Chapter 17: GIT- Congenital Abnorm-Hirschsprung Disease

Question 1

What is the epidemiology of Hirschsprung disease?

Answer 1

occurs in approximately 1 of 5000 live births.

It may be isolated or occur
in combination with other developmental abnormalities; 10% of all cases occur in children with
Down syndromeandserious neurologic abnormalities are present in another 5%.

Question 2

Hirschsprung Disease may be isolated or occur
in combination with other developmental abnormalities.

T or F

Answer 2

True

Question 3

10% of all cases of Hirschsprung Disease occur in children with what syndrome?

Answer 3

Down syndrome ( Trisomy 21 ) and serious neurologic abnormalities are present in another 5%.

Question 4

What is the pathogenesis of Hirschsprung Disease?

Answer 4

You may recall that the enteric neuronal plexus develops from neural crest cells that migrate
into the bowel wall during embryogenesis.

Hirschsprung disease, also known as congenital
aganglionic megacolon, results _when the normal migration of neural crest cells from cecum to
rectum is arrested prematurely_orwhen the ganglion cells undergo premature death.

This produces a **distal intestinal segment that lacks both the Meissner submucosal and the Auerbach
myenteric plexus (“aganglionosis”)**.

• *Coordinated peristaltic contractions are absent** and
• *functional obstruction occurs**, resulting in dilation proximal to the affected segment.

Question 5

irschsprung disease, also known as what?

Answer 5

congenital aganglionic megacolon

Question 6

The mechanisms underlying defective neural crest cell migration in Hirschsprung disease are
unknown, but a genetic component is present in nearly all cases and 4% of patients’ siblings
are affected.

T or F

Answer 6

TRUE

[2] However, simple Mendelian inheritance is not involved in most cases.

Heterozygous loss-of-function mutations in the receptor tyrosine kinase RET account for the
majority of familial cases and approximately 15% of sporadic cases. [3]

Mutations also occur in
at least seven other genes encoding proteins involved in enteric neurodevelopment, including
the RET ligand glial-derived neurotrophic factor, endothelin, and the endothelin receptor, but, in
aggregate, these account for fewer than 30% of patients, suggesting that other defects are yet
to be discovered.

Because penetrance is incomplete, modifying genes or environmental factors
must also be important. In addition, it is clear that sex-linked factors exist, since males are
affected preferentially while disease tends to be more extensive in females.

Question 7

simple Mendelian inheritance is not involved in most cases of Hirschsprung disease.

So what accounts for the majority of the cases?

Answer 7

• *Heterozygous loss-of-function mutations** in the receptor tyrosine kinase RET account for the
• *majority of familial cases** and approximately 15% of sporadic cases. [3]

Mutations also occur in
at least seven other genes encoding proteins involved in enteric neurodevelopment, including
the RET ligand glial-derived neurotrophic factor, endothelin, and the endothelin receptor, but, in
aggregate, these account for fewer than 30% of patients, suggesting that other defects are yet
to be discovered.

Because penetrance is incomplete, modifying genes or environmental factors must also be important. In addition, it is clear that sex-linked factors exist, since males are affected preferentially while disease tends to be more extensive in females.

Question 8

What are the other mutations occur in at least seven genes encoding proteins involved in enteric neurodevelopment?

Answer 8

• RET ligand glial-derived neurotrophic factor,
• endothelin,
• and the endothelin receptor, but, in aggregate, these account for fewer than 30% of patients, suggesting that other defects are yet to be discovered.

Because penetrance is incomplete, modifying genes or environmental factors must also be important.

In addition, it is clear that sex-linked factors exist, since males are affected preferentially while disease tends to be more extensive in females.

Question 9

Diagnosis of Hirschsprung disease requires

Answer 9

documenting the _absence of
ganglion cells within the affected segment_.

Because migration of neural crest cells in the
Meissner and Auerbach plexi are linked, it is possible to establish the diagnosis preoperatively
by examining suction biopsy specimens.

Question 10

In addition to characteristic morphology of Hirschprung disease in
hematoxylin and eosin (H&E)-stained sections, ganglion cells can be identified using what?

Answer 10

immunohistochemical stains for acetylcholinesterase

Question 11

What is always affected in the GIT by Hirschsprung disease?

Answer 11

The rectum is always affected, but the length of the additional involved segments varies
widely.

Most cases are limited to the rectum and sigmoid colon, but severe cases can involve
the entire colon.

Question 12

What is the gross appearance of the aganglionic region?

Answer 12

may have a grossly normal or contracted
appearance, while thenormally innervated proximal colon may undergo progressive dilation (
Fig. 17-3 ).

With time the proximal colon may become massively distended (megacolon) reaching diameters of as much as 20 cm.

Dilation may stretch and thin the colonic wall to the
point of rupture, which occurs most frequently near the cecum.

Mucosal inflammation or
shallow ulcers may also be present. These changes proximal to the diseased segment can
make gross identification of the extent of aganglionosis difficult.

Hence, intraoperative frozensection
analysis of transmural sections is commonly used to confirm the presence of ganglion
cells at the anastamotic margin.

Question 13

In Hirschsprung Dilation may stretch and thin the colonic wall to the point of rupture, which occurs most frequently near where ?

Answer 13

cecum.

Question 14

What make gross identification of the extent of aganglionosis difficult in Hirschprung disease?

Answer 14

Mucosal inflammation or
shallow ulcers may also be present.

These changes proximal to the diseased segment can

Hence, intraoperative frozensection
analysis of transmural sections is commonly used to confirm the presence of ganglion
cells at the anastamotic margin.

Question 15

What is commonly used to confirm the presence of ganlion cells at the anastomotic margin?

Answer 15

intraoperative frozensection
analysis of transmural sections is commonly used to confirm the presence of ganglion
cells at the anastamotic margin.

Its because mucosal inflammation or
shallow ulcers may also be present.

Question 16

What is the presentation of Hirschsprung disease?

Answer 16

Patients typically present neonatally, often with a failure to pass meconium in the immediate
postnatal period.

Obstructive constipation follows, although in cases where only a few centimeters of the rectum are involved there may be occasional passage of stool.

Question 17

What are the major threats to life in patients with Hirschsprung disease?

Answer 17

• enterocolitis,
• fluid and electrolyte disturbances,
• perforation,
• and peritonitis.

Question 18

What is the primary mode of treatment in Hirschsprung disease?

Answer 18

surgical resection of the aganglionic segment and anastamosis of the normal colon to the rectum.

Even after successful surgery, it may take years

for patients to attain normal bowel function and continence.

Question 19

In contrast to the congenital megacolon of Hirschsprung disease, acquired megacolon may
occur at any age as a result of what?

Answer 19

• Chagas disease
• obstruction by a neoplasm or
• inflammatory stricture,
• toxic megacolon complicating ulcerative colitis, visceral myopathy, or
• in association with functional psychosomatic disorders.

Of these, only Chagas disease (discussed later) is
associated with loss of ganglia.