pancreas Flashcards
robbins
composition of the exocrine pancreas
= >80% of the pancreas
composed of acinar cells that secrete enzymes for digestion, i.e. trypsinogen, chymotrypsinogen, procarcboxypeptidase, proelastase, kallikreinogen, prophospholipase A+B
composition of the endocrine pancreas
contain islets of langehans,
secrete insulin, glucagon, and somatostatin
why are congenital anomalies so common in the pancreas
the dorsal and ventral foregut outpouchings have a very complex way that they fuse
dorsal pancreatic primordium gives rise to
body
tail
superior/anterior part of the head of the pancreas
drains though accessory duct of the santorini
ventral pancreatic primordium gives rise to
poster/inferior part of the head of the pancreas
drains through main pancreatic duct to papilla of vater
most common congenital anomaly of the pancreas
pancreas divisum
normal pancreatic drainage
where the main pancreatic duct (of Wirsung) joins the common bile duct just proximal to the papilla of vater, and the accessory pancreatic duct (of Santorini) drains into the duodenum through a separate minor papilla
what is pancreatic divisum
failure of fetal duct systems–> the bulk of the pancreas drains into the duodenum through the small caliber minor papilla
which means it backs up bc the sphincter is so small
individuals with pancreatic divisum are predisposed to _____ because of the inadequate drainage of the pancreatic secretions through the minor papilla
chronic pancreatitis
what is annular pancreas
a band like ring of normal pancreatic tissue that completely encircles the second portion of the duodenum
can lead to duodenal obstrunction
where is ectopic pancreatic tissue most commonly found
most to least =
stomach+duodenum
jejunum
meckel diverticula
ileum
prognosis of having an ectopic pancreas
usually an incidental finding, but also can cause localized into or incite mucosal bleeding
what germline mutation is associated with pancreatic agenesis
PDX1
what is the role of trypsin in the protection of the pancreas from self-digestion
most proenzymes are activated by trypsin,
trypsin is activated by duodenal enteropeptidase within the small bowel
acinar and ductal cells secrete trypsin inhibitors, including SPINK1, which further limits intrapancreatic trypsin activity
acute pancreatitis = ____ pancreatic perenchymal injury, due to EtOH toxicity, obstruction, vascular injury, mutations, or infection
reversible
___ and ____ account for ~ 80% of acute pancreatitis in the west
alcoholism (mostly male) and biliary tract ds (mostly female)
etiology of acute pancreatitis
inappropriate release and activation of pancreatic enzymes, which destroy pancreatic tissue and elicit an inflammatory response
intrapancreatic trypsin activation
intrapancreatic trypsin activation of prophospholipase causes what
degrade fat cells of the pancreas
intrapancreatic trypsin activation proelastase causes what
damage elastic fibers of BVs
intrapancreatic trypsin activation prekalikrein causes what
activates the kinin system–> activated clotting and complement systems –> inflammation and small essel thromboses–> damage to acinar cells,
how can pancreatic duct obstruction lead to acute pancreatitis
pancreatic duct obstruction –> accumulation of fluid in the interstitium that has proenzymes and active lipase –> fat necrosis –> edema –> impaired bloow flow –> ischemia
causes of pancreatic obstruction
cholelithiasis ampullary obstruction chronic alc ductal concretions parasites- Ascaris lumbricoides, Clonorchis sinensis pancreas divisum
what vascular etiologies can cause acute pancreatitis
shock, atheroembolism, vasculitis
what infections can cause acute pancreatitis
mumps
A. lumbricoides and C. sinensis parastial infections can lead to pancreatic obstruction –> acute pancreatitis
how can primary acinar cell injury lead to acute pancreatitis
release of digestive enzymes, inflammation, and autodigestion of pancreatic tissues
caused by ischmiea–> oxidative free radicals –> activate AP1 and NF-KB
increased Ca influx–> triggers inappropriate activation of enzymes
alc, drugs, trauma,
how can defective intracellular transport of proenzymes within the acinar cells lead to acute pancreatitis
(caused by alc or obstruction)
panreatic proenzymes are incorrectly sent to the intracellular compartment containing lysosomal hydrolases
leading to intracellular activation–> acinar cell injury
etiology of EtOH toxicity pancreatitis
alc consumption increases contraction of the sphincter of Oddi and chronic alc ingestion leads to deposition of thick protein plugs and obstruction of small pancreatic ducts
also direct toxicity to acinar cells
cause oxidative stress–> alter intracellular Ca levels–> promote intracinar trypsin activation
acinar cell injury –> activated enzymes –> _____ (4) —> acute pancreatitis
- interstitial inflammation and edema
- proteolysis
- fat necrosis
- damage to vessel walls, hemorrhage
what genetic mutations are associated with predisposition to pancreatitis
CFTR= cystic fibrosis PRSS1= serine protease 1 SPINK1= serine peptidase inhibitor, CASR= Ca-sensing receptor CTRC= chymotrypsin C CPA1= carboxypeptidase A1
what metabolic disorders predisopose one to developing acute pancreatitis
hypertriglyceridemia
hypercalcemia
hyperparathyroid
what meds predispose one to developing acute pancreatitis
furosemide azathioprine 2-3-dideoxyinosine estrogens etc.
