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1.1 Introduction:
Peptic ulcer disease embraces both gastric and duodenal ulcers and has been a
major threat to the world’s population over the past two centuries, with a high
morbidity and substantial mortality. Epidemiological data for this disease and its
complications have shown striking geographical variations in incidence and
prevalence (Malfertheiner et al,2009).
Peptic ulcer has unquestionably been a disease of the twentieth century. Rare
before the end of the previous century, peptic ulcer became increasingly frequent,
reaching a peak during the next 50 years and afflicting as many as 10 per cent of
men. (Christie and Tansey, 2002). Every year peptic ulcer disease (PUD) affects 4
the highest risk of contracting peptic ulcer disease are those generations born
around the middle of the 20th century. Ulcer disease has become a disease
predominantly affecting the older population, with the peak incidence occurring
The disease continues to have a substantial impact on our society’s health care
system. Although 70% of ulcer patients are between the ages of 25 and 64, the
group 65 to 74 years.
Peptic ulcer disease is one of several disorders of the upper gastrointestinal tract
Gastric and duodenal ulcers are breaks in the gastric and duodenal mucosa. Both
gastric and duodenal ulcers relate to the corrosive action of pepsin and
Peptic ulcer disease (PUD) results from an imbalance of acid secretion and
mucosal defenses that resist acid digestion. Moreover, studies have confirmed the
strong association between gastric antral infection with H pylori and peptic
ulceration. More than 90% of patients with peptic ulcer disease are infected with H
pylori, and eradication of this infection not only heals most uncomplicated ulcers
G, Md (2011)
1.2.1.1.Symptoms
Most patients with peptic ulcer disease present with abdominal discomfort, pain or
nausea. The pain is located in the epigastrium and usually does not radiate.
However, these symptoms are neither sensitive nor specific. Pain radiating to the
back may suggest that an ulcer has penetrated posteriorly, or the pain may be
pancreatic in origin. Pain radiating to the right upper quadrant may suggest disease
Patients may describe the pain of peptic ulcer as burning or gnawing, or as hunger
pains slowly building up for 1–2 hours, then gradually decreasing. Use of antacids
may provide temporary relief. Classically, gastric ulcer pain is aggravated by
meals, whereas the pain of duodenal ulcers is relieved by meals. Hence, patients
with gastric ulcers tend to avoid food and present with weight loss, while those
with duodenal ulcers do not lose weight. It is important to remember that although
these patterns are typical, they are not pathognomonic. The nature of the presenting
symptoms alone does not permit a clear differentiation between benign ulcers and
gastric neoplasm.
secretion is only one factor in the pathogenesis of peptic ulcer disease. Decreased
mucosal defense against gastric acid is another cause. The integrity of the upper
gastrointestinal tract is dependent upon the balance between “hostile” factors such
as gastric acid, H. pylori, NSAIDs and pepsin, and “protective” factors such as
gastrointestinal mucosa
Injury to gastric and duodenal mucosa develops when deleterious effects of gastric
factors such as acid, pepsin, and bile salts as well as exogenous factors such as
1.2.1.2.2.Helicobacter pylori
H. pylori is the etiologic factor in most patients with peptic ulcer disease and may
but seems to be person-to person spread via a fecal-oral route. The prevalence of
associated with NSAID use that results in substantial morbidity and mortality. Risk
disorders. The concept of gastroduodenal mucosal injury has evolved from the
the hydrophobicity of gastric mucus, endogenous gastric acid and pepsin may
Although NSAIDs can inhibit both pathways, only the gene for cyclo-oxygenase-2
oxygenase-1.
patients with gastric ulcers than those with duodenal ulcers is presumably the result
of NSAID use. NSAIDs are more likely to cause gastric than duodenal ulcers.
