Peptic Ulcer Disease

Introduction

In 1982, two young Australian doctors named Barry Marshall and Robin Warren suspected that the bacteria known as Helicobacter pylori, or H. pylori, was responsible for ulcers. . Desperate to prove their theory, they did what few others would dare: Dr. Marshall drank a beaker of the bacteria. Dr. Marshall subsequently developed a stomach ulcer and the two began a revolution in our understanding and treatment of peptic ulcer disease. In 2005, Drs. Warren and Marshall were awarded the Nobel Prize in Medicine for the discovery of H. pylori?s role in causing peptic ulcer disease.

What is it?

Peptic Ulcer Disease (PUD) is the presence of an ulcer, a crater-like sore, in the lining of the stomach or upper part of the small intestine. There are two types of ulcers related to PUD:

  1. Gastric Ulcers- which are ulcers found in the stomach

  2. Duodenal Ulcers- which are ulcers formed in the upper part of the small intestine

The first part of the small intestine is called the duodenum. This name comes from what it is, about the first twelve fingers length of the small intestine.

Left untreated, ulcers can cause serious complications that can include:

  • bleeding into the stomach or intestine
  • holes in the stomach or intestine that causes digested food and bacteria to spill into other areas of the body
  • narrowing or blockage of the intestinal opening

What causes it?

PUD can start when the protective barrier that lines the stomach or intestines is injured, exposing the underlying tissue to stomach acid. A variety of things can harm the protective lining of the stomach or intestines. These include:

  • Infection - H. pylori breaks down the stomach and/or intestinal lining, making them more susceptible to acid, which can lead to ulcers. H. pylori is present in more than 90% of patients who have intestinal ulcers and more than 80% of patients with stomach ulcers.

  • Chronic use of prescription or non-prescription drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin - NSAIDs lower the stomach's resistance to the harmful effects of acid. Ulcers caused by NSAIDs often heal on their own after the medication is discontinued. Examples of common NSAIDs: aspirin, ibuprofen (Advil, Motrin), and naproxen (Aleve).

  • Smoking - Smoking can increase the risk of developing an ulcer, prolong the healing of existing ulcers and contribute to ulcer reoccurrence.

  • Physical stress - such as surgery or extreme injury.

  • Alcohol - Ulcers are more common in patients with cirrhosis of the liver, a disease that has been linked to heavy alcohol consumption, but the link between alcohol and ulcers is still vague.

Emotional stress is no longer thought to be a cause of ulcers.

Learn more about the development of PUD

The function of the stomach is to store, dissolve and partially digest the contents of a meal and deliver this partially digested food to the small intestine in quantities that optimize digestion and absorption. In the stomach, food is digested and sterilized by gastric acid that consists of a mixture of hydrochloric acid and digestive enzymes like pepsin. This highly acidic mixture is produced by parietal cells within gastric glands in the folds of the stomach wall. Gastric acid is secreted by parietal cells in the stomach in response to three different substances: acetylcholine, histamine, and gastrin. Acetylcholine is released in response to chewing. Gastrin is released by G cells in the stomach in response to both swelling of the stomach wall and acetylcholine. High gastrin levels cause histamine to be released from mast cells in the tissues of the digestive tract.
Hydrochloric acid (H+) production is stimulated by three substances: gastrin, acetylcholine, and histamine.

During a meal, the rate of acid production greatly increases. Sensations like seeing, smelling, tasting and chewing food send signals via the vagus nerves to the parietal cells, causing them to increase acid production. More nerve messages follow as the stomach stretches, hydrogen ion concentration increases, and as a result of the presence of peptides. This increases release of gastrin, which in turn increases production of hydrochloric acid. On average, the stomach produces 2 liters of hydrochloric acid daily.

The cells of the stomach and duodenum have two defenses against their acidic environment. They multiply quickly and they secrete a protective layer of mucus.

An ulcer starts when the protective barrier that lines the gastrointestinal tract is injured, exposing the underlying tissue to the strong stomach acids and enzymes that are responsible for disinfecting and digesting the food that we eat. In the absence of a protective barrier, prolonged contact with acid leads to inflammation, erosion, and ulceration of the stomach's or duodenum's lining.

