ANATOMY

1 The anatomy of the appendix tells the story of the epidemiology of appendicitis. Embryologically,

the appendix is part of the cecum from which it originates where the three tenia coli coalesce on the

cecum. Not surprisingly, the appendix resembles the cecum histologically and includes circular and

longitudinal muscle layers. In addition, the appendix contains an abundance of lymph follicles in the

submucosa, numbering approximately 200. The highest number of lymph follicles occurs in the 10-

to 20-year-old age group, with a decline in number after age 30; lymph follicles are typically absent

after age 60.

The appendix arises from the cecum approximately 2.5 cm below the ileocecal valve. It varies in

length from complete agenesis to more than 30 cm, but it is usually 5 to 10 cm in length. The mean

width is 0.5 to 1.0 cm. The various positions of the appendix are conveniently categorized into the

following locations: paracolic (the appendix lies in the right paracolic gutter lateral to the cecum),

retrocecal (the appendix lies posterior to the cecum and may be partially or totally extraperitoneal),

preileal (the appendix is anterior to the terminal ileum), postileal (the appendix is posterior to the

ileum), promontoric (the tip of the appendix lies in the vicinity of the sacral promontory), pelvic (the

tip of the appendix lies in or toward the pelvis), and subcecal (the appendix lies inferior to the cecum).

Wakeley2 performed a postmortem analysis of 10,000 cases and described the frequency of the location

of the appendix as follows: retrocecal, 65.3%; pelvic, 31%; subcecal, 2.3%; preileal, 1%; and right

paracolic and postileal, 0.4%. In essence, the appendix may lie in multiple locations, essentially at

virtually any position in a clockwise rotation from the base of the cecum. The clinician must appreciate

that the anatomic location of the appendix determines the presentation of symptoms and signs during an

episode of appendicitis.

PATHOPHYSIOLOGY

Wangensteen and Dennis

3 demonstrated experimentally that luminal obstruction leads to the

development of acute appendicitis. The appendix has a small luminal diameter in relation to its length.

Conventional wisdom holds that this configuration predisposes the appendix to closed-loop obstruction

and subsequent inflammation. Specifically, proximal obstruction (by any number of initiating factors)

leads to ongoing mucous secretion of the appendiceal mucosa distal to the obstruction into a closed

lumen with elevation of intraluminal pressure. Rapid distention of the appendix ensues because of its

small luminal capacity and intraluminal pressures can reach 50 to 65 mm Hg. Distension of the appendix

stimulates visceral afferent pain fibers, producing a somewhat vague and diffuse periumbilical pain.

Distention of the appendix often causes reflex nausea and/or vomiting with a progressive increase in the

severity of the visceral pain.

As luminal pressure increases, venous pressure is exceeded and mucosal ischemia develops. Once

luminal pressure exceeds 85 mm Hg, thrombosis of the venules that drain the appendix occurs and, in

the setting of continued arteriolar inflow, vascular congestion and engorgement of the appendix become

manifest. With vascular congestion, the appendiceal mucosa becomes hypoxic and begins to ulcerate,

resulting in compromise of the mucosal barrier, and leading to invasion of the appendiceal wall by

intraluminal bacteria. This sets in motion an inflammatory process that leads to mucosal disruption

followed by serosal involvement and finally inflammation of the nearby parietal peritoneum, resulting

in the characteristic shift in location of pain to the right lower quadrant along with localized tenderness.

If unimpeded, luminal pressure rises to a level that induces venous infarction, full-thickness necrosis,

and perforation. The length of time required for the disease to progress to gangrene and perforation is

highly variable. One study demonstrated a mean duration of abdominal pain of 46.2 hours in patients

with gangrene and 70.9 hours for perforation.4

Fecal stasis and fecaliths are the most common cause of appendiceal obstruction, followed by

lymphoid hyperplasia, vegetable matter and fruit seeds, inspissated barium from previous radiographic

studies, intestinal worms (especially ascarids), and tumors (such as carcinoid). It is important to note

that the offending agent causing obstruction is only found in 50% of the cases. Accordingly, it is fair to

state that luminal obstruction appears to account for many cases of appendicitis, but the cause for a

substantial number of cases remains elusive.

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DIAGNOSIS OF ACUTE APPENDICITIS

Despite knowing about the disease process for over 300 years, identifying which patients have it still

poses a significant challenge today. In the United States, approximately 11 of 10,000 people will

develop acute appendicitis over their lifetime, with the typical age of onset between the ages of 11 and

19 years.5 Appendicitis is a common problem; there are more than 300,000 hospital discharges for

appendicitis in the United States per year. Due to its frequent epidemiology it is often thought of as a

straightforward diagnosis, but this is rarely the case. Diagnostic errors are common, with overdiagnosis

leading to negative appendectomies, and with delays in diagnosis leading to perforations. The

misdiagnosis of appendicitis has significant economic ramifications; in a nationwide study of

administrative data, a negative appendectomy rate of 15% resulted in more than $740 million in

hospital charges.6 On the other end of the spectrum, delay or error in diagnosis of acute appendicitis is

now one of the most frequent allegations of medical malpractice that are leveled against general

surgeons, emergency medicine physicians, and primary care physicians.

