Appendicitis

• Luminal obstruction and pressure dynamics: The appendical lumen becomes obstructed by lymphoid hyperplasia (most common, especially in viral infections), fecoliths, strictures, malignancy, or rarely parasites. As intraluminal pressure rises and exceeds capillary perfusion pressure (normally 15-20 mmHg), mucosal blood flow becomes compromised. Further pressure elevation (>60 mmHg) produces full-thickness ischemia. This mechanical obstruction creates a closed-loop phenomenon unique to the appendix, distinguishing it from other segments of bowel where proximal and distal decompression can occur.

• Mucosal barrier breakdown and bacterial translocation: Ischemia initiates loss of mucosal integrity, allowing invasion by luminal bacteria (predominantly aerobic gram-negatives like E. coli and anaerobes like Bacteroides fragilis). The appendix harbors high bacterial concentrations (up to 10⁸ organisms per mL) as part of normal gut flora. Without adequate blood supply, the mucosa cannot maintain its barrier function or mount a protective immune response. Bacterial lipopolysaccharides (LPS) and other pathogen-associated molecular patterns (PAMPs) trigger toll-like receptor (TLR) signaling, particularly TLR4, activating innate immunity.

• Transmural inflammation and cytokine cascade: Tissue macrophages and infiltrating neutrophils release pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8). These cytokines increase vascular permeability, promote neutrophil chemotaxis, and activate the complement cascade (particularly the alternative pathway via bacterial LPS). Nuclear factor-kappa B (NF-κB) translocation amplifies inflammatory gene transcription. The inflammation initially remains localized due to the appendix's peritoneal investment and omentum, but progressive transmural involvement leads to visceral peritoneal involvement, causing characteristic pain migration and peritoneal signs.

• Perforation and abscess formation: Continued ischemia and inflammation lead to full-thickness necrosis and perforation, typically 24-72 hours after symptom onset if untreated. Perforation releases purulent material into the peritoneal cavity. In some patients, omentum and adjacent bowel wall off the perforation site, creating a localized abscess rather than diffuse peritonitis. Factors favoring localization include delayed presentation (>48 hours), development of adhesions, and intact visceral peritoneal covering. This "contained perforation" may be associated with a palpable mass on examination.

• Inflammatory mediator amplification: Bacterial lipopolysaccharides stimulate production of phospholipase A₂, generating arachidonic acid metabolites (prostaglandins and leukotrienes) that further enhance inflammation and promote visceral smooth muscle contractions. Substance P and other neuropeptides released from nerve endings contribute to the visceral pain perception and can potentiate smooth muscle contraction.

• Lymphoid hyperplasia (most common cause, 60% of cases): Enlargement of lymphoid follicles within the appendical wall, often triggered by viral infections (adenovirus, norovirus, rotavirus) or bacterial infection. This hyperplasia compresses the appendical lumen and is particularly common in children and young adults. Often precedes appendicitis by 1-2 weeks, explaining the prodromal symptoms some patients report. No specific preventive measure exists, though vaccination programs may theoretically reduce viral gastroenteritis incidence.

• Fecoliths (20-35% of cases): Hard, stone-like accumulations of fecal material, bacteria, and inorganic material. More common in Western developed nations with low-fiber diets, increasing stasis within the appendix. Fecoliths >5 mm have higher association with appendicitis. When fecoliths perforate, they are associated with worse outcomes including higher perforation rates and more complex abscess formations. Computed tomography can identify these radiodense structures.

• Malignancy and strictures (rare, <1-2%): Carcinoid tumors of the appendix are the most common appendiceal neoplasm (accounts for 40% of appendiceal tumors), though only 1-3% of appendices resected for presumed appendicitis contain malignancy. Adenocarcinoma, mucinous lesions, and lymphomas occur less frequently. Strictures may result from prior inflammation, Crohn's disease, or TB. These should be suspected in elderly patients without typical prodrome or those with atypical presentations.

