DIP Episode 113 - Comprehensive USMLE Step 1 GI Review (Part 1)

Okay, good afternoon. My name is Divine. I am a PGOI-1, a transitional year resident that's ultimately going to be transitioning into radiology. This is episode 113 of the Divine Intervention Podcasts. And in this podcast, I am going to begin a comprehensive review series for the USML Step 1 that is targeted specifically towards gastroenterology. Okay, targeted specifically towards gastroenterology. So I will try to use a case to introduce a concept and then I will discuss the basic science details relevant to that concept. And again, I will tell you this. The USML Step 1 is kind of different from Step 2, C, K, and Step 3 because the basic like the needy-gritty basic science details, you do need to know them. There's some things you don't need to know, but I'll say like the great majority in general, you need to know. And the thing is when you actually know those things and understand these basic science details, it just makes it much easier for you to want to see through an NV Me question, answer it correctly. And it also prepares you tremendously for future exams like the 2 CK exam and the Step 3 exam. So let's go ahead and get started. Right?

So what if you get a question about a patient and it can be the pediatric question or an older person question and they tell you that, oh, this person, they've been having like diarrhea for like the last six months and they've been having a lot of like episodes of gastroenteritis and they give you some labs and you notice that this person's potassium is like 2.4. So this patient is hypokylic, right? And then they now tell you that, oh, you perform imaging and you see like a mass in the pancreas. What kind of mass are you thinking about? I hope you're thinking about a vaipuma, okay? Because this person is having diarrhea. So like watery diarrhea, they have hypokylenia and I will discuss how the gastroenteritis relates to the echelohedria in a second, okay? And again, remember, they can also give you another question about a GI mass that's kind of like relating to a person that has a history of like MEN1, right? And they tell you that this person has like general ulcers. If you ever see that having ulcers in the genomics like pathonomonic fozzolanger, elicin syndrome with a gastronoma, okay? So we'll talk about those things. So really in view of these, I mean, you kind of see that I want to talk about the GI, like the different chemicals and hormones that you find in the GI tract, right? So the thing is the big, big one first of is gastric, right? We know that gastric, it's ultimate job is to increase the secretion of gastric acid.

And that thing it also does is it actually makes the gastric meocosa grow, right? And it sort of makes things flocks faster through the stomach. And the thing is gastrin accomplishes this aim by doing multiple things, right? So for example, it can act on CCKB receptors that you find on the surfaces of parietal cells, right? But actually on those CCKB receptors, you essentially promotes the secretion of a gastric acid. Another thing in fact, I will say that and this is actually how you'll know that this is the major pathway that the, that gastrin uses to make gastric acid. It talks to the endotherochromophine like cells, the ECL cells, they make histamine and then when they make histamine, that histamine acts on H2 receptors, okay? So that histamine acts on H2 receptors. And then when you act on H2 receptors on the surface of parietal cells, you promote the release of acid, okay? And remember that this gastrin, right? It comes from like G cells that you find in the antrim of the stomach. And the thing is, right, think about it. Anything that puts, it basically puts food in the stomach will make you secret more gastrin, right? So let's say there's like protein in the stomach or the stomach distant, remember the stomach would distant if there's food in it, right? That would again make you secret gastrin. But under like thin that they love to test on the USML Es that release to gastrin secretion is your parasympathetic nervous system, right?

So for example, the thing is your parasympathetic nervous system. So this will be an example of some kind of like neurocrain secretion, right? Your parasympathetic nervous system will secretacidol cooling. That acidol cooling can directly act on the parietal cells through like the mosquito M3 receptors and that makes you secret acid. But your parasympathetic system also releases something called gastrin-releasing peptide. GRP will act on G cells in the antrim of the stomach, the meat gastrin and then that gastrin does all those things I mentioned to increase the release of acid, right? So you can already see that if a person takes acropin, remember acropin is a most grainy receptor antagonist. It would not necessarily, I mean it would decrease the release of acid in the stomach but it's not going to completely cut off the release of acid in the stomach. Because yes, acropin will work on the most grainy chem through receptors, they will block those receptors under surfaces of parietal cells, but it does absolutely nothing to a gastrin-releasing peptide acting on the surface of G cells that we find in the antrim of the stomach. So those are kind of like the big things you want to keep at the back of your mind. And then there are some things that can make you not release gastrin, right? So one is like somatosetatin. I mean you already know somatosetatin, somatosetatin basically decreases the release of everything in the GI tract. And then also don't forget secretin.

