DIP Episode 434 - USMLE Step 2/3 Rapid Review Series 90

Okay, welcome. My name is Divine. This is episode 434 of the Divine Intervention podcasts. And in today's podcast I'm going to be continuing the Rapid Review series for the US Emily step 2 C-Cans step 3 exams. This is going to be series 90. This is going to be series 90 and first off I want to welcome you to the new year. Thank you for supporting me last year and I really hope that you find this podcast to be even more helpful to your studies for all the US Emily exams and also for some of your residency board exams this year. I have great plans for this year. I'm trusting or to help me make some really really high quality material this year. So what if they give you a question about a 35-year old male? They tell you that he's undergoing surgery and he's persistently hypotensive during the surgery and they try to give this person fluids, they give the person phenol effrin and the person is not remains hypotensive and then they tell you that this patient has a history of some autoimmune disease or they have a history of asthma and then they ask for the mechanism behind the findings you observe. I really hope you're saying oh Divine this sounds a lot like a adrenaline sufficiency. So I know you may be like divine how do you mean adrenaline sufficiency? Well let me explain. The thing is this person has a history of some autoimmune disease or asthma or whatever. So this person is probably on clinical sterile therapy.

When you're on clinical steroids that's gonna cause atrophy of your HPA axis, your hypothalamic, the tertiary, adrenal axis. That cortisol will suppress all those things. When it does the unfortunate thing that's gonna happen is that you will shut down CRH production so corticotropin release in hormone so that's gonna be low. You will also shut down ACTH production so that's gonna be low as well and then so these people should not have skin hyperpigmentation because the ACTH is low and then you will also shut down the production of endogenous cortisol. In fact you essentially cause an atrophy of this system. Remember atrophy is a process that happens or is kickstarted at the genetic level. You stop making proteins and things like that. So that's fine as long as you're taking enough of a steroid dose to hold you over. But when you get to a situation where you're stressed or you're undergoing a big metabolic stress like surgery or pressing gets an amortovicol accident or has a very significant acute illness and then you notice that this person is persistently hypotensive and we're giving pressers and this person is not getting better. That atrophy of the adrenal gland has caused an adrenal insufficiency. It's a relative adrenal insufficiency because you're like oh divine, can't the adrenal glands, the adrenal cortex more specific to it. Can't the adrenal cortex just go ahead and make more steroid? I mean can they just adapt?

Well think about it is a genetic process so it requires our ramp up is not something that can happen immediately. So these people they cannot make cortisol to deal with that extra stress above baseline that's the usually deal with. So because that's happening the thing that's going to occur in this person is they're going to have adrenal insufficiency and remember your steroids your cortisol has a permissive effect on the sympathetic nervous system. If you actually really think about it when you want to go from nori been referring to a been referring the enzyme that does that is a PNMT I believe is phenyl ethenolamine and methyl transferase. That enzyme I'm certain is activated by cortisol. So cortisol has a permissive effect on the sympathetic nervous system. So if you have adrenal insufficiency you will not respond to the administration of pro sympathetic agents. Like we see for example this person was getting phenyl effring phenyl effring is an alpha one against. So you're supposed to cause visual constriction and raise your blood pressures but this person was not responding to that. This person was not responding to that. So since this person was not responding to that that tells us all we need to know that. Something that is permissive for the sympathetic nervous system like steroids are not available. So this person has an adrenal insufficiency again. Adrenaline insufficiency does you know weasemain at a sense disease.

