A
peptic ulcer, also known as
ulcus
pepticum,
PUD or
peptic ulcer
disease, is an ulcer (defined as mucosal erosions equal to
or greater than 0.5 cm) of an area of the
gastrointestinal tract that is
usually acidic and thus extremely painful. As many as 80% of ulcers
are associated with
Helicobacter
pylori, a spiral-shaped bacterium that lives in the acidic
environment of the stomach, however only 40% of those cases go to a
doctor. Ulcers can also be caused or worsened by drugs such as
aspirin and other
NSAIDs.
Contrary to general belief, more peptic ulcers arise in the
duodenum (first part of the
small intestine, just after the stomach)
than in the
stomach. About 4% of stomach
ulcers are caused by a
malignant tumor, so
multiple biopsies are needed to exclude cancer. Duodenal ulcers are
generally
benign.
Classification
Types of peptic ulcers:
- Type I: Ulcer along the lesser curve of stomach
- Type II: Two ulcers present - one gastric, one duodenal
- Type III: Prepyloric ulcer
- Type IV: Proximal gastroesophageal ulcer
- Type V: Anywhere along gastric body, NSAID induced
Signs and symptoms
Symptoms of a peptic ulcer can be
- abdominal pain, classically
epigastric with severity relating to mealtimes, after around 3
hours of taking a meal (duodenal ulcers are classically relieved by
food, while gastric ulcers are exacerbated by it);
- bloating and abdominal fullness;
- waterbrash (rush of saliva after an episode of regurgitation to
dilute the acid in esophagus);
- nausea, and copious vomiting;
- loss of appetite and weight loss;
- hematemesis (vomiting of blood);
this can occur due to bleeding directly from a gastric ulcer, or
from damage to the esophagus from severe/continuing vomiting.
- melena (tarry, foul-smelling feces due to
oxidized iron from hemoglobin);
- rarely, an ulcer can lead to a gastric or duodenal perforation. This is extremely painful and
requires immediate surgery.
A history of
heartburn,
gastroesophageal reflux
disease (GERD) and use of certain forms of medication can raise
the suspicion for peptic ulcer. Medicines associated with peptic
ulcer include
NSAID (non-steroid
anti-inflammatory drugs) that inhibit
cyclooxygenase, and most
glucocorticoids (e.g.
dexamethasone and
prednisolone).
In patients over 45 with more than two weeks of the above symptoms,
the odds for peptic ulceration are high enough to warrant rapid
investigation by EGD (see below).
The timing of the symptoms in relation to the meal may
differentiate between
gastric and
duodenal
ulcers: A gastric ulcer would give
epigastric pain
during the meal, as
gastric acid is secreted, or
after the meal, as the alkaline duodenal contents reflux
into the
stomach. Symptoms of duodenal
ulcers would manifest mostly
before the meal—when acid
(production stimulated by hunger) is passed into the
duodenum. However, this is not a reliable sign in
clinical practice.
Complications
- Gastrointestinal
bleeding is the most common complication. Sudden large
bleeding can be life-threatening. It occurs when the ulcer erodes
one of the blood vessels.
- Perforation (a hole in the wall) often leads
to catastrophic consequences. Erosion of the gastro-intestinal wall
by the ulcer leads to spillage of stomach or intestinal content
into the abdominal cavity. Perforation at the anterior surface of
the stomach leads to acute peritonitis,
initially chemical and later bacterial peritonitis. The first sign
is often sudden intense abdominal pain. Posterior wall perforation
leads to pancreatitis; pain in this
situation often radiates to the back.
- Penetration is when
the ulcer continues into adjacent organs such as the liver and
pancreas.
- Scarring and swelling due to ulcers causes narrowing in the
duodenum and gastric
outlet obstruction. Patient often presents with severe
vomiting.
