1. Pathology and pathophsiolgy of peptic ulcer
Dr. Mamlook Elmagraby

2. 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

3. Gastric Ulceration

4. 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.

5. 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

6. Peptic Ulcer Disease (PUD)

7. 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

8. 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%

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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. 

16. 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

17. 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

18. Stress-Related Mucosal Disease

19. 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

20. 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

21. 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

22. 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

23. 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

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

25. 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

26. 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