Pancreas I, Acute & Chronic Pancreatitis: Marino

Question 1

Describe the 4 ways by which enzymes of the pancreas are produced/trafficked that keep them from degrading the pancreas under normal, healthy circumstances.

Answer 1

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

Question 2

Describe two intracellular derangement that may lead to pancreatitis.

Answer 2

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

Question 3

Describe how cytokines fit into the picture of acute pancreatitis.

Answer 3

Proteases activate complement

• –> C3a and C5a recruit PMNs and MPGs
• –> inflammatory cells release cytokines (TNFa, IL-1, PAF, NO)
• –> vascular injury and inflammatory processes

Question 4

Describe the local pathology associated with pancreatitis. (grossly)

Answer 4

Autodigestion of pancreas
Pancreatic edema (as with any inflammatory process)
Fat necrosis and hemorrhage (from destruction of BVs)

Question 5

How does pancreatitis present clinically?

Answer 5

Pain, n/v

Question 6

How do you know the pancreatitis has progressed to acute necrotizing pancreatitis?

Answer 6

Islets of Langerhans (aka the cockroaches of the endocrine world) begin to die off.

Question 7

Describe the systemic containment response to pancreatitis.

Answer 7

Circulating a1-antitrypsin: inactivates circulating proteases

Circulating a-macroglobulin: binds circulating trypsin and facilitates its removal by monocytes

Question 8

Describe the systemic consequences of failed containment of products of pancreatitis in the following systems:
General inflammation
Vascular
Respiratory
Metabolic

Answer 8

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!

Question 9

MCC of pancreatitis?

Answer 9

Gallstones (block ducts) 40% of cases
EtOH abuse (constriction of sphincter of Odi, obstructed duct) 40% of cases

Question 10

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?

Answer 10

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

Question 11

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

Answer 11

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

Question 12

Describe the laboratory predictors of poor outcome in pancreatitis.

Answer 12

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

Question 13

Define chronic pancreatitis.
MCC?
Symptoms?
Dx?
Management?

Answer 13

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

Question 14

Describe chronic pancreatitis on histological examination.

Answer 14

Fibrosis
Variable dilation of pancreatic ducts
Dropout of acini

Question 15

Describe pain management in chronic pancreatitis.

Answer 15

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)

Question 16

How do we tx steatorrhea of chronic pancreatitis?

Answer 16

Reduce oral fat intake
Enzyme (lipase) supplement
acid suppression therapy (keeps secreted lipases active)