if you have beta thal major both beta globin genes are gone so you're not making any beta globin so any hemoglobin that depends on the presence of a beta globin a gene is not existed right like hemoglobin A which is the case in point and remember that your thalcemias remember like you have the inherited like in an autosomal recessive fashion and again particularly prevalent in like Africa right because it's kind of protective against like malaria right against like a plusmodium infections right and I mean there's many theories behind that but in general like red lot cells that have a lot of like hemoglobin apathy's they tend to associate more with with immun

oglobulins right and if you associate it more and more with immunoglobulins you are more likely to like be protective against bugs that attack red blood cells like malaria in this instance and not that you need to know the mechanism or anything like that but just remember that remember that association and yeah I think that's all I'm gonna say with regards to these thalcemias don't forget your target cells and remember that your thalcemias are a kind of micro-city canemia right and usually for the most part I am studies you know pretty normal with with phalcemias I mean obviously for person has a severe phalcemia you give them like blood transfusions but that blood transfusion can also cause like a secondary like hemochromatosis so those people occasionally may need like ion chelidiar therapy right so like deferoxamine or like deferacereox.

So yeah I think that's all I'm gonna say that's all I'm gonna say with these phalcemias so let's go ahead and jump to the next next slide so this versus that right again is super high yield for the USM list right so the first one I've kind of talked about it already right I say that this person has a coffee ole spots right but in addition to having coffee ole spots they have they have problems with your thumbs right so they have like thumb abnormalities so let's say like a hypoplastic thumb or an absent thumb and then their head circumference is in the circum percentile and they have panside opinion so what do I mean by panside opinion by panside opinion I mean that all their cell lines are down so their ribloids cells are down their ribloids cells are down their platelets are down right if you see this you want to think about fancone anemia okay microcephaly small head thumb problems coffee ole spots and all your cell lines are down think about fancone anemia okay now the next vineyard says fish and anomalies plus thumb issues plus pure etsyloplesia right so notice these people also have problems with your thumbs but they have like craniofacial abnormalities versus like the skin problems and the microcephaly that are found in a fancone anemia but notice the only cell line that is down have your ribloids cells their ribloids cells your platelet cancer just fine if you see this you really want to think about a diamond a black fan anemia basically it's like some issues with like their ribloid cell precursors so they have like a pure etsyloplesia usually around the age of two you just notice that man these people see moglobin is like super super it's like super super low and I mean it's basically like a mutation in like some proteins you need for like your ribosomes like your eukaryodica ribosomes so you essentially don't make a ribloid cells right and it's I mean like i

t's not a great condition but it's not as fatal as the many genetic disorders like the biochem disorders where like oh this person has like this like this evil like Lycosomal storage disease so just to keep that at the back of your mind so the only thing again if you see thumb issues with the only cell line being down at the red blood cells you really want to think about a dab wonder a black fan anemia and again it arises because you have issues with with your red blood cell precursors because you have like ribosomal protein mutations and it's actually a cause of macrositic anemia so like your mcv will be greater than 100 right now notice the next question short stature skeletal anomalies malabsorption secondary to pancreatic insufficiency and utropinia so notice here the cell count that is down adjust your white blood cells if you see this you want to think about another hematologic problem it's known as schwaqman diamond syndrome and the way schwaqman is spelled is it's spelled as s let me think about this for a second I think it's s h let me look this up schwaqman diamond yeah the spelling is kind of weird schwaqman yeah it's s h w a c h ma n and then diamond right so why do you think I'm making a big fuss about this I'm making a big fuss about this for actually multiple reasons the first thing is your friends at the USML you know that oh hmm people may confuse diamond black fan anemia with schwaqman diamond syndrome they both have diamond in the knee right and some kind of cell count is down in both disorders but notice it's your neutrophil counts that is down in schwaqman diamond syndrome and it's your red cell that is red cell count that is down in diamond black fan anemia okay so a schwaqman diamond they have skeletal problems okay and the basically you need to look out for pancreatic ins efficiency so you may have like fat malabsorption on your test you see th

at and you see like a low white blood cell count think about schwaqman diamond but if it's only your red cells that are down and they have thumb issues think about diamond black fan and then if all the cell lines are down and you have like small head thumb problems and like skin like hypo pigmentation or like coffee only spots think about a fanconianemia and then the last question here says like I guess second the last question says increase levels of multiple electrolytes in the urine in the setting of a type 2 RTA I really hope you're thinking about fang coni syndrome right please don't confuse fang coni syndrome fang conianemia right fang coni syndrome is a kidney problem fang conianemia is like a hematologic problem fang coni syndrome you basically have like a global transporter issue in your proximal tubio right so you don't reabsorb any thin right so like the phosphate levels in the urine are high everything in the urine is high right it's a kind of a type 2 RTA remember a type 2 RTA is a proximal renal tubular sedosis and then I guess as an aside how can you increase the absorption of supplemental iron let's say you're taking like iron tablets how do you increase the absorption basically you give vitamin like orange juice right so like remember vitamin C activates I think it's called like it's like methemoglobin reductase so it converts like Fe3 plus to Fe2 plus remember Fe2 plus Ferris iron is the only iron we can absorb we do not have the ability to absorb a ferric iron right so I remember that iron is reabsorbed in the Duodenum right so yeah you take orange juice and you're taking iron supplements the iron supplements you just reabsorb more right so very nicely you can test that on the USML step one is just to ask about an intervention that will increase the bioavailability of iron supplementation that'll be the administration of anything that contains ascor

