Random physiology (pancreatic secretions, etc)

Question 1

Pancreas can be divided into exocrine and endocrine. What does each function produce, where and how is it released?

Answer 1

Exocrine pancreas 80-85%: released into GI tract (outside of blood) = macromolecules (like enzymes) and electrolytes (HCO3- (bicarb) is major); released into duodenum; made in acinar (grape) and ductal cells Endocrine: hormones released into bloodstream like insulin and glucagon, as well as somatostatin made in islet cells of the pancreas

Question 2

How is bicarb secreted from the pancreas? discuss 2 models

Answer 2

Model 1: at low secretion rates of bicarb, CO2 enters pancreatic cells, converted to H2CO2 by carbonic anhydrase, then exported as HCO3- and H+ (on different sides of the cell for obvious reasons)

HCO3- is pumped out by anion exchanger (AE), which exchanges HCO3- for Cl-, Cl- then leaves out via CFTR channel - cystic fibrosis transmembrane conductance regulator, which both pumps out Cl- and digests mucous (so in CF you get extra mucous in lungs)

these secretions are stimulated by: Secretin and VIP (via cAMP -> phosporylation of CFTR) and CCK (stimulates hormonal pancreatic secretions mostly, with some electrolyte ones)

Model 2: HCO3- is needed urgently

then HCO3- is delivered from the blood, enters cell with Na+ via NBC (Na+ bicarb channel, which essentially uses low Na+ in cell to drive both Na+ and 2 HCO3- into cell)

from cell, bicarb can leave into lumen via:

CFTR channel (with some Cl- leaving that way too ) #1

anion exchanger (same as previously, HCO3- out, Cl- in, which then leaves via CFTR) #2

some evidence of direct HCO3- channel

Question 3

Describe via cell anatomy how proteins are secrted from pancreatic cells?

Answer 3

synthesized in RER -> Golgi (packaging/modification) -> condensing vacuoles which concentrate to form -> zymogen granules -> stored until stimulated in response to meals

( ACh, VIP, secretin, CCK, etc can stimulate)

Question 4

how are pancreatic enzymes activated?

Answer 4

• stored in pancreas in inactive form (zymogens) otherwise would digest pancreas
• trypsin inhibitor is co-packaged with zymogens in case some trypsin activates (pancreatic secretory trypsin inhibitor) to protect from autodigestion
• when trypsinogen released into duodenum, duodenal brush border enzymes enteropeptidase (enterokinase) cleave off tripsin activating peptide (TAP), making trypsin active
• trypsin than activates more trypsinogen -> trypsin, as well as other zymogens
• trypsin and chymotrypsin C in pancreas can inactivate itself to prevent autodigestion by cleaving itself off (protein digestion enzyme digesting protein)

Question 5

Cephalic phase of pancreatic secretion?

Answer 5

• taste/smell/sight of food induces neural response -> dorsal vagal motor nucleus (parasympa) -> intrinsic nerve ganglia via ACh, VIP -> small amount of pancreatic seccretions (usually HCO3- ), also mobilization of enzymes so they are ready near duct lumen when food gets to duodenum

Question 6

Explain gastric phase of pancreatic secretions?

Answer 6

• stomach -> stretch receptors -> nodose gangion to brain -> dorsal vagal motor nucleus out -> intrinsic ganglia (which are hooked up to secretory cells of pancreas) -> ACh and VIP - enzymes and bicarb
• mostly via secretin stimulation (secretin good at ions)
• and CCK stimulation (good at hormone secretions)

Question 7

Explain intestinal phase of pancreatic secretions?

Answer 7

• chyme enters duodenum -> secretin and CCK released in response
• secretin, mainly triggers release of electrolytes and water, so triggered by low pH in duodenum as food enters from stomach (electrolyte H+), only weak stimulus for pancreatic enzyme release
• CCK, mainly triggers release of digestive enzymes, so its release triggered by products of digestion - amino acids, and free fatty acids liberated in stomach -> transported into blood, stimulates acinoar cells to release enzymes

Question 8

How does CCK cause enzyme release (think nerves, blood, etc)?

Answer 8

• CCK can act on acinar ducts via blood (needs to get from duodenum where it is produced to pancreas)
• CCK can act on acinar cells via vagus nerve: vagal afferent fibres (nodose ganglion) -> dorsal vagal motor nucleus (efferent fibres) -> intrinsic pancreatic cholinergic neurons -> Ach, VIP released -> pancreatic enzymes released
• CCK has a small effect on increasing secretin-induced fluid secretion from ducts
• CCK also stimulates gallbladder contraction and relaxxation of sphincter of Oddi (want bile in duodenum to help with lipid digestion!)
• CCK contributes to enterogastrone response when food in duodenum (to make sure it is properly digested, not just pushed through) - > decreased acid secretion in stomach, decreased gastric emptying, increased pancreatic enzyme secretion