Role of Helicobacter pylori in diseases.
Toufiq Shaikh.
11/12/07
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Index.
• • • • • Introduction. Discovery of H. pylori. Mode of transmission. Mode of infection. Role of H. pylori in:-Gastritis. Peptic ulcer disease (P.U.D). Gastric carcinoma. MALT lymphoma. • Diagnosis. • Treatment. • Conclusion.
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Important facts about H. pylori.
• It is a non-sporing, flagellated, helical, motile, gram -ve bacillus. • Size: 3.5X0.5 um. • It mainly infects the pylorus of the stomach. • H. pylori genome is 1.6 million bp long & encodes 1500 proteins. • Key to survival in stomach is synthesis of urease. • It infects 2/3rd of worlds population.
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Worldwide distribution of H. pylori .
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Discovery of H. pylori .
• In 1899 first discovered by Prof. Walery Jaworski & was named “Vibrio rugula”. • In 1979 rediscovered by Robin Warren & Barry Marshall. • Causal relationship proved between gastric diseases & H.pylori. • In 2005 were awarded Nobel prize in physiology & medicine.
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Virulence factors.
• Cag A:-- “Cytotoxin associated gene A”. > Morphological changes & degenerative changes in the cell. • Vac A:-- “Vacuolating toxin gene A” > membrane channel formation. > disruption of endosomal & lysosomal activity. > cell apoptosis. • Bab A:-- “Bacterial adhesins”. > Bind to the LewisB antigen. > Adhesion to gastric mucosa.
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Mode of Transmission.
• In the lifecycle of H.pylori human beings are the only hosts.
• 1)
Three routes of transmission:-Faeco-oral route.
2)
3)
Oral-oral route.
Gastro-oral route.
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Mode of infection.
• H. pylori colonizes in the mucous layer.
• Synthesizes urease enzyme.
• NH3 neutralizes the gastric acid. • Thus, H. pylori thrives in the gastric acid environment.
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Diseases caused by H. pylori.
• Gastritis. Acute Gastritis. Chronic gastrits. • Peptic ulcer disease (PUD). • Gastric carcinoma. • MALT lymphoma.
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Gastritis.
• Inflammation of gastric mucosa by H. pylori
Signs & symptoms:-• Nausea, vomiting, upper abdominal discomfort.
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Acute gastritis.
• Acute gastritis is a rapid mucosal inflammatory process. • H. pylori an important etiologic factor. Features:-• Vascular changes. • Redness, warmth, pain, swelling. • Edema formation.
Signs & symptoms:-• Nausea, vomiting, epigastric pain, hematemesis, melena.
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Chronic gastritis.
• It is a prolonged inflammation following acute gastritis. Features:-• Tissue destruction. • Mononuclear cell infiltration. • Fibrosis & gastric atrophy. Signs & symptoms:-• Nausea, vomiting & upper abdominal pain.
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Peptic ulcer disease.
• Peptic ulcers are chronic lesions that occur in any portion of the GIT exposed to excessive action of gastric acid. • Two types:-Gastric ulcers. Duodenal ulcers. Signs & symptoms:-• Epigastric- gnawing, burning, aching pain. • Black stools & haemorrhage. • Fe-deficiency anaemia.
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• Gastric ulcers:-• Site of ulceration is the inner lining of stomach. • Infection of H. pylori occurs in the body of the stomach. • Characterized by gastric atrophy. • Pain occurs after the meal.
• Duodenal ulcers:-• • • • Site of ulceration is the duodenum of the small intestine. Infection of H. pylori occurs in the antrum of the stomach. Excessive production of gastric acid. Pain occurs before the meal.
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Pathogenesis.
Infection of the gastric mucosa by H. pylori.
Cytotoxins & bacterial proteins released by the bacillus. These are immunogenic.
Cause inflammation (Gastritis). IL-1, IL-8, TNF-α, Ig-G, histamine & 5-HT are released by T-cells, B-cells, mast cells & platelets respectively. Histamine acts on H-2 receptors of parietal cells & increases acid production. Hyperacidity causes peptic ulcers (PUD).
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Gastric carcinoma.
• Gastric carcinoma is the uncontrolled growth of gastric mucosa. • Second most common tumor in the world. • Infection by H. pylori increases risk by 5-6 times. Signs & symptoms:-• Weight loss, anorexia, vomiting, abdominal pain. • Altered bowel habits. • Dysphagia, anaemic symptoms. • Haemorrhage.
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MALT lymphoma.
• MALT-Mucosa associated lymphoid tissue.
• B-cell proliferation in the lymphoid follicles.
• H. pylori infection is an etiologic factor. • Gastric lymphoma represents 5% of all gastric malignancies. Signs & symptoms:-• Swelling, loss of appetite. • Weight loss, fatigue.
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Pathogenesis.
Chronic gastritis. Gastric atrophy. Loss of gastric function due to fibrosis. Metaplasia. Replacement of squamous cells by columnar cells. Dysplasia. Change in size & shape of the cells. Gastric carcinoma. Uncontrolled growth & division of cells. 11/12/07 Chronic gastritis. Immunogenic proteins are released by H. pylori.