Adrenaline insufficiency does you know weasemain what a house fridge or xin syndrome which is something we find with my seramine ingitidus that spreads to the level of the adrenal glands. So this is something I want to keep in mind. So since I'm talking about this concept of acute illness causing issues with some hormone or some compound in the body let's extend that concept a little bit further. What if they give you a question about a patient? They tell you that this patient is a 54 year old male and he presented two days ago with significant right-up or cordial pain and fever and they got an ultrasound which showed the station of the wall of the gallbladder wall pericolacistic fluid and things like that. Obviously this person has acute colicestitis and then they tell you that this person is referred for surgery and that three days after the surgery the patient is noted to have yellowing of the skin and then they tell you that the performer repeat ultrasound and there is no common bowel talk dilution they tell you that they does not appear to be any signs of peritonitis the person is just John Dist and you notice that this person's indirect bilirubin is elevated. If you see all those things what should you be thinking about? I really hope you're saying divine this sounds an awful lot like Gilbert's syndrome. Gilbert's syndrome. So what's the deal with Gilbert's syndrome?

Or I guess maybe let me discuss this case and talk about why certain things should not be the correct answer in this circumstance. One thing our friends at the NBM is we'll try to slow it in as an answer is they will tell you who could this be a retained stone but the normal diameter of the common bowel doctor rose that out a retained stone sometimes is a complication of gallbladder surgery that stone going to occupy the common bowel doctor is going to cause an obstruction and that can cause it to dilute. He's also no bilirubin is because this person literally does not have signs and symptoms of bowel peritonitis they don't have this acute onset like rebound, cardio, whatever they don't have it. So this person has Gilbert's syndrome. Again Gilbert's syndrome is something that happens. You see a person they get very bad metabolic stress, very significant medical stress like an acute illness, they get in a car accident, they have the ghost surgery or whatever and that causes them to not have enough ability with UDP GT with UDP glucoronocel transferaries and if UDP glucoronocel transferaries is not working as well as is should then you're not going to be able to conjugate bilirubin. So you're going to have an indirect hyper bilirubinemia and I imagine that the mechanism here because people that have Gilbert's syndrome they already have reduced activity of UDP glucoronocel transferaries at baseline.

But sickness or stress kind of worsens that because I imagine that when a person is stressed when a person is going through a lot of issues, your UDP GT system is probably working over time or trying to attend to other problems like get rid of toxins and that that that that in the body. So one of the lowest things on his priorities is let's say normally there were 10 UDP G Ts assigned to help you break down in the air bilirubin, help you conjugate it, not break down conjugate it. But now because you're in the way metabolic stress is like man we're stretched is like think of it like a COVID surge, man we're stressed we need to ship we need to take some of these people that are normally conjugate bilirubin and put them to work in other parts of the body. If that happens, if that happens in the metabolism of other things, then your UDP GT is not going to be you're not going to have a lot for interibiliorobin. So you're going to have an indirect hyperbiliorobinemia. You're going to have an indirect hyperbiliorobinemia. Remember Gilbert's syndrome is not treated. Gilbert's syndrome is not treated. These people they're going to recover. It's been nine. They're going to be okay. Now on this same bent and mantra of a person gets sick and something weird is triggered. Wouldn't they give you a question about a 25 year old male?

They tell you that he comes to the physician because he has been having you know he's noticed that he's skin has turned yellow over the last two, three days and then they tell you that on labs this person has an increase in indirect bilirubin. But you notice that this person could be like a African American for example and then they tell you that the blood smear shows characteristic findings. Again this person is African American. Of course the MVM is in their wisdom will put Gilbert's syndrome as an answer. Okay, wait let me complete this vignette. So we also told that you know a week ago this person had an upper respiratory infection that resolved without antibiotics. Okay. So now that I have that extra bit of information. So let me summarize. African American male yellowing of the skin aka jaundice and they tell you that's labs shown indirect hyperbular bignini. And then you're told that this person had a URI like a week ago that resolved with that on antibiotics and then the blood smear shows characteristic findings. Okay. Now one of the best extractor answers here easily will be Gilbert's syndrome. They put Gilbert's syndrome as an answer. They're like hmm at uleoness indirect hyperbular bignimia. Okay. That fits some of the story but it doesn't fit all of the story that you're given because as far as I know there are no characteristic blood smear findings in a person that has Gilbert's syndrome.

