Chap 2 - Hepatobiliary System and exocrine pancreas.pptx

Normal Functions of the liver glucose to glycogen production and degradation of plasma lipids Foreign substances conversion to water- soluble forms...

Normal Functions of the liver glucose to glycogen production and degradation of plasma lipids Foreign substances conversion to water- soluble forms Synthesis of 15% of body proteins 10% of the cells in the liver are adaptive immune system (T and B lymphocytes) or the innate immune system (Kupffer cells) 3  Morphologic Classification of Hepatobiliary Disease Liver injury should be characterized by : – pattern of involvement (multifocal random, zonal, or massive) – type of inflammatory cells involved ( Lym Mac,) – evidence of necrosis or fibrosis – severity of these processes, evidence of regeneration,,etc. 2  Acute Hepatitis Inflammation of the liver parenchyma Characterized by hepatocellular necrosis, and apoptosis. In bacterial and protozoal hepatitis, neutrophils accumulate in response to the usual chemotactic stimuli. Acute hepatitis produced by viral infections  random distribution of necrosis and apoptosis with minimal inflammation or infiltrations of lymphocytes. Chronic Hepatitis It results when there is continued inflammation. It is characterized by fibrosis Different types of chronic hepatitis: o Granulomatous hepatitis : granulomas of sufficient size (focal, multifocal, or diffuse). o Chronic suppurative hepatitis : manifested as multiple abscesses. 3  Nonspecific Reactive Hepatitis It is a diffuse process distributed throughout the liver in response to some systemic illness (GI tract), or prior liver inflammation. In acute cases, there is a minimal to mild infiltrate of neutrophils within the connective tissue of the portal tracts. Mononuclear cells predominate in more chronic manifestations. Cholangitis. Inflammation of the biliary ducts A- Neutrophilic Cholangitis : presence of neutrophils within the lumen or epithelium of the bile ducts (Acute and chronic forms). In chronic form : Fibrosis and mononuclear inflammatory cells It is caused by ascending bacterial infections from the intestine. 4  Cholangitis. B-Lymphocytic Cholangitis. C- Destructive Cholangitis: Necrosis of the epithelium of bile ducts Inflammation is around the areas of biliary destruction characterized by the destruction of bile duct epithelium, followed by regeneration in some instances. Histological findings: hemosiderin and mononuclear inflammatory cells in portal tracts 5  Cholangiohepatitis Inflammation that affects both the biliary ducts and hepatic parenchyma The primary focus of inflammation can be identified as affecting either the hepatocytes or the biliary tree (intrahepatic disease), but occasionally both components of the liver are affected Usually as an extension of biliary disease, such as neutrophilic cholangitis, to involve the periportal hepatocytes. 6  Necrosis and Apoptosis Hepatocytes and biliary epithelium, are the principal targets of most liver diseases. Sublethal injury to hepatocytes is characterized by cell swelling or atrophy. Cells that have sustained a sublethal injury often remove damaged organelles by forming autophagosomes. Material that cannot be digested further is retained as lipofuscin 7  Disturbances of Bile Flow and Icterus Cholestasis: disturbance of bile flow Lead to Hyperbilirubinemia : increased blood bilirubin level 2 types: intrahepatic & extrahepatic. Can cause greenish brown liver discoloration Intrahepatic cholestasis can occur by: liver injury, hemolysis and inherited abnormalities of bile synthesis  Acute Intrahepatic Cholestasis: Bile plugs in canaliculi.  Chronic Intrahepatic Cholestasis: Bile taken up by Kupffer cells. Extrahepatic cholestasis can occur by: intraluminal obstruction or extraluminal constriction (often involving the pancreas).  Acute Extrahepatic Obstruction: Portal area edema, neutrophilic infiltrate, proliferative reaction.  Chronic Extrahepatic Obstruction: Fibrosis in portal areas. 8  Disturbances of Bile Flow and Icterus Cause of icterus : – Hepatic dysfunction. – Prehepatic causes such as intravascular hemolysis It is a common cause in ruminants Horses often manifest icterus with acute hepatic dysfunction or obstruction, but icterus may or may not occur in horses with chronic hepatic disease. "Physiologic icterus" in horses when feed-deprived for days, due to decreased bilirubin uptake by hepatocytes. 9  Biliary Hyperplasia and Ductular Reaction Ductular reaction: is when special cells at the edges of the portal tract grow and can become either bile ducts or liver cells Ductular reaction can develop: in injuries, in cholestasis, and in regions of hypoxia. Ductular reaction can happen in response to many different types of liver damage. Regeneration The liver can quickly regrow lost tissue. A healthy animal can lose 2/3 of its liver without showing liver problems because the liver regrows through compensatory hyperplasia. 