Hirschsprung Disease

Hirschsprung disease is a developmental disorder of the enteric nervous system and is characterized by an absence of ganglion cells in the distal colon resulting in a functional obstruction. Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century when Whitehouse and Kernohan described the aganglionosis of the distal intestine as the cause of obstruction in their series of patients (Whitehouse, 1948). In 1949, Swenson described the first consistent definitive procedure for Hirschsprung disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have been described, including the Duhamel and Soave techniques. More recently, advances in surgical technique, including minimally invasive procedures, and earlier diagnosis have resulted in decreased morbidity and mortality for patients with Hirschsprung disease.

Most cases are now diagnosed in the newborn period. Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours after birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard. Once the diagnosis is confirmed, the basic treatment is to remove the poorly functioning aganglionic bowel and create an anastomosis to the distal rectum with the healthy innervated bowel (with or without an initial diversion).

Congenital aganglionosis of the distal bowel defines Hirschsprung disease. Aganglionosis begins with the anus, which is always involved, and continues proximally for a variable distance. Both the myenteric (Auerbach) and submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function. The precise mechanism underlying the development of Hirschsprung disease is unknown.

Enteric ganglion cells are derived from the neural crest. During normal development, neuroblasts will be found in the small intestine by the 7th week of gestation and will reach the colon by the 12th week of gestation (Okamoto, 1967). One possible etiology for Hirschsprung disease is a defect in the migration of these neuroblasts down their path to the distal intestine. Alternatively, normal migration may occur with a failure of neuroblasts to survive, proliferate, or differentiate in the distal aganglionic segment. Abnormal distribution in affected intestine of components required for neuronal growth and development, such as fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors, may be responsible for this theory (Gaillard, 1982; Langer, 1994; Tosney, 1986).

Additionally, the observation that the smooth muscle cells of aganglionic colon are electrically inactive when undergoing electrophysiologic studies also points to a myogenic component in the development of Hirschsprung disease (Kubota, 2002). Finally, abnormalities in the interstitial cells of Cajal, pacemaker cells connecting enteric nerves and intestinal smooth muscle have also been postulated as an important contributing factor (Ward, 2001; Vanderwinden, 1996).

Three neuronal plexus innervate the intestine: the submucosal (ie, Meissner) plexus, the intermuscular (ie, Auerbach) plexus, and the smaller mucosal plexus. All of these plexus are finely integrated and involved in all aspects of bowel function, including absorption, secretion, motility, and blood flow.

Normal motility is primarily under the control of intrinsic neurons. Bowel function is adequate, despite a loss of extrinsic innervation. These ganglia control both contraction and relaxation of smooth muscle, with relaxation predominating. Extrinsic control is mainly through the cholinergic and adrenergic fibers. The cholinergic fibers cause contraction, and the adrenergic fibers mainly cause inhibition.

In patients with Hirschsprung disease, ganglion cells are absent, leading to a marked increase in extrinsic intestinal innervation. The innervation of both the cholinergic and adrenergic systems is 2-3 times that of normal innervation. The adrenergic (excitatory) system is thought to predominate over the cholinergic (inhibitory) system, leading to an increase in smooth muscle tone. With the loss of the intrinsic enteric inhibitory nerves, the increased tone is unopposed and leads to an imbalance of smooth muscle contractility, uncoordinated peristalsis, and a functional obstruction.