**1.1 History of gastritis**

Warren and Marshall in 1983 first recorded *H. pylori's* relationship of gastric mucosa in adults with antral gastritis [1]. Shortly thereafter, Hill *et al.,* four children who were afflicted with *H. pylori* had identified chronic mononuclear cell gastritis [2]. That same year, Cadranel and colleagues described organisms present in eight children with chronic, lymphocytic gastritis [3]. Subsequently, Drumm *et al.* observed *Helicobacter-like* organisms in 70% of 67 pediatric patients with a chronic-active

Gastritis [4]. Related findings have been made of spiral-shaped species colonizing the mucosa and the overlying gastric-epithelium mucus layer Infiltrate gastric inflammatory cells Czinn and Carrl in 25 children. More studies indicate that *H. pylori* colonization in the gastritis of a primarily chronic inflammatory cell infiltrate is almost always linked to gastritis in children [5, 6]. Reports of *H. pylori* eradication from gastric mucus suggest that the antral gastritis is resolved in combination with a single core case sequence. However, *H. pylori*-infected children have not undergone multicenter randomized controlled eradication trials and are important [6].

Studies in adults established the presence of the organism in nearly all cases of chronic gastritis [7]. At first, *H. pylori* was proposed to colonize inflamed tissue, rather than to induce inflammation, since gastritis is widespread in adults [7]. However, the prevalence of gastritis is less frequent in children thereby enabling the investigation of *H. pylori* as a cause for gastritis rather than an opportunistic colonizer of inflamed tissue [8]. Studies have observed that colonization of *H. pylori* in children with secondary causes, such as NSAID, eosinophilic gastroenteritis and Crohn's disease is not normal in the gastric mucosa [8]. These findings together show clearly the pathogenic role of *H. pylori* in the development of chronic antral gastritis in infants.

For over a century, bacteria have been known to be found in the human body [9]. These bacteria, however, were thought to be contaminants from digested food rather than true gastric colonizers. Around 20 years ago, the isolation and culture of a bacterial spiral species known later as *Helicobacter pylori* was announced successfully by Barry and Robin Warren [10], from the human stomach. Self-ingestion experiments by Marshall [11] and Morris [12] and later experiments with volunteers [13] demonstrated that these bacteria can colonize the human stomach, thereby inducing inflammation of the gastric mucosa. After ingestion of *H. pylori*, Marshall produced intermittent gastritis; Morris' condition progressed into more persistent gastritis, which cleared doxycycline and sub-salicylate bismuth after sequential care. These initial data were closely used as a stimulus in further studies, demonstrating that gastrointestinal disorders such as chronic gastric gastritis, peptic ulcer, lymphoma associated with gastric mucous membrane and stomach cancer can lead to a variety of upper gastrointestinal disorders. This knowledge has a direct therapeutic influence on disease control. In addition, insights into the pathogenesis of chronic disease are provided by the persistence of a pathogen in an area long believed to be sterile. This discovery has resulted in Robin Warren and Barry Marshall's "discovery of the bacterium *Helicobacter pylori* and his role in gastritis and peptic ulcer diseases" won the 2005 Nobel Prize in physiology or medicine.

The genus *Helicobacter* belongs to the subdivision of the *Proteobacteria*, order *Campylobacterales*, family *Helicobacteraceae*. This family also includes the genera *Wolinella*, *Flexispira*, *Sulfurimonas*, *Thiomicrospira*, and *Thiovulum*. The Helicobacter genus consists of more than 20 species, all of which have been recognized officially. Members of the Helicobacter family are all microaerophile organisms and most of them are positive for catalase and oxidase and many but not all species also are positive for urease [14].

It is possible to separate Helicobacter species into two main lines, the gastric helicobacter species and the enterohepatic (nongastric) species of Helicobacter. They have a strong degree of organ specificity, which in general indicates gastric helicobacter cannot colonize the intestine or liver, and vice versa.

#### **2. Gastric** *Helicobacter* **species**

Gastric Helicobacter organisms have evolved to the unfriendly environments at the stomach surface and are currently suspected to colonize the stomachs of all *Pathophysiology of* H. pylori *DOI: http://dx.doi.org/10.5772/intechopen.96763*

mammals through Helicobacter members. The urease is positive and extremely mobile by flagella are all recognized gastric Helicobacter species [15, 16]. Urease is believed to enable brief survival in a very acidic gastric lumen, but motility has been thought to allow quick travel into the more neutral pH of gastric mucosa; this may explain why the colonization of gastric mucosa is conditional upon both factors [17]. When joining, the Helicobacter gastric species display a chemical motility of urea and bicarbonate to the mucus layer [16]. The spiral morphology and flagellate motility help the viscous mucus layer penetrate, where the more pH-neutral conditions allow the genital Helicobacter species to grow.

i.*Helicobacter felis*

ii.*Helicobacter mustelae*

iii.*Helicobacter acinonychis*

iv.*Helicobacter heilmannii*.

