ADVANCE PATHO: HEPATOBILIARY SYSTEM ASTRERO, Lea Lourdes G.

THE LIVER Reddish-brown highly vascular organ. Largest gland in the body and largest gland associated w/ the digestive system The liver weighs approximately 1500 g. Located in the right upper quadrant of the abdomen in the peritoneal space just below the right side of the diaphragm and under the rib cage. It is anatomically separated into two predominant lobes, a right and a left lobe. Blood Supply of the Liver It receives nearly 25% of the cardiac output, approximately 1500 mL of blood flow per minute, via two sources: a. venous flow from the portal vein, which is crucial to performance of the liver's roles in bodily functions, b. arterial flow from the hepatic artery, which is important for liver oxygenation. PORTAL VEIN has low hydrostatic pressure: 10mmHg It runs for approximately 69 cm Carries venous blood from the small intestine, rich in freshly absorbed nutrientsas well as drugs and poisons directly to the liver. LIVER HISTOLOGY: HEPATOCYTES Liver cells or hepatocytes (Gr. hepar, liver, + kytos, cell) are epithelial cells grouped in interconnected plates. portal triad - The portal zones at the corners of the lobules consist of connective tissue in which are embedded a venule (a branch of the portal vein), an arteriole (a branch of the hepatic artery), and a duct of cuboidal epithelium (a branch of the bile duct system). Hepatocytes make up each of the interconnected plates like the bricks of a wall and the plates are arranged radially around the central vein The spaces between these plates contain important microvascular components, the liver sinusoids Two noteworthy cells are associated with these sinusoids in addition to the endothelial cells: stellate macrophages, also known as Kupffer cells, Their main functions are to break down aged erythrocytes and free heme for re-use, remove bacteria or debris that may enter the portal blood from the gut, and act as antigenpresenting cells in adaptive immunity. stellate fat storing cells (or Ito cells) with small lipid droplets containing vitamin A, store much of the body's vitamin A. Space b/n the lining of the sinusoids & the hepatocytes is called the Spaces of Disse

Occupied by numerous irregularly oriented microvilli on the perisinusoidal surface of the hepatocytes The surface of each hepatocyte is in contact with the wall of a sinusoid, through the perisinusoidal space, and with the surfaces of other hepatocytes. two hepatocytes abut, they delimit a tubular space between them known as the bile canaliculus . The canaliculi, the first portions of the bile duct system, are long spaces 12 m in diameter Minute canals w/c receive bile from the hepatocytes The bile flow therefore progresses in a direction opposite to that of the blood. liver architecture has been traditionally described in terms of the lobule Neat arrays of hepatocyte plates are organized around individual central veins to form hexagons with portal triads or tracts at their corners. LIVER PHYSIOLOGY 1. Glucose/CHO Metabolism Storage of glycogen Liver is a sensitive organ: when it detects that glucose is lowered, it degrades glycogen to form glucose ( glucose is the major fuel)- via glycogenolysis Abundance of glucose: liver stores glucose in the form of glycogen PC: insulin; glucagon; glucose delivered Fasting: glucagon; insulin= glucogenolysis/gluconeogenesis

2. CHON Metabolism Deamination of amino acids (for eventual conversion to CHO and fats) Formation of urea for the removal of ammonia from body fluids Formation of plasma proteins (except gamma globulins) Interconversions among the different amino acids (transamination)/other compounds for important metabolic processes Liver synthesizes: plasma proteins ,coagulation factors. 3. Lipoprotein Metabolism The liver is the center of lipid metabolism It manufactures nearly 80% of the cholesterol synthesized in the body

the liver can synthesize, store, and export triglycerides The liver is also the site of keto acid production 4. Bile Formation The main components of bile are water, electrolytes, and a variety of organic molecules including bile pigments, bile salts, phospholipids (lecithin), and cholesterol. Bile is produced by hepatocytes and secreted through the biliary system The two fundamental roles of bile: to aid in the digestion and absorption of lipids and lipid-soluble vitamins to eliminate waste products (bilirubin and cholesterol) through secretion into bile and elimination in feces. 5. Bilirubin Excretion Bilirubin is a component of the heme When it reaches spleen, heme separates from globin part When it reaches liver, it undergoes chem. Process(conjugation: addition of glucoronic acid) Conjugated bilirubin secreted by hepatocyte and carried by bile. Some of the bile is reabsorbed via portal vein and goes back to liver via enterohepatic circulation Extra bilirubin excreted gives color to the stool

