Functions and Secretions of the Pancreas

Question 1

What are the 3 main functions of the pancreas?

Answer 1

• digestion of nutrients (zymogens)
• neutralising acidic chyme (bicarbonate)
• regulation fed and fasted states (endocrine)

Question 2

What is the ampulla of Vater and the sphincter of Odi?

Answer 2

Ampulla of Vater - major pancreatic duct merges with the common bile duct to form a swelling in the duodenal wall (major duodenal papilla)
Sphincter of Odi - thickened muscular wall, controlled exocrine secretions through the ampulla of vater

Question 3

Why is the sphincter of oddi required?

Answer 3

Prevents reflux of duodenal contents into pancreas which could damage it

Question 4

What is each secretory unit of the pancreas made up of?

Answer 4

an acinus (a cluster of acinar cells that secrete zymogens) and a small intercalated duct

Question 5

What are the 2 functions of duct cells?

Answer 5

Make bicarbonate rich fluid - neutralise acidic chyme

Bath proteins to prevent thick secretions blocking ducts

Question 6

What are centroacinar cells?

What are goblet cells?

Answer 6

• first cells of the intercalated duct, located at the junction of the pancreatic acinar cells and duct cells, function unknown
• mucus production, lubrication, hydration, mechanical protection of surface of epithelial cells

Question 7

What are the 2 routes of activation of protein secretion from the pancreatic acinar cells?

Answer 7

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

Question 8

What, along with protein, is secreted from the acinar cells? What activates its secretion?

Answer 8

secrete isotonic, Na-Cl ich fluid which hydrates the protein rich material.
same triggers as protein secretion ensure they occur simultaneously, ACh and CCK receptors

Question 9

What is the principal function of pancreatic duct cells?

Answer 9

secrete a bicarbonate rich fluid that alkalinises and hydrates the protein-rich primary secretions

Question 10

What triggers duct cell secretions?

1. What the exchanger involved?
2. Which enzyme is generated?
3. Which is the most powerful trigger?

Answer 10

Ach and secretin

1. Cl-HCO3 exchanger and CFTR
2. carbonic anhydrase
3. secretin and ACh to an extend

Question 11

How does cystic fibrosis affect the pancreas/

Answer 11

CFTR, less Cl- can diffuse from cytoplasm into the lumen
Lowers activity of Cl–HCO3 transporter
Decreased secretion of bicarbonate and water by the duct cells
Results in thick protein rich secretions –>ductal obstruction.
Can lead to steatorrhea and diabetes

Question 12

Give some examples of inactive zymogens secreted by the pancreas.
Give some examples of active digestive enzymes secreted by the pancreas.

Answer 12

• trypsinogen, chymotripsinogen, proelatase, procarboixupeptidase A, procarboxypeptidase B
• lipase and co-lipase

Question 13

What is the role of CCK in pancreatic stimulation?

Answer 13

Released of duodenal I cells, stimulates acinar cells to increase protein secretion
Fatty meal increases CCK levels

Question 14

What inhibits pancreatic secretion?

What are the clinical applications of this?

Answer 14

somatostatin
inhibits the release of CCK and secretion, as well as insulin and glucagon
analogues of somatostatin used clinically to inhibit pancreatic secretion

Question 15

What are the 4 phases of pancreatic secretion?

Answer 15

Basilic - baseline secretions of the pancreas that doesn’t change
Cephalic - sight, taste and smell of food, mediated by ACh on acinar cell
Gastric - gastrin –> CCK receptor on acinar cells, vasovagal gastropancreatic reflex (distention of stomach)
Intestinal - gastric acid in duodenum stimlulates secretin from S cells, duct cells secrete HCO3.
- lipids stimulate CCK –> acinar cells –> proteins
- lipids stimulate vagovagal enteropancreatic reflex –> acinar cells

Question 16

How does the pancreas prevent autodigestion? x4

Answer 16

1. digestive proteins are store in secretory granules as inactive precursors
   Zymogens only become activated after coming into contact with the small intestine brush border enzyme eneterokinase. This converts trypsinogen into tyrosine which in turn initiates the activation of all other zymogens to their active forms.
2. The secretory granule membrane is impermeable to proteins.
3. Enyzme inhibitors such as pancreatic trypsin inhibitor SPINK1 are co-packaged in the granule
4. the condensation of zymogens, the low pH, and the ionic condition within the secretory pathway further limit enzyme activity

Question 17

What happens when the mechanisms to prevent autosuggestion fail?
What are the causes of this?
What are the 3 factors, of which 2 are needed to diagnose acute pancreatitis?

Answer 17

acute pancreatitis
GETSMASHED: gallstones, ethanol, trauma, steroids, mumps, autoimmune, scorption sting, hypercalcaemia, ERCP, drugs
1. epigastric pain that radiates to the back, associated with nausea and vomitting
2. serum amylase and/or lipase more than 3x upper limit of normal
3. characteristic findings of pancreatitis on CT scan

Question 18

What are the 3 stages of the pathophysiology of acute pancreatitis?

Answer 18

Phase 1:
- premature activation of trypsin caused by disruption of Ca2+ signalling or cleavage to trypsin by cathepsin-B, decreased activity of SPINK1
Phase 2:
- intra pancreatic inflammation (confined to pancreas)
Phase 3:
- extra-pancreatic inflammation including systemic sepsis and multi-organ failure

Question 19

What is the treatment of acute pancreatitis?

Answer 19

Therapy tends to be supportive
Resting the pancreas, IV fluids, hourly fluid balance, pain management
If severe, may require intestine care and multi-organ support
Therapeutic ERCP to treat complications such as gallstones, blockage, leaks, pseudocyst

Question 20

What is chronic pancreatitis?
What is the most common cause?
What are the other possible causes?

Answer 20

inflammation of the pancreas that does not heal or improve - it gets worse over time and leads to permanent damage
Chronic alcohol use 
Other causes:
hereditarry disorders of the pancreas
CF
hypercalcaemia 
hyperlipidemia

Question 21

What is the treatment of chronic pancreatitis?

Answer 21

hospitalisation for pain management, IV hydration, nutritional support
synthetic pancreatic enzymes
low fat diet, small frequent meals
stent to keep open a narrowed pancreatic or bile duct
may need insulin for diabetes