Secretin is something that's released by some cells in the guardnum, I'll talk about that in a bit. But basically by having a lot of secretin on board, that also decreases the release of gastric acid. Because I sort of think of secretin as saying that, okay, duardnum, you're dealing with too much acid, let's sort of try to stem the tide. So secretin shuts down a gastric acid secretion. Another thing that also shuts down gastric acid secretion is visoactive intestinal peptide. That's why if a person has a viperma where they're secreting a crap ton of VIP, VIP, right? Remember, it's normal to decrease gastric acid secretion. That is why those patients tend to have echlohedria because they are just not making gastric acid. That is why echlohedria is part of the triad of the WDHA syndrome. And the thing is if you are not making gastric acid, guess what happens? Bacteria are more likely to overgrow in your GI tract because that, I say, takes care of a lot of them. So if you have bacterial overgrowth, that can increase your risk of gastroenteritis, okay? So that's one of those weird things you kind of want to keep at the back of your mind. And again, remember, I already talked about how Zollinjale since syndrome is actually not like ME and type 1. Remember parapanthit, right? So the parapyroid problems, mostly parathyroid hyperplision, or the adenoma, and then they get pancreatic problems, right? Like the pancreatic neuroendocrine tumors, like the gastronoma, right?

And then the thing is if a person has like atrophy gastritis, right? Where they have autoimmune antibodies being made against like the parietal cell or parietal cell components, then you're not making acid. So that acid, as it's not being secretated into the stomach, there's no negative feedback that tells your body's like, you know what, maybe you should stop the secretion of gastrin, right? So if you destroy parietal cells and their components or their products, there's no acidity in the stomach. So the pH in the stomach never drops. If it doesn't drop, you will keep secreting gastrin, okay? That's why gastric hypertrophies, actually something that accompanies chronic autoimmune gastritis, because again, you're secretive and autonogastrin because there's no negative feedback. And one of the things gastrin does is to build up the gastric mucosa. And another thing that can also cause elevated levels of gastrin on an MBME is if a person is taking a PPI. Remember, PPI's, right? The inhibit that hydrogen potassium antiporter that you find on the surfaces of parietal cells. Remember, that antiporter, remember, it gets one potassium into the cell and then in exchange hydrogen ions come out. You may say divine, why does that thing use ATP? Use this ATP because potassium is primarily an intracellular iron, right?

So because it's primarily an intracellular iron, if you, if you want to get it into the cell, you're basically getting it into the cell against this concentration ingredient. So that's an example of like you, that thing comes in what again, to sort of maintain an electron neutrality as you're bringing a positive charge into the cell, you want to bring a positive charge out, right? So that's how hydrogen ion comes out and then chloride sort of pairs up with it and then you'll secret a gastric acid that way. So that's all I think I'm going to say about gastrin. Again, somatosatin, the big big thing you want to know about somatosatin basically shuts down the release of pretty much every gastric hormone. That's why again, you use it to treat many things, right? So like you can use it to treat insulinomas, you can use it to treat carcinoid syndrome, or you have a tumor that's making serotonin, you can use it to treat a vipoma, right? Because it actually decreases the release of visoactive intestinal peptide, you can use it to treat certain pituitary tumors, right? So like acromegaly, so you have like a growth hormone secretion tumor, you can actually treat those with a somatosatin or somatosatin analog like octriotite, right? And then don't forget that in the acute phase, very high you to know this, in the acute phase of a varicil bleed, you can actually treat that acute phase by giving an octriotite, again, which is a somatosatin analog.

But if you chronically want to treat a person that is high risk for having a varicil bleed, you can give them a nonselective bit of blocker like proprenolone, and you can also give them an outdo-strone receptor antagonist like sperinolactone, and remember that your somatosatin, right, is made, it's made in multiple parts of the body, right? You can make it like in Bintesanum, you can make it actually in the pancreatic eyelets, right? So like there's like decals in the pancreatic eyelets, there are actually some cells in the hypothalamus that actually also make a somatosatin. So again, remember, somatosatin basically shots, if you're blank out somatosatin, basically, shots down the secretion of many things, gastric acid, visoactive intestinal peptide, just many, many things, okay? So that's kind of like the big thing, you want to keep at the back of your mind. Now, let's jump to the next thing, right? So I already sort of talked about how secretion, right, is used to decrease, secreting decreases like gastric acid as secretion. The thing is, the easy way to remember the functions of secretion is I think of secretion as something that helps you deal with an acid problem. Okay, if you remember that one concept, many of the actions of secretion begin to make sense. Think of secretion as the agent that helps you deal with your acid problem, right?

