Acute Gastritis Due to H-Pylori Infection, Essay Example

Helicobacter pylori was the first, formally recognized bacterial pathogen and one of the most successful. Estimates predict that over half of the world’s population suffer from various levels of H. pylori colonization and infection^{[1](p. 450).}

Pathophysiology

Colonization of this bacterium is almost always associated with active gastritis. The condition will persist as long as the colonization remains and will slowly disappear (within 6 to 24 months) after H. pylori eradication. Self-ingestion experiments by Marshall^[2] and Morris^[3] showed that H. pylori colonization in the human stomach induces inflammation of the gastric mucosa, thus leading to gastritis.  Inflammation occurs in both the antrum and corpus with neutrophilic and mononuclear cells^[1](p.458)

Gastritis can be detected in both acute and chronic phases. Acute gastritis is less commonly detected since it is normally asymptomatic. In some patients with acute gastritis, normally those who have either “deliberately or inadvertently ingested H. pylori or underwent procedures with contaminated material” ^1(p.458) may cause gastrointestinal upset for a period of months and then will suddenly resolve itself.  Most cases of acute gastritis, however, do not resolve on their own.

A 2004 set of controlled studies of acute gastritis (caused by deliberate infection of healthy volunteers with H. pylori), showed this phase tends be associated considerable inflammation of both the proximal and distal stomach mucosa, as well as hypochlorihydria.^[4]. The bacterium imbeds itself in the mucous layer of the gastric mucosa and releases large amounts of urease, in order to breakdown urea to alkaline ammonia and carbon dioxide. This neutralizes the gastric acid in the immediate area and conveys a bubble of protection for the H. pylori.

The pathogen further protects itself by creating an inflammatory cascade. As this cascade progresses acute gastritis can slowly progress to a more chronic condition.^[5] Once the infection has reached a chronic level, T- and B-cell lymphocytes will be present and be followed by infiltration of numerous polymorphonuclear leukocytes cells in the lamina propria and gastric epithelium. These leukocytes will eventually phagocytize the bacteria and their presence is a key diagnostic detector of active gastritis^[6].

The inflammatory cascade process begins with the attachment of H pylori with the surface mucosa. This results in the release of the pro-inflammatory cytokine, interleukin (IL)-8, and leads to activation of polymorphonuclear cells. High levels of cytokines, particularly tumor necrosis factor-a (TNF-?)5 and multiple interleukins (e.g., IL-6, IL-8, IL-10), are detected in the gastric mucosa of patients with H pylori gastritis.^[7] Leukotriene levels, especially Leukotriene B4 will also be elevated^[8].

This inflammatory response leads to functional changes in the stomach. For example, according to Kusters report in the 2006 Clinical Microbiology Review, research has show there to be a close correlation between acid secretion levels and the distribution of the gastritis.^{1(p. 458)} A  2006 article published in the Clinical Microbiology Review by Holly Scott Algood and Timothy L. Cover showed that by releasing Leukotriene B4, which is cytotoxic to gastric epithelium, parietal cells are inhibited, leading to reduced acid secretion^[9]. The cycle continues in this manner, continued inflammation, continued loss of parietal cells, continued acid secretion allow the bacterium to further colonize.

Signs and Symptoms

The symptoms of gastritis do not always correspond to the extent of damage and histological changes in the stomach mucosa, or the level of inflammatory markers present. Severe gastritis symptoms may be present despite only minor changes of the stomach lining and low levels of detected inflammation. Likewise, histological damage might be significant, in a patient with few or no symptoms. For this reason a comprehensive diagnostic protocol is normally followed when ever gastritis is suspected^[10].

Patients often report pain in the upper portion of the abdomen and back. They might also complain of nausea and vomiting, feelings of stomach fullness, burning, bloating and/or belching. In cases of extremely severe gastritis, bleeding may occur inside the stomach, in which case the patient might report vomiting blood or bloody stools^[11].

Diagnostic Tests and Procedures

A combination of invasive and non invasive test are available to determine the presence of h. pylori, the severity of infection and progression of histological damage. An upper gastrointestinal endoscopy tend to be the most common course of action. It gives the clinician the ability to both view the upper gastrointestinal tract and collect a biopsy to be evaluated.

Standard endoscopy technology has many drawbacks, which has lead to the development of alternative techniques. A primary problem with endoscopy is the limited visual data it allows the clinician to collect^[12](p.282). This drawback has spurred more  recent advances, which are able to further magnify gastric mucosal abnormalities.

