hello and welcome back to part three of the chapter on the gastrointestinal tract we had just finished off uh part two uh talking about some malabsorption issues and we are going to continue um again related to the malabsorption in order to absorb any of the macromolecules the the proteins the lipids the carbohydrates we need to digest them first so to put it in simpler terms digestion means to cut up those larger macromolecules into the subunits and the subunits we can absorb we can bring those into the cells if we cannot break them up we can't digest them we cannot absorb them uh so let's now talk about uh the organ that helps us with this the most and that is the pancreas um the pancreas Works in a few different ways and one of the ways it works is it is as an exocrine gland exocrine usually usually we think of that about that as like secreting to the outside um and this is a little bit confusing but it's secreting onto an epithelial surface and if you remember the the the the tube that goes through us from mouth to anus that's Hollow tube and what's in there is like being inside the whole of the donut it's inside but it's not really inside so when this secretes onto the surface of the small intestine it's secreting to the outside of us if you will and onto an epithelial surface um and there are multiple safeguards against Auto digestion the the pancreas like digesting itself with these enzymes uh you know spoiler alert it still happens um but there are several mechanisms that can back they they don't work as well as they need to um so some of these safeguards are this um production of zymogens this term means um it's an enzyme but it's not completely in its final shape it's an enzyme precursor sometimes you'll call the you'll hear these called Pro enzymes it just means like they're they're gonna be enzymes but they're not there yet and then um the the pancreas packages these zymogens into granules kind of little pods um in the interest of having it not digest the pancreatic gland cells and on top of that the pancreatic cells produce a protease inhibitor just in case any of these get activated there's a mechanism to turn it off so the way it's supposed to happen is the pancreatic enzymes are supposed to go into the gut Lumen that is the inside of the small intestine then they get cleaved they get cut or activated by kinase that's an enzyme that's going to activate something and Tarot meaning it's in the digestive system it's in the it's in the cells of the digestive system it's supposed to activate these enzymes and the different enzymes digest different things so the proteins remember proteins are made of amino acids lots of different you know the 20 different amino acids and so the enzymes that digest those are called proteases and there's a bunch of them because the amino acids are shaped differently from each other the the different R groups are shaped differently and so not the same pair of scissors will work between each of the different amino acids and so that's why the different proteases are necessary they're like different specialized scissors for cutting the different amino acids apart then carbohydrates are a lot simpler they're just you know mostly with starch and it's mostly glucose hooked together the same way every time and so the enzymes that digest starches are amylase and we make amylase in our mouth salivary amylase and the pancreas also makes it so it's called pancreatic amylase and it just it cuts up the the sugars apart from each other and then finally the light Paces these are for digesting the lipids um so we have to cut those fatty acid Tails apart from the glycerol molecule and in addition to these enzymes the pancreas is also making fluid that's rich in bicarbonate and that is again to neutralize that very acidic stuff that's coming out of the stomach and it's supposed to protect the duodenum that very first part of the small intestine foreign sometimes things go wrong and the pancreas is affected by these enzymes and it leads to inflammation of the pancreas or pancreatitis acute pancreatitis can be caused by gallstones now gallstones are structures in the gallbladder which is associated with liver but we'll talk a little bit next week about how this happens um excessive use of alcohol again can be irritating to the pancreas and some drug reactions can can lead to this problem what happens is we're increasing inflammation an oxidant uh stress um here's what's important is we're destabilizing the the zymogen granules those things that have the enzyme precursors in them that releases and activates the enzymes the enzymes are going to start acting on whatever proteins available whatever lipids are available and whatever carbohydrates are available but the most important part is the the proteases they're going to just start chopping up the cells um and so that's how these pancreatic cells get damaged and ultimately get the get killed uh what do we need to deal with with pancreatitis if we're diagnosing there's a blood test that we can do for those enzymes so I mentioned there's amylases for digesting carbs there's proteases for digesting proteins and there's lipid lipases for digesting lipids we look for amylases and lipases because there are other proteases that you might find in the blood but there's no reason that we should ever have amylases or lipases in the blood except that they're leaking out of the pancreas and it's leaking out because the pancreas is damaged this is an extremely painful