What are the causes of Peptic Ulcer Disease (PUD)

Peptic Ulcer Disease (PUD for short) is the term used to describe wounds or sores that develop in the lining of the stomach (gastric ulcers) or in the lining of the upper part of the small intestine (duodenal ulcers). These ulcers can not only be uncomfortable causing you pain, but can also lead to other complications that may be dangerous. Ulcers can heal of their own accord but in the majority of people who do not get treatment, the ulcers tend to recur.
Ulcers can heal of their own accord but in the majority of people who do not get treatment, the ulcers tend to recur.



How did I get Peptic Ulcer Disease?

Hostile vs protective factor




“No gastric acid, no peptic ulcer” is a misconception. Excessive gastric acid secretion is only one factor in the pathogenesis of peptic ulcer disease. Decreased mucosal defense against gastric acid is another cause. The integrity of the upper gastrointestinal tract is dependent upon the balance between “hostile” factors such as gastric acid, H. pylori, NSAIDs and pepsin, and “protective” factors such as prostaglandins, mucus, bicarbonate, and blood flow to mucosa affecting gastrointestinal mucosa.
Injury to gastric and duodenal mucosa develops when deleterious effects of gastric acid overwhelm the defensive properties of the mucosa. Inhibition of endogenous prostaglandin synthesis leads to a decrease in epithelial mucus, bicarbonate secretion, mucosal blood flow, epithelial proliferation, and mucosal resistance to injury. Lower mucosal resistance increases the incidence of injury by endogenous factors such as acid, pepsin, and bile salts as well as exogenous factors such as NSAIDs, ethanol and other noxious agents

Other causes

1. Use of non-steroid anti-inflammatory drugs (NSAID)

A small but important percentage of patients have adverse gastrointestinal events associated with NSAID use that results in substantial morbidity and mortality. Risk factors for the development of NSAID-associated gastric and duodenal ulcers include advanced age, history of previous ulcer disease, concomitant use of corticosteroids and anticoagulants, higher doses of NSAIDs, and serious systemic disorders. The concept of gastroduodenal mucosal injury has evolved from the notion of topical injury to concepts that involve multiple mechanisms.

NSAIDs initiate mucosal injury topically by their acidic properties. By diminishing the hydrophobicity of gastric mucus, endogenous gastric acid and pepsin may injure surface epithelium. Systemic effects of NSAIDs appear to play a predominant role through the decreased synthesis of mucosal prostaglandins. The precursor of prostaglandins, arachidonic acid, is catalyzed by the two cyclo-oxygenase isoenzymes, cyclo-oxygenase-1 and cyclo-oxygenase-2. The gene for cyclo-oxygenase-1, the housekeeping enzyme, maintains the homeostasis of organs. Cyclo-oxygenase-2, the inflammatory enzyme, is inducible. Although NSAIDs can inhibit both pathways, only the gene for cyclo-oxygenase-2 contains a corticosteroid-responsive repressor element. Literature suggests that the anti-inflammatory properties of NSAIDs are mediated through inhibition of cyclo-oxgenase-2, and adverse effects, such as gastric and duodenal ulceration, occur as a result of effects on the constitutively expressed cyclo-oxygenase-1.

H. pylori is prevalent among 22–63% of patients taking NSAIDs. Most studies do not show a significant difference in H. pylori prevalence between NSAID users and nonusers. Gastritis in patients on NSAID therapy appears to be related to underlying H. pylori rather than drug use. The lower incidence of H. pylori among patients with gastric ulcers than those with duodenal ulcers is presumably the result of NSAID use. NSAIDs are more likely to cause gastric than duodenal ulcers. NSAIDs appear to cause ulcers by a mechanism independent of H. pylori based on the inhibition of prostaglandin synthesis.

2. Bacterium Helicobacter pylori.

H. pylori is the etiologic factor in most patients with peptic ulcer disease and may predispose individuals to the development of gastric carcinoma. H. pylori colonizes in the human stomach. The method of H. pylori transmission is unclear, but seems to be person-to-person spread via a fecal-oral route. The prevalence of H. pylori in adults appears to be inversely related to the socioeconomic status. It is also thought that water is a reservoir for transmission of H. pylori.

3. Gastrinoma (Zollinger-Ellison Syndrome)

The classic triad of Zollinger-Ellison syndrome involves peptic ulcers in unusual locations (i.e., the jejunum), massive gastric acid hypersecretion, and a gastrinproducing islet cell tumor of the pancreas (gastrinoma). Gastrinoma in the pancreas appears in approximately 50% of patients. Another 20% of patients have it in the duodenum and others have it in the stomach, peripancreatic lymph nodes, liver, ovary, or small-bowel mesentery.

