Hirschsprung disease

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ΕΤΥΜΟΛΟΓΙΑ

Described in 1888[1] by Harald Hirschsprung, a Danish physician of German extraction. Initially, the dilated segment of bowel was thought to be the diseased segment until 1901 when Tittel described a case where no ganglia were found within the undilated distal segment.[2]

Also known as congenital aganglionic megacolon. A condition where a section of gut section lacks the nervous plexuses which controls peristalsis. The rectum is invariably involved, but the distal colon may be affected too, with variation in the extent of proximal extra-rectal involvement. If the segment is very short, the condition may be difficult or take some time to diagnose. Megacolon can ensue. Where the entire colon is affected, this is termed total colonic agangliosis. The concept of a ultra-short Hirschsprung's disease as a cause of constipation in adults is controversial as the distal rectum is normally relatively hypoganglionic.

The symptoms usually manifest in the neonatal period. Passage of meconium is delayed (this usually occurs within 24 hours), but as the obstruction takes several days to develop, affected babies usually present with poor feeding, vomiting, constipation and abdominal distension.

The incidence varies between ethnic groups, but occurs in roughly 1 in 5000 live births, with a male predilection (M:F about 4:1). This male predilection is reduced in total colonic agangliosis. Up to a third of cases associated with various syndromes. About 10% of cases occur in association with Down syndrome (conversely, about 1% of trisomy 21 patients have the condition).

Contents

Aetiology

During fetal development, there is migration of neural crest cells from the caecum to the rectum. If this process is disrupted or if ganglion cells are damaged, a segment of bowel without the Auerbach and Meissner's myenteric plexuses results. The segment is unable to produce or propagate peristalsis and is rendered amotile - in essence a functional obstruction. For this reason, the terms pseudo-obstruction is sometimes used. Dilatation of the proximal bowel occurs, hence the description of megacolon.

The precise mechanisms behind the failure of neural crest cell migration is not clear. Loss-of-function mutations in the RET gene, a tyrosine kinase receptor, are implicated in most familial cases and in a proportion of sporadic cases. The inheritance pattern is autosomal dominant with incomplete penetrance. However, the disease is genetically heterogeneous with several other mutations implicated, including components of the endothelin signalling pathway. As might be expected, many of the mutations are in genes thought to be involved in the development of the enteric nervous system (reviewed in [3]).

Investigations

Barium enema will show a narrowed distal rectum with impaired or abnormal motility along with a dilated proximal segment.

When suspected, rectal suction biopsies can be taken endoscopically are sent for histology. The suction ensures that the submucosa of the bowel is included.

Once diagnosed, biopsies from the opposite side (seromuscular biopsies) are taken to define the extent of the disease so as to plan surgery.

Histology

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  1. Absence of ganglia
  2. Thickened, hypertrophied nerve trunks
  3. Increased acetylcholinesterase staining of nerve trunks

Biopsies of the large bowel are examined for the presence of myenteric ganglia which excludes Hirschsprung's disease. However, a positive diagnosis of Hirschsprung's disease requires absence of ganglia. As the standard tissue thickness on a histological slide is about 4 microns, absence of ganglia in a single slide section is insufficient to diagnose Hirschsprung's disease and multiple levels must be examined (in some protocols, up to 60 serial sections).

Parasympathetic innervation to the affected segments is preserved and often show increased coarse fibres throughout the lamina propria and muscularis mucosa. In affected bowel, submucosal nerve trunks can become hypertrophied (usually >40μm as nerve trunks in normal distal rectum can be up to 35μm) and lose calretinin staining. These same nerve trunks enhance with histochemistry for acetylcholinesterase, which is performed on frozen tissue.

Treatment

Treatment may be by one of the various pull-through operations, eliminating the defective segment and anastomosing the working parts in one or more operations.

References


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