So you can do that by again, decreasing the secretion of gastric acid, you can do that by making your pancreas make more bicarb, right? Because bicarb will neutralize the acid, right? So those are kind of things you want to keep at the back of your mind with a secretion, although secretion technically also makes you essentially don't mobile into the doggone. And remember that secretion is made by S cells, remember the S in secretion for the S cells in the doggone. So secretion made by the S cells, they basically, you release the secretion from these S cells and you accomplish all these things. And again, one of the most powerful stimulants for you to release secretion is you see acid in the doggone, your doggone starts freaking out, right? flips out your S cells begin to make that secretion to deal with that acid problem. Also, if you also put fatty acids in the lumen of the doggone, that also increases the production of secretion. And again, that should make sense, right? Because if you put more fatty acids in the doggone, your body is like, okay, I need some bile. And I just told you that one of the actions of secretion is to produce, is to make your goal, essentially make you secret mobile from the gall bladder. Okay? So again, that's one of those weird things you want to keep at the back of your mind for tests. And then let's talk about this other hormone, colicisto-kining, right? So, colicisto-kining, right? So C-C-K. So, colic, colic, right, means gall bladder.

Cisto-kining makes things that come from your coli, your gall bladder move along, right? So, colicisto-kining, just think of it as something that promotes the gall bladder's job, right? So it makes the gall bladder contract better. It makes your sphincter of ody relax, because if that, if that relaxes, right? You'll be able to put more bile into the doggone, right? And the thing is colicisto-kining as well, right? Kind of like secretion. It makes your pancreas shoot out more stuff, right? And again, the thing is your doggone can only deal with so much at a time. So colicisto-kining also decreases gastric emptying. So that wants you to like deal with digestion in a more control process, right? Like, you get a small amount of fat, you digest it, and then you get the next bolosa fat, right? So if you're sort of getting like fat overload from the stomach, your, your body is like, okay, let's make more, let's make more CCK. If you make more CCK, guess what happens? You decrease the, you basically slow down a gastric emptying, and CCK is made again by cells in the doggone, right? Like your eye cells in the doggone, and again, if you put fatty acids in the doggone, that will make you secret more CCK. Okay? Because again, CCK helps you secret more bowel from the gobladder, which helps you deal with your fat problem. And again, I told you that CCK also increases the release of pancreatic like secretions. Remember, your pancreatic enzymes include a lot of proteases, right?

So amino acids in the doggone also stimulates the release of CCK. Now, let me sort of take, I guess, a more measured look at, at the different mechanisms behind acyssecretion, right? Because this is kind of something you want to be able to understand, for exams. So I told you that gastrin is made by G cells in the pancreas, right? I mean, sorry, not in the pancreas, in the, in the, in the, and trim of the stomach, and that gastrin acts on, can act on CCKB receptors on the surface of parietal cells, so that you make more acid or through the major pathway can act on gastrin receptors on the surfaces of enterochromophine like cells, and then those secret histamine that acts on H2 receptors, that it makes you secret acid from the parietal cells. The thing is gastrin works through an endocrine pathway to make you secret more acid. That's like that boss phrase endocrine pathway is something you want to remember. Contrast that with gastrin-releasing peptide that comes from a parasympathetic system, to make you secret more acid. Remember, gastrin-releasing peptide can act on GRP receptors on the, on the G cells that you find in the atrium of the stomach, so you make more gastrin, right? But also remember that acetylcholine from your parasympathetic system will act on most chrannic receptors, most chrannic M3 receptors, on the surfaces of your parietal cells, and again, that makes you secret more acid. So that's a neurocreen mechanism, so neurocreen mechanism of acid secretion.

But remember that your enterochromophine like cells, you'll find them in the stomach, they are in very close proximity to the parietal cells that you find in the stomach. So the thing is, your enterochromophine like cells secreting histamine to act on H2 receptors that we find on the parietal cells is an example of paracrine secretion. Again, you may say, oh, define, this is so loyal. I promise you, none of this stuff I just mentioned is loyal by any stretch for the USM Li step one exam. So that's something you absolutely positively want to make sure you know. So that's all I'm going to say about kind of like those of three pathways, right? So histamine again, from ECL cells acts on the histamine H2 receptors that you'll find on the surfaces of parietal cells. And that makes you secret more gastric acid. And I said that again, those ECL cells, they can be stimulated by gastric, okay? To make, to squared out more histamine, they can actually also be stimulated by acetylcholine through your parasympathetic system. They're actually most chrannic receptors on the surfaces of your ECL cells. So if acetylcholine activates those most chrannic receptors, that also makes you squared out more histamine. And then that histamine acts on histamine receptors on the surfaces of parietal cells. And then a band, you make more gastric acid. And then already talked about a VIP, right? So visoactive intestinal peptide, the thing is a VIP again, it does a bunch of things, right?

