Pathology

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 Hirschsprung's disease (HD) is characterized by lack of enteric ganglion cells, hyperplasia of abnormal nerve fibers and a non-propulsive, non-relaxing segment of bowel. Classically the etiology is attributed to a failure of cranio-caudal migration of parasympathetic neural crest cells to the distal bowel. Hirschsprung's is the congenital absence of parasympathetic innervation of the distal intestine. Aganglionic colon does not permit normal peristalsis to occur. Functional obstruction therefore supervenes, and the infant may present with complete colon obstruction or with a devastating enterocolitis. The colon proximal to the aganglionic segment, in an effort to overcome the partial
 obstruction, becomes distended and its wall markedly thickened because of muscle hypertrophy. A plausible explanation for the failure of relaxation of the bowel involved is a deficiency of enteric inhibitory nerves that mediates the relaxation phase of peristalsis. These nerves are intrinsic to the gut and are classify as non-adrenergic and non-cholinergic. Nitric oxide (NO) has recently been implicated as the neurotransmitter which mediates the relaxation of smooth muscle of the GI tract in HD. It's absence
 in aganglionic bowel might account for the failure of relaxation during peristalsis. Besides, adhesions molecules (absent in aganglionic bowel) during early embryogenesis might restrict the neuro-ectodermal origin involved in the initial contact between nerves and muscle cell (synaptogenesis) suggesting that developmental anomaly of innervated muscle and absent NO causes the spasticity characteristic of HD.