HIRSCHSPRUNG'S DISEASE (aganglionic megacolon)
Due to failure in the cephalo-caudal migration of the neuro
Definition
Presence of large, non-functional distal intestine usually the
rectum with variable involvement of the colon and small gut
 Hirschsprung disease results from an absence of ganglion
cells in the mucosal and muscular layers of the colon.
 Hirschsprung disease is caused by a failure of neuronal
migration to the myenteric plexus of the distal bowel so that
the distal bowel lacks ganglion cells, causing a lack of
peristalsis in that region with a functional obstruction
 Neural crest cells fail to migrate to the mesodermal layers,
possibly mediated by abnormalities in end-organ cell surface
receptors or local deficiency of nitric oxide synthesis.
Sites
-Only the terminal rectum occurs in about 10% of cases
-Extension to the sigmoid colon in 65%
-More proximal colon in 10%
-Entire colon with small bowel involvement in 10-15%
- Aganglionosis is limited to the rectum and sigmoid in
approximately 75% of cases; it includes the total colon in
approximately 8% and occasionally may affect the whole of the
intestine
 Segmental aganglionosis is very rare and may be an
acquired lesion.
 The aganglionic segment is narrowed, with dilation of the
proximal normal colon.
 The mucosa of the dilated colonic segment may become thin
and inflamed (enterocolitis), resulting in diarrhea, bleeding,
and protein loss.
Race
More common in Caucasians, then blacks. Least common
among the Asians Whites >Blacks
Sex
-Males are affected X5 more frequently than females in cases in
which the diseased segment is of the usual length.
-Up to 70-80 % of the involved patients are male.
-Females tend to have longer aganglionic segments.
A familial association occurs in 5-10% of cases--more frequently
when females are affected.
Incidence
KNH-12 cases per year 0 r 1: 4 500
Etiology
Can be broadly classified as Sporadic-up to 80-90% of cases or
Familial 15-17%.
Familial cases:
-Maternal transmission more common than paternal
transmission. If both parents are involved risk of 12.5% of the
offspring getting affected. In familial cases 20% have associated
congenital anomaly compared to 10% in sporadic case.
-Autosomal dominant inheritance with incomplete
penetrance is responsible for the long segment familial
disease.
- Autosomal recessive in short segment disease.
3 genes have been identified
i) RET gene in chromosome 10-Autosomal dominant inheritance
ii) Endothelial Receptor B gene in chromosome 13-autosomal
Recessive
iii) Endothelial 3 gene chromosome 20-Autosomal recessive
Pathophysiology
Exact cause unknown -2 theories
JUDY WAWIRA GICHOYA YR 2007
1.
crest cells into the distal bowel. during weeks 4 through 12 of
gestation
-Therefore, the absence of ganglion cells always begins at the
anus and extends a varying distance proximally.
-The aganglionic bowel produces a functional obstruction,
because the bowel does not have normal propulsive waves and
contracts en masse in response to distention.
2.Hostile microenviroment in the colon that damages already
present neuroblasts.It is thought that the abnormality in
chromosome causes the hostile enviroment
Other associations
-Trisomy 21 (Down's syndrome);
-Genitourinary abnormalities.
-Neural crest abnormalities, such as congenital central
hypoventilation syndrome (Ondine's curse)
- Waardenburg's syndrome
-Anorectal malformations
-The histological hallmark of Hirschsprung's disease is
Aganglinosis in the submucosal plexus of Meissner and in the
intermyenteric plexus of Auerbach.
-The nerves affected are the non-cholinergic non adrenergic ie
NO ,VIP and NADPH transmitters
-This leads to unopposed autonomic nervous system
functioning which causes;
1-Reduced or absent peristaltic(propulsive) activity
2-Increased intestinal sphincter tone
NB:
 These are receptors on the migrating NCCs and
neurotrophic factors secreted by mesenchymal cells, which
are required by the neural crest cells for survival,
proliferation, and differentiation.
 Expression of these molecules is probably controlled by the
Hox and Sox homeobox genes.
 Two signaling systems have been clearly defined ret/glial-
derived neurotrophic factor and endothelin receptor
B/endothelin 3.
 Because of the loss of intrinsic innervation of the rectum,
there is an overexpression of extrinsic parasympathetic and
sympathetic nerves that is particularly noticeable in the
lamina propria and muscularis mucosae.
 The contractile action of neuropeptide Y and other agents in
these nerves on the rectal smooth muscle is unopposed
because of the loss of vasoactive intestinal polypeptide and
nitric oxide-synthesizing enteric nerves that cause relaxation.
 The aganglionic segment, internal sphincter, and anal canal
remain constantly contracted, thus causing obstructive
symptoms with proximal dilatation and hypertrophy of the
colon.
The pathological hallmark is
1.There is marked distension & hypertrophy of gut proximal to the
aganglionic segment
2.There is funnelling (coning) of the gut between the two -
transition zone
3.Constricted or collapsed gut at & distal to the aganglionic
portion
Spectrum of the disease
1. Complete absence.
2. Hypoganglionosis.
3. Abnormal ganglion cells ( hirshprung like disease).
4.Also Intestinal neuronal dysplasia
Acquired hirshsprungs disease
-Vascular causes e.g. Post-op 2° to Pull-through operation, with
damage to the mesenteric vessels
1
-Non-vascular e.g. TB, Diabetes
-Abnormal connective tissue and smooth muscle
DDX
