HIRSCHSPRUNG'S DISEASE (aganglionic megacolon) 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.

1. Due to failure in the cephalo-caudal migration of the neuro 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/glialderived 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

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

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-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

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

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


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

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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-toside 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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