intestinal secretions

Question 1

what does the stomach secrete?

Answer 1

• H+, pepsinogen, mucus, HCO3-, intrinsic factor (for vit B12 absorption in ileum)
• Also releases humoral factors: histamine and gastrin + somatostatin (antagonist functions)

Question 2

what are the cells of the gastric epithelium?

Answer 2

base: parietal (oxyntic): secrete HCl + IF
chief: secrete pepsinogen
endocrine: secrete gastrin, somatostatin

neck: mucous neck cells: secrete mucous

pit: superficial epithelial cells: secrete mucus + HCO3-

Question 3

what happens in the unstimulated stomach?

Answer 3

Isotonic saline supplemented w HCO3- to alkalinise mucus + neutralise acid

at low secretory rates see high Na+ and Cl- and low H+

Question 4

what happens to gastric juice composition in the stimulated stomach?

Answer 4

isotonic replaced w juice from parietal cells, there is high HCl and low Na+ in stomach lumen

Question 5

what is the mech of recruitment of TBVs?

Answer 5

a. Secretory canaliculus (deep invagination on apical membrane), increased in SA by TBVs

b. TBVs have H/K ATPase in membrane (P type), occur in subapical cytoplasm

c. Therefore pumps H+ from cytoplasm to lumen of vesicle and pumps K+ out of vesicle. Impermeable to K+ so cannot recycle so although ATP can bind, low K+ ‘brakes’ pump

d. TBVs cannot affect cytoplasmic pH in unstimulated parietal cells

e. TBVs fusing w apical membrane stimulates acid secretion, confers H/K ATPase onto apical membrane

Question 6

what is the mechanism of secretion of gastric acid?

Answer 6

a. CA catalyses H2O + CO2 to make H+ and HCO3-

b. H+ leave across apical membrane using H/K ATPase, K+ recycles back out through apical channels

c. HCO3- leave across BL membrane thru anion Xchanger for Cl-, Cl- leave to lumen through apical membrane through channels

d. Cl and H united in lumen, blood is alkalinised

Question 7

what are the phases of secretion and what happens in each?

Answer 7

• Cephalic: stimulation of vagus nerve, ACh, GRP release, 30% of secretion
• Gastric: distention initiates vasovagal reflex + protein digestion products promote gastrin release from G cells, 60% of secretion
  o Levels of acid + pepsin secretion can be adjusted based on effectiveness of protein digestion
• Intestinal: protein digestion products stimulate duodenal G cells, 10% of secretion

Question 8

what are the 3 strands of regulation? what are their chemicals of action?

Answer 8

neurocrine: ACh
endocrine: gastrin
paracrine: histamine

Question 9

what is the method of action of neurocrine regulation?

Answer 9

ACh from vagus binds M3 receptors, initiate IP3 cascade, elevation of Ca2+, activation of PKC (phosphs H/K ATPase at N terminus Ser 27), activates the pump, decreases luminal pH

Question 10

what is the method of action of endocrine regulation?

Answer 10

gastrin (G cells) due to stimulation of GRP-containing neurons by ACh or protein digestion products. Binds CCK type B receptors: IP3 cascade as ACh

Question 11

what is the method of action of paracrine regulation?

Answer 11

histamine: mediator from enterochromaffin cells: binds H2 receptors, activates adenylyl cyclase: increase PKA: phosph C-terminal (or Ser 27) of H/K ATPase

Question 12

what is the common mediator hypothesis?

Answer 12

• Histamine = final mediator to bring about actions of ACh and gastrin on parietal cells
  o Combine to M3 and CCK type B on enterochromaffin cells to release histamine
• Large component of ACh/CCK action = stimulate histamine, not direct actions in BL receptors. Histamine antagonist therefore reduces indirectly actions of ACh and gastrin

Question 13

how to raise pH of gastric juice naturally?

Answer 13

somatostatin
from D cells

released due to stimulation of secretin by low luminal pH (from S cells)

inhibits cAMP prodution and therefore PKA stimulation of TBV fusion, reduces acid secretion (antagonised histamine)

Question 14

what drugs raise pH of gastrin juice?

Answer 14

H2 antagonists: ranitidine
anticholinergics: atropine

both decrease cAMP, = decreased apical availability of proton pumps (H/K ATPases), or:

o H+ pump inhibitors: pantoprazole, omeprazole

= less H+ secreted into lumen, less acidic secretion

Question 15

what are the 3 types of salivary glands? what do they secrete?

Answer 15

• parotid: serous secretion, 25%: supplemented w amylase
• submandibular: serous + mucous secretion, 70%
• sublingual: mucous, 5%, contains mucin (anti-pathogenic glycoprotein)

Question 16

functions of serous secretion?

Answer 16

moistens oral mucosa, vehicle for enzyme, lubrication for speech, germicidal

Question 17

functions of mucous secretion?

Answer 17

lubrication, diffusion barrier to nutrients, drugs + toxins, binds bacteria, viruses + parasites, protects against proteases

Question 18

what is the process of priamry secretion?

Answer 18

nearly isotonic (Na+, Cl-, K+, HCO3- similar to plasma)
o NKCC accumulates Cl- in the cell: Cl- diffuse across apical membrane into lumen
o Na+ pumped out at BL membrane, K+ diffuses out thru channels
o Na+ ions diffuse thru paracellular pathway along electrical gradient from Cl- movement
o H2O follows by osmosis (transcellular, AQP3 + 4)

Question 19

what is the process of 2ry modification?

Answer 19

principally NaCl absorption, creates gradient for H2O to follow
o Na replaced by K, Cl- replaced by HCO3-
o Na+ absorbed through ENaC and NHE4, exits on Na/K ATPase
o Cl- absorbed through Cl-/HCO3- Xchanger, exits through BL channels
o HCO3- excreted in exchange for Cl- formed from CO2 hydration in cell: H+ lost through NHE1 (BL)
o K+ accumulated in cells, lost to lumen through K/H ATPase
o H2O permeability low

Question 20

what is final composition of saliva?

Answer 20

o hypotonic to plasma: becomes isotonic as flow increases since 2ry modification cannot occur
o slightly acidic at rest, increasingly basic when stimulated as agonists that drive salivary secretion also drive HCO3- secretion: more time for 2ry modification

proteins:
enzymes: alpha amylase, lingual lipase
mucisn
lysozymes, lactoperoxidase, IgA

Question 21

how do you regulate salivary secretion>?

Answer 21

• peripheral NS: ACh increases 1ry secretion, decreases 2ry secretion: lots of watery saliva
• ACh = M3 = IP3 = Ca2+ = PKs = incr
• Phosphorylation of cytoskeleton induces export of protein (enzyme) containing vesicles
• Noradr also mobilises Ca2+ through IP3
• Increases secretion

Question 22

how does pancreatic secretion differ from salivary?

Answer 22

• Apical Cl- channel = CFTR protein
• Zymogens supplement secretions: prevents autodigestion
  o Proteases, trypsinogens, procarboxypeptidases: activated by truncation in lumen
• Amylases, lactases, lipases, nucleases
• Regulation: neural reflexes (ACh), GI hormones (gastrin + secretin) and absorbed nutroents: ensure adequate but not excess HCO3- + enzyme secretion
• Intestinal phase modulated by Ach, secretin and CCK, not histamine

o ACh, CCK, gastrin uses IP3 cascade to increase conductance of A membrane for Cl- and BL for K+