What are the causes of peptic ulcer?

Classical causes of ulcers (tobacco smoking, blood groups, spices and a large array of strange things) are of relatively minor importance in the development of peptic ulcers.

A major causative factor (75% of gastric and 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori, a spirochaete that inhabits the antral mucosa and increases gastrin production. Gastrin, in turn, stimulates the production of gastric acid by parietal cells.

Another major cause is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucous, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins. Newer NSAIDs (celecoxib, rofecoxib) only inhibit cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration.

Glucocorticoids lead to atrophy of all epithelial tissues. Their role in ulcerogenesis is relatively small.

Stress in the psychological sense has not been proven to influence the development of peptic ulcers. Burns and head trauma, however, can lead to "stress ulcers", and it is reported in many patients who are on mechanical ventilation.

Smoking leads to atherosclerosis and vascular spasms, causing vascular insufficiency and promoting the development of ulcers through ischemia.

A family history is often present in duodenal ulcers, especially when blood group O is also present. Inheritance appears to be unimportant in gastric ulcers.

Macroscopically: Gastric ulcer is most often localized on the lesser curvature of the stomach. It is a round to oval parietal defect ("hole"), 2 to 4 cm diameter, with a smooth base and perpendicular borders. These borders are not elevated or irreguliar as in gastric cancer - ulcerative form. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.

Microscopically: Gastric peptic ulcer is a mucosal defect which penetrates the muscularis mucosae and muscularis propria, produced by acid-pepsin aggression. Ulcer margins are perpendicular and present chronic gastritis. During the active phase, the base of the ulcer shows 4 zones: inflammatory exudate, fibrinoid necrosis, granulation tissue and fibrous tissue. The fibrous base of the ulcer may contain vessels with thickened wall or with thrombosis.

A peptic ulcer is a sore on the lining of the stomach or duodenum, which is the beginning of the small intestine. Peptic ulcers are common: One in 10 Americans develops an ulcer at some time in his or her life. One cause of peptic ulcer is bacterial infection, but some ulcers are caused by long-term use of nonsteroidal anti-inflammatory agents (NSAIDs), like aspirin and ibuprofen. In a few cases, cancerous tumors in the stomach or pancreas can cause ulcers. Peptic ulcers are not caused by stress or eating spicy food, but these can make ulcers worse

Normally, the lining of the stomach and small intestines have protection against the irritating acids produced in your stomach. For a variety of reasons, the protective mechanisms may become faulty, leading to a breakdown of the lining. This results in inflammation (gastritis ) or an ulcer.

The most common cause of such damage is infection of the stomach with a bacterium called Helicobacter pylori (H.pylori). Most people with peptic ulcers have this organism living in their gastrointestinal (GI) tract. On the other hand, many people have this organism living in their GI tract but they don't get an ulcer.

Other factors can make it more likely for you to get an ulcer, including:

Using aspirin, ibuprofen, or naproxen
Drinking alcohol excessively
Smoking cigarettes and using tobacco
In addition, if you have a family history of ulcers or you are blood type O, you are more likely to get a duodenal ulcer. There is also a rare condition called Zolliger-Ellison syndrome in which a tumor in the pancreas secretes a substance that causes ulcers throughout the stomach and duodenum.

Many people believe that stress causes ulcers. It is not clear if this is true. While critically ill patients who are on a breathing machine are at risk of so-called 鈥渟tress ulceration,锟? everyday stress at work or home doesn't appear to cause peptic ulcers.

bacteria
as found by nobel prize winning australian doctor
cure
a combination of anitbiotics and bizmuth

Eating too much of spicy foods and also taking food not in time

Bacteria is the most frequent cause. This can be treated with an antibiotic. Production of excess stomach acid can also be a cause. This is treated with medication such as Nexium.

Peptic Ulcer Disease

Synonyms and related keywords: PUD, Helicobacter pylori infection, H pylori infection, nonsteroidal

WORKUP

Lab Studies:

* In most patients with uncomplicated PUD, routine laboratory tests are usually unhelpful. Documentation of PUD depends on radiographic and endoscopic confirmation.

* If the diagnosis of PUD is unclear or complicated and PUD is suspected, obtaining CBC, liver function tests (LFTs), amylase, and lipase might be useful.

