The Digestive system
L3.
Malabsorptive Disorders
Gluten-Sensitive Enteropathy (Celiac Disease)
It is an immune-mediated enteropathy caused by permanent sensitivity to gluten in
genetically susceptible individuals, in which the proximal small bowel (jejunal)
mucosa is damaged as a result of dietary exposure to gluten.
The most common period of presentation is between 6 mo and 2 yr of age.
Pathogenesis
Celiac disease develops only after dietary exposure to the protein gluten, which is
found in wheat, rye, and barley.
Oats???
The activity of gluten resides in the gliadin fraction, which contains certain
repetitious amino acid sequences (motifs) that lead to sensitization of lamina propria
lymphocytes.
A genetic predisposition is suggested by concordance in monozygotic twins
approaching 100%. Two to 5% of first-degree relatives have symptomatic gluten-
sensitive enteropathy, and as many as 10% of first-degree relatives have
asymptomatic damage to small bowel mucosa consistent with this disorder.
An increased prevalence of gluten-sensitive enteropathy has been noted in children
with selective IgA deficiency, diabetes mellitus, chronic rheumatoid arthritis,
thyroiditis, hypothyroidism, Addison disease, pernicious anemia, alopecia, and Down
syndrome.
Clinical Manifestations
Intestinal symptoms are common in children within the 1st 2 yr of life; failure to
thrive, chronic diarrhea, vomiting, abdominal distention, muscle wasting, anorexia,
and irritability are present in most cases.
Occasionally there is constipation, rectal prolapse, or intussusception.
As the age at presentation of the disease shifts to later in childhood, extraintestinal
manifestations without any accompanying digestive symptoms become recognized,
affecting almost all organs.
The most common extraintestinal manifestation of celiac disease is iron-deficiency
anemia, unresponsive to iron therapy.
Rickets &osteoporosis (Calcium/vitamin D malabsorption)
Short stature, arthritis and arthralgia.
Epilepsy, peripheral neuropathies, hypotonia, & cerebellar ataxia (Thiamine/vitamin
B12 deficiency).
Dermatitis herpetiformis, alopecia, erythema nodosum(autoimmunity).
Cardiomyopathy.
Aphthous stomatitis.
Digital clubbing.
Pancreatic insufficiency
Delayed puberty.
Silent celiac disease:
No apparent symptoms in spite of histologic evidence of villous
atrophy. In most cases identified by serologic screening in at-risk groups.
Potential celiac disease: Subjects with positive celiac disease serology but without
evidence of altered jejunal histology.
Screening and Diagnosis
1. CBP: mild dimorphic anemia (iron deficiency with microcytic anemia & rare, a
macrocytic megaloblastic anemia); the blood smear may show target cells, Howell-
Jolly bodies, & Heinz bodies.
2. Hypoproteinemia, Hypoprothrombinemia can occur as a result of malabsorption.
3. Serologic markers:
The anti-endomysium IgA antibody and anti-tissue transglutaminase IgA & IgG
antibody tests are highly sensitive and specific.
*Antiendomysial antibodies, the sensitivity is nearly 100%, and the specificity is
around 98%.
The tTG IgA assay has a specificity of 95-98% and a sensitivity of 92-94%.
The anti-endomysium IgA and anti-tissue transglutaminase IgA antibody test can be
falsely negative with IgA deficiency, which is associated with an increased incidence
of celiac disease. Those patients are positive for anti-tissue transglutaminase IgG
antibodies.
4. Small Intestinal Biopsy
The characteristic histologic changes include partial or total villous atrophy, crypt
elongation, increased number of intraepithelial lymphocytes.
Small bowel biopsy returned to normal within 1-2 yr after starting a gluten-free diet
For children younger than 2 yr, and when the diagnosis is in question, a rechallenge is
recommended. This necessitates three biopsies: an initial biopsy at presentation, the
2nd to document healing with gluten withdrawal, and the 3rd to show recurrent
damage with reintroduction of gluten.
