Hello, my name is Tamara Taddy, and I'm from Yale University, Department of Medicine, Section of Digestive Diseases. If you have any questions, please do not hesitate to click on the button, Ask the Forum, where common issues regarding liver diseases are discussed. The title of my module is Anatomy and Physiology of the Liver. During this talk, I will discuss the anatomy and physiology of the liver parenchyma, vascular, and biliary system. I have disclosed that I receive grant and research support from Bayer Healthcare Pharmaceuticals, and I've provided consulting for Onyx Pharmaceuticals. There will be no discussion of any unapproved, off-label, or investigational uses of a product during this presentation. At the conclusion of the program, you should be able to understand the anatomy of the liver, both the vascular and the parenchymal anatomy, describe the structure and function of the hepatic lobule, understand the anatomy and physiology of the biliary system, and appreciate the many vital functions of the liver in metabolism, synthesis, detoxification, immunity, and digestion. The liver anatomy can be divided into vascular, parenchymal, and biliary anatomy. The liver is a complex, highly vascularized organ with multiple functions, and so it's helpful to think of liver anatomy in three distinct but interrelated compartments, the vascular compartment, the parenchymal compartment, and the biliary compartment. Starting with the vascular anatomy of the liver, it's important to remember that the liver has a dual blood supply. The blood flowing to the liver comes from two sources. The most important source is blood that arrives to the liver from the portal vein. The portal vein supplies 75% of blood to the liver, and this blood is really the outflow of blood from the gut for detoxification by the liver. The hepatic artery supplies oxygen-rich blood to the liver, but this only makes up about 25% of inflow into the liver. The venous outflow from the liver is via the hepatic vein into the vena cava. It's important to understand that the liver is divided into segments, and these anatomical segments are distinct. The liver is divided into a right and left hepatic lobe, but there are eight anatomically distinct segments, q-node segments, as they were first described by q-node. And each segment has its own hepatic artery branch, portal vein branch, hepatic vein branch, and biliary branch. And this is very important when you're considering hepatic resection, because oftentimes if we look at the liver as a homogeneous structure, we may be misled by the fact that, for example, a tumor in the middle of the right lobe would require a very large resection encompassing many segments. Parenchymal anatomy of the liver is really when we think about the way the liver is arranged architecturally. So this is really divided into hepatic lobules, and hepatic lobules are the building blocks of the liver parenchyma. The lobule is shaped like a hexagon with portal tracks at each apex, and hepatocytes are arranged in linear cords from the periphery of the lobule to the central vein. In this cartoon at the top, you can see depicted the liver in its sort of cartoon form here, and then in a blown-up cartoon, we look at the lobule where you see these hexagonal hepatic lobules with a central vein, connective tissue separating each lobule, and then obviously the lobules arranged together. But when we break this down and really look at the architecture of the lobule by itself, each distinct lobule, you can see here that at the periphery of each lobule, we have a portal venule, a portal arteriole, and a bile duct, and then we have sinusoids running in between the hepatic cords of hepatocytes. So let's talk a little bit more about the hepatic lobule. So as I said, surrounding each hepatic lobule are portal tracks. The portal tract contains a terminal portal venule, a hepatic arteriole, and a bile duct. The central vein is the outflow from the lobule, ultimately leading to the hepatic vein. So in a way, the hepatic lobule is a microcosm of a segment. So let's talk about supporting cells. Now as I said, hepatocytes are arranged in the lobule, in cords, but there are other cells that we find in the lobule, very important cells. Starting with probably the most unique cell that we see amongst the lobule is the Kupfer cell. Kupfer cells are mononuclear phagocytes that are located in the sinusoidal space. They are specialized macrophages that break down red blood cells, eliminate bacteria, and mop up after injury. They're specialized because they're exposed to portal blood, and as such, they have to understand keenly what is foreign and what is not foreign. And so these cells are very highly adept at surveying their environment. Stellate cells are found in the perisinusoidal space. This is the space between the sinusoids and the hepatocytes. This is also known as the space of dis. The stellate cell is responsible for vitamin A storage and metabolism. When activated by injury or inflammation, these cells transform into collagen scar-producing myofibroblasts. These cells play a central role in hepatic fibrosis. So let's look at all key components of the hepatic lobule. The portal tract is composed of the portal venule, the hepatic arteriole, and the bile ductile. Engaged in cords from the periphery to the central vein are the hepatocytes. Between these cords are the hepatic sinusoids, a specialized fenestrated capillary network that is perfused by the hepatic arteriole and portal venule. This fenestrated capillary network is unique to the liver. At the level of the sinusoid, arteriole, and portal blood mix, in this slide you can also see our supporting cells, the Kupfer cell that lives within the sinusoid, and the stellate cell, which is located in the space of dis. You can also see the bile ductile, which