BMS 150 Week 13 Pancreas Diseases PDF

Pancreas Part II - Diseases of the Pancreas BMS 150 Week 13 Acute pancreatitis Basics: Severity ranges from life-threatening to a self-limited illness that causes mild-moderate abdominal pain ▪ Acute, reversible pancreatic injury associated w...

Pancreas Part II - Diseases of the Pancreas BMS 150 Week 13 Acute pancreatitis Basics: Severity ranges from life-threatening to a self-limited illness that causes mild-moderate abdominal pain ▪ Acute, reversible pancreatic injury associated with inflammation Reasonably common – incidence of 10-20/100,000 ▪ Major risk factors are excessive alcohol intake and cholelithiasis 80% of acute pancreatitis is due to these two risk factors ▪ 5% of those with gallstones will have an episode  Etiologic Factors in Acute Pancreatitis Metabolic Acute pancreatitis - Alcoholism - Hyperlipoproteinemia - Hypercalcemia Etiologies - Drugs (e.g. azathioprine) Particularly notable are the Genetic genetic causes – why might it - Mutations in the cationic be a bad idea to have mutations trypsinogen (PRSS1) and trypsin in trypsinogen and trypsinogen inhibitor (SPINK1) genes inhibitors? Mechanical Helps understand the - Gallstones pathology of more common - Trauma causes of acute pancreatitis - Iatrogenic Injury (operative/ endoscopic procedures with dye) A huge list of drugs – around 80 Vascular – have been shown to incite - Shock acute pancreatitis; thankfully, - Atheroembolism it’s a rare adverse effect - Vasculitis Infectious - Mumps Acute pancreatitis What is the role of trypsinogen activation in acute pancreatitis? ▪ It’s a digestive enzyme (trypsin) capable of activating other zymogens Reasonable to hypothesize that this leads to a straightforward autodigestion of the pancreas However, genetic knock-out studies that remove trypsinogen from transgenic mice demonstrate local and systemic inflammation that are very similar to chronic pancreatitis ▪ This suggests it may be important in activation of acute pancreatitis BUT there are other factors and/or mechanisms are involved Acute pancreatitis Pathophysiology ▪ Alcohol ingestion: Leads to excessive protein in pancreatic secretions, “plugs” the ducts Direct toxic effects on acinar cells Causes contraction of the sphincter of Oddi ▪ Biliary tract obstruction: Pancreatic secretions are stuck in the ducts, due to a gallstone or sludge blocking outflow Common factor = blockage of ducts Acute pancreatitis Duct blockage and acinar cell injury result in profound pancreatic damage Acute pancreatitis Pathophysiology More than just auto-digestion: ▪ Injured tissues, periacinar myofibroblasts, and leukocytes release proinflammatory cytokines including IL-1β, IL-6, tumor necrosis factor, platelet-activating factor, and substance P Inflammation and edema increase ▪ Activation of complement and clotting cascades, as well as elevated interstitial pressures lead to impairment of blood flow ▪ Can result in a systemic inflammatory response, resulting in leukocytosis, hemolysis, disseminated intravascular coagulation (DIC), acute respiratory distress syndrome  Acute pancreatitis Pathological features: 1. Microvascular leakage causing edema Mild injury 2. Digestion of fat by lipolytic enzymes 3. Acute inflammation 4. Proteolytic destruction of pancreatic parenchyma 5. Destruction of blood vessels and subsequent interstitial hemorrhage Severe injury, hemorrhage and third-spacing of fluid Fat necrosis can be seen in any stage – smaller areas in mild injury, larger areas in more severe injur Free pancreatic lipases cleave triglycerides in the abdominal cavity → fatty acids that combine with extracellular calcium (known as saponification) Saponification can be severe enough to cause hypocalcemia (bad prognostic factor) Acute pancreatitis Clinical features: ▪ Abdominal pain is the cardinal manifestation of acute pancreatitis Constant, intense and often referred to the upper back or shoulder Severity varies (moderate to quite severe) Anorexia, nausea, and vomiting frequently accompany the pain ▪ Systemic effects of severe acute pancreatitis (systemic inflammation, hemorrhage, and fluid loss into abdomen) result in a medical emergency Patients can rapidly proceed to shock and kidney failure Acute pancreatitis Complications: ▪ Pseudocysts ▪ Chronic pancreatitis ▪ Infection of fluid collections and/or necrotic debris by bacteria ▪ Hemorrhage, shock (ARDs and kidney failure can complicate shock) ▪ 5% with severe acute pancreatitis die from shock during the first week of illness Chronic pancreatitis Inflammation of the pancreas with irreversible destruction of exocrine parenchyma, fibrosis, and, in the late stages, the destruction of endocrine parenchyma ▪ Usually caused by repeated bouts of acute pancreatitis ▪ Usually caused by long-term alcohol abuse Don’t usually keep a gallbladder in if you keep getting pancreatitis from stones… Less common causes include cystic fibrosis and hereditary pancreatic disease, as well as other causes of obstruction (tumours, pancreatis divisum) Chronic pancreatitis Pathophysiology: ▪ Thought to be related to multiple episodes of acute pancreatitis ▪ Ductal obstruction by concretions – due to increased protein concentrations in the pancreatic juice, forms plugs that can become calcified ▪ Alcohol has a toxic effect on pancreatic acinar cells Oxidative stress on pancreatic cells (from alcohol abuse) may result in the activation of pancreatic enzymes and damage Chronic pancreatitis Chronic pancreatitis Pathology: ▪ Parenchymal fibrosis ▪ Reduced number and size of acini Islets of Langerhans usually remain spared, until end- stage disease ▪ Variable dilation of the pancreatic ducts ▪ Chronic inflammatory infiltrate around lobules and ducts The interlobular and intralobular ducts are frequently dilated and contain protein plugs in their lumens Chronic pancreatitis Clinical findings: ▪ Repeated attacks of mild or moderately severe abdominal pain or back pain The disease may be entirely silent until pancreatic insufficiency and diabetes mellitus develop ▪ 50% mortality after 25 years, usually linked to development of malabsorption and diabetes Pseudocysts Localized collections of necrotic-hemorrhagic material rich in pancreatic enzymes ▪ No epithelial lining (hence the prefix “pseudo”) and account for approximately 75% of cysts in the pancreas (rest being neoplastic cysts) ▪ Usually arise after an episode of acute pancreatitis or in the setting of chronic alcoholic pancreatitis Can also be caused by traumatic injury to the pancreas  Pseudocysts Pathogenesis: ▪ Usually, solitary ▪ Locations: Within the pancreas Lesser omentum Retroperitoneum between the stomach and transverse colon or between the stomach and liver Rarely subdiaphragmatic ▪ Formed by the walling off of fat necrosis with fibrous tissue ▪ Usually are composed of central necrotic-hemorrhagic material rich in pancreatic enzymes surrounded by non- epithelial-lined fibrous walls of granulation Can range in size from 2 to 30 cm in diameter Pseudocysts Pseudocysts Clinical features ▪ Symptoms are those of the underlying illness, usually (i.e. chronic pancreatitis) ▪ Can become complicated by secondary infection or perforation Can cause peritonitis if they rupture Larger pseudocysts can compress adjacent structures, thus causing symptoms References Junquiera’s Basic Histology: Text and Atlas (13th edition) – pg. 326-329 Guyton’s Medical Physiology – pg. 780-783 Moore’s Clinically-Oriented Anatomy, pages 265 - 268 Robbin’s and Cotran’s Pathologic Basis of Disease, Chapter 19