So I said that it decreases the secretion of gastric acid. That's why you'll find acylhedria as a portion of a viperma, like the WDH syndrome. The water diria basically occurs because visoactive intestinal peptide increases like your intestinal secretions. It also increases your pancreatic secretions. And those things are very osmotically active. So when those things make their way into the lumen of your digestive tract, that attracts water alongside. And if you have more water, guess what happens? You poop and poop and poop a lot, right? A lot of water diria. And one thing is, let me go ahead and mention, let me introduce this concept because it will help you understand why hypochylemia is a finding in a viperma, right? So in a WDH syndrome. The thing is out those tyrone, in fact, let me put it, let me introduce it this way. If you remember from the renal reviews, right? So there are never reviews that I have earlier on this one on the website. I talked about how the principal cell has an innec channel, right? And then the principal cell also has potassium channels on its surface. And the thing is that innec channel helps you reabsorb sodium, right, in the collecting duct of the nephrine, right? But at that potassium channel that you find on the principal cell, you don't potassium into the urine. So basically that innec channel helps you reabsorb sodium, right?

And also in the potassium channel that is in close proximity on the surface of your principal cell, of your collecting duct, you dump potassium, you basically waste potassium in the urine, right? And the thing is, those two transporters, right, they are kind of like activated by outdoster. So whenever you have high levels of outdoster, you reabsorb more sodium in the principal cell, you waste more potassium in the principles into the like the lumen of the nephrine, right? So you peel out potassiums, so you become hypochilimic, right? So a lot of outdoster on board makes those, makes your reabsorb sodium and waste potassium. But one other thing I will go ahead and mention, right, is that whenever you have fast flow through the lumen of your nephrine, it's like that fast flow sort of like pools potassium. And that basically, I sort of think of like you have this potassium rock at the principle cell of your collecting duct. Whenever you have fast flow across the principle cell of your collecting duct, that washes away potassium and the person again becomes hypochilimic. So that is why you see, right, many of these diuretics cause hypochilimia because they make your volume down, the activity urine and retention outdoster system. So you have a ton, like you essentially have like a hypochilimia and then you basically activate those mechanisms I've just described and you get a hypochilimia.

So the thing is, essentially, translate that knowledge about principle cells of the collecting duct to your colon, your large bowel, right? Your large intestine. The thing is your large intestine has many transporters kind of like inek channels that help your reabsorb sodium. But it also actually has a lot of potassium channels that basically waste potassium in the lumen of the colon, okay? And actually those transporters and channels guess what? They are all responsive to our dust urn. But remember this fast flow thing I just described about the lumen of the nephron? That fast flow business also actually happens in the colon. Whenever you have fast flow through the colon, that washes away more potassium and the person becomes hypochilimic. So if a person has a viper where they have a lot of watered diarrhea because they are increasing the secretions of osmoticly active stuff from the pancreas and from the small intestine, right? Especially like small intestine, think about like the doodnam with those with those are crypts of lubricant, right? So you make a ton of like secretions, those raw water, you have watered diarrhea. That water that's making its way to the colon, guess what happens? That flushes potassium through your colon and you basically become hypochilimic. So that explains why you get the watered diarrhea, the hypochilimia and the echlohedria in a person that has viperm again. Viperm is also known as the dub is basically code word for the WDHA syndrome.

And remember a viperm can be found in the setting of an MEN1 syndrome. Now the next thing I'll talk about is this thing known as a GIP, right? So like the gastric inhibitorin, inhibitory peptide. So people call it like the glucose dependent insulinotropic peptide. And the reason people call it this is pretty much what it does is if you consume glucose early, right? Your K cells that you find in the doodnam of your small intestine, you can also kind of find some in the genome, but that's lower you would think more about the doodnam with your K cells. Your K cells in the doodnam when the Cian-oral glucose load, they begin to make a ton of GIP. And the thing is GIP, guess what? It actually it's almost like it promotes the release of insulin from the beta cells in the pancreatic eyelets of long hands, right? So this is why your insulin levels tend to rise a lot more when you take glucose early versus when you take glucose IV, okay? Because again, yes, if you take IV glucose, your pancreatic eyelets cells will make a ton of insulin, but you make a lot more insulin because your GIP cells effectively tell, I mean your K cells in your doodnam make more GIP. So and that GIP goes to the pancreatic eyelets beta cells and says make a ton of insulin, okay? So an Oro glucose load raises the secretion of insulin a lot more than an IV glucose load. That is a very high-yout concept you want to know for the USMLE exams.

