Peptic ulcer overview

# Overview
Peptic ulcer disease is a defect in muscularis mucosa of gastrointestinal tract. Peptic ulcer is classified into 2 depending upon the location of ulcer, gastric ulcer and duodenal ulcer. The most common cause of peptic ulcer disease is H.pylori infection which is acquired in childhood but presents in adulthood. Other causes of peptic ulcer disease are chronic use of NSAID, family history of peptic ulcer disease. Persistant use of NSAIDS or chronic infection with H.Pylori results in inflammation of antral mucosa and ultimately causes the ulcer. The most common symptoms of peptic ulcer disease include episodic epigastric pain, heartburn, loss of appettite, gastroesophageal reflux, waterbrash, hematemesis and melena. Common physical examination findings of peptic ulcer disease include epigastric tenderness, tachycardia. Endoscopy is the gold standard test for the diagnosis of the peptic ulcer disease. Treatment of helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal ulceration. Pharmacologic therapies for peptic ulcer disease due to H. pylori is either triple or quadruple pharmacologic agents that include a Proton pump inhibitors plus a combination of antimicrobial agents.

# Historical Perspective
Hundred years ago, Polish clinical researcher, professor W.Jaworski  was the first to describe the spiral-shaped microorganism  at Cracow Jagiellonian University but it was later confirmed in the animal by G.Bizzazero.  Asklepios was the first to describe an association between GI bleeding and peptic ulcer disease. In 1982 Warren and B.J marshall cultured the organism and found a strong association between Helicobacter pylori and inflammation of gastric mucosa, not due to spicy food and stress and were awarded the noble prize.

# Classification
Peptic ulcer disease may be classified into two types based on the location, gastric ulcer and duodenal ulcer. Gastric ulcers are present mostly at lesser curvature of the stomach. Duodenal ulcers are mostly present at the duodenal bulb.

# Pathophysiology
A major causative factor (60% of gastric and 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonize the antral mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a defect in the regulation of gastrin production. Excess Gastrin stimulates the production of gastric acid by parietal cells. The acid erodes the mucosa and causes the ulcer. Another major cause of PUD is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the activity of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins.

# Causes
Common causes of peptic ulcer disease include Helicobacter pylori infection and NSAID use.  Less common causes of peptic ulcer disease include Crohn's disease, Zollinger-Ellison syndrome, Cushing and Curling ulcers, Carcinoid tumors, and carcinoid syndrome.

# Differentiating Peptic ulcer overview from Other Diseases
Peptic ulcer disease must be differentiated from other causes of acute upper gastrointestinal bleeding such as esophageal varices, Mallory-Weiss syndrome, gastrointestinal cancer, arteriovenous malformations, esophagitis, and esophageal ulcer.  Peptic ulcer disease must also be differentiated from gastroesophageal reflux disease (GERD,pancreatitis, Zollinger-Ellison Syndrome, Cholelithiasis, gastric outlet syndrome, myocardial infarction ,pleural empyema and  appendicitis.

# Epidemiology and Demographics
The incidence and prevalence of Helicobacter pylori infection are generally higher among people born outside North America. Within North America, the prevalence of the infection is higher in certain racial and ethnic groups, and people who have immigrated to North America. Peptic ulcer disease is acquired during childhood.The incidence of Peptic ulcer disease increases with age; the median age at diagnosis is 18-30 years. Peptic ulcer disease affect equally in childhood. Men are more commonly affected by peptic ulcer disease than women in adulthood.

# Risk Factors
Common risk factors in the development of peptic ulcer disease include infection from Helicobacter pylori, chronic use of NSAIDs, cigarette smoking, alcohol intake, family history of peptic ulcer, and age >50 years. Less common risk factors in the development of peptic ulcer disease include  psychological stress, nosocomial stress ulcers, and coagulopathy. Rare conditions associated with gastric acid hypersecretion, such as zollinger-ellison syndrome, mastocytosis, or a retained antrum following partial gastrectomy gastrinoma or multiple endocrine neoplasia types I (MEN-I), antral G cell hyperplasia, basophilic leukemias, short bowel syndrome.

