Pancreas

Pancreas

1. Powerhouse of activity for enzyme secretion

   • Produces Zyomgen = digests chyme

2. 95% can be removed but will still be functional

3. Secretes an alkaline fluid that provides optimum pH

   • For digestion
   • For micelle formation
     • To contain zymogens

4. Exocrine and endocrine function

   • Endocrine function
     • Glucagon and insulin
       • Travel around the blood
   • Exocrine function
     • Pancreas is divided into lobules
       • Lobules drain into ductular network
         • Intralobular duct
         • Interlobular duct
         • Main duct
           • Merges with the bile duct
             • Forms the Ampula of vater
               • Secretions controlled by the sphincter of Oddie
         • That connects entire gland to lumen of GI tract
           • Secretions enters dudodenum
       • Lobules are made of acinar cells
         • Acinar cells secrete
           • Zymogens
             • Inactive precursors of the enzyme
               • Prevent the development of pancreatitis
             • Exocytosed at apical pole
             • Triggers for zymogen secretion
               • Ach and CCK
                 • through Gq / PLC / PIP2 / IP3/DAG / PKC pathway
                 • CCK release stimulated by fat in the small intestine
                   • I cells make CCK - I cells triggered by fat
                     • Triggered by CCK releasing factors
               • VIP and Secretin
                 • through Gs/ AC / cAMP / PLA pathway
             • Inactivated = low levels of secretion
               • Via a constituitive secretory pathway
             • Example of a zymogen
               • Trypsinogen
                 • Goes to trypsin
                 • The most important zymogen
                   • Activates all the other zymogens
                     • Needs to only be active in the small intestine
                       • Becomes activated by enteropeptidase
                         • Only present on the brush border of epithelial cells on small intestine
                       • Trypsin activates all other zymogens
                   • How to prevent auto-digestion
                     • Granules = impermebale
                     • Granules contain inhibitors - SPINK1
                     • Condensed in low pH
             • Rate of zymogen secretion = linked to fed or fasted state
               • Fasted = decreased Ach etc
               • Fed = increased HCO3- in lumen
           • NaCL rich fluid
             • Hydrates zymogens
             • Trigger for this production is ACh and CCK
               • Involves multiple transport proteins
               • Increases Cl- and Na+ secretion
         • Also contain centroacinar cells and pancreatic duct epithelial cells and goblet cells
           • Duct cells
             • Morpholgical heterogeneity
               • Secrete bicarbonate rich fluid
                 • Provides optimum pH for the enzymes to work
                 • Comes from a Cl- / HCO3- exchanger
                   • HCO3- comes from breakdown of H2CO3
                     • From H20 and CO2
                     • By carbonic anhydrase
                     • H+ goes into the blood
                       • This is complete opposite to what happens in the stomach
                         • LOOK AT SGT
                         • H+ will neutralise alklaine tide from stomach
                     • Will neutralise H+ in lumen from stomach
                   • Cl- is in lumen of duct
                     • Due to CFTR
                       • Mutation in CF gene = mutant CFTR = cystic fibrosis
                         • Can't recycle Cl-
                           • Can't secrete bicarbonate
                             • Also decreased water secretion by duct cells
                               • Leads to thick secretions
                                 • Blocks the ducts
                                   • Leads to pancreatic damage
                                     • Get steatorrhea
                                       • Fatty stool
                                     • Get diabetes
                                       • No insulin/glucagon secretion
                                     • Zymogens attack cells
                     • Chloride recycling occurrs
                 • Secretin = most potent stimuls for HCO3-
                   • Then ACh
                   • Secretin from S cells
                     • When dectects acid
           • Centroacinar cells
             • Function unknown
           • Goblet cells
             • Produce mucus
         • Acinar cells contain a lot of RER
           • Make a lot of protein/zymogen
             • Zymogen --> Golgi
               • Zymogen enters vesicles

5. Inhibit the secretions of the pancreas

   • Use somatostatin
     • Produced by D cells
     • Inhibits the release of
       • CCK and Secretin
     • Competitive inhibitor of adenylyl cyclase
     • Drugs designed to be like somatostatin

6. Phases of pancreatic secretion

   • Cephalic
     • Sight
     • Smell
     • Taste
     • 25%
   • Gastric
     • 10-20%
     • Gastrin = CCK agonist
       • Stimulates zymogen release
   • Basal
   • Intestinal
     • 50-80%
     • Chyme in the intestine
       • Duodenal acidification causes S cells --> secretin
         • Secretin --> zymogen and HCO3-
     • Fats stimulate CCK
       • Zymogen release

7. What happens when autodigestion goes wrong?

   • Get acute pancreaitits
     • Due to GET SMASHED
       • Gallstones
         • Ethanol
           • Trauma
       • Steroids
         • Mumps
           • Autoimmune
             • Scorpion
               • Hyper
                 • Calcaemia
                 • triglyceridaemia
                 • Hypothermia
                   • ERCP
                     • Drugs
     • Chronic pancreatitis
       • Long term damage
       • Treatment
         • ERCP
           • Stents
         • Need artificial enzymes
     • Treatment
       • IV fluids
         • ERCP
           • To get rid of obstruction