Principles of Nutrition for the USMLE Step 1 2 CK updated June 2026 changes

Hello everyone. hope you all are doing well. apologize there was some glitch with the link, so am getting that to everyone. Excellent. So great to see everyone. If you don't mind saying hello in the chat box and where you are logging in from. also would love for you to tag me on Instagram @highguruprep. Let everybody know that you are attending today's wonderful webinar. I'm so excited that you all are here. We're going to get started in just little bit. think there was slight issue or glitch, so I'm just going to give it about 3 minutes past our time to start. If you all don't mind saying hello where you are logging in from. Amazing. We have an international audience. Thank you so much for joining. We're going to get started in just little bit. Hello everyone. Good morning, good afternoon, good evening from wherever you are logging in from. really appreciate the engagement in the chat box already. This is going to be jam-packed session. 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Let's go ahead and get started with the principles of nutrition review. Ladies and gentlemen, am so excited for you to watch this review. This review is going to encompass some core gastrointestinal and nutrition concepts. As many of you preparing for either Step 1, Step 2, or even Step 3 have noted, the USMLE is going to start to emphasize questions related to nutrition throughout all three Step exams. I'm going to give you some background moving forward, but will say that this review is perfect for getting those free points on exam day. For many of you who have not met me yet, welcome. My name is Rahul. I'm pediatric critical care physician, and over the past 10 years I've been absolutely passionate about helping students just like you prepare for and excel on the USMLE. And to that end, created High-Yield Guru, which is very innovative way of preparing for the USMLE, and not just the exam, but beyond that, whether you're going into residency or an international medical graduate. All in all, High-Yield Guru is very strategic active learning approach to USMLE preparation. And I'm I'm to give you some of the core tenants that focus each and every one of my lectures on. The first is vignette focused learning. Today, what you're going to be seeing are not just facts on slide, you're going to see exactly how they are tested. My goal is to integrate focusing primarily on pathophysiologic integrations, specifically how do we look at symptomatology or signs within vignette and correlate it to mechanisms of disease. The third thing that like to focus on is test-taking. You'll notice systematic approach to questions. And even have test-taking strategies course that is just focused on how to break down questions. And hope that my positive energy is emanating through to your study space today because want to make sure that we stay positive whether you're in dedicated or preparing for this very challenging exam long-term. know that USMLE is not just about content and test-taking, but it's about making sure you have peak psychology, not doubting yourself, and staying positive throughout the process. One thing that am very interested in, and you'll see this throughout my resources and courses, I'm interested in how can we leverage large language models, generative AI such as ChatGPT, Claude, etc. in our preparation to optimize our learning. And so, today you're going to be seeing some GPT-generated images, and have verified them for accuracy, but this is my way of trying to be at the cutting edge of both technology and USMLE preparation. Many of you know that if we are going to be learning medicine in linear way, we may be subject to the forgetting curve. So, in order for us to optimize our learning, we have to make sure we focus on application and drawing connections between schemas and that is the methodology that am going to utilize as we prepare today. Most importantly, and this is evident with the over 500 people who have joined us today, High-Yield Guru is lifelong community of learners in medicine. understand that this exam is very stressful. My goal is to not only prepare you for Step 1 and Step 2 CK, but it's also to make sure that you have the foundational clinical reasoning principles that you need when you become fourth-year resident and beyond. I'm going to save the Q&A for this towards the end, but if you all are interested in joining my video-based course, feel free to check out highyieldguru.com. I'm always looking to optimize the courses, so anytime you enroll, you will get the most newest videos and content. just added some vignette-based Anki cards. I've also made sure to add sections on public health, ethics, even chart-based questions. So, you will see some innovative courses whether you are studying for Step 1 or Step 2 CK. also wanted to share with you all very exciting update. have partnered with Med School Bro, and together we have created unique practice test known as the Free 120. This is question bank that is going to be up-and-coming, and our goal is to give you yet another data point to assess yourself. You have your NBMEs, your UWorld self-assessments, even the Prometric Free 120s, but what we have created is integrated and innovative Free 120 that is absolutely free, so you can check out our question bank. This is for whether or not you studied for Step you're studying for Step 1 or Step 2 CK. All right. And with that, we're going to go ahead and get started with our nutrition-based review. One thing that would recommend is right now, please go ahead and turn off any tab or device that you are not using. Throughout this next hour, my goal is to give you the most optimized review for your Step 1 or Step 2 CK as you're preparing for these nutrition-based questions. would recommend you to just take out blank piece of paper and write out notes as we go through this webinar. And anytime you are going to encounter question, I'd recommend you to pause the video if you're watching it at another time, and make sure that you can actively recall some of the vignettes and questions that will be posting. All right. So, go ahead and type it to the chatbot, yes, if you are ready to get started. Everybody ready to go? Excellent. Let's go ahead and get started with our review today. Just as background, the USMLE just posted in June 2026, there will be enhancements to nutrition content on all three Step exams. One important point that want to emphasize here is that nutrition-based questions or competencies will also appear on your final score report. Now, lot of these changes were driven by this JAMA Open Network study that was entitled Proposed Nutritional Competencies for Medical Students and Physician Trainees. And in addition, actually looked at the supplemental content, which provides few objectives that are related to nutrition-based questions and interfaces nutrition with pathophysiologic sciences. And so, created this webinar by hybrid in that supplemental content with the USMLE content outline, and this is synthesized review for you all, whether you're studying for Step 1 or Step 2 CK. I'm so grateful to have worked on this because this is such excellent series of notes. So, please do stay locked in as you watch this whole webinar today. Just as an overview, the first area that we're going to be focusing on is the biochemistry of nutrition. also wanted to emphasize vitamin excess and deficiencies. think this is core of where your nutrition questions are going to be, whether it's for Step 1 or Step 2 CK. Then, we're going to be pivoting into little bit of GI physiology. We'll also be reviewing some biochemistry as well as path disorders. I'll be talking little bit about hematologic interfaces with nutrition. We'll focus on pediatric considerations. I'll also be going through endocrinological diseases, such as obesity. We'll talk little bit about how GLPs and DPP-4 inhibitors are going to work. And then, finally, because the USMLE is going for many of these types of questions, you may get two or three of these ethics and social sciences in your blocks. did want to create some vignettes surrounding that. Okay? All right, very good. Going into this, we're first going to start out with gastrointestinal physiology. Now, when you're thinking about the biochemistry of nutrition, would think about it as if you are tracking your calories and macronutrients. There are three macronutrients that you need to be focused on: carbohydrate, lipids, as well as protein. Now, think that fat absorption is one of the core pathophysiologic frameworks that you need to know. And so, what I'm going to do in this slide is I'm going to first go through normal fat absorption. So, the first step here is that the liver and the gallbladder are going to synthesize bile salt. And those bile salts are going to enter the duodenum to emulsify fats, which means that it is going to break down these fats so that then there's increased surface area. And when there's increased surface area, you are going to get optimal absorption of the fats. Now, do want to emphasize here that with bile salt metabolism, if you're thinking about bile acids, which are component of bile salt, you do need to know that 7 alpha hydroxylase is the rate-limiting enzyme for bile acid synthesis. Second, you also have the pancreas that is going to play role in fat digestion. Remember the pancreas is going to have lipase that digests the triglycerides. And what happens is that these triglycerides get broken up into smaller components, monoglycerides and free fatty acids. The pancreas is going to break down even fat-soluble vitamins. The goal is that the gallbladder, liver, and pancreas, they all work in concert to create these micelles. And what micelles are are they are shuttles that are going to have hydrophilic outside and hydrophobic inside. And those micelles are going to aid in lipid digestion. Because what these micelles do is they are going to enter the enterocytes of the duodenum, and they are going to be repackaged as chylomicrons and enter the lymphatic system, and then get drained into the thoracic duct. Now, what's high yield for us to know here is that chylomicrons are going to have an important apolipoprotein. Go ahead and type into the chat what is the apolipoprotein that is associated with chylomicrons. Excellent. If you are saying ApoB48, you're absolutely correct. Remember, ApoB48 is to chylomicrons as ApoB100 is to VLDL. Now, one of the things that you note here is that as you are going to reabsorb the micelle and repackage it as chylomicron, bile salts continue along the small intestine until we get to the distal ileum. want you to recognize here that at the distal ileum, you are going to get reabsorption of two things. Number one, B12 and intrinsic factor, and number two, these bile salts. Because these bile salts are then going to be recirculated, what we call enterohepatic recirculation. And those bile salts then are going to be recycled, so you can keep emulsifying fats and forming these micelles that are going to be turning into chylomicrons. Now, remember, within the micelles, not only are you going to have fat, but you're also going to be having your vitamin and And that will come into play as we talk about fat-soluble vitamin deficiency. But the whole goal here for us to note from normal physiology standpoint is that there are some major players when it comes to reabsorbing nutrients in