Functions and Secretions of the Pancreas Flashcards
What are the 3 overall functions of the pancreas?
1 - Important in digestion of fats and proteins.
2 - Providing the appropriate environment for enzymatic digestion in the small bowel.
3 - Important in regulating the fed and fasted states (insulin, glucagon etc.).
What is the ampulla of Vater?
A swelling in the duodenal wall where the main pancreatic duct merges with the common bile duct.
Where is the sphincter of Oddi?
At the ampulla of Vater.
Where are secretions from the pancreas emptied?
Into the descending part of the duodenum.
Which structures compose the secretory units of the pancreas?
An acinus and a small intercalated duct.
What is the function of the acinus?
- Contains acinar cells that synthesise and secrete proteins into the lumen of the epithelia.
- Secretions include zymogens, digestive enzymes and an isotonic fluid that accompanies the secretions.
List the pancreatic cell types.
1 - Acinar cells.
2 - Ductal cells.
3 - Centroacinar cells.
4 - Goblet cells.
Describe the cellular architecture of acinar cells.
- Many RER.
- Many secretory granules and golgi bodies.
- Exocytosis at apical poles.
What is the function of ductal cells?
To facilitate the transport of electrolytes by hydrating and alkalinising the secretions of the acinar cells.
What are centroacinar cells?
- Function unknown.
- Exist at the junction of the acinar cells and the ductal cells.
What is the importance of mucus secretion in the digestive tract?
1 - Lubrication.
2 - Hydration.
3 - Mechanical protection of epithelia.
4 - Immunological role (binding of pathogens and interactin with immune cells).
What mediates stimulation of pancreatic acinar cells to secrete proteins?
- In an unstimulated state, constantly secrete low levels of proteins via a constitutive pathway.
- CCK receptors and AChRs on the basolateral membrane regulate secretion through the Gq pathway.
- VIP and secretin receptors regulate secretion through the Gs pathway.
How do acinar cells secrete the isotonic, NaCl rich fluid?
1 - Na-K pump on the basolateral membrane pumps 3 Na+ out and 2 K+ in.
2 - Na / K / Cl cotransporter pumps on the basolateral membrane 3 Na+, 3K+ and 6Cl- in.
3 - K+ leaves the basolateral membrane via K+ channels4
4 - High intracellular Cl- establishes the electrochemical gradient for apical Cl- secretion.
5 - Secretion increases as Cl- in the lumen makes the transepithelial voltage more lumen-negative, driving Na+ into the tight junctions between acinar cells, where they can pass into the lumen.
- Same triggers as protein secretion.
How do pancreatic ductal cells hydrate and alkalinise the secretions of the acinar cells?
1 - The Na+ / HCO3- cotransporter (basolateral) pumps Na+ and HCO3 - in the ductal cell.
2 - The cystic fibrosis transmembrane regulator (CFTR, apical) is cAMP activated and pumps Cl- out of the ductal cell.
3 - The Cl- / HCO3- exchanger (apical) pumps Cl- back into the cell and HCO3- out (Cl- recycling).
What is the function of secretin?
To stimulate HCO3- and fluid secretion by the ductal cells, predominantly in response to duodenal acidification.
Where is secretin secreted from?
From S cells in the small bowel mucosa.
What stimulates ductal cells to hydrate and alkalinise the secretions of the acinar cells?
- Secretin stimulates the CFTR and Na+ / HCO3- cotransporter.
- Muscarinic AChRs cause increased intracellular Ca2+, and activation of Ca2+-dependent kinases (e.g. PKC).
List 5 zymogens found in pancreatic juice.
1 - Trypsinogen.
2 - Chymotrypsinogen.
3 - Proelastase.
4 - Procarboxypeptidase A.
5 - Procarboxypeptidase B.
List 3 active digestive enzymes found in pancreatic juice.
1 - Amylase.
2 - Lipase.
3 - Co-lipase.
Where is CCK secreted from?
Duodenal I cells.
What is the function of CCK?
To stimulate pancreatic acinar cells to increase protein secretion.
How does CCK stimulate its effector cells?
- Directly, by binding to CCKa receptors.
- Indirectly, through the parasympathetic nervous system.
