Helicobacter pylori

S- shaped gram negative microaerophilic rod with multiple sheated flagella which can transform into coccoid form ( dormant
state)
Bacterial urease aids in infection by producing ammonia from urea, which then alkanizes surrounding pH.

RISK FACTORS of Helicobacter pylori infection

Contaminated food and water Helicobacter pylori is found commonly on contaminated food or water then spread from person to
person through closed contact with infected saliva (e.g sharing eating utensils, drinking glasses, or kissing), vomit and feces.
Living in a crowded community ( developing countries) where in unsanitary living conditions are common thus increasing the risk
of acquiring the infection.
Maternal colonization- the mother has Helicobacter pylori infection and theres a tendency of transmission to the baby
Age common in older people but it is usually acquired during childhood
Poor hygiene and contaminated sewage exposure

CLINICAL MANIFESTATIONS:
For all patients- histologic gastritis
10- 15% of patients develop associated illnesses:
o peptic ulceration
>80% of duodenal ulcers and >60% of gastriculcers are related to H. pyloriinfection
o gastric adenocarcinoma
Commonly adenocarcinomas of the distal(noncardia) stomach
o gastric lymphoma
Less common condition
Many low-grade gastric B cell lymphomas arising from MALT are driven by T cell proliferation (driven by H.
pylori antigen stimulation) H. pylori antigendriven tumorsmay regress either fully or partially after H. pylori
eradication butrequire careful long-term monitoring.
Rates among women are less than half of those among men for both diseases
Other clinical manifestations:
o Functional dyspepsia
upper gastrointestinal symptomsbut have normal results in upper gastrointestinalendoscopy (so-called
functional or non- ulcer dyspepsia)
o Protection Against Peptic Esophageal Disease including Esophageal Adenocarcinoma
Much interest has focused on a possible protective role for H. pylori against GERD, Barrettsesophagus and
adenocarcinoma of theesophagus and gastric cardia
The mechanism underlyingthis protective effect appears to include H. pylori inducedhypochlorhydria.
Other pathologies:
o Initialprecipitant of autoimmune gastritis and perniciousanemia
o May predispose some patients to iron deficiencythrough occult blood loss and/or hypochlorhydria andreduced iron
absorption.
o Extragastrointestinal pathologies- evidence of causality is less strong

PATHOGENESIS

1. Bacterial virulence factors

The cag island is a group of genes that encodes a bacterial secretion system.

CagAis translocated into epithelial cells affects host cell signal transduction
inducing proliferative, cytoskeletal, and inflammatory changes
secretion system also translocates soluble components of the peptidoglycan cell wall into the gastric
epithelial cell
components are recognized by the intracellular emergency bacterial receptor Nod1
stimulates a proinflammatory cytokine response
enhanced gastric inflammation

Patients with peptic ulcer disease or gastric adenocarcinoma are more likely to be colonized by cag -positive strains.
 Other bacterial factors that areassociated with increased disease risk:
o adhesins(BabA, SabA, dupA)

2. Host genetic and environmental factors

The best-characterized host determinants of disease are geneticpolymorphisms leading to enhanced activation of the
innateimmune response, such as polymorphisms in cytokine genes orgenes encoding bacterial recognition proteins such as
Toll-likereceptors (TLRs).

Colonized people with polymorphisms in the interleukin (IL) 1 gene plus H. pylori infection the production of large
quantities of this cytokine increased risk of gastric adenocarcinoma.

Environmental cofactors:
o Smoking - increases the risks of ulcers and cancer in H. pylori positiveindividuals.
o Diets high in salt and preserved foods increase cancer risk
o Diets high in antioxidants and vitamin C are protective

3. Duodenal ulceration
H. pylori induced inflammation
diminishes the number of somatostatin-producing D cells
somatostatin inhibits gastrin release
gastrin levels are higher than in H. pylori negative persons
increased meal-stimulated acid secretion in the gastric

Gastric metaplasia in the duodenum may become colonizedby H. pylori and subsequently inflamed and ulcerated.

4. Gastric ulceration and gastric adenocarcinoma

The pathogenesis of gastric ulceration and that of gastric adenocarcinomaare less well understood, although both
conditions arisein association with pan- or corpus-predominant gastritis.
The hormonal changes still occur but the inflammation inthe gastric corpus means that it produces less acid
(hypochlorhydria)despite hypergastrinemia.
Gastric ulcer
o usually occur at the junctionof antral and corpus-type mucosa, and this region is particularlyinflamed.
Gastric cancer
o Inflammation
Reactiveoxygen and nitrogen species arising from inflammatory cells + survival of abnormal epithelial
cell clones
progressive DNA damage and the survival of abnormal epithelial cell clones
CANCER
Common intestinaltype of gastric adenocarcinoma
- stepwise changes from simple gastritis gastric atrophy, intestinal metaplasia, and dysplasia.
A second, diffuse type of gastric adenocarcinoma may arise directlyfrom chronic gastritis alone.