hereditary pancreatitis is associated with ____ attacks of ____ often beginning _____ and ultimately leading to _____
reccurent
severe acute pancreatitis
in childhood
chronic pancreatitis
what three genes are associated with hereditary pancreatitis and what do they have in common
PRSS1 (AD) most
SPINK1 (AR)
CFTR
= all increase or sustain the activity of trypsin
patient with hereditary pancreatitis have a 40% lifetime risk of developing ___
pancreatic CA
characteristic morphology of acute pancreatitis
microvascular leak and edema
fat necrosis (of pancreas, omentum, or mesentery)
acute inflammation
destruction of pancreatic parenchyma, acinar and duct cells, and islets of langerhan (more severe forms)
destruction of BVs and interstitial hemorrhage (more severe forms)
pancreas is red-black from hemorrhage with foci of yellow-white fat necrosis
most severe form=hemorrhagic pancreatitis
clinical presentation of acute pancreatitis
constant and intense abd pain referred to the upper back and occasionally the left shoulder
anorexia, N/V,
elevated amylase and lipase
prognosis of acute pancreatitis
full blown acute pancreatitis is a medical emergency
–> explosive release of toxins into the systemic circulation–> leukocytosis, DIC, edema, and acute respiratory distress –> shock and acute renal tubular necrosis
can lead to systemic organ failure
5% die within the first week
40-60% with necrotic pancreatitis will get a G+ infection
lab findings associated with acute pancreatitis
marked elevation of serum amylase in the first 24 hours
rising serum lipase between 72-96 hours
glycosuria in 10% of cases
hypocalcemia from precipitation of calcium soaps in necrotic fat
define chronic pancreatitis
prolonged pancreatic inflammation with irreversible destruction of the exocrine parenchyma, fibrosis, and destruction of endocrine parenchyma in the late stages
population associated with chronic pancreatitis
middle aged males
most common cause of chronic pancreatitis
and other causes
alcohol abuse
-long standing obstruction, autoimmune, hereditary
etiology of chronic pancreatitis
repeated episodes of acute pancreatitis will initiate a sequence of perilobular fibrosis, duct distortion and altered pancreatic secretions
chronic pancreatic injury leads to local production of ______ that activate ___ (aka ___) to promote ___ and ____
inflammatory mediators (TGF-B, PDGF)
periacinar myofibroblasts/pancreatic stellate cells
fibrosis and acinar cell loss
etiology of autoimmune pancreatitis
IgG4 secreting plasma cells in the pancreas
can mimic signs of pancreatic carcinoma
characteristic morphology of chronic pancreatitis
fibrosis, atrophy and dropout of acini, and variable dilation of pancreatic ducts
acinar loss is a constant feature while loss of islets of langerhan is more variable
caused by alc abuse: characterized by ductal dilation and intraluminal protein plugs and calcification
clinical features of chronic pancreatitis
follows repeated bouts of acute pancreatitis
repeated attacks of abd pain or persistant abd/back pain
pain precipitated by alc abuse, overeating, or use of opiates and other drugs that increase sphincter of oddi tone
can also be silent until insufficiency or DM develop
can have mild fever, elevations of serum amylase, weight loss, edema due to low albumin
gallstone obstruction–> jaundice or elevations in serum alkaline phosphatase
diagnostic tools for chronic pancreatitis
visualize calcification by CT or US
prognosis of acute pancreatitis
poor
morbidity with insufficiency, chronic malabsorption, and DM
if survive, severe chronic pain is a problem
can develop pancreatic pseudocysts or CA
trx for IgG4 autoimmune ds
glucocorticoids (immune suppressant)
necrotic and hemorrhagic material that are rick in pancreatic enzymes and lack an epithelial lining
pseudocyst
75% of cysts in the pancreas are
pseudocysts
when do pseudocysts usually arise
usually following a bout of acute pancreatitis, particularly one superimposed on chronic alcoholic pancreatitis
post trauma to the pancreas
where do pseudocysts usually occur
