Transcribed by Amit Amin

April 04th, 2014

[Organ Systems] [24] [Gastrointestinal Physiology: Regulation and motility] by [Dr. Pavlov] [1] [title of slide] [Pavlov]- This is a new subject that we will be studying. The title is regulation and motility [2] [title of slide] [Pavlov] this is the first lecture out of three for gastrointestinal physiology. I decided here I would follow the textbook. It will be Johnson. I hope you like it better. It will be more uniform. So anyways, I just based presentation on Johnson and it will be mostly figures (from Johnson) along w/ the logic as in terms of how they are presented. They will be 3 themes covered. First is today (regulation and motility). Then it will be secretion and digestion and absorption. I will be skipping some parts that I will not be telling about. They are in the textbook but they will not be tested. I will not follow everything but I will try to follow the order. [3] [title of slide] [Pavlov] This is Part 5 of the textbook. I will not do GI from the other book, but the lecture of the liver will be from the other book. It will follow the GI physiology section. [4] [title of slide] [Pavlov] I will like to review first. This is much easier than respiratory since there arent too many laws we need to learn. There isnt physics (log and function). It will be mostly cartoons, signaling pathways, and some biochemistry stuff. In my impression its an easier subject in this respect. The overall role of GI system is to take food and process it and digest it. Its called digestive system for that but actually there are a few functions we will begin so we will be reviewing we will be looking at different functions and that will be the motility of the system (move food and break down due to physical movement), secretion to secrete substances to help w/ second process of digestion, and after digested, food needs to be absorbed by GI system. They are all interconnected in terms of relationship. You need to coordinate digestion and secretion. It is key to figure out how the parameters are related. [5] [title of slide] [Pavlov] The overall general structure so Ill just remind you. There are key compartments of the system. Starts w/ mouth, stomach, duodenum, small and large intestines. They are key so when we will be looking at different themes, we will be looking at different areas and see how they function. Step by step ways. [6] [title of slide] [Pavlov] The fist kind of general overview of the GI wall structure. This is the general structure. We need to review the major components that are responsible for its function. Overall the wall structure is more or less the same from the esophagus to the large intestine w/ the only difference being the shape. You can appreciate the difference of shape epithelial and lamina propria b/w different parts of the system. Overall the parts are all the same. Compositions of epithelium cells are also different. They are cells that underlie the major functions in that they contain receptors, which have absorption, and secretion cells. Define where they are located and the function and the part of the digestive tract. The overall important parameter 1

Transcribed by Amit Amin

April 04th, 2014

is blood vessels and connective tissue. One of the important parameters in terms of function that would be a muscle layer, relatively thin smooth layer called muscularis mucosa, which is responsible for movement and shape change of epithelial surface. Two important muscle layers are the layer of circular muscle and longitudinal muscle. They are important for movement of the GI wall and whats important here is that they are positioned differently. Circular muscle forms the circle around the GI tract and when they contract they change the diameter of the tract while the longitudinal run along the wall and when they contract they shorten down. Combination is critical for proper movement of the food as you will see. One of the important things here is that the principle is more or less the same. Two contractions that are working in coordination producing food movement and propulsion. Couple of important features here in terms of structure and function. There are two sub mucosal and myentric plexuses, which are groups of nerves that innervate the muscles. They are important in terms of signal transduction. The best way of doing it is through stimulation. Those two groups of nerves play a big part of that. There is another layer underneath which is elastic structure layer. [7] [title of slide] [Pavlov] First we will look at innervation. First big part is regulation (two ways to regulate it). Neuronal function and hormonal function. First we will look at innervation of the tract. Like any other system its obviously like the big extent of the neuronal system. The features we need to know like its autonomic nervous system. We dont have conscious control over the function. It responds to different change in the environment in the GI tract. It produces an appropriate. The innervation of GI is combination of extrinsic and intrinsic innervation. Intrinsic is enteric innervation. Its independent on the central nervous system. They have a brain of their own pretty much. Produce things independently. The extrinsic system is wired by parasympathetic and sympathetic. [8] [title of slide] [Pavlov] This is the extrinsic branch. Here you can see the parasympathetic system is controlled by the Vagus nerve and this is bidirectional signaling b/w afferent and efferent nerves. The data will be collected from the function of the upper part of the tract and then they transduce the central system and then send back for the response. The lower will be the pelvic nerve, which controls the large intestine. The sympathethic system is not connected directly but through gangliar regions. Its connected through celiac region, superior/ inferior mesenteric. [9] [title of slide] [Pavlov] Overall for integration for extrinsic and intrinsic. You can appreciate the mechanisms involved. Few important players. First you would have receptors on the surface of the GI tract and then you would have mechanoreceptors and chemoreceptors. Those would be places, which send information to intrinsic system, and it can go to extrinsic next. Some signal sensed would send signal along enteric system, which lines up on different areas of the tract and coordinates the response. The info can go back to the CNS and then depending on what the process is, it can come back and stimulate the enteric system to process this movement of some kin or it can stimulate some endocrine cells to reduce signaling molecules or it can stimulate secretory cells. Here is an integrated pattern where you would have 2

