Digestive System Mod 8 Video 2

Well, welcome back. Here we are in the second hour of the digestive system. Here we are at the stomach. We've moved through some general concepts. We've passed the oral cavity down through the esophagus. As we pick up with this diagram right here is where your lower esophageal sphincter will be. That physiological sphincter there that keeps the... bottom end of the esophagus closed unless some food bolus or liquid is coming down the esophagus to enter the stomach all right so when we take a look at the stomach here there's some general general anatomy this is stuff you probably picked up the vocabulary in the lecture lab i mean so we have the the outer curvature here they call it the greater curvature inside we have the lesser curvature We have the layers here. We have a serosa. We have the muscularis externa. We have the mucosa on the inside. Here in the GI tract is the one exception to the muscularis externa having two layers. We learned that there's an outer longitudinal layer and an inner circular layer. With the stomach alone, out of all the tract, there's a third layer, and that's the oblique. muscle layer. You only find it in the stomach. The stomach is a great big old bag of muscle, and its sole job physically is to take the food that you have ingested and mushing it down into the consistency of toothpaste. Now, there's chemical processes that are helping this, but really, it's far more of a physical squeeze bag than most people give it credit for. It's also terrifically extensible. It can expand greatly from its smallest size to its larger size. That's these rugae here. The rugae are these expansion folds on the inside. So an empty stomach is quite small. A full stomach can be quite large. All right, from functioning here, let's start at the top with the esophagus and the esophageal opening. We have... the cardia region here and I'll draw some little dotted lines here like that. So here's that cardia region and that's really a physiological region where the mucosal lining in this area, their secretions of the glands contain a high concentration of sodium bicarbonate secreting gland. cells. And this creates a little cloud, so to speak, of sodium bicarbonate around the opening of the esophagus. And what happens is every time the esophagus opens and closes, there's the chance here for acid to reflux back up into the esophagus. And so there's a a chemical buffering cloud there of bicarbonate ion that's meant to kind of neutralize that acid as it sneaks up past the sphincter region and into the esophagus right let me get rid of this here okay so uh there's your there's your cardia all right um You talk about the fundus up here, here's the fundus region. I can kind of make a little dotted line like that. So here's the fundus. That just represents this portion of the stomach that is at or superior to the opening of the esophagus. So all of this is all fundus. Anatomically, that's an interesting term. From the Latin, fundus means the bottom of something. But in anatomy, it indicates the portion of an organ that's farthest away from its opening. So if you know anything about the fundus of the uterus, you know that that is the portion of the uterus that is farthest away from the cervix. And you're thinking, hey, wait a minute, the fundus of the stomach is about as close as it gets to the esophagus. How can it be the farthest away? Well... see the issue is in anatomy they're considering a pyloric opening into the duodenum to be the opening and so the fundus is the point farthest away. from the pyloric opening uh anatomy wise the the other thing i want to do is kind of draw a line here and on one side here we have the pylorus here all right or sometimes you'll hear called the pyloric stomach or the pylorus and up here we have the body of the stomach It's all one big sack, but physiologically there's going to be different processes happening in the body than in the pylorus. And we'll talk about that in a slide or two here in a few minutes. All right, well, here we are. Let's take a look at a close-up of the stomach lining. And what I want to do here is kind of zoom in on this diagram. here so we take a look at the top part first all right what do we have here this is the the lumen up here right the oh let me get my pen activated here so there's the lumen right the food's out here food is here hey um so the the stomach lining here uh is lined i guess with gastric pits. So they're showing, let me try my little highlighter here, gastric pits. And so look what's going on here. The lining of the stomach has these folds that come up and around and down and up and down and up, much like the gyrus and sulcus pattern on the surface of the cerebral cortex. right so we have these folds of of tissue up and down and where they go down in that creates these pits and what we want to do is we want to understand the difference in vocabulary between a gastric pit and a gastric gland okay so up here like this region here i'll do it on one of these side ones right So everything I've outlined in black there, I'll do this one over here, right? Those are the gastric pits. Well, what's going on there? Take a look at these cells, right? And I'll kind of color them in green. There's one, there's one, there's one. You look at these cells. These are the simple columnar cells of the mucosal epithelium. And so these cells are no different from any other. They're just kind of the working stiffs on the surface of the epithelium, okay? And they've color-coded these pink. I'm coloring them in green, but on the diagram, they're pink, right? And you watch these, and these go all the way down until you get to a different kind of cell. See on the diagram here, they've turned blue now. All right. So these blue cells have a different job than the green cells. The green cells are just the outer stomach lining, just the standard stomach epithelial lining. Once you get down into here, into the blue cells, now you're in the glands. So there's a gastric gland here. The blue cells are the start of the gland. So we have gastric glands, and then we have pyloric glands. So gastric glands, these are in the body of the stomach. Pyloric glands are in the pylorus of the stomach. So we said it's all one bag of muscle, but physiologically, you've got different things going on in the body versus the pylorus, right? So this diagram will get to some of that. So you have the... The gastric pits, these are where the invaginations of the gastric surface go down. And where you end, where your normal everyday epithelial cells end, that begins the gland. And then once you're in a gland, whether it's gastric or pyloric, the first set of cells lining this are going to be mucus cells. So let's go here. they call them mucus neck cells all right and so you can see here right and they're just what they sound like mucus cells their sole job is to produce a lot of mucus And this mucus here flows outward. So the mucus is produced down in the gland itself and comes out through the pits. And it's constantly being extruded out through the pits. So that your stomach lining is, the lumen of the stomach is lined with a thick layer of mucus. And that protects the stomach wall. from some of the fairly nasty chemical reactions that are going to be occurring there. You'll notice here in the gastric glands, like the mucous neck cells, are a very discrete portion of the gland, the first portion here. If you come over to pyloric glands, you'll notice that the mucous cells are prevalent throughout the entire gland structure. So that might give you a hint about... pyloric gland function there. What else we got here? Just down here real quick, there's a lymphatic nodule. When you see lymphatic, something to do with the lymph system, there's lymph vessels, and then these lymphatic nodules, these are immune structures. Remember, everything you eat is covered with tons of bacteria, and some of them are nasty, and some of them are going to try to invade your body. And so all layers, you know, all points along your GI tract, oral cavity, esophagus, stomach, and on the south, are all going to have these lymphatic nodules, which are aggregations of white blood cells that are ready. You know, it's kind of like a little guard post there, waiting to see if somebody's going to be a bad actor in the stomach. All right, I'm going to reset this down. All right, hey, look, everything got really small. All right, taking a larger look here, or at least a different look, down here we have a look at the specific cell types in the gastric gland versus the pyloric gland. All right, so I'm going to zoom in on these now. Okay. All right, what do we got? You got a fun little micrograph over here showing, you know, probably a scanning electron micrograph of those. pits in that surface it's kind of fun you can actually see individual columnar cells there that's the the fun part of electron microscopy you can see individual cells really well i'm not looking over there though i'm looking over here so let's take a look here at some of these cell types in the glands and notice they've truncated it so this is not actually the surface here they've just shown us the deepest portions of the glands so you got your mucous neck cells And then here's the transition in a gastric gland to the actual deep gland. So what do we got in here? We got some cells called parietal cells. So we have parietal cells we're going to pay attention to and chief cells we're going to pay attention to. Our first look here. Parietal cells and chief cells. These have very different functions, but they work together. Notice that there are... More chief cells and fewer parietal cells. So what do we have going on here? Parietal cells here, these make