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H. Pylori as an etiological factor in Peptic ulcer disease.

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Peptic ulcer disease(PUD) is one of the most common gastroenterological diseases warranting GP consultation. This presentation takes a deep look at H. Pylori; The structure of this bacterium and it's patho-physiology in Peptic ulcer disease(causes about 80-85%).

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H. Pylori as an etiological factor in Peptic ulcer disease.

  1. 1. H. Pylori “for and against” in etiology of peptic ulcer. BY GBAJIE NNAMDI PETER.
  2. 2. H. Pylori and Peptic ulcer disease  Peptic ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum. These sores/ulcers produce many constitutional symptoms that make the patient seek medical help. Such symptoms as; • A gnawing or burning pain in the middle or upper stomach between meals or at night • Bloating • Heartburn • Nausea or vomiting  In severe cases, symptoms can include: • Dark or black stool (due to bleeding) • Vomiting blood (that can look like "coffee-grounds") • Weight loss • Severe pain in the mid to upper abdomen
  3. 3. H. Pylori as major cause of PUD  It is believed that H. pylori causes about 90% of duodenal ulcers and about 80-85% of gastric ulcers. With this, it’s clear that majority of ulcers are caused by this bacterium and the study of it’s pathogenesis/pathophysiology and method of elimination would bring an end to disease progression and relief to PUD patients. Other minor causes of PUD include;  NSAIDs  Smoking and stress  Heredity  As complication of other diseases.  Since scientists and Gastroenterologists world wide are in agreement about H. pylori being the major cause(ave 85-90%) of PUD, there is no much argument abt this FACT so, let’s proceed to know about this bacterium and it’s pathogenesis in PUD.
  4. 4. H. Pylori- Pathogenesis in PUD.  Helicobacter pylori is a Gram-negative, helix-shaped bacterium that is about 3 micrometers long with a diameter of 0.5 micrometers. H. pylori is a microaerophilic bacterium which means that it requires oxygen to function. However, H. pylori requires much lower concentrations of oxygen than those found in our atmosphere. This bacterium contains a hydrogenase which it can use to obtain energy by oxidizing molecular hydrogen (in the form of H2) produced by intestinal bacteria. H. pylori also produces oxidase, catalase, and urease.
  5. 5. H. Pylori contd  It has an outer-membrane consisting of phospholipids and lipopolysaccharide which are characteristic of typical Gram-negative bacteria. H. pylori bacteria are known to inhabit various areas of the stomach and duodenum. Infections caused by this bacteria lead to chronic inflammation in the stomach lining (Gastritis). H. pylori infections are also strongly associated to the development of gastric ulcers and even stomach cancer. Although H. pylori is known to cause several problems, over 80% of individuals infected with this bacterium show no symptoms. Over half of all people in the world are thought to harbor this bacterium in their upper gastrointestinal tract.
  6. 6. Pathogenesis  There is no single pathway of transmission for Helicobacter pylori that has been clearly identified. Scientists have had difficulty locating the bacterium anywhere outside of gastric tissue. Because of this, it has been difficult for scientists to locate the portal by which the bacterium is spread. However, scientists do believe the bacterium is passed from person to person and most transmissions occur during early life. It has been suggested that transmission may occur in faecal-oral and oral-oral pathways. Other pathways have not been ruled out. However the bacterium enters the body it eventually makes its way to the gastrointestinal tract. H. pylori makes its way into the stomach to begin colonization. In order to colonize the stomach H. pylori must survive the acidic pH of its environment. It burrows into the mucous lining that coats the stomach. An H. pylori bacterium has flagella and uses them to move through the stomach lumen and drill into the mucous lining of the stomach.
