Pathology and pathophsiolgy of peptic ulcer Dr. Mamlook Elmagraby

Objectives of the lecture: Upon completion of this lecture, students should be able to: Understand the Pathophysiology of acute and chronic peptic ulcer Know the possible causes of gastric and duodenal ulcers with emphasis on most common causes (H pylori and drugs) Recognize the gross and microscopic features of peptic ulcer Recognize the clinical features and consequences of acute and chronic peptic ulcer

Gastric Ulceration

Overview Ulcers of the GIT are a gap (opening) in the mucosa that extends through the muscularis mucosae into the submucosa or deeper In erosions, there is a breach in the epithelium of the mucosa only Erosions may heal within days, whereas healing of ulcers takes much longer Ulcers may occur anywhere in the alimentary tract The most common are the peptic ulcers that occur in the duodenum and stomach.

Mechanisms of gastric injury and protection Mechanisms of gastric injury and protection. This diagram illustrates the progression from mild forms of injury to ulceration that may occur with acute or chronic gastritis. Ulcers include layers of necrotic debris (N), inflammation (I), and granulation tissue (G); scarring (S), which develops over time, is present only in chronic lesions

Peptic Ulcer Disease (PUD)

Peptic ulcer disease (PUD) Peptic ulcers are chronic, recurring lesions PUD may occur in any portion of the gastrointestinal tract exposed to acidic gastric juices Most often diagnosed in middle-aged to older adults The male/female ratio for duodenal ulcers is about 3:1 Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century Since the last decades of the 20th century, there is an impressive fall in its incidence

Peptic ulcer disease (PUD) The incidence of PUD is falling in developed countries along with reduced prevalence of H. pylori infection A new group of duodenal PUD patients older than 60 years of age has emerged as a result of increased NSAID use The lifetime risk for developing a peptic ulcer is 5% to 10%

Peptic ulcer disease (PUD) Pathogenesis. The imbalances of mucosal defenses and damaging forces that cause chronic gastritis are also responsible for PUD PUD most often is associated with H. pylori infection or NSAID use More than 70% of PUD cases are associated with H. pylori infection It is probable that host factors as well as variation among H. pylori strains also contribute to the pathogenesis

Peptic ulcer disease (PUD) Gastric acid is fundamental to the pathogenesis of PUD Cofactors in peptic ulcerogenesis include: Chronic NSAID use Cigarette smoking High-dose corticosteroids Peptic ulcers are more frequent in individuals with: Alcoholic cirrhosis Chronic obstructive pulmonary disease Chronic renal failure Hyperparathyroidism

Risk factors for Peptic Ulcer Disease H. pylori infection Cigarette use (synergizes with H. pylori for gastric PUD) Chronic obstructive pulmonary disease Illicit drugs (cocaine) that reduce mucosal blood flow NSAIDs (potentiated by corticosteroids) Alcoholic cirrhosis (primarily duodenal PUD) Psychological stress (can increase gastric acid secretion) Endocrine cell hyperplasia (can stimulate parietal cell growth and gastric acid secretion) Zollinger-Ellison Syndrome (PUD of stomach, duodenum, jejunum) Viral infection (CMV, herpes simplex virus) Illicit an act that is unlawful or otherwise not permitted

Peptic ulcer disease (PUD) Morphology Favored sites are: The anterior and posterior walls of the first portion of the duodenum The lesser curvature of the stomach Most are round, sharply punched-out craters, 2 to 4 cm in diameter The margins of the crater are not overhanging The base of the crater appears clean

Peptic ulcer of the duodenum. Note that the ulcer is small (2 cm) with a sharply punched-out appearance. Unlike cancerous ulcers, the margins are not elevated. The ulcer base is clean

Peptic ulcer disease (PUD) The histologic appearance varies with the activity, Chronicity degree of healing In a chronic ulcer, four zones can be distinguished : A thin layer of necrotic fibrinoid debris A zone of active nonspecific inflammatory infiltration with neutrophils predominating Granulation tissue Fibrous, collagenous scar

Stomach, chronic peptic ulcer - Very low power  This image shows a chronic peptic ulcer surrounded by elevated gastric mucosal margins Stomach, chronic peptic ulcer - Low power  An ulcer base containing a superficial thin layer of necrotic fibrinoid debris overlying a zone of inflammatory infiltrate with neutrophils predominating under which is a lower thick zone of granulation tissue with dilated blood vessels and lymphocytes. a deep zone of fibrous tissue, which extends into the superficial muscularis propria. 

Peptic ulcer disease (PUD) Clinical Features. A majority of peptic ulcers come to clinical attention after patient complaints of epigastric burning or aching pain   The pain tends to occur 1 to 3 hours after meals during the day The pain is worse at night, and is relieved by alkali or food Nausea, vomiting, bloating, and belching may be present Healing may occur with or without therapy, but the tendency to develop subsequent ulcers remains

Peptic ulcer disease (PUD) A significant fraction manifest with complications such as: Iron deficiency anemia Frank hemorrhage Perforation   The current therapies are aimed at H. pylori eradication with antibiotics and neutralization of gastric acid Surgical management is reserved primarily for treatment of ulcers with uncontrollable bleeding or perforation PUD causes much more morbidity than mortality

Stress-Related Mucosal Disease

Stress-Related Mucosal Disease More than 75% of critically ill patients develop endoscopically visible gastric lesions during the first 3 days of their illness Most critically ill patients admitted to hospital intensive care units have histologic evidence of gastric mucosal damage Stress-related gastric injury occurs in patients with: Severe trauma Extensive burns Intracranial disease Major surgery Serious medical disease Other forms of severe physiologic stress

Stress-Related Mucosal Disease In some cases, the associated ulcers are given specific names based on location and clinical associations: Stress ulcers Curling ulcers Cushing ulcers

Stress-Related Mucosal Disease Pathogenesis. The pathogenesis of stress-related gastric mucosal injury is most often due to local ischemia   This may be caused by systemic hypotension or reduced blood flow resulting from stress-induced splanchnic vasoconstriction Upregulation and increased release of the vasoconstrictor endothelin-1 also contributes to ischemic gastric mucosal injury

Stress-Related Mucosal Disease while increased COX-2 expression appears to be protective.   Cushing ulcers are thought to be caused by direct stimulation of vagal nuclei resulting acid hypersecretion Systemic acidosis may also contribute to mucosal injury by lowering the intracellular pH of mucosal cells

Stress-Related Mucosal Disease Morphology Stress-related gastric mucosal injury ranges from shallow erosions to deeper lesions that involve the entire mucosal thickness (true ulceration)   Acute stress ulcers are found anywhere in the stomach and are often multiple Acute ulcers are rounded, typically less than 1 cm in diameter The ulcer base is stained brown to black by acid-digested extravasated red cells

Multiple stress ulcers of the stomach, highlighted by the dark digested blood in their bases

Stress-Related Mucosal Disease The lesions are sharply demarcated Adjacent mucosa is normal, although there may be stain of blood into the mucosa and submucosa and some inflammatory reaction Healing with complete reepithelialization occurs days or weeks after the injurious factors are removed

Stress-Related Mucosal Disease Clinical Features Ulcers are associated with nausea, vomiting, melena, and coffee-ground hematemesis   Bleeding from superficial gastric erosions or ulcers that may require transfusion develop in 1% to 4% of these patients Other complications, including perforation, also may occur Prophylaxis with proton pump inhibitors may reduce the impact of stress ulceration The most important determinant of outcome is the severity of the underlying condition