how helicobacter pylori can cause gastric ulcerations and how this can lead to cancers of the...
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Welcome to my presenta/on, Here I will be discussing how helicobacter pylori causes gastric ulcera/ons and how this can be linked to cancers of the stomach. I hope you enjoy the following slides
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It affects around 50% of the world’s popula/on. It’s one of the most common infec/ons in the U.K. Unless it is treated, the infec/on will stay for the rest of an individuals life. Now this is due to the fact that H.pylori will not show any symptoms or problems caused by H.pylori and so will not even know that they are affected. However, further complica/ons may indicate the presents of H.pylori in the gut and will then allow individuals to seek medical help. Helicobacter Pylori is a gram-‐nega/ve spiral shaped bacterium that grows in mucus layer that coats the inside of the human stomach. Gram-‐nega/ve refers to the thin layer of pep/doglycan and presents of a outer membrane in the helicobacter cell wall Helicobacter was detected by Robin Warren who was a pathologist and a physician named Barry Marshall in Australia. Although many individuals did not believe Warren & Marshall as H.pylori did not show symptoms. Barry Marshall had decided to do something dras/c and drank a solu/on of H.pylori and within 2 weeks developed acute symptoms which we will discuss later on
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The prevalence of H.Pylori infected varies widely by geographic area it can be seen that countries such as South America and Africa have the highest prevalence. This is due to the transmission of H.pylori. It is mostly transmiSed through contamina/on of water and food which is much more likely to occur in 3rd world countries and when we compare these percentages with those such as The united states or united kingdom or even Australia, we can see here that the sani/za/on are much beSer and therefore the prevalence is much more lower. Next Slide
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There are 4 different steps that helicobacter pylori does in order to affect the human host. 1. Firstly there is the addi/on of Helicobacter Pylori to the host cell 2. Secondly, and most importantly helicobacter pylori minimizes the content of the acid in the stomach 3. it colonizes 4. and finally the degrades the epithelial cells 1à The addi/on of helicobacter pylori is enabled by the flagella which allows the bacterium to be mo/le and also permits the bacteria to propel itself through the gastric fluid, mucus layer and finally adheres itself to the epithelial lipopolysaccharides and membrane proteins, using this it interacts with epithelial cells of stomach 2à The hydrochloric acid keeps the pH of the stomach strongly acidic, between a pH of one and two, H.pylori is able to survive in acidic condi/ons but as the stomach pH is a liSle too acidic for the bacteria it uses an enzyme to raise the pH around the bacteria to a more survivable level. Urease enzyme is used where it will breakdown urea and water to produce carbon dioxide and ammonia. As we know that ammonia is a base and HCl is an acid this allows a neutralizing reac/on making the pH of the stomach increase. 3àThis creates a microenvironment for the bacterium to survive this allows the coloniza/on of more and more H.Pylori to thrive in this environment
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Now the degrada/on of the epithelial cells occurs in many different ways: The Vac A exotoxin causes injury to the mucosal membrane by inducing altera/ons in mitochondrial membrane permeability and apoptosis, it also s/mulates pro-‐inflammatory signaling and increases the permeability of the plasma membrane. Type IV secre/on system uses a pillus to inject effectors such as Cytotoxin-‐associated gene A -‐ cagA is a needle-‐like appendage that injects a toxin which remodels ac/n the cytoskeleton of the cell thereby disrup/ng the epithelial barrier and facilita/ng the passage of Vac A, it is also found to inhibit apoptosis. These responses altogether inhibits immune response by T cell ac/va/on and prolifera/on so the body cannot produce an immune response against Helicobacter pylori and this is the development of gastric ulcera/ons Next Slide
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So this image shows the propor/ons of individuals with differing disease severity The 50% of the worlds popula/on who has helicobacter pylori is more suscep/ble in developing duodenal ulcers about 90% compared to the unaffected popula/on. The development of gastri/s is more likely when affected with the bacterium. There is a nine fold risk of developing precancerous gastric condi/ons when compared with individuals with and without the bacterium. Also almost all cases of gastric lymphoma is linked to helicobacter pylori being present in the human host. As discussed before the prevalence of helicobacter pylori in individuals and country is strongly associated with poor socioeconomic condi/ons. Next slide
