Greetings, today, we're going to start our discussion of the gastrointestinal tract or I'll call it the GI tract. This is the tract that enables us to bring nutrients, electrolytes, and water into the body. So we're moving it from our external environment to the inside of the body and then into the bloodstream for delivery to all the cells of the body. So, how does this thing work? So, the GI tract is a tube which is about five metres in length and this tube has an opening at the top which is your mouth and that's what's shown here. So here is the mouth and at the end of the tube we have the anus. And the tube is going to allow then food materials to be coming in to the mouth from your diet and these are going to be complex foods such as steak and potatoes. And we need to convert this steak and potatoes into simple molecules which can be used by the cells of the body for fuel. So we want to be able to convert then, the steak and the potatoes into amino acids and into simple sugars. This is done by the gastrointestinal tract and sort of acts like a processing plant. So the first thing that happens is that these complex food materials enter through the mouth, and as they enter into the mouth, then we chew on them and break them down into smaller and smaller particles. This increases the surface area of the particle and allows them for attack by enzymes. So we're increasing the surface area and this material then is very rapidly going to be transmitted from the oral cavity, through the esophagus which is essentially a tube, down to the stomach. Once we reach the stomach, once we're in the stomach, then we're going to start the process of digestion. And this is going to be converting the complex materials such as a steak into polypeptides, and then from polypeptides into amino acids. Digestion is going to occur within the stomach, but it's also going to occur within the next region, which is called the small intestine. And in the small intestine we will further break down this particles to very simple molecule such as glucose and amino acids. And then we're going to absorb these things, these small molecules across the epithelial cells which are lining these tube and entering into the body. Material that's left over is going to be released from the anus as a fecal material. So this is going to be the waste products that cannot be used by the body. In a typical day you take in something like a liter to two liters of solids as well as fluids in a given meal. And as it passes through the GI tract you will add about seven liters of secretions which can be acids, it can be buffers, and it can be enzymes. And as it moves through the small intestines then, we could have as much as nine liters of fluid. But most of this fluid is going to be reabsorbed as it's moving through the small intestine and so that we end up with fecal matter which is only about 200 to 500 millilitres. And the rest of the material then will be reabsorbed as we're moving through the small intestine and into the large intestine. So that means that along this tract, we're going to have regions that'll have specific functions. And we're going to want to be moving our material in a unidirectional manner. So we start at the mouth and we're going to be moving towards the anus. And this unidirectional manner is going to be due to smooth muscle contraction which is propelling the bolus of food and food stuffs through the tract. In addition to having the GI tract itself or GI tract proper, we have other organs which are going to help in this process, in this processing of food. The first of this is the salivary gland, the salivary gland secretes saliva which moistens the food particle as it's coming into the mouth and as we're chewing. And then allows then for the food particles to easily slide down the esophagus to the stomach. The second is that we have the liver and we have the pancreas and these two organs are going to be secreting materials which are going to aid in the digestion of the food stuffs within the GI tract itself. And that's going to be predominately within the small intestine. As we're moving down this tract, we have specific sphincters which are gating the entry and exit from the tract. And these at the top, we have a voluntary sphincter which is for swallowing, and at the bottom we have a voluntary sphincter, which is for avoiding the feces under our control. So we have skeletal muscle sphincters at the top and at the bottom of the tube. There are also sphincters within different regions of this tube, which are smooth muscle sphincters, these are under involuntary control. And the smooth muscle sphincter, for instance, resides here as we're moving from the esophagus into the stomach, and then from the stomach as we're moving from the stomach into the beginning of the small intestine which is the duodenum. And then again we have an involuntary sphincter as we're moving them from one region of the colon to the anus. So the tract then is going to be this movement of food materials along the tract, and as it's moving along the tract, we're going to be changing the actual structure of these materials and then absorbing the materials. And so that at the end we have waste product, which is not useful to the body and that will be what's expelled from the body. So let's look a little bit more at the anatomy of the GI tract itself. So I told you that the tube is a