Ulcer: A disruption of the mucosal integrity of the stomach and/or duodenum leading to

a local defect or excavation due to active inflammation.

• Ulcers are defined as a break in the mucosal surface >5 mm in size, with depth to the

submucosa.

Types

• PUD encompasses both

Gastric ulcers (GU)

Duodenal ulcers (DU)

• Duodenal (DU) and gastric ulcers (GU) share many common features in terms of

pathogenesis, diagnosis, and treatment, but several factors distinguish them from one

another

• Ulcers occur within the stomach and/or duodenum are often chronic in nature

Pathology

Gastroduodenal Mucosal Defense

• The gastric epithelium is under constant assault by a series of endogenous noxious

factors including hydrochloric acid (HCl), pepsinogen/pepsin, and bile salts.

• In addition, a steady flow of exogenous substances such as medications, alcohol, and

bacteria encounter the gastric mucosa.

• A highly intricate biologic system is in place to provide defense from mucosal injury and

to repair any injury that may occur.

• The mucosal defense system is a three-level barrier, composed of pre epithelial,

epithelial, and subepithelial elements.

• The first line of defense is a mucus-bicarbonate layer, which serves as a physicochemical

the barrier to multiple molecules including hydrogen ions.

• Surface epithelial cells provide the next line of defense through several factors, including

mucus production, epithelial cell ionic transporters that maintain intracellular pH and

bicarbonate production, and intracellular tight junctions.

• If the pre-epithelial barrier was breached, gastric epithelial cells bordering a site of

injury can migrate to restore a damaged region (restitution).

• Larger defects that are not effectively repaired by restitution require cell proliferation.

• The elaborate microvascular system within the gastric submucosal layer is the key

component of the subepithelial defense/repair system. A rich submucosal circulatory bed

provides bicarbonate (HCO3⁺), which neutralizes the acid generated by the parietal cell

secretion of HCl.

• Prostaglandins play a central role in gastric epithelial defense/repair. The gastric mucosa

contains abundant levels of prostaglandins.

• Hydrochloric acid and pepsinogen are the two principal gastric secretory products

capable of inducing mucosal injury.

Epidemiology & Aetiology

Duodenal Ulcers (DU)

• DUs are estimated to occur in 6 to 15% of the western population.

• Before the discovery of H. pylori, the natural history of DUs was typified by frequent

recurrences after initial therapy.

• Eradication of H. pylori has greatly reduced these recurrence rates.

• DUs occur most often in the first portion of the duodenum (>95%), with ~90% located

within 3 cm of the pylorus.

• Malignant duodenal ulcers are extremely rare.

Gastric Ulcers (GU)

• Gus tends to occur later in life than duodenal lesions, with a peak incidence reported in

the sixth decade.

• More then half of Gus occurs in males.

• Are less common than DUs, perhaps due to the higher likelihood of Gus being silent and

presenting only after a complication develops.

• Autopsy studies suggest a similar incidence of DUs and Gus.

• In contrast to DUs, Gus can represent a malignancy.

• Benign Gus associated with H. pylori is associated with antral gastritis.

• In, In contrast, NSAID-related Gus is not accompanied by chronic active gastritis but may

instead have evidence of a chemical gastropathy.

Etiology

• It is now clear that H. pylori and NSAID-induced injury account for the majority of DUs

and Gus.

• Gastric acid contributes to mucosal injury but does not play a primary role.

H. Pylori and Acid Peptic Disorders

• Gastric infection with the bacterium H. pylori accounts for the majority of PUD.

• This organism also plays a role in the development of gastric mucosal-associated

lymphoid tissue (MALT) lymphoma and gastric adenocarcinoma.

• It is still not clear how this organism, which is in the stomach, causes ulceration in the

duodenum, or whether its eradication will lead to a decrease in gastric cancer.

NSAIDs-Induced Disease

• NSAIDs represent one of the most commonly used medications

• The spectrum of NSAID-induced morbidity ranges from nausea and dyspepsia to a

serious gastrointestinal complication such as frank peptic ulceration complicated by

bleeding or perforation.

• Unfortunately, dyspeptic symptoms do not correlate with NSAID-induced pathology.

• Over 80% of patients with serious NSAID-related complications do not have preceding

dyspepsia.

• In view of the lack of warning signs, it is important to identify patients who are at

increased risk for morbidity and mortality related to NSAID usage.

