Exocrine Pancreas

Exocrine Pancreas

1. Anatomy

   • Histology
     • Islets of Langerhans
       • Endocrine
     • Blood vessels
     • Ganglion
     • Interlobular ducts
   • Gross
     • Left Lobe
     • Right Lobe
     • Body of the pancreas
     • Common bile ducts
   • Species Difference
     • Pancreatic ducts
       • Variable arrangement
     • Pacinian Corpuscles
       • Cats
     • Giant Islets of langerhans
       • Some snakes
     • Hepatopancreas/Splenopancreas
       • some fish/reptiles/amphibians

2. Physiology

   • Regulation
     • Hormonal
     • Neural
     • Paracrine
   • Phases of secretion
     • Cephalic
     • Intestinal
     • Gastric
   • Enzymes
     • Pancreatic Amylase
       • Secreted in active form
     • Pancreatic Lipase
       • Secreted in active form
     • Proteolytic Enzymes
       • Trypsinogen
       • Chymotrypsinogen
       • Procarboxypeptidase
       • Others
       • Secreted inactive (zymogens)
         • Activated in duodenum by:
           • Trypsin
           • Enterokinase

3. Defensive Mechanisms

   • Continuous Flow
     • Prevents Reflux
   • Enzymes in zymogen
   • Proenzymes
   • Trypsion inhibitor secretion
   • Acinar cells have innate resistance
   • Degradation of prematurely active enzymes
   • Lysosomal enzymes can degrade zymogen

