 So, welcome back to the NPTEL lecture series on animal physiology. So, we are in section 12 with the lecture 3. This is basically in the gastrointestinal physiology. So, we talked about the in the first lecture we talked about the overall architecture of the digestive system. We talked about how the nervous innervation of sympathetic and parasympathetic systems are kind of controlling the whole system, the whole architecture. And then on in the second lecture we talked about the first part where the first intake of food takes place that is in the mouth, in the saliva the function of the saliva, how saliva secretion is being regulated. And how the first phase of the food is being broken down into pieces before through bolus movement in the form of peristaltic movement it moves to the stomach. The stomach is the I should say the first after the mouth it is the first station through the esophagus it reaches the stomach. Stomach is the first station where the food is exposed to one of the most acidic environment in its whole tract all the way, excuse me all the way from mouth to excretion from anus. This particular structure is the most acidic where the pH almost hits upon one and even possible less. And that is because of hydrochloric acid which is being produced by their different cells their parietal cells, safe shells and everything. So, the way we are dividing the this particular classes we will talk about the anatomical feature of stomach from there we will move on to the different cellular structure and how they regulate the movement of H plus and C l minus ions which leads to the formation of hydrochloric acid. And then we will talk about the different phases which regulate the whole digestion process. So, anatomically speaking so if you look at the structure let us get back to the section 12, section 12 lecture 3. So, the overall structure if you look at the stomach the way it looks like it is a structure is physically looks something like this and of course, not this one second let me just redraw it something like where the food moves through the whole path this is the wrong way to put it let me redraw it something like this. So, the food is coming I am showing you the arrow this is how the food is entering and this is where the food moves to the small intestine and whatsoever happened everything happens in this zone. So, if you look at the very basic structure of it is divided into four different parts parts are named as cardiac fundus the body and the pylorus pylorus these are the four anatomical feature of stomach and each one of them have their own function and what I will do and there is something called pyloric sphincter which is present somewhere out here which ensures this pyloric sphincter ensures that the when the food should be sent to the intestine till. So, it is kind of a control mechanism by which food is being ensured that all the regurgitation all the chemical reactions takes place in such a way that the food is now ready to be transported to the small intestine for further absorption and all other metabolic metabolism related events. So, now coming back to the structure with anatomical feature of the structure. So, let me redraw this so that I can label all it for you people. So, this is the entry port of the food. So, this is esophagus then the food is entering this is the fundus region and this whole vessel if I have to take a cross section of this something like this if you see across if I take the upper view of it you will see lot of blood vessels all over the place like likewise. It is completely innervated with blood vessels. So, this is just the kind of a cross view what I am trying to draw for you people if you get an over up a view then this zone is called cardia and here you have a bunch of longitudinal muscle layer there are two kinds of muscle arrangement here longitudinal and these are all smooth muscles longitudinal muscle layer and second one is series of circular muscle layer. These longitudinal and circular muscle layer helps in the movement of the stomach circular muscle layer and then you have this is the fundus this is cardia and here is the body the body part and this surface is called rugae surface this zone is called pyloric antrum and here is the pyloric sphincter pyloric sphincter and this part is called pyloric canal. So, this is the overall geometry of the stomach. So, all these organs most of these digestive organs or any of the secretory organs needs a site or needs a geometry or anatomy by which it can secrete. So, think of it you have. So, when you have to if you think of a pipe what happens a pipe which hose and the it started dumping out the fluid. So, what kind of pipe like a structure this stomach has. So, there we are entering after giving you this whole overall anatomical idea of it I will move on to the cellular structure how the cellular structure of stomach looks like. Let us move on to the cellular structure and how these the histology and the cell and where all these different cells are. So, basically what we will be doing we will take up a cross section of this and we will move on to the cellular histological feature. So, the cellular structure way it looks like if you go through the cross section of the cellular structure it looks something like this. So, bit of a complex