H.pylori peptic ulcer disease 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

H. pylori is closely associated with both duodenal and gastric ulcers. The estimated lifetime risk for the development of peptic ulcer disease is 10-20%, in patients with H. pylori infection. H. pylori causes up to 90% of duodenal ulcers and 60-80% of gastric ulcers.

Pathophysiology

Duodenal Ulceration

  • The patients with higher gastric acid secretion have increased risk of developing duodenal ulcers compared to normal, healthy individuals.
  • The most important requirements for the development of duodenal ulceration are:

Pathogenesis

The three stages in the pathogenesis of duodenal ulcer include:[2]

Gastric metaplasia

  • H. pylori causes hypergastrinemia and increased sensitivity to gastrin.
  • Gastric metaplasia (the presence of gastric-type mucus secreting cells in the surface epithelium of the duodenum) occurs as a part of host defence mechanism to protect against the repeated injury caused by arrival of unneutralized acid in the first part of duodenum.[3][4]
  • In response to inflammatory process following arrival of unneutralized acid into duodenum, in the goblet cells transforms to gastric phenotype cells.[3]

Active chronic duodenitis

  • The gastric metaplasia provide sites for H. pylori to colonize, passing through the duodenum. The organism do not colonize the native duodenal epithelial cells.[4]
  • After colonization, H. pylori stimulates an active chronic inflammatory response similar to that seen in the gastric mucosa.

Ulceration

  • Due to gastric metaplasia, the pH of the duodenal mucosa alters.[2]
  • This along with chronic inflammation and direct bacterial effects on epithelium, the integrity of duodenal mucosa is impaired and more susceptible to acid attack leading to ulcer formation.

Gastric ulceration

  • The bacteria (particularly more virulent CagA-positive strains) either proliferates maximally at the transitional zone because of the favorable local environment( optimal pH) or generates inflammatory products due to induction of stress proteins.
  • Hence it is an optimal site for adhesion, growth and release of inflammatory products and cytokine release.
  • The maximal development of atrophy and intestinal metaplasia occurs at this site and is at greatest risk of ulceration.
  • The release of inflammatory products leads to surface epithelial degeneration and increased exfoliation (downregulation of E-cadherin expression by bacterial factors) of the surface epithelial cells.[5][6].
  • Following exfoliation, compensatory cell proliferation occurs which leads to accumulation of immature cells in the foveolae and surface.
  • The bicarbonate and mucin production is impaired, and the mucosal integrity is compromised.
  • The release of chemical mediators by activated polymorphs and mast cells, and activation of complement system leads to microvascular thrombosis and focal ischemic damage to surface epithelium leading to ulcer formation.
  • The formation of ulcer is also promoted by intestinal metaplasia and atrophy found immediately distal to translational zone.[7][8]
  • The proximal shift of the antral-corpus transitional zone is a consequence of inflammation, atrophy, and metaplasia. This explains that as age increases, the gastric ulcers are found progressively at higher level of the lesser curve.

References

  1. Kuipers EJ, Thijs JC, Festen HP (1995). "The prevalence of Helicobacter pylori in peptic ulcer disease". Aliment Pharmacol Ther. 9 Suppl 2: 59–69. PMID 8547530.
  2. 2.0 2.1 Wyatt JI, Rathbone BJ, Dixon MF, Heatley RV (1987). "Campylobacter pyloridis and acid induced gastric metaplasia in the pathogenesis of duodenitis". J Clin Pathol. 40 (8): 841–8. PMC 1141122. PMID 3654985.
  3. 3.0 3.1 Kreuning J, vd Wal AM, Kuiper G, Lindeman J (1989). "Chronic nonspecific duodenitis. A multiple biopsy study of the duodenal bulb in health and disease". Scand J Gastroenterol Suppl. 167: 16–20. PMID 2617162.
  4. 4.0 4.1 Walker MM, Dixon MF (1996). "Gastric metaplasia: its role in duodenal ulceration". Aliment Pharmacol Ther. 10 Suppl 1: 119–28. PMID 8730266.
  5. Warburton VJ, Everett S, Mapstone NP, Axon AT, Hawkey P, Dixon MF (1998). "Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis". J Clin Pathol. 51 (1): 55–61. PMC 500433. PMID 9577374.
  6. Terrés AM, Pajares JM, O'Toole D, Ahern S, Kelleher D (1998). "H pylori infection is associated with downregulation of E-cadherin, a molecule involved in epithelial cell adhesion and proliferation control". J Clin Pathol. 51 (5): 410–2. PMC 500709. PMID 9708215.
  7. Dixon MF (1994). "Pathophysiology of Helicobacter pylori infection". Scand J Gastroenterol Suppl. 201: 7–10. PMID 8047828.
  8. Atuma C, Engstrand L, Holm L (1998). "Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA- and CagA-independent pathway in rats". Scand J Gastroenterol. 33 (12): 1256–61. PMID 9930388.

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