3/22 Disease of Pancreas - Wondisford Flashcards
acute pancreatitis
what is it?
pathogenesis/causes
2 types
symptoms
dx
caused by autodigestion of pancreas by pancreatic enzymes (edema surrounding pancreas)
- intracellular protective mechs exit to prevent trypsinogen activation/reduce trypsin activity
- synthesis of trypsin as trypsinogen (inactive)
- autolysis of activated trypsin
- synthesis of SPINK1 (specific trypsin inhibitor serine protease inhibitor Kazal type 1)
- low intracellular Ca conc
- when these mechs are overwhelmed → acute pancreas
two forms:
- interstitial (80) → usually mild, self limiting
- necrotizing → severe, can be fatal
- 70% sterile, 30% infected
why?
gallstones 50, ethanol 25, ERCP 10, drugs, hyperTG, etc
symptoms:
- severe epigastric pain (radiating to back)
- aggravated by food
- relieved by sitting up, leaning forward
- elevated lipase (more specific than amylase)
* height of peak does NOT correlate to severity - n/v, low grade fever
dx: abd ultrasound
biliary pancreatitis
pathogenesis depends on presence of common bile duct stone(s)
- more likely if LFTs also elevated (AST, ALT, Tbili)
if. .. - evidence of ascending cholangitis (rising WBC count, incr fever/LFTs)
- immediate ERCP
- gallstone pancreatitis
- consider cholecystectomy (bc risk of recurrence)
- not surgical candidates?
- consider endoscopic biliary sphincterotomy
hyperlipidemic acute pancreatisis
occurs when serum TG levels > 1000
- elevated TG falsely normalizes amylase levels
also see eruptive xanthomas
pancreas divisum
congenital variant of pancreatic duct: dorsal and ventral ducts fail to fuse
5% develop sx
genetic pancreatitis
mutations in three genes associated
-
PRSS1 → trypsinogen
- dominant mutations cause pancreatitis
-
SPINK1 → trypsin inhibitor
- lack of effective inhibition allows premature activation of trypsinogen
- CFTR → Cl channel associated with CF/thick secretions
pancreatitis severity linked to…
- age → old is worse
- alcoholic pancreatitis → incr risk of rectosis
- fast onset of sx
- obesity (risk for severe disease)
- organ failure
- hemoconcentration, incr BUN
- bc fluid leaking out due to infl
- systemic infl (organ failure)
- fat necrosis and bleeding
markers of organ failure
inc activation of trypsin → activation of Hageman factor, kallikrein, complement
- promotes vascular abnormalities
- shock (systolic bp < 90)
- pulmonary insuff (PaO2 < 60)
- renal failure (creatinine >2)
- GI bleed (over 500mL/24h
incr morbidity and mortality assoc with persistent organ failure
Cullen’s sign
Grey Turner’s sign
liberated pancreatic enzymes cause diffusion of fat necrosis and infl → discoloration
- Cullen : diffusion from retroperitoneum to umbilicus through round ligament
- Grey Turner : diffusion from retroperitoneum to subcut tissues of flanks
associated with severe acute pancreatitis (usually necrotizing) and high mortality
insterstitial vs necrotizing pancreatitis
interstitial : diffuse enlargement w homogeneous enhancement w contrast
necrotizing : pancreas swollen but most of gland non-enhancing (no perfusion)
chronic pancreattis
- alcohol (60) - compounded by cig smoking
- idiopathic (25)
- autoimmune, obstructive, genetic/hereditary, devpt
kids? CF most likely cause
clinical sx:
- recurrent epigastric pain, assoc w nerve involvement and/or dilatation of duct (early manifestation)
- steatorrhea
- DM (late manifestation)
- pancreatic calculi (dystrophic calcification in pancreatic duct) (late manifestation)
mgmt:
- strict abstinence (alc, cig)
- analgesics (opiates) for pain
- pancreatic enzyme replacement for stearorrhea (lipase; carb/protein malabs is uncommon)
- surgery
- DM management
pancreatic adenocarcinoma
basics
location
risk factors
genes involved
v aggressive tumor arising from pancreatic ducts (disorg glandular structure w cellular infiltration)
often metastatic at presentation
avg survival: 1-2y postdx
tumors in panc head (60%) → obstructive jaundice
symptoms:
- pain (90) - persisent, aching, incr by supine position/eating
- obstructive jaundice in most pancreatic head tumors (jaundice is late manifestation in body/tail tumors)
- clay colored stools (no bile in gut)
- 10+% weight loss
- glucose intol
risk factors:
- tobacco use
- chronic pancreatitis (long dur)
- DM
- age 50+
four key genes mutated/inactivated
- KRAS (75)
- tumor supp p16/CDKN2A (deleted 95%)
- p53 (inactivated 70%)
- SMAD4 (deleted 50%)
Courvoisier’s Law
distended gallbladder in pt with obstructive jaundice = likely cancer!!!
- slow distention
- less acute pain
gallstone obstr results in acute pain - doesn’t generally result in distention (bc that takes much longer)
signs indicating metastatic abd disease
VIRCHOW’S NODE
- L supraclavicular lymphadenopathy
SISTER MARY JOSEPH’S NODE
- periumbilical nodule
MIGRATORY THROMBOPHLEBITIS
- “Trousseau’s other sign”
pancreatic adenocarcinoma tx
- surgical tx is only chance for cure (but only 10% of cancers are resectable)
- palliative procedures to relieve CBD obst, pain mgmt
- chemo
- 5FU
- gemcitabine