bic acid which is vitamin C okay so I think that's all I want to say in this slide just trying to think is Daniel the Hyalfin I want to discuss here no I think I'm good I feel pretty good about this slide okay again I have to like sort of think on the fly because I plan all these lectures but I give them from memory basically so just bear with me with these arms and us okay so next slide right so we have multiple strokes plus hypotonia in an infant plus elevated methylmalonic acid levels plus hyper ammonemia in fact I want you to contrast the first question the second one where like this person has second person has like upper moron neurons symptoms low moron neurons symptoms but notice they are not infants they are adults and they also have a history of like autoimmune problems like Vidaligo and they have elevated like a methylmalonic acidemia right so remember for the USM Ls there are two things you should actually there are only two things you should think about on the USM Ls when you're thinking about a methylmalonic acidemia right so one is a bit of deficiency that will very likely show up in an adult one is from a mutation in like methyl malonoco amutase that'll be more in an infant right and the key things that will sort of help you differentiate is if you see like a newborn or like a very young kid like you know less than two years old having like many strokes like super hypotonic and they're having like urea cycle like issues where like oh their levels of abonia are like super high and they have a methylmalonic acidemia you literally want to think about metal mal actually the disease condition is called methylmalonic acidemia okay but remember that if you have a B12 deficiency remember B12 is a cofactor for methylmalonoco amutase remember that converts if I'm remembering correctly methylmalonoco am I am remembering correctly I love biochem so methylmalonoco amu

tase converts methylmalonoco to succino coa and uses B12 as a cofactor so if you have a B12 deficiency you will not have a propagativity of methylmalonoco amutase so you will not convert malonoco to succino coa so your levels of malonoco will build up so you have a methylmalonial acidemia right so if you see a person that has like macrosylic anemia right and they have a methylmalonic acidemia you can pretty much stop reading the question on the USML Es you are dealing solely with a B12 deficiency and that will be again more likely in an dot and the reason that this person in the second question has the B12 deficiency is that they likely have pernicious anemia where they have like an autoimmune destruction of like the aparidol cells right and it may not necessarily be the aparidol cells that are like you know destroyed it can be components of the paridol cells that are destroyed right so you may form autoantibodies against intrinsic factor or you may form autoantibodies against that sodium hydrogen sodium hydrogen anti-pointer that you find on the surface of a paridol cell right that's inhibited by inhibited by your PPI's you are put on pump inhibitors like omega-prizol and you can form autoantibodies against that and that will cause a pernicious anemia right and remember that those if you have B12 deficiency you from pernicious anemia you can make the diagnosis by checking for anti-intrinsic factor antibodies there is this test that used to do back in the day like the shilling test but essentially no one does that anymore but even if they don't do that in the real world anymore it still shows of fairly commonly on the USM Ls right so it's just one of those things you want to keep at the keep at the back of your mind so and the the reason that this person in the second question has like the upper motor neuron symptoms and the lower motor neuron symptoms is because they h

ave a subacute combined in generation of the cord right so remember B12 deficiency can cause a subacute combined in generation where you basically destroy the dorsal columns in the spinal cord and then you destroy the lateral cortical spinal tract right so if you destroy your dorsal columns right you have problems with like fine touch and vibratory sensation and perception and then if you damage the lateral cortical spinal tract that's in the dorsum of the spinal cord right those people have upper motor neuron symptoms because remember your cortical spinal tract basically has like upper motor neuron fibers yeah so next question says like macrosidic versus megaloblastic anemia so remember that a macrosidic anemia right is just an anemia where your MCV is within a hundred right but don't forget that macrosidic anemia does not mean megaloblastic anemia okay if I let me make this clear to you megaloblastic anemia is any anemia that is associated with a B12 of full its deficiency okay so if you have a B12 or fully deficiency as the cause of your macrosidic anemia that is a megaloblastic anemia okay think about megaloblastic anemia as a subset of macrosidic anemias okay megaloblastic anemias are a subset of macrosidic anemias right because there are many other kinds of problems that can cause an MCV greater than a hundred right an anemia where your MCV is greater than a hundred the liver disease can do that if you're a boost master or so you consume a ton of alcohol and that can do that a damon black fan anemia right presents with a macrosidic anemia right but B12 fully deficiency the cause macrosidic anemias but if you want to be a little more specific the cause of megaloblastic anemias okay because a lot of plastic anemia is in general anemias where you have problems with like DNA synthesis right so because remember right if can make DNA remember the first thing that basi

