IV Gastrointestinal Disorders

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					Zyady Pediatrics                         Gastrointestinal Disorders

                           Chapter IV
           Gastrointestinal Disorders

       11. PERITONITIS

 Zyady Pediatrics                                                                  Gastrointestinal Disorders

            ABDOMINAL PAIN                                                     APPENDICITIS
                                                             Appendicitis is the most commo         n surgical
                    ACUTE PAIN                               emergency in childhood. The incidence peaks in the
                                                             late teenage years, with only 5% of cases occurring
          APPROACH TO THE PATIENT                            in children < 5 years old. There is a slight male
The most urgent consideration in a child who has
acute abdominal pain is to determine whether there           ETIOLOGY
is an underlying cause requiring surgery. Most
causes of abdominal pain in children do not require            Appendicitis begins with obstruction of the lumen,
surgical treatment.                                            most commonly by fecal matter (fecalith), but
                                                               appendiceal obstruction also can occur secondary
IMPORTANT CAUSES OF ABDOMINAL PAIN POSSIBLY                    to hyperplasia of lymphoid tissue associated with
REQUIRING SURGERY                                              viral infections or the presence of neoplastic
                                                               tissue, commonly an appendiceal carcinoid tumor.
  1. Intestinal obstruction
                                                               Trapped bacteria proliferate and begin to invade
  2. Appendicitis, Meckel's diverticulum, or an                the appendiceal wall, inducing inflammation and
     abdominal abscess                                         secretion. The obstructed appendix becomes
  3. Toxic megacolon                                           engorged, its blood supply is compromised, and it
                                                               finally ruptures.
  4. Perforated duodenal ulcer or perforation of
     intestine secondary to another process                    The entire process is rapid, with appendiceal
                                                               rupture usually occurring within 48 hours of the
  5. Cholecystitis                                             onset of symptoms.
  6. Rupture spleen or other organ due to trauma
IMPORTANT CAUSES OF ABDOMINAL PAIN NOT                         1. Symptoms: Classic appendicitis begins with
REQUIRING SURGERY                                                 visceral pain, localized to the periumbilical
                                                                  region. Nausea and vomiting occur soon after.
  1. Enteritis; colitis of any cause
                                                                  As the inflammation begins to irritate the
  2. H-S purpura, HUS, other types of vasculitis                  parietal peritoneum adjacent to the appendix,
  3. Fecal impaction                                              somatic pain fibers are activated, and the pain
                                                                  localizes to the right lower quadrant.
  4. Hepatitis
                                                               2. Signs: Examination reveals a tender right
  5. Pancreatitis                                                 lower quadrant. Voluntary guarding is present
                                                                  initially, progressing to rigidity, then to
  6. Vaso-occlusive crisis of sickle cell anemia
                                                                  rebound tenderness with rupture and
  7. Primary peritonitis                                          peritonitis. These classic findings may not be
  8. Mesenteric adenitis                                          present, however, especially in young
                                                                  children, if the appendix is retrocecal, covered
  9. UTI or urinary calculi                                       by omentum, or in another unusual location.
  10. Extra-abdominal causes (e.g., pneumonia,                 When doubt exists, imaging is helpful to rule out
      osteomyelitis, acute neurologic processes)               complications (right lower quadrant abscess, liver
                                                               disease) and other disorders, such as mesenteric
  11. Unusual causes [e.g., porphyria, familial
      Mediterranean fever, DKA, Kawasaki disease               adenitis and ovarian or fallopian tube disorders. If
      (gallbladder hydrops)]                                   the workup is negative but some doubt remains,
                                                               the child should be admitted to the hospital for
                                                               close observation and serial examinations.
  1. Vomiting, especially if it is bilious or feculent
  2. Sudden onset of abdominal distention
  3. Absent bowel sounds or high-pitched sounds
     suggestive of intestinal obstruction
  4. Abdominal signs of peritonitis (e.g., rigidity,
     guarding, rebound tenderness)
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INVESTIGATIONS                                                             INTUSSUSCEPTION
 The history and examination are often enough to            Intussusception is the "telescoping" of a segment of
 make the diagnosis, but laboratory and imaging             proximal     bowel     (the    intussusceptum)  into
 studies are helpful when the diagnosis is uncertain.       downstream bowel (the intussuscipiens). Most cases
 A. A WBC count > 10,000/mm3 is found in 89%                occur in infants 1 to 2 years old. There is a slight
    of patients with appendicitis and 93% with              male predominance.
    perforated appendicitis. This criterion is met
    by 62% of abdominal pain patients without               PATHOGENESIS
    appendicitis, however. The specificity of an              Most intussusceptions are ileocolic.
    elevated WBC count is low.
                                                              1. In patients younger than the age of 2 years
 B. Urinalysis is done to rule out UTI.                          (the period of peak incidence), no lead point
 C. Amylase, lipase, and liver enzymes are done                  of the intussusception is typically found. A
    to look for pancreatic or liver and gallbladder              previous      viral    infection may    ause
    disease.                                                     hypertrophy of the Peyer's patches or
                                                                 mesenteric nodes, which are hypothesized to
 D. CXR rules out pneumonia masquerading as                      play a role in intussusception.
    abdominal pain.
                                                              2. A specific lead point is identified in only
 E. The plain abdominal x-ray may reveal a                       approximately 5% of patients. However,
    calcified fecalith, which strongly suggests the              specific anatomic abnormalities leading to
    diagnosis.                                                   intussusception are more common in children
 F. When these studies are inconclusive, imaging                 older than 5 years of age. Recognizable causes
    is indicated with a CT scan or abdominal US,                 of the intussusception include Meckel's
    which may reveal the presence of an enlarged,                diverticulum, an intestinal polyp, lymphoma,
    thick-walled appendix with surrounding fluid.                or a foreign body. Meckel's diverticulum
    Diameter of > 6 mm is considered diagnostic.                 usually manifests as melena unassociated with
                                                                 abdominal pain or intussusception.
TREATMENT                                                     3. As a result of impaired venous return, the
 Treatment of appendicitis is surgical. Simple                   affected bowel may swell, become ischemic
 appendectomy is curative if performed before                    and necrotic, and perforate.
 perforation. With perforation, a course of
 postoperative IV antibiotics is required. Broad-           MANIFESTATIONS
 spectrum coverage is necessary to cover the mixed            1. Sudden onset of crampy abdominal pain; a
 bowel flora.                                                    colicky pattern occurring every 15-20
                                                                 minutes. Feedings are refused. Between
                                                                 episodes of pain, the infant is glassy-eyed and
                                                                 groggy and appears to have been sedated.
                                                              2. As intussusception progresses, obstruction
                                                                 becomes      prolonged, bilious        vomiting
                                                                 becomes prominent, and the dilated, fatigued
                                                                 intestine generates less pressure and less pain.
                                                              3. The venous outflow from the intussus-ceptum
                                                                 is obstructed, leading to edema, weeping of
                                                                 fluid, and congestion with bleeding. Third
                                                                 space fluid losses and "currant jelly" stools
                                                              4. Another unexpected feature of intussusception
                                                                 is lethargy.
                                                              5. A sausage-shaped mass caused by the
                                                                 swollen, intussuscepted bowel may be
                                                                 palpable in the right upper quadrant or

