Infection-stomach

Question 1

Link between H. pylori and acid resistance

Answer 1

Urease

• Hydrolyzes endogenous urea to ammonia and CO2
• Increases cytoplasmic pH
• Buffers periplasm

Question 2

Virulence factors

Answer 2

BabA- adhesion to gastric epithelial cells, induce inflammation
cagA- cag pathogenicity island, gene product strongly associated with peptic ulcer, gastric/duodenal cancer
vacA gene- epithelial cell membrane- to form voltage gated channel, pores for anions and small neutral molecules (incl urea). Secreted endotoxin, endocytosed and affected endosomal compartments and mitochondria

Question 3

H. pyloris methods to evade immune response

Answer 3

• changes in LPS and flagellin (PAMPS) reduced recognition by innate immune response (PRR/TLR)
• inhibit NO production macrophages
• enzymes that combat bactericidal oxidative stress

Question 4

Gastric ulcer caused by H. pylori

Answer 4

• Associated with pan gastric inflammation
• Reduced or normal acid secretion
• Dense colonization and inflammation
• H. pylori comprises mucosal defenses leading to epithelial damage

Question 5

Duodenal ulcers caused by H. pylori

Answer 5

• Inflammation of the gastric mucosa in non-acid secreting antral region of the stomach
• 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 colonisation)

Question 6

How does H. pylori cause gastric adenocarcinoma?

Answer 6

• epithelial proliferation in the bckground of chronic inflammation
• pangastric or corpus-predominant gastritis
• associated with gastric atrophy and intestinal metaplasia
• carcinogenesis associated with gastric atrophy
• ROS and RNS (nitrogen) associated with inflammation
• possibly other bacteria within the now achlorhydric stomach

Question 7

How does H. pylori cause gastric lymphoma?

Answer 7

• Norml stomach does not have mucosa-associated lymphoid tissue (MALT)
• MALT acquisition depends on infection with helicobacter species
• Transformation into low grade extra-nodal b cell lymphoma
• direct antigen stimulation by H. pylori
• mutations caused by oxidative damage

Question 8

Host genetic factors influencing infection

Answer 8

• Host pro-inflammatory cytokine variations predispose to adenocarcinoma
• Cytokine gene polymorphisms
• IL-1 gene cluster
• Innate immune response gene polymorphisms
• TLR
• HLA polymorphisms

Question 9

Other causes of Peptic Ulcer Disease

Answer 9

• gastric hyperacidity
• chronic use of NSAIDs, esp. aspirin
• use of corticosteroids
• tobacco smoking (impair mucosal blood flow and affect healing)
• alcohol

Question 10

Treatment and prevention

Answer 10

Antibiotics + proton pump inhibitor

Question 11

Challenges in treatment and prevention

Answer 11

• Antibiotic efficacy in acidic environment
• Effective vaccine development- induction of effective immune response
• Finding the role of H. pylori in other disease (GERD)