Gastric ulcer

Overview

Gastric ulcers are a frequent clinical presentation in the United States, and they frequently result in the expenditure of millions of dollars on healthcare. They are larger than 5 mm in diameter and are a break in the mucosal barrier of the stomach lining that penetrates through the muscularis mucosa.

It is critical to recognize that this illness process is both preventable and treated. Depending on the cause of the gastric ulcer, patients may be treated differently. The stomach mucosa is naturally protected by the body from the hazardous acidic environment of the gastric lumen. When these defenses are compromised, it can cause changes in the stomach mucosa, which can lead to erosion and finally ulceration.

Prostaglandins, mucus, growth factors, and proper blood supply protect the gastric mucosa. Smoking, hydrochloric acid, ischemia, NSAID drugs, hypoxia, alcohol, and Helicobacter pylori infection are all known to be harmful to this barrier. 

What causes Gastric ulcer?

1. H. pylori:

Helicobacter pylori is one of the most common causes of peptic ulcer disease. It secretes urease to provide an alkaline conditions favorable to survival. It expresses blood group antigen adhesin (BabA) and outer inflammatory protein adhesin (OipA), allowing it to bind to the stomach epithelium. The bacterium also expresses virulence proteins such CagA and PicB, which promote mucosal inflammation in the stomach.

This type of stomach mucosal inflammation can be accompanied with hyperchlorhydria (increased stomach acid secretion) or hypochlorhydria (decreased stomach acid secretion) (reduced stomach acid secretion). Inflammatory cytokines reduce acid production from parietal cells.

H. pylori also secretes molecules that inhibit hydrogen potassium ATPase, activate calcitonin gene-related peptide sensory neurons, increasing somatostatin secretion to reduce parietal cell acid generation, and inhibit gastrin secretion. Gastric ulcers are caused by a decrease in acid production.

Increased acid production at the pyloric antrum, on the other hand, is related with duodenal ulcers in 10% to 15% of H. pylori infection patients. In this situation, somatostatin production is reduced while gastrin production is raised, resulting in greater histamine secretion from enterochromaffin cells and, as a result, increased acid generation. An acidic environment at the antrum induces duodenal cell metaplasia, resulting in duodenal ulcers.

2. NSAIDs:

When compared to non-users, taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin can increase the risk of peptic ulcer disease by four times. Aspirin users are twice as likely to develop a peptic ulcer. When NSAIDs are used with a selective serotonin reuptake inhibitor (SSRI), corticosteroids, antimineralocorticoids, or anticoagulants, the risk of bleeding increases.

The gastric mucosa shields itself against gastric acid by secreting mucus, which is triggered by specific prostaglandins. NSAIDs inhibit the function of cyclooxygenase 1 (COX-1) in the generation of these prostaglandins. NSAIDs also limit stomach mucosa cell proliferation and mucosal blood flow, lowering bicarbonate and mucus output and thereby mucosal integrity.

COX-2 selective anti-inflammatory medications (such as celecoxib) are another type of NSAID that preferentially inhibit COX-2, which is less important in the gastric mucosa. This lessens the likelihood of developing peptic ulcers; nevertheless, it can still cause ulcer healing to be delayed in people who already have a peptic ulcer.

Peptic ulcers caused by NSAIDs differ from those caused by H. pylori in that the latter appear as a result of mucosal inflammation (presence of neutrophils and submucosal edema), whereas the former appear as a result of direct NSAID molecule damage to COX enzymes, altering the hydrophobic state of the mucus, permeability of the lining epithelium, and mitochondrial machinery of the cell itself.

As a result, NSAID-induced ulcers tend to worsen faster and dig deeper into the tissue, creating greater difficulties, frequently asymptomatically until a large amount of the tissue is affected.

3. Stress:

Stress caused by major health conditions, such as those requiring intensive care unit treatment, is well recognized as a cause of peptic ulcers, often known as stress ulcers.

Chronic life stress was originally thought to be the primary cause of ulcers, but this is no longer the case. It is, however, occasionally thought to play a role. This may be due to the well-documented effects of stress on gastric physiology, increasing the risk in those with other causes, such as H. pylori or NSAID use.

4. Diet:

Until the late twentieth century, dietary factors such as spice consumption were thought to cause ulcers, but they were later proved to be of minor significance. Caffeine and coffee, which are often assumed to cause or worsen ulcers, appear to have minimal effect. 

Similarly, while studies have shown that alcohol use increases risk when combined with H. pylori infection, it does not appear to raise risk on its own. Even when H. pylori infection is present, the increase is minor in relation to the underlying risk factor. It is still unclear if smoking increases the risk of getting peptic ulcers. 

5. Infections and chronic diseases:

Other causes of peptic ulcer disease include gastric ischaemia, drugs, metabolic disturbances, cytomegalovirus (CMV), upper abdominal radiotherapy, Crohn's disease, and vasculitis. Gastrinomas (Zollinger–Ellison syndrome), or rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers.

How Gastric ulcer happens?

