Secretions of the Stomach Flashcards
Functions of the stomach?
- store food
- mixes food with secretions
- regulates release of food into duodenum
- secretes gastic juices
Moving from the duodenum to the oesophagus, what are the sections of the stomach?
- pylorus
- antrum
- corpus (next to cardia which joins to the oesophagus)
- fundus
What are the cell types of the stomach and what do they secrete?
- mucous neck cell (mucous and bicarbonate)
- parietal cell (acid and IF)
- ECL cell (histamine)
- chief cell (somatostatin)
- G cell (gastrin)
- D cell (somastatin)
What are the layers of the stomach?
- peritoneum
- longitudinal muscle
- circular muscle
- oblique muscle
- submucosa
- muscularis mucosa
- mucosa (containing gastric glands)
What types of cell does the antrum consist of?
- G cells
- D cells
What cells does the corpus consist of?
- mainly parietal and chief
- some ECL and D
- mainly acid producing cells
What is acid secretion mediated by?
-parietal H-K pump
What are the two subunits of the H-K pump and what do they do?
- α for catalytic function
- beta for which is apical membrane targeting and is needed for full activity
How are H+ ions produced in the parietal cells and how do they enter the lumen?
- carbonic anhydrase catalyses (the forward and backward reaction) converting CO2 and H2O into carbonic acid and then into HCO3- (bicarbonate) and H+
- The H+ is exchanged by the H-K pump for K+ which enters the parietal cell
What happens to the bicarbonate produced?
-exits across the basolaterla membrane via the Cl-HCO3 exchanger
What is the alkaline tide?
increasing PH in the blood due to bicarbonate entering it
What are the 3 triggers that make the parietal cells produce acid?
- Ach
- histamine
- gastrin
What are the direct causes of acid release?
- Ach
- gastrin
- histamine
What is the indirect cause of acid release?
-Ach and gastrin mediated histamine release by ECL cells
Where does Ach come from?
vagus nerve
Why does gastrin bind to?
CCK(small B) receptor
What does histamine bind to?
H2 histamine receptor
Where does histamine come from?
ECL cells
Where is gastrin produced?
G cells
What stimulates the ECL cells to produce histamine?
Gastrin and Ach
What trigger has the biggest contribution to acid production and why?
histamine because gastrin and Ach can act on the ECL cells to produce more histamine
How do the secretagogues impact on the H-K pump?
- histamine does to through a cAMP and PKA pathway
- gastrin and Ach do it through a PKC pathway
What does somatostatin inhibit?
acid production by antagonising histamine mediated acid production
In what ways can soma statin be produced?
- D cells in the corpus triggered by neural and hormonal mechanisms
- D cells on the antrum of the stomach triggered by low intra-luminal PH
How is histamine indirectly regulated by somastatin?
- somatostatin released by D cells of corpus can inhibit release of histamine from ECL cells
- somatostatin released by D cells can inhibit the release of gastrin from G cells in the antrum
What happens in the corpus during distension of the stomach?
-Ach please by vagus nerve
Ach acts:
-direct stimulation of parietal cell to induce acid release
-direct stimulation of ECL cells enhancing histamine release
-stimulation of D cells in corpus culminates in inhibition of somatostatin release
-all trigger acid secretion
What happens in the antrum when G and D cells are stimulated by the vagus nerve?
- vagal stimukation of G cells promotes gastrin release which causes direct and indirect release of acid
- vagal stimulation of D cells inhibits the release of somatostatin
What happens when there is a high luminal H+ conc in the antrum?
-stimulates D cells to release somatostatin
What do products of protein digestion stimulate?
G cells to release gastrin stimulating acid secretion
What are the inhibitors of acid secretion?
- somatostain
- CCK
- VIP
- GIP
- neurotensin
- peptide YY
- prostaglandins
- secretin
How does secretin work?
- released by duodenal S cells and is stimulated by fat and acid in the duodenum
- inhibits acid secretion by: inhibiting astral gastrin release and by causing release of somatostatin
How does CCK work?
- produced by I cells of duodenum and jejunum in response to fat
- directly reduced parietal cell acid secretion
What are the pharmacological inhibitors of acid secretion?
- proton pump inhibitors
- H2 receptor antagonists (competitive antagonists of histamine at the parietal cell H2 receptor)
What are the 4 phases of gastric acid secretion?
- basal
- cephalic
- gastric
- intestinal
What is the basal phase?
- follows a circadian rhythm (low acid in am, high acid pm)
- acid secretion is a direction function of the number of parietal cells
What is the cephalic phase?
-smell, sight, taste, thought and swallowing initiate it which is mediated by vagus nerve (triggering acid secretion)
Which phase causes the most acid release
-gastric (50-60%)
then cephalic
What is the gastric phase?
acid release when the food is in the stomach
What is the intestinal phase?
partially digested peptides in the proximal portion of small intestine stimulates acid secretion mainly by stimulation of G cells to secrete gastrin
What are pepsinogens?
proteolytic proenzymes secreted by chief cells
What is the main trigger for pepsinogen secretion?
Ach
When is pepsinogen active?
spontaneously active at PH5
Most active at below a PH of 3
What is pepsin?
an endopeptidase that initiates protein digestion (auto-activates pepsinogen)
How does the stomach protect itself?
- mucous layer which traps HCO3- to maintain a PH of around 7
- prostaglandins maintain the mucosal diffusion barrier (inhibit acid secretion and stimulating HCO3- and mucus secretion)
What are prostaglandins made from?
arachidonic acid
What type of enzyme is COX1 and what does it produce?
-constitutive enzyme (always present) creates prostaglandins which are involved in platelet aggregation, gastric mucosa and kidney
What type of enzyme is COX2 and what does it produce?
- inducible enzyme
- produces prostaglandins that induce inflammation
What is helicobacter pylori and what do they do?
-gram-neg bacterium
-cause acid production and barrier damage
(peptic ulceration)
What diseases can helicobacter pylori cause?
- gastritis
- gastric and duodenal ulcers
- gastric cancer
How does helicobacter pylori survive in the stomach?
- produces urease
- urease converts urea into ammonia, CO2 and H2O and then into ammonium and bicarbonate
- bicarbonate neutralises stomach acid
What does Hp infection in the antrum cause?
- G cells to hyper secrete gastrin
- decrease D cell somatostatin release
- leading to hypergastrinaemia and duodenal ulcers
What does Hp infection in the corpus lead to?
- reduced acid secretion
- hypochlorhydria (loss of stomach acid secretion)
- association with gastric ulcers
Why is intrinsic factor important and where is it made?
important in absorption of vit B12
important in red blood cells
-parietal cells
How is megaloblastic anaemia caused?
- red cells are mature but larger than normal
- parietal cells are destroyed in pernicious anaemia so no intrinsic factor us produced
- B12 not absorbed