general, specifically fat. Liver, gallbladder, pancreas, as well as the duodenal villi. All of them need to work together, and then you will reabsorb nutrients. If they don't work together or there's pathology in one of the areas, for example, you are going to have chronic pancreatitis, you then can reduce the fat reabsorption because you don't have the lipases, for example, that are going to contribute to your fat reabsorption. So, I'm going to go ahead and put some application-based questions here. What medication lowers LDL by inhibiting enterohepatic recirculation? What do you think is the medication from cholesterol metabolism or cholesterol drugs? Excellent. If you are going to be saying cholestyramine, you're absolutely correct. Remember what cholestyramine does is it reduces the amount of bile salts and bile acids that go back to the liver. So, the liver has to use its cholesterol up. So, cholestyramine disrupts bile acid circulation, so the liver uses up more cholesterol, and it is going to then have little bit more reverse transport of the LDL because now the liver is going to be using its reserve of cholesterol. What lipid-lowering agent activates PPAR alpha and causes gallstones as an adverse drug event? And if you are saying fibrates, you're absolutely correct. Remember what fibrates do is that they cause gallstones and the supersaturation of cholesterol due to the inhibition of the rate-limiting enzyme of bile acid synthesis, which is CYP3A4 7A1 or also known as 7-alpha hydroxylase. So, fibrates are going to be associated with two things. Number one, they are going to be associated with myopathy if combined with statins, and number two, they can cause gallstones due to the rate-limiting enzyme inhibition. This slide is going to be focusing on integrating and incorporating the various pathologies in this framework that we created. So, when we're thinking about patient who is going to be on long-term TPN, which is total parenteral nutrition. That means that there is an IV or central line that is providing the nutrition and you're not necessarily having the gut be stimulated, you can end up getting cholestasis. What cholestasis means is that the bile is just going to be in the gallbladder and sometimes you can see elevations in direct bilirubin, elevations in and GGT. Another area that we need to be focusing on is the duodenum. Remember that if the duodenum is going to be messed up, you're going to be thinking of celiac and Crohn's disease. You're also going to be thinking of iron deficiency anemia. Remember that the duodenum is going to be the workhorse of the GI system. Majority of your nutritional reabsorption is going to be at the level of the duodenum. What's high-yield for us to note or maybe integrate is that the duodenum is to the GI tract as the proximal convoluted tubule is to the renal nephron. Again, these are the workhorses of the organ system. Next, we need to be talking about the colon. When we're thinking about the colon, primarily it is to dehydrate the stool. So, pathologies such as gastroenteritis that are going to affect the colon can cause you to have diarrhea in your vignette. Also, remember that antibiotics are going to affect the colonic mucosa. And if you are going to have the colonic mucosa have less of the gut microbiome, i.e. you are not going to be having the good gut bacteria, you're going to be thinking of pathologies such as diff, things such as vitamin deficiency, as well as even small bowel overgrowth syndrome. And this is where you are going to have hypoperistalsis of the colon and all of the bacteria going to overgrowth, and you may get bloating, etc. That is pathology that is tested on NBMEs. So, remember that the colon's job is to dehydrate the stool, and thus propel the stool ball forward. Other areas that want to be focusing on here, stomach. The stomach, they want you to know the fact that intrinsic factor is going to be made from the parietal cells of the stomach. The parietal cells make two things, acid and intrinsic factor. Intrinsic factor is going to be essential for B12 reabsorption in the terminal ileum. So, if they give you patient on the USMLE that has thyroid issues and is also going to be having anemia, you should be thinking of an autoimmune stigmata, specifically pernicious anemia, which is autoantibodies to intrinsic factor. And what's going to happen then is that these patients are going to have low B12, and low B12 gives you megaloblastic anemia. Another point that want to make is patients who are going to have chronic pancreatitis, either from alcohol or cystic fibrosis. These patients are going to have pancreatic insufficiency. And with pancreatic insufficiency, you are going to get fat malabsorption. If you have pancreatic insufficiency and you have chronic pancreatitis, some of the imaging findings will be calcification of the pancreas. And when you see calcification of the pancreas, you should be thinking that maybe in the social history, they were alcoholics, or maybe they have recurrent pancreatitis due to cystic fibrosis and those thick duct secretions. So, why put calcium on the slide is there's surgery shelf question that says, if you see calcification of the gallbladder, what is the next step in management? And that is going to be cholecystectomy. That is that porcelain gallbladder that is going to be precursor to cholangiocarcinoma. And if you see chronic calcifications in the pancreas, think about pancreatic insufficiency because you're going to get recurrent saponification as you keep it inflaming the pancreas. Jejunum, in general, the jejunum is going to do nutrient reabsorption, particularly folate. And the terminal ileum, we talked about two things, the two B's for the terminal ileum, which is going to be number one, B12, and number two is going to be bile salts. Now, one thing that want to note in this image is the fact that when you have terminal ileal disease, you are going to be thinking of Crohn's disease. You could even think of the fish tapeworm. And you want to be thinking in the past medical history of anybody who has necrotizing enterocolitis, like little premature baby who ended up having pneumatosis intestinalis and subsequent bowel necrosis, and they had to get their ileum resected. This is what we call short gut syndrome. And these are patients who are going to have the general surgeons come and take long segment, large segment of their small intestine. And these are patients who may need to have total parenteral nutrition long term. And the reason why is because they have less surface area for the reabsorption of nutrients. All right. So, what want to do is want to go through some of the pathophysiologic mechanisms one more time. But before go through that, is everybody having good time with this review? Go ahead and type in yes into the chat box. Everybody doing okay? All right. Excellent. see many yeses, we'll keep going forward. When we're thinking about the GI tract, just want to emphasize for step one, you do need to know that the GI tract is going to be primarily derived from endoderm. Other things that we want to note is that in the stomach, we are going to be dealing with acid as well as intrinsic factor. In the duodenum, you're going to be thinking about iron reabsorption. You're even going to be thinking about this whole oxalate binding pathophysiology. And this is going to be really important for patients who are going to have Crohn's disease. When you have Crohn's disease, you are going to get so much inflammation in the duodenum that you are going to preferentially reabsorb lot of oxalate, and you can get calcium oxalate stones. And those stones are going to present as flank pain that radiates to the groin with microscopic hematuria. I.e., it's going to present as nephrolithiasis. Now, with the jejunum, primarily, it's going to be folate. There is some folate reabsorption in the duodenum as well. Terminal ileum, we talk about B12 and bile salts. And then in the colon, this is where you're going to have the gut flora make vitamin Now, what ends up happening here is that if they give you vignette in which patient has long-standing antibiotics, and the patient with long-standing antibiotics is going to have bleeding, think about deficiency in vitamin So, you can get vitamin deficiency not only due to malabsorption, but also if you have long-standing antibiotics that reduce the good bacteria in the colon, and thus you are not going to have any vitamin production. No vitamin production means that you are not going to activate your 27910 clotting factors and as result you're going to be predisposed to bleeding. Another thing for us to note is if you have long-standing antibiotics and they say watery diarrhea, what is going to be the pathogen? Go ahead and type that into the chat. Excellent. Clostridium difficile. You're absolutely correct. And remember the treatment for diff is going to be oral vancomycin. Excellent. So, what we're going to do now is we're going to be focusing on how do we apply these concepts? gave you the normal, then gave you the pathophys, and now we're going to be talking about application. child on prolonged TPN due to history of necrotizing enterocolitis who now presents with elevated direct bilirubin and GGT. What is the diagnosis here? Well, remember the patient is not using the gut. So, they can end up having cholestasis. When you're thinking about cholestasis, that means the gallbladder is lazy and it is not going to be contracting as much. So, your direct bilirubin is going to be building up along with your GGT indicating that the bile ducts are going to be inflamed. So, TPN causes no villi stimulation. You are going to have reduced CCK and thus reduced gallbladder contraction. All right, next vignette. female with pustular rash on the extensor surfaces and positive tissue transglutaminase. What is going to be the likely diagnosis here? Excellent. If you are going to be saying celiac disease, you're absolutely correct. What is the rash that was going for? Dermatitis herpetiformis. Remember that the management for dermatitis herpetiformis, they can dapsone as well as avoid gluten-containing foods. Now, what celiac disease is is autoimmune infiltration of the small intestine by lymphocyte. And what that causes then is flattened duodenal villi. If say flattened podocytes, think minimal change disease. If say flattened duodenal villi, think about celiac disease. Now, remember that dermatitis herpetiformis is going to be due to IgA immune complexes in the dermal papillae. And again, they will say that it is vesicular-like lesion on the extensor surfaces. And that's why they call it herpetiformis because it is going to resemble somewhat like herpes. All right, here's the next one. female with chronic non-bloody diarrhea with red rash on the lower shins and this very characteristic necrotic-looking lesion with heaped-up edges. Excellent. If you are saying Crohn's disease, you're absolutely correct. Anybody who has chronic diarrhea, will tell you you should just be thinking of malabsorption. If you have chronic diarrhea, think malabsorption. Malabsorption could be due to duodenal pathologies like Crohn's, could also be due to pancreas issues, or gallbladder or liver issues. Now, with Crohn's disease, there are two major skin findings. This red rash on the lower shins, what do you think was going for here? That is going to be erythema nodosum. And then, what about this necrotic skin ulcer? That