2. The ulceration can develop at any part of
alimentary canal but it occurs majorly in 3 parts and
names are given accordingly to them.
Gastric ulcers--Gastric ulcers occur when the mucus
layer of stomach that protects stomach from digestive
juices is reduced. This allows the digestive acids to
destruct the tissues that line the stomach, causing an
ulcer. Generally the lesser curvature of stomach shows
the development of ulcers. The peoples above age of 50
years are generally affected with this problem.
Esophageal ulcers--Ulcers that develop inside the
esophagus.
Duodenal ulcers--It is most common type of peptic
ulcers. The age group of 40 -50 years get affected with
this type of ulcer.
3. In stomach both type of factors are present one who are
protectors of the stomach mucosal lining and the other which
are harmful to stomach mucosal cells. There is balance
between these two factors. If this balance disturbs then it
causes the injury to stomach mucosallining.
The epithelial cells of the stomach and duodenum
secrete mucus in response to irritation of the stomach lining.
The foveolar cells produce mucus and bicarbonate, which
protects the mucosal cells from aggressive factors (acid and
pepsin). During injury, some mechanisms help to prevent the
entry of acid and pepsin in to the epithelial cells. For example,
increased blood flow removes acid at injured area and
provides adequate bicarbonate level in the gel layer. Removal
of excess of hydrogen ions controls the intracellular pH.
Aggressive factors include H. pylori infection, NSAIDs,
alcohol, bile salts, acid, and pepsin. The defensive mechanism
includes mucous, bicarbonate, prostaglandins, adequate
mucosal blood flow, and ability to epithelial renewal.
4. 1) Superficial Gel Layer--The mucus cells of stomach secretes mucus continuously and
forms a layer over stomach lining. The layer has the ability to retain the bicarbonate
ions secreted by surface epithelial cells and to maintain pH near 7 in proximity to
mucosa. This mucous layer protects from proteolytic actions of pepsin on
epithelium. The mucus gel secreted by foveolar cells is formed in nearly 95% of
water and various kinds of mucin glycoproteins, such as MUC2, MUC5AC, MUC6,
and others. Gel formation is possible due to the ability of mucin units to polymerize
into large mucin polymers. The presence of bicarbonate ions provides a first line
protection against ulceration secretion.
2) Prostaglandins--The gastric mucosa constantly produces prostaglandins (PGE2 and
PGI2). These prostaglandins has role in each protective mechanism. They are having
potential to reduce acid output, stimulate mucus and bicarbonate production and to
increase mucosal blood flow. Prostaglandins also accelerate the rate of healing.
Furthermore, prostaglandins have the ability to inhibit mast cell activation and
leukocyte adhesion to vascular endothelium.
3) Epithelial Cells--The next defense mechanism involves the presence of closely
connected (tight junctions) epithelial cells. These tight arrangements of epithelial
cells prevent the entry of acid and pepsin towards deeper layers. Epithelial cells
contain phospholipids on the surface which are hydrophobic in nature and cells can
repulse produce acid- cathelicidins and beta defensins having anti microbial
properties.
5. 1) Helicobacter pylori--The gram-negative H. pylori, because of its property
of producing urease it can survive in the acidic, unfavorable environment,
where it causes inflammation and triggers peptic ulcer. The process of
development of disease can be divided in two steps. In the first step, the
bacteria disrupt the antimicrobial activity of gastric acid barrier, enter the
mucous layer, and adapt to environmental conditions of gastric mucus.
In the next step, H. pylori adhere to the host gastric mucosa. This
avoids the gastric clearance of bacteria due to peristalsis (a series of
muscle contractions). It also shows expression of genes which allows the
bacteria to persist in this environment. The enzyme urease produced by
bacteria has ability to convert urea into ammonia and carbon dioxide. This
conversion increases the pH protecting bacterium from acidic environment
due to neutralization.
