Peptic ulcer disease
Peptic ulcer disease refers to damage of the inner part of the stomach's gastric mucosa, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines is a duodenal ulcer. The most common symptoms of a duodenal ulcer are waking at night with upper abdominal pain, and upper abdominal pain that improves with eating. With a gastric ulcer, the pain may worsen with eating. The pain is often described as a burning or dull ache. Other symptoms include belching, vomiting, weight loss, or poor appetite. About a third of older people with peptic ulcers have no symptoms. Complications may include bleeding, perforation, and blockage of the stomach. Bleeding occurs in as many as 15% of cases.
Common causes include infection with Helicobacter pylori and non-steroidal anti-inflammatory drugs. Other, less common causes include tobacco smoking, stress as a result of other serious health conditions, Behçet's disease, Zollinger–Ellison syndrome, Crohn's disease, and liver cirrhosis. Older people are more sensitive to the ulcer-causing effects of NSAIDs. The diagnosis is typically suspected due to the presenting symptoms with confirmation by either endoscopy or barium swallow. H. pylori can be diagnosed by testing the blood for antibodies, a urea breath test, testing the stool for signs of the bacteria, or a biopsy of the stomach. Other conditions that produce similar symptoms include stomach cancer, coronary heart disease, and inflammation of the stomach lining or gallbladder inflammation.
Diet does not play an important role in either causing or preventing ulcers. Treatment includes stopping smoking, stopping use of NSAIDs, stopping alcohol, and taking medications to decrease stomach acid. The medication used to decrease acid is usually either a proton pump inhibitor or an H2 blocker, with four weeks of treatment initially recommended. Ulcers due to H. pylori are treated with a combination of medications, such as amoxicillin, clarithromycin, and a PPI. Antibiotic resistance is increasing and thus treatment may not always be effective. Bleeding ulcers may be treated by endoscopy, with open surgery typically only used in cases in which it is not successful.
Peptic ulcers are present in around 4% of the population. New ulcers were found in around 87.4 million people worldwide during 2015. About 10% of people develop a peptic ulcer at some point in their life. Peptic ulcers resulted in 267,500 deaths in 2015, down from 327,000 in 1990. The first description of a perforated peptic ulcer was in 1670, in Princess Henrietta of England. H. pylori was first identified as causing peptic ulcers by Barry Marshall and Robin Warren in the late 20th century, a discovery for which they received the Nobel Prize in 2005.
Signs and symptoms
Signs and symptoms of a peptic ulcer can include one or more of the following:- abdominal pain, classically epigastric, strongly correlated with mealtimes. In case of duodenal ulcers, the pain appears about three hours after taking a meal and wakes the person from sleep;
- bloating and abdominal fullness;
- waterbrash ;
- nausea and copious vomiting;
- loss of appetite and weight loss, in gastric ulcer;
- weight gain, in duodenal ulcer, as the pain is relieved by eating;
- hematemesis ; this can occur due to bleeding directly from a gastric ulcer or from damage to the esophagus from severe/continuing vomiting.
- melena ;
- rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis and extreme, stabbing pain, and requires immediate surgery.
In people over the age of 45 with more than two weeks of the above symptoms, the odds for peptic ulceration are high enough to warrant rapid investigation by esophagogastroduodenoscopy.
The timing of symptoms in relation to the meal may differentiate between gastric and duodenal ulcers. A gastric ulcer would give epigastric pain during the meal, associated with nausea and vomiting, as gastric acid production is increased as food enters the stomach. Pain in duodenal ulcers would be aggravated by hunger and relieved by a meal and is associated with night pain.
Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the person's age. Furthermore, typical ulcers tend to heal and recur, and as a result the pain may occur for few days and weeks and then wane or disappear. Usually, children and the elderly do not develop any symptoms unless complications have arisen.
A burning or gnawing feeling in the stomach area lasting between 30 minutes and 3 hours commonly accompanies ulcers. This pain can be misinterpreted as hunger, indigestion, or heartburn. Pain is usually caused by the ulcer, but it may be aggravated by the stomach acid when it comes into contact with the ulcerated area. The pain caused by peptic ulcers can be felt anywhere from the navel up to the sternum, it may last from a few minutes to several hours, and it may be worse when the stomach is empty. Also, sometimes the pain may flare at night, and it can commonly be temporarily relieved by eating foods that buffer stomach acid or by taking anti-acid medication. However, peptic ulcer disease symptoms may be different for everyone.
Complications
- Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It is associated with 5% to 10% death rate.
- Perforation following a gastric ulcer often leads to catastrophic consequences if left untreated. Erosion of the gastrointestinal wall by the ulcer leads to spillage of the stomach or intestinal contents into the abdominal cavity, leading to an acute chemical peritonitis. The first sign is often sudden intense abdominal pain, as seen in Valentino's syndrome. Posterior gastric wall perforation may lead to bleeding due to the involvement of gastroduodenal artery that lies posterior to the first part of the duodenum. The death rate in this case is 20%.
- Penetration is a form of perforation in which the hole leads to and the ulcer continues into adjacent organs such as the liver and pancreas.
- Gastric outlet obstruction is a narrowing of the pyloric canal by scarring and swelling of the gastric antrum and duodenum due to peptic ulcers. The person often presents with severe vomiting.
- Cancer is included in the differential diagnosis, Helicobacter pylori as the etiological factor making it 3 to 6 times more likely to develop stomach cancer from the ulcer. The risk for developing gastrointestinal cancer also appears to be slightly higher with gastric ulcers.
Cause
''H. pylori''
Helicobacter pylori is one of the major causative factors of peptic ulcer disease. It secretes urease to create an alkaline environment, which is suitable for its survival. It expresses blood group antigen-binding adhesin and outer inflammatory protein adhesin, which enables it to attach to the gastric epithelium. The bacterium also expresses virulence factors such as CagA and PicB, which cause stomach mucosal inflammation. The VacA gene encodes for vacuolating cytotoxin, but its mechanism of causing peptic ulcers is unclear. Such stomach mucosal inflammation can be associated with hyperchlorhydria or hypochlorhydria. Inflammatory cytokines inhibit the parietal cell acid secretion. H. pylori also secretes certain products that inhibit hydrogen potassium ATPase; activate calcitonin gene-related peptide sensory neurons, which increases somatostatin secretion to inhibit acid production by parietal cells; and inhibit gastrin secretion. This reduction in acid production causes gastric ulcers. On the other hand, increased acid production at the pyloric antrum is associated with duodenal ulcers in 10% to 15% of H. pylori infection cases. In this case, somatostatin production is reduced and gastrin production is increased, leading to increased histamine secretion from the enterochromaffin cells, thus increasing acid production. An acidic environment at the antrum causes metaplasia of the duodenal cells, causing duodenal ulcers.Human immune response toward the bacteria also determines the emergence of peptic ulcer disease. The human IL1B gene encodes for Interleukin 1 beta, and other genes that encode for tumour necrosis factor and Lymphotoxin alpha also play a role in gastric inflammation.