Peptic ulcer pathophysiology
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2017 ACG Guidelines for Peptic Ulcer Disease |
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Guidelines for the Indications to Test for, and to Treat, H. pylori Infection |
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Peptic ulcer pathophysiology On the Web |
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American Roentgen Ray Society Images of Peptic ulcer pathophysiology |
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Risk calculators and risk factors for Peptic ulcer pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ;Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
Pathophysiology
A major causative factor (60% of gastric and 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonizes (i.e. settles there after entering the body) the antral mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a defect in the regulation of gastrin production by that part of the stomach, and gastrin secretion is increased. Gastrin, in turn, stimulates the production of gastric acid by parietal cells. The acid erodes the mucosa and causes the ulcer.
Another major cause is the use of NSAIDs (see above). The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins. Newer NSAIDs (celecoxib, rofecoxib) only inhibitcox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.
Tobacco smoking, blood group, spices and other factors that were suspected to cause ulcers until late in the 20th century, are actually of relatively minor importance in the development of peptic ulcers.[1]
Glucocorticoids lead to atrophy of all epithelial tissues. Their role in ulcerogenesis is relatively small.
There is debate as to whether Stress in the psychological sense can influence the development of peptic ulcers (see Stress and ulcers above). Burns and head trauma, however, can lead to "stress ulcers", and it is reported in many patients who are on mechanical ventilation.
Smoking leads to atherosclerosis and vascular spasms, causing vascular insufficiency and promoting the development of ulcers through ischemia.
- It is found that peptic ulcer disease is the result of self-digestion which occurs due to an excess of auto-peptic activity in gastric juice over the defensive activity of gastric mucosa and is mediated by two major factors which disrupt mucosal resistance to injury: Helicobacter pylori (formerly Campylobacter pylori) infection in 75% cases[2] and nonsteroidal anti-inflammatory drugs (NSAIDs)[2][3]
- Helicobacter pylori:gram negative bacteria,spiral-shaped, urease positive and highly motile through flagella .Upon entry ,it display urea- and bicarbonate-mediated chemotactic motility toward the mucus layer . The spiral morphology and flagellar motility then assist in penetration into the viscous mucus layer, where the more pH-neutral conditions allow growth of the gastric Helicobacter species.[4][5]
- It secrete cytotoxins and produce virulence factors like Cag A, VacA, and OipA.Cytotoxin-associated gene pathogenicity encodes protein CagA and vacuolating cytotoxin VacA aids in the colonization of gastric mucosa and it modulates host's immune system.It causes local production of a range of proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T- and B- cell responses and the development of gastric lymphoid follicles.Bacterial factors and complement activation leads to neutrophilic activation including reactive oxygen me*It is found that peptic ulcer disease is the result of self-digestion which occurs due to an excess of auto-peptic power in gastric juice over the defensive power of gastric mucosa and is mediated by two major factors which disrupt mucosal resistance to injury: Helicobacter pylori (formerly Campylobacter pylori) infection in 75% cases[2] and nonsteroidal anti-inflammatory drugs (NSAIDs)[2][6]
- Helicobacter pylori-gram negative bacteria,spiral-shaped, urease positive and highly motile through flagella .Upon entry ,it display urea- and bicarbonate-mediated chemotactic motabolite.Following injury to astric mucosa it secretes interleukns and chemokines ,which further leads to neutrophilic migration to the site of infection.Cag A and Vac A leads to activation of IL-8 which leads to inflammation of gastric mucosa [7][8][9]
- NSAIDs:
Approach to endoscopic therapy:*
| NSAIDs | |||||||||||||||||||||||||||||||||||||
| COX-1 inhibitor | Topical irritation | COX-2 inhibitor | |||||||||||||||||||||||||||||||||||
| Decreased blood flow | Epithelial damage | Leucocyte adhesion | |||||||||||||||||||||||||||||||||||
| Mucosal injury | |||||||||||||||||||||||||||||||||||||
- Other factors responsible for peptic ulcer disease:
- Duodenal ulcer:
- Abnormalities of acid secretion:
- Decreased in bicarbonate secretion and low ph leads to gastric metaplasia induced duodenitis which further increases the risk of acid damage and leads to ulcer .[19]
- Gastric ulcer:
There is decrease in acid and decrease in parietal cell volume which further predisposes to development to ulcer formation.[20] Overuse of laxatives is also known to cause peptic ulcers.
A family history is often present in duodenal ulcers, especially when blood group O is also present. Inheritance appears to be unimportant in gastric ulcers.
