Pathophysiology

The hallmark of diagnosis is the absence of ganglionic cells from the myenteric and submu-cosal plexuses, as seen on a full-thickness or suction (mucosal-submucosal) biopsy of the rectum. Proximal contents fail to enter the unre-laxed, aganglionic segment. The lack of non-adrenergic-non cholinergic (NANC) inhibitory innervation is responsible for a tonic contraction of the affected segment, with absence of peristalsis and proximal dilatation of the gut.6

Morphologically, ganglionic cells are absent from the narrowed segment and for some distance (usually 1-5 cm) into the dilated segment. The pattern of nerve fibers is also abnormal; they are hypertrophic with abundant, thickened bundles. Specific stains for acetylcholinesterase are used to highlight the abnormal morphology.7,8

In recent years, new insights into the pathophysi-ology of Hirschsprung's disease have been gained. There is growing evidence suggesting that the disease might be the expression of a genetic alteration, as reported in the genetic section of this chapter.

It has also been suggested that abnormal expression of the muscular neural cell adhesion molecule is likely to be associated with an arrest in the craniocaudal migration of neural cells to their most distal location.9 Furthermore, the lack of nitric oxide (NO)-producing nerve fibers in the aganglionic intestine probably contributes to the inability of the smooth muscle to relax, thereby causing lack of peristalsis.10 In addition, in the aganglionic segments, interstitial cells of Cajal are scarce and their network appears to be disrupted.11

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