Secretions of the Stomach Flashcards
1
Q
What are the functions of the stomach
A
- Stores food
- Mixes food with secretions
- Regulates release of food into duodenum
- Secretes gastric juices
2
Q
Anatomy
A
of stomach
3
Q
What substances do mucous neck cells secrete
A
- Mucous
- Bicarbonate
4
Q
What substances do parietal cells secrete
A
- Acid
- IF (intrinsic factor)
5
Q
What substances do EC like cells secrete
A
- Histamine
6
Q
What substances do chief cells secrete
A
- Pepsinogen
- Lipase
7
Q
What substances do D cells secrete
A
- Somatostatin
8
Q
What substances do G cells secrete
A
- Gastrin
9
Q
Where in the stomach are a majority of parietal cells found
A
- The corpus (or body) of the stomach
10
Q
Where in the stomach are a majority of G cells found
A
- The antrum of the stomach
11
Q
Where in the stomach are a majority of D cells found
A
- They are distributed across the stomach
12
Q
What mediates the acid secretion in parietal cell and where is this located
A
- H+/K+ pump that requires energy in the form of ATP
- It is located in the apical membrane of the parietal cells
13
Q
What 2 types of subunits does the H-K pump require for full activity and state a reason for requiring each subunit
A
- Alpha subunit for catalytic function
- Beta subunit for apical membrane targeting
14
Q
What is the action of the H-K pump and why does this occurs
A
- Action - Extrudes H+ into the lumen of the gastric gland
- Why - The H+ is exchanged for a K+ ion which is recycled in the lumen via K+ channels
15
Q
How is the original H+ ion that is forced into the lumen of the gastric gland generated generated
A
- Generated from carbonic acid using carbonic anhydrase
16
Q
What happens to the H+ ion that is forced into the lumen of the gastric gland
A
- It combines with Cl- that has left cells through ion channels to produce HCl
17
Q
Give the carbonic anhydrase catalysed reaction
A
H20+CO2->H2CO3->HCO3-+H+
18
Q
What happens to the HCO3- produced when generating H+
A
It exists the basolateral membrane via the Cl-, HCO3- exchanger then enters the blood
19
Q
What is the movement of HC03- ions into the blood called
A
- Alkaline tide
20
Q
What are the 2 types of regulation of acid secretion by parietal cells
A
- Direct Regulation - Action triggers proton efflux via H+/ K+ pumps
- Indirect regulation - Releasing another substance (histamine) that stimulates acid production
21
Q
What are the 3 stimuli that directly regulate acid production
A
- Ach
- Histamine
- Gastrin
22
Q
How does Ach directly regulate acid production
A
- Eating a meal causes stretching in the stomach which stimulates the vagus nerve releasing Ach as the neurotransmitter.
- Ach binds to M3 receptor which stimulates acid production in parietal cells4
23
Q
How does histamine directly regulate acid production
A
-Produced by ECL cells
-Binds to H2 receptor on parietal cells and triggers acid production.
24
Q
How does gastrin directly regulate acid production
A
- Produced by G cells.
- Binds to Gastrin receptor on parietal cells and stimulates acid production
25
How does indirect regulation of acid production occur via histamine
- Ach and gastrin stimulate ECL cells to produce histamine
- Histamine stimulates acid production in parietal cells.
26
Out of Ach, histamine and gastrin which has the most impact on regulating acid production and why
- Histamine
- Has both direct and indirect effects
27
What pathway stimulates H+/K+ pumps when histamine binds to a H2 receptor
- An adenyl cyclase-camp-PKA pathway
28
What pathway stimulates H+/K+ pumps when gastrin or Ach bind to their respective receptors.
- PLC/PKC/Ca2+ pathway
29
What is the name of the major inhibitor for acid production
- Somatostatin
30
How does somatostatin inhibit acid production
- It antagonises the adenyl cyclase pathway (inhibiting the action of histamine)
31
What inhibits somatostatin production
- Vagus nerve stimulation
32
What happens in the corpus of the stomach
- Ach is released from the vagus nerve due to distension of stomach
33
What effects does Ach have in the stomach
- Direct stimulation of parietal cells to induce acid release.
- indirect stimulation of parietal cells by causing E cells to release histamine.
- Stimulates D cell which inhibits the release of somatostatin.
34
What 2 types of cells are stimulated in the antrum by vagal stimulation
- G cells - via GRP
- D cells - via Ach
35
What stimulates D cells to release somatostatin (not vagal nerve stimulation)
- Products of protein digestion such as peptides and amino acids
36
What stimulates G cells to release somatostatin (not vagal nerve stimulation)
- High luminal H+
37
What is secretin and how does it work
- Inhibitor of acid secretion
- Works by inhibiting the release of gastrin in the antrum and releasing somatostatin
38
What releases secretin
- Duodenal S cells
39
What stimulates secretin production
- Fat and acid in duodenum
40
What is CCK and how does it work
- Inhibitor of acid production
- Works by directly decreasing parietal-cell acid secretion
41
What releases CCK
- I cells in Duodenum and jejunum
42
What stimulates CCK production
- Fat
43
Give examples of pharmacological inhibitors of acid secretion
- Proton pump inhibitors
- H2 receptive antagonist
44
How do H2 receptor antagonist work
- Competitive antagonist of histamine at parietal cell H2 receptor.