Imaging Studies:

* Upper gastrointestinal series

o Double-contrast radiography performed by an experienced radiologist might approach the diagnostic accuracy of upper GI endoscopy. However, it has been replaced largely by diagnostic endoscopy, when available.

o It is not as sensitive as endoscopy for the diagnosis of small ulcers (<0.5 cm).

o It does not allow for obtaining a biopsy to rule out malignancy in the setting of a gastric ulcer or to assess for H pylori infection in the setting of a gastroduodenal ulcer.

Other Tests:

* Detection of H pylori infection is essential in all patients with peptic ulcers.

* Endoscopic or invasive tests include a rapid urease test, histopathology, and culture.

o Rapid urease tests are considered the endoscopic diagnostic test of choice. The presence of H pylori in gastric mucosal biopsy specimens is detected by testing for the bacterial product urease. Three kits (CLOtest, Hpfast, Pyloritek) are commercially available, each containing a combination of a urea substrate and a pH sensitive indicator. One or more gastric biopsy specimens are placed in the rapid urease test kit. If H pylori are present, bacterial urease converts urea to ammonia, which changes pH and produces a color change.

o Obtain histopathology, often considered the criterion standard for the diagnosis of H pylori, if the rapid urease test result is negative and a high suspicion for H pylori persists (presence of a duodenal ulcer).

o Culture primarily is used in research studies and is not available routinely for clinical use.

* Nonendoscopic or noninvasive tests include serum H pylori antibody detection, fecal antigen tests, and urea breath tests.

o Antibodies (immunoglobulin G [IgG]) to H pylori can be measured in serum, plasma, or whole blood. Results with whole blood tests obtained from finger sticks are less reliable.

o Urea breath tests detect active H pylori infection by testing for the enzymatic activity of bacterial urease. In the presence of urease produced by H pylori, labeled carbon dioxide (heavy isotope, carbon-13, or radioactive isotope, carbon-14) is produced in the stomach, absorbed into the bloodstream, diffused into the lungs, and exhaled.

o Fecal antigen testing identifies active H pylori infection by detecting the presence of H pylori antigens in stools. This test is more accurate than antibody testing and less expensive than urea breath tests.

* Special studies

o Obtaining a serum gastrin is useful in patients with recurrent, refractory, or complicated PUD and is useful in patients with a family history of PUD to screen for Zollinger-Ellison syndrome.

o A secretin stimulation test can be performed to distinguish Zollinger-Ellison syndrome from other conditions with a high serum gastrin, such as achlorhydria and antisecretory therapy with a proton pump inhibitor.

o Measurement of acid secretion is not useful in the routine evaluation of PUD.

Procedures:

* Upper GI endoscopy

o Preferred diagnostic test in the evaluation of patients with suspected PUD

o Highly sensitive for the diagnosis of gastric and duodenal ulcers

o Allows for biopsies and cytologic brushings in the setting of a gastric ulcer in order to differentiate a benign ulcer from a malignant lesion

o Allows for detection of H pylori infection with antral biopsies for a rapid urease test and/or histopathology in patients with PUD

TREATMENT

Medical Care:

* Given current understanding of the pathogenesis of PUD, the majority of patients with PUD are treated successfully medically with cure of H pylori infection and/or avoidance of NSAIDs, along with appropriate use of antisecretory therapy.

* A number of treatment options exist for patients presenting with symptoms suggestive of PUD or ulcerlike dyspepsia, including empiric antisecretory therapy, empiric triple therapy for H pylori infection, endoscopy followed by appropriate therapy based on findings, and H pylori serology followed by triple therapy for infected patients. Breath testing for active H pylori infection may be used.

* Computer models have suggested that obtaining an H pylori serology followed by triple therapy for those infected is the most cost-effective approach; however, no direct evidence from clinical trials confirms this.

* Perform endoscopy early in patients older than 45-50 years and in patients with associated so-called alarm symptoms, such as dysphagia, recurrent vomiting, weight loss, or with signs of bleeding.

Surgical Care: With the success of medical therapy, surgery has a very limited role in the management of PUD.