condition um and so we unfortunately manage the pain of the patient it can perceive the critical illness and having repeated episodes of acute pancreatitis makes the patient more likely to develop chronic pancreatitis hmm let's go back to a disorder that we have talked about before cystic fibrosis where we've dealt with it before has been with respirations uh we talked about it first when we're talking about genetic disorders um and you actually in your first case study questions that you had to deal with you know what exactly is going wrong um and so it's coming back um so this cftr transporter that's the cystic fibrosis trans men brain I don't remember what the r stands for anyway um that protein um is defective and it's not moving the chloride properly well the same consequences that we had in the lungs we're having now um because it's the muc this Transporters and the mucus producing cells and so the mucus it's going to be made is going to be really thick and it's going to block the pancreatic duct so the enzymes are still being made inside the pancreas here inside the pancreas and it's supposed to be delivered through these ducts here into the duodenum but these ducks get blocked in the pancreas and the the stuff can't move and it ends up becoming the enzymes become activated inside the pancreas and it starts to to digest the pancreas even if they don't get activated you're still not getting them into the small intestine when you're supposed to get them and so what ends up happening to these patients with cystic fibrosis is they have a limitation they can eat just fine they can eat the protein they can eat the carbs they can eat the lipids they can't digest them because they don't have the enzymes getting to the gut at the right time and so these patients have to take oral uh enzymes when they when they when they have their meals this is going to be especially important during childhood during the growth periods um often our sister our patients who are adults now um who survive a childhood with cystic fibrosis they tend to be smaller than other members of their family it doesn't make them miniature or anything but they they don't get to full grown as full grown as they could have been had they been able to get the nutrients that they needed when they were younger now there are some much much better treatments for Cystic Fibrosis or some of the kids who would have been smaller are catching up in their growth and if you're interested about that I'm going to drop a question in the discussion board but yeah this is really important so with somebody who has chronic pancreatitis or they have cystic fibrosis and they're not able uh to make to get the enzymes in the right place they have trouble growing during childhood but then even in adulthood they have trouble maintaining weight because they can't get all the nutrients out of the food that that they need so they're not able to maintain their muscle mass for example all right principles of gut digestion and absorption we've been over this uh the nutrients get absorbed mostly in the small intestine and mostly in the duodenum and jejunum and as we've gone over this is reviewed in detail in that um review video the carbs get broken down to individual sugars called monosaccharides mostly it's glucose proteins get broken down to individual amino acids 20 different ones and the lipids are the kind of complicated story there's different kinds of lipids triglycerides are the most common ones with the Three fatty acid tails and we have to separate we have to take those fatty acid tails off and the phospholipids there's two fatty acid tails and the thumb phospho part and to you know take these things apart and then cholesterol Esters there's the cholesterol that's that four ring structures and then there's usually a fat one fatty acid tail on that and that has to get cut off and then if you can cut these things right that's the stuff that can be absorbed that's the stuff can that can be brought across into the cell foreign dietary starch carbs the term hydrolysis it means breaking down lysis cutting or splitting and hydro it doesn't matter but you need a hydrogen and an oxygen and a hydrogen to to split the thing apart um so the enzyme is amylase um the the two sugar units um get split apart by enzymes that are like in place in that brush border and so for example sucrose um table sugar that gets taken apart by sucrase which is in the brush border and same with the lactose gets taken apart by lactase if the patient has lactase and then the monosaccharides get taken in and check it out remember the sglt2 transporter and the kidney well here's the SG sglt1 transporter and it's working the same way the glucose and the sodium remember this is in the Club come on in friend come with me and so we transport it that way same deal with the proteins we have to hydrolyze the the protein but break it up with the proteases and there's lots of different kinds of proteases um break it up to individual amino acids that's what can get transported and it was I guess it's not on this diagram um but you transport the individual amino acids this way too and then here's the complicated story The lipid digestion it's a multi-step process because we're talking about fats these are nonpolar it's mostly carbons and hydrogens they bond they share the electrons equally so they're they're bonds are not polar bonds they're non-polar bonds and so there's no difference there's no poles there's no positive and