GI secretion Flashcards
- Describe the mechanism of gastric acid generation and secretion, including the role of K+, Cl-/HC03, carbonic anhydrase and H+-K+ ATPase.
H/K ATPase on apical membrane pumps H into lumen > bicarb/Cl exchanger in basolateral membrane pumps bicarb into blood and Cl into cell > Cl accumulates in cell then is transported into cell by facilitated diffusion > water follows HCl into lumen by osmosis
What kind of transport is the H/K ATPase, bicarb/Cl exchanger, and Cl facilitated diffusion?
H/K ATPase: primary active transport. bicarb/Cl exchanger: secondary active transport. Cl facilitated diffusion: passive transport
What is alkaline tide
pH of venous blood leaving the stomach is high because of the bicarb transport from the cell into the blood
Where is acid secreted in GI tract
Parietal cells in stomach (also secrete intrinsic factor) pump H via a H/K ATPase. Cl is pumped into cell from blood via Na/K/2Cl co transporter, then Cl is pumped out of cell into lumen via CFTR
Function of acid in stomach
denatures proteins, activates pepsinogen, kills bacteria
Defenses in stomach from acid
mucus layer from mucus cells (prostaglandins increase mucus production), bicarb from mucus cells, tight junctions btw cells prevent acid from infiltrating layers of wall, rapid cell turnover
Describe B12 absorption
B12 binds R protein in stomach > pancreatic proteases remove R protein in duodenum >intrinsic factor from parietal cells binds B12 in duodenum > IF/ B12 complex binds receptor in terminal ileum for absorption
Phases of HCl secretion
- Interdigestive (basal) phase – between meals following circadian rhythm 2. Cephalic phase – mostly neural regulation. 3. Gastric phase – initially neural followed by endocrine (gastrin) and neural regulation. 4. Intestinal phase – mostly endocrine regulation
- Describe the modulation of gastric acid secretion throughout the day and night.
highest in the evening and lowest in the morning prior to waking due to basal phase of acid secretion
describe cephalic phase of HCl secretion
Mediated by vagus nerve upon smell, sight, taste and swallowing of food- (1) release of ACh; (2) triggering of the histamine release from ECL cells; (3) release of gastrin-releasing peptide (GRP) from the vagal and enteric neurons (ENS); and (4) inhibition of somatostatin release from the delta cells (D cells) in the stomach.
describe gastric phase of HCl secretion
First, the food distends the gastric mucosa, which activates a vagovagal reflex as well as local ENS reflexes. Second, partially digested proteins stimulate antral gastrin (G) cells, which release gastrin. The gastric phase accounts for about 50% to 60% of total acid secretion
describe intestinal phase of HCl secretion
presence of amino acid and partially digested peptides in the proximal portion of the small intestine stimulates acid secretion by stimulating duodenal gastrin (G) cells to secrete gastrin.
regulation of acid production
parietal cells undergo amplification of apical surface area with increased density of H/K ATPase. Ach and gastrin signal via Ca, and histamine signals via cAMP
Direct vs indirect acid secretion stimulation
direct: Ach, gastrin and histamine directly stimulate parietal cell. Indirect: Ach and gastrin stimulate enterochromaffin-like cells, resulting in histamine secretion which then acts on parietal cells
risk factors for peptic ulcer disease
NSAID use, tumors (Zollinger Ellison syndrome) and H pylori