hello and welcome back to part two of the chapter on gastrointestinal tract we had left off at the colon and we were picking up with things that go wrong with the disorders uh I'm in the interest of keeping this not too too long um I'm going to end up stopping in a weird place but um this way we can have two shorter sections all right so let's go with the disorders we'll start at the top with the esophagus one of the biggest things that we run into in the clinical setting is gastroesophageal reflux disease or bird the problem here is that the lower esophageal sphincter that is at the bottom end of the esophagus this doesn't close adequately for the amount of pressure that's going on in here and so the stomach which is very well protected against the very low PH that's here unfortunately some of the fluid that's in the stomach leaks up into the esophagus that is not prepared and it starts having an impact on the tissues here of the of the esophagus and so the acidic stomach contents don't successfully stay down in the stomach things that contribute to this problem are anything that's going to increase the pressure on the stomach like blind down after eating valsalva maneuver that's the pressing gas or bearing down just obesity having extra weight of the abdomen it's going to be pressing down on the stomach uh um pregnancy when there's something inhabiting the uterus it presses up on the stomach and that so often our pregnant patients suffer from this reflux uh the problem is this can damage the tissues here um it can lead to a stenosis it can lead to obstruction of the food passing through because of this difficulty because of the chronic inflammation in extreme cases it can lead to esophageal cancers adenocarcinoma that results from here secondary to GERD and then what we get is dysplasia if you'll remember way back when we were talking about cells and what happens there um remember dysplasia's growth of cells that are not quite right they're not being quite right so here um we would ordinarily have a certain kind of epithelial tissue and instead of looking like epithelial tissue from an esophagus it starts looking like epithelial tissue from an intestine which sounds like a great thing the body's trying I mean it's trying to accommodate you know I guess you know you want this acidic I guess we'll try to deal with that but it's not good you know it's it I mean it's a short-term solution um but it but it indicates that there's damage happening to this tissue and that damage so when you get that dysplasia it's referred to as Barrett esophagus and it's a pre it can be a precursor to the development of an esophageal cancer uh so the adenocarcinoma is the most common kind of esophageal cancer in this country in other countries the squamous cell carcinoma is more common um this gerd's not as big a problem in other countries hmm why is that I wonder um yeah I have hypotheses about that all right continuing with problems let's move on down a little bit lower we're in this stomach now it's this strong Hollow muscular organ its job is to mash things up secretions come from these gastric pits we'll see those in more detail in a moment what I want to tell you about this oh here it is um so we have the secretions by the by the parietal cells as we've mentioned that drops the stomach pH and let me remind you dropping pH means more acidic drop acid um can be as low as two so this activates so we so there's something called pepsinogen it's a precursor to this uh protease called this enzyme pepsin um so once the stomach pH is low enough that'll activate this thing called pepsin um and it will the the pepsin can start digesting some of the proteins um that very low PH also can digest some bacteria there is one famous bacterium that can survive it and we'll talk about that one separately but most bacteria are done away at this very low ph and as I've mentioned you make the pepsinogen which is the pepsin precursor you make mucus and the hormone gastrin gastrin was the signal to make hydrochloric acid to make more hydrochloric acid and make intrinsic factor and release those all right some more gastric glands and gastric pits all right so we're looking at the surface of the inside surface of the stomach there's lots of pits down here gastric pits what do we want to point out to you the parietal cells these are the ones that we're making the hydrochloric acid and making intrinsic factor so here we go parietal cells hydrochloric acid and intrinsic factor then we have the pepsic peptic cells they make pepsinogen that's the thing that's going to get activated to pepsin and then mucous cells and they make uh bicarbonate Rich mucus and you might say wait a minute wouldn't that neutralize the acid well kinda and you kind of want that because you want that mucus right on the surface of the stomach cells themselves and that's how the stomach cells are protected from this very low PH nobody can really tolerate this very low ph and so we have to have mechanisms to kind of try to protect uh the stomach so you're not pumping huge amounts of bicarbonate into the Lumen you're just making this very basic I don't know I think of it as like a salve you know that you're gonna smear on the inside of the the cells or the inside of the stomach on the cells that are lining the stomach um to keep the acid from touching them now we're going to look at this in some detail we're looking at a parietal cell this is a parietal cell it has the potential to secrete hydrochloric acid and it does that by pumping hydrogen ions also known as protons pumping those across the cell membrane at the same time that chloride ions are coming out a different hole and voila you have hydrochloric acid so there is that pump is called a hydrogen potassium atpase also known as a proton pump whenever I highlight things in yellow other than the page numbers the the highlighting in yellow I try to be consistent this is what I'm referring to a medication so this is where proton pump inhibitors act things like Omeprazole for example they block that proton pump so they inhibit the pumping of all this acid out into the stomach now there's a couple of other medications that can also be used here but you have to understand a little bit some a few other things to understand