Peptic ulcer disease is a chronic illness manifested by recurrent ulcerations
in the stomach and proximal duodenum. Acid and pepsin are thought
to be crucial to ulcer development, but the great majority of peptic
ulcers are directly related to infection with Helicobacter
pylori or NSAID use.1,2 Gastritis is acute
or chronic inflammation of the gastric mucosa and has various etiologies. Dyspepsia is
continuous or recurrent upper abdominal pain or discomfort with
or without associated symptoms (nausea, bloating, etc.).3 Dyspepsia
may be caused by a number of diseases or may be functional.
About 500,000 new cases and about 4 million recurrent cases of peptic
ulcer disease are diagnosed each year in the U.S.4 Most
cases occur between the ages of 25 and 64 years.1 There
is a lifetime prevalence of peptic ulcer disease of between 8% and
14%, and an estimated U.S. $10 billion is spent
per year in total direct and indirect costs.1,4 H.
pylori infection is one of the most prevalent human infections
in the world, and approximately 30% to 40% of
the U.S. population is affected.5 The prevalence
of H. pylori infection is inversely related to
socioeconomic status and is particularly related to density of living
and household income during childhood.6 The age-adjusted
prevalence of H. pylori infection is decreasing
in industrialized countries, likely due to an improved standard
of living, especially during childhood, as well as spontaneous loss
of infection.5,6 This may explain the decreasing
incidence of peptic ulcer disease in the U.S., although increased
use of proton pump inhibitors (PPIs) may also be a factor.1 In
any given 6-month period about 40% of the population describes
some upper GI symptoms (including both dyspepsia and heartburn),
and investigation of these symptoms accounts for about 50% of
a gastroenterologist’s workload.7 The
point prevalence of dyspepsia alone is about 25%.3
Hydrochloric acid and pepsin destroy gastric and duodenal mucosa.
Mucus and bicarbonate ion secretions protect mucosa. Prostaglandins
protect mucosa by enhancing mucus and bicarbonate production and
by enhancing mucosal blood flow, thereby supporting metabolism.
The balance between these protective and destructive forces determines
whether peptic ulcer disease occurs. H. pylori infection
or NSAIDs are thought to be the causal agents of peptic ulcer disease
in almost all cases.2,8 H. pylori infection
is present in about 95% of patients who develop duodenal
ulcer and about 70% of those who develop gastric ulcer.9 Although
traditional treatment of peptic ulcers by various modalities heals
most ulcers, eradication of H. pylori reduces 1-year
recurrence rates from 35% to 2% for duodenal ulcers
and from 39% to 3% for gastric ulcers.5 H.
pylori is a spiral, gram-negative, urease-producing, flagellated
bacterium that is found living between the mucous gel and the mucosa.
The bacterium’s production of urease, cytotoxins, proteases,
and other compounds is thought to disturb the mucous gel and cause
tissue injury. In addition, increased gastrin levels and decreased
mucus and bicarbonate production are associated with H.
pylori infection.1 Chronic active (usually
asymptomatic) gastritis is an almost universal finding with H.
pylori infection, but only 10% to 20% of
infected people develop peptic ulcer disease.1,8,10 It
is unclear why most infected persons do not develop symptomatic
peptic ulcer disease, but it most likely reflects an interaction
of factors, including characteristics of host and pathogen (different
virulence of strains of bacteria).1,8 In 2005,
Marshal and Warren were awarded the Nobel Prize in Physiology or
Medicine for their discovery of “the bacterium H.
pylori and its role in gastritis and peptic ulcer disease.”11
H. pylori is a causative agent of mucosa-associated
lymphoid tissue lymphoma, and eradication
of infection causes a remission in a sizable percentage of patients
with low-grade tumors.5,8 In addition, H.
pylori infection is a definite risk factor for adenocarcinoma
of the stomach. However, because the prevalence of gastric cancer
in the U.S. is very low and the H. pylori infection
rate is very high, other factors undoubtedly are involved. Eradication
of H. pylori may be indicated in a subset of patients
at high risk for the development of gastric cancer.5,8 Recently, H.
pylori infection has been associated with the development
of iron deficiency anemia, with possible mechanisms including decreased iron
absorption and/or occult blood loss from chronic gastritis.
A direct cause-and-effect relationship is yet to be determined.5,10 Improvement
in the platelet count in some patients with idiopathic thrombocytopenic
purpura has been demonstrated with H. pylori eradication,
but much more work remains to be done in this regard.8,10
NSAIDs inhibit prostaglandin synthesis, thereby decreasing mucus
and bicarbonate production and mucosal blood flow, which allows
ulcer formation.1 Gastrin-secreting tumors produce
ulceration due to high levels of acid and pepsin production, but
acid alone rarely causes ulceration. However, inhibition of acid
secretion may allow ulcers to heal and is the basis for traditional
Hereditary factors cause a predisposition to peptic ulcer disease,
as does smoking. There is an association between chronic renal failure,
renal transplantation, cirrhosis, chronic obstructive pulmonary
disease, and peptic ulceration, but the precise mechanism is unclear.
Emotional stress may predispose to peptic ulcer disease, but diet
and alcohol use do not.
Acute gastritis may be related to ischemia from severe illness (shock,
trauma, severe burns, organ failure, etc.) or to the direct toxic
effects of agents (NSAIDs, steroids, bile acids, etc.). H.
pylori infection causes acute and chronic gastritis (both
usually asymptomatic). Chronic gastritis may also be caused by autoimmune
factors that destroy gastric parietal cells; this results in the loss
of acid production and the loss of intrinsic factor production,
which in turn cause malabsorption of vitamin B12 and, hence,
Dyspepsia has multiple causes. Endoscopy of patients with dyspepsia documents
that about 20% have “esophagitis, about 20% have
endoscopy-negative reflux disease, 10% have peptic ulcer
disease, 2% develop Barrett esophagus, ...