Cigarette Smoking

• Not only have smokers been found to have ulcers more frequently than do nonsmokers,

but smoking appears to decrease healing rates, impair response to therapy, and increase

ulcer-related complications such as perforation.

• The mechanism responsible for increased ulcer diathesis in smokers is unknown.

Genetic Predisposition

• First-degree relatives of DU patients are three times as likely to develop an ulcer.

However, the potential role of H. pylori infection in contacts is a major consideration.

• Increased frequency in people with blood group O.

• However, H. pylori preferentially bind to group O antigens. Therefore, the role of genetic

predisposition in common PUD has not been established

Psychological Stress

• But studies examining the role of psychological factors in its pathogenesis have

generated conflicting results.

• Although PUD is associated with certain personality traits (neuroticism), these same

traits are also present in individuals with non-ulcer dyspepsia (NUD) and other functional

and organic disorders.

• Although more work in this area is needed, no typical PUD personality has been found.

Diet

• Certain foods can cause dyspepsia, but no convincing studies indicate an association

between ulcer formation and a specific diet.

• This is also true for beverages containing alcohol and caffeine

Conclusion

• Multiple factors play a role in the pathogenesis of PUD

• The two predominant causes are H. pylori infection and NSAID ingestion

• Independent of the inciting or injurious agent, peptic ulcers develop as a result of an

imbalance between mucosal protection/repair and aggressive factors

• Gastric acid plays an essential role in mucosal injury

History

• Epigastric pain – has poor predictive value for the presence of either DU or GU

Epigastric pain is described as a burning or gnawing discomfort can be present in both

DU and GU

The discomfort is also described as an ill-defined, aching sensation or as a hunger pain.

The typical pain pattern in DU occurs 90 min to 3 hours after a meal and is frequently

relieved by antacids or food

Pain that awakes the patient from sleep (between midnight and 3 A.M.) is the most

discriminating symptom, with two-thirds of DU patients describing this complaint.

Unfortunately, this symptom is also present in one-third of patients with NUD.

The pain pattern in GU patients maybe different from that in DU patients, where

discomfort may actually be precipitated by food.

• Nausea and weight loss occurs more commonly in GU patients.

• Dyspepsia that becomes constant, is no longer relieved by food or antacids, or radiates to

the back may indicate a penetrating ulcer.

• Sudden onset of severe, generalized abdominal pain may indicate a perforation.

• Pain worsening with meals, nausea, and vomiting of undigested food suggest gastrically

outlet obstruction.

• Tarry stools or coffee-ground emesis indicate bleeding.

Physical Examination

• Epigastric tenderness is the most frequent finding in patients with GU or DU.

• Physical examination is critically important for discovering evidence of ulcer

complication. Tachycardia and orthostasis suggest dehydration secondary to vomiting or

active gastrointestinal blood loss.

• A severely tender, board-like abdomen suggests perforation.

• Presence of a succussion splash indicates retained fluid in the stomach, suggesting gastric

outlet obstruction.

PUD-Related Complications

• Gastrointestinal Bleeding is the most common complication.

• Perforation is the second most common ulcer-related complication.

• Penetration is a form of perforation in which the ulcer bed tunnels into an adjacent organ.

DUs tend to penetrate posteriorly into the pancreas, leading to pancreatitis.

Gus tends to penetrate into the left hepatic lobe.

• Gastric Outlet Obstruction is the least common ulcer-related complication.

Differential Diagnosis and Investigations

• The most commonly encountered diagnosis among patients seen for upper abdominal

discomfort is non-ulcer dyspepsia (NUD).

• NUD, also known as functional dyspepsia or essential dyspepsia, refers to a group of

heterogeneous disorders typified by upper abdominal pain without the presence of an

ulcer.

• Several additional disease processes that may present with ‘ulcer-like symptoms include

Gastroesophageal reflux

Pancreasticcobiliary disease (biliary colic, chronic pancreatitis)

Proximal gastrointestinal tumors

Vascular disease

Crohn's disease

Investigations

• No investigation for the peptic ulcer that can be done at the dispensary or health center level,

hence patients with suspected peptic ulcers should be referred for investigations.

• Documentation of an ulcer requires either a radiographic (barium study) or an endoscopic

procedure.

Barium Meal

• Barium studies of the proximal gastrointestinal tract are still commonly used as a first test

for documenting an ulcer.

• The sensitivity of older single-contrast barium meals for detecting a DU is as high as

80%, with a double-contrast study providing detection rates as high as 90%.

