Helicobacter pylori infection pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yamuna Kondapally, M.B.B.S[2]

Overview

Person to person transmission is considered to be the most likely route of transmission of Helicobacter pylori. H. pylori is a noninvasive organism. It is found over mucus secreting cells but not in deeper gastric glands. Hence it can only inhabit gastric-type mucus but cannot colonize the esophagus or duodenum. Pathogenesis of H. pylori infection depends on bacterial, host and environmental factors.

Pathophysiology

  • Iatrogenic
  • Via tubes and endoscopes that have been in contact with the gastric mucosa of one individual are used for another patient
  • Between patient and staff especially among endoscopists and gastroenterologists
  • Fecal-oral route
  • Fecal contamination of water and food may be the source of infection especially in developing countries[4]
  • Oral-oral route
  • Via saliva especially in developed countries[4]
  • Motility of H. pylori (The corkscrew motility is due to its multiple flagella and spiral shape)
  • Chemotaxis
  • Environmental sensing
  • Acid resistance
  • Iron acquisition

Pathogenesis

  • The pathogenesis involves four important steps. They are:

For further information on pathogenesis please click here

Factors Associated With Pathogenesis

Factors Associated With H. pylori Pathogenesis
Bacterial Host Environmental
Flagella Immune response to H. pylori
Bacterial enzymes
Hormonal and acid homeostasis changes
Bacterial Virulence factors
  • CagA
  • Outer inflammatory protein A (OipA)
  • Duodenal ulcer promoting gene A (dupA)
  • Blood group antigen binding adhesion A (BabA)
  • RNA polymerase β-subunit (RpoB)
  • Vacuolating cytotoxin (VacA)

1: Bacterial factors

A. Flagella

H. pylori propels through the mucus layer with the help of flagella and adheres to the gastric epithelial cells through fimbriae which are the extension of bacterial cytoplasm.

B. Bacterial enzymes

The bacterial enzymes associated with pathogenesis of H. pylori infection include:[7]

C. Bacterial Virulence factors

The cytotoxin-associated gene (Cag) pathogenecity island (PAI) and cytotoxin-associated gene A (cagA)

  • Large amounts of the pro-inflammatory cytokine interleukin-8 are expressed in H. pylori strains with CagPaI.
  • The protein CagA is encoded by CagA gene and type IV bacterial secretion system (T4SS) is encoded by CagPAI.
  • Type IV bacterial secretion apparatus helps in translocation of CagA into host target cells and stimulates epithelial cell pro-inflammatory cytokine expression and gastric inflammation
  • CagA undergoes phosphorylation in host target cells

The following are the bacterial virulence factors associated with H. pylori pathogenesis:

CagA

Outer inflammatory protein A (OipA)

Duodenal ulcer promoting gene A (dupA)

This gene is associated with duodenal ulceration but appeared to protect from gastric cancer in patients from columbia, Japan and South Korea.[24]

Blood group antigen binding adhesion A (BabA)

The RNA polymerase β-subunit (RpoB)

  • The RpoBThr is associated with increased secretion of IL-8 from MKN45 cells compared to RpoBAla.
  • H. pylori strains possessing RpoBThr is seen in 67.6% of East Asians and hence associated with increased risk of development of more severe gastroduodenal diseases.[27]

The vacuolating cytotoxin (VacA)

  • VacA is an exotoxin which is associated with cellular damage rather than pro-inflammatory cytokine release.[28]
  • The active forms of VacA are associated with increased risk of gastric carcinoma

2. Host genetic susceptibility

The risk of gastric carcinoma increases due to :[29][30]

A.The immune response to H.Pylori

The innate immune response

The acquired immune response

B. Hormonal changes and acid homeostasis changes

Somatostatin and gastrin changes

3. Environmental cofactors

The environmental co-factors associated with H. pylori are:

Gross pathology

On gross pathology, H. pylori infection is associated with thickened gastric folds and erythema.[49]

Microscopic pathology

The microscopic pathology depends on the the following stages:[50]

Acute H.pylori infection

  • Most of the initial H. pylori colonization occur during childhood but new infections may occur in adults occasionally.[51][52]
  • Associated with transient profound gastric hypochlorhydria

Microscopic pathology

Chronic H.pylori infection

  • Chronic antral predominant inflammation:
  • Chronic corpus-predominant or pangastritis

Microscopic pathology

Pathogenesis of H.pylori Infection

References

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