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The Pathology of the Pancreas, • Presence of inciting agent - Coggle…

- - - - Results from defective pancreas formation
    - - Mutation of the PDX1 gene
    - - Partial agenesis
        
        the pancreas body is of varied size
        
        remnant of the accessory duct exists
        
        the minor papilla
        is present
      - Complete agenesis
        
        the neck, body & tail of the pancreas are absent as well as the accessory duct and the minor
        duodenal papilla
  - - - The main pancreatic duct drains only a small
        portion of the head of the gland
      - The bulk of the pancreas drains through the
        minor sphincter (narrow opening)
        
        Predisposes to acute/chronic pancreatitis
  - - - risk of
        
        duodenum obstruction
  - - - Common sites:
        
        • Stomach & Duodenum
        
        • Jejunum
        
        • Ileum
  - - - Unilocular cyst (up to 5cm)
        
        Lined by either uniform cuboidal or flattened epithelium
        
        Enclosed in a thin, fibrous capsule
- - - - Function can return to normal if the underlying cause of inflammation is removed
      - Inflammation and hemorrhage of the pancreas
      - Due to
        
        autodigestion of pancreatic parenchyma
        
        by
        
        pancreatic enzymes
        
        premature activation of trypsin leads to activation of other pancreatic enzyme
      - Causes
        
        Non‐traumatic (75%)
        
        • Biliary tract disease
        
        • Alcohol
        
        • Viral Infection (EBV, CMV, mumps)
        
        • Hyperlipidemia
        
        • Hyperparathyroidism
        
        Traumatic (5%)
        
        • Operative trauma
        
        • Endoscopic procedure with dye injection
        
        Idiopathic (20%)
      - Pathogenesis of AP
        
        AP occur as a Result of
        
        inappropriate activation of pancreatic enzymes
        
        which cause
        
        auto‐digestion of the pancreas and triggers an inflammatory cascade
        
        which can result in
        
        1 more item...
      - Morphology
        
        microscopically
        
        Basic alterations:
        
        Necrosis of fat by lipases
        
        An acute inflammatory reaction
        
        Proteolytic destruction of pancreatic parenchyma
        
        Destruction of blood vessels leading to interstitial hemorrhage
        
        Microvascular leakage causing edema
        
        Mild acute pancreatitis:
        
        • Acinar cell necrosis, intense acute inflammation and foci of necrotic adipocytes
        
        • Fat necrosis results from enzymatic destruction of fat cells
        
        released fatty acids combine with calcium to form insoluble salts that precipitate in situ
        
        Severe acute pancreatitis:
        
        Severe acute pancreatitis:
        
        Vascular damage
        
        Causes hemorrhage into the parenchyma of the pancreas
        
        Macroscopically:
        
        The pancreas exhibits red‐black hemorrhagic areas interspersed with foci of yellow‐ white, chalky fat necrosis
      - Symptoms & signs
        
        most common
        
        • Severe epigastric pain radiating to the upper back, relieved by leaning forward
        
        • Nausea, vomiting, diarrhea and loss of appetite
        
        • Fever/chills
        
        • Hemodynamic instability, including shock
        
        • In severe case may present with tenderness, guarding, rebound
        
        less common (indicate severe disease)
        
        Grey‐Turner's sign (hemorrhagic discoloration of the flanks)
        
        • Cullen's sign (hemorrhagic discoloration of the umbilicus)
      - scoring
      - complications
        
        Atlanta classification
        
        Fluid collections associated with interstitial oedematous pancreatitis s (i.e. minimal or no necrosis)
        
        • Acute peripancreatic fluid collections (APFC): in the first 4 weeks; non‐encapsulated peripancreatic fluid collections
        
        • Pseudocysts: develop after 4 weeks; encapsulated peripancreatic or remote fluid collections
        
        Fluid collections associated with necrotising pancreatitis
        
        • Acute necrotic collections (ANCs): in the first 4 weeks; non‐encapsulated heterogeneous non‐liquefied material
        
        • Walled‐off necrosis (WON or WOPN): develop after 4 weeks; encapsulated heterogeneous non‐liquefied material
    - - Irreversible destruction of exocrine pancreatic parenchyma
        
        Long standing inflammation of the pancreases
      - Characterized by
        
         Irreversible destruction of the exocrine pancreas
        
         Loss of the islets of Langerhans
        
         Loss of pancreatic function
      - Causes
        
         Most factors that cause acute pancreatitis can also lead to chronic pancreatitis
        
         Chronic pancreatitis is often characterized by intermittent “acute” attacks and followed by periods of quiescence suggests that it may evolve from repeated bouts of acute pancreatitis
        
         Heavy alcohol consumption ( 70‐80%)
        
         Chronic duct obstruction (by pseudocysts, calculi, neoplasms or pancreas divisum)
        
         Trauma
        
         Hyperparathyroidism
        
         Hypertriglyceridemia
        
         Autoimmune pancreatitis
        
         Type 1 AIP is also called IgG4‐related: attack pancreas, bile duct, Liver, kidney and lymph node
        
         Type 2 AIP, also called idiopathic duct‐centric pancreatitis, associated inflammatory bowel disease.
        
         Tropical pancreatitis
        
         Hereditary pancreatitis
        
         Mutations in the pancreatic trypsinogen gene (PRRS1) or the SPINK1 gene encoding a trypsin inhibitor
        
         Idiopathic
      - Pathogenesis
        
         Ductal obstruction by concretions (Alcoholic, Tropical, Hereditary)
        
        • These proteins can form ductal plugs
        
         Toxic Metabolic
        
        • Toxins, including alcohol and its metabolites, can exert a direct toxic effect on acinar cells
        
        leading to:
        
        • Acinar cell loss
        
        • Eventually parenchymal fibrosis
        
        • Lipid accumulation
        
         Oxidative stress
        
        Stress may generate free radicals in acinar cells (Leading to membrane damage)
        
        • Subsequent expression of chemokines (IL‐8), which recruits mononuclear inflammatory cells
        
        Oxidative stress also promotes the fusion of lysosomes and zymogen granules
        
        • Acinar cell necrosis, Inflammation & fibrosis
        
         Inappropriate activation of pancreatic enzymes due to mutations affecting genes
        
        • Mutations in the pancreatic trypsinogen gene (PRRS1), or the SPINK1 gene encoding a trypsin inhibitor
        
         Unlike Acute Pancreatitis
        
        Several of profibrogenic cytokines, such as transforming growth factor‐β (TGF‐β), connective tissue growth factor, and platelet‐derived growth factor, are secreted in chronic pancreatitis by infiltrating immune cells such as macrophages
        
        These cytokines induce the activation and proliferation of periacinar myofibroblasts (“pancreatic stellate cells')
        
        Which deposit collagen and give rise to fibrosis