Stomach

Anatomy and
histology of the
stomach.
A, Gross anatomy.
B, Microscopic
view of antral
mucosa.
C, Microscopic
view of fundic
mucosa.
Gastric disorders frequently cause clinical disease, ranging
from bland chronic gastritis to gastric carcinoma.
Gastric infection with Helicobacter pylori represents the
most common gastrointestinal infection.
Occasionally, congenital anomalies are encountered;
Congenital Gastric Anomalies
1. Pyloric stenosis : 1 in 300-900 live births ,Male-
to-female ratio 3:1
Pathology: muscular hypertrophy of pyloric smooth
muscle wall, the Symptoms: persistent, nonbilious
projectile vomiting in young infant
2. Diaphragmatic hernia, Rare condition,
Pathology: herniation of stomach and other
abdominal contents into thorax through a
diaphragmatic defect
Symptoms: acute respiratory distress in newborn
3. Gastric heterotopia ,Uncommon
Pathology: a nidus of gastric mucosa in the
esophagus or small intestine ("ectopic rest")
Symptoms: asymptomatic, or an anomalous peptic
ulcer in adult
Gastric disorders give rise to symptoms similar
to esophageal disorders, primarily heartburn
and vague epigastric pain.
With breach of the gastric mucosa and
bleeding, hematemesis or melena may
ensue.
Unlike esophageal bleeding, however, blood
quickly congeals and turns brown in the acid
environment of the stomach lumen.
Vomited blood hence has the appearance of
coffee
GASTRITIS
This diagnosis is both overused and often
missed-overused when it is applied loosely
to any transient upper abdominal complaint
in the absence of validating evidence, and
missed because most persons with chronic
gastritis are asymptomatic.
Gastritis is simply defined as inflammation of
the gastric mucosa.
By far the majority of cases are chronic
gastritis, but occasionally, distinct forms of
acute gastritis are encountered.
Chronic Gastritis
Chronic gastritis is defined as the presence
of chronic inflammatory changes in the
mucosa leading eventually to mucosal
atrophy and epithelial metaplasia.
In the Western world, the prevalence of
histologic changes indicative of chronic
gastritis is higher than 50% in the later
decades of life
Pathogenesis
• By far the most important etiologic association is
chronic infection by the bacillus H. pylori.
• This organism is a worldwide pathogen that has the
highest infection rates in developing countries.
• American adults older than age 50 show prevalence
rates approaching 50%.
• In areas where the infection is endemic, it seems to
be acquired in childhood and persists for decades.
• Most individuals with the infection also have the
associated gastritis but are asymptomatic.
Gastritis is often accompanied by infection with Helicobacter
pylori. This small curved to spiral rod-shaped bacterium is found
in the surface epithelial mucus of most patients with active
gastritis. The rods are seen here with a methylene blue stain
Helicobacter pylori.
A Steiner silver stain
demonstrates the
numerous darkly
stained Helicobacter
organisms along the
luminal surface of
the gastric epithelial
cells. Note
that there is no
tissue invasion by
bacteria
H. pylori is a noninvasive, non-spore-forming,
S-shaped gram-negative rod measuring
approximately 3.5 μm × 0.5 μm.
Although H. pylori does not invade the tissues,
it induces an intense inflammatory and
immune response.
There is increased production of
proinflammatory cytokines such as
interleukin IL-1, IL-6, tumor necrosis factor,
and, most notably, IL-8.
IL-8 is produced by the mucosal epithelial
cells, and it recruits and activates
neutrophils.
• Several bacterial gene products are involved in
causing epithelial cell injury and induction of
inflammation.
• Epithelial injury is mostly caused by a
vacuolating toxin called VacA, which is
regulated by the cytotoxin-associated gene A
(CagA).
• In addition, H. pylori secretes a urease that
breaks down urea to form toxic compounds
such as ammonium chloride and
monochloramine.
The organisms also elaborate
phospholipases that damage surface
epithelial cells.
Bacterial proteases and phospholipases
break down the glycoprotein-lipid
complexes in the gastric mucus, thus
weakening the first line of mucosal
defense.
H. pylori enhances gastric acid secretion and
impairs duodenal bicarbonate production,
thus reducing luminal pH in the
duodenum
This altered milieu seems to favor gastric
metaplasia (the presence of gastric
epithelium) in the first part of the
duodenum.
Such metaplastic foci provide areas for H.
pylori colonization.
Several H. pylori proteins are
immunogenic, and they evoke a robust
immune response in the mucosa.
