Peptic ulcer

Introduction A stomach or gastric ulcer is a break in the tissue lining the stomach. The term 'peptic ulcer' refers to those that occur in either the stomach or the first part of the small intestine that leads out of the stomach, called the duodenum. It was once commonly thought that stress, smoking and diet were the principal causes of stomach ulcers. However, the Helicobacter pylori (H. pylori) bacterium is now known to be responsible for most duodenal ulcers and 60 per cent of stomach ulcers. The H. pylori bacterium also prompts many symptoms of dyspepsia, or indigestion. Treatment for stomach ulcers includes the use of antibiotics to kill the infection, and acid-suppressing drugs.

Cause
Another possible reason why people develop the duodenal ulcer disease is because of a condition known as Zollinger-Ellison syndrome that causes excessive production of acids which will then overpower the stomachs protective layering and cause duodenal ulcers. A major causative factor (60% of gastric and up to 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonizes 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 by that part of the stomach, and gastrin secretion can either be decreased (most cases) resulting in hypo- or achlorhydria or increased. Gastrin stimulates the production of gastric acid by parietal cells and, in H. pylori colonization responses that increase gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation. Another major cause is the use of NSAIDs (see above). 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 function of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins. COX-2 selective anti-inflammatories (such as celecoxib or the since withdrawn rofecoxib) preferentially inhibit cox-2, which is less essential in the gastric mucosa, and roughly halve the risk of NSAID-related gastric ulceration. As the prevalence of H. pyloricaused ulceration declines in the Western world due to increased medical treatment, a greater proportion of ulcers will be due to increasing NSAID use among individuals with pain syndromes as well as the growth of aging populations that develop arthritis. The incidence of duodenal ulcers has dropped significantly during the last 30 years, while the incidence of gastric ulcers has shown a small increase, mainly caused by the widespread use of NSAIDs. The drop in incidence is considered to be a cohort-phenomena independent of the

progress in treatment of the disease. The cohort-phenomena is probably explained by improved standards of living which has lowered the incidence of H. pylori infections.[4] Tobacco smoking leads to atherosclerosis and vascular spasms, causing vascular insufficiency and promoting the development of ulcers through ischemia. Nicotine contained in cigarettes can increase parasympathetic nerve activity to the gastrointestinal tract by acting on the nicotinic receptors at synapses - increased stimulation to the enterochromaffin-like cells and G cells increases the amount of histamine and gastrin secreted and therefore increases the acidity of the gastric juice. Similarly, glucocorticoids lead to atrophy of all epithelial tissues. However, these factors, along with diet or spices, blood type, and other factors suspected to cause ulcers until late in the 20th century, are actually of relatively minor importance in the development of peptic ulcers.[5] Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors, also cause multiple and difficult to heal ulcers.

[edit] Stress
Researchers also continue to look at stress as a possible cause, or at least complication, in the development of ulcers. There is debate as to whether psychological stress can influence the development of peptic ulcers. Burns and head trauma, however, can lead to physiologic stress ulcers, which are reported in many patients who are on mechanical ventilation. An expert panel convened by the Academy of Behavioral Medicine Research concluded that ulcers are not purely an infectious disease and that psychological factors do play a significant role.[1] Researchers are examining how stress might promote H. pylori infection. For example, Helicobacter pylori thrives in an acidic environment, and stress has been demonstrated to cause the production of excess stomach acid. This was supported by a study on mice showing that both long-term water-immersion-restraint stress and H. pylori infection were independently associated with the development of peptic ulcers.[6] A study of peptic ulcer patients in a Thai hospital showed that chronic stress was strongly associated with an increased risk of peptic ulcer, and a combination of chronic stress and irregular mealtimes was a significant risk factor.[7]

Symptoms Some stomach ulcers are asymptomatic. The symptoms of a stomach ulcer can include:

Abdominal pain just below the ribcage Indigestion Nausea

Loss of appetite Vomiting Weight loss Altered blood present in the vomit or in the bowel motions (occasionally) Symptoms of anaemia, such as light-headedness.

