Acute appendicitis probably begins with an obstruction of the lumen. The obstruction can result from food matter, adhesions, or lymphoid hyperplasia. Despite the obstruction, mucosal secretion continues, leading to an increase in intraluminal pressure. This pressure will eventually exceed capillary perfusion pressure and will obstruct venous and lymphatic drainage. With such vascular compromise, the epithelial mucosa begins to break down, allowing bacterial invasion by bowel flora. The subsequent inflammatory response and edema further exacerbate the increased intraluminal pressure. Eventually, this increased pressure leads to arterial stasis and tissue infarction. The end result is perforation and spillage of the infected appendiceal contents into the peritoneum.

In order to understand the clinical presentation and the clinical progression of acute appendicitis, it is important to consider the innervation and anatomic variability of the appendix. Presumably, the initial lumenal distention triggers the visceral afferent pain fibers from the appendix, which enter the spinal cord at the tenth thoracic vertebra. As is characteristic of visceral afferent innervation, this pain is generally vague and poorly localized. Based on the anatomic level of these afferent fibers at the tenth thoracic level, the pain is generally perceived by the patient at the periumbilical or epigastric region. Eventually, as the inflammatory process continues, the appendiceal serosa and adjacent structures become inflamed. This inflammation triggers the somatic pain fibers, which innervate the peritoneal structures, typically localizing the pain in the right lower quadrant. This explains the migration of pain from the periumbilical area to the right lower quadrant, classically associated with acute appendicitis.

The clinician must be aware, however, that there are many exceptions to this classic presentation of the pain of acute appendicitis. These exceptions are often due to the variability of the anatomic location of the appendix. In a study of 71,000 human appendix specimens removed over a 40-year period, 26 percent were retrocecal, and 4 percent were located in the right upper quadrant.3 With the retrocecal appendix, the pain of acute appendicitis may localize to the flank rather than the right lower quadrant. Similarly, in pregnant patients, the gravid uterus may displace the appendix, leading to a presentation of right upper quadrant or flank pain. In male patients, a retroileal appendicitis may irritate the ureter, causing pain in the testicle. A pelvic appendix may irritate the bladder or rectum and cause suprapubic pain, pain with urination, or the feeling of a need to defecate. These anatomically based variations in presentation help to explain the difficulty in making the diagnosis of acute appendicitis.

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