Nervous elements in the human colon of hirschsprung's disease (with comparative remarks on neuronal profiles in the normal human and monkey colon and sphincter ani internus).

Abstract

Neuronal profiles in the human and monkey colon and sphincter ani internus were analyzed microscopically and compared to those in the constricted aganglionic transitional and dilated, hypertrophic sections of colon from 3 cases of Hirschsprung's disease. Light microscopy revealed two different types of nerve bundles in the normal colon: 1. aniline-blue-positive nerve trunks (conventional peripheral type) containing endoneural collagen and layers of perineural sheath cells, in all probability of extrinsic origin and autonomic in nature, and 2. azocarmine-positive, large multiaxonal Schwann units in Auerbach's plexus, devoid of collagen and hardly ensheathed by perineurium (bundles of intrinsic type), resembling central nervous neurophil formations (with or without ganglion cells interspersed). Preterminal and terminal varicose axons in Auerbach's plexus—not distinguishable by light microscopy—were classified according to their vesicle populations and suspected transmitter type into adrenergic, cholinergic, p-type and sensory fibres. The internal anal sphincter receives predominantly large bundles of the conventional peripheral type containing a conspicuous amount of myelinated axons, as does the aganglionic portion of the Hirschsprung colon. Vesicle-filled profiles among the smooth muscle cells of the sphincter are considered adrenergic and cholinergic, but p-type fibres are present in the junctional area of the lower rectum and upper sphincter. In the aganglionic, constricted section of the colon from two cases of Hirschsprung's disease, adrenergic and cholinergic axons establish frequent synaptic contacts with smooth muscle cells by exposed varicosities. Throughout the aganglionic colon section, processes of intrinsic neurons are absent; but close to the cone-shaped transitional section abnormal nerve fascicles are present, bound by hypertrophic perineurium, and contain masses of collagen in distended endoneurial interspaces. Schwann cell units inside these bundles are mono- or oligoaxonal. The ultramorphology of supporting glial cells reveals features of immature, undifferentiated Schwann cells. These findings are interpreted as indicative of abortive regeneration and axonal sprouting from intact intrinsic pericarya in the transitional section of the Hirschsprung colon. Noradrenaline concentrations in both the normal internal anal sphincter and the aganglionic colon section from one case of Hirschsprung's disease are similar and about twice as high as in all colon sections from healthy individuals, indicating a functionally important, direct adrenergic innervation of smooth musculature in both situations. The lack of inhibitory extrinsic and intrinsic innervation in the constricted gut section in Hirschsprung's disease is considered to be the cause of its spastic contraction in vivo. Similarities and differences in innervation and pharmacological behavior of the internal anal sphincter in man and monkey and in the aganglionic colon section in Hirschsprung's disease are pointed out.