As with any patient presenting with abdominal pain the evaluation should begin with a thorough

history and physical examination. In certain populations, appendicitis remains one of the disease

processes cared for by surgeons that can be diagnosed with a careful history and physical examination

alone, sparing the patient the cost and discomfort of imaging. Published guidelines note that the

combination of clinical and laboratory findings of characteristic abdominal pain, localized tenderness,

and laboratory evidence of inflammation will identify most patients with suspected appendicitis.7 Other

diagnostic strategies may include radiologic imaging or the use of scoring systems with or without

computer support. Ultimately, the “gold standard” for a positive diagnosis is the histopathologic

confirmation of appendicitis, although standard criteria are lacking.

HISTORY AND PHYSICAL EXAMINATION

2 Despite advances in diagnostic tests, appendicitis remains a clinical diagnosis. Clinical symptoms

elicited by the history may include fever, nausea, vomiting, anorexia, migration of pain to the right

lower quadrant, and aggravation of pain by movement. Physical examination may reveal signs of

peritoneal irritation in the right lower quadrant or diffusely. Rectal examination may reveal

tenderness. There is evidence that the order that the symptoms present in is often diagnostic.

Authors have suggested that pain usually comes before nausea or fever and if the order is reversed

then the diagnosis is not appendicitis. Furthermore, there are a variety of named signs that may be

associated with appendicitis depending upon the location of the inflamed appendix (Table 71-1). The

signs and symptoms are common and nonspecific; each individual sign and symptom is only weakly

predictive of appendicitis.8 Furthermore, the differential diagnosis for right lower-quadrant

abdominal pain is wide and varies with age and gender. When signs and symptoms were compared

between children and adults, they were similarly predictive of appendicitis, with the exception of

right lower-quadrant pain which had a much higher likelihood ratio in adults than in children.9,10

Another limitation of relying on clinical findings alone is that elicitation of physical signs is

subjective; multiple studies have demonstrated poor interrater reliability between trainees and

attending physicians, as well as between subspecialists.11,12 However, when used in combination

with laboratory values, the diagnostic utility of clinical findings increases significantly.

LABORATORY VALUES

Laboratory values that have been associated with acute appendicitis include leukocytosis, left shift, and

elevated markers of inflammation such as C-reactive protein (CRP) and erythrocyte sedimentation

rate.8,10 As with the clinical symptoms and signs, each individual laboratory test value is only weakly

discriminatory and predictive of acute appendicitis.8 However, combinations of clinical findings and

laboratory values or combinations of multiple laboratory values are more accurate and predictive.8 A

meta-analysis revealed that the greatest discriminators and predictors of acute appendicitis included a

history of migration of pain, clinical findings of peritoneal irritation, and laboratory values reflecting an

inflammatory response (i.e., CRP).8

Table 71-1 Named Clinical Signs Associated With Appendicitis

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Table 71-2 Alvarado or MANTRELS Scoring System

There have been numerous studies evaluating other potential serum and urinary markers of

appendicitis, including but not limited to inflammatory cytokines such as serum interleukin-6,

interleukin-8, and tumor necrosis factor alpha; serum neutrophil proteins such as lactoferrin and

calprotectin; and urinary markers such as leucine-rich α-2-glycoprotein. None of these have been shown

to be superior to traditional markers of inflammation in a prospective trial.

There are several clinical scoring systems that have been used in the diagnosis of acute appendicitis.

The most common is the Alvarado scoring system published in 1986, also referred to as MANTRELS

based on the mnemonic for remembering the combination of eight signs and symptoms (Table 71-2).13

The score ranges from 0 to 10; a patient with a score of 5 or 6 is typically observed, whereas a patient

with a score of 7 or greater should undergo operation.13 Since then, there have been several studies

evaluating the diagnostic accuracy of the Alvarado score, as well as modified versions of the Alvarado

score such as the Pediatric Appendicitis Score,14 and other scores such as the Kharbanda15 and Lintula16

scores. In general, these clinical scoring systems have better predictive ability than individual symptoms

or signs alone. However, these scoring systems do not have sufficient discriminatory or predictive

ability to routinely be used alone to diagnose appendicitis. They have been used to determine the need

for further radiologic studies

17 or as a guide for dictating clinical management.18

RADIOLOGIC IMAGING

At one time, surgical clinical acumen was graded on the ability to diagnose appendicitis on physical

examination, but currently, more and more patients are diagnosed using imaging studies. Populationbased analyses of regional administrative data in the 1980s and 1990s demonstrated a significant

increase in the use of ultrasound (US) and computed tomography (CT). One would hope that this

increase in imaging would lead to a decrease in the number of ruptured or negative appendectomies,

but that is not the case.19,20 On one hand, imaging may be helpful in the evaluation of patients with

abdominal pain for excluding other diagnoses or for preventing unnecessary operations.19 On the other

hand, imaging could potentially delay operative intervention, and in the case of CT, radiologic imaging

exposes patients to the risks of ionizing radiation. Ultrasonography does not expose patients to ionizing

radiation but is more operator dependent. In a meta-analysis of US and CT in children and adults, both

US and CT were highly specific (93% to 95%) in children and adults, whereas CT was more sensitive

than US.21

3 The Surgical Infection Society and Infectious Disease Society of America guidelines recommend helical

CT with IV contrast as the test of choice when imaging is indicated in patients with suspected

appendicitis. There is moderate supporting evidence for this from well-designed but nonrandomized

trials.7,22 A recent meta-analysis evaluated the effect of CT on negative appendectomies, rates of

perforation, and time to surgery in patients with acute right lower-quadrant pain.23 The meta-analysis

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