• Infectious triggers: Viral gastroenteritis, bacterial infections (salmonellosis, shigellosis, campylobacteriosis, tuberculosis in endemic areas), measles (historically), and parasitic infections (amebiasis, schistosomiasis in endemic regions) can precipitate lymphoid hyperplasia leading to obstruction.

• Inflammatory bowel disease (IBD): Patients with Crohn's disease have 5-10 times increased appendicitis risk. Appendiceal involvement in ulcerative colitis is less common, though mucosal inflammation can predispose to secondary bacterial overgrowth.

• Cystic fibrosis: Inspissated secretions and abnormal mucus increase appendiceal obstruction risk; incidence of appendicitis in CF patients is markedly elevated.

• Dietary and lifestyle factors: Low-fiber diet, high processed food intake, and constipation may increase fecal stasis and fecalith formation, though evidence is not definitive.

• Visceral pain (initial manifestation): Begins periumbilically or in the epigastrium as poorly localized visceral pain because the appendix, derived from midgut, maintains visceral innervation via sympathetic fibers entering at T10 spinal cord level. This pain results from visceral distension and ischemia rather than peritoneal irritation. Patients describe it as constant, dull, and non-colicky (distinguishing it from obstruction). This visceral phase typically lasts 6-12 hours. The periumbilical location reflects referred pain patterns via dermatomes T10, not true appendiceal localization.

• Pain migration to right lower quadrant (highly specific finding): As inflammation progresses to involve the parietal peritoneum, somatic innervation becomes involved via spinal nerves T12 and L1, producing localized, sharp pain at McBurney's point (junction of lateral and medial thirds of line from anterior superior iliac spine to umbilicus, approximately 2-3 cm above the inguinal ligament). This migration typically occurs 12-24 hours into illness and represents visceral-to-somatic pain transition. The presence of this migration is highly suggestive of appendicitis and strongly influences diagnostic probability.

• Anorexia, nausea, and vomiting: These develop after pain onset (important historical point—pain precedes vomiting, distinguishing appendicitis from gastroenteritis). Results from visceral irritation and increased intraluminal pressure stimulating chemoreceptor trigger zone. Vomiting typically occurs once per several hours, not the profuse vomiting of gastroenteritis. Occurs in 70-75% of patients.

• Fever: Develops insidiously, typically low-grade (37.5-38.5°C) early in disease, though higher temperatures suggest perforation or abscess. Fever results from inflammatory cytokine release and bacterial invasion. Absence of fever does not exclude appendicitis and may be seen in early disease.

• Diarrhea or constipation: Variable presentation. Some patients report loose stools (from colonic irritation or pelvic appendiceal position), while others have constipation (from ileal involvement). This distinguishes appendicitis from pure gastroenteritis, which typically causes diarrhea.

• Right lower quadrant tenderness (cardinal physical exam finding): Localized tenderness at McBurney's point or generalized RLQ tenderness represents the sine qua non of appendicitis. Initially mild with early disease, progressively worsens with advancing inflammation and peritoneal involvement. Must be distinguished from referred tenderness by careful palpation technique.

• Rebound tenderness and guarding (peritoneal signs): Develop as visceral peritoneum becomes inflamed. Rebound tenderness (increased pain when examining hand rapidly released from abdomen) represents parietal peritoneal irritation. Rigidity and guarding indicate more advanced peritoneal inflammation. These findings worsen with perforation. Presence of rigidity suggests either perforation or advanced localized inflammation.

• Rovsing's sign: Pain in RLQ elicited by palpating the left lower quadrant, due to transmitted peritoneal irritation. Sensitivity 25-88% (highly variable), specificity 86%, making it less reliable than direct RLQ tenderness but useful when present.

• Psoas sign: Right hip flexion causes pain due to anatomic irritation when appendix lies retroperitoneally near the psoas muscle. Occurs in only 10-20% of patients but highly specific when present, as it suggests retroperitoneal or deep pelvic inflammation.