Protease and lipase produced by H. pylori is responsible for
degradation of gastric mucus and cell injury from back infusion of gastric
acid. Moreover, ammonia produced through urease activity maybe toxic to
gastric epithelial cells. Also H. pylori infection induces chronic oxidative
stress on gastric mucosa.
6. 2) Gastric Acid and Pepsin--Infection with H. pylori
decreases the amount of acid secretion may is due to
apoptosis induced by pro-inflammatory mediators. On the
other hand, H. pylori infection may cause an increase in
gastric acid secretion through its increasing action on
release of gastrin. Elevated gastric acid secretion
increases the duodenal acid load, which damages the
mucosa, causing ulceration. The chief cells synthesize
and release the proenzyme pepsinogen, the precursor of
pepsin. Pepsin is a protease kind of enzyme which can
damage the adherent gel layer. This damage is
characterized by focal areas of discontinuity in the
adherent mucus gel layer, localized hemorrhagic
punctuate ulcers with bleeding into the lumen, and no
evidence of re-epithelialization.
7. 3) NSAIDs--Prostaglandins are produced from arachidonic
acid in the presence of cyclooxygenases (COX-1 and
COX-2) and prostaglandin synthases. NSAIDs block the
cyclooxygenases. Inhibition of cyclooxygenases results
in suppression of a number of prostaglandin-related.
protective functions.
For example--Prostaglandins reduce the activation of mast
cells as well as inhibit leukocyte adhesion to vascular
endothelium. Prostaglandins play a role in maintaining
adequate blood flow in mucosal microcirculation.
Administration of NSAIDs results in cyclooxygenase-
dependent inhibition of bicarbonate secretion.
8. i) Presence of H. Pylori infection--H. pylori bacterium has ability to produce enzyme
urease. This urease splits urea into ammonia and CO2. This action is particularly
responsible for its survival in acid media of stomach where it causes inflammation
and triggers peptic ulcer. H. Pylori adheres to the gastric mucosa and avoids gastric
clearance. H. Pylori proves harmful in many ways given as follows-
H. Pylori induce inflammatory response and gastric epithelial cell injury.
Protease and lipase produced by H. pylori is responsible for degradation of gastric
mucus and cell injury from back infusion of gastric acid. Moreover, ammonia
produced through urease activity may be toxic to gastric epithelial cells. H. pylori
infection induces chronic oxidative stress on gastric mucosa, thereby causing
mucosal damage and retardation in mucosal repair
ii) Non-steroidal anti-inflammatory drugs—NSAIDs are well known for development
of PU. NSAIDs and H. pylori infection account for approximately 90% of gastric
and duodenal ulcers. Up to half of regular NSAID takers report gastrointestinal
intolerance, 15-25% of them have an endoscopically confirmed ulcer, and up to
4.5% develop serious gastrointestinal complication. These drugs disrupt the
mucosal permeability barrier and damage the mucosa in a cyclooxygenase
dependent and cyclooxygenase-independent way. Aspirin used in a low dose for
prophylaxis of cardiovascular disease is associated with significant increase in the
risk of ulcer presence and ulcer.
iii) Family history--The polygenic inheritance pattern may be responsible for familiar
aggregation of peptic ulcer. Familiar aggregation pattern differs between gastric and
duodenal ulcers. First-degree relatives of patients with gastric ulcers have a
threefold increase in the prevalence of gastriculcers but no duodenal ulcers. On the
other hand, first-degree relatives of patients with duodenal ulcers have a three fold
increase in the prevalence of duodenal ulcers but no gastric ulcers.
9. Obesity--Visceral adipose tissue is recognized to be metabolically active and has been associated with increased levels of
pro-inflammatory cytokinesisy contribute to the development of inflammation in the GI tract. Thus, obesity has been
proposed to have increasing effect on peptic ulcer. Obesity increases risk for both peptic ulcer as well as duodenal ulcer.
