Secretions of the stomach Flashcards
What are the functions of the stomach?
Store food
Mixes food with secretions
Regulates release of food into duodenum
secretes gastric juices
What is the anatomy of the stomach?
Oesophagus Caria Fundus Corpus Antrum Pylorus Duodenum
What are the different cell types within the stomach?
Mucous Neck cells Parietal Cell ECL cells Chief cells D cell G cells
How do the parietal cells produce acid?
Mediated ultimately by the parietal H-K pump embedded in apical membrane
The H-K pump requires both and alpha and beta subunit for full activity
What is the process of the parietal cell making stomach acid?
- CO2 from the blood enters into the parietal cell
- The CO2 combines with H2O to form H2CO3 (carbonic acid).
- The carbonic acid splits into H+ ion and HCO3- ions via the Carbonic anhydrase enzyme
- The H+ ion travels in the lumen of the gastric gland in exchange for a K+ ion via a H-K pump.
- The HCO3- ion exits the parietal cell across the basolateral membrane via a Cl-HCO3- exchanger.
- The Cl brought into the parietal cell diffuses into the lumen through a Cl ion channel where it combines with the H+ ion to form HCl
- The K+ ion in the parietal cell returns to the lumen through its own ion channel.
What regulates acid secretion?
Paritetal cell has 3 Direct triggers:
Ach (from vagus nerve) via PKC pathway
Histamine - onto H2 histamine receptor via PKA pathway (greatest contribution)
Gastrin - locks onto the CCKb receptor via PKC pathway
Indirect Triggers:
Ach and gastrin mediated by histamine release by ECL cells (Ach triggers ECL cells to release histamine)
How is acid secretion stimulated?
mediated by a intracellular signal-transduction processes involving G-protein-coupled receptors on the parietal-cell membrane . Notably PKA and PKC
Explain how the 3 secretagogues (ACh, gastrin and histamine) stimulate secretion
- Acetylcholine binds to an M3 muscarinic receptor. This culminates in activation of protein kinase Ca2+ channel (PKC) and intracellular calcium
- Gastrin binds to the cholecystokinin B (CCKB) receptor. Similarly activates PKC.
- Histamine activation of the H2 receptor stimulates the enzyme adenyl cyclase, which results in production of cAMP and activation of PKA.
How are G cells involved with cell acid secretion in the corpus?
G cells are stimulated by GRP which indirectly stimulates the parietal cells.
What affect does ACh have on D cells?
ACh inhibits D cells preventing the release of somatostatin which antagonises histamine production
What affect do amino acids have on G cells?
peptides and amino acids are able to stimulate G cells to produce gastrin which can directly interact with the parietal cells and trigger acid secretion.
How does the D cell regulate the amount of acid in the corpus?
D cells in the antrum detect high acid levels and therefore secrete somatostatin inhibiting the function of the G cells
What are the inhibitors of acid secretion?
Somatostatin - main inhibitor
Secretin - stimulated release by fat and low pH in duodenum. Secretin inhibits antral gastrin release and stimulates somatostatin release
CCK - produced by I cells and release in response to fat. CCK directly reduces parietal cell acid secretion
How can we pharmacologically inhibit acid secretion?
By inhibiting the proton pump we can prevent acid secretion instead of reducing it by only targeting one of the 3 triggers
Give an example of a drug which blocks the proton pump
Omeprazole has direct interaction on the proton pump itself
Give an example of a drug which inhibits the H2 receptors
Cimetidine and ranitidine are H2 antagonists which prevent histamine trigger on acid secretion. (histamine targeted as this is the most effecting trigger)
What are the 4 phases of gastric acid secretion?
- Basal
2. Cephalic 3.Gastric 4.Intestinal
What happens in the basal phase of acid secretion?
Follows a circadian rhythm; acid secretion is low a.m. and high p.m.
• Acid secretion is a direct function of the number of parietal cells, so size does matter
What happens in the Cephalic phase of acid secretion
The smell, sight, taste, thought, and swallowing of food initiate the cephalic phase, which is mediated by the vagus nerve, thus triggering acid secretion
• Accounts for approximately 30% of total acid secretion and occurs before the entry of any food into the stomach
What happens in the Gastric phase of acid secretion
Digestion of food in the stomach releases ACh which then triggers both directly and indirectly acid secretion in the parietal cell
(accounts for 50-60% of total gastric secretion)
What happens in the Intestinal phase of acid secretion
Partially digested peptides/amino acids in the proximal portion of the small intestine stimulates acid secretion predominantly by stimulation of duodenal G cells to secrete gastrin
What are pepsinogens?
Proteolytic proenzymes secreted by chief cells
What is the trigger for pepsinogen secretion?
Acetylcholine
How does pepsinogen work?
Conversion of pepsinogen to pepsin occurs spontaneously at pH<5. Most active at <3
• Pepsin auto-activates pepsinogen
• Irreversibly inactivated at pH 7.2
• Interlinked with acid secretion because of similar trigger (Ach) and resulting peptides trigger antral Gcell gastrin secretion
• Pepsin is an endopeptidase which initiates protein digestion
What is gastric mucosal protection?
Protection from the harsh pH environment by a mucous layer which traps HCO3- ions and maintains the mucosal pH at 7
Why are Prostaglandins important?
Important in maintaining the mucosal diffusion barrier by inhibiting acid secretion.
What are the functions of prostaglandins?
Functions in both physiology and pathology. Maintains pH levels and has a role in inflammation
What do COX-2 enzymes do?
Inhibit prostaglandins and therefore can be uses to purposefully cause an inflammatory response
What are some common side effects of COX enzyme inhibitors?
Common GI side effects experienced in (non selective) NSAID users including gastric ulceration and dyspepsia
What are Helicobacter pylori?
Gram-negative microaerophilic bacteria
They are acid loving microbes colonising in the stomach of 40% of humans.
What do Helicobacter Pylori do to infected individuals?
Cause peptic ulceration
How does Helicobacter Pylori cause Peptic Ulcer disease?
By urease which causes urea to be converted into ammonium and bicarbonate ions which will neutralise the stomach acid.
Urea—->NH3 + CO2+ H20 —-> NH4+ + HCO3-
What does Helicobacter Pylori infection cause in the antrum?
G-cells to hypersecrete gastrin 2. Decrease antral D-cell somotastatin release
This leads to hypergastinaemia and duodenal ulcers
What does Helicobacter Pylori infection cause in the corpus?
Hyperchlorhydria largely associated with gastric ulcers
What is intrinsic factor?
produced by parietal cells
Necessary for the absorption of vitamin B12
What is the result of a loss of intrinsic factor?
causes megaloblastic anaemia or pernicious anaemia which is an autoimmune atrophic gastritis.
What do the mucous neck cells secrete?
Mucous and bicarbonate
What do the parietal cells secrete?
Acid and intrinsic factors
What do the ECL cells secrete?
Histamine
What do the Chief cells secrete?
Pepsinogen and lipase
What do the D cells secrete?
Somatostatin
What do the G cells secrete?
Gastrin
What is Alkaline tide?
The process of bicarbonate ions entering the blood as a consequence of acid secretion.
What is vitamin B12 important for?
normal function of brain and nervous system and for the production of red blood cells.
What is hypergastrinaemia?
presence of excess gastrin in the blood
What is hyperchlorhydria?
excess stomach acid levels
What is megaloblastic / pernicious anaemia?
deficiency in red blood cell production.