this so just another way of of getting the oh how to say this uh the proton pump activity is modulated it can be made to go more to stimulate it and it can be inhibited and the stimulation comes from acetylcholine that's parasympathetic nervous system stimulation the hormone gastrin we've mentioned this before and check it out histamine wait a minute we talked about histamine before we talked about it with mast cells what on Earth does it have to do here well histamine here stimulates acid secretion so there are receptors let me see if I can find it quick okay here there's a histamine receptor so when histamine binds here it causes more stimulation to make more acid that's another place for an inhibitor so the histamine the H2 receptor antagonist this is where they act they say don't stimulate the pump don't stimulate the proton pump and these are medications like famotidine all right so both of these act to make less acid um we'll have to come back to this but prostaglandins which we've also talked about before prostaglandins inhibit acid secretion so here's the prostaglandin there's a receptor for it and it says you can't see this very well but there's a negative sign here it basically says don't make a lot of acid so prostaglandins work against making acid foreign they are protective of the stomach and we'll get back to that all right so stomach protection from gastric acid as we've said uh we've got some cells that are making this very bicarbonate Rich mucus uh the um delay that mucous layer closely lines the stomach and then the gastric acid you still have to make it but it shoots out like a little jet through the mucous layer and so it remains on the Lumen side so most of that acid is actually not touching our own stomach cells and then prostaglandins as I've mentioned they reduce the acid secretion so they inhibit that proton pump they increase this very basic mucus I'm not going to go through the details there um but here's what I want to get to and that is when patients take medications that block prostaglandin production and why they would ever take medications like this we're talking about NSAIDs the non-steroidal anti-inflammatory drugs they're great they're great for pain relief because remember prostaglandins are the things that stimulate our pain receptors and say something hurts and so we cleverly say I'm going to take an NSAID so I'm going to uh decrease the production of these prostaglandins so I don't feel that pain the downside is if somebody's taking NSAIDs chronically they're taking it all the time every day all day every day they're they're reducing the amount of mucus that they're making to line the stomach and that's why NSAIDs are associated with the production or the the development of peptic ulcers uh it's not the intention you know we don't want it to have an impact on the stomach and this is true even if the person is taking an NSAID topically you know they don't even have to be taking it in through their mouths they can be absorbing it through their skin it's still going to inhibit prostaglandins and it's still going to have this impact on the gastrointestinal tract all right so that brings us to peptic ulcers so the most common sites for peptic ulcers um are the duodenum and the stomach well the stomach of course um but duodenate so think stomach and then a little bit below the stomach the duodenum the very first bit of the small intestine and then go up a little bit from the stomach and that's the the esophagus those are the places where you're likely to see peptic ulcers and it's mostly in the stomach and then blocking them The increased risk of peptic ulcers with Hyper acidity um smoking will do this because it reduces the gastric mucosal blood flow so you're not going to make as much mucus um reflux NSAIDs as I've already said here's a really important one most bacteria are toast in the stomach with one notable exception there's a bacterium called helicobacter pylori or just H pylori oh my gosh these things are so clever they have this mechanism where they can burrow into the mucus that very you know basic mucus that we have in our stomachs and they kind of protect themselves that way they also um it doesn't matter they have mechanisms that protect themselves from stomach acid that infection is the explanation for most of the peptic ulcers that we see many of the peptic ulcers that we see um so at least a chronic gastric inflammation this increases the risk of developing stomach cancer so when somebody has a peptic ulcer disease we have to manage the gerd um well if they have a h pylori infection you absolutely have to get rid of the H pylori infection that means being on antibiotics for an extended period and being on acid reducers for an extended period so we use histamine H2 blocking drugs the proton pump inhibitors as we've said and short-term antacids to just neutralize the acid in the stomach we're talking about tones things like that a different problem with the stomach is known as gastroparesis so paralysis of the stomach it's reduced motility and what leads to it is there's an alteration in the nervous system stimulation um one of the things that causes this and we haven't talked about diabetes very much yet we've mentioned it in passing um but we'll we'll talk about it in more detail at the end of the semester um basically the high blood sugar is really damaging to capillaries it's really damaging to the blood supply it's really damaging to the blood supply to the neurons and so the the nerves that are supposed to be stimulating the stomach to move things along after eating those neurons aren't working as well as they're supposed to because of the excess blood sugar problem one of the biggest problems if this is due to the diabetes is the patients who have this problem often dependent on insulin and so you you know you have to coordinate the intake of the food with the injection of the insulin to hopefully match the rise of the blood glucose with the you know the activity of the insulin and keep the blood sugar oh my gosh so you take the insulin the patient eats the food the insulin is still going to do its job but the food's just sitting in the stomach and so we have these huge crashes in blood sugar because it's really hard to coordinate the