Transcribed by Amit Amin [Organ Systems] [27] [Digestion and Absorption] by [Dr.

Pavlov]

04/13/2014

[1] [Title] [Dr. Pavlov] So lets start our third lecture for gastrointestinal physiology and so todays the last lecture which completes this section of GI system. The main subject of today is digestion and absorption. Pretty much as we discussed before there are four main functions and this will be the last function that will be accomplished by the GI system after the food has been moved into the system and broken down. Then some secretion occurs which is a regulated process. Following the secretion of the enzymes and the other solutes, digestion can accomplish and finished by absorption so this pretty much will be it for the whole system. [2] [Overview] [Dr. Pavlov] So heres an overview of what Im doing today. I will review general principles of digestion and absorption processes. I will look at specifics of digestion/ absorption. So for key dietary products: carbs, proteins, and lipids and Ill mention something about Vitamins very briefly. I will end w/ the process of absorption of water and electrolytes by the digestive system. Overall it follows closely Johnson as I mentioned I tried to do for GI. Not much deviation for these chapters 35/36 including figures and main figures. [3] [Definitions] [Dr. Pavlov] In terms of definitions as I mentioned, digestion is the process of chemical breakdown of the ingested food in order to make it absorbable by the epithelial cells. Absorption itself is the movement of nutrients, water, and electrolytes through the epithelial cell lining towards the blood and lymph systems. [4] [Structural organization with respect to the function of the individual cells] [Dr. Pavlov] Before we look at details of this process. First we will say a few words of the structural organization (functional) of the epithelial cells that are responsible for the absorption of the material. Heres one of the important observations: Almost all digestion/absorption occurs in small intestine. Although we talked a little bit about digestion in some other parts like the mouth or stomach, essentially the small intestine is the main location for digestion/ absorption process. I will not be focusing too much on the specific locations. Pretty much its all more or less relevant for the small intestine. For the structure of the small intestine its not (I replayed the podcast 5 times and still dont know what word he said here. I dont think its important) of this is the kind of the surface of the intestine, you can see that its actually covered by these villi structures which are thick, finger-like, structures called villus and the idea here that is in order to improve to the process of absorption you would need a bigger surface. What they aaccomplished on the relatively flat small surface you can increase the surface for absorption by manyfold. This surface layer is made up of enterocytes that are the main cells for absorption. There are also other major components that are filled in w/ Goblet cells (secretion cells) need for mucus secretion. Its important for the media for different functions. Theres no exception here. Goblet cells would be the source of mucus. In terms of structural organization a couple important considerations: villi responsible for the increase in surface area but actually the surface area is increased even 1

Transcribed by Amit Amin

04/13/2014

further by introduction of microvilli. These are processes on top of the enterocyte cells and when combined this is further. The small surface is increased many-folds with the microvilli and there will be some cartoon later on showing some more detail on how this structure is made. To finish w/ the structural considerations there is also an invagination here so they are kind of In contact with villi. Whats important here for this subject is that this whole surface for the absorbance and digestion is really active. There are lots of enzymatic activities going on and it needs constant renewal accomplished by proliferative cells in the crypts. They are mitotic and keep dividing and bring in new cells towards the villi. This is the most important role of the cells in the crypt regions here. [5] [Classification of the digestive enzymes] [Dr. Pavlov] In terms of classification, most of the digestion is done by enzymatic activity. Theres a large family of enzymes, each of which will be special at a certain type of food. This is the list. We will kind of talk about this and that enzymes throughout this lecture. This is an overview with some important notes. Youve seen things like amylase, lipase in terms of salivary glands and stomach but here you can see it is important for intestinal digestion. Most of the enzymes are secreted from the pancreases or they are produced by intestinal mucosa. You can see the bulk of the enzymes are really related to the small intestine. Some of the enzymes youve already heard like trypsin, phospholipase, and others. From the names you can guess if they will be proteins, lipases, or disaccharides. Its pretty straightforward in terms of classification. I will go through these enzymes through time in the lecture. Another important breakdown apart of specificity and source is also their location. Where they function. There are two key locations. One is luminal digestion that is in digestion juice (water media) inside the small intestine. Electrolyte media. Another location would be membrane digestion enzymes. This is part of digestion which happens on the surface so enterocytes synthesis and secrete a number of enzymes located in microvilli. They stay attached to the membrane. This is important in terms of digestion and absorption coordination and in some conditions such as the ones we will see. One of the important notes here, most of the enzymes are present in excess. There are more enzymes than food to digest. Theres a big reserve mechanism for the source of enzymes to digest food. They are mostly in the intestine and they are sufficient do the job. [6] [Absorption mechanisms: barriers to cross] [Dr. Pavlov] To look at the specific transport in terms of absorption, heres the overview. Ill just briefly mention a few layers/ barriers that need to be crossed by food to get from lumen to capillary. Here they are all listed. First we will start w/ unstirred layer like here that is small water like layer close to the microvilli. After stuff is diffused towards microvilli you will have a special surface membrane that has transporters and some lipid composition. This is one of the important barriers to cross that we will talk in more details. Then diffusion through cytoplasm and then crossing the serosal side of the membrane and crossing basal membrane capillary. In terms of specific transport we will talk about crossing these two membranes. The luminal side, mucosal side and serosal side. [7] [Absorption mechanisms: transport mechanisms]