These new technologies include; arrow band imaging^[13], endocytoscopy^[14] and most recently confocal laser endomicroscopy^[15]. Kiesslich, et alt. detailed the use of confocal laser endomicroscopy in the Journal of Gastroenterology in 2005 as a way to detect H. pylori using surface microscopy imaging of living tissue, during the endoscopy. By using two contrast strains, the researchers were able to see the bacterium both on the surface and in deeper layers of the gastric epithelium.

Some clinicians are opting to avoid endoscopy altogether and obtain gastric juice using a nasogastric tube. The juice then undergoes a staining test, urease test and PCR to detect the presence of H. pylori^{10(p. 285)}. Another recent measure that is gaining appeal and has proven more reliable than employing the use of gastric juice is the use of an extendable oro-gastric brush, first used in 2005 by Graham, et alt of US Endoscopy. Texas. The brush is swallowed and extended into the stomach to where it brushes the mucosa three or four times. It then retracts into a protective sleeve, and is withdrawn from the patient.^[16]

Non-invasive procedures are becoming the preferred option in many cases due to the cost, discomfort and risk of their invasive peers. 13C-urea breath test (13C-UBT), is able to measure the level of H. pylori associate inflammation in the subject. A study published in the 2005 Journal of Gastroenterology and Hematology, used a confirmed “The 13C-UBT is a reproducible determinant of H. pylori infection and non-invasively assesses the severity of antral inflammation”^{[17](p. 270)}

Stool tests are also often used. The offer a certain advantage in many cases because they are able to detect either the bacteria or part of it (DNA, antigen) in a specimen which is easily obtained.

Numerous studies have focused on evaluating the sensitivity, specificity, accuracy, and positive and negative predictive values of the tests used to detect H. pylori.  As a general rule, cases are considered positive for H. pylori when either the culture is positive or both the histological and ureases tests are positive.^10(p.299) In a recent study, culture was positive in 88% of the cases and histology plus urease test were positive in 12%^[18].

Sensitivity will also vary if the test is performed 4 to 6 weeks after an H. pylori eradication treatment because, even if the bacteria are still present, there is most likely a much smaller colonization.^10(p.299).

Treatments

Treatment regimes have include mono, dual and triple therapies. According the Kusters “Although H. pylori is sensitive to a wide range of antibiotics in vitro, they all fail as mono-therapy in vivo.” This has led most clinicians to rely on triple therapies .

Due to the fact that H. pylori infect the mucosal surface, therapy must include a antimicrobial agent to which the bacteria is sensitive. This is why the single most effective mono-therapy is clarithromycin, with an approximate eradication rate of 40% when given twice daily for a course of 10-14 days.^1(p.464)

Several triple therapy regimes have been approved by the FDA for the treatment of H. pylori. One of the most commonly used is currently sold commercially under the name Helidac and includes a combination of bismuth, metronidazole, and tetracycline. This combination is administered for a course of 14 days. The accepted definition of a cure is that no evidence of H pylori exists for 4 or more weeks after ending the antimicrobial therapy.^[19]

A 2008 study out of the University of Helsinki, examined the use of multispecies probiotic combinations for H. pylori eradication. Results indicated that all probiotics strains inhibited H. pylori adhesion. The exact combination of probiotic strains used highly effected the levels of IL-8, PGE₂ and LTB₄ released from eradicated cells and whether the probiotic treatment proved to be pro or anti-inflammatory^[20]. More research is needed in this area.

Course of Disease (Treated and Untreated)

If left untreated H. pylori infections and subsequent gastritis seem to be able to take a wide variety of courses. Some infections clear themselves up on their own. Patients are often asymptomatic or experience slight nonspecific dyspeptic symptoms^{(p. 458)}. The clinical course is less optimistic if patients develop any of the possible complications of H pylori infection such as peptic ulcer or gastric malignancy. pylori gastritis is also the most frequent cause of MALT lymphoma, with patients having 12-16 times the increased risk of developing gastric carcinoma. Eradication of h. pylori results in rapid curing of the infection with disappearance of the neutrophilic infiltration of the gastric mucosa.^[21]

^[1] Kusters, J., van Vliet, A.H.M., Kuipers, E., Pathogenesis of Helicobacter pylori Infection, Clin Microbiol Rev. 2006 July; 19(3): 449–490.

