KINE 451 - Gastric Emptying, Digestion, and Absorption

Hello and welcome back. Now that we have talked about how different nutrients are specifically used as fuel during exercise, we can start to dive a little bit more into the nitty-gritty of how those nutrients get to where they're going so that they can be metabolized. In order to do that, we need to talk about three essential processes and the anatomical locations and physiological processes that underlie gastric emptying, digestion, and absorption.

First, let's begin by defining some key terms and identifying some structures. The first and most important term that we need to establish is the gastrointestinal tract. Now, when we're referring to the gastrointestinal tract, which you can see depicted anatomically in the graphic on the right side of the slide, we're referring to a long tubular structure. The purpose of this long tubular structure is to provide the body with nutrients, water, and electrolytes. This structure and system includes several anatomical locations and organs; specifically, ones that play really big roles in either digestion or absorption or both are the mouth, the esophagus, the stomach, the small intestine, and the large intestine.

Now, in conjunction with all of these organs, there are several accessory digestive glands that also participate in this process. You can see some of these depicted here: the salivary glands, the gallbladder, the liver, and the pancreas. All contribute in some accessory fashion to these processes that go on in the gastrointestinal tract.

Now, one of the most essential processes that has to occur in order for nutrients to be delivered is that the food that is ingested has to evacuate from the stomach into the small intestine. That process of the emptying of stomach contents into the small intestine, specifically in the duodenum, which is this initial portion of the small intestine, is known as gastric emptying. The second essential process that has to occur is digestion. When we are referring to digestion, remember that the foods that we ingest are oftentimes made up of several different types of nutrients that need to be broken down into individual smaller units so that those nutrients can ultimately be absorbed. And, of course, when we're referring to absorption, once these nutrients have been digested, they'll be in the intestine—specifically, the small intestine is where the majority of this process occurs. The process of absorption involves transporting these nutrients from the intestine either into the bloodstream, in the case of certain nutrients, or the lymphatic system, or the lymph—the lymph system. So, depending upon the nutrient and even the subclass of nutrient in some cases, how these nutrients are absorbed so that they can then be delivered is going to be slightly different. We'll talk about all three of these processes in detail over the course of this lecture, as well as where the digestion and absorption of our key energy-yielding nutrients are occurring in the gastrointestinal tract.

All of this begins in the mouth, and it begins immediately as soon as we start eating a piece of food or drinking something that has energy-yielding nutrients in it. There are three specific roles that the mouth plays. The first is simply mastication, or chewing, which serves the function of reducing the size of food particles. Now, why is this important? Well, A, it's going to be easier to swallow, and we're not going to choke; but in terms of the function and in terms of digestive function, this is going to help increase the rate of gastric emptying, or the rate at which food can be emptied from the stomach into the small intestine. This is logical because if you think about it, smaller particles are going to have an easier time getting from point A to point B than larger particles are.

The second related role that the mouth plays is that it increases the surface area of foods. So, through this process of mastication and mechanical reduction of the size of food particles, by doing that we are also exposing a greater area of the food surface so that there's more contact area for some of our digestive enzymes. Now, some of those digestive enzymes actually begin taking their action in the mouth. Those food particles that are reduced in size by the process of mastication are also mixed with saliva, which contains certain digestive enzymes that begin the process of breaking down food into nutrients. These enzymes and saliva come from three different glands that are all connected to the mouth, and we can see those glands depicted here. We have the parotid gland, which feeds saliva into the mouth through the paratha duct. We have the sublingual glands, which are located underneath of the tongue, um, and again they also empty saliva into the mouth and share a common duct with the submandibular glands. So, all three of these glands serve to mix the food particles that are masticated in the mouth with saliva and expose these food particles to some of the digestive enzymes, which will allow them to begin being broken down into smaller units for further digestion and absorption.

The next step is to start moving these food particles down towards the stomach, and we do this via the esophagus. Now, the esophagus is a tubular structure made of smooth muscle cells, and those smooth muscle cells actually contract in order to move these food particles down the esophagus and ultimately into the stomach. So, this is not a passive process; it's not that we eat food and then we voluntarily try to swallow and it just falls down through this esophageal chute into the stomach. It's actually an active process that's facilitated by the contraction of smooth muscle. This is intuitive design because if we were to put you in space and remove gravity, or we were to put you in a position where you were hanging upside down, you would still be able to swallow and still be able to move food particles from the mouth down into the stomach. So that's the first role of the esophagus. The second role of the esophagus is to allow food into the stomach. The esophagus does this via a specific part of the esophagus known as the esophageal sphincter. When that sphincter relaxes, it lets foods into the stomach; so it increases the diameter that those food particles are able to move through. So, when this esophageal sphincter is relaxed, more food and fluid will be able to flow into the stomach. When this esophageal sphincter is contracted, well, then that's going to prevent foods and fluids from entering, but also more importantly, it's going to prevent the reflux of some of these foods and fluids back into the esophagus. This is important because, as we'll mention when we talk about what goes on in the stomach, some of the secretions that enter the stomach that aid in the process of digestion and absorption are quite acidic, and therefore we don't want them to reflux or leak back downstream into the esophagus. This is a classic hallmark symptom of heartburn, and the cause, again, is these acids from the stomach being secreted back into the esophagus, into a region where lower pH is going to cause some discomforts.