hydrochloric acid. HCl production, that's their job. Because the chemistry of the digestive process in the stomach is dependent upon pH. And the lower the pH, the better. So we're looking to, during meal times, after you've ingested a full load, you're looking at trying to get the pH of the stomach contents down below 2. And that's very acidic. Now we have chief cells here. These chief cells, their purpose, so to speak, is to do pepsinogen production. pepsinogen is a pro enzyme i'm going to show you how this works all right so that's what that's what the in the gastric glands the the majority of glandular production the exocrine secretions are going to be pepsinogen and hydrochloric acid we've got in here some g cells i'll use a different highlighter color here g cells and these are these are common in both pyloric gland and gastric glands These G cells, these are responsible for gastrin production. Gastrin is a hormone, so that's going to go into the bloodstream. So these gastric and pyloric glands are a curious mixture of exocrine and endocrine glands. So G cells are single-celled endocrine cells, and they're going to be producing and distributing their output into the bloodstream as a hormone, instead of into the gland lumen and out into the stomach. That's what we got here. I'm gonna let's uh there we go. I'm gonna shrink that back down now and I'm gonna Take a some time with you on your lecture outline and kind of diagram some of this stuff and write it down for you And I'm just kind of giving us some some orientation here to the glands. Okay next All right, let's talk about hydrochloric acid production and secretion in a parietal cell. So remember, we have a parietal cell here, okay? That's what we're looking at. Follow the bouncing biochemistry ball here. So to make hydrochloric acid, you need hydrogen ions and chloride ions. You put those together in a solution, and they make hydrochloric acid. Boom. That's all you need. So the question is, where do they come from? The hydrogen ions come from this pathway. In cells, a very common enzyme is carbonic anhydrase. Some of us might remember this from blood gases in red blood cells, the way that our red blood cells carry carbon dioxide from the tissues back to the lungs and vice versa. Carbonic anhydrase is pretty common. What it does, it's a reversible enzyme, but it'll take carbon dioxide and water, combine them into carbonic acid, H2CO3. Now, carbonic acid is an acid. It does what acids do, and that's donate hydrogen ions to solutions. So once you make that carbonic acid, it very easily dissociates into a bicarbonate ion. and a hydrogen ion all right so what do we do we take those hydrogen ions because basically carbonic anhydrase is creating an acid right it's dissociating and now this yellow ball represents active transport where we use atp to pump the hydrogen ions out into the lumen of the gland right so that's where we get the hydrogen ion from where does the chloride ion come from well The bicarbonate ion that's produced from this, now it's going to have a countertransporter over here where it pumps the bicarbonate ion out into the bloodstream. It actually goes into the interstitial fluid first, but it enters the bloodstream. And this countertransporter or antiporter, we might have learned, is a transport membrane. Protein that will move two solute species in two directions. So as the bicarbonate is going out, it's actually trading it for chloride or chloride ion coming in. So there's another active process here. And once the chloride's in here, it builds up in concentration and there is a simple chloride channel on this side of the cell. And so as it builds up in concentration and creates a gradient, it just flows out. So here's how we get the hydrogen ion and the chloride ion. And once they enter the lumen of the gland, they just come together as hydrochloric acid. And that's how a parietal cell works. So what do the chief cells do? Look at this slide. Okay, now we're on to the chief cells. There we go, my purple highlighter. Now we're on to the chief cells. So they produce pepsinogen, we said, right? So here's that on the actual pen. There we go. They produce this pepsinogen. Now, let's take a look at pepsinogen. This is what we call a proenzyme. So this is an inactive enzyme. This is a really common pattern in physiology is to create proenzymes ahead of schedule so that you have a supply of them potentially on hand. And the idea here is that They're just showing this schematically. This is a fairly complex protein. And remember how proteins are right there. These amino acid chains that fold up into complex shapes. We have primary, secondary, tertiary, quaternary structure. And this is an enzyme. So that means there's an active site. And in order for the active site to be active, it's got to be folded properly. Well, these proenzymes, they're produced with an extra set of amino acids on one tail, and what that does is that blocks the active site so that the enzyme is ready to go. It just needs to be unlocked, so to speak. So what happens here is the chief cells produce these pepsinogen molecules in large quantities. They store them in storage vesicles, and then when the time comes, And they're stimulated to release this pepsinogen into the duct so that it can go into the stomach. The pepsinogen molecules here meet up with the hydrochloric acid molecules here. And what happens is the hydrochloric acid catalyzes or helps catalyze the locking peptide sequence off of the proenzyme. When it does that, it activates the enzyme. So we call this enzyme activation. And it goes from being a pro-enzyme to an active enzyme. You just remove that excess piece of tail using the hydrochloric acid. And what does pepsin do? Pepsin is a protein cleaving enzyme here. So when you take dietary proteins in, you know, have a protein-rich meal, what pepsin does is it starts cleaving those polypeptide chains into smaller bits. Not complete digestion, partially digested protein. Pepsin gets protein digestion started by taking very complex dietary proteins and breaking them up into smaller chunks. Another fun thing is once you start having active pepsin, the active pepsin can also catalyze activation of other pepsinogen molecules. And so not only can the hydrochloric acid do it, active pepsin can do it. And so it just speeds up the activation process. So that's what's coming out of these gastric glands here. We got a lot of hydrochloric acid and pepsinogen and all of that plus the mucus. comes out into the stomach and the pepsinogen turned to pepsin starts protein digestion going a pretty good clip so here we are i thought i'd pull up a section here of our outline so i could help you fill in a few things um so remember let me get my pen set so in the gastric pits here The first thing you find once you go deep enough for the mucus cells here, mucus production, I think that's pretty self-explanatory. When you get into the actual glands, you know, on the outline here, I've got gastric glands, but this applies to pyloric glands in general also. So for parietal cells here, remember we're producing hydrochloric acid. All right. And the production here, right, C diagram, right, and the roles, remember, activating pepsinogen. And then also, so pepsin here is an enzyme. Ideally, you had some cellular biology background where you learned about enzymes. And one of the things you would have learned is that enzymes have response curves. I can actually draw one over here. For example, let's say we had O enzyme activity here on the x-axis. And then we had pH here on the y-axis. Actually, no, I did that backwards. I'm a bit of an idiot. Hold on. Yeah. sorry ph here and enzyme activity and uh every every enzyme has a response curve uh for ph where in some some spots it's really happy and in other spots it's not so much okay so if we were to uh apply this to pepsin okay That happy spot is pH of 1.5. Pepsin is at its most active for catalytic activity at a very low pH. And so the hydrochloric acid is what's getting our stomach contents down to that ideal pH for pepsin to break down proteins. All right, what else we got going on here? Something I didn't mention was this intrinsic factor. Okay. Parietal cells produce intrinsic factor. So this is a coenzyme, and this promotes vitamin B12 absorption in the small intestine. All right, so without that intrinsic factor, that particular vitamin doesn't get absorbed very well. Well, we have then the chief cells here producing what we talked about here, C diagram, right? This is protein digestion. All right, and down here we have some endocrine cells. We talked about gastrin. Now, these cells have names. Gastrin producing cells, those were on that diagram. These are called G cells. G for gastrin, I guess. Now, what does gastrin do? Gastrin has a hormone. Remember, it's a hormone. It goes into the bloodstream. but it's a very local hormone and almost acts like a paracontractor. It goes into the bloodstream, but it has its target activity very close at hand. Gastrin in the bloodstream stimulates chief and parietal cells. So it causes chief and parietal cells to produce and release more hydrochloric acid and pepsinogen. We have a couple of other hormones, endocrine-producing cells with hormones here too. We've got somatostatin. Now, the cells that release somatostatin are called D-cells. And what somatostatin does, anytime you see statin, That's an inhibitor, right? Somatostatin as a hormone inhibits G cells. So it shuts down gastrin production or slows it down. Then we have histamine as a hormone in this case. Histamine can be a paracrine factor, but it also can be a hormone. Here we have MAST. cells. And these are in the lamina propria. All right. And mast cells produce and