Pancreatitis Flashcards
Explain the Secretin Feedback Pathway in the pancreas
Gastric acid produced upon eating a meal –> enters duodenum –> stimulates duodenal enteroendocrine cells to produce secretin –> secretin binds to receptors on intercalated ducts –> release water and bicarbonate –> increases pH (neutralizing gastric acid, keeping trypsinogen from activating and closing loop)
Explain CCK Feedback Pathway in the pancreas
Protein meal causes release of proteins that have competitive reduction on proteolytic enzymes in lumen –> more CCK is released from duodenum –> CCK binds to receptors on acinar cells to release digestive proenzymes –> enter the lumen and increase activity of enzyes (closing loop)
What enzyme activates trypsinogen to trypsin? Where is this enzyme found?
Enterokinase in brush border of enterocytes in duodenum
Acute pancreatitis results from…
auto-digestion
What are the 5 models discussed for pathogenesis of acute pancreatitis?
Secretagogue Hyperstimulation
Duct Obstruction and Bile Acid
Basic Amino Acids
Diet Induced
Immune-Mediated
Explain how Secretagogue Hyperstimulation can cause acute pancreatitis
Basically, too much cholinergic stimulation can lead to very high concentrations of CCK –> damage and proenzyme release from acinar cells
What is Caerulein?
A CCK analogue used in mouse models to induce pancreatitis (supports secretagogue hyperstimulation pathway)
Can scorpion venom cause acute pancreatitis?
Yes. Stimulates excessive release of Ach (supports secretagogue hyperstimulation pathway)
Explain how duct obstruction and bile acid causes acute pancreatitis
Pancreatic obstruction alone is sufficient to cause pancreatitis
- leads to release of calcium from stores (activate trypsin)
- activates zymogens
What diet deficiency can cause acute pancreatitis? How does this deficiency do this?
Choline deficient diet with ethionine
Disrupts stimulus-secretion coupling in acinar cells –> activation of proteases
Has been shown to cause more severe acute pancreatitis than secretagogues
What are the two types of autoimmune pancreatitis and what differentiates them?
Type 1 (classic AIP) - no neutrophils and abundant IgG
Type 2 (IDCP) - neutrophils and granulocytic epithelial lesions
What is the pathogenesis of acute autoimmune pancreatitis?
Acinar cells respond to initial insult by activating transcription factors –> production of cytokines that initiate inflammatory response –> inflammation also mediated by DAMPs from damaged or dying cells, which activate inflammasomes –> inflammation recruits neutrophils, macrophages and T cells –> cytokine storm and systemic inflammation
What are the key histological features of chronic pancreatitis?
Fibrosis, calcifications, inflammation
What are the mutations of hereditary chronic pancreatitis? What do they do?
Mutation in PRSS1 on chromosome 7
Mutations on R122H and N291 make the trypsin molecule hyperactive (even when calcium ins’t bound, the trypsin remains “on’)
Can cystic fibrosis lead to chronic pancreatitis?
Apparently yes, but he didn’t explain it at all
