Lecture 9 Flashcards
What is the major digestive function of the stomach?
The vagovagal reflex enables relatively higher amounts of food to enter the corpus (starting at the fundus) of the stomach
Digestion of this bolis begins in the corpus
Moves to the antrum for churning to reduce it to chyme that is small enough to pass through the pyloric sphincter
Slide 3-4
What are the 6 types of cell in the stomach?
Superficial epithelial cell- located in corpus, secretes bicarbonate & mucus
Mucous neck cell
Stem/progenitor cell
Parietal (oxyntic) cell- located in corpus, secretes acid (HCl)
Chief cell- located in corpus, secretes pepsinogen & gastric lipase
Endocrine cell- four type of cells
Slide 5
What are the 4 types of endocrine cells?
Cell of interest in the corpus:
- Enterochromaffin-like (ECL) cells, which secrete histamine
- D cells, which secrete somatostatin
Cell of interest in the antrum:
- G cells, which secrete gastrin
- D cells, which secrete somatostatin
Slide 5
Slide 13
What is gastric acids role in digestive function?
Key role
Secretions can be 2L per day
Acid secretions can reduce the intraluminal pH < 2 which is important for disentangling folded proteins
The reduction in pH is also essential for pepsin activity
Slide 7
How is pepsin activated upon a bolus entering the stomach?
Parietal cells substantially increase acid secretion, while chief cells release pepsinogen
Pepsinogen is a zymogen that is spontaneously cleaved into the protease pepsin at a pH of 3-5
At pH > 3.5 pepsin remains inactive
When pH drops below 3.5 pepsin activity rises dramatically and rapidly digests ingested protein
Slide 8
What are the adaptations by stimulated parietal cells enabling large increases in acid secretion?
Tubulovesicular membranes carrying H-K ATPase fuse with plasma membrane (>surface area)
This causes ATP consumption
K is recycled back to lumen through potassium channels, Cl moves to lumen through CFTR channel (net secretion of hydrochloride acid HCl to lumen)
Rise in pH caused by H secretion is balanced by an influx of CO2 and water that is used to generate bicarbonate and H by carbonic anhydrase (CA)
Bicarbonate is exchanged for Cl by AE2, which replaces Cl secretes to the lumen
Slide 9
What are the adaptations that guard against cellular damage?
Parietal cells can drive the pH within the lumen to <1 for long periods and pepsin could potentially digest cells too (how fome stomach isn’t destroyed?)
Epithelial cells remain healthy due to a gastric diffusion barrier
Surface epithelial cells secrete bicarbonate and mucins to create a protected & buffered gel layer with a normal pH level
Requires an apical Cl-bicarbonate exchanger and a basolateral Na-bicarbonate exchanger
Slide 11
How does stomach move digested material (chyme) to the duodenum at the proper time?
Feedback mechanisms are required to ensure proper timing
Slide 12
What are the key molecular players at the cellular level involved in gastric acid secretion?
Vague nerve releases ACh
ECL cells secrete histamine which stims gastric acid secretion by increase cAMP
G cells secrete gastrin, which stims gastric acid secretion by increasing PKC activity
D cells secrete somatostatin which inhibits gastric acid secretion by suppressing cAMP levels
Slide 13-14
What is the importance of vagal input?
In the corpus, the vagal nerve regulates parietal cells and ECL cells whereas in the antrum the vagus nerve stimulates G cells
ACh also inhibits D cells
Vagal input has a broad modulatory effect on secretion rates as well as other activities in the stomach
Slide 15
What is the key roles for somatostatin and enterogastrones in feedback inhibition?
Broad role for somatostatin as a negative regulator of gastric acid secretion
D cells are under control of neural and endocrine factors
When secreted somatostatin exhibits a paracrine effect to inhibit histamine secretion from ECL cells and inhibit acid secretion from parietal cells
In the antrum D cells secrete somatostatin in response to low pH
Enterogastrones are any enteric peptide hormones that inhibit gastric acid secretion
Slide 15
What are the 3 pathologies that alter feedback systems involved in gastric acid secretion?
- H. Pylori and duodenal and gastric ulcers- elevated levels of gastric acid secretion in these patients is thought to cause inflammatory signals that suppress secretion of somatostatin by D cells
- Gastrinoma- ulcers can be caused by a gastrinoma that secretes gastrin into the circulation
- Pernicious anemia- lack parietal cells in pernicious anemia, gastric acid secretion is low
Slide 16