it in the duodenum and others have it in the stomach, peripancreatic lymph nodes,
only 0.1% of all duodenal ulcer disease. One fourth of patients have this syndrome
Patients with gastrinoma may have intractable ulcer disease. Because gastrin is
the gastric rugae. Patients may also experience diarrhea (including steatorrhea from
acid inactivation of lipase) and gastroesophageal reflux. These symptoms are
1.2.1.2.5.Hypercalcemia
Hypercalcemia has a direct bearing on the gastric acid hypersecretory state found
calcium has been demonstrated in vivo and in vitro to stimulate gastrin release
reduces the basal acid output and serum gastrin concentration in fasting gastrinoma
patients and those with MEN I, suggesting that resolution of hypercalcemia plays
1.2.1.2.6.Genetic Factors
Genetic factors play a role in the pathogenesis of ulcer disease. The lifetime
about three times greater than the general population. Approximately 20–50% of
duodenal ulcer patients report a positive family history; gastric ulcer patients also
1.2.1.2.7.Smoking
The literature reveals a strong positive correlation between cigarette smoking and
than nonsmokers. Cigarette smoking and H. pylori are co-factors for the formation
and cigarette smoking in patients with and without peptic ulcers. Cigarette
1.2.1.2.8.Stress
disease. The role of psychological factors is far from established. Acute stress
results in increases in pulse rate, blood pressure and anxiety, but only in those
patients with duodenal ulcers did acute stress actually result in significant increases
Ulcer patients typically exhibit the same psychological makeup as the general
population, but they appear to perceive greater degrees of stress. In addition, there
disease.
Pure ethanol is lipid soluble and results in frank, acute mucosal damage. Because
most humans do not drink absolute ethanol, it is unlikely there is mucosal injury at
ethanol concentrations of less than 10% (20 proof). Ethanol at low concentrations
diminish acid secretion. Though physiologically interesting, this has no direct link
cause dyspepsia. There is no convincing evidence that indicates any specific diet
increased risk of ulcer disease. Dietary alteration, other than avoidance of pain-
NSAIDS
Peptic ulcer disease is suspect in patients with epigastric distress and pain;
treatment for peptic ulcer disease should suggest conditions other than benign
1.2.1.2.2.1.Types of Diagnosis:
1.2.1.2.2.1.1.History taking
The history should include careful attention to aspirin and NSAID use. Peptic ulcer
1.2.1.2.2.1.2.Laboratory tests
Laboratory findings of hypochromic anemia and occult blood in the stools indicate
bleeding.
1.2.1.2.2.1.3.Radiologic imaging
X-ray studies with a contrast medium such as barium are used to detect the
Though less invasive than endoscopy, the barium x-ray is limited by being less
difficult to interpret. Generally, these x-rays have up to a 30% false negative and a
10% false positive rate. Until 1970, peptic ulcers were diagnosed almost
Endoscopy (i.e., gastroscopy and duodenoscopy) can be used to visualize the ulcer
area and obtin biopsy speciments to test for H.pylori and exclude ,alignant disease.
Methods for establishing the presence of H.pylori include the C urea breath test
using a radioactive isotope (13C or 14 C), the stool antigen test, and endoscopic
biopsy for urease testing. Blood tests to obtain serologic titers of H.pylori
antibodies also can be done. The serologic test can establish that a person has been
infected with H.pylori, but it cannot distinguish how recently the infection
occurred.