So even if the vignette sounds similar you should scratch that out of your memory. The thing you should really be thinking about here is glucose 6.5 d hydrogenase deficiency, gizic speedy deficiency. First things first is going to be a disorder that shows up in males. Why? Because it has excellent, excessive inheritance. So you should only show up in males on exams. So how do this infection trigger this person's issue? Well if you think about it in gizic speedy deficiency you literally have a deficiency of glucose 6.5 d hydrogenase. You're going to have very significant issues with making any DPH. If you can't make any DPH whenever your body undergoes a lot of oxidative stress you're going to be in some very big trouble. Let me explain. When you undergo oxidative stress you're making all these reactive oxygen species. One of the systems that your body uses to deal with that problem if you may is glutathione. Glutathione in the process of helping you deal with that problem gets oxidized because glutathione reduces stuff gets rid of those reactive oxygen species. So it's almost like it's taken on that burden of the reactive oxygen species. When it takes on that burden of the reactive oxygen species when it takes on that burden it's going to get oxidized itself as it's reducing those things. That's why it's called a redox reaction in the first place. As redoxion is happening, oxidation is also happening at the same time.

So glutathione is helping other things get reduced but on its own it's getting oxidized. If you want glutathione to keep doing that job and keep doing it well you need to reduce it back to its neutral form so that I can go back and deal with more reactive oxygen species. What do you think helps us reduce glutathione? It's NADPH. So if you cannot make NADPH then you cannot regenerate reduced glutathione. You have a decreased or diminished ability to deal with reactive oxygen species. That's how glutathione factors into this story. So how does this operator infection then come in? This operator infection comes in because because when you have an infection your neutral fills getting to overdrive. Your neutral fills start running that reactive burst pathway. If you remember where for example you make superoxide with NADPH oxidize and then that's superoxide. Superoxide dismute is converted to hydrogen peroxide and then remember that hydrogen peroxide can ultimately be converted to hypochlorosacid with myeloperoxidase. If you notice and make sure a lot of oxygen related things that are very nasty, very gnarly. I mean that's good though. We want those gnarly things to arise so we can kill whatever bacteria whatever is causing issues for us but it generates a lot of oxidative stress with those circumstances. That oxidative stress your glutathione system is the thing that's going to help you deal with some of it. So it does is that damaging things like your red blood cells.

So if you have an infection that puts you in a high oxidative stress state but if you have g6pd deficiency you cannot deal with that oxidative stress. So the person is ultimately going to get into trouble. So that's why many times people that have g6pd deficiency infections are a very big trigger of many of their attacks and again since they cannot deal with that oxidative stress that's going to cause damage to the red cell. As you damage the red cell you have in himolosis that himolosis is going to be manifested as an increase in indirect bilirubin. So please don't always think only of father beings as the thing that can trigger acute attacks and people that have glucose 6-4-3 dehydrogenase deficiency that is not the only thing that can trigger acute attacks in a person that has g6pd deficiency. It's not the only thing that can trigger acute attacks. It's not just father beings, not just primacoin many things especially infection can trigger acute attacks. So what are these characteristic blood smear findings? What are the characteristic blood smear findings? There will be Heinz-Buddy's and bite cells. Heinz-Buddy's and bite cells. Those bite cells are created when your splinic macrophages say you know what? We are not very happy with these things. These Heinz-Buddy's were seen in the red cells. So splinic macrophages will literally take a bite out of your red cell. That's what creates those bite cells. That's clear what creates those bite cells.

So again your bare syndrome does not have characteristic blood smear findings. But in this question I mentioned characteristic blood smear findings. So that's why you should cross out your bare syndrome. I'm going to glucose 6-4-3 dehydrogenase deficiency. I'm going to glucose 6-4-3 dehydrogenase deficiency. And just by world announcement if you're taking your step two or step three exams I have a bunch of courses coming up this month. I have a biostatistics bootcamp that's very helpful for step one to step three. I have a 20-hour step two step three review course that's taking place within I believe the next 10 days. And then I also have, and obviously it's helpful for complex two and three. And then I have an in-be-me-test-taking strategies class. It's two and a half hours. Many people have taken these classes and they've done extremely well on the exams. Just go ahead and I have announcement podcasts on these. Just look those up. We can shoot me an email through the website and I'll give you some more information. And also have a social sciences and ethics review that is going to be taking place at the tail end of this month as well. It's five hours is for step one to step three. Because about 10 to 20 percent of all the US military exams these days focus on social sciences and ethics. Those things involving QI and many other subjects. I deal with those in that course. And then I have a step one review class that's also going to be taking place next month.