1. Anatomic Anorectal malformation
2. Metabolic
DM mothers-electrolyte imbalances
Hypothyroidism or hyperthyroidism
3. Drugs-Heavy sedation eg in eclampsia of mother
4. Meconium plug/ileus
5. Sepsis
6. Immaturity
7. hypoganglionosis, and hollow visceral myopathy.
Clinical presentation
Symptoms
 Hirschsprung disease presents in one of three ways:
1. Complete intestinal obstruction, with bilious vomiting,
obstipation, and massive abdominal distension
2. Delayed passage of meconium (The first intestinal
discharges of the newborn infant, greenish in color
and consisting of epithelial cells, mucus, and bile)
3. Enterocolitis
-Vary widely in severity but almost always occur shortly after
birth.
-The time of presentation depends on amount of intestine
involved as long segment –present early.
1-Delayed passage of meconium
2-Chronic or intermittent constipation with diarrhea
3-.Passage of flatus and stool requires great effort, and the stools
are small in caliber.
4-Progressive abdominal distention
5-Vomiting and Reluctance to feed/anorexia
6-Listlessness, irritability,
7-Poor growth and development These children are sluggish,
with wasted extremities and flared costal margins
NB. Some pts present with acute enterocolitis or toxic megacolon
with gross abdominal distension,vomiting, shock,septic and
febrile
 Enterocolitis most often occurs during the second to fourth
weeks, and it results as a consequence of delayed
diagnosis.
 It is characterized by fever; explosive, foul-smelling, and
often bloody diarrheal stools; and abdominal distension.
 Enterocolitis carries with it a poor prognosis, with an overall
mortality rate of 4 to 33%.
 Enterocolitis also occurs in the postoperative period in 13%
of cases.
 Less common presentations include only constipation in
approximately 5% of patients, perforation occurring during
the neonatal period in 3%, fecal soiling similar to that in
functional megacolon in 3%, rectal bleeding from an anal
fissure in 5%, and hydroureter from urethral compression.
Signs
-Small for age infant, irritable ,dehydrated,
P/A
Impacted stools in the greatly dilated and distended sigmoid
colon can be palpated across the lower abdomen
Abdominal distension-increased bowel movts
DRE
-Normal anal tone.
-Rectum collapsed, tight and empty (no feccal matter).
-Rectal examination in the infant may be followed by expulsion of
stool and flatus, with remarkable decompression of abdominal
distention passage of foul-smelling diarrhea
JUDY WAWIRA GICHOYA YR 2007
INVESTIGATIONS
Imaging
1.Plain abdominal x-rays
-In infants show dilated loops of bowel, but it is difficult to
distinguish small and large bowel in infancy.
-Air fluid levels
-Absence of air in the rectum
2.Barium enema
-Should be done at least 48 hrs after birth.
-The aganglionic segment appears relatively narrow compared to
the dilated proximal bowel.
-The proximal intestine can be dilated by impacted stool or
enema, giving a false impression of the level of the normal colon.
-The contrast is left and another x-ray taken after 24hours and
failure to evacuate the contrast is very suggestive of the disease.
3. Manometric studies
-Normal resting pressure of the rectum taken before inflation of
the balloon and its shown to be elevated.
-It also reveals abnormal irregularly, irregular contractions.
- Rectal distention by a balloon inflation, a failure of relaxation of
the internal sphincter.
Biopsy
Definitive diagnosis is made by rectal biopsy 2 methods
1. Mucosal biopsies may be taken from the posterior rectal wall
with a suction biopsy capsule without anesthesia.
Features:
-Aganglionic segment
-Nerve trunk hyperplasia
-Increased acetyl cholinesterase level
-Immunohistochemistry
 In short-segment Hirschsprung disease, the submucosal and
myenteric plexuses contain hypertrophic nerve trunks.
 Acetylcholinesterase staining shows their presence in the
muscularis mucosae, a pattern that is pathognomonic for the
disease
 In total colonic aganglionosis, however, the
acetylcholinesterase activity is not always increased, and the
thickened nerve trunks, which are found in short-segment
Hirschsprung disease, are not always present.
 Therefore, a normal acetylcholinesterase pattern is
insufficient to exclude total colonic aganglionosis, and if the
condition is clinically suspected, the biopsy must contain
sufficient submucosa to reliably diagnose the absence of
enteric neurons
2.Full thickness biopsy
If equivocal, it is necessary to remove a 1- x 2-cm full-thickness
strip of mucosa and muscularis from the posterior rectum
proximal to the dentate line under general anesthesia or at
laparatomy.
MANAGEMENT
Supportive
1.Manage fluid and Electrolyte imbalances
2. Insert a soft rectal tube & give patient soft enemas - 5ml/kg
warm Normal Saline (NOT SOAP) & irrigate GIT until patient
settles
3..Antibiotics- if fever and peritonism
Definitive management
Principles
a)Decompression and improve nutrition
b)Establish extent of disease
c)Definitive surgery
2
Temporary colostomy and serial biopsy
-Laparatomy and serial biopsy on the rectum and colon with aim
of determining extent of disease.
-A colostomy is fashioned at the transitional zone to continue the
decompression and allow the patient to gain weight before
definitive surgery.
-The points of biopsy are marked with non-absorbable sutures.
Function of the colostomy
-To decompress normal gut to allow normal growth &
development until when definitive management can be instituted.
-Reduce - NOT eliminate risk of enterocolitis

