GASTRITIS AND
OTHER ACID
RELATED DISEASE
Lecture
Palangka Raya University
Faculty of Medicine
GASTRITIS
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Histologically documented inflammation of
gastric mucosa
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not the mucosal erythema seen during endoscopy and not
interchangeable with dyspepsia
Classification
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Acute or chronic
Histologic features
Anatomical distribution or proposed pathogenic
mechanism
GASTRITIS
ACUTE GASTRITIS
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Most common cause is infection
H. pylori acute gastritis has not been extensively studied
Sudden onset of epigastric pain, nausea, vomiting
Mucosal histologic studies demonstrate a marked
infiltrate of neutrophils with edema and hyperemia.
If not treated  chronic gastritis
Hypochlorhydria lasting for up to 1 year may follow
acute H. pylori infection
ACUTE GASTRITIS
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Other causes of bacterial infection are rare
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due to acidic environment of the stomach
Other types of infectious gastritis may
occur in immunocompromised individuals
such as AIDS patients
CHRONIC GASTRITIS
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Identified histologically by an inflammatory cell
consisting of lymphocytes and plasma cell with scanty
neutrophil
Patchy, superficial and glandular inflammation 
severe glandular destruction, atrophy and metaplasia
Intestinal metaplasia - conversion of gastric glands into
a small intestinal phenotype with small bowel mucosal
glands containing goblet cells
Intestinal metaplasia  gastric cancer
CHRONIC GASTRITIS
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Phases of chronic gastritis
1. Superficial gastritis - early phase, inflammatory changes limited
to the lamina propria of the surface
mucosa, with edema and cellular infiltrates
separating intact gastric glands
2. Atrophic gastritis - inflammatory infiltrate extends deeper into
the mucosa with progressive distortion and
destruction of glands
3. Gastric atrophy - glandular structures are lost, with paucity of
inflammatory infiltrates
- thin mucosa with clear visualization of
underlying vessels endoscopically
CHRONIC GASTRITIS
Normal
Superficial gastritis
Gastric atrophy
CHRONIC GASTRITIS
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Classified according to predominant site of
involvement
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Type A - Body predominant form (autoimmune)
Type B - Antral predominant form (H. pylori-related)
AB gastritis - mixed antral and body
CHRONIC GASTRITIS
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Type A Gastritis (Autoimmune gastritis)
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Involves primarily the fundus and body, with antral sparing
Associated with Pernicious anemia in the presence of
circulating antibodies against parietal cell and Intrinsic factor
Parietal cell containing gastric gland is the preferential target
Parietal cell antibody is directed against H+,K+-ATPase
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Leads into achlorydia
Destruction of parietal cell  decrease Intrinsic Factor 
Vitamin B 12 (Cobalamin) deficiency
Vitamin B 12 deficiency (megaloblastic anemia, neurologic
dysfunction)
Patients with Pernicious anemia may also have vitiligo,
Addison’s disease, thyroiditis, hypoparathyroidism
CHRONIC GASTRITIS
 Type A Gastritis
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Hypergastrinemia
due to achlorydia
and sparing of antral
mucosa where G
cells are located
May lead to gastric
carcinoid tumor due
to the gastrin trophic
effect of ECL cell
hyperplasia

Positive effect
Gastrin
CHRONIC GASTRITIS
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Type B Gastritis
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Antral-predominant
More common than Type A Gastritis
H. pylori infection
Converts to pangastritis over time
Risk for gastric adenocarcinoma due to metaplasia
brought about by chronic H. pylori induced gastritis
H. pylori infection is also associated with low-grade B cell
lymphoma (gastric MALT lymphoma)
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Eradication of H. pylori may result in complete regression of
tumor
High grade lymphoma is unresponsive to H. pylori
eradication
CHRONIC GASTRITIS
 Treatment
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aimed at the sequelae and not the
underlying inflammation
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Patients with pernicious anemia will require
parenteral vitamin B12 supplementation on a
long-term basis
Eradication of H. pylori infection
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Gastric acid hypersecretion due to unregulated
GASTRIN release from a non – B cell endocrine tumor
(Gastrinoma)
Gastrinomas are classified as sporadic tumor or
associated with Multiple Endocrine Neoplasia (MEN)
type 1 syndrome
Results into aggressive and refractory ulceration
More common in male than female
Majority are diagnosed 30-50 years old
