acute and chronic pancereatitis (pathology) Flashcards
pancreas parenchima
80% exocrine
1-2% langrhans islands, endcrine
exocrine cells
acinic cells
proenzymes: trypsinogen + chymotrypsinogen
active enzemys: amylase+ lipase
ductular (small ducts) cells: bicarbonate 2-7mm
ductal (large ducts) cells: mucin
exocrine self digestion defense mechanism
proenzymes
zymogenic granular secrition
entrokinase dependant activation
chymotryapsinogen activator?
tyrapsin
trypsinogen activator?
entrokinase in brush border
trypsin (high ca+2)
trypsin inhibition?
acinar and ductal secretions: serine protease inhibitor kazal type 1 (SPINK1)
auto self inhibition of trypsin (low ca+2)
acute pancreatitis etiology
metabolic: alchohol, drugs, hyperlipoproteinemia
mechanical:
obstructions- gallstones,tumors
injuries- endoscopic
vascular- shock, emboli
infections- mumps, m.pneumoniae
idiopathic
genetic etiology of acute pancreatitis
cationic trypsinogen (serine protease 1 PRSS1, 7q35)
GOF- self inactivation cleavage site germline mutation
AD 0.8 penetrance
CFTR (7q31)
LOF
duct obstruction
SPINK1
GOF
AR
etiology of acute pancreatitis
30-60% due to gall stones
alcholism
acute pancreatitis - duct obstruction pathopysiology
obstruction interstitial edema impaired blood flow ischemia acinar cell injury activation of enzymes
acute pancreatitis -defective intracellular transport pathopisiology (not prooven yet)
transport of pancreatic proenzymes to lysosome
activation of enzymes
alchol (usually chronic) induced acute pancreatitis pathopysiology
contraction of spinchter of oddi-obstruction
higher exocrine viscosity- obstruction
free radicals -> ca+2 is up -> self activation of trypsin
acute pancreatitis morphology
microvascular leakage -edema
necrosis of fat (lypase and amylase endocrinic dissemination) ->
saponification- ca+2 + phospholipds addhition
destruction of BV- hemmorage
chronic pancreatitis 2 types
calcific / obstructive
autoimmune
calcific / obstructive chronic pancreatitis definition
chronic inflammation with irreversible changes in structure which lead to 100% loss of exocrine activity
calcific / obstructive chronic pancreatitis etiology
long standing obstruction
chronic alchoholism 10-20
smoking (strongest advansor of acute to chronic pancreatitis)
calcific / obstructive chronic pancreatitis chimokins
IL 8
TGFb
PDGF
all proliferate myofibroblasts -> collagen deposition and fibrosis
calcific / obstructive chronic pancreatitis morphology
fibrosis and chronic inflammation infiltrations
acini atrophy
relative sparing of endocrin pancease
dialition of ducts
PRSS1 heredetary pancreatitis morphology
lipomatous atrophy
autoimmune chronic pancreatitis types
type 1-
elevated IGg4
infiltration by IGg4 plasma cells (peri-ductal!)
obliterative phlebitis- narrowing venuls due to inflammation and fibrosis
no calcification in ducts
type 2-
neutrophilic epithelial infiltration (granulocytic epithelial lessions)
both exocrine and endocrine disfunction
autoimmune chronic pancreatitis treatment
prominant recover after oral steroids
pancreatic pseudocyst
necrotic hemorrhagic material rich in p.enzymes
solitary
no epithel - “pseudo”
pancreatic pseudocyst locations
in pancease
peripancreatic tissue
lesser omental sac
retroperitoneal
pancreatic neoplasms
endocrine
exocrine
solid
cyctic
pancreatic cyctic neoplasms
solid pseudopapillary tumor
serous cyst neoplasm
mucinous cytic neoplasms
intraductal papillary mucinuos neoplasms (IPMN)
solid pseudopapillary tumor epidimeology
young females
childhood
solid pseudopapillary tumor morpholgy
large (abdominal discomffort)
resective
mostly bening
solid pseudopapillary tumor etiology
CTNNB1
serous cyst neoplasm epidemiology
M:F 2:1
60’s
serous cyst neoplasm favored lacation
2/3 in body tail region
serous cyst neoplasm morphology
many tightly packed small thin walled cyts (da!) honecomb appearance
serous cyst neoplasm etiology
von hipple-lindau gene mutes 40% of cases
IPMN epidemiology
M3:F2
60’s
IPMN morphology
main pancreatic duct of branches , mostly in head
dialition of ducts (grossl visible)
papillary intraductal mucin producing epithelial tumors (adenoma to cacinoma insitu)
IPMN etiology
Petz-heghers
familial adenomatous polyposis syndromes
1/3 with history of malignancy (aspecialy gastric or colonic)
GNAS, 80%, 20q13, alfa stimulatory G protein subunit GOF
KRAS @ RNF43
TP53 @ SMAD4 when invasive
mucinous cytic neoplasms epidemiology
females
perimenopausal
mucinous cytic neoplasms favord location
tail
body
mucinous cytic neoplasms etiology
RNF43
KRAS
TP53
pancreatic ductal carcinoma epidemiology
mostly elderly (60's >80%) 5yr survival <5% familial clusters (10% of cases)
pancreatic ductal carcinoma causes (risks)
smoking
chronic pancreatitis
heredetary pancreatitis (40% life time risk)
obesity and diabetes
pancreatic ductal carcinoma familial clusters etiology
HNPCC (lynch syndrome) BRCA2, PALB2 (breast and ovary cancer) Peutz-jegher li fraumeni (p53) CDKN2A
pancreatic ductal carcinogenesis precursor lessions
IPMN
Mucinous cystic neoplasms
pancreatic intraepithelial neoplasias (PanIN)-90%!
pancreatic ductal carcinoma mulecular alternations
kras 90% oncogene
cdkn2a 30%
smad4 55% supressor
p53 60% supressor