negative charges so they do not interact well with the water the aqueous solution that the water is polar and so what ends up happening is the nonpolar fat they want to climb onto each other and make this great giant bubble well that's what the bile salts are about um the bile salts have hydrophobic side and they have a hydrophilic side a nonpolar and a polar side and so they can break up these droplets into these my seals these these tiny little droplets and by breaking things up this way we can get the digestive enzymes lipase and colipase to like digest the stuff cut it apart so that we can absorb it um this is oh oh in case you come across this term again amphipathic that means having two Natures um amphi like amphibian which has part of its life cycle in the water and part of its life cycle on land or like Amphitheater partly enclosed partly Outdoors um so amphipathic means polar and nonpolar that's what the bile salts are for it's busting up those big balls of fat so that we can get our enzymes in here to digest that fat this is an absolutely minor note but I thought might be of interest to you um there's a medication that's not popular at all uh called oralistat and it goes by the names Ally and xenical um its job this medication blocks the action of lipase enzymes and so because it interferes with the enzyme that's supposed to break up the fat it makes it impossible for us to absorb the fat because we can't absorb what we cannot digest so we can't cut it you can't absorb it um and so fat gets consumed and then passes right through the digestive system it was supposed to be this great medication to help people with weight loss they can still eat their potato chips but then they wouldn't absorb sorry the problem is if you don't absorb the fat then the fat stays in the stool and you end up with fat in the stool scatteria which makes the stool very oily and may make the patient prone to anal leakage that was the polite way of saying the problem so stuff will come out of the digestive system it's more liquid and it's harder to keep the stool in all right so my point about that is I want you to really appreciate that what the light Paces what these enzymes do they have to break up the molecules if they don't break up the molecules we cannot absorb them we cannot bring them into our cells and use them for anything um all right so the bile salts they bring the um the fat digestion products to the brush border and that can get absorbed as soon as it gets into the cell once it's across the cell membrane then you regenerate the thing you regenerate the triglycerides you regenerate the phospholipid remake the cholesterol and pass it along it's just getting it across the cell membrane that's why you have to bust it up that's why you have to digest it first all right so that's the end of the macronutrient absorption now we're getting to the micronutrients and on this slide we're just covering uh some of the vitamins and specifically iron absorption the fat soluble vitamins are pretty easy those get absorbed with fat if the person doesn't have enough fat in their diet they're not going to be able to absorb the fat soluble vitamins those are a deck vitamins a d e and K um let's see if somebody has a deficiency in any of these of the vitamin D that's going to interfere if you don't have vitamin D you're not going to be able to absorb calcium if you don't have vitamin K that's going to interfere with uh production of clotting factors um then let's go to the water soluble vitamins some of the bees most of the B vitamins and vitamin C those are the water soluble ones and when I say most of them because remember vitamin B12 is that little special case um it has to bind to intrinsic factor so that it can be absorbed as a complex and then iron is the one mineral we're going to talk about this one is just poorly absorbed we're just not good at it no matter how good we are at it the best we do is maybe 10 of what we consume we're able to absorb iron I'll remind you iron is really hard on the body and so we don't Let It Go by itself it has to be bound to a protein to be taken anywhere and so we have to bind it to transfer in for its trip from the goat from the gut um to the bone marrow which is where we need most of it for making the red blood cells for making the hemoglobin so we bind it to transfer and for that trip to the bone marrow or if it's going to be taken to the liver for storage because we for whatever reason we have an excessive of iron then it gets taken to the liver and it gets stored in that big ferritin molecule with hundreds of other iron atoms uh moving on into other disorders diarrhea this is excessive fluid excretion with the feces children are especially at risk for dehydration adults are too but children especially because there's so little they don't have very big reserves of fluid and so dehydration really does a number on kids um even more than it does on adults there's lots of different mechanisms that can lead to diarrhea here are the big four first one is secretory that means that we are pushing water out into the the Lumen into the the gastrointestinal tract this can happen with infections like for example with cholera the the toxins of the bacterium cause the human body to push water out into the gut and that's no matter how hard our our large intestine is trying to pull water back in it it gets overwhelmed and we just lose lots and lots and lots of water with just very watery diarrhea um and that's the case