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| PEPTIC ULCER |
What is a peptic ulcer?
A peptic ulcer is a break in the inner lining of the esophagus, stomach, or duodenum. A peptic ulcer of the stomach is called a gastric ulcer; of the duodenum, a duodenal ulcer; and of the esophagus, an esophageal ulcer. Peptic ulcers occur when the lining of these organs is corroded by the acidic digestive (peptic) juices which are secreted by the cells of the stomach. A peptic ulcer differs from an erosion because it extends deeper into the lining of the esophagus, stomach, or duodenum and excites more of an inflammatory reaction from the tissues that are eroded.
Classification
By Region/Location
Duodenum (called duodenal ulcer)
Esophagus (called esophageal ulcer)
Stomach (called gastric ulcer)
Meckel's diverticulum (called Meckel's diverticulum ulcer; is very tender with palpation)
Modified Johnson Classification of peptic ulcers:
Type I: Ulcer along the body of the stomach, most often along the lesser curve at incisura angularis along the locus minoris resistantiae.
Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion.
Type III: In the pyloric channel within 3 cm of pylorus. Associated with acid oversecretion.
Type IV: Proximal gastroesophageal ulcer
Type V: Can occur throughout the stomach. Associated with chronic NSAID use (such as aspirin)
Cause
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 increased, or as in most cases, decreased, resulting in hypo- or achlorhydria. Gastrin stimulates the production of gastric acid by parietal cells. In H. pylori colonization responses to increased gastrin, the increase in acid can contribute to the erosion of the mucosa and therefore ulcer formation.
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 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.
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-phenomenon independent of the progress in treatment of the disease. The cohort-phenomenon is probably explained by improved standards of living which has lowered the incidence of H. pylori infections.
Although some studies have found correlations between smoking and ulcer formation, others have been more specific in exploring the risks involved and have found that smoking by itself may not be much of a risk factor unless associated with H. pylori infection. Some suggested risk factors such as diet, and spice consumption, were hypothesized as ulcerogens (helping cause ulcers) until late in the 20th century, but have been shown to be of relatively minor importance in the development of peptic ulcers. Similarly, while studies have found that alcohol consumption increases risk when associated with H. pylori infection, it does not seem to independently increase risk, and even when coupled with H. pylori infection, the increase is modest in comparison to the primary risk factor.
Gastrinomas (Zollinger Ellison syndrome), rare gastrin-secreting tumors, also cause multiple and difficult-to-heal ulcers.
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.
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.
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.
SIGNS AND SYMPTOMS
Symptoms of a peptic ulcer can be
-abdominal pain, classically epigastric with severity relating to mealtimes, after around three 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 - although this is more associated with gastroesophageal reflux disease);
-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, which leads to acute peritonitis. 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 esophagogastroduodenoscopy.
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 production is increased as food enters the stomach. Symptoms of duodenal ulcers would initially be relieved by a meal, as the pyloric sphincter closes to concentrate the stomach contents, therefore acid is not reaching the duodenum. Duodenal ulcer pain would manifest mostly 2–3 hours after the meal, when the stomach begins to release digested food and acid into the duodenum.
-Also, the symptoms of peptic ulcers may vary with the location of the ulcer and the patient'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.
-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 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 every sufferer.
DIAGNOSIS
Endoscopic image of gastric ulcer, biopsy proven to be gastric cancer.
The diagnosis is mainly established based on the characteristic symptoms. Stomach pain is usually the first signal of a peptic ulcer. In some cases, doctors may treat ulcers without diagnosing them with specific tests and observe whether the symptoms resolve, thus indicating that their primary diagnosis was accurate.
Confirmation of the diagnosis is made with the help of tests such as endoscopies or barium contrast x-rays. The tests are typically ordered if the symptoms do not resolve after a few weeks of treatment, or when they first appear in a person who is over age 45 or who has other symptoms such as weight loss, because stomach cancer can cause similar symptoms. Also, when severe ulcers resist treatment, particularly if a person has several ulcers or the ulcers are in unusual places, a doctor may suspect an underlying condition that causes the stomach to overproduce acid.
1. 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.
One of the reasons that blood tests are not reliable for accurate peptic ulcer diagnosis on their own is their inability to differentiate between past exposure to the bacteria and current infection. Additionally, a false negative result is possible with a blood test if the patient has recently been taking certain drugs, such as antibiotics or proton pump inhibitors.
The diagnosis of Helicobacter pylori can be made by:
A) Urea breath test (noninvasive and does not require EGD);
B) 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;
C) Direct detection of urease activity in a biopsy specimen by rapid urease test;
D)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;
E) Stool antigen test;
F) Histological examination and staining of an EGD biopsy.
The breath test uses radioactive carbon atom to detect H. pylori. To perform this exam the patient will be asked to drink a tasteless liquid which contains the carbon as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive carbon dioxide. This test provides the advantage of being able to monitor the response to treatment used to kill the bacteria.
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 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.
TREATMENTS
The goal of ulcer treatment is to relieve pain, heal the ulcer, and prevent complications. The first step in treatment involves the reduction of risk factors (NSAIDs and cigarettes). The next step is medications.
