PEPTIC ULCER DISEASE

Dr. Saelinger Microbiology

Dr. Noffsinger Pathophysiology

Dr. Long Clinical presentation

Dr. Goldberg Treatment

HELICOBACTER PYLORI

Background

Human stomach long considered inhospitable forbacteria

Spiral shaped organisms occasionally visualized ingastric mucous layer, but no evidence of diseaseassociation

Organism classified first as Campylobacter pylori

Now Helicobacter pylori

Other species of Helicobacter isolated fromstomach, intestine of other animals

Marshall and Warren culture organism from humangastric mucosa and show association with gastricinflammation

A silver stain of H. pylori on gastric mucus-secreting epithelial cells (x1000). From Dr. Marshall's stomach biopsy taken 8 days after he drank a culture of H. pylori (1985).

MICROBIOLOGY

1. Gram negative, spiral, flagellated(motile) bacilli

2. Slow growing, requires complexmedia, microaerophilic

3. Oxidase and catalase positive

4. Produces urease

5. Noninvasive; proliferates inmucus overlying gastric typemucosa

6. Not cleared by host immuneresponse

TRANSMISSION

1. Humans are major - if not only - reservoir

2. Transmission believed to be by fecal-oralroute

organism can be cultured from feces family members often carry same strain prevalence of infection likely related to

inferior hygienic conditions and poorsanitation

infection from environment or from animalscannot be totally excluded

EPIDEMIOLOGY

1. Gastric colonization rate in developing countries isabout 80%

Very high from early childhood

2. Gastric colonization rate in US and otherdeveloped countries is about 30%

3. Prevalence of infection increases with age

Age 10 = ~5%Age 30 = ~ 25%Age 60 = ~ 50%

4. In US, prevalence rates are higher in African-Americans and Hispanics

5. Age and low income = main risk factors for H.pylori infection

Nearly all H. pylori colonized persons have gastric inflammation - but this - by itself is asymptomatic.

Symptoms are due to illness - such as peptic ulceration or gastric malignancy.

Develop in <10% individuals colonized with H. pylori.

Over 80% peptic ulcers related to H. pylori colonization.

Evidence supporting H. pylori as major causeof peptic ulcer disease

1. H. pylori is found in almost all cases of PUD, whenthe use of NSAIDs is definitely excluded

2. When H. pylori is treated and eradicated, the rateof ulcer recurrence is dramatically reduced

3. H. pylori induced changes in acid secretion andmucosal resistance provide a plausiblepathophysiologic explanation

PATHOGENESIS

Colonization

1. Most bacteria killed in hostile environment of gastriclumen

2. H. pylori proliferates in mucus layer over epitheliumand is not cleared by host immune response

3. H. pylori survives and grows there because of avariety of virulence factors that contribute to gastricinflammation, alter gastric acid production, and causetissue destruction.

VIRULENCE FACTORS

Initial colonization facilitated by:

Acid inhibitory protein - blocks acid secretion from parietal cells during acute infection

Urease - neutralizes gastric acids due to ammonia production. [also stimulates monocytes and neutrophil chemotaxis; stimulates production of inflammatory cytokines]

Heat shock protein - enhances urease expression; co-expressed with urease on bacterial surface

Flagella - allows penetration into gastric mucous layer

Adhesins - mediate binding to host cells

Localized tissue damage mediated by:

Mucinases and phospholipases - disrupt gastric mucus

Vacuolating cytotoxin - induces vacuolation in epithelial cells that results in epithelial cell damage

All these factors plus LPS stimulate inflammatory response

SOD and catalase - prevent from phagocytosis and intracellular killing

Plus other poorly defined factors that stimulate IL-8 secretion by epithelial cells, that induce nitric oxide synthase which mediates tissue injury, and that induce programmed death of gastric epithelial cells.

Cag pathogenicity island - includes genes that confer enhanced pathogenicity, in part by inducing epithelial cells to produce proinflammatory cytokines