Pancreatic, Salivary and Gastric Secretions

Question 1

Functions of saliva

Answer 1

Lubricate food
Form protective buffer
Initiates starch digestion

Question 2

Function of pancreatic juice

Answer 2

Neutralises stomach acids (as is alkaline)

Completes digestion

Question 3

Outline the structure or a salivary/pancreatic gland (passage of secretions)

Answer 3

Lobules are one secretory unit, comprised of an acinus (group of secretory cells) lining an intercalated duct
Intercalated ducts drain into intralobular duct
Intralobular ducts drain into interlobular/extralobular ducts
These drain into salivary/pancreatic duct

Question 4

Three types of salivary gland, their contents and contribution to total?

Answer 4

Parotid - serous secretion (amylase containing), 25%

Submandibular - serous (amylase containing) and mucous (mucin containing), 70%

Sublingual - mucous secretion (mucin containing), 5%

Question 5

Functions of serous salivary component?

Answer 5

Lubrication (speech) and moistening (enzymes)
Germicidal
Protects teeth

Question 6

Functions of mucous salivary component?

Answer 6

Lubrication
Diffusion barrier to nutrients, drugs, toxins
Traps microbes
Protects against proteases

Question 7

How is saliva secreted?

Answer 7

Primary secretion
— basolateral NKCC accumulates Cl- in acinar cell, so Cl- diffuses across apical
—basolateral Na/K pumps Na out to power above transporter, high interstitial Na and negative charge of Cl- in lumen sets up paracellular diffusion gradient for Na into lumen through tight junctions
— Water follows
— Primary secretion therefore isotonic saline (like plasma)

Secondary Modification
— Ductal cells modify primary secretion
— Na reabsorbed through eNaC and Na/H exchanger powered by basolateral Na/K
— Cl reabsorbed through Cl/HCO3 exchanger exiting through Cl channel
— HCO3 consequently secreted
— K lost through apical K/H exchanger powered by Na/K
— water content not modified as ductal cells have low permeability
— more ions exit than enter though, so final saliva is hypotonic

Question 8

What regulates salivary secretions?

Answer 8

ANS

Para = ACh (M3–> IP3–>Ca->protein kinases—> increase apical cl permeability and basolateral k permeability/cytoskeletal elements export protein containing vesicles increases primary secretion, decreases secondary secretion
— large volumes of watery saliva

Sym (less pronounced) = NA (A—>phospholipase C same mech as above) or (B—>raises cAMP and PKA—> amylase secretion producing viscous saliva

Question 9

Acinar cell secretion mechanism?

Answer 9

Same as salivary primary secretion, except chloride channel is CFTR

Question 10

Ductal cell mechanism of secretion?

Answer 10

Same as secondary modification in salivary glands

Question 11

What enzymes are present in pancreatic secretions?

Answer 11

Proteases, amylases, lipases, nucleases

Question 12

How is autodigestion prevented?

Answer 12

Packaging as zymogens (inactive enzymes activated in SI)

Protease inhibitors in secretory vesicles

Nondigestive proteases to degrade prematurely activated enzymes

Question 13

Which digestive phases regulate pancreatic secretion, by what mechanism?

Answer 13

Cephalic phase — ACh (vagal nerve)
Gastric phase — ACh and gastrin (G cells, stimulated by vagus)
Intestinal phase — ACh, secretin (S cells) and CCK (I cells)

Question 14

Which pancreatic cells do ACh, CCK, gastrin and secretin act on?

Answer 14

ACh - ductal and acinar
CCK - ductal and acinar
Gastrin - ductal
Secretin - ductal

Question 15

Mechanism by which ACh induces secretion?

Answer 15

M3 is Gq coupled, IP3 induces Ca2+ release
Ca2+ and DAG activate PKC, PKC activates apical chloride channels and basolateral potassium channels, increasing chloride secretion

Question 16

Mechanism of action of secretin?

Answer 16

Gs coupled, PKA activating channels

Question 17

How many litres of GI secretions per day?

Answer 17

7

Question 18

What are the components of gastric secretion, and functions?