is going to be pyoderma gangrenosum. Very good. So, what is Crohn's disease in terms of pathophys? Immune dysregulation, you get transmural inflammation. Why is that important? Because you can see in your vignettes, fistulas as well as stricture formation. And remember when you think of the biopsy of Crohn's disease, you are going to get non-caseating granulomas. That's very high yield for you to know. Remember ulcerative colitis has crypt abscesses, Crohn's disease has non-caseating granulomas. All right, we talked lot about B12 and what want to emphasize is that B12 can be deficient with three major pathophysiologic mechanisms. First is malabsorption, second is terminal ileal disease, and third is going to be decreased intake. So, let's go through this. When it comes to malabsorption, I'm going to be thinking of any patient who has autoimmune gastritis in which they have low intrinsic factor. Also, if they are going to have pernicious anemia, that is another pathophysiologic mechanism. Remember that patients may even get pylori and pylori is urease-positive organism that can knock out the mucosal layer of the stomach and what is part of the mucosal layer? The parietal cell. What are the two functions of parietal cell? Number one, acid secretion. Number two, producing intrinsic factor. Another high yield point is malabsorption could be due to Diphyllobothrium latum. This is the fish tapeworm. And on the USMLE, they may give certain demographic, but in the CBC, when you're thinking of parasitic infections, think about eosinophilia. Terminal ileal disease, such as Crohn's, can also lead to B12 deficiency. Again, you are thinking about the area where the intrinsic factor and the B12 are going to be reabsorbed together. Crohn's disease in USMLE vignettes, they'll say chronic diarrhea, weight loss, and increased CRP. Remember, if your CRP is normal and you have chronic diarrhea, you should be thinking of IBS, irritable bowel syndrome, not IBD. IBD has an elevated CRP, IBS has normal CRP. We also talked about patient who undergoes extensive surgery. They can have short gut syndrome if they are going to have reduced absorption capability. They can get not only fat-soluble vitamin issues, but vitamin B12. And then finally, decreased intake. And this usually occurs when you're avoiding animal products for many, many years. Now, want to emphasize when it comes to your questions related to vegan diets, remember that vegan diets, you're not going to have any animal-derived foods. No meat, no dairy, no egg. And the potential benefits of vegan diet is it reduces your cardiovascular risk factor, things like heart disease and stroke. However, the nutritional deficiencies that can occur is vitamin B12. You can also have deficiencies in vitamin and even iron. So, just something for you to note that with veganism, you are prone to nutritional deficiencies. Now, remember that vitamin B12 normally is needed for DNA replication and cytokinesis of red blood cells, i.e. splitting apart. So, if you do not have B12, you don't have good DNA replication, and you end up having big red blood cell that can't split apart. And that big red blood cell is going to be known as macrocyte, so you get macrocytic anemia. Typically in your USMLE questions, they will give you an elevated MCV. You have to interpret that number. And with B12, because you can't have cells cytokinesis, you will get hypersegmented neutrophils, which means that they have more than five lobes. Now, B12 deficiency is very unique in the sense that if you have B12 deficiency, you're going to be increasing your levels of methylmalonic acid. And that's because odd-chain fatty acids can't enter the TCA cycle as succinyl-CoA. And so, if you can't get methylmalonyl-CoA to succinyl-CoA, what ends up happening is you develop an increase in methylmalonic acid that is neurotoxic. And it's neurotoxic in the sense that it is going to affect the lateral corticospinal tracts, as well as the dorsal column medial lemniscus system. This is extremely high-yield for us to know. Why? Because the USMLE wants you to know that this is the pathophysiology of subacute combined degeneration of the cord. And what these patients will have is they will have upper motor neuron signs, let's say hyperreflexia, as well as issues with proprioception. So, they may even say that they can't feel vibrations, or they may have positive Romberg sign, indicating that the DCML is going to be abnormal. The other thing that the USMLE wants you to know is what are some of the foods that are going to be high in certain nutrients. The ones think that are high-yield, high folate foods, high vitamin foods. So, with vitamin and folate, typically, it's leafy green vegetables that are going to be high in vitamin and folate. As you can see here, there's spinach, kale, cabbage, brussels sprouts, broccoli. Those are all high in vitamin Other leafy green vegetables like spinach, romaine lettuce, etc. are going to be high in folate. In addition, lentils as well as avocado are going to be high in folate. Now, one of the things that wanted to just emphasize here is if you are going to have issues with eating vitamin what ends up happening is that if you have issues with vitamin you may get warfarin that is going to be more potent. What's important for us to note is that patients who are on warfarin, they need to have high vitamin diet over long period of time. Why is that? Because vitamin is important for the gamma carboxylation of your clotting factors. Specifically, vitamin is going to activate your epoxide reductase and that then allows for you to have good gamma carboxylation and more active 27910 and you have good clotting cascade. So, if you have reduced vitamin intake, your warfarin can actually be more potent and you may get an elevated INR and increased bleeding risk. The other point that wanted to bring up is if you have reduced folate, let's say that in the vignette they say the mom lacked prenatal care. One of the pathophysiologies and that you have to note is you're not going to have body surfaces that are going to fuse. And so that is going to be associated with myelomeningocele. And myelomeningocele is going to be form of spina bifida and remember you are going to have elevations in your alpha fetal protein, which you can see in your OB questions. All right. We're going to move on to nutrient metabolism. Now, when it comes to nutrient metabolism, here is going to be quick overview. The reason why the USMLE likes to go for lot of nutrition-based questions is because nutrition and nutritional deficiencies affect every organ system. So, as you can see this visual vignette here, if you're thinking about the eye, you need vitamin You need vitamin for good cellular turnover, such as the cells of your cornea need to turn over thanks to vitamin If you don't have vitamin you get these Bitot spots as well as night blindness. For good neurological function, you need thiamine. You need B12. You need B6. We've are going to be talking about the deficiencies, but just think about your Wernicke's syndrome that can be integrated here. For good thyroid function, you need good iodine as well as selenium. For good heart function, you need thiamine, which is vitamin B12 or B1, excuse me. For good blood function, you need iron, B12, folate. You need good B6 and vitamin Remember that with blood, your iron deficiency anemia is microcytic anemia. Your B12 and folate is going to be macrocytic megaloblastic anemia. If you have B6 issues, you can get sideroblastic anemia. And if you have issues with vitamin you can get bleeding because your coagulation cascade is not working well. For good bone health, you need vitamin because vitamin allows for you to reabsorb calcium and phos. And for good skin health, you need zinc, vitamin niacin, and biotin. Remember that zinc, very very important for you to know, is that it is implicated in wound healing. think this is high yield concept because even as pediatrician when we're thinking about diaper dermatitis or any sort of diaper rash, zinc-based emollients are going to help with wound healing. Also recognize that if you have niacin deficiency, you get the three D's: diarrhea, dermatitis, dementia. Biotin, really important for hair and nail function. All you aspiring dermatologists may see some of these vitamins in the serums or creams that may be part of skin routine. So this is the multi-system approach and what want to do now is want to think little bit about the pathophysiology of malabsorption that we've been building on. When you're thinking about malabsorption, especially when you are going to have malabsorption of fat or even protein, you're going to get fatigue and cachexia because you just have reduced calories coming in for biochemical processes. If you have malabsorption, let's say at the duodenal level, you can end up getting iron that is going to not be reabsorbed and as result, you will get microcytic anemia. They may even give you smear showing that you have very small red blood cells. Remember that iron deficiency anemia, the way you differentiate it from thalassemia is that iron deficiency anemia has high red cell distribution with. When you're thinking about malabsorption, you could end up having poor vitamin reabsorption and as result, you will have weak bones. So those bones are going to be prone to fracture. You might even get bone pain. So that's why say, "Hey, the USMLE loves how are bones going to be strong?" The bones are going to be strong thanks to vitamin and what hormone? Go ahead and type that into the chat. What female hormone is going to keep bones strong? Excellent. If you're saying estradiol, you're absolutely correct. That's why postmenopausal patients are going to have high likelihood of developing osteoporosis. All right? If you are going to have malabsorption, we've talked about how with vitamin deficiency you can get poor hemostasis and maybe on your exam they can say that the patient has easy bruising. What we're going to do now is we're going to be focused on integrating step one and step two CK and we're going to be talking about fat-soluble vitamins first, and Remember, in order for you to reabsorb fat-soluble vitamins, you do need good micelle formation and good duodenal villi. If you don't have any of that, you are going to get malabsorption and typically malabsorptive diarrhea presents as chronic, greasy, foul-smelling stools. Go ahead and type into the chat box, what is going to be infectious etiology that can give you signs of malabsorption, i.e. greasy, foul-smelling stools? Excellent. If you are saying the pear-shaped Giardia, you're absolutely correct. And remember that Giardia is going to be treated with metronidazole. All right, let's go through this. Vitamin the physiology here is that it allows for good retinal pigments as well as cell differentiation. In fact, vitamin is important for taking blasts, for example, and turning them into more mature cells. And so, if you are going to have mutation in the retinoic acid receptor, you are going to then have lot more myeloblasts. And this is the classic pathophysiology of acute promyelocytic leukemia. So, if you have vitamin deficiency, think about night blindness because your retina is not working and your corneal cells are going to be super thick. You also can have poor immune response. Toxicity of vitamin if you have too much vitamin let's say that there is excess vitamin pigment and or sorry, excess vitamin cream