DYSPEPSIA/INDIGESTION

A. Mechanism/Causes
The most common causes of indigestion are gastroesophageal reflux and functional
dyspepsia. Other cases are a consequence of a more serious organic illness.
1. GASTROESOPHAGEAL REFLUX
o Gastroesophageal reflux can result from a variety of physiologic defects.
Reduced lower esophageal sphincter (LES) tone is an important cause of
reflux in scleroderma and pregnancy; it may also be a factor in patients
without other systemic conditions.
o Many individuals exhibit frequent transient LES relaxations during which
acid or nonacidic fluid bathes the esophagus. Overeating and aerophagia
can transiently override the barrier function of the LES, whereas impaired
esophageal body motility and reduced salivary secretion prolong fluid
exposure. The role of hiatal hernias is controversial--although most reflux
patients exhibit hiatal hernias, most individuals with hiatal hernias do not
have excess heartburn.

2. GASTRIC MOTOR DYSFUNCTION

o Disturbed gastric motility is purported to cause gastroesophageal reflux in
some cases of indigestion. Delayed gastric emptying is also found in
25--50% of functional dyspeptics. Impaired gastric fundus relaxation after
eating may underlie selected dyspeptic symptoms like bloating, nausea,
and early satiety.

3. VISCERAL AFFERENT HYPERSENSITIVITY

o Disturbed gastric sensory function is proposed as a pathogenic factor in
functional dyspepsia. Visceral afferent hypersensitivity was first
demonstrated in patients with IBS who had heightened perception of
rectal balloon inflation without changes in rectal compliance.
o Similarly, dyspeptic patients experience discomfort with fundic distention
to lower pressures than healthy controls. Some patients with heartburn
exhibit no increase in reflux of acid or nonacidic fluid. These individuals
with functional heartburn are believed to have heightened perception of
normal esophageal pH and volume.

4. OTHER FACTORS
o Helicobacter pylori has a clear etiologic role in peptic ulcer disease, but
ulcers cause a minority of cases of dyspepsia. H. pylori is considered to be
a minor factor in the genesis of functional dyspepsia.
o In contrast, functional dyspepsia is associated with a reduced sense of
physical and mental well--being and is exacerbated by stress,
suggesting important roles for psychological factors.
o Analgesics cause dyspepsia, while nitrates, calcium channel blockers,
theophylline, and progesterone promote gastroesophageal reflux. Other
stimuli that induce reflux include ethanol, tobacco, and caffeine via LES
relaxation. Genetic factors may promote development of reflux.

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B. Differential Diagnosis
1. GASTROESOPHAGEAL REFLUX DISEASE
o Gastroesophageal reflux disease (GERD) is prevalent in Western society. Most cases of
heartburn occur because of excess acid reflux, although reflux of non--acidic fluid
may produce similar symptoms.
o Alkaline reflux esophagitis produces GERD--like symptoms most often in patients who have
had surgery for peptic ulcer disease. Approximately 10% of patients with heartburn of a
functional nature exhibit normal degrees of esophageal acid exposure and no increase in
nonacidic reflux.

2. FUNCTIONAL DYSPEPSIA
o Functional dyspepsia, the cause of symptoms in 60% of dyspeptic patients, is defined as 3
months of bothersome postprandial fullness, early satiety, or epigastric pain or burning
with symptom onset at least 6 months before diagnosis in the absence of organic cause.
o Most cases follow a benign course, but some patients with H. pylori infection or on
nonsteroidal anti--inflammatory drugs (NSAIDs) develop ulcers. As with idiopathic
gastroparesis, some cases of functional dyspepsia result from prior gastrointestinal
infection.

3. ULCER DISEASE
o In most cases of GERD, there is no destruction of the esophagus. However, 5% of patients
develop esophageal ulcers, and some form strictures. Symptoms do not reliably distinguish
nonerosive from erosive or ulcerative esophagitis.
o Some 15--25% of cases of dyspepsia stem from ulcers of the stomach or duodenum. The
most common causes of ulcer disease are gastric infection with H. pylori and use of
NSAIDs.
o Other rare causes of gastroduodenal ulcer include Crohn's disease and Zollinger--
Ellison syndrome, a condition resulting from gastrin overproduction by an endocrine tumor.

4. MALIGNANCY
o Dyspeptic patients often seek care because of fear of cancer. However, <2% of cases result
from gastroesophageal malignancy.
o Between 8 and 20% of GERD patients exhibit intestinal metaplasia of the esophagus,
termed Barrett's metaplasia. This condition predisposes to esophageal adenocarcinoma
(Chap. 91). Gastric malignancies include adenocarcinoma, which is prevalent in certain
Asian societies, and lymphoma.