And don't forget that there are drugs that are GIP, like essentially like GIP analogs, right? Drugs like Exenatide and Lira Glutide, those are drugs that are used to treat treat diabetes, right? Remember those drugs are contraindicated in people that have a histro-metallery thyroid cancer and also those drugs are associated with pancreatitis. And remember that you can also boost your levels because there is this enzyme that breaks down GIP, or like another name for GIP is like GIP one, right? So there is an enzyme that breaks down GIP, it's known as DPP-4, dipeptidol, peptidase-4. The thing is if you inhibit DPP-4, your levels of GIP, GIP-1 will increase, right? And again you will produce more insulin. So that can sort of help you in the person that has diabetes. So there are DPP-4 inhibitors, your glyptin drops, like your glyptin drops, like alo-glyptin, lina-glyptin, sacsaglyptin, cedar-glyptin, those drugs in HIP-DPP-4 and those boost your levels of GIP-1 or again you can also call it GIP. So those are high-yout things you want to keep at the back of your mind for tests, right? And then don't forget this hormone motylene. Remember motylene basically just promotes flocks through your through your GI tract. Remember if a person has a diabetic gastro-parasis you can actually give a very thromising for those purposes because remember a very thromising in addition to being a macrolid, right? So it's like a bacterostatic 50s inhibitor.

It also has agonist activity on motylene receptors. In fact that explains why diarrhea is a classic side effect in a patient that's taking a macrolid because macrolid is like a re-thromising for example, have agonist activity on motylene receptors and motylene promotes movement through your GI tract. Now I want to also sort of talk about concept, right? About like let's say some more things about this hormone. So GIP-1, right? So GIP-1, right? So I said that GIP-1 promotes the release of insulin, right? The thing is GIP-1 actually suppresses appetite, right? GIP-1 is kind of like leptin. GIP-1 actually suppresses appetite. So you mean see? Hmm, divine. Why does that make any sense? Well, I mean why is that important to know? Let's put it that way. Why is that important to know? The reason is important to know is right. If you remember with your diabetes drugs, if you start again for as young people listen to this podcast and starting for step one, if you remember your diabetes drugs, remember that diabetes, right? Some of the drugs for diabetes like you're met forming a weak neutral, drugs like your sulfonial ureas, right? So like your clopropomide, your gliburite, glipeside, and then drugs like your phyazolydine dions, like rosy gliderzone, pyoglyderson, those drugs are all associated with gain, right? Your GIP-1 agonist actually has a weak loss. So you can already think about a potential mechanism behind the weak loss that is associated with taking a GIP-1 agonist, right?

If you sort of think about it, your drugs like your drugs like exenatide and lera glutide, those are those are again, essentially acting like GIP. And when they act like when they act like GIP, they suppress your appetite. So if they suppress your appetite, you probably will not have this big inclination to eat. And if you don't have this big inclination to eat, you could potentially lose weight. So believe it or not, lera glutide, if I'm not mistaken, has actually been approved by the FDA for the treatment or for actually for weak loss, okay, for weak loss. So that's one thing you kind of want to keep at the back of your mind again. I know this podcast is probably taken a while and maybe I wouldn't be able to cover as much as I want for this first GIP podcast. And again, I will make and I'm going to be on relenting this month in making a podcast. But I can tell you that again, if you sort of have like a mechanistic basis for something, it's a lot easier to remember, okay? So remember leptin and GIP-1, your GIP-1 agents, the actually suppressor appetite. Contrast this with like grilling, right? Grilling actually makes you hungry, right? So it actually stimulates your appetite. And then the last thing I will go ahead and mention here is this whole concept of actually there are two last things I want to mention, right? So the thing is I told you that your parietal cells, they make hydrogen ions, right? So that you can basically make a gastric acid.