that you are placing, you could even get pseudotumor cerebri, which typically is going to present in females who use tetracyclines, vitamin derivatives, and who are obese on oral contraceptives. And the key physical exam finding that you'll see in the vignette is going to be papilledema. Also, if you are going to have excess vitamin or vitamin modulation, you can end up having teratogenicity. And that's really important when patients are going to be on systemic vitamin such as isotretinoin, that's known as Accutane, they actually need birth control as the next best step in management because systemic vitamin therapy can actually be teratogenic for these patients. Now, next thing that you have to note here is vitamin Vitamin is going to be activated in the kidney via 1-alpha hydroxylase. The storage vitamin then gets activated to 1,25 vitamin which increases the calcium phos reabsorption in the intestines. always like to say 1,25 vitamin increases calcium and increases phos, but if you're thinking about parathyroid hormone, it's the exact opposite. It increases calcium, but it reduces phos. So, you got to know the difference between PTH and active vitamin Remember that vitamin deficiency is going to lead to osteomalacia and rickets, whereas vitamin excess can cause you to have hypercalcemia because you're going to reabsorb more calcium. For vitamin the normal physiology, it is going to be an antioxidant. It's going to decrease reactive oxygen species. What are other reducers of reactive oxygen species? Well, things like G6PD, things like vitamin things like vitamin These are all going to be helpful in redox reactions. And so, if you have vitamin deficiency, you actually can end up getting hemolytic anemia as well as even demyelination of the posterior columns. Again, this is due to too much free radicals. If you have too many free radicals, you are going to have neuronal instability and RBC fragility. Toxicity of vitamin not as high yield, but you can have increased chance of necrotizing enterocolitis or increased effects of warfarin. Vitamin the physiology here is that it is going to help with gamma carboxylating your coagulation factors. Remember that it is going to activate your epoxide reductase as cofactor, so you get good 27910, and majority of those, especially the nine factor nine, for example, is going to be part of your extrinsic clotting cascade, whereas your factor seven is going to be measured via the PT. And apologize, factor nine is going to be extrinsic clotting cascade and intrinsic. Sorry. And factor seven is going to be your extrinsic clotting cascade, okay? So, if you are going to have vitamin deficiency, you may have patient who is going to have hemorrhage, and And high yield for us to note. Typically, they'll say premature infant who was born at home who now has bulging fontanelle. They want you to know that intraventricular hemorrhage can be due to the fact that the baby didn't get the vitamin shot at home. When you're thinking about excess vitamin the toxicity is going to be kernicterus jaundice, hyperbilirubinemia. Again, vitamin excess and vitamin excess are pretty low-yield, but added this for completeness sake. Let's move on to the water-soluble vitamins. With water-soluble vitamins, we're going to be thinking of vitamin B1 first, thiamine. Remember that thiamine is an important cofactor in dehydrogenase reactions. Thiamine is also going to be an important cofactor in the non-oxidative portion of your hexose monophosphate shunt because it is cofactor for transketolase. deficiency in thiamine, this you need to star. And this is because you're going to be getting questions on Wernicke's syndrome, Korsakoff syndrome, and beriberi. Remember Wernicke's syndrome has the triad. What is the triad? Confusion, ophthalmoplegia, and ataxia. Korsakoff, you're going to have confabulations. And remember wet beriberi presents as cardiomyopathy, so they may have an S3 gallop on physical exam. lot of these patients are going to be in the social history. They may say tea and toast diet, poor nutrition. They may say long-standing alcoholism. Vitamin B2, that is going to help with FAD and FADH2, and that is an important cofactor for succinate dehydrogenase. Remember that if you have vitamin B2 deficiency, you can get issues with your eyes, specifically conjunctivitis and cheilosis, issues with your lips. Vitamin B3, kind of related to FAD, it is NAD. And remember that vitamin B3 is going to be helpful in not only NAD, but very anabolic cofactor NADPH. Remember that NADPH is what is going to be driving many anabolic processes such as fat, steroid production, as well as even the G6PD pathway, all need NADPH. When you have issue with vitamin B3, i.e., you have niacin deficiency, you can get the triad of pellagra. Go ahead and type into the chat, what is one of the symptomatologies of pellagra? Excellent. If you're saying diarrhea, dermatitis, and dementia, you are absolutely correct. Vitamin B6, this is going to be important for pyridoxal phosphate. And vitamin B6 is going to be important in your cystathionine beta synthase. Remember that is going to take homocysteine to cysteine. If you don't have B6 or you have CBS deficiency, that is one of the characteristic pathologies known as homocystinuria. And if you have CBS deficiency or B6 deficiency, you can develop homocystinuria in which you get elevated homocysteine. And if it's genetic, you will have the downward dislocation of the lens. Remember that glycine and your succinyl CoA come together to form delta-ALA thanks to the cofactor B6. And basically what I'm going for here is the heme synthesis pathway, which is going to be helpful in creating that porphyrin ring. So, if you are going to be having B6 deficiency, let's say for example, the patient is treated with isoniazid. They may not even say treated with isoniazid, they'll say treated for latent TB or active TB. And then they develop numbness and tingling, you're going to be thinking of INH induced B6 deficiency. And that's why when patients start isoniazid, they are going to need concurrent B6 administration. Now, if you have B6 deficiency, you can also develop sideroblastic anemia. And those ring sideroblasts are going to be aggregates of rRNA. They may even point to in picture the ring sideroblasts and they'll say, "Hey, what is this going to represent?" And that is going to be rRNA aggregates. Moving on, we're going to be thinking about B7. Now, B7 is going to be biotin. And biotin is going to be cofactor that is needed in many carboxylases, things like pyruvic carboxylase, which is going to take pyruvate and turn it into oxaloacetate, to acetyl-CoA carboxylase. lot of carboxylase reactions are going to need three things. And carboxylases need ABC. They are going to need ATP, biotin, and CO2. Now, deficiency in biotin is going to cause you to have issues with hair, so you can get alopecia. One of the things that you want to note is that there is high amount of avidin, and avidin is in raw egg yolks. And if you have high avidin intake, or you have bodybuilder that they say raw egg yolk intake, you could get biotin deficiency. B9, folate, remember folate is going to be important for methyl donation. It's also going to be important for DNA and RNA synthesis. If you have folate deficiency, you are going to be getting megaloblastic anemia, which is going to be high MCV anemia. They'll say for an arrow question, high MCV, low hemoglobin, and you are going to get hypersegmented neutrophils. So, compared to B12 deficiency, folate deficiency has normal methylmalonic acid levels. And if you have normal methylmalonic acid levels, you are going to have no neurological symptoms. Recall that patients who are going to have folate deficiency, they may say that they have tea and toast diet, i.e., they do not have the intake of those leafy green vegetables that we were talking about. All right, everyone. We talked about the fat-soluble vitamins, then we talked about the water-soluble vitamins, but on your nutrition-based questions, you may even get trace minerals that are going to be tested, and that's why wanted to place this in the review. Is everybody having good time so far? see lot of action in the chat box, which is excellent. Who all is paying attention? Everybody's paying attention here? All right, very good. Thank you so much for your engagement. Let's go through this. So, what want you to note is that trace mineral deficiencies are going to be in your USMLE questions. If they say prolonged total parenteral nutrition use or TPN use, they may say bowel resection, or they may even say gastric bypass surgery. Again, what's happening here is you are going to have increased predilection to develop trace mineral deficiencies. Now, let's say that they say brittle hair, ataxia, osteoporosis, and skin depigmentation. This is going to be related to copper deficiency. Now, remember with copper deficiency, they want you to know that if you have defective copper transport, that is related to ATP7A mutation known as Menkes disease. They can say that there is kinky or coiled hair. They may even give you the picture of that in your NBME question. Now, remember Menkes disease is going to be genetic condition in which you have defective copper transport from the enterocytes to the liver and peripheral tissues, and you can get brittle hair, ataxia, etc. Another important point that want to note here is that copper is cofactor for many different enzymes in the body. Lysyl oxidase, which is important in collagen cross-linking. Remember, your bone is going to be made up of collagen along with your hair, so that's why you have brittle hair and osteoporosis because lysyl oxidase is important in collagen cross-linking. Cytochrome oxidase, that's in your electron transport chain, that needs copper, so that's why if you don't have good copper, you may have fatigue or low energy because you can't make ATP. And then finally, you need copper for the conversion of dopa to melanin, and that conversion is going to be thanks to tyrosinase, which needs copper, and so that's why these patients may have skin depigmentation when you have copper deficiency. Go ahead and type into the chat. What if said that the patient is going to have flat affect and they are going to have abnormalities in your ceruloplasmin levels. What do you think I'm going for here? Not copper deficiency, but copper excess, and what do we call that? You got it. Very good. If you're saying Wilson's disease, you're absolutely correct. And remember that ceruloplasmin levels are going to be low in Wilson's disease due to excess amount of copper. All right, let's go through this trace mineral deficiency, low hemoglobin, low MCV, high red cell distribution with Good. If you're saying iron deficiency anemia, you're absolutely correct. What about this one? Thyroid dysfunction as well as S3 gallop indicating that there's cardiomyopathy. This is an interesting one. This is selenium deficiency. How about this one? Impaired glucose control. If you get refractory diabetes, think about chromium deficiencies. All right, next question. How does zinc deficiency present? Go ahead and type it to the chat. What do you think are some of the things NBME can give you for zinc deficiency? Wonderful, Priya. Impaired wound healing. Excellent. Dermatitis. Lack of taste. Excellent. So, what did here is created visual vignette for zinc deficiency. And zinc deficiency is known as acrodermatitis enteropathica. pathica. Think