*H. pylori* is a demanding micro-organism that needs complex media for development. Sometimes, blood or serum was applied to these medias. These supplements are additional food sources and can also be used for defending against long-chain fatty acid toxic effects [18].

*H. pylori* associated gastritis is characterized by the presence of acute and chronic inflammation, with immature surface epithelial cells [19]. Mucus degeneration is also found by successful cell renewal of epithelial cells. The degree of mucosal infection ranges from the lowest inflammatory infiltration in lamina propria to the extreme gastritis with thick mucoal inflammation with retained architecture. In extreme cases, all surface epithelium and gastric wells can be used as microabscesses for intraepithelial neutrophils [20].

Previously, it was believed that in *H. pylori* gastritis, fundic inflammation was less important than that of the antral mucosa [21]. However, *H. pylori* and gastroesophageal reflux disease create, or arise concurrently, may also be caused by the anatomical role of the inflammatory cell infiltrate [22]. Moreover, patients who have been receiving a proton pump inhibitor for acid suppression frequently have colonization of fundic and cardia mucosa by *H. pylori.* Carditis, of both a chronic and active phenotype, is frequent in *H. pylori*-infected adults [23]. Children require research to help establish the association between *H. pylori* infection, gastric inflammation sites and sequalae of long-term diseases.

*H. pylori-associated* gastritis in children is commonly not apparent at endoscopy, thereby making biopsy essential for definitive diagnosis [24]. Nodularity of the antral mucosa has been described in association with *H. pylori* gastritis in children [25]. Its value has not yet been identified. However, antral nodularity was found in *H. pylori* infected adults and less common in children [26].

Columbia or Brucella agar, (lysed) horse or sheep blood agar, or fetal calf serum as substitute, is widely used as a solid medium for regular isolation and *H. pylori* culture.

#### **3. Transmission and sources of infection**

Most unknown are the precise processes by which *H. pylori* is obtained. *H. pylori* has a small host range and is present in people and some non-human primates nearly exclusively.

In rare cases, the presence of pets may be a concern for *H. pylori* infection; hence, pets should be isolated [27]. There is also no definitive proof for zoonotic *H. pylori* transmission [28]. The direct transmission from person to person, either oral or fecal-oral route or both, is expected to lead to new infections. In saliva, vomit, gastric refluxate and diarrhea, *H. pylori* has been detected [29]. Yet there is no definitive proof that either of these products had the predominant transmission. This may be because most transmission research has concentrated on adults.

It indicates that for dentists, gastroenterologist, nurses, spousal partners or physicians with sexually transmitted diseases there was no clear rise in risk of carrying *H. pylori* [30]. As a result of these and other investigations, it is generally believed that acquisition mostly occurs in early childhood, most likely from close family members [31].

Crowding inside and outside families with children are both linked to the occurrence of *H. pylori* [32], Although the adult crowd seems less significant, except for some situations, for example amongst military recruits [33]. Several experiments have shown that *H. pylori* DNA is found in environmental bodies of water [34].

Spread via fecal contaminants is supported by the occurrence of *H. pylori* infections among institutionalized young people during outbreaks of gastroenteritis [35]. Additional sources are infected food, as *H. pylori* can briefly live on cooled food [36]. In tandem with *H. pylori's* intense exposure to oxygen demand, nutrient exclusion and temperatures outside 34–40°C [37]. The most likely path of direct person-to-person transmission.

The incidence of gastric cancer is higher in poor areas and in developing and advanced countries in lower socioeconomic groups [38]. Gastric cancer remains the most prevalent malignancy among men and the second most commonly identified among women in many countries of Latin America and Asia. Colombia and Japan recorded incidence rates of up to 80 per 100,000 populations. The gastric cancer in the United States and Western Europe, by comparison, affects less than 10 per 100,000 individuals per year [39]. However, ethnic groups with elevated risk remain in low-risk nations. For instance, in the US, gastric cancer is nearly double that prevalent among Blacks, Asians and Hispanics. It is noteworthy that *H. pylori* prevalence rates are 2-l0 times higher in all of these populations than in the total population [40].

### **4. Clinical aspects of** *H. pylori***-associated diseases**

*H. pylori* colonization is not an infection itself, but it impacts the relative likelihood that multiple pathological conditions of the upper gastrointestinal tract and even the hepatobiliary tract will grow. Therefore, *H. pylori* examination alone is not relevant but can be done in order to ascertain the cause of a basic disorder, such as peptic ulcer disease or to avoid disease, for example in subjects with family gastric carcinoma. A positive test result will validate the procedure, and a negative test result can suggest that other etiological causes or prevention steps needs to be examined.

#### **4.1 Types of Disease**

Although gastric *H. pylori* colonization causes histologic gastritis in all infected persons, only a minority experience any apparent clinical symptoms. *H. pylori*positive patients are estimated to have a 10–20 percent life-cycle risk for ulcer and a 1–2 percent risk for distal gastric cancer [41]. The probability of developing *H. pylori* disorders depends on a range of bacterial, host, and environmental factors, most of which are related to gastritis pattern and severity (**Figure 1**).