One thing you sort of kind of want to remember is that remember the primary enzyme in the body that helps you make hydrogen ions is carbonic and hydrates, right? Carbonic and hydrates. The thing is carbonic and hydrates, if you sort of think back to the renal again, the renal review video slash podcast that I have, carbonic and hydrates it makes, as it makes hydrogen ions to go off on one side of a cell, it makes by carb go off on the other side of the cell. But again, you kind of want to think about this whole principle of electronic neutrality, right? If you get a positive charging to a cell, you try to get a positive charge out to maintain electrical balance or if you get a negative charging to a cell, you send a negative charge out again to maintain a electrolyte balance, right? So I mean, electronic neutrality. So the thing is the parietal cell, through that hydrogen potassium ATP is pump, it brings potassium into the cell against its radion, that's why it needs ATP in the first place. To maintain electronic neutrality sends hydrogen ions in the reverse direction, right? But remember, carbonic and hydrates also make that by carb. That by carb finds this way out through the basal lateral side of the parietal cell, okay? But again, as you're sending that by carb out, chloride has to come, like a negative charge has to come into counterbalance so chloride comes in, okay?

So the thing is, think about it if you're dumping as you're secreting gastric acid, you're dumping by carb into your blood, right? So that's the, that's the mechanism behind the alkaline tide that's associated with, that is associated with digestion. So in general, your blood pH rises when you're digesting food, okay? Because of that alkaline tide. And then don't forget opioids, right? They also kind of have like multiple effects on your GI tract, right? So your opioids, remember, there are two kinds of smooth muscle in your GI tract. We have like the circular smooth muscle and then we have the longitudinal smooth muscle. The thing is, if you want to sort of mix food in your GI tract, your circular smooth muscle helps with that. If you want to propel food through your GI tract, your longitudinal smooth muscle helps with that. So the thing is that circular smooth muscle can actually be activated by opioids, right? By opioids. And that longitudinal smooth muscle is actually inhibited by opioids. So you can see that by inhibiting the longitudinal smooth muscle in your GI tract, things are not moving. Parastosis is basically not happening. That's the that's essentially explains how opioids like lopera mitre, right?

Immodium that people buy in stores all the time actually can treat diarrhea because it basically makes parastosis not happen, but if you're activating those circular smooth muscles, you can see that you're like turning, turning, turning, turning, turning, turning things in the GI tract. That's potentially how like the stomach cramps and like the constipation, sort of companies are pressing that sort of takes in opioids, right? So, and remember the way you can sort of treat the constipation associated with opioids is you can give something that makes your GI tract go. Remember, your parastosis pathetic system makes your GI tract go. So that's why you could give a drug like a Bethany call, which is a most chronic receptor agonist, or Nio-Stigmin, which is an acetylcholine estriase inhibitor that would essentially by inhibiting acetylcholine estriase boosts your levels of acetylcholine, again, Mico-Gi-Tract-Gone. Okay? So those are things you kind of want to keep at the back of your mind. And again, remember, I've probably repeated this in like five or six podcasts, but it bears more repetition. Remember, it's very high up to know you endogenous opiões and the opioid receptors, the actone, right? So remember, like your betaendorphine acts on new receptors. Okay? Remember your, you end kephaly, acts on delta receptors, delta opioid receptors, and then remember that your dinorphine acts on copper receptors. Okay?

Those are again, all high yield things you kind of want to keep at the back of your mind. Okay. So I think that's all I'm going to say about these GI tract hormones. And let's see, let me just think of something else that's sure that I can discuss. And then I'll round up this podcast. But again, the thing is, again, I know you're like, you're like, you're divine. This podcast is super, super, super annoying. I promise you, if you understand this basic, then like this, like sort of like basic podcast, you'll make it a lot easier, a lot, lot, lot, lot easier for you to remember things down the line, especially as they begin to talk about a different GI pathologies. I mean, you can see I've talked about the hormones, but you've also seen, I've also spent a lot of time like integrating other pathologies along the way. Okay? So again, kind of how you to understand these things, right? So let's assume you consume, actually, let me ask you this question, right? So if a person has pancreatitis, right? Classically, if a person has pancreatitis, what are the two things that I elevated in there? Like you measure the markers and they're elevated. It's your what? Your amylase, right? And your lipis. Now between those two, which is more sensitive for pancreatitis, that's actually lipis, right? In fact, in general, I mean, as an intern, taking care of patients with pancreatitis, I never checked amylase. Lipis is the high you thing you want to check right?