cally like doubles like when a cell is prepared to divide right you double your DNA content and then you double the cell size and then you basically cleave the two daughter cells and what not well if I feel if you can double your DNA because you don't have B12 or fully but your cell is like wait I'm getting bigger where is the DNA I need then your cell will not divide as well as it should right but because the cell is getting bigger and bigger and cytoplasm right obviously your cell then if it's a red blood cell it will begin to have like a higher MCV okay so that's why you get macrosidic anemias in the setting of a B12 and a full litre deficiency now next thing here is I guess B12 versus fully deficiency I've talked about this in multiple podcasts if you listen to any of my podcasts you probably heard this like two or three times remember both of those things cause again megablastic anemias which again are subset of macrosidic anemias I remember that in B12 deficiency and fully deficiency you have like a homocyste anemia so your levels of homocysteine will go up right but remember that you have a met themalonic acidemia in B12 deficiency we will not have that in a full litre deficiency and remember that fully deficiency does not cause a neurological deficits B12 deficiency causes your logic deficits like the subacuda combined in generation of the court and then also don't forget that you get full it from plants right from like plants so vegans hopefully don't get a full litre deficiencies and then you get B12 more from like animal products right so vegans especially if you're like an onwise vegan that doesn't take like B12 or supplementation you can get vitamin B12 deficiency that way and next question is like iron deficiency anemia versus anemia of chronic disease so in deficiency anemia right it's is the most common cause of a macrosidic anemia these are basically

both causes of anemia where your MCV is less than 80 right so macrosidic anemias and the thing is if a person has an iron deficiency anemia right they're just not consuming iron right so I mean can I write for many reasons let's see you have like super heavy mancies that can cause iron deficiency right and then you get an iron deficiency anemia with that anemia of chronic disease like literally as this term goes like chronic disease where so these people have literally chronic disease so they may have like rheumatoid arthritis or they may have like cancer right anemia of chronic disease actually one of the most common anemia is in people that have cancer and in fact let me put it this way the most common cause of anemia in a patient that's in the hospital if it's macrosid if it's macrosidic is an emia of chronic disease okay so again one of those weird things to sort of keep at the back of your at the back of your mind and I guess as a compare and contrast right so in iron deficiency anemia right your iron stores are down so your ferritin should be low okay contrast out anemia of chronic disease where your ferritin is high because the thing is anemia of chronic disease you have chronic inflammation bacteria need iron so your body is like well hello bacteria you need iron okay well I don't want to die of this infection from you so guess what I'm gonna do I'm gonna prevent you from having iron right so your body is like okay well for bacteria not to have iron let's just sequester this iron within like macrophages and enterocytes right and the thing that happens is there is this thing called ferritin it's a transporter now you find on the surfaces of like enterocytes in the GI tract on the surfaces of bone marrow macrophages right so ferritin is basically the thing that takes iron from those cell types like say for example right you eat your consume iron and you get into

your enterocytes in your GI tract and you want to send it to the bone marrow so that your rethroid precursors can make red blood cells you use ferritin to sort of make that process happen right so the thing that happens anemia of chronic disease is that if you have chronic inflammation that will increase the synthesis of interlooking one and interlooking six when you have those things release now will increase the synthesis of something called hepsidin and when you have high levels of hepsidin the thing is hepsidin essentially marines ferritin and when hepsidin marines ferritin ferritin is then like endosite toast into the cells that have it right so like the entire sites of your GI tract your bone marrow macrophages so you basically have iron but it's just not available right so it's just like having like a great depression where it's like there's money in the bank but banks are not open to give you that money right so you have iron in the bank you have iron being stored but you cannot bring it out for your red blood cell precursors to use it right so your ferritin is actually high your iron stores are really high in the setting of anemia of chronic disease and remember that your ferritin has an inverse relationship to your TIBC right so the ferritin is high in anemia of chronic disease so your TIBC your binding capacity for iron is actually low in anemia of chronic disease contrast that with iron deficiency anemia where the TIBC is actually high right because think about it if your iron deficient right you want to try to bind as much iron as possible right so you open up more slots right for iron to bind right so that's why your total iron binding capacity goes up right so again ferritin is low in iron deficiency anemia it's high in anemia of chronic disease TIBC is high in iron deficiency anemia but low in anemia of chronic disease right and obviously if you have

