Stomach

Case
A 45-year-old man has had vague abdominal pain and nausea for the
past 3 years. This pain is unrelieved by antacid medications. He has
no difficulty swallowing and no heartburn following meals. On physical
examination there are no abnormal findings. Upper GI endoscopy
reveals antral mucosal erythema, but no ulcerations or masses.
Biopsies are taken, and microscopically there is a chronic non-specific
gastritis. Which of the following conditions is most likely to be
present in this man?

A. Stress ulcer
B. Pernicious anemia
C. Helicobacter pylori infection
D. Adenocarcinoma
BODY ANTRUM
• Acid • Endocrine cells
• Pepsinogen • Eg G cells
• IF
pH in gastric lumen = 1
Mucosal protection: The mucosal barrier protects
the gastric mucosa from autodigestion.

• Mucus secretion:
• Bicarbonate secretion: create pH neutral microenvironment adjacent
to cell surface
• Mucosal blood flow : provides O2 , bicarbonate, nutrients; removes
back diffused acid
• Epithelial barrier : intercellular tight junctions
• Epithelial regeneration
• Prostaglandin synthesis :
 H.pylori
Surface NSAIDs
Tobacco
mucin Alcohol
HCO3- Gastric
Blood flow hyperacidity
Duodenal-
Epithelium gastric reflux
PGs Ischemia
Shock
NSAID
• NSAIDS – inhibition of COX
• mucus, bicarbonate, and phospholipid secretion; mucosal blood flow; and epithelial restitution.

• Uremia and H.pylori – inhibition of gastric HCO3- transporters by

ammonium ions
• Elderly - ↓mucin and HCO3-
• High altitudes - ↓O2
• Harsh chemicals – direct injury
Acute gastritis
• Transient acute mucosal infl

• Asymp/ epigastric pain, nausea, vomiting

• Erosion (sloughing of mucosa, limited to lamina propria)

• Hemorrhage, Ulceration
• Hematemesis, melena
 Causes
• NSAIDs
• Alcohol
• Heavy smoking
• Cancer chemo / radiotherapy
• Bacterial / viral infs
• Severe stress – trauma, burns, surgery
• Ischemia and shock
• Suicidal attempts with acids and alkali
Morphology
• Lamina propria shows moderate edema & vasc congestion
• Surface epithelium intact
• Scattered neutrophils among epi cells or mucosal glands

• Severe –
• Erosions

• Acute erosive hemorrhagic gastritis – concurrent erosion &

hmge
 Stress-Related Mucosal Disease
• Severe trauma, extensive burns, intracranial disease, major
surgery, serious medical disease
• Curling & Cushing ulcers.
• Sharply demarcated < 1cm
• Gastric rugae-normal i,e. normal surrounding mucosa
• Complications:
1. bleeding
2. perforation
3. obstruction-edema & scarring. (more in pyloric ulcers)
Chronic gastritis

• Chronic mucosal infl changes leading to mucosal

atrophy and intestinal metaplasia, usually in the
absence of erosions

• Epithelial changes may become dysplastic →

carcinoma
 Causes

• Chronic H.pylori infection (90%)

• Autoimmune gastritis (<10%)
• radiation injury
• chronic bile reflux
• mechanical injury (e.g., an indwelling nasogastric
tube)
• involvement by systemic diseases such as Crohn
disease, amyloidosis, or graft-versus-host disease.
c/f
• less severe but more persistent.
• Nausea and upper abdominal pain are typical,
• sometimes with vomiting,
• hematemesis is uncommon.
 Gastro-
host
duodenal
immune
mucosal
defenses
responses

bacterial
virulence
factors
Helicobacter pylori

• Chronic gastritis
• Peptic ulcer disease
• Gastric carcinoma
• Gastric MALT lymphoma
 Helicobacter pylori
• Non-sporing, curvilinear gram negative rod
• 3.5 x 0.5 µm
• Flagella → motile
• Produce urease → converts urea to ammonia →
↑local gastric pH
• Toxins CagA (cytotoxin associated gene A) –
ulcer / cancer
 Nobel Prize in Physiology & Medicine
2005

Barry J. Marshall and J. Robin

Warren
for their discovery of "the
bacterium Helicobacter pylori
and its role in gastritis and
peptic ulcer disease"
H. pylori
• Antral type
• High acid production, hypogastrinemia
•  risk of duodenal ulcer
• Pangastritis
• Multifocal atrophic gastritis
• Lower gastric acid secretion
• TNF, IL-1β, IL-10
• Intestinal metaplasia
•  risk of adenocarcinoma
Morphology
• H.pylori –
• antrum
• pangastritis
• (Autoimmune – body and fundus)

• Mucosa is red; coarser texture than normal

• In long standing atrophic disease, mucosa is
thinned and flattened
 MORPHOLOGY
Site of colonisation of organism :
H.pylori conc in superficial mucus overlying epith cells
in surface and neck regions

Lumen of foveolar, mucus neck cells

Gastric pits
Site of involvement:
Antrum > Cardia > Body
Inflammatory infiltrate

• Neutrophils in lamina propria, intraepithelial & lumen of

gastric pits (pit abscesses)

• Plasma cells & Lymphocytes in lamina propria

• Lymphoid follicles

• “active” inflammation – neutrophils within the glandular and

surface epithelial layer

• Long standing H.pylori gastritis → atrophy

Diagnostic
• Intraepithelial neutrophils and subepithelial plasma cells
Diagnosis
• Noninvasive
• Serology for Abs
• Fecal bacterial detection
• Urea breath test
• Biopsy
• Histology – H&E, Giemsa, silver stains
• Rapid urease test
• Bacterial culture
• PCR for bacterial detection
 Autoimmune gastritis
• <10% of chr gastritis

• Abs to parietal cells & IF

• Reduced S. pepsinogen I conc
• Endocrine cell hyperplasia
• Vit B 12 def
• Achlorhydria
Autoimmune gastritis
• Defective gastric acid secretion (achlorhydria)
• A/w Hashimoto thyroiditis, type I diabetes
•  risk of gastric carcinoma & carcinoid tumor
Autoimmune gastritis: pathogenesis
1. Gland destruction & mucosal atrophy (body & fundus)
⇣
loss of acid production
⇣
gastrin release+
hypergastrinemia
⇣
hyperplasia of G cells in antrum.