about it like this. Acro, meaning the extremities. Dermatitis, so you get skin rash of the extremities. And enteropathica, that means that it is going to be GI pathology. So, you may even get issues with wound healing, you may get impaired taste, you may get hair loss as well. So, let's go through this. When it comes to zinc, the core mechanisms that you have to know is that zinc fingers are important for transcription. So, if you don't have zinc, you don't have good transcription. No good transcription, no good translation or protein synthesis. Zinc is also needed for collagenesis. Remember you have those wound healing step one concepts? Well, in order for the wound to change, you are going to need collagenesis, which kind of chop up the extracellular matrix. And guess what cofactor of collagenesis is? Zinc. So, no zinc, no good collagenesis, that means poor wound healing. And then zinc is also needed for membrane stability. So, if you are going to have lack of zinc, you may not have good taste buds, you may have poor skin, and so that's why place that as core mechanism. Things that are going to help with membrane stability, vitamin helps with membrane stability, zinc helps with membrane stability. There are also questions that can come up related to bariatric surgery. Now, bariatric surgery is indicated in patients who have morbid obesity, and the interesting part of bariatric surgery is it's actually on the decline now. And why is that? It's because these GLPs are starting to become more conservative options and more effective options, and so bariatric surgery is definitely on the decline. But, you have patient who is status post bariatric surgery, you do need to know what they actually did. And usually what they did is they created small gastric pouch, and then what they ended up doing is bypassing majority of the stomach and create Roux-en-Y, in which you have bypassed small intestine that is directly going to have stomach that is connected to the jejunum. So, this is why you are going to note the fact that if you bypass the small intestine, specifically the duodenum, you get less nutrient reabsorption. If you have smaller stomach, you are going to eat less calories, i.e. you're going to be full longer. So, complications of gastric bypass on the USMLE, an anastomotic leak, which means that one of these suture lines ended up bursting, you're going to be thinking of patient post-op day 1 to 3 status post gastric bypass and who has fever, abdominal pain, and even peritoneal signs indicating that the patient is going to have leakage of that gut contents irritating the peritoneum causing rebound rigidity and guarding. Another point, strictures. When you're thinking about strictures, this is going to be little bit long-term. Post-op day 14 status post gastric bypass, the patient is going to have progressive vomiting. Now, these strictures could be due to the strictures that form status post surgery or even adhesions, which is important. Anytime you have patient with past surgical history, think about adhesions that can lead to obstruction. And then finally, status post gastric bypass, you can get dumping syndrome. And these patients are going to have voluminous diarrhea, they may even have sweating and palpitations shortly after the meal, which indicates that they are going to be having profound hypoglycemia. And this dumping syndrome is basically due to increased transit of the food as they are going to be feeding themselves. And so, if you're going to get very hypoglycemic or there's more transit, the way you combat that is small frequent meals status post bariatric surgery. Now, one of the things that focused on in this review is kind of talking little bit about, okay, they give you patient that is going to be losing lot of weight. And now this patient is going to have chronic abdominal pain. What you want to be thinking about is SMA syndrome. So, the superior mesenteric artery, remember, comes off of the aorta, that is going to be held little bit more erect thanks to fat pad. And the fat pad gives the SMA nice erect shape or configuration, so that then you are not going to have compression on the gastric outlet. But in patient who is going to have rapid weight loss, let's say from bariatric surgery or from GLPs, you could lose that fat pad, and that narrows the SMA angle. So, now you go from little bit perpendicular to more acute angle, and that causes duodenal compression. And the USMLE wants you to know that these patients present with postprandial vomiting, and that's because you now have narrow SMA angle that is causing duodenal compression. And when you eat bolus of food, that proximal dilation coupled with the compression can lead to that postprandial vomiting. This vomiting, remember, is at the level of the duodenum, and so you're going to be thinking of bilious emesis. Remember, non-bilious emesis is usually prepyloric, whereas postpyloric emesis, i.e., compression of the duodenum, that is going to be green or bilious. All right. Let's go ahead and integrate and apply some of the things that we have just been talking about. Remember that thiamine, you're going to be watching out in the NBME question for alcohol use. They may say that the patient has confusion, which is unable to answer questions on the mini mental status exam. Wide base gait, that's your clue for ataxia, and abnormal eye movements. Let's say that they are testing the eye movement with the test on physical exam. If you can't move the eyes or they're stuck in configuration, that is going to be your ophthalmoplegia. You can also have nystagmus in the vignette. All right, what do you think this one is? Newborn with bleeding in the ventricles and an elevated PT indicating that the extrinsic clotting cascade and vitamin dependent factors are messed up? Yep, exactly. And they may say baby born at home. All right, what about this patient who has these acanthocytes as well as schistocytes? What do you think is the diagnosis here? Very good, vitamin deficiency, which usually presents as hemolytic anemia. All right, how about this one? skin rash that is described as itchy and tingling with intense redness. Abdominal pain and watery diarrhea. Disorientation or psychosis. Wonderful. If you are saying niacin deficiency, you're absolutely correct. Remember, diarrhea, dermatitis, dementia, but this is the power of thinking like the test maker, and this is what like to do in my courses, is like to just focus on, "Hey, if we are having this triad, what are the wordings that will be in the UWorld or NBME question?" And that's exactly why create these tables. Another point that just want to make is you can get niacin deficiency whenever patient is going to have increased serotonergic demand. And what is tumor that causes lot of tryptophan to serotonin conversion? That is going to be carcinoid. So, the reason why is because if you have carcinoid syndrome, you are going to be having lot of tryptophan that is not diverted to niacin, it's diverted to serotonin, and thus you can get pellagra due to carcinoid syndrome. All right, I'm going to now pivot and talk little bit about vitamin metabolism. is everybody having good time so far? Go ahead and type in yes into the chat box. Everybody good? see lot of great answers and promise I'll stick around for the Q&A afterwards as well. Very nice. So, when we're thinking about vitamin remember the goal is to get to active vitamin because active vitamin is going to help you reabsorb calcium and phos. So, what ends up happening is that you have seven dehydrocholesterol that is going to be in the phospholipid bilayer of your skin, and UVB lights are going to hit that, and then you are going to produce vitamin And that vitamin is going to be stored as 25 vitamin in the liver. Now, what are going to be some foods high in vitamin You can see that here. Things such as fortified milk, mushrooms, even fish products are going to be high in vitamin Now, what we have to know is that the kidney is going to be the primary area where you are going to get conversion of 25 vitamin to the active 125 vitamin And remember, the 125 vitamin brings in calcium and phos. So, what stimulates the one out one alpha hydroxylase, and that is going to be your parathyroid hormone. This is extremely high yield, so let me go ahead and integrate some concepts here. The USMLE loves this concept of one alpha hydroxylase. And one alpha hydroxylase is going to help you with 25 to 125 vitamin in the kidney but then the other area that they like for you to know is if they give you an African-American female with hilar lymphadenopathy you're going to be thinking of sarcoid and sarcoidosis has these granulomas and they want you to know that patients with sarcoidosis they can get hypercalcemic and the reason why is because the granuloma itself also has one alpha hydroxylase activity and if the granuloma has one alpha hydroxylase activity you can get 25 to 125 vitamin because you have granuloma in your body and that then causes you to have hypercalcemia. Another point that just want to emphasize here is that if you are going to be having chronic kidney disease in CKD the two things that they like for you to know is that you can actually get an increase in parathyroid hormone because you have low calcium and why do you have low calcium? Well, it's because the CKD knocked out your one alpha hydroxylase. And if you don't have one alpha hydroxylase you then have no active vitamin no active vitamin means you become hypocalcemic and in addition what you have to know is that if you have hypocalcemia that shoots up your PTH because of the lack of negative feedback. Another point that want to bring up with chronic kidney disease is if you have patient with chronic kidney disease they like for you to know that they also don't have erythropoietin so you can't make red blood cells as well. So what want to emphasize here is if this is going to be graph and this graph is going to have PTH levels as well as calcium levels. Where do you think you are going to have secondary hyperparathyroidism. Is secondary hyperparathyroidism in quadrant or Go ahead and type that into the chat. What quadrant is secondary hyperparathyroidism, which is due to kidney disease? Excellent. If you're saying quadrant you're absolutely correct. Remember that you in secondary hyperparathyroidism, the arrow is going to be low calcium, low 125 vitamin because you don't have 1 alpha hydroxylase, you have high PTH because you have low calcium, and because your kidney is not working, you can't do phosphate trashing, i.e., you have impaired excretion of your phos, and so you are going to be having hyperphosphatemia. And that's important for us to know because your kidney doesn't work, you can't pee out the phos. And that leads to hyperphosphatemia. So, want to pivot and talk little bit about vitamin deficiency. In adults, vitamin deficiency is known as osteomalacia. In kids, it's going to be known as rickets. Now, patients with rickets are is going to in your physical exam have frontal bossing. They may have rachitic rosary underneath their ribs. They also will have enlarged epiphysis indicating that the growth plates can't fuse. Because they have weak bones, they have bowed legs, and all in all they'll have short stature. Now, the core mechanisms that drive this is if you have vitamin deficiency, you are going to be having decreased calcium and phos reabsorption, and these soft bones are going to deform