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INVESTIGATIONS                                                             CHRONIC PAIN
 The diagnosis depends on the direct demonstration         Chronic abdominal pain is a frequent problem in
 of bowel-within-bowel.                                    children. Most often, no specific cause can be
                                                           documented. Two particularly vexing problems are
 A. Abdominal US is a simple and direct way of             infantile colic and irritable bowel syndrome.
    showing intussusception.                               Infantile colic is discussed elsewhere.
 B. A pneumatic or contrast enema under
    fluoroscopy. This is the most direct and                       IRRITABLE BOWEL SYNDROME
    potentially useful way to show and treat               Irritable bowel syndrome may represent the most
    intussusception.                                       common cause of chronic abdominal pain, yet it is
     Air and barium can show the intussusception           probably the least characterized.
     quickly and, when administered with
     controlled pressure, usually can reduce it            PATHOGENESIS
     completely. The success rate for pneumatic
                                                             The precise pathogenesis of IBS is unknown, but
     reduction is probably a bit higher than
                                                             visceral hypersensitivity (reaction to gut
     hydrostatic reduction with barium and
                                                             distention) and abnormal intestinal (primarily
     approaches 90% if done when symptoms have
                                                             colonic) motility have been described.
     been present for < 24 hours.
     The pneumatic enema has the additional                MANIFESTATIONS
     advantage over barium of not preventing
                                                             1. Abdominal cramping is a cardinal feature and
     subsequent radiologic studies, such as upper
                                                                may be described in virtually any part of the
     GI series or CT scan.
                                                                abdomen. It frequently is paroxysmal and
     Nonoperative reduction should not be                       severe. Pain is often relieved by defecation.
     attempted if the patient is unstable or has
                                                             2. Stool consistency may frequently vary from
     evidence of perforation or peritonitis.
                                                                hard to loose.
TREATMENT                                                    3. Nausea, diaphoresis, and lightheadedness are
                                                                occasionally seen.
 Therapy must begin with placement of an IV
 catheter and a nasogastric tube.                            4. Anxiety often provokes an attack.
 1. Before radiologic intervention is attempted,
    the child must have adequate fuid           l
    resuscitation to correct the often severe                A clinical diagnosis is based on a characteristic
    dehydration caused by vomiting and third                 history and negative findings from physical
    space losses. Ultrasound may be performed                examination. Other disorders (e.g., lactose
    before the fluid resuscitation is complete.              intolerance, IBD, giardiasis) must be excluded.
 2. Surgical consultation should be obtained early
    because the surgeon often prefers to be
    present during non-operative reduction.                  1. Reassurance that the symptoms, although they
     If pneumatic or hydrostatic reduction is                   are frequent, do not suggest a life-threatening
     successful, the child should be admitted to the            disease
     hospital for overnight observation of possible          2. Dietary fiber supplementation
     recurrence (risk is 5-10%).
                                                             3. Medications (e.g., anticholinergic       drugs,
     If reduction is not complete, emergency                    tricyclic antidepressants)
     surgery is required. The surgeon attempts
     gentle manual reduction, but may need to                4. Psychotherapy     (if      stress        ently
     resect the involved bowel after failed                     exacerbates symptoms)
     radiologic reduction because of severe edema,
     perforation, a pathologic lead point (polyp,          PROGNOSIS
     Meckel diverticulum), or necrosis.                    Little is known about the natural history of IBS in
                                                           children, although clinical experience suggests that
                                                           the problem may persist for intervals of months to