Transcribed by Amit Amin

04/13/2014

[Dr. Pavlov] By the mechanism, for absorption whatever food stuff you are talking about, it needs to cross the barrier. It can be achieved in several different ways. Here are the general classifications of the transporting mechanism that occur. There will be some specific examples in future sides. Its kind of nice to have a big picture of how this can happen. First is simple diffusion when you have the molecules flowing by due to some dragging force like concentration gradient. Then active transport when something goes against the gradient or electrical force. Here the active means you need to use energy (ATP) to produce this movement. Secondary transport is similar where you try to cross against the gradient. The difference here the energy occurs w/ some separate part of the transporting molecule. Not direct consumption of energy by transporter that carries the molecule but rather some coupled process. Some other process consumes energy and this energy is used to facilitate transport. Facilitated diffusion is similar to simple diffusion when the molecule just goes through but in this case some certain transporting mechanism is involved. In facilitated diffusion you would have passive transport without energy use. You would need some molecular machinery rather than just bilayer for example. Pinocytosis is when the membrane has vesicle like transport when you would have membrane vesicles fuse w/ the membrane and release some stuff. [8] [Starch: the major dietary form of carbohydrates] [Dr. Pavlov] Now we will just go step by step for digestion/ absorption process and the key components. The carbohydrates, proteins, and lipids. First we wills start w/ carbs and some example molecules. Carbs are polysaccharides and you will have a lot of monosaccharide here. Most dietary food comes in starch that is a gigantic molecule. Its not just this, but its pretty much large branches all over. Theres no sugar here but you could kind of imagine that youd have this gigantic with many monosaccharide. This first gets broken down by amylase that is the enzyme that recognizes certain patterns in terms of the structure of the polysaccharides. The breakdown products would be maltose, dextrin, and maltotriose. This is kind of the first process when the starch is broken to small pieces. [9] [Enzymes involved in carbohydrate digestion] [Dr. Pavlov] Heres the overview of all enzymes involved in carbohydrate digestion in general. The overall idea that actually occurs is that sugars come as polysaccharides but the problem is that they are too big. They cannot be absorbed by the system. The whole idea of the enzymes would be to break them down to glucose, galatctose, and fructose that are three monosacrraides that can be absorbed by the intestinal membrane. Here are the key starting products which probably most important lactose, sucrose, and as I mentioned products of the starch. As you can see theres specific enzyme that are located on the membrane part of the system of the villi and here you can see this location so after they receive this more than one saccharide (starting w/ di-) certain enzymes can break them down. Sucrose would be sucrase breaking to glucose and fructose. The overall idea these things cannot be absorbed and these things can be absorbed so for digestion its breaking down to monosaccrides. [10] [Absorption] [Dr. Pavlov] This is the process of absorption. After this job is done, glucose, galatose, and fructose, they are absorbed by similar mechanism. This is an example 3

