Peptic ulcers

• Peptic ulcers are open sores that develop on the mucosal lining of the duodenum, esophagus and stomach.
• Peptic ulcers develop when the balance between the digestive acids and the protective mucosal layer is disrupted.
• Thus, gastric ulcers are a type of peptic ulcer that affects the stomach lining due to an imbalance between gastric acid and the gastric mucosa

Four common areas affected by peptic ulcers.

•  Peptic ulcers were once thought to be caused primarily by emotional stress and eating too much spicy food.
• However, recent studies estimate that at least 70%, and possibly as high as 90%, of gastric ulcers are caused by Helicobacter pylori bacterial colonization.
• H. pylori infection is also involved in about 50% of gastric cancers.
• H. pylori are corkscrew-shaped bacteria that commonly live within the mucous layer of the stomach and duodenum.
• The presence of H. pylori is usually benign.
• However, due to factors that are not entirely understood, H. pylori sometimes overgrow and is unable to be contained by the immune system.
• The bacteria penetrate and disrupt the mucous layer and inflame the stomach lining, leading to chronic inflammation or gastritis.

                                              Close-up view of H. pylori penetrating mucous layer

Chronic gastritis

• Chronic gastritis results in an inability to regulate gastrin, which is a peptide hormone that stimulates the secretion of gastric acid by the parietal cells of the stomach.
• Reduced regulation sometimes results in an increase of gastrin secretion and over-acidity.
• However, sometimes gastrin production is decreased, which results in either hypochlorhydria or achlorhydria.
• Normal plasma gastrin concentration should fluctuate between 0-200 pg/mL depending on diet.
• Most H. pylori infections lead to an increase of gastrin production (up to 4,100 pg/mL in the plasma, but an average of about 1,500 pg/mL), which causes erosion of the stomach lining and incites ulcer formation.
• It’s not clear if transmitting H. pylori through saliva is a significant risk factor in developing gastric ulcers, or if a biochemical change in the bacteria’s host environment is the main causal factor.

Cause of Gastric Ulceration

• Another major cause of gastric ulceration is the regular use of non-steroidal anti-inflammatory drugs (NSAIDs).
• COX-1 inhibitors, such as aspirin, ibuprofen, naproxen and ketoprofen, block the function of cyclooxygenase-1, which
  is essential to make the gastric mucosal lining.
• COX-2 inhibitors, such as Celebrex or the since withdrawn Vioxx, inhibit cyclooxygenase-2, which is less essential for
  gastric mucosa growth.
• Thus, use of COX-2 drugs represent about half the risk of NSAID-related gastric ulcers compared to COX-1 drugs.
• Bacterial infection and NSAID abuse play dominant roles in the development of gastric and other peptic ulcers, but

Other Important Factors

Other risk factors that have been identified for gastric ulcers include

• Emotional stress
• Alcoholism
• Radiation therapy
• Burns and physical trauma to the abdomen
• Over-use of other pharmaceuticals, especially bisphosphonates
• Tobacco smoking and chewing
• Moderate-to-high levels of coffee consumption
• High-stress occupations
• Surgical procedures and chronic pain
• Advancing age
• Heredity

Location of Gastric Ulcers

• Gastric ulcers are usually round or oval, between 2 and 4 cm in diameter, and located on the lesser curvature of the
  stomach.
• The ulcer is usually smooth with regular and perpendicular borders. In contrast, irregular borders are often a sign of ulceration due to stomach cancer.
• Gastric ulcers penetrate the muscularis mucosae and muscularis propria layers of the stomach by acid-pepsin
  aggression.

The incidence of duodenal ulcers has dropped significantly during the last few decades.

• However, the incidence of gastric ulcers has shown a small increase in recent years, which is mainly caused by
  the widespread use of NSAIDs.
• The two most important developments associated with the overall decreased rates of peptic ulcer disease are the
  discovery of effective acid suppressants and the identification of H. pylori as the main cause.
• In most industrialized countries, the prevalence of H. pylori infections leading to gastric symptoms roughly matches age (i.e., 20% at age 20, 30% at age 30, 60% at age 60 etc.).
• Prevalence is even higher in third-world countries.
• Only a minority of cases of H. pylori infections lead to ulceration, but a large proportion develop non-specific discomfort, abdominal pain and/or gastritis.
• Gastric ulcers are more common in males, especially between the ages of 55 and 65.

Symptoms

• Gastric ulcers often bleed and produce distinctive symptoms.
• Bleeding from gastric ulcers usually leads to black or tarry stool and vomit that looks like coffee grounds or colored
  bright red.
• Tarry stool from internal bleeding, known as melena, is especially foul-smelling.
• Other signs and symptoms of gastric ulcers include loss of appetite, unexplained weight loss, heartburn, indigestion,
  belching, bloating and nausea.
• Left untreated, gastric ulcers can result in anemia, infection (peritonitis) from tissue perforation, and scar tissue that can block passage of food through the digestive tract.
• Sudden, excessive bleeding can be life-threatening, especially if the ulcer erodes through a major blood vessel.
• Stomach cancer is between 3 – 6X more likely to develop from gastric ulceration caused by H. pylori infection.
• About 4% of gastric ulcers are caused by malignant tumors, so stomach biopsies are sometimes done to rule-out cancer.

Diagnosis

• The diagnosis of gastric ulceration is initially based on a physical exam, thorough history and the presence of characteristic symptoms, such as burning stomach pain.
• H. pylori can be detected by a blood test, stool test or breath test.
• Breath tests are the least invasive and are about 95% accurate.
• Confirmation is also made with endoscopy and barium x-rays.
• If an ulcer is detected, it can be classified as one of five different types, with Type-1 representing about 60% of cases

Prevention

• Prevention of gastric ulcers often involves reducing NSAID use and finding different medications or
  alternative approaches to relieve pain.
• Lifestyle is important and includes eating foods rich in fiber and antioxidants, especially fruits and vegetables.
• Quitting smoking and reducing the consumption of alcohol, coffee and soda pop are also important strategies.
• Controlling stress and anxiety is also helpful.
• Flavonoids and antioxidants such as anthocyanidins and resveratrol (found in blueberries, cherries, red grapes and tomatoes) inhibit the growth of H. pylori.
• Probiotic supplements containing Lactobacillus acidophilus balance GI bacteria, suppress H. pylori infection, and reduce the side effects from taking antibiotics.
• Vitamin C supplements (500 to 1,000 mg 1-3 times daily) deter the proliferation of H. pylori and are helpful in treating bleeding gastric ulcers caused by aspirin use.
• Omega-3 fatty acids are anti-inflammatory and can help to protect the stomach and intestinal tract from ulcers.