Functions And Secretions Of The Pancreas Flashcards
What are the main functions of the pancreas
- Provide the correct environment for enzymatic digestion within the small bowel.
- Secretions aid in the digestion of fats, proteins, carbohydrates etc.
- Regulates the fed and fasted states by neutralising acidic chyme through bicarbonate secretion
Describe the structure of the pancreas.
The pancreas is composed of multiple lobules, which drain into ducts connecting the pancreas to the lumen of the duodenum.
What are the three types of ducts within the pancreas lobules?
Intralobular duct, interlobular duct and the main duct
How does the pancreas connect to the duodenum?
The major ducts of the pancreas merge with the common bile duct to form the ampulla of vater in the duodenal wall
What is the Ampulla of vater?
A swelling in the wall of the duodenal. Secretions from the Ampulla of vater are regulated by the sphincter of Oddi.
Where does the pancreas empty into?
The pancreas empties into the descending part of duodenum, via the Ampulla of vater, at the major papilla. This is the point where the celiac trunk stops supplying the gut and superior mesenteric artery takes over.
What are the functional units of the pancreas?
Functional units of the pancreas are the acinus, which are clusters of acinar cells.
What do acinar cells secrete ?
Acinar cells secrete a large number of zymogens, digestive enzymes and an isotonic, plasma like fluid.
How are the acinar cells connected?
They are connected via intercalated ducts.
What special feature do the intercalated ducts have?
Intercalated ducts are lined by ductal cells which have duct cells that secrete a bicarbonate rich fluid that dilutes the thick acinar secretion.
What are the different pancreatic cells?
- Acinar cells
- Duct cells
- Goblet cells
Main function of acinar cells ?
How is acinar secretion mediated?
Secretes digestive enzymes.
It is mediated by stimulation of cholecystokinin (CCK) and muscarinic ACH receptors of the basal membrane of of acinar cells. Or through the binding of VIP and secretin.
What pathways are activated by the activation of CCK and muscarinic ACH and VIP and secretin receptors ?
CCK and muscarinic ACH activate the phospholipase C (PKC/PLC) pathway and release Calcium leading to increase enzyme secretion.
VIP and secretin activate adenyly Cyclase leading to cAMP production and activation of PKA
Stimulation of what nervous system leads to release of muscarinic ACH?
The parasympathetic system
What is the principle function of the pancreatic duct cells ?
Secrete a bicarbonate (HCO3-) rich fluid that alkalises and hydrates the zymogen rich secretions of the acinar cells.
What is the fluid secreted by duct cells important for?
It is important in providing the optimal pH for enzymes, Michelle formation and neutralising acid.
What is cystic fibrosis?
A disease caused by a mutation in the CF gene leading to an alteration in the function of the CFTR channel. The CFTR is then prematurely degraded leading to loss of expression disrupting apical transport of duct cells and decreased secretions of bicarbonate and water by duct cells.
Protein rich secretion builds up in the lumen of duct cells leading to obstruction. Leading to maldigestion of nutrients.
Which organ exhibits the highest rate of protein synthesis and secretion?
The pancreas. Producing 1.5l of pancreatic fluid containing 5-15g of protein.
Give an example of the zymogens and active digestive enzymes that are secreted by the pancreas?
Zymogens
Trypsinogen, chymotrypsinogen, protelastase, procarboxypeptidase A, procarboxypeptidase B.
Active digestive enzymes
Lipase and co-lipase
What is the difference between pancreatic secretions in the fed and fasted state?
In the fasted state, there is a low level of release of pancreatic enzymes.
In the fed state, pancreatic secretion increase 5 to 20 fold over basal levels.
Composition of the pancreatic secretion also changes.
What is the role of CCK in pancreatic stimulation?
It stimulates pancreatic acinar cells to increase protein secretion.
Which cells is CCK released from ?
CCK is released from duodenal I cells.
What happens to CCK levels after a fatty meal?
CCK levels rise 5 to 10 fold. This could be due to direct and indirect stimulation through CCKa receptors or the parasympathetic nervous system.