release histamine. And what histamine does in this context is it also stimulates chief and parietal cells. So you have a couple of hormones here that make hydrochloric acid and pepsinogen production increase and we have a hormone here that makes them decrease. Now from context here, these endocrine cells, these are more common in pyloric glands. Remember those pyloric glands from the previous diagram? They're mostly mucous cells all the way down to the gland. And add a few little other cells pocketed in there. Those are G cells, D cells, and in the lamina propria region, mast cells. So really in the pyloric portion of the stomach, the glandular activity there is in a lot of ways more endocrine than exocrine. All right, the extra-crime portion is really mucus, and then the endocrine portion becomes important, as we'll see. And one last thing here with the roles of hydrochloric acid. I'll put this up here. So we have activating the pepsinogen to pepsin. Great. And then over here we had, you know, making sure that the pH is right for pepsin to do its job. There's another important role for this really intense, nasty pH inside the stomach. This hydrochloric acid kills just about anything. Look, if you consume bacteria every time you take a bite of food, chewing on that food is not going to kill that bacteria. And what's going to kill that bacteria is a pH of 1.5. That's going to kill that bacteria. The vast majority of pathogenic bad things that might enter your body through your GI tract, they hit the acid vat in the stomach, and they just end up being part of the food chain at that point. Okay. They also... Hydrochloric acid and low pH have a lot to do with denaturing proteins. So the food you eat, the proteins, the dietary proteins in the food you eat, when they hit that vat of acid in the stomach, they begin to denature. And so their quaternary shapes fall apart, their tertiary shapes fall apart in that acid. And that makes pepsin's job easier. Because it's easier for it to break those chains into smaller pieces if they're not folded up. So denaturing proteins is also an important part of that acidic environment to the stomach. All right, so let's take a look at some fun stuff here. So there's generally thought to be three kind of stages or phases of gastric function. All right, so we got one, two, three in these diagrams in a row. The first one here is the... Cephalic phase. Cephalic means head, right? Notice if you look down here on this diagram, this stomach is empty. There's nothing there, right? But what do we have is we have the sight, smell, taste, or thoughts of food. If you are hungry, and you walk into your favorite restaurant whether it's five guys or chipotle or moe's or panera or wherever else buffalo wild wings i don't care where you go if you're hungry and you walk in that door the sight the smell the thoughts all of that your brain then central nervous system right here right your brain starts sending action potentials down the vagus nerve these are parasympathetic action potentials so The stomach is dual innervated by the autonomic nervous system, like we've learned all of these visceral organs are. In the case of the GI tract, the parasympathetic nervous system is what normally has control of autonomic tone. So the parasympathetic is the portion of the autonomic nervous system that drives the GI tract, you know, under normal circumstances. So when you smell, taste, think about food and you're hungry, what you've got here is that vagus nerve is sending impulses down from the brain, right, the syphallic phase. And it's doing two things. One is those actin potentials are coming to the submucosal plexus of the stomach wall. And remember, we said the submucosal plexus is responsible for controlling the glandular activities of the GI tract. So what happens? Notice our color coordination here, stimulation, red arrows are stimulation, right? Mucus cells are being stimulated by the vagus nerve. just the thought of food and all of a sudden mucus starts spewing out of the gastric pits. Chief cells are being, you know, stimulated here. All of a sudden, coming out of those gastric pits, you have a whole bunch of pepsinogen and parietal cells are being stimulated. All that hydrochloric acid, boom, HCL, pepsinogen, mucus. All of these are being produced rapidly. at just the mere thought, sight, or smell or taste of food. Your stomach gets going before food even arrives. All right, I have G cells being stimulated here. These are the endocrine ones, right? And then look, I think this green arrow may be supposed to be over here, but look at this. This is a part of the diagram I don't want you to be confused about. So I'm going to draw this better for you. So the G cells here are being stimulated by the parasympathetic, and they produce gastrin as a hormone, right? What I don't like about this diagram is the biological illustrator who did this, unfortunately, put the arrow going out through the pyloric sphincter and into the duodenum. And many students in the past have interpreted this as... the gastrin goes out of the stomach and into the duodenum no no no no this is a hormone okay so this hormone gastrin is going into the bloodstream and then remember what g cells and gastrin do right so gastrin here stimulates chief and parietal cells so it comes back here and actually let me do this differently i got to use green arrows here because my key at the bottom stimulation the gastrin goes into the bloodstream and targets the chief and parietal cells through the bloodstream and that up regulates hydrochloric acid and pepsinogen production so mucosally glandular wise just the thought smell taste or sight of food will get all of this machinery going before food even hits the stomach now we also have over here another red arrow which is curiously unlabeled on this diagram because over here we have the myenteric plexus And remember the myenteric plexus controls the muscularis externa, the longitudinal and circular, and in this case with the stomach, the oblique muscle layers, the thick, smooth muscle layers, you know, lining this bag. And what this does is it stimulates muscularis externa. contractions and have you ever noticed that when you are hungry and you do get that good whiff of something in sight and smell of something then you're start anticipating that food in your stomach and your stomach starts to churn and growl and you feel that kind of funniness in your in your gut where your stomach's like give me some food right because not only is it starting to produce all the juices, the mucus and pepsinogen and hydrochloric acid and all that, it's actually physically contorting in muscular waves, trying to anticipate that food coming in. So this is the cephalic phase, where food ever arrives. This diagram here represents step two, the gastric phase. So notice in this diagram now there's stuff in the stomach now they they use this this lovely shade of i don't even know what that color is to represent stuff in the stomach okay it doesn't really just kind of ooze up the esophagus like that at least it shouldn't in a normally operating person but here we go now remember there was a slide in the first hour talking about what drives the the digestive system was a big slide had three things on it Right. And number one, always, always, always number one, local factors drive the activities of the digestive system. Right. That's number one. So look what's happening here. When we have, let me get my pointer here, when we have all this food enter, what's going to happen is a couple of things. One is you have distension of the stomach wall, right? Because you're filling it with food, it's stretching out. That's picked up by stretch receptors. Two, by adding the food in, Remember, before the food even arrived, we were putting hydrochloric acid in there. So the pH was dropping in your stomach before the food arrived, right? Then you started eating, and then the food goes down in there. That actually raises the pH above where, you know, normal activity is taking place. So that actually triggers chemoreceptors. So distension of the stomach wall and elevated pH, these are local factors, right? Stuff arrives in that area of the GI tract. These are picked up on by receptors. And look, here we have two reflex arcs, short reflex arcs of the autonomic nervous system where we bypass the central nervous system and go back to the plexus here, back to the ganglia, the intramural ganglia in the stomach wall. of the submucosal and myoteric plexuses. So these local conditions of distension and elevated pH are picked up by receptors, ferried by local short reflexes back into the submucosal and myoteric plexuses, and starts what we call positive feedback loops. So the short autonomic reflex of stretch and chemoreception Coming back to the submucosal plexus, causes mucus cells, chief cells, parietal cells, and G cells to increase their output. So we are causing them to produce more mucus, more pepsinogen, more hydrochloric acid, and more gastrin. It's a positive feedback loop. The local factors of distension and elevated pH causing these short autonomic reflex arcs. When they feed back to the myenteric plexus, they cause stronger contractions of the myenteric plexus and the muscularis externa. So this is local factors causing immediate impacts on stomach activity. It produces more of the digestive juices, mucus, pepsinogen, and hydrochloric acid. And it churns and muscular contracts even stronger. We also have down here partly digested peptides. I show a little box here. Here's another local factor, right? As soon as proteins make it down in here, they're getting hit with the acid. They're getting hit with the pepsin now that's been activated. And they're getting chopped