L13: H. Pylori

Question 1

Mechanical barriers

Answer 1

Epithelial cells with tight junctions
Air flow
Movement of mucus by cilia
Tears

Question 2

Chemical factors

Answer 2

Fatty acids
Enzymes/peptides
pH
Surfactant

Question 3

Stomach morphology and secretions

Answer 3

• Cardia - mucin secreting cells
• Fundus - acid and enzyme secretion
• Corpus - acid and enzyme secretion
• Antrum - gastrin and mucin secreting cells

Question 4

Chronic gastritis

Answer 4

The presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia.
Few symptoms…nausea, vomiting, upper abdominal discomfort

Question 5

Gastric adenocarcinoma

Answer 5

• Most common malignancy of the stomach (90% of all gastric cancers)
• Leading cause of cancer related death
• Early symptoms resemble those of chronic gastritis and peptic ulcer disease. Advanced symptoms such as weight loss, anorexia, early satiety, anemia, and hemorrhage trigger further diagnostic evaluation
• Gastric tumors with an intestinal morphology tend to form bulky tumours, while cancers with a diffuse infiltrative growth pattern are more difficult to appreciate.

Question 6

Lymphoma

Answer 6

• Derived from mucosa-associated lymphoid tissue (MALT
therefore MALToma)
• 5% of gastric malignancies are primary lymphomas
• Symptoms and endoscopic investigation are similar to chronic gastritis
• Histology will reveal lymphoepithelial lesions and the presence of reactive B-cell follicles

Question 7

Peptic ulcer

Answer 7

• Ulcer- breach in the mucosa of the alimentary tract, which extends through the muscularis mucosa into the submucosa or deeper.
• Epigastric gnawing, burning, or aching pain
• Peptic ulcers occur in any part of the GIT exposed to acid-peptic juices

Question 8

Role of Helicobacter pylori infection in GIT diseases

Answer 8

• CHRONIC GASTRITIS - strong causal
• PEPTIC ULCER - strong causal (1-10% of patients infected with H. pylori)
• GASTRIC ADENOCARCINOMA - strong causal (0.1-3% of patients infected with H. pylori). First bacterium classified as a carcinogen
• GASTRIC LYMPHOMA – strong causal (<0.01% of patients infected with H. pylori)

Question 9

Helicobacter pylori

Answer 9

• Non-sporing, curvilinear, gram-negative rod
• Only bacterium to persistently inhabit the human gastric mucosa
• Uniquely adapted to stomach environment (gastric acid and mucus)
• Motility - spiral shape and multiple flagella confer corkscrew motility
• Acid resistance: urease, most abundant protein in H. Pylori, hydrolyses endogenous urea to ammonia and CO2, increasing cytoplasmic pH and buffering periplasm

Question 10

Virulence genes in H. Pylori

Answer 10

1. BabA – facilitates adhesion to gastric epithelial cells, allowing epithelial proliferation and inflammation
2. cagA gene - (cytotoxin-associated gene A) part of cag pathogenicity island, causes changes in cellular function, effects proliferation and epithelial barrier that can contribute to disease.
3. vacA gene - secreted exotoxin forms hexameric pores which are selective for anions and small neutral molecules including urea. Endocytosed and affect mitochondrial membrane, releasing cytochrome C and triggering apoptosis.

Question 11

Host response to H. pylori infection

Answer 11

• All H. pylori strains induce a marked immune response
• Host immune response is generally ineffective in clearing infection:
- Changes in LPS and flagellin (PAMPS) reduce recognition by innate immune response (PRR/TLR)
- Inhibit NO production by macrophages
- Enzymes that combat bactericidal oxidative stress
• Immune response is important to pathogenesis
• Inflammation is greater in strains that express specific
virulence factors
• H. Pylori extracellular pathogen - should result Th2 help, but generally Th1

Question 12

Consequences of severe gastritis

Answer 12

In antral predominant gastritis: increased acid production leading to risk of duodenal ulceration
In corpus-predominant gastritis: decreased acid production, risk of gastric ulceration and gastric adenocarcinoma

Question 13

Duodenal ulcers caused by H. pylori

infection

Answer 13

Inflammation of the gastric mucosa in non-acid secreting antral region of the stomach leads to increased stimulation of acid secretion from the less affected proximal acid secreting fundus mucosa. Causes higher levels of acid in duodenum and ulceration.
May cause gastric metaplasia into duodenum in response
to increased acid (enabling H. pylori colonization)

Question 14

Treatment and Prevention

Answer 14

Antibiotics + proton pump inhibitor to reduce acidity