drawing, but bear with me which need to look very straight forward. So, something like this is how the structure looks like and even if you make a cross section look like this only. So, and these are line by different cells like this and I will give the different nomenclature. So, imagine it if you reverse it it looks more like a pipe. So, I am just drawing one of them and I will leave the rest for you to for your imagination to take over. These are the different cells which are forming the structure these are the nucleus I am putting. So, these are called these structures are called this gap what you see is called the gastric pit and this these cells are called mucous cell lining, mucous epithelium and within the mucous epithelium you have some series of cells and underneath it and I will come in depth after I will just give you the overall underneath this you have the all the blood vessels which are moving through all this likewise these are the blood vessels you see and along with the lymphatic vessels which are running along. Now, if I take a complete cross section of this something like this and redraw it how that will look like. So, where I will be talking about the different cell types which are involved in it. So, that will look like more like this again redraw that one small fragment that will help you to realize it better I just picked up one of those gastric pits. Now, let put all the cells which are present in the gastric pit I am just doing in the river side drawing the cells that makes life little bit easier. So, these are the cellular lining which are forming the gastric pits and underneath the gastric pits you have another series of cells which are forming the supporting cell to the gastric pits and. So, these are the nucleus. So, in this so I told you that these are the mucous cells and this zone what you see here is called the neck of the pit and within the neck of the pit underneath that you have some cells which I am now putting in red these are called parietal cells and underneath that I am putting them in green the series of cells which are called chef cells and you have series of smooth muscles around that very underneath out here you have certain cells which are called g cells. So, each one of these are formed of each one of those pits what I have drawn formed out of chef cells parietal cells and the g cells. So, we started with the overall architecture we talked about the position of the pylorus fundus body and the connecting tube and then we talked about the basic cellular anatomy and we showed you the location of the gastric pits. So, through this gastric pits what I have drawn basically through this pits you see the secretion of hydrochloric acid how that happens. Now, we will move on to the production of hydrochloric acid none of this the cells which are involved in it they do not produce hydrochloric acid they produce. So, let me give you the way they do it they produce H plus ion and C l minus ion and they secreted and then they interact and form hydrochloric acid. So, if a cell in its cytoplasm starts producing hydrochloric acid then that cell is it is very difficult for that individual cell to survive. So, they do not do it like that and it is a mucus cell lining which prevents these cells from getting destroyed. So, now what we will do we will pick up the individual cell here and then we will talk about how it is forming the how it is helping in the formation of the hydrochloric acid is going back to the cellular geometry of it. So, we talked about the parietal cells. So, within the gastric pit now we are inside the gastric pit within the gastric pit you have two types of secretory cells. So, first one is the parietal cells this parietal cells are especially common along the proximal portion or you must have seen that in the picture. So, these are the these are the proximal section where they are fairly common they are along the proximal portion of the gastric pit portion of gastric pit and they secrete intrinsic factors like vitamin B 12 if you remember that this was helpful in vitamin B 12 is helpful in the R B C production. So, parietal cells the other function of parietal cells are acl production. So, how it does so? So, let us look at the geometry of the parietal cells they. So, I am now I am at the cellular level what I have drawn the just before this now I am talking about the individual cells. So, let us take up this section what is happening is that we have talked about this reaction CO 2 plus H 2 in the presence of carbonic and hydraase carbonic and hydraase enzyme it form H 2 CO 3. H 2 CO 3 immediately dissociates into H plus and A CO 3 minus ions. Then what happens once this gets dissociated. So, this bicarbonate ion which is released here. So, there is these ions 2 3 things happen this H plus ion through transporter moves inside. So, this side is the lumen side of it and this side is the interstitial fluid. So, essentially what is happening is that these 2 ions are transported independently by a mechanism. So, hydrogen ion generated inside the parietal cell as the as the enzyme carbonic and hydraase converts the carbon dioxide and water to carbonic acid which is H 2 CO 3 what you could see here. Then the carbonic acid promptly dissociate into H plus and H CO 3 minus the hydrogen are actively