C h a p t e r 2 9
Disorders of Gastrointestinal Function
703
are paresthesias and numbness. Cerebral manifestations
range from mild personality changes and memory loss to
psychosis. In contrast to the anemia, neurologic changes
are not reversed by vitamin B
12
replacement therapy.
6
Chemical Gastropathy.
Chemical gastropathy repre-
sents the effects of chronic gastric injury resulting from
reflux of alkaline duodenal contents, pancreatic secre-
tions, and bile into the stomach. It is most commonly
seen in persons who have had gastroduodenostomy or
gastrojejunostomy surgery. A milder form may occur in
persons with gastric ulcer, gallbladder disease, or vari-
ous motility disorders of the distal stomach.
Ulcerative Disorders
The lumen of the stomach is strongly acidic, a condition
that contributes to digestion, but also has the potential
to damage the mucosa and produce an ulcer. Among
the conditions associated with ulceration of the gastric
mucosa are peptic ulcer disease, Zollinger-Ellison syn-
drome, and stress ulcers.
Peptic Ulcer Disease
Peptic ulcer disease
is a term used to describe a group of
ulcerative disorders that occur in areas of the gastric and
intestinal mucosa, mainly the proximal duodenum, that
are exposed to acid–pepsin secretions.
6,7,20,21
Although
the incidence and prevalence of peptic ulcer has declined
substantially during the past 30 years, approximately
10% of people in Western industrial countries will
develop a peptic ulcer during their lifetime.
7
A peptic ulcer can affect one or all layers of the stom-
ach or duodenum (Fig. 29-4). The ulcer may penetrate
only the mucosal surface, or it may extend into the
smooth muscle layers. Occasionally, an ulcer penetrates
the outer wall of the stomach or duodenum. Spontaneous
remissions and exacerbations are common. Healing of the
muscularis layer involves replacement with scar tissue;
although the mucosal layers that cover the scarred muscle
layer regenerate, the regeneration often is less than per-
fect, which contributes to repeated episodes of ulceration.
Etiology and Pathogenesis.
A variety of risk factors
have been shown to have an association with peptic ulcer
disease. The two most important are infection with the
bacteria
H. pylori
and use of aspirin and/or NSAIDs.
20,21
In contrast to peptic ulcer from other causes, NSAID-
induced gastric injury often occurs without symptoms,
and life-threatening complications can develop without
warning. There is reportedly less gastric irritation with
the newer class of NSAIDs that selectively inhibit cylco-
oxygenase-2 (COX-2–selective NSAIDs), the principal
enzyme involved in prostaglandin synthesis at the site of
inflammation, than with the nonselective NSAIDs that
also inhibit COX-1, the enzyme involved in prostaglan-
din production in the gastric mucosa.
Epidemiologic studies have identified independent
factors that augment the effect of
H. pylori
infection
and NSAID-produced peptic ulcer disease. These fac-
tors include advancing age, a prior history of peptic
ulcer, NSAID use, and concurrent use of corticosteroid
drugs. Smoking may augment the risk of peptic ulcer
by impairing healing. Genetic factors may also play a
role as supported by the fact that blood-group antigens
correlate with peptic ulcer disease. People with type
O blood and those who do not secrete antigens in their
saliva or gastric juices are at greater risk of developing
duodenal ulcers.
7
Clinical Manifestations.
The clinical manifestations
of uncomplicated peptic ulcer focus on discomfort and
pain. The pain, which is described as burning, gnawing,
or cramplike, usually is rhythmic and frequently occurs
when the stomach is empty—between meals and at 1 or
2 o’clock in the morning. The pain usually is located over
a small area near the midline in the epigastrium near the
xiphoid, and may radiate below the costal margins, into
the back, or, rarely, to the right shoulder. Superficial and
deep epigastric tenderness and voluntary muscle guard-
ing may occur with more extensive lesions. An additional
characteristic of ulcer pain is periodicity. The pain tends
to recur at intervals of weeks or months. During an exac-
erbation, it occurs daily for a period of several weeks and
then remits until the next recurrence. Characteristically,
the pain is relieved by food or antacids.
Complications.
The most common complications of
peptic ulcer are hemorrhage, perforation, and gastric
outlet obstruction. Hemorrhage is caused by bleeding
from granulation tissue or from erosion of an ulcer into
FIGURE 29-4.
Gastric ulcer.The stomach has been opened
to reveal a sharply demarcated, deep peptic ulcer on the
lesser curvature. (From Rubin E, Farber JL, eds. Rubin’s
Pathology: Clinicopathologic Foundations of Medicine. 3rd ed.
Philadelphia, PA: Lippincott Williams &Wilkins; 1999:693.)
