Lecture 21: Gastric Secretion Flashcards
Chyme
Mixture of food particles + gastric secretions
Anatomical sections of stomach
Upper = fundus
Lower = antrum (thicker muscle)
Gastric gland cells
- Parietal cells
- Chief cells
- Mucus neck/surface cells
- G cells
- Enterochromaffin-like (ECL) cells
- D cells
Parietal cells (stomach)
Secrete HCl and intrinsic factor; responsible for alkaline tide. Have apical canaliculi and receptors for gastrin, ACh, histamine, and somatostatin. Secretion depends on [proton pumps]; activation -> vesicle fusion -> increased pumps at membrane
Chief cells (stomach)
Secrete pepsinogen, which autocatalyzes to pepsin in low pH and is then inactivated at neutral pH. Secretion parallels H+, but pepsin only accelerates protein/collagen digestion (not essential).
Mucus neck/surface cells (stomach)
Secrete mucus + bicarb to protect epithelial wall from acid, pathogens.
G cells
Secrete gastrin hormone, stimulating acid secretion directly (parietal cell CCK-2 receptor) and indirectly (ECL cell CCK2 receptor)
Enterochromaffin-like (ECL) cells
Secrete histamine, which promotes HCl secretion by binding to H2 receptors on parietal cells.
D cells
Secrete somatostatin, which inhibits gastric acid secretion by reducing secretions from G cells, ECL cells, and parietal cells directly. Able to sample gastric lumen.
Function of stomach acid
Stomach acid denatures proteins and kills pathogens, but has little impact on polysaccharides/fats
Mechanism of gastric HCl production and secretion
- Production of IC H+ from CO2 via carbonic anhydrase
- H+/K+ ATPases + K+ leak channels move H+ to gastric lumen
- Bicarb exchanged downhill basally w/ Cl- (electroneutral.), bicarb coupled w/ H+ to lumen
- Cl- moves uphill apically w/ H+ (electroneutral.)
Alkaline tide
Refers to the more alkaline blood immediately flowing from the stomach due to basal bicarb secretion coupled with apical H+ secretion.
Vitamin B12 absorption factors
- R-protein (saliva, higher affinity)
- Intrinsic factor (gastric)
Vitamin B12 absorption process
Salivary R-protein binds most B12 but is degraded by pancreatic proteases in the proximal intestine. Intrinsic factor binds the free B12 and the complex is uptaken by distal ileal eneterocytes w/ receptors -> transferred to transcobalamin transporter
Pernicious anemia
Anemia due to B12 deficiency, which is required for DNA synthesis and RBC synthesis. 95% of these patients have autoimmunity vs. parietal cells/intrinsic factor.
Gastric mucosal barrier components
- Tight junctions preventing H+ diffusion past epithelium
- Thick alkaline mucus
- Mucus phosphoplipid layer
- Prostaglandin E2 release increasing mucus secretion on irritation
- Constant cell renewal
GI epithelial sloughing/restitution
Damaged epithelial cells in the GI slough off over time. Restitution = repair of mucosal barrier.
3 phases of gastric secretion
- Cephalic
- Gastric
- Intestinal
Cephalic phase of gastric secretion
- Food enjoyment -> G/ECL/parietal cell vagal tone (ACh) -> more acid secretion
- D cells sense acid -> somatostatin secretion
- Overall mild acid secretion stimulation
Gastric phase of gastric secretion
- Distension -> local+long reflex arcs via stretch receptors, CNS increase vagal tone -> more acid
- Early gastric phase food buffers lumen, raises pH -> more acid secretion
- AAs/peptides stimulate G cells (gastrin) and stop D cells (somatostatin)
- Overall sharp increase in acid w/ eventual negative feedback when acid overwhelms food buffer (D cell activating)
Intestinal phase of gastric secretion (inhibitory)
Intestinal hormones inhib. acid secretion:
- S cell secretin / K cell gastric inhibitory peptide / I cell CCK -> stimulate D cells (e.g. CCK1 receptor)
- L cell peptide YY inhib. ECL cells (D cell also makes peptide YY)
CCK also v. weak agonist for CCK2R on ECL/parietal cells; competes w/ gastrin.
Stimulation of intestinal phase gastric inhibition
Low pH -> S cell secretin
Free FAs -> I cell CCK, K cell GIP, L cell PYY
Peptides -> I cell CCK
Glucose -> L cell PYY, K cell GIP
- Gastric inhibitory peptide aka glucose-dependent insulinotropic peptide
Ulcer
Erosion of gastric surface resulting in corrosion of underlying tissue. Can be caused by genes, drugs, alcohol, bile salts, excess acid/pepsin, and often H. pylori infection