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How helicobacter pylori leads to gastric cancer is not well understood but some ideas are put forward by scien/st, it is unclear whether it is one specific cause or a collec/on of all of these effects of helicobacter pylori which increases the chance of gastric cancer. Long-‐term exposure to cagA toxin causes chronic inflamma/on and can induce oncogenesis, this inflamma/on leads to a damaged mucosal membrane and can increase the carcinogenic effect of risk factors leading to gastric cancer such as high salt intake and smoking. Recent research suggest that cagA may lead to inac/va/on and altera/on of tumor suppressor proteins such as p53 which normally leads to apoptosis and therefore inac/va/on can promote the development and progression of gastric cancer Next Slide
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80% of individuals who suffer with helicobacter pylori will experience chronic gastri/s which is characterized by chronic inflamma/on of the stomach mucosa which is caused by injury to the gastric mucosa resul/ng from reflux of bile and pancrea/c secre/ons into the stomach acer adhesion of helicobacter pylori.15-‐20% of theses individuals will further develop chronic atrophic gastri/s known as Type A or B gastri/s is a process of chronic inflamma/on of the stomach mucosa leading to loss of gastric glandular cells and their eventual replacement by intes/nal and fibrous /ssues. A duodenal ulcer can also develop due to the corrosive HCl in the stomach causing inflamma/on and ulcers to area of epithelial cells that are infected with helicobacter pylori. Furthermore 1% of these individuals can finally be presented with gastric carcinoma Next Slide
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Indiges/on is the main symptom of helicobacter pylori due to a induced ulcer however this symptom is common among many types of disorders, so can be difficult to link to helicobacter induced disorder. Indiges/on can further be accompanied by dull and burning pain which is worse on an empty stomach and can be relieved by antacids very briefly. This burning pain can last for minutes to hours and comes and goes over days an weeks. Gastric carcinoma can present itself as weight loss, vomi/ng, dysphagia and anemia. Next Slide
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Blood tests are used to measure an/bodies to Helicobacter pylori. An/bodies are proteins made by the body’s immune system when it detects harmful substances such as bacteria. Blood tests for Helicobacter pylori can only tell if your body has Helicobacter pylori an/bodies. It cannot however tell if you have a current infec/on or how long you have had it, this is because the test can be posi/ve for years even if the infec/on is cured. As a result blood tests cannot be used to see if the infec/on has been cured acer treatment. During breath tests the pa/ent is asked to swallow a special substance that has urea labeled with carbon 14. Urea is a waste product the body produces as it breaks down protein. The urea used in the test has been made harmlessly radioac/ve. If Helicobacter pylori is present, the bacteria convert the urea into CO2, which is detected and recorded in your exhaled breath acer 10 minutes. This test can iden/fy almost all people who have Helicobacter pylori. A biopsy may also be taken from the stomach lining which is the most accurate way to tell if an individual has Helicobacter pylori.. To remove the /ssue sample the pa/ent undergoes an endoscopy. Common complica/ons of helicobacter pylori infec/on are gastri/s and ulcers. To check for ulcers, you may have a special stomach x-‐ray examina/on acer a barium meal which becomes visible on x-‐rays. Next Slide
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I found it interes/ng when doing my research about helicobacter pylori the origins and geographic distribu/on worldwide affec/ng 50% of the worlds popula/on and genomic interac/ons universally. Helicobacter pylori was first originated in the African content and mutated across the world and has undergone gene/c muta/ons along this spread. Where the old world met the new world the co-‐evolu/on was disrupted and helicobacter pylori was not dependent on infec/ng host cells in the African content. Individuals started to become infec/on with helicobacter pylori. Helicobacter pylori encountered new gene/c material and evolved differently than compared to its origin. If an individual did not contain the resistant genomic sequence to helicobacter pylori it could become cancerous. Scien/sts in Tumaco Colombia had found the majority of their DNA ancestry and helicobacter pylori strains come from Africa. The mountain popula/on from Tuquerres is 67% American/Indian and 31% European. Their helicobacter pylori are mostly from European which replaced the na/ve strains. If the H.pylori strains have a different origin to their hosts, they are more likely to cause cancer. Strains origina/ng in Africa are mostly harmless to Africans, but caused cancer in people with a largely American/Indian background Next Slide
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Helicobacter pylori is treated with a double-‐dose Proton pump inhibitors such as omeprazole, lansoprazole and pantoprazole which decreases the stomach’s produc/on of acid allowing damaged /ssue to heal, this is accompanied with 2 an/bio/cs which increases treatment success and an/bio/c resistance. These two an/bio/cs can either be metronidazole, clarithromycin and amoxicillin Next Slide
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