iron deficiency anemia your serum iron will be low but actually in anemia of chronic disease because your iron is sequestered but it's not like free flowing in the bloodstream for bacteria to use your serum iron is also low in the setting of anemia of chronic disease okay so I will say that I mean there are other labs and all that crap that they try to emphasize we really don't need those for exams the things you want to look out for your exams you want to look out for your ferritin you want to look out for your TIBC you want to look out for your serum iron and I mean if you also want to go with transfer and saturation fine whatever your transfer and saturation for the most part is low in iron deficiency anemia and it can be low or like normal in anemia of chronic disease so that's not super useful focus more on the TIBC the ferritin and the serum iron and that will give you what you need for your exams and don't forget that your retsell distribution with is actually decreased I mean increased in the setting of iron deficiency anemia okay and then differences in iron folate and beta absorption is an easy question iron is reabsorbed in the in the do addnam right folate is the gijunum there is actually an enzyme that helps you reabsorbed folate is known as conjugase I learn this from a doctor goleian conjugase helps with a fully reabsorption that conjugase is actually inhibited by phenitone that's why phenitone can cause a fully deficiency and that's how white phenitone can cause like neuro tube defect right because you're basically causing a full-liter deficiency and then don't forget that beta of is reabsorbed in terminal area okay so let's do some quick experiments here in step one of this experiment both patients you essentially have two patients patient a and b both patients you're like okay this will have beta of the efficiency fine whatever and then in step two y

ou give both patients like a super high dose of like you know like IV vitamin B12 to essentially like saturated with the a B12 receptors and the B12 stores in their bodies right and then in step three you then give them oral vitamin B12 we are like I'm not seeing your B12 in the urine of these two people that I'm giving oral vitamin B12 right and you would expect normally on the like normal circumstance for like normal people to see B12 in the urine if you give oral vitamin B12 because by giving that initial high dose IV vitamin B12 you'll cover every store vitamin B12 you've covered every receptor of vitamin B12 right so everything is all covered right so any oral vitamin B12 you're taking it has nowhere to go so it just shows up in the urine but for these patients you're like it's kind of weird I'm giving you oral vitamin B12 I'm not seeing B12 in the urine right so I'm not giving you two scenarios and I want you to make a potential diagnosis for these two patients right so let's see for one patient so you then say okay I gave you just oral vitamin B12 nothing is happening you then decide to add intrinsic factor but even after adding intrinsic factor you notice that yeah I'm not still finding B12 in the urine that basically tells you that this person has a problem with absorption of vitamin B12 okay so let's say their terminal ilium may be gone let's see for example they have like Croz disease basically if you have a reabsorptive issue then given intrinsic factor is not gonna fix the problem right because yeah you have intrinsic factor you have all you need but you do not have the reabsorptive surface for B12 in the terminal ilium right contrasting with the next patient where you do find B12 in the urine after you give intrinsic factor so that means oh the addition of intrinsic factor to the oral vitamin B12 fix the problem right so that tells you that likely this p

erson had an intrinsic factor deficiency as the cause of their problems right so this is more that like basically telling that this person has a pernicious anemia right because again given intrinsic factor fixed fixed the problem and basically this question I post is essentially the shilling test right so it's just something you want to be able to reason through on your test and I guess it's not necessarily on this slide but I guess I'll talk about it was kind of high-yield but I think it's here let's talk about the metabolism of B12 right so that you can essentially know all the potential causes of a B12 deficiency right so if you consume B12 there is something known as R factor I believe it's like part of the saliva it sort of binds that B12 that you consume right and that B12 with the R factor travels all the way to the Duodenum okay but in your stomach we have parietal cells right that make intrinsic factor basically that intrinsic factor and the intrinsic factor on its own doesn't actually bind B12 in the stomach the intrinsic factor actually travels all the way all the way to the Duodenum okay what the thing is in the Duodenum pancreatic enzymes essentially break up that marriage between B12 and R factor and then that B12 goes along and marries intrinsic factor okay and then that intrinsic factor and B12 complex is then we absorb through the terminal ilium okay into the body so you can basically see that and really maybe like divine okay why the rigmarine with R factor thin is R factor is like a protecting group for vitamin B12 if you're thinking about like organic chemistry where if you have like a like a reactive carboxylic group you can protect it by like converting it to like like an acyl ester or something like that again I don't want to give people a nightmares because I'm sure as you start basically like oh thank god I never have to worry about who came a

