GI Secretion & Digestion

Question 1

Mechanism of gastric secretion

Answer 1

• Parietal cells secrete hydrochloric acid & intrinstic factor into stomach

1. H⁺ actively transported across apical membrane in exchange for K⁺ by H⁺/K⁺ ATP-ase [primary active transport]
   
   1. drives uphill movement of Cl^- and H₂O
2. HCO₃^- transported across basolateral membrane in exchange for Cl^- via Cl^-/HC0₃^- anion exchanger [secondary active transport]
3. Cl^- transported across apical membrane via facilitated diffusion [passive transport]
4. H₂O follows net transport of HCl for osmotic reasons (==> alkaline tide = high pH of venous blood leaving stomach)

Question 2

Characteristics of acid secretion stimulation

Answer 2

• acid secretion stimulated by ACh, gastrin, paracrine histamine (via direct and indirect pathways)
• ACh ==[muscarinic receptors @ basolateral] ==> activate G-protein ==> increase intracell Ca²⁺
• Gastrin ==> increased intracell Ca²⁺
• Histamine =={histaminergic H₂ receptors] ==> activate G-protein ==> activate adenylate cyclase ==> increased cAMP
• Ca²⁺ and cAMP ==> protein kinase activation ==> phosphorylation of H⁺/K⁺ ATPase ==> increase in H+/K+ ATPase activity

Question 3

Indirect vs. Direct pathway of acid secretion stimulation

Answer 3

• direct pathway: ACh, gastrin and histamine directly stimulate the parietal cell, triggering the secretion of H+ into the lumen
• indirect pathway: ACh and gastrin stimulate the ECL (enterochromaffin-like) cells, resulting in secretion of histamine ==> histamine then acts on the parietal cell

Question 4

Phases of gastric acid secretion (general)

Answer 4

• basal phase = interdigestive phase
  
  • rate of acid secretion follows circadian rhythm:
  • morning = lowest
  • evening = highest
  • resting pH = 3-7
• 3 phases assoc. w/eating

Question 5

Gastric secretion during eating

Answer 5

• cephalic phase = @ sight, smell, taste and swallowing of food; mediated by vagus nerve
  
  • ACh release
  • histamine release from ECL cells
  • gastrin-releasing peptide (vagal/enteric neurons)
  • inhibition of somatostatin release from delta cells
• gastric phase = @ entry of food in stomach
  
  • distension ==> vasovagal reflex + ENS reflexes
  • proteins ==> gastrin release from G cells
• intestinal phase = @ amino acids/peptides @ proximal small intestine
  
  • duodenal G cells secrete gastrin

Question 6

Characteristics of protective barrier of gastric surface

Answer 6

• barrier = surface epithelial cells + mucous + bicarbonate secretion
  
  • protects from harmful effect of acid
  • aids in maintenance of pH gradient
• mucous secreted by goblet cells (= specialized epithelial cells)