Smoking--Smoking is the most preventable risk factor of human disease. These ingredients include alkaloids, phenolic
compounds, polycyclic aromatic hydrocarbons, nitrosamines, and heavy metals. Nowadays, there is strong evidence that
cigarette smoking is a major cause of gastrointestinal disorders in which a major role is played by chronic inflammation.
These include inflammatory bowel disease, cancers of the GI tract, peptic ulcers. Some studies shown that the prevalence
of ulcers in current and former smokers is almost double of that of nonsmokers. The risk of peptic ulcer is associated with
the quantity of cigarette smoking. That means the risk of peptic ulcer increases in smokers with increasing smoking.
Cigarette smoking does not induce peptic ulcer but it affects the gastric mucosal protective mechanism increasing the risk
of H. pylori infection. The effects of smoking on gastric health are as follows.
It decreases the rate of epithelial cell renewal.
Reduces level of epithelial growth factor (EGF) and thus inhibits mucosal cell proliferation.
It increases synthesis of gastric acid and decreases bicarbonate synthesis.
vii)Alcohol Consumption--Alcohol consumption interfere with stomach functioning in several ways. Forinstance, alcohol can
alter gastric acid secretion as well as induce acute gastricmucosal injury. Alcoholic beverages having low alcoholic
concentration strongly increase gastric acid and gastrin release. Alcohol-induced mucosal injury is associated with the
decreased formation of prostaglandins.
Alcohol consumption can cause mucosal inflammation. Alcohol disrupts the gastric mucosal barrier and increases the
mucosal permeability. Changes induced by short termexposure toalcoholic beverages are rapidly reversible, while
prolonged alcohol drinking may lead to disruption in microcirculation and progression in structural mucosal injury.
viii) Coffee Consumption--Coffee drinking has been reported to be associated with peptic ulcer disease and gastroesophageal
reflux disease (GERD). Although caffeine has never been clearly implicated in the pathogenesis of peptic ulcer disease, it
is generally recommended that coffee drinks should be avoided. Caffeine is believed to stimulate gastric acid secretion by
its action as a phosphodiesterase inhibitor and its effect in increasing cyclic AMP.
10. A number of symptoms are associated with peptic ulcers. The
level of symptoms depends on the severity of ulcer. The most
common symptom is a burning sensation or pain in the middle
of the abdomen. Typically, the pain will be more intense when
stomach is empty, and it can last for a few minutes to several
hours.
Other common signs and symptoms of ulcers include:
Dull pain in the stomach, loss of weight, not willing to
eat due to pain, nausea or vomiting, feeling easily full of
stomach, burning sensation in the chest, pain that may
improve when eating, drinking.
More specifically duodenal ulcers shows symptoms like
Burning, soreness, midmorning pain relieved after food or
milk intake etc. While gastric ulcer shows symptoms like,
daytime pain, bloating, nausea, vomiting.
11. Bleeding--Ulcers may cause bleeding at affected area which
results in tar-like stools (called melaena). Due to bleeding
person may feel weakness, he may have vomiting with
blood. The blood in the stomach is usually changed by
gastric acid, giving it a grainy, black appearance (like
coffee grains).
Pyloric obstruction--Person may have a pyloric obstruction
caused by an ulcer, it results in increase in abdominal
pain, vomit of undigested or partially digested food.
Perforation--In the case of a perforated ulcer, gastric
contents will leak into abdominal cavity.This causes acute
peritonitis (inflammation of the abdominal cavity). Person
will have sudden and severe abdominal pain, which
worsens with movements.
12. The treatment of peptic ulcers
involves the withdrawal of agents which causes
ulcers and a specific treatment with drugs for early
healing of damaged tissues. The changes in life
style can avoid the development of ulcers. These
changes includes control on smoking, excessive
intake of coffee, intake of alcohol, fixed schedule
of timing of meal and sleeping etc.
The drugs include, Antacids
(Sodium bicarbonate), H2 receptor antagonist
(Ranitidine), Proton pump inhibitors (omeprazole),
ulcer protective (colloidal bismuth), antibiotics
(metronidazole).