Transcribed by Amit Amin

April 04th, 2014

internal wiring. Sending info up and down the epithelial cells. There is a connection to the outside environment. There is a connection to the central nervous system. [10] [title of slide] [Pavlov] So the second regulation as I mentioned (endocrine cells). It would be the second way for the GI system to provide the regulation and its provided by GI peptides. The roles regulate many different processes. Mostly summarized are secretions of some substances. The future lectures you will see digestion needs continuous regulation of certain conditions through peptides and electrolyte concentrations for appropriate digestion to occur. Then there are some situations where they regulate muscle contraction and relaxation and have a trophic effect when they regulate the growth of different parts of epithelial parts of mucosal of the GI system. There are two parts where they are located (nerves and endocrine cellsscattered throughout the GI tract). The cells can specialize but dont have a specific location [11] [title of slide] [Pavlov] At the structural level they are peptides. There are a bunch of amino acids. This is just one of the examples (gastrin). It has 17 amino acids and it will have some active groups. This fragment is sufficient to fulfill gastrin function. There is this picture here that shows it can be found in different forms (the sulfur group). Gastrin can be found in different types of forms. In the textbook there are different structures for many hormones but I figured Id show you just one example. Overall they go b/w 1 and 30 and have some active groups. [12] [title of slide] [Pavlov] In terms of how GI peptides classify (through mechanism). Its a typical classification. It can be endocrine action, paracrine, and neorcrine. Here is the summary of how these three are different. The target cell needs to be located far away from the first cell. The hormone needs to be released in blood and then it must travel to reach target cell. It is important for any type of mechanism. Paracrine is where the target cell is really close. There is no mechanism on how its carried. Its really close. Neurocrine is really similar to paracrine but the hormones are released by neurons. [13] [title of slide] [Pavlov] Those are the properties that define GI hormones. First they need to released to physiological stimulus. There response cannot involve neuronal features. This is wrong here. This writing is my mistake. Whats happening here is that the response cannot be neuronal. Hormone will be released and it has to be carried to other regions by blood. So response cannot involve neuronal signal. Its an important mistake I made. IT has to induce the release of some other substance. It has to then effect the target cell. Those conditions need to be fulfilled and in terms of the GI system, for all this criteria (there are only 5 that fulfill it). For now we can only talk about 5 even though there might be others. They are all listed in this table. [14] [title of slide] [Pavlov] This subject is much easier as its not much to understand here. Its nice to remember all of them. Its not too many but you should try to know the general features of the peptides. Here its classified gastrin. They classify by the releaser. In exception to motilin, which is stimulated by nerves, they respond to the 3