• Obturator sign: Pain with internal hip rotation due to irritation of obturator internus muscle; suggests pelvic appendix location. Less specific than psoas sign.

• Important clinical variants:
• Retrocecal appendix (most common anatomic variant): Appendix lies behind the cecum and can present with flank tenderness, back pain, or minimal peritoneal signs; may be confused with renal pathology
• Pelvic appendix: Can present with suprapubic pain, urinary symptoms (dysuria, frequency), diarrhea; often delayed diagnosis; gynecologic exam may reveal adnexal tenderness
• Paracolic appendix: Can present with pain more medial to typical McBurney's point
• Pregnancy (second and third trimester): Pain and tenderness shift cephalad as uterus enlarges; RLQ tenderness occurs higher and more lateral than expected; higher perforation rate due to diagnostic delays
• Elderly patients: Often present with minimal signs and late in disease; perforation rate exceeds 50% at presentation; systemic symptoms (malaise, confusion) may predominate; delayed presentation leads to worse outcomes
• Immunocompromised patients: May have blunted inflammatory response with minimal symptoms despite advanced disease

• Clinical scoring systems—Alvarado Score (most widely used): Provides systematic scoring of historical and physical findings to estimate pretest probability. Components include: Migration of pain to RLQ (1 point), Anorexia (1), Nausea/vomiting (1), Tenderness at McBurney's point (2), Rebound tenderness (1), Elevated temperature ≥37.3°C (1), Leukocytosis ≥10,000/μL (2), Left shift of WBC differential ≥75% (1). Total score ranges from 0-10. Score ≥7 = likely appendicitis (sensitivity 92%, specificity 72% in derivation cohort); score 5-6 = possible appendicitis (requires imaging); score ≤4 = appendicitis unlikely (but does not completely exclude). However, Alvarado score shows variable performance in different populations and should not replace clinical judgment or imaging.

• Complete blood count (CBC): Leukocytosis (WBC >10,000/μL) occurs in approximately 80% of appendicitis cases; median count 13,000-15,000/μL. Leukopenia or normal WBC does not exclude appendicitis. Left shift (increased band forms and immature neutrophils, or left shift percentage >75%) is more specific than absolute leukocytosis and reflects acute bacterial infection. CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) are elevated in 90% and 60% of cases respectively, but lack specificity as they reflect any inflammatory process. Procalcitonin may have utility in detecting bacterial vs. viral causes but is not standard.

• Urinalysis: Critical to obtain to exclude urinary tract pathology. Should be normal or show only mild changes; significant proteinuria, bacteriuria, or pyuria suggests pyelonephritis, ureterolithiasis, or cystitis. However, pyuria can occur with appendicitis if inflamed appendix contacts bladder or ureter, so urinalysis abnormalities do not exclude appendicitis.

• Imaging—Ultrasound: Often first-line imaging, particularly in pregnancy, pediatric patients, and resource-limited settings. Graded compression ultrasound uses progressive transducer pressure to displace bowel gas and visualize the appendix. Diagnostic criteria for appendicitis include: (1) non-compressible appendiceal diameter >6 mm (sensitivity 86%, specificity 97%), (2) appendiceal wall thickening >2 mm, (3) target sign appearance (concentric layers of alternating echogenicity), (4) loss of echogenic submucosal layer, (5) fluid collection suggesting perforation or abscess, (6) periappendiceal echogenicity reflecting edema. Hyperemia on color Doppler indicates inflammation. Sensitivity ranges 75-92%, specificity 86-98% depending on operator experience. Advantages include no radiation, real-time assessment, and dynamic compression. Limitations include operator dependency, poor visualization in obese patients, and gas artifact.

