702
U N I T 8
Gastrointestinal and Hepatobiliary Function
the glandular epithelium of the stomach. There are three
major types of chronic gastritis:
Helicobacter pylori
gas-
tritis, autoimmune gastritis, and chemical gastropathy.
7
Helicobacter pylori Gastritis.
H. pylori
gastritis is a
chronic inflammatory disease of the antrum and body of
the stomach caused by the bacterium
H. pylori
.
6,7,18,19
It is
the most common cause of chronic gastritis in the United
States and is estimated to infect more than half of the
world’s population, particularly in developing countries.
H. pylori
are small, S-shaped, gram-negative rods
that can colonize the mucus-secreting epithelial cells of
the stomach (Fig. 29-3). The mode of transmission is not
well-defined, although oral–oral, fecal–oral, and environ-
mental spread are among the possible routes.
H. pylori
have multiple flagella, which allow them to move through
the mucous layer of the stomach, and they secrete urease,
which enables them to produce sufficient ammonia to
buffer the acidity of their immediate environment. These
properties help to explain why the organism is able to
survive in the acidic environment of the stomach.
H. pylori
produce enzymes and toxins that have the
capacity to interfere with the local protection of the
gastric mucosa against acid and produce a continuous
inflammatory response. This inflammatory response ini-
tially consists of recruitment of neutrophils, followed by
T and B lymphocytes. The inflammation may be confined
to the superficial gastric epithelium or extend deeper
into the gastric glands, resulting in varying degrees of
atrophy (atrophic gastritis) and metaplasia that converts
the gastric epithelium into intestinal-type epithelium.
Several
H. pylori
proteins are immunogenic and may
induce intense systemic and mucosal immune responses.
This antibody production does not lead to eradication
of infection but may contribute to tissue damage.
The clinical course of
H. pylori
infection is highly
variable and is influenced by both microbial and host
factors. Acute infection with
H. pylori
may cause a tran-
sient illness characterized by nausea and abdominal pain
that lasts for several days. After these symptoms resolve,
most individuals progress to an asymptomatic infection
with chronic mucosal inflammation. Chronic infection
with
H. pylori
can lead to gastric atrophy and peptic
ulcer, and is associated with increased risk of gastric ade-
nocarcinoma and low-grade B-cell gastric lymphoma.
Noninvasive testing for the presence of
H. pylori
infec-
tion can be performedwith the urea breath test or fecal anti-
gen test. Blood tests to obtain serologic titers of
H. pylori
antibodies also can be done. The serologic test can estab-
lish that a person has been infected with
H. pylori,
but it
cannot distinguish how recently the infection occurred.
The goal for
H. pylori
gastritis treatment is complete
elimination of the organism. Current treatment requires
combination therapy that includes the use of two antibi-
otics (clarithromycin, amoxicillin, metronidazole) with
a proton pump inhibitor.
H. pylori
mutate rapidly to
develop antibiotic-resistant strains. The combination of
two or more antimicrobial agents increases the rates of
cure and reduces the risk of resistant strains developing.
In geographic areas with clarithromycin resistant strains
of
H. pylori
, quadruple therapy that includes bismuth
is recommended. The proton pump inhibitors raise the
intragastric pH to suppress bacterial growth and opti-
mize antibiotic efficacy.
Chronic Autoimmune Gastritis.
Autoimmune gastri-
tis accounts for less than 10% of cases of chronic gas-
tritis and is often associated with other autoimmune
disorders such as type 1 diabetes mellitus, Hashimoto
thyroiditis, and Addison disease.
6
The disorder is char-
acterized by autoantibodies to the gastric parietal cells
and the intrinsic factor, defective gastric acid secretion,
and vitamin B
12
deficiency.
6,7
In contrast to
H. pylori
gastritis, autoimmune gastritis typically affects the body
and fundus of the stomach, sparing the antrum. Lack of
intrinsic factor disables vitamin B
12
absorption, leading
to a B
12
deficiency and slow-onset megaloblastic anemia
(pernicious anemia, see Chapter 13). Atrophy of the
fundic pyloric and chief cells can lead to development of
metaplastic changes that predispose to the development
of gastric adenocarcinoma.
Chronic autoimmune gastritis is noted for its slow onset
and progression. Antibodies to parietal cells and intrinsic
factor are present early in disease; progression to gastric
atrophy probably occurs over several decades. Because
of the slow onset and variable progression, persons with
the disorder are diagnosed only after being affected for a
number of years. Clinical presentation may be related to
anemia. In addition, vitamin B
12
deficiency may cause atro-
phic glossitis, in which the tongue becomes smooth and
beefy red; malabsorptive diarrhea; and neuropathies. The
most frequent manifestations of peripheral neuropathy
FIGURE 29-3.
Infective gastritis. Helicobacter pylori appear
on silver staining as small, curved rods on the surface of the
gastric mucosa. (From Mitros FA. Atlas of Gastrointestinal
Pathology. NewYork, NY: Grower Medical Publishing; 1988.)
