Exocrine Pancreas PDF

Section 8: The Exocrine Pancreas I. Functions of the pancreas A. Endocrine function: to be covered in endocrine physiology 1. Insulin from  cell of Islets of Langerhans...

Section 8: The Exocrine Pancreas I. Functions of the pancreas A. Endocrine function: to be covered in endocrine physiology 1. Insulin from  cell of Islets of Langerhans in IP4 2. Glucagon from  cell of Islets of Langerhans typically located at the junction at the proximal duodenum and stomach some species have several pancreatic ducts empyting Acini - found in pancreatic enzymes into duodenum proenzyme 81  B. Exocrine function: 1. Enzymes of digestion - Ecbolic secretion a. Proenzymes (aka zymogens) produced in acinar cells b. Enzymes function in intraluminal digestion of protein, carbohydrates and fat in upper small intestine. Fig. 57 Functional exocrine unit of pancreas 2. Alkaline (HCO3- rich) watery secretion - Hydrolatic secretion a. Produced by active ion transport in ductule epithelium b. Function: Neutralize acid in lumen of upper small intestine. Acid chyme entering duodenum + creates optimal pH for enzyme action * Ecobolic and hydrolatic secretions typically secreted simultaneously but differ in their neuroendocrine control. Has 3 classic phases (like II. Neuroendocrine control of exocrine pancreatic secretion gastric secretion) A. Cephalic phase (5%): Primarily neural 1. Afferent: Conditioned reflexes associated with appetite (CNS) 2. Efferent: Vagal (Parasympathetic) activity at effector neurons increases CFTR activity a. VIPergic effector (at ducts): VIP hydrolatic secr. (via  cAMP) more durable action - stimulate epithelium b. Cholinergic effector(at acini): ACh ecbolic secretion (via  Cai2+) (muscarinic) Stimulates exocytosis of proenzymes 82  B. Gastric phase (15%): Primarily neural unconditied reflex 1. Afferent: Stomach distension/presence of food activates a general visceral afferent to CNS 2. Efferent: Vagal (Parasympathetic) activity at effector neurons. *Same as cephalic phase. VIP (ducts) Ach (acini) cephalic and gastric phases prepare duodenum for acid chyme C. Intestinal phase (80%): Primarily endocrine action. 1. Hydrolatic secretion: (at pancreatic ducts) Stimulus: H+ in small intestinal lumen Main Response: Secretin released from intestinal enteroendocrine (S) cells → Enters circulation Binds at duct epithelium  cAMP Minor Response: General visceral afferent (neurocrine activation via secretin) CNS Vagal activity VIPergic neurons  cAMP Secretin + VIP > Increases cAMP in duct epithelium > Stimulates CFTR 2. Ecbolic secretion: *still endocrine (at acini) Stimulus: Fats, Amino acids in small intestinal lumen @Micelles Main Response: CCK released from intestinal enteroendocrine(I) cells Enters circulation Binds at CCKA receptor on acinar cells  Cai2+ (also remember that gastrin levels in the circulation can alter ecbolic secretion) Minor Response: General visceral afferent (neurocrine activation via CCK) CNS Vagal activity cholinergic neurons  Cai2+ CCK + Ach > Increase CA2+ in acini > REWATCH FOR NOTES * CCK and secretin potentiate each other’s action on enzyme and HCO3- secretion. 83 84  III. Composition of pancreatic exocrine secretions A. Hydrolatic secretion (HCO3- rich, watery fluid) ~isotonic NaHCO3 solution 1. Acinar cells - Small amount of active Cl- secretion. Flushes proenzymes into ductules 2. Centroacinar and duct epithelium - Large amount of active bicarbonate secretion. *Secretes alot of bicarb CFTR coupled wth Cl -/HCO3- exchanger Fig. 58. Anion transport of the luminal membrane in acinar and duct epithelia. Not CFTR 3. Reciprocal change in anion content of pancreatic juice At low flow rates, Cl- is main anion. At high flow rates, HCO3- is main anion. Low High Secretin VIP Fig. 59 Isotonic NaHCO3 Dogs, Cats 85  B. Ecbolic secretion (Digestive enzymes) 1. Digestive enzyme production and activation Fig. 60 Digest fat Digest protein Digest nucleic acids Digest starch Colipase anchors lipase to micelles Anti-trypsin Pancreatic acini: highest rate of protein synthesis in the body Protection against autodigestion involves: a. Inactive proenzymes (aka zymogens) are synthesized. Protects acinar cells b. Proenzymes are stored in membrane-covered vesicles c. Anti-trypsin production in acinar cells Prevents spontaneous trypsin activation Protect ducts d. Proenzymes are activated in intestinal lumen. brush border enzyme 'Enterokinase' Fig. 61 1) Trypsinogen cleaved to form trypsin by enterokinase at brush border 2) Trypsin activates trypsinogen and other proenzymes 86 Clinical Relevance: Pancreatitis Impaired flow in pancreatic ducts → (inflammation, edema, fibrosis) Can be insidious in dogs, cats Proenzymes (including trypsinogen) trapped in ducts→ Spontaneous trypsinogen cleavage overwhelms trypsin inhibitor→ Autodigestion of duct Active enzyme leak into pancreas peritoneal cavity, blood > Sick animal 2. Types of digestive enzymes a. Proteolytic enzymes: 1) Endopeptidases: trypsin, chymotrypsin, elastase -Hydrolyze proteins at specific amino acids -Yield oligopeptides and di-,tri- peptides 2) Exopeptidases: carboxypeptidases -hydrolyze amino acids sequentially from C-terminus of peptides -yield amino acids b. Pancreatic amylase oligosaccharides Acts at  1,4 glycosidic linkages disaccharides c. Nucleases RNA, DNA - cleavage generate nitrogen bases (ex: purines) d. Lipases (Lipase, phospholipase, carboxylesterase) 1) Lipase (and phospholipase) Hydrolyze triglycerides at 1 and 3 ester links 2) Carboxylesterase (bile salt activated) binds to bile to be activate in lumen *Full enzymatic digestion of fat by lipases requires bile salt emulsification. = micelles 87 Objectives: 1. Know the cell types where pancreatic enzymes and bicarbonate are secreted. 2. Know where the pancreatic duct enters the alimentary tract. 3. Know the three phases of pancreatic secretion. 4. Describe the neuroendocrine control of ecobolic and hydolatic secretions, and what the main second messenger that is used for each type secretion. Relate this regulation to the events occurring in the stomach after a meal. 5. Know four ways that the pancreas is protected from autodigestion. 6. Know where enterokinase is located and its role in pancreatic enzyme digestion. 7. Know the types of pancreatic digestive enzymes. 8. Know how the ionic composition of the hydrolatic secretion changes during high and low flow rates, and what is responsible for these changes. Related Questions: 1. What is the relationship between the changes in the pH of the plasma after meal ingestion and the major digestive events in the alimentary tract? 2. What is coprophagy? 3. Name two essential fatty acids. 88