Treatment
1. Lifelong, strict gluten-free diet. All wheat, rye, and barley products should be
eliminated from the diet.
2. Vitamin and iron supplementation.
3. Pancreatic enzyme treatment: improve poor weight gain in the first months after
diagnosis.
*Celiac disease can also present as severe diarrhea, weight loss, hypocalcemia, and
hypoproteinemia, a condition known as a celiac crisis. Treatment of a celiac crisis is
supportive and includes the use of corticosteroids.
Osteopenia is usually reversed with a strict gluten-free diet.
Long-term complications:
Intestinal lymphoma, adenocarcinoma of the small intestine, of the pharynx, and of
the esophagus, especially with poor adherence to the strict gluten-free diet.
Non-Hodgkin lymphoma is the main cause of death.
Constipation
A hard stool passed with difficulty every 3rd day.
Causes of Constipation
1. Nonorganic (functional)
2. Organic
*Anatomic: Anal stenosis, Imperforate anus
*Abnormal Musculature: Prune-belly syndrome, Down syndrome
*Intestinal Nerve abnormalities: Hirschsprung disease
*Spinal Cord Defects: Spinal cord trauma, Spina bifida
*Drugs: Anticholinergics, Narcotics, Lead
*Metabolic Disorders: Hypokalemia, Hypercalcemia, Hypothyroidism
*Intestinal Disorders: Celiac disease, Cystic fibrosis, Inflammatory bowel disease,
Cow's milk protein intolerance
*Systemic lupus erythematosus, Anorexia nervosa.
Functional Constipation
It is differentiated from constipation secondary to organic causes on the basis of a
history and physical examination.
History:
Functional constipation typically starts after the neonatal period.
Daytime encopresis is common, and some children will have a history of blood in
e the stool noted with the passage of a large bowel movement.
Encopresis
:
involuntary fecal soiling in children. Occurs w
hen child's colon is full of
impacted stool, liquid stool can leak around the impacted stool and out of the anus,
staining the child's underwear.
Findings suggestive of underlying pathology include failure to thrive, weight loss,
abdominal pain, vomiting, or persistent anal fissure or fistula.
Physical examination: demonstrates a large volume of stool palpated in the
suprapubic area; rectal examination demonstrates a dilated rectal vault filled with a
large fecal mass
.
Therapy for functional constipation
1. Patient education: regular bowel training program, including sitting on the toilet
for 5–10 min after meals,
2. Relief of impaction, and softening of the stool: If an impaction is present, an
enema is usually required to clear the impaction while bowel softeners are started
as maintenance medications.
Typical regimens include the use of polyethylene glycol preparations, glycerin
suppositories, lactulose (1 mL/kg/day – 3 mL/kg/day in divided doses), or mineral
oil.
3. Dietary modification
*A balanced diet that includes whole grains, fruits and vegetables is recommended.
*Carbohydrates (especially sorbitol) found in prune, pear and apple juices can cause
increased frequency and water content in stools.
*Adequate fluid intake with a bulking agent such as fiber.
Distinguishing Features of Hirschsprung Disease and Functional
Constipation
Variable Functional (Acquired) Hirschsprung Disease
History
Onset of constipation
After 2 yr of age At birth
Encopresis Common Very rare
Failure to thrive Uncommon Possible
Enterocolitis None Possible
Examination
Abdominal distention Uncommon Common
Poor weight gain Rare Common
Anal tone Normal Normal
Rectal examination Stool in ampulla Ampulla empty
Malnutrition None Possible
Laboratory
Anorectal manometry Distention of the rectum causes
relaxation of the internal sphincter No sphincter relaxation or
paradoxical I
increase in pressure
Rectal biopsy Normal No ganglion cells
Barium enema Massive amounts of stool, no transition zone Transition zone, delayed evacuation
(>24 hr)
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