Causes And Risk Factors
The lining of the stomach and intestine is covered by a thick mucus layer that functions as a physical barrier between the outside environment and the body (Chai 2011). The formation of peptic ulcers results from disruption of the mucosal barrier by factors such as stomach acid, pepsin, H. pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs), alcohol, and cigarette smoking (Ferri 2016).
Gastric ulcers develop in the lining of the stomach. Pain from a gastric ulcer may be aggravated or alleviated by eating. Duodenal ulcers form in the first few centimeters of the lining of the duodenum (the upper part of the small intestine). Pain associated with duodenal ulcers is typically relieved by eating but often returns two to three hours later, and frequently awakens patients at night (DiMarino 2016a).
Helicobacter pylori infection. H. pylori infection is the primary cause of peptic ulcer disease; it is present in 30% to 50% of patients with gastric ulcers and 50% to 70% of those with duodenal ulcers (Kuipers 2015; DiMarino 2016a).
H. pylori bacteria bore into the protective mucus layer of the stomach or small intestine (duodenum) and cause an inflammatory response. Chronic inflammation induced by H. pylori damages the mucosa and disrupts pH regulation. These effects can lead to ulcer formation (UMMC 2015; Chai 2011). H. pylori infection can also increase the risk of gastric cancer (Waldum 2014).
Nonsteroidal anti-inflammatory drugs (NSAIDs). Chronic use of NSAIDs such as ibuprofen, naproxen, and aspirin is the second-leading cause of peptic ulcer disease, and the occurrence of NSAID-related ulcers is increasing, particularly in older individuals (UMMC 2015; Kuipers 2012).
By inhibiting cyclooxygenase (COX) enzymes, NSAIDs cause a decrease in the synthesis of prostaglandins that stimulate production of protective mucus and acid-buffering bicarbonate in the digestive tract. This increases vulnerability to ulcer formation. NSAIDs also increase risk of gastrointestinal bleeding (Chai 2011; UMMC 2015).
Our Complex Relationship with Helicobacter pylori
The association of H. pylori with peptic ulcer disease was discovered in 1984, and this discovery has fundamentally altered the treatment, as well as the prevalence, of peptic ulcers (Owyang 2011; Malfertheiner 2009; Kuipers 2012). However, only 10‒15% of adults infected with H. pylori ever develop peptic ulcers—additional factors are necessary to trigger disease (UMMC 2012; Malfertheiner 2009; Owyang 2011). In addition, more recent discoveries have found that H. pylori may be protective against asthma and allergy, inflammatory bowel disease, gastroesophageal reflux disease (GERD), esophageal cancer, and obesity, which suggests that, at least for some, there may be a benefit to colonization with this microbe (Owyang 2011; Chen 2007; McNeil 2008; Malfertheiner 2010).
While H. pylori has inhabited the human digestive tract for well over 50 000 years (Owyang 2011), peptic ulcer disease is believed to be a relatively recent phenomenon of the past two centuries, associated with changes in diet and lifestyle (Graham 2014). In recent decades, the prevalence of H. pylori colonization has been on the decline in Western societies, possibly resulting from rising standards of living, improved hygienic conditions, and broader use of antibiotics (Kuipers 2012; den Hoed 2011).
Some researchers believe these dualistic properties of H pylori—to both cause peptic ulcer disease and gastric cancer under some conditions while possibly protecting against other diseases—deserve serious scientific attention. Specifically, scientists speculate that the host-microbe interaction is of critical importance, and a new concept should replace the idea that H. pylori is always harmful and should be eradicated even in asymptomatic individuals. It has even been proposed that inoculation with H. pylori might be beneficial in certain individuals (Blaser 1998; Blaser 2008). Continuing research in this field promises to increase our understanding of the role of H. pylori in health and disease, as well as of the importance of each individual’s host-microbe relationship.
Additional Risk Factors
- Age and gender. Ulcers can develop at any age, but are most common in middle-aged adults. Men are twice as likely as women to develop ulcers (UMMC 2015).
- Smoking. Cigarette smoking increases the risk of ulcers, increases the rate of recurrence, and delays ulcer healing (DiMarino 2016a).
- Alcohol abuse. Alcohol use promotes secretion of stomach acid and damages the gastric mucosa; heavy drinkers are at increased ulcer risk. Light-to-moderate drinking has not been definitively linked to ulcers (Lee 2013; DiMarino 2016a).
- Family history. Risk of ulcers is higher in those with a relative who has a history of peptic ulcers (Lee 2013).
- Previous history of ulcers. About 80% of individuals with bleeding ulcers have had symptomatic ulcers in the past (Kuipers 2012).
- Stress. Stress is correlated with peptic ulcer disease and may compound the effects of H. pylori infection (Overmier 2013; Herszenyi 2015).
- Medication combinations. The combination of NSAIDs with corticosteroids, bisphosphonates, and certain other medications is associated with an increased risk of peptic ulcers (Lee 2013).