Now, once food makes it into the stomach, it's stored there until it can be accommodated in the small intestine. While it's being stored in the stomach, there's some further digestion that is going on for some of our key nutrients. And primarily, one of the things that contributes to this is there are more gastric secretions—a gastric secretion being something that is actually secreted by the stomach itself, um, from either the body of the stomach, um, or the antrum of the stomach. We'll talk a little bit more about specific gastric secretions and their role in digestion later on in the lecture, um, but primarily what this mixing creates is this homogeneous, um, acidic—so one of the things that makes it acidic, and the one that's the most important for us to talk about, is the secretion of hydrochloric acid. This is going to be the primary reason why we don't want things to reflux back into the esophagus. But these food particles are going to mix with this homogenous acidic secretion to form a paste known as chyme. As you can imagine, this liquid paste is going to facilitate the rate of gastric emptying and facilitate the movement of chyme to the small intestine where it can begin to undergo further digestion as well as absorption. Now, again, remember that we can only take enough food, um, or take a threshold amount of food that the do—that the small intestine is able to accommodate. So, we need to regulate how this chyme is emptied into the duodenum of the small intestine. This is regulated by the relaxation and contraction of the pyloric sphincter. So, the pyloric sphincter is the gate between the stomach and the small intestine, and in a similar fashion to the esophageal sphincter, when it relaxes, it's going to allow more food or fluids or chyme to—to move into the small intestine, and when it contracts, it's going to limit the entry of substances into the small intestine. We're going to talk about some specific feed-forward and feedback mechanisms that send messages to the pyloric sphincter about when to relax and contract.

The small intestine is where the vast majority of the absorption of nutrients occurs, specifically in two parts of the small intestine: the duodenum and then the jejunum. Now, it's important though not to be fooled by the name of the small intestine. Given that 95% of absorption takes place here, it means that while this organ may not be large, especially in relation to the large intestine—we look at what the intestine looks like as a cylinder here—the absorptive area of the small intestine is quite vast. The reason that we're able to pack so much absorptive area into a relatively small space are due to several structural features of how the small intestine is designed. The first is that the inside of these—of the small intestine—we take a look at how things are arranged here—contains these circular folds. So, these larger-scale folds that are known as the folds of Kerckring. By arranging these mucosa and these intestinal cells in this fashion, these folds of Kerckring, one of the things that it allows us to do is to pack in more absorptive area in the intestine than would be able to be packed in series or in non-folded arrangements. This is beneficial in that it increases the surface area of the intestine by threefold. If we go another level down, within each one of these circular folds, within each of these mucosa are, um, going to be these sort of finger-like projections—these small, one-millimeter structures known as villi. Each fold is going to contain many, many villi, and this is another way to increase the intestinal surface area of, um, or increase the surface area of the small intestine. When we then think about the effect of villi on overall intestinal area—as where these larger folds of Kerckring increased intestinal surface area by threefold—these add an additional tenfold increase in intestinal surface area. Within each one of those villi that make up each fold, each of those villi are then covered in microvilli, and these microvilli are a part of the epithelial cell. This is where the majority of absorption actually takes place—is at the microvilli level. These are going to be in contact, or in the most direct contact, with these nutrients as they are absorbed into the bloodstream. Each one of these villi are covered in several microvilli, again, and this provides us with another 20-fold increase in the surface area of the small intestine. So, if we compare the surface area of the small intestine with all of these particular structures to if they were not arranged in this way, we get about a 600-fold increase in intestinal surface area. If you want to think about what that looks like kind of stretched out—if you were to take the absorptive surface area of the small intestine and lay it out flat—you'd have about, on average, depending on the size of the person, you'd have about 2700 square feet worth of absorptive area, and that's about the size of a tennis court. So, all of that is packed into a 2- to 3-meter by 3- to 5-centimeter, um, cylindrical organ. An entire tennis court's worth of absorptive area is packed in there via these arrangements, um, in folds, villi, and microvilli.

This is a good place to start talking about the role of some of our accessory digestive organs, and two in particular are going to provide a strong assist to the small intestine in terms of being able to absorb, digest, and absorb these nutrients, and those are the gallbladder and the pancreas. So let's take a look at the gallbladder specifically. The gallbladder's role in this whole scheme is to store, concentrate, and release a substance known as bile. Bile is going to be key in the digestion and absorption of fats. We'll talk about specifically how bile facilitates those processes when we get into the key aspects of digestion and absorption for specific nutrients, uh, but this bile is actually made in the liver, and the liver transports bile both directly into the small intestine as well as into the gallbladder via this common hepatic duct or shared liver duct. And again, this bile is going to be used to facilitate the digestion and absorption of our fats. So the gallbladder is a place where we store bile that is made in the liver.