transported into the lumen. So, this hydrogen is actively transported into the once again into the lumen area and whereas, the bicarbonate ion which are produced here is CO 3 is transported into the interstitial fluid. So, these they follow a 2 different. So, there is a counter transport mechanism. So, this is a classic case of between these 2 this 1 and this 1 there is a counter transport. So, after this what happens this H plus which is being moved out there from outside from the interstitial fluid the chloride is being transported like this. This chloride transport and H CO 3 ejection is a reversible. So, on 1 direction what is happening is that the bicarbonate is being released out of the cell and chloride is being taken up the cell. So, it is a kind of a. So, there is a mechanism by which there are 2 reverse processes of which are happening. So, chloride is getting inside the cell and bicarbonate is send out of the cell counter transport. There is a co transport there is a counter transport taking place. So, after this what happens is that once this chloride is being sent here then this chloride for diffusion process moves inside the lumen. So, now you have the source of H plus and C L minus and this side what you are seeing this side is the pit. So, this is where they are throwing out these 2 and whereas, when this H CO 3 is coming on this side this leads to an event which is called alkaline tide. This makes the interstitial fluid fairly alkaline is a sudden influx of the bicarbonate ion. So, what this H CO does? So, the P H goes to 1.5 to 2 and what is essentially does it kills all the microbes this is the major job it does. The second thing is does it denatures the protein and inactivate most of the enzyme of the food most of the enzymes of food. The third important thing it does is that it helps to break down the plant cell wall and a connective tissue in the meat. So, plants because we have a lot of vegetarian diet plant cell wall breakage and connective tissue of meat is being broken down. And lastly this acidic environment does a second set of job acidic environment leads to the activation of essentially the activation and function of pepsin which is basically a protein digestive enzymes secreted by the chef cells which are just underneath it. So, it follows 4 actions once it creates an acidic environment by which most of the microbes are being killed. The second thing it does it denatures all the proteins and the enzymes present in the food. Third thing it does it get rid of it breaks down chops down the plant cell walls and the connective tissue of the non vegetarian part of the food. And lastly what it does it promotes the secretion of pepsin which is secreted by the chief cells. We talked about the parietal cells underneath you have the chief cells. So, now we will talk about what the chief cells are doing out there. So, coming to the chief cells. So, what the chief cells are essentially doing is that they are more abundant near the base as you must remember like I was when I was drawing the pit like this they were mostly concentrated out here along the pit. And this is the pit where all the H plus and C L minus are falling this is the H C L pit. So, they are more towards the base of the gastric pit. So, the major location of it and these cells secretes pepsinogen and which is an inactive proenzyme and it has inactive proenzyme. And this pepsinogen is converted pepsinogen is converted to pepsin presence of acid. And this acid is being supplied by the parietal cells which are present there. So, essentially this pepsin is most functions most effectively at the pH of 1.5 to 2 that is the zone where it acts its activity is maximum. So, we talked about the parietal cells we talked about the chief cells still there is one more cell at the bottom of the pit. If you remember while I was drawing it I showed you that there are certain cells which are present here which I call the G cells. So, if I go back you will see that next one these are the cells we have not talked about this. So, we have talked about this we have talked about this. So, this is the one. So, from here coming H plus and C L minus and these are the ones which are secreting pepsin. Now, let us talk about the third one in the line which is the second which are the G cells. So, pyloric gland which is secreting the. So, these are basically the secret hormone called gastrin produced by the G cells and what gastrin does. So, basically gastrin is produced by the G cells and G cells are most abundant in the gastric pit of the pyloric antrum and gastrin stimulates that this is what gastrin does. So, function of gastrin is that it stimulates couple of things it stimulates the secretion of the parietal and the chief cells. So, secretion of parietal and chief cells this is its major function this is one of the function of it and it has a second function second function is that. So, there is along this there is a contractile movement which is essential. So, contractile movement of the gastric wall this contractile movement is being supported by this gastrin and this is extremely essential it is something like this the food has to be continuously in motion it is just like you are you take you know how you mix the dough while you are making bread it is just you have to mix it