Antacids:
Antacids neutralize existing acid in the stomach. Antacids such as Maalox, Mylanta, and Amphojel are safe and effective treatments. However, the neutralizing action of these agents is short-lived, and frequent dosing is required. Magnesium containing antacids, such as Maalox and Mylanta, can cause diarrhea, while aluminum containing agents like Amphojel can cause constipation. Ulcers frequently return when antacids are discontinued.
H2 blockers:
Studies have shown that a protein released in the stomach called histamine stimulates gastric acid secretion. Histamine antagonists (H2 blockers) are drugs designed to block the action of histamine on gastric cells and reduce the production of acid. Examples of H2 blockers are cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid). While H2 blockers are effective in ulcer healing, they have a limited role in eradicating H. pylori without antibiotics. Therefore, ulcers frequently return when H2 blockers are stopped.
Generally, H2 blockers are well tolerated and have few side effects even with long term use. In rare instances, patients report headache, confusion, lethargy, or hallucinations. Chronic use of cimetidine may rarely cause impotence or breast swelling. Both cimetidine and ranitidine can interfere with the body's ability to handle alcohol. Patients on these drugs who drink alcohol may have elevated blood alcohol levels. These drugs may also interfere with the liver's handling of other medications like phenytoin (Dilantin), warfarin (Coumadin), and theophylline. Frequent monitoring and adjustments of the dosages of these medications may be needed.
Proton-pump inhibitors (PPIs):
Proton-pump inhibitors such as omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium), and rabeprazole (Aciphex) are more potent than H2 blockers in suppressing acid secretion. The different proton-pump inhibitors are very similar in action and there is no evidence that one is more effective than the other in healing ulcers. While proton-pump inhibitors are comparable to H2 blockers in effectiveness in treating gastric and duodenal ulcers, they are superior to H2 blockers in treating esophageal ulcers. Esophageal ulcers are more sensitive than gastric and duodenal ulcers to minute amounts of acid. Therefore, more complete acid suppression accomplished by proton-pump inhibitors is important for esophageal ulcer healing.
Proton-pump inhibitors are well tolerated. Side effects are uncommon; they include headache, diarrhea, constipation, nausea and rash. Interestingly, proton-pump inhibitors do not have any effect on a person's ability to digest and absorb nutrients. Proton-pump inhibitors have also been found to be safe when used long term, without serious adverse health effects. Although they may promote loss of bone (osteoporosis) and low magnesium levels, both of these side effects are easily identified and treated.
Sucralfate (Carafate) and misoprostol (Cytotec):
Sucralfate (Carafate) and misoprostol (Cytotec) are agents that strengthen the gut lining against attacks by acidic digestive juices. Sucralfate coats the ulcer surface and promotes healing. Sucralfate has very few side effects. The most common side effect is constipation and the interference with the absorption of other medications. Misoprostol is a prostaglandin-like substance commonly used to counteract the ulcerogenic effects of NSAIDs. Studies suggest that misoprostol may protect the stomach from ulceration among people who take NSAIDs chronically. Diarrhea is a common side effect. Misoprostol can cause miscarriages when given to pregnant women, and should be avoided by women of childbearing age.
H. pylori treatment:
Many people harbor H. pylori in their stomachs without ever having pain or ulcers. It is not completely clear whether these patients should be treated with antibiotics. More studies are needed to answer this question. Patients with documented ulcer disease and H. pylori infection should be treated for both the ulcer and the H. pylori. H. pylori can be very difficult to completely eradicate. Treatment requires a combination of several antibiotics, sometimes in combination with a proton-pump inhibitor, H2 blockers, or Pepto-Bismol. Commonly used antibiotics are tetracycline, amoxicillin, metronidazole (Flagyl), clarithromycin (Biaxin), and levofloxacin (Levaquin). Eradication of H. pylori prevents the return of ulcers (a major problem with all other ulcer treatment options). Elimination of this bacteria also may decrease the risk of developing gastric cancer in the future. Treatment with antibiotics carries the risk of allergic reactions, diarrhea, and sometimes severe antibiotic-induced colitis (inflammation of the colon).
Diet:
There is no conclusive evidence that dietary restrictions and bland diets play a role in ulcer healing. No proven relationship exists between peptic ulcer disease and the intake of coffee and alcohol. However, since coffee stimulates gastric acid secretion, and alcohol can cause gastritis, moderation in alcohol and coffee consumption is recommended.
DIFFERENTIAL DIAGNOSIS
Gastritis
Stomach cancer
Gastroesophageal reflux disease
Pancreatitis
Hepatic congestion
Cholecystitis
Biliary colic
Inferior myocardial infarction
Referred pain (pleurisy, pericarditis)
Superior mesenteric artery syndrome
COMPLICATIONS
Gastrointestinal bleeding is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels, such as the gastroduodenal artery.
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 bleeding due to involvement of gastroduodenal artery that lies posterior to the 1st part of duodenum.
Penetration is when the ulcer continues into adjacent organs such as the liver and pancreas.
Scarring and swelling due to ulcers causes narrowing in the duodenum and gastric outlet obstruction. Patient often presents with severe vomiting.
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
