l10 hirschprung& celiac+t sprue

Developmental AnomaliesHirschsprung Disease

Congenital aganglionic Megacolon

Lecture 10 f

Developmental Anomalies• Atresia The complete failure of development of the intestinal lumen.

• Stenosis Narrowing of the intestinal lumen with incomplete obstruction.

• Duplication• Meckel diverticulum (A pouch or sac branching out from a hollow organ or structure, such as the intestine).

It results from failure of involution of the omphalomesenteric duct, leaving a persistent blind-ended tubular protrusion as long as 5 to 6 cm.

• Omphalocele a congenital defect of the periumblical abdominal musculature that creates a membranous sac, into which the intestines herniate.

• Gastroschisis- extrusion of the intestines through the absent portion of the abd. Wall.

• Malrotation

•Hirschsprung disease

Hirschsprung disease• Hirschsprung disease is a developmental disorder

of the enteric nervous system and is characterized by an absence of ganglion cells in the distal colon resulting in a functional obstruction.

Congenital Aganglionic Megacolon

Hirschsprung's disease, or congenital aganglionic megacolon

involves an enlargement of the colon, caused by bowel obstruction resulting from an aganglionic section of bowel (the normal enteric nerves are absent) that starts at the anus and progresses upwards.

• The length of bowel that is affected varies but seldom stretches for more than about 30 cm.

• This disease is named after Harald Hirschsprung, the Danish physician who first described the disease in 1886

Ruysch in 1691 a Dutch anatomist, described a 5-year-old girl who died of intestinal obstruction

• The first clinical description of Hirschsprung's Disease was presented at the Berlin Society of Pediatrics in 1886 by Hirschsprung. He thought that

the disease was caused by distention of the colon, as evidenced by the title of his

presentation: "Constipation in Newborns Due to Dilation and Hypertrophy of the Colon."

Pathophysiology• Congenital aganglionosis of the distal bowel defines

Hirschsprung disease. Both the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function. The precise mechanism underlying the development of Hirschsprung disease is unknown.

Enteric ganglion cells are derived from the

neural crest.

During normal development, neuroblasts will be found in the small intestine by the 7th week of gestation and will reach the colon by the 12th week of gestation. One possible etiology for Hirschsprung disease is a defect in the migration of these neuroblasts down their path to the distal intestine.

• Alternatively, normal migration may occur with a failure of neuroblasts to survive, proliferate, or differentiate in the distal aganglionic segment.

• Abnormal distribution in affected intestine of components required for neuronal growth and development, such as fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors, may be responsible for this theory.

• Additionally, the observation that the smooth muscle cells of aganglionic colon are electrically inactive when undergoing electrophysiologic studies also points to a myogenic component in the development of Hirschsprung disease.

Short Segment

BKMC

Epidemiology• Rate of occurence 1 case per 5000 live births.• Race• Hirschsprung disease has no racial predilection.• Sex• Hirschsprung disease occurs more often in

males than in females, with a male-to-female

ratio of approximately 4:1. • However, with long-segment disease, the incidence

increases in females.

• Age• Hirschsprung disease is uncommon in

premature infants.• The age at which Hirschsprung disease is

diagnosed has progressively decreased over the past century. In the early 1900s, the median age at diagnosis was 2-3 years; from the 1950s to 1970s, the median age was 2-6 months.

• Currently, approximately 90% of patients with Hirschsprung disease are diagnosed in the

newborn period.

Clinical features 1) Delayed passage of meconium 2) Abdominal distension 3) Constipation

Diagnosis

Suspect Hirschsprung's in a baby who has not passed meconium within 48 hours of delivery. Recall that 90% of babies pass their first meconium within 24 hours, and the next 9% within 48 hours. Definitive diagnosis is made by suction biopsy of the distally narrowed segment.

Abdominal x-ray - show a lack of stool in the large intestine or near the anus and dilated segments of the large and small intestine.

Barium enema - An x-ray of the abdomen shows strictures (narrowed areas), obstructions (blockages), and dilated intestine above the obstruction.

Anorectal manometry - a test that measures nerve reflexes which are missing in Hirschsprung's disease.

Biopsy of the rectum or large intestine - a test that takes a sample of the cells in the rectum or large intestine and then looks for nerve cells under a microscope.