2. Severe : ↓↓ IF production : Pernicious Anemia

3. CD4+ T cells: against parietal cell components are cause of injury.

Morphology: autoimmune gastritis
• Diffuse atrophy of body, fundus
• Thinned out mucosa, loss of rugae
• Mic:
• atrophy-glands
• lymphocytes, plasma cells around gastric glands
• deeper and centered on the gastric glands

• Intestinal metaplasia+ (goblet cells & columnar cells)

• ECL hyperplasia in antrum
Autoimmune gastritis: cl/f
• Pernicious anemia: features of megaloblastic anemia
• Nausea, vomiting, upper abd discomfort
• Hypo or achlorhydria
• Other autoimmune diseases
Feature H. pylori –Associated Autoimmune
Location Antrum Body
Inflammatory infiltrate Neutrophils, subepithelial plasma Lymphocytes, macrophages
cells

Acid production Increased to slightly decreased Decreased

Gastrin Normal to markedly increased Markedly increased
Other lesions Hyperplastic/inflammatory polyps Neuroendocrine hyperplasia
+ +
Serology Antibodies to H. pylori Antibodies to parietal cells (H ,K -
ATPase, intrinsic factor)

Sequelae Peptic ulcer, adenocarcinoma, Atrophy, pernicious anemia,

lymphoma adenocarcinoma, carcinoid tumor

Associations Low socioeconomic status, poverty, Autoimmune disease; thyroiditis,

residence in rural areas diabetes mellitus, Graves disease
Complications of chronic gastritis:
1.peptic ulcer
2.mucosal atrophy & intestinal metaplasia
3.dysplasia
 Peptic ulcer
Ulcers are defined histologically as a
• Breach in the mucosa of the alimentary tract that
• Extends through the muscularis mucosa into the
submucosa or deeper.
• Occur in any portion of the GIT exposed to the aggressive
action of acid/ peptic juices.
• Solitary
• Peptic ulcer disease: associated with H pylori –induced
hyperchlorhydric chronic gastritis
 Peptic Ulcer Disease

chronic mucosal ulceration affecting the duodenum

or stomach
❖a/w H. pylori infection, NSAIDs, or cigarette
smoking.
❖Location :
º Duodenum- First part
º Stomach – antrum
º Ectopic gastric mucosa – Duo & Meckel diverticulum
º Eso – GERD/ inlet patch
º Zollinger Ellison syndrome - multiple ulcers in the
duodenum, stomach & jejunum
Etio-pathogenesis of Peptic ulcer Disease

• Duodenal – M:F::3:1
• Gastric – M:F::1.5 to 2: 1

Imbalance between gastroduodenal

mucosal mechanisms and the damaging
forces.
 Etiology:
• H. pylori infection
• Cigarette use (synergizes with H. pylori for gastric PUD)
• Chronic obstructive pulmonary disease
• Illicit drugs, e.g. cocaine, that reduce mucosal blood flow
• NSAIDs (potentiated by corticosteroids)
• Alcoholic cirrhosis (primarily duodenal PUD)
• Psychological stress (can increase gastric acid secretion)
• Endocrine cell hyperplasia (can stimulate parietal cell
growth and gastric acid secretion)
• Zollinger-Ellison Syndrome (PUD of stomach, duodenum, and
jejunum)
• Viral infection (CMV, herpes simplex virus)
Increased Attack
H.pylori,
Hyperacidity eg : ZE syndr,
Drugs :NSAIDs
Chr. Renal Failure

Weak defense
Ischemia ,
Delayed emptying,
host factors
 Morphology- Gross
❑Usually < 2 cm
❑ Round to oval, sharply punched out, straight wall

❑Margins - level/ slightly elevated than the

surrounding mucosa

❑Floor : Clean

❑Thrombosed / patent vessels (bleeding)

 Morphology - Gross
Heaping up of the margins -
feature of malignancy

Deep ulcer – tendency to

perforate

Sharply delimited chronic peptic ulcer

converging folds of mucosa in the upper half.
Ulcer bed is covered by fibrinopurulent exudate
 Endoscopy

• Clean, non-elevated edge

• Granulation tissue-floor
 Microscopy
4 zones
Superficial thin layer of Fibrinoid necrosis
in floor and margins
Zone of Non specific inflammation –
neutrophils
Active granulation tissue
with mononuclear cells
Collagenous scar
• Vessels in the scarred area typically
thickened or thrombosed
• Mucosal defect with clean
edges.

• The necrotic ulcer base is

composed of granulation tissue.
 Clinical features

 Epigastric discomfort, gnawing, burning and

aching
 Pain
Iron deficiency anemia
Frank hemorrhage or perforation
Complications:
Bleeding Obstruction
• Occurs in 15% to 20% of patients • Mostly in chronic ulcers
• Accounts for 25% of ulcer deaths • Secondary to edema or scarring
• May be the first indication of an ulcer • Occurs in about 2% of patients
Perforation • Most often associated with pyloric
• Occurs in up to 5% of patients channel ulcers

• Accounts for two thirds of ulcer • May occur with duodenal ulcers
deaths
• Is rarely first indication of an ulcer