Gastric Physiology 1: Parietal cells and peptic ulcers

Question 1

What are the functions of the stomach?

Answer 1

• Store and mix food
• Dissolve and continue digestion
• Regulate emptying into duodenum
• Kill microbes
• Secrete proteases
• Secrete intrinsic factor
• Activate proteases
• Lubrication
• Mucosal protection

Question 2

What does intrinsic factor do?

Answer 2

Helps absorb Vitamin B12

Question 3

What does mucosal protection do?

Answer 3

Stops stomach digesting itself

Question 4

What are four key cell types in the stomach lining?

Answer 4

• Mucous cells
• Parietal cells
• Chief cells
• Enteroendocrine cells

Question 5

What do Parietal cells secrete?

Answer 5

• Secrete HCl
• Secrete intrinsic factor

Question 6

What do chief cells secrete?

Answer 6

Secrete proteases

Question 7

What do enteroendocrine cells secrete?

Answer 7

Hormones, they are a type of epithelial cells

Question 8

What acid is gastric acid secretion?

Answer 8

Hydrochloric acid
(secrete approx 2 litres/day)

Question 9

What ion is pumped out in gastric acid secretion?

Answer 9

H+ is pumped out at a very high concentration against a concentration gradients so it is very energy dependent

Question 10

What is HCl secretion regulated by?

Answer 10

• Neural (via vagus nerve)
• Hormones

Question 11

What ions are pumped out of the parietal cell and into the stomach lumen?

Answer 11

K+, Cl-, H+

Question 12

What ions are pumped from the stomach lumen into the parietal cell?

Answer 12

K+

Question 13

Which ions don’t require any energy to be pumped (e.g. passive diffusion)?

Answer 13

• K+ going into parietal cell
• Cl- being pumped out of cell

Question 14

Where are the H+ ions that are being pumped out of cell coming from?

Answer 14

• From cellular respiration
• From the formation of H2CO3 from CO2 and H20
• H2CO3 then broken down into HCO3 and H+ ions

Question 15

What ions are pumped into parietal cell from capillary and vice versa?

Answer 15

• HCO3- pumped out of cell and into capillary
• Cl- pumped into parietal cell from capillary

Question 16

What is the cephalic phase of gastric acid secretion?

Answer 16

It is turning it on phase and part of regulation

Question 17

What activates the cephalic phase?

Answer 17

• Parasympathetic nervous system
• Sight, smell, taste of food and chewing

Question 18

What does the release of acetylcholine do during the cephalic phase?

Answer 18

• It is a neurotransmitter (through the vagus nerve to the stomach)
• Acts directly on parietal cells
• Triggers the release of gastrin and histamine (which turns parietal cells on)

Question 19

What does the release of acetylcholine do during the cephalic phase?

Answer 19

• It is a neurotransmitter (through the vagus nerve to the stomach)
• Acts directly on parietal cells
• Triggers the release of gastrin and histamine (which turns parietal cells on

Question 20

What is the net effect from the release of acetylcholine in the cephalic phase?

Answer 20

Increased acid production (HCl)

Question 21

What stimulates the turning on during the gastric phase?

Answer 21

• Gastric distension (stretching)
• Presence of peptides and amino acids

Question 22

What is released during the gastric phase?

Answer 22

Gastrin (hormone)

Question 23

What does the release of gastrin do in the gastric phase?

Answer 23

• Acts directly on parietal cells
• Triggers the release of histamine (which acts directly on parietal cells)
• The net effect is an increase in acid production

Question 24

What does histamine do?

Answer 24

• Acts directly on parietal cells
• Mediates the effects of gastrin and acetylcholine

Question 25

What does having protein in the stomach do?

Answer 25

Direct stimulus for gastrin release

Question 26

What do proteins in the lumen do?

Answer 26

- Acts as a buffer, mopping up H+ ions, causing pH to rise (which further increases HCl production) - Decreases the secretion of somatostatin (turns parietal cells off) so a decrease in this means more parietal cell activity

Question 27

What stimulates the turning off of gastric secretion in the gastric phase?

