Peptic ulcer pathophysiology: Difference between revisions
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*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 and nonsteroidal anti-inflammatory drugs (NSAIDs)<ref name="urlPathogenesis of Peptic Ulcer and Implications for Therapy — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307 |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}</ref><ref>url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307<nowiki> |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}</nowiki></ref><ref name="pmid10383497">{{cite journal |vauthors=Hawkey CJ |title=Personal review: Helicobacter pylori, NSAIDs and cognitive dissonance |journal=Aliment. Pharmacol. Ther. |volume=13 |issue=6 |pages=695–702 |year=1999 |pmid=10383497 |doi= |url=}}</ref> | *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 and nonsteroidal anti-inflammatory drugs (NSAIDs)<ref name="urlPathogenesis of Peptic Ulcer and Implications for Therapy — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307 |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}</ref><ref>url=http://www.nejm.org/doi/full/10.1056/NEJM199003293221307<nowiki> |title=Pathogenesis of Peptic Ulcer and Implications for Therapy — NEJM |format= |work= |accessdate=}}</nowiki></ref><ref name="pmid10383497">{{cite journal |vauthors=Hawkey CJ |title=Personal review: Helicobacter pylori, NSAIDs and cognitive dissonance |journal=Aliment. Pharmacol. Ther. |volume=13 |issue=6 |pages=695–702 |year=1999 |pmid=10383497 |doi= |url=}}</ref> | ||
===Helicobacter pylori=== | ===Helicobacter pylori=== | ||
H.pylori is gram negative , spiral -shaped ,motile bacteria which penetrate into viscous mucus layer and neutral ph | H.pylori is gram-negative, spiral-shaped , motile bacteria which penetrate into viscous mucus layer and neutral ph allow more growth of gastric helicobacter. | ||
*On entry ,it shows urea- and bicarbonate-mediated chemotactic motility toward the mucus layer .<ref name="pmid16847081">{{cite journal |vauthors=Kusters JG, van Vliet AH, Kuipers EJ |title=Pathogenesis of Helicobacter pylori infection |journal=Clin. Microbiol. Rev. |volume=19 |issue=3 |pages=449–90 |year=2006 |pmid=16847081 |pmc=1539101 |doi=10.1128/CMR.00054-05 |url=}}</ref><ref name="pmid118091812">{{cite journal |vauthors=Huang JQ, Sridhar S, Hunt RH |title=Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis |journal=Lancet |volume=359 |issue=9300 |pages=14–22 |year=2002 |pmid=11809181 |doi=10.1016/S0140-6736(02)07273-2 |url=}}</ref> | |||
**It secrete cytotoxins and produce virulence factors like Cag A, VacA, and OipA. | **It secrete cytotoxins and produce virulence factors like Cag A, VacA, and OipA. | ||
**Protein CagA and vacuolating cytotoxin VacA aids in the colonization of gastric mucosa and modulates host's immune system. | **Protein CagA and vacuolating cytotoxin VacA aids in the colonization of gastric mucosa and modulates host's immune system. | ||
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{{Familytree/end}} | {{Familytree/end}} | ||
===Role of NSAIDS=== | ===Role of NSAIDS=== | ||
*NSAID's inhibit systemic prostaglandins production and cause ulcers<ref name="pmid1882793">{{cite journal |vauthors=Borody TJ, George LL, Brandl S, Andrews P, Ostapowicz N, Hyland L, Devine M |title=Helicobacter pylori-negative duodenal ulcer |journal=Am. J. Gastroenterol. |volume=86 |issue=9 |pages=1154–7 |year=1991 |pmid=1882793 |doi= |url=}}</ref> | *NSAID's inhibit systemic prostaglandins production and cause ulcers<ref name="pmid1882793">{{cite journal |vauthors=Borody TJ, George LL, Brandl S, Andrews P, Ostapowicz N, Hyland L, Devine M |title=Helicobacter pylori-negative duodenal ulcer |journal=Am. J. Gastroenterol. |volume=86 |issue=9 |pages=1154–7 |year=1991 |pmid=1882793 |doi= |url=}}</ref> | ||
Revision as of 23:27, 14 November 2017
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Peptic ulcer Microchapters |
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Diagnosis |
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Treatment |
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Surgery |
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Case Studies |
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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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Guidlines for factors that predict the successful eradication when treating H. pylori infection |
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Guidelines to document H. pylori antimicrobial resistance in the North America |
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Guidelines for evaluation and testing of H. pylori antibiotic resistance |
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Guidelines for when to test for treatment success after H. pylori eradication therapy |
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Guidelines for penicillin allergy in patients with 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 and nonsteroidal anti-inflammatory drugs (NSAIDs)[2][3][4]
Helicobacter pylori
H.pylori is gram-negative, spiral-shaped , motile bacteria which penetrate into viscous mucus layer and neutral ph allow more growth of gastric helicobacter.
