H. pylori: Gastritis, Ulcers, Cancer
Sections
Helicobacter pylori - GI Infections
Gastric helicobacter colonizes the stomach.
Transmission is human to human; exact mechanisms uncertain.
Life-long colonization; infection typically occurs during childhood and produces symptoms during adulthood.
Gatalase, oxidase, and urease positive.
Spiral, Gram-negative rods that can appear as coccoid in older cultures.
Microaerobic: Grow in conditions of reduced oxygen and increased carbon dioxide.
Virulence Factors
Helicobacter pylori has several adaptations that allow it to survive the acidic environment of the human stomach and persist for decades.
Urease converts urea to ammonia and bicarbonate to neutralize gastric acids.
Multiple flagella provide corkscrew motility.
Mucinase production allows the bacteria migrate through the viscous mucus that covers the surface of the stomach.
Infection triggers host production of IL-8, which is a pro-inflammatory cytokine that recruits neutrophils that release harmful molecules and damage host tissues.
The bacteria protect themselves from these harmful molecules by producing superoxide dismutase and catalase, which detoxify reactive oxygen species.
Lipopolysaccharide endotoxin; however, as compared with many other Gram-negative bacteria, its endotoxin has low toxicity.
Vacuolating cytotoxin A promotes pore formation, disrupts cell signaling, and induces apoptosis and necrosis of host cells.
Cytotoxin-associated gene A (cagA) product promotes proliferation and morphological changes in host tissues, and induces T-cell apoptosis.
Type IV secretion systems inject the cagA effector protein into host cells.
Infections
Gastritis is inflammation of the stomach lining with infiltration of neutrophils and mononuclear cells; T-1 helper cells are also implicated.
Some individuals are asymptomatic, and others experience an acute phase of nausea, bloating, and vomiting.
Inflammation can be localized to one area, usually the pyloric antrum, or widespread
In a subset of patients, gastritis progresses to more serious conditions.
Peptic ulcers
10-20% of patients with gastritis will develop peptic ulcers, in which inflammation erodes the stomach tissues.
Ulcers can be located in the stomach, or they can be in the duodenum, which is the first portion of the small intestine.
Gastric adenocarcinoma
In approximately 1-2%, chronic inflammation will lead to gastric adenocarcinoma.
This occurs when inflammation leads to metaplasia; over time, the gastric mucosa is replaced by fibrotic tissue, and can become neoplastic.
Reduced gastric acid secretion is associated with a higher risk of adenocarcinoma.
Gastric-associated lymphoid tissue B-cell lymphomas
In response to Helicobacter pylori infection, lymphoid tissues infiltrate the stomach; in some cases, monoclonal B cells proliferate and form MALT lymphomas (MALT = Mucosa-Associated Lymphoid Tissue).
Summary Illustration:
We draw the stomach, esophagus, and duodenum.
Gastritis can be localized in the pyloric antrum, and indicate that this is associated with increased acid production and formation of duodenal ulcers.
Multifocal inflammation, as in pangastritis, is associated with atrophy and reduced acid production; this is associated with gastric metaplasia and cancer.
Helicobacter pylori infection causes destruction of the mucosa, which allows acids and toxins, as well as the microbes themselves, access to deeper tissues.
- Ulceration leads to bleeding, perforation, and, in severe cases, metaplasia.
Treatment:
Because chronic gastritis can lead to severe consequences, treatment is important.
Macrolides, Beta-lactams, and proton-pump inhibitors.
Enterohepatic helicobacters:
Helicobacter cinaedi and Helicobacter fenneliae
Invade the intestines and liver, and can cause gastroenteritis and bacteremia, particularly in immunocompromised individuals.
Full-Length Text
Here we will learn about Helicobacter pylori, which causes gastritis; these bacteria were previously considered members of the Campylobacter genera.
To begin, write that Helicobacter pylori is a gastric helicobacter because it colonizes the stomach.
Though the exact mechanisms are uncertain, transmission is human to human.
And, colonization is life-long; infection typically occurs during childhood and produces symptoms during adulthood.
Indicate that Helicobacter pylori are catalase, oxidase, and urease positive.
They are spiral, Gram-negative rods that can appear as coccoid in older cultures.
They grow in conditions of reduced oxygen and increased carbon dioxide.
Helicobacter pylori has several adaptations that allow it to survive the acidic environment of the human stomach and persist for decades.
Indicate that virulence factors include the following:
Urease converts urea to ammonia and bicarbonate to neutralize gastric acids.