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        DIARRHEA DISORDERS                                       DIARRHEA AS A RESULT OF VIRAL
     ACUTE INFECTIOUS DIARRHEA                              EPIDEMIOLOGY
Acute infectious diarrhea remains a leading cause of
                                                             Rotavirus is the primary viral pathogen associated
morbidity and mortality throughout the world.
                                                             with diarrhea in children. Rotavirus is found
                                                             worldwide, generally in children from 6 months to
   DIARRHEA AS A RESULT OF BACTERIAL                         2 years of age, and is most common during the
              PATHOGENS                                      winter months.

PATHOGENIC MECHANISMS                                       PATHOGENESIS
  1. Toxin production (e.g.,        Vibrio cholerae,         Rotavirus infects and destroys mature villous cells
     Clostridium difficile)                                  of the small intestine, not small intestinal crypt
  2. Adherence to intestinal mucosa, with a local            cells or colonic epithelial cells. Functionally
     cytopathic effect (e.g., enteroadherent E. coli)        immature     crypt    cells    predominate,    and
                                                             abnormalities in electrolyte and carbohydrate
  3. Invasion (e.g., Shigella sp)                            absorption ensue.
  4. Other (enterohemorrhagic E. coh)
MANIFESTATIONS                                               Clinical features are seen after a 48-72 hour
  Bacterial diarrhea may occur as   either a cholera-        incubation period and include a predictable
  like condition with profuse,      watery diarrhea          sequence of fever, vomiting, and subsequent
  caused by bacterial toxins, or    a dysentery-like         diarrhea, which lasts several days.
  condition with bloody stools       associated with
  invasive bacteria.                                        DIAGNOSIS
  C. difficile-induced "pseudomembranous colitis"            Rotavirus can be identified from stool with a
  typically follows antibiotic therapy that allows           commercially available ELISA kit.
  overgrowth of this organism.
  Verotoxin-producing E. coli (type 0157:H7) and
  some other bacteria (e.g., Shigella) may lead to           Therapy is supportive, and oral rehydration is
  hemolytic-uremic syndrome. Bloody diarrhea is              usually successful. Lactose intolerance is seen in
  associated with microangiopathic hemolytic                 approximately 50% of infants suffering rotavirus
  anemia, uremia, and thrombocytopenia.                      infection, and this condition may last for several
                                                             weeks. Early refeeding after rehydration is
DIAGNOSIS                                                    recommended.
  Diagnosis depends on isolation of the particular          NORWALK AGENT
  organism by stool culture. A Gram's stain of the
  stool may reveal leukocytes, and this usually is           Norwalk agent is the prototype of a larger group
  indicative of an invasive pathogen.                        of viruses that are associated with outbreaks of
                                                             GE. This microorganism is found more commonly
TREATMENT                                                    in older children than in infants. After a 48-hour
                                                             incubation period, vomiting, diarrhea, or both may
  Therapy with antibiotics is not always indicated.          be seen. Therapy is supportive and similar to that
  1. Salmonella gastroenteritis should not be                for rotavirus infection.
     treated with antibiotics unless it is
     accompanied by septicemia, because use of              ENTERIC ADENOVIRUS
     antibiotics may prolong fecal excretion of this         Enteric adenovirus (serotypes 40 and 41 ) has been
     organism.                                               increasingly recognized as a cause of diarrhea in
  2. If symptoms associated with other bacterial             young children. Clinically, this infection
     pathogens have abated by the time of                    resembles that seen with rotavirus, although the
     diagnosis, treatment is usually unnecessary.            diarrhea may last somewhat longer (mean
                                                             duration, 5-6 days). Infection is seen year-round.
  3. Drugs that slow intestinal motility (e.g.,
     Ioperamide) are contraindicated for bacterial
                                                              DIARRHEA AS A RESULT OF PROTOZOAL
                                                             PATHOGENS (SEE INFECTIOUS DISORDERS)
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     FOOD-ASSOCIATED DIARRHEA                                      2. COW'S MILK AND SOY PROTEIN
                                                                 INTOLERANCE (ALLERGIC ENTEROCOLITIS)
          PROTEIN HYPERSENSITIVITY                           Dietary proteins are a common cause of intestinal
