@ Hp is a Gram negative,@ S-shaped or curved bacterium, with a length of 2.5~4.0μm and a width of 0.5~1.0μm. It has multiple flagella in single polarity.
Publication of several complete genomic sequences of H. pylori since 1997 has led to significant advances in the understanding of the organism's biology.
Helicobacter pylori (Hp) was first recognized in 1983 by Marshall and Warren. Now the concept that Hp is a crucial causal factor for development of peptic ulcer is accepted worldwide.
The prevalence of H. pylori among adults is 30% in the United States and other developed countries as opposed to >80% in most developing countries.
In the United States, prevalence varies with age: 50% of 60-year-old persons, 20% of 30-year-old persons, and <10% of children are colonized.
The age association is due mostly to a birth-cohort effect whereby current 60-year-olds were more commonly colonized as children than are current children. #Children may acquire the organism from their parents (more often from the mother) or from other children.
The gastric epithelial lining consists of rugae that contain microscopic gastric pits, each branching into four or five gastric glands made up of highly specialized epithelial cells. The makeup of gastric glands varies with their anatomic location. Glands within the gastric cardia comprise <5% of the gastric gland area and contain mucous and endocrine cells. The 75% of gastric glands are found within the oxyntic mucosa and contain mucous neck, parietal, chief, endocrine, enterochromaffin, and enterochromaffin-like (ECL) cells (Fig. 293-1). Pyloric glands contain mucous and endocrine cells (including gastrin cells) and are found in the antrum.
The parietal cell, also known as the oxyntic cell, is usually found in the neck, or isthmus, or in the oxyntic gland. The resting, or unstimulated, parietal cell has prominent cytoplasmic tubulovesicles and intracellular canaliculi containing short microvilli along its apical surface (Fig. 293-2). H+,K+-adenosine triphosphatase (ATPase) is expressed in the tubulovesicle membrane; upon cell stimulation, this membrane, along with apical membranes, transforms into a dense network of apical intracellular canaliculi containing long microvilli. Acid secretion, a process requiring high energy, occurs at the apical canalicular surface. Numerous mitochondria (30–40% of total cell volume) generate the energy required for secretion.
Components involved in providing gastroduodenal mucosal defense and repair. CCK, cholecystokinin; CRF, corticotropin-releasing factor; EGF, epidermal growth factor; HCl, hydrochloride; IGF, insulin-like growth factor; TGF, transforming growth factor ; TRF, thyrotropin releasing factor. (Modified and updated from Tarnawski A. Cellular and molecular mechanisms of mucosal defense and repair.
H. pylori infection is virtually always associated with a chronic active gastritis, but only 10–15% of infected individuals develop frank peptic ulceration. The basis for this difference is unknown, but is likely due to a combination of host and bacterial factors some of which are outlined below.
PEPTIC ULCER DISEASEDefinitionPeptic ulcer is a break of the mucosa lining the stomach or the duodenum. According to their anatomical location, peptic ulcers are divided into gastric ulcers, i.e., peptic ulcers of the gastric fundus, body or antrum, prepyloric and pylori ulcers, i.e., located within 3 cm from the pyloric ring and in the pyloric ring respectively, and duodenal ulcers, i.e., located into the bulb or in the second portion of the duodenum
Active chronic H. pylori gastritis. The gastric mucosa contains large numbers of lymphocytes and plasma cells while polymorphs infiltrate the foveolar epithelium. The surface epithelium shows marked degenerative changes. Hematoxylin and eosin; magnification, ×100.Chronic H. pylori gastritis. This low-power view shows marked glandular atrophy, lymphoid follicles, and centrally a focus of intestinal metaplasia. H&E ×25.From: Chapter 38, Pathology of Gastritis and Peptic Ulceration
Figure 2: Lymphoid Follicle Formation in Gastric MucosaFigure 3: Hemorrhage in Gastric MucosaThe slides were assessed under light microscope for all parameters as per the revised Sydney System and in addition infiltration by eosinophils, histiocytes, lymphoid follicle with germinal centers, hemorrhages, dysplasia and carcinoma in situ.The morphologic of graded (mild, moderate and severe) variables and ungraded variables. The graded variables included atrophy, chronic inflammation, activity, H. pylori density, eosinophilic infiltration, histiocytes, hemorrhages and dysplasia. The
1. Antisecretory drugs, such as PPIs, can interfere with the indirect delivery of antibiotics (as has already been suggested for metronidazole and clarithromycin), may decrease gastric juice volume, and may reduce the washout of antibiotics, hence increasing luminal antibiotic concentration.[12-14] In addition, the increased absorption and tissue penetration of antimicrobial agents that occur with elevated gastric mucosal levels caused by omeprazole may contribute to the observed synergy. 2. Bismuth compounds exert their topical antimicrobial activity, acting directly on bacterial cell walls to disrupt their integrity by accumulating in the periplasmic space and along membranes.
