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Physiology, Liver

The liver is a critical organ in the human body that is responsible for an array of functions that help support metabolism, immunity, digestion, detoxification, vitamin storage among other functions. It comprises around 2% of an adult's body weight. The liver is a unique organ due to its dual blood supply from the portal vein (approximately 75%) and the hepatic artery (approximately 25%).

By virajPublished 2 years ago 3 min read
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Cellular

The functional unit of the liver is the lobule. Each lobule is hexagonal and a portal triad (portal vein, hepatic artery, bile duct) sits at each corner of the hexagon. The foundation of the lobule is composed of hepatocytes, which have physiologically distinct apical and basolateral membranes. Based on function and perfusion, hepatocytes are divided into 3 zones.

Zone I is considered to be the periportal region of hepatocytes and are the best perfused and first to regenerate due to their proximity to oxygenated blood and nutrients. Due to its high perfusion, zone I plays a large role in oxidative metabolisms such as beta-oxidation, gluconeogenesis, bile formation, cholesterol formation, and amino acid catabolism.

Zone II is defined as the pericentral region of the hepatocytes and zone II sits between zones I and III.

Zone III has the lowest perfusion due to its distance from the portal triad. It plays the largest role in detoxification, biotransformation of drugs, ketogenesis, glycolysis, lipogenesis, glycogen synthesis, and glutamine formation.

Bile flow is further facilitated by bile canaliculi, which are formed by apical membranes of neighboring hepatocytes. Due to the 3-dimensional arrangements of hepatocytes, the canaliculi form a lattice-like network or “chicken-wire pattern,” that helps increase the surface area of flow. It is important to recognize that bile and blood flow in opposite directions to each other. This makes sense as the liver produces bile, so bile in the ducts are leaving the liver; whereas, the dual blood supply is entering the liver to perfuse it. Blood drains into the branch of the hepatic vein that lies in the lobule's center via sinusoidal lumens of the lobule.The space between the sinusoidal lumen and the surrounding basolateral membrane of hepatocytes is called the space of Disse. This space is occupied by microvilli extending from the basolateral membrane of the hepatocytes that communicate with the capillary, allowing the hepatocyte to reach its' blood supply. The space of Disse houses an extracellular matrix composed of a variety of collagens, proteoglycans, and other proteins that help provide scaffolding for the hepatocytes and, by extension, the lobule as a whole. The importance of the scaffolding that takes place in the space of Disse is amplified further by the fact that hepatocytes do not contain a true basement membrane. The space of Disse also contains Kupffer cells (macrophages) and Ito cells (stellate cells). The Kupffer cells sit in the space to filter out unnecessary or pathologic material from the circulation. The Ito cells serve as storage for fat, such as vitamin A. In the right setting, they can also serve as myofibroblasts and aid in the regeneration of the liver.

The liver arises as a part of the foregut. It stems from endodermal cells and starts as the hepatic diverticulum around the fourth week of development. It forms within the peritoneum and is anchored to the abdominal wall by the falciform ligament which arises from the ventral mesentery. The umbilical vein passes through the falciform ligament on its way from the umbilical cord to the liver.

The diverticulum is believed to be induced by a combination of several pathways, mainly the Wnt/B-catenin pathway and fibroblast growth factors (FGF), which are secreted by fetal cardiac cells, which is induced by the MAPK pathway.[2] The diverticulum then grows and interacts with the septum transversum, a structure that divides the heart from the abdominal cavity and later contributes to the formation of the diaphragm. The diverticulum then differentiates into the primordium of the liver or the gallbladder. As the primordium liver grows, it develops into hepatic cords that anastomose around spaces lined by endothelium, forming the primordium of the hepatic sinusoids. VEGF plays an important role in the formation of the hepatic sinusoids.

The portal vein, which arises from umbilical and vitelline veins is the central vessel in which the hepatic cords form around. This helps explain why the portal vein is the primary blood supply for the liver as opposed to the hepatic artery. The hepatic artery develops with the biliary tract and continues to develop post-birth.[1] Around the sixth week, the liver becomes responsible for hematopoiesis, and hepatocytes create bile around the 12th week.

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