                                                             inflammation with rectal bleeding in infants. The
               1. CELIAC DISEASE                             most commonly implicated agents are cow's milk
Celiac disease is an injury to the mucosa of the small       and less often soy proteins.
intestine caused by the ingestion of gluten (a toxic
protein component) from wheat, rye, barley, and              MANIFESTATIONS
related grains. Rice does not contain toxic gluten and        Most symptoms develop in the first 3 mo of life.
can be eaten freely, as can pure preparations of oats.
                                                              1. Vomiting and diarrhea are most commonly
1 in 250 persons in the U.S. have celiac disease, only           seen and if prolonged may lead to FTT.
a few of which have been diagnosed. The disease is
seen in association with diabetes and trisomy 21.             2. Rectal bleeding may be seen if allergic colitis
                                                                 is present.
MANIFESTATIONS                                                3. Edema secondary to excessive enteric protein
  Symptoms can begin at any age when gluten-                     loss may be dramatic and often is associated
  containing foods are given. Diarrhea, abdominal                with anemia.
  bloating, FTT, decreased appetite, and ascites              4. Rhinorrhea,     wheezing,       and eczema
  caused by hypoproteinemia are classic. Children                occasionally may be seen and frequently are
  may be minimally symptomatic or may be                         accompanied by eosinophilia and an elevated
  severely malnourished. A careful inspection of the             serum immunoglobulin E (IgE) level.
  child's growth curve and determination of reduced              Anaphylaxis is rarely observed.
  SC fat and abdominal distention are crucial.
                                                              Diagnosis is usually made empirically. Skin and
  A. Serologic markers: IgA antiendomysial                    IgE radioallergosorbent test results to the
     antibody and IgA tissue transglutaminase                 offending protein are frequently negative.
     antibody. Because IgA deficiency is common
                                                              For children with persistent symptoms the
     in celiac disease, total serum IgA also must be
     measured to document the accuracy of these               diagnosis can be confirmed safely and easily by
     tests. In the absence of IgA deficiency, either          rectal mucosal biopsy; this shows eosinophilic
     test yields a sensitivity and specificity of 95%.        inflammation of the mucosa. Visual findings at
                                                              proctoscopy usually include mucosal friability and
  B. Small bowel biopsy is essential to confirm               lymphoid    hyperplasia,    giving     a lumpy,
     diagnosis and should be performed while the              "mosquito-bitten" appearance to rectal mucosa.
     patient is still taking gluten. Biopsy specimen
     shows various degrees of villous atrophy                TREATMENT
     (short or absent villi), mucosal inflammation,
     crypt hyperplasia, and increased numbers of              1. Infants who are bottle-fed should be switched
     intraepithelial lymphocytes.                                to a hydrolyzed protein formula (e.g.,
                                                                 Nutramigen, Pregestamil, or Alimentum).
  C. Other laboratory studies should be
     performed to rule out complications, including           2. Breastfed infants may continue breastfeeding,
     CBC, calcium, phosphate, total protein and                  but the mother should restrict soy and dairy
     albumin, and liver function tests. Mild                     products from her diet.
     elevations of the transaminases are common.              3. Visible blood in the stools typically resolves
                                                                 within a few days, although occult blood
TREATMENT                                                        persists for several weeks. For infants with
                                                                 persistent bleeding, an amino acid-based
  Treatment is complete elimination of gluten from
  the diet. Starchy foods that are safe include rice,            formula is occasionally necessary.
  soy, tapioca, buckwheat, potatoes, and (pure) oats.         Nearly all of these infants lose their sensitivity to
                                                              the offending protein by 1 year. The first
  Most patients respond clinically within a few
  weeks with weight gain, improved appetite, and              intentional exposure to cow's milk should be
                                                              performed in the physician's office because of a
  improved sense of well-being. Histologic
                                                              small risk of anaphylaxis. Treatment of iron
  improvement lags behind clinical response,
  requiring several months to normalize.                      deficiency also is indicated.