insulin with the food intake because this isn't predictable like when the stomach is finally going to move things along we don't know um and so this just it complicates the care of diabetic patients even more than it's already complicated and then sometimes we don't know why this happens and for some people it's after surgery but anyway if there's if there's insulin involved this just increases the complexity of caring for this patient um small intestine uh structures facilitate absorption I'm going to look forward a second okay a few more slides um all right so I've already mentioned there's a lot of surface area in the small intestines the Villi are these larger multicellular structures they've got their own blood supply in them and then what we call microvilli if you if you zoom in on one of the individual cells you've got these like ridges on the cells themselves those are the so-called microvilli and all together they're sometimes referred to as brush border because it looks like a you know a brush it's got multiple bristles it just increases the surface area it's available to contact the chyme I haven't used this word or maybe I've used it um it's a mixture of stuff that comes from the stomach and so the more surface area you have the more likely you are to be able to absorb nutrients from there speaking of nutrients um we'll talk about digestion of the the macro molecules but I'll mention here because yeah I'll mention here so you remember carbohydrates get broken down they're polysaccharides they get broken down to the individual monosaccharides mostly glucose and proteins get broken down to their subunits which are amino acids interestingly just like in the kidney remember we had the sodium potassium pump that all the cells have and they create that gradient we have more sodium on the outside and less on the inside and sodium is welcomed in welcomed back into the cell and then in the proximal convoluted tubule um we used that sodium could come in but it would bring along a glucose or it would bring along an amino acid oh my goodness exactly the same setup here this is that that nightclub situation so on the one side of the cell this is intestinal epithelial cell we've got the regular sodium potassium pump that's all the cells have that um but then on the apical side this is the side that's in contact with the food um that's where we have the secondary active transport so the sodium is being welcomed back in and it's bringing along here's the sodium being welcomed back in and it's bringing along a glucose or in a different transporter here's the sodium being welcomed back in and it's bringing along an amino acid with it foreign so fantastic the other point I want to make here is about oral drugs this is how you've taken medications um so a few different things can happen with oral medications they could if you're lucky you take them in they get absorbed and they get through both sides of the membrane and nothing nothing's changed they just come in unchanged um or um you absorb the drug it comes in and then it passes through it gets metabolized somehow and what you absorb into the bloodstream is some metabolized form of the drug the the drug gets in and then it's kicked right back and that is um not something that the pharmacological activity is happy about you want to be able to get the drug across and into the the person's bloodstream but it doesn't always work easily okay and then this is the last slide in this section um we can have malabsorption issues there can be a problem with taking stuff in the way it's supposed to be brought in and we'll talk about two of them on on this slide um one I alluded to in the reviews uh video and that is lactose intolerance I'll remind you lactose is a sugar a disaccharide it's got two sugars hooked together one of which is a galactose and the other one might be a glucose or fructose I can't remember but it doesn't matter it's too it's two monosaccharides hooked together um the deal is all of us as infants have an enzyme called lactase and its job is to break apart these two sugars from each other and as infants every human being we've got this I shouldn't say every most human beings have this some of us retain that lactase activity after childhood and some of us don't and those of us who don't retain that activity are known as lactose intolerant and so you can consume the dairy product that has the lactose in it but lacking this enzyme lactase we don't have the ability to break those two sugars apart and we also don't have the ability to die to absorb this two sugar unit we can't bring it across the cell it can't come in through the brush border um and so that lactose remains in the lumen if you know this sugars are very attractive to water so the water remains in the lumen and that leads to the so-called osmotic diarrhea because we have this undigested sugar and it's just staying in the Lumen we are feeding the microbes further along in the digestive tract they produce gases that's where the bloating comes from and so yeah so this malabsorption problem can lead to this osmotic diarrhea problem foreign but also related to malabsorption is vitamin B12 deficiency and we've addressed this before when again when we were talking about red blood cell production the absorption of vitamin B12 absolutely depends on the production of intrinsic factor in the stomach the parietal cells of the stomach have to make intrinsic factor and somewhere between the stomach and the ilium the B12 an intrinsic factor need to bind to each other so that in the ilium that complex can be brought in can be brought across this brush border and into the cells and so a B12 deficiency can result from a malabsorption either because we're missing the receptors or in fact we may be missing a whole section of small intestine because of surgery surgical resection due to cancer or some other reason or there's not enough intrinsic factor being made either because of gastrectomy or because of an autoimmune problem the point is there's no intrinsic factor so even though the person may be consuming B12 they can't absorb it and that leads to the B12 deficiency and this needs to be remedied usually with injections of B12 and that is the end of this section of the lecture see you in part three