• Radiographic studies that show a GU must be followed by endoscopy and biopsy.

Endoscopy (Esophagogastroduodenoscopy -OGD)

• Provides the most sensitive and specific approach for examining the upper

gastrointestinal tract.

• Permits direct visualization of the mucosa, endoscopy facilitates photographic

documentation of a mucosal defect and tissue biopsy to rule out malignancy (GU) or

H. pylori

Diagnosis of H. Pylori

• The tests for these are done in more specialized hospitals and maybe for research

purposes.

• Several H. pylori tests are available. They are classified as either non-endoscopy

based or endoscopy based.

• Non-endoscopy-based H. pylori tests are available.

H. pylori stool antigen test (HpSA)

Urea breathe test

Presence of antibodies to H. pylori in the serum

• Three endoscopy-based H. pylori tests are available

Rapid urease test (RUT)

Bacterial culture H. pylori

Histologic detection of H. pylori in the biopsy specimen

Treatment

• Essentially treatment is initiated at the hospital, at dispensary what is done is follow-up,

and pre-referral treatment of suspected PUD is the same as in Gastritis.

• Before the discovery of H. pylori, the therapy of PUD disease was centered on the old

dictum by Schwartz of ‘no acid, no ulcer.’

• Although acid secretion is still important in the pathogenesis of PUD, eradication of

H. pylori and therapy/prevention of NSAID-induced disease is the mainstay.

• The clinician's goal in treating PUD is to

Provide relief of symptoms (pain or dyspepsia)

Promote ulcer healing

Prevent ulcer recurrence and complications

• Once an ulcer (GU or DU) is documented, then the main issue at stake is whether

H. pylori or an NSAID is involved.

• With H. pylori present, independent of the NSAID status, triple therapy is recommended

for 14 days, followed by continued acid-suppressing drugs (H2 receptor antagonist or

PPIs) for a total of 4 to 6 weeks.

Therapy for H. Pylori

• H. pylori should be eradicated in patients with documented PUD

• This holds true independent of time of presentation (first episode or not), severity of

symptoms, presence of confounding factors such as ingestion of NSAIDs, or whether the

an ulcer is in remission.

• Documented eradication of H. pylori in patients with PUD is associated with a dramatic

decrease in ulcer recurrence.

• Combination therapy for 14 days provides the greatest efficacy.

• The agents used with the greatest frequency include amoxicillin, metronidazole,

tetracycline, clarithromycin, and bismuth compounds.

Triple Therapy

• The most common regime in our environment is Amoxicillin, Metronidazole and

omeprazole other regimens include

Lansoprazole, clarithromycin, and amoxicillin

Bismuth subsalicylate, tetracycline, and metronidazole, etc.

Dosing

• Amoxicillin 500 mg PO every 8 hours

• Metronidazole 400 mg PO every 8 hours

• Clarithromycin 500 mg PO every 12 hours

• Omeprazole 20 mg once a day

• Lansoprazole 20-40 mg once a day

Therapy of NSAID-Related Gastric or Duodenal Injury

• Medical intervention for NSAID-related mucosal injury includes treatment of an active

ulcer and prevention of future injury.

• Ideally the injurious agent should be stopped as the first step in the therapy of an active

NSAID-induced ulcer.

• If that is possible, then treatment with one of the acid inhibitory agents (H2 blockers or

PPIs) is indicated.

• Cessation of NSAIDs is not always possible because of the patient's severe underlying

disease (e.g. Arthritis).

• Only PPIs can heal Gus or DUs, independent of whether NSAIDs are discontinued.

• Prevention of NSAID-induced ulceration can be accomplished by misoprostol (200μg

qid) or a PPI.

• High-dose H2 blockers (famotidine, 40 mg bid) have also shown some promise.

• The majority (>90%) of Gus and DUs heal with the conventional therapy outlined above

• GU that fails to heal after 12 weeks and a DU that doesn't heal after 8 weeks of therapy

should be considered refractory.

• Once poor compliance and persistent H. pylori infection have been excluded, NSAID use,

either inadvertent or surreptitious, must be excluded.

• In addition, cigarette smoking must be eliminated.

• For a GU, malignancy must be meticulously excluded.

• More than 90% of refractory ulcers (either DUs or Gus) heal after 8 weeks of treatment

with higher doses of PPI (omeprazole, 40 mg/d). This higher dose is also effective in

maintaining remission.                                                                                     

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