What stimulates CCK release in the fasted state?
Luminal CCK releasing factor ( LCRF) are digested by digestive enzymes so there is no CCK stimulation.
During a meal, digestive enzymes will work on the chyme and LCRFs are free to stimulate duodenal i cells to release CCK which then stimulates the pancreas
What is an inhibitor of pancreatic secretions?
Somatostatin, S-14, secreted by the D cells in the islets of larger hand inhibits the release of CCK and secretin. As well as insulin and glucagon.
What are the stages of pancreatic secretion and which one provides the highest secretions of pancreatic fluids?
Cephalic phase - 25% of pancreatic secretions
Gastric phase - 10% - 20% of pancreatic secretions
Intestinal phase - 50% to 80% of pancreatic secretions
What mediates cephalic pancreas secretion?
Stimulation of ACH receptors on acinar cells and duct cells (lesser extent). No involvement of CCK or secretin.
What mediates gastrin pancreatic secretion?
Hormone release- gastrin in G cells of Antrum.
Stimulation of neuronal pathways. Distension activates vagovagal gastropancreatic reflex
What stimulates intestinal pancreatic secretion?
- Gastric acid stimulating duodenal S cells to release secretin, stimulating duct cells in the pancreas to secrete HCO3
- Lipids stimulating I cells to release CCK, which stimulates acinar cells to release digestive enzymes
- Lipids also activate vagovagal eneteropancreatic reflex stimulating acinar cells.
How does the pancreas avoid auto-digestion?
- Proteins being stored as zymogens
- Use of secretory granules, the membrane is impermeable to proteins. Zymogens and active digestive enzymes sequestered from proteins in the cytoplasm and intercellular compartments.
- Enzyme inhibitors that are co-package within the secretory vesicles
- Low pH and ionic conditions within secretory pathways.
How are zymogens activated?
Zymogens are activated when they come in contact with enterokinase, which is present in the brush bordered the small bowel. This converts trypsinogen to trypsin which in turn initiates the conversion of all other zymogens to their active form.
What problem occurs when auto-digestion goes wrong?
Acute pancreatitis
What causes acute pancreatitis?
GET SMASHED G - Gallstones E - Ethanol T - Trauma S - Steroids M - Mumps A - Autoimmune S - Scorpion sting H - Hypercalcaemia E - ERCP D - Drugs
What the features help diagnose pancreatitis?
- Abdominal pain - associated with nausea and committing.
- Serum amylase and/or lipase which is 3 times the upper limit of normal levels and high serum levels.
- Characteristic finding of pancreatitis on CY scan
What are the phases of acute pancreatitis?
Phase 1: premature activation of trypsin within the pancreatic acinar cells, which inhibits acinar secretion.
Phase 2: intra- pancreatic inflammation ( activation of inflammatory and endothelial cells).
Phase 3: extra-pancreatic inflammation including systemic sepsis and multi-organ failure
What mechanisms have been proposed in phase 1 ?
- Disruption of calcium signalling in acinar cells
- Cleavage of trypsinogen to trypsin by lysomal hydrolyse cathepsin-B
- Decreased activity of the intra cellular pancreatic trypsin inhibitor SPINK1
Treatment for mild form of pancreatitis?
Supportive therapy:
Resting pancreas - I’ve fluid to combat dehydration
Hourly fluid balance via catheter
Pain relief
Ultrasound scan
Therapeutic endoscope retrograde cholangiopancreatography (ERCP)
What is chronic pancreatitis?
Common causes of pancreatitis?
Inflammation of the pancreas that does not heal or get better over time.
Chronic alcohol abuse, cystic fibrosis, hypercalcemia and hyperlipidemia
Treatment of chronic pancreatitis?
May require hospitalisation m, hydration and nutritional support. Diet supplemented by synthetic in pancreatic enzymes. Change in diet. ERCP. Enlarge duct openings, drown pseudocysts. Stent placement and balloon dilation.
What is the problem with balloon dilation?
It can lead to calcification of the the fibrotic pancreas leading to destruction of pancreatic tissue leading to diabetes.