0.1 to 1.0% incidence with individuals presenting with
PUD
Mostly malignant (>60%) and 30-50 % have mutiple or
metastatic lesion upon diagnosis
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Pathophysiology
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Hypergastrinemia from endocrine tumor
stimulates acid secretion through gastric
receptors on parietal cell and by inducing
histamine release from ECL cells
Hypergastrinemia leads to increased gastric acid
secretion through parietal cell stimulation and
increased parietal cell mass
Increase gastric acid output leads to PUD,
erosive esophagitis and diarrhea
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Tumor distribution (80% are found w/in the gastrinoma
triangle)
 Confluence of the cystic duct and common bile duct superiorly,
junction of the second and third portion of the
duodenum inferiorly and junction of the neck and
body of the pancreas medially
 Significant number of lesions are extrapancreatic
 Duodenum (50-75% of non-pancreatic lesion)
 Less common site: stomach,
bones, ovaries, heart, liver,
lymph nodes
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Clinical Manifestation
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Peptic ulcer - most common
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Unusual ulcer location (second part of the duodenum
and beyond)
Ulcer refractory to standard medical therapy
Ulcer recurrence after acid-reducing surgery
Mild esophagitis to frank ulceration with stricture and
Barrett’s mucosa
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Clinical Manifestation
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Diarrhea - 2nd most common
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Marked volume overload to small intestine
Pancreatic enzyme inactivation by acid
Damage of intestinal epithelial surface by acid which
leads to maldigestion and malabsorption of nutrients
Secretory component due to direct stimulatory effect of
gastrin on enterocytes or co-secretion of additional
hormones from tumor such as Vasoactive Intestinal
Peptide (VIP)
ZOLLINGER-ELLISON
SYNDROME (ZES)
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Gastrinoma associated MEN 1 Syndrome
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(parathyroid + pancreas + pituitary gland)
Autosomal dominant disorder
Long arm of chromosome 11 (11q11-q13)
Associated with hypercalcemia  direct secretory effect on
gastric secretion
Parathyroidectomy reduces gastrin and gastric acid output
Higher incidence of gastric carcinoid tumor development
compared to sporadic ZES
Smaller, multiple and more often located at the duodenal wall
compared to sporadic ZES
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Diagnosis
A. Obtained a biochemical diagnosis
1. Elevated fasting gastrin level (>150-200 pg/mL)
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Normal FG <150pg/mL
Other causes of elevated gastrin
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H. pylori infection
Used of anti-secretory agents for ulcer
Fasting gastrin 10x above normal suggest ZES
ZOLLINGER-ELLISON
SYNDROME (ZES)
When to Obtain a Fasting Serum Gastrin Level
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Multiple ulcers
Ulcers in unusual locations; associated with severe esophagitis; resistant to
therapy with frequent recurrences; in the absence of NSAID ingestion or H.
pylori infection
Ulcer patients awaiting surgery
Extensive family history for peptic ulcer disease
Postoperative ulcer recurrence
Basal hyperchlorhydria
Unexplained diarrhea or steatorrhea
Hypercalcemia
Family history of pancreatic islet, pituitary, or parathyroid tumor
Prominent gastric or duodenal folds
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Diagnosis
2. Elevated acid secretion measurement (BAO/MAO > 0.6)
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basal gastric pH > 3 virtually excludes a gastrinoma
3. Gastrin provocative test (Secretin study)
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developed in an effort to differentiate between the causes of
hypergastrinemia and are especially helpful in patients with
indeterminate acid secretory studies
most sensitive and specific gastrin provocative test for the
diagnosis of gastrinoma
increase in gastrin of 120 pg within 15 min of secretin
injection has a sensitivity and specificity of >90% for ZES
ZOLLINGER-ELLISON
SYNDROME (ZES)
B. Tumor localization after biochemical diagnosis
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Octreoscan (Nuclear Imaging that utilizes a
Somatostatin analogue)
 Several endocrine tumors (i.e. Gastrinoma) express
cell-surface receptors for Somatostatin
 Localization of
gastrinomas by
measuring the
uptake of the
stable Somatostatin
analogue
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Treatment
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Ameliorating signs and symptoms related to hormone
overproduction
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High dose proton pump inhibitor
Somatostatin analogue (Octreotide) as adjunct
- inhibitory effects on gastrin release from receptor-bearing tumors and
inhibits gastric acid secretion to some extent