Transcribed by Amit Amin

04/13/2014

of the glucose transporter where you need glucose and sodium to bind in order for this transporter to diffuse into the cytoplasm and release glucose inside. To cross the membrane you would actually need sodium and glucose binding. Here you can appreciate this is driven by a second directive transport which removes sodium content from the cytoplasm against the concentration gradient. Use this energy here. Due to decreased sodium inside the cytoplasm this thing can move in. This is like a recycling process which on its own doesnt need energy but does require the work of this pump. For fructose is kind of facilitated diffusion when you can see fructose bind to glut5 transport and this can be diffused inside. Only these three can be transported this way. This is why the sugars need to be broken down to monosaccharaides. After that all three go to facilitated transport. [11] [Protein digestion: luminal enzymes] [Dr. Pavlov] So for protein digestion theres a large family of enzymes. Here I just want to bring a couple of points based on this cartoon. When you work with the protein digestion, protein is a long change of amino acids. You have two families of enzyme. Endopeptides and exopeptides. The difference b/w the two. Endo cleaves this long polypeptide chain in the middle somewhere. They cut it into small pieces. Either in two or in different pieces. Exopeptides they chew one by one the amino acids form the terminal regions of the polypeptide chains. This would be the classification of the peptidases by the mechanism of action. In terms of specificity of what they do for example take pepsin what it will do. If you have protein built of many amino acids, some of them will be aromatic rings. Pepsin will not cut at random positions but it will cut them in specific regions that contain aromatic amino acids. It will be smaller pieces cut in these specific regions. The same true for these enzymes. They recognize certain patterns (amino acids) big protein shorter peptides. In terms of overall results you will both have a single amino acids produced by exact peptidases and then you have short peptides. Very long proteins cleaved into shorter peptides. [12] [Activation of proteases] [Dr. Pavlov] Another important concept that is linked to the activity of proteases is that need to be activated. The problems here that actually occur is that cells that have their own proteins produce proteases. You dont really want the proteases to work at that stage. You rather have them work at the site where they can digest food rather than digest the cell itself. This is achieved by a two step process of first Trypsinogen released that is actually a precursor for trypsin. Trypsinogen gets activated by enterokinase to cleave it to trypsin. Trypsin on its own can produce other catalytic activities to activate trypsinogen and other proteases. This is the process of how these proteases can be produced inside the cell w/o doing much harm to them and how they need to be activated later on. [13] [Absorption of the peptides and amino acids] [Dr. Pavlov] So in terms of final absorption, protein can be digested into different things. What happening is about 40% of the digestion on the lumen side it occurs to amino acids and di/tri- peptides. Two and three amino acids long small pieces that can be absorbed. About 60% of the digestion for the peptides is finalized on the microvilli area where you have peptidases where they finish the job. Then you get amino acids and di/tripeptides that can be transported inside the cytoplasm 4

Transcribed by Amit Amin

04/13/2014

through specific transporters. Then they can go into the blood. The only notion here which is I guess is material is theres also some cytoplasmic peptidase present which help to break down di/tri-peptides to single amino acids which are much simpler to transport. In terms of what blood receives is 75% single amino acids and 25% di/tri-peptides. [14] [Digestion of lipids] [Dr. Pavlov] Now moving on to lipids or fats. Pretty much the main content of lipids are triglycerides so Ill look at the molecule in a second. It has a glycerol and three fatty acids. Those lipids are digested in the stomach but the big part comes in the intestinal region and here as you can see one of the problems is that they are not well emulsified in the stomach. They are in the form of pretty large lipidic droplets since they cant be dissolved in the water. In the small intestine you have much better environment due to the presence of bile as we discussed in the second lecture. Bile helps form these nice small micelles. It can be attacked and digested by pancreatic lipase that is the key enzyme and then move towards digestion. [15] [Three major classes of fat and their digestion products] [Dr. Pavlov] These are the three main classes of fat in terms of not of amount (mostly triglycerides) but also cholesterolester and lecithin which are made up of phosolipids. Phospholipids are important for building membranes. Cholesterol is very important for generation of this steroid hormones. Overall the idea here is that the trigylercerides have three long change fatty acids that are 16 or 18 carbon long. The first step is pancreatic lipase. It cleaves two amino acids and produces two monoglycerides. Two monoglycerides means in addition to glycerol you have amino acids attached. Cholesterol through hydrolysis does two things. It hydrolyzes further monoglyceride to produce glycerol and free fatty acids. It also cleaves fatty acids from cholesterol. The other enzyme is phospholipase II that is specific for phospholipid. Phospholipid is different from triglyceride b/c it has a phosphate group attached in position 3. Phospholipase II cleaves fatty acids in position 2 of the phospholipid and releases lysolecithin and lecithin. After this has been done, the result will be a bunch of fat and cholesterol. [16] [Absorption of fat digestion products ] [Dr. Pavlov] After that they can be absorbed. There are a few steps here. They follow the overall logic of border crossing except its not as trivial as in previous processes in terms of how its transported through the cytoplasm. What happens here is the first process that is miscelle that brings cholesterol, fatty acids, and monoglycerides towards brush border/ microvilli area. Since they are hydrophobic they diffuse w/ no problem through the membrane. Since they are hydrophobic they have a problem to hang out in the cytoplasm that is water. Here the big help comes from fatty acid binding proteins that attach to the molecules that arrive as monoglycerides and fatty acids and help carry them to the smooth ER where the following reaction occurs. Essentially overall the whole idea of this reaction is essentially to resynthesize triglycerides from fatty acids and monoglycerides. Its an interesting way in which the organism deals w/ the process. It gets cleaved in the lumen and then it gets resynthesized. Here this process is ATP consumption and then coenzyme A w/ two fatty acids attached to it. Progressively this process leads to the formation of triglycerides. This occurs in the smooth ER. Theres some 5