# Screening
According to the American Society of Gastroenterology, screening for the Peptic Ulcer Disease is not recommended.

# Natural History, Complications, and Prognosis

## Natural History
The infection of Helicobacter pylori, a common cause of peptic ulcer disease is acquired usually during the childhood but presents in second to the fifth decade of life.Patient presents with episodic epigastric pain, indigestion, bloating, hematemesis and melena. Peptic ulcers tend to come back if untreated.

## Complications
Peptic ulcer disease if not treated, the patient can develop complications like bleeding, perforation, obstruction, stricture.Chronic infection of Helicobacter pylori leads to gastric cancer, MALT lymphoma, Iron deficiency anemia, Idiopathic thrombocytopenic purpura.

## Prognosis
Prognosis is good if the eradication therapy of Helicobacter pylori is taken.The recurrence rate of patients with peptic ulcer disease is less than 20%.

# Diagnosis

## Diagnostic Study of choice
Endoscopy is the gold standard test for the diagnosis of the peptic ulcer disease.

## History and Symptoms
The hallmark of peptic ulcer disease is an episodic epigastric pain which cause awakening at night.A positive history of epigastric pain, use of drugs like NSAIDs including aspirin  which inhibit cyclooxygenase, use of antiplatelets, steroids and family history of peptic ulcer disease is suggestive of peptic ulcer disease. The most common symptoms of peptic ulcer disease include episodic epigastric pain, heartburn, loss of appettite,  gastroesophageal reflux, waterbrash, hematemesis and melena. Less common symptoms of peptic ulcer disease include intolerance to fatty food.

## Physical Examination
Peptic ulcer disease patient appears in severe stress due to abdominal pain. Common physical examination findings of peptic ulcer disease include epigastric tenderness, tachycardia.Perforated peptic ulcer disease patient presents with  classic triad of severe epigastric tenderness, tachycardia and abdominal rigidity. Clinical signs of perforated peptic ulcer comes in 3 stages: In the initial stage within first 2 hours, the patient presents with tachycardia, epigastric pain and cool extremities. In next 2 to 12 hours, the patient presents with lower right quadrant tenderness and abdominal rigidity. In more than 12 hours, the patient presents with abdominal distension, hypotension, and pyrexia with acute circulatory collapse.

## Laboratory Findings
There is no specific diagnostic laboratory test for peptic ulcer disease but in the patient with the history of peptic ulcer disease, the laboratory test is used to rule out bleeding and to document the status of eradication therapy and to test refractory ulcers.

## Imaging Findings
If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to "free gas" within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease. An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis.

## Other diagnostic studies
Testing of  H.pylori infection is very important for treating ulcers. H.pylori tested by 2 methods : invasive and non-invasive. Rapid urease testing is invasive test which is used as diagnostic study of choice. Stool monoclonal antigen test is one of the non-invasive test which is used to diagnose active infection.

# Treatment

## Medical Therapy
Peptic ulcer disease is the cause of dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal peptic ulceration, who are colonized with H. pylori, and patients with MALT lymphoma. Eradication therapy should also be considered in patients with immune thrombocytopenic purpura who are H. pylori-positive and patients who have undergone resection for early-stage gastric cancer. Pharmacologic therapies for peptic ulcer disease due to H. pylori is either triple or quadruple pharmacologic agents that include a Proton pump inhibitors plus a combination of antimicrobial agents. The use of antimicrobial therapy is discouraged among asymptomatic carriers.

## Surgery
Surgery for peptic ulcer is indicated for bleeding and perforated peptic ulcer.Bleeding ulcers are usually treated  first with endoscopic therapy but if they bleed after endoscopic therapy, surgery is done to control bleeding. Perforated peptic ulcer is an emergency, immediate laparoscopic closure of ulcer is done.

## Prevention
Helicobacter pylori eradication has been proved as the most cost-effective strategy for primary prevention of NSAID-associated peptic ulcer, especially for patients above the age of 50 years.