Because again, amylase can rise or can increase from many things. If you're vomiting, your amylase will be up. If you have pancreatitis, your amylase will be up, right? So amylase, it's not because you can get it from so many parts of the body. It's not exactly specific for pancreatitis, okay? So that's something you want to keep at the back of your mind versus lipis. That's a little more specific for pancreatitis at least compared with amylase. So the thing is, why is amylase important, right? If you go to McDonald's and buy a burger, right? All those carbs, right? Their digestion is sort of kickstarted with a salivary amylase, right? So salivary amylase sort of breaks down some of those bonds that you find in carbs, right? They break down like those alpha-14 linkages. Remember, I talked about the alpha-14 linkages and the alpha-16 linkages in the biochem video, okay? That's something you definitely want to know for the USM Lase, right? So salivary amylase breaks down the alpha-14 linkages. And then remember, your pancreas also makes alpha amylase, right? So that alpha amylase, and also again, breaks down alpha-14 linkages that you find in your carbs. But the thing is, when you break down carbs, you break, break, break, break, break, break, break, break them. You break them down to like, dipeptides, okay? So the thing is, you need a dip, like a dysacharides, right?

So essentially, break down, to break down these dysacharides to, sorry, I don't know if I think I may have said a dipeptides. Dysacharides. So you need a dysacharides to break down the dysacharides to mono-sacharides. And when do you find those dysacharides? Is, guess what? You'll find them on the surface of your small intestine. You find them on the V-line or the micro-V-line of your small intestine, okay? So for example, if you want to break down more tools, you use more teas for that. If you want to break down sugars, you use sucrose for that. If you want to break down lactose, right? The combination of glucose and the lactose. You use lactose for that. So you can already see that again, you break down this dysacharides to a mono-sacharides with these enzymes. Now, what are some high-yield integrations you want to keep at the back of your mind here? The thing is, if you remember, right? If a person has a lot of like bloating and they have a lot of diarrhea and is temporarily associated to the consumption of food, you can already begin to think of a person having some kind of brush-border issue, like a lactase deficiency, right? Lactase deficiency is the mechanism behind lactose intolerance, right? Another one you may also see on MBM Es, right? If a person has like gastroenteritis and they denote the surface of their, essentially denote the microv-light that you find on the surfaces of their small intestinal mucosa, right?

Those people can also have a malabsorption for those reasons. And remember, right? One of the reasons people get malabsorption in celiac diseases, guess what? They nuke those, they're like their v-light. Remember one boss phrase that you find on histology in a person that has celiac diseases, virus atrophy? If your villia are not there, your dysaccharides are not there, so you also have malabsorption for those reasons, right? And the thing is, right, those monosaccharides, after you've found them on the surfaces of your of your GI mucosa, remember that those monosaccharides you use kind of like something called facilitated diffusion to get them into the lumen of the interracite. So like into the intercellular space of the interracite, you use facilitated diffusion, and you use more of your sodium glucose and linked transporters. If you want to be a little more specific, you use your SGLT1 transporters, your sodium glucose linked transporters, one transporters, okay? So remember sodium is primary and extracellular iron, right? So sodium flows down its gradient into the cell, right? And then by doing that, you basically pump glucose, your monosaccharides into the intracellular environment of the interracite. This is literally an example of secondary active.

This is basically an example of almost like a secondary active transporter, because we essentially move in your glucose, because glucose is actually in pretty high concentrations inside the interracite, so you're moving it against this concentration gradient into the interracite, so I think I may have me spoke. I mean, it's a facilitated process, right? Because it's a transporter that's helping you make that happen, but it's actually like a secondary active transport process, but you're using the gradient energy of sodium, flowing down its gradient into the interracite, okay? Remember, SGLT1 transporters, you'll find them in your GI mucosa, SGLT2 transporters, you'll find them in the proximal convoluted tubio. Remember those SGLT2 transporters are blocked by your SGLT2 inhibitors, like canagly flows in, the pagly flows in and pagly flows in, and those are used in the treatment of diabetes, because you essentially stop reabsorbing glucose in your urine, right? So I mean, in your kidneys, so you basically pee out glucose, although that glucose will increase your risk of having a UT Is. And then, the thing is, once the glucose are sort of going into entherocytes, the thing that then happens next is that through a facilitated diffusion, right?

