Unit VI- Pancreatic and Biliary Secretion Flashcards
Digestive Enzymes
Salivary- Amylase, Lingual lipase
Gastric- pepsin
Pancreatic- amylase, trypsin, chymotrypsin, carboxypeptidase, elastase, lipase-colpase, phospholipase A2, cholesterol esterase- nonspecfic lipase (1 L digestive juices/day)
Intestinal- enterokinase, disaccharidases (maltase, sucrase, lactase, trehalase, isomaltase), peptidases (aminooligopeptidase, dipeptidase)
Proteases
- digest proteins
- Trypsinogen
- chymotrypsinogen
- procarboxypeptidase A and B
- zymogens have no enzymatic activity until activated in the gut
Lipases
- digest fats
- lipase
- phospholipase
Amylases
-digest carbohydrates
Nucleases
- digest nucleic acid
- ribonuclease
- deoxyribonuclease
Pancreatitis
-the pancreas becomes inflamed and the digestive enzymes are activated before they reach the intestine causing damage to the pancreas
Pancreas
- most important digestive gland
- 1 L of fluid secreted per day
- Exocrine secretions(into ducts thence to the lumen) : aqueous juice high in HCO2- from centro-acinar and duct cells; enzyme juice from acinar cells and centro-acinar cells into the intercalary ducts which merge into the secretory ducts- then the secretion flow through the ducts of Wirsung and Santorini and are delivered into the duodenum
-endocrine secretions (into blood) from islets of langerhands regulate blood sugar and metabolism; glucagon secreted by alpha cells, insulin secreted by beta cells, somatostatin secreted by delta cells
Pancreatic Aqueous Secretion
- bicarbonate neutralizes acid from stomach and allows pancreatic enzymes to function at their optimal neutral pH
- pepsin is inactivated at neutral pH, and thus cannot attack the duodenal mucosa
- neutralization of pH prevents damage to duodenal and intestinal mucosa by gastric acid
- aqueous secretion also serves to dilute the enzyme juice
- aqueous secretion originates in the centro-acinar cells and epithelial cells of intercalary ducts
Organization of the Exocrine Pancreas
- fundamental secretory unit is composed of an acinus and an intercalated duct
- intercalacted ducts merge to form intralobular ducts which in turn merge to form interlobular ducts and then the main pancreatic duct
- the acinar cell is specialized for protein secretion
- large condensing vacuoles are gradually reduced in size and form mature zymogen
Synthesis and Secretion of Enzymes
- originates in pancreatic acinar cells
- formed on ribosomes accumulate in rough surfaced cisternae
- smooth surfaced vesicles containing enzymes bud off, coalesce to form zymogen granules that usually contain pro-enzymes
- mature zymogen granules fuse with apical membrane and contents are discharged into lumen of acinus during secretion
Pancreatic Acinar Cells Showing Potentiation of Enzyme secretion by secretin and CCK
- vagal stimulation is via ACh
- CCK, ACh, and gastrin increase intracellular calcium
- secretin and VIP increase cAMP via G coupled receptor which activates Gs, which adenylate cyclase which activates cAMP
- ACh- binds muscarinic receptor Gq coupled increase PLC make PIP2 and DAG
- secretin and CCK act synergistically- their effect when both are present is greater than the sum of their effects when either is acting alone
- VIP is a neurotransmitter in the gut normally not important in pancreatic secretion, but it becomes important in certain pancreatic tumors known as vipomas, which result in a watery diarrhea
- note that secretin and CCK potentiate each others actions both on pancreatic enzyme secretion
VIP
- vasoactive intestinal peptide
- neurotransmitter in the gut normally not important in pancreatic secretion but it becomes important in certain pancreatic tumors which result in watery diarrhea
Secretion of Chloride by the Acinar Cells
- the Na-K pump creates the inwardly directly Na+ gradient across the basolateral membrane
- the Na/K/Cl cotransporter produces the net Cl- uptake, driven by the Na+ gradient, which is generated by the Na-K pump
- rise in intracellular K+ that results from the activity of the pump and cotransporter is shunted by basolateral K_channels that provide an exit pathway for K+ (CCK and cholinergic neurotransmitter ACh stimulators of Cl- secretion-probably through phosphorylation of basolateral and apical ion channels)
- intracellular Cl- establishes the electrochemical gradient that drives Cl- secretion into the acinar lumen through apical membrane Cl- channels
- the movement of Cl- into the lumen makes the transepithelial voltage more lumen negative, driving Na into the lumen via tight junctions
Na and HCO3- secretion by pancreatic duct cells
- diffusion of CO2 from the blood across the basolateral membrane into the duct cell
- hydrated by carbonic anhydrase to carbonic acid which dissociates to form H+ and HCO3-
- proton moves across basolateral membrane by Na+/H+ exchanger or an electrogenic proton pump
- bicarbonate accumulates in duct cell and exits across apical membrane via Cl-/HCO3- exchanger
- chloride channel is CFTR which is activated by secretin using cAMP, which stimulates PKA
- there is also a Ca2+ activated K channel
- CCK uses Ca2+ as second messenger to potentiate action of secretin
- K+ leaves the cell to to prime the Na+/K+ pump increasing the rate of secretion by the duct cell
- this generates negative transmembrane PD- driving force to move Na+ and K+ ions into the lumen via cation selective paracellular pathway
Features of Aqueous Secretion
- venous blood is acidified during secretion by an electrogenic proton pump and by Na+/H+ exchange in the basolateral membrane; tends to negate “akaline tide”
- in the intestinal phase both secretin and cholecystokinin (CCK) stimulate aqueous secretion by pancreatic duct cells