Functions and Secretions of the Pancreas

Question 1

What is the function of the pancreas?

Answer 1

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

Question 2

What is the exocrine structure of the pancreas?

Answer 2

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.

Question 3

What is the function of the sphincter of Oddi?

Answer 3

Function of Oddi is to regulate and prevent reflux

Question 4

What is the structure of the pancreatic lobules?

Answer 4

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.

Question 5

How many grams of protein a day does the pancreas make?

Answer 5

15g of protein a day.

Question 6

In an unstimulated state how do acinar cells in the pancreas secrete the enzymes?

Answer 6

Acinar cells secrete digestive proteins at a low level via a constitutive secretory pathway.

Question 7

Stimulation of acinar cells in the pancreas what mechanism is initiated?

Answer 7

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.

Question 8

What are the centroacinar cells function and where are they located in the pancreas?

Answer 8

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.

Question 9

Goblet cell function in the pancreas?

Answer 9

Produce mucus important for

1. Lubrication
2. Hydration
3. Mechanical protection of surface epithelium
4. Immunologic role - binding of pathogens and interacting with immune-competent cells ultimately preventing pancreatic infections.

Question 10

When acinar cells in the pancreas are stimulated what are the routes of activation?

Answer 10

1. Ach and CCK both ultimately activate PKC and the release of calcium.
2. VIP and secretin both activate adenylyl cyclase, leading to the production of cAMP and the activation of PKA.

Question 11

What do I cells secrete in the pancreas?

Answer 11

CCK.

In response to fat, stimulating the release of CKK, this goes to the gall bladder and contracts.

Question 12

What is the role of pancreatic duct cells?

Answer 12

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.

Question 13

What is the role of the CFTR and cAMP Cl- channel?

Answer 13

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.

Question 14

What is secretin and how is it secreted?

Answer 14

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.

Question 15

How is HCO3- secreted?

Answer 15

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.

Question 16

What is cystic fibrosis, how is it caused and what are the effects in the pancreas?

Answer 16

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.

Question 17

What is the composition and function of pancreatic secretion?

Answer 17

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.

Question 18

Describe the change in pancreatic secretion between the fed and fasted state.

Answer 18

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.

Question 19

Describe the role of CCK in pancreatic stimulation and how it is secreted?

Answer 19

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.

Question 20

Why is there no CCK stimulation in the fasted state?

Answer 20

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.

Question 21

What inhibits pancreatic secretions?

Answer 21

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.

Question 22

Describe the first phase of pancreatic secretion

Answer 22

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).

Question 23

Describe the second phase of pancreatic secretion

Answer 23

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.

Question 24

Describe the third phase of pancreatic secretion

Answer 24

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)

Question 25

What is the reason for the pancreas to secrete zymogens?

Answer 25

Digestive proteins are stored in secretory granules as inactive precursors. Zymogens become active after coming into contact with the small bowel brush border enzyme enterokinase. This converts trypsinogen into trypsin which in turn initiates the conversion of all other zymogens to their active forms.

Question 26

Why are secretory granule membrane impermeable to proteins?

Answer 26

So that the zymogens and active digestive enzymes are isolated from proteins in the cytoplasm and other intracellular compartments and so that they don’t digest them.

Question 27

How does the pancreas prevent autodigestion?

Answer 27

1. Digestive proteins are stored as zymogens in secretory granules.
2. The secretory granule membrane is impermeable to zymogens and active proteins to prevent digestion of the cells proteins.
3. Enzyme inhibitors (e.g pancreatic trypsin inhibitor SPINK 1) are co-packaged in the secretory granule.
4. The condensation of zymogens, the low pH, and the ionic conditions within the secretory pathway further limit enzyme activity.

Question 28

What happens the pancreas fails?

Answer 28

Causes acute pancreatitis (inflammation)

GET SMASHED: Gallstone; Ethanol; Trauma

Question 29

How is acute pancreatitis characterised?

Answer 29

1. Characteristic abdominal pain - associated with nausea and vomiting.
2. Serum analysis and of lipase is >3 times the upper limit
3. CT scan shows characteristic findings of acute pancreatitis.

Question 30

What are the phases of an acute pancreatitis?

Answer 30

1. Premature activation of trypsin within the pancreatic acinar cells due to: disruption of Ca2+ signalling in the acinar cells; cleavage of trypsinogen to trypin by the lysosomal hydrolase cathepsin-B; decrease activity of the intracellular pancreatic trypsin inhibitor SPINK 1.
2. Intra-pancreatic inflammation
3. Extra-pancreatic inflammation including systemic sepsis and multi-organ failure.

Question 31

How can acute pancreatitis be treated?

Answer 31

IV fluids to combat dehydration. Pain relief. May need a Therapeutic Endoscopic Retrograde Cholangiopancreatography (EPCP) to treat problems in the biliary or pancreatic duct system eg. gallstones or blockages.

Question 32

What is chronic pancreatitis?

Answer 32

Inflammation of the pancreas that does not heal causes permanent damage. Common cause is chronic alcohol abuse, can he hereditary, CF, hypercalcemia or hyperlipidemia.

Question 33

How can chronic pancreatitis be treated?

Answer 33

Pain management, IV hydration and nutritional support. Supplemented with synthetic pancreatic enzymes if the pancreas does not secrete enough of its own.
Chronic pancreatitis can lead to calcification of the fibrotic pancreas causing the tissue to harden.
Diabetes can commonly cause.

Question 34

What is the difference between acute and chronic pancreatitis?

Answer 34

Acute = occurs slowly, causing acute pain lasting for several hours to days and resolves on its own. 
Chronic = Lasts more than 6 months even up to years, due to constant scarring of the pancreas and inflammation.