with stress. When you have osteomalacia, another interesting radiographic finding are these pseudo fractures, also known as looser zones. And these are going to be perpendicular to the periosteal surface that are going to be throughout all of the areas in your body like your scapula, your humerus, as well as your femur. And basically this represents again weakening of the bone and it looks like fracture and that's why it's called pseudo fractures. And associate this with osteomalacia and vitamin deficiency. Speaking of children with rickets, also wanted to integrate this high-yield nutrition point of various milks that children can drink and the nutritional deficiencies associated. So, what is this patient's diet? Let's say you have 6-month-old drinking milk and has megaloblastic anemia. What kind of milk is this child drinking? The milk is actually going to be goat milk. And it's interesting because goat milk actually has decreased amount of folate concentration. All right, how about this next one? An 8-month-old with increased milk intake and now presents with microcytic anemia, fatigue, and pallor. This is going to be cow's milk. And with cow's milk, got to know that number one, you don't introduce cow's milk until after the age of 12 year 12 months old, okay? If you have early initiation of cow's milk, you have an increased likelihood of developing iron deficiency anemia. The reason why is actually twofold. Cow's milk is going to have low iron content. The gut before the age of one is immature and cannot reabsorb iron. And then finally, the cow's milk iron and calcium in particular, the cow's milk calcium is going to be irritative and can cause you to have microscopic colitis. And if you have microscopic colitis, you then are going to have GI bleeding. And if you have GI bleeding, you can get microcytic anemia from cow's milk. So, excess cow's milk intake, think about iron deficiency anemia. All right, last question. This one shows up lot on NBMEs. Primary care provider should prescribe all breastfed children for the first 6 months of life with what vitamin supplementation? If you're saying vitamin you're absolutely correct. That's because breast milk has poor concentrations of vitamin We're going to pivot and talk little bit now about metabolic pathways. Now, metabolic pathways are going to again be grouped based on macronutrients, carbs, fats, and proteins. So, let's think about carbs. What are the biochemical pathways? You have your fructose, galactose, and lactose. Watch for patient who had, for example, rotavirus and suddenly upon reinitiation of milk or juice, they are going to have voluminous diarrhea. That's because they have transient lactase deficiency. Glycolysis is the process of breaking down the carbs. Glycogen metabolism, synthesis is anabolic, breakdown of glycogen is catabolic, and then gluconeogenesis, this typically is going to occur in the fasted or starvation state. Other things we have to note is protein. Remember that proteins have lot of ammonia groups, and so that ammonia needs to be turned into the urea into urea. And remember, where does the urea cycle occur? It occurs primarily in the hepatocyte. So ammonia to urea, that is going to be in the hepatocyte. Proteins are also going to be collagen based. Remember, type 1 collagen is for bones, whereas type 2 collagen is going to be for cartilage. And proteins are also going to have components that are amino acids and those amino acids are going to be derivatives to various things. We already talked little bit about how tryptophan is going to be precursor to niacin as well as serotonin. The final macronutrient, which we talked about with malabsorption, that is going to be lipid. And remember that lipids are going to be anabolically made via fatty acids and the rate-limiting enzyme is acetyl-CoA carboxylase. But then in the mitochondria, you can also get beta oxidation of fatty acids in which long fatty acid is going to be broken down into small acetyl-CoAs that then are going to enter the TCA cycle. Now, if you have increased amount of acetyl-CoA entering the TCA cycle and over time you are in diabetic ketoacidosis state or in very prolonged starvation state, lot of that acetyl-CoA then is going to go and get acted upon via HMG-CoA synthase. And with HMG-CoA synthase, you make lot of acetoacetate. So that's why when you have prolonged lipid metabolism or lipid breakdown, you actually shunt lot of those extra acetyl-CoAs to ketone metabolism. All right. So what we're going to do in this table is we're going to be focused on the metabolic state, the dominant pathway, and the rate-limiting enzymes. Remember, step one loves to test the rate-limiting enzymes, so that's why put it all on one slide. When we're thinking about the fed state, remember that that is going to be related to increase in insulin. You just ate something. So, when you ate something, you're going to have glycolysis, breaking down the sugar, glycogenolysis, making sure that you have storage of that sugar, and fatty acid synthesis. And the rate-limiting enzymes that are going to be doing the work of these pathways are going to be PFK1 for glycolysis. Remember that there is an allosteric activator known as fructose-2,6-bisphosphate. Remember that fructose-2,6-bisphosphate is going to be produced by PFK2. And when that fructose-2,6-bisphosphate is going to sit in the active site of PFK1, you are going to get more glycolysis, which means that glucose will turn into pyruvate more. Another important rate-limiting enzyme is glycogen synthase. And finally, acetyl-CoA carboxylase. Now, if asked you what hormones activate what hormone activates all of these three, the answer is going to be insulin, because you are going to be in the fed state. Now, let's talk little bit about the fasting state. This is typically going to be that intermittent fasting regimen, 12 to 16 hours without meal. You're going to be getting an increase in glucagon. Now, with this increase in glucagon, you are going to get glycogenolysis, gluconeogenesis, and you're going to get breakdown of your fats, and that's called lipolysis. So, the way you think about this is if this is your triglyceride, now, thanks to your glucagon, you're going to activate your hormone-sensitive lipase and release those triglycerides as free fatty acids. Now, what's important for us to know is that the rate-limiting enzymes of these dominant pathways are going to be glycogen phosphorylase for glycogenolysis, fructose-1,6-bisphosphatase for gluconeogenesis. Remember, gluconeogenesis is kind of the reverse of glycolysis. And then for lipolysis, you are going to have CPT1, which is going to be activating the free fatty acid as it makes its way into the mitochondrial matrix. With prolonged fasting or starvation, you're going to be getting an increase in your counterregulatory hormones. This is where you are going to get an excess of not only glucagon, but epinephrine, norepinephrine, growth hormone, as well as cortisol. And guys, guess what cortisol does? Proteolysis. They love for you to know that. Excess cortisol is going to break down muscle. Now, what other processes? Well, it's similar to the fasting state. You're going to get gluconeogenesis. And in particular, you're going to make lot of ketones in your starvation state. And so, what are the rate-limiting enzymes? Well, for gluconeogenesis, not surprisingly, you have your fructose-1,6-bisphosphatase. For ketogenesis, you have HMG-CoA synthase. Remember, HMG-CoA reductase, that's for statins. HMG-CoA synthase, that is going to be ketone production. And then finally, for proteolysis, you are going to have CPS1. Basically, what CPS1 is going to do is CPS1 is going to be rate-limiting enzyme for your urea cycle. This is where you are going to be taking lot of the NH3 groups, and you are going to be releasing them into the urea cycle. What is an amino acid that has high amount of NH3 groups? They really like this question. That is going to be glutamine. Glutamine has high number of NH3 groups, ammonia, that need to be turned into urea. All right. This is an NBME style question. We're going to be going through this together. Which of the following pathophysiologic mechanisms best explains this clinical deterioration? So, we have 19-year-old woman who is hospitalized for severe malnutrition due to anorexia nervosa. Her BMI is 13, and nasogastric feeds are initiated. After these nasogastric feeds, she has generalized muscle weakness, dyspnea, and palpitations. So, these systemic symptoms. Physical exam shows bibasilar crackles and two plus pitting edema in the lower extremities. Labs today show very critically low serum phosphate at one. Which of the following pathophysiologic mechanisms best explains this deterioration? impaired myocardial contractility due to thiamine depletion. increased intracellular electrolyte shifts. osmotic diuresis due to hyperglycemia. renal wasting of electrolytes due to tubular dysfunction. Or SIRS response. So, here you have patient who is going to be having refeeding syndrome. Remember, with refeeding syndrome, it's an anorexic patient that is going to get excess amount of calories. And once they get refed, insulin spikes, and that shifts your electrolytes, and that's why you have hypokalemia leading to cardiac dysfunction, as well as your phosphate level being critically low, as you have transcellular shift from the blood space to the intracellular space. So, let's go through this. With refeeding syndrome, rapid food reintroduction causes sudden spike in insulin, and that insulin drives phos, mag, and potassium into cells. Now, what does this do? Remember, if the phos is going into the cell, you are likely going to be making ATP because adenosine triphosphate. And finally, what you will get is this marked hypophosphatemia, and organs then are going to shut down like your heart. So, couple things you want to note. If you have hypophosphatemia, hypokalemia, hypomagnesemia, you need to get an echo and EKG cuz you got to make sure that the heart structurally and electrically is going to be okay. You're also going to be giving electrolyte repletion. So, in refeeding syndrome patient, check electrolytes every 6 hours, and replace magnesium, phos, potassium, and even thiamine. The next section that we're going to be focusing on is weight-related disorders. With weight-related disorders, kind of thought of this as weight loss and weight gain. So, let's talk little bit about pediatric-based questions. One of the things that you want to know is that growth, the growth chart in particular, is vital sign for child. always, even in my epic electronic medical record, have one of the tabs after vitals, results, etc., have it as growth chart. Why? Because if you are seeing children drop growth percentiles or cross two growth lines, that is no bueno. So, that means that the child may be dealing with failure to thrive. And when you're thinking about failure to thrive, the two pathophysiologic schemas that like to be thinking about is either decreased intake or increased metabolic demand. Either they are going to be having calorie or protein issue or even vitamin deficiency secondary to malabsorption. Maybe the child has cystic fibrosis and they are going to have pancreatic insufficiency or poor growth because of malabsorption. So, those are all under decreased intake or the child's body is always on treadmill, i.e. increased metabolic demand. And there are various systems-based