What is the pathophysiology of appendicitis?

Pathophysiology of Appendicitis

Appendicitis develops when obstruction of the appendiceal lumen leads to increased intraluminal pressure, causing venous congestion, mucosal ischemia, bacterial overgrowth, and progressive inflammation that can advance to necrosis and perforation if untreated. 1, 2

Primary Mechanism: Luminal Obstruction

The initiating event in most cases involves obstruction of the appendiceal orifice, which triggers a cascade of pathological changes 1:

• Fecaliths (inspissated stool) are the most common obstructing agents 1, 3
• Lymphoid hyperplasia can occlude the lumen, particularly in younger patients 1, 3
• Appendicoliths (calcified fecal material) strongly predict progression to complicated disease 4
• Parasites may cause obstruction in endemic regions 1, 3
• Neoplasms (benign or malignant tumors at the appendiceal base) can mechanically obstruct outflow 1, 5

Sequential Pathophysiological Cascade

Once obstruction occurs, the following progression unfolds 1, 5:

1. Increased intraluminal pressure develops as mucus secretion continues despite blocked outflow 1, 2
2. Venous congestion and lymphatic stasis occur as intramural pressure rises and compresses small vessels 2, 5
3. Mucosal ischemia results from compromised blood flow to the appendiceal wall 1, 2
4. Bacterial overgrowth proliferates in the obstructed, ischemic environment 5
5. Transmural inflammation extends through all layers of the appendiceal wall 5
6. Necrosis and gangrene develop as ischemia progresses 5
7. Perforation occurs when necrotic tissue breaks down, releasing bacteria into the peritoneal cavity 4

Clinical Stages of Disease Progression

The natural history follows three distinct stages 4:

• Stage 1: Normal appendix with no pathological changes
• Stage 2: Uncomplicated acute appendicitis with inflammation but intact wall (represents approximately two-thirds of cases) 4
• Stage 3: Complicated appendicitis including gangrenous changes, perforation, periappendiceal abscess, or diffuse peritonitis 4

Perforation rates range from 16% to 40% overall, but increase dramatically to 55-70% in elderly patients due to age-related vascular changes 4.

Age-Related Pathophysiological Differences

Elderly patients experience distinct pathophysiological vulnerabilities 4:

• Vascular sclerosis of appendiceal blood vessels reduces perfusion capacity 4
• Fatty infiltration of muscular layers creates structural weakness 4
• Early perforation tendency results from compromised tissue integrity 4
• Delayed inflammatory response may mask clinical severity 4

Alternative and Uncommon Mechanisms

While obstruction dominates, other mechanisms exist 2, 3, 6:

• External compression from adhesive bands can create outflow obstruction without intraluminal pathology 2
• Blunt abdominal trauma may theoretically trigger appendicitis through direct injury or vascular compromise 3
• Primary mucosal inflammation without clear obstruction may occur, though this challenges traditional models 6

Critical Caveat on Obstruction Theory

Contrary to widespread belief, the best available evidence suggests that luminal obstruction may not be the primary cause in the majority of cases 6. While obstruction is frequently taught as the universal mechanism, pathological studies indicate that many appendicitis cases lack identifiable obstructing lesions, suggesting alternative inflammatory pathways may initiate disease 6. However, when obstruction is present—particularly with appendicoliths—it strongly predicts progression to complicated disease 4.

Clinical Implications of Pathophysiology

Understanding the pathophysiological progression directly impacts clinical outcomes 4:

• Mortality varies by stage: <0.1% for non-gangrenous appendicitis, 0.6% for gangrenous appendicitis, and approximately 5% for perforated appendicitis 4
• Time-dependent progression means delayed diagnosis significantly increases perforation risk, with median duration to complicated disease being approximately 4 days from symptom onset 4
• Pain migration from periumbilical to right lower quadrant reflects progression from visceral (luminal distension) to parietal peritoneal inflammation 4