Definitive Surgery
Principles
1.Resection of aganglionic segment
2.Anastomosis of proximal to the distal segment
Modes of surgery
1 .Swenson Operation:
In the Swenson procedure, the overly dilated and aganglionic
colon and rectum are excised to within 2cm above the dentate
line.
-The transected end of the normally ganglionated bowel is
sutured end-to- end with the distal anorectal segment.

2. Duhamel:
Operation the rectum is oversewn, and the proximal bowel is
brought between the sacrum and the rectum and sutured end-to-
side to the rectum above the dentate line. The intervening spur
of rectum and bowel is divided, and a side-to-side anastomosis
is made with a stapler
There is risk of faecaloma forming in the aganglionated rectal cuff
- Lester-Martin modification takes care of this complication

3. Soave Operation:
The Soave operation consists of dissecting between the mucosa
and the muscularis layer, pulling the proximal bowel through out
of the residual rectal stump and suturing it to the rectum just 2
cm above the dentate line.

4.Lynn Operation:
Rectal myectomy is used for distal rectal (short-segment)
aganglionosis

5. Total colonic aganglionosis - Martin's procedure;

Some colon is left for absorption of water & storage of faeces.
Ileum is anastomosed at the dentate line & a side to side
anastomosis of ileum to remaining colon. The ileum will provide
peristalsis.

Approaches
1.Open Laparatomy
2.Laparascopy
3.Transanal

Age at Surgery
Depends on the age at which the diagnosis is confirmed –tissue)
and the availability of care.

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