What are the 5 most important componetns of gastric secretions?
Where does the H+ ion in gastric secretions come from?
parietal cells secrete HCl at high concentrations
What are the roles of the H+ in gastric secretions?
-activates conversion of pepsinogen to pepsin
-helps denature protein to make them better substrates for pepsin
How does pepsin work?
it is an endopeptidase that digests proteins by cleaving interior peptide bonds
What is intrinsic factor?
this is produced by parietal cells in the stomach to allow absorption of vit B12 in the ileum
What are the major cells of glands of the stomach?
-chief cells (secrete pepsinogen)
-ECL cells (secrete histamine)
-Parietal cells (acid, intrinsic factor secretion)
-Mucuous neck cells (stem cell compartment)
-Surface mucous cells (mucus, trfoil peptide, HCO3- secretion)
What is the purpose of ECL cells secretin histamine?
these are primarily located on the periphery of the gastric glands so they dont secrete into the lumen of the gland, but only in a paracrine way to activate parietal and chief cells via histamine
How are pyloric glands different from oxyntoxic glands?
they dont have parietal cells, but do have G cells which secrete gastrin
What is outlined in black in this parietal cell?
the intercellular canalilus which opens into the glandular lumen
NOTE: the white fat looking circles are tubular vesicles which house the H/K+ ATPase needed to pump acid into the lumen and the brown things are mitochondria needed to generate ATP
What happens when parietal cells are stimulated?
the tubulovesicles fuse into the canalulus (right on last slide)
What is the conc of acid in the stomach?
Can be up to 0.15-0.16 mN (4x million fold gradient from epithelium- thus, energy is required to secrete it)
How is H+ secreted into the GI lumen?
Water in the cell dissociates into H+ and OH- and the H+ is exchanged into the GI lumen for K+ via a H+/K+ ATPase while the OH- combines with CO2 to form carbonic acid and then HCO3- which exits via the basolateral membrane into blood in exchange for Cl- which then passively diffuses into the GI lumen
What drug can inhibit the H/K ATPase?
What happens to the K+ once it's inside the gastric epithelium?
It diffuses passively back into the GI lumen via a channel so that the lumenal concentration of K+ always remains similar
H+ and Cl- cannot backflux into the epithelium from the lumen due to the high electrical gradient maintained by pumping a lot of Cl- into the lumen
What is the clinical utilty of understanding that the electrical gradient of the GI epithelium is -60 to -80?
Since this is normal, a less negative gradient (due to things like ethanol and NSAIDs which can allow Cl- backflow into the epithelium via loosened tight junctions) signifies epithelial dysfunction
T or F. The electrolyte composition of gastric secretions vary
T. They vary depending on the rate of secretion.
What are the major stimulants of gastric acid secretion?
gastrin from G cells in the antrum (released in endocrine mechanism- into circulation to induce acid secretion via binding to parietal cells)
Ach binding to parietal cells
histamine (most potent) released by ECL cells which bind to H2 receptors on parietal cells
How do Ach and gastrin work once they bind to parietal cells?
Gq mechanisms (PL-C, to IP3)
How does histamine work once it binds to parietal cells?
via Gs mechanisms (AC, and cAMP)
How does gastrin promote acid release from parietal cells?
It can directly bind to parietal cells via CCK-2 receptors but mostly works by binding to ECL cells to promote histamine release which then binds to parietal cells (similarly Ach can do both of these)
T or F. There is a synergistic effect of Ach, histamine, and gastrin in promoting acid release
When is acid output highest during the day?
very low in the morning and rising to highest around 10 pm. it doesnt appear that this is due to gastrin since gastrin levels remain the same throughout the day
Gastrin acid output increased immediately, even before food gets into your GI suggesting that acid can be stimulated mechanically through chewing
What are the phases of gastrin secretion?
What occurs in the cephalic phase of gastrin output?
sham feeding shows immediate increase in acid secretion based on what kind of food you are eating via a central process (can be stopped via vagotomy- vagus nerve mediates)
The cephalic phase represents what percentage of total gastrin output?
T or F. The cephalic phase does not involve gastrin production
F. BUT this contribution is very minor (Ach from the vagus nerve is by far the main contributor during this phase). Digestion is better when all senses are involved, and stress attenuates this response because the sympathetic NS is more activated)
Carbs dont need acid to be digested while proteins do because they need to be denatured (this is mediated by the gastric phase)