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                                                          INTRACT ABLE DIARRHEA OF INFANCY
Carbohydrate intolerance is a very common cause of
diarrhea in childhood.                                    ETIOLOGY
PATHOGENESIS                                               Intractable diarrhea of infancy is an uncommon
                                                           problem but one that may have life-threatening
  Dietary carbohydrate is processed by several             consequences. Multiple disease states may be
  enzymes, beginning with amylase (which                   responsible for this clinical entity.
  metabolizes starch) and ending with the brush
  border enzymes lactase, sucrase, isomaltase, and          1. Congenital enzymatic/transport defects
  glucoamylase. Any process (congenital or
  acquired) that diminishes the activities of these               −   Glucose-galactose malabsorption
  enzymes may lead to carbohydrate malabsorption.                 −   Primary bile acid malabsorption
                                                                  −   Enterokinase deficiency
MANIFESTATIONS                                                    −   Acrodermatitis enteropathica

  Diarrhea, vomiting, flatulence, borborygmus, and          2. Secretory tumors
  cramping may be present; however, blood is not            3. Infection
  seen in the stool.
                                                                  −   Enteroadherent E coli
DIAGNOSIS                                                         −   Bacterial overgrowth

  1. Breath hydrogen testing is the most accurate           4. Hirschsprung's enterocolitis
     diagnostic test.                                       5. Immunodeficiency
  2. Stool pH and examination of stool for                  6. Congenital microvillous inclusion disease
     reducing substances (e.g., lactose, glucose,
     fructose) are less helpful in making the               7. Pancreatic insufficiency
     diagnosis, but a stool pH < 5 and the presence               −   Cystic fibrosis
     of reducing substances suggest carbohydrate                  −   Shwachman-Diamond syndrome
     malabsorption.                                               −   Lipase deficiency
  3. Intestinal biopsy with direct assay of brush           8. Iatrogenic
     border enzyme activity.
                                                                  −   Laxatives
TREATMENT                                                         −   Sorbitol