Suffice it to say that gastritis develops as a
result of the combined influence of
bacterial enzymes and toxins and release
of noxious chemicals by the recruited
neutrophils.
After initial exposure to H. pylori, gastritis
may develop in two patterns:
(1)an antral-type with high acid production
and higher risk for the development of
duodenal ulcer, and
(2) a pangastritis with multifocal mucosal
atrophy, with low acid secretion and
increased risk for adenocarcinoma
Persons with chronic gastritis and H. pylori
usually improve symptomatically when
treated with antibiotics and proton pump
inhibitors.
Improvement in the underlying chronic gastritis
may take much longer.
Relapses are associated with reappearance of
this organism.
Other forms of chronic gastritis are much less
common in the United States;
Autoimmune gastritis, which represents no
more than 10% of cases of chronic gastritis,
results from the production of auto antibodies
to the gastric gland parietal cells, in particular
to the acid-producing enzyme H+,K+-ATPase.
The autoimmune injury leads to gland
destruction and mucosal atrophy, with
concomitant loss of acid and intrinsic factor
production.
Chronic atrophic gastritis,autoantibody demonstrated here is anti-
parietal cell antibody.
The bright green immunofluorescence is seen in the paritetal cells
of the gastric mucosa.
The resultant deficiency of intrinsic factor leads to
pernicious anemia.
This form of gastritis is seen most often in
Scandinavia, in association with other
autoimmune disorders such as Hashimoto
thyroiditis and Addison disease.

Morphology
Regardless of the cause or histologic distribution of
chronic gastritis, the inflammatory changes consist
of a lymphocytic and plasma cell infiltrate in the
lamina propria , occasionally accompanied by
neutrophilic inflammation of the neck region of
the mucosal pits.
The inflammation may be accompanied by
variable gland loss and mucosal atrophy.
When present, H. pylori organisms are found
nestled within the mucus layer overlying the
superficial mucosal epithelium.
In the autoimmune variant, loss of parietal cells
is particularly prominent.
Two additional features are of note. Intestinal
metaplasia refers to the replacement of
gastric epithelium with columnar and goblet
cells of intestinal variety.
Chronic gastritis, showing partial replacement of
the gastric mucosal epithelium by intestinal
metaplasia (upper left) and inflammation of the
lamina propria (right) containing lymphocytes and
plasma cells.
This is significant, because
gastrointestinal-type carcinomas
seem to arise from dysplasia of this
metaplastic epithelium.
Second, H. pylori-induced proliferation
of lymphoid tissue within the gastric
mucosa has been implicated as a
precursor of gastric lymphoma.
Lymphoid hyperplasia
of the stomach
presenting as multiple
small intramucosal
nodules, with Multiple
reactive germinal
follicles are situated in
the deep aspect of the
gastric mucosa adjacent
to the muscularis
mucosae.
Acute Gastritis
Acute gastritis is an acute mucosal inflammatory
process, usually of a transient nature.
The inflammation may be accompanied by
hemorrhage into the mucosa and, in more severe
circumstances, by sloughing of the superficial
mucosal epithelium (erosion).
This severe erosive form of the disease is an
important cause of acute gastrointestinal bleeding.
Pathogenesis
The pathogenesis is poorly understood, in part because normal
mechanisms for gastric mucosal protection are not totally
clear.
Acute gastritis is frequently associated with:
1. Heavy use of nonsteroidal anti-inflammatory drugs (NSAIDs),
particularly aspirin
2. Excessive alcohol consumption
3. Heavy smoking
4. Treatment with cancer chemotherapeutic drugs
5. Uremia
6. Systemic infections (e.g., salmonellosis)
7. Severe stress (e.g., trauma, burns, surgery)
8. Ischemia and shock
9. Suicide attempts with acids and alkali
10.Mechanical trauma (e.g., nasogastric intubation)
11.Reflux of bilious material after distal gastrectomy
Morphology
Acute gastritis ranges from extremely localized (as
occurs in NSAID-induced injury) to diffuse, and from
superficial inflammation to involvement of the
entire mucosal thickness with hemorrhage and
focal erosions.
Concurrent erosion and hemorrhage are readily
visible by endoscopy and termed acute erosive
gastritis.
All variants are marked by mucosal edema and an
inflammatory infiltrate of neutrophils and possibly
by chronic inflammatory cells.
Regenerative replication of epithelial cells in the
gastric pits is usually prominent.
Provided that the noxious event is short lived, acute
gastritis may disappear within days with complete
restitution of the normal mucosa.
