Secretions of the Stomach

Question 1

Function of the stomach?

Answer 1

Stores food, mixes food with gastric secretions, regulates release of food into the duodenum and secretes gastric juices.

Question 2

Anatomy of the stomach

Answer 2

Thick muscle wall to help ground down food to less than 2cm in diameter which is then propelled through the duodenum.

Question 3

What are exocrine secretions in the stomach?

Answer 3

Released into the stomach lumen are digestive juices, collectively known as gastric juices.

Question 4

What are paracrine secretions in the stomach?

Answer 4

Histamine a substance that stimulates gastric acid secretion.

Question 5

What are endocrine secretions in the stomach?

Answer 5

Hormone gastrin, which acts locally on the stomach smooth and mucosa to stimulate gastric acid motility and acid secretion and distally on the intestine, pancreas and liver.

Question 6

What do parietal cells secrete?

Answer 6

Acid producing and secreting cells

Question 7

What do mucous neck cell secrete?

Answer 7

Produce mucous which is very important in protecting cells, with bicarbonate incorporated this helps to protect the stomach cells from the pH1 environment.

Question 8

What do D cells secrete?

Answer 8

Somatostatin

Question 9

What do G cells secrete?

Answer 9

Gastrin

Question 10

What do EC like cells secrete?

Answer 10

Histamine

Question 11

What do chief cells secrete?

Answer 11

Pepsinogen and lipase

Question 12

Describe the biological mechanism of acid secretion

Answer 12

Mediated ultimately by the parietal H-K pump embedded in apical membrane. It pumps H+ against its concentration gradient into the lumen of the stomach. The H-K pump requires both an alpha subunit (required for catalytic function) and a B subunit (apical membrane targeting) for full activity.

Question 13

How do parietal cells produce and secrete acid?

Answer 13

1. H-K pump extrudes H+ into the lumen of the gastric gland in exchange for K+.
2. K+ is recycled via K+ channels
3. Carbonic anhydrase has a very important function
   HCO3- + H+ = H2CO3 = CO2 + H2O
4. The HCO3- exits across the basolateral membrane via the Cl-HCO3 exchanger = alkaline tide!
   Acid is made by the combination of CO2 and H2O to make carbonic acid H2CO3 this is then broken down into HCO3- and H+

Question 14

What regulates acid secretion?

Answer 14

Direct = ACh, histamine, gastrin
Indirect = ACh and gastrin mediated Histamin release by ECL cells.

ECL cell make histamine, gastrin from G cells and ACh from the vagus nerves. Gastrin and ACh can also stimulate ECL cells to release histamine which causes parietal cells to be activated indirectly.

Question 15

How does Acteylcholine stimulate acid secretion from parietal cells?

Answer 15

Actelycholine binds to an M3 muscarinic receptor. This culminates in activation of protein kinase Ca2+ channel (PKC) and intracellular calcium

Question 16

How does Gastrin simulate acid secretion from parietal cells?

Answer 16

Gastrin binds to the cholecystokinin B (CCK B) receptor. This culminates in activation of protein kinase Ca2+ channel (PKC) and intracellular calcium.

Question 17

How does Histamine stimulate acid secretion from parietal cells?

Answer 17

Histamine activates the H2 receptor stimulation the enzyme adenyl cyclase, which results in production of cAMP and activation of PKA.

Question 18

What is somatostatin?

Answer 18

A peptide hormone made by D-cells which acts as a direct and indirect inhibitor of parietal cell acid stimulation.

Question 19

How does somatostatin work?

Answer 19

Somatostatin binds to a G alpha-coupled receptor (SST) on parietal cells and inhibits adenylyl cyclase, antagonizing the stimulatory effect of histamine.

Question 20

How can somatostatin be produced?

Answer 20

1. D cells in the corpus of the stomach (paracrine). Triggered by Neural and hormonal mechanisms by inhibiting the release of histamine from ECL cells in the corpus.
2. D cells in the antrum of the stomach (endocrine). Triggered by low intra-luminal pH inhibits the release of gastrin from G cells in the antrum.
   Both these functions antagonise the stimulatory effect of histamine at the level of the parietal cell = no more acid production

Question 21

How does various stimuli impact on parietal cell acid secretion?

Answer 21

ECL cells release histamine which activates parietal cells. The ECL cell is stimulated by ACh released by vagus nerve and Gastrin from G cells.
G cells can also be stimulated by products of digestion e.g. by products of protein digestion this produces gastrin which stimulates acid release from parietal cells.
Ach is stimulating acid production of the parietal cell, its stimulating production of gastrin from G cells therefore activates parietal cells more, however it inhibits D cells and therefore somatostatin is not released.

Question 22

What happens in the antrum (vagal stimulation of G and D cells)?

Answer 22

Vagal stimulation of G cells is mediated via GRP and promotes gastrin release. Gastrin triggers parietal cell acid release directly and indirectly via the ECL cell.
Vagal stimulation of D cells via ACh, inhibits the release of somatostatin.