It's a 25-hour course and it's going to be five hours HD for five days. It's going to be taking place around I believe the 9th of February or there about. So if you're interested in any of these classes, shoot me an email and I'll be happy to give you some more information. So what if they give you a question about a patient? The tell you that this patient is 65 years old and he notices that for the past three weeks his breasts have been getting bigger that his wife has even commented on it. And the tell you that this patient has a history of heart failure with reduced ejection fraction and the patient was recently placed on a drug. If you see that what drug is causing this problem. I hope you're seeing the vine. This sounds a lot more fun like Spirino lactone. This patient has gynecomastia. Gynecomastia is a very time-honored side effect of Spirino lactone because Spirino lactone we know first things first. This guy has heart failure with reduced ejection fraction. So it makes sense that he's on Spirino lactone. Spirino lactone happens to be one of those drugs that has the ability to improve survival in people that have CHF. It improves survival in people that have CHF. So Spirino lactone is an outdoor syndrome receptor antagonist. It's a potassium-spirino diuretic but one other mechanism of action that Spirino lactone has is that it's also an Androgen receptor blocker. Spirino lactone has anti-androgenic effects. It's an Androgen receptor blocker.

So because an Androgen receptor blocker it can absolutely cause gynecomastia. It can absolutely cause gynecomastia. Remember we don't find this same problem with a plerinone. A plerinone is another outdoor syndrome receptor antagonist. It also can help with improving survival in CHF. But it works only on outdoor syndrome receptors. It has no effect on Androgen receptors. And one other thing I also want to say about Spirino lactone with regards to its anti-androgen effects. Remember Spirino lactone also inhibits 5-hour for adoptees in the skin. Not generalized 5-hour for adoptees. The one in the skin. And inhibits 5-hour for adoptees in the skin. And that can be beneficial in people that have hersotism. Because in hersotism you have a lot of hair. All that hair is being driven by DHT production in the skin. So if inhibits 5-hour for adoptees we know that 5-hour for adoptees converts testosterone to DHT. When you have less DHT synthesis and that can be very helpful in hersotism. Now what are some other things or drugs that can cause gynecomastia? Well, don't forget, the joxin is very strongly associated with gynecomastia. Cymetidine is one of these anti-histamine energy agents. It's a H2 blocker. Remember it has anti-androgen effects. Also if you're a big-time alcoholic, I mean think about if you're an alcoholic for a long time, you mess up your liver, your liver is tasked with helping you break down estrogen.

So if your liver doesn't work, you're going to have a lot of issues breaking down estrogen. Even if you don't have cirrhosis, you can still have higher estrogen because again, if you're a big-time drinker, your liver is working over time to deal with that alcohol problem. So you're going to have a buildup of estrogen. You're going to have decreased breakdown of estrogen. And that can cause problems for you. Don't forget Kirokonazo. Kirokonazo is something that inhibits, I believe, desmolees. It inhibits desmolees. It's a drug that, you know, it's an anti-fungal. But by inhibiting desmolees, I believe it's desmolees. Don't put me on that, but I'm almost certain is desmolees. One thing it does is that it pretty much prevents you from making androgens. If you're preventing a person from making androgens, they're going to be in a net estrogenic state. And that can certainly cause gynecomastia. So when you have that low androgen and net estrogen state, you're definitely going to get gynecomastia in those circumstances. So Kirokonazo, don't forget, it inhibits desmolees. It inhibits desmolees. I'm pretty sure of all that. It inhibits desmolees. Desmolees is very necessary for androgen synthesis, especially in the adrenal glands. Especially in the adrenal glands. And by the way, Kirokonazo, believe it or not, is also an androgen receptor blocker. So you can cause gynecomastia. Again, don't forget that there are some other conditions that can cause gynecomastia as well.