• Imaging—CT scan (now often first-line imaging in many centers): Multidetector CT with oral, rectal, or IV contrast provides excellent sensitivity (94-98%) and specificity (95-98%). Diagnostic criteria include: (1) appendiceal diameter >6 mm (>7 mm with wall thickening), (2) appendiceal wall enhancement/thickening, (3) appendicolith (if visible, increases certainty), (4) periappendiceal fat stranding (inflammation of mesoappendix and adjacent fat), (5) free fluid in pelvis (suggests perforation or contained abscess), (6) abscess or mass effect. CT can identify alternative diagnoses (diverticulitis, pyelonephritis, gynecologic pathology, etc.), reducing negative appendectomy rates. CT is particularly valuable in atypical presentations, equivocal clinical findings, and when perforation is suspected. MRI is an alternative in pregnancy and younger patients to avoid radiation, with similar accuracy to CT.

• Diagnostic criteria summary: Integration of clinical presentation, lab findings, and imaging produces diagnostic certainty. Imaging criteria most specific for appendicitis (when using CT or high-quality ultrasound): appendiceal diameter >6 mm + appendiceal wall thickening + periappendiceal fat stranding. Isolated appendicolith without other findings is insufficient for diagnosis, as fecoliths can be incidental. Appendiceal diameter 5-6 mm in a symptomatic patient with clinical signs warrants either close observation or repeat imaging in 4-6 hours if clinical presentation is borderline.

• Differential diagnosis considerations: Mesenteric adenitis (viral, with normal appendiceal caliber on imaging), acute gastroenteritis (prodromal diarrhea, diffuse symptoms, pain does not migrate), gynecologic pathology (ectopic pregnancy, ovarian torsion, pelvic inflammatory disease—careful history and imaging essential, especially in women of reproductive age), pyelonephritis/ureterolithiasis (dysuria, hematuria, CVA tenderness), ileitis (terminal ileitis in Crohn's disease—clinical context

Immediate stabilisation

• Resuscitation and NPO status: isotonic crystalloid (lactated Ringer's or normal saline) for the volume deficit from vomiting and third-spacing; nothing by mouth in anticipation of general anesthesia. Correct electrolytes before induction.
• Analgesia: opioid analgesia (e.g., morphine or fentanyl) should not be withheld. The old teaching that analgesia "masks" peritoneal signs has been refuted; the American College of Emergency Physicians supports early analgesia in undifferentiated abdominal pain.

Antibiotics (pre-operative, not a substitute for source control)

• Coverage of enteric gram-negatives and anaerobes: a second-generation cephalosporin with anaerobic activity (cefoxitin) or a third-generation cephalosporin plus an imidazole (ceftriaxone + metronidazole) for uncomplicated disease; piperacillin-tazobactam or a carbapenem for complicated (perforated, abscess) or high-risk patients, per Surgical Infection Society and IDSA intra-abdominal infection guidance.
• Penicillin allergy: cephalosporins with dissimilar R1 side chains are generally safe — true cross-reactivity is roughly 1–3%, not the historical 10%. Alternatives include a fluoroquinolone or aztreonam plus metronidazole.

Definitive management

• Laparoscopic appendectomy is the standard of care and is favored over open appendectomy by the World Society of Emergency Surgery for lower wound infection rates and faster recovery. Surgery should not be delayed for prolonged observation once the diagnosis is made.
• Non-operative management with antibiotics alone is an accepted alternative in selected adults with uncomplicated appendicitis (supported by the CODA and APPAC trials); counsel that a substantial minority ultimately require appendectomy, and failure is markedly more likely when an appendicolith is present.
• Perforation with a walled-off abscess or phlegmon: broad-spectrum antibiotics plus percutaneous drainage, with interval appendectomy considered later. Adults over 40 warrant colonoscopy afterward to exclude an obstructing colonic neoplasm.
• Pregnancy: appendectomy in any trimester; delay raises perforation and fetal-loss risk.