we'll talk about in the next slide. And so this is sort of the most basic building block of the liver. We've sort of dissected the anatomy of the lobule in this slide. So let's focus just a little bit more now in the biliary ductile, all right? So we haven't really talked about bile. Bile is produced by hepatocytes and secreted into the bile canaliculus. Bile canaliculi are lined by cholangiocytes, yet another cell we find in the liver. And these are the cells that contribute to bile formation. Canaliculi merge and form bile ductiles, and ductiles merge to form larger ducts. So when we think about the anatomy of the biliary system, the microcosm is the bile ductile. But you can see that the biliary tree is actually the arborization of smaller and smaller ducts into bigger and bigger ducts, leading to the large bile ducts. So if we think about all of the canaliculi, they're sort of the terminal branches of this tree. And then we think about the smaller bile ductiles, and then we think about the right hepatic duct and the left hepatic duct, and these converge to make the common hepatic duct. The common hepatic duct then, as it traverses the liver and exits the liver, becomes the common bile duct. When bile exits the biliary system through the ampullae of water into the second portion of the duodenum. The gallbladder is a repository for bile, sort of a storage sack, if you will. And it's radical to the common bile duct, or the common hepatic duct, depending upon where it enters, is the cystic duct. So bile drains from the gallbladder via the cystic duct. So now we're talking about bile, but we always look at this value called bilirubin. So let's digress and talk a little bit about bilirubin metabolism. So bilirubin is a component of bile, and it comes from heme liberated from red blood cells. Heme is converted to bilirubin in mononuclear phagocytes. Insoluble or unconjugated bilirubin is bound to albumin and taken up by hepatocytes. And bilirubin becomes soluble once conjugated, and this is done by UDP-glucuronyl transferase. And this UDP-glucuronyl transferase of bilirubin is excreted into bile and reaches the bowel, where it is deconjugated by colonic bacteria and eliminated in the feces. So when we talk about bile, bilirubin being a component of bile, it's bilirubin that actually gives us this jaundiced appearance, and we'll talk more in later modules about jaundice. But there is a sort of almost normal type of jaundice that you may see if you're working with children, or specifically with neonates, and this is called physiologic neonatal jaundice. This occurs in 60% of term and 80% of preterm neonates. Fetal erythrocytes have a short life, and neonates have a higher erythrocyte mass, leading to excess bilirubin production after birth. At birth, the liver has low activity of UDP-glucuronyl transferase, leading to less conjugation. Typically, jaundice presents 48 to 72 hours after birth and resolves within the first one to two weeks of life. Hyperbilirubinemia is mostly indirect, greater than 90%, and the rate of rise of bilirubin is usually less than 5 mg per deciliter per day, peaking at less than 15 mg per deciliter. So the liver performs many vital functions. We're now going to talk about liver metabolism and synthesis. The liver plays a central role in all metabolic processes in the body. For example, glucose homeostasis. The liver plays a central role in glycogenesis and gluconeogenesis. The liver is instrumental in fat metabolism, lipogenesis and lipolysis, cholesterol synthesis, and amino acid metabolism. And the liver synthesizes essential plasma proteins like albumin, prothrombin, fibrinogen, and clotting factors, which is why bleeding is often a symptom of liver failure. The liver also performs vital functions of detoxification and immune surveillance. The liver detoxifies endogenous and exogenous substances. Most medications are metabolized by the liver via multiple pathways. Urea is a toxic byproduct of protein metabolism that is mostly produced in the intestine and is transformed by the liver into urea and then excreted in the urine. The liver conducts immune surveillance. It's populated by numerous innate and adaptive immune cells that detect pathogens from the blood. And the liver must also be tolerant of antigens derived from food. The liver is the site of unique balance between immune activation and tolerance. When the liver plays a key role in digestion, we talked about bilirubin as a component of bile. But actually, bile is what helps us digest our food. The liver makes up to a liter of bile daily, and bile flows into the intestine via the biliary system. Bile salts are essential for the digestion of fats and fat-soluble vitamins like vitamins A, D, E, and K. Enterohepatic circulation allows for continual circulation of bile salts that are absorbed from the intestine and carried to the liver, where they are secreted into the bile and again enter the intestine. This process is essential for fat absorption and cholesterol metabolism. So in summary, liver anatomy may be understood in three distinct but interrelated compartments, vascular, parenchymal, and biliary. The hepatic lobule is the building block of the liver parenchyma and is composed of a portal triad, hepatocytes arranged in linear cords between a highly specialized capillary network and a central vein. Bile is produced by hepatocytes and secreted into the biliary canaliculus, the tiniest branch of the biliary tree. The liver plays a vital role in metabolism, glucose, fat, cholesterol, and bilirubin, protein synthesis, detoxification, immunity, and digestion. I hope you've enjoyed this presentation and I invite you to access additional content on liver learning on this topic or any other related topics at your leisure. Thank you.

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