GI 2 - acid Flashcards
1
Q
how much gastric juice does a human secrete per day
A
2.5 litres
2
Q
what do peptic/ chief cells release
A
pro enzymes like prorennin and pepsinogen
3
Q
what do parietal cells secrete
A
HCl
4
Q
what are 3 reasons that gastric secretions are so acidic?
A
to promote proteolysis (convert pepsinogen to pepsin)
kill pathogens
aids in iron absorption
5
Q
which form of iron is better to be absorbed, which is favoured in acidic?
A
Fe2+ is better absorbed than Fe3+
Fe2+ is made in acidic environment
6
Q
what is the main protective mechanism of the stomach wall from acid
A
mucosal cells that secrete prostaglandins
7
Q
what are the 2 main prostaglandins that mucosal cells secrete
A
PGE2 and PGI2
8
Q
what do mucosal cells secrete
A
PGE2 and PGI2 (prostaglandins), also mucus and bicarbonate
9
Q
what are the targets for PGE2 and PGI2
A
EP1, EP2, EP3, EP4
10
Q
where do prostaglandins act to stimulate mucous secretion
A
EP4 receptors on mucosal cells
11
Q
where do prostaglandins act to stimulate bicarbonate ion secretion
A
EP1/2 receptors on mucosal cells
12
Q
what happens when EP4 receptors on mucosal cells are activated
A
release mucus
13
Q
what happens when EP1/2 receptors on mucosal cells are activated
A
stimulate bicarbonate ion secretion
14
Q
what is the pH of the stomach lumen
A
1-2
15
Q
how is the stomach wall physically protected from mucous? What is the ph of this?
A
mucosal surface forms gel-like protective surface, pH 6-7
16
Q
what kind of prostaglandins receptors are on enterochromaffin like cells
A
EP2/3
17
Q
what happens when EP2/3 on enterochromaffin like cells are activated
A
inhibits release of histamine
18
Q
what does histamine do and how
A
stimulates acid production via H2 receptors
19
Q
what kind of prostaglandins receptors are on vascular cells
A
EP2/4
20
Q
what happens when prostaglandins act on vascular EP2/4 receptors
A
vasodilation, improve blood flow to mucosal layer
21
Q
what are the 3 cell targets of prostaglandins
A
mucosal cells, enterochromaffin like cells (ECL), vascular cells
22
Q
what is the concentration of HCL secretion by parietal cells
A
150mM
23
Q
how is Cl- secreted by parietal cells
A
actively (alongside K+) (on lumen side)
24
Q
how is K+ secreted by parietal cells
A
actively (alongside Cl-) (on lumen side)
25
what kind of transporter is the Cl- K+ mechanism in parietal cells
it is co transport, 2ary active (on lumen side)
26
what provides the energy for the Cl- K+ co transport
K+ being exchanged in a H+/K+ ATPase (H+ into lumen, K+ back inside)
27
what is the pH inside the parietal cell
7.2
28
what is the pH inside the stomach lumen
1-2
29
what kind of gradient is the ATPase pumping against in the parietal cell
HUGE gradient, 10^5 fold gradient
30
what is the source of H+ in parietal cells
carbonic anhydrase generating H+ and HCO3- from H2O and CO2
31
what is the source of Cl- in parietal cells
HCO3- exchanges for Cl- (on blood side)
32
what is the pH of the HCl secreted by parietal cells
less than 1!
33
where is histamine released (and where in the cell specifically)
basally released from ECL cells
34
which cell releases histamine
ECL cells
35
where does histamine from ECL cells act
on parietal cell H2 receptors
36
what happens once histamine acts on parietal H2 receptors
activates Gs, cAMP --> proton pump
37
which cells release gastrin
G cells
38
what causes the release of gastrin by G cells
nerve stimulation and stomach contents
39
what are 2 example of stomch contents that stimulate HCl release
amino acids, Ca++
40
what does gastrin do? where does it act?
it acts on CCK2 receptors on ECL cells, elevates [Ca++]i to stimulate release of histamine
41
what do G cells release
gastrin
42
what do ECL cells release
histamine
43
where is ACh released
postganglionic cholinergic neurons
44
where does ACh act (2)
on parietal M3 receptors AND D cells
45
what happens when ACh acts on M3 receptors (where are they)
parietal cell, stimulates proton pump via elevation of [Ca++]i
46
what does ACh do to D cells
inhibits somatostatin release
47
what does ACh do to somatostatin release and how
inhibits its release from D cells
48
what do prostaglandins do in the HCl pathway (3)
inhibit histamine production, increase HCO3- and mucous secretion, vasodilation
49
where is somatostatin released (and what cell types)
from D cell in stomach
50
where does somatostatin act
SST2 receptors on G cells, ECL cells, parietal cells
51
what does somatostatin do to G cells
acts on SST2 receptors on G cells to inhibit gastrin release
52
what does somatostatin do to ECL cells
inhibit histamine release
53
what does somatostatin do to parietal cells cells
inhibit acid secretion
54
what are stomach ulcers and how can they be serious?
