Download Evaluating, definition, causes, infections, intolerance to protein

This lecture was conducted during the Nephrology Unit
Grand Ground by Registrar under Nephrology Division
under the supervision and administration of Prof. Jamal Al
Wakeel, Head of Nephrology Unit, Department of Medicine
and Dr. Abdulkareem Al Suwaida, Chairman of Department
of Medicine. Nephrology Division is not responsible for the
content of the presentation for it is intended for learning
and /or education purpose only.
Evaluating the child with
chronic diarrhea
Presented by:
Dr.Habib-ur-Rahman
Registrar
August 2008
Definition.
• Diarrhea is loosely defined as passage of
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abnormally liquid or unformed stools at an
increased frequency.
For adults on a typical Western diet, stool weight
>200 g/d can generally be considered diarrheal.
Acute;
< 2 weeks.
Persistent;
2- 4 weeks
Chronic ;
> 4 weeks.
causes of chronic diarrhea in
children
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Infections
Intolerance to cow's milk or soy protein
Chronic nonspecific diarrhea of childhood
Overfeeding
Disaccharidase deficiencies
Glucose-galactose malabsorption
Celiac disease
Pancreatic disorders
Cystic fibrosis
Shwachman-Diamond syndrome
Inflammatory bowel diseases Ulcerative colitis Crohn's disease
causes of chronic diarrhea in
children
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Drug-induced diarrhea Antibiotics Laxatives
Immunodeficiency states
Short-bowel syndrome
Chronic constipation with overflow diarrhea
Hyperthyroidism
Functional tumors
Acrodermatitis enteropathica
Intestinal lymphangiectasia
Abetalipoproteinemia
Congenital chloride-losing diarrhea
INFECTIONS
• Gastrointestinal infection is by far the most common cause of
chronic diarrhea in children.The major bacterial pathogens include
enteropathogenic and enterohemorrhagic Escherichia coli,
Salmonella species, Shigella species, Yersinia enterocolitica and
Campylobacter jejuni.Major parasitic causes of chronic diarrhea
include Giardia lamblia, Entamoeba histolytica and Cryptosporidium
species. Common viral agents include rotavirus, adenovirus, Norwalk
virus and the enteroviruses.
• Acute infectious gastroenteritis may be complicated by postenteritis
diarrhea occurring after damage to the small intestinal mucosa, with
resulting secondary disaccharidase deficiency and carbohydrate
intolerance. Typically, patients with postenteritis diarrhea relapse
with diarrhea when lactose-containing foods are reintroduced into
the diet. In infants and young children, systemic infections, such as
a urinary tract infection, may occasionally be associated with chronic
diarrhea.
INTOLERANCE TO PROTEIN
• Protein intolerance, especially to cow's
milk or soy protein, is a common cause of
chronic diarrhea. Symptoms usually occur
before six months of age. Associated
manifestations include bloody diarrhea,
anemia, protein-losing enteropathy and
extraintestinal manifestations of allergy,
such as eczema, hives or asthma.
CHRONIC NONSPECIFIC DIARRHEA
• Chronic nonspecific diarrhea of childhood is one of the
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most common causes of chronic diarrhea. This benign,
self-limited disorder usually presents in children between
the ages of six months and three years.The male to
female ratio is 2:1.
The syndrome is characterized by persistent or recurrent
episodes of voluminous loose stools, usually with six or
more stools per day. Undigested food particles may be
noted in the stools. Nocturnal diarrhea is absent. Despite
having diarrhea, children with this disorder thrive and
appear healthy.
CHRONIC NONSPECIFIC DIARRHEA
• The exact etiology of chronic nonspecific
diarrhea of childhood is not clear. The syndrome
may occur after a viral infection or the institution
of dietary restrictions, such as the elimination of
milk and dairy products. In one study, the
mouth-to-anus transit time of food in children
with chronic nonspecific diarrhea was found to
be shorter than in age-matched control subjects.
Emotional stress and excessive ingestion of cold
or hyperosmolar fluid (fruit juice) have also been
implicated as possible causative factors
OVERFEEDING
Excessive intake of fluids, especially hyperosmolar
fruit juice, may cause chronic diarrhea.Osmotic
diarrhea can be caused by common dietary
sugars such as sorbitol and fructose. Sorbitol is
found in significant concentrations in prunes,
pears, peaches, apple juice and sugar-free gum.
Fructose is found in honey, dried figs, dried
dates, prunes and some soft drinks.In children
with diarrhea resulting from excess
hyperosmolar fluid intake, the first stools of the
day are usually formed.