pathologies that can cause this increased caloric expenditure. So, when we're thinking about failure to thrive, before we say, just eat more." We want to think about an organic etiology. Things like pediatric heart failure is good example. Some sort of immune deficiency is another good example. When you think of an organic etiology like an immunodeficiency, your child's body is just having so much increased metabolic demand to let's say fight off infections and that then is burning more calories than they are taking in and that is going to be related to failure to thrive. Now, with organic etiologies, here is table that you should commit to not only memory, but understanding. What is going to burn lot of calories in child? Well, if you have tachypnea, tiring out during feeding and sweating during feeding, think about congenital heart defect like unrepaired VSD. Increased metabolic rates in hypothyroidism can cause failure to thrive. When you have child who has chronic inflammation due to lupus or rheumatoid arthritis, all of your proteins are being utilized for acute-phase reactants like CRP, ESR. Chronic infections, let's say think about TORCH infections in which the USMLE vignette may say the mother had poor for care. Immunodeficiencies in which you are trying to fight chronic infections and thus increasing the caloric expenditure. And also oncological etiologies. So, any sort of rapid growth of cancer cells, all of the nutrients that you are taking in when you have an underlying cancer are getting absorbed by the cancer cells requiring the cancer to grow. And that's why you have weight loss as one of your constitutional symptoms indicating, especially in subacute or chronic tempo, that we're dealing with cancer. So, here is going to be case-based question for you all. 5-year-old is adopted from rural Kenya. He is noted to have temporal wasting and growth less than the fifth percentile. So, he has failed to thrive. The patient's abdomen is scaphoid with no liver or spleen enlargement. Extremities are normal. Which patient do you think I'm talking about here? Is it patient or patient What do you think? Excellent. If you are saying marasmus, you're absolutely correct. Remember that marasmus is going to be general protein calorie malnutrition. And as result, you get temporal wasting. And the characteristic thing is no edema. That's why put extremities are normal. With kwashiorkor, it's primarily protein issue that is going to have low oncotic pressure and you can get protuberant abdomen and pitting edema. So, let's go through kwashiorkor and marasmus. Marasmus is general malnutrition. And some of the markers for malnutrition that just want to emphasize here, things like prealbumin, transferrin, albumin. Those are going to be low when you're very malnourished. Marasmus, think for marasmus, for muscle wasting. You have no edema, normal height percentiles, and reduced weight percentiles. In the vignette, the child was less than the fifth percentile. For kwashiorkor, it's primarily protein malnutrition. And if you don't have good albumin, you have low oncotic pressure, so you get third spacing and edema. You also are going to get an increase in the fatty liver due to poor apolipoprotein metabolism. Again, kwashiorkor, they're edematous like the Michelin Man, and they may have dyslipidemia as result. We talked about pediatric weight loss. Now, let's talk little bit about adult weight loss. Now, with adult weight loss, let's say you have an adult who presents with unintentional weight loss. And on top of that, with the weight loss, they're older adult, and they have microcytosis on their peripheral blood smear. What is the next best step in management? Go ahead and type this into the chat. Well, here is an important adage. Iron deficiency anemia in an elderly patient is colon cancer until proven otherwise. So, colonoscopy is your best answer. What about weight loss plus 40 pack year smoking history and blood tinged sputum? What is your next step in management here? Okay, so you're worried about lung cancer, so you're going to get chest imaging. Maybe you'll start with the chest x-ray and then move on to CT. did want to put little bit of family medicine integration here. Remember, there are screening guidelines for low-dose chest CT in patients aged 50 to 80 years old who are going to be long-standing greater than 20 pack year smokers or who have recently quit. And this is going to be annual low-dose chest CT to screen for lung cancer. Guys, just have to say, anytime see lung cancer, please pay your respects to paraneoplastic syndromes. Everything from hypercalcemia due to PTHrP all the way to hyponatremia due to SIADH. All right, how about this one? Tremor, feeling hot and anxious, and diarrhea plus weight loss. Next best step is to get thyroid studies. And if you're worried about hyperthyroidism, you need to get radioactive iodine uptake scan. All right, how about this one? patient who has weight loss, is sad, lost interest in hobbies, has poor appetite. What's the next step here? So, many of you are thinking major depressive disorder. And whenever you're worried about that, you need to screen for suicidality. Specifically an active plan or access to firearms. Weight loss plus difficulty with swallowing solids, then progressing to liquids. What's the next best step here? So, progressive dysphagia first with solids, then liquids, you're going to be thinking of esophageal cancer. And you want to visualize that with an upper endoscopy. All right. Patient with weight loss who's smoker, yellowing of skin and an abdominal exam that is unremarkable. What is the next best step here? So, what was going for here is quote painless jaundice. This is where the pancreatic head has adenocarcinoma that is going to be compressing the bile duct. And you may start with an abdominal CT scan to diagnose pancreatic cancer and also get direct bilirubin just to really prove the external compression. All right. Last question that is little bit more step one, but comes up. What cytokine is related to generalized cachexia that we see in HIV as well as in tumors. Excellent. If you're saying TNF alpha, you are absolutely correct. The USMLE in psych questions as well as nutrition-based questions may ask you to differentiate between bulimia and anorexia. Remember, patients with bulimia are going to have normal to elevated BMI. They are going to potentially have purging behaviors that are going to manifest as just chronic vomiting, so they will have acid that corrode their enamel. So, enamel erosions, esophageal irritation. Another esophageal irritation. If they say blood tinge, think about Mallory-Weiss tear that is going to be at the GE junction. Remember that patients who are going to have lot of vomiting, they can end up getting hypokalemic metabolic alkalosis. And that's because the patient is just vomiting hydrochloric acid. So, they have lot of base left in their body, so they have metabolic alkalosis. Next step in management, because these patients may be dehydrated and they may be hypochloremic, you need to give them normal saline. For anorexia, these patients truly have low BMI. They may say BMI less than 18.5. And they're going to have dry skin, fine hair. That's called lanugo. Because they are going to have overall shutdown of their body, they can get bradycardia. These patients may also have increased parasympathetic tone and decreased sympathetic tone, and thus they can get bradycardia and orthostasis. In addition, these patients can have irregular periods. And if they have irregular periods, that's because they have shutdown of their pulsatile GnRH, LH, FSH, and gonadal axis. And if they have irregular periods, they have low estrogen and they are prone to stress fractures. And that is secondary osteoporosis due to anorexia. And so, next step for anorexia is going to be psychotherapy and nutritional rehabilitation. All right, let's go through this question together. 12-year-old boy is brought in due to bullying and his prior weight percentile being greater than the 98th. His parents know that he knows that he needs to eat, quote, more fruits and vegetables. He is involved in after-school activities, and on his way home, his mother stops to, quote, grab quick meal before starting homework. What is the next response by the physician? So, this is child who is going to be obese and is also going to have some socioeconomic and familial factors that are going to be driving his obesity. And so, the next response would be something along the lines of educating the family. Remember, you don't want to talk down to the child who's struggling with weight. You want to have gentle tone with scheduling follow-ups and counseling longitudinally of good nutrition habits, as well as referral to dietitian. Now, guys, will say, for ethics questions, usually the wrong answer is referral to the ethics committee. I.e., never refer to the ethics committee. But for nutrition questions, here I'm going to say it. They will like for you to say, refer to dietitian. Refer to nutritionist." Especially if there is nutrition-based problem that is related to education. One of the domains they like to test is, "Hey, when do you refer?" And if there's nutrition-based problem that is impacting, let's say, BMI, you do want to counsel personally and refer to registered dietitian. We talked about malnutrition. Let's talk about the other spectrum, which is going to be high BMI. Remember that obesity is also going to be multi-system disease. Obesity can lead to insulin resistance, and that can cause you to have poor fatty acid metabolism, especially in the liver, so you can get metabolic syndrome associated steatohepatitis. This used to be known as non-alcoholic fatty liver disease. Obesity can cause you to have obstructive sleep apnea. Watch for patients who have morning headaches or daytime somnolence. Next best step is polysomnogram. You can also have restrictive lung disease with obesity hypoventilation syndrome. Hypertension is also complication of obesity, and then you can get increased biomechanical wear and tear, and so you can get osteoarthritis. That's joint pain worse at the end of the day. Now, you do want to note the categories of obesity. For example, 25 to 29.9, that is going to be overweight. Obesity starts at greater than 30, and you can see class two and class three are sequential. Another thing that just want to emphasize is let's say that you have pregnant patient, and the pregnant patient is going to have obese BMI prior to the pregnancy. Well, they need to gain less weight compared to somebody who is normal weight during the pregnancy. So, what want to emphasize here is during pregnancy, you expect to gain weight. But, the baseline BMI makes difference. And so, if you're obese coming into pregnancy, you have to gain less weight. Now, metabolic syndrome is going to be an important point and obesity is one of the criteria. So, metabolic syndrome is defined by any of the three of the five criteria, hyperglycemia, hypertriglyceridemia, hypertension, hyper waist greater than 40 cm in male, for example, and low HDL. want to emphasize this that if you are going to have metabolic syndrome, think about the four hypers and the one low. High glucose, so diabetes, hypertriglyceridemia, remember that can cause you to have asymptomatic elevation in AST and ALT, so an obese patient with abnormalities in liver function, think about metabolic associated steatohepatitis. Hypertension, which