The second accessory digestive organ that we'll take a look at here is the pancreas. Now, the pancreas, um, primarily one of its functions is to buffer off the hydrochloric acid that is added to these food particles when chyme is created. So, it releases a substance known as sodium bicarbonate, and that sodium bicarbonate is released via the pancreatic duct, which also feeds into the duodenum of the small intestine. It's important that this acidic chyme from the stomach is somewhat neutralized because the pancreas is also going to secrete, through the pancreatic duct into the small intestine, some enzymes that will further the digestion of our energy-yielding nutrients: carb, protein, and fat. We'll talk specifically about the activity of some of those digestive enzymes and why it's important to create either a more neutral or—more acidic environment—in this case, a more neutral environment for those enzymes to function.

Now, if our small intestine is primarily considered our agent of absorption, we can think of the large intestine as our agent of removal. So, once nutrients have been absorbed from the chyme, what's going to happen is that through this final portion of the small intestine known as the ileum, we're going to start to move this chyme into the initial portion of the large intestine, which is known as the cecum. This is going to be regulated by the opening and closing of the ileocecal valve—so the gateway between the ileum of the small intestine and the cecum of the large intestine. This valve, again, also functions to prevent the backflow of what is now considered feces. So, as soon as chyme reaches the large intestine, it's now considered feces. The ileocecal valve prevents the backflow of these feces back into the small intestine. Now, once that chyme becomes feces, several things happen in the various regions of the colon that will facilitate the removal of waste. One of the first things that happens is that the water from what was formally chyme and also the electrolytes—and remember those two things are going to be related because water is going to follow the concentration of electrolytes or osmotically active particles—that process is going to happen primarily in the initial portions of the colon or the ascending colon and the transverse colon. So that's where the majority of water and electrolytes are being absorbed out of that, um, out of that feces. And then, as it moves on to the more distal portions of the colon, um, the descending and sigmoid colon before it goes to the rectum and anus to be expelled, it is stored in these more distal portions of the colon.

Now that we've established what some of the roles are of the individual parts of the gastrointestinal tract, let's start talking about some of the specifics in terms of what actually happens to our energy-yielding nutrients and in which portions of the gastrointestinal tract these processes occur. So let's start with carbohydrates, and let's start at the beginning of the tract, in the mouth. Now, again, we already established that the act of chewing, or mastication, is going to increase the release of saliva from our three salivary glands through the associated ducts. This saliva contains, um, a couple different digestive enzymes, but the one that is particularly important in terms of carbohydrate digestion is this enzyme known as amylase. This salivary amylase is going to begin the digestion of our starches. So remember, starches are going to be our most common dietary form of polysaccharide, and if we remember the structure of our starches, they are simply large, branched arrays of individual glucose units. Amylase begins the process in the mouth of breaking these starches down into smaller units, um, so primarily when a starch is broken down, one of the—the functional units that's created here is going to be a disaccharide, um, known as maltose. Remember, this is going to end up being maltose because these are all going to be glucose units, and maltose is simply two glucose units bonded together.

Now, once these partially digested starches reach the stomach, they're going to continue being digested, but at a slightly slower rate. This is due, again, to the fact that the stomach environment, because of the release of hydrochloric acid, is acidic, and this amylase enzyme—its activity is reduced in a more—in acidic environment. So, when these partially digested carbohydrates reach the stomach, they're gonna—the rate of their breakdown will decrease, but they'll still continue, just at a slightly slower rate. So, by the time carbohydrates, or starches particularly, have gone through the mouth and entered the stomach, they're about 30 to 40 percent digested before they actually be—uh, reach the small intestine. So, some further digestion is going to continue to occur in the small intestine, and this is going to be facilitated by the entry of sodium bicarbonate from the pancreas into the small intestine. That's going to start to bring that environment back closer to a more neutral pH where the enzyme amylase is going to be able to function and increase the rate of carbohydrate digestion. What's also functionally relevant about the pancreas is that it not only provides sodium bicarbonate, which buffers or neutralizes the stomach acids that are present in this chyme, it also adds in its own amylase. So, salivary amylase has started the job of breaking down some of these starches into smaller units, and the pancreas is going to help by secreting pancreatic amylase, which will continue that process of digestion. Now, additionally, what will happen in the small intestine is any maltose that is created from the breakdown of these starches, as well as any of our other disaccharides—lactose and sucrose—that are ingested are going to be broken down into their individual monosaccharides. It's these monosaccharides, which are produced from specific enzymes—so each enzyme is specific to the disaccharide that it breaks down into monosaccharides—these monosaccharides are what actually get absorbed into the bloodstream. We're going to talk about that process of how each monosaccharide is absorbed on the next slide. But again, remember that these are—this is occurring primarily in the small intestine. So, the small intestine continues the digestion of carbohydrates with some assist from the pancreas, and it also breaks down our disaccharides into monosaccharides so that they can undergo absorption into the bloodstream. And then, of course, in the large intestine, remember that certain carbohydrates, particularly fiber, because of their, uh, the cellulose that is contained in fiber and the lack of human enzymes to digest those carbohydrate sources, are going to be expelled in our fecal matter.