  Therapy is restriction of the offending
  carbohydrate. Lactase and sucrase replacement           MANIFESTATIONS
  enzymes are now commercially available and may
                                                           1. Diarrhea is severe and persists even when the
  be ingested along with lactose or sucrose-
                                                              patient is given NPO (secretory diarrhea).
  containing foods, respectively. If lactose
  restriction is severe and prolonged, calcium             2. Vomiting is common.
  supplementation is needed.
                                                           3. Fluid, electrolyte, and enteric protein losses
                                                              may be excessive, resulting in dehydration,
                                                              acidosis,     hyponatremia,      hypokalemia,
                                                              hypoalbuminemia, and edema.
                                                           4. Severe FTT is evident.

                                                           A systematic approach to diagnose readily
                                                           treatable conditions must be made. This includes:
                                                           A. Culture of stool, urine, and blood.
                                                           B. Stool examination for blood, leukocytes, pH,
                                                              reducing sugars, ova, and parasites.
                                                           C. Assessment of renal and hepatic function.
                                                           D. Sweat test for cystic fibrosis.
                                                           E. Immunologic evaluation.
                                                           F. Small intestinal biopsy and sigmoidoscopy.

 Zyady Pediatrics                                                                   Gastrointestinal Disorders
TREATMENT                                                                  CONSTIPATION
  If the underlying condition permits specific
                                                             Constipation can be defined as a decrease in the
  treatment, that treatment should be given. In most
                                                             frequency or fluidity of bowel movements. Fewer
  cases of idiopathic intractable diarrhea, the
                                                             than three bowel movements per week is considered
  primary treatment is nutritional support.
                                                             abnormal. Most constipated children have no
  1. Central      venous      hyperalimentation     is       underlying disorder, and treatment can be directed
     frequently required and should be instituted            solely at the symptom. Formal evaluation is reserved
     early to reverse the severely catabolic state.          for cases beginning at birth and those that are not
                                                             responsive to standard symptomatic treatment.
  2. Semi-elemental or elemental formulas are
     required when enteric nutrition is initiated.
   CHRONIC NONSPECIFIC DIARRHEA                                A. Functional constipation occurs in the
                                                                  absence of an organic cause. In an otherwise
Chronic nonspecific diarrhea, thought to be a                     healthy child, constipation may result simply
manifestation of IBS, is the most common cause of                 from an episode of painful def            ecation,
chronic diarrhea in otherwise healthy children.                   difficulties during the period of toilet training,
Although the precise pathogenesis is unknown,                     inattention to the urge to defecate because of
alterations in GI motility are thought to be of                   involvement in other activities, or discomfort
primary importance. A number of additional factors                with toilet facilities in school. Frequently, a
have been noted to increase symptoms, including:                  family history of constipation may be elicited.
                                                                  Inadequate fiber in the diet may also play role.
  1.   Chilled foods or fluids
  2.   Excessive fluid intake, especially fruit juices         B. Specific causes
  3.   A low-fat, high-carbohydrate diet                           1. Structural lesions, including anal fissure,
  4.   Stress and anxiety                                             anterior ectopic anus, stenosis of the
                                                                      bowel, inflammatory proctitis, and
MANIFESTATIONS                                                        extrinsic    lesions     causing     bowe l
  It usually manifests between 9 and 36 mo of age.                    obstruction.