Answer 18

H+ = acidify contents of stomach
Pepsinogen = precursor to pepsin, digests proteins
Mucus and HCO3- = protective layer to prevent digestion of stomach
Intrinsic factor = used in SI to promote VitB12 absorption

Question 19

Which cells secrete gastric acid and intrinsic factor?

Answer 19

Oxyntic glands

Question 20

What endocrine factors released where in stomach by endocrine cells?

Answer 20

Gastrin = stims
Somatostatin = inhibits
Histamine = paracrine, stims 

Pyloric antrum

Question 21

Which cells secrete pepsinogen?

Answer 21

Chief cells

Question 22

Which cells secrete mucous?

Answer 22

Mucous cells

Question 23

What do superficial epithelial cells secrete in stomach?

Answer 23

Mucus and HCO3-

Question 24

When unstimulated, what kind of solution does the stomach secrete? From which cells?

Answer 24

Isotonic solution - from superficial epithelial cells

Question 25

When stimulated, how does the ionic content of the gastric secretion change and why?

Answer 25

Parietal cells begin secreting gastric acid, Na+ content goes down and H+ and Cl- content goes up

Question 26

What happens between unstimulated to stimulated parietal, oxyntic cell?

Answer 26

When unstimulated, lots of tubulovesicles in the subapical cytoplasm containing H/K ATPase - the apical cytoplasm is deeply invaginated

When stimulated, these tubulovesicles fuse with the apical membrane, forming canaliculi to increase surface area for secretion

Question 27

Mechanism of action for producing gastric acid when parietal cell is stimulated

Answer 27

Carbonic anhydrase catalyses hydration of CO2 —> HCO3- and H+

H+ moves out into lumen via H/K ATPase exchanger (K recycled through apical channels)

HCO3- moves out of basolateral membrane into interstitial fluid through Cl-/HCO3- exchanger

Cl- moves through apical into lumen to form HCl

Water follows

Question 28

What prevents H/K tubulovesicles from acidifying parietal cells?W

Answer 28

Tubulovesicles have low potassium permeability, so H/K exchanger doesn’t work until it fuses with the apical membrane

Question 29

What happens to blood during and just after meal?

Answer 29

Alkalinisation due to HCO3- being moved into blood from parietal cells

Question 30

Which drug can inhibit the H/K ATPase?

Answer 30

Omeprazole

Question 31

What three mechanisms trigger the cytoskeletal arrangement induced by protein kinase activation that mediates the insertion of tubulovesicles in parietal cells? (Basically, what causes gastric acid secretion?)

Answer 31

Neurocrine
— ACh from vagus (M3-Gq coupled-IP3-Ca-PKC)

Endocrine
— Gastrin from G cells (CCKb receptor-Gq coupled-IP3-Ca-PKC)

Paracrine
— Histamine from Enterochromaffin-like cells (H2-Gs coupled-PKA)

Question 32

What does ranitidine do? Why is it SO effective if there are two other mechanisms stimulating gastric acid release?

Answer 32

Antagonises H2 receptors

Because ACh and Gastrin also cause histamine release and it is thought that the common mediator of gastric secretion is actually histamine, even-though neurocrine and endocrine pathways have a part to play

Question 33

Explain Helicobacter pylori association with peptic ulceration

Answer 33

H.pylori inhibits somatostatin release
Somatostatin is released from D cells and acts on a Gi coupled receptor inhibiting PKA
It therefore reduces gastric acid secretion, so inhibiting somatostatin would lead to uncontrolled gastric acid secretion

Question 34

What stimulates neurocrine stimulation of gastric secretion?

Answer 34

Thought, sight, smell, taste of food

Distension of stomach

Question 35

What stimulates endocrine stimulation of gastric secretion?

Answer 35

Protein digestion products stimulate gastric and duodenal G cells

Question 36

What stimulates pepsin release from which cells?

Answer 36

Chief cells and fusion of pepsinogen containing secretory granules

ACh (M3 receptor), gastrin, CCK —> Gq
Secretin —> Gs

Question 37

What stimulates mucous secretion from mucous cells?

Answer 37

ACh via M3 Gq coupled receptor