* Potential indications for surgery include refractory disease, and complications of PUD include the following:

o Refractory, symptomatic peptic ulcers, though rare with the cure of H pylori and the appropriate use of antisecretory therapy, are a potential complication of PUD.

o Perforation usually is managed emergently with surgical repair. However, this is not mandatory for all patients.

o Obstruction can complicate PUD, particularly if PUD is refractory to aggressive antisecretory therapy, H pylori eradication, or avoidance of NSAIDs. Obstruction may persist or recur despite endoscopic balloon dilation.

o Penetration, particularly if not walled-off or if a gastrocolic fistula develops, is a potential complication of PUD.

o Bleeding can complicate PUD, particularly in patients with massive hemorrhage and hemodynamic instability, recurrent bleeding on medical therapy, and failure of therapeutic endoscopy to control bleeding.

* The appropriate surgical procedure depends on the location and nature of the ulcer.

o Many authorities recommend simple oversewing of the ulcer with treatment of underlying H pylori infection or cessation of NSAIDs for bleeding PUD.

o Additional surgical options for refractory or complicated PUD include vagotomy and pyloroplasty, vagotomy and antrectomy with gastroduodenal reconstruction (Billroth I) or gastrojejunal reconstruction (Billroth II), or a highly selective vagotomy.

Consultations: Consult a general surgeon if the clinical presentation suggests a complicated peptic ulcer.

Diet: No special diet is required.

MEDICATION

Treat all patients with peptic ulcers and associated H pylori infection with triple therapy, which results in a cure rate of infection and healing in approximately 85-90% of cases. In addition to effectiveness, consider compliance, adverse effects, drug interactions, and cost when choosing a regimen.

Dual therapies, which are alternative regimens for treating H pylori infection, are usually not recommended as first-line therapy because of a variable cure rate that is significantly less than the cure rate achieved with triple therapy.

Treat NSAID-induced ulcers with cessation of NSAIDs, if possible, and an appropriate course of standard ulcer therapy with a histamine 2 (H2)鈥搑eceptor antagonist or a proton pump inhibitor. If NSAIDs are continued, prescribe a proton pump inhibitor.

H pylori鈥搉egative ulcers that are not caused by NSAIDs can be treated with appropriate antisecretory therapy, either H2-receptor antagonists or proton pump inhibitors. Begin testing for other causes.

