This document summarizes key information about various gastric conditions: 1) It describes acute and chronic gastritis, their causes, pathogenesis, and morphology. 2) It explains gastric ulcer, its types, causes, pathogenesis, and morphology. 3) It provides an overview of gastric carcinoma, including risk factors, pathogenesis, locations, histological types and clinical presentation.

2. Learning Outcomes
Describe acute gastritis, its types, pathogenesis and morphology
Describe chronic gastritis, variant, pathogenesis & morphology
Describe gastric ulcer, its types, pathogenesis & morphology
Classify tumours of stomach
Describe epidemiology, pathogenesis, morphology and clinical features of
gastric carcinoma

3. Acute Gastritis
Frequently associated with:
Heavy use of NSAIDs
Excessive Alcohol consumption
Heavy smoking
Chemotherapeutic drugs
Uremia
Systemic infections (Salmonella, CMV)
Severe stress –trauma, burns, surgery
Ischemia and shock
Nasogastric intubation

4. Acute Gastritis
Pathogenesis
Increased acid secretion with back
diffusion
Decreased production of HCO3 buffer
Reduced blood flow
Disruption of adherent Mucus layer
Direct damage to epithelium
Regurgitation of bile acids from
duodenum
Inadequate PG’s synthesis leads to
increase HCL, decrease HCO3 & mucin

5. Acute Gastritis
Morphology
Mild: Mucosa hyperemic, red, edematous, congested
Intact surface epithelium
Intraepithelial and intraluminal neutrophils
Severe: Mucosal erosion (loss of surface epithelium)
Hemorrhages, as punctate dark spots
Inflammatory and fibrinous purulent exudate
Acute erosive hemorrhagic gastritis
Concurrent erosion and hemorrhage with extensive
mucosal damage, seen in alcoholics and NSAIDs users
Clinical Presentation
May be asymptomatic, epigastric pain, nausea and vomiting,
open hemorrhage, hematemesis and melena

7. Chronic Gastritis
Chronic mucosal inflammatory changes leading to mucosal atrophy and
intestinal metaplasia usually in the absence of erosions
Classification based on pathogenesis
Type A or immune gastritis: (autoimmune gastritis)
Type B or non immune gastritis: (H. pylori associated)
Pathogenesis of Type A / Immune Gastritis
Antibodies mediated parietal cells damage, decrease IF and acid
production, results in Vit B-12 deficiency and increase serum gastrin levels
Association with Hashimoto thyroiditis, Addison's disease and Type I DM
Patient at risk of developing gastric carcinoma/carcinoid tumors

8. Chronic Gastritis
Pathogenesis of Type B/ Non-immune gastritis: seen association with;
H. Pylori infection
Alcoholism
Cigarette smoking
Post surgical (antrectomy with gastroenterostomy with bile reflux)
Radiation
Crohn disease
Uremia
GVHD

9. Chronic Gastritis
Morphology
Chronic Inflammation with or without
activity
Regenerative epithelial change
Complications of Chronic Gastritis
Peptic ulcer disease
Mucosal atrophy
Intestinal metaplasia, dysplasia, gastric
carcinoma
H.Pylori associated MALT lymphoma

10. H. Pylori – gastritis VS Autoimmune Gastritis
Location Antrum Body (corpus)
Inflammatory cells Neutrophils, subepithelial
plasma cells
Lymphocytes,
macrophages
Acid production Increased to slightly decreased decreased
Gastrin Normal or decreased Increased
Other lesions Hyperplastic/inflammatory
polyps
Neuroendocrine
hyperplasia
Serology Antibodies to H.pylori Ab.to parietal cells
Sequelae Peptic ulcer, Adenocarcinoma,
MALT -lymphoma
Atrophy, P.anemia, Adeno
ca, Carcinoid tumor
Associations Low socioeconomic status,
residence in rural areas
Autoimmune thyroiditis,
DM

11. PEPTIC ULCER DISEASE (PUD)
Acid induced gastric injury resulting in breach in mucosa (ulcer) that may
extends into submucosa or deeper
Epidemiology
In USA 4 million people have peptic ulcer
5000 die each year as a result of peptic acid disease
Middle age to older adults, may be seen in young adult
M:F ratio for duodenal ulcer is 3:1 and for gastric ulcer is 1.5-2:1

13. PUD
Pathogenesis: Imbalance between gastroduodenal mucosal defense
mechanisms results in hyperacidity and pepsin release; caused by:
• H.pylori infection, 10-20% of individuals worldwide
• Chronic use of NSAID suppress PG synthesis
• Hyperacidity as in Zollinger-Ellison syndrome
• Cigarette smoking impair mucosal blood flow and healing
• Alcoholic cirrhosis, increase incidence of peptic ulcer
• Corticosteroid in high dose or repeated use
• Chronic renal failure-uremia
• Hyperparathyroidism –hypercalcemia stimulate gastrin and acid secretion
• Personality and psychological stress