Activation of B-cells by bacterial proteins.
B-cells proliferate in the follicles of the lymphoid tissue (MALT).
MALT – lymphoma. 19
Diagnosis.
• • • • • • •
Breath-urea test. Biopsy test. Culture typing. Histological test. PCR test. Serological test. Stool-Antigen test.
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Breath-Urea test.(CUBT)
C13 or C14 urea capsules
administered.
Urease secreted by H.pylori breaksdown urea into CO2 &
NH3.
Radiolabelled carbon in CO2 released is detected in the breath. If radiolabelled carbon is present then test is + ve.
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Biopsy test – Rapid urease test.
Endoscopic extraction of biopsy sample.
Sample is placed in petridish containing urea & PH – indicator.
Urease secreted by H. pylori breaksdown urea into CO2 & NH3. NH3 produced causes alkalinity & causes colour change.
Colour change indicates + ve test.
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• Culture typing:-- Biopsy material is cultured in a medium containing selective antibiotics. Growth of H. pylori colony is observed after incubation. Strains can be distinguished after incubation.
• Serological test:-- Anti-bodies (Ig-G) formed against H. pylori are detected in the blood of the individual. Most of this tests are ELISA – based assays. It is 95 – 98% sensitive & specific.
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• P C R test:-- Polymerase chain reaction is a DNA based analysis for typing of H. pylori .
• Histological test:-- Microscopic examination of biopsy material for H. pylori .
• Stool - Antigen test:-- Detection of H. pylori antigen in the stool with the help of Monoclonal Antibodies (MA).
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Curative treatment.
• Medications involved:- 4 types
1) Antibiotics. 2) Proton pump inhibitors. 3) H2 blockers.
4) Cytoprotectives.
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Antibiotics.
Anti-microbial activity on H. pylori. Curbs its infestation.
• • • •
Amoxicillin Clarithromycin Metronidazole Tetracycline
Side effects:-• Mild diarrhoea, nausea, vomiting. • Yellowing of teeth.
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Proton Pump Inhibitor.
Irreversibly inhibit the gastric H+K+ATPase (proton pump). Thus, reduce gastric acid secretion.
• • • •
Lansoprazole. Omeprazole. Pantoprazole. Rabeprazole.
Side effects:• Dizziness. • Drowsiness.
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H2 Blockers.
Reduce acid secretion by blocking H2 receptors of parietal cells.
• • • •
Cimetidine Famotidine Nizatidine Ranitidine
Side effects:-• Hepatotoxicity. • Diarrhoea, fatigue. • Bradycardia.
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Cytoprotectives.
These are toxic to H. pylori. Coat the ulcers & acts as barrier to gastric acid.
• Bismuth subsalicylate (Pepto Bismol). • Bismuth sucralfate.
Side effects:-• Black stools, constipation. • Rarely neurotoxicity.
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Therapy.
Multi-drug combination. • Double therapy:-- An antibiotic & acid suppressor. • Triple therapy:-- Two antibiotics & acid suppressor. • Quadruple therapy:-- Two antibiotics & cytoprotective & acid suppressor.
Two weeks therapy is more effective than one week.
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Prophylactic treatment.
• 1)
Vaccines are under development with the help of :-Live bacteria.
2)
3) 4)
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Attenuated bacteria.
Urease enzyme. Live vectors.
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Prophylactic measures.
• Washing of hands after visiting latrine & before eating. • Proper underground drainage system should be developed. • Boiled water & well cooked food should be consumed.
• Endoscopic intruments should be thoroughly sterilized.
• Avoiding endemic areas where infection is more common.
• Avoiding oral sexual contact with the infected person.
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Probiotics.
• Probiotics are dietary supplement containing potentially beneficial bacteria or yeasts. They confer the following health benefits:Keeps the immune system competent. Improve the gut flora. Prevent other harmful micro-organism growth.
• 1) 2) 3)
•
e.g Lactobacillus & Bifidobacterium.
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Conclusion.
• Role of H. pylori in gastro-duodenal diseases is established. • H. pylori is the most successful pathogen. • H. pylori infection starts with:-gastritis peptic ulceration g. carcinoma • H. pylori is a bacterial carcinogen. • Eradication of H. pylori by immunization would be possible in the near future.
g. lymphoma
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References.
• “7th Pathologic basis of disease” by Robbins & Cotran pg. no. 812-847.
• “17th Pharmacology & pharmacotherapeutics” by R.S. Satoskar pg. no. 602-604.
• “14th Practical medical microbiology” by Mackie & McCartney pg. no. 439-441. • “6th Microbiology” by Prescott, Harley & Klein pg. no. 685-686, 895-896. • • • www.gastrointestinalatlas.com www.medline.com www.emedicine.com
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THANK
YOU!
Robin. Warren
11/12/07
Barry. Marshall
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