In this video, we're going to examine the phases and digestive processes that occur in the stomach. So, while the stomach is primarily responsible for sort of holding or warehousing the material we're consuming, there is some minimal amount of digestion that occurs in the stomach. And we previously had talked about the oblique muscle groups that are responsible for sort of the contraction of the muscle to allow for the churning of food items into smaller morsels. So the stomach is involved in partially the mechanical breakdown of food. In addition, the highly acidic environment that is found in the stomach is key in denaturing the overall three-dimensional structure of proteins. And this loss in three-dimensional structure provides greater surface area access to enzymes. And one of the enzymes that are found uh to have uh working sorry found to be working in the stomach is the protein pepsin. So we previously talked about uh pepsin as it relates to the gastric pits. The low pH environment activates pepsinogen the inactive form into the active form pepsin. And this begins but doesn't complete the breakdown of proteins. Additionally, in infants, uh they do have a second enzyme called renin. Renin helps to break down the milk protein cassine and it kind of converts it into sort of like this curdling um product. So, it's almost as if you added lemon juice uh to milk. It kind of curdles the milk. So the protein is called cassine here. So the other effect of the stomach is to deliver the material which at this time is no longer a bolus. Uh it's referred to as kim because it has mixed with acid. So there is some absorption that occurs in the stomach. Uh very very few examples. uh alcohol which is lipid soluble as well as aspirin. These are basically the only two compounds that are going to be directly absorbed through the lining of the stomach into circulation. Now if we remove the stomach, the stomach doesn't really serve uh uh an essential uh function to life with one notable exception and that is some of the mucosal cells will secrete a factor called intrinsic factor and intrinsic factor is needed to bind to consumed vitamin B12 and only this complex of intrinsic factors and vitamin B12 is absorbed in the small intestine. So keep in mind that the absorption of vitamin B12 happens in the small intestine but it's not just vitamin B12. It has to be complexed with this intrinsic factor. So the issue is in individuals that might have gastric bypass surgery or maybe complete stomach removal or there's actually an autoimmune condition called pernitious anemia that specifically attacks the mucosal cells that secrete intrinsic factor. All of this will result in anemia because now you don't have the raw materials for athropoesis that is the production of red blood cells. Now, this can be treated uh through vitamin B12 injection. So, we're bypassing absorption. Uh and interestingly enough, there are nasal gels. So, you could absorb it through the capillaries in the nose as well. So, it doesn't necessarily have to be just in an injection. So, how do we regulate what's going on in the stomach? So regulation is going to be neural as well as hormonal. Uh so just to give you an idea, the stomach is going to be producing about 3 lers of gastric juice. So low pH, high acidity material. And a lot of this stimulation is uh with regards to the nervous system, it has to be parasympathetic. So parasympathetic is pro- digestion while sympathetic is anti-igestion. So the vagus nerve which is your cranial nerve number 10 this is going to stimulate these gastric cells to produce more stomach acid. While sympathetic stimulation which usually kicks in during the fight or flight response is going to make this a really low priority. So it's going to decrease secretion. Now with regards to hormones, there's a hormone that is made by the stomach. Uh and some of it is actually made by the small intestines as well. This hormone is called gastrin. And so gastrin is going to tremendously increase the amount of hydrochlor hydrochloric acid secretion. So the production of the acidity of that gastric juice. Now that's going to be countered by a few other hormones that are secreted by the dadnum by the small intestine that will lower the efficacy of gastrin. So they're going to be gastrin antagonist and we'll talk about those shortly. So when we look at gastric secretion there are three main phases. So there's going to be a control uh in your head. So sort of central nervous system control. there is control via the stomach and then there's control via the intestines. So the syphalic reflex or the syphalic phase is usually going to be triggered before you're consuming the food. So if you think about chocolate chip cookies, right? Or foods that you like. This usually doesn't apply to foods that you dislike, uh but foods that you like the smell of or the taste of. You begin to salivate, right? You've probably heard of the Pavlovian response where uh you know you ring the dinner bell and you start salivating in anticipation of the food that you're about to eat. This is a very similar type of reflex where you're conditioning the stomach to already start increasing the acidity in preparation for the food items you are eating. Now this is usually a very short-lived reflex. Um it's going to be reinforced however through the gastric phase. So the gastric phase is also going to be stimulatory. And one of the main ways to stimulate is the consumption of food is going to stretch the stomach. So recall our earlier discussion on the gross anatomy of the stomach, how it kind of collapses via the ruga uh and doesn't really hold a lot of volume. It's only about 50 mls. But once you start putting food in there, it has this tremendous compliant ability and that stretching or distension that is going to be detected specifically by stretch receptors or mechano receptors that's going to stimulate the entendocrine cells in the base part of the gastric pits. Now these specific intereroendocrine cells are called GC cells because they are primarily secretreting gastrin which will then stimulate the parietal cells to produce that hydrochloric acid. Another stimulatory component are peptides or proteins. So this kind of ties handinhand with low acidity. So remember the main component of a peptide are amino acids. So the general structure of an amino acid is you have a central carbon that is bound to a variable group and that's different for each of the 20 amino acids. You have a caroxile group and you have an amino group. Now the amino group can act like a base and remove a hydrogen ion from solution while the caroxile group can become ionized and donate a hydrogen into solution. So this is why it's called an amino acid. Right? The caroxile group behaves like an acid because it donates a hydrogen while the amino