Clinical Features
Depending on the severity of the anatomic changes,
acute gastritis may be entirely asymptomatic, may
cause variable epigastric pain with nausea and
vomiting, or may present as overt hematemesis,
melena, and potentially fatal blood loss.
Overall, it is one of the major causes of hematemesis,
particularly in alcoholics
GASTRIC ULCERATION
Ulcers of the alimentary tract are defined
histologically as a breach in the mucosa that
extends through the muscularis mucosae into the
submucosa or deeper.
This is to be contrasted to erosions, in which there
is a breach in the epithelium of the mucosa only.
Erosions may heal within days, whereas healing of
ulcers takes much longer.
Although ulcers may occur anywhere in the
alimentary tract, by far, the most common are the
peptic ulcers that occur in the duodenum and
stomach.
Peptic Ulcers
Peptic ulcers are chronic, most often solitary, lesions
that occur in any portion of the gastrointestinal
tract exposed to the aggressive action of acidic
peptic juices.
At least 98% of peptic ulcers are either in the first
portion of the duodenum or in the stomach, in a
ratio of about 4:1
Epidemiology
Peptic ulcers are remitting, relapsing lesions that are
most often diagnosed in middle-aged to older
adults, but they may first become evident in
young adult life.
They often appear without obvious precipitating
influences and may then heal after a period of
weeks to months of active disease.
Even with healing, however, the propensity to
develop peptic ulcers remains, in part because of
recurrent infection with H. pylori.
The male/female ratio for duodenal ulcers is about
3:1.
Genetic or racial influences seem to have little or no
role in the causation of peptic ulcers.
Duodenal ulcers are more frequent in persons with
alcoholic cirrhosis, chronic obstructive pulmonary
disease, chronic renal failure, and
hyperparathyroidism.
With respect to the last two conditions,
hypercalcemia, whatever its cause, stimulates
gastrin production and therefore acid secretion
Pathogenesis
Two conditions are key for the development of peptic
ulcers:
(1) H. pylori infection, which has a strong causal
relationship with peptic ulcer development, and
(2) mucosal exposure to gastric acid and pepsin.
Nevertheless, many aspects of the pathogenesis of
mucosal ulceration remain murky.
It is best perhaps to consider that peptic ulcers are
created by an imbalance between the
gastroduodenal mucosal defenses and the
damaging forces that overcome such defenses
Both sides of the imbalance are considered
H. pylori infection is the most important condition in
the pathogenesis of peptic ulcer.
The infection is present in 70% to 90% of persons with
duodenal ulcers and in about 70% of those with
gastric ulcers.
Furthermore, antibiotic treatment of H. pylori
infection promotes healing of ulcers and tends to
prevent their recurrence.
Hence, much interest is focused on the possible
mechanisms by which this tiny noninvasive spiral
organism tips the balance of mucosal defenses.
Only 10% to 20% of individuals worldwide who are
infected with H. pylori actually develop peptic ulcer.
NSAIDs are the major cause of peptic ulcer disease
in persons who do not have H. pylori infection.
The gastroduodenal effects of NSAIDs range from
acute erosive gastritis and acute gastric ulceration
to peptic ulceration in 1% to 3% of users.
Because NSAIDs are among the most commonly
used medications, the magnitude of
gastroduodenal toxicity caused by these agents is
quite large.
Risk factors for NSAID-induced gastroduodenal
toxicity are increasing age, higher dose, and
prolonged usage.
Thus, those who take these drugs for chronic rheumatic
conditions are at particularly high risk.
Suppression of mucosal prostaglandin synthesis, which
increases secretion of hydrochloric acid and reduces
bicarbonate and mucin production, is the key to NSAID-
induced peptic ulceration.
Loss of mucin degrades the mucosal barrier that
normally prevents acid from reaching the epithelium.
Synthesis of glutathione, a free-radical scavenger, is also
reduced. Some NSAIDs can penetrate the gut mucosal
cells as well. Whether coexisting H. pylori infection
affects NSAID-induced ulceration is not entirely settled.
*Other events may act alone or in concert with H. pylori
and NSAIDs to promote peptic ulceration.
Morphology
All peptic ulcers, whether gastric or duodenal, have an
identical gross and microscopic appearance.
By definition, they are defects in the mucosa that
penetrate at least into the submucosa, and often
into the muscularis propria or deeper.
Most are round, sharply punched-out craters 2 to 4
cm in diameter; those in the duodenum tend to be
smaller, and occasional gastric lesions are
significantly larger.
Favored sites are the anterior and posterior walls of
the first portion of the duodenum and the lesser
curvature of the stomach.