with cholera as well as with some other bacterial infections then the problem may not be an infection it may be a malabsorption problem um and why that would happen is if we lose the gut surface area for example remember we have the the Villi and then on top of that the microbilay on the individual cells we lose a lot of that um surface like it kind of gets smoothed out um when there are autoimmune problems like for example with silly celiac disease a patient who has celiac disease is sensitive to the proteins in in some plants gluten um and the the immune system is attacking the cells because you know the the the breakdown products of gluten are present and the immune system attacks that as if it's some kind of threat and it ends up damaging the brush border well if you lose the brush border you lose the ability to absorb nutrients and you lose the ability to absorb water and so the patients end up with this watery diarrhea there's osmotic diarrhea as in for example uh those people who are lactose intolerant the the lactose sugar stays undigested so we can't absorb it stays in the gut that draws water into the gut leading to osmotic diarrhea foreign ly inflammatory bowel diseases again they they end up with a loss of gut surface area there's persistent inflammation and we're not able to reabsorb enough of the water and so managing the patient's fluid balance is an important part of managing these diseases let's talk about we're going to talk about three immune-based gut disorders the first one we'll mention is celiac disease so the immune protections that are supposed to be there to protect us from infection end up attacking our own cells because individuals who have celiac disease are sensitive to this partial digestion of gluten that that protein gluten starts being broken down and the products that are produced are are identified as if they are a threat and the immune system goes after them and so in the absence of that of that those protein products the patient's fine there is no autoimmune problem it's just when the patient consumes food that has those proteins in it that's when the problem comes up I would love to go into this in more detail I have a personal story about this and um almost losing a parent to this condition before finally somebody said she doesn't have cancer she should stop eating bread and unbelievable but uh yeah I'll tell you my mom was in the hospital I was 12 years old I had no idea how bad things were um but my dad had the conversation with my brother about your mom may not be coming home and it turns out it was this um and I I'm amazed sometimes when when we don't identify that a GI problem is as simple as change the diet fix the problem going to the fundamental thing that is causing the patient to to react to something all right I'll get on my soapbox again when we talk about diabetes let's talk about inflammatory bowel disease um again this was an autoimmune problem um the immune system should not be attacking the body and yet it does um and here are the two two major presentations of inflammatory bowel diseases Crohn's disease um this one like with many autoimmune disorders the problems come and they go remitting relapsing and remitting abdominal pain with diarrhea the with crohn's disease it could be anywhere from the mouth to the anus anywhere along that course the auto the immune system can be attacking the cells um because the the lesions occur here and here in spots like this they're referred to as skipped lesions um there can be uh lesions all the way through transmural means all through the walls all through those different layers um remember we covered the different layers starting at the um for what we went to the from the outside in all the different layers can be eaten away um with the with the immune system this can lead to fistulas uh connections between two Loops of intestine for example this can complicate the care of patients A variation on this is ulcerative colitis this one it it's limited to the colon um but unlike this with the skip lesions it often will affect larger areas of of the colon um only extends to the some submucosa but there's a lot more blood loss than what we see with crohn's disease um and these disorders are managed with immunosuppressive drugs steroids Etc to keep the immune system knocked down and then our last slide here um there are multiple kinds of GI cancers as we've mentioned there's esophageal cancer that can do stomach cancers there can be cancers in the small intestine but uh colorectal cancers are the most common kind of GI cancers I mean of all the cancers is the fourth most common in the U.S thank you screenings for colorectal cancers are done annually for occult blood what you're looking for is the presence of iron in the stool that's why patients can't have taken an iron supplement before doing this test but then especially by the age of 50 but earlier if if there's a family history of of colorectal cancers the patients are recommended to have colonoscopies now they don't have to be done all the time um but every 10 at least every 10 years um until the age of 75 or sometimes 80. and and again this goes back to the you know yes the cancers are more common as we get older but they're slower growing and the patients may not do very well with some of the treatments that are available for colorectal cancers later in their lives okay and that is all we have time for so that's the end of the chapter on the GI tract hope you have a great week