ICL 12.2: Exocrine Pancreas

Question 1

what are the 2 major types of glands of the pancreas?

Answer 1

1. acini = secrete digestive enzymes into the duodenum

2. islets of Langerhans = secrete endocrine hormones like insulin and glucagon and somatostain directly into the blood

Question 2

what are the characteristics of pancreatic juice?

Answer 2

alkaline (pH = 8) so that once the food gets to the duodenum, the duodenal contents are pH = 6-7 and by the time it gets to the jejunum it’s totally neutral

pancreatic juice has really high HCO3- content

it works with the bile and intestinal juices to neutralize the gastric acid so that the digestive enzymes can function properly

Question 3

which cells secrete somatostatin?

Answer 3

delta cells of the islets of Langerhnas in the pancreas

Question 4

what is the function of somatostatin?

Answer 4

1. acts locally to depress secretion of both insulin and glucagon
2. decreases motility of the stomach, duodenum, and gallbladder
3. decreases both secretion and absorption in the GI tract

it does this so we can sustain ourselves for a longer period of time

Question 5

the water that gets secreted into the duodenum from the pancreas come from which type of cell?

Answer 5

duct cells!

the epithelial cells of the ductules and ducts that lead from the acini also secrete bicarbonate

so the acini secrete digestive enzymes that then need water from the duct cells to move to the duodenum and it won’t happen without them

Question 6

if there is acidic content in the duodenum, which hormone is secreted by the duodenum and by which cells?

Answer 6

secretin

secretin is secreted by S-cells which enters the pancreas and stimulates the secretion of HCO3 by duct cells

CCK regulates the secretion of digestive enzymes by the acini

Question 7

how is HCO3 secreted by the pancreas?

Answer 7

it’s secreted by the gut cells

there’s a Na/HCO3 cotransporter that brings in HCO3 from the blood into the pancreatic duct cell – there is also diffusion of CO2 and H2O into the pancreatic duct cells which then combine to form H2CO3 via carbonic anhydrase

there’s a Na/H exchanger that pumps H+ out and Na+ in so that the H+ from H2CO3 isn’t just hanging out in the cell AND there’s a Na/K ATPase pump to pump that Na+ back out and K+ in AND a K+ channel to pump the K+ out that’s being pumped in by the Na/K ATPase pump

then the HCO3 in the duct cell gets secreted into the duct lumen via a HCO3/Cl antiporter that pumps HCO3 out and Cl into the duct cell –> there’s also a separate Cl channel pumping Cl into the duct lumen to make sure there’s enough Cl to sustain this pump

Question 8

what are the steps of bicarbonate secretion

Answer 8

1. carbon dioxide diffuses to the interior of the cell from the blood and combines with H2O to form carbonic acid.
2. the carbonic acid dissociates into bicarbonate ions and hydrogen ions (HCO3−and H+).
3. additional bicarbonate ions enter the cell through the basolateral membrane by co-transport with Na+ ions.
4. the bicarbonate ions are then exchanged for chloride ions (Cl−) by secondary active transport through the luminal border of the cell into the lumen of the duct
5. the chloride that enters the cell is recycled back into the lumen by special chloride channels
6. the hydrogen ions formed by dissociation of carbonic acid inside the cell areexchanged for sodium ions through the basolateral membrane of the cellby secondary active transport
7. sodium ions also enter the cell by co-transport with bicarbonate across the basolateral membrane
8. sodium ions are then transported across theluminal borderinto thepancreaticduct lumen. The negative voltage of the lumen also pulls the positively charged sodium ions across the tight junctions between the cells
9. the overall movement of sodium and bicarbonate ions from the blood into the duct lumen creates an osmotic pressure gradient that causes osmosis of water also into thepancreaticduct, thus forming an almost completely isosmotic bicarbonate solution.

Question 9

how does secretin increase HCO3 secretion by the pancreas?

Answer 9

it binds to its receptor on the pancreatic duct cell and increases cAMP levels

cAMP increases Cl- secretion into the duct via CFTR channel which then stimulates the HCO3/Cl antiporter to pump HCO3 out of the pancreatic duct cells and Cl- into the cell

Question 10

which enzymes are responsible for protein digestion?

