Pancreas 1: Acute and Chronic Pancreatitis

Question 1

Protective mechanisms to prevent self digestion:

Answer 1

• -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

Question 2

What stimulates release of zymogen from acinar cell?

Answer 2

VIP (neural, cAMP)
secretin (intestines, cAMP)
ACh (vagus, Ca++)
CCK (intestines, Ca++)

Question 3

earliest event in the pathogenesis of acute pancreatitis

Answer 3

conversion of pancreatic zymogens to their active forms within the acinar cell

Question 4

Mechanisms of pancreatic injury?

Answer 4

1. blockage of secretions

2. co-localization of ZG + lysosomes, which leads to premature ZG activation and autodigestion

Question 5

How do cytokines cause acute pancreatitis?

Answer 5

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

Question 6

Local effects of acute pancreatic injurt

Answer 6

1. Autodigestion of the pancreas
2. Pancreatic swelling (edema)
3. Fat necrosis and hemorrhage

Question 7

Clinical manifestations of acute pancreatitis?

Answer 7

abd pain (radiating to back)

NV

Question 8

Histopath of acute pancreatitis?

Answer 8

coagulative necrosis (with ghost cells) + hemorrhage + degenerating polys

fat necrosis between lobules

Question 9

Gross pathology of acute pancreatitis?

Answer 9

fat necrosis between lobules

Severe acute hemorrhage

Question 10

What is the function of circulating a1-antitrypsin?

Answer 10

inactivates circulating proteases

Question 11

What is the function of circulating a-macroglobulin?

Answer 11

binds to circulating trypsin

facilitates monocyte clearance of macroglobulin-trypsin complexes

Question 12

Severe Pancreatitis:

Fat saponification causes what clinical correlate?

Answer 12

hypocalcemia

Question 13

Severe Pancreatitis:

phospholipase A2 causes what clinical correlate?

Answer 13

hypoxemia

Question 14

Severe Pancreatitis:

kallikrein activation causes what clinical correlate?

Answer 14

hypotension

Question 15

Severe Pancreatitis:

thrombin activation causes what clinical correlate?

Answer 15

DIC, hemorrhage

Question 16

Severe Pancreatitis:

elastase + chymotrypsin cause what clinical correlate?

Answer 16

hemorrhage

Question 17

Severe Pancreatitis:

TNF-alpha and IL-6 activation cause what clinical correlate?

Answer 17

fever
malaise
confusion

Question 18

Acute Pancreatitis:

Main causes?

Answer 18

Gallstones and alcohol

Question 19

Acute Pancreatitis:

Main symptoms?

Answer 19

abd pain, NV

Question 20

Acute Pancreatitis:

Diagnosis?

Answer 20

elevated serum amylase and lipase

inflamed pancreas on CT

Question 21

Acute Pancreatitis:

Trx?

Answer 21

VERY AGGRESIVE IV fluids

pain meds

remove stones if causitive

abx if biliary

NPO

Question 22

What causes hereditary pancreatitis?

Answer 22

Trypsinogen Mutation, which prevents its degradation

Question 23

Diagnostic criteria for acute pancreatitis?

Answer 23

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

Question 24

Factors Suggesting Gallstone Etiology?

Answer 24

1. Age > 50
2. amylase >4000 IU/L
3. Female
4. AST >100 U/L
5. alk. phos. >300 IU/L

Question 25

Pancreatitis: | Predictors of Poor Outcome?

Answer 25

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)

Question 26

Which has a better prognosis: Interstitial Pancreatitis or Necrotizing Pancreatitis?

Answer 26

interstitial! Necrotizing Pancreatitis has a multi-organ failure rate of 50%, infection rate 15-20%, mortality 17%

Question 27

Complications of Acute Pancreatitis

Answer 27

Fluid collections Pseudocysts Fistulas (ascites, pleural effusions) Splenic vein thrombosis

Question 28

Chronic Pancreatitis: | Pathophysiology?

Answer 28

recurrent injury with tissue destruction and fibrosis

Question 29

Chronic Pancreatitis: | Cause?

Answer 29

chronic alcohol (80%)

Question 30

Chronic Pancreatitis: | Symptoms?

Answer 30

chronic abdominal pain, diabetes, steatorrhea

Question 31

Chronic Pancreatitis:Dx?

Answer 31

Imaging studies

Question 32

Chronic Pancreatitis: | Management?

Answer 32

Pain medications, insulin, enzyme supplements

Question 33

Chronic Pancreatitis: Pathophysiology, chr ETOH Ingestion

Answer 33

--> abn secretion --> protein plugs and ductal obst --> calcification, pain --> recurrent bouts of pancreatitis --> stellate cell activation --> fibrosis --> pain + cell death (which causes malabs DM)

Question 34

Chronic Pancreatitis: Pathophysiology, Genetic Abn

Answer 34

--> recurrent bouts of pancreatitis --> stellate cell activation --> fibrosis --> pain + cell death (which causes malabs DM)

Question 35

Chronic Pancreatitis: | Histopath?

Answer 35

``` lymphocytes acini = gone ducts still present (empty) residual necrotic debris early fibrosis prolif/dysplasia of epith around duct ```

Question 36

Chronic pancreatitis: end-stage | Histopath?

Answer 36

replacement of exocrine acini and ducts by fibroadipose tissue, but with preservation of islets of Langerhans (because they don't autodigest)

Question 37

Chronic Pancreatitis: | Clinical Presentation

Answer 37

Chronic abdominal pain Malabsorption (steatorrhea) Diabetes **Malabsorption + DM = advanced stages

Question 38

Causes of Pain in Chronic Pancreatitis:

Answer 38

- -Increased pressure from fibrosis - -Pseudocysts trying to expand against fibrotic area - -Neural Inflammation

Question 39

Pain Management in CP: | Any cause?

Answer 39

Narcotics

Question 40

Pain Management in CP: | Acute exacerbations?

Answer 40

abstinence | enzymes

Question 41

Pain Management in CP: | Neural inflammation?

Answer 41

nerve block splanchniectomy

Question 42

Pain Management in CP: | Ductal hypertension?

Answer 42

drainage (stent or surgery)

Question 43

Pain Management in CP: | Pseudocyst pressure?

Answer 43

drainage (stent or surgery)

Question 44

Steatorrhea in CP: | Cause?

Answer 44

lipase deficiency = fat malabsorption

Question 45

Steatorrhea in CP: | Trx?

Answer 45

1. reduce dietary fat intake 2. oral enzyme supplementation 3. acid suppression therapy (for effectiveness of oral enzymes)

Question 46

Diabetes in CP: | Cause?

Answer 46

Only seen in severe disease with 80% destruction of pancreas: Loss of both insulin and glucagon

Question 47

Diabetes in CP: | Is this easy to manage?

Answer 47

no--Loss of both insulin and glucagon = brittle but low insulin requirements, and DKA is rare