Answer 27

- Low luminal pH (high H+ ions)

Question 28

What happens in order to turn off gastric acid secretion in the gastric phase?

Answer 28

Having a low luminal pH... - Directly inhibits gastrin secretion - Indirectly inhibits histamine release (via gastrin) - Stimulates somatostatin release which inhibits parietal cell activity

Question 29

What are the stimuli in the duodenum that turns off gastric acid secretion?

Answer 29

- Duodenal distension (stretching) - Low luminal pH - Hypertonic luminal contents (large number of ions) - Presence of amino acids and fatty acids Duodenum senses these and sends message to stomach to turn off via hormone (enterogastrones)

Question 30

What does the release of enterogastrones do?

Answer 30

- Secretin released (inhibits gastrin release, promotes somatostatin release) - Cholecystokinin (CCK) - Short and long neural pathways, reducing the Acetylcholine release (because the duodenum is innervated by vagus nerve)

Question 31

Conclusion: What affects the gastric acid secretion?

Answer 31

- 1 parasympathetic neurotransmitter (ACh +) - 1 hormone (gastrin +) - 2 paracrine factors (histamine +, somatostatin -) - 2 Key enterogastrones (secretin -, CCK-) + turns stomach on - turns stomach off

Question 32

What is autocrine factor?

Answer 32

Acts on own cell surface

Question 33

What is a paracrine factor?

Answer 33

Cells talk to neighbouring cells

Question 34

What does a hormone do?

Answer 34

Acts of other cells at a distant sites

Question 35

What is the definition of an ulcer?

Answer 35

It is a breach in a mucosal surface So a peptic ulcer is one caused by gastric enzymes

Question 36

What bacteria causes peptic ulcers?

Answer 36

Helicobacter Pylori infection

Question 37

What else can cause peptic ulcers?

Answer 37

- Drugs (NSAIDS e.g. aspirin, ibuprofen) - Chemical irritants (alcohol, bile salts) - Gastrinoma (tumours of enteroendocrine cells that produce gastrin)

Question 38

What can cause an ulcer in terms of mucosal attack/defence?

Answer 38

- Normal defences sufficient to resist attack means no ulcer - Increased mucosal attack creates an ulcer - Reduced mucosal defence creates an ulcer

Question 39

How does the gastric mucosa defend itself?

Answer 39

- Alkaline mucus (So can resist acid attack) - Tight junctions between epithelial cells (prevents liquid getting into tissues) - Replacement of damaged cells (so epithelial stays in tact) - Feedback loops prevent overproduction of gastric acid

Question 40

Where does helicobacter pylori live?

Answer 40

In gastric mucus

Question 41

How does helicobacter pylori cause a reduced mucosal defence?

Answer 41

- Secretes urease, splitting urea into CO2 and ammonia - Ammonia reacts with H+ ions and forms ammonium which is toxic to gastric epithelium - Ammonium secretes proteases, phospholipases which damage gastric epithelium - This causes an inflammatory response - Reducing mucosal defence

Question 42

How do NSAIDs cause peptic ulcers?

Answer 42

- Non-steroidal anti-inflammatory drugs - Mucus secretion is stimulated by prostaglandins - Cyclo-oxygenase 1 needed for prostaglandin synthesis (important in inflammatory process) - NSAIDs inhibit cyclo-oxygenase 1 - Reduced mucosal defence - So increased risk of peptic ulcers

Question 43

How do bile salts create peptic ulcers?

Answer 43

- Duodeno-gastric reflux (throwing up bile) - Regurgitated bile strips away mucus layer - Reduced mucosal defence

Question 44

How to treat peptic ulcer disease?

Answer 44

- proton pump inhibitor - antibiotics (e.g. amoxicillin)

Question 45

How to treat a peptic ulcer caused by NSAIDs?

Answer 45

- Prostaglandin analogues - misoprostol (stimulates gastric mucus production) - Reduce acid secretion - Could also use proton inhibitor

Question 46

What are some proton pump inhibitors?

Answer 46

Omeprazole, Lansoprazole, Esomeprazole

Question 47

What are some H2 (Histamine) receptor antagonists?

Answer 47

Cimetidine, Ranitidine