What triggers the release of CCK and how are CCK levels maintained?
- CCK-releasing factors, e.g. luminal CCK releasing factor (LCRF) stimulate CCK release.
- In the fasting state, LCRFs are degraded by digestive enzymes. During a meal, the digestive enzymes act on the chyme rather than the LCRFs, allowing LCRFs to stimulate I cells.
What is the function of somatostatin?
To inhibit the release of CCK and secretin.
Where is somatostatin secreted from?
D cells of the islets of Langerhans.
What is octreotide and what is its function?
An analogue of somatostatin used clinically to inhibit pancreatic secretions.
What are the phases of pancreatic secretion?
1 - Cephalic phase (25%).
2 - Gastric phase (10-20%).
3 - Intestinal phase (50-80%).
What triggers the cephalic phase of pancreatic secretion?
- Sight.
- Taste.
- Smell.
How are the effects of the cephalic phase of pancreatic secretion brought about?
By stimulation of ACh receptors on the acinar cells and ductal cells.
How are the effects of the gastric phase of pancreatic secretion phase brought about?
- By the release of hormones such as gastrin.
- By stimulating neural pathways (gastric distension stimulates pancreatic secretion through a vagovagal gastropancreatic reflex).
What is the function of gastrin?
To act as a weak CCK agonist by binding to CCK receptors on acinar cells.
Where is gastrin secreted from?
G cells of the antrum.
List the mechanisms by which pancreatic secretion is stimulated during the intestinal phase.
1 - Gastric acid stimulates duodenal S cells to release secretin, stimulating duct cells to secrete HCO3 and fluid.
2 - Lipids stimulate duodenal I cells to release CCK, stimulating acinar cells to release digestive enzymes.
3 - Lipids also activate a vagovagal enteropancreatic reflex that stimulates acinar cells.
How does the pancreas prevent autodigestion?
By preventing enzymatic activity:
1 - Digestive proteins are stored in secretory granules as inactive precursors (zymogens). Trypsinogen is only activated once it reaches enterokinase.
2 - The secretory granules are impermeable to proteins.
3 - Enzyme inhibitors such as SPINK1 are co-packaged in the secretory granule.
4 - The low pH and ionic conditions in the secretory granules inhibit enzyme activity.
What is the function of enterokinase?
- To convert trypsinogen intor trypsin (active).
- Helps prevent autodigestion of the pancreas as enzymes are only activated once at the small bowel.
Where is it found?
In the brush border of the small bowel.
Which condition may result from the failure of measures to prevent autodigestion of the pancreas?
Acute pancreatitis.
List 3 possible causes of pancreatitis.
1 - Gallstones.
2 - Alcohol.
3 - Trauma.
List 5 features that are a sign of acute pancreatitis.
1 - Abdominal pain in the epigastrium radiating to the back.
2 - Nausea.
3 - Vomiting.
4 - Serum amylase and / or lipase >= 3x upper limit.
5 - Findings of acute pancreatitis on CT scan.
List the phases of acute pancreatitis.
1 - Premature activation of trypsin in acinar cells.
2 - Intra-pancreatic inflammation via activation of inflammatory and endothelial cells.
3 - Extra-pancreatic inflammation, including systemic sepsis and multi-organ failure.
List 4 treatments of acute pancreatitis.
Normally mild, so supportive therapy:
1 - Intravenous fluids to combat dehydration.
2 - Pain relief
If severe:
3 - Intensive care and multi-organ support (to combat sepsis).
4 - Therapeutic endoscopic retrograde cholangiopancreatography (ERCP), e.g. for gallstone removal.
List 5 causes of chronic pancreatitis.
1 - Alcohol abuse.
2 - hereditary disroders.
3 - Cystic fibrosis.
4 - Hypercalcaemia.
5 - Hyperlipidaemia.
List 6 treatments of chronic pancreatitis.
1 - Pain relief.
2 - Intravenous fluids to combat dehydration.
3 - Nutritional support (low fat, small and frequent meals).
4 - Synthetic pancreatic enzyme supplementation.
5 - ERCP.
Give an example of a complication of pancreatitis.
Diabetes.