gain so I won't bring back those those are nasty memories for many people okay so so that's why you need that rigmarine with R factor because it basically protects B12 from like the rough neighborhood of the stomach okay that's why basically goes all the way with B12 from the from the from the so yeah so that's the deal with R factor right so so basically you know the causes of a B12 deficiency right so if for example you have prenexious anemia wave attacked your Pridal cells you get a B12 deficiency that way or if you have if you're taking a Prudome Pump inhibitor remember Prudome Pump inhibitors literally they cause like a functional Pridal cell insufficiency that also increases your risk of B12 deficiency if you have a pancreatic enzyme if you have like a pancreatic issue right you're not releasing those pancreatic enzymes because remember B12 cannot be merged to two people at the same time no it's either married to R factor or to intrinsic factor so if it's married to R factor well that marriage with intrinsic factor cannot happen right it's like if you don't take the Mkite can get into Met School so if if you don't have pan cr- if you have pancreatic insufficiency you do not make the pancreatic enzymes that cleave the R factor from B12 so that can also cause a B12 deficiency if you have terminal ilial disease right so like Crohn's disease or like Tropical Spur that can also cause or like Celiac disease that can also cause like a B12 deficiency also if you have like I think it's called like the giant tip worm I think it's like Diphiloboth 3-amuladum from Numbestaking that also loves B12 for some bizarre reason right that can also cause that can also cause a B12 deficiency so I really hope you find this slide to be helpful but again I promise you you're gonna see these things probably more than 20 times before you graduate from Met School right so again one of thos

e high-ill things you want to know so I think I'm gonna move on to the next slide so next slide says 33-year-old Greek female presenting with Palor and dyspnea five days after starting a 70-course of nitrofyrantone for symptomatic cystitis as an aside why would nitrofyrantone potentially cause lung disease with an increased slash normal FVV1 to FVC ratio and a reduced DLCO and then the second question says how is the oxyhemoglobin dissociation curve shifted in a patient with pyruvate kinase deficiency okay so in this question right so this person first question the person took nitrofyrantone right the thing is nitrofyrantone commonly known in the hospital as macrobate it's a great drug for trillionsistitis and actually for the future please for future US ML exams please do not choose nitrofyrantone as a drug for trillions of pylonofritis nitrofyrantone concentrates really well in the bladder so it's good for cystitis but it is awful for pylonofritis the common US ML question do not pick nitrofyrantone for for pylonofritis that will result in lower scores on exams don't do that to yourself so back to the real world so nitrofyrantone right it's a drug that causes pretty severe oxidative stress so if a person I don't know maybe has a g6pd deficiency right see Greek female hope you're getting my drift right so Greek female g6pd deficiency oxidative stress nitrofyrantone that oxidative stress right can basically put them in trouble and they get like a hemolytic anemia with that right so remember in g6pd deficiency glucose 6-phosphid dehydrogenase is and facts the rate limiting enzyme for the synthesis for I guess the oxidative phase of the pentals phosphate pathway right remember that oxidative phase the key thing you want to know from that is really helps you making any DPH right so if you have a g6pd deficiency you're not making any DPH from the oxidative phase of the he

xes monophosphatiant also called the pentals phosphate pathway if you're not making any DPH well guess what?

Glutathione reductase will have no cofactors because usually what happens is glutathione can exist in an oxidized state or in a reduced state the oxidized form of a glutathione is converted by glutathione reductase to reduced glutathione okay and then that reduced glutathione can work with an enzyme known as glutathione peroxides to help you deal with oxidative stress right so like hydrogen peroxide and what not okay so if if a person has g6pd deficiency they are not making any DPH and then yes subjected to oxidative stress the user for their reduced glutathione what they have no ability to recover that reduced glutathione I mean to convert the oxidized glutathione you've now formed back to reduce the the thion because glutathione reductase that uses any DPH as a cofactor is not working those people will then have like oxidative damage to their red blood cells so they'll begin to form things like kinds bodies and then when they are splinic microfagicy those kinds bodies they literally take a bite out of those red blood cells and you form bite cells okay so that's the big thing with a g6pd deficiency and the thing is for g6pd deficiency you do not make the diagnosis during the acute episode of hemolysis you actually wait like six weeks after the hemolytic episode has resolved when the and then you check you then check their g6pd you then go ahead and check their g6pd levels on other circumstances that's more for step two but yeah they love to tempt people with like oh check g6pd levels or do the g6pd essay during the acute hemolytic episode that again we're resulting lower scores on exams you want to test weeks after the hemolytic episode has resolved and remember again anything that can cause oxidative stress right so like prima quen that kills like that latent form of malaria or phaba beans right all that stuff those can all or trimethoprym so from a thox is alright

