Chronic Gastritis fLecture 7

This organism, formerly known as Campylobacter pylori, is a curved spirochete-like bacterium, of which two major genotypes exist.This organism colonizes the gastric mucosa (particularly the antrum and cardia) in a variety of ways: free in mucus, surface adhesion, and intercellularly.

H. pylori has been found in 90% of patients with chronic gastritis, 95% with duodenal ulcer disease, 70% with gastric ulcer, and 50% with gastric carcinoma.

StomachAnatomical Regions: Cardia, Fundus, Body, Pyloric antrum, Pylorus.Lesser curvature, Greater curvature.Histological Layers: Serosa, Muscularis m, Submucosa , Mucosa.Microscopic types of Gastric Mucosa: Cardiac, Fundic, Pyloric (antral).Glands of Stomach: Cardiac, Fundic, Pyloric.Cells of Fundic Epithelium: Mucous neck cells, Parietal cells, Chief cells,

Enteroendocrine cells, Stem cells. Gastric gland are comprised of two major components: foveola (crypt,

pit) and secretory portion (adenomere).

DefinitionChronic gastritis is defined as the

presence of

chronic inflammatory changes in the mucosa leading eventually to

mucosal atrophy &epithelial metaplasia.The two main features of this disease are infiltration of the lamina propria by

inflammatory cells and atrophy of the glandular epithelium.

BEtiology/types/classification

90%

Less than 10%

Nonimmune gastritis

Body-predominant

Antral-predominant

Less common etiologies• RADIATION INJURY, • CHRONIC BILE REFLUX, • MECHANICAL INJURY, AND • SYSTEMIC DISEASE such as Crohn disease, amyloidosis, or graft-versus-

host disease.

Nonimmune Gastritis

Autoimmune gastritis is characterized by:

• Antibodies to parietal cells (Oxyntic Cells) and intrinsic factor

• Reduced serum pepsinogen I concentration • Antral endocrine cell hyperplasia • Vitamin B12 deficiency

• Defective gastric acid secretion (achlorhydria)

Body Predominant

Pathogenesis Autoimmune gastritis is associated with

loss of parietal cells, which are responsible for secretion of gastric acid (HCl) and intrinsic factor.

The absence of acid production stimulates gastrin release, resulting in hypergastrinemia and hyperplasia of antral gastrin-producing

G cells.

• Lack of intrinsic factor disables ileal vitamin B12 absorption, leading to B12 deficiency and a slow-onset megaloblastic anemia

(pernicious anemia).

• The reduced serum pepsinogen I concentration

results from chief cell (Zymogenic cells or Peptic cells) destruction.

Clinical features• Chronic gastritis usually causes few or no

symptoms; 1.Upper abdominal discomfort 2.Nausea3.Vomiting 4.symptoms of anemia 5.atrophic glossitis,6. diarrhea. 7.peripheral neuropathy (B12 deficiency).

The median age at diagnosis is 60 years. Slightly more women than men are affected.

>90%

Antral-predominant

Pan-gastritis

EpidemiologyAssociated with :Poverty, Household crowding,Llimited education, African-American or Mexican-American

ethnicity, Residence in rural areas.

The mode of H. pylori transmission

is not well defined, but humans are the only known host, making

Oral-oral, Fecal-oral, and Environmental spread the most

likely routes of infection.

Pathogenesis• The most import cause is infection by H. pylori. Gastritis develops as a result of the combined

influence of• bacterial enzymes (Urease,Protease,Phospholipase)and

• Toxins (CagA, VacA) and release of• noxious chemicals by the recruited

neutrophils.Alcohol, tobacco, duodenal reflux (reflux gastritis), allergy to foods, and various drugs (particularly anti-inflammatory agents).

• After initial exposure to H.pylori, gastritis may

develop in two patterns:

•1. antral- type (Hypersecretory)

with high acid production and higher risk for the

development of duodenal ULCER, and

• 2. pangastritis (Environmental Gastritis)with multifocal mucosal atrophy, with low acid secretion and increased risk for

carcinoma.

Four features are linked to H. pylori virulence:

1. Flagella, which allow the bacteria to be motile in viscous mucus

2.Urease, which generates ammonia from endogenous urea and thereby elevates local gastric pH

3.Adhesins that enhance their bacterial adherence to surface foveolar cells

4. Toxins, such as cytotoxin-associated gene A (CagA), that may be involved in ulcer or cancer development by poorly defined mechanisms

• Chronic Inflammatory cell infiltration

• Mucosal Atrophy ( Autoimmune Gastritis)

• Intestinal (Goblet Cell) metaplasiaSeen in H Pylori & Autoimmune gastritis not chemical.

Pyloric MetaplasiaIntestinal Metaplasia

Intestinal metaplasia: Type I (complete), Type II (Incomplete)

Neutrophils, plasma cells

Type B Type A

AntPan

Ant Pan

Clinical Features /DiagnosisHistologic identification of the organism, Serologic test for antibodies to H. pylori,Fecal bacterial detection, The urea breath test based on the generation of ammonia by the bacterial urease.

• Gastric biopsy specimens can also be analyzed by

• the rapid UREASE test,

• bacterial culture, or• bacterial DNA detection by PCR.

Treatment• Combinations of antibiotics and proton pump

inhibitors. • Individuals with H. pylori gastritis usually improve

after treatment, although RELAPSES can occur after incomplete eradication or re-infection.

• Prophylactic and therapeutic vaccine development is still at an early stage of development.

Clarithromycin, Amoxicillin/ Flagyl, Omeprazole

Chronic superficial gastritis• If the inflammatory infiltrate is limited to the

foveolar region and unaccompanied by glandular atrophy, the condition is designated as chronic superficial gastritis.

• Subtle epithelial abnormalities seen in this form include a reduced amount of cytoplasmic mucin, nuclear and nucleolar enlargement, and some increase in foveolar mitoses.

UNCOMMON FORMS OF GASTRITIS

Reactive GastropathyEosinophilic gastritisLymphocytic gastritis

Chronic atrophic gastritis• When the inflammation is more extensive and

accompanied by glandular atrophy, the condition is termed Chronic atrophic gastritis and

is further categorized as mild, moderate, or severe by roughly estimating the thickness of the glandular portion in relation to the thickness of the whole mucosa.

Consequences of Chronic Gastritis

•PEPTIC ULCER DISEASE•Adenocarcinomas

Cancer Risk• The long-term risk of gastric carcinoma for

persons with H. pylori-associated chronic gastritis is

increased about fivefold relative to the normal population.

• For autoimmune gastritis, the risk for cancer is in the range of 2% to 4% of affected individuals, which is well above that of the normal population.

Other types of Gastritis• Nonspecific Gastritis• Acute infectious nonbacterial gastroenteritis• Hemorrhagic gastritis• Collagenous gastritis• Lymphocytic gastritis• Allergic gastroenteritis• Diffuse eosinophilic gastroenteritis• Granulomatous gastritis• Syphillis,, CMV, Cryptococcosis, Bacillary

angiomatosis, Graft-versus-host disease