Hirschsprung's Disease - Congenital Mega Colon

Transition Zone Normal Bowel

Hirschsprung Disease

Definition: HD is characterized by absence of ganglion cells in the distal bowel and extending proximally for varying distances with dilatation and hyper trophy of the proximal colon with abrupt or gradual transition to narrow distal afflicted colon.

Intrinsic

Enteric Nervous System

and Extrinsic

Parasympathetic

Vagus Nerve Enhances peristaltic Activity Auerbachs Inter Myentric Plexus

Sympathetic

Splanchnic Nerves ending in Plexuses Coeliac, Lumbar, Hypo gastric Sub Mucosal Meissners Plexus

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 3

Development of Enteric Nervous System

Source
Caudal

Hind brain Enteric Neural Crest Posterior part of Rhombomere 8 Adjacent to Somites 4 and 5
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 4

Development of Enteric Nervous System

Migration
Posterior

rhombomeres migrate through Ventero lateral pathway and anterior path of somites eg. GIT Anterior rhombomeres migrate through dorso lateral pathway and pharyngeal arches eg. Thyroid Migration to bowel is at Vagal, Truncal and Sacral regions
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 5

Chronology of Development of Enteric Nervous System

Migration

month Mid gut 6.5 month Caecum 8th month Migration complete
5th

Arrest

of caudal migration leads to

HD
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 6

Genetics of Enteric Nervous System

Neurotrophic
GDNF

factors

Glial cell line derived Neuronotropic factor Transforming growth factor (TGF - ) Laminin extra cellular matrix present in basal lamina of smooth muscle, presence of which may inhibit migration by formation of neurons
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 7

Pigmentation abnormalities

Wardenburg Syndrome

White fore lock, eye brows, hetero chromia irides Inner ear degeneration causing sensori neural deafness Hyper, Hypoganglionosis, aganglionosis

Cranial and Spinal Nerve abnormalities

Bowel dysfunction

Facial abnormalities

Membranous bones of face and palate

Chromosome 2q and identified as PAXm3 Chromosome 3

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 8

Genes
C

Genetics of HD

RET Proto Oncogene (Receptor Tyrosine Kinase Super family) Chromosome 10 Endothelin 3 (EDN 3)

Lethal spotted - Chromosome 20

Endothelin

B Receptor - (EDNRB)

Piebald Lethal Dominant Mega colon (DOM) - Chromosome 13

1 gene Catecholaminergic Deletion Chromosome 2, 10, 13 Partial Trisomy 11, 12 Trisomy 21

MASH
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 9

Genetics of Hirschsprung Disease Increased sibling history (4%) Unbalanced sex ratio (4:1) Associations
Downs
MEN

2 Wardenburg Syndrome Smith Lemli Opitz Syndrome Chromosomal deletions or rearrangements in 10 or 13

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 10

Micro Anatomy of Bowel

Mucosa

Columnar & goblet Lamina Propria

Epithelium

Sub

Mucosa
Mucosa

Muscularis

Muscular
Inner

L. or Muscularis Propria

Circular muscle Inter muscular space Outer Longitudinal Muscle layer

Serosa
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 11

Micro Anatomy Intrinsic Nerves

Sub
Meissners

Mucosal plexus

Henles

Sub mucosal plexus lying below muscularis mucosa Predominantly adrenergic

plexus

Stachs

plexus Nervous plexus lying on the mucosal surface of inner circular muscular layer
Synonyms:

Close to the surface of the circular muscle

Plexus submucosus extremus Plexus externus extremus

Interstitial

cells of Cajal which form a mono layer of specialized epithelial network over the Stachs plexus Auer Bach's Plexus in the inter muscular space - Parasympathetic

Normal Neurological Innervation Of Bowel

33

Colonic motility

Slow wave paces governing rhythmic contractions

Caecum and Ascending colon Purpose is mixing, stasis and absorption Whereas pace making signals spread ante grade in stomach and small intestine the here it is retro grade peristaltic contractions (anti peristalsis) Slow waves arise in the Interstitial cells of Cajal Slow waves are ante grade in the distal colon

