Function of the exocrine pancreas

• secretes an enzyme rich fluid into the GI tract • secretion is mainly via the pancreatic duct • secretes into the duodenum

• made up of acinar cells and duct cells • has a main pancreatic duct • has accessory pancreatic ducts

• produce 80% of the fluid secreted by the pancreatic ducts • secrete enzymes and chloride ions

• account for 5% of the cells within the pancreas • secrete a bicarbonate rich component which neutralises the acidic contents of the stomach

• post ganglionic parasympathetic nerve fibres (vagal) • innervation of the blood vessels (sympathetic and parasympathetic)

• aqueous component • enzymes

• high in bicarbonate • the initial flid is hypertonic • the composition is dependent on the rate of secretion

• enzymes are stored in their inactive form in zymogen granules within acinar cells • one of the main enzymes is trypsin

• acinar cells are stimulated by CCK and acetylcholine • duct cells are stimulated by secretin

• Na/K/Cl cotransporter allows chloride ions to enter the cell • chloride ions are released into the lumen of the acinus causing a slight negative charge • sodium ions are pumped out on the basolateral side by a Na/K pump and potassium ions move into the cell • K+ channels on the basolateral side will provide an exit pathway for potassium ions • water and sodium ions move into the lumen of the acinus transcellularly due to the negative charge of the lumen • aquaporins are inserted into the membrane on the lumen side to allow water to enter the lumen through cells • acinar cells secrete an isotonic plasma like fluid rich in NaCl and this accounts for 25% of all pancreatic secretions • this helps to hydrate the dense and protein rich material secreted by zymogen granules

• a chloride bicarbonate exchanger will secrete intracellular bicarbonate into the duct lumen • calcium activated chloride ion channels allow chloride ions to enter the duct lumen to allow them to enter back into the cell in exchange for bicarbonate • the bicarbonate that will enter the lumen enters the cell via a Na/HCO3 transporter • bicarbonate is also generated by the activity of carbonic anhydrase

75%

25%

1) cephalic phase - food hasn’t yet entered the GI tract 2) gastric phase - food has entered the body and into the stomach 3) intestinal phase - food leaves the stomach and enters the small intestine

• less than 20% of pancreatic secretion occurs in this phase 1) the sight, smell and taste of food will stimulate parasympathetic vagal activity 2) this will cause secretion of acetylcholine and VIP by nerve endings 3) this will cause secretion of gastrin by G cells of the stomach but also enzyme rich secretion by acinar cells and bicarbonate rich fluid by duct cells 4) secretion of gastrin by G cells of the stomach also causes enzyme rich secretion by acinar cells and bicarbonate rich fluid by duct cells

• less than 10% of pancreatic secretion occurs in this phase 1) distension of the stomach stimulates a vago-vagal reflex 2) this causes secretion of acetylcholine and VIP by nerve endings and also secretion of gastrin by G cells of the stomach 3) this leads to enzyme rich secretion by acinar cells and bicarbonate rich fluid by duct cells

• more than 70% of pancreatic secretion occurs in this phase • this is the most important phase 1) the products of protein and fat digestion in the duodenum will cause secretion of CCK by I cells 2) this will lead to enzyme rich secretion by acinar cells and bicarbonate rich fluid by duct cells 1) a low pH in the duodenum causes secretion of secretin by S cells 2) this causes secretion of bicarbonate rich fluid by duct cells

• proteolytic • lipolytic • amylolytic

• enzymes are stored in their inactive form in zymogen granules in the acinar cells of the pancreas • the activation of these enzymes are prevented by the acidic environment • a trypsin inhibitor is also present in the cytoplasm of these cells which helps trypsin to remain inactive

• trypsin • chymotrypsin • elastase • carboxypeptidase

• lipase • phospholipase A2

α-amylase

• the zymogen is trypsinogen • it cleaves internal peptide bonds • it cleaves all other enzymes into their active forms • it is activated by membrane bound enterokinase

• zymogen is chymotripsinogen • it cleaves internal peptide bonds