up in little bits, partly digested peptides. Well, partly digested peptides are a local factor picked up by G cells, and G cells then produce more gastrin when that happens. So another immediate impact from a local factor. The gastrin goes into the bloodstream. Guess what? It feedbacks as a positive feedback loop, causes chief cells and parietal cells to produce more of their stuff. Also at high concentrations, gastrin... feeds back through the bloodstream and causes the myenteric plexus the the muscular contractions to increase so then when food hits the stomach a lot of things happen all these local factors here are causing up regulation of all of this activity and what happens is the stomach wall just kind of contracts and mixes and squeezes and does this segmentation style effort here to mix and mash and mulch and puree the material you've eaten where the hydrochloric acid and pepsinogen and mucus are turning it into an acidic you know ball of toothpastey consistency slime that's just nasty acidic And in doing so, you're ideally killing any pathogens you ingested and helping to do some beginnings of protein digestion. And this soup that we're creating in here, so food plus digestive juices plus time plus contractions makes a material we call chyme. C-H-Y-M-E, chyme. It's a hard C. And that chyme there, that's, like I've said before, your stomach is trying to get whatever you ate, whether it's a house salad or a double bacon cheeseburger, is trying to get that material into a mush, the consistency of toothpaste. And that's what chyme is, right? And so what we say is the stomach is conditioning the chyme. It is mulching it and churning it and squeezing it and turning it and chemically, you know, digesting it and getting it to the point where it is physically ready to leave the stomach because it's really, it's about a physical readiness. It's about a consistency, right? So that the physical materials have broken down to such an extent that you don't have chunks leaving the stomach okay so what happens when we are ready with the when the chyme has been conditioned properly the stomach has done its job which could be as little as an hour on an easy meal or it could be several hours three or four hours on some big complex meal what happens then well When that chyme reaches a certain consistency, I want us to now pay attention to the pyloric sphincter region, which should be pinched shut here while the stomach is in the gastric phase. Once the chyme reaches a certain level of consistency, what's going to happen is little bits of that chyme are going to leak past the valve and leak past the sphincter. Okay, so that's when that happens that's going to trigger a new set of reflexes here First of all when chyme enters the duodenum here duodenal stretch and chemoreceptors Activate, you know, so stuff enters the duodenum the wall stretch and chemoreceptors pick up and then add acidity, right? So I'll write this in here these chemoreceptors Low pH. Okay. That chyme is nasty acidic stuff. What happens then is that triggers negative feedback through what we call the enterogastric reflex. So duodenal stretch in chemoreceptors, detecting stretch and low pH, cause a shutdown. It doesn't like turn it off, but it calms down the myenteric plexus. So what happens is the mixing activities, the churning of the stomach wall slows down, right? Once you've got that chyme condition, you don't have to go at it, you know, real hard like you were an hour before. So the enterogastric reflex calms down the muscles of the stomach wall, okay? Then also the chyme entering the duodenum. Picks gets picked up by other receptors. So presence of lipids and carbohydrates in the duodenum again local conditions. Nothing was happening until that time arrived. Then once the time arrives, it triggers a response. Local factors. So lipids are picked up on by chemosensory cells. Carbohydrates are picked up on by chemosensory cells. And what this does is it causes the release of two other hormones cck and gip these are hormones right look carried by the bloodstream so cck is cholecystokinin and gip is gastro inhibitory peptide these hormones feed back through the bloodstream and look what they do they inhibit chief cells and prital cells they also inhibit the my enteric plexus here inhibit peristalsis they they inhibit this movement of the stomach wall right and then pH receptors here you know low ph are picked up by chemoreceptors of the enterogastric reflex they're also picked up by chemoreceptors here that cause the release of another hormone called secretin and so when the chyme enters the duodenum secretin is released and again that's carried by the bloodstream shuts down chief cells parietal cells and peristalsis so the stomach can get going pretty good during the gastric phase But what happens is when that chyme starts to leach out into the duodenum, these are the off switches. There is a nervous reflex. These are short autonomic reflexes that shut down the my interior plexus. And we have hormonal reflexes that shut down the submucosal plexus, the glandular cells of the mucosa. Again, local conditions. Now in reality what happens is, as this process starts, and that first set of chyme leaches out past the pyloric sphincter, that starts a, what's the term I'm trying to come up with, that starts a pattern of contraction and relaxation of the pyloric sphincter. And what happens is, is it... stays closed and then it opens for a moment or two and muscular contraction of the stomach squeezes some chyme into the duodenum like you're squeezing some toothpaste out of the tube and then it closes back down again and keeps the rest of it in the stomach so that you put a little bit of chyme at a time every five minutes or so you squirt some more chyme into the duodenum periodically okay and that can go on for over an hour or more where it just kind of squirts chyme into the duodenum. The role of the duodenum we will see is really mostly about reconditioning the chyme now to bring it from its nasty low pH coming out of the stomach and bringing that chyme up to neutral and then also dumping in a whole bunch of other enzymes that can go to work to finish. properly the process of digestion. So this is the intestinal phase. This is how you shut down the stomach and say enough's enough. You've done your job. Let's squirt some of this chyme out a little bit of a time and we'll let it out into the duodenum and we'll continue with the process. This diagram here shows us a larger view here when food enters the stomach. There's actually a couple of what we call central reflexes, right? Central gastric reflexes. That means these are long autonomic reflexes. And these are through the vagus nerve, cranial nerve 10. Remember, cranial nerve 10 is what fed the initial action potentials to the stomach. when you thought about food in the cephalic phase. All right, well, these long autonomic reflexes, this is what happens when food enters the stomach and causes distension of the stomach, right? That's the only trigger here is when the stomach gets extended outward because you filled it with something. When that happens, that kicks off two different central reflexes. We have the gastroenteric reflex and look what here stimulates the motility and secretion along the entire small intestine all right so think about that meal that you've just taken into the stomach here you know the stomach is going to deal with that and then it's going to pass it out into the duodenum well there's probably food or whatever value still left in the small intestine from a previous meal. You know, this could be hours that that material is in the small intestine. So what happens is when you take a new meal in, there's a signal that goes out through this central reflex, the gastroenteric reflex, that tells the small intestine, all right, time's up. I don't care what you got in there, but you better move that along because we have a new batch coming. So that stimulates motility and secretion along the entire small intestine that up regulates the activities of the small intestine so that you can make room for this new meal you just took in. The gastroilial reflex here, down below here, they show the ileocecal valve. That is another sphincter. So the pyloric sphincter controlled the emptying of the stomach. The ileocecal valve right here controls the emptying of the small intestine into the colon, into the large intestine. So the gastroilial reflex here can trigger the opening of the ileocecal valve, allowing materials to pass from the small intestine to the large intestine. Again, if you take a big meal in, the gastroenteric reflex kicks the small intestine into high gear. The gastroilial reflex says, well, I better open up here so this material can pass out. What's left over then becomes waste. It's going to be fecal material. And it just kind of makes the path ahead of this big kneel clear out. Two central reflexes are kind of important. There's another reflex here. We talk about the emetic reflex, and that's the regurgitation reflex. So when you throw up, just to give you an idea, when whatever would cause this, there's a lot of things that would cause you to vomit. But something delightful to think about is with the emetic reflex, when you vomit, what happens is you get reverse peristalsis. So that's the only example in the GI tract where you see peristalsis go towards the mouth. And it's not just the stomach. It's the duodenum, too. So what happens is when you throw up, the... pyloric sphincter opens and you actually throw up from the duodenum, the deep portion of the duodenum, back through the stomach and out through the esophagus. It's not just stomach contents. You're getting that conditioned chyme there too. It's nasty.