If you have a prolectinoma that can cause you to have gynecomastia, if your hypothyroid, well, your TRH is going to go up. TRH increases prolectin release, that's going to cause gynecomastia. If you're an anti-psychotic, anti-psychotic through the tuberum for developed pathway, the ratio-productive, that's going to cause gynecomastia. So there are many, many things that can cause gynecomastia. Certain genetic diseases, like for example, in a brain sense, client-filter syndrome. Gynecomastia is pretty common and classic in people that have client-filter. It's going to be a guy that's tall, has gynecomastia, has a micro penis, may have infertility, and things like that. I remember those people that have client-filter syndrome. Do you have a slightly little bit of risk on breast cancer? When you never see male breast cancer, think of either a broken mutation of some sort, or also think about client-filter syndrome. Okay, so since this is a rapid review podcast, I'm going to go ahead and stop. As I do at the end of every podcast, I'll offer one or one to run for all the USML exams, step 1-2-3 and complex 1-2-3. And then I'll also tutor to pre-clean cool medical exams and 30-ish-off exams. I help with personal statements, errors, applications, mock interviews. I've done this for years, worked with many, many people that are now successful residents. And then I'll offer review courses for step 1, for step 2, for step 3.

I offer a bio-statistics bootcamp, an MBA-me-testing and strategy course, and a social sciences and ethics review. And then I have these podcasts on the major podcast apps, Apple podcasts, Google podcasts, and Spotify. I also have a You Tube channel, Divine Intervention USML podcast and videos. That's where you can find the videos that I make. And I also upload some video versions, or I'll see, I'll upload to You Tube some of these podcasts that I make. So please subscribe, any little bit of support, certainly helps. And then I also have another website known as Divine Intervention Lifelessens.com. Divine Intervention Lifelessens.com. It has an associated Apple podcast, it's called The Divine Intervention Life Lessons Podcast. And in that podcast, I make two podcasts every week, usually on Friday and Sunday. And I address a life lesson from a biblical perspective. Many of you know I'm a Christian. I do address life lessons from a biblical perspective. So if that's something you're listening, you're interested in, feel free to check them out. They usually tend to 20 minute podcasts, but they are very high yield and from a biblical perspective, they address common problems that are faced by lots of people. So thank you for listening to me today. Have a wonderful rest of your day. God bless you. Bye for now.

Atrophy of the HPA axis due to negative feedback suppression of CRH and ACTH production.

Cortisol has a permissive effect on the sympathetic nervous system (via PNMT); without cortisol, this tone is lost.

Heinz bodies and bite cells.

UDP glucuronosyltransferase (UGT).

Spironolactone or Cyproterone Acetate.

Inability to regenerate reduced glutathione ($\text{NADPH}$), leading to overwhelming oxidative stress and red blood cell damage.

The Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in low ACTH/CRH.

Maintenance of sympathetic nervous system tone and vascular responsiveness.

Gilbert's involves reduced UGT activity exacerbated by stress; G6 PD involves acute hemolysis triggered by oxidative stress.

Presence of Heinz bodies and bite cells.

Cyproterone Acetate (or other agents that block androgen receptors).

Prolactinoma or hypothyroidism (due to TRH stimulation).

The Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in low ACTH/CRH.

Maintenance of sympathetic nervous system tone and vascular responsiveness.

Gilbert's involves reduced UGT activity exacerbated by stress; G6 PD involves acute hemolysis triggered by oxidative stress.

Presence of Heinz bodies and bite cells.

Cyproterone Acetate (or other agents that block androgen receptors).

Prolactinoma or hypothyroidism (due to TRH stimulation).