Peptic Ulcer Disease PDF

# Peptic Ulcer Disease Peptic ulcer is defined as a chronic mucosal ulceration/defect that penetrates muscularis mucosae. It usually affects → duodenum (duodenal ulcer) or stomach (gastric ulcer). Peptic ulcer disease (PUD) is one of complications of chronic gastritis. It is most often associate...

# Peptic Ulcer Disease Peptic ulcer is defined as a chronic mucosal ulceration/defect that penetrates muscularis mucosae. It usually affects → duodenum (duodenal ulcer) or stomach (gastric ulcer). Peptic ulcer disease (PUD) is one of complications of chronic gastritis. It is most often associated with colonization with *H. pylori* and *H. pylori*-induced chronic gastritis (with hyperchlorhydria), NSAIDs, or cigarette smoking. ## Two Opposing Sets of Forces Keep Stomach in a Normal State: - **Damaging Forces** - **Defensive Forces** ### Damaging Forces: 1. **Gastric Acidity** → - Hydrochloric acid plays main role in digestion but it also can damage gastric mucosa. - Enzyme H+/K+ ATPase is responsible for producing the large concentration of H+. - Acid is secreted by parietal cell located in the oxyntic gland. 2. **Peptic Enzymes** They can also damage the gastric mucosa. - Pepsinogen, which is an inactive precursor of pepsin, is synthesized and secreted by the chief cell, found mainly in the gastric fundus. - The acid environment within the stomach leads to conversion of pepsinogen to pepsin and provides the low pH (required for activity of pepsin). - Many of the substances, which stimulate acid secretion, also stimulate pepsinogen release. ### Defensive Forces: - These are a three-level barrier composed of: - 1) Pre-epithelial - 2) epithelial - 3) subepithelial element #### Pre-epithelial Barrier - It is a mucus-bicarbonate layer of stomach. - It is formed by several factors produced by surface epithelial cells, such as: - a) Production of mucus - b) bicarbonate secretion - c) epithelial cell ionic transporters that maintain intracellular pH - d) intracellular tight junctions. #### Surface Mucus Secretion - Mucin is secreted by surface foveolar cells. - Actions of mucus are: - Mucus layer promotes formation of an "unstirred" protective layer of fluid on the mucosa. - Prevents the direct contact of large food particles to the epithelium. #### Prostaglandins - Prostaglandins protect gastric mucosa by: - 1. Increasing secretion of bicarbonate - 2. Increasing vascular perfusion - 3. Inhibition of acid secretion - 4. Promoting synthesis of mucin. ## Pathogenesis of PUD: Imbalances between mucosal defenses and damaging forces cause chronic gastritis and also PUD. ## Risk Factors ### Direct Mucosal Injury/Increased Damage 1. **H. pylori infection** → - Is one of the most important, common, primary cause of PUD. - H. pylori is detected from gastric antrum in almost all patients with duodenal ulcers. - It is associated with increased secretion of gastric acid and reduced duodenal secretion of bicarbonate. 2. **Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin:** - It causes - 1) direct chemical irritation of mucosa - 2) suppresses mucosal prostaglandin synthesis - 3) reduces the bicarbonate secretion. 3. **Cigarette smoking:** - Impairs blood flow to the mucosa and healing of mucosal damage. 4. **Alcohol, radiation therapy and chemotherapy:** - They cause direct injury to mucosal cells. 5. **Ingestion of chemicals:** - These include acids or bases and cause direct injury. 6. **Gastric hyperacidity:** - The causes of hyperacidity include H. pylori infection, parietal cell hyperplasia and Zollinger-Ellison syndrome 7. **High-dose corticosteroids:** - They suppress prostaglandin synthesis and impair healing process. ## Morphology ### Gross **Sites of peptic ulcer:** - 1. Duodenum - 2. Stomach - 3. Esophagus - 4. Jejunum - They can develop in any portion of the GI tract exposed to acidic gastric juices. **Duodenum:** - More common in the first portion of the duodenum (anterior or posterior wall) within a few centimeters of the pyloric valve than in the stomach. **Stomach:** - Lesser curvature near junction (transitional zone) of the body and antrum ## Gastric and Duodenal Ulcers are Microscopically Similar: - From the lumen outward four layers can be identified and are known as Askanazy zones. - → **Necrotic zone:** It is the most superficial zone. - → **Superficial exudative zone:** It consists of fibrinopurulent exudates with predominantly neutrophilic inflammatory infiltrate - → **Granulation tissue zone:** It consists of granulation tissue infiltrated with mononuclear leukocytes. - → **Zone of cicatrization:** It consists of fibrous tissue or collagenous scar which forms the base of the ulcer and may show chronic inflammatory cells ## Clinical Features Peptic Ulcer: - Peptic ulcers are chronic, recurring lesions with more morbidity than mortality. - Age: Young adults but are most often diagnosed in middle-aged to older adults. - Periodicity: After a period of weeks to months of active disease, healing may occur with or without treatment. - Pain: Epigastric burning or aching pain exacerbated by fasting and improved with alkali or food. - It usually develops 1-3 hours after meals during the day and is worse during night between 11 PM and 2 AM. - Other symptoms: These include nausea, vomiting, bloating, belching and significant weight loss ## Complications of Gastric Ulcers - **Bleeding:** Most common complication of peptic ulcer. - Chronic blood loss may lead to iron deficiency anemia. - Severe bleeding may cause "coffee ground" vomitus or melena and may be life-threatening. - **Perforation:** Develops in ~ 5% of patients and is most common complication of gastric ulcer. - **Pyloric obstruction (gastric outlet obstruction):** - It is associated with ulcers in the pyloric region and occurs in ~ 10% of ulcer patients. - It is secondary to either edema or scarring - **PUD:** Peptic ulcers in the duodenum never become malignant. - Small percentage of gastric ulcers may undergo malignant transformation. | Feature | Gastric Ulcer | Duodenal Ulcer | | -------------- | -------------------------------------------------------- | -------------------------------------------------------- | | Commonest Site | Along the lesser curvature | First part of duodenum | | Incidence | Less common | More common | | Age | Beyond 6th decade, M>F | Between 25 and 50 years, M>F | | Association with H. pylori infection | Less common | Strong association | | Acid level | Usually normal | High | | Clinical features | Relief of pain not consistent | Prompt relief of pain | | Relationship of pain to antacids | Aggravates the pain | Relieves the pain | | Relationship of pain to food | Not observed | Common | | Night pain | Not common | Common | | Heart burn | Hematemesis more common | Melena more common | | Hematemesis/melena | Common | Common | | Vomiting | Common | No vomiting | | Weight loss | Present | Absent | | Complication | Rarely undergo, malignant change | No malignant change | - Gastroduodenal artery is the source of bleeding in duodenal ulcer. - Left gastric artery is the source of bleeding in gastric ulcer. - Urea breath test is used to ensure the efficacy of the treatment for peptic ulcer disease caused by H. pylori. ## Peptic Ulcer Types - Duodenal Ulcer - Gastric Ulcer - Esophageal Ulcer **Causes:** - *H. pylori* - NSAIDs