Appendix 4: Gastrointestinal Tract Podcast Transcript
Hey, welcome back everyone! This is our last podcast, we’re looking at the Gastrointestinal tract today. Okay so we’ll give a little intro then get into directionality, which is a super important concept that will be coming up throughout the rest of the unit. So when we’re looking at the GI tract, we want to keep in mind that, even though it seems like it travels through the body, technically, the GI tract is located outside the body, starting with the opening of the mouth and ending at the anus. On the outside of the GIT, we have the epithelium, made of epithelial cells. These are asymmetrical with the apical side facing into the lumen and the basolateral side facing into the body. Think about the epithelial cells as like a bridge connecting the basolateral and apical layers.
In the gastrointestinal tract, which we call the GIT, the key terms here for directionality are Motility, secretions, digestion, and absorption, all happening at the same time. So we’ll look at the key words associated with this concept. Motility is happening down the gut. Digestion occurs outside the body, since the GIT is outside the body. That means secretions are also happening outside the body, coming from tissues lining the GIT. On the other hand, absorption occurs from outside to inside the body. So from the GIT to the body, unlike those other terms. We’re bringing nutrients inside. We’re now going to talk about slow waves and spike potentials. One question we see a lot of students have is about the difference between slow waves and spike potentials. So let’s think about what’s the difference?
These are slightly different than action potentials, they can initiate an action potential in certain situations. So small movements of ions create small fluctuations of membrane potential, so from like -60mV to -40mV and those fluctuations are the slow waves. I know that might seem like it would reach a threshold and cause an action potential but it just barely reaches threshold here, and that would create a spike potential. This creates a small amount of force, and this force will affect motility of food through the GIT. If this slow wave goes higher than -40mV, more spike potentials will be created, and therefore more force, ‘cause we can now consider the sum of all those small forces. The one key here is that the force is proportional to the change in membrane potential. So when we see big spikes, this is often the result of spike waves and a slight depolarization of the cell membrane.
We can think about in the GIT, how and why would you want to create more force? So more force can increase the motility of the food passing through the GIT. Full spike potentials, and therefore increased force, is often a result of the combination of a slow wave and a partial depolarization of a smooth muscle caused by stimulation from food.
A distinctive character of the apical side that shows the cell’s asymmetry is microvilli. The microvilli extend into the lumen and increases the surface area that can come into contact with foodstuffs. This is important for absorption of nutrients- the more contact a food has with the epithelial layer, the more absorption can occur.
Now we’re going to think about digesting food. We know that there are lots of different secretions needed for digesting carbs, fats, and proteins. Why is that? Carbs, fats and proteins are all built differently and have different properties. This means that different enzymes and processes are used to break them down for the body to use.
What about bile? Bile has lots of roles and can even be recycled, so let’s discuss that. Hopefully you know that bile is produced by the liver and stored in the gallbladder and gets secreted for use in the small intestine. It is also amphipathic, meaning it has both hydrophobic and hydrophilic parts. Bile targets lipids, which are water insoluble and will clump together, making them difficult to digest. Bile will act on these clumps of lipids to break them down into more, smaller pieces. More smaller pieces of something will have more surface area than fewer, bigger balls of the lipid, and this makes it easier for pancreatic lipases to come in and break them down from there.
Bile also gets recycled by getting reabsorbed into the blood found in the ileum. This blood travels into the portal vein to the liver, and is extracted by the liver cells. They can then be re-secreted or recycled.
When looking at carbohydrates, you may wonder why are there multiple enzymes necessary to be able to absorb carbohydrates? This is because carbohydrates are made up of glucose, and it is important that we break down carbohydrates into their monosaccharides. This process begins in the mouth, where salivary amylase mixes with food and breaks down carbohydrates by turning polysaccharides into disaccharides. When the bolus, which is a mixture of food and saliva, reaches the stomach, salivary amylase is inactivated because it can’t function in the environmental conditions of the stomach, like the low pH. Once chyme, which is the partially digested food and juices from the stomach, reach the small intestine, carbohydrates are digested further.
We know that salivary amylase couldn’t break down carbohydrates any further than disaccharides, and we can also think about how there aren’t salivary glands in the small intestine, so salivary amylase couldn’t be secreted. Instead, the enzyme pancreatic amylase from the pancreas digests the remaining polysaccharides and disaccharides . To finish the job, brush border enzymes in the small intestine, sucrase, lactase and maltase breakdown the disaccharides into monosaccharides. Monosaccharides are the smallest units, and can be absorbed in the small intestine.
When we look at protein digesting enzymes, we find that most require activation. We can think about how if the body produced proteins in their active form, cells and organs that secrete these proteins may get broken down in addition to the proteins that need to be broken down in food. We definitely don’t want to degrade our own proteins in the body that are needed to function, so our body has a complex activation system for many of our digestive enzymes to prevent self-inflicted digestion of our body cells. We see that protein digestion occurs in the stomach and small intestine, remember that we don’t have protein digestion in the mouth because, again, there’s that problem with the body possibly digesting proteins in the mouth which we do not want.