@Assessment should be done atleast 4 weeks after completion of anti H.Pylori therapy.@In the assessment of treatment success non invasive test are normally preferred.
DefinitionHelicobacter pylori colonizes thestomach of 50% of the worlds humanpopulation throughout their lifetimes.Colonization with this organism is themain risk factor for peptic ulceration aswell as for gastric adenocarcinoma andgastric MALT lymphoma.
• It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria.It produces oxidase, catalase, and urease.• H. pylori possesses five major outer membrane protein (OMP) families.1. putative adhesins.2. porins.3. iron transporters.4. flagellum-associated proteins5. proteins of unknown function.
The genome of the strain "26695" consists of about 1.7 million base pairs, with some 1,550 genes.. The cagA gene codes for one of the major H. pylori virulence proteins. Bacterial strains that have the cagA gene are associated with an ability to cause ulcers.
Winners of 2005 Nobel prizefor physiology and medicine
Winners of 2005 Nobel prizefor physiology and medicine
Etiologic Agent H. pylori is a gram-negative bacillus that has naturally colonized humans for at least 50,000 years—and probably throughout human evolution. It lives in gastric mucus, with a small proportion of the bacteria adherent to the mucosa and possibly a very small number of the organisms entering cells or penetrating the mucosa; its distribution is never systemic. Its spiral shape and flagella render H. pylori motile in the mucus environment. The organism has several acid-resistance mechanisms, most notably a highly expressed urease that catalyzes urea hydrolysis to produce buffering ammonia. H. pylori is microaerophilic (requiring low levels of oxygen), is slow-growing, and requires complex growth media in vitro.
Prevalence of H.Pylori in developed AND developed countries80%70%60% Pr eval ence i n50% devel oped count r i es40% Pr eval ence i n30% devel opi ng count i r es20%10%0%
H.Pylori Infection Prevalence Varies with Age In Developed Country50%45%40%35% 60- year - ol d per son30% 30- year - ol d per son25%20% 3- 20 year ol d15% per son10% 5% 0%
# Strains producing cag pathogenicity DNA island) are morelikely to give rise to severe gastritis, peptic ulceration andgastric cancer than strains without it.DNA island or cag pathogenicity island is a large region ofDNA which has genes that control production of toxins.Vacuolating toxin (VaC A)Cytotoxin ( cytotoxin associated gene Cag- A)# Humans are the only important reservoir of H. pylori andacquisition in adulthood is uncommon.# Whether transmission takes place more often by the fecal-oralor the oral-oral route is unknown, but H. pylori is easily culturedfrom vomitus and gastroesophageal refluxate and is less easilycultured from stool.
Diagrammatic representation of the oxyntic gastric gland
Bacterial factors Host factors H. pylori is able to facilitate gastric The inflammatory response to H. pylori residence, induce mucosal injury, and includes recruitment of neutrophils, avoid host defense. lymphocytes (T and B), macrophages, A specific region of the bacterial and plasma cells. genome, the pathogenicity island (cag- The pathogen leads to local injury by PAI), encodes the virulence factors binding to class II major Cag A and pic B. histocompatability complex (MHC) molecules expressed on gastric Vac A targets human CD4 T cells, epithelial cells, leading to cell death inhibiting their proliferation and in addition can disrupt normal function of (apoptosis). B cells, CD8 T cells, macrophages and Bacterial strains that encode cag- mast cells. PAI can introduce Cag A into the host cells, leading to further cell injury Multiple studies have demonstrated and activation of cellular pathways that H. pylori strains that are cag-PAI positive are associated with a higher involved in cytokine production. risk of peptic ulcer disease, Elevated concentrations of multiple premalignant gastric lesions and cytokines are found in the gastric gastric cancer than are strains that lack the cag-PAI. epithelium of H. pylori–infected individuals, including interleukin (IL) Urease, which allows the bacteria to 1/, IL-2, IL-6, IL-8, tumor necrosis reside in the acidic stomach, factor (TNF) , and interferon (IFN-). generates NH3, which can damage epithelial cells.