Definitive cure
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Surgical resection led to immediate cure rates as high as 60%
10 year disease free survival as high as 34% in sporadic
gastrinoma
Only 6% of MEN 1 patients are disease free 5 years after surgery
ZOLLINGER-ELLISON
SYNDROME (ZES)
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Outcome
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Complete tumor resection (5-10 year survival rate of >90%)
Incomplete tumor resection (5-10 year survival rate of 43% and
25% respectively)
Hepatic metastasis (< 20% 5 year survival rate)
Poor outcome factors: shorter disease duration; higher gastrin
level (>10,000 pg/mL); large pancreatic primary tumor (>3cm);
metastatic disease to lymph nodes and bone; and Cushing’s
disease
Favorable outcome factors: primary duodenal wall tumor;
isolated lymph node tumor, undetectable tumor upon surgical
exploration
STRESS- RELATED MUCOSAL
INJURY
STRESS- RELATED MUCOSAL
INJURY
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Stressors
 shock, sepsis, massive burns, severe trauma, head injury
 can cause acute erosive gastric mucosal changes or frank
ulceration with bleeding
Mucosal injury commonly seen in the acid producing portion of the
stomach (fundus and body)
Most common presentation is GI bleeding which usually occur 4872 h after acute injury
Risk factor for bleeding
 Patient on mechanical ventilator
 Underlying coagulopathy
STRESS- RELATED MUCOSAL
INJURY
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Pathophysiology
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Mucosal ischemia
Breakdown of normal protective barriers of stomach
Acid
Curling’s ulcer - severe burn
Cushing’s ulcer - head trauma
Proton pump inhibitor
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Treatment of choice for stress prophylaxis
Maintain gastric pH > 3.5
OTHER FORMS OF GASTRITIS
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Lymphocytic gastritis
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is characterized histologically by intense infiltration of the
surface epithelium with lymphocytes
infiltrative process is primarily in the body of the stomach
and consists of mature T cells and plasmacytes.
A subgroup of patients have thickened folds noted on
endoscopy.
These folds are often capped by small nodules that
contain a central depression or erosion; this form of the
disease is called varioliform gastritis.
Varioliform gastritis
OTHER FORMS OF GASTRITIS
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Eosinophilic gastritis
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Marked eosinophilic infiltration involving any layer of the
stomach (mucosa, muscularis propria, and serosa)
Clinical manifestation of systemic allergy
Affected individuals will often have circulating eosinophilia
Antral involvement predominates, with prominent
edematous folds being observed on endoscopy
Prominent antral folds can lead to outlet obstruction.
Treatment with glucocorticoids has been successful
OTHER FORMS OF GASTRITIS
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Granulomatous gastritis
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Crohn's disease
Involvement may range from granulomatous
infiltrates noted only on gastric biopsies to frank
ulceration and stricture formation.
Occurs in the presence of small-intestinal
disease.
OTHER FORMS OF GASTRITIS
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Granulomatous gastritis
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Several rare infectious processes that can lead
to granulomatous gastritis
histoplasmosis, candidiasis, syphilis, and
tuberculosis
 sarcoidosis, idiopathic granulomatous
gastritis, and eosinophilic granulomas
involving the stomach
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OTHER FORMS OF GASTRITIS
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Ménétrier's Disease
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Rare disease
Characterized by large, tortuous gastric mucosal folds mostly in
the fundus and body
Histologically, massive foveolar hyperplasia (hyperplasia of
surface and glandular mucous cells) is noted which replaces
most of the chief cell and parietal cell
Over expression of growth factors such as TGF may be
involved in the process
Twenty to 100% of patients (depending on time of presentation)
develop a protein-losing gastropathy accompanied by
hypoalbuminemia and edema.
OTHER FORMS OF GASTRITIS
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Ménétrier's Disease
OTHER FORMS OF GASTRITIS
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Ménétrier's Disease
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Diagnosis
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Medical Treatment
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Large gastric folds on barium swallow and endoscopy (do
biopsy)
Anticholinergics decrease protein loss
High protein diet
Ulcers should be treated with a standard approach
Surgical
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Severe disease with persistent and substantial protein loss
may require total gastrectomy
END