so think about an eight patient kind of question on your USM at least or dapsone think about a leprosy patient kind of question on your USM at least although nemocysis rewet you can also actually cover it with a dapsone like the prophylaxis right so again those are all different ways they can test a g6pd deficiency on you exam and don't forget that mitrofiorantoin can actually cause pulmonary fibrosis right so remember pulmonary fibrosis is a kind of restrictive lung disease so FVV1 FVC reshubin like normal or increased and they reduce DLC already because again if you fibrosy on lungs you have issues with lung diffusion I'm really looking forward to giving a poem podcast or like video review in the future but we'll see how that we'll see how that works out with my schedule so and then the final question on this slide that says oh how is the oxyhemoglobin decision curve shifted in a patient pervary kinase deficiency so let's mean again don't have to memorize anything if you understand right so think about it if a person has a pervary kinase deficiency right everything prior to pervary kinase which is the last step of glycolysis will begin to back up right so like first find out pyruvate will back up and then one three bsphosphoglycerate will back up and the thing is one three bsphosphoglycerate can be converted to three phosphoglycerate that's one pathway but it also so happens that one three bpg can also be converted to two three bpg which is also known as two three dpg under the action of an enzyme known as bpg mutate okay bpg mutate so if you have a pervary kinase deficiency you want three bpg will build up and according to Lushatley principle because that pathway of one three bpg to three phosphoglycerate is all bunched up then everything will start working from one three bpg to two three bpg you have more flux through that pathway and two three bpg remember it bind

s to the beta globin chain of hemoglobin and basically causes it to have less affinity for oxygen right so I sort of think of it as an adaptation in a sense right again mix biochemical sense if you're lacking if you have a pervary kinase deficiency and that's making your red blood cells explode fairly frequently right you want whatever little you have in the world red blood cells to be very good at just release and release and release in oxygen to the surrounding so though that's also bad because if they're releasing releasing releasing oxygen to the surroundings guess what they're not doing they are also not picking picking picking up oxygen from the lungs right so it's kind of like a double-ledged sword and you may ask so to answer the question the oxy-hemoglobin institution cover will be your right shift that because they are giving up more oxygen remember right your hemoglobin f has alpha 2 gamma 2 doesn't have a beta globin chain so they have no ability to bind a two three bpg remember two three bpg bind specifically to the beta globin chain of hemoglobin okay so if you have a kind of hemoglobin that does not have a beta globin chain like hemoglobin f then you're naturally left shifted okay just one of those weird things you want to keep at the back of your mind now you may say okay to find out I will pyruvic anis deficiency cause anemia well I mean think about it right so for presents pyruvic anis deficiency remember glycolysis is the only way red blood cells can make a ATP right because remember ribyloses and don't have mitochondria right so if you're and remember that that part remembering glycolysis you invest to ATP's initially and then you have S4 ATP's at the end for a net of two ATP's right so the thing is we remember that those ATP's that you get from from glycolysis they come at two steps right so one ATP is made when you convert let's see so just give

me one second here let me think about the glycolysis pathway so the pyruvic anis step is one of those steps and then another step that makes ATP is so there's pyruvic anis so there's the pyruvic anis step hmm come on divine think so there's a pyruvic anis step and actually there is yeah the step where you go from one three bisphosphoglycerate to three phosphoglycerate I believe that's under the action of phosphoglycerate kinase yep that is the second step that also helps you make ATP right so if you have a pyruvic anis deficiency your stock it's like you invest at two ATP's at the beginning of glycolysis but the phosphoglycerate kinase step works so you make two ATP's but a pyruvic anis step is not working so you're not making those extra two ATP's that gives you your net harvest of two ATP's at the end of glycolysis so guess what you are effectively not making any ATP's from glycolysis so why is that a bad thing well if you're not making any net ATP's is there a particular transmitter that stops working I hope you're telling me the sodium potassium ATP is pump if it's not working guess what happens sodium flows down is gradient into the your red blood cells a sodium comes in what happens your red blood cells water will come in as well the red blood cells will swell and will explode so you get a hemolytic anemia that way okay so that so it's basically like an intravascular hemolosis I guess and with that right you have like the uncondugated hyperbularibinemia and the jaundice and all that stuff okay in fact pyruvic anis deficiency is actually one of the most common causes most common enzyme deficiency causes of hemolytic anemia g6 pd deficiency is another another classic one okay so that's all I think I want to say about this slide so let's go ahead and move on to the final slide so this is basically like a test taken strategy slide they are just certain things I want

to basically if you see like these kinds of questions there's like one thing I want you to think of first on any mbme exam and this slide is helpful for step one through step three so first question decrease them CV Greek national that should get you thinking about phalacemia okay and to be more specific I want you to think about beta thalacemia minor okay beta thal minor some kind of beta thalacemia next one decrease them CV immigrant from Vietnam okay I really want you to think more about an alpha thalacemia to be more specific let's in general think of an alpha thalacemia but if you are thinking alpha thaltryd I really hope you're thinking about the trans kind okay remember that's common in Asians next one decrease them CV history of rheumatoid arthritis right rheumatoid arthritis is a chronic disease so I really hope you're thinking of a knee of chronic disease with this next one decrease them CV history of omelibrand disease and heavy men or Asia I really really really hope you're thinking about ion deficiency andemia right so if you have an omelibrand disease that would deficiency of omelibrand factor so the first step of like primary hemostesis doesn't work so you just bleed out a lot so you have like very heavy periods so if you have very heavy periods you're chronically losing blood so you get an ion deficiency andemia with that okay now increased MCHC and genetic history basically if you ever see an increased mean composculy hemoglobin concentration on your exam on any USMLE there's only one thing I want you to think about and that's hereditary sphyrocyteosis remember that's an Orozomo dominant disorder so it's transmitted from brain to offspring that's why again there'll be a they'll say like oh that died of this that's better died of this kid has this okay there'll be a story the genetic history in the question think about hereditary sphyrocyteosis rememb