Although lipopolysaccharide (LPS) cause epithelial cell injury include (1) of gram-negative bacteria often activated neutrophil-mediated plays an important role in the production of reactive oxygen or infection, H. pylori LPS has low nitrogen species and enhanced immunologic activity compared to epithelial cell turnover and (2) that of other organisms. It may apoptosis related to interaction with T promote a smoldering chronic cells (T helper 1, or TH1, cells) and inflammation. IFN-.
Outline of the bacterial and host factors important in determining H. pylori–induced gastrointestinal disease. MALT, mucosal-associated lymphoid tissue.
Differnece between Gastric Ulcer and Duodenal Ulcer DUODENAL ULCER GASTRIC ULCEREpidemiology:Worldwide, >80% are related to H. >60% of gastric ulcers are related topylori colonization. H. Pylori colonization.Pathology:1st part of the duodenum (>95%), with In contrast GUs can represent a~90% located within 3 cm of the malignancy and should be biopsiedpylorus. They are usually 1 cm in upon discovery. Benign GUs are mostdiameter but can occasionally reach often found distal to the junction3–6 cm (giant ulcer). Ulcers are between the antrum and the acidsharply demarcated, with depth at secretory mucosa..times reaching the muscularis propria.The base of the ulcer often consists of Benign GUs are quite rare in thea zone of eosinophilic necrosis with gastric fundus and are histologicallysurrounding fibrosis. Malignant DUs similar to DUs. Benign GUsare extremely rare. associated with H. pylori are also associated with antral gastritis.
Pathophysiology: GUs that occur in the prepyloric area orH. pylori and NSAID-induced injury those in the body associated with a DU oraccount for the majority of DUs. a duodenal scar are similar in pathogenesis to DUs.Of these, average basal and nocturnal Gastric acid output (basal and stimulated)gastric acid secretion appears to be tends to be normal or decreased in GUincreased in DU patients as compared to patients.controls.Chronic duodenal ulcer usually occurs in Chronic gastric ulcer is usually single; 90%the 1st part of the duodenum just distal to are situated on the lesser curve within thethe junction of pyloric and duodenal antrum or at the junction between bodymucosa; 50% are on the anterior wall. and antral mucosa.The male to female ratio for duodenal ulcer gastric ulcer is 2:1 or less.varies from 5:1 to 2:1,Blood group: O A
Common feature Bleeding : Gastric ArteryComplication : Penetration occur gradually slowly …Bleeding Posterior : develop pseudopancreaticPosterior > Anterior cyst, Pancreatits.Gastroduodenal artery( UGIE+Cauterization) Anterior : transverse colon causes fecal fistula.Perforation: Anterior>Posterior Laterally : liver cirrhosis. Fluid in greater sac. Perforation :Gastric outlet obstruction: Fluid in lesser sac. metabilc alkalosis. Malignancy :Pain 2hour relieved by food Gastric outlet obstructionepigastric pain metabilc alkalosisHunger pain causes obesity Pain <1/2 causes epigastric painRx: UGIE+CAUTERIZATION Rx: Fluid resusciation A chronic ulcer extends to below theGastric and duodenal ulcers coexist in muscularis mucosae and the histology10% of patients and more than one shows four layers: surface debris, anpeptic ulcer is found in 10-15% of infiltrate of neutrophils, granulation tissuepatients. and collagen.
GASTRIC CARCINOMAThere is marked geographical variation in incidence. It isextremely common in China, Japan and parts of South America(mortality rate 30-40 per 100 000), less common in the UK (12-13deaths per 100 000) and uncommon in the USA.Studies of Japanese migrants to the USA have revealed a much lowerincidence in second-generation migrants, confirming the importanceof environmental factors.Gastric cancer is more common in men and the incidence risessharply after 50 years of age.
Aetiology of GCH. pylori is associated with chronic atrophic gastritis and gastric cancer .H. pylori infection may be responsible for 60-70% of cases andacquisition of infection at an early age may be important.Although the majority of H. pylori-infected individuals have normal orincreased acid secretion, a few become hypo- or achlorhydric and thesepeople are thought to be at greatest risk.Chronic inflammation with generation of reactive oxygen species anddepletion of the normally abundant antioxidant ascorbic acid are alsoimportant.
Gastric lymphoma• Primary gastric lymphoma accounts for less than 5% of all gastric malignancies. The stomach is, however, the most common site for extranodal non-Hodgkins lymphoma and 60% of all primary gastrointestinal lymphomas occur at this site.• Lymphoid tissue is not found in the normal stomach but lymphoid aggregates develop in the presence of H. pylori infection. Indeed, H. pylori infection is closely associated with the development of a low-grade lymphoma (MALToma).
