Chapter 19: Diseases, Disorders, and Neoplasms of the Pancreas Flashcards
What is a Pancreas Divisum, Annular Pancreas, and Ectopic Pancreas?
PD: MOST COMMON congenital pancreas anomaly
- failure of fusion of ventral and dorsal duct systems
- minor papilla drain majority, Duct of Wirsung (head)
AP: ventral bud travels anterior and constricts 2nd part of duodenum, causing obstruction
EP: pancreas tissue usually in stomach or duodenum
- usually asymptomatic
- can cause pain (inflamm) and mucosal bleed (RARE)
What is Acute Pancreatitis and who is it most common in?
- reversible pancreatic parenchymal injury associated with inflammation due to diverse etiologies
80% due to alcohol (more common in MALES)
20% due to biliary disease (MC in FEMALES)
How do Pancreatic Duct Obstruction and Acinar Cell Injury cause Acute Pancreatitis?
PDO: accumulation of lipase can cause local fat necrosis, while tissue death leads to inflammation (interstitial edema)
- both compromise vasculature = ischemia
- usually caused by gallstones
ACI: release of digestive enzymes causing inflammation and autodigestion
- oxidative stress = inc. free radicals = AP1/NFkB
- high Ca = activation of trypsinogen by trypsin
- usually due to alcohol/drugs/trauma
What are 3 medications that can leads to Acute Pancreatitis? (F/A/E)
furosemide, azathioprine, estrogens
What are 3 genetic alterations related to Hereditary Pancreatitis? (P/S/C)
PRSS1: AD GOF of trypsinogen making trypsin resistant to self-inactivation or prone to activation
SPINK1: AR LOF preventing trypsin inhibition
CFTR: dec. bicarbonate secretion = protein plugging, duct obstruction, and pancreatitis
Hereditary –> recurrent severe acute pancreatitis that leads to chronic pancreatitis
Acute Pancreatitis
What does it look like and how does it present clinically?
M: fat necrosis (granular blue fat cells = saponification), proteolytic pancreatic parenchyma destruction, red-black vasculature with yellow-white chalky fat necrosis
- peritoneal cavity = brown fluid w/fat globules
C: constant abdominal pain is CARDINAL MANIFESTATION, inc. plasma amylase and lipase (SPECIFIC), hypocalcemia (saponification), glycosuria
- also anorexia, nausea, vomiting
Acute Pancreatitis
How is it treated and what are 3 major complications it can cause? (A/P/I)
T: total oral intake restriction to “rest” pancreas
- IV fluids, pain meds, nutrition/volume support
C: ARDS/acute renal failure, pancreatic pseudocysts, and infection of debris by GRAM (-) pathogens
Chronic Pancreatitis
What is it caused by, how does it develop, and what does it look like?
- prolonged inflammation of pancreas due to IRREVERSIBLE destruction of exocrine parenchyma and eventually endocrine parenchyma
- middle aged males w/LONG-TERM EtOH abuse
- follows repeated acute pancreatitis; TGFb and PDGF induce activation/prolif. of periacinar myofibroblasts that deposit collagen = FIBROSIS
M: hard pancreas w/focal calcification, spares Islets of Langerhans, ductal dilation and intraluminal plugs
Chronic Pancreatitis
How does it present clinically, how is it diagnosed, and what are 3 complications it can cause?
C: usually clinically silent, but sometimes with recurrent pain or jaundice
- triggers: EtOH, overeating, opiates (inc. Oddi tone)
- not usually life threatening
D: clinical suspicion; visualize calcifications by CT/US
- WL and edema due to hypoalbuminemia (malabsp)
C: malabsorption, DM, pseudocysts
What is Autoimmune Pancreatitis?
- pathologically distinct chronic pancreatitis associated with IgG4-secreting plasma cells in pancreas (Type 1)
- duct-centric mixed inflammatory cell infiltrate, venulitis, inc. plasma cells (can mimic pancreatic carcinoma)
Non-neoplastic Pancreatic Cysts
Congenital Cysts vs Pseudocysts
C: due to anomalous development of pancreatic ducts
- thin-walled, cuboidal epithelial lining
- thin fibrous capsule w/clear serous fluid
- from polycystic kidney disease/von Hippel Lindau
P: most common pancreatic cyst (75%)
- localized necrotic/hemorrhagic material
- rich in pancreatic enzymes
- lacks epithelial lining (walled off by granulation)
- spontaneously resolve, can be infected
What is Pancreatic Intraepithelial Neoplasia? (PanIN)
- well-defined non-invasive precursor lesions in SMALL DUCTS that give rise to invasive pancreatic cancer
- have dramatic telomere shortening
Infiltrating Ductal Adenocarcinoma
What are its major risk factors, where does it commonly occur in the pancreas, and what does it look like?
RF: SMOKING (leading preventable cause); high fat diet, family history, or DM; Ashkenazi Jews and African Americans
- commonly occurs in HEAD of pancreas and can obstruct distal common bile duct = PAINLESS JAUNDICE (inc. DIRECT bilirubin); 15% in BODY
M: glands lined with pleomorphic cuboidal-columnar epithelium (cell clusters that are deep infiltrative)
Pancreatic Adenocarcinoma
What does it look like clinically, where does it commonly metastasize, and who does it commonly affect?
What are Trousseau and Courvoisier Signs?
- disease of OLDER ADULTS (80% 60-80 yo) and has NO RELIABLE markers to catch early involvement
- remain clinically silent until invasion (metastasizes to LIVER and LUNGS)
- causes pain (grows on nerves - Celiac Ganglion), obstructive jaundice, WL, anorexia, weakness
Trousseau Sign: migratory thrombophlebitis (pro-coagulants) and Courvoisier Sign: palpable enlarged gallbladder (nontender) w/painless jaundice
Pancreatic Adenocarcinoma
What are the 4 genetic alterations that are commonly seen in disease? (K/C/S/T)
KRAS - most frequently altered oncogene (90-95% activated)
- act. GTP-binding protein w/RTK: growth/survival
CDKN2A - most frequently altered tumor suppressor (95% inactivated)
- seen in families with inc. incidence of melanoma
SMAD4 - inactivated in 55% of pancreatic cancers
- encodes protein for TGFb signal transduction
TP53 - inactivated in 70-75% of pancreatic cancers
- induce cell-cycle arrest due to DNA damage