  7. 7. Pathogenesis  H. pylori produces adhesins that bind to membrane-associated lipids and carbohydrates which helps it to adhere to the epithelial cells. The bacterium also produces great quantities of urease, and enzyme located inside and outside of the cell. This enzyme is capable of breaking down urea that is secreted into the stomach. It breaks down the urea into carbon dioxide and ammonia. The ammonia is converted into an ammonium ion by accepting a hydrogen ion from self-ionized water. The left-over hydroxyl ions then react with the carbon dioxide to produce bicarbonate which neutralizes gastric acid. Therefore, H. pylori is dependent upon urease for its survival in the acidic environment found in the stomach. Without the urease enzyme the bacterium would almost inevitably die. The ammonia that is a byproduct of the urease reaction is toxic to epithelial cells of the stomach. H. pylori also produces protease (an enzyme that breaks down proteins), vacuolating cytotoxin A (VacA), and phospholipases (enzymes that hydrolyze phospholipids into fatty acids and other lipophilic substances). All of these products are damaging to the epithelial cells of the stomach.
  8. 8. Pathogenesis  When H. pylori colonizes the stomach it often results in chronic gastritis, an inflammation of the stomach lining. Stomach and duodenal ulcers occur when the inflammation allows the acid and pepsin in the stomach lumen to overpower the mechanisms that protect the stomach and duodenal mucosa from these substances. The location of the chronic gastritis (which occurs at the site of H. pylori colonization) dictates the type of ulcer that subsequently develops. The amount of acid within the stomach lumen has an effect on the colonization patterns of the bacteriumH. pylori. It will therefore, in the end, establish the location at which the gastric or duodenal ulcer will form. For example, in people that produce large amounts of acid, H. pylori will colonize the pyloric antrum of the stomach to avoid the parietal cells in the corpus of the stomach that secrete acid.
  9. 9.  The inflammatory response to the bacteria induces G cells in the antrum to secrete the hormone gastrin. Gastrin travels through the bloodstream to the corpus of the stomach.[8] Gastrin excites the parietal cells in the corpus to release even more acid into the stomach lumen. Persistently increased gastrin levels eventually cause the number of parietal cells to also increase, further increasing the amount of acid secreted.[9] The increased amount of acid damages the duodenum and may consequently result in the formation of duodenal ulcers. Gastric ulcers on the other hand are often linked with reduced or normal levels of acid production. This suggests that the mechanisms that protect the gastric mucosa are faulty in that individual.[9] H. pylori capitalizes on this defect and begins to colonize the corpus of the stomach where the parietal cells are located. The chronic inflammation caused by the colonization of this bacterium causes further reduction in the stomach’s acid production, causing atrophy of the stomach lining. The deterioration of the stomach’s lining may lead to future gastric ulceration and even an increased risk for stomach cancer.
  10. 10. Diagnosis and Identification of H. pylori in PUD.  Once a patient presents with symptoms of Peptic ulcer disease(Epigastric pain relating to food in take or hunger, heartburn, nausea or vomiting, stomach bloating, meteorism, tarry stool, abdominal discomfort after in take of spicy foods etc) , doctor normally prescribe H. pylori test as one of the major and most important tests in management and follow up. This is simple, elimination of the causative agent plays a great role in complete treatment of any condition. H. pylori being a major cause of peptic ulcer disease(85-90%), needs to be checked to rule out H. pylori +ve PUD or rule in.
  11. 11. Invasive and non-invasive method of H. pylori testing.  NON-INVASIVE TESTS  Blood antibody test  Urea breath test  Stool antigen test  INVASIVE TESTS  Endoscopic Biopsy providing samples for;  1) histology  2)cytology  3)Rapid urease test  4) Bacterial culture
  12. 12. Non-Invasive method of H. pylori test  Blood antibody test/Serological test: This is done using the patient’s blood to test for H. pylori antibodies. Laboratory and office-based serologic assays for antibodies to H. pylori have sensitivity and specificity of > 85% and are considered the noninvasive tests of choice for initial documentation of H. pylori infection. However, because qualitative assays remain positive for up to 3 yr after successful treatment and because quantitative antibody levels do not decline significantly for 6 to 12 months after treatment, serologic assays are not usually used to assess cure
  13. 13. H. Pylori serology test kit
  14. 14. InstaTest for H. pylori serological test
  15. 15. NONIVASIVE TEST contd  Urea Breath test:  Urea breath tests use an oral dose of 13C- or 14C-labeled urea. In an infected patient, the organism metabolizes the urea and liberates labeled CO2, which is exhaled and can be quantified in breath samples taken 20 to 30 min after ingestion of the urea. Sensitivity and specificity are > 90%. Urea breath tests are well suited for confirming eradication of the organism after therapy. False-negative results are possible with recent antibiotic use or concomitant proton pump inhibitor therapy; therefore, follow-up testing should be delayed ≥ 4 wk after antibiotic therapy and 1 wk after proton pump inhibitor therapy. H2 blockers do not affect the test. 