The Pharmaceutical Treatment of Gastric Ulcers
The modern history of peptic ulcer disease has followed a remarkable course and
lead to widespread acceptance of the notion that the majority of gastric ulcers are
therapy,” which has had dramatic effects (greater than 90 percent initial eradication
rate and less than 10 percent re-infection rate at five years).37 Triple therapy is the
acid suppressants and the identification of the largely bacteria cause of peptic
ulceration are the two most important developments that are associated with the
overall decreased rates seen with peptic ulcer disease.14 Additionally, the
Although the overall rates of peptic ulcer disease have decreased, incidence of
gastric ulceration has increased over the last few decades due to increased NSAID
use. Thus, antibiotics or triple therapy are not given to patients with gastric ulcers
caused by NSAIDs; rather, their pain medications are either reduced, eliminated or
Proton-pump inhibitors are a group of drugs that display pronounced and long-
lasting reduction of stomach acid production. They are among the most widely sold
drugs in the world and are generally considered the most potent inhibitors of acid
the gastric proton pump) of the stomach’s parietal cells. The proton-pump is the
final stage in stomach acid secretion, being directly responsible for secreting
hydrogen ions into the gastric lumen and making it an ideal target for inhibiting
crosses cell membranes and enters into parietal cells, where they become activated
The lack of stomach acid aids in the healing of gastric ulcers and reduces the pain
from indigestion and heartburn, but hydrochloric acid is required for the digestion
increased risk of bone fracture, increased risk of certain heart arrhythmias and
interstitial nephritis, low serum magnesium levels (hypomagnesemia), headaches
recent data suggests that there may be a rebound effect when proton-pump
inhibitors are discontinued.39 In other words, stopping use can cause an increase in
stomach acid production above that of normallevels that lasts for several weeks.
Aciphex, Pariet, Rabeloc). The vast majority of these drugs are known as
2) H2 Blockers
secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells
when the H2- receptors are blocked. H2 blockers are still commonly used for the
treatment of dyspepsia, but they have been surpassed in popularity by the more
In the U.S., all four FDA-approved members of the H2 blocker group (cimetidine,
low doses, or by prescription in larger doses. Brand names for these drugs include
tolerated, with the exception of cimetidine (Tagamet), which was the first H2
“blockbuster drug” (a drug generating more than one billion USD of revenue per
year), but it was discovered to interfere with the body's mechanisms of drug
metabolism and elimination through the liver cytochrome P450 pathway. As such,
cimetidine use increases the risk of drug toxicity, and has also been linked to
Ranitidine (Zantac) was introduced in 1981 and was found to have a far better
tolerability profile (fewer adverse drug reactions), longer-lasting action, and ten-
times the biochemical activity of cimetidine. However, the most common side
too greatly reduce the production of hydrochloric acid, which is needed for healthy
digestion and the absorption of vitamin B-12 and calcium. Due to their adverse
3) Antibiotics
Antibiotics are prescribed to kill bacteria such as H. pylori, but due to resistance
and adaptability, more than one type is often recommended to be taken at the same
time. Antibiotic regimens are different throughout the world, but in the U.S.,
Antibiotics are usually prescribed for only two weeks at a time in order to avoid
side effects. Relatively common side effects of antibiotic use include acquired
nausea, upset stomach, diarrhea, sun sensitivity, disruption of the intestinal flora
difficile) and yeast species (such as Candida albicans), and numerous potential
inhibitor and either amoxicillin or metronidazole for 10-14 days) is considered the
standard treatment for an ulcer caused by H. pylori; however, other protocols are
also popular. Research shows higher cure rates with 14 days of treatment, although
side effects become much more probable and severe beyond this time frame.38
At least four weeks after the initiation of antibiotic treatment, the patient is tested
by the doctor using a breath or stool test to be sure the H. pylori infection has been
eradicated. Blood tests are not useful after treatment because a patient's blood can
test positive for H. pylori even after the bacteria have been eliminated. If the
4) Bismuth Salicylate
Medications that protect the lining of the stomach and small intestine from the
damaging effects of acid are called cytoprotective agents and include the
may also directly kill H. pylori, although its antibacterial actions should not be
viewed as a replacement for conventional antibiotics. Bismuth salicylate, like all
salicylates (especially aspirin), can cause serious bleeding problems when used
alone in patients with bleeding ulcers. Bismuth quadruple therapy usually involves
The main reasons to add bismuth salicylate to a treatment regime for gastric ulcers
is if the patient is still infected with H. pylori after a trial of triple therapy, or if the
allergy, or if the patient has been treated before with a macrolide antibiotic, such as
clarithromycin.22 Side effects from bismuth salicylate are considered rare, but the
most common are benign and include darkening of the stools and/or tongue, and a
salicylate
salicylate
Antacids:
Antacids are available over-the-counter. They neutralize existing stomach acid,
which can provide relief of burning stomach pain, heartburn, and indigestion, but
they are not considered as a treatment for gastric ulcers. Antacids do not kill H.
