Pancreas I, Acute & Chronic Pancreatitis: Marino Flashcards
Describe the 4 ways by which enzymes of the pancreas are produced/trafficked that keep them from degrading the pancreas under normal, healthy circumstances.
1) produced as proenzymes that have to be activated once in the lumen of the duodenum
2) membrane bound while in pancreatic acinar cells
3) transported separately from lysozymes that may cause them to be activated and degrade the membranes that enclose them
4) trypsin inhibitor is present to scavenge any proteases that may accidentally become activated
Describe two intracellular derangement that may lead to pancreatitis.
1) blockage of zymogen secretion
2) co-localization of zymogen granules and lysosomes (fuse and result in activation of zymogens and degradation of vesicles that enclose them)—> autodigestion from within cell
Describe how cytokines fit into the picture of acute pancreatitis.
Proteases activate complement
- –> C3a and C5a recruit PMNs and MPGs
- –> inflammatory cells release cytokines (TNFa, IL-1, PAF, NO)
- –> vascular injury and inflammatory processes
Describe the local pathology associated with pancreatitis. (grossly)
Autodigestion of pancreas Pancreatic edema (as with any inflammatory process) Fat necrosis and hemorrhage (from destruction of BVs)
How does pancreatitis present clinically?
Pain, n/v
How do you know the pancreatitis has progressed to acute necrotizing pancreatitis?
Islets of Langerhans (aka the cockroaches of the endocrine world) begin to die off.
Describe the systemic containment response to pancreatitis.
Circulating a1-antitrypsin: inactivates circulating proteases
Circulating a-macroglobulin: binds circulating trypsin and facilitates its removal by monocytes
Describe the systemic consequences of failed containment of products of pancreatitis in the following systems: General inflammation Vascular Respiratory Metabolic
Inflammatory: TNFa, IL-6—> fever, malaise, confusion
Vascular: kallikrein activation, thrombin act., elastase, chymotrypsin—> hypoTN, DIC, hemorrhage
Respiratory: Phospholipase A2—> alveolar damage—> gas exchange probs
Metabolic: fat saponification—> hypoCa++
*DON’T FORGET SIRS—> multi-organ failure!
MCC of pancreatitis?
Gallstones (block ducts) 40% of cases EtOH abuse (constriction of sphincter of Odi, obstructed duct) 40% of cases
Using labs and a CT scanner, how would you Dx pancreatitis?
Then how would you treat it, if the cause is obstruction by stones or EtOH?
Elevated serum amylase and lipase ( >3x upper limit of normal)
Observation of pancreatic inflammation on CT
Tx: remove stones, very aggressive IV fluid replacement, pain meds, NPO
Describe how hereditary pancreatitis can be caused by mutations to the trypsinogen gene.
Name the two genes associated with hereditary pancreatitis due to:
1) persistence of trypsin’s activity
2) inability to adequately secrete bicarb
An Arg—> His mutation in the portion of trypsinogen’s gene that codes for degradation can result in difficulty inactivating trypsin in circulation, that can lead to familial pancreatitis.
PRSS1- Gain of Fxn mutations lead prevent self-inactivation of trypsin
CFTR (cystic fibrosis gene)- loss of fxn mutation in Cl- transport regulator —> limit bicarb secretion and promotes mucousy protein plugging of ducts—> pancreatitis
Describe the laboratory predictors of poor outcome in pancreatitis.
Hct remains above 44% after aggressive admin of fluids (means fluids are escaping into extravascular space, not contributing to blood volume)
Admission BUN > 25mg/dl with further increase after 24hrs of IV fluid replacement (means kidneys sense hypovolemia)
CRP >150mg/L @ 48 hrs
Define chronic pancreatitis. MCC? Symptoms? Dx? Management?
Recurrent pancreatic injury with tissue destruction and fibrosis.
MCC: EtOH abuse
Symptoms: Chronic abdominal pain, diabetes (destruction of islets- only in severe dz), steatorrhea (no lipase)
Dx: Imaging
Management: Pain meds, insulin, enzyme supplements
Describe chronic pancreatitis on histological examination.
Fibrosis
Variable dilation of pancreatic ducts
Dropout of acini
Describe pain management in chronic pancreatitis.
Pain due to any cause: narcotics (most pts)
Acute exacerbations: stop EtOH use. Pancreatic enzymes (neg. feedback to rest pancreas)
Neural inflammation: nerve blocks, splanchniectomy
Ductal HTN or pseudocyst: drainage (stent or surgery)