Well, welcome back. Here we are in the second hour of the digestive system. Here we are at the stomach.

We've moved through some general concepts. We've passed the oral cavity down through the esophagus. As we pick up with this diagram right here is where your lower esophageal sphincter will be. That physiological sphincter there that keeps the... bottom end of the esophagus closed unless some food bolus or liquid is coming down the esophagus to enter the stomach all right so when we take a look at the stomach here there's some general general anatomy this is stuff you probably picked up the vocabulary in the lecture lab i mean so we have the the outer curvature here they call it the greater curvature inside we have the lesser curvature We have the layers here.

We have a serosa. We have the muscularis externa. We have the mucosa on the inside. Here in the GI tract is the one exception to the muscularis externa having two layers. We learned that there's an outer longitudinal layer and an inner circular layer.

With the stomach alone, out of all the tract, there's a third layer, and that's the oblique. muscle layer. You only find it in the stomach. The stomach is a great big old bag of muscle, and its sole job physically is to take the food that you have ingested and mushing it down into the consistency of toothpaste.

Now, there's chemical processes that are helping this, but really, it's far more of a physical squeeze bag than most people give it credit for. It's also terrifically extensible. It can expand greatly from its smallest size to its larger size.

That's these rugae here. The rugae are these expansion folds on the inside. So an empty stomach is quite small.

A full stomach can be quite large. All right, from functioning here, let's start at the top with the esophagus and the esophageal opening. We have... the cardia region here and I'll draw some little dotted lines here like that.

So here's that cardia region and that's really a physiological region where the mucosal lining in this area, their secretions of the glands contain a high concentration of sodium bicarbonate secreting gland. cells. And this creates a little cloud, so to speak, of sodium bicarbonate around the opening of the esophagus.

And what happens is every time the esophagus opens and closes, there's the chance here for acid to reflux back up into the esophagus. And so there's a a chemical buffering cloud there of bicarbonate ion that's meant to kind of neutralize that acid as it sneaks up past the sphincter region and into the esophagus right let me get rid of this here okay so uh there's your there's your cardia all right um You talk about the fundus up here, here's the fundus region. I can kind of make a little dotted line like that. So here's the fundus.

That just represents this portion of the stomach that is at or superior to the opening of the esophagus. So all of this is all fundus. Anatomically, that's an interesting term. From the Latin, fundus means the bottom of something. But in anatomy, it indicates the portion of an organ that's farthest away from its opening.

So if you know anything about the fundus of the uterus, you know that that is the portion of the uterus that is farthest away from the cervix. And you're thinking, hey, wait a minute, the fundus of the stomach is about as close as it gets to the esophagus. How can it be the farthest away?

Well... see the issue is in anatomy they're considering a pyloric opening into the duodenum to be the opening and so the fundus is the point farthest away. from the pyloric opening uh anatomy wise the the other thing i want to do is kind of draw a line here and on one side here we have the pylorus here all right or sometimes you'll hear called the pyloric stomach or the pylorus and up here we have the body of the stomach It's all one big sack, but physiologically there's going to be different processes happening in the body than in the pylorus.

And we'll talk about that in a slide or two here in a few minutes. All right, well, here we are. Let's take a look at a close-up of the stomach lining. And what I want to do here is kind of zoom in on this diagram.

here so we take a look at the top part first all right what do we have here this is the the lumen up here right the oh let me get my pen activated here so there's the lumen right the food's out here food is here hey um so the the stomach lining here uh is lined i guess with gastric pits. So they're showing, let me try my little highlighter here, gastric pits. And so look what's going on here.

The lining of the stomach has these folds that come up and around and down and up and down and up, much like the gyrus and sulcus pattern on the surface of the cerebral cortex. right so we have these folds of of tissue up and down and where they go down in that creates these pits and what we want to do is we want to understand the difference in vocabulary between a gastric pit and a gastric gland okay so up here like this region here i'll do it on one of these side ones right So everything I've outlined in black there, I'll do this one over here, right? Those are the gastric pits.

Well, what's going on there? Take a look at these cells, right? And I'll kind of color them in green. There's one, there's one, there's one. You look at these cells.

These are the simple columnar cells of the mucosal epithelium. And so these cells are no different from any other. They're just kind of the working stiffs on the surface of the epithelium, okay?

And they've color-coded these pink. I'm coloring them in green, but on the diagram, they're pink, right? And you watch these, and these go all the way down until you get to a different kind of cell.

See on the diagram here, they've turned blue now. All right. So these blue cells have a different job than the green cells. The green cells are just the outer stomach lining, just the standard stomach epithelial lining.

Once you get down into here, into the blue cells, now you're in the glands. So there's a gastric gland here. The blue cells are the start of the gland. So we have gastric glands, and then we have pyloric glands.

So gastric glands, these are in the body of the stomach. Pyloric glands are in the pylorus of the stomach. So we said it's all one bag of muscle, but physiologically, you've got different things going on in the body versus the pylorus, right? So this diagram will get to some of that.

So you have the... The gastric pits, these are where the invaginations of the gastric surface go down. And where you end, where your normal everyday epithelial cells end, that begins the gland. And then once you're in a gland, whether it's gastric or pyloric, the first set of cells lining this are going to be mucus cells. So let's go here.

they call them mucus neck cells all right and so you can see here right and they're just what they sound like mucus cells their sole job is to produce a lot of mucus And this mucus here flows outward. So the mucus is produced down in the gland itself and comes out through the pits. And it's constantly being extruded out through the pits. So that your stomach lining is, the lumen of the stomach is lined with a thick layer of mucus.

And that protects the stomach wall. from some of the fairly nasty chemical reactions that are going to be occurring there. You'll notice here in the gastric glands, like the mucous neck cells, are a very discrete portion of the gland, the first portion here.

If you come over to pyloric glands, you'll notice that the mucous cells are prevalent throughout the entire gland structure. So that might give you a hint about... pyloric gland function there.

What else we got here? Just down here real quick, there's a lymphatic nodule. When you see lymphatic, something to do with the lymph system, there's lymph vessels, and then these lymphatic nodules, these are immune structures.

Remember, everything you eat is covered with tons of bacteria, and some of them are nasty, and some of them are going to try to invade your body. And so all layers, you know, all points along your GI tract, oral cavity, esophagus, stomach, and on the south, are all going to have these lymphatic nodules, which are aggregations of white blood cells that are ready. You know, it's kind of like a little guard post there, waiting to see if somebody's going to be a bad actor in the stomach. All right, I'm going to reset this down.

All right, hey, look, everything got really small. All right, taking a larger look here, or at least a different look, down here we have a look at the specific cell types in the gastric gland versus the pyloric gland. All right, so I'm going to zoom in on these now. Okay. All right, what do we got?

You got a fun little micrograph over here showing, you know, probably a scanning electron micrograph of those. pits in that surface it's kind of fun you can actually see individual columnar cells there that's the the fun part of electron microscopy you can see individual cells really well i'm not looking over there though i'm looking over here so let's take a look here at some of these cell types in the glands and notice they've truncated it so this is not actually the surface here they've just shown us the deepest portions of the glands so you got your mucous neck cells And then here's the transition in a gastric gland to the actual deep gland. So what do we got in here? We got some cells called parietal cells. So we have parietal cells we're going to pay attention to and chief cells we're going to pay attention to.

Our first look here. Parietal cells and chief cells. These have very different functions, but they work together. Notice that there are... More chief cells and fewer parietal cells.

So what do we have going on here? Parietal cells here, these make hydrochloric acid. HCl production, that's their job. Because the chemistry of the digestive process in the stomach is dependent upon pH. And the lower the pH, the better.

