02-20 PATH: Pancreatitis

Question 1

Clinical vs. Path Categorization of Pancreatitis

Answer 1

Path much simpler:

• Acute (two types)
  
  1. mild
  2. severe
• Chronic
  
  • many causes, but basically one pathologic picture

Question 2

Clinical and Pathological Presentation of Acute Pancreatitis?

Answer 2

The clinician sees:

• a patient with abdominal pain and high serum amylase and/or lipase

The pathologist sees:

• acute inflammation in the pancreas, often with necrosis, that is either mild or severe

Question 3

Mild Pancreatitis

• Histo
• Clinical Course

Answer 3

Pathology (See image here)

– Edema with inflammatory infiltrate.

– Minimal or no parenchymal or fat necrosis (thus sometimes called “interstitial pancreatitis”)

Course

– Pathologic changes are fully reversible if transient

– But if persistant, it may progress to chronic pancreatitis

Question 4

Severe Acute Pancreatitis

• A.K.A.
• Histo
• Course

Answer 4

A.K.A.

• necrotizing pancreatitis
• hemorrhagic pancreatitis

Pathology

• Necrosis and inflammation (often already cleared by time of bx, but image here is early on)
  
  • Acinar tissue > ducts > islets
  • Fat necrosis (can be in surroundings)
• Grossly: nodular, discolored, charred looking when hemorrhagic, fat necrosis in surrounding tissue, pseudocyst

Course: Depends on severity

• Focal → focal scar
• Multifocal→ patchy scarring→ chronic pancreatitis
• Extensive→ systemic inflam response, death, or complications:
  
  • pseudocyst, abscess

Question 5

What is a pseudocyst?

Answer 5

A pseudocyst is a walled-off collection of fluid or liquified tissue within or adjacent to pancreas in acute pancreatitis.

• wall may include adjacent organs such as stomach, small intestine, colon, or spleen, and becomes progressively fibrotic.
• Can become infected from intestinal bacteria and form abscess (implies liquifed tissue)

Image here: old pseudocyst wall (nl pancratitic tissue on L; note hemosidderin-laden M0s

Question 6

Chronic Pancreatitis

• Pathology
• Course

Note gross image here: normal tissue is more lobular vs. the smooth tissue on upper/left side which is fibrosis

Answer 6

Histo

• Lymphocytic infiltrate + atrophy/fibrosis (see image here)
• May see pseudocysts in cases of acute pancreatitis that became chronic

Course

• – If progressive so that there is extensive fibrosis and atrophy:
  
  • Exocrine insufficiency
  • Diabetes (late, islets preserved ‘til end)
• ↑ risk of panc. carcinoma
  
  • 14X for all CP patients
  • 50X for hereditary CP patients.

Question 7

What are the two mechanisms by which acute pancreatitis develops?

Answer 7

Pathogenesis is either:

1. Injury of acinar cells
   
   • Inappropriate basolateral seceretion + Intracellular/interstitial activation of pancreatic enzymes (esp trypsin)
     
     • Usu. leak is in an intralobular ductule b/c small, no collagen in wall
   • Lipase begins fat necrosis
   • Leads to autodigestion and inflammation
   • Causes even more cells to leak
2. Duct obstruction with increased intraductal pressure
   
   • Obstruction occurs
     
     • stone
     • CF
     • intraductal papillary-mucinous neoplasms
     • external compression
     • parasites
   • Interstitial leakage and activation of pancreatic enzymes
   • Mild, moderate or severe acute pancreatitis
   • Persistent mild or recurrent acute can progress to chronic

Question 8

What are the two main causes of pancreatitis in the U.S.? Can you list 3 others?

Answer 8

In the U.S.

• EtOH by far most commone
• gallstones 2nd

Others

• viral
• drug toxicity
• hereditary
• traumatic
• auto-immune

Question 9

Chronic Pancreatitis Pathogenesis

Answer 9

Caused by persistent or recurring inflammation in the pancreas

Major players include

• Alcoholism (~65%)
• Hereditary pancreatitis
• Duct obstruction

Current hypothesis: Necrosis-fibrosis hypothesis

• Repeated acute episodes → Focal necrosis → Patchy scarring → Duct distortion
• Never get back to baseline (see image)

Question 10

Hereditary Familial Pancreatitis

• Pathogenesis?
• Inheritance pattern?
• Risk of developing cancer if you have?

Answer 10

Pathogenesis

• Mutant cationic trypsinogen gene (PRSS1) either:
  
  • HP1 R117H mutation (85%)
  • HP2 N21I mutation
• Eliminates a “fail-safe” trypsin self-destruction site

Inheritance

• Autosomal dominant pattern w/ high penetrance

Cumulative incidence of pancreatic carcinoma:

• 40% by 70 y/o

Question 11

Autoimmune Pancreatitis

Answer 11

• historically there has been some debate about whether it’s real, but evidence includes
  
  • steroids work
  • assoc’d with other IgG4 auto-immune dz:
  • Type 1 AIP (60%): sialadenitis, sclerosing cholangitis, retroperitoneal fibrosis, GN, pneumonitis
  • Type 2 AIP (40%): IBD
• can be Tx w/ pred
• often mis-diagnosed causing unncessary pancreatectomies b/c this is completely treatable