is high blood pressure, they'll ask you to interpret the number. High waist circumference, that's the obesity part, and then low HDL. I'm going to conclude this webinar by focusing on public health and social sciences, again, major push on the USMLE. On blocks, you may see two or three of these questions in your block, as well as even some of the chart-based questions, which we'll also be going through. Now, what want to emphasize here, if you see food insecurity and an infant with hyponatremia, this is common when there is food insecurity and the mom, to extend the duration or use of the formula, is putting more free water that the baby's kidneys cannot handle, those patients can come in with hyponatremic seizures, and if you have hyponatremic seizures, the next best step in management is going to be 3% hypertonic saline. So, with food insecurity and an infant who is going to have bad mixing of formula, you obviously want to educate for proper mixing technique. This is where you're going to get social work if the parents are saying, don't have enough food." For example, and then there is the women, infants, and children program that is going to help with getting basic groceries, formula, as well as cow's milk. How about this? If you see elevated BMI greater than 30.5 and the patient says, don't have problem at all." Well, one of the things that want to note here is the fact that patients who are not ready for change are pre-contemplative. And so, whenever they are ready, you want to refer to the nutritionist. This is important for you to pick up in vignette. All right, how about this one? If you see BMI less than 15 and routine labs showing low potassium and history of an eating disorder. What are you going to be worried about here? Well, critically low BMI and labs starting to show some refeeding syndrome. You're absolutely correct if you're saying hospitalization for refeeding syndrome. This is where you would want to potentially involuntarily hospitalize these patients with eating disorders and start obtaining EKGs and nutritional rehabilitation in supervised setting. The last section that will be focusing on is routes of nutrition delivery. There's an Amboss article that talks about this and guess what did? ended up taking that article and just summarizing it for you in few slides. know this is little bit of longer review, but hey, want it to be comprehensive here. And so, that is why want to focus on delivering these concepts in an integrative high-yield active recall way. So, let's go through this. We feed patients especially in the ICU in two ways, enteral or parenteral. Parenteral means blood, enteral means using the gut. So, how which one do you think is going to be more preferred? Go ahead and type into the chat. Which one is more preferred, enteral or parenteral? Excellent. Using the gut, enteral, is going to be more physiologic. So, you could be thinking of PO, which is going to be oral intake, nasogastric tube in which you insert tube in the nose and it ends in the stomach, or you can feed the duodenum or the jejunum, and that's called postpyloric. Now, what's important is if you're thinking of nasogastric administration, you can do bolus feeds, whereas if you're thinking of nasoduodenal or nasojejunal, you cannot bolus these patients in terms of their feeding regimen. Why? Because if you go back to normal GI physiology, the duodenum doesn't get boluses, it gets continuous trickle of food, and so you have to do continuous feeding when you're thinking of postpyloric. Now, one of the things that like to do in the ICU is whenever child is going to get NG tube placed, you want to look at the tube and have it end in the stomach if you have nasogastric tube, or if it crosses the vertebral bodies, you're going to be thinking of postpyloric nasoduodenal tube. But if it coils in the esophagus, that means that there could be malplacement of the esophageal and nasogastric tube, or it got coiled in the esophagus, or you could be thinking of esophageal atresia, which is going to be associated sometimes with tracheoesophageal fistula and genetic bacterial syndrome. Now, parenteral nutrition, this is going to be blood nutrition. And this is where patient cannot tolerate enteral nutrition. Let's say that they are just post-surgery and you have bad ileus, the gut's not peristalsing, they're having recurrent vomiting, or they have so much gut that is resected, i.e. short gut, that they are going to need their nutrition delivered via blood. Now, what's important is when you're thinking about total parenteral nutrition, the patient needs central line. That's surgery or procedure that gives them the ability to have higher dextrose that then can be circulated into the heart and then everywhere throughout the body. But whenever you have central line, you're worried about hospital-acquired or nosocomial infections. And that's called central line-associated bloodstream infection. So, let's go through this chart-based question. 46-year-old female in the ICU has fever and chills. This is 6 days after central venous catheter placement. The patient develops rigors during TPN infusion. Past medical history is short bowel syndrome. The lines that the patient has is right internal jugular, which is central line. Meds are TPN and broad-spectrum antibiotics. The patient is hospitalized. You notice that the patient is going to be tachycardic, febrile, and borderline hypotensive. She has shaking chills, and the skin surrounding the central line site is mildly erythematous. Labs are going to show leukocytosis, anaerobic metabolism, so lactic acidosis, and her blood cultures actually are going to grow staph, which is gram-positive cocci in clusters. So, what do you all think is the next best step in management for this patient? Go ahead and type into the chat. Excellent. If you have infection due to plastic, whether that's in the urethra for Foley catheter or central line, the USMLE wants you to know source control. Remove the central line and initiate antibiotics. Very high yield for you to recognize these central line infections. And again, it's because from Step 1 land, the staff creates biofilm surrounding the plastic of the central venous lines. And as result, you can get colonization, especially if you are placing glucose in there via the TPN. All right. This is my last slide of the review. And am just first off so grateful you all have joined me today. know it is marathon of review, but hope that this provides you value as you go into Step 1, Step 2 CK, or even Step 3. This was so fun to make. Basically, what did here is wanted to focus on disease and dietary consideration. So, what we're going to do is we're going to play an emoji game. These are the emojis on, let's say, your iPhone, for example. And so, here we go. High fruits and vegetables diet. That is going to be known as the DASH diet. And when you're thinking about the DASH diet, yes, you can even think of vegan diet as well. That is going to be fruits and vegetables. That's very good. But remember that the DASH diet is going to be helpful in reducing your systolic blood pressure. DASH stands for Dietary Approaches to Stop Hypertension. So, it's high fruits, high whole grains, and that can actually reduce your blood pressure. How about this one? Limiting salt intake as well as fluid intake. That is going to be for patients with heart failure or chronic kidney disease. How about this one? Avocado, fish, legumes, nuts, and cypress, which is in the Mediterranean region. Yes, exactly. Mediterranean diets are going to be helpful as they avoid saturated fats, they are going to be helpful for lipid control. How about this one? No cake or candy or cookies or limited amount. Yes, if you are going to be saying diabetes-based or glucose-controlled diet, you're absolutely correct. All right, how about this one? This one is tough one. High sodium, high protein, high meat diet, high water intake, and moderate yogurt intake. What are we worried about here? What are we preventing? And if you're saying kidney stone prevention, you're absolutely correct. Remember, kidney stone prevention, you are going to have high oxalate diet, moderate calcium intake, and you want to flush those kidneys out with high water intake. All right, what are you preventing with this one? No red meat as well as beer. Very good. You are preventing gout. All right, how about this one? What does grapefruit do to warfarin levels? Excellent. Grapefruit is sip inhibitor, so it can increase the warfarin levels and increase your INR and make you more predisposing to bleeding. All right, how about this one? What reduces uptake of levothyroxine? Good. Any divalent cation. So, for example, taking levothyroxine with milk products that are calcium based, that can reduce the uptake. So, sometimes you want to take levothyroxine on empty stomach. All right, this one. Orange juice has what effect on iron absorption? Orange juice. You got it. It is going to increase your iron absorption. It actually changes the configuration because the orange juice has the vitamin It changes the iron moiety so that then it is better absorbed. All right, everyone. That is the end of our review. I'd recommend you just to stick around for few announcements. After the recording of this session today, will remind you that starting tomorrow and mid-May, USMLE is switching from 40 question blocks to 20 question blocks. And want to emphasize that. The other thing that you're going to see on your USMLE exams is GLPs. And remember, GLPs are exenatide and liraglutide. And what do these do? Well, GLPs are endogenous incretins. So, they increase insulin release. They reduce glucagon release. And they are going to, very importantly, they are going to delay gastric emptying. And so, if you delay gastric emptying, you are full for longer. And if you're full for longer, you don't have lot of caloric needs. Now, when you are thinking of GLP as protein, it is going to be broken down normally. Active GLP gets broken down into inactive GLP by what enzyme? And that is going to be DPP-4. And what DPP-4 does is DPP-4 is going to break down active GLP. So, if you have DPP-4 inhibitor like sitagliptin and saxagliptin, these gliptin medications are going to increase the levels of GLP and then produce the same effects. So, do want to place this pharmacology tie-in at the end of the review as this is such popular medication and they're probably going to test you on it on these licensing exams. So, with that, if you are hungry for more, please do check out my courses. Here it is, hyguru.com. Also, kindly do follow me on Instagram at hyguruprep. Check out my new free 120 with Med School Bro. am going to put the free 120 here as link. And then finally, if you all loved today's session, it will only take just few minutes, but if you loved the delivery and content of today's session, please do write review. My goal is to make sure one lecture at time, one slide at time, one vignette at time, and one student at time, we continue this Hyguru mission of thinking like the test maker. So, more to come with my courses. have courses for both Step 1 and Step 2 CK. They are mapped to these QIDs, which is super helpful for direct application. And before you leave today, please do type in one thing that you learned from today's nutrition webinar, and wish you the absolute best for your Step 1 and Step 2 CK exam. Thank you so much for your attention and will see you in the next webinar.