Flashcards in Pancreas 1: Acute and Chronic Pancreatitis Deck (47)
Protective mechanisms to prevent self digestion:
--production of enzyme in inactive form
--enclosed within membrane to protect against low levels of activated enzyme
--activated enzyme not co-localized with pro-enzyme
What stimulates release of zymogen from acinar cell?
VIP (neural, cAMP)
secretin (intestines, cAMP)
ACh (vagus, Ca++)
CCK (intestines, Ca++)
earliest event in the pathogenesis of acute pancreatitis
conversion of pancreatic zymogens to their active forms within the acinar cell
Mechanisms of pancreatic injury?
1. blockage of secretions
2. co-localization of ZG + lysosomes, which leads to premature ZG activation and autodigestion
How do cytokines cause acute pancreatitis?
1. Proteases activate complement
2. C3a and C5a recruit PMNs and macrophages
3. Inflammatory cells release cytokines (TNF-a, IL-1, PAF, and nitric oxide)
=Vascular injury and inflammatory responses
Local effects of acute pancreatic injurt
1. Autodigestion of the pancreas
2. Pancreatic swelling (edema)
3. Fat necrosis and hemorrhage
Clinical manifestations of acute pancreatitis?
abd pain (radiating to back)
Histopath of acute pancreatitis?
coagulative necrosis (with ghost cells) + hemorrhage + degenerating polys
fat necrosis between lobules
Gross pathology of acute pancreatitis?
fat necrosis between lobules
Severe acute hemorrhage
What is the function of circulating a1-antitrypsin?
inactivates circulating proteases
What is the function of circulating a-macroglobulin?
binds to circulating trypsin
facilitates monocyte clearance of macroglobulin-trypsin complexes
Fat saponification causes what clinical correlate?
phospholipase A2 causes what clinical correlate?
kallikrein activation causes what clinical correlate?
thrombin activation causes what clinical correlate?
elastase + chymotrypsin cause what clinical correlate?
TNF-alpha and IL-6 activation cause what clinical correlate?
Gallstones and alcohol
abd pain, NV
elevated serum amylase and lipase
inflamed pancreas on CT
VERY AGGRESIVE IV fluids
remove stones if causitive
abx if biliary
What causes hereditary pancreatitis?
Trypsinogen Mutation, which prevents its degradation
Diagnostic criteria for acute pancreatitis?
Two of the following Three:
1. abdominal pain, nausea/vomiting
2. elevated serum amylase and lipase more than 3x upper limit of normal
3. CT imaging showing pancreatic inflammation
Factors Suggesting Gallstone Etiology?
1. Age > 50
2. amylase >4000 IU/L
4. AST >100 U/L
5. alk. phos. >300 IU/L
Predictors of Poor Outcome?
Admission hct >44% with failure to decr after 24h of IV fluids.
Admission BUN > 25 mg/dl with an incr after 24h of IV fluids.
(hct incr due to loss of plasma w/ retention of RBC)
Which has a better prognosis: Interstitial Pancreatitis or Necrotizing Pancreatitis?
Necrotizing Pancreatitis has a multi-organ failure rate of 50%, infection rate 15-20%, mortality 17%
Complications of Acute Pancreatitis
Fistulas (ascites, pleural effusions)
Splenic vein thrombosis
recurrent injury with tissue destruction and fibrosis
chronic alcohol (80%)