you. So, mush it up you have to really you know push it through. So, it has to go through this whole motion that motion is being promoted by the by this hormone called gastrin which is secreted by those G cells which are at the base of the gastric pit. So, that is the function of it. So, now we have pretty much enumerated there is couple of more small details which. So, this pyrrolate gland also contain there is something called D cells which I have not mentioned in that picture they are very few in numbers and they release something called somatostatin which is an hormone that inhibits gastrin release. So, this is kind of this is the inhibitory signal I am drawing gastrin. So, in other word the D cells which are present in the gastric pit are regulating the secretion of the G cells which are secreting gastrin. So, it is a auto mechanism which regulates when the gastrin has to secrete because when the gastrin is secreting when the G cell is secreting gastrin. So, that will stimulate the parietal cells and the chief cells and eventually the secretion of acid by the parietal cell will be enhanced and the secretion of pepsin by the chief cells will be enhanced. So, somatostatin is the one which comes into play and ensures the gastrin secretion is being regulated and thereby preventing the excess secretion of acid. So, overall if I have to summarize the cellular structure. So, we talked about the anatomy now we are the cellular structure. So, there are three types of cells parietal cells chief cells G cells and D cells parietal cells are involved in hydrochloric acid formation. Chief cells are involved in pepsin formation and your G cells are involved in gastrin formation and D cells are involved in somatostatin formation which regulates the gastrin secretion. So, now after this after talking telling you the anatomy overall anatomy cellular anatomy and the structure of the gastric pit just one more just kind of understanding sake. So, if you look at this structure which is more like this. So, this whole thing has pits like this. So, these are the pits where all the processes in a three dimension just imagine this picture in a three dimension the structure section I have drawn. So, from here we will move on to the regulation of the gastric activity and gastric activity is regulated at three different stages. So, one of the stages called the cephalic stage and it is called the intestinal stage and in between there is another stage which will be talking about soon. So, let us get back to the slides about once again about the regulation of gastric activity. So, we have the I was telling you there are three phases by which it is being regulated cephalic phase, gastric phase and intestinal phase. So, what is cephalic phase? It is very interesting that is all the secretion process if we talk about the cephalic phase starts much before the food reaches the stomach. You might wonder how that happens because whenever you smell a good food or some really nice something is frying you get a temptation wow I should eat that. By that time the nerve innervation along the stomach leads to the secretion of a whole bunch of chemicals and that is where the cephalic phase gets initiated. So, the food has not reached there by the way you just smell something and you just taste may be do like this you taste something and already your stomach is getting ready oh something is coming I have to secrete you know hydrochloric acid pepsin and all other things to ensure I can break the stuff. So, that is where we are talking about the cephalic phase and that is why in the first class I was telling you be very careful this is very well innervated network of neurons and blood vessels. They are continuously helping this system like autonomous unit to do its function. So, let us get some of the details of the cephalic phase cephalic phase cephalic phase starts with these are the stimulus a site even the site of the food is smell taste or the most important thought for food initiates. These are the signal which initiates the cephalic phase and interestingly what is happening in the stomach during that time these are the reactions which are taking place in the stomach. So, from the central nervous system I am putting them in red sorry in maroon from the central nervous system these signals are coming through the vagus nerves and they are stimulating the mucus cells, chief cells, parietal cells and the G cells. And mucus starts secreting these are the mucus cells mucus this G cells start secreting pepsinogen and they start secreting HCl and the G cells you know it starts secreting the gastrin. So, this duration is very short it is a short duration event and essentially what is happening during this phase the stomach is priming up itself. That some food will be arriving and there is some degree of secretion. So, if you continuously think about food there will already be a secretion of hydrochloric acid which you may not even be aware of just by the sheer thinking of the food it could you know change your like you know milieu within the stomach from here we move on to the phase 2 which is slightly longer phase which is the gastric phase. So, one to the gastric phase. So, gastric phase last for around 3 to 4 hours and gastric phase of course, 3 to 4 hours and it basically what it