We are going to go talk about a couple enzymes involved in protein digestion – you should have a grasp on where these enzymes are coming from and what activates these enzymes. I like to remember these examples by thinking about how the inactive form of an enzyme is called a “zymogen”. Because of this, most often the inactive form of an enzyme ends with the word fragment “ogen”. Once the enzyme is active, it is called a protease, which is defined as an enzyme that breaks down peptides and proteins.
The first example is pepsinogen, a zymogen, which comes from the chief cells and is inactive. It is activated by low pH, and turns into the active enzyme, pepsin, so the low pH like we would find in the stomach. Another example is trypsinogen, a zymogen, which is inactive, again, and comes from the pancreas, and is activated by enteropeptidase, which is secreted from the jejunum and duodenum cells. Trypsinogen is converted into the active form of the enzyme, trypsin.
Now we’re going to look at lipid digestion and absorption. To prepare lipids for absorption, which means moving them from the lumen of the intestine to the internal environment in the body, they need to be packaged. And as absorption occurs, these packaging methods change.
It is important to know the difference between micelles and chylomicrons when thinking about this packaging. Remember that lipids can’t travel through the blood freely, they must be packaged with amphipathic molecules, which means molecules that have both hydrophilic and hydrophobic components. Micelles and chylomicrons both package lipids, but micelles package lipids in the environment, or the lumen, while chylomicrons package lipids in the cell.
Micelles are formed when bile salts surround monoglycerides and long chain fatty acids creating a tiny sphere. When the micelle reaches a brush border cell, the long chain fatty acids and monoglycerides diffuse across the cells and into the internal environment. The long chain fatty acids and monoglycerides then combine to form triglycerides, which stick to each other and are then coated with proteins. This larger sphere, coated in proteins, is called a chylomicron, and it is larger than the little tiny spheres in the lumen that we call micelles.
Now we’re going to briefly discuss water because, as you probably know, H2O comes up in a lot of processes in the human body, so water absorption is so important. In a day we may drink 2L of water, but internal sources (such as saliva, gastric, pancreatic, liver, and small intestine secretions) will contribute approximately 6-7L to this. That’s a total of almost 9L of water entering in the small intestine, which is the primary site of water absorption. The large intestine also functions to absorb water and can absorb 6.5L a day, that’s a lot of water.
The reason most of the water is absorbed in the small intestine is because of the concentration gradient that has occurred. We can think back to our communications: principles unit about the idea of concentration gradients and diffusion. In this case, the huge volume of water in the small intestine (remember- this is outside the body) will want to travel to where there is a lower concentration of water, inside the body. It is also important to remember that water follows sodium to maintain its concentration gradient, and sodium is constantly being brought into the epithelial cells during absorption. Therefore, water would want to move into the body from the small intestine, and this is what we call absorption.
We’re going to talk about how calcium and phosphate absorption is related to vitamin D. We know that Vitamin D is used to make 1,25-OH-D. This process was discussed in our previous podcast, in the communications: hormones unit. 1,25-OH-D is lipid soluble and can diffuse into the epithelial cell, where it acts on the nucleus to produce proteins that help with absorption. For calcium, 1,25-OH-D increases protein synthesis of 3 things: calbindin, the calcium pump/exchanger, and calcium transporter. These are all needed for calcium absorption.
Calbindin is particularly important because without it, calcium is used as a secondary messenger for various mechanisms that we may not want to occur. Calbindin binds to calcium to prevent this from happening, until it can be pumped out on the basolateral side. 1,25-OH-D is also needed for phosphate absorption, with a similar mechanism to calcium. 1,25-OH-D diffuses into the cell, and acts on the nucleus to increase protein synthesis of the phosphate symporter and ATPase that maintains the concentration gradient for the symporter. Overall, when there is low vitamin D, there would be low 1,25-OH-D, and consequently less synthesis of the proteins needed for nutrient absorption so this would result in lower nutrient absorption.
We can think about how all the processes in this chapter work together. Food comes through the GIT, which causes depolarization of the membrane, which is coupled with slow wave which causes action potentials which generate force. This force is what causes the movement of the bolus of food. We can think about how this bolus moves in terms of directionality- how it moves down the GIT which we now know is “outside the body”. The movement helps the bolus to reach epithelial tissue that will absorb it, remember that the directionality is that it moves from the outside of the body across the apical side into epithelial cells, where villi increase surface area and allow more interactions to allow for optimal absorption.
Okay now that we’ve talked about the integration of everything, how it all fits together, we are officially done our podcasts. Thanks everyone for listening. Tune in to the next 3 podcasts when you take Physiology 2, HK 3810!