1 0  Fibrosis Chronic liver injury leads to Fibrosis Severe Hepatic fibrosis can be lethal. In the normal liver, collagens I and III for connective tissue of the portal tracts and around the terminal hepatic venule (central vein). Collagen IV : most abundant collagen type in the sinusoids. Hepatic fibrosis involves increased ECM and changes in collagen types and their locations. A severely fibrotic liver can contain up to six times more collagen and proteoglycans than a healthy liver. 1 1  End-Stage Liver or Cirrhosis Cirrhosis involves widespread fibrosis, transforming the liver's architecture into abnormal lobules. It includes loss of liver parenchyma, condensation of the reticulin framework , and the development of fibrous tissue tracts. Regeneration of liver tissue within these tracts forms variable-sized nodules. 1 2  Hepatic Failure In healthy animals, > 2/3 of the hepatic parenchyma can be removed without significant impairment of hepatic function, and normal hepatic mass can be regenerated. This process of tissue removal can be repeated several times in younger animals, and function is retained. 1 3  Normal Function The gallbladder stores and concentrates bile. When food containing fat enters the intestinal tract  secretion of cholecystokinin (CCK) from the duodenum and jejunum  contracts and releases its contents into the cystic duct  the common bile duct and into the duodenum. The bile emulsifies fats and assists their absorption. In dogs and cats, bile is concentrated by moving sodium and other particles across gallbladder cells. Horses don't have a gallbladder and release bile directly into their intestines. Animals that haven't eaten for 24 to 48 hours or are starving might have larger gallbladders because they lack the signals needed to make the gallbladder contract. 1 4  Dysfunction/Responses to Injury When the entrance to the gallbladder become obstructed by a cholelith (gallstone) the gallbladder cannot release bile Obstruction can lead to hyperbilirubinemia and cholecystitis Larger choleliths can cause pressure necrosis and ulceration of the gallbladder mucosa or formation of saccular diverticula rupture. Rupture leads to leakage of bile into the peritoneal cavity, which is very irritating  acute peritonitis. 1 5  Portals of Entry/Pathways of Spread Infectious agents can spread from the gallbladder through the venous circulation or through the bile into the intestine, where they can then be absorbed and distributed via the systemic circulation. Defense Mechanisms/Barrier Systems The common bile duct is protected bcz is surrounded by the liver lobes and with a sphincter at its end. This barrier prevents intestinal bacteria from moving upward and ensures a constant flow of bile 1 6  III- Exocrine Pancreas Function : contribute to digestion. The secretions contain enzymes that break down lipids , proteins, and carbohydrates + electrolytes, which maintain the pH of the intestinal contents within a range that is optimal for enzymatic activity. Pancreatic enzymes act on the products of gastric digestion. These proenzymes prevent degradation of the pancreas by its own digestive enzymes. These are activated within the intestine. Inhibitors of pancreatic enzymes are present in the pancreatic tissue. Secretion is controlled by neural stimulation (vagus nerve) & humoral factors. 1 7  Dysfunction/Responses to Injury Dysfunction of the pancreas = pancreatitis. Pancreatic injury results in the release of pancreatic enzymes into the surrounding parenchyma  enzyme activation and autodigestion of the pancreatic tissue. Trypsin, can activate the kinin system, complement, and clotting cascades  inflammation and necrosis and disseminated intravascular coagulopathy. The pancreas possesses modest regenerative capacity after necrosis of exocrine pancreatic acinar cells. 1 8  Portals of Entry/Pathways of Spread Damage to the pancreas results in activation of pancreatic enzymes and autodigestion These activated enzymes, can be released into the systemic circulation  systemic inflammatory response syndrome (SIRS). If pancreatitis is initiated by reflux of intestinal bacteria through the pancreatic duct, which is more common in human, the infectious agent can be released into systemic circulation septicemia. 4 9  Defense Mechanisms/Barrier Systems The pancreas is protected by the continuous flow of secretions into the duodenum, which prevents reflux of duodenal contents. The normal secretion of the pancreas contains trypsin, chymotrypsin, elastase, aminopeptidases, lipase, phospholipases, amylase, and nucleases. Trypsin : activation of several of the other pancreatic enzymes. 5 0  Defense Mechanisms/Barrier Systems Most enzymes, except amylase and lipase, are secreted as proenzymes to prevent pancreatic injury. In particular, trypsin activation is tightly controlled. Trypsinogen is not normally activated until it enters the lumen of the duodenum through duodenal enteropeptidase. The chance of inappropriate trypsin activation in acinar cells or ducts of the pancreas is reduced by secretion of protective trypsin inhibitors. 5 1