Transcribed by Amit Amin

04/13/2014

resynthesize of phospholipids using phosphaticidic acid here. Overall this end result of this rebuilding process that all of these molecules come together into structures called chylomicrons. What is here is that 90% of triglycerides which are hydrophobic which are located inside. On top of it are phospholipids that have polar groups so they can shape it up and feel good in water. Other proteins are important. Theres a whole big family that are very little in amount but they are essential for this structure to be moved into the lymph system. Its about 1% but its located on the surface. They recognize certain receptors that help for the exocytosis of this large formation into the lymph. [17] [Dietary vitamins absorbed by small intestine] [Dr. Pavlov] Couple of other things which get absorbed. First is vitamins. We will not talk about specific mechanism. They are fairly similar on how it happens. Some through facilitated transporters, diffusion, or not known. One of the interesting factors to know is that they can be of two different ways. Some are water soluble while others are fat soluble. In terms of absorption follow the same patterns. Water soluble would be the same way and the fats a similar way. This is probably it. Ill just remind you that at this stage B12 absorption which requires intrinsic factor. Its an important factor that gets released in the stomach. Its the proper way to remind about intrinsic factor. [18] [Most important mineral absorbed are calcium and iron] [Dr. Pavlov] Another important class is the absorbance of minerals. A couple of minerals Ill mention are calcium and iron. We will not talk about calcium. Its important for calcium signaling and bone formation. Its very important mineral. Theres a separate chapter for that in the textbook that we will not really look at in this context. Another important is Iron that is one of the key catalytic components of heme. Its required for processes like hemoglobin production and activity or cytochrome activity in the respiratory chain. Its important and is transported in terms of heme, linked to the heme of protein, or it can be transported on its own in a free form by a known mechanism. Heres facilitated diffusion. Overall what happens, is that iron cannot be in a free form so it binds to intestinal transferrin or to ferritin. This just for storage ad heres for transport. Intestinal transferrin that is a protein that is recognized by a specific transporter. It gets into blood and can get to storage or Fe-ferritin or utilization sites for the synthesis of heme proteins. [19] [Water and sodium input-output balance] [Dr. Pavlov] The very last couple of concepts is the absorption of water and sodium by the digestive system. Here when we talked through the lecture about secretion you can see that the secretion comes with a lot of liquid coming out into the system. This is the breakdown of the daily volume secretion in terms of what secretes what. You can see that only 2L gets taken up w/ the food. You can see the saliva, gastric secretion, bile, pancreatic section, and small intestinal secretion all move a lot of water into the system. Obviously its very critical that the organism will get the water back and does it efficiently. Only 100-200mL gets excreted. The rest gets absorbed. Its mostly in the small intestine here. All of this absorbance including liquid comes in the small intestine. The other component that we will discuss is sodium. Also see in the secretion part that a lot of sodium gets out in to the system that the organism needs to get back somehow for reuse. 6