So we're looking to, during meal times, after you've ingested a full load, you're looking at trying to get the pH of the stomach contents down below 2. And that's very acidic. Now we have chief cells here. These chief cells, their purpose, so to speak, is to do pepsinogen production.

pepsinogen is a pro enzyme i'm going to show you how this works all right so that's what that's what the in the gastric glands the the majority of glandular production the exocrine secretions are going to be pepsinogen and hydrochloric acid we've got in here some g cells i'll use a different highlighter color here g cells and these are these are common in both pyloric gland and gastric glands These G cells, these are responsible for gastrin production. Gastrin is a hormone, so that's going to go into the bloodstream. So these gastric and pyloric glands are a curious mixture of exocrine and endocrine glands.

So G cells are single-celled endocrine cells, and they're going to be producing and distributing their output into the bloodstream as a hormone, instead of into the gland lumen and out into the stomach. That's what we got here. I'm gonna let's uh there we go. I'm gonna shrink that back down now and I'm gonna Take a some time with you on your lecture outline and kind of diagram some of this stuff and write it down for you And I'm just kind of giving us some some orientation here to the glands. Okay next All right, let's talk about hydrochloric acid production and secretion in a parietal cell.

So remember, we have a parietal cell here, okay? That's what we're looking at. Follow the bouncing biochemistry ball here. So to make hydrochloric acid, you need hydrogen ions and chloride ions. You put those together in a solution, and they make hydrochloric acid.

Boom. That's all you need. So the question is, where do they come from?

The hydrogen ions come from this pathway. In cells, a very common enzyme is carbonic anhydrase. Some of us might remember this from blood gases in red blood cells, the way that our red blood cells carry carbon dioxide from the tissues back to the lungs and vice versa.

Carbonic anhydrase is pretty common. What it does, it's a reversible enzyme, but it'll take carbon dioxide and water, combine them into carbonic acid, H2CO3. Now, carbonic acid is an acid. It does what acids do, and that's donate hydrogen ions to solutions. So once you make that carbonic acid, it very easily dissociates into a bicarbonate ion.

and a hydrogen ion all right so what do we do we take those hydrogen ions because basically carbonic anhydrase is creating an acid right it's dissociating and now this yellow ball represents active transport where we use atp to pump the hydrogen ions out into the lumen of the gland right so that's where we get the hydrogen ion from where does the chloride ion come from well The bicarbonate ion that's produced from this, now it's going to have a countertransporter over here where it pumps the bicarbonate ion out into the bloodstream. It actually goes into the interstitial fluid first, but it enters the bloodstream. And this countertransporter or antiporter, we might have learned, is a transport membrane.

Protein that will move two solute species in two directions. So as the bicarbonate is going out, it's actually trading it for chloride or chloride ion coming in. So there's another active process here. And once the chloride's in here, it builds up in concentration and there is a simple chloride channel on this side of the cell. And so as it builds up in concentration and creates a gradient, it just flows out.

So here's how we get the hydrogen ion and the chloride ion. And once they enter the lumen of the gland, they just come together as hydrochloric acid. And that's how a parietal cell works.

So what do the chief cells do? Look at this slide. Okay, now we're on to the chief cells. There we go, my purple highlighter.

Now we're on to the chief cells. So they produce pepsinogen, we said, right? So here's that on the actual pen.

There we go. They produce this pepsinogen. Now, let's take a look at pepsinogen.

This is what we call a proenzyme. So this is an inactive enzyme. This is a really common pattern in physiology is to create proenzymes ahead of schedule so that you have a supply of them potentially on hand.

And the idea here is that They're just showing this schematically. This is a fairly complex protein. And remember how proteins are right there. These amino acid chains that fold up into complex shapes.

We have primary, secondary, tertiary, quaternary structure. And this is an enzyme. So that means there's an active site. And in order for the active site to be active, it's got to be folded properly. Well, these proenzymes, they're produced with an extra set of amino acids on one tail, and what that does is that blocks the active site so that the enzyme is ready to go.

It just needs to be unlocked, so to speak. So what happens here is the chief cells produce these pepsinogen molecules in large quantities. They store them in storage vesicles, and then when the time comes, And they're stimulated to release this pepsinogen into the duct so that it can go into the stomach. The pepsinogen molecules here meet up with the hydrochloric acid molecules here. And what happens is the hydrochloric acid catalyzes or helps catalyze the locking peptide sequence off of the proenzyme.

When it does that, it activates the enzyme. So we call this enzyme activation. And it goes from being a pro-enzyme to an active enzyme.

You just remove that excess piece of tail using the hydrochloric acid. And what does pepsin do? Pepsin is a protein cleaving enzyme here.

So when you take dietary proteins in, you know, have a protein-rich meal, what pepsin does is it starts cleaving those polypeptide chains into smaller bits. Not complete digestion, partially digested protein. Pepsin gets protein digestion started by taking very complex dietary proteins and breaking them up into smaller chunks. Another fun thing is once you start having active pepsin, the active pepsin can also catalyze activation of other pepsinogen molecules. And so not only can the hydrochloric acid do it, active pepsin can do it.

And so it just speeds up the activation process. So that's what's coming out of these gastric glands here. We got a lot of hydrochloric acid and pepsinogen and all of that plus the mucus. comes out into the stomach and the pepsinogen turned to pepsin starts protein digestion going a pretty good clip so here we are i thought i'd pull up a section here of our outline so i could help you fill in a few things um so remember let me get my pen set so in the gastric pits here The first thing you find once you go deep enough for the mucus cells here, mucus production, I think that's pretty self-explanatory. When you get into the actual glands, you know, on the outline here, I've got gastric glands, but this applies to pyloric glands in general also.

So for parietal cells here, remember we're producing hydrochloric acid. All right. And the production here, right, C diagram, right, and the roles, remember, activating pepsinogen.

And then also, so pepsin here is an enzyme. Ideally, you had some cellular biology background where you learned about enzymes. And one of the things you would have learned is that enzymes have response curves. I can actually draw one over here. For example, let's say we had O enzyme activity here on the x-axis.

And then we had pH here on the y-axis. Actually, no, I did that backwards. I'm a bit of an idiot.

Hold on. Yeah. sorry ph here and enzyme activity and uh every every enzyme has a response curve uh for ph where in some some spots it's really happy and in other spots it's not so much okay so if we were to uh apply this to pepsin okay That happy spot is pH of 1.5.

Pepsin is at its most active for catalytic activity at a very low pH. And so the hydrochloric acid is what's getting our stomach contents down to that ideal pH for pepsin to break down proteins. All right, what else we got going on here? Something I didn't mention was this intrinsic factor.

Okay. Parietal cells produce intrinsic factor. So this is a coenzyme, and this promotes vitamin B12 absorption in the small intestine. All right, so without that intrinsic factor, that particular vitamin doesn't get absorbed very well.

Well, we have then the chief cells here producing what we talked about here, C diagram, right? This is protein digestion. All right, and down here we have some endocrine cells.

We talked about gastrin. Now, these cells have names. Gastrin producing cells, those were on that diagram. These are called G cells. G for gastrin, I guess.

Now, what does gastrin do? Gastrin has a hormone. Remember, it's a hormone.

It goes into the bloodstream. but it's a very local hormone and almost acts like a paracontractor. It goes into the bloodstream, but it has its target activity very close at hand. Gastrin in the bloodstream stimulates chief and parietal cells.

So it causes chief and parietal cells to produce and release more hydrochloric acid and pepsinogen. We have a couple of other hormones, endocrine-producing cells with hormones here too. We've got somatostatin. Now, the cells that release somatostatin are called D-cells.

And what somatostatin does, anytime you see statin, That's an inhibitor, right? Somatostatin as a hormone inhibits G cells. So it shuts down gastrin production or slows it down.

Then we have histamine as a hormone in this case. Histamine can be a paracrine factor, but it also can be a hormone. Here we have MAST.

cells. And these are in the lamina propria. All right.