#### **Figure 1.**

*Schematic representation of the factors contributing to gastric pathology and disease outcome in* H. pylori *infection [42].*

#### **4.2 Acute and chronic gastritis**

The scale of *H. pylori* colonization nearly always contributes to gastric mucosa invasion of neutrophilic and mononuclear cells in the antrum and corpus. The principal condition of this chronic active gastritis is *H. pylori* colonization, in particular as consequence of this chronic inflammation phase, and other *H. pylori*-related conditions [42].

#### *4.2.1 Acute gastritis*

Acute infection results are uncommon and come mostly from accounts of subjects who knowingly or accidentally took *H. pylori* or were exposed to hazardous substance procedures [43]. Recently, an *H. pylori* infection human challenge model was introduced, which permitted managed acute infection analysis with deliberate safe volunteer infection by a well-characterized *H. pylori* laboratory strain [44]. Along with these findings, these reports have shown that the acute process of *H. pylori* colonization can include temporary non-specific dyspeptic symptoms, including completeness, nausea, vomiting, and severe inflammation of the proximal, and distal stomach mucus or pangastritis. This process is also related to the period of months of hypochlorhydria. It is uncertain whether spontaneous clearing and resolution of gastritis can be accompanied by this initial colonization and, if so, how often that happens. Further trials in young children with serology or breathing tests have shown that certain patients in this age group might spontaneously lose the infection [45]; This was not found in the development of atrophic gastritis other than under particular circumstances.

Studies of homozygotic twins however demonstrated a concordance with their classification as *H. pylori* regardless of their cohabitation or break [46]. This consensus between heterozygous twins has not been observed. This indicates that some people are likely to be colonized with *H. pylori* while others may avoid or eradicate a proven infection. This theory is also backed by the finding that *H. pylori* sensitivity in many developing countries is very strong in young age and yet chronic *H. pylori* infections are never acquired by any individuals.

#### *4.2.2 Chronic gastritis*

When colonization becomes persistent, the acid secretion level and the gastritis distribution interact closely (**Figure 2**). The association between acid and bacterial growth arises from the counteractive effects of acid against bacterial growth and subsequent mutation inflammation on the acid separation and regulation. The effect of *H. pylori* infection is important in this relationship. *H. pylori* particularly colonizes the gastric antrum in subjects with intact acid secretion, where there are only a few parietal acid secretory cells present [42].

This pattern of colonization is linked to gastritis which prevails. Histological examination of the gastric corpus specimens shows that the amount of superficially colonized *H. pylori* bacteria is reduced by chronically dormant inflammation and that. Those of which the secretion of acid is affected by some process have a more equal distribution of bacteria in the antrum and corpus and are in closer proximity of the mucosa bacteria, inducing pangastritis, which are predominate [47].

The acid secretion may be diminished by loss of parietal cells due to atrophic gastritis, but it can also happen when acid's secretive potential is intact, although the work of parietal cells is inhibited by vagotomy or acid-suppressive drugs, particularly proton pump inhibitors (PPIs) [47]. The subsequent active inflammation of the corpses raises hypochlorhydra parallel to an acute period of infection with a strong suppressive effect on the celestial function, since local inflammatory factors, including cytokines, like interleukin-1 beta (IL-1 β) are strongly suppressive. Different findings illustrate that. The first argument is that *H. pylori*-corpus gastritis frequently is related to hypochlorhydrate, and eradication treatment leads to greater secretion of acid [48].

Secondly, *H. pylori* corpus gastritis augments the acid-suppressive effects of PPIs [49]. As a result, *H. pylori-*positive patients with gastroesophageal reflux disease (GERD) may respond somewhat faster to PPI treatment both with respect to symptom resolution and with healing of esophagitis [50], However, this effect of everyday clinical practice is marginal and essentially negligible. This means that the status of *H. pylori* is not general in decision-making regarding GERD dose of PPI medication. A third observation in favor of the acid repression effects of active corpus gastritis has been made in more recent significant research that indicates the risk of corpus predominant pangastritis from subject with proinflammatory genotype predisposing people to atrophic gastritis, intestinal metaplasia and gastric cancer [51].


#### **Figure 2.**

*Acid secretion and the associated pattern of gastritis play an important role in disease outcome in* H. pylori *infection. The figure displays the correlations between the pattern of* H. pylori *colonization, inflammation, acid secretion, gastric and duodenal histology, and clinical outcome [42].*

Although colonization by *H. pylori* is almost invariably associated with gastritis, and gastritis is mainly attributed to colonization by *H. pylori*, gastritis is due to other causes of gastritis, such as cytomegalovirus, chronic inflammatory idiopathic diseases, and auto-immune disease such as Crohn's disease and pernicious anemia.