does it enhance the enhance secretion of HCl, pepsin and the gastrin and all other things which are involved in it and it creates a prolonged acidic environment for the food to you know kind of the gastric phase. Kind of get ready for absorption in the stomach this is what it does and during that phase there are few other receptors which are getting activated. So, this is the stomach out here. So, from the central nervous system we have talked about the mucus cells I am just putting at m s m c mucus cells a secreting the mucus by m and you have the parietal cells secreting HCl you have the chaff cells c c the secreting the pepsin. So, here this all these are helping the food I am just representing the bolus of the food to mix and apart from it there is a huge rise of the pH in the situation and the stretch receptors here these are the stretch receptors which I told you that they are longitudinal muscles and there are circular muscle stretch receptor chemo receptors all gets activated. So, this is the zone where there is huge amount of blood starts flowing into this all this area and it is kind of action like this I had to kind of action like this is a lot of movement which is taking place because of this different stretch receptors which are there. So, this is a phase where the food is kind of going through just like imagine when your mother in the mother in the kitchen uses a grinder the food is like you know churning churning churning churning. So, this is exactly the churning phase when the food is kind of getting churned up just like a mixy there is a lot of movement there is a circular motion like this there is longitudinal motion like this and it is kind of in different dimension it moves and this is where your food is kind of getting all mixed up with pepsin hydrochloric acid ensuring that it every bit of molecule the HCl and all other pepsin and other component reaches and ensure the food is broken down to as much smaller fragments as possible because the smaller the fragment it will be easier for the intestine to absorb as much nutrient it can afford to absorb from food. So, this is our gastric phase from gastric phase we move on to the cephalic phase which is the third and the final phase of it. So, sorry the intestinal phase I am sorry just pardon me intestinal phase this is just before entering the intestine. So, at this phase there are basically what is happening this is also a very long phase this last for hours. The cephalic phase is the smallest one then come three to four hours phase of churning and this phase is when most of the other things which are involved in circulation. So, this is the phase when your if you remember the D cells get activated ensuring the gastrin secretion is being blocked this is one thing which happens then there are few other controllers which comes into play at this time from the blood vessel which stops the different cells. So, via circulation you have the chief cells for itel cells they are being asked to stop by different factors like C C K G I P and C C K is basically called a cystokinin called a cystokinin and G I P is basically gastrin inhibitory peptide. The name itself is self-explanatory but the stuff this shift cells P cells and everything to you know stop secretion the P H starts falling down or I mean start to go up out here and there is something called my enteric plexus which stops the movement there is a huge amount of churning which is it is something like that just before this I was telling you there is a lot of churning which is taking place like this. So, now it is just like a grinder or a food grinder is slowing down it is now slowing down and the food is almost ready through the pyloric sphincter to move to the intestine for the next series of action. So, this is the overall function at the basic level what is happening in the intestine. So, the food from esophagus enters the intestine and it is exposed to the acid pits which are formed by the gorge like structures of the cell like this by the parietal cells chief cells G cells D cells and this parietal cells secreting hydrochloric acid helps in the formation of hydrochloric acid not the secret hydrochloric acid the secret H plus ion and chloride ion. So, pardon me that statement is wrong that is actually the secret H plus ion and chloride ions into the pit and chief cells are secreting pepsin and this is being further enhanced by the gastrin secreted by the G cells and then there is a lot of mixing of the food taking place. So, initially the first phase is the cephalic phase when just by the thought of food or thinking about it or smelling about it or just tasting about it leads to priming up the stomach. Next phase is the gastric phase where there is a huge amount of movement of the longitudinal circular muscle of the stomach and the third phase is the intestinal phase when the food everything this things started slowing down and food is almost ready as a burlase to move on to the next phase which is the intestinal phase. So, here I will close in. So, if people can go through some of the very nice pictures given online and go through Google and you can give and you will see the whole structure what I have drawn you can see much nice three dimensional views of it and how all these transporters are functioning. Thanks a lot.