Pancreas Path/Pathophys I Flashcards
What are the four protective mechanisms of the acinar cell that prevent autodigestion?
Inactive proenzymes
membrane enclosed
Separate pathways
Trypsin inhibitor
What stimuli act through cAMP on the acinar cell?
VIP, Secretin
What stimuli act through Ca2+ signaling on the acinar cell?
ACh
CCK
What is the earliest event in the pathogenesis of acute pancreatitis?
Conversion of zymogens to active forms within the acinar cells
What are the two mechanisms of injury in acute pancreatitis?
Block secretion and/or co-localization of ZG and lysosomes
Explain the pathogenesis of cytokines/inflammation and acute pancreatitis
- Proteases activate complement
- C3a and C5a recruit PMNs and macros
- Inflammatory cells release cytokines (TNF, etc)
- Vascular injury and inflammation
What are the ‘local effects’ of acute pancreatitis?
Autodigestion
Pancreatic edema
Fat necrosis and hemorrhage
Produces pain, nausea, vomiting
What kind of necrosis does acute pancreatitis cause?
Fat AND coagulative
What are some microscopic pathology findings in acute pancreatitis?
Fat necrosis between lobules
hemorrhage
coagulative necrosis
What mechanisms does the body have to contain pancreatitis?
Circulating alpha-antitrypsin
(inactivates proteases)
Circulating alpha macroglobulin
(binds trypsin and facilitates monocyte clearance)
What substance is responsible for fever, malaise, and confusion in severe pancreatitis?
TNF-alpha, IL-6
What are some vascular pathological mediators of severe pancreatitis?
kallikrein >hypotension
thrombin > DIC, hemorrhage
elastase > hemorrhage
chymotrypsin > hemorrhage
Explain the respiratory pathogenesis of acute pancreatitis?
PLA2 causes hypoxemia
Explain why acute pancreatitis causes hypocalcemia
Fat saponification of calcium and lipids depletes plasma levels
What are the main causes of acute pancreatitis?
Gallstones
Alcohol
How do you diagnose acute pancreatitis (methods)?
Elevated serum amylase
Elevated lipase
Inflammed pancreas on CT
What is the cause of hereditary pancreatitis?
Trypsinogen mutation
Diagnostic criteria for acute pancreatitis?
2/3 of:
-Abdominal pain, N, V
-Elevated amylase and lipase > 3x normal
Ct imaging showing inflammation
What are some risk factors for gallstones?
Age > 50 Female High amylase High AST High Alk Phos
What is involved in the supportive management of acute pancreatitis?
NPO Very aggressive fluids Pain relief Nutrition Antibiotics if biliary
What are some predictors of poor outcome in acute pancreatitis?
Admit w/ HCT > 44% w fail to dec in 24h
Admit w/ BUN > 25 w inc after 24h fluids
What is the cause of chronic pancreatitis?
Chronic alcoholism (also CF)
What are S/S of chronic pancreatitis?
Chronic abdominal pain
Diabetes
Steatorrhea
Chronic pancreatitis pathophysiology
Chronic alcohol ingestion leads to abnormal secretions that cause protein plugs and ductal obstruction. This leads to calcification, recurrent acute episodes, and pain. Recurrent episodes cause stellate cell activation leading to fibrosis and further pain. The fibrosis and recurrent pancreas injury together cause cell death, leading to malabsorption and diabetes.
Elevated liver enzymes and dilated common bile duct suggest this cause of acute pancreatitis?
gallstones
Describe the chronic pancreatitis pathology
End-stage replacement of exocrine acini and ducts with fibroadipose tissue, BUT preservation of islets of Langerhans (because not digesting themselves)
What is the first type of malabsorption to begin in CP?
Fat before protein or carbohydrate
Due to lipase deficiency
Describe diabetes in CP
Only in severe disease (>80% destruction)
Loss of BOTH insulin and glucagon makes difficult to control
Low insulin requirements
Ketoacidosis is rare