And mast cells produce and release histamine. And what histamine does in this context is it also stimulates chief and parietal cells. So you have a couple of hormones here that make hydrochloric acid and pepsinogen production increase and we have a hormone here that makes them decrease. Now from context here, these endocrine cells, these are more common in pyloric glands.

Remember those pyloric glands from the previous diagram? They're mostly mucous cells all the way down to the gland. And add a few little other cells pocketed in there. Those are G cells, D cells, and in the lamina propria region, mast cells.

So really in the pyloric portion of the stomach, the glandular activity there is in a lot of ways more endocrine than exocrine. All right, the extra-crime portion is really mucus, and then the endocrine portion becomes important, as we'll see. And one last thing here with the roles of hydrochloric acid. I'll put this up here.

So we have activating the pepsinogen to pepsin. Great. And then over here we had, you know, making sure that the pH is right for pepsin to do its job.

There's another important role for this really intense, nasty pH inside the stomach. This hydrochloric acid kills just about anything. Look, if you consume bacteria every time you take a bite of food, chewing on that food is not going to kill that bacteria.

And what's going to kill that bacteria is a pH of 1.5. That's going to kill that bacteria. The vast majority of pathogenic bad things that might enter your body through your GI tract, they hit the acid vat in the stomach, and they just end up being part of the food chain at that point. Okay. They also...

Hydrochloric acid and low pH have a lot to do with denaturing proteins. So the food you eat, the proteins, the dietary proteins in the food you eat, when they hit that vat of acid in the stomach, they begin to denature. And so their quaternary shapes fall apart, their tertiary shapes fall apart in that acid. And that makes pepsin's job easier. Because it's easier for it to break those chains into smaller pieces if they're not folded up.

So denaturing proteins is also an important part of that acidic environment to the stomach. All right, so let's take a look at some fun stuff here. So there's generally thought to be three kind of stages or phases of gastric function.

All right, so we got one, two, three in these diagrams in a row. The first one here is the... Cephalic phase.

Cephalic means head, right? Notice if you look down here on this diagram, this stomach is empty. There's nothing there, right? But what do we have is we have the sight, smell, taste, or thoughts of food. If you are hungry, and you walk into your favorite restaurant whether it's five guys or chipotle or moe's or panera or wherever else buffalo wild wings i don't care where you go if you're hungry and you walk in that door the sight the smell the thoughts all of that your brain then central nervous system right here right your brain starts sending action potentials down the vagus nerve these are parasympathetic action potentials so The stomach is dual innervated by the autonomic nervous system, like we've learned all of these visceral organs are.

In the case of the GI tract, the parasympathetic nervous system is what normally has control of autonomic tone. So the parasympathetic is the portion of the autonomic nervous system that drives the GI tract, you know, under normal circumstances. So when you smell, taste, think about food and you're hungry, what you've got here is that vagus nerve is sending impulses down from the brain, right, the syphallic phase. And it's doing two things. One is those actin potentials are coming to the submucosal plexus of the stomach wall.

And remember, we said the submucosal plexus is responsible for controlling the glandular activities of the GI tract. So what happens? Notice our color coordination here, stimulation, red arrows are stimulation, right? Mucus cells are being stimulated by the vagus nerve.

just the thought of food and all of a sudden mucus starts spewing out of the gastric pits. Chief cells are being, you know, stimulated here. All of a sudden, coming out of those gastric pits, you have a whole bunch of pepsinogen and parietal cells are being stimulated. All that hydrochloric acid, boom, HCL, pepsinogen, mucus.

All of these are being produced rapidly. at just the mere thought, sight, or smell or taste of food. Your stomach gets going before food even arrives. All right, I have G cells being stimulated here. These are the endocrine ones, right?

And then look, I think this green arrow may be supposed to be over here, but look at this. This is a part of the diagram I don't want you to be confused about. So I'm going to draw this better for you.

So the G cells here are being stimulated by the parasympathetic, and they produce gastrin as a hormone, right? What I don't like about this diagram is the biological illustrator who did this, unfortunately, put the arrow going out through the pyloric sphincter and into the duodenum. And many students in the past have interpreted this as...

the gastrin goes out of the stomach and into the duodenum no no no no this is a hormone okay so this hormone gastrin is going into the bloodstream and then remember what g cells and gastrin do right so gastrin here stimulates chief and parietal cells so it comes back here and actually let me do this differently i got to use green arrows here because my key at the bottom stimulation the gastrin goes into the bloodstream and targets the chief and parietal cells through the bloodstream and that up regulates hydrochloric acid and pepsinogen production so mucosally glandular wise just the thought smell taste or sight of food will get all of this machinery going before food even hits the stomach now we also have over here another red arrow which is curiously unlabeled on this diagram because over here we have the myenteric plexus And remember the myenteric plexus controls the muscularis externa, the longitudinal and circular, and in this case with the stomach, the oblique muscle layers, the thick, smooth muscle layers, you know, lining this bag. And what this does is it stimulates muscularis externa. contractions and have you ever noticed that when you are hungry and you do get that good whiff of something in sight and smell of something then you're start anticipating that food in your stomach and your stomach starts to churn and growl and you feel that kind of funniness in your in your gut where your stomach's like give me some food right because not only is it starting to produce all the juices, the mucus and pepsinogen and hydrochloric acid and all that, it's actually physically contorting in muscular waves, trying to anticipate that food coming in.

So this is the cephalic phase, where food ever arrives. This diagram here represents step two, the gastric phase. So notice in this diagram now there's stuff in the stomach now they they use this this lovely shade of i don't even know what that color is to represent stuff in the stomach okay it doesn't really just kind of ooze up the esophagus like that at least it shouldn't in a normally operating person but here we go now remember there was a slide in the first hour talking about what drives the the digestive system was a big slide had three things on it Right. And number one, always, always, always number one, local factors drive the activities of the digestive system. Right.

That's number one. So look what's happening here. When we have, let me get my pointer here, when we have all this food enter, what's going to happen is a couple of things.

One is you have distension of the stomach wall, right? Because you're filling it with food, it's stretching out. That's picked up by stretch receptors. Two, by adding the food in, Remember, before the food even arrived, we were putting hydrochloric acid in there.

So the pH was dropping in your stomach before the food arrived, right? Then you started eating, and then the food goes down in there. That actually raises the pH above where, you know, normal activity is taking place. So that actually triggers chemoreceptors. So distension of the stomach wall and elevated pH, these are local factors, right?

Stuff arrives in that area of the GI tract. These are picked up on by receptors. And look, here we have two reflex arcs, short reflex arcs of the autonomic nervous system where we bypass the central nervous system and go back to the plexus here, back to the ganglia, the intramural ganglia in the stomach wall. of the submucosal and myoteric plexuses. So these local conditions of distension and elevated pH are picked up by receptors, ferried by local short reflexes back into the submucosal and myoteric plexuses, and starts what we call positive feedback loops.

So the short autonomic reflex of stretch and chemoreception Coming back to the submucosal plexus, causes mucus cells, chief cells, parietal cells, and G cells to increase their output. So we are causing them to produce more mucus, more pepsinogen, more hydrochloric acid, and more gastrin. It's a positive feedback loop.

The local factors of distension and elevated pH causing these short autonomic reflex arcs. When they feed back to the myenteric plexus, they cause stronger contractions of the myenteric plexus and the muscularis externa. So this is local factors causing immediate impacts on stomach activity.

It produces more of the digestive juices, mucus, pepsinogen, and hydrochloric acid. And it churns and muscular contracts even stronger. We also have down here partly digested peptides.

I show a little box here. Here's another local factor, right? As soon as proteins make it down in here, they're getting hit with the acid.

They're getting hit with the pepsin now that's been activated. And they're getting chopped up in little bits, partly digested peptides. Well, partly digested peptides are a local factor picked up by G cells, and G cells then produce more gastrin when that happens.