Drug Category: Triple therapies for H pylori infection -- Triple therapy for 14 days is considered the treatment of choice for H pylori infection. Two forms of triple therapy are available, including proton pump inhibitor鈥揵ased triple therapy and bismuth-based triple therapy. Proton pump inhibitor鈥揵ased triple therapy consists of a proton pump inhibitor and 2 antibiotics, each bid for 2 weeks. In the setting of an active ulcer, continue qd proton pump inhibitor therapy for additional 2 weeks. Bismuth-based triple therapy consists of bismuth subsalicylate and 2 antibiotics, each qid for 2 weeks. In the setting of an active ulcer, addition of an antisecretory agent, such as an H2-receptor antagonist, is recommended to optimize ulcer healing.
Drug Name
Omeprazole (or other PPI) plus clarithromycin and amoxicillin -- Proton pump inhibitor鈥揵ased triple therapy.
Adult DoseOmeprazole (Prilosec): 20 mg PO bid for 14 d or
Lansoprazole (Prevacid): 30 mg PO bid for 14 d or
Rabeprazole (Aciphex): 20 mg PO bid for 14 d or
Esomeprazole (Nexium): 40 mg PO qd for 14 d plus
Clarithromycin (Biaxin): 500 mg PO bid for 14 and
Amoxicillin (Amoxil): 1 g PO bid for 14 d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsOmeprazole can prolong elimination of drugs metabolized by cytochrome P-450 system in liver (eg, diazepam, warfarin, phenytoin); omeprazole and lansoprazole can interfere with absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts)
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsAdjust dose in liver impairment; patients with a CrCl <30 mL/min should receive half the dose; also might choose double dosing interval; consider the possibility of pseudomembranous colitis in diarrhea subsequent to administration of antimicrobial agent; risk of secondary infections exists if antibacterial therapy is prolonged or repeated; take appropriate measures if superinfection occurs
Drug Name
Omeprazole (or other PPI) plus clarithromycin and metronidazole -- Alternative proton pump inhibitor鈥揵ased triple therapy, particularly useful in patients with a penicillin allergy.
Adult DoseOmeprazole (Prilosec): 20 mg PO bid for 14 d or
Lansoprazole (Prevacid): 30 mg PO bid for 14 d or
Rabeprazole (Aciphex): 20 mg PO bid for 14 d or
Esomeprazole (Nexium): 40 mg PO qd for 14 d plus
Clarithromycin (Biaxin): 500 mg PO bid for 14 d and
Metronidazole (Flagyl): 500 mg PO bid for 14 d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; concomitant treatment with cisapride
InteractionsOmeprazole and metronidazole can prolong the elimination of drugs metabolized by cytochrome P-450 system in liver (eg, diazepam, warfarin, phenytoin); omeprazole and lansoprazole can interfere with absorption of drugs where gastric pH is important determinant of bioavailability (eg, ketoconazole, iron salts)
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsAvoid alcohol consumption because abdominal cramps, nausea, and vomiting might occur
Drug Name
Bismuth subsalicylate, tetracycline, and metronidazole (Helidac) -- Drug combination used to treat active duodenal ulcer associated with H pylori.
Adult DoseBismuth subsalicylate: 2 tab PO qid for 10-14 d
Tetracycline: 500 mg PO qid for 10-14 d
Metronidazole: 250 mg PO qid for 10-14 d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; known allergy to aspirin or salicylates
InteractionsSalicylates might cause an increased risk of bleeding when administered with anticoagulants; metronidazole might potentiate anticoagulant effect of warfarin
PregnancyD - Unsafe in pregnancy
PrecautionsMight cause temporary harmless darkening of tongue and/or black stool; avoid alcohol consumption because abdominal cramps, nausea, and vomiting might occur
Drug Category: Proton pump inhibitors -- Proton pump inhibitors bind to and inhibit the H+/K+-adenosine triphosphatase (ATPase) pump of the parietal cell, resulting in a marked decrease in acid secretion. These drugs are an important part of triple therapy, the treatment of choice for H pylori infection. Proton pump inhibitors have some direct antibacterial effect, and their antisecretory properties aid in ulcer healing. Can be used as primary therapy to heal ulcers not associated with H pylori infection.
Drug Name
Omeprazole (Prilosec) -- Decreases gastric acid secretion by inhibiting parietal cell H+/K+-ATP pump. Might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in chronic NSAID users at high risk.
Adult Dose20 mg/d PO for 4 wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsMay decrease effects of itraconazole and ketoconazole; may increase toxicity of warfarin, digoxin, and phenytoin
PregnancyC - Safety for use during pregnancy has not been established.
PrecautionsBioavailability might increase in elderly patients
Drug Name
Lansoprazole (Prevacid) -- Decreases gastric acid secretion by inhibiting parietal cell H+/K+-ATP pump. Might decrease the incidence of NSAID-induced peptic ulcers and can be used to help prevent peptic ulcers in chronic NSAID users at high risk.
Adult Dose15-30 mg/d PO for 4 wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsMay decrease effects of ketoconazole and itraconazole; may increase theophylline clearance
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsConsider adjusting dose in liver impairment
Drug Name
Esomeprazole (Nexium) -- Inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells.
Adult Dose20-40 mg PO qd for 4-8 wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsSymptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy
Drug Name
Rabeprazole (Aciphex) -- Inhibits gastric acid secretion by inhibiting H+/K+鈥揂TPase enzyme system at secretory surface of gastric parietal cells.
Adult Dose20 mg PO qd for 4 wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsSymptomatic relief with proton pump inhibitors may mask symptoms of gastric malignancy
Drug Category: Cytoprotectants -- Agents with the ability to induce prostaglandin synthesis have cytoprotective effects in the GI tract.
Drug Name
Misoprostol (Cytotec) -- Prostaglandin analog can be used to decrease incidence of peptic ulcers and complications in chronic NSAID users at high risk.
Adult Dose200 mcg PO qid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; do not use in women of childbearing age unless patient requires NSAID therapy and is at high risk for complications of PUD
InteractionsNone reported
PregnancyX - Contraindicated in pregnancy
PrecautionsCaution in renal impairment and elderly patients; adverse gastrointestinal effects (eg, abdominal pain, diarrhea) are common; lower doses have fewer adverse effects but are slightly less effective; the dose can be titrated to optimal therapeutic dose
Drug Category: H2-receptor blockers -- H2-receptor antagonists selectively block H2-receptors on parietal cells, resulting in diminished acid secretion and ulcer healing.
Drug Name
Cimetidine (Tagamet) -- Can be used as primary therapy to heal ulcers not associated with H pylori infection.
Treatment duration is 6-8 wk. A longer treatment course might be required for gastric ulcers.
Adult Dose400 mg PO bid or 800 mg PO qhs for 6-8 wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsCan increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsElderly patients might experience confusional states; might cause impotence and gynecomastia in young males; might increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur
Drug Name
Ranitidine (Zantac) -- Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which in turn reduces gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
Adult Dose150 mg PO bid or 300 mg PO qhs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsMay decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Drug Name
Famotidine (Pepcid) -- Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Adult Dose20 mg PO bid or 40 mg PO qhs
Pediatric DoseNot established; suggested dose is 1-2 mg/kg/d PO/IV divided q6h; not to exceed 40 mg per dose
ContraindicationsDocumented hypersensitivity
InteractionsMay decrease effects of ketoconazole and itraconazole
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsIf changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Drug Name
Nizatidine (Axid) -- Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Adult Dose150 mg PO bid or 300 mg PO qhs
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyB - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal or liver impairment (if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment)
FOLLOW-UP

