Peptic ulcer disease

SYAHARA

Peptic ulcer disease

PathophysiologyThe normal stomach maintains a balancebetween : protective factors such as :

-mucus and bicarbonate secretion aggressive factors such as :

-acid secretion and pepsin. Gastric ulcers develop when aggressive

factors overcome protective mechanisms.

The two major etiological factors for PUD are :1. Helicobacter pylori infection 2. Nonsteroidal anti-inflammatory drug (NSAID) consumption.

3. Helicobacter pylori infection Currently, 70% of all gastric ulcers occurring in the United States can beattributed to H pylori infection. The bacterium's spiral shape and flagella facilitate its penetration into themucous layer and its attachment to the epithelial layer it releases :

-phospholipase and proteases, which cause further mucosal damage. -A cytotoxin-associated gene (cag A) has been isolated in approximately 65% of the bacteria. The products of this gene are associated with more :

- severe gastritis, - gastric ulcer- gastric cancer, and lymphoma

2. Nonsteroidal anti-inflammatory drug (NSAID) consumption.

NSAID-induced ulcers account for approximately 26% of gastric ulcers, and they are believed to be secondary to a decrease in prostaglandin production resulting from the inhibition of cyclooxygenase. The topical effects of NSAIDs are :

-superficial gastric erosions and petechial lesions. However, the risk of gastroduodenal ulcer is not diminished with parental or rectal use of NSAIDs indicating injury occurring from the systemic effect of NSAIDs on the gastrointestinal mucosa.

Selective COX-2 (cyclooxygenase) inhibitors, like celecoxib (Celebrex), In the Celecoxib Long-term Arthritis Safety Study (CLASS), they found a significantly lower incidence of symptomatic ulcers in patients taking celecoxib for the initial 6 months as compared to patients taking ibuprofen or diclofenac.

Currently, the only US Food and Drug Administration (FDA)-approved COX-2 inhibitor available is celecoxib, as rofecoxib and valdecoxib were withdrawn from the market by the FDA because of increased cardiovascular risk.

Cigarette smoking can affect gastric mucosal defense adversely. People who smoke tend to develop more frequent and recurrent ulcers and their ulcers are more resistant to therapy.

No evidence indicates that dietary habits or alcohol consumption predisposes individuals to gastric ulcer.

HISTORYIn 1875, German scientists found spiral-shaped bacteria in the lining of the human stomach. The bacteria could not be grown in culture and the results were eventually forgotten.[2]

In 1892, the Italian researcher Giulio Bizzozero described spiral-shaped bacteria living in the acidic environment of the stomach of dogs.

The bacterium was rediscovered in 1979 by Australian pathologist Robin Warren, who did further research on it with Barry Marshall beginning in 1981; they isolated the organisms from mucosal specimens from human stomachs and were the first to successfully culture them.[4] In their original paper,[5]

Warren and Marshall contended that most stomach ulcers and gastritis were caused by infection by this bacterium and not by stress or spicy food as had been assumed before.[6]

In 2005, Warren and Marshall were awarded the Nobel Prize in Medicine for their work on H. pylori.[10]

• Helicobacter pylori is a • Gram-negative bacterium that infects the lining of the stomach and duodenum.• Many cases of peptic ulcers, gastritis, and duodenitis are caused by H. pylori

infection. • However, many who are infected do not show any symptoms of disease. • Helicobacter spp. are the only known microorganisms that can thrive in the

highly acidic environment of the stomach. • Its helical shape (from which its name is derived) is thought to have evolved to

penetrate and colonize the mucus lining.[1]

StructureH. pylori is a spiral-shaped gram-negative bacterium, about 3 micrometres long with a diameter of about 0.5 micrometre. It has 4–6 flagella. It is microaerophilic, i.e. it requires oxygen but at lower levels than those contained in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) that is produced by other intestinal bacteria.[12] It tests positive for oxidase and catalase.

With its flagella, the bacterium moves through the stomach lumen and drills into the mucus gel layer of the stomach. It then finds ways to live in various areas of the stomach.

- inside the mucus gel layer - above epithelial cells- and inside vacuoles in epithelial cells.

It produces large amounts of urease enzymes which are localized inside and outside of the bacterium. Urease metabolizes urea (which is normally secreted into the stomach) to ammonia and carbon dioxide which neutralizes stomach acid.

The survival of H. pylori in the acidic stomach is dependant on urease and eventually dies without it.

The ammonia that is produced is toxic to the epithelial cells, and with other products of H. pylori, including protease, catalase, and phospholipases, causes damage to those cells.

Mucus cells.

Schematic of typical animal cell, showing subcellular components. Organelles: (1) nucleolus (2) nucleus (3) ribosome (4) vesicle (5) rough endoplasmic reticulum (ER) (6) Golgi apparatus (7) Cytoskeleton (8) smooth ER (9) mitochondria (10) vacuole (11) cytoplasm (12) lysosome (13) centrioles

Diagnosis of infection is usually made by checking for dyspepetic symptoms and then doing tests which can suggest H. pylori infection.

One can test noninvasively for H. pylori infection with a- blood antibody test-stool antigen test,

-carbon urea breath test (in which the patient drinks 14C- or 13C-labelled urea, which the bacterium metabolizes producing labelled carbon dioxide that can be detected in the breath). However, the most reliable method for detecting H .pylori infection is a biopsy check during endoscopy with a rapid urease test, histological examination, and microbial culture. Except for the biopsy check, none of the test methods are completely failsafe. Blood antibody tests, for example, range from 76% to 84% sensitivity. Some drugs can affect H. pylori urease activity and give "false negatives" with the urea-based tests.Infection may be symptomatic or asymptomatic It is estimated that up to 70% of infection is asymptomaticThe bacteria have been isolated from feces, saliva and dental plaque of infected patients, which suggests gastro-oral or fecal-oral as possible transmission routes.

 

Immunohistochemical staining of H. pylori from a gastric biopsy.

Treatment of infectionIn peptic ulcer patients where infection is detected, the normal procedure is eradicating H. pylori to allow the ulcer to heal.

Today the standard triple therapy is ( 7- 14 days ):

Triple therapies are used. Worldwide, accepted treatment regimens are -BMT,-LAC, -OAC.

BMT regimen is based on the administration of bismuth subsalicylate, metronidazole, and tetracycline. Add an H2-receptor antagonist for an additional 4 wk.

LAC regimen is based on the administration of lansoprazole, amoxicillin, and clarithromycin.

OAC regimen is based on the administration of omeprazole, amoxicillin, and clarithromycin.

Gastric cancer associationGastric cancer and gastric MALT lymphoma (lymphoma of the mucosa-associated lymphoid tissue) have been associated with H. pylori, and the

bacterium has been categorized as a group I carcinogen by the International Agency for Research on Cancer (IARC).

Photograph of H. pylori

Graham patch