bleeding, perforation leading to stomach contents entering body cavity and causing peritonitis
55
what is GERD and how can it be serious?
damage to esophageal epithelium can lead to barretts esophagus (damaged, precancerous)
56
what are 3 examples of these GI diseases
ulcer, GERD, hiatal hernia
57
what is the problem with Hiatal hernia
similar with GERD and esophageal acid reflux, similar treatment
(dw too much bout this one)
58
what are 3 main causes of ulcers
stress, cyclooxygenase, helicobacter pylori infection
59
how does stress cause ulcers
vagal stimulation increases ACh release
60
how can NSAIDs cause ulcers
they decrease production of protective mucosal prostaglandins
61
what does COX-1 do
basal prostaglandin production
62
when is COX-2 induced
inflammation and growth
63
what % of gastric ulcers has helicobacter pylori infection
80-90%
64
what % of duodenal ulcers has helicobacter pylori infection
95%
65
what usually protects the duodenum from stomach acid
high levels of bicarbonate secretion there
66
what are the 3 main treatment goals with ulcers
relieve symptoms, allow damaged tissue to heal, eliminate cause
67
which gram is helicobacter pylori
negative
68
what % of population has helicobacter pylori in their stomach lining
50%
69
what % of population gets peptic ulcer disease in helicobacter pylori affected population
20%
70
how does helicobacter pylori cause ulcers (general)
asymptomatic inflammation of stomach lining, eventually causes ulcers and is linked to cancer
71
what class carcinogen is having helicobacter pylori
apparently WHO says class 1
72
what are 4 main ways that H. pylori survives in stomach acid
- burrowing into stomach lining
- urease (helps them neutralize acid)
- produces toxins
- local inflammation
73
what happens once helicobacter pylori burrows into stomach lining
the damage permits acid and pepsin to reach stomach epithelium
74
how does urease work (helicobacter pylori)
converts urea to HCO3 and ammonia (forms ammonium) to neutralize the acid
75
where does the urea come from for helicobacter pylori
the breakdown of amino acids from food
76
what happens once helicobacter pylori prouces toxins
it kills epithelial cells
77
how does helicobacter pylori cause local inflammation
immune cells spill destructive agents (like superoxide radicals) on stomach lining cells, leading to sores and ulcers
78
how can you test for helicobacter pylori? (Simple, name of test)
urea breath test
79
how does the urea breath test work
-drink solution containing urea labelled with 13C or 14C, collect exhaled breath and analyze for labelled CO2
80
what are 3 pros of the urea breath test
it is a quick, cheap and non invasive way to test for helicobacter pylori
81
what are 4 therapeutic strategies for ulcers/GERD/hiatal hernia
antibiotics, decrease acid secretion, neutralize secreted acid, protect mucosa
82
what is the point in using antibiotics for ulcers/GERD/hiatal hernia
to eliminate H. pylori
83
how can you decrease gastric acid secretion for ulcers/GERD/hiatal hernia
proton pump inhibitors or H2 receptor antagonists
84
how can you neutralize gastric acid for ulcers/GERD/hiatal hernia
antacids
85
what is the only cure for ulcers/GERD/hiatal hernia
antibiotics for H. pylori infection
86
what is Triple Therapy
proton pump inhibitor
+
antibacterial drugs (2 of them)
87
what are 2 mechanisms antibiotics used in triple therapy
a macrolide that inhibits bacterial protein synthesis + broad spectrum penicillin to inhibit bacterial wall synthesis
88
what are 2 antibiotic drugs used in triple therapy
clarithromycin and amoxicillin
89
what is an example of a proton pump inhibitor
omeprazole
90
how does clarithromycin work
a macrolide that inhibits bacterial protein synthesis
91
how does amoxicillin work
broad spectrum penicillin to inhibit bacterial wall synthesis
92
is triple therapy always useful
maybe, 2 week treatments is usually effective, but re infection can occur
93
what is the last step in the gastric acid secretion pathway
H+/K+ ATPase
94
what is first line therapy for reducing acid secretion
proton pump inhibitors
95
what is the mechanism of action of proton pump inhibitors (omeprazole)
a prodrug, when activated it binds covalently with cysteines in active site on outside of cell
-inhibits both basal and stimulated acid secretion
96
do proton pump inhibitors (omeprazole) inhibits basal or stimulated acid secretion
both
97
how long does omeprazole last and why
2-3 days because it is irreversible (but half life is only 1 hour)
98
what kind of pKa for omeprazole and what is its significance
around 8, so weak base/ ionized form accumulates on outside of cell in acid environment (perfect targeting, promotes conversion of prodrug)
99
what is the lipid solubility of omeprazole
low (BH+ B + H+
100
why may omeprazole have some drug interactions
because it inhibits some cytochrome P450 enzymes, potentiates actions of other drugs
101
what other drugs does omeprazole potentiate the action of
warfarin (anticoagulant) clodipogrel (antiplatelet), anti-epileptic phenytoin, benzos, TCAs
102
what kind of bad side effect may happen with omeprazole (2)
osteoporosis, cardio issues
103
what is cimetidine
H2 receptor antagonist (selective, competitive)
104
what is omeprazole
proton pump inhibitor
105
where are the H2 receptors that cimetidine targets
parietal cells
106
what kind of secretion does cimetidine reduce
histamine and gastrin stimulated acid secretion
107
what decrease in acid level happens?