Avoid

• Non-operative management in generalized peritonitis or hemodynamic instability — this is an operative emergency.
• Prolonged post-operative antibiotics after uncomplicated appendectomy; for complicated disease with adequate source control, a short fixed course suffices (STOP-IT trial).

Complications of the disease

• Perforation: transmural necrosis from unrelieved closed-loop pressure. Signaled by sudden transient pain relief followed by worsening diffuse pain, high fever, tachycardia, and rigidity. Highest rates in children under 5, the elderly, and pregnancy because of diagnostic delay. Emergency.
• Diffuse purulent peritonitis and septic shock: free spillage overwhelms omental containment; board-out abdomen, absent bowel sounds, hypotension with warm extremities. Emergency — resuscitate and operate.
• Periappendiceal abscess or phlegmon: contained perforation walled off by omentum and small bowel; presents with a tender RLQ mass, spiking fevers, and a rim-enhancing fluid collection on CT. Managed with antibiotics and percutaneous drainage rather than immediate appendectomy.
• Pylephlebitis: septic thrombophlebitis of the portal venous system from bacteremic seeding along the ileocolic vein. High fever with rigors, jaundice, and multiple hepatic abscesses; blood cultures often grow Bacteroides or E. coli. Rare but life-threatening.
• Small bowel obstruction: from inflammatory adhesions or paralytic ileus; bilious vomiting, distension, air-fluid levels.
• Obstetric loss and preterm labor: risk rises sharply with perforation, which is the main argument against delaying surgery in pregnancy.

Complications of treatment

• Surgical site infection: more common after open than laparoscopic appendectomy and after perforated disease.
• Post-operative intra-abdominal abscess: paradoxically more frequent after laparoscopy for perforated appendicitis; suspect with persistent fever and leukocytosis on post-operative days 5–7 — obtain CT.
• Stump appendicitis: inflammation of a retained appendiceal remnant; recurrent RLQ pain in a patient with a prior appendectomy — a classic diagnostic trap.
• Negative appendectomy: removal of a normal appendix; incidence has fallen with CT and ultrasound.
• Incidental appendiceal neoplasm: most often a neuroendocrine (carcinoid) tumor found on pathology; rupture of a mucinous neoplasm can seed pseudomyxoma peritonei.

• Pain precedes vomiting: the single most useful historical discriminator from gastroenteritis, where vomiting and diarrhea come first. Anorexia is nearly universal — a hungry patient asking for food makes the diagnosis less likely.
• Migration is the most specific symptom: dull periumbilical (T10 visceral, midgut) pain localizing to McBurney's point as the parietal peritoneum becomes inflamed. Examiners test this visceral-to-somatic transition as a pain-referral concept, not just a fact.
• Best next step in any woman of reproductive age is a urine or serum β-hCG, before imaging or the operating room. Ectopic pregnancy is the distractor the stem is usually built around; ovarian torsion and PID are the others.
• Imaging by population: ultrasound first in children and pregnancy; CT with IV contrast in most non-pregnant adults; MRI without gadolinium if ultrasound is non-diagnostic in pregnancy, per ACR Appropriateness Criteria. Do not order CT in a pregnant patient as the first step.
• Do not delay surgery for imaging in a patient with peritonitis — rigidity plus hemodynamic instability means the operating room, not the scanner.
• An appendicolith predicts failure of antibiotics-alone therapy (CODA trial) and higher perforation risk; its presence pushes toward appendectomy.
• Analgesia does not obscure the exam — withholding opioids is the wrong answer.
• Appendiceal neuroendocrine tumor is the classic incidental pathology finding: a small tumor at the appendiceal tip is cured by appendectomy alone, whereas a large tumor or one involving the base/mesoappendix prompts right hemicolectomy.
• Atypical anatomy explains atypical stems: retrocecal appendix gives flank/back pain with a positive psoas sign and few peritoneal signs; pelvic appendix gives dysuria, diarrhea, and a positive obturator sign.