Developmental AnomaliesHirscHsprung DiseaseCongenitalaganglionicMegacolonLecture 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 tubularprotrusion 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 disorderof the enteric nervous system and ischaracterized by an absence of ganglion cells in thedistal colon resulting in a functional obstruction.CongenitalAganglionicMegacolon
Hirschsprungs disease, orcongenital aganglionic megacoloninvolves an enlargement of the colon, caused bybowel obstruction resulting from an aganglionicsection of bowel (the normal enteric nerves areabsent) that starts at the anus and progressesupwards.• The length of bowel that is affected varies but seldomstretches for more than about 30 cm.• This disease is named after Harald Hirschsprung, theDanish physician who first described the disease in1886Ruysch in 1691 a Dutch anatomist, described a 5-year-old girl who died of intestinal obstruction
• The first clinical description of HirschsprungsDisease was presented at the Berlin Society ofPediatrics in 1886 by Hirschsprung. He thought thatthe disease was caused by distention ofthe colon, as evidenced by the title of hispresentation: "Constipation inNewborns Due to Dilation andHypertrophy of the Colon."
Pathophysiology• Congenital aganglionosis of the distal bowel definesHirschsprung disease. Both the myenteric(Auerbach) plexus and the submucosal (Meissner)plexus are absent, resulting in reduced bowelperistalsis and function. The precise mechanismunderlying the development of Hirschsprungdisease is unknown.
Enteric ganglion cells are derived from theneural crest.During normal development, neuroblasts will befound in the small intestine by the 7th week ofgestation and will reach the colon by the 12th weekof gestation. One possible etiology for Hirschsprungdisease is a defect in the migration of theseneuroblasts down their path to the distal intestine.
• Alternatively, normal migration may occur with afailure of neuroblasts to survive, proliferate, ordifferentiate in the distal aganglionic segment.• Abnormal distribution in affected intestine ofcomponents required for neuronal growth anddevelopment, such as fibronectin, laminin, neuralcell adhesion molecule (NCAM), and neurotrophicfactors, may be responsible for this theory.
• Additionally, the observation that the smoothmuscle cells of aganglionic colon areelectrically inactive when undergoingelectrophysiologic studies also points to amyogenic component in the development ofHirschsprung disease.
Epidemiology• Rate of occurence 1 case per 5000 live births.• Race• Hirschsprung disease has no racial predilection.• Sex• Hirschsprung disease occurs more often inmalesthan in females, with a male-to-femaleratio of approximately 4:1.• However, with long-segment disease, the incidenceincreases in females.
• Age• Hirschsprung disease is uncommon inpremature infants.• The age at which Hirschsprung disease isdiagnosed has progressively decreased overthe past century. In the early 1900s, themedian age at diagnosis was 2-3 years; fromthe 1950s to 1970s, the median age was 2-6months.
• Currently, approximately 90% of patients withHirschsprung disease are diagnosed in thenewborn period.
Clinical features1) Delayed passage of meconium2) Abdominal distension3) Constipation
DiagnosisSuspect Hirschsprungs in a baby who has not passedmeconium within 48 hours of delivery. Recall that90% of babies pass their first meconium within 24hours, and the next 9% within 48 hours. Definitivediagnosis is made by suction biopsy of thedistally narrowed segment.
Abdominal x-ray - show a lack of stool in the largeintestine or near the anus and dilated segments ofthe large and small intestine.Barium enema - An x-ray of the abdomen showsstrictures (narrowed areas), obstructions(blockages), and dilated intestine above theobstruction.
Anorectal manometry - a test that measuresnerve reflexes which are missing inHirschsprungs disease.Biopsy of the rectum or large intestine - a testthat takes a sample of the cells in the rectumor large intestine and then looks for nervecells under a microscope.
TreatmentSurgical removal (resection) ofthe abnormal section of the colon,followed by reanastomosis.
Definitions• celiac sprue is an immune disorder(autoimmune)characterized by inflammation of theproximal small intestine induced by the ingestion ofgluten• also known as celiac disease and gluten-sensitive enteropathy
• Celiac disease is a condition that damages thelining of the small intestine and prevents itfrom absorbing parts of food that areimportant for staying healthy. The damage isdue to a reaction to eating gluten, which isfound in wheat, barley, rye, and possibly oats.
23• Occurs in genetically susceptible individuals• A unique autoimmune disorder because:– both the environmental trigger (gluten) andthe autoantigen (tissue Transglutaminase) areknown–elimination of the environmentaltrigger leads to a completeresolution of the disease
Pathogenesis: Environmental• glutens are water-insoluble grain proteins(prolamins and glutenins)• taxonomy of grains predicts their toxicity in patientsGramineaeTriticum Secale Hordeum Avena Oryza Zea Sorghum Pennisetumfamilygenuswheat rye barley oats rice corn sorghum millet graingliadinsecalin hordein avenin oryzenin zein kafirin panicin glutenimmunologiccross-reactivity
25Pathogenesis•Geneticpredisposition• Environmentaltriggers– Dietary– Non dietary?
26Normal small intestineCeliac Disease Villous atrophyNormal villi
UNDER THE MICROSCOPEHealthy normal villi ofthe small intestineDamaged villi of a personwith undiagnosed coeliacdisease
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
30Diagnosis of Coeliac Diseaseand pitfalls•Clinical•Serological•Histological
31Treatment OptionsOption #1:Remove the genesOption #2:Remove the grains
32Treatment• Only treatment for celiacdisease is a gluten-freediet (GFD)– Strict, lifelong diet– Avoid:• Wheat• Rye• Barley
What is the tropical sprue?Tropical sprue: is a malabsorption diseasecommonly found in the tropical regions,marked with abnormal flattening of the villiand inflammation of the small intestinalmucosa.
Causes- No specific causal agent has been clearlyassociated with tropical sprue, butbacterial overgrowth by enterotoxigenicorganisms ( e.g., E.coli and hemophilus )has been implicated.
Morphology- Intestinal changes range from near normal tosevere diffuse enteritis.- Unlike celiac sprue, injury is seen at all levelsof the small intestine.
-Patients frequently have folate and vitaminB12 deficiency, leading to enlargement ofthe nuclei of epithelial cells , reminiscent ofthe changes seen in pernicious anemia.
SymptomsThe symptoms of tropical sprue are:- Diarrhea.- Indigestion.- Cramps.- Weight loss and malnutrition.- Fatigue.
Signs- Abnormal flattening of villi and inflammationof the lining of the small intestine, observedduring an endoscopic procedure.- Presence of inflammatory cell in the biopsy ofsmall 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 includeavoiding travel to the affected regions.If you have to travel, remember to use onlybottled water for drinking, brushing teeth,and washing food .-Nutritional deficiencies must also be corrected.
Treatment:-Treatment is usually 3 to 6 months ofantibiotics (tetracycline) and folic acidsupplements. People with vitamin B12deficiency will receive vitamin supplements as well.