DISACCHARIDASE DEFICIENCIES
• Primary deficiencies of disaccharidase (i.e.,
lactase, sucrase or isomaltase) are rare.
However, secondary disaccharidase deficiencies
are common, and they are associated with other
gastrointestinal disorders, including infection,
bacterial over-growth and untreated celiac
disease. Typically, diarrhea resulting from
disaccharidase deficiency is explosive and
watery. Other symptoms include abdominal pain,
bloating and flatulence
GLUCOSE-GALACTOSE
MALABSORPTION
• Primary monosaccharide malabsorption is rare
and is inherited as an autosomal recessive trait.
The characteristic defect is an impairment in the
ability of cells in the intestinal mucosa to actively
transport glucose and galactose, so that only
about 10 percent of the ingested glucose and
galactose can be absorbed.This absorption
disorder, which usually presents in neonates, is
characterized by watery diarrhea with an acidic
stool.
CELIAC DISEASE
• Celiac disease is associated with villous atrophy of the proximal
small intestine. This condition is the result of a permanent
intolerance to the gliadin fraction of gluten protein. Celiac disease
has a strong association with histocompatibihty-type human
leukocyte antigens (HLAs), such as HLA-B8 and class II HLA-DR3,
HLA-DR7, HLA-DQ, HLA-W2 and HLA-DR4.
• Symptoms can develop any time after gluten (e.g., wheat, barley,
rye) is introduced into the diet. Most children with celiac disease
present at six to 24 months of age. Major manifestations include
chronic diarrhea, anorexia, failure to thrive, muscle wasting,
irritability and abdominal distention. Characteristically, the stools are
pale, loose, bulky and oily, and they have a pungent odor.
PANCREATIC DISORDERS
• Cystic fibrosis, the most common pancreatic disorder causing
chronic diarrhea, is inherited as an autosomal recessive trait. The
gene responsible for cystic fibrosis has been localized to the long
arm of chromosome 7.
• The triad of pancreatic exocrine deficiency, chronic obstructive
pulmonary disease and an abnormally high level of chloride in the
sweat is present in most patients.Clinically, the disease may
manifest as steatorrhea (fat-containing stools) with malabsorption,
meconium inspissation in the neonatal period, prolonged neonatal
jaundice, growth retardation, anasarca, recurrent or chronic chest
infections, nasal polyps, rectal prolapse or digital clubbing. Even
though they have voracious appetites, most children with cystic
fibrosis remain malnourished
Shwachman-Diamond syndrome
• characterized by neutropenia and pancreatic
insufficiency. Other features include short
stature and skeletal abnormalities. The disease
is usually inherited as an autosomal recessive
trait, but an autosomal dominant mode of
inheritance has also been reported. Shwachmandiamond syndrome may be differentiated from
cystic fibrosis by the presence of normal levels
of sweat chloride and the absence of pulmonary
disease.
INFLAMMATORY BOWEL DISEASE
• Inflammatory bowel disease frequently develops in late childhood or
during adolescence. This disorder is characterized by unpredictable
remissions and exacerbations. The etiology of inflammatory bowel
disease is unknown, but genetic factors appear to make persons
with this disorder more vulnerable to an immunologically related
inflammatory reaction.
• Ulcerative colitis is an inflammatory disease that most commonly
involves the mucosa of the colon and rectum. Predominant
symptoms include bloody diarrhea, lower abdominal cramps and
tenesmus. Anorexia, malaise, weight loss and growth failure occur
as the disease progresses.
• Older children may have extraintestinal manifestations, including
arthritis, erythema nodosum, pyoderma gangrenosum, iritis,
hepatitis, digital clubbing and intermittent fever.
INFLAMMATORY BOWEL DISEASE
• Crohn's disease is a segmental transmural inflammatory
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disease that may affect one or more segments of the
gastrointestinal tract, from the mouth to the anus. The
distal ileum and colon are the bowel segments most
commonly affected.
The classic symptom triad includes bloody diarrhea,
abdominal pain and weight loss.
Stomatitis and chronic perianal lesions, such as fissures,
fistulas and abscesses, may be present bullous and
eczematous lesions symmetrically distributed in the
perioral, acral and perineal areas.
INTESTINAL LYMPHANGIECTASIA
• In children with intestinal
lymphangiectasia, rupture of the intestinal
mucosal lacteals may result in massive
gastrointestinal loss of fat and protein.
