The gastric mucosa is equipped with specific physiological
functions and can trigger off a range of inflammatory and immune reactions according
to aggression mechanism. The term gastritis designates any inflammatory
lesion of the gastric mucosa in response to an aggression of the stomach. The
discovery of Helicobacter pylori (H. pylori) in 1982 showed it
to be responsible for the most frequent forms of chronic gastritis and led to
the histopathological classification of gastritis being re-organised (Sydney
system, etc.).
CHRONIC H. PYLORI GASTRITIS
H. pylori is a flagellate bacterium whose great mobility allows
it to cross the thick layer of mucus and reach the gastric epithelium. Here,
it can attach itself and propagate, while protecting itself from acidity by
alkalinising the ambient milieu through its urease activity. H. pylori
infection results in an acute, then chronic, inflammation of the gastric mucosa,
as shown by experimental infections of the human volunteer, and in
the animal. The inflammation regresses following antimicrobial treatment.
H. pylori can break down the protective mucus layer and damage the
gastric epithelium by various means, primarily toxins. Deterioration of
intercellular junctions allows it to penetrate between the epithelial cells.
The first host response to infection is acute inflammation resulting
from the arrival of numerous polymorphonuclear cells (PMNs) attracted by the
chemotactic factors produced by the bacteria and the aggressed mucosa
(cytokines by the epithelial cells and inflammatory cells). The PMNs migrate
to the surface of the mucosa and phagocytise the bacteria. In doing so, they
release toxic substances which contribute towards maintaining the lesions in
the mucosa. If the infection is not eliminated, the second phase comes
into play, characterised by an active, chronic inflammation and a specific
mucosal immune response with the large-scale production of cytokines (interleukins
6 and 8, TNF alpha, etc.). The PMNs are less numerous (their persistence
is a sign of the gastritic activity) and the inflammatory infiltrate is essentially
made up of mononuclear cells: macrophages, B and T lymphocytes, and plasma
cells producing specific immunoglobulins (secretory IgA, etc.). One
of the characteristics of H. pylori infection is the growth of lymphoid
follicles, indicating the gastric mucosa's possible acquisition of an organised
lymphoid tissue named MALT (mucosa-associated lymphoid tissue). Crossed
immune reactions between H. pylori and host antigens (homologous "stress"
proteins, antibacterial antibodies directed against the mucosa components) could
become involved in the lesions' pathogenesis. H. pylori strains
producing cytotoxins and/or expressing particular markers (type I strains
expressing the CagA protein, etc.) are found more commonly in cases of peptic
ulceration and atrophic gastritis. They are associated with an increase
of the inflammatory reaction (recruitment and activation of the PMNs) and
of the immune response (epithelial cell production of interleukin 8), probably
responsible for a greater disease severity. The influence of the host is also
determinant in expression of the infection, particularly as concerns control
of the immune response (negative regulation to attenuate the lesional consequences)
and disturbances to the gastric physiology associated with H. pylori
infection ...
Although H. pylori is always associated with an active chronic
inflammatory reaction, deteriorations to the epithelial surface, degree of spread
of inflammation (antral gastritis or pangastritis), development of atrophy and
intestinal metaplasia seem to be variable aspects of response to the infection.
Their appearance seems to depend on factors proper to the bacterium ("ulcerogenic"
or "cytotoxic" strains) and/or the host (inflammatory and
immune responses, extent and functional condition of the acid-secreting fundal
mucosa), plus contributions from endogenous (action of the bile, etc.) and exogenous
factors (role of diet, etc.) ...
H. PYLORI GASTRITIS AND ASSOCIATED PATHOLOGIES
Chronic H. pylori-induced gastritis is generally asymptomatic
and without major lesional consequence (superficial chronic gastritis).
Some subjects, however, do develop multifactorial gastroduodenal diseases along
with the infectious gastritis: duodenal ulcer, gastric ulcer, primitive gastric
lymphoma, gastric adenocarcinoma. These fundamental differences in expression
seem to be related to the host-bacterium interactions associated with environmental
factors.