4. Pathology (DAMNITV)

   • Inflammation (Pancreatitis)
     • Acute
       • Necrosis
       • 3 Major mechanisms
         • Obstruction of ducts
           • Calculi/parasites
         • Direct injury to acinar cells
           • Infectious
           • Ischemia
           • Toxins (lead/mycotoxin/sulfonamides)
         • Disturbance of enzyme trafficking within acinar cells
       • preceded by Pancreatic Autolysis
         • More dogs > cats
         • Caused by premature release of pancreatic enzymes
           • Trypsin activation from trypsinogen
             • Active enzymes digest pancreas, cause damage
             • Activates kinin system (prekallekrein)
               • Complement cascade
                 • Clotting cascade
                   • Thrombosis + hemorrhage + inflamm
       • Clinical signs
         • Common in obese, inactive, middle aged, female dogs
         • Predisposition:
           • Diet: High fat foods
             • except cats
           • Alot of drugs: corticosteroids
           • Endocrine disease: Hyperthy, Hyperadreno
           • Hyperlipidemia
           • Hypercalcemia
         • Concurrent disease
           • Diabetes mellitus
           • Inflammatory bowel disease
           • Cholangitis/cholangiohepatitis
           • Hepatic lipidosis
         • Insidious in cats
         • Mild Cases clinically silent
       • Gross Appearance
         • Often multifocal, but varied distribution
           • Normal parenchyma patches
           • Often starts in interlobular septa
             • Extend into lobules
         • Foci of Fat Necrosis
         • Swollen/Mottled pancreas
           • Red Black (hemorrhage) and Gray white (necrosis)
         • May see peritonitis with fibrinous adhesions
       • Consequence
         • Mild cases recover
         • Severe cases: Systemic effects
           • Vascular injury
             • DIC/hemorrhage/shock/death
             • Myocardial depressant from ischemic pancreas
               • arrhythmia
               • Liver secondary disease
                 • Cholestasis
                 • Secondary bacterial infection (rare)
     • Chronic
       • Relapsing syndrome
         • Progressive damage by acute pancreatitis/CS
           • Fibrosis
       • Significant Damage
         • Exocrine pancreatic insufficiency
           • Primary
             • Secondary
               • Pancreatic duct obstruction
               • Chronic Pancreatitis
               • Extensive pancreatic necrosis
             • Juvenile Pancreatic atrophy
               • Genetic, young dogs
           • Pancreatic hypoplasia
             • Rare, in calves
           • Pancreatic agenesis
           • Leads to
             • Maldigestion
             • Malabsorption
             • Diabetes mellitus
           • Clinical Signs
             • Diarrhea
             • Weight loss
             • Pale, soft, smelly feces
             • Flatulence, borborygmus
             • Concurrent SIBO common
           • Lab Investigation
             • Trypsin like Immunoreactivity (TLI)
               • K9/F9/horse immunoassays
               • Detects serum trypsinogen, trypsin bound to protease inhibitors
               • Values decrease with EPI
                 • VERY sensitive/specific EPI Test
               • Inconsistently increased with acute pancreatitis
                 • Non-specific, don't rely
               • Also elevates with azotemia, cobalamin deficiency
                 • Cats only
             • Serum folate and cobalamin (B12)
               • high sensitivity and specificity for EPI
               • Folate
                 • Increased
                   • Bacterial overgrowth/EPI
                 • Decreased
                   • Proximal SI damage
               • Cobalamin
                 • Decreased
                   • SI Damage/Bacterial overgrowth/EPI
         • Diabetes mellitus
       • Gross Appearance
         • Distorted, shrunken, irregular, pale, lobulated
         • Fibrous adhesions
     • Testing
       • Markers
         • Amylase
           • Use in Dogs only
           • Leakage enzyme
             • Pancreas
             • Liver
             • Small intestine
           • Higher = likelihood of disease
             • Mild to moderate can be non-pancreatic
         • Total Lipase
           • DGGR
             • Dogs and Cats ONLY
             • high sensitivity/specificity
           • Use in Dogs only
           • Leakage enzyme
             • Pancreas
             • Gastric mucosa
             • >3x = pancreatitis
             • Mild to moderate can be non-pancreatic
               • Renal/GIT/steroids/hepatic/neoplasia
           • Pancreatic Specific Lipase (cPL/fPL), or Specific lipase Immunoreactivity (PLI)
             • Detects pancreatic lipase, total activity
             • Least affected by GIT/ renal disease/corticosteroids
             • Requires fasting
             • Quantitative Canine PLI (cPLI)
               • >80% sensitive
             • Quantitative Feline PLI (fPLI)
               • 100% sensitive
           • In house ELISA/snap test
         • C reactive protein (CRP)
           • Acute phase reactant from liver
           • Elevated with any inflammation/trauma
           • Poor specificity
         • Trypsin activation peptide
           • Released during trypsin activation from trypsinogen
           • Not very specific, can increase in many cases
           • Not widely available, hard to interpret
         • Non-specific
           • Not recommended
       • Haematology
         • Biochemistry Panel
           • Increased ALP, ALT, AST
           • Hyperbilirubinemia
           • Urea and Creatinine: Dehydration
             • Pre renal azotemia
           • Hypercholesterolemia, hypoalbuminemia, hypertriglyceridemia
           • electrolyte abnormalities
         • CBC
           • Elevated PCV and TP
             • Dehydration (Haemoconcentration)
           • Neutrophilia with left shift and toxic changes
           • Thrombocytopenia with DIC (PT/APTT longer)
       • Ultrasound/Imaging
       • Exploratory laporoscopy
       • Cytology
         • FNA/Wet Prep
       • Histopathology
         • Trucut/incision
     • In CATS:
       • Commonly incidental
         • clinical Dx Hard
       • Risk factors: NOT FAT DIET
         • Drugs
           • Organophosphates
         • Infectious
           • Toxoplasma/pancreatic fluke/herpesvirus, FIP, calicivirus
         • Hypercalcemia
         • Hypertriglyceridemia
         • Blunt Trauma
       • Concurrent Disease
         • Diabetes mellitus
         • Inflammatory bowel disease
         • Cholangitis/Cholagniohepatitis
         • Hepatic lipidosis
       • amylase and total lipase not useful
         • Use DGGR/fPL/fPLI/snap fPL/ultrasound