decrease basal and stimulated by >90%
108
do H2 receptor antagonists (cimetidine) inhibits basal or stimulated acid secretion
both
109
what happens to pH when you use cimetidine
it increases to above 4
110
what protein gets affected by cimetidine
pepsin, less gets activated
111
what does cimetidine do to ulcer healing
promotes healing
112
what is the KD for cimetidine with H1, H2 and H3 (what does this mean for affinity)
lowest for H2, then H3 then H1
| so highest affinity for H2
113
does cimetidine have any drug interactions and why
yes because it inhibits some cytochrome P450 enzymes (CYP 2C9, 2D6, 3A4)
114
what are some examples of drug interactions with cimetidine
warfarin, felodipine (Ca++ channel antagonist), lovastatin, phenytoin, benzos, TCAs
115
what is an unwanted issue in men caused my cimetidine
gynaecomastia
116
how does cimetidine cause gynaecomastia
affinity for estrogen receptors and increase prolactin secretion
117
what kind of compounds are most antacids
basic inorganic salts
118
how do basic inorganic salts work
taken orally to directly neutralize gastric acid and thus inhibit peptide enzymes
119
what pH do peptide enzymes need to work
under 5 I think
120
what is the mechanism of action of antacids
chemical antagonism
121
Are antacids absorbed?
no, just act in the lumen anyways
122
how can antacids help with ulcers
sufficient doses for prolonged periods can help heal them
123
what is inside antacids
micture of salts (Mg and Al hydroxyde) to help preserve normal bowel function
124
what does magnesium cause generally
diarrhea
125
what does aluminium cause generally
constipation
126
what is the stomach acid neutralization reaction with aluminum hydroxide
Al(OH)3 + 3HCl --> AlCl3 + 3H2O
127
what are alginates
negatively charged polysaccharides from algal cell wall
128
how do alginates work (2)
absorb water to form a viscous gum, maybe increase viscosity and adherence of mucous to stomach lining
129
what are 3 examples of alginates
tums, gaviscon, mylanta
130
what is the active ingredient in tums
CaCO3
131
what is the active ingredient in gaviscon
MgCO3 + alginic acid
132
what is the active ingredient in mylanta
MgCO3 + Al(OH)3
133
what is bismuth chelate
a colloid, used with triple therapy to treat H. pyloria
134
how does bismuth chelate work
kills bacteria (maybe) and prevents adherence
135
what are 2 ways to protect the mucosa (general, not drugs)
enhance endogenous mucosal protective mechanisms and/or provide physical barrier over ulcer
136
what are 2 drugs used to protect the mucosa
bismuth chelate, sucralfate
137
how does sucralfate work, what is it (big answer)
complex of Al(OH)3 and sulfated sucrose which releases Al in acidic enviro to leave -ve charged complex which binds to proteins and glycoproteins in mucous to form gel
138
what are 4 other things that bismuth chelate and sucralfate do other than mucous protection
affect absorption of other drugs, adsorb pepsin, enhance PG synthesis, stimulate HCO3 secretion
139
what is misoprostal
a stable PGE1 analog
140
how can misoprostal help protect mucosa (4 general things)
inhibit HCl release from parietal cells, enhance mucous production and mucosal blood flow, stimulates HCO3- release
141
what are 3 main targets for misoprostol (cellular targets+what does it cause)
EP1/2 on mucosal cells (increase HCO3-), EP4 on mucosal cells (increase mucous), EP2/3 on ECL cells (inhibit histamine)
142
what is the main mechanism of action of misoprostol (1 thing)
adenylyl cyclase inhibition
143
which peptic ulcer drug is most likely to cause breast enlargement?
cimetidine