er those people tend to have sphyrocyte some blood smear that's basically a red blood cell without a central power and then they will also have I mean the pathophysiology involves like spectrina and crina defects those are like cytoskeletal proteins in red blood cells now if you see decreased ferritin and that's literally all you you see in the question you want to think about ion deficiency andemia right I only decrease ferritin again there are many things that can cause decrease ferritin but you don't care about those things on your USML Es the thing you care about is the right answer and in this case that's ion deficiency andemia now if you see increased ferritin with a decreased TIBC really want to think about anemia of chronic disease or some kind of iron overload state but more commonly think about anemia of chronic disease now microcytic anemia abdominal pain plus low IQ abdominal pain low IQ that's this is lead poisoning right lead poisoning remember lead right if you have a ton of lead double inhibite I've talked about this in one of the early human podcasts about ferrokyletes and LED hydrities will not work right so these people essentially have like a pseudo-blastic anemia sort of picture and remember right if you want to make him right you need iron and put up porthry right so the thing is if you're not making put up porthryn because early the hydrities and ferrokyletes are all screwed up then iron will just keep hanging hanging hanging around it's like wait where is my wife that I want to get married to why is my wife not here right because again you have these enzyme deficiencies and you're not making a put up of her so the iron just keeps hanging hanging hanging out so the labs in iron I mean in lead poisoning actually mirror iron overload fairly well okay so basically thing that happens is the a ferritin is actually high the TIBC is actually low the ser

um iron is actually high right because again it's almost like iron overload because you have all this iron but you have nothing to do with it because it's like you have iron standing at the altar because the wife is not there and their transferring saturation will actually be high as well okay so those are the labs with a lead a poison remember lead right if your presence has like lead toxicity you can throw like succimer or dimacapral or EDTA and all that stuff and don't forget that don't forget the association like moon shining right or like pottery from a foreign country or living in an old home okay but really if you see a kid and this very classic as well on the pediatric shelf abdominal pain neurologic problems headaches think about really like the only thing you should think about is lead poisoning with that next one increase reticuloside count northern European ancestry this is again heritage research I toast this the retic count will be high because you have a hemorrhidic anemia so your blood cells your bone marrow will be trying to keep up with the demand by but I mean think about it right it's like if you take time to craft a good product let's say you accompany and you make products for sale and you take your time everything is handcrafted it comes out high quality right but if you're like trying to mass produce things at very high quantity then you begin to court corners right in that production process right so you begin to make crap basically right so whenever you have a hemorrhidic anemia your bone marrow cannot like handcraft your red blood cells so your bone marrow begins to make like a ton of crap right a ton of like immature red blood cells like reticulosides so usually in hemorrhidic anemia your retic count is actually high now anemia and an increased reticel distribution with there's only one thing you think about on your exam that's our own defi

ciency anemia end of story increase hemoglobin 80 on electrophoresis think about beta thal minor okay that's the first thing you want to think about thalassemia with in uterodemis so this will be alpha thal this will be hemoglobin barks okay this is where you've lost all four alpha globin genes this is obviously not a good outcome and then thalassemia with symptoms six months after birth this is beta thal major because beta thal minor is usually not symptomatic so this so beta thal minor usually not symptomatic but yeah thalassemia severe symptoms six months after birth think more about beta thal major okay and again you don't get the problems until six months after birth because guess what you have for the first six months hemoglobin F which is alpha 2 gamma 2 does not you don't really need watching the little beta globin chains right so you're fine for the first six months of life now thalassemia with severe symptoms from birth right so this will be hemoglobin H disease this is where you've lost three of your four alpha globin genes okay those kids are born but they have very severe amaneemias and again I've talked about the reasoning behind all that stuff for earlier now mcv of 60 positive fecal local blood test in a 50 year old male this is not good right this person probably has colon cancer remember if you ever see a micrositic anemia in a person more than 50 years old you're thinking about like a bleeding colonic malignancy okay so the next step in management is colonoscopy simple as that and also don't forget right other indications for colonoscopy if you're more than 50 you should get a colonoscopy if you're if you do a blood culture and you find strebobus right or you find something called a clostridium septicum in the blood so clostridium septicum strebobus in the blood go ahead and go colonoscopy because those are associated with the presence of a colonic