gallbladder is divided into four anatomic areas: the fundus, the corpus (body), the infundibulum, and the neck The fundus contains most of the smooth muscles of the organ the body is the main storage area and contains most of the elastic tissue the neck, a funnel-shaped area that connects with the cystic duct a gentle curve,to form the infundibulum or Hartmann's pouch Blood Supply The cystic artery that supplies the gallbladder is usually a branch of the right hepatic artery When the cystic artery reaches the neck of the gallbladder, it divides into anterior and posterior divisions. BILIARY TRACKS The bile produced by the hepatocytes flows through the bile canaliculi, bile ductules, and bile ducts. These structures gradually merge, forming a network that converges to form the hepatic duct The left and right hepatic duct join to form a common hepatic duct. The common hepatic duct is joined at an acute angle by the cystic duct to form the common bile duct. The common bile duct runs obliquely downward within the wall of the duodenum. The sphincter of Oddi, a thick coat of circular smooth muscle, surrounds the common bile duct at the ampulla of Vater. It controls the flow of bile, and in some cases pancreatic juice, into the duodenum GALLBLADDER PHYSIOLOGY The gallbladder, the bile ducts, and the sphincter of Oddi act together to store and regulate the flow of bile. The main function of the gallbladder is to concentrate and store hepatic bile and to deliver bile into the duodenum in response to a meal. This storage is made possible because of the remarkable absorptive capacity of the gallbladder Gallbladder concentrates bile as much as 10fold and leading to a marked change in bile composition. It is stored there until stimulation of gallbladder contraction expels the contents of the gallbladder back through the cystic duct into the common bile duct and through the sphincter of Oddi into the duodenum BILE SECRETION Bile is mainly composed of water, electrolytes, bile salts, proteins, lipids, and bile pigments. Sodium, potassium, calcium, and chlorine Liver produces 500 to 1000 mL of bile a day The primary bile salts, are synthesized in the liver from cholesterol. They are conjugated there with taurine and glycine

6. Other functions: storage of vitamins- A,D B12 blood coagulation fibrinogen, Prothrombin, accelerator globulin, factor VII Vit K dependent factors: II, VII, IX, X Iron storage Storage form: ferritin Combines with apoferritin Excretion of drugs, hormones, and other substances THE GALLBLADDER pear-shaped sac about 7 to 10 cm long, with an average capacity of 30 to 50 mL gallbladder is located in a fossa on the inferior surface of the liver

Bile salts are excreted into the bile by the hepatocyte and aid in the digestion and absorption of fats in the intestines. In the intestines, about 80% of the conjugated bile acids are absorbed in the terminal ileum. The remainder is deconjugated by gut bacteria, forming secondary bile acids. These are absorbed in the colon, transported to the liver, conjugated, and secreted into the bile. About 95% of the bile acid pool is reabsorbed and returned via the portal venous system to the liver, the so-called enterohepatic circulation. 5% is excreted in the stool. The color of the bile is due to the presence of the pigment bilirubin, which is the metabolic product from the breakdown of hemoglobin BILE Bile acts to some extent as a surfactant, helping to emulsify the fats in food. Bile salt anions are hydrophilic on one side andhydrophobic on the other side; consequently, they tend to aggregate around droplets of fat to form micelles, with the hydrophobic sides towards the fat and hydrophilic sides facing outwards. The hydrophilic sides are negatively charged, and this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles. The dispersion of food fat into micelles thus provides a greatly increased surface area for the action of the enzyme pancreatic lipase which actually digests the triglycerides. A triglyceride is broken down into two fatty acids and a monoglyceride, which are absorbed by the villi on the intestine walls