Transcribed by Amit Amin

April 04th, 2014

environment inside the GI (amino acids and peptides). This one here is also peptides, amino acids, and fatty acids. This one is most specific to glucose. We will go back to this part when we talk about secretions. We will come into this peptides. I just wanted to stress this . They are classified by what releases them and the site of the release. This is the function. It can stimulate or have a trophic effect (growth). That one can stimulate gal bladder contraction. They can also stimulate secretion of certain enzymes of pancreas and trophic function. All of this conditions secretin (bicarbonate secretion/ pepsin secretion). We will look at this but use this table as a summary so use this to learn them. The only exception is motilin. Its somewhat different b/c it doesnt stimulate secretion, it stimulates the motility of gastric contraction. The name applies to the motion. Its slightly different. [15] [title of slide] [Pavlov] Paracrines, which are short action, are even simpler. Somatostatin and histamine (not peptide but they are released and inhibited by the Vagus or by gastrin. This is the site of release and gastrointestinal mucosa). This is similar in a way that the principle of action is very similar but they are not transferred by blood. They are released and have an immediate action. [16] [title of slide] [Pavlov] The last is neurocrine. The are released from a neuron and its action is a right of way in the vicinity of the release site. The inhibitory peptides cause relaxation in two areas. It relaxes gastric muscles. It stimulates intestinal and pancreatic secretion. Bombesin stimulates gastrin release and gastric mucosa. Enkephalin stimulates smooth muscle contraction. This is it for regulation peptides. [17] [title of slide] [Pavlov] Two ways to control GI system. One is neuronal way and the other is through the peptides. They are obviously integrated so they are closely related. One can cause a change in another. We have two systems for neuronal. Intrinsic and extrinsic. We have hormones, paracrine and neurocrine. GI hormones are endocrine cells throughout the large area of the mucosa. The GI tract is regulated by parasympathetic and sympathetic. Neuronal system is autonomous so it cannot be controlled. Here are the main features for regulation. [18 ] [title of slide] [Pavlov] Going into the section chapter which would be motility. Overall it is very straightforward and uniform. You have different areas of the GI tract. The motility is similar in terms of principles. We would consider these movements as step by step. The first would be chewing and swallowing movement. Moving through the esophagus and then stomach gastric motility here and then travelling through small and large intestine motility. The are all different but the principles should be similar. [19] [title of slide] [Pavlov] The motility is due to contraction of the muscles as in other systems. Here is the general principle. What underlies the motility is this layer of circular muscles here and longitudinal muscles here. They are responsible for the contraction of the smaller diameter. The other is making it shorter. This contraction would created the movement needed for motility. Nerves generally regulate it. Firing of nerves would stimulate contraction. One of the important features that are underlying contraction in a coordinated way is that all the muscle is muscle fibers. The cells are connected 4

Transcribed by Amit Amin

April 04th, 2014

through gap junctions. Its considered as one big cell. Stimulation of one cell will quickly propagate throughout the population. Coordinated contraction of the whole fiber. This is the kind of cell physiology mechanism that underlies the motility of the GI tract. [20] [title of slide] [Pavlov] The first step is chewing and swallowing. The food needs to break down. The chemical breakdown starts there too w/ chemical enzyme. Makes life easier late on. Increase surface area of food that helps the digestion down the road. Overall the important feature is that the same passage is used for swallowing and respiration. The epiglottis helps to protect the trachea so you cannot swallow and respire at the same time. The mechanism here pushes the epiglottis down. [21] [title of slide] [Pavlov] Here is the neuronal regulation of the esophageal movement. Once the food gets to the pharynx the nervous system receives a signal (swallowing center) and the signal is processed and sent back to open upper esophageal sphincter. This food is kind of hard enough to pushed and this continues. This circle of signal continues. Contraction occurs b/c of signal. [22] [title of slide] [Pavlov] Mechanism of movement is peristaltic. The movement in terms of pressure (whats happening in the esophagus). You can appreciate that theres not much activity happening. When food is swallowed, what would happen, there will be a large area of high pressure. Its a contraction of the circular muscle. They will contract and create pressure to push food further and further down. It would be normally closed to protect the back flow from gastric content. As food arrives there, there would be an opening and food can go into the stomach. This is the principle of the esophagus movement of food. [23] [title of slide] [Pavlov] Then it goes to gastric motility. Similar since its coordinated movement of gastric muscles. It surrounds the gut. Here you will see a couple of main principles of the function of the stomach smooth muscles. You need to do three things. First you need to relax to allow food to come in. Then you need to contract to mix the food w/ digestive material. You then need to move food down towards the duodenum for further absorption steps. Each area is responsible for certain responses. The area that is responsible for accepting and accommodating the food (initial receptionfundus). Caudate area is for mixing. [24] [title of slide] [Pavlov] This is a picture of what is happening. The pressure change during the food movement during the mixing. There are a couple modes for stomach function. When there is fasting, it is quiet most of the time. There are intense contractions that occur every roughly 90 minutes. These are slow wave contractions, which are there slow waves (last about 3-5 minutes). What is believed that they clear the stomach if there is something left over. Actually if food occurs, the pattern changes and you have 3-5 contractions/ minute lasting 2-20 seconds. Must more action and frequency during the food process. Whats happening here are two things. First the mixing of the food and then the movement of the food after it is mixed enough. Its moved to the duodenum. The pressure is increasing as the muscle contraction going 5