Consequently, lymph may leak into the
bowel lumen. Children with this condition
typically have steatorrhea, protein-losing
enteropathy, anemia, malnutrition and
growth retardation.
ABETALIPOPROTEINEMIA
• Abetalipoproteinemia is a disorder
resulting from the inability to form
chylomicrons in the intestinal mucosa.
• Typically, children with this rare autosomal
recessive disorder present with diarrhea,
failure to thrive, acanthocytosis, retinitis
pigmentosa and cerebellar ataxia
CONGENITAL CHLORIDE-LOSING
DIARRHEA
• Chronic diarrhea may occur because of the
absence of a normal ileal mechanism for
active absorption of chloride in exchange
for bicarbonate.
• Typically, this congenital problem presents
in neonates and is characterized by watery
diarrhea and metabolic alkalosis
Clinical Evaluation
• A thorough history and a complete
physical examination are important in the
evaluation of chronic diarrhea
Laboratory Evaluation
• Certain basic laboratory studies can be helpful in many
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patients with chronic diarrhea.
The stool should be analyzed for pH, reducing
substances, occult blood, fatty acid crystals, fat globules,
red blood cells, white blood cells, and ova and parasites.
The stool culture may also yield important information.
Other potentially useful tests include a complete blood
count with differential and peripheral smear, an
erythrocyte sedimentation rate, serum electrolyte
concentrations, total protein and albumin levels, and a
serum carotene level
Laboratory Evaluation
• The presence of reducing substances in a stool
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with a pH less than 6 suggests carbohydrate
malabsorption.
A positive stool guaiac test indicates intestinal
mucosal breakdown, which may be caused by
gastrointestinal infection, protein intolerance or
inflammatory bowel disease.
The guaiac test may also be positive if the diet
contains meat
Laboratory Evaluation
• Fat globules in the stool may be normal in the
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first few months of life.
In an older child, the presence of fat globules
suggests steatorrhea. Lubricants used during a
digital examination to obtain a stool specimen
may give a false-positive result for stool fat.
Refractile fatty-acid crystals suggest a mucosal
problem such as celiac disease
Laboratory Evaluation
• A fresh stool sample should be examined microscopically.
• The presence of a large number of neutrophils or red
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blood cells indicates bacterial gastroenteritis or
inflammatory bowel disease. The presence of eosinophils
suggests protein intolerance or parasitic infestation.
Mobile parasites (G. lamblia or E. histolytica), cysts
(protozoa or nematodes) and ova (nematodes and
trematodes) may be seen.
Stool cultures for specific organisms should also be
performed.
Laboratory Evaluation
• A complete blood count is often helpful. Neutrophilia and
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an increased number of band forms or toxic granulations
are suggestive of bacterial infection. Neutropenia may be
present in some immunodeficiency disorders, while
eosinophilia may occur in parasitic infestation or protein
intolerance.
Hypochromic microcytic anemia suggests chronic
gastrointestinal blood loss or malabsorption of iron.
Acanthocytes in the peripheral smear suggest
abetalipoproteinemia, while macrocytosis suggests
vitamin [B.sub.12] or folate deficiency. An elevated
erythrocyte sedimentation rate suggests active infection
or inflammatory bowel disease.
Laboratory Evaluation
• In malnutrition, the serum albumin and globulin
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levels are decreased proportionally In contrast,
protein-losing enteropathy is characterized by a
greater loss of albumin and therefore a
disproportionately depressed serum albumin
level.
The serum carotene level is an inexpensive and
simple marker for fat malabsorption, assuming
dietary carotene intake is adequate.
Laboratory Evaluation
• In watery diarrhea, calculation of the stool
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osmotic gap may help to differentiate diarrhea
caused by osmotic agents such as sugars from
diarrhea caused by abnormalities in the ionic
transport of electrolytes.
The stool osmotic gap is calculated by the
following formula: stool osmolality - [2 x (stool
sodium + stool potassium)].
Laboratory Evaluation
• If the stool osmotic gap is increased, the
diarrhea may be caused by an osmotically
active agent, such as a sugar. If there is
no osmolar gap, the diarrhea is more likely
the result of impairment of the ionic
transport of an electrolyte, which is
common in infectious gastroenteritis, bile
salt malabsorption, bacterial overgrowth,
laxative abuse and short-bowel syndrome
Laboratory Evaluation
• Other tests that should be performed when indicated
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include serum immunoglobulin levels for
immunodeficiency.
hydrogen breath test for carbohydrate malabsorption,
72-hour fecal fat test for fat malabsorption,
sweat chloride test for cystic fibrosis,
upper gastrointestinal series with small-bowel followthrough for anatomic abnormalities and Crohn's disease,
Laboratory Evaluation
• barium enema for Hirschsprung's disease
and inflammatory bowel disease,
• Sigmoidoscopy for inflammatory bowel
disease and pseudomembranous colitis,
• stool assay for giardiasis and a
• jejunal biopsy for celiac disease.
