Gastric Acid Secretion: Disorders
This session will include:
• Outline how gastric acid secretion may become elevated and play a
role in the pathogenesis of duodenal ulcers describing the role of
Helicobacter pylori.
• The pharmacological basis of the action of anti-secretory drugs acting
on the 'proton' pump (e.g. omeprazole) histamine2 receptors (e.g.
cimetidine, ranitidine) will be discussed in this and subsequent lectures
(overtime peptides increase acidity)
GIT (gastro-intestinal tract) is involved in absorption of nutrients, salts, water and
elimination of undigested waste.
Malformation of GIT can lead to a decreased nutrient status (malnutrition)
Mechanism of peptic ulcer (generic term of ulcers, if want to be more specific say gastric
or duodenal ulcers) formation
-> There is breakage of mucosal barrier, then if there is an imbalance between the
protective factors and damaging factors (HCl) it can cause damage
->Exposure of tissues to the erosive effects of HCl and pepsin
But some sufferers can have normal or even subnormal levels of acid secretion
10% of the population are effected by ulcers, sites commonly effected are the
oesophagus, stomach and duodenum (areas usually exposed to HCl and pepsin,
especially duodenum as its not as well protected and the food going here is very acidic)
There are various factors responsible for gastric acid secretion, these are hence
damaging factors, these include
-> Histamine
-> Ach
-> Gastrin
-> Alcohol, smoking, caffeine, NSAIDs
-> etc.
Stress may also play a role, possibly aggravating existing ulcers. Bile acids are also
irritants and genetics may play a part in ulcer formation.
What are factors predisposing to peptic ulceration?
-> Gastric and duodenal infection with H.pylori is a major risk factor
-> Peptic ulcers can be acquired in childhood
Environmental and host factors can determine the distribution and colonization of
H.pylori in the stomach.
So smoking, genetic factors, stress can all promote acid/pepsin secretion which impairs
the mucosal defence mechanisms leading to a peptic ulcers.
, NSAIDs also impair the mucosal defence mechanisms by removing PGE2 (gastro-
protective effects, increase mucus secretion and bicarb secretion) and thromboxane A2
(involved in healing).
Do HCl and pepsin serve any useful purposes?
-> Yes! They help kill aerobic microorganisms and reduce risk of infection of the gastric
mucosa
-> Also role in pepsinogen activation
-> Stimulate release of bile and pancreatic juice release
Other factors that prevent infection of gastric mucosa are the mucus production, the
peristalsis/fluid movement, having a seamless epithelium with tight junctions, a fast cell
turnover and IgA secretion at the mucosal surfaces.
Very importantly we also have Peyers patches!!
Protective Factors that Prevent Autodigestion of the Stomach
The gut is exposed to a very hostile environment, the gastric juices contain about
150mM HCl as well as the presence of pepsin.
The protective mechanisms have generally been already discussed, but include
-> Secretion of an alkaline mucus and HCO3-
-> The protein content of food
-> Presence of tight junctions
-> Replacement of damaged cells within the gastric pits
-> Prostaglandins (E and I) which inhibit acid secretion and enhance blood flow
The mucus layer protects the gastric mucosa from the low pH
H. Pylori and Peptic Ulcer
H. Pylori is a gram negative spiral shaped aerobic bacterium. It penetrates the gastric
mucosa/mucus (like a corkscrew) (as able to survive under the harsh conditions of the
stomach).
H. Pylori is highly pathogenic with many virulence factors
Virulence factors of H.Pylori include its motility, it can move (by a corkscrew
movement) through the mucus and down close to the epithelium where the pH is
around 7.
It also produces urease, which converts urea to ammonia which buffers gastric acid and
produces CO2, this helps it survive the hostile environment.