15. H. Pylori role in Pathogenesis of PUD
Four factors, linked to H. pylori virulence; its flagella and secretion of
Urease, Adhesins, Vacuolating Cytotoxin A (VacA)
Induces intense inflammatory and immune response by increase production
of cytokines IL 1,6, & TNF and IL8 by mucosal epithelial cells which recruits
neutrophils and activate T and B lymphocytes
Elaborate phospholipases, damage surface epithelial cells
Enhances gastric acid secretion, impair duodenal HCO3 production,
lowering luminal pH in duodenum, favors gastric metaplasia in 1st part of
duodenum and H. pylori colonization

17. H. pylori Infection
Associated diseases
Chronic gastritis; Strong causal
association
Peptic ulcer disease; Strong causal
association
Gastric carcinoma; Strong causal
association
Gastric MALT lymphoma;
Definitive etiologic role
Diagnosis
Serological tests for H. pylori
antibodies
Fecal bacterial detection
Urea breath test (production of NH3
by bacterial urease)
Gastric biopsy for demonstration of;
- H. pylori (Giemsa)
- Bacterial culture
- Rapid urease test
- Bacterial DNA detection by PCR

18. PUD - Peptic Ulcer
Location and Size
• Up to 98%, located in 1st part of duodenum or in stomach in ratio of 4:1
• Anterior wall of duodenum and lesser curvature of stomach (95% usually
antrum) are the common sites
• G-E junction in setting of GERD/Barrett esophagus
• 10 to 20% of cases may have coexistent duodenal ulcer

20. Peptic Ulcer
Gross Morphology
Lesion less than 0.3cm are erosions over 0.6cm are
ulcers 10% of the ulcers are greater than 4cm in
diameter
Mostly single oval to round
Sharply punched out with relatively straight wall
Converging mucosal folds
Ulcer margins, level with surrounding mucosa
Undermine edges
Base smooth and clean due to peptic digestion of any
exudate

21. Peptic Ulcer
Microscopy
Active ulcer shows four layers:
1.Surface purulent exudate, bacteria & necrotic
fibrinoid debris
2.Inflammatory infiltrate includes neutrophils
3.Granulation tissue infiltrated by mononuclear
inflammatory cells
4.Fibrous or collagenous scar
Healing phase: seen in chronic peptic ulcer
comprising of regenerating epithelium growing
over ulcer surface
Note: Malignant transformation does not occur
Active ulcer

22. Complications of Peptic Ulcer Disease
Bleeding; 15% to 20% of patients, may be life threatening
Perforation; about 5% of patients and accounts for two
thirds of ulcer deaths
Obstruction from edema or scarring; in about 2% of
patients, causes severe crampy abdominal pain

23. Stress-Related Mucosal Ulcers
Causes:
1. NSAIDs/Aspirin ingestion
2. Long term steroid
3. Extensive burns
4. Severe trauma
5. Shock
6. Sepsis
7. Intracranial injury
8. Radiotherapy or chemotherapy
Stress ulcers
Severe physiologic stress, multiple
lesions in stomach
Curling ulcers
Severe burns or trauma, occurs in
proximal duodenum
Cushing ulcers
Intracranial injury, operations or
tumors, ulcers may be gastric,
duodenal or esophageal

24. Stress-Related Mucosal Ulcers
Morphology
Gross:
Usually less than 1 cm in diameter, anywhere in
stomach
Circular, small, single or multiple
Ulcer base dark brown by acid digestion of
extruded blood
Margins and base not indurated
Microscopy:
Mucosal erosion (shedding of superficial
epithelium) to ulceration (defects involving full
mucosal thickness)
Abrupt lesions, unremarkable adjacent mucosa
Healing, re-epithelialization, days to weeks, no
scarring

25. WHO Histologic Classification of Gastric Neoplasm
NON-NEOPLASTIC POLYPS
EPITHELIAL NEOPLASM
Benign Malignant
Adenoma Intraepithelial neoplasia (dysplasia)
Adenocarcinoma *
•Papillary adenocarcinoma
•Tubular adenocarcinoma
•Mucinous adenocarcinoma
•Signet-ring cell carcinoma
Small-cell carcinoma
Carcinoid tumor
(Laurén classification subdivides adenocarcinomas into intestinal & diffuse type)
NON-EPITHELIAL NOPLASM
Benign Malignant
Leiomyoma Leiomyosarcoma
Gastrointestinal stromal tumor Gastrointestinal stromal tumor (GIST)
Schwannoma Kaposi sarcoma
Lymphoma