- Pyloric stenosis
Cause
A major causative factor (60% of gastric and up to 90% of duodenal
ulcers) is chronic
inflammation due to
Helicobacter pylori
that
colonizes the
antral mucosa. The
immune system is unable to clear the infection, despite the
appearance of antibodies. Thus, the
bacterium can cause a chronic active
gastritis (type B gastritis), resulting in a
defect in the regulation of
gastrin
production by that part of the stomach, and gastrin secretion can
either be decreased (most cases) resulting in hypo- or
achlorhydria or increased.
Gastrin stimulates the production of
gastric acid by parietal cells and, in H.
pylori colonization responses that increase gastrin, the increase
in acid can contribute to the erosion of the
mucosa and therefore ulcer formation.
Another major cause is the use of
NSAIDs (see
above). The gastric mucosa protects itself from
gastric acid with a layer of mucus, the
secretion of which is stimulated by certain prostaglandins. NSAIDs
block the function of
cyclooxygenase
1 (
cox-1), which is essential for the production of these
prostaglandins. COX-2 selective anti-inflammatories (
celecoxib,
rofecoxib
"Vioxx" withdrawn from market) preferentially inhibit
cox-2, which is less essential in the gastric mucosa, and
roughly halve the risk of NSAID-related gastric ulceration. As the
prevalence of H. pylori-caused ulceration declines in the Western
world due to increased medical treatment, a greater proportion of
ulcers will be due to increasing NSAID use among individuals with
pain syndromes as well as the growth of aging populations that
develop arthritis.
The incidence of duodenal ulcers has dropped significantly during
the last 30 years, while the incidence of gastric ulcers has shown
a small increase, mainly caused by the widespread use of NSAIDs.
The drop in incidence is considered to be a cohort-phenomena
independent of the progress in treatment of the disease. The
cohort-phenomena is probably explained by improved standards of
living which has lowered the incidence of H. pylori
infections.
Tobacco smoking leads to
atherosclerosis and vascular spasms, causing
vascular insufficiency and promoting the development of ulcers
through
ischemia.
Nicotine contained in
cigarettes can increase
parasympathetic nerve
activity to the gastrointestinal tract by acting on the nicotinic
receptors at synapses - increased stimulation to the
enterochromaffin-like cells and
G cells increases the amount of
histamine and
gastrin
secreted and therefore increases the acidity of the gastric juice.
Similarly,
glucocorticoids lead to
atrophy of all
epithelial tissues.
However, these factors, along with
diet or
spices,
blood type,
and other factors suspected to cause ulcers until late in the 20th
century, are actually of relatively minor importance in the
development of peptic ulcers.
Gastrinomas (
Zollinger Ellison syndrome), rare
gastrin-secreting tumors, also cause multiple and difficult to heal
ulcers.
Stress
Researchers also continue to look at
stress as a possible cause, or at least
complication, in the development of ulcers. There is debate as to
whether psychological stress can influence the development of
peptic ulcers.
Burns and
head trauma, however, can lead to physiologic
stress ulcers, which are reported in
many patients who are on
mechanical ventilation.
An expert panel convened by the Academy of Behavioral Medicine
Research concluded that ulcers are not purely an
infectious disease and that psychological
factors do play a significant role. Researchers are examining how
stress might promote
H. pylori infection. For example,
Helicobacter pylori thrives in an acidic environment, and
stress has been demonstrated to cause the production of excess
stomach acid. This was supported by a study on mice showing that
both long-term water-immersion-restraint stress and
H.
pylori infection were independently associated with the
development of peptic ulcers.
A study of peptic ulcer patients in a Thai hospital showed that
chronic stress was strongly associated with an increased risk of
peptic ulcer, and a combination of chronic stress and irregular
mealtimes was a significant risk factor.
Diagnosis
An
esophagogastroduodenoscopy (EGD),
a form of
endoscopy, also known as a
gastroscopy, is carried out on patients
in whom a peptic ulcer is suspected. By direct visual
identification, the location and severity of an ulcer can be
described. Moreover, if no ulcer is present, EGD can often provide
an alternative diagnosis.
