incredibly complex system. What Jennifer and Femi have done is taken you through the luminal digestive tract, and I am going to walk you through the other component of the digestive tract, which is the extraluminal organs. And that includes the liver, the biliary system, and the pancreas. We are not going to spend much time this morning talking about diseases of these organs, really mostly so we can concentrate more time talking about EOE in your program. But if you have any questions, and I'll try to touch on some of the disease states of the liver, gallbladder, and pancreas as we go through. But here you can see that the liver, gallbladder, and pancreas are the digestive organs, and the luminal digestive tract is really the esophagus, stomach, and small and large intestine. And really it could include the mouth and the salivary glands, but our ENT colleagues tend to manage most of the diseases of those sites. So the liver is really a fascinating organ. It has over 500 functions. In fact, there is a whole training program or fellowship where individuals go to spend a year and sometimes 18 months just learning about the liver. It has the three basic functions of the liver are synthesis, storage, and breakdown. And we'll kind of cover that. That's really what the liver does in three basic functions, but when you break it down into the granular details, there's over 500 functions that the liver actually performs. From an anatomic standpoint, it's located in the right upper quadrant, and it's made up of both a left and a right lobe. It weighs, just a trivia question, about three to four pounds, and it is the largest solid organ in the human body. It has two distinct blood supplies. One is an arterial blood supply that provides about 30 percent of the blood flow to liver through the hepatic artery, and then there's a venous blood supply, the portal vein that supplies the other two-thirds of blood flow, and that portal vein carries all of the absorptive contents from the intestines, the luminal digestive tract, if you will. And the liver serves to be the first organ in the body or the first site in the body that actually sees any nutrients or foreign material that's coming into the human body once it's absorbed by the intestine. And so you can imagine the important function that the liver serves in terms of breaking down, further breaking down nutrients and storing them, but also detoxifying anything that comes in, any foreign substances that come into the body, and that includes drugs. Okay, this is really a little bit more detail on the anatomy. You can see that there are the blue structures here are veins. Often in medical illustration, veins are blue in color because the blood flow through them flowing through them is lower in oxygen content, so it's often darker, the blood is darker. And then the arterial supply is the hepatic artery, which is often depicted as a red structure because the blood is more oxygenated and red in color. So you see, as I mentioned, the portal vein is the vein that's bringing all of the blood flow from the intestinal tract, the mesenteric circulation, and it goes into the liver. The liver filters it, and then the blood returns back to the systemic circulation and into the heart through the hepatic veins. The blood that comes into from the hepatic artery, likewise, is returned after going through the capillaries of the liver parenchyma, or tissue, back into the hepatic veins, back into the heart, eventually into the rest of the body. So the liver is the filter, if you will. It really has an important job of removing anything that could be toxic to the human body. The biliary system is isolated here, and one of the main functions of the liver is to synthesize bile and excrete certain toxins in the bile, and that is drained down through the common bile duct. There is a sphincter at the bottom of the bile duct called the sphincter of ody, which is closed, typically, unless we're eating. When it's closed, the bile builds up in the bile duct and actually is shuttered over for storage into the gallbladder. So the gallbladder really serves as a storage function for the bile, and then when we need it, that is when we're eating, the gallbladder contracts, the sphincter of ody opens, and bile is dumped into our duodenum, as Femi mentioned, to help mix with our food and really foster the digestion. People can obviously live without a gallbladder. Many people have their gallbladder removed, and you can imagine, from an evolutionary standpoint, when humans really didn't come across food as frequently and as regularly as we do now, that it's an evolutionary advantage to have that storage organ and really optimize the absorption when they did consume food. But we don't really need it as a functioning organ, and that's why it's expendable and can be removed when it has disease states such as stones. And that is one of the most common disease states that we see in the biliary system is stone disease. Those stones will frequently cause blockage in the cystic duct. That's the duct out of the gallbladder into the bile duct. And when that happens, a patient can develop acute cholecystitis. That's an infection of the gallbladder. If those stones make it down into the bile duct, they can actually cause obstruction of the bile duct, and then the whole liver is obstructed. And that's a relative emergency, medical emergency also, and especially if there's an infection set upstream, and that's called cholangitis. And then those bile duct stones, as they pass down and through the ampulla, they can actually trigger inflammation of the pancreas, because the pancreas is located right here, and we'll talk about the pancreas more specifically in a moment. But as those stones pass through the ampulla, they can trigger pancreatitis. So stones are a