muscular tube, on the outermost regions of the tube we have two layers of muscle, and that's what's diagramed here. The inner layer, which is here, the innermost layer of this muscle is called the muscularis externus. This muscle, this smooth muscle is oriented extra conferentially around the lumen. So when it contracts then it's going to make the diameter of the tube smaller. Conversely, if it relaxes, it will make the diameter of the tube larger, so it's governing, then, the diameter of the tube. The muscle, which is present on the outermost layer, the muscularis externis, then this muscle is oriented along the long axis of the tube. When it shortens, we're going to shorten the tube and this is going to allow for a peristaltic movement of the bolus of food as it moves down the tract. Sort of a milking kind of an action, as it moves down the tract. On the inner most aspect of the tube, this is a lumen and the lumen is obviously where the food particles are first delivered. And surrounding that lumen we have an epithelium, this is simple layer of cells. At the top of the tract there is multiple layers of cells which are very flat and very much like what you see on your skin. This is a wear and tear surface because we're it's for abrasion. We're having food materials coming in which can be a bit rough and it's simply a conduit from the mouth down to the esophagus, down to the stomach. And so within the esophagus, we have this wear and tear epithelium, no absorption, and no secretion. We had a similar type of epithelium on the anus. So wear and tear at the top of the tube and wear and tear epithelium at the bottom of the tube. In the stomach, the epithelium is a single layer of cells and these cells are going to be secretory and we'll talk about what they're secreting in just a second. And then as we move into the small intestine, in the small intestine the cells are also a single layer of cells, but here we have an absorptive function. So we're moving the small particles which we have generated in the lumen of the track, across these cells and into the body. So the first part of the tract that I want to talk about today is going to be the stomach and we're going to talk about what secretions the stomach makes and how it starts the process of digestion. And the next time we come in we'll talk about how this process is actually regulated. So the stomach has essentially three types of cells, and the major portion of the stomach. The major portion of the stomach is called the fundic, the fundic region of the stomach. Here, the cells which are on the very surface, which are facing the lumen, are called surface cells. And then going down into the glands, into the invaginations, so it looks like this, so these would be our surface cells. And then going into the invagination which is the gland, we will have the neck cells. So these epithelial cells are lining these surfaces, looks like this. The surface cells and the neck cells are secreting mucus. This is a complex carbohydrate containing material, which is a protective coating which is going to prevent the acid, which is generated by the stomach from eroding through this epithelial layer. The second type of cell is called the parietal cell and the parietal cells are located also within the grands themselves. The parietal cells have two major functions, one is they make HCL they make this acid which is going to starting the digestion of protein. And secondly, they make a factor which is called intrinsic factor, this is a carrier and this carrier bonds vitamin B12 which in the human must come from the diet. So you cannot make this vitamin and the vitamin is absolutely necessary for making red blood cells. Vitamin B12 comes in from the diet, it binds to this intrinsic factor, this carrier and then it passes through the small intestine to the distal region of the small intestine which is called the ileum. And in the ileum, that carrier then has the receptor, and so the vitamin B12 can move across those cells, across the ileum epithelial cells, and the vitamin B12 is now entering into the body. In the absence of intrinsic factor, the individual will have profound anemia. So it has pernicious anemia and this anemia simply means you can't make these red blood cells and so you will have a lower oxygen carrying capacity within the body. The third type of cell which is present within this region of the stomach is called the chief cells, and the chief cells sit down here in the very base of the glands. The chief cells secrete what's called pepsinogen, pepsinogen is an inactive enzyme which is called pepsin. Anything that has an ogen on the end of is an inactive enzyme, these are classified as zymogens. So they're inactive enzymes and we'll talk about inactive enzyme more when we talk about the pancreas. So this is an inactive enzyme pepsin, pepsinogen, which when it is secreted and into the lumen of the stomach, the pepsinogen in the presence of acid is converted to pepsin. And that requires HCL, so we have to have a very acidic condition for this enzyme to become activated. The pepsin starts to break down protein into polypeptides, so we're starting our digestion of protein with this enzyme. Now because the secretion of acid is so important, I want to spend some time talking about it. So the secretion of gastric acid is done by the parietal cells, so these are our parietal cells. And we're still