The three major monosaccharides that are produced from the digestion of our polysaccharides now need to undergo a couple of different transport steps in order to ultimately be absorbed. The first thing that needs to happen is these monosaccharides will now be in the lumen of the small intestine. Well, we need to now get them into the epithelial cells. In order to do that, for both glucose and galactose, this transport is dependent upon a sodium-dependent glucose transporter. This is a transport protein that facilitates the diffusion of glucose and galactose into the epithelium. Because of its sodium dependence, sodium then also follows this into the epithelium. Now, in order for this process to continue, that sodium is going to have to be pumped back out into the lumen, and the process of pumping that sodium back out into the lumen actually requires the breakdown of ATP via what's known as a sodium-potassium ATPase pump. This is necessary in order to take the sodium that followed the sodium-dependent glucose transporter into the epithelium back out into the lumen so that it can continue to facilitate the transport of glucose and galactose into the epithelium. Now, in the case of fructose, fructose has its own specific transporter that gets it from the lumen into the epithelium, and that transporter is known as GLUT5. You'll notice a difference here: this transporter is not sodium-dependent, and therefore it doesn't require any ATP breakdown or any energy-costing pump systems in order to facilitate the movement of sodium back across that membrane. So now we're in the epithelium, and we've got our three monosaccharides, and now what we're going to have to do is transport those…

Monosaccharides from the epithelium enter the circulatory bloodstream via the capillaries. These capillaries come into direct contact with our epithelial cells. Unlike luminal transport into the epithelium, epithelial transport into the capillary of these monosaccharides relies completely on one transporter. So, all three monosaccharides are transported into the capillaries via a transporter known as GLUT2. Once those monosaccharides are in the capillary, they're going to enter circulation via the hepatic portal vein. Again, wherever we're talking about something hepatic, we're talking about the liver. So this hepatic portal vein is going to serve to transport these three monosaccharides to the liver where they can then undergo further processing to either be stored as glycogen, or broken down into glucose and used to facilitate or augment blood glucose.

Similar to the digestion of carbohydrates, the digestion of fats and lipids also begins in the mouth. It also begins the enzymatic activity and the act of chewing, which will trigger the release of saliva. In addition to enzymes that break carbohydrates down, that saliva also contains small amounts of an enzyme known as lingual lipase. Lingual lipase is going to kind of get the party started in terms of breaking down fat. Now we know that the process of breaking down fat is a little bit more complex than breaking down carbohydrate, but we get that process going here in the mouth, and lingual lipase begins to take the triglycerides. These are the three fatty acid chains that could be different in length, bound to a glycerol backbone. Remember, we need to ultimately begin to release those fatty acids from that backbone in order to use them in energy metabolism. So that process begins in the mouth and it begins via the activity of the enzyme lingual lipase.

Now, once the food moves into the stomach, what will begin to happen is that lingual lipase will continue to do its job. It will continue the process of breaking down fatty acids off of those triglycerides and from their glycerol backbones. It's actually able to do so in the acidic environment of the stomach. However, while this continued breakdown of triglycerides is happening in the stomach, remember that these are lipids, and unlike carbohydrates, lipids are not water-soluble. So the process of this breakdown of triglycerides continues on in the stomach; it slows down a bit, but it's enough time for it to act mainly on those short and medium-chain fatty acids off of triglycerides. The slow nature, or the slowing down due to the non-water solubility in the stomach, allows enough time for those shorter and medium-chain triglycerides to have their fatty acids freed, but not quite enough yet for us to have released a lot of the long-chain fatty acids from their triglyceride form. But one of the things that is going to help and assist in further digestion of lipids that is occurring in the stomach is that the stomach undergoes a grinding action. So there's actually some mechanical smooth muscle grinding that goes on in the stomach. The purpose of this grinding in relation to the digestion of lipids is to now break these fats into large droplets. You can see that sort of depicted here as it will go into the small intestine: a large lipid droplet. One of the things that allows these droplets to form off of a larger macromolecule of lipid is this grinding action in the stomach that allows those droplets to form.

