<h1>Hirschsprung's disease </h1>

What is hirschsprung's disease

Hirschsprung disease is characterized by a narrowing of a intestinal segment, in which the ganglion cells are absent from the intestinal wall, and an enlargement in the segment situated proximal to it.
The disease affects 1 in every 5000 newborns, males having an increased predisposition

What causes Hirschsprung disease?

 There is a genetic factor involved in the development of hischsprung disease, which also influences the clinical form of disease:

1. The recto-sigmoid form is cause by a gene with reduced penetrance
2. A dominant gene with incomplete penetrance is associated with disease that affects a long segment of the gastrointestinal tract 
3. The genetic transmission of the disease is considered to be a dependable multiple factors that are influenced by sex, given the fact that there is only one female affected to every 5 males affected

 The exact process leading to the absence of the glanglion cells from the intestinal wall is yet to be determined. Ganglionic cells develop from nervous cells that migrate from the neural tube to primitive intestine. A common theory is that in people suffering from Hirschsprung disease these cells are either destroyed by the immune system or don't migrate at all

Pathogenesis of Hirschsprung disease

The intestinal area in which ganglion cells are absent is in a state of permanent contraction, leading to a narrowing of the intestinal lumen and stagnation of feces followed by obstruction. At first the intestine behind (proximal to) the obstruction tries to push the feces through by contracting harder (accentuated peristaltic)  but with no results. In a second time the intestine further tries to increase its contraction power by adding more muscular mass, by enlarging the muscle cells from the intestinal wall in a process called hypertrophy. The muscular hypertrophy leads to dilatation and a increase in size of the intestinal segment. Thus are explained the intestinal narrowing and proximal dilatation that are found in Hirschsprung  disease.

Morphologic changes found in Hirschsprung disease

Examination revels a dilated intestinal segment followed by a funnel segment and a narrowed segment.
Microscopic examination reveals a reduced number of ganglion cells in the mienteric and submuccoussal nervous plexus. Also a thickening (hyperplasia) of the parasympathetic nerve fibers
Immunohistochemical  examination revelas a increased activity of acetylcholinesterase .
There is also an reduced activity of nitric oxide, a neurotransmitter  in patients suffering from Hirschsprung disease
A reduced activity  of tissue hormones:

1. Vasoactive Intestinal Peptide (VIP)
2. P substance
3. Met-enkephalins
4. Somatostatine

Signs and symptoms in Hirschsprung disease

Malignant Hirschsprung disease in newborns

The clinical presentation is consistent  with low intestinal occlusion

Medical History

1. The newborn is unable to eliminate meconium
2. Enema that at first contain bile secretion and, as the disase progreses, feces.

Cinical examination

1. General inspections reveals

• Agitated patient
• Superficial respirations wih high frequency
• Dehydration 

1.  Inspection of the abdomen reveals superficial collateral venous circulation
2. Percussion of the abdomen reveals tympanites
3. Digital rectal examination reveals leads to explosive elimination of meconium and gases uppon drawing of the exploratory finger 

Benign Hirschsprung disease in toddlers

There is a delay in meconium elimination
Diversifying the alimentationleads to constipation
Palpation reveals a doughy mass, with or without superjacent distension
Malnutrition signs

Malignant Hirschsprung disease in toddlers

Usually this clinical presentation appears in case of deficient nursing
The clinical findings are consistent with low intestinal occlusion. A series of complications may occur such as

1. Enterocolitis, frequently with Clostridium difficile present in stool. It may evolve leading to sepsis with gram negative bacteria
2. Superjacent perforation with complicated peritonitis 

Hirschsprung diseasein childrens

Chronic constipation that does not remit with medication, usually without encompresis
Signs of malnutrition are present:

1. Anemia
2. Hypoproteinemia
3. splayed thorax
4. Distended abdomen with pasty masses present
5. Dry and desquamate  skin 

Radiological findings in Hirschsprung disease

On the simple plain abdominal radiography sings of low occlusion or sub-oclusion can be seen
Profile irigography reveals:

1. In the clasic form of disease a normal or narowed rectum can be seen, followed by a transition zone, he funnel shape dilatation zone and then the dilated proximal segent
2. The short segment form of the disease in which the narrowed segment is situated lower and the rectum is dilated 
3. In both cases the contrast medium is eliminated with difficulty, repeated enemas being necessary  

Rectal biopsy for Hisrschsprung disease

The biopsy is made 2-3 cm superior to the pectinate line by:

1. Harvest of mucosal and submucosal tissue through aspiration
2. biopsy of all the layers of the intestinal wall
3. Through pinch biopsy, although there is an increased risk of bleeding with this technique  

Anorectal manometry in Hirschsprung disease

1. Absence of internal anal sphincter relaxation in response to rectal distention
2. Absent peristaltic in the aganglionic segment, with normal pressure
3. Preset peristaltic with increased pressure in the proximal segment

Differential diagnosis of Hirschsprung disease

For newborns 

1. Functional microcolon
2. Meconium plug syndrome
3. Meconium ileus
4. Anorectal agenesis
5. Megavesica-Megacolon-Decreased peristalsis syndrome

 For toddlers and childrens

1. Idiopathic megacolon 
2. Megacolon due to a congenital anal stenosis