Transcribed by Amit Amin

April 04th, 2014

to the upper region to caudate/ duodenum region. Depending on the state of the food, it can either go into duodenum or be pulled back and allow propulsion of food into duodenum. [25] [title of slide] [Pavlov] This is to show how relationship b/w mechanical and electrical activity b/w food movement. Muscle contraction is coordinated by neuronal activity. Here is the membrane potential and electrical activity in neurons. Depending on the value of membrane depolarization, you will have two types of events. If there is too small depolarization you will not have much contraction (not enough stimulus). Increased stimulation will be the feedback that food is in stomach and tells you that you need to produce some electrical activity. W/ this activity you can develop enough action potential in muscle to get contraction w/ enough calcium influx. It is proportional to neuronal and smooth muscle action potential firing. Lot of activity is longer duration and larger strength of the contractions during food movement. [26] [title of slide] [Pavlov] The next step is in the small intestine. The small intestine, it will be since the main role would be digestion and absorption you basically would have a couple of things. The movement is what is required to mix digestion enzymes w/ material to help prepare food for absorption. Cause further reduction of particle size. Physically mixing things. Then it will be circulation. This food which has been digested, it must be circulated to be absorbed through the intestine which allows the digestive material to be exposed to the intestinal cells to be absorbed. All this movement needs to be coordinated for the propulsion to the large intestine. [27] [title of slide] [Pavlov] Overall the principle is the same. Circular and longitudinal muscles. Here is just some frequency of whats happening. In fasting humans the movement is spaced unevenly. Contraction is 1-5cm and its not really active except for every 90 minutes (intensive contractions- coordinated in a way such that any food unabsorbed it will be cleared during the contraction). After the meal, the contractions become more uniform and occur all over the small intestine. The purpose of the contractions is to mix food well and help it better dissolve. It will then move to the large intestine when this process is done. [28] [title of slide] [Pavlov] It starts/ with the ileum and the ascending, transverse, descending, sigmoidal colon ending in the rectum. I want to point out the curves which are regions organized due to the specifics of the contraction pattern of the large intestine. Heres a carton showing this. [29] [title of slide] [Pavlov] skip [30] [title of slide] [Pavlov] Basically what will happen here, food becomes more tightly packed. The idea is that it gets accumulated and it forms contractile units. They contract and help food to get absorb as much water and material as possible. Then what is happening is this structure after the contraction, is the movement of large food. The intestine becomes stretched. It gets pushed forward towards the rectum. As you can see, in

Transcribed by Amit Amin

April 04th, 2014

case of intestine, it moves in very big parts. The big pieces are moved and the process of absorption occurs. It proceeds until the rectum.. [31] [title of slide] [Pavlov] This is the parameter of the large intestine. Proximal movements are segmental. Mix contents to expose surface to absorb liquid. Most absorption occurs in the proximal colon. The segmental contraction lasts 12-60 seconds. Big movement occurs 1-3 times a day (moves significant amount each time). Content will move 20 cm. It will move from one segment to the next one. It pretty much is as mentioned is movement processes. Coordinated movement and propulsion of food. [32] [title of slide] [Pavlov] To summarize movement part, it occurs due to coordinated contraction of GI smooth muscle cells. Movement occurs due to high to low pressure areas. Movement in stomach is responsible to storage, mixing, and emptying. Small intestine is after meal movements due to repetitive contractions. Large intestine has large peristaltic phase that moves large amount of food at each time.