Now, once we move into the small intestine, remember the lipids that have not yet been freed into fatty acids are going to be in these large lipid droplets. So a lot of our long-chain fatty acids and triglycerides are going to be in these droplets. What we are going to now do—and we referenced this previously in the small intestine—is that bile, which is stored in the gallbladder and made in the liver, is going to start to take these larger fat droplets that were created in the stomach via the mechanical grinding action. It's going to now coat them with these bile acids, which are going to act as an emulsifying agent. From a functional standpoint, the purpose of doing that is so that these large droplets can now be broken into smaller droplets, which will facilitate the continued transport of these lipids.

Now, once these lipids have been emulsified and coated with bile into smaller droplets, what we then have is an increased surface area. The increased surface area of this lipid is now going to be exposed to the pancreatic lipase. Pancreatic lipase is going to function the same way that lingual lipase functions. Lingual lipase has kind of gotten the job started, and we've gotten a lot of digestion of shortened medium-chain triglycerides that's happened in the stomach. Now, we can, through further lipase activity from pancreatic lipase—pancreatic lipase is secreted into the duodenum—break down those long-chain triglycerides, and we will be left with free fatty acids that will be able to eventually be absorbed into the bloodstream. We'll talk about that process on the next slide.

Now, because they're not very soluble in water, these long-chain fatty acids actually aggregate into these compounds known as micelles. These micelles, as you can see here, are a series of long-chain fatty acids that are aggregated together in this case. What they all have is their polar end, or their end that's going to react better when exposed to water, are all facing outward. It allows this aggregated unit of long-chain fatty acids, again known as a micelle, to transport these long-chain fatty acids into the villi, where they can then begin to move through into the epithelium from spaces between the microvilli. These micelles are created in order to transport these long-chain fatty acids to this point and allow them to then diffuse into the epithelium.

Now, what happens from here is actually kind of interesting because the fatty acids, after the micelles move away and go to pick up more fatty acids in order to bring them over to the villi and microvilli, but once the fatty acids from that micelle get into the actual epithelium, they are re-esterified to form triglycerides again. They find glycerol backbones and are once again bound to them. In this particular part of the process, something that we already referenced is that an apolipoprotein is going to be formed. We talked about the role of chylomicrons as one of our types of protein structures that is primarily responsible for the transport of triglycerides and delivering fatty acids through the bloodstream to places where they will be used. That process actually takes place here in the epithelium of the small intestine, and these chylomicrons are combined—they are a combination of triglyceride, cholesterol, and then a phospholipid that form and will be important in terms of transporting these fatty acids into circulation. The site where that happens is through the lymphatic system. So these chylomicrons, now packages that contain triglycerides, can now move through the lymph into the subclavian vein in order to now enter the bloodstream.

Now, if we take a look at our medium and short-chain fatty acids, because of the size of the molecules, they don't have quite as much trouble diffusing into the epithelium. You can see down here depicted, as opposed to these longer-chain fatty acids which need to be transported in the intestine via micelles, micelles which then deliver them to this membrane of the villi and in between the microvilli, they can then go into the epithelium and then have to be repackaged into triglycerides and chylomicrons. Our medium-chain fatty acids are actually able to just diffuse right into the epithelium. Now, remember short and medium-chain fatty acids are not as abundant dietary, but we will talk about medium-chain triglyceride oil in our discussion of dietary supplements and what some of the physiological mechanisms that that particular supplement could improve performance. But short and medium-chain fatty acids are going to have an easier time diffusing into the epithelium and ultimately also into the bloodstream. So they are not re-esterified into triglycerides in the epithelium in the way that our long-chain fatty acids are re-esterified and then repackaged into chylomicrons and delivered through the lymphatic system. Our medium and short-chain fatty acids can diffuse directly into the epithelium, and then they can diffuse into the hepatic portal vein and are bound to the plasma protein albumin once they are then transported in the blood. So albumin is going to be the primary transport protein that's going to pick up any free fatty acids; those that are not being transported via chylomicrons will be bound to the plasma protein albumin so that they can ultimately be transported to the liver for further processing.

Now, unlike carbohydrate and fats, the digestion of proteins doesn't begin until food reaches the stomach. The first step in the digestion of protein is going to be stimulated by the hydrochloric acid that is released into the stomach. Now, that acid is going to activate an enzyme known as pepsin. Pepsin is one of our first-acting proteases, or enzymes that are going to break down these larger proteins into smaller peptide units such as tripeptides, dipeptides, and single amino acids. That process is going to continue once we get out of the stomach and go into the small intestine, but via this enzyme pepsin is how we'll start breaking these proteins down into smaller peptides, actually in the stomach. The activity of pepsin will account for about 10 to 20 percent of that process, of that overall protein digestion that will need to continue in the small intestine.