very common pathology of the biliary system, and one of the more common conditions that gastroenterologists see that can be emergent and life-threatening conditions. So what is the function of bile? It's stored in the gallbladder, like we just mentioned. It is often either a greenish or a yellow fluid. Many times when we're doing upper endoscopy, we will see bile in the stomach, or obviously we will see it in the duodenum, because that's where it's emptying into the digestive tract. Many of you have probably seen individuals, or maybe little kids, that have vomited, and the green stuff comes up. Well, that's bile. That green stuff that you see comes up is bile, and it was produced in the liver. When it is stored in the gallbladder, there is a very intricate system of coordinated activity that occurs that allows the gallbladder to empty when we need it, and that is when food gets into the stomach and starts to go into the small intestine, there's a hormone released called CCK, or cholecystokinin, and what that cholecystokinin does is it causes contraction of the gallbladder and relaxation of that sphincter muscle to really promote the flow of bile into the intestine when that food is needed, when that food is present in the small intestine. That's when we need the bile there to help really emulsify it and optimize the breakdown of our nutrients and subsequent absorption of the nutrients. Bile is very important for the absorption of fats. Bile acids are an important component of bile, and you can think of bile acids as a detergent. So when you have oil slick, if you put a detergent in that oil slick, what it does is it emulsifies. It breaks it up into, instead of one big slick, it's smaller little particles, and that's really what's needed to help facilitate the absorption of fat in the digestive tract. There are fat-soluble vitamins, A, D, E, and K, that will not be absorbed appropriately if our fats are not being absorbed or our lipids are not being absorbed in the digestive tract. As I mentioned, synthesis, storage, and breakdown, those are the main functions of the liver. It is a very important organ for the synthesis of clotting factors. So if individuals have advanced liver disease, they may not produce normal levels of blood clotting factors, and they may be prone to developing bleeding. And that includes GI bleeding, which gastroenterologists are obviously potentially going to be involved in. It is also a very important site of glucose metabolism, both in terms of the storage and the production of glucose through gluconeogenesis. So just like insulin from the pancreas is important for our glucose control, liver is also a very important part of our glucose regulation and plays an important role in our ability to maintain a healthy level of glucose in our bloodstream. It is the site of production of many proteins, including the clotting factors that I mentioned earlier, that are important in both lipid metabolism and our lipid state, as well as many other body functions in metabolism and our ability to break down products that we'll talk about. And cholesterol. Liver is the site of the synthesis of cholesterol, and cholesterol is excreted in the bile. And one of the ways that people can develop stones is the cholesterol content in the bile becomes supersaturated, and the cholesterol can precipitate. And that is one of the more common types of bile duct stones, is cholesterol stones. And cholesterol metabolism is very reliant on the function of the liver. In fact, in people that have very advanced liver disease, you will find that their cholesterol level is often very low. Not in a healthy way, though. Not in a healthy way. Okay, storage is another main function of the liver. And as I mentioned, it helps to store glucose in the form of glycogen, which is a macromolecular compound made up of multiple glucose and other sugar molecules. And that storage serves as a source of energy when we don't have access to glucose. Let's say we're not eating for a while. The glycogen can be broken down, and the sugar can be released into the system to help maintain body function. And you've heard of glycogen loading, the marathoners trying to build up storage of energy for long periods where they need that caloric energy. Glycogen is a big part of that storage. There are many vitamins that are stored in the liver, including vitamin B12, and AD, and K. Vitamin K is important for our clotting factor production. Vitamin B12 is a very important vitamin involved in a number of different body functions. And the liver stores a large amount of it. So even if you stop eating, or taking in, or absorbing vitamin B12, it does often take years to become deficient in vitamin B12 because of the storage in the liver. Iron and copper are likewise stored in the liver, and excess amounts of those can result in liver disease. So excess amounts of iron are associated with a condition called hemochromatosis, which is often associated with cirrhosis. And excess amounts of copper is associated with a rare genetic disease called Wilson's disease that can also result in cirrhosis, as well as a number of neurologic complications. So from a pharmaceutical standpoint, the liver is very important for a breakdown of compounds. And that includes medications. Many, if not most, medications are actually broken down through metabolic pathways in the liver. And the liver helps to not just break them down, but actually, in many cases, excrete it through the bile. Some are broken down and made water soluble, and they can then be excreted in the urine. Again, that's all done in the liver. But many are actually excreted in the bile, and that's the main mechanism of removal from the body. There are many drugs, exogenous drugs, that are not necessarily pharmaceutical agents that are also broken