Gastrinomas (Zollinger-Ellison syndrome), rare gastrin-secreting tumors, cause multiple and difficult to heal ulcers.
Gross Pathology
Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer is a round to oval parietal defect ("hole"), 2 to 4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irregular as in the ulcerative form of gastric cancer. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.
Microscopic Pathology
A gastric peptic ulcer is a mucosal defect which penetrates the muscularis mucosae and muscularis propria, produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.[21]
References
- ↑ For nearly 100 years, scientists and doctors thought that ulcers were caused by stress, spicy food, and alcohol. Treatment involved bed rest and a bland diet. Later, researchers added stomach acid to the list of causes and began treating ulcers with antacids.National Digestive Diseases Information Clearinghouse
- ↑ 2.0 2.1 2.2 2.3 "Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM".
- ↑ url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307 |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}
- ↑ Kusters JG, van Vliet AH, Kuipers EJ (2006). "Pathogenesis of Helicobacter pylori infection". Clin. Microbiol. Rev. 19 (3): 449–90. doi:10.1128/CMR.00054-05. PMC 1539101. PMID 16847081.
- ↑ Huang JQ, Sridhar S, Hunt RH (2002). "Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis". Lancet. 359 (9300): 14–22. doi:10.1016/S0140-6736(02)07273-2. PMID 11809181.
- ↑ url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307 |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}
- ↑ Logan RP (1996). "Adherence of Helicobacter pylori". Aliment. Pharmacol. Ther. 10 Suppl 1: 3–15. PMID 8730255.
- ↑ Crabtree JE (1996). "Gastric mucosal inflammatory responses to Helicobacter pylori". Aliment. Pharmacol. Ther. 10 Suppl 1: 29–37. PMID 8730257.
- ↑ Ernst PB, Jin Y, Reyes VE, Crowe SE (1994). "The role of the local immune response in the pathogenesis of peptic ulcer formation". Scand. J. Gastroenterol. Suppl. 205: 22–8. PMID 7863238.
- ↑ Mobley HL (1996). "The role of Helicobacter pylori urease in the pathogenesis of gastritis and peptic ulceration". Aliment. Pharmacol. Ther. 10 Suppl 1: 57–64. PMID 8730260.
- ↑ Nilius M, Malfertheiner P (1996). "Helicobacter pylori enzymes". Aliment. Pharmacol. Ther. 10 Suppl 1: 65–71. PMID 8730261.
- ↑ Slomiany BL, Kasinathan C, Slomiany A (1989). "Lipolytic activity of Campylobacter pylori: effect of colloidal bismuth subcitrate (De-Nol)". Am. J. Gastroenterol. 84 (10): 1273–7. PMID 2801678.
- ↑ Borody TJ, George LL, Brandl S, Andrews P, Ostapowicz N, Hyland L, Devine M (1991). "Helicobacter pylori-negative duodenal ulcer". Am. J. Gastroenterol. 86 (9): 1154–7. PMID 1882793.
- ↑ Huang JQ, Sridhar S, Hunt RH (2002). "Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis". Lancet. 359 (9300): 14–22. doi:10.1016/S0140-6736(02)07273-2. PMID 11809181.
- ↑ Quimby GF, Bonnice CA, Burstein SH, Eastwood GL (1986). "Active smoking depresses prostaglandin synthesis in human gastric mucosa". Ann. Intern. Med. 104 (5): 616–9. PMID 3457547.
- ↑ Müller-Lissner SA (1986). "Bile reflux is increased in cigarette smokers". Gastroenterology. 90 (5 Pt 1): 1205–9. PMID 3956939.
- ↑ el-Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE (1995). "Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease". Gastroenterology. 109 (3): 681–91. PMID 7657096.
- ↑ el-Omar E, Penman I, Dorrian CA, Ardill JE, McColl KE (1993). "Eradicating Helicobacter pylori infection lowers gastrin mediated acid secretion by two thirds in patients with duodenal ulcer". Gut. 34 (8): 1060–5. PMC 1374354. PMID 8174954.
- ↑ 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.
- ↑ Malaty HM, Graham DY, Isaksson I, Engstrand L, Pedersen NL (2000). "Are genetic influences on peptic ulcer dependent or independent of genetic influences for Helicobacter pylori infection?". Arch. Intern. Med. 160 (1): 105–9. PMID 10632311.
- ↑ "ATLAS OF PATHOLOGY". Retrieved 2007-08-26.