- On entry ,it shows urea- and bicarbonate-mediated chemotactic motility toward the mucus layer .[5][6]
- It secrete cytotoxins and produce virulence factors like Cag A, VacA, and OipA.
- Protein CagA and vacuolating cytotoxin VacA aids in the colonization of gastric mucosa and 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[2][7] [8][9][10]
- H.pylori secretes various enzyme :Urease,Phospholipases,Alcohol dehydrogenase and Catalases- causes damage the host gastric muscosa by generating toxic metabolities[11][12][13]
| Helicobacter pylori infection | |||||||||||||||||||||||||||||||||||||
| Inflammatory response secretes IL-8 ,IL-1b | Production of alkaline ammonia | Production of urease bacterial phospholipase A | |||||||||||||||||||||||||||||||||||
| Infux of neutophils and macrophages release of lysosomal enzymes leukotrienes (LT)and reactive oxygen | inhibition of D-cells leads to inappropriate release of somatostatin and hypergastrinemia | Production of urease ,phospholipase A and C release toxic metabolities | |||||||||||||||||||||||||||||||||||
| Mucosal injury | |||||||||||||||||||||||||||||||||||||
Role of NSAIDS
- NSAID's inhibit systemic prostaglandins production and cause ulcers[14]
- Inhibition of prostaglandins results in decreased blood flow and decreased mucus production resulting in mucosal damage.
- NSAID's are more commonly responsible for gasrtic ulcers than duodenal ulcers.[15][16]
| NSAIDs | |||||||||||||||||||||||||||||||||||||
| COX-1 inhibitor | Topical irritation | COX-2 inhibitor | |||||||||||||||||||||||||||||||||||
| Decreased blood flow | Epithelial damage | Leucocyte adhesion | |||||||||||||||||||||||||||||||||||
| Mucosal injury | |||||||||||||||||||||||||||||||||||||
Other factors
Other factors responsible for peptic ulcer disease:
Smoking
- Smoking decreases the production of prostaglandins in fundic and antral part of stomach and results in mucosal damage similar to NSAID's[17]
- Smoking is also triggers reflux of bile acids into the duodenum which results in alteration of blood flow leading to ischaemia .[18]
Duodenal ulcer
Duodenal ulcer Abnormalities of acid secretion:
- Increase in basal acid output.
- Increase in acid response to GRP
- Increased maximal acid response to exogenous gastrin
- Increased ratio of basal acid output to maximal gastrin-stimulated output
- Increased ratio of maximal GRP-stimulated acid output to maximal gastrin-stimulated output.[19][20]
- 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 .[21]
- Gastric ulcer:
There is decrease in acid and decrease in parietal cell volume which further predisposes to development to ulcer formation.[22]
Gross Pathology
- Gastric ulcers are most often localized on the lesser curvature of the stomach.
- Characteristic findings of a gastric ulcer on gross pathology include:
- Round to oval
- 2 to 4 cm diameter
- Smooth base with perpendicular borders.
- Parietal scarring with radial folds may be evident in the surrounding mucosa.
Microscopic Pathology
- A gastric peptic ulcer is a mucosal defect produced by acid-pepsin aggression which penetrates the muscularis mucosae and muscularis propria.
- During the active phase, the base of the ulcer shows 4 zones:
- Inflammatory exudate
- Fibrinoid necrosis
- Granulation tissue
- Fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.[23]
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 "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=}}
- ↑ Hawkey CJ (1999). "Personal review: Helicobacter pylori, NSAIDs and cognitive dissonance". Aliment. Pharmacol. Ther. 13 (6): 695–702. PMID 10383497.
- ↑ 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.
- ↑ Holvoet J, Terriere L, Van Hee W, Verbist L, Fierens E, Hautekeete ML (1991). "Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study". Gut. 32 (7): 730–4. PMC 1378985. PMID 1855677.
- ↑ 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.