Mass movement occurring at long intervals and occupying only a part of the colon Movement of propulsion Mass movement can be withheld temporarily by Voluntary Muscles
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 14

 Normal

Muscle behaviour is attributed to the neural reflux Normal Colonic motility:

Contraction

Colonic motility in Hirschsprung

of Circular and relaxation of Longitudinal Muscle proximally Contraction of Longitudinal and relaxation of Circular Muscle distally
Patho

Physiology would include

function of segmental intestinal

Defective

motility Lack of propagation of peristaltic waves Abnormal or absent opening reflux in the Internal Anal Sphincter
Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 15

 Reservoir
Slower

function (cf: stomach)

and more continuous Concentration rather than dilution Emptying is abrupt and complete Accommodation and receptive relaxation is capricious
Closure

of anal canal

Continence

Internal

sphincter Involuntary

Thickening of visceral circular muscle Maintains tone constantly Major determinant of continence at rest
External

sphincter Voluntary

Pubo rectalis, Subcutaneous External, Superficial External, Deep Internal Contraction is predominantly voluntary Muscle mass complex Slide No: 16 Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Sensory

Initiation by excitation of sensations Ano rectal receptors are triggered by mechanical stimulation Distension is a better stimulus than chemical

First: Urge to defaecate Second: Reflex relaxation of Sphincters Third: Mass Propulsion

Gastro colic reflex is initiated by entry of food into the duodenum Closure of airway Descent of diaphragm Contraction of abdominal muscles Relaxation of the striated anal muscles Peristaltic contractions Mass Relaxation of internal sphincter

Voluntary actions

Defaecation

Involuntary actions

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Slide No: 17

Absence of three types of ganglion cells

Cholinergic neurons Inter Neurons NANC Neurons

Cholinergic and adrenergic fibres proliferate in number and size Absence of NANC Nerves Over production of Acetyl Choline This leads to Acetyl Cholinesterase excess measured in

Biopsy Serum Erythrocytes

Thickening of muscle layer No peptidergic neurons Fewer VIP and Substance P Higher Nor epinephrine content Abnormal expression of NCAM Lack of Glial Fibrillary acid protein

Histological Findings in Hirschsprungs Disease

Histology Of Hirschsprung's Disease

Mucosa
v

Sub Mucosa Thickened Nerve

(Note Absence of Ganglion)

Myentric Plexus

Classification of HD based on segment involved

Ultra

short Segment Short Segment Recto Sigmoid (Classical) Long Segment Total Colonic Aganglionosis Total Intestinal Aganglionosis
Zuelzer

Wilson Syndrome
Slide No: 20

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Neural Pathway Eye abnormalities Abnormalities RET expressing gene and sympathoblasts from somites 5 to 7 contribute to Cervical ganglion as well as ganglion cells to distal colon
Bowel
Interruption

of bowel by a vascular accident as in atresia prevents distal migration of the neural crest cells through the Vagus.
Slide No: 21

Hirschsprung's Disease - Dept. of Paed. Surgery, Madurai Medical College.

Types of MEN
Organs

Type 1 Wermer Syndrome

Para thyroids Pancreas Pituitary

Type 2 A Sipple Syndrome

Thyroid Para thyroids Adrenals

Type 2 B Froboese Syndrome

Thyroid Adrenals Mucosa - Neuromas Alimentary Tracts Musculo Skeletal Phaeochromocytoma Thyroid ( C Cell Hyperplasia, MTC) Alimentary Tract ganglioneuromatosis Mega colon HD

Tumours

Hyperplasia, Adenoma, Malignancy: Gastrinoma Insulinoma Hyper Parathyroidism VIP oma Lipoma

Phaeochromocytoma Thyroid ( C Cell Hyperplasia, MTC) Parathyroid Hyperplasia

Gene Locus

Chromosome 11 (11q13)

Chromosome 10 (10q11.2)

Chromosome 11 (10q11.2)