The diagnosis of
Helicobacter
pylori can be made by:
- Urea breath test (noninvasive
and does not require EGD);
- Direct culture from an EGD biopsy specimen; this is difficult
to do, and can be expensive. Most labs are not set up to perform H.
pylori cultures;
- Direct detection of urease activity in a
biopsy specimen by rapid urease
test;
- Measurement of antibody levels in
blood (does not require EGD). It is still
somewhat controversial whether a positive antibody without EGD is
enough to warrant eradication therapy;
- Stool antigen test;
- Histological examination and staining of an EGD biopsy.
The possibility of other causes of ulcers, notably
malignancy (
gastric
cancer) needs to be kept in mind. This is especially true in
ulcers of the
greater (large) curvature of the
stomach; most are also a consequence of chronic
H. pylori infection.
If a peptic ulcer perforates, air will leak from the inside of the
gastrointestinal tract (which always contains some air) to the
peritoneal cavity (which normally never contains air). This leads
to "free gas" within the peritoneal cavity. If the patient stands
erect, as when having a chest X-ray, the gas will float to a
position underneath the diaphragm. Therefore, gas in the peritoneal
cavity, shown on an erect chest X-ray or supine lateral abdominal
X-ray, is an omen of perforated peptic ulcer disease.
Macroscopic appearance
Three duodenal ulcers.
Gastric ulcers are most often localized on the lesser curvature of
the stomach. The ulcer is a round to oval parietal defect ("hole"),
2 to 4 cm diameter, with a smooth base and perpendicular
borders. These borders are not elevated or irregular in the acute
form of peptic ulcer, regular but with elevated borders and
inflammatory surrounding in the chronic form. In the ulcerative
form of gastric cancer the borders are irregular. Surrounding
mucosa may present radial folds, as a consequence of the parietal
scarring.
Microscopic appearance
A gastric peptic ulcer is a mucosal defect which penetrates the
muscularis mucosae and muscularis
propria, produced by acid-pepsin aggression. Ulcer margins are
perpendicular and present chronic gastritis. During the active
phase, the base of the ulcer shows 4 zones: inflammatory exudate,
fibrinoid necrosis, granulation tissue and fibrous tissue. The
fibrous base of the ulcer may contain vessels with thickened wall
or with thrombosis.
Differential diagnosis of epigastric pain
Treatment
Younger patients with ulcer-like symptoms are often treated with
antacids or
H2
antagonists before EGD is undertaken.
Bismuth compounds may actually reduce
or even clear organisms, though it should be noted that the warning
labels of some bismuth subsalicylate products indicate that the
product should not be used by someone with an ulcer.
Patients who are taking
nonsteroidal
anti-inflammatories (NSAIDs) may also be prescribed a
prostaglandin analogue (
Misoprostol) in order to help prevent peptic
ulcers, which may be a
side-effect of
the NSAIDs.
When
H. pylori infection is present, the most effective
treatments are combinations of 2 antibiotics (e.g.
Clarithromycin,
Amoxicillin,
Tetracycline,
Metronidazole) and 1
proton pump inhibitor (PPI), sometimes
together with a bismuth compound. In complicated,
treatment-resistant cases, 3 antibiotics (e.g. amoxicillin +
clarithromycin + metronidazole) may be used together with a PPI and
sometimes with bismuth compound. An effective first-line therapy
for uncomplicated cases would be
Amoxicillin +
Metronidazole +
Pantoprazole (a PPI). In the absence of
H.
pylori, long-term higher dose PPIs are often used.
Treatment of
H. pylori usually leads to clearing of
infection, relief of symptoms and eventual healing of ulcers.
Recurrence of infection can occur and retreatment may be required,
if necessary with other antibiotics. Since the widespread use of
PPI's in the 1990s, surgical procedures (like "highly selective
vagotomy") for uncomplicated peptic ulcers
became obsolete.
Perforated peptic ulcer is a surgical emergency and requires
surgical repair of the perforation. Most bleeding ulcers require
endoscopy urgently to stop bleeding with cautery, injection, or
clipping.