45
Which pharmacological inhibitor of acid secretion is the best and why
- PPI
- RA's only supress acid production via histamine, however histamine is still a large proportion of acid production stimulation so RAs are still used
46
What are the 4 phases of gastric acid secretion
1) Basal Phase
2) Cephalic (30%)
3) Gastric (50%-60%)
4) Intestinal (5%-10%)
47
What type of rhythm does the basal phase follow
- Circadian rhythm - Low acid production in a.m high acid production in p.m
- No. of parietal cells determines acid production (size of stomach)
48
What can trigger the cephalic phase
- Smell
- Sight
- Taste
- Thought
- Swallowing
49
What stimulates acid production in the gastric phase
- Distension of the stomach by food
50
What stimulates acid production in the intestinal phase
- Partially digested peptides and amino acids
51
What are Pepsinogens
- Proteolytic proenzymes secreted by chief cells
52
What is a major trigger for pepsinogen secretion
- Ach
53
How does pepsinogen become is active form (pepsin)
- Conversion happens spontaneously at pH <5
54
What effect does pepsin have on pepsinogen
- Cascade effect - Pepsin autoactivates pepsinogen
55
When does pepsin become irreversibly inactivated
- pH of 7.2
- In the small intestines
56
What is an endopeptidase
- Protease
- A protease enzyme that initiates protein digestion by cleaving amino acids anywhere but their terminal ends.
57
What is the link between acid secretion and pepsinogen activity
- Smaller peptides and amino acids cleaved by pepsinogen trigger G cell gastrin secretion the antrum
58
Why is gastric mucosal protection needed
- The contents of stomach lumen create a harsh environment
59
How is the lining of the stomach protected
- Mucousal layer traps HCO3- which maintains a pH of around 7
60
How do prostaglandins maintain the mucosal diffusion barrier
- Inhibit acid secretion stimulating HCO3- and mucus secretion
61
Give an example that proves the importance of prostaglandins
- Effects of non selective NSAIDS on gastric mucosa
62
What makes prostaglandins
- A precursor called arachidonic acid
63
What 2 types of prostaglandins does arachidonic acid produce
- Prostaglandins involved in pathology (inflammation)
- Prostaglandins involved in physiology
64
What enzyme is responsible for the production of prostaglandins that are involved in inflammation and what is important about this enzyme
- Cyclooxygenase - 2 (COX 2)
- It is inducible - not switched on all the time
65
What enzyme is responsible for the production of prostaglandins that are involved in physiology and what is important about this enzyme
- Cyclooxygenase - 1 (COX 1)
- Constitutively active - always there
66
What issue does inhibiting the effect of arachidonic acid have when taking NSAIDs
- COX -1 and COX - 1 are both inhibited
- This means that the prostaglandins involved in gastric mucosal protection are not produced either.
67
What are some common side effects of using non selective NSAIDs to treat inflamation
- Gastric ulceration
- Dyspepsia
68
Give an example of a selective COX-2 inhibitor and why it has been withdrawn
- Vioxx
- Increases risk of heart attack
69
What is Helicobacter Pylori (H. Pylori) and what is it classified as
- Gram-negative microaerophilic bacterium
- Classified as a carcinogen.
70
What percentage of human stomachs are colonised by H. Pylori
- 40%
71
What can H. Pylori cause
- Gastritis
- Peptic, gastric and duodenal ulcers
- Gastric cancer
72
How does H. Pylori cause stomach ulcers
- Flagellum moves H. Pylori to stomach/duodenum
- Produces mucinase to breakdown mucin to weaken mucosal coating
- H. Pylori binds to gastric mucosal cells via lipopolysaccharides
- Also allows acid to reach mucosa causing peptic ulcer
73
How does H. Pylori survive the pH of stomach acid
- Synthesises urease enzyme which breaks down urea into an ammonium ion and a bicarbonate ion.
- The bicarbonate ion neutralises stomach acid
74
How does H. Pyloris infection in the antrum cause hypergastrinemia and ultimately duodenal ulcers
- Causes G cells to hyper secrete gastrin leading to lots of acid being produced
- Decreases antral D-cell somatostatin production
75
What does H. Pyloris infection in the corpus cause
- Reduced acid secretion
- Hypochlorhydria (highly associated with gastric ulcers)
76
What is triple therapy
- Treatment using 2 antibiotics (amoxicillin and clarithromycin) and a proton pump inhibitor
77
What is intrinsic factor produced by and why is it necessary
- Produced by parietal cells
- Necessary for Vitamin B12 production in the terminal ileum
78
What is the effect of a lack of Vitamin B12
Addison's Anaemia/ Percinicous anaemia
79
What is Addison's Anaemia/ Percinicous anaemia and what does it cause
- Autoimmune atrophic gastritis, autoantibodies destroy parietal cells
- Can cause megaloblastic anaemia