Multiple flagella provide corkscrew motility, mucinase production allows the bacteria migrate through the viscous mucus that covers the surface of the stomach.
Helicobacter pylori infection triggers host production of IL-8, which is a pro-inflammatory cytokine that recruits neutrophils that release harmful molecules and damage host tissues.
The bacteria protect themselves from these harmful molecules by producing superoxide dismutase and catalase, which detoxify reactive oxygen species.
Helicobacter pylori produces lipopolysaccharide endotoxin; however, as compared with many other Gram-negative bacteria, its endotoxin has low toxicity.
Indicate two important exotoxins:
Vacuolating cytotoxin A promotes pore formation, disrupts cell signaling, and induces apoptosis and necrosis of host cells.
Cytotoxin-associated gene A (cagA) product promotes proliferation and morphological changes in host tissues, and induces T-cell apoptosis.
Indicate that Type IV secretion systems inject the cagA effector protein into host cells.
Next, let's learn about Helicobacter pylori infection.
Indicate that it causes gastritis, which is inflammation of the stomach lining with infiltration of neutrophils and mononuclear cells; T-1 helper cells are also implicated.
Some individuals are asymptomatic, and others experience an acute phase of nausea, bloating, and vomiting.
Inflammation can be localized to one area, usually the pyloric antrum, or, inflammation can be widespread, as in pangastritis, which affects the entire stomach.
In a subset of patients, gastritis progresses to more serious conditions.
Write that 10-20% of patients with gastritis will develop peptic ulcers, in which inflammation erodes the stomach tissues.
Ulcers can be located in the stomach, or they can be in the duodenum, which is the first portion of the small intestine.
In approximately 1-2%, chronic inflammation will lead to gastric adenocarcinoma.
Indicate that this occurs when inflammation leads to metaplasia; over time, the gastric mucosa is replaced by fibrotic tissue, and can become neoplastic.
Write that reduced gastric acid secretion is associated with a higher risk of adenocarcinoma.
Lastly, indicate that gastritis can lead to gastric-associated lymphoid tissue B-cell lymphomas.
In response to Helicobacter pylori infection, lymphoid tissues infiltrate the stomach; in some cases, monoclonal B cells proliferate and form MALT lymphomas (MALT = Mucosa-Associated Lymphoid Tissue).
To illustrate and summarize the patterns of Helicobacter pylori infection, draw the stomach.
Indicate the esophagus, proximally, and, the duodenum, distally.
Label the body and pyloric antrum of the stomach.
Then, show that gastritis can be localized in the pyloric antrum, and indicate that this is associated with increased acid production and formation of duodenal ulcers.
Indicate that multifocal inflammation, as in pangastritis, is associated with atrophy and reduced acid production; this is associated with gastric metaplasia and cancer.
In a histological sample of the gastric mucsoa, label the epithelial cells that line the stomach, the gastric pits and glands, and the lamina propria.
Indicate that Helicobacter pylori infection causes destruction of the mucosa, which allows acids and toxins, as well as the microbes themselves, access to deeper tissues.
Ulceration leads to bleeding, perforation, and, in severe cases, metaplasia.
Because chronic gastritis can lead to severe consequences, treatment is important; write that patients are typically given macrolides, Beta-lactams, and proton-pump inhibitors.
Before we conclude, indicate that Helicobacter cinaedi and Helicobacter fenneliae are enterohepatic helicobacters.
They invade the intestines and liver, and can cause gastroenteritis and bacteremia, particularly in immunocompromised individuals.
References
Murray, P. R., Rosenthal, K. S., & Pfaller, M. A. Medical microbiology. Philadelphia: Elsevier/Saunders. (2013).
Levinson, W. E. Review of Medical Microbiology and Immunology. 14th Ed. Lange (2016).
Kusters, J.G., van Vliet, A.H.M., Kuipers, E.J. (2006). Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews. 19(3): 449-490.
Yamaoka, Y. (2010). Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 7(11): 629-641.
Salama, N.R., Hartung, M.L., Muller, A. (2013). Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 11(6): 385-399.
McColl, K.E.L. (2010). Helicobacter pylori infection. N Engl J Med 362:1597-1604.
Wroblewski, L.E., Peek, R.M., Wilson, K.T. (2010). Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clinical Microbiology Reviews. 23(4): 713-739.
Images:
Stomach mucosa (Mark Braun, MD; http://medsci.indiana.edu/c602web/602/c602web/toc.htm).
Peptic ulcer (Wikipedia; Author Samir_Grover).
Gastric adenocarcionoma (Centers for Disease Control and Prevention, Dr Edwin P Ewing, Jr.)