Pancreas and Biliary Secretion

Question 1

What percentage of the pancreas is endocrine and what percentage is exocrine?

Answer 1

Exocrine = 99%

Endocrine = 1%

Question 2

What is the function of pancreatic secretions?

Answer 2

Digestion of lipids, proteins, and carbohydrates

Neutralizing pH of acid chyme entering the duodenum

Creating suitable pH for pancreatic digestive enzymes.

Question 3

What are pancreatic secretions composed of?

Answer 3

HCO3-, Na+, K+, and water secreted by epithelial cells that line pancreatic ducts.

Enzymes secreted by acinar cells.

Question 4

What is the pH of pancreatic secretions?

Answer 4

~8.0

Question 5

What is the sphincter that holds the duodenal papilla closed when pancreatic juices are not required called?

Answer 5

Spincter of Oddi (they are regulated by endocrine control)

Question 6

What cells are located in the pancreatic acinus?

Answer 6

Duct cells: Produce + secrete alkaline fluid

Acinar cells: Produce + secrete enzymes

Question 7

Which enzymes does the pancreas produce for protein breakdown?

Answer 7

Trypsin

Chymotrypsin

Carboxypeptidases

Elastases

Question 8

Which pancreatic enzymes cleave nucleic acids?

Answer 8

Nuclease

Question 9

Which pancreatic enzymes break down carbohydrates?

Answer 9

Pancreatic amylase

Question 10

Which pancreatic enzymes break down lipids?

Answer 10

Pancreatic lipase

Cholesterol esterase

Phospholipase

Question 11

Why is the pancreas itself not digested by the enzymes it produces?

Answer 11

Proteases are synthesized in inactive form:

Trypsinogen is activated by enterokinase which is produced in the small intestine and then trypsin activates chymotrypsin and carboxypeptidase.

Trypsin inhibitor is also produced in acini

Pancreas can digest itself within hours in the case of acute pancreatitis.

Question 12

How do acinar cells secrete enzymes?

Answer 12

Inactive proteases are constantly synthesised and stored as zymogen granules (secretory vesicles)

Constitutive secretory pathway - very low levels

Regulated secretory pathways - Receptors for cholecystokinin and ACh which activate phospholipase - C which activates PKC pathways leading to production of enzymes. No specific enzyme is produced rather all are produced simultaneously.

Question 13

Where does bicarbonate come from in duct cells?

Answer 13

CO2 diffuses in blood and combines with H2O to form H2CO3 via carbonic anhydrase.

Bicarbonate produced by stomach when producing acid is then used by the pancreas. This bicarbonate is taken in by NBC (sodium-bicarbonate cotransporter)

Question 14

How does bicarbonate get produced into the lumen?

Answer 14

HCO3- is exchanged for Cl-

Question 15

How is H+ from H2CO3 taken out of the lumen into the blood?

Answer 15

Via a Na+/H+ exchanger (Aka NHE-1)

Na+ gradient drives NHE-1 and this is set up by Na+/K+ ATPase

K+ and Cl- are leaked out

The movement of HCO3 ions to the lumen sets up an osmotic gradient and water moves from blood to duct cells to lumen creating an isometric HCO3 solution

Question 16

Summary:

Answer 16

On basolateral side we have the following transporters:

Na+/H+ exchanger allowing us to remove H+ from the cytosol after production by carbonic anhydrase.

Na+/2HCO3- co-transporter allowing HCO3 entry into the cell using alkaline drag.

Na+/K+ ATPase which removes Na from the cell in exchange for K+ entering the cell

A K+ channel to release K+ from inside the cell after entry through Na+/K+ ATPase

How do we get HCO3 into the cell???

CO2 can diffuse into the cell from the blood and combines with H2O in the cytosol to form HCO3 + H.

Production of gastric acid creates HCO3 which is released into blood creating an alkaline drag. This HCO3 can get into the cell by being co-transported with Na+.

How do we get the HCO3 to the lumen???

On luminal side:

CFTR in response to cAMP pumps Cl- out of the cell into the lumen. The Cl- gradient produced by this pump is exchanged for HCO3 using a Cl/HCO3 exchanger on the lumen side.

Question 17

How is pancreatic secretion regulated?

Answer 17

ACh: vagus nerve (stimulates HCO3 and enzyme release)

Secretin: from duodenal S cells (stimulates production of HCO3)

CCK from gut mucosal I cells (stimulates enzyme production/secretion and relaxes the sphincter of Oddi)

Somatostatin from intestinal D cells. (generally inhibitory)

Question 18

How is the spincter of Oddi relaxed?

Answer 18

In response to CCK production

Question 19

What are the phases of pancreatic secretion?

Answer 19

Cephalic phase: Vagus nerve. Ach, 10 - 20% of total secretion

Gastric phase: Gastric phase adds anoher 5 - 10% (gastrin binds CCK receptors)

Intestinal phase: Most important phase (80%) (huge increase in CCK, secretin, and ACh)

Question 20

Where is secretin produced?

Answer 20

Chemosensitive S cells of the duodenum

Question 21

what is the stimulus for secretin production?

Answer 21

Acid: H+ ion contract with mucosa (S cells): pH<4

Also protein catabolites (minor trigger)

Question 22

What is the main action of secretin?

Answer 22

Stimulates HCO3 secretion by pancreas duct cells, also a neuropeptide, decreases gastric H+ secretion and causes pyloric sphincter contraction.

Question 23

What kind of signalling does secretin stimulate?

Answer 23

cAMP signalling.

Question 24

What is the half life of secretin?

Answer 24

5 minutes

Question 25

What kind of structure does secretin have?

Answer 25

Single isoform with similar structure to glucagon VIP and GIP

Question 26

Where is CCK produced?

Answer 26

Synthesized by chemosensitive I cells in the gut mucosa

Question 27

What is the stimulus for CCk secretion?

Answer 27

Long chain fatty acids

Peptides, AAs (protein digestion products)

Inhibited by trypsin in lumen and somatostatin from D cells in small intestine

CCK-releasing peptide (produced in intestine) and monitor peptide (produced by pancreas) provides positive feedback

Question 28

What are the main actions of CCK?

Answer 28

Stimulates pancreatic acinar cell enzyme production + secretion

Relaxation of the sphincter of Oddi (+GB contraction)

Also functions as a neuropeptide (CNS: regulates food intake, anxiety, analgesia)

Inhibits gastric emptying, stimulates enterokinase synthesis enhances intestinal motility and glucagon release.

Question 29

What does bile do?

Answer 29

Emulsifies fats to increase access of lipases to fats

Absorption facilitates diffusion into intestinal epithelial cells.

Question 30

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Answer 30

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