GASTRIC OR DUODENAL PEPTIC ULCER
Excluding those caused by non-steroidal anti-inflammatory drugs (NSAIDs),
duodenal and gastric ulcers are both closely associated with H. pylori
infection. Eradicating H. pylori promotes healing of duodenal ulcers
and eliminates virtually all gastric or duodenal ulcer relapse, i.e.
the ulcer is cured. H. pylori - gastritis possibly plays a facilitating
role in ulcers resulting from NSAIDs, but this remains a matter of debate.
The mode of action of H. pylori infection has been studied most
in duodenal ulcerogenesis. H. pylori is often found in the duodenal mucosa
of ulcer patients, solely at the gastric metaplasia which develops there because
of the hyperacidity. Colonisation of the duodenal mucosa, generally at
the cap, is said to be the cause of the active chronic duodenitis which persists
between ulcerous attacks. The relative risk of developing a duodenal ulcer
is very high (51 times) in the event of H. pylori being present in the
duodenum. Chronic H. pylori infection generally elicits hyperacid
secretion (reversible after the bacterium has been eradicated) which is even
more so in patients with duodenal ulcer. Clinical and experimental data
suggest a chain of phenomena. The bacterium are thought to decrease antral D-cell
production of somatostatin, thus suppressing the physiological brake to gastrin
secretion by antral G-cells. The resulting hypergastrinaemia (perhaps also
elicited by the gastric inflammatory reaction) would stimulate the fundal parietal
cells, causing the proton pumps to increase H+ ion release and, in ulcer patients
perhaps, the parietal cell mass to increase. The acid hypersecretion would
result in an increase of duodenal acid load, predisposing ulcers to occur at
the duodenal mucosa weakened by inflammation.
GASTRIC NEOPLASIAS
Given the almost constant association of mucosal infection with these
tumoral proliferations and their regression following eradication of the bacterium,
H. pylori is probably involved in MALT gastric lymphomas. T lymphocyte
stimulation by bacterial antigens seems to be an essential mechanism of lymphocyte
proliferation in MALT gastric lymphomas, which probably develop from the
lymphoid follicle reaction typical of H. pylori infection.
A statistical association between H. pylori infection and gastric
adenocarcinoma (intestinal or diffuse) has been demonstrated. The active
chronic gastritis induced by H. pylori seems the starting point of carcinogenesis.
H. pylori is also implicated in the atrophying development
of chronic gastritis, the necessary condition for the emergence of intestinal
metaplasia and dysplasia lesions, the stages preceding the development of gastric
cancer under the influence of mutagenic factors.
H. pylori gastritis could also be involved in decreasing the gastric lumen vitamin C concentration
and in increasing epithelial cell proliferation, factors acknowledged to be
of influence in carcinogenesis. For these reasons, in 1994 the WHO decided
to put H. pylori in stomach carcinogen class 1.
DYSPEPSIA NON-ULCER
H. pylori's responsibility in functional or non-ulcer dyspepsia
(NUD), a rather mixed and elusive bag, has not been demonstrated. H. pylori
infection seems commoner in patients with NUD than in the population at large.
Nevertheless, the various therapeutic studies published on the subject
showed conflicting results. Whereas some highlight particular symptomatic
profiles, such as ulcer-like pain, others do not. Be this as it may,
the improvement of symptoms after the treatment, observed only after the bacterium
has been eradicated, indicates the role of H. pylori in non-ulcer patients
presenting epigastralgias. Rigorous methodological research is the solution.
CONCLUSION
The discovery of H. pylori triggered off a revival in interest
for gastric inflammatory pathology. This led to an overhaul in the classification
of chronic gastritis and a better understanding of the gastric mucosal barrier
and its means of defence, in which mucus occupies a key place. Mucosal infection
by H. pylori results in active chronic inflammation and lymphoid follicle
reaction. It is the common denominator of frequent and multifactorial gastroduodenal
diseases (duodenal ulcer, gastric ulcer, MALT gastric lymphoma, gastric adenocarcinoma,
etc.). Host-H. pylori interactions and their consequences on gastric
physiological functions (acid secretion, etc.) and environmental factors together
determine expression of the disease.
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