Epidemiology
[[Image:peptic ulcer disease world map - DALY -
WHO2004.svg|thumb|
Disability-adjusted life year
for peptic ulcer disease per 100,000 inhabitants in 2004.
]]The lifetime risk for developing a peptic ulcer is approximately
10%.
In Western countries the prevalence of Helicobacter pylori
infections roughly matches age (i.e., 20% at age 20, 30% at age 30,
80% at age 80 etc). Prevalence is higher in third world countries.
Transmission is by food, contaminated groundwater, and through
human saliva (such as from kissing or sharing food utensils.)
According
to Mayo
Clinic
, however, there is evidence that the infection can
be transmitted by kissing.
A minority of cases of Helicobacter infection will eventually lead
to an ulcer and a larger proportion of people will get non-specific
discomfort, abdominal pain or gastritis.
History
John Lykoudis, a general practitioner in Greece
, treated
patients for peptic ulcer
disease with antibiotics, beginning
in 1958, long before it was commonly recognized that bacteria were a dominant cause for the
disease.
Helicobacter pylori was
rediscovered in 1982 by two
Australian
scientists,
Robin Warren and
Barry J. Marshall as a causative factor for ulcers. In
their original paper, Warren and Marshall contended that most
stomach ulcers and gastritis were caused by colonization with this
bacterium, not by
stress or
spicy food as had been assumed
before.
The
H. pylori hypothesis was
poorly received, so in an act of self-experimentation Marshall
drank a
Petri dish containing a culture
of organisms extracted from a patient and soon developed gastritis.
His symptoms disappeared after two weeks, but he took antibiotics
to kill the remaining bacteria at the urging of his wife, since
halitosis is one of the symptoms of
infection. This experiment was published in 1984 in the Australian
Medical Journal and is among the most cited articles from the
journal.
In 1997, the
Centers for Disease
Control and Prevention, with other government agencies,
academic institutions, and industry, launched a national education
campaign to inform health care providers and consumers about the
link between
H. pylori and
ulcers. This campaign reinforced the news that ulcers are a curable
infection, and that health can be greatly improved and money saved
by disseminating information about
H. pylori.
In 2005,
the Karolinska
Institute in Stockholm
awarded the Nobel Prize in Physiology
or Medicine to Dr. Marshall and his long-time collaborator Dr.
Warren "for their discovery of the bacterium Helicobacter
pylori and its role in gastritis and
peptic ulcer disease". Professor Marshall continues research
related to
H. pylori and runs a molecular biology lab at
UWA in Perth,
Western Australia.
It was a previously widely accepted misunderstanding that the use
of chewing gum resulted in gastric ulcers. The medical profession
believed that this was because the action of masticating on gum
caused the over-stimulation of the production of hydrochloric acid
in the stomach. The low (acidic) pH (pH 2), or
hyperchlorhydria was then believed to cause
erosion of the stomach lining in the absence of food, thus causing
the development of the gastric ulcers.
On the other hand, in the recent past, some believed that natural
tree resin extract,
mastic gum, actively
eliminates the
H. pylori bacteria. However, multiple
subsequent studies have found no effect of using mastic gum on
reducing
H. pylori levels.
References
- For nearly 100 years, scientists and doctors thought that
ulcers were caused by stress, spicy food, and alcohol. Treatment
involved bed rest and
a bland diet. Later, researchers added stomach acid to the list of
causes and began treating ulcers with antacids. National Digestive Diseases Information
Clearinghouse
- Marshall B.J., ed. (2002), "Helicobacter Pioneers: Firsthand
accounts from the scientists who discovered helicobacters,
1892–1982", ISBN 0-86793-035-7. Basil Rigas, Efstathios D.
Papavasassiliou. John Lykoudis. The general practitioner in Greece
who in 1958 discovered the etiology of, and a treatment for, peptic
ulcer disease.
- Ulcer, Diagnosis and Treatment - CDC Bacterial, Mycotic
Diseases
- Medicine for Nurses (Toohey, 1974)
- See also their corrections in the next volume.
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