What is the pathophysiology of acute appendicitis?

Pathophysiology of Acute Appendicitis

Acute appendicitis is primarily caused by obstruction of the appendiceal lumen leading to increased intraluminal pressure, venous congestion, and subsequent mucosal ischemia, which triggers an inflammatory cascade resulting in tissue damage and potential perforation. 1

Initial Pathological Process

• Obstruction of the appendiceal lumen is the initiating event in most cases, though contrary to popular belief, it may not be the primary cause in all instances 2
• Common causes of obstruction include:
  • Fecaliths (hardened fecal material)
  • Lymphoid hyperplasia (especially in younger patients)
  • Parasites
  • Tumors or neoplasms
  • External compression from adhesive bands (rare) 3, 4
• Obstruction leads to increased intraluminal pressure within the appendix 1
• The increased pressure causes venous congestion, impaired arterial blood flow, and subsequent mucosal ischemia 3

Inflammatory Cascade

• Following obstruction and ischemia, bacterial overgrowth occurs within the appendix 1
• The inflammatory process progresses through several stages:
  • Intraluminal inflammation (earliest stage)
  • Acute mucosal inflammation
  • Acute mucosal and submucosal inflammation
  • Suppurative (phlegmonous) appendicitis - transmural inflammation
  • Gangrenous appendicitis - tissue necrosis
  • Perforation - complete tissue breakdown 2
• The appendix develops vascular sclerosis in elderly patients, with muscular layers infiltrated with fat, creating structural weakness and tendency toward early perforation 5

Clinical Progression

• The natural history of appendicitis follows three stages:
  1. Normal appendix
  2. Uncomplicated acute appendicitis
  3. Complicated appendicitis (gangrenous or perforated) 5
• The inflammatory process typically begins at the base of the appendix and progresses distally 1
• Pain typically begins periumbilically and migrates to the right lower quadrant as the parietal peritoneum becomes inflamed 6
• Perforation rates vary from 16% to 40%, with higher frequencies in younger children and patients older than 50 years (55-70%) 5

Risk Factors for Complicated Disease

• Advanced age significantly increases risk of perforation, with elderly patients (>65 years) having perforation rates of 18-70% compared to 3-29% in younger patients 5
• Delayed presentation and diagnosis significantly increase perforation risk 5
• The median duration from symptom onset to definitive care in complicated cases is approximately 4 days 5
• Vascular sclerosis and structural weakness of the appendix in elderly patients predispose to early perforation 5

Laboratory Findings

• Leukocytosis (WBC count >10,000/mm³) has a positive likelihood ratio of 2.47 for appendicitis 7
• Higher WBC counts (>15,000/mm³) increase the likelihood ratio to 3.47, indicating stronger association with appendicitis 7
• Combined elevated WBC count and C-reactive protein has a positive likelihood ratio of 23.32 for acute appendicitis 7
• Normal values of both WBC and CRP can effectively exclude appendicitis with a negative predictive value of 100% 7

Complications

• Perforation leads to localized or generalized peritonitis 6
• Abscess formation is a common complication of ruptured appendicitis 6
• Complicated appendicitis is associated with:
  • Increased hospital stays (median 5 days)
  • Higher reoperation rates (up to 40%)
  • Increased ICU admission rates (approximately 10%)
  • Mortality risk of approximately 1% 6

Special Considerations

• Appendicitis is the most common cause of intra-abdominal sepsis worldwide, accounting for 34.2% of cases 5
• The incidence varies geographically, with lower rates in sub-Saharan Africa and parts of Asia and Latin America, though rates are increasing in urban centers in these regions 5
• Elderly patients have higher post-operative mortality, morbidity, longer hospital stays, and often require more complex procedures 5
• The mortality risk increases threefold with each decade of age beyond 65 years 5