Now, once in the small intestine, the pH in the small intestine, because it's not exposed to stomach acid, is going to be higher. So it's going to be more basic, and remember that's going to now slow down the activity or deactivate pepsin. But the pancreas secretes several alkaline proteases. These are also enzymes that are going to catalyze the breakdown of proteins into smaller peptides and ultimately into single amino acids. These proteases that come from the pancreas prefer to work in a more alkaline environment such as the small intestine. So the three primary proteases that come from the pancreas are trypsin, chymotrypsin, and carboxypeptidase. These enzymes are going to digest the remaining proteins into amino acids, dipeptides, and tripeptides so that they can then be transported into the small intestine for absorption. We can see that process beginning here where now we are again in the lumen of the small intestine, and we can see that we have formed dipeptides and tripeptides, so smaller polypeptides from the breakdown of proteins via our proteases in the stomach as well as in the small intestine that came from the pancreas. We're also going to have some amino acids that have been formed in that process as well. In order for these molecules to get into the epithelium where they can come in contact with the capillary and be absorbed into circulation, this is going to be very similar to how the majority of our monosaccharides get into the small intestine, and that's going to be via, again, a sodium pump. This is facilitated by the entry of sodium and by the maintenance of this electrochemical gradient. These amino acids and peptides are able to transport into the epithelial cell, and this process, again to run these sodium-potassium ATPase pumps, the breakdown of ATP is required. So there is a little bit of energy that has to be invested in this particular part of the process.

Now, once these dipeptides and tripeptides that are not yet in their single amino acid form get into the epithelial cell, they then, via their specific enzymes, will be broken down further into single amino acids. It's only single amino acids that are going to diffuse into the capillary and into the bloodstream. So any further breakdown of these larger polypeptides that are in di- and tripeptide form will occur via these enzymes, dipeptidase and tripeptidase. So now what we're left with at this point are all amino acids that can then be transported into the bloodstream. Each one of the amino acids can be picked up by a variety of different amino acid transport proteins that carry amino acids in circulation; seven different ones have been identified, and it just depends on which amino acid you're talking about, but several amino acids can use more than one type of these seven transporters that have been identified. So we won't get into any of the specific transporters, but just know that that process requires a transport protein. In order for those amino acids to reach their destination, they can go to either one of two places. The first place that they can go is they can be transported to the liver, and in the liver they could have several potential fates: they could be converted into glucose, they could also be used and converted into fat, or they can be used to make new proteins. The other potential fate of these amino acids is that they can be added to what's known as the free amino acid pool in the blood. When we talk about protein and protein recommendations and the role of protein, dietary protein, and amino acids in recovery from exercise and rebuilding proteins that are broken down during exercise, this concept of the free amino acid pool is going to be very important.

Now let's talk a little bit about how food is emptied from the stomach into the small intestine in this process known as gastric emptying, and a little bit about how that process is regulated and controlled. This is important because after we ingest food, it typically spends between one and four hours in the stomach before it can be moved on for complete absorption in the small intestine. This is going to have a pretty large impact on how available those nutrients are for their intended purpose. We'll want to think about this when we start thinking about before, during, and after exercise nutritional recommendations. But in general, most food spends about one to four hours in the stomach, and that's going to depend really largely on the content of the meal. We'll talk a little more specifically about that, but the greatest factors you can imagine that is going to dictate whether or not, or dictate the rate of gastric emptying in regards to a meal, is going to be the energy content or the caloric content of the meal itself. But at any rate, when we think about how the process of moving food from the stomach into the small intestine, or gastric emptying, is regulated, this process is somewhat automatic. The stomach wall itself actually has pacemaker cells that are embedded within the wall of the stomach. Some of the firing of those stomach wall cells, or the contraction of stomach wall cells that help facilitate the movement of chyme into the small intestine, are automatically generated by these pacemakers.

Gastric emptying rate is also further controlled—as you can see on this diagram here—there are some feed-forward mechanisms as well as some feedback mechanisms that send signals to this specific part of the stomach. Remember, the pylorus and the pyloric sphincter is going to be what controls the rate that food and chyme is able to be moved out of the stomach into the small intestine. One of the primary mechanisms by which this rate of gastric emptying is regulated is that when we ingest food and fill the stomach—so bringing food and fluid into the stomach is going to expand or distend the stomach wall—and that's going to occur to a greater degree as the volume of the meal increases. What this does is it actually sends signals to the pylorus to relax. The opening here will get wider, and more of that volume in the stomach will be able to move into the duodenum of the small intestine. That would be an increase in the rate of gastric emptying.