The location within the stomach is dictated
by the extent of the associated gastritis:
antral gastritis is most common, and the
ulcer is often along the lesser curvature
at the margin of the inflamed area.
Occasional gastric ulcers occur on the
greater curvature or anterior or posterior
walls of the stomach, the very same
locations of most ulcerative cancers.
Classically, the margins of the crater are
perpendicular and there is some mild edema of
the immediately adjacent mucosa, but unlike
ulcerated cancers there is no significant elevation
or beading of the edges.
The surrounding mucosal folds may radiate like wheel
spokes.
The base of the crater appears remarkably clean, as a
result of peptic digestion of the inflammatory
exudate and necrotic tissue.
Infrequently, an eroded artery is visible in the ulcer
(usually associated with a history of significant
bleeding)
The histologic appearance varies with the activity,
chronicity, and degree of healing.
In a chronic, open ulcer, four zones can be
distinguished :
(1)the base and margins have a thin layer of necrotic
fibrinoid debris underlain by
(2) a zone of active nonspecific inflammatory
infiltration with neutrophils predominating,
underlain by
(3) granulation tissue, deep to which is
(4) fibrous, collagenous scar that fans out widely from
the margins of the ulcer.
Chronic gastritis is extremely common among persons
with peptic ulcer disease, and H. pylori infection is
almost always demonstrable in those persons with
gastritis.
Similarly, individuals with NSAID-associated peptic
ulcers do not have gastritis unless there is
coexistent H. pylori infection. This feature is helpful
in distinguishing peptic ulcers from acute gastric
ulceration, because gastritis in adjacent mucosa is
generally absent in the latter condition.
Clinical Features
Most peptic ulcers cause epigastric pain, often
described as burning but a significant minority first
come to light with complications such as
hemorrhage or perforation.
The pain tends to be worse at night and occurs usually
1 to 3 hours after meals during the day.
Classically, the pain is relieved by alkalis or food, but
there are many exceptions.
Nausea, vomiting, bloating, belching, and significant
weight loss (raising the specter of some hidden
malignancy) are additional manifestations
Bleeding is the chief complication, occurring in as
many as one-third of patients, and may be life-
threatening.
Perforation occurs in about 5% of patients but
accounts for two-thirds of deaths from this disease
in the United States.
Obstruction of the pyloric channel is rare.
Malignant transformation occurs in about 2% of
patients, generally from ulcers in the pyloric
channel, and is very rare with gastric ulcers.
In the latter event, it is often difficult to exclude the
possibility that carcinoma was present from the
outset.
Acute Gastric Ulceration
Focal, acutely developing gastric mucosal defects that may
appear after severe physiologic stress are called stress
ulcers.
Generally, there are many lesions located mainly in the
stomach and occasionally in the duodenum. Stress ulcers
are most commonly encountered in these conditions:
1. Severe trauma, including major surgical procedures, sepsis,
shock, or grave illness of any type
2. Chronic exposure to gastric irritant drugs, particularly
NSAIDs and corticosteroids
3. Extensive burns (these ulcers are known as Curling ulcers)
4. Traumatic or surgical injury to the central nervous system
or an intracerebral hemorrhage (called Cushing ulcers;
carry high risk of perforation).
The pathogenesis of these lesions is uncertain
and may vary with the setting.
NSAID-induced ulcers are linked to decreased
prostaglandin production.
The systemic acidosis that can accompany severe
trauma and burns may contribute to mucosal injury
presumably by lowering the intracellular pH of
mucosal cells already rendered hypoxic by impaired
mucosal blood flow.
With cranial lesions, direct stimulation of vagal nuclei
by increased intracranial pressure may cause gastric
acid hypersecretion, which is common in these
patients.
Morphology
Acute stress ulcers are usually circular and small (<1
cm in diameter).
The ulcer base is frequently stained dark brown by
the acid digestion of extruded blood.
Unlike chronic peptic ulcers, acute stress ulcers are
found anywhere in the stomach.
They may occur singly, but more often there are
several, located throughout the stomach and
duodenum
Microscopically,
acute stress ulcers are abrupt lesions, with essentially
unremarkable adjacent mucosa.
They range in depth from very superficial lesions
(erosion) to deeper lesions that involve the entire
mucosal thickness (true ulceration).
The shallow erosions are, an extension of acute
erosive gastritis.
The deeper lesions comprise well-defined ulcerations
but are not precursors of chronic peptic ulcers.
Even the deeper lesions do not penetrate the
muscularis propria.