Signs and symptoms

Symptoms of a peptic ulcer can be

abdominal pain, classically epigastric with severity relating to mealtimes, after around 3 hours of taking a meal (duodenal ulcers are classically relieved by food, while gastric ulcers are exacerbated by it); bloating and abdominal fullness; waterbrash (rush of saliva after an episode of regurgitation to dilute the acid in esophagus); nausea, and copious vomiting; loss of appetite and weight loss; hematemesis (vomiting of blood); this can occur due to bleeding directly from a gastric ulcer, or from damage to the esophagus from severe/continuing vomiting. melena (tarry, foul-smelling feces due to oxidized iron from hemoglobin); rarely, an ulcer can lead to a gastric or duodenal perforation. This is extremely painful and requires immediate surgery.

A history of heartburn, gastroesophageal reflux disease (GERD) and use of certain forms of medication can raise the suspicion for peptic ulcer. Medicines associated with peptic ulcer include NSAID (non-steroid anti-inflammatory drugs) that inhibit cyclooxygenase, and most glucocorticoids (e.g. dexamethasone and prednisolone). In patients over 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by EGD (see below). The timing of the symptoms in relation to the meal may differentiate between gastric and duodenal ulcers: A gastric ulcer would give epigastric pain during the meal, as gastric acid is secreted, or after the meal, as the alkaline duodenal contents reflux into the stomach. Symptoms of duodenal ulcers would manifest mostly before the mealwhen acid (production stimulated by hunger) is passed into the duodenum. However, this is not a reliable sign in clinical practice.

[edit] Complications

Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening.[2] It occurs when the ulcer erodes one of the blood vessels. Perforation (a hole in the wall) often leads to catastrophic consequences. Erosion of the gastro-intestinal wall by the ulcer leads to spillage of stomach or intestinal content into the abdominal cavity. Perforation at the anterior surface of the stomach leads to acute peritonitis, initially chemical and later bacterial peritonitis. The first sign is often sudden intense abdominal pain. Posterior wall perforation leads to pancreatitis; pain in this situation often radiates to the back. Penetration is when the ulcer continues into adjacent organs such as the liver and pancreas.[3] Scarring and swelling due to ulcers causes narrowing in the duodenum and gastric outlet obstruction. Patient often presents with severe vomiting. Pyloric stenosis

Diagnosis methods Diagnosing a stomach ulcer is done using a range of methods, including: Endoscopy - a thin flexible tube is threaded down the oesophagus into the stomach under light anaesthesia. The endoscope is fitted with a small camera so the physician can see if there is an ulcer. Barium meal - a chalky liquid is drunk and an x-ray is performed, showing the stomach lining. These tests are less common nowadays, but may be useful where endoscopy is unavailable.

Biopsy - a small tissue sample is taken during an endoscopy and tested in a laboratory. This biopsy should always be done if a gastric ulcer is found. C14 breath test - to check for the presence of H. pylori. The bacteria convert urea into carbon dioxide. The test involves swallowing an amount of radioactive carbon (C14) and testing the air exhaled from the lungs. A non-radioactive test can be used for children and pregnant women.

Diagnosis

Endoscopic image of gastric ulcer, biopsy proven to be gastric cancer. 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. The diagnosis of Helicobacter pylori can be made by:

Urea breath test (noninvasive and does not require EGD); Direct culture from an EGD biopsy specimen; this is difficult to do, and can be expensive. Most labs are not set up to perform H. pylori cultures; Direct detection of urease activity in a biopsy specimen by rapid urease test; Measurement of antibody levels in blood (does not require EGD). It is still somewhat controversial whether a positive antibody without EGD is enough to warrant eradication therapy; Stool antigen test; Histological examination and staining of an EGD biopsy.

The possibility of other causes of ulcers, notably malignancy (gastric cancer) needs to be kept in mind. This is especially true in ulcers of the greater (large) curvature of the stomach; most are also a consequence of chronic H. pylori infection. 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 Xray, 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.