TreatmentSurgical removal (resection) of

the abnormal section of the colon, followed by reanastomosis.

Celiac SprueCeliac Disease

Gluten SensitiveEnteropathy

Definitions

• celiac sprue is an immune disorder(autoimmune) characterized by inflammation of the

proximal small intestine induced by the ingestion of

gluten• also known as celiac disease and gluten-sensitive enteropathy

• Celiac disease is a condition that damages the lining of the small intestine and prevents it from absorbing parts of food that are important for staying healthy. The damage is due to a reaction to eating gluten, which is found in wheat, barley, rye, and possibly oats.

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• Occurs in genetically susceptible individuals• A unique autoimmune disorder because:

– both the environmental trigger (gluten) and the autoantigen (tissue Transglutaminase) are known

–elimination of the environmental trigger leads to a complete resolution of the disease

Pathogenesis: Environmental• glutens are water-insoluble grain proteins

(prolamins and glutenins)• taxonomy of grains predicts their toxicity in patients

Gramineae

Triticum Secale Hordeum Avena Oryza Zea Sorghum Pennisetum

family

genus

wheat rye barley oats rice corn sorghum millet grain

gliadinsecalin hordein avenin oryzenin zein kafirin panicin gluten

immunologiccross-reactivity

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Pathogenesis•Genetic

predisposition

• Environmental triggers– Dietary – Non dietary?

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Normal small intestine

Celiac Disease Villous atrophy

Normal villi

UNDER THE MICROSCOPE

Healthy normal villi of the small intestine

Damaged villi of a person with undiagnosed coeliac disease

Clinical PresentationChildhood Presentation

• typical– failure to thrive– diarrhea/steatorrhea– anorexia– vomiting– abdominal distension– abdominal pain

• atypical– aphthous ulcers– short stature– anemia– rickets

Adult Presentation

• typical– diarrhea/steatorrhea (75-80%)– weight loss– abdominal bloating/flatulence– mild abdominal pain

• atypical– anemia (85%)– osteoporosis (15-30%)– coagulopathy (10%)– aphthous ulcers– infertility/menstrual abnormalities– neurologic symptoms– short stature– weakness/myopathy

Associated Conditions• dermatitis herpetiformis• type I diabetes mellitus• IgA deficiency• thyroid disease (5% of sprue patients)• autoimmune diseases• hyposplenism (~50% of sprue patients)• microscopic colitis

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Diagnosis of Coeliac Disease and pitfalls

• Clinical• Serological• Histological

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Treatment OptionsOption #1:

Remove the genesOption #2:

Remove the grains

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Treatment

• Only treatment for celiac disease is a gluten-free diet (GFD)– Strict, lifelong diet– Avoid:

• Wheat• Rye• Barley

Tropical Sprue

What is the tropical sprue?

Tropical sprue: is a malabsorption disease

commonly found in the tropical regions,

marked with abnormal flattening of the villi

and inflammation of the small intestinal mucosa.

Causes- No specific causal agent has been clearly associated with tropical sprue, but

bacterial overgrowth by enterotoxigenic

organisms ( e.g., E.coli and hemophilus )

has been implicated.

Morphology- Intestinal changes range from near normal to

severe diffuse enteritis.

- Unlike celiac sprue, injury is seen at all levels of the small intestine.

-Patients frequently have folate and vitamin

B12 deficiency, leading to enlargement of

the nuclei of epithelial cells , reminiscent of

the changes seen in pernicious anemia.

Symptoms

The symptoms of tropical sprue are:- Diarrhea.- Indigestion.- Cramps.- Weight loss and malnutrition.- Fatigue.

Signs

- Abnormal flattening of villi and inflammation of the lining of the small intestine, observed during an endoscopic procedure.

- Presence of inflammatory cell in the biopsy of small intestine tissue .

- Low levels of vitamins A, B12, E, D, and K, as well as albumin, calcium, and folate,

revealed by a blood test.

- Excess fat in feces

Management- Prevention:-

Preventions of tropical sprue include avoiding travel to the affected regions.

If you have to travel, remember to use only bottled water for drinking, brushing teeth,

and washing food .

-Nutritional deficiencies must also be corrected.

Treatment:-Treatment is usually 3 to 6 months of

antibiotics (tetracycline) and folic acid

supplements. People with vitamin B12

deficiency will receive vitamin supplements as well.