Because remember, glucose is very high in tracelularly in those entherocytes, so it can just literally flow down its gradient out of the entherocytes to the basalateral surface, and then essentially gets transmitted to like your bloodstream, and your portal vein, and all that stuff. And the thing is, it's your Glute 2 trans, your Glute 2 transporter that makes that happen. Remember, Glute 2, Glute 2 usually is is a bi-directional, let's things come either into a cell or out of a cell, but the thing is the Glute 2 transporters that you actually find on the basal surface of your entherocytes, they actually glutes to kind of like unipoder, so it allows things to only flow in one direction. Down the concentration gradient from the high concentration, you find inside your entherocytes to the low concentration, you find outside your entherocytes, okay? But remember, I said that all like your glucose, your galactose, all that stuff, they come in through the SGLT1 transporters on the apical surface of your entherocytes. Your fructose is actually different, fructose comes in through a Glute 5 transporter on the apical surface, but once it gets into the entherocytes, fructose uses the same Glute 2 transporters to leave the basal lateral surface of the entherocytes to get into again like your portal vein, your bloodstream and whatnot.

So again, your Glute 5 transporters, it's kind of high to remember that you find them on the apical surfaces of your entherocytes, you also find them on spermato sites. Remember, spermato sites use fructose as the primary source of energy. And then the last thing I will say is again, if your your entherocytes, right? So your your your Vili on the surface of the entherocytes are not working, you have an abnormal DZILOS test, right? An abnormal DZILOS test. So if you ever see like an abnormal DZILOS test on your USMLE exams, think about a problem at the level of the microvili, okay? Because you need an intact intestinal brush motor to be able to absorb DZILOS across the surface of your entherocytes. So if your microvili is all screwed up, guess what? You will not be able to reabsorb that DZILOS, okay? So you have an abnormal DZILOS test. So again, I know you may say, oh, divine, this is why again, I'm sort of taking my time with GI because GI is a big, I mean, GI is what? It's maybe like 5% of the first day, first step one book. So I'm sort of taking my time here because I want to make sure that you have a very sound solid basis for understanding GI. And as I also, as I always say at the end of every podcast, I'd offer one on one tutoring for the USMLE Step 1, 2 CK, 2 CS and Step 3 exams, and then like pre-clinical medical exams, 30-ish off exams.

And then if you have a college mate that's studying for like biochemistry and college of physiology or OEM, Gen CAM, physics, histology, I do offer tutoring for all those things. And then if you're a med student applying to residency so like an ERAS application or a college student applying to med school, so I'm a gas application, I'd offer like one on one consulting for those so like interview prep, personal statement writing, application prep, all that stuff. I mean, I've been on the admissions committee of a top two med school for about a year. So I've see through like thousands of applications, high quality applications, and I can basically essentially prepare you really well to have your best foot forward if you're applying for any of these things. And again, pretty much everyone I've worked with matched into like their residency of choice. Most people, they have first choice. So take that for what you will. So as I round up, I really hope that the Raptors win at the Oracle Arena today. And we can finally put this MBC's into rest and I'm really, really praying hard that Anthony Davis gets treated to the leakers because I am a LeBron fan so I want to see him succeed. So I'll see you in the next podcast which will be coming relatively shortly. So have a wonderful rest of your day and God bless you. Thank you.

Gastrin (acting indirectly through histamine).

Cholecystokinin ($\text{CCK}$).

WDHA syndrome (Watery Diarrhea, Hypochyloremia, Achlorea).

$\text{SGLT1}$ ($\text{Na}^+$-glucose linked transporter).

Opioids activate circular muscle (peristalsis) but inhibit longitudinal muscle. Their anti-diarrheal effect is due to reducing motility/propulsion.

Dipeptidyl peptidase-4 ($\text{DPP-4}$). Inhibitors are called gliptins (e.g., sitagliptin).

Aldosterone increases $\text{Na}^+$ reabsorption via E NaC, creating a negative electrical gradient that drives increased $\text{K}^+$ secretion into the lumen.

Secretin and Vasoactive Intestinal Peptide ($\text{VIP}$).

Oral glucose stimulates a much higher insulin response because it triggers $\text{GIP}$ release from intestinal K cells.

$\text{GLUT2}$ (on the basolateral membrane).

Suppressing appetite (it acts similarly to leptin).

Longitudinal smooth muscle.

Aldosterone increases $\text{Na}^+$ reabsorption via E NaC, creating a negative electrical gradient that drives increased $\text{K}^+$ secretion into the lumen.

Secretin and Vasoactive Intestinal Peptide ($\text{VIP}$).

Oral glucose stimulates a much higher insulin response because it triggers $\text{GIP}$ release from intestinal K cells.

$\text{GLUT2}$ (on the basolateral membrane).

Suppressing appetite (it acts similarly to leptin).

Longitudinal smooth muscle.