pylori nor do they block the production of stomach acid. Commonly used antacids
at least one hour before or two hours after taking other medications because
antacids may block the medications from being absorbed and effectively
Peptic ulcers that don't heal with treatment are called refractory ulcers and may
Common reasons why ulcers fail to heal include: not taking medications according
pain relievers that increase the risk of ulcers. Less often, refractory ulcers may be a
Ellison syndrome.
Natural Remedies
blueberries, cherries, red grapes, and tomatoes) inhibit the growth of H. pylori,
balance in the digestive system between beneficial and harmful bacteria, suppress
H. pylori infection, and help reduce side effects from taking antibiotics.29 Vitamin
pylori and are helpful in treating bleeding gastric ulcers caused by aspirin use.30
Herbs have also proven helpful with treating gastric ulcers and can be taken fresh
enteric coated peppermint (Mentha piperita), black pepper (Piper nigrum), DGL-
licorice (Glycyrrhiza glabra), green tea (Camellia sinensis) and mastic (Pistacia
lentiscus) all help to inhibit H. pylori growth and protect the stomach against
homeopathic tinctures for gastric ulcers, many years of anecdotal reports suggests
the following may be of help: Argentum nitricum (for bloating, belching and
gastric pain), Arsenicum album (for ulcers with intense burning pain and nausea),
Kali bichromicum (for burning or shooting abdominal pain that is worse in the
night), Lycopodium (for bloating after eating), Nitric acid (for sharp, shooting pain
that is worse at night), Nux vomica (for heartburn and indigestion), Phosphorus
(for burning stomach pain that worsens at night), Pulsatilla (for symptoms that
change abruptly).34
Other natural therapies which may be of some benefit for those who suffer from
related to the digestive tract, including peptic ulcers) and chiropractic spinal
manipulation.35,36 The nerves that innervate the stomach travel out from the
thoracic spine, where they may become impinged and cause digestive dysfunction.
Chiropractic spinal adjustments may take pressure off spinal nerves and restore
Prevention
Prevention of gastric ulcers often involves reducing NSAID use and finding
acetaminophen (Tylenol, others) has not been linked to peptic ulcers. If NSAIDs
Lifestyle is also important for reducing the risks of peptic ulcers. Doctors used to
recommend eating bland foods, dairy products and small portions during meals,
but newer recommendations include eating foods rich in fiber, especially fruits and
vegetables. Fruits, vegetables and whole grains are also vitamin-rich, which may
enhance the body’s ability to heal stomach irritation and prevent ulceration. Foods
containing flavonoids, such as apples, cranberries, onions, garlic and tea may
inhibit the growth of H. pylori. Avoiding refined foods (white breads, pastas and
sugar), eating less red meat and more cold-water fish, using healthy oils (olive oil
or coconut oil), and reducing trans-fatty acids are all common dietary
interfere with the protective lining of the stomach, making it more susceptible to
Reducing alcohol, coffee, and soda pop consumption can also help prevent ulcers
as excessive use of these acidic beverages irritates and erodes the mucous lining of
although not as vital as once thought. At the very least, stress may worsen the signs
and symptoms of gastric ulcers. Relaxation techniques such as meditation, yoga,
and tai chi are known to be able to reduce stress levels and impact peptic ulcer
symptomatology.
Objective:
References:
Christie D A, Tansey E M. (eds) (2002) Peptic Ulcer: Rise and Fall. Wellcome
Centre
www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/
http://www.wjes.org/content/9/1/4
Diagnosis and treatment of perforated or