  16. 16. Urea breath test
  17. 17. NON-INVASIVE TESTS contd  Stool antigen test: Stool antigen assays seem to have a sensitivity and specificity near that of urea breath tests, particularly for initial diagnosis; an office-based stool test is under development.
  18. 18. INVASIVE TEST  In other to perform any of the previously listed invasive methods, Endoscopy is used to obtain mucosal biopsy samples for a rapid urease test (RUT) or histologic staining. Bacterial culture is of limited use because of the fastidious nature of the organism. Endoscopy is not recommended solely for diagnosis of H. pylori; noninvasive tests are preferred unless endoscopy is indicated for other reasons.
  19. 19. INVASIVE TEST  The RUT, in which presence of bacterial urease in the biopsy sample causes a color change on a special medium, is the diagnostic method of choice on tissue samples. Histologic staining of biopsy samples should be done for patients with negative RUT results but suspicious clinical findings, recent antibiotic use, or treatment with proton pump inhibitors. RUT and histologic staining each have a sensitivity and specificity of > 90%. 
  20. 20. Endoscopic biopsy
  21. 21. Rapid urease test
  22. 22. Histology of biopsy showing H. pylori
  23. 23. Bacteriological culture of H. pylori
  24. 24. The case for or against H. pylori in PUD  It’s been proved through various studies that H. pylori is the key etiological factor in PUD based on prevalence and incidence. It is worth elaborating also that, some other etiological or better still, risk factors like heredity, long term use of NSAIDs, smoking, stress and association of other diseases play little roles as etiological factors. In some cases, there might be multiple factors like; combination of H. pylori and NSAIDs or Heredity and NSAIDs.  It is known that NSAIDs when used for a long period( aspirin, ibuprofen (Advil, Motrin IB, others), naproxen (Aleve, Anaprox, others), ketoprofen and others) damage gastric mucosal barrier and are important etiologic factor in abt 30% cases.
  25. 25.  Heredity: Peptic ulcer tends to run in families and 2 specific factors identified are;  1) Larger parietal cell mass with increased gastric acid output in patients with duodenal ulcer perhaps represents an inborn characteristic of the individual.  2) Blood group and Blood group antigen; Those with blood group O and those unable to secrete their blood group antigen into the saliva and gastric juice are more predisposed to peptic ulcer.  The hereditary component analyzed above contribute about 5-10% as an etiological factor and can’t be compared to the whooping 80-90% case in H. pylori incidence.
  26. 26. Summary  Due to the overwhelming believe that H. pylori is the major cause of peptic ulcer(though other factors like listed earlier are also acknowledged but, their roles re so little), the H. pylori eradication therapy has been included in guidelines for treatment of patients with PUD and chronic gastritis or gastroduodenitis.  The H. pylori therapy is divided into two: triple and quadruple therapy.  Triple therapy is recommended. Oral omeprazole 20 mg bid or lansoprazole30 mg bid, plus clarithromycin 500 mg bid, plus amoxicillin1 g bid (or, for penicillin-allergic patients, metronidazole 500 mg bid) for 14 days, cures infection
  27. 27. Summary  Quadruple therapy with a proton pump inhibitor bid, tetracycline 500 mg and bismuth subsalicylate or subcitrate 525 mg qid, and metronidazole 500 mg tid is also effective but more cumbersome.  Infected patients with duodenal or gastric ulcer require continuation of the acid suppression for at least 4 wk.  Treatment is repeated if H. pylori is not eradicated. If two courses are unsuccessful, some authorities recommend endoscopy to obtain cultures for sensitivity testing.  Lastly, it is worth pointing out that, although H. pylori dominates as the etiological factor in PUD, the roles of stress, heredity, long-term use of NSAIDs, smoking and association of other diseases should not be neglected.  THANK YOU

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