in the stomach in that fundic region of the stomach. I've drawn here a parietal cell, where the lumen of the stomach is on this side, and the blood portion of the cells are facing, the basal portion of the cell is facing the blood on this side. So the apical portion faces the lumen and that basal side is facing the blood, so we have a capillary that's running right here. Now these cells are going to use a reaction which is dependent on carbonic anhydrase to generate protons. And these protons are what's going to be then moved into the lumen of the stomach and that's going to give us our acid. So the enzyme is able to take carbon dioxide, which comes from the blood, it passes across the plasma membrane of these cells, and it reacts with water in the presence of carbonic anhydrase and we get bicarbonate and we get a proton. The proton is going to be extruded from the cells into the lumen by a pump. So this is going to be an ATPase, and this particular ATPase is a hydrogen-potassium ATPase. And it's so important that it has another name and we call that the proton pump. The bicarbonate which came from our carbonic anhydrase reaction, the bicarbonate shown here, is extruded from the cells and enters into the blood in exchange for chloride. So we use an antiporter to move bicarbonate out of the cells and chloride into the cells. The chloride will diffuse across the cells and leave the cells to enter into the lumen of the stomach. So we now have chloride and hydrogen within the lumen of the stomach and so we've just generated hydrochloric acid In order to keep the proton pump active, we have to have potassium and this potassium is being furnished by the sodium-potassium ATPase, which is sitting in on the basal surface of these cells. Potassium comes into the cells from the blood, potassium will then be extruded from the cell through the lead channel and then potassium is used by the pump to get potassium into the cell and the proton out of the cell and into the lumen. The pH of this region can get as low as pH 2.0 and pH as you recall, is the logarithmic scale for free hydrogen ions. So, this is extremely concentrated, very strong acid. So, this is a very, very acidic condition. Acid is made by the stomach under two conditions. One is in the fed state, we increase the amount of acid that's going to be made. So our acid secretion, so if we have a food coming into the body at this point acid secretion will increase rapidly. So the cells are sensing that the food is present and they're going to be making a lot of HCL. And by 19 minutes after eating, we have a peak of secretion of acid within the stomach, within this region of the stomach. And then, the peak acid output drops by four hours after a meal, then the peak acids secretion drops and we are making a basal amount of acid within this region. If you know this, the pH of the area is changing as well. So pH is our free proton, and initially we have a movement from a very acidic condition that has a pH of two up towards a pH of five. So we're going toward a basic condition and that's due to the protons binding to the food materials which are coming into the stomach lumen. So the food is buffering the free proton and eventually, the amount of food that's within the stomach is leaving the stomach slowly to enter into the small intestine. And as it leaves the stomach, then the amount of free proton increases, and our pH then falls. Such that by two hours after feeding, to four hours after feeding, we have again, a very low pH within the lumen. So the next time we come in here we're going to talk about how we're going to control turning on the production of acid when we have food coming into the body, and how we turn off the production of acid when we don't need very high amounts of acid because the stomach is empty. So the general concepts are the gastrointestinal tract is a muscular tube in which nutrients are going to move in an unidirectional manner from mouth to anus. Secondly, we have regional specializations along this tract, which enable fragmentation of the food particles so we make them smaller, we have larger surface areas. Digestion we break the particles from complex proteins into polypeptides, and then change into amino acids. And then the absorption of nutrients, so we can absorb the amino acids across the epithelium that's lining the tract and allow them to enter the body. Third, acids will be secreted by the parietal cells of the stomach and this is in a specific region of the stomach called the fundic stomach. And that this process requires carbonic anhydrase activity to generate the proton and the bicarbonate. And it's generated from water and CO2, which is being delivered to these cells by the blood. The protons are secreted into the stomach lumen by a hydrogen potassium ATPase, and this is our proton pump. Bicarbonate is secreted in to the blood in exchange for chloride ions and as the chloride enters, it crosses the cells and then it's transferred by diffusion across the membrane, facilitated diffusion into the lumen, and then we generate hydrochloric acid. And fourth, the acid secretion can be increased in our fed states and is decreased in the fasted states. And the regulation of moving from a high acid secretion to a lower acid secretion, that regulation requires several factors and we'll talk about that next time you come in here. So see you at that time, bye bye.