bile serves also as the route of excretion for bilirubin. Bile is alkaline and also has the function of neutralizing any excess stomach acid before it enters the duodenum. BILE SECRETION (motor activity) In response to a meal, the gallbladder empties by a coordinated motor response of gallbladder contraction and sphincter of Oddi relaxation. One of the main stimuli to gallbladder emptying is the hormone cholecystokinin (CCK). CCK is released endogenously from the duodenal mucosa in response to a meal. BILE SECRETION (Neurohhormonal Regulation) The vagus nerve stimulates contraction of the gallbladder, and splanchnic sympathetic stimulation is inhibitory to its motor activity CCK acts directly on smooth muscle receptors of the gallbladder and stimulates gallbladder contraction. It also relaxes the terminal bile duct, the sphincter of Oddi, and the duodenum. Sphincter of Oddi The sphincter of Oddi regulates flow of bile (and pancreatic juice) into the duodenum, prevents the regurgitation of duodenal contents into the biliary tree, and diverts bile into the gallbladder THE PANCREAS a retroperitoneal organ that lies in an oblique position, sloping upward from the C-loop of the duodenum to the splenic hilum In an adult, the pancreas weighs 75 to 100 g and is about 15 to 20 cm long. four regions: the head, neck, body, and tail. The main pancreatic duct (the duct of Wirsung) courses along the gland from the tail to the head and joins the common bile duct just before entering the duodenum at the ampulla of Vater. The accessory pancreatic duct (the duct of Santorini) enters the duodenum 22.5 cm proximal to the ampulla of Vater The main pancreatic duct is usually only 2 to 3 mm in diameter Pressure inside the pancreatic duct is about twice that in the common bile duct, which is thought to prevent reflux of bile into the pancreatic duct. The main pancreatic duct joins with the common bile duct and empties at the ampulla of Vater. Most of the pancreatic mass is composed of exocrine cells that are clustered in lobules (acini) divided by connective tissue and connected to a duct that drains into the pancreatic duct and into the duodenum. The product of the pancreatic exocrine cells is an alkaline fluid rich with digestive enzymes, which is secreted into the small intestine to aid in the digestive process Embedded within the acini are richly vascularized, small clusters of endocrine cells called the islets of Langerhans, in which 2 endocrine cell types ( and ) predominate.

Since bile increases the absorption of fats, it is an important part of the absorption of the fatsoluble substances, such as the vitaminsD, E, K and A.

The arterial blood supply to the pancreas is derived from the splenic artery and the superior and inferior pancreaticoduodenal arteries. ACINAR CELLS Pancreatic acinar cells are specialized exocrine secretory cells that are the source of the majority of the proteinaceous components of the pancreatic juice packed at rest with large numbers of zymogen granules that contain the digestive enzymes and other regulatory factors.

PHYSIOLOGY (Exocrine)

The external secretion of the pancreas consists of a clear, alkaline (pH 7.08.3) solution of 12 L/d containing digestive enzymes. Secretion is stimulated by the hormones secretin and cholecystokinin (CCK) and by parasympathetic vagal discharge. Secretin and cholecystokinin are synthesized, stored, and released from duodenal mucosal cells in response to specific stimuli. Acid in the lumen of the duodenum causes the release of secretin, and luminal digestion products of fat and protein cause the release of cholecystokinin. Pancreatic juice helps neutralize gastric acid in the duodenum and adjusts luminal pH to the level that gives optimal activity of pancreatic enzymes. Pancreatic enzymes are synthesized, stored (as zymogen granules), and released by the acinar cells of the gland, principally in response to cholecystokinin and vagal stimulation. Pancreatic enzymes are proteolytic, lipolytic, and amylolytic. Lipase and amylase are stored and secreted in active forms. The proteolytic enzymes are secreted as inactive precursors and are activated by the duodenal enzyme enterokinase.

Physiology (Endocrine) The function of the endocrine pancreas is to facilitate storage of foodstuffs by release of insulin after a meal and to provide a mechanism for their mobilization by release of glucagon during periods of fasting. Insulin and glucagonand somatostatin are produced by the islets of Langerhans. Insulin Insulin, is formed in the cells of thepancreas via the precursor proinsulin. Insulin secretion is stimulated by rising or high serum concentrations of metabolic substrates such as glucose, amino acids. The major normal stimulus for insulin release appears to be glucose. Glucagon Glucagon. The release of glucagon is stimulated by a low blood glucose concentration, amino acids, catecholamines, sympathetic nervous discharge, and cholecystokinin. It is suppressed by hyperglycemia and insulin. Glucagon stimulates glycogenolysis from the liver and proteolysis and lipolysis in adipose tissue as well as in the liver. The short-term regulation of gluconeogenesis depends on the balance between insulin and glucagon.