Transcribed by Amit Amin

04/13/2014

[20] [Functional organization of the absorptive cells] [Dr. Pavlov] For functional organization we will look at the general rules of the absorptive cells like the lining cells in the small intestine. There are only a couple membranes that need to be crossed. This is the apical membrane that faces the lumen and the basolateral membrane that faces the blood side. Overall theres one rule to which they can cross in order to be reabsorbed which is transcellular route. We just talked about it in different molecule context. This transcellular route is similar (mechanism different) in terms of philosophy (needs to go through membranes). For water and small molecules like sodium theres the Para cellular route that is located in tight junctions b/w the cells. Depending on the exact locations these junctions can be very tight and not let anything through or they can be selectively permeable and not let some things like sugars or amino acids but they will allow small ions like sodium to go through and get absorbed. These are the main two routes for liquid and ion absorption. [21] [Sodium absorption mechanisms] [Dr. Pavlov] For the sodium we will look at the main mechanism for the active transport. Transcellular transport. Heres two key points. This figure is flipped compared to this picture. Overall to cross the luminal membrane, apical membrane. Overall there are 4 different mechanisms. Whats important about them is that they are all passive. They all go down the energy gradient so they dont require any energy use. Here you can see they can go through single channels, singular water/ sodium, or go co-transport with some organic molecules. They can go as cotransport w/ negatively charged chlorides to keep electroneutrality. They can go as an exchange (positive to positive) keeping electroneutrality. Its passive. Overall its passive transport to cross the first membrane. This can be different for different mechanisms. They exchange at different parts of the small intestine. For the transport into the blood part its different b/c here the sodium needs to go from low conc. to high conc. This process occurs through the exchanger. You can see here you would have potassium low inside going up against the gradient. The same for sodium. This is going against the normal downhill energy. Trying to buildup more gradient and obviously this is active transport that uses energy of ATP to produce this movement. [22] [Water absorption: direct relationship between water and solute absorption] [Dr. Pavlov] The last is for water absorption. Pretty much, one of the important concept of water is very simple is a diffusion driven by osmotic forces. Heres just one example of how it works. Osmotic force is when you have a barrier of water. Pure water on one side and water with some material inside on the right side. Water will try to move to spread out the material where you have more molecules of the solutes present. Heres the result of this osmotic force. When solute absorption occurs it naturally carries water along with it. Heres two examples of how this would happen. The principle is the same in leaky epithelia where isnt tight junctions not allowing water flow through and stuff can only go through the cells. The principles are the same but the rates are different. Its more efficiently to move water through leaky epithelia than tight. Overall the principle the more solutes you absorb the more water comes along. 7

Transcribed by Amit Amin

04/13/2014

[23] [Water absorption] [Dr. Pavlov] This is the basic mechanism. Its not like solutes will come in one cell and water in another. They come in parallel in the same cell. Heres an example of driving forces. In leaky epithelia you will have buildup of the solutes in the cell that will increase the osmolality that will drag water along the cell membrane. Because of this, solutes try to build up in this intracellular space. The osmolality will increase compared to luminal space. It will cause an influx of water through these leaky junctions. There will be much easier for water to go through since in will go through the cell and the leaky cell. Thats why transport is higher in leaky compared to tight epithelia. Where as in tight it will have the same buildup of the solutes but there will be no shortcut pathway for water to go. Water will need to cross 2 barriers. It can do it but its not as efficient as it can like the leaky epithelia. Thats the basic principle. Overall its a passive force driven by osmotic forces. Molecules build up in cell/ blood and youll have the driving forces for water to go along. [24] [Summary] [Dr. Pavlov] To summarize this small intestine is the main place where digestion and absorption occurs. Digestion is catalyzed by a number of specific enzymes and it can occur at the lumen as well at the membrane regions depending on specific enzyme locations. Three main classes of foods: proteins, carbs, and lipids each of which has specific enzymes and transporting systems. Sodium transport by trans cellular route is passive at the apical (mucosal) membrane and active and the basolateral (serosal) membrane. For water its also the passive process that is driven by osmotic forces.