Further Outpatient Care:

* Endoscopy is required to document healing of gastric ulcers and to rule out gastric cancer. This usually is performed 6-8 weeks after the initial diagnosis of PUD.

* Documentation of H pylori cure with a noninvasive test, such as the urea breath test or fecal antigen test, is appropriate in patients with complicated ulcers.

In/Out Patient Meds:

* Consider maintenance therapy with half standard doses of H2-receptor antagonists at bedtime in patients with recurrent, refractory, or complicated ulcers, particularly if cure of H pylori has not been documented or if a H pylori鈥搉egative ulcer is present.

Deterrence/Prevention:

* Primary prevention of NSAID-induced ulcers includes the following:

o Avoid unnecessary use of NSAIDs.

o Use acetaminophen or nonacetylated salicylates when possible.

o Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the newer NSAIDs or cyclooxygenase-2 (COX-2) inhibitors, in high-risk patients without cardiovascular disease.

* Consider prophylactic or preventive therapy for the following patients:

o Patients with NSAID-induced ulcers who require chronic, daily NSAID therapy

o Patients older than 60 years

o Patients with a history of PUD or a complication such as gastrointestinal bleeding

o Patients taking concomitant steroids or anticoagulants or patients with significant comorbid medical illnesses

* Prophylactic regimens that have been shown to dramatically reduce (prevent) the risk of NSAID-induced gastric and duodenal ulcers include the use of a prostaglandin analogue or a proton pump inhibitor.

o Misoprostol 100-200 mcg PO 4 times per day

o Omeprazole 20-40 mg PO every day

o Lansoprazole 15-30 mg PO every day

Complications:

* Perforation

* Penetration

* Obstruction

* Bleeding

Prognosis:

* When the underlying cause is addressed, the prognosis is excellent. Most patients are treated successfully with the cure of H pylori infection, avoidance of NSAIDs, and the appropriate use of antisecretory therapy.

* Cure of H pylori infection changes the natural history of the disease, with a decrease in the ulcer recurrence rate from 60-90% to approximately 10-20%. However, this is a higher recurrence rate than previously reported, suggesting an increased number of ulcers not caused by H pylori infection.

Patient Education:

* Stop smoking.

* Avoid NSAID and aspirin use.

* Avoid heavy alcohol use.

* Stress reduction counseling might be helpful in individual cases but is not needed routinely.

* For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center. Also, see eMedicine's patient education articles Peptic Ulcers, Heartburn, and Understanding Heartburn/GERD Medications.

MISCELLANEOUS


Medical/Legal Pitfalls:

* Failure to assess for H pylori infection in patients with PUD is a potential pitfall.

* Choosing an inadequate treatment regimen for patients with H pylori infection, such as the wrong combination of drugs, wrong dosage, or too short duration of treatment, is a potential pitfall.

* Failure to obtain a detailed medical history regarding potential NSAID use is a potential pitfall.

bad diet stress