The insult determines the pathophysiology of stomach ulcer formation. Because Helicobacter pylori and/or NSAID use cause around 80 to 90 percent of stomach ulcers, a full discussion will focus on each in depth.

To begin, Helicobacter pylori colonizes approximately 45-50 percent of the stomach mucosa worldwide. It is a bacterium that gets introduced into children at a young age, particularly in underdeveloped nations with low socioeconomic level and crowded houses. These bacteria cause an inflammatory reaction in the host, resulting in gastritis, which is characterized by an epithelial response, degeneration, and damage.

Pan-gastritis is a common complication of this infection. This impairs antral somatostatin release, causing an increase in gastrin secretion and, as a result, increased acid generation. Patients who develop stomach ulcers have bacteria that has stayed in the antrum. Parietal cells in the more proximal stomach body continue to produce fully, preventing ulcer formation in this location.

It should be noted that not all individuals with this infection experience symptom; this is determined by the virulence of the bacterium as well as other host risk factors. CagA production is a frequent bacterial virulence factor that leads to increased cytokine cell death and mucosal injury.

NSAID drugs are the second most common cause of stomach ulcers. Patients who take these drugs have a four-fold increased chance of getting stomach ulcers as compared to those who do not. There are several mechanisms by which NSAIDs cause ulceration. When the medications are subjected to gastric acid, they become weak acids.

They persist in the epithelial cells, increasing cellular permeability and causing physical cellular harm. The decrease in prostaglandin synthesis is the major mechanism of NSAID-induced ulceration. NSAIDs block the cyclooxygenase-1 enzyme, which promotes prostaglandin synthesis, resulting in gastric bicarbonate secretion, mucus barrier creation, enhanced mucosal blood flow, and quicker epithelial cell restitution and repair following injury or cell death.

NSAIDs make the stomach mucosa more sensitive to injury from gastric acid and pepsin. Overall, the most dangerous physiological damage is caused by a decrease in gastric blood flow and the mild ischemia it generates in the gastric mucosa.

Overall, the pathophysiology of gastric ulcer development is determined by the etiology, although all result in the loss or destruction of stomach mucosal integrity.

Microscopic Changes happens in Gastric ulcer

On histopathology, one will see an ulcer base with clear margins that penetrate the muscularis propria and into the submucosa. Inflammatory debris on the epithelial surface is often present. In the submucosa, one will see fibrosis and thickened blood vessels.

Signs and symptoms of Gastric ulcer

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 (a rush of saliva after an episode of regurgitation to dilute the acid in esophagus, although this is more associated with gastroesophageal reflux disease).
• 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 (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 presence of oxidized iron from hemoglobin).
• Rarely, an ulcer can lead to a gastric or duodenal perforation, which leads to acute peritonitis and extreme, stabbing pain,and requires immediate surgery.

A history of heartburn or gastroesophageal reflux disease (GERD), as well as the use of certain drugs, can raise the possibility of peptic ulcer. NSAIDs (non-steroidal anti-inflammatory medicines) that block cyclooxygenase and most glucocorticoids have been linked to peptic ulcer (e.g., dexamethasone and prednisolone).

The odds of peptic ulceration in adults over the age of 45 with more than two weeks of the above symptoms are high enough to justify immediate evaluation by esophagogastroduodenoscopy.

The timing of symptoms in relation to meals can help distinguish between gastric and duodenal ulcers. Because gastric acid production increases when food enters the stomach, a gastric ulcer would cause epigastric pain during the meal, along with nausea and vomiting. Duodenal ulcer pain is increased by hunger and reduced by eating, and it is related with nocturnal discomfort.

Furthermore, the symptoms of peptic ulcers can vary depending on the location of the ulcer and the person's age. Furthermore, because ordinary ulcers heal and reoccur, the pain may last for a few days or weeks before fading or disappearing. Unless difficulties arise, children and the elderly usually do not exhibit any symptoms.

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. 

Diagnosis of Gastric ulcer 

The diagnosis is primarily determined by the distinctive symptoms. Stomach pain is often the initial symptom of a gastric ulcer. In other circumstances, doctors may treat ulcers without performing particular tests and then observe whether the symptoms resolve, indicating that their basic diagnosis was correct.

Tests such as endoscopies and barium contrast x-rays are used to confirm the diagnosis. Because stomach cancer can cause similar symptoms, the tests are often requested if the symptoms do not resolve after a few weeks of treatment, or if they first develop in a person over the age of 45 or who has other symptoms such as weight loss. In addition, when serious ulcers resist therapy, especially if a person has numerous ulcers or the ulcers are in strange spots, a doctor may suspect an underlying illness that causes the stomach to overproduce acid.

When a peptic ulcer is suspected, an esophagogastroduodenoscopy (EGD), a type of endoscopy commonly known as a gastroscopy, is performed. It is also the gold standard for peptic ulcer disease diagnosis. The location and severity of an ulcer can be described by direct visual identification. Furthermore, if no ulcer is evident, EGD can frequently offer a different 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 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 the 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 breath test detects H. pylori using radioactive carbon. The person is instructed to drink a tasteless liquid that contains carbon as part of the component that the bacteria breaks down in order to complete this exam. After an hour, the subject is instructed to blow into a sealed bag. The breath sample will contain radioactive carbon dioxide if the person is afflicted with H. pylori. This test has the advantage of allowing you to track the reaction to the bacteria-killing medication.