^[2] Marshall, B. J., J. A. Armstrong, D. B. McGechie, and R. J. Glancy.  Attempt to fulfil Koch’s postulates for pyloric Campylobacter. Med. J. Austr. 1985. 142:436-439.

^[3] Morris, A., and G. Nicholson. Ingestion of Campylobacter pyloridis causes gastritis and raised fasting gastric pH. Am. J. Gastroenterol. 1987. 82:192-199.

^[4] Graham, D. Y., A. R. Opekun, M. S. Osato, H. M. El-Zimaity, C. K. Lee, Y. Yamaoka, W. A. Qureshi, M. Cadoz, and T. P. Monath. Challenge model for Helicobacter pylori infection in human volunteers. Gut . 2004.53:1235-1243.

^[5] Andersen LP. Colonization and infection by Helicobacter pylori in humans. Helicobacter. Nov 2007;12 Suppl 2:12-5.

^[6] Gologan A, Graham DY, Sepulveda AR. Molecular markers in Helicobacter pylori-associated gastric carcinogenesis. Clin Lab Med. Mar 2005;25(1):197-222.

^[7] Zalewska-Ziob M, Adamek B, Strzelczyk JK, Gawron K, Jarzab B, Gubala E, et al. TNF-alpha expression in gastric mucosa of individuals infected with different virulent Helicobacter pylori strains. Med Sci Monit. Jun 2009;15(6):BR166-71

^[8] Sepulveda AR, Patil M. Practical approach to the pathologic diagnosis of gastritis. Arch Pathol Lab Med. Oct 2008;132(10):1586-93.

^[9] Scott Algood, H., Cover, T., Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses Clin Microbiol Rev. 2006 October; 19(4): 597–613.

^[10] Graham DY. Therapy of Helicobacter pylori: current status and issues. Gastroenterology. Feb 2000;118(2 Suppl 1):S2-8.

^[11] Rugge M, Genta RM. Staging and grading of chronic gastritis. Hum Pathol. Mar 2005;36(3):228-33.

^[12] Megraud, F., Lehours, P., Helicobacter pylori Detection and Antimicrobial susceptibility Testing, Clin Microbiol Rev. 2007 April; 20(2): 280–322.

^[13] Anagnostopoulos GK, Ragunath K, Shonde A, Hawkey CJ, Yao K. Diagnosis of autoimmune gastritis by high resolution magnification endoscopy. World J Gastroenterol. Jul 28 2006;12(28):4586-7

^[14] Inoue, H., T. Kazawa, Y. Sato, H. Satodate, K. Sasajima, S. E. Kudo, and A. Shiokawa. In vivo observation of living cancer cells in the esophagus, stomach, and colon using catheter-type contact endoscope, EndoCytoscopy system. Gastrointest. Endosc. Clin. N. Am. 2005. 14:589–594,253.

^[15] Kiesslich, R., M. Goetz, J. Burg, M. Stolte, E. Siegel, M. J. Maeurer, S. Thomas, D. Strand, P. R. Galle, and M. F. Neurath. Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy. Gastroenterology. 2005.128:2119–2123.

^[16] Graham, D. Y., M. Kudo, R. Reddy, and A. R. Opekun. Practical rapid, minimally invasive, reliable nonendoscopic method to obtain Helicobacter pylori for culture. Helicobacter. 2005. 10:1-3

^[17] Matthews, G., Cummins, A., Lawrence, A., Johnson, B., Campbell, F., Butler, R., 13C-Urea Breath Test: Reproducibility and Association With the Severity of Helicobacter pylori-associated Antral Gastritis. J Gastroenterol Hepatol. 2005;20(2):270-274

^[18] Megraud, F., and E. P. T. Force. 2005. Comparison of non-invasive tests to detect Helicobacter pylori infection in children and adolescents: results of a multicenter European study. J. Pediatr. 146:198-203

^[19] Duck WM, Sobel J, Pruckler JM, Song Q, Swerdlow D, Friedman C. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg Infect Dis. Jun 2004;10(6):1088-94.

^[20] Myllyluoma, E., Ahonen, A.M., Korpela, R.,Effects of Multispecies Probiotic Combination on Helicobacter pylori Infection In Vitro. Clin Vaccine Immunol. 2008 September; 15(9): 1472–1482

^[21] Weck MN, Gao L, Brenner H. Helicobacter pylori infection and chronic atrophic gastritis: associations according to severity of disease. Epidemiology. Jul 2009;20(4):569-74.