So another immediate impact from a local factor. The gastrin goes into the bloodstream. Guess what?

It feedbacks as a positive feedback loop, causes chief cells and parietal cells to produce more of their stuff. Also at high concentrations, gastrin... feeds back through the bloodstream and causes the myenteric plexus the the muscular contractions to increase so then when food hits the stomach a lot of things happen all these local factors here are causing up regulation of all of this activity and what happens is the stomach wall just kind of contracts and mixes and squeezes and does this segmentation style effort here to mix and mash and mulch and puree the material you've eaten where the hydrochloric acid and pepsinogen and mucus are turning it into an acidic you know ball of toothpastey consistency slime that's just nasty acidic And in doing so, you're ideally killing any pathogens you ingested and helping to do some beginnings of protein digestion. And this soup that we're creating in here, so food plus digestive juices plus time plus contractions makes a material we call chyme.

C-H-Y-M-E, chyme. It's a hard C. And that chyme there, that's, like I've said before, your stomach is trying to get whatever you ate, whether it's a house salad or a double bacon cheeseburger, is trying to get that material into a mush, the consistency of toothpaste. And that's what chyme is, right? And so what we say is the stomach is conditioning the chyme.

It is mulching it and churning it and squeezing it and turning it and chemically, you know, digesting it and getting it to the point where it is physically ready to leave the stomach because it's really, it's about a physical readiness. It's about a consistency, right? So that the physical materials have broken down to such an extent that you don't have chunks leaving the stomach okay so what happens when we are ready with the when the chyme has been conditioned properly the stomach has done its job which could be as little as an hour on an easy meal or it could be several hours three or four hours on some big complex meal what happens then well When that chyme reaches a certain consistency, I want us to now pay attention to the pyloric sphincter region, which should be pinched shut here while the stomach is in the gastric phase. Once the chyme reaches a certain level of consistency, what's going to happen is little bits of that chyme are going to leak past the valve and leak past the sphincter. Okay, so that's when that happens that's going to trigger a new set of reflexes here First of all when chyme enters the duodenum here duodenal stretch and chemoreceptors Activate, you know, so stuff enters the duodenum the wall stretch and chemoreceptors pick up and then add acidity, right?

So I'll write this in here these chemoreceptors Low pH. Okay. That chyme is nasty acidic stuff. What happens then is that triggers negative feedback through what we call the enterogastric reflex.

So duodenal stretch in chemoreceptors, detecting stretch and low pH, cause a shutdown. It doesn't like turn it off, but it calms down the myenteric plexus. So what happens is the mixing activities, the churning of the stomach wall slows down, right? Once you've got that chyme condition, you don't have to go at it, you know, real hard like you were an hour before.

So the enterogastric reflex calms down the muscles of the stomach wall, okay? Then also the chyme entering the duodenum. Picks gets picked up by other receptors. So presence of lipids and carbohydrates in the duodenum again local conditions.

Nothing was happening until that time arrived. Then once the time arrives, it triggers a response. Local factors.

So lipids are picked up on by chemosensory cells. Carbohydrates are picked up on by chemosensory cells. And what this does is it causes the release of two other hormones cck and gip these are hormones right look carried by the bloodstream so cck is cholecystokinin and gip is gastro inhibitory peptide these hormones feed back through the bloodstream and look what they do they inhibit chief cells and prital cells they also inhibit the my enteric plexus here inhibit peristalsis they they inhibit this movement of the stomach wall right and then pH receptors here you know low ph are picked up by chemoreceptors of the enterogastric reflex they're also picked up by chemoreceptors here that cause the release of another hormone called secretin and so when the chyme enters the duodenum secretin is released and again that's carried by the bloodstream shuts down chief cells parietal cells and peristalsis so the stomach can get going pretty good during the gastric phase But what happens is when that chyme starts to leach out into the duodenum, these are the off switches. There is a nervous reflex. These are short autonomic reflexes that shut down the my interior plexus.

And we have hormonal reflexes that shut down the submucosal plexus, the glandular cells of the mucosa. Again, local conditions. Now in reality what happens is, as this process starts, and that first set of chyme leaches out past the pyloric sphincter, that starts a, what's the term I'm trying to come up with, that starts a pattern of contraction and relaxation of the pyloric sphincter.

And what happens is, is it... stays closed and then it opens for a moment or two and muscular contraction of the stomach squeezes some chyme into the duodenum like you're squeezing some toothpaste out of the tube and then it closes back down again and keeps the rest of it in the stomach so that you put a little bit of chyme at a time every five minutes or so you squirt some more chyme into the duodenum periodically okay and that can go on for over an hour or more where it just kind of squirts chyme into the duodenum. The role of the duodenum we will see is really mostly about reconditioning the chyme now to bring it from its nasty low pH coming out of the stomach and bringing that chyme up to neutral and then also dumping in a whole bunch of other enzymes that can go to work to finish.

properly the process of digestion. So this is the intestinal phase. This is how you shut down the stomach and say enough's enough. You've done your job. Let's squirt some of this chyme out a little bit of a time and we'll let it out into the duodenum and we'll continue with the process.

This diagram here shows us a larger view here when food enters the stomach. There's actually a couple of what we call central reflexes, right? Central gastric reflexes.

That means these are long autonomic reflexes. And these are through the vagus nerve, cranial nerve 10. Remember, cranial nerve 10 is what fed the initial action potentials to the stomach. when you thought about food in the cephalic phase. All right, well, these long autonomic reflexes, this is what happens when food enters the stomach and causes distension of the stomach, right? That's the only trigger here is when the stomach gets extended outward because you filled it with something.

When that happens, that kicks off two different central reflexes. We have the gastroenteric reflex and look what here stimulates the motility and secretion along the entire small intestine all right so think about that meal that you've just taken into the stomach here you know the stomach is going to deal with that and then it's going to pass it out into the duodenum well there's probably food or whatever value still left in the small intestine from a previous meal. You know, this could be hours that that material is in the small intestine. So what happens is when you take a new meal in, there's a signal that goes out through this central reflex, the gastroenteric reflex, that tells the small intestine, all right, time's up.

I don't care what you got in there, but you better move that along because we have a new batch coming. So that stimulates motility and secretion along the entire small intestine that up regulates the activities of the small intestine so that you can make room for this new meal you just took in. The gastroilial reflex here, down below here, they show the ileocecal valve. That is another sphincter. So the pyloric sphincter controlled the emptying of the stomach.

The ileocecal valve right here controls the emptying of the small intestine into the colon, into the large intestine. So the gastroilial reflex here can trigger the opening of the ileocecal valve, allowing materials to pass from the small intestine to the large intestine. Again, if you take a big meal in, the gastroenteric reflex kicks the small intestine into high gear.

The gastroilial reflex says, well, I better open up here so this material can pass out. What's left over then becomes waste. It's going to be fecal material. And it just kind of makes the path ahead of this big kneel clear out.

Two central reflexes are kind of important. There's another reflex here. We talk about the emetic reflex, and that's the regurgitation reflex. So when you throw up, just to give you an idea, when whatever would cause this, there's a lot of things that would cause you to vomit. But something delightful to think about is with the emetic reflex, when you vomit, what happens is you get reverse peristalsis.

So that's the only example in the GI tract where you see peristalsis go towards the mouth. And it's not just the stomach. It's the duodenum, too. So what happens is when you throw up, the...

pyloric sphincter opens and you actually throw up from the duodenum, the deep portion of the duodenum, back through the stomach and out through the esophagus. It's not just stomach contents. You're getting that conditioned chyme there too.

It's nasty.

Transcript for:Digestive System Mod 8 Video 2

Transcript for:
Digestive System Mod 8 Video 2