most commonly in the lesser omental sac or in the retroperotineum between the stomach an transverse colon or stomach and liver
also in the pancreas, but less commonly
prognosis of pseudocyst
many spontaneously resolve
many become secondarily infected, larger ones may compress or even perforate into adjacent structures
prognosis of cystic neoplasms
range from harmless benign to precursors that become lethal CA
serous cystic neoplasms
where histology genetic mutation population prognosis trx
in the tail of the pancreas
small, lined by glycogen rich cuboidal cells and contain thin straw colored film
most common genetic abn = x VHL
women, 60s-70s
mostly benign, including serous cystic neoplasms, including serous cystadenomas
surgery is curative
mucinous cystic neoplasms
where histology genetic mutation population prognosis trx
in tail of pancreas
painless, slow growing LARGE, filled with mucin and lined by columnar mucin-producing epithelium associated with a dense stroma similar to ovarian stroma
most common gene mutation= KRAS , TP53, RNF43
women,
can be precursors to invasive carcinomas, up to a third are associated with invasive adenocarcinoma
half with invasive versions will die
surgery is curative if non-invasive- critical for early dx and trx
intraductal papillary mucinous neoplasms (IPMNs)
where histology genetic mutation population prognosis trx
mucin producing neoplasms that involve the larger ducts of the pancreas, more often in the head
- absence of ovarian stroma 2. involvement of the pancreatic duct
genes= GNAS, KRAS, TP53, SMAD4, RNF43
men
can progress to invasive CA-critical for early dx and trx
solid-pseudopapillary neoplasm
where histology genetic mutation population prognosis trx
large, well circumscribed malignant neoplasms, solid and cystic components filled with hemorrhagic debris
grow in pseudopapillary projections
mainly young women, cause abd dicomfort as they grow
always associated w hyper-activation of Wnt s/p CTNNB1 (B catenin) oncogene
trx= surgical resection- most people are cured after
pancreatic CA is synonymous with
infiltrating ductal adenocarcinoma of the pancreas
prognosis of pancreatic CA
one of the highest mortality rates of any CA
5 year survival less than 5%
invasive pancreatic CA is though to arise from well-defined noninvasive precursor lesions in ____, called ______
small ducts
pancreatic intraepithelial neoplasia
compare the three stages of progression in invasive carcinoma in the colon and the pancreas
COLON
nonneoplastic epithelium –> ademona –>invasive carcinoma
PANCREAS
nonneoplastic epithelium–> PanIN –> invasive carcinoma
sequence of genetic mutations that leads to pancreatic carcinoma
KRAS mutations
CDKN2A
TP53, SMAD4, BRCA2
sx of pancreatic CA
silent until the invade into adjacent structures
pain is the sx that brings people in, though by that time it really is too late
jaundice, anorexia, weight loss, malaise
DVT
migratory thrombophlebitis aka Trousseau sign
genetic mutations seen in pancreatic CA
KRAS = x MAPK
CDKN2A= most frequently inactivated tumor suppressor gene
SMAD4= x TGF-B
TP53
population associated with pancreatic CA
older adults, mostly 60s-80s
blacks and Ashkenazi Jews
strongest environmental influence lead
others
cigarette smoke doubles the risk
fatty diets
___ and ___ are associated with pancreatic CA, either caused by it or cause it
chronic pancreatitis
DM
genetic mutations associated with pancreatic CA
BRCA2
CDKN2A
(pancreas) while most carcinomas of the ____ of the pancreas obstruct the distal __ bile duct, carcinomas of the ___&____ do not impinge on the biliary tract and hence remain ___ for some time,
head
common
body and tail
pancreatic CA can lead to ______, also known as ______, due to elaboration of platelet-activating factors and procoagulants from the carcinoma or necrotic products
migratory thrombophlebitis
Trousseau sign
dx and trx for pancreatic CA
tests to detect: carinoembryonic Ag and CA19-9 Ag are elevated –> are nonspecific
US and CT are more specific but not useful for screening
fewer than 20% are resectable at the time of diagnosis
most have invaded vessels or metastasized by that point