[edit] Macroscopic appearance

A benign gastric ulcer (from the antrum) of a gastrectomy specimen. Gastric ulcers are most often localized on the lesser curvature of the stomach. The ulcer 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 irregular in the acute form of peptic ulcer, regular but with elevated borders and inflammatory surrounding in the chronic form. In the ulcerative form of gastric cancer the borders are irregular. Surrounding mucosa may present radial folds, as a consequence of the parietal scarring.

[edit] Microscopic appearance

A 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.[8]

[edit] Differential diagnosis of epigastric pain

Peptic ulcer Gastritis Stomach cancer Gastroesophageal reflux disease Pancreatitis Hepatic congestion Cholecystitis Biliary colic Inferior myocardial infarction

Referred pain (pleurisy, pericarditis) Superior mesenteric artery syndrome

Treatment options Special diets are now known to have very little impact on the prevention or treatment of stomach ulcers. Treatment options can include: Medications - including antibiotics, to destroy the H. pylori colony, and drugs to help speed the healing process. Different drugs need to be used in combination; some of the side effects can include diarrhoea and rashes. Resistance to some of these antibiotics is becoming more common. Subsequent breath tests - used to make sure the H. pylori infection has been treated successfully.

Changes to existing medications - the doses of arthritis medications, aspirin or other anti-inflammatory drugs can be altered slightly to reduce their contributing effects on the stomach ulcer. Reducing acid - tablets are available to reduce the acid content in the gastric juices. Lifestyle modifications - such as quitting cigarettes, since smoking reduces the natural defences in the stomach and impairs the healing process.

Treatment
Younger patients with ulcer-like symptoms are often treated with antacids or H2 antagonists before EGD is undertaken. Bismuth compounds may actually reduce or even clear organisms, though it should be noted that the warning labels of some bismuth subsalicylate products indicate that the product should not be used by someone with an ulcer. Patients who are taking nonsteroidal anti-inflammatories (NSAIDs) may also be prescribed a prostaglandin analogue (Misoprostol) in order to help prevent peptic ulcers, which may be a side-effect of the NSAIDs. When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. Clarithromycin, Amoxicillin, Tetracycline, Metronidazole) and 1 proton pump

inhibitor (PPI), sometimes together with a bismuth compound. In complicated, treatmentresistant cases, 3 antibiotics (e.g. amoxicillin + clarithromycin + metronidazole) may be used together with a PPI and sometimes with bismuth compound. An effective first-line therapy for uncomplicated cases would be Amoxicillin + Metronidazole + Pantoprazole (a PPI). In the absence of H. pylori, long-term higher dose PPIs are often used. Treatment of H. pylori usually leads to clearing of infection, relief of symptoms and eventual healing of ulcers. Recurrence of infection can occur and retreatment may be required, if necessary with other antibiotics. Since the widespread use of PPI's in the 1990s, surgical procedures (like "highly selective vagotomy") for uncomplicated peptic ulcers became obsolete. Perforated peptic ulcer is a surgical emergency and requires surgical repair of the perforation. Most bleeding ulcers require endoscopy urgently to stop bleeding with cautery, injection, or clipping.

What are some complications from ulcers? People with ulcers may experience serious complications if they do not get treatment. The most common problems include:

bleeding As an ulcer eats into the muscles of the stomach or duodenal wall, blood vessels may also be damaged, causing bleeding.

perforation Sometimes an ulcer eats a hole in the wall of the stomach or duodenum, and bacteria and partially digested food can spill through the opening into the sterile abdominal cavity (peritoneum) and cause peritonitis, an inflammation of the abdominal cavity and wall.

narrowing and obstruction Ulcers located at the end of the stomach, where the duodenum is attached, can cause swelling and scarring, which can narrow or close the intestinal opening. This obstruction can prevent food from leaving the stomach and entering the small intestine, resulting in vomiting the contents of the stomach.