Answer 10

1. trypsinogen
2. chymotrypsinogen
3. proelastase
4. procarboxypeptidase

these are all inactive until they get to the duodenum

all of these are from the pancreas and without them you wouldn’t digest enzymes because only 10% of digestion happens in the stomach! same with lipid digestion, the lipid degrading enzymes are the pancreas

Question 11

what are the functions of trypsin inhibitor?

Answer 11

it prevents trypsin from digesting the pancreas

trypsinogen gets activated by an enzyme secreted in the duodenum called enterokinase – once it’s activated into trypsin, it can autocatalytically activate itself along with chymotrypsin and proelastase

so trypsin inhibitor is around to make sure trypsinogen doesn’t get activated into trypsin on accident in the pancreas

Question 12

what is the function of trypsin, chymotrypsin, and carboxypolypeptidase?

Answer 12

they’re secreted as inactive forms then activated in the Small intestinal tract

trypsin is the most abundant

trypsin/chymotrypsin split proteins into poly- and oligo-peptides
carboxypolypeptidase splits peptides into amino acids

Question 13

what is the function of pancreatic amylase?

Answer 13

hydrolyzes starches, glycogen, and most other carbohydrates (except cellulose) to form mostly disaccharides and a few trisaccharides

it does this by breaking alpha 1-4 bonds

Question 14

what is the function of pancreatic lipase?

Answer 14

hydrolyzes neutral fat into fatty acids and monoglycerides

Question 15

what is the function of cholesterol esterase?

Answer 15

hydrolyzes cholesterol esters

Question 16

what is the function of phospholipase?

Answer 16

splits fatty acids from phospholipids

Question 17

what is Zollinger-Ellison syndrome?

Answer 17

inactivation of pancreatic enzymes in the duodenum due to excess acid secretion in the stomach → diarrhea and Peptic ulcer

there’s usually a benign tumor in the duodenum increasing gastrin secretion –> the gastrin enters the bloodstream and goes to the stomach so the intestinal gastrin increases HCl secretion by parietal cells of the stomach which causes peptic ulcers!!

the low pH also inactivates pancreatic enzymes which causes diarrhea because the nutrients aren’t being dissolved anymore and there’s osmotic movement of water into the intestinal lumen!

Question 18

what is acute pancreatitis?

Answer 18

severe damage of pancreas/duct blockagepools pancreaticsecretion –> alcohol can also cause the trypsin inhibitor to be overwhelmed

trypsin inhibitor overwhelmed and enzymes gets activated

leads to lifetime ofpancreatic insufficiency/lethal

Question 19

which basic stimuli cause pancreatic secretion?

Answer 19

1. acetylcholine
2. cholecystokinin
3. secretin

acetylcholine and CSK stimulate the production of digestive enzymes by acinar cells

secretin stimulatessecretionof water and bicarbonate by theductal epithelium

Question 20

what enzymes are being activated during the cephalic and gastric phase?

Answer 20

1. acetylcholine (vagus nerve) in cephalic phase
2. acetyl choline and gastrin in gastric phase once the food actually reaches the stomach

moderate secretion of enzymes in the pancreas = 20 % cephalic, 5-10 % gastric

these enzymes do not reach duodenum so there’s no fluidsecretion! they are just stored in the acini

Question 21

what enzyme activity is happening during the intestinal phase?

Answer 21

1. secretin secreted byS cellsof the duodenum and jejunum when acid chyme enters the duodenum

leads to ecretion of HCO3-

2. cholecystokinin (CCK) secreted byI cells of the duodenum and upper jejunum due to the presence ofpartial protein digestion products andfatty acidsin the chime.

leads to secretion of digestive enzymes and bile (70-80%)

Question 22

how is the pancreas associated with cystic fibrosis?

Answer 22

there is pancreatic insufficiency with cystic fibrosis!!

this is because CFTR CL/HCO3 exchanger is essential for formation and release of HCO3 into the lumen of the duct and without it, digestive enzymes will get stuck in the acini

if that happens, they get autocatylitically activated and they start to digest the pancreas and you eventually get pancreatitis