Pancreatic Diseases Flashcards
what hormone stimulates release of pancreatic enzymes
gastrin
what pancreatic enzymes do not require trypsin activation
amylase & lipase
small ducts secrete…….. and large ducts secret……….
bicarbonate; mucin
what protease inhibitor is secreted by pancreatic acinar & ductal cells to inhibit intrapancreatic trypsin activity
SPINK1
what parts of the pancreas are derived from the dorsal primordium
body; tail; anterior head; accessory duct
what parts of the pancrease are derived from the ventral promordium
posterior head; main pancreatic duct
what is the pathogenesis of pancreas divisum
failure of foregut duct systems of dorsal & ventral primordia to fuse
describe the malformation of annular pancreas
ventral pancreatic bud wraps around duodenum adhering to the duodenum but before rotation begins; that results in narrowing of the duodenum
For pancreas divisum, what duct secretes most of the enzymes and why
main pancreatic duct is significantly shortened making the accessory duct the primary secreter
what are the physiological consequences of a pancreas divisum
most pts. are asymptomatic but does increase risk of chronic pancreatitis due to chronic backpressure and relative outflow obstruction
what are the physiological consequences of an annular pancreas
GI obstructive symptoms most commonly vomiting
what is an ectopic pancreas
normal appearing pancreatic glands & ducts as sites outside the pancreas
what are the 2 main causes of acute pancreatitis in the US
alcoholism & biliary tract diseases
what are the proposed mechanisms for alcohol-induced pancreatitis
transient contraction of sphincter of Oddi and oxidative stress leading to local inflammation
increased IC Ca promotes release and activation of trypsin and other digestive enzymes
chronic alcohol consumption leads to what physioligcal outcome in the pancreas
secretion of protein-rich pancreatic fluid may form protein plugs leading to obstruction of small pancreatic ducts
hereditary pancreatitis typically presents in which decade of life
within the 1st two
what are the main genetic mutations assoc. w/ hereditary pancreatitis
Gain of function to Cationic trypsinogen gene resulting in a more resistant trypsinogen isotype to trypsin inhibitors
inactivating mutations of SPINK1 leaving trypsin activity unregulated
CFTR mutations decrease bicarb secretion in pancreatic duct cells
what are secondary complications that can arrise from hereditary pancreatitis
PRSS1: results in a more resilient trypsinogen to inactivating mechanisms; long-term complications: pancreatic adenocarcinoma
CFTR: long term complications are duct obstruction b/c of decreased bicaronbate excretion leading to protein plugging
SPINK1: inhibits trypsin activity
describe the histopahtology of acute pancreatitis
fat necrosis of peripancreatic fat
liquefactive hemorrhagic necrosis
inflammatory neutrophil infiltration
edema
describe the histopahtology of fat necrosis
hypocalcemia due to dystrophic calcification and saponification to form insoulble calcium soaps
What pancreatic enzyme would you expect to find elevated within the first 24 hrs. of acute pancreatitis symptoms
amylase
what pancreatic enzyme would you find elevated within 72-96 hrs. of onset acute pancreatitis
lipase
accumulation of lipase leads to what physiologic consequence
hypocalcemia due to precipitation of calcium fat salts
what is cullen sign
purple-blue periumbilical and flank discoloration
what is Gray-Turner sign
retroperitoneal hemorrhage through through fascial skin layers
what extrapacreatic manifestations would you expect to see with acute pancreatitis
ascending cholangitis leading to sepsis
renal failure (aqotemia) and acute tubular necrosis; ARDS; Ileus
what histolical findings would you expect within the 1st 4 weeks of acute pancreatitis
peripancreatic homogenous fluid collection w/o discernable borders
accute hetrogenous necrotic fluid collection
what histoligical findgins would you expect to see after 4 wks of AP onset
Pseudocyst: well circumscribed grandular abdominal mass hemogenous in nature
wall off necrosis: encapsulated collection of heterogenous fluid
List the sequelae for acute pancreatitis
pancreatic abscesses, pseduocytsts, duodenal obstruction
what is the most common cause of chronic pancreatitis
long-term alcohol abuse
what factors predominate in chronic pancreatitis
fibrogenic: TGF beta & PDFG
describe the mechanism for aalcholo inducted increases Ca activity
pancreatic hypixia and oxidative damage increases total pancreatic protein activation forming calcified plugs which prevents excretion of enzymes and subsequently resulting in autodigestion of parenchyma
pancreatic stellate cells have the same functions of hepatic stellate cells. chronic pancreatitis = ?