Zollinger-Ellison syndrome accounts for only 0.1% of all duodenal ulcer disease. One fourth of patients have this syndrome as part of the multiple neoplasia syndrome Type I (MEN I).
Patients with gastrinoma may have intractable ulcer disease. Because gastrin is trophic to the gastric mucosa, endoscopy or x-ray may demonstrate hypertrophy of the gastric rugae. Patients may also experience diarrhea (including steatorrhea from acid inactivation of lipase) and gastroesophageal reflux. These symptoms are episodic in 75% of patients.

4. Hypercalcemia

Hypercalcemia has a direct bearing on the gastric acid hypersecretory state found in patients with Zollinger-Ellison syndrome and MEN I. Intravenous calcium infusion in normal volunteers induces gastric acid hypersecretion. Additionally, calcium has been demonstrated in vivo and in vitro to stimulate gastrin release directly from gastrinomas. Resolution of hypercalcemia (by parathyroidectomy) reduces the basal acid output and serum gastrin concentration in fasting gastrinoma patients and those with MEN I, suggesting that resolution of hypercalcemia plays an important role in the therapy of this subgroup of patients.

5. Genetic Factors

Genetic factors play a role in the pathogenesis of ulcer disease. The lifetime prevalence of developing ulcer disease in first-degree relatives of ulcer patients is about three times greater than the general population. Approximately 20–50% of duodenal ulcer patients report a positive family history; gastric ulcer patients also report clusters of family members who are likewise affected.

6. Smoking

The literature reveals a strong positive correlation between cigarette smoking and the incidence of ulcer disease, mortality, complications, recurrences and delay in healing rates. Smokers are about two times more likely to develop ulcer disease than nonsmokers. Cigarette smoking and H. pylori are co-factors for the formation of peptic ulcer disease. There is a strong association between H. pylori infection and cigarette smoking in patients with and without peptic ulcers. Cigarette smoking may increase susceptibility, diminish the gastric mucosal defensive factors, or may provide a more favorable milieu for H. pylori infection.

7. Stress

Numerous studies have revealed conflicting conclusions regarding the role of psychological factors in the pathogenesis and natural history of peptic ulcer disease. The role of psychological factors is far from established. Acute stress results in increases in pulse rate, blood pressure and anxiety, but only in those patients with duodenal ulcers did acute stress actually result in significant increases in basal acid secretion. There is no clearly established “ulcer-type” personality. Ulcer patients typically exhibit the same psychological makeup as the general population, but they appear to perceive greater degrees of stress. In addition, there is no evidence that distinct occupational factors influence the incidence of ulcer disease.

8. Alcohol and Diet

Although alcohol has been shown to induce damage to the gastric mucosa in animals, it seems to be related to the absolute ethanol administered (200 proof). Pure ethanol is lipid soluble and results in frank, acute mucosal damage. Because most humans do not drink absolute ethanol, it is unlikely there is mucosal injury at ethanol concentrations of less than 10% (20 proof). Ethanol at low concentrations (5%) may modestly stimulate gastric acid secretions; higher concentrations diminish acid secretion. Though physiologically interesting, this has no direct link to ulcerogenesis or therapy.
Some types of food and beverages are reported to cause dyspepsia. There is no convincing evidence that indicates any specific diet causes ulcer disease.

Epidemiologic studies have failed to reveal a correlation between caffeinated, decaffeinated, or cola-type beverages, beer, or milk with an increased risk of ulcer disease. Dietary alteration, other than avoidance of pain-causing foods, is unnecessary in ulcer patients.




Reference
https://emedicine.medscape.com/article/181753-overview
https://www.mayoclinic.org/diseases-conditions/peptic-ulcer/symptoms-causes/syc-20354223
https://www.webmd.com/digestive-disorders/peptic-ulcer-overview
https://my.clevelandclinic.org/health/diseases/10350-peptic-ulcer-disease
https://www.ncbi.nlm.nih.gov/books/NBK534792/
https://www.aafp.org/afp/2015/0215/p236.html
https://www.healthline.com/health/peptic-ulcer
http://www.pathwaymedicine.org/peptic-ulcer-disease
What are the causes of Peptic Ulcer Disease (PUD) What are the causes of Peptic Ulcer Disease (PUD) Reviewed by gafacom on July 04, 2020 Rating: 5

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