Now, these—the pylorus and the pyloric sphincter—are also getting feedback signals from receptors that are actually located in the duodenum. The purpose of these duodenal receptors and their feedback that they deliver to the pylorus is ultimately going to be directed at contracting the pylorus or slowing the rate of gastric emptying. The reason for this is because we want to prevent an excess amount of chyme from being released into the duodenum because we need to have enough time for the complete digestion and absorption of these nutrients that we just discussed in outline to finish occurring in the small intestine so that they can be absorbed and utilized. So these receptors are again their feedback receptors that are going to send messages to the pylorus about things like an increase in the fat, carbohydrate, or protein, or even just the overall energy content of chyme. Again, these receptors are sensing that the rate of absorption is beginning to increase, so we might need to slow down and contract the pylorus and limit some of the entry of chyme into the duodenum to give the small intestine a chance to finish absorbing and digesting what it already has in it. Something else that is sensed in the duodenum and sent as a feedback mechanism into the pylorus that can slow down the rate of gastric emptying is an increase in the osmolarity of that content. Theoretically, because this could change the gradient of osmotically active particles in the stomach and small intestine relative to places like the blood or serum where we might be trying to move fluid for absorption and replace plasma volume that is lost via sweating during exercise, this could theoretically slow the rate down at which this happens.

When we think about the osmolarity of carbohydrates and sports drinks that contain a lot of simple carbohydrates as well as electrolytes, remember the purpose of most of these sport drink beverages is to promote hydration and to provide a quick source of energy for the working muscles. So they're going to be very rich in simple sugars, and they also are going to have a lot of electrolytes, things like sodium and potassium that are osmotically active and are going to increase that osmolarity. So if we take a look at what these drinks do to performance, well we know that supplying these types of nutrients can improve performance, help maintain hydration, give more energy for the muscle. So how is it that the increased osmolarity of these beverages is not necessarily impairing the rate of gastric emptying? If increasing osmolarity in the duodenum is a feedback mechanism that's going to signal for us to slow the rate of gastric emptying, and if we take a look at the research that has been done on these sports drinks or has been done in the development of these sports drinks, it works out that when we are at osmolarities between 200 and 400 milliosmoles per liter—you can see the osmolarity of different body fluids as well as different beverages that are available for commercial purchase—if we take a look at just the sports drinks that are listed on this particular table, you'll see that the osmolarities all fall within this range of 200 to 400 milliosmoles per liter. That is intuitive design because, between these osmolarities, in this osmolarity range, research has shown that these beverages can provide the electrolytes and sugars that they need to without significantly altering the rate of gastric emptying. They don't cause enough of an increase in osmolarity to where it alters the rate of emptying and impairs fluid absorption. But once we start to get above that range, we see All Sport was actually an early 90s, mid-90s sports drink that had a little bit more of a soda-like feel to it, and it has since stopped being produced. However, one of the problems with it is that it was too hyperosmolar. The osmolarity of it was too great; it fell outside of this range for optimal emptying from the stomach and subsequent nutrient delivery and fluid absorption. The same would be true for some more over-the-counter, or I guess commercially popular beverages such as sodas and fruit juices. The osmolarity of those beverages could impair the rate of gastric emptying and could impair the rate of fluid absorption compared to beverages that fall within the optimal range.

Now, one of the concepts that you might hear talked about a lot, or something you might just hear people say when they're talking about food and gastric emptying, is this idea that fat slows down the rate of gastric emptying more so than carbohydrate or protein. I'll invite us to take a look again at the summary here, zoomed in a little bit more specifically on these feedback pathways that the duodenum uses to communicate and tell the pylorus to close or slow the rate of gastric emptying. All of our energy-yielding nutrients—if we look at fat, carbohydrate, and protein—an increase in the duodenum of the content of any of these nutrients is going to slow the rate of gastric emptying. The reason that fat, per unit of mass—now this is comparing, let's say, 10 grams of fat to 10 grams of carbohydrate—that 10 grams of fat versus 10 grams of either carbohydrate or protein...

Will slow gastric emptying to a greater degree, and it's due primarily to the fact that carbohydrate and protein contain less energy per gram. So if we remember, on average carbs and protein have about four calories per gram, as opposed to a gram of fat, which has more than twice the overall energy content. And it's this increased energy density—so the fact that 10 grams of fat would have 900 calories worth of energy as opposed to 400 calories worth of energy if it were 10 grams of carbohydrate or protein—if we control for that energy content, the nutrients would actually have a very similar effect. So it's not necessarily that fat, um, that fat specifically causes a greater decrease in the rate of gastric emptying per unit of mass; it's that fat has more energy, and therefore the energy content of meals that contain a lot of fat are higher than meals that don't contain a lot of fat.

And so, in looking at studies that have compared the effects of energy density and controlling for energy density when looking at the effects of different nutrients and total energy content on the decrease in gastric emptying, it's been shown that the energy content of the meal by far has the greatest impact on how fast it empties from the stomach, regardless of what the macronutrient content that makes up that energy is comprised of. However, we know that because fat is highly energy dense, high-fat meals typically have greater energy content and therefore will release from the stomach and empty from the stomach at a slower rate compared to less energy-dense meals. All of these things can start to become an even more significant challenge when we start to factor in exercise.

