19-1: Pancreas Flashcards
what are the primary roles of the pancreas?
exocrine – secretes enzymes for digestion (trypsinogen, chymotrypsinogen, procarboxypeptidase, etc.)
endocrine – secretes insulin, glucagon, and somatostatin
what is the most common congenital anomaly of the pancreas?
pancreas divisum due to failure of ventral and dorsal bud fusion
*associated with chronic pancreatitis
what complication is associated with a congenital annular pancreas?
duodenal obstruction
what is an ectopic pancreas?
a congenital anamoly in which the pancreas is formed within an abnormal place
usually stomach or duodenum
can cause pain or mucosal bleeding
what are some pancreatic protective mechanisms that prevent autodigestion?
enzymes are synthesized as inactive proenzymes and packaged within secretory granules
proenzymes are not activated until they come into contact with activated trypsin. Trypsin is activated by enterokinase within the duodenum
acinar and ductal cells secrete trypsin inhibitors
what is the clinical presentation of acute pancreatitis?
constant, intense, upper or bid back pain
occasionally radiates to left shoulder
anorexia
N/V
what lab findings are associated with acute pancreatitis?
elevated serum amylase and lipase
what lab finding is most specific for acute pancreatitis?
lipase - remains elevated for 8-14 days
what is the etiology of acute pancreatitis?
release of toxic enymes and cytokines activating a systemic inflammatory response
what PE findings are highly associated with high mortality in severe acute pancreatitis?
Cullen’s sign (periumbilical ecchymosis)
Grey Turner’s sign (flank ecchymosis)
what metabolic processes are associated with pancreatitis?
alcohol
hyperlipoproteinemia
hypercalcemia
drugs
what genetic mutations are associated with pancreatitis?
PRSS1 - encodes trypsin
SPINK1 - encodes trypsin regulators
CASR - encodes calcium metabolism regulators
CFTR
what mechanical processes are associated with pancreatitis?
gallstones trauma iatrogenic injury operative injury endoscopic procedures with dye injection (ERCP)
what vascular processes are associated with pancreatitis?
shock
atheroembolism
vasculitis
what infectious agents are associated with pancreatitis?
Mumps
Coxsackievirus (of course)
what is the pathogenesis of pancreatitis?
after tissue damage occurs, trypsin can directly or indirectly activate factors found in the blood
the resulting inflammation and small-vessel thrombosis causes further damage to the acinar cells which amplifies intrapancreatic enzyme activation
what are the basic abnormalities associated with pancreatitis?
microvascular leak and edema fat necrosis acute inflammation autodigestion of pancreatic parenchyma blood vessel destruction and interstitial hemorrhage
what are some possible systemic complications of pancreatitis?
acute respiratory distress syndrome
acute renal failure
what is the definition of chronic pancreatitis?
prolonged inflammation of the pancreas associated with irriversible destruction of exocrine parenchyma, fibrosis and eventual loss of endocrine parenchyma
what is the most common cause of chronic pancreatitis?
long-term alcohol use (yikes, we’re in trouble)
what cytokine is associated with chronic pancreatitis?
TGF-B – involved in scar formation and fibrosis
what is autoimmune pancreatitis type 1?
associated with the presence of IgG4 secreting plasma cells in the pancreas
one manifestation of systemic IgG related disease
What is autoimmune pancreatitis type 2?
restricted to the pancreas except in a subset of patients with ulcerative colitis
what is the clinical presentation of autoimmune pancreatitis?
mimic pancreatic carcinoma
mass lesion in the pancreatic head on imaging
what is the clinical presentation of chronic pancreatitis?
repeated bouts of abdominal pain
persistent back pain
on imaging: calcifications and pseudocysts
labs: pancreatic exocrine insufficiency and DM
what mainfestations of chronic pancreatitis lead to morbidity and contribute to mortality?
pancreatic exocrine insufficiency
chronic malabsorption
DM
patients with herediatry pancreatitis associated with PRSS1 have a risk of developing what?
pancreatic cancer
what are congenital pancreatic cysts?
thin-walled cysts that likely result from anamalous pancreatic duct development
extremely rare
what are pancreatic pseudocysts?
arise following a bout of pancreatitis - usually from chronic alcoholic pancreatitis
lack an epithelial lining
many resolve spontaneously but some may become secondarily infected, compress adjacent structures or perforate
what are serous cystic neoplasms?
always benign
F > M
60 y/o +
most common in the pancreatic tail
what are mucinous cystic neoplasms?
95% women
may be precursors to invasive carcinoma
usually located in the pancreatic tail
what are solid-pseudopapillary neoplasms?
young women
pancreatic tail
locally agressive malignancy
what are intraductal papillary mucinous neoplasms (IPMNs)?
mucin-producing neoplasms that involve the duct of the pancreas
M > F
located in the pancreatic head
precursor to invasive carcinoma
what demographics are associated with pancreatic cancer?
60 y/o +
African Americans, Japanese Americans, Native Americans, Hawaiian islanders and Ashkenazi Jews
what risk factors are associated with pancreatic cancer?
cigarette smoking (2x risk)
chronic pancreatitis
visceral obesity and high BMI
DM
what hereditary conditions have an increased risk of pancreatic cancer?
PJ syndrome (STK11) Hereditary pancreatitis (PRSS1 or SPINK1) Familial atypical multiple mole melanoma syndrome (CDKN2A)
Family hx of pancreatic cancer (> 3 relatives)
Hereditary breast and ovarian cancer
Hereditary non-polyposis colorectal cancer
which gene mutations are highly associated with pancreatic ductal carcinoma?
KRAS
TP53
CDKN2A
SMAD4
where are pancreatic cancers most likely to occur?
in the head of the pancreas
why are pancreatic cancers hard to detect?
they are asymptomatic until they invade into adjacent structures
what are the classic presentations of pancreatic cancer?
pain
weight loss
anorexia
general malaise and weakness
what symptoms are associated with a tumor within the head of the pancreas?
obstructive jaundice caused by the head of the pancreas obstructing the distal common bile duct
Courvoisier sign - a palpably enlarged, nontender gallbladder with mild, painless, jaundice
what is the growth pattern of pancreatic cancer?
grows along nerves and invades into blood vessels and the retroperitoneum
what is frequently involved in pancreatic cancer via direct invasion?
spleen adrenals transverse colon stomach local lymph nodes
where are primary pancreatic metastases most common?
liver and lungs
what are the microscopic features of pancreatic adenocarcinomas?
dense desmoplasic reaction
what is Trousseau sign?
migratory thrombophlebitis - caused by elaboration of platelet activating factors and procoagulants from the tumors or its necrotic products
what is the precursor lesion associated with pancreatic cancer?
pancreatic intraepithelial neoplasia (PanIN)
often found in the pancreatic parenchyma
microscopically show dramatic telomere shortening
what is the model of progression from normal tissue to invasive carcinoma in the pancreas?
- normal pancreas
- PanIN-1A: telomere shortening
- PanIN-1B: KRAS activation
- PanIN-2: CDKN2A inactivation
- PanIN-3: TP53, SMAD4, and BRCA2 inactivation
- invasive carcinoma
what is the prognosis of pancreatic cancer?
typically survival after diagnosis is unlikely (usually die within 1-2 years)
> 80% of pancreatic cancers are unresectable at the time of diagnosis due to invasion