malignancies now mcv of 60 in a five month old so this child is probably like just exclusively breastfed not getting enough iron supplementation because remember breast milk does not contain a ton of iron right so kids can actually get iron deficiency anemia if they are exclusively breastfed exclusive breastfeeding is actually great but you need to supplement some other stuff that's why you should see your pediatrician regularly if you have kids right I mean you carry that kid for nine months when throw that trouble probably makes sense to see a pediatrician regularly talking back to this so mcv of 60 with difficulty swallowing okay this is a tricky one micrositic anemia difficulty swallowing I really hope you're thinking about plumorovins in syndrome remember it's a triad right like iron deficiency anemia dysphysian like the beefy retongue um from the uh and dysphysias from the esophageal webs right and then rinse your cedar oblasts right you can see them in many things like lead poisoning you can see them in um like isonazet toxicity remember isonazet deplete your b6 and if you deplete your b6 early synthase doesn't work as well if early synthase doesn't work as well you're gonna have problems with hym synthesis um if you have a b6 deficiency as well already that can cause a cedar oblastic anemia if you have lead poisoning that can cause a cedar oblastic anemia um um um your myelodisplastic syndrome can actually also present with a cedar oblastic anemia in fact there's a myelodisplastic syndrome known as RARS I think it's like refractory anemia with rind cedar oblasts um so again rind cedar oblasts on histology are not always lead poisoning they can also be um a myelodisplastic syndrome lead poisoning remember is also as we said like bizophilic astypline right because that ribonuclease um that helps you uh uh essentially breakdown those that are ribosomo proteins an

d uh like ribosomo RNA is essentially destroyed by the lead right so you cannot uh break down your like your ribosomo RNA so they sort of sharp as like blue stipples in a red blot cell so I think that's all I'm gonna talk about today I am again I apologize that this is going along but um again if you listen to all these hymon podcasts you will be a hymon expert because my goal is to cover essentially everything that is tested on the USML is from a hymon perspective so have one more podcast I'll probably talk about the hymonic anemia in that podcast so a few more like basic science things and then we'll officially be done with hemock um so I wish all the best uh it is like 3am right now uh because again this is just one of those three times I have on a busy medicine service and as I round up right um again I offer one on one tutoring for um the USML is step one step two c case step two c s step three the internal medicine in training exam and also the internal medicine board exams um believe it or not um and then I also offer tutoring for organic chemistry I do application advising so like pre-meds going to med school like for like the amcass application or med students going into residency for the era's application like mock interviews writing personal statements I consult for all those things um I mean I have actually have a lot of admissions committee experience um you can private message me and I'll tell you what kind of experience I have but I have admissions committee experience at a major medical school one of the best med schools in this country so uh sort of have a lot of experience with that so I can help you with that process and then again if you really have a relative that needs help with organic chemistry I also offer a tutoring for that like organic synthesis and all that stuff so I wish all the best have a great rest of the day and I will see you in epi

sode 84 have a wonderful day and God bless thank you

Atrial fibrillation ($\text{A Fib}$).

Clozapine and Pyrimethamine (or Methimazole/Propranolol).

Beta Thalassemia Major symptoms typically appear after six months of life, whereas Hemoglobin H Disease causes severe anemia from birth.

It suggests that the body is compensating for reduced $\beta$-chain production by increasing other globin chains (e.g., $\alpha_2\delta_2$).

High ferritin, low TIBC, and high serum iron.

Glucose-6-phosphate dehydrogenase ($\text{G6 PD}$) deficiency.

Pancytopenia, microcephaly, thumb abnormalities, and café-au-lait spots.

Hemoglobin $\text{A}_2$ ($\alpha_2\delta_2$).

Increased hepcidin synthesis due to chronic inflammation, leading to macrophage/enterocyte trapping of iron.

Vitamin $\text{B}_{12}$ deficiency (as a cofactor for methylmalonyl-CoA mutase).

In Beta Thalassemia Major, no $\text{HbA}$ is detectable; in Beta Thalassemia Minor, $\text{HbA}$ is still detectable.

Pancreatic enzyme insufficiency (e.g., due to chronic pancreatitis).

Megaloblastic anemia; causes include $\text{B}_{12}$ or folate deficiency.

Pancytopenia, microcephaly, thumb abnormalities, and café-au-lait spots.

Hemoglobin $\text{A}_2$ ($\alpha_2\delta_2$).

Increased hepcidin synthesis due to chronic inflammation, leading to macrophage/enterocyte trapping of iron.

Vitamin $\text{B}_{12}$ deficiency (as a cofactor for methylmalonyl-CoA mutase).

In Beta Thalassemia Major, no $\text{HbA}$ is detectable; in Beta Thalassemia Minor, $\text{HbA}$ is still detectable.

Pancreatic enzyme insufficiency (e.g., due to chronic pancreatitis).

Megaloblastic anemia; causes include $\text{B}_{12}$ or folate deficiency.