Pancreatitis • Inflammation of pancreas associated with injury to exocrine parenchyma
Acute pancreatitis • Reversible pancreatic parenchymal injury associated with inflammation • Relatively common • Biliary tract disease and alcoholism account for approximately 80% of cases
Etiologic Factors Metabolic • Alcoholism • Hyperlipoproteinemia • Hypercalcemia • Drugs (e.g., azathioprine) Genetic • Mutations in cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1) genes
Mechanical • Gallstones • Trauma • Iatrogenic injury Vascular • Shock • Atheroembolism • Vasculitis Infectious • Mumps
Morphology • Macroscopically ďƒ areas of red-black hemorrhage interspersed with foci of yellow-white, chalky fat necrosis Hemorrhagic area
Microscopic • Ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage • Basic alterations Microvascular leakage causing edema Necrosis of fat by lipolytic enzymes
Acute inflammation Proteolytic destruction of pancreatic parenchyma Destruction of blood vessels and subsequent interstitial hemorrhage
• Region of fat necrosis on the right and focal pancreatic parenchymal necrosis(center) Fat necrosis
Pathogenesis • Autodigestion of pancreatic substance by inappropriately activated pancreatic enzymes • Inappropriate activation of trypsin can activate other proenzymes
• Trypsin also converts prekallikrein to its activated form and activate clotting and complement systems by activation of Hageman factor (factor XII)
Pathogenesis of acute pancreatitis.
Clinical Features • Abdominal pain constant and intense, often referred to upper back, can be associated with referred pain to left shoulder • Anorexia, nausea, and vomiting • Diagnosed by elevated plasma levels of amylase and lipase
• Release of toxic enzymes, cytokines, and other mediators into circulation and activation of systemic inflammatory response results in – – Leukocytosis – Hemolysis – DIC – Fluid sequestration – ARDS
– Diffuse fat necrosis – Peripheral vascular collapse and shock with acute renal tubular necrosis may occur
Laboratory findings • Marked elevation of serum amylase during first 24 hours • Within 72 to 96 hours – rise in serum lipase • Glycosuria - in 10% of cases • Hypocalcemia – due to precipitation of calcium soaps in necrotic fat
Sequelae : • Sterile pancreatic abscess • Pancreatic pseudocyst
Chronic pancreatitis • Inflammation of pancreas with irreversible destruction of exocrine parenchyma, fibrosis • Later - destruction of endocrine parenchyma
• Most common cause of chronic pancreatitis is long-term alcohol abuse
Other causes of chronic pancreatitis • Long-standing obstruction of pancreatic duct by pseudocysts, calculi, trauma, neoplasms • Hereditary pancreatitis, caused by germline mutations in PRSS1 (cationic trypsinogen gene) or SPINK1 (serine protease inhibitor Kazal type 1 gene)
• Cystic fibrosis - CFTR gene mutation decrease bicarbonate secretion by pancreatic ductal cells, thereby promoting protein plugging and development of chronic pancreatitis
Pathogenesis 1. Ductal obstruction by concretions• Some agents responsible for chronic pancreatitis increase protein concentrations in pancreatic juice which form ductal plugs
• Ductal plugs may calcify, forming calculi composed of calcium carbonate precipitates and further obstruct pancreatic ducts 2. Toxic effects - alcohol and its metabolites, can exert direct toxic effect on acinar cells
3. Oxidative stress - alcohol-induced oxidative stress may generate free radicals in acinar cells, leading to membrane lipid oxidation and activation of transcription factors NF-ÎşB
• Transcription factors induce expression of chemokines that attract mononuclear cells • Oxidative stress may promote fusion of lysosomes and zymogen granules, acinar cell necrosis, inflammation, and fibrosis
Morphology • Grossly - gland is hard, with dilated ducts and visible calcified concretions • Microscopic - parenchymal fibrosis, reduced number and size of acini and dilation of pancreatic ducts • Chronic inflammatory infiltrate around lobules and ducts
• Ductal epithelium - atrophied or hyperplastic or may show squamous metaplasia • Remaining islets of Langerhans embedded in sclerotic tissue, may fuse and appear enlarged
Chronic pancreatitis Extensive fibrosis and atrophy
Dilated ducts with inspissated eosinophilic ductal concretions
Clinical Features • Repeated attacks of moderately severe abdominal pain and back pain • Recurrent attacks of jaundice or vague attacks of indigestion may occur
Sequelae of acute and chronic pancreatitis