And the reason for that is because exercise in itself is a physical stressor that can actually slow the rate of gastric emptying. How does this occur? Primarily the mechanisms—now this depends on things like the exercise intensity and duration and the environment—um, but the most likely factors are due to the fact that um there is some vasoconstriction that occurs to the blood vessels that supply blood to the gastrointestinal tract, um, as well as some dehydration that can occur via thermoregulation and fluid loss during exercise.

And if we look at the effects of exercise intensity—so this is taken from a study where they looked at the relationship between exercise intensity as a percentage of VO2 max and the volume of fluid that was residing in the stomach after 15 minutes of ingesting 400 milliliters of fluid—and what we can see here is that as exercise intensity increases, specifically as it increases to intensities above 60 percent of VO2 max, there was more residue left in the stomach, so less fluid was being emptied from the stomach into the small intestine, indicating a decrease in the rate of gastric emptying. And you can see this starts to become really, really pronounced as we go on into even higher and higher intensities.

And if we think about what's causing this to occur, well, part of the reason this is happening—a major reason that this is happening—is because we need to shunt a greater proportion of cardiac output and blood flow to the peripheral muscles, and one of the ways that we do that is by vasoconstricting more centrally to places like the gastrointestinal tract. So now the GI tract is receiving significantly less blood, significantly less fluid, so that more of that blood can go to the working muscles. However, this is going to uh impair the rate of gastric emptying and potentially cause some significant gastrointestinal issues, particularly in sports where fluid and nutrient delivery become an issue and a limiter to performance.

If we start to look at the causes of gastrointestinal issues that are reported during exercise, we will undoubtedly find that these issues are far more prevalent in endurance athletes. Um, this is because these types of sport provide the most significant challenges uh in terms of nutrient delivery as well as fluid delivery. And when we look at the causes of GI distress in endurance athletes, some of the primary causes can be dictated by the impacts and/or the posture that these activities are performed in. And this is interesting because if we look at upper abdominal GI symptoms—which you can see listed here um to the left in this table from the Gatorade Sport Science Institute—so these would all be symptoms that the gastrointestinal distress could be coming from the upper portion of the GI system as opposed to symptoms that are more related to problems going on in the lower end of the GI system—we see that running, because of its ground reaction forces and high impacts that occur when the foot comes into contact with the ground, that mechanical impact actually is related to runners reporting more lower GI issues. So the most prevalent types of gastrointestinal issues seen in runners are those of issues on the lower gastrointestinal tract.

And if we compare that to cycling, interestingly cyclists report higher incidence of upper GI problems, and compared to running, this is thought to be due to the posture at which cycling is performed in many cases. So if we see here, um, this kind of classic case of a cyclist in sort of a crouched-over posture, that crouched-over posture actually causes an increase in the intra-abdominal pressure, specifically in the upper portion of the GI tract, and for this reason cyclists, compared to runners or other endurance athletes, report significantly higher incidents of upper abdominal GI stress occurring during, during exercise.

Now there are also several nutritional causes that can, um, that can lead to GI distress during exercise, and this is going to be related to their effects on gastric emptying and their effects on nutrient absorption. And some of the key things that can cause gastric distress during exercise are ingesting foods that are too energy dense, either before or during competition or performance. We've talked about how the energy content of a food can slow the rate of gastric emptying. Fiber is going to slow down the rate of gastric emptying, um, so because fiber is not digestible by human enzymes, high-fiber meals will typically slow down the rate of gastric emptying and potentially cause some discomfort during exercise. Increasing the content of fat—again, mainly because this is related to higher energy density—but high-fat meals before or during competitions uh can be causes of gastrointestinal distress during exercise. And then, um, ingesting foods that are too high in fructose. Now remember that fructose doesn't rely on the common sodium-dependent glucose transporter that our other monosaccharides utilize, so it has to compete for fewer transport molecules, and for that reason, while that can help with glucose delivery, and we'll talk about that in our discussion of multiple transportable carbohydrates later in the quarter, remember that fructose has its own specific transporter that regulates its entry into the epithelium from the intestinal lumen. So foods that are too high in fructose may slow down the rate of gastric emptying and therefore also cause some gastrointestinal distress as well. And the same is uh true for lactose. We know that human beings don't have um really high concentrations of lactase; some individuals are intolerant of lactose because they have very, very low levels of lactase, and lactose can also potentially cause gastrointestinal discomfort during exercise when ingested pre- or post-competition.

While the nutritional demands of providing fuel during exercise can cause some gastrointestinal problems, there are some training strategies that can be employed in order to lessen the chance of those outcomes coming to fruition. And this is a process in sport nutrition known as training the gut. So this idea that the gut is an adaptable organ, just like skeletal muscle is an adaptable organ, and that if you train and expose it to nutritional stimuli during exercise training that mirror those that might be employed during competition, that there may be some improvement in the rate at which things are emptied from the stomach and at the rate at which nutrients are able to be absorbed, and potentially reducing some of the gastrointestinal problems that can occur during exercise, especially when nutrient intake is necessary for maintaining or improving performance.