group can remove a hydrogen. Therefore it acts like a base. So peptides, amino acids, proteins, these are all buffers. And so when you eat food items that are rich in proteins, that is going to lower the acidity of the gastric juices. So that's why uh these two topics of peptides and low acidity kind of work hand in hand. and it helps to sort of negatively feed back the pH level of the gastric juices to optimize it for digestion. So again, the secretion of gastrin is going to be very important that can be stimulated by all of these events as well as the parasympathetic nervous system. So the bulk of the gastric juice is going to be stimulated through this particular manner. Uh there are some other chemicals that are responsible. We mentioned serotonin before. Histamin is another one and of course acetylcholine from the parasympathetic nervous system. All of these are going to stimulate sort of the uh ultimately the production of stomach acid via gastrin release. So then we have our third phase which is the intestinal phase. And the intestinal phase is sort of a two-pronged phase where initially it is excitatory but the bulk of it is going to be inhibitory. So the initial excitatory a stimulatory component is engaged when partially digested food enters the small intestine. So you have partially digested peptides and that causes a brief uptick in gastrin release to reinforce um gastric secretion. But as material begins to accumulate in the dadnum, you don't want to overwhelm the dadum. Uh you don't want to overload it. Uh or this it's called dumping. Uh this could lead to nausea and vomiting. And so the bulk of the intestinal phase is going to be an inhibitory effect. So this is courtesy of various hormones. So we call this the interogastric reflex. And the class of hormones that are going to impact this are known as interogasts. And these include hormones like serritin. And again we'll talk more about these hormones as we go. uh choleiccestokinine or cck. Uh and then lastly, hold on the name kind of oh yes uh vasoactive inhibitory peptide or VIP. So these ultimately lead to the lowering of gastrin. So it's antagonizing gastrin signaling. Now these hormones also have other effects on the small intestine as well as the accessory glands like the the liver and the pancreas to for example in the pancreas to increase bicarbonate secretion to facilitate the neutralization of the kind that comes in. So just sort of as a as an overview again we've talked about the various stimuli for the gastric phase. Gastrin is going to be the chief regulator of hydrochloric acid release into the stomach. So the main component of the gastric juice. Low pH is going to inhibit gastrin secretion which is why we don't continue to release HCL during periods of fasting. um any kind of proteins that we ingest that's going to cause a rise in pH and that rise in pH triggers again our gastrin release. Uh and then three chemical signals that can directly stimulate the parietal cells acetylcholine, histamin, and gastrin. So if you only have one of them, you're going to have only a trickle of hydrochloric acid. But if you have all three, it has sort of this synergistic effect. So you're going to get maximal hydrochloric acid secretion. So let's look at the hydrochloric acid secretion. We had mentioned this previously in the gastric pit uh discussion but the fundamental chemical reaction that is important here is water and carbon dioxide gets converted into a weak acid called carbonic acid and that carbonic acid will dissociate into hydrogen ions and the bicarbonate ions. So this is the chemical reaction courtesy of the enzyme carbonic andhydrates shown over here that is occurring within the parietal cell. However, there is a shift a chloride shift. You also see this in red blood cells where chloride ions from the interstatial fluid are brought in while that bicarbonate ion goes out into the ISF adjacent to the capillaries. Now the bicarbonate ion is going to go into circulation. So it increases the buffering capacity of the blood uh locally. So it makes the blood there slightly more alkaline than usual. Once the chloride ion is in, the chloride ion goes down its concentration gradient into the stomach lumen. The hydrogen ion that we produced during this reaction however is using an antiporter mechanism where hydrogen ion goes out and potassium is allowed to come in. Um, and this is using ATP, right? So, it's using the energy of ATP to move both of these up their concentration gradient. The result H+ and Cl minus in the stomach lumen is the hydrochloric acid that we generate in the stomach. All right. So, let's look at that entastric reflex. So the interogastric reflex which is happening is going to combine basically three reflexes. Uh it can be inhibited by the uh veagal stimulation. So the parasympathetic stimulation. It can be inhibited by local reflexes. It can also be activated by the sympathetic nervous system that results in the tightening of the pyloric sphincter. So this is preventing excessive dumping into the small intestine. So remember this is the inhibitory effect of the intestinal phase. We don't want to overwhelm the dadnum because we need to neutralize any acidic content that comes into the dadum. So the intestinal phase focuses really on these three hormones secretin choleiccystokinine and vasoactive intestinal peptide. All of them will secrete will prevent the secretion of gastrin and thus the result uh is lower hydrochloric acid uh production. Um if for example this system doesn't kick in correctly or somebody overeats um then this can lead to excessive amount of kime entering the small intestine. This is known as the dumping syndrome which results in nausea and of course vomiting. Uh so people that have had gastric bypass surgery and overeat this is a fairly common effect. So, here's a scary little chart just to uh summarize everything that we've talked about. The three phases, the syphalic, the gastric, and the intestinal. For the syphalic and the gastric, you're going to have stimulatory effects that result in an increase in production of hydrochloric acid. This can be inhibited by the sympathetic nervous system or when you have loss of appetite or maybe the food item you don't like uh that's not going to stimulate the uh effects from the syphalic phase. When we go into the intestinal phase, the initial movement of material is going to reinforce gastrin secretion. But as more material gets dumped into the dadum, you have local reflexes that will detect the presence of partially digested protein that will detect fatty material in the kim within the dadum. Uh distension of the dadum and that's going to cause the release of these interoges that inhibit gastrin secretion. So that lowers the amount of hydrochloric acid being secreted into the gastric juices.