down and metabolized in the liver. And of course, alcohol. You know, alcohol is broken down, starts to break down a little bit in the stomach. But its main site of metabolism is the liver. And of course, if you have too much of any good thing, it can lead to a problem. And excess amounts of alcohol can lead to toxicity, where the liver is overwhelmed. And that causes liver cell death. And eventually, over time, in many individuals, not all, interestingly, but in many individuals, to cirrhosis. And there are a lot of toxins, too, that are metabolized and broken down in the liver. Some of those may be in, for example, there are certain mushrooms that have a toxin that is broken down and excreted in the liver. So let's move from the liver and the gallbladder to the pancreas. The pancreas, many of you probably know about the pancreas because of its importance for insulin production. But it does have a lot of other functions besides just insulin production. This is an overview of the anatomy. The head of the pancreas is kind of the largest section. And that is really tucked into the groove of the duodenum. And as we've talked about, Femi touched on this, and we talked about it earlier, the bile duct and the pancreas duct both drain into the duodenum at the ampulla vater. The neck of the pancreas and body of the pancreas and tail of the pancreas are the other sections that we often refer to anatomically. There are a couple of different, the main pancreas duct is this large duct that drains into the ampulla. It's actually a minor pancreas duct that drains into usually a separate opening called the minor ampulla up above the main ampulla. And about 7% to 10% of patients, these ducts do not connect. They're completely separate. And the main duct drains into the minor ampulla. And then there's a little residual major pancreatic duct here in the head that's not connected with the rest of the main pancreatic duct. And that relates to a congenital anomaly of the pancreas. So the functions of the pancreas include not just the endocrine with the hormone production that I alluded to, but exocrine function. There are enzymes and proteins and electrolytes that the glandular component of the pancreas makes that is very instrumental in our digestive process. Those enzymes include enzymes that help to break down fats, and that is lipase and colipase. And then there are enzymes that also help to break down carbohydrates and enzymes that help to break down proteins into smaller units that can then be absorbed further down in the small intestine through those villi that Femi discussed. Those enzymes are really quite important, but particularly for the absorption of fat. When you have a deficiency of the production of pancreatic enzymes, usually it will manifest as an inability to absorb fats, and the patients will experience steatorrhea, which is excess fat in the stool. The pancreas also does produce bicarbonate that helps to neutralize the acid that's produced in the stomach. And you can imagine if all this acid is flowing out of the stomach into the duodenum, it might cause a lot of damage to the lining of the small intestine, and that bicarbonate secretion helps to protect that lining of the upper part of the small intestine. A very intricate network of hormones, the endocrine function, if you will, of the pancreas is operational as part of our digestive process, and those hormones produced by the pancreas include insulin, glucagon, and somatostatin and others, and they really help to balance the glucose content, as well as many of the other functions of the digestive tract. The motility, the overall health, and the ability to absorb nutrients is really maintained by many of these hormones that are produced by the pancreas. This is just an example of the incredibly very artful feedback that we get from the feedback and control mechanisms that are under play when hormones are operational in the digestive tract. So secretin is a hormone that's really very important for pancreas function, particularly the bicarbonate excretion of pancreas, and this is just one example of the many hormones that you'll see. So acid comes in from the stomach and enters the duodenum. That then triggers the release of secretin from the endocrine cells in and around the duodenum. That secretin goes into the bloodstream, then stimulates the pancreas to produce bicarbonate, and that bicarbonate then flows into the duodenum through this main pancreatic duct to help neutralize the acid. And so that intricate network of connection, and then once it's neutralized, it decreases the synthesis and then the production of secretin, so it shuts off when it's not needed anymore. So what you've reviewed is that we've reviewed that the GI tract and health is really important for the breakdown of food and nutrients. It's really critical for the absorption of water and minerals. And the movement from the esophagus to the stomach to the small bowel to the colon, as well as the movement from the gallbladder to the intestine and the pancreas to the intestine, is really very well-coordinated through both neural components as well as hormonal components. And storage of waste is really the main function of the last part of the digestive tract until elimination is necessary. So with that, I'm going to stop. And I think we're just about on time. Do we have any questions before we move on to the exciting tools of the trade that we get to use in digestive tract, digestive diseases? OK. If not, I'm going to turn things over to my colleague, John Martin, who's going to share with you all the great tools that we get to use. And you'll get a chance to get your hands on some, not all, of these tools a little bit later on today.

digestive tract

extraluminal organs

liver

biliary system

pancreas

nutrient absorption