H. pylori thrives in the harsh chemical environment of the stomach by secreting an enzyme that neutralizes the acid in the area where the bacteria are growing. This allows the bacteria to become established and to grow within the epithelial tissue. The bacteria are often found in grooves between cells under a stable layer of mucus that shields the organisms from gastric acid. Once it is established in the stomach wall, H. pylori produces substances that cause tissue damage. The body's immune system reacts with an inflammation to fight the infection, and this causes further local tissue damage. After a time, the damaged tissue no longer can secrete mucous properly, which allows the acid and enzymes to also begin to attack the tissue. Eventually, the mucosal cell layer wears away in an ulcer, exposing the underlying tissue to the harsh digestive chemicals. When a blood vessel is exposed the acid and digestive enzymes can open up the blood vessel making it a bleeding ulcer.

Who has it?

Approximately 25 million (or 1 in 12) people in the United States have had PUD during their lifetimes, according to the Centers for Disease Control and Prevention. About four million adults have the disease at any one time, with about 500,000 new cases each year. More than 85% of people with ulcers are older than age 45. Most ulcers that appear on their own resolve within six to eight weeks without treatment, but half of these cases reoccur within a year.

Medical researchers all over the world have found H. pylori responsible for infecting the gastric mucous layer of almost all patients with duodenal ulcer disease, most patients with gastric ulcer disease, and almost all patients with gastritis(an inflammation of the stomach lining). Almost half of North Americans over age 50 are infected with H. pylori. In some developing countries, H. pylori infects almost all adults.

What are the risk factors?

Risk factors are characteristics that may increase your chance for developing a condition. Risk factors for PUD include:

  • H. pylori infection
  • High-dose or multiple NSAID use
  • Age older than 60
  • Previous ulcer or GI bleeding
  • Cigarette smoking
  • Corticosteroid use
  • Anticoagulant use
  • Family history of PUD

What are the symptoms?

The most common symptoms of PUD are:

  • Stomach pain - typically a sharp pain that may last hours or minutes and is usually relieved by eating or by taking antacids. This pain is usually located in the middle of the abdomen, between the navel and the breastbone.
  • Burning in the abdomen - most often experienced between meals or early in the morning. The burning may be so severe that it wakes you from sleep.
  • Weight loss
  • Upset stomach
  • Vomiting
  • Bloating
  • Blood may appear in the vomit or stool. Blood that originates in the stomach or small intestines usually appears dark red or black and tarry in the stool. Depending on where the blood comes from in the intestinal track, if it is vomited, it may be dark red or brown, resembling coffee grounds.
  • Obstruction or perforation of the stomach or small intestines can occur if the ulcer is left untreated. Perforation is potentially life-threatening since it can result in a serious infection in the abdomen.

How is it treated?

Treatment recommendations of the American College of Gastroenterology are based on the understanding that PUD is usually the result of H. pylori infection, or is caused by taking aspirin and other NSAIDs. Thus, the first step is to stop taking NSAIDs or aspirin. Successful elimination of H. pylori cures most patients who are not continuing to take aspirin or an NSAID.

Patients with a prior history of PUD, active peptic ulcer disease, or gastric lymphoma (stomach cancer), should be tested for H. pylori infection. If they test positive, they should be treated with antibiotic therapy. If the tests are negative for H. pylori infection, patients are treated with traditional ulcer therapy that blocks the production of stomach acid and protects the tissues lining the stomach and duodenum.

For NSAID-induced ulcers, cytoprotective agents, or drugs that coat and protect the stomach mucosa, may be used.