Other causes of ulcers, most notably malignancy (gastric cancer), must be considered. This is especially true for ulcers of the greater curvature of the stomach, the majority of which are caused by persistent H. pylori infection.

When a peptic ulcer ruptures, air leaks from the gastrointestinal system (which always includes some air) to the peritoneal cavity (which normally never contains air). As a result, "free gas" accumulates within the peritoneal cavity. When a person stands, such as when having a chest X-ray, the gas floats to a place behind the diaphragm. As a result, gas in the peritoneal cavity, as seen on an erect chest X-ray or a supine lateral abdominal X-ray, is an indication of perforated peptic ulcer illness.

Treatment / Management of Gastric ulcer

The goal of gastric ulcer treatment and management is to first raise the gastric pH and allow the gastric mucosa to heal, which can be accomplished by providing proton pump inhibitors such as pantoprazole. The next step should be to decide whether or not to proceed with an EGD. Alarm symptoms should be identified, making the need for an EGD even more pressing. Unintentional weight loss, bleeding, being above the age of 50, nausea, and vomiting are all red flags. 

If an EGD reveals a stomach ulcer, biopsies of the mucosa surrounding the ulcer will be required to rule out gastritis, Helicobacter pylori infection, and cancer. These individuals must take PPIs twice daily for 8 weeks before having a repeat endoscopy to confirm healing.

If the patient is taking NSAIDs, they must be stopped as away. If the biopsies or lab testing show that you have Helicobacter pylori infection, you will need antibiotics to treat it, and eradication must be proved.

If the gastric ulcer is bleeding or has a higher Forrest classification, many techniques can be used to stop and prevent further bleeding. Epinephrine injection with cautery or insertion of a metal or absorbable clip is usually effective.

When endoscopic therapy is insufficient or not advised, surgical intervention may be required. Perforation, uncontrolled bleeding, significant gastric outlet obstruction, and ulcers that have not healed with medicinal therapy are all indications for surgical intervention. 

Complications of Gastric ulcer

1. Gastrointestinal bleeding: it is the most common complication. Sudden large bleeding can be life-threatening. It is associated with 5% to 10% death rate.
2. Perforation: (a hole in the gastrointestinal tract's wall) caused by a stomach ulcer can have disastrous effects if left untreated. The ulcer's erosion of the gastrointestinal wall causes leakage of stomach or intestine contents into the abdominal cavity, resulting in severe chemical peritonitis. The first symptom is frequently severe abdominal discomfort, as observed in Valentino's syndrome. Due to the involvement of the gastroduodenal artery, which sits posterior to the first part of the duodenum, posterior gastric wall perforation may result in bleeding. In this situation, the death rate is 20%.
3. Penetration: it is a form of perforation in which the hole leads to and the ulcer continues into adjacent organs such as the liver and pancreas.
4. Gastric outlet obstruction (stenosis): it 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.
5. Gastric tumor: Cancer is included in the differential diagnosis (elucidated by biopsy), 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.

Conclusion

A gastric ulcer is a break in the stomach's inner lining, the first section of the small intestine, or, in some cases, the lower esophagus. 

The most typical symptoms include waking up in the middle of the night with upper abdominal pain and upper abdominal pain that worsens after you eat. The sensation is frequently described as a burning or dull aching. Other signs include belching, vomiting, weight loss, and a loss of appetite. A third of the elderly show no symptoms. Complications may include bleeding, perforation, and stomach obstruction. Bleeding can occur in up to 15% of cases.

The bacteria Helicobacter pylori and nonsteroidal anti-inflammatory medications are two common causes (NSAIDs). Tobacco usage, stress as a result of other major health disorders, Behçet's illness, Zollinger–Ellison syndrome, Crohn's disease, and liver cirrhosis are some of the less prevalent reasons.

The ulcer-causing effects of NSAIDs are particularly marked in the elderly. The diagnosis is usually suspected based on the presenting symptoms, and it is confirmed by endoscopy or barium swallow. H. pylori can be diagnosed through blood testing for antibodies, urea breath testing, stool testing for indications of the bacteria, or a stomach biopsy. Stomach cancer, coronary heart disease, and stomach lining or gallbladder inflammation are all illnesses that cause comparable symptoms.

Diet has no effect on the development or prevention of ulcers. Treatment involves quitting smoking, discontinuing NSAIDs, abstaining from alcohol, and taking drugs to reduce stomach acid. A proton pump inhibitor (PPI) or an H2 blocker is typically used to reduce acid, with four weeks of treatment initially advised. H. pylori ulcers are treated with a mix of drugs, including amoxicillin, clarithromycin, and a PPI. Because antibiotic resistance is on the rise, treatment may not always be successful. Endoscopy can be used to treat bleeding ulcers, with surgical surgery being reserved for cases when endoscopy fails.