Methods for the diagnosis of Helicobacter Pylori infection Invasive Non Invasive1. Endoscopy based Biopsy 1. Urea Breath tests:Urease test Here patient drinks a labelled ureaHere specimen from antral biopsy are solution and blows into a tube.tested for ―urease‖. If H.Pylori urease is present, theIt is most convenient endoscopy urea is hydrolysed and labelled co2based test. is detected in breath samples. It is thus a simple, safe test andIt is quick and simple however it is cheaper than endoscopy.neither fully sensitive nor fully specific. 2. Serological :2. Histology : Here specific IgG lelvels in serumHere the biopsy specimen is are assessed.subjected to histological examination, Does not differentiate betweenIt is accurate, but time consuming. active and remote infection.3. Culture: Nevertheless it is particularly suited as an epidemiological tool.Here the biopsy specimen put in a 3. Stool antigen test:culture medium. New test appears less accurate thanThis is accurate and permits urea breath test.determination of antibiotic Useful for follow up after treatment.susceptiblities, but is also timeconsuming
DiagnosisInvasive tests:Endoscopy often is not performed in the initial management of youngdyspeptic patients without "alarm" symptoms but is commonly usedto exclude malignancy in older patients.If endoscopy is performed, the most convenient biopsy-based test isthe biopsy urease test, in which one large or two small antral biopsyspecimens are placed into a gel containing urea and an indicator. Thepresence of H. pylori urease leads to a pH alteration and therefore to acolor change, which often occurs within minutes but can require up to24 h.Histologic examination of biopsy specimens for H. pylori also isaccurate, provided that a special stain (e.g., a modified Giemsa orsilver stain) permitting optimal visualization of the organism is used.
Noninvasive Tests:H. pylori testing is the norm if gastric cancer does not need to beexcluded by endoscopy. The most consistently accurate test is theurea breath test.In this simple test, the patient drinks a solution of urea labeled with thenonradioactive isotope 13C and then blows into a tube. If H. pyloriurease is present, the urea is hydrolyzed and labeled carbon dioxide isdetected in breath samples.The stool antigen test.The simplest tests for ascertaining H. pylori status are serologic assaysmeasuring specific IgG levels in serum by enzyme-linkedimmunosorbent assay or immunoblot.—do not perform well.
Pathology of Gastritis and Peptic Ulceration Hematoxylin and eosin; magnification, ×100. H&E ×25.
Indications of treatment :H. Pylori related duodenal and gastric ulceration Low garde B cellMALT lymphoma
TREATMENT FOR GASTRIC ADENOCARCINOMAResectable tumours•Complete surgical removal of the tumor with resection of adjacent lymph nodes offersthe only chance for cure. However, this is possible in less than a third of patients.• A subtotal gastrectomy is the treatment of choice for patients with distal carcinomas.The inclusion of extended lymph node dissection in these procedures appears to conferan added risk for complications without enhancing survival.Unresectable tumours•The management of inoperable, locally advanced cancer is unsatisfactory.•Modest palliation of symptoms can be achieved in some patients with chemotherapyusing FAM (5-fluorouracil, doxorubicin and mitomycin C) or ECF (epirubicin, cisplatinand 5-fluorouracil).•Endoscopic laser ablation of tumour tissue for control of dysphagia or recurrentbleeding benefits some patients.
Treatment of Gastric LymphomaSuperficial MALTomas may be cured by H. pylorieradication.The clinical presentation is similar to that of gastriccancer and endoscopically the tumour appears asa polypoid or ulcerating mass.While initial treatment of low-grade MALTomasconsists of H. pylori eradication and closeobservation, high-grade B-cell lymphomas aretreated by a combination of chemotherapy, surgeryand radiotherapy.
Assessing success of treatment/eradication of H.pyloriNon invasive test are Invasive tests are notpreferred preferred UREA BREATH TEST: BIOPSY BASED TESTSTest of chioce for documenting (Biopsy Ureaseeradication. Test,Histology/culture) STOOL ANTIGEN TEST: are invasive tests based onIf UBT is not available a stool Endoscopic biosy. antigen test should be considered for documenting eradication. SEROLOGICAL TESTING: Is These may be used to document not useful for purpose of eradication but are not documentation of eradication preferred for this purpose. as antibody titres fall slowly and often do not become undetectable.