26. Gastric Polyps
Non-neoplastic 90%: Hyperplastic or Inflammatory polyps
Neoplastic 10%: Adenomatous polyps
Hyperplastic or Inflammatory polyps
Approx. 75% develops in the back ground of chronic H. pylori associated
gastritis (may regress after H.pylori eradication)
Gross: Oval shaped frequently multiple, less than 1cm in diameter, in antrum
Microscopy: Irregular, cystically dilated, elongated foveolar glands
L. propria edematous, variable degrees of acute and chronic inflammation
Clinical Significance: Increase risk of dysplasia if larger than 1.5 cm

27. Adenomatous Polyps/Adenomas
Develops in background of chronic gastritis
/intestinal metaplasia, dysplasia, location antrum
Gross:
Single, sessile or pedunculated, 3-4cm in diameter
Microscopy:
Gastric or intestinal type, low to high grade
epithelial dysplasia, 40% contain carcinoma at time
of diagnosis
Clinical Significance:
Above 2cm risk of malignancy increases and risk
of malignancy in adjacent mucosa is 30%

28. Gastric Cancer
Epidemiology:
Second most common tumor in the world
High in Japan, Chile, Costa Rica, China, Colombia, Portugal, Russia and
Bulgaria
Four to six fold less common in USA, UK, Canada, Australia, New Zealand,
France & Sweden
Intestinal type develops in high risk areas from precursor lesion with mean
age of incidence 55yrs, male to female ratio of 2:1
Diffuse type no precursor lesion with mean age of incidence 48yrs, male to
female ratio is equal

29. Risk Factors for Gastric Carcinoma
Risk Factors - Intestinal Type
Environmental Factors
Infection by H. pylori
Diet; Nitrites derived from nitrates (water, preserved food), Smoked and salted
foods, pickled vegetables, chili peppers, lack of fresh fruit and vegetables
Cigarette smoking
Host Factors
Chronic gastritis; H. pylori, colonization, Intestinal metaplasia and dysplasia
Partial gastrectomy; Favors reflux of bilious, alkaline intestinal fluid
Gastric adenomas; 40% have cancer, 30% have adjacent cancer at diagnosis
Barrett esophagus
Genetic Factors
Slightly increased risk with blood group A
Family history of gastric cancer
Hereditary non-polyposis colon cancer syndrome
Risk Factors - Diffuse Type
Familial gastric carcinoma syndrome (E-cadherin mutation)

30. Pathogenesis of Gastric Cancer
H. pylori associated chronic gastritis
Germline mutations in CDH1; results in loss of E-cadherin function -
associated with familial gastric cancers (50% of diffuse type gastric cancer)
Germline mutations in APC genes; at increased risk of intestinal-type
gastric cancer in patients with familial adenomatous polyposis (FAP)
Mutations of β-catenin, microsatellite instability; and hyper methylation
of genes including TGFβRII, BAX, IGFRII, and p16/INK4a: associated with
sporadic intestinal-type gastric cancer
TP53 mutations; majority sporadic gastric cancers of both histologic types

31. Gastric Cancer
Location:
Pylorus and Antrum 50-60%
Body and Fundus 25%
Lesser curvature 40%
Greater curvature 12%
Clinically classified on the basis of
1. Depth of invasion (greatest impact on clinical out come)
2. Macroscopic growth pattern
3. Histologic subtype

32. Gastric Cancer
1. Depth of Invasion
Early gastric carcinoma : confined to
mucosa and submucosa, regardless of
perigastric lymph node metastases
Advanced gastric carcinoma: extended
below submucosa into muscular wall
2. Macroscopic Growth Pattern
Exophytic
Flat /Depressed
Excavated (Ulcerated)
3. Histologic Types (Lauren Classification)
-Intestinal-Glandular
-Diffuse-Signet Ring Cell

33. Gastric cancer
Morphology
Intestinal type; Ulcer having heaped-up, beaded
margins, shaggy necrotic base and neoplastic
Glands, invading adjacent mucosa and wall
Diffuse type; Signet ring cell , Infiltrative
pattern, desmoplastic reaction stiffens gastric
wall; rigid thickened wall a "leather bottle"
appearance - linitis plastica, Diffuse rugal
Flattening, PAS positive signet ring cells

34. Clinical Presentation
Generally asymptomatic
Anorexia, vomiting
Abdominal pain
Weight loss
Dysphagia
Hemorrhage and anemia
Virchow node: Mets from carcinoma of stomach to left supraclavicular
lymph node (Sentinel node)
Diagnosis: Endoscopy and Biopsy

35. MCQ
Q. Which one of the following factors act as an aggression force in gastric
ulcer?
a. Cigarette smoking.
b. Bicarbonate secretion.
c. Epithelial regenerative capacity.
d. Surface mucous secretion.

36. Home Assignment
Q1. Make a comparison between H.pylori associated chronic gastritis with
autoimmune gastritis.
Q2. Explain why it is clinically important to know the normal anatomy and
histology of esophagus.

37. References
Basic Pathology, 10th Edition Kumar, Abbas, Aster
www.studentconsult.com
www.webPathology.com