Question 23

What is the consequence of the antral luminal environment of D and G cells?

Answer 23

High luminal H+ stimulates D cells to release somatostatin (negative regulatory loop)
Products of digestion stimulates the G cells to release gastrin, simulating acid secretion (positive loop).

Question 24

What other inhibitor of acid secretion are there?

Answer 24

Somatostatin, CCK, VIP, GIP, Neurotensin, Peptide YY, Prostaglandins and Secretin.

Question 25

How does secretin inhibit acid secretion?

Answer 25

Secretin (released by duodenal S-cells) stimulated by fat and acid in the duodenum can inhibit acid secretion by: Inhibiting Antral gastrin release
Simulating somatostatin release

Question 26

How does CCK inhibit acid secretion?

Answer 26

CCK is produced by I-cells of the duodenum and jejenum in response to fat. Directly reduces parietal-cell acid secretion.

Question 27

How do proton pump inhibitors work?

Answer 27

Proton pump inhibitors work by inhibiting the proton pump. H2 receptor antagonists are competitive antagonists of histamine at the parietal cell H2 receptor. Acid cannot be made because the inhibitors are inhibiting the proton pump.

Question 28

What are proton pump inhibitors used for?

Answer 28

Treatment of peptic ulcer disease, GOD, Barrett’s dysplasia, Zollinger Ellison syndrome.

Question 29

What is the first phase of gastric acid secretion?

Answer 29

Basal Phase:
Acid secretion is low a.m. and high at p.m. Acid secretion is a direct function of the number of parietal cells so size does matter. Acid secretion is enhanced several-fold matter.

Question 30

What is the second phase of gastric acid secretion?

Answer 30

The Cephalic Phase:
The smell, sight, taste, thought and swallowing of food initiates the cephalic phase, which is mediated by the vagus nerve, releases ACh, thus triggering acid secretion.
It accounts for 30% of total acid secretion and occurs before the entry of any food into the stomach.

Question 31

What is the third phase of gastric acid secretion?

Answer 31

The Gastric Phase:

Food is in the stomach, therefore a lot of acid is needed. It accounts for 50-60% total gastric secretion.

Question 32

What is the fourth phase of gastric acid secretion?

Answer 32

Intestinal Phase:
Partially digested peptide/amino acids in the proximal portion of the small intestine stimulates acid secretion predominantly by stimulation of duodenal G cells to secrete gastrin.
Accounts for 5 - 10% of total gastric acid secretion.

Question 33

What is pepsinogen and what is its function?

Answer 33

Pepsinogens are proteolytic proenzymes secreted by chief cells when stimulated by Ach. They are inactive enzymes but when activated by acid at pH<5 it is converted to pepsin. Pepsin then auto-activates pepsinogen. Interlinked with acid secretion because of similar trigger (Ach) and resulting peptides trigger antral G-cell gastrin secretion.
Pepsin is an endopeptidase which initiates protein digestion by cleaving peptide bonds at the end of the polypeptide.
They are irreversibly inactive at pH 7.2

Question 34

What is the role of the gastric mucosal protection

Answer 34

Contents of the stomach lumen = harsh environment pH <1. Protection comes from the mucous layer which traps local HCO3- secretion to maintain a pH of around 7. Prostaglandins are important in maintaining the mucosal diffusion barrier. They inhibit acid secretion, stimulation HCO3- secretion and mucus secretion. Importance of prostaglandings exemplified by the effects of NSAIDS on gastric mucosa.

Question 35

What does NSAID mean?

Answer 35

Anti-inflammatory drug aspirin

Question 36

What are the effects of NSAID?

Answer 36

NSAID inhibit the production of COX -1 prostaglandins from arachidonic acid therefore decrease inflammation. However due to the similar enzyme structure of COX-1 and COX-2 NSAID also prevents the formation of gastric mucosa protection and so causes stomach ulcers to form.

Question 37

What are the effects of Helicobacter pylori infection?

Answer 37

Gram-negative microaerophilic bacterium. It leads to causing peptic ulceration by acid production and barrier damage leading to inflammation (gastritis) and damage in the stomach, gastric and duodenal ulcers and gastric cancer (class 1 carcinogen). 
HP also produces urea that produces HCO3- and neutralises the stomach acid.

Question 38

What does a Helicobacter pylori infection in the antrum cause?

Answer 38

1. G-cells to hypersecrete gastrin
2. Decrease antral D-cell somatostatin release.
   This leads to hypergastrinaemia and ultimately duodenal ulcers.

Question 39

What does a Helicobacter pylori infection in the corpus cause?

Answer 39

Reduced acid secretion and hypochlorhydria. This is largely associated with gastric ulcers.

Question 40

What is Pernicious anaemia

Answer 40

Autoimmune atrophic gastritis, in which anti-bodies are directed against parietal cells and results in their destruction. Resulting in megaloblastic anaemia.