Other important virulence factors include
Cytotoxin-associated antigen (CagA), this inserts pathogenicity islands inside the host
and this confers ulcer-forming potential (cause apoptosis of cells and affect tight
junctions)
This session will include:
• Outline how gastric acid secretion may become elevated and play a
role in the pathogenesis of duodenal ulcers describing the role of
Helicobacter pylori.
• The pharmacological basis of the action of anti-secretory drugs acting
on the 'proton' pump (e.g. omeprazole) histamine2 receptors (e.g.
cimetidine, ranitidine) will be discussed in this and subsequent lectures
(overtime peptides increase acidity)
GIT (gastro-intestinal tract) is involved in absorption of nutrients, salts, water and
elimination of undigested waste.
Malformation of GIT can lead to a decreased nutrient status (malnutrition)
Mechanism of peptic ulcer (generic term of ulcers, if want to be more specific say gastric
or duodenal ulcers) formation
-> There is breakage of mucosal barrier, then if there is an imbalance between the
protective factors and damaging factors (HCl) it can cause damage
->Exposure of tissues to the erosive effects of HCl and pepsin
But some sufferers can have normal or even subnormal levels of acid secretion
10% of the population are effected by ulcers, sites commonly effected are the
oesophagus, stomach and duodenum (areas usually exposed to HCl and pepsin,
especially duodenum as its not as well protected and the food going here is very acidic)
There are various factors responsible for gastric acid secretion, these are hence
damaging factors, these include
-> Histamine
-> Ach
-> Gastrin
-> Alcohol, smoking, caffeine, NSAIDs
-> etc.
Stress may also play a role, possibly aggravating existing ulcers. Bile acids are also
irritants and genetics may play a part in ulcer formation.
What are factors predisposing to peptic ulceration?
-> Gastric and duodenal infection with H.pylori is a major risk factor
-> Peptic ulcers can be acquired in childhood
Environmental and host factors can determine the distribution and colonization of
H.pylori in the stomach.
So smoking, genetic factors, stress can all promote acid/pepsin secretion which impairs
the mucosal defence mechanisms leading to a peptic ulcers.
, NSAIDs also impair the mucosal defence mechanisms by removing PGE2 (gastro-
protective effects, increase mucus secretion and bicarb secretion) and thromboxane A2
(involved in healing).
Do HCl and pepsin serve any useful purposes?
-> Yes! They help kill aerobic microorganisms and reduce risk of infection of the gastric
mucosa
-> Also role in pepsinogen activation
-> Stimulate release of bile and pancreatic juice release
Other factors that prevent infection of gastric mucosa are the mucus production, the
peristalsis/fluid movement, having a seamless epithelium with tight junctions, a fast cell
turnover and IgA secretion at the mucosal surfaces.
Very importantly we also have Peyers patches!!
Protective Factors that Prevent Autodigestion of the Stomach
The gut is exposed to a very hostile environment, the gastric juices contain about
150mM HCl as well as the presence of pepsin.
The protective mechanisms have generally been already discussed, but include
-> Secretion of an alkaline mucus and HCO3-
-> The protein content of food
-> Presence of tight junctions
-> Replacement of damaged cells within the gastric pits
-> Prostaglandins (E and I) which inhibit acid secretion and enhance blood flow
The mucus layer protects the gastric mucosa from the low pH
H. Pylori and Peptic Ulcer
H. Pylori is a gram negative spiral shaped aerobic bacterium. It penetrates the gastric
mucosa/mucus (like a corkscrew) (as able to survive under the harsh conditions of the
stomach).
H. Pylori is highly pathogenic with many virulence factors
Virulence factors of H.Pylori include its motility, it can move (by a corkscrew
movement) through the mucus and down close to the epithelium where the pH is
around 7.
It also produces urease, which converts urea to ammonia which buffers gastric acid and
produces CO2, this helps it survive the hostile environment.
Other important virulence factors include
Cytotoxin-associated antigen (CagA), this inserts pathogenicity islands inside the host
and this confers ulcer-forming potential (cause apoptosis of cells and affect tight
junctions)
