Chapter 19 - Pancreas Flashcards
What is the most common pancreatic congenital anomaly? Key features
Pancreas division: failure of ventral and dorsal fetal duct systems to fuse
Bulk of pancreatic secretions to drain through smaller minor papilla; stenosis predisposes to chronic pancreatitis
Annular pancreas
Congenital anomaly
Bandlike ring around second portion of duodenum -> duodenal obstruction
Ectopic pancreas key features
Congenital anomaly
Common incidence
Sites: stomach, duodenum, jejunum, Meckel diverticulum and ileum
Submucosal
Mostly asymptomatic
Can cause inflammation, pain or rarely mucosal bleeding from ulcer
Agenesis of the pancreas key features
Fatal if complete
Homozygous PDX1 gene (homeobox TF)
Acute pancreatitis key features
Reversible parenchymal damage associated w damage
majority associated with biliary tract disease (gallstones0 or alcoholism
Enzymes digest parenchyma
What are the most common mechanisms of acute pancreatitis?
Pancreatic duct obstruction: gallstones - females, older
Alcohol: direct toxic effect on pancreatic acinar cells and increases oxidative stress -> functional obstruction - male, younger age of onset
Cystic fibrosis: SPINK1 mutations and CFTR mutations -> protein plugging and duct obstruction
Morphology of acute pancreatitis
Mild interstitial edema and inflammation to extensive necrosis and hemorrhage
Acute necrotizing pancreatitis - gray-white parenchymal necrosis and chalky white fat necrosis
Hemorrhagic: patchy red-black hemorrhage w fat necrosis
Clinical features of acute pancreatitis
Abdominal pain, nausea, anorexia
Elevated plasma lvls of pancreatic enzymes
Full-blown = medical emergency: intense abd pain, peripheral vascular collapse and shock from explosive activation of systemic inflammatory response
Death from: shock, ARDS, acute renal failure
Lab: marked serum amylase and lipase elevations
Hypocalcemia -> calcium soaps in fat necrosis
Treatment of acute pancreatitis
What are the possible sequalae?
Restrict oral intake - rest pancreas
Analgesia, nutrition, and volume support
Sequelae: sterile pancreatic abscesses and pancreatic pseudocysts
What are the features of chronic pancreatitis?
Inflammation with irreversible parenchymal destruction and fibrosis
Late stages: endocrine or exocrine parenchyma is destroyed -> malabsorption, DM, pseudocysts
Middle aged male
Long-term alcohol abuse most common
Most pts w recurrent bouts of acute pancreatitis develop chronic pancreatitis
Prognosis: long-term poor
What do repeated episodes of acinar cell injury induce in chronic pancreatitis?
profibrogenic cytokines - TGF-B and PDGF
Drive myofibroblast proliferation, colalagen secretion and ECM remodeling -> irreversible fibrosis -> pancreatic insufficiency
What is the MOST COMMON cyst of the pancreas?
Pseudocysts
What are pseudocysts?
Collection of necrotic, hemorrhagic material rick in pancreatic enzymes
75% of pancreatic cysts
Cysts NOT lined by epithelium
Encircled by fibrosis granulation tissue
Occur after bouts of acute pancreatitis or following trauma
Many spontaneously resolve
Can compress gallbladder ducts
What is pancreatic carcinoma ?
Infiltrating ductal adenocarcinoma
Most aggressive of solid malignancies
What are the precursors to pancreatic cancer?
Non-neoplastic epithelium-> small ductal noninvasive lesions-> invasive carcinoma
Lesions are called pancreatic intraepithelial neoplasms (PanINs)
What is the pathogenesis of pancreatic cancer?
KRAS (chr 12) - MC altered oncogene
CDKN2A/p16 (Chr 9) - MC tumor suppressor gene (hypermethylation)
SMAD4 (Chr 18) - second most common tumor suppressor gene; important bc this mutation is rare in other cancers (important for TGF-B receptor signal transduction)
What is the epidemiology and inheritance of pancreatic cancer?
80% are 60-80
MC in blacks
Smoking increases risk 2x
Modestly increase risk: Chronic pancreatitis, consumption of diet rick in fats, FH of pancreatic cancer, germline mutations in CDKN2A, and DM
What is the morphology of pancreatic cancer
Most arise in head of gland
Highly invasive
Obstruct distal common bile duct -> jaundice
Dense desmoplastic reaction
What are the clinical features of pancreatic cancer?
WL and pain typical presenting sx
Jaundice
Courvoisier’s sign: jaundice, palpable gallbladder
Metastases common
Most unresectable at presentation
Poor prognosis
Migratory thrombophlebitis - Trousseau syndrome, can occur with pancreatic neoplasms as well as other adenocarcinomas
