What is the pathophysiology of appendicitis?

Pathophysiology of Appendicitis

Appendicitis develops when the appendiceal lumen becomes obstructed, leading to increased intraluminal pressure, mucosal ischemia, bacterial overgrowth, and progressive inflammation that can advance to gangrene and perforation if untreated. 1

Mechanism of Obstruction

The pathophysiological cascade begins with obstruction of the appendiceal orifice, which can result from several causes:

• Fecaliths and fecal material are the most common obstructing agents in adults, creating a mechanical blockage of the appendiceal lumen 1, 2
• Lymphoid hyperplasia is a frequent cause, particularly in younger patients, where enlarged lymphoid follicles within the appendiceal wall narrow or occlude the lumen 2, 3, 4
• Parasitic infections, most commonly Enterobius vermicularis and Taenia species, can physically obstruct the lumen, though this accounts for less than 1% of cases 5, 3
• Foreign bodies, including seeds and other ingested materials, rarely cause obstruction but have been documented 5
• Neoplastic growth, such as colonic adenocarcinoma, can obstruct the appendiceal orifice, particularly in older patients, though this is an uncommon etiology 2

Progressive Inflammatory Cascade

Once obstruction occurs, a predictable sequence of pathological events unfolds:

• Increased intraluminal pressure develops as continued mucus secretion accumulates behind the obstruction, distending the appendix 1
• Mucosal ischemia results from the elevated pressure compressing the appendiceal blood vessels, compromising tissue perfusion 1
• Bacterial overgrowth occurs within the obstructed lumen as normal intestinal flora proliferate in the stagnant environment 1
• Transmural inflammation progresses as bacteria invade the ischemic appendiceal wall, extending from mucosa through all layers 1

Clinical Stages of Disease Progression

The natural history follows three distinct stages:

• Stage 1: Normal appendix with no pathological changes 1
• Stage 2: Uncomplicated acute appendicitis characterized by inflammation without gangrene or perforation, representing approximately two-thirds of all cases 1
• Stage 3: Complicated appendicitis including gangrenous appendicitis (with vascular compromise and tissue necrosis), perforated appendicitis (with breach of the appendiceal wall), periappendiceal abscess formation, or diffuse peritonitis 1

Pain Mechanism and Migration

The characteristic pain pattern reflects the underlying pathophysiology:

• Periumbilical pain occurs initially as visceral pain fibers respond to appendiceal distension and increased intraluminal pressure 1, 4
• Migration to the right lower quadrant develops as inflammation extends through the appendiceal wall to involve the parietal peritoneum, which has somatic innervation providing precise localization 1, 4

Age-Related Pathophysiological Variations

Elderly patients (>65 years) have distinct anatomical changes that alter disease progression:

• Vascular sclerosis of the appendiceal blood supply reduces tissue perfusion and accelerates ischemia 1, 6
• Muscular layer infiltration with fat creates structural weakness and increases the tendency toward early perforation 1, 6
• These anatomical changes contribute to perforation rates of 18-70% in elderly patients compared to only 3-29% in younger patients 1, 6

Pediatric patients demonstrate different pathophysiology:

• Lymphoid follicles are larger and more numerous in children and young adults, with diameter decreasing significantly with advancing age (from 0.62 mm in ages 0-20 years to 0.45 mm in ages >50 years) 7
• This abundant lymphoid tissue makes lymphoid hyperplasia a more common cause of obstruction in the pediatric population 3, 7

Risk Factors for Complicated Disease

Certain features predict progression to complicated appendicitis:

• Presence of an appendicolith is strongly associated with progression to perforation and complicated disease 1
• Delayed presentation significantly increases perforation risk, with median duration from symptom onset to care in complicated cases being approximately 4 days 1
• Advanced age dramatically increases perforation risk, with elderly patients having 18-70% perforation rates versus 3-29% in younger patients 1, 6

Mortality by Disease Stage

The severity of inflammation directly correlates with mortality risk:

• Non-gangrenous appendicitis: <0.1% mortality 1, 6
• Gangrenous appendicitis: 0.6% mortality 1, 6
• Perforated appendicitis: approximately 5% mortality 1, 6
• Elderly patients (>65 years) have overall mortality reaching 8%, with case fatality rates increasing threefold with each decade beyond age 65, exceeding 16% in nonagenarians 6