Management
• Treat the cause.
Congenital chloride diarrhea
Definition.
Congenital chloride diarrhea is a rare specific congenital
defect of ileal chloride transport. The result is persistent
osmotic diarrhea. Maternal polyhydramnios, abdominal
distension, watery diarrhea and a high fecal chloride
level > 90 mmol/l are the major features in the neonatal
Congenital chloride diarrhea
• History:
• Congenital chloride diarrhea was first described in Finland in 1945
and has most often been seen in this country and in Kuwait.
• Prevalence:
Congenital chloride diarrhea is a rare disorder, reported mainly in
Finland. It is a recessive inherited disorder of chloride transport in
the distal ileum and colon. It is a common disorder in Kuwait with
an incidence of 1/3200 due to a high prevalence of consanguinity
marriages in that country.
• Etiology:
• Anomaly of chloride transport in the distal ileum and colon, and
that is why there is a polyhydramnios and intestinal distention,
during intra-uterine period
Pathogenesis:
• Congenital chloride diarrhea is autosomal recessive
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disorder of intestinal Cl/HCO3 exchange caused by
mutations in the SLC26A3 gene and it is characterized by
a persistent chloride diarrhea after birth.
The underlying defect is in chloride reabsorption by cells
of the intestinal mucosa, associated with impaired
transport of bicarbonate. The result is water diarrhea in
utero and polyhydramnios, commonly leading to
premature delivery.
After birth, the infants become hypochloremic,
hyponatremic, hypokalemic and alkalotic
Diagnosis
• Ultrasound findings: In spite of the classical features
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of the disease, 75% of the Kuwait cases are diagnosed
beyond the neonatal period and all demonstrated chronic
diarrhea and failure to thrive, with hypochloremia,
hypokalemia and metabolic alkalosis. Nevertheless, the
prenatal scan showed dilated intestinal loops with
polyhydramnios, which suggested a congenital chloride
diarrhea. The diagnosis is confirmed by a high fecal
chloride level.
Implications for Targeted Examinations: When we
observed the typical aspect of regular dilated intestinal
loops, with polyhydramnios, we should think about the
congenital chloride diarrhea diagnosis.
Differential Diagnosis:
• Ano-rectal atresia or imperforation:
There is essentially dilatation of the colon. And polyhydramnios can
be absent.
• Colon aganglionosis or Hirschsprung disease:
There is a total absence of ganglion cells in both submucosal
(Meissner’s) and myenteric (Auerbach’s) plexuses of the intestine.
When the disease involves the ileum and, less often, the jejunum,
the disease is call Jirasek-Zuelzer-Wilson disease.
• Intestinal occlusion:
caused by anatomic anomalies (Meconial occlusion, intestinal
stenosis, brides, etc.). Nevertheless, the dilated intestinal loops are
not so regular and can be filled of meconium as in Mucoviscidosis.
Associated Anomalies:
• A fecal chloride concentration exceeding
the sum of the sodium and potassium
concentrations suggest the diagnosis. The
condition may also be diagnosed
antenatally. Ultrasound examinations may
reveal a regular distension of intestinal
loops after 25 weeks. Polyhydramnios with
premature delivered is always present
Management:
• Treatment is usually symptomatic. Replacement therapy with NaCl
and KCl has been shown to be effective, but the long-term
prognosis remains unclear.
• Nevertheless, early diagnosis and aggressive salt replacement
therapy were associated with normal growth and development, in
addition to significancy reduced mortality rates.
• Enuresis, slight soiling and hospitalization for gastroenteritis are
common, especially during early childhood.
• Complications can be end-stage renal disease, hyperuricemia,
infertility, spermatoceles, intestinal inflammation, inguinal hernias
and increased concentrations of sweat Cl.
Prognosis:
• Unfortunately, there is no treatment to the
diarrhea of congenital chloride diarrhea,
but children with this condition become
toilet trained at a normal age. Their social
adjustment can be impaired, but the
prognosis is good if potassium as well as
sodium and chloride are replaced
regularly.
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THANKS.