A benign gastric ulcer (from the antrum) of a
gastrectomy specimen.
A 'peptic ulcer', also known as 'PUD' or 'peptic ulcer disease'
[1] is an
ulcer of an area of the
gastrointestinal tract that is usually acidic and thus extremely painful. 80% of ulcers are associated with ''
Helicobacter pylori'', a spiral-shaped bacterium that lives in the acidic environment of the stomach, however only 20% 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 make sure. Duodenal ulcers are generally
benign.
Classification
A peptic ulcer may arise at various locations:
★
Stomach (called 'gastric ulcer')
★
Duodenum (called 'duodenal ulcer')
★
Esophagus (called 'esophageal ulcer')
★ A
Meckel's diverticulum
Symptoms and signs
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 lots of vomiting
★ Loss of appetite and weight loss;
★
Hematemesis (vomiting of blood);
★
Melena (tarry, foul-smelling faeces 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 2 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
★ Perforated ulcer (anterior. Surface) with sudden onset of the pain, a chemical peritonitis followed by bacterial peritonitis
★ Posterior penetration (posterior. Surface), maybe to pancreas=>increased amylase-pain=>radiating to back, unrelated to meals.
★ Hemorrhage (post. Surface), bleeding from Gasteroduodenal artery.
★ Gastric Outlet Obstruction (Goo) which happens usually because of edema or scarring, most often occurs in the setting of duodenal or pyloric channel ulcers
Stress and ulcers
Despite the finding that a
bacterial infection is the cause of ulcers in 80% of cases,
bacterial infection does not appear to explain all ulcers and researchers continue to look at stress as a possible cause, or at least a complication in the development of ulcers.
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.
The discovery that ''Helicobacter pylori'' is a cause of peptic ulcer has tempted many to conclude that psychological factors are unimportant. But this is dichotomised thinking. There is solid evidence that
psychological stress triggers many ulcers and impairs response to treatment, while helicobacter is inadequate as a monocausal explanation as most infected people do not develop ulcers. Psychological stress probably functions most often as a cofactor with ''H pylori''. It may act by stimulating the production of
gastric acid or by promoting behavior that causes a risk to health. Unravelling the aetiology of peptic ulcer will make an important contribution to the
biopsychosocial model of disease.
[2]
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 (PMID 12948263).
A study on mice showed that both long-term water-immersion-restraint stress and ''H. pylori'' infection were independently associated with the development of peptic ulcers (PMID 12465722).
Pathophysiology
Tobacco smoking,
blood group,
spices and other factors that were suspected to cause ulcers until late in the 20th century, are actually of relatively minor importance in the development of peptic ulcers.
[3]
A major causative factor (60% of gastric and 90% of duodenal ulcers) is chronic
inflammation due to ''
Helicobacter pylori'' that colonizes (''i.e.'' settles there after entering the body) 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 is increased.
Gastrin, in turn, stimulates the production of
gastric acid by parietal cells. The acid erodes the
mucosa and causes the ulcer.
Another major cause is the use of
NSAIDs (see above). The gastric mucosa protects itself from
gastric acid with a layer of mucous, 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. Newer NSAIDs (
celecoxib,
rofecoxib) only inhibit ''cox-2'', which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.
Glucocorticoids lead to atrophy of all
epithelial tissues. Their role in ulcerogenesis is relatively small.
There is debate as to whether ''Stress'' in the psychological sense can influence the development of peptic ulcers (see
Stress and ulcers).
Burns and
head trauma, however, can lead to "stress ulcers", and it is reported in many patients who are on
mechanical ventilation.
Smoking leads to
atherosclerosis and vascular spasms, causing vascular insufficiency and promoting the development of ulcers through
ischemia.
Overuse of Laxatives are also known to cause peptic ulcers.
A
family history is often present in duodenal ulcers, especially when
blood group O is also present. Inheritance appears to be unimportant in gastric ulcers.
Gastrinomas (
Zollinger Ellison syndrome), rare gastrin-secreting tumors, cause multiple and difficult to heal ulcers.
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 by:
★ Breath testing (does not require EGD);
★ Direct culture from an EGD biopsy specimen;
★ Direct detection of
urease activity in a biopsy specimen;
★ 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.
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.
Macroscopical appearance
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 as in the ulcerative form of gastric cancer. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.
Microscopical 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.
[4]
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.
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.
Erythromycin,
Ampicillin,
Amoxicillin,
Tetracycline,
Metronidazole) and 1
proton pump inhibitor (PPI). An effective combination 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 or injection.
Epidemiology
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.)
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
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 the fact that health can be greatly improved and money saved by disseminating information about ''H. pylori''.
[5]
''
Helicobacter pylori'' was rediscovered in 1982 by two
Australian scientists
Robin Warren and
Barry Marshall[6]. 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.
[7]
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.
[8] This experiment was published in 1984 in the
Australian Medical Journal and is among the most cited articles from the journal.
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.
John Lykoudis was a
general practitioner in
Greece who treated patients from
peptic ulcer disease with
antibiotics long before it was commonly recognized that
bacteria were a dominant cause for the disease.
[Basil Rigas, Efstathios D. Papavasassiliou. John Lykoudis. The general parctitioner in Greece who in 1958 discovered the etiology of, and a treatment for, peptic ulcer disease. in Barry Marshall (editor), ''Helicobacter Pioneers. Firsthand accounts from the scientists who discovered helicobacters, 1892-1982'', 2002, ISBN 0-86793-035-7.]
References
1. GI Consult: Perforated Peptic Ulcer
2. Stress and peptic ulcer: life beyond helicobacter
3. 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
4. ATLAS OF PATHOLOGY
5. Ulcer, Diagnosis and Treatment - CDC Bacterial, Mycotic Diseases
6. Unidentified curved bacillus on gastric epithelium in active chronic gastritis, Marshall BJ, , , Lancet, 1983
7. Unidentified curved bacilli in the stomach patients with gastritis and peptic ulceration, Marshall BJ, Warren JR, , , Lancet, 1984
8. Research Enterprise, The 2005 Nobel Prize in Physiology or Medicine
External links
★
Pathology specimen of Gastric ulcer
★
A case report and tutorial on perforated duodenal ulcer
العربية
中国
Français
Deutsch
Ελληνική
हिन्दी
Italiano
日本語
Português
Русский
Español
