Functions and Secretions of the Pancreas Flashcards
What is the function of the pancreas?
Digestion of nutrients: fat, protein…
Provides the appropriate environment for enzymatic digestion in the small bowel = bicarbonate and enzyme secretion, neutralise stomach acid.
The pancreas has an endocrine and exocrine function
What is the exocrine structure of the pancreas?
Pancreas is divided into lobules - intralobular duct, interlobular duct and then into a main duct going into the lumen of the GI tract.
The main pancreatic duct merges with the common bile duct to form a swelling in the duodenal wall called the ampulla of Vater. The muscular wall is thickened, forming the sphincter of Oddi.
The pancreas empties secretions into the descending part of the duodenum at the papilla the point where the celiac trunk stops supplying the gut and the superior mesenteric artery takes over.
What is the function of the sphincter of Oddi?
Function of Oddi is to regulate and prevent reflux
What is the structure of the pancreatic lobules?
Within each lobule resides the functional secretory unit of the gland composed of an acinus and a small intercalated duct.
Acinus = ‘berry-like’ structure. Cluster of acinar cells that synthesize and secrete proteins into the lumen of the epithelial structure. They secrete zymogens (inactive enzyme precursors), digestive enzymes and an isotonic, plasma-like fluid that accompanies the secretory proteins.
How many grams of protein a day does the pancreas make?
15g of protein a day.
In an unstimulated state how do acinar cells in the pancreas secrete the enzymes?
Acinar cells secrete digestive proteins at a low level via a constitutive secretory pathway.
Stimulation of acinar cells in the pancreas what mechanism is initiated?
Stimulation activats CCK receptors and the muscarinic acetylcholine (ACh) receptors located on the basolateral cell membrane.
These receptors signal through a common pathway - the phospholipase C (PLC/PKC) Ca2+ signal transduction pathway, leading to increased enzyme secretion.
What are the centroacinar cells function and where are they located in the pancreas?
Centroacinar cells are the very first of the intercalated duct and thus are located at the junction of the pancreatic acinar cells and duct cell. Their function is questioned.
Goblet cell function in the pancreas?
Produce mucus important for
- Lubrication
- Hydration
- Mechanical protection of surface epithelium
- Immunologic role - binding of pathogens and interacting with immune-competent cells ultimately preventing pancreatic infections.
When acinar cells in the pancreas are stimulated what are the routes of activation?
- Ach and CCK both ultimately activate PKC and the release of calcium.
- VIP and secretin both activate adenylyl cyclase, leading to the production of cAMP and the activation of PKA.
What do I cells secrete in the pancreas?
CCK.
In response to fat, stimulating the release of CKK, this goes to the gall bladder and contracts.
What is the role of pancreatic duct cells?
Secretes HCO3- rich fluid that alkalinizes and hydrates the protein-rich primary secretions of the acinar cell.
Mechanism of secretion:
1. Cl- HCO3- exchanger
2. Carbonic anhydrase generated
3. Secretin most powerful stimulus for HCO3-. This induces CFTR and Na-HCO3-
4. Ach activation also impacts on HCO3- secretion.
What is the role of the CFTR and cAMP Cl- channel?
Cystic fibrosis transmembrane conductance regulator (CFTR), and a cAMP-activated Cl- channel present on the apical membrane of pancreatic duct cells. When the CFTP is open it allows Cl- to diffuse from the cytoplasm into the lumen, after which the Cl- cycles back into the cell via the Cl-HCO3 exchanger. This process is termed Cl- recycling.
What is secretin and how is it secreted?
S cells secrete Secretin in the small bowel mucosa stimulates HCO3- and fluid secretion by the Ducts, predominantly in response to duodenal acidification. In the fed state this increases.
Secretin is the most important humoral regulator of ductal secretion. Activation of secretin receptors on the duct cell stimulates adenylyl cyclase, increasing [cAMP]and triggers PKA, causing stimulation of the apical CFTR Cl- channel and the basolateral Na/HCO3 cotransporter.
How is HCO3- secreted?
Secretin stimulates the release of HCO3- from the basolateral Na/HCO3- cotransporter. HCO3- secretion is also regulated by acetylcholine and the muscarinic receptors on the duct cell causes increased [Ca2+] and activation of Ca2+ dependent PKC in pancreatic duct cells.
What is cystic fibrosis, how is it caused and what are the effects in the pancreas?
CF is a disease caused by a mutation in the CF gene, this alters the function of CFTR because it is prematurely degraded. The loss of CFTR expression at the plasma membrane disrupts apical transport processes of the duct cell and results in the decreased secretion of HCO3- and water by the ducts.
This results in a protein-rich primary secretion which thickens within the duct lumen and leads to ductal obstruction and eventually pancreatic tissue destruction. Causing a deficiency of pancreatic enzymes leading to maldigestion of nutrients. Diabetes is commonly seen.
What is the composition and function of pancreatic secretion?
The product of acinar, duct and goblet cells results in secretion of a pancreatic juice which is protein-rich embedded within an alkaline fluid.
1.5L produced a day. 5-15g of protein in it. The pancreas secretes over 20 different proteins, most of which are zymogens or an active digestive enzyme.
Describe the change in pancreatic secretion between the fed and fasted state.
Fasted state = low level release of pancreatic enzymes.
Fed state = Increases to levels that are 5 -20 fold over the basal levels. The composition of the pancreatic fluid will also alter with stimulation.
Describe the role of CCK in pancreatic stimulation and how it is secreted?
CCK from Duodenal I cells stimulates pancreatic acinar cells to increase protein secretion.
Fatty meal - Increase CCK by 5-10 fold, directly via CCK A receptor or indirectly via the parasympathetic NS.
CCK secretion is also stimulated by CCK - releasing factors eg. LCRF (Luminal CCK Releasing Factor), they secrete into the gut lumen which stimulates CCK.
Why is there no CCK stimulation in the fasted state?
In the fasted state, LCRFs are degraded by digestive enzymes so there is no CCK stimulation. However, during a meal, the digestive enzymes act on the chime and LCRFs stimulating I-cells to release CCK and pancreatic secretion.
What inhibits pancreatic secretions?
Somatostatin released from D-cells and from pancreatic somatostatin from S-cells is found in 14 forms.
It works by inhibiting the release of CCK and Secretin as well as insulin and glucagon.
Octreotide is clinically used to inhibit pancreatic secretions.
Describe the first phase of pancreatic secretion
Cephalic Phase:
Sight, taste, smell of food. Accounts for 25%. Stimulation of Ach receptors on the acinar cell and a bit to duct cells. (No involvement of CCK or secretin as there is no fat to stimulate them).
Describe the second phase of pancreatic secretion
Gastric Phase:
Accounts of 10-20%.
1. The release of hormones notably Gastrin (stimulated by luminal peptides/amino acids) in G cells of the antrum. This signals through CCK receptor on acinar cells (gastrin is a weak CCK agonist)
2. Stimulating neural pathways. Gastric distention stimulates low levels of pancreatic secretion, through a vagovagal gastropancreatic reflex.
Describe the third phase of pancreatic secretion
Intestinal Phase:
Accounts for 50-80%.
Chyme entering the proximal small intestine stimulates a pancreatic secretion by three major mechanisms:
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, which stimulates acinar cells to release digestive enzymes.
3. Lipids also activate a vagovagal enteropancreatic reflex that stimulates acinar cells.
Pattern of pancreatic enzymatic secretion depends on the relative composition of chime (e.g. high carb vs fat)