Helping Yourself

Successful treatment of ulcers relies on your compliance to the lifestyle changes and medications recommended by your doctor. Therapies to treat PUD can prevent serious complications and the need for surgery. You can help yourself by taking the following steps:

  • Avoid foods that seem to bring on your symptoms. For many people, spicy foods make ulcer pain worse.
  • Avoid alcohol and caffeine, which may worsen ulcer pain.
  • Avoid or limit dairy products while your ulcer is flaring up. Milk and milk products seem to delay healing of ulcers.
  • Do not take aspirin, ibuprofen, naproxen, or other NSAIDs. Try acetaminophen instead, if needed for pain or fever.
  • Over-the-counter antacids such as Tums, Maalox or Mylanta may be used to relieve symptoms of ulcer pain and indigestion. Antacids need to be used around-the-clock for them to help promote ulcer healing. Therefore they are generally used as needed to help treat symptoms.
  • Over-the-counter acid-reducers such as famotidine (Pepcid AC) and ranitidine (Zantac 75), or acid-blockers such as Prilosec OTC are effective treatments for acid suppression in treating PUD.
  • Discuss prescription treatment options with your physician. Many over-the-counter treatments are not indicated for long-term use without the supervision of a doctor.

What is on the horizon?

In recent years, many changes have occurred in the treatment of PUD. First, H. pylori was identified as a cause of PUD. Next, the H2 blockers became available as generic drugs. Then, all the H2 blockers went over-the-counter in reduced strengths that do not need prescriptions.

The most active area of new drug research involves a drug class called proton pump inhibitors (PPIs) PPIs work quickly and well to treat PUD. Currently, there are five PPIs available in the US, but a number of similar compounds still in development may compete with these drugs in the future. Omeprazole is the only PPI available in a generic formulation, and will likely be the only one for the next few years.

Prilosec OTC (omeprazole), the only PPI available over the counter, will soon have a generic available. This will substantially reduce the cost, and provide additional treatment options for this very popular product.

Vaccines for H. pylori are being developed by multiple research teams around the world. A vaccine may become available for public use some time in the next three to five years.

References

Guidelines for the Management of Helicobacter pylori Infection. American College of Gastroenterology. Availabe at: http://www.acg.gi.org/physicians/guidelines/ManagementofHpylori.pdf Accessed September 2007

A Guideline for the Treatment and Prevention of NSAID Induced Ulcers. American College of Gastroenterology. Available at: http://www.acg.gi.org/physicians/guidelines/TreatmentofNSAID-Ulcers.pdf Accessed September 2007

AGA Patient Center: Peptic Ulcer Disease & H. pylori. American Gastroenterological Association. Available at: http://www.gastro.org/wmspage.cfm?parm1=857 Accessed September 2007

AGA Patient Center: Peptic Ulcer Disease. American Gastroenterological Association. Available at: http://www.gastro.org/wmspage.cfm?parm1=856 Accessed September 2007

Impact of Helicobacter pylori eradication on dyspepsia, health resource use, and quality of life in the Bristol helicobacter project: randomised controlled trial. British Medical Journal. Available at: http://bmj.bmjjournals.com/cgi/content/full/332/7535/199 Accessed September 2007. BMJ 2006;332:199-204

A historical perspective on the treatment of PUD. FDA Consumer magazine. Available at: http://www.fda.gov/bbs/topics/CONSUMER/CON0292d.html Accessed September 2007

American Digestive Health Foundation Digestive Health Initiative.The report of the international update conference on Helicobacter pylori The American Gastroenterological Association; Gastroenterology. 1997 Dec;113(6 Suppl):S4-8.

Dzierba S. Antibiotic therapy for peptic ulcer disease. For The Pharmacist. Program #401-000-97-002-H01; January 1998

Soll A. Medical treatment of peptic ulcer disease. Journal of the American Medical Association 1996;275(8):622-29

Salcedo JA. Al-Kawas F. Treatment of Helicobacter pylori infection. Archives of Internal Medicine. 158(8):842-51, 1998 Apr 27

Berardi, Rosemary and Welage, Lynda. Peptic Ulcer Disease. In: Pharmacotherapy: a pathophysiologic approach. 6th ed. Dipiro JT, Talbert RL, Yee GC et. al., eds. New York: McGraw-Hill; 2005:629-648.

Peptic Ulcer Disease Health Condition Last Updated: September 2007

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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