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Helicobacter

Helicobacter pylori is a gram-negative bacterium that causes gastric infection. It is the most well known and clinically significant species of Helicobacter. Transmission is believed to occur by ingestion of contaminated food or water; therefore, a higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of infection is seen in areas with poor sanitation Sanitation The development and establishment of environmental conditions favorable to the health of the public. Hepatitis E Virus. Certain bacterial features contribute to the pathogenicity of H. pylori: urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis production (allowing survival in an acidic environment), motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility (permitting movement to the gastric epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology), and several toxins (creating local damage and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation). Chronic infection with H. pylori can lead to peptic ulcer disease Peptic ulcer disease Peptic ulcer disease (PUD) refers to the full-thickness ulcerations of duodenal or gastric mucosa. The ulcerations form when exposure to acid and digestive enzymes overcomes mucosal defense mechanisms. The most common etiologies include Helicobacter pylori (H. pylori) infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Peptic Ulcer Disease or even gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer in severe cases.

Last updated: 3 May, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Classification

Gram negative bacteria classification flowchart

Gram-negative bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be classified according to a lab procedure called Gram staining Gram staining Bacteriology.
Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology with cell walls that have a thin layer of peptidoglycan Peptidoglycan Penicillins do not retain the crystal violet stain utilized in Gram staining Gram staining Bacteriology. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative Gram negative Bacteria which lose crystal violet stain but are stained pink when treated by gram’s method. Yersinia spp./Yersiniosis. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be further classified according to morphology (diplococci, curved rods, bacilli Bacilli Shigella, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology can be more narrowly identified by growing them on specific media ( triple sugar iron Triple sugar iron Shigella ( TSI TSI Shigella) agar) where their enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes can be identified ( urease Urease An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. Nocardia/Nocardiosis, oxidase Oxidase Neisseria) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain Gram stain Klebsiella
** Pleomorphic Pleomorphic Bacteroides rod/coccobacillus
*** Require special transport media

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Characteristics

Features:

  • Stains:
    • Gram-negative
    • Detected with silver stain Silver stain The use of silver, usually silver nitrate, as a reagent for producing contrast or coloration in tissue specimens. Legionella/Legionellosis 
  • Morphology:
    • Motile rod
    • Curved shape
    • Contains multiple flagella
  • Growth and culture:
    • Microaerophilic
    • Complex growth requirements (special transport media required)
    • Oxidase-positive, catalase-positive
    • Urease-positive production: creates alkaline environment that permits survival of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology in acidic mucosa

Helicobacter genus contains about 35 species, with H. pylori being the most well known.

Electron micrograph of helicobacter pylori

Electron micrograph of Helicobacter pylori possessing multiple flagella (negative staining)

Image: “Electron micrograph of helicobacter pylori” by Yutaka Tsutsumi, M.D. License: Public Domain

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Pathogenesis

Transmission

  • Ubiquitous organism 
  • Humans are the primary reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.
  • Acquired by: 
    • Ingestion:
      • Oral–oral transmission: bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology regurgitated with gastric content and temporarily colonize oral cavity
      • Fecal–oral transmission: contaminated food and water supplies (poor sanitation Sanitation The development and establishment of environmental conditions favorable to the health of the public. Hepatitis E Virus)
    • Person-to-person contact: clusters of infection noted in families
  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of infection:
    • Low during childhood
    • 40%–50% in older adults
    • Highest in developing countries
Infection with helicobacter pylori

Infection by Helicobacter pylori via ingestion of a pathogen results in gastric ulcers or gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis.

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Pathogenic features of Helicobacter pylori

  • Urease-positive organism that produces ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Acid-Base Balance:
  • Multiple flagella allow for rapid penetration Penetration X-rays of the mucosa.
  • Contains mucinase and cytotoxins:
    •  Produces local tissue damage
    • Acts as chemoattractant and activates host inflammatory response 
  • Effects: gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis, development of ulcer(s), gastric carcinoma and gastric MALT MALT Colon, Cecum, and Appendix: Anatomy lymphomas
Pathogenic features of helicobacter pylori

Pathogenic features of Helicobacter pylori

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Associated Diseases

Gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis

  • Increased production of stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy acid or damage of the gastric mucosal barrier → irritate the sensitive stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy lining → gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis
  • H. pylori infection is one of the most common etiologies. 
  • May be asymptomatic, or symptoms may include burning abdominal pain Abdominal Pain Acute Abdomen, dyspepsia Dyspepsia Impaired digestion, especially after eating. Lactose Intolerance, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia 
  • Management of H. pylori infection: proton pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols inhibitors with antibiotics

Gastric and duodenal ulcers

  • Two most common types of peptic ulcers:
    • Gastric ulcers:
      • Located in the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy
      • Classically associated with pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that is worse when eating
    • Duodenal ulcers:
      • Located in the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy
      • Typically have improvement in the level of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways while eating, followed by worsening of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways after the conclusion of the meal. 
  • Most common etiologies include H. pylori infection and prolonged use of NSAIDs NSAIDS Primary vs Secondary Headaches
  • Management: 

Gastric adenocarcinoma Gastric adenocarcinoma Gastric Cancer

  • Gastric cancer Gastric cancer Gastric cancer is the 3rd-most common cause of cancer-related deaths worldwide. The majority of cases are from adenocarcinoma. The modifiable risk factors include Helicobacter pylori infection, smoking, and nitrate-rich diets. Gastric Cancer is the formation of malignant neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy lining. 
  • Second most common cancer of the GI tract
  • Chronic H. pylori infection: associated with an increased risk of gastric adenocarcinoma Gastric adenocarcinoma Gastric Cancer

Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements deficiency anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types and vitamin B12 deficiency

In H. pylori infection:

  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements in the GI tract is observed, as uptake of iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements requires an acidic environment. 
  • Chronic gastritis Gastritis Gastritis refers to inflammation of the gastric mucosa. Gastritis may occur suddenly (acute gastritis) or slowly over time (chronic gastritis). Gastritis may be asymptomatic or with symptoms, including burning abdominal pain (which either worsens or improves with eating), dyspepsia, nausea, and vomiting. Gastritis creates inflammatory damage to acid-producing cells → loss of acid production → reduced iron absorption Iron absorption Digestion and Absorption
  • Ongoing inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation likewise leads to loss of parietal Parietal One of a pair of irregularly shaped quadrilateral bones situated between the frontal bone and occipital bone, which together form the sides of the cranium. Skull: Anatomy cells from which intrinsic factor Intrinsic factor A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to vitamin B12 deficiency and anemia, pernicious. Gastritis is produced. 
  • Without intrinsic factor Intrinsic factor A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to vitamin B12 deficiency and anemia, pernicious. Gastritis, vitamin B12 deficiency develops.

References

  1. Jensen P. J., Feldman M. (2020). Acute and chronic gastritis due to Helicobacter pylori. Retrieved 20 April 2021, from https://www.uptodate.com/contents/acute-and-chronic-gastritis-due-to-helicobacter-pylori
  2. Kusters J. G., van Vliet A. H. M., Kuipers E. J. (2006). Pathogenesis of Helicobacter pylori infection. Clinical Microbiology Reviews 19:449–490.
  3. Riedel S., Hobden J. A., Miller S., et al. (Eds.). (2019). Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill.
  4. Lamont, J. T., Feldman M. (2020). Bacteriology and epidemiology of Helicobacter pylori infection. Retrieved 20 April 2021, from https://www.uptodate.com/contents/bacteriology-and-epidemiology-of-helicobacter-pylori-infection

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