Hirschsprung disease
- Lesion
Nerve cells never reach the end of the colon, so that segment cannot relax; stool backs up and the bowel above swells.
What it is
Hirschsprung disease (congenital aganglionic megacolon) is a functional obstruction of the distal colon. Neural crest cells that form the enteric nerve plexuses normally migrate from the caecum to the rectum; when migration stops early or the cells die, a distal segment lacks both the submucosal (Meissner) and myenteric (Auerbach) plexuses. That segment stays contracted, and the normal bowel above it dilates.
Structure
- Gross: a narrow or normal-looking distal segment with marked dilation of the proximal colon (megacolon).
- Micro: no ganglion cells in submucosal or myenteric plexuses; often thick hypertrophic nerve fibres.
- Acetylcholinesterase staining shows the thick nerve fibres; calretinin staining is lost in the aganglionic segment.
- The stretched proximal wall may ulcerate or rupture, most often near the caecum.
Step by step
- Neural crest cells migrate along the gut from proximal to distal during embryonic life.
- RET or endothelin signalling fails, so migration stops or the cells die early.
- The distal segment has no enteric neurons and cannot relax.
- Peristalsis cannot pass the segment: a functional obstruction.
- Stool accumulates and the innervated colon above dilates.
Markers
- Absent ganglion cells (H&E)
- Acetylcholinesterase: thick nerve fibres
- Calretinin: lost
Clinical notes
- Hirschsprung-associated enterocolitis is a dangerous complication before or after surgery.
- Acquired megacolon with ganglion cell loss occurs in Chagas disease (Trypanosoma cruzi), a Latin American cause to remember; other acquired megacolons (tumour, stricture, ulcerative colitis) keep their ganglia.
Test yourself
Think of the answer, then tap the question to see it.
Which segment of the colon is always aganglionic in Hirschsprung disease?
The rectum; the disease extends proximally from there for a variable distance.
In Hirschsprung disease, which part of the bowel is dilated?
The normally innervated bowel proximal to the aganglionic segment.
Which gene is most often mutated in familial Hirschsprung disease?
RET, a receptor tyrosine kinase needed for migration of neural crest precursors.
Which infection causes acquired megacolon with loss of ganglion cells?
Chagas disease, through destruction of the myenteric plexus by Trypanosoma cruzi.
Elsewhere in DurgiPedia
- Hirschsprung disease (congenital aganglionic megacolon)
- The enteric nervous system, slow waves and GI control
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hirschsprung disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Hirschsprung disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.