cirrhosis of the pancrease
describe the hisotlogical characterisitcs of CP
Acinar hypoplasia & atrophy
fusion of dilated pancreatic ducts embedded in sclerotic tissue
squamous metaplasia of ductal epithelium
Islets of langerhans spared
how do opiates contribute to pancreatitis
increases tone of sphincter of oddi
what are lower GI complications of CP
steatorrhea & diarrhea
Vit. K. def
Vit. D. def
DM (very late stage)
amylase & lipase serum levels are normal in pts. w/ chronic pancreatits. what lab test can be ordered instead
fectal elastase
low in CP
what a classic CT indications of CP
pancreatic calcifications in a “chain of lake pattern”; gladular atrophy and dilaton of the pancreatic ducts
what is the pathogenesis of type 1 autoimmune CP
IgG4 secreting plasma cells cause dense lymphoplasmacytic inflammation
describe the pathogenesis of type 2 autoimmune CP
neutrophilic inflitrates
lymphoplasmacytic infiltrates also seen but no IgG4-secreting plasma cells are seen
what is also assoc. w/ type 1 AI CP
phlebitis
review the following
slide 38 on pancreasePath ppt
describe the hitological findings of pancreatic pseudocysts
pseudocyst: NO EPITHERLIAL LINING
hemorrhagic fat necrosis w/ notable fibrosis & granulation tissue
rich in pancreatic enzymes
suspect a pseudocyst in pts. with all the clinical presentations of acute pancreatic in addition to having a h/o what?
abdominal trauma or persistent abdominal pain w/ a palpable epigastric mass
OR
if acute pancreatitis persists beyond 6 wks. of onset
serous cystadeomas are commonly found in which part of the pancreas
tail
tail
tail
what are the epidemiological factors assoc. w/ cystademonas
twice as common in women; onset avearge in 7th decade
what mutation is the most commonly assoc. w/ serous cystadenomas
inactivation of VHL tumor supressor gene on ch. 3
describe the histologic characteristics of serous cystademonmas
glycogen rish cuboidal cells surrounding small cysts
what are epidemi. factors of mucinous cystic neoplams
almost exculsivley in females
what is the most common sporatic mutaion assoc. w/ mucinous nps
KRAS
what are the histological characteristics of mucinous cystic nep
columnar mucin-producing epithelium lining cysts
dense stroma similar to ovarian stroma
what hormones would you expect to be upregulated for pts. w/ mucinous cystic nep
estrogen
progesterone
inhibin
review the following slide
pacnreas path. ppt slide 48
mucinous cystic neoplasia typically occurins in what part of the pancrease
body
Is PIMNs more common in men or women
men
80% of IPMNs are assoc. w/ sporatic KRAS mutations; what additional mutations occur when the neoplasm transitions to invasive cancer
TP53, GNAS, & SMAD4
solid-pseuopapillary tumors are commonly seen in which pt. population
adolescent girls and young women
what mutation is assoc. w/ solid pseudopapillary tumors
activatoin mutations of CTNNB1 (beta-catenin)
most pts. w/ solid-pseudopapillary tumors expreifecne pain why
these tumors are massive
85% of pancreatic adenocarcinomas are derived from what cells
ductal epitehlium
what is the main malignant precursor for adenocarcinoma
PanINs
what are epidemilogical factors of pancreatic carcinoma
increasesd prevelance:
African & japanese americans
native hawaiians
ashkenazi jews
smoking doubles risk
other comorbidies:
metabolic syndrome & chronic pancreatitis
review this slide
parncreaepath ppt. slide 56
describe the gross features of pancreas adenocarcinoma
hard, stellate, grey-whit mass w/ poorly defined borders
pancreatic carcinomas located in the head are more likely to present with this symptoms
head
obstruction of distal common bile duct
develop jaundice
why are cancers of the body & tail not assoc. w/ jaundice
these do not impinge on the biliary tract
what is trousseau sign
superficial migratory thrombophlebitis
what is Courvoiser’s sign
RUQ mass; enlarged palpable gallbladder in pts. w/ obstructive jaundice
what tumor maker can be used to monitor progression of pancreatic carcinomas
CEA & carbohydrate antigen 19-9
what pancreatic neoplasm is almost exculeivly diagnosed in ped. pts.
pancreatoblastoma
distinck squamous islands admixed w/ undifferentiated cells
