Liver, Gallbladder, and Pancreas
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Digestive system III: Liver, Gallbladder, And Pancreas Liver Introduction - The embryology , gross morphology , and histology of the normal human liver ”the single largest organ in the human body ”are described in this chapter . - In many instances, immunohistologic studies of liver tissue have the potential to yield more information than electron microscopy. Embryology - The liver arises as the hepatic diverticulum from the endodermal lining of the most distal portion of the foregut during the 3 to 5 week of gestation. - In embryos 4 to 5 mm in length. - The hepatic diverticulum differentiates cranially into proliferating hepatic cords and caudally into the gallbladder and extrahepatic bile ducts. - The anastomosing cords of hepatic epithelial cells grow into the mesenchyme of the septum transversum. - As the hepatic cords extend outward during the 5 week of gestation, they are interpenetrated by the inwardly growing capillary plexus, which arises from the vitelline veins in the outer margins of the septum transversum and forms the primitive hepatic sinusoids. - Scattered mesenchymal cells lie between the endothelial wall of the sinusoids and the hepatic cords and form the hepatic stroma, as well as the capsule. - Hematopoietic tissue and Kupffer cells also derive from splanchnic mesenchyme, begins during the 6 week. - By 9 weeks' gestation accounts for approximately 10% of the total weight of the embryo. - The bile canaliculi appear in the 10-mm embryo (9weeks) as intercellular spaces between immature hepatocytes (hepatoblasts). - The epithelium of the intrahepatic bile ducts arises from the proximal part of the primitive hepatic cords. - the epithelial layer in direct contact with the mesenchyme around the portal vein transforms into bile duct “type cells. - The canals of Hering, which connect bile canaliculi to bile ducts, include both typical hepatocytes and bile duct cells. - Hepatocyte bile formation by the 11 week. - Excretion of bile into the duodenum by the 16 week. * The liver accounts for approximately 5% of the newborn 's body weight. * Apoptosis - Apoptosis occurs at all stages during fetal growth and development of ductal plates and hepatoblasts. - There is a good correlation between the proliferative and the apoptotic activities in the ductal plate, depending on the remodeling process. - Apoptosis, is induced by transforming growth factor-²1 Ductal plate ( arrows ) developing around the portal vein mesenchyme in the liver of a 10- week-old embryo. There is extramedullary hematopoiesis in the sinusoids. Gross Morphology Liver is the largest gland in the body, weighing about 1500 gr , it has endocrine and exocrine functions It is relatively larger in infancy, due to a large left lobe. - The liver resides in the abdominal right upper quadrant . - It measures about 10 cm in vertical span, 12 to 15 cm in thickness , and 15 to 20 cm in its greatest transverse diameter. - It is divided by deep grooves into two large lobes ”the right (lateral to falciform ligament) and left (medial to falciform ligament) ”and two smaller lobes ”the caudate and quadrate lobes. - Functionally, the division into eight segments. Each segment is served by its own vascular pedicle of arterial and portal venous blood supply and branch of the biliary tree. - The superior , anterior, and lateral surfaces of the liver are smooth and almost completely covered by peritoneum. - A thin layer of fibrous connective tissue, the Glisson's capsule, surrounds the liver and extends into the parenchyma to form extensions that support arterial and biliary structures, except at porta hepatis where blood and lymph vessels and bile ducts enter or exit the gland - Liver has a lobular organization - Classical lobule in which hepatocytes arranged as an hexagon - Receives portal blood (75%) from small intestine via portal vein and oxygenated blood from hepatic arteries (25%). - Anteriorly, the falciform and round ligaments, connect the liver to the abdominal wall. - Inferior vena cava, to which two to four hepatic veins connect. - The fossa of the gallbladder and the round ligament separate the quadrate lobe from the right and left liver lobes, respectively. Anatomic structure of the liver. This diagram shows the gross view of the diaphragmatic and visceral surfaces of the liver, with labeled anatomic landmarks found on both surfaces. The enlarged cross- sectional area of the liver (bottom) shows the general microscopic organization of the liver into lobules. Note the presence of hepatic portal triads at the periphery of each lobule, with the terminal hepatic venule (central vein) in the center of the lobule. Glisson' capsule The major functions of the liver may be summarised as follows: Fat metabolism - Oxidising triglycerides to produce energy - Synthesis of plasma lipoproteins - Synthesis of cholesterol and phospholipid Carbohydrate metabolism. - Converting carbohydrates and proteins into fatty acids and triglyceride. - Regulation of blood glucose concentration by .glycogenesis, glycogenolysis and gluconeogenesis Protein metabolism. - Synthesis of plasma proteins, including albumin and clotting factors (e.g. prothrombin and fibrinogen), transporter proteins (e.g. haptoglobin, transferrin, and hemopexin), globulins. - Synthesis of non-essential amino acids. Detoxification of metabolic waste products (e.g. deamination of amino acids and production of urea). Phagocytosis - Kupffer cells phagocytize worn-out and dying red and white blood cells, some bacteria Storage - Storage of glycogen, vitamins (A,D & K) , iron, copper, folic acid. Intermediary metabolism - Detoxification of various drugs and toxins (e.g. alcohol). Secretion - Synthesis and secretion of bile ( 600-1000 mL/day.) . Bile salts (bilirubin), cholesterol, fats, fat-soluble hormones, lecithin. - Neutralizes and dilutes stomach acid. - Bile salts emulsify fats. Most are reabsorbed in the ileum. CLINICAL POINT - Because of its strategic location, large mass, and fragile capsule (that provides relatively little protection to the organ), the liver is prone to many injuries. - Its complex vascular supply and enormous blood reserve also make it vulnerable to bleeding with extensive blood loss (exsanguination) into the abdominal cavity. - Blunt and penetrating traumas are the most common causes of subcapsular hepatic hematomas localized collections of extravasated blood contained by Glisson capsule that may subsequently rupture and be life threatening. - Subcapsular hematomas may also occur as a complication of preeclampsia in pregnancy (a leading cause of maternal death) or in some parasitic infestations (e.g., amebiasis, schistosomiasis) of the liver, which cause hemorrhage, liver necrosis, inflammation, and subsequent fibrosis. - Although most patients are managed conservatively, some require urgent surgical intervention. Blood Supply to the Liver - To appreciate the myriad functions of the liver introduced previously, one must first understand its unique blood supply and how blood is distributed to the hepatocytes. The liver has a dual blood supply consisting of: - a venous (portal) supply via the hepatic portal vein provides deoxygenated blood Nutrients, drugs, toxins, microbes and - an arterial supply via the hepatic artery. - Both vessels enter the liver at a hilum or porta hepatis, the same site at which the common bile duct, carrying the bile secreted by the liver, and the lymphatic vessels leave the liver. - Bile flows in a direction opposite to that of the blood. Blood supply to the liver: the portal triad Structural Organization of the Liver The structural components of the liver include: - parenchyma, consisting of organized plates of hepatocytes, which in the adult are normally one cell thick and are separated by sinusoidal capillaries. In young individuals up to 6 years of age, the liver cells are arranged in plates two cells thick. - connective tissue stroma that is continuous with the fibrous capsule of Glisson. - Blood vessels, nerves, lymphatic vessels, and bile ducts travel within the connective tissue stroma. - sinusoidal capillaries (sinusoids), the vascular channels between the plates of hepatocytes. - perisinusoidal spaces (spaces of Disse), which lie between the sinusoidal endothelium and the hepatocytes. - the organization of these structural elements to understand the major functions of the liver. Liver Lobules There are three ways to describe the structure of the liver in terms of a functional unit: - The classic lobule, - The portal lobule, and - The liver acinus. Classic hepatic lobules - Longitudinal axis of each classical lobule is occupied by central vein - Hepatocytes radiate from central vein and separating from each other by vascular spaces known as hepatic sinusoids - Limiting membrane pierced by inlet venules and inlet arterioles to join hepatic sinusoids - Blood from periphery flows slowly through sinusoids into central vein Diagram of a classic liver lobule Photomicrographs of pig and human livers Cut transversely hepatic lobules are polygonal units showing plates of epithelial cells called hepatocytes radiating from a central venule (C). In all cases peripheral connective tissue of portal areas with microvasculature and small bile duct (D) branches can be seen and in humans as in other mammals these are present at the boundaries between two or more hepatic lobules. The vessels near the bile ducts branches are a venule (V) off the portal vein and an arteriole (A) off the hepatic artery. Both X150. H&E. Structure and function of the liver portal lobule The portal