  1. Diarrhea is variable in severity and may occur                2. Neuromuscular disorders, such as spinal
     up to six times each day.                                        cord defects, disorders of smooth muscle,
                                                                      and Hirschsprung's disease.
  2. Undigested food (particularly vegetables) and
     mucus are observed in the stools.                             3. Medications,       particularly     opiates,
                                                                      antidepressants, anticholinergic agents.
  3. Abdominal cramping may be present.
                                                                   4. Metabolic          causes,       including
  4. Activity and appetite are usually normal, and                    hypothyroidism,             hypercalcemia,
     growth is generally unaffected.                                  hypokalemia, uremia, pregnancy, and
                                                                      disorders causing dehydration.
                                                                   5. Toxins,     particularly      chronic    lead
  Diagnosis is based on a compatible clinical history                 intoxication.
  and the exclusion of other disorders.
                                                                   6. Infection with Clostridium botulinum in
                                                                      infants (infant botulism).
  Frequently, no treatment other than parental                     7. Psychosocial factors, including sexual
                                                                      abuse and fear of using school bathroom.
  reassurance is needed. Symptoms usually resolve
  spontaneously by 3 to 4 years of age. Specific
  measures that can be of help include:
  1. Decreasing fluid intake, particularly fruit
     juices, and providing high-fat foods to slow
     gastric emptying
  2. h. Increasing fiber intake through the use of
     bulking agents

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                                                           THERAPY FOR FUNCTIONAL CONSTIPATION
                                                             An individualized, multifaceted treatment program
 1. Pattern of defecation. A detailed history of
                                                             should be designed.
    the pattern of defecation may be difficult to
    obtain. Even a history of regular bowel                  1. Medications are continued until a regular
    movements does not exclude constipation if                  pattern of defecation is established, and then
    evacuation is incomplete. In a child who has                they are slowly tapered. In older children,
    large stools, stool-withholding behavior--such              laxation therapy is commonly required for at
    as squatting, pushing, and crying--may be                   least 6 to 12 months and occasionally longer.
    misinterpreted as an attempt to defecate.
                                                                 a- In infants, laxation may be accomplished
 2. Accompanying symptoms include pain,                              by adding apple or pear juice. Extra fiber
    abdominal      distention,    and      u
                                        flat lence.                  in the form of barley malt extracts or
    Occasional symptoms include rectal bleeding,                     methylcellulose may also help. Because
    poor appetite, enuresis, and a history of                        of the risk of pneumonitis if it is
    urinary tract infection. Rectal prolapse may                     aspirated, mineral oil is usually avoided in
    rarely be seen with defecation.                                  children < 12 months of age.
 3. Encopresis. In cases of long         -standing               b- In older children, mineral oil or mild
    constipation,     children    may      become                    laxatives such as senna derivatives are
    incontinent of liquid stool and be thought to                    commonly used.
    have diarrhea. This overflow incontinence is
                                                                 c- In cases of severe constipation, a period
    called encopresis and is present in > 50% of
                                                                     of aggressive treatment including enemas
    children who have long-standing constipation.
                                                                     (otherwise avoided) may be required.
DIAGNOSIS                                                        d- A balanced polythylene glycol-electrolyte
                                                                     solution administered by the oral or
 A. Physical examination of the abdomen may
                                                                     nasogastric route is safe, prompt, and
    reveal distention or palpable fecal masses. The
                                                                     effective in cleansing the bowel and may
    perianal area should be examined for
                                                                     avoid prolonged use of enemas or the
    congenital     or    acquired     abnormalities,                 need for manual disimpaction.
    including trauma. Digital rectal examination is
    necessary to evaluate the sphincter and                  2. Other measures
    estimate the amount of stool in the ampulla.                 a- High-fiber diet and fiber supplements.
 B. When no underlying disorder is identified by                 b- Reinforcement of regular toilet use.
    history and physical examination, a favorable
    response to treatment supports the diagnosis                 c- Psychological evaluation, which may be
    of functional constipation.                                      necessary to address emotional factors
                                                                     resulting in voluntary withholding.
 C. Treatment failure or relapse should prompt
    investigation of an underlying disorder with                 d- Biofeedback training may be beneficial,
    appropriate radiographic and laboratory                          especially in those children who have
    studies.                                                         chronic functional constipation and rectal
                                                                     dyssynergia on anorectal manometry.
     1. A barium enema may help to identify
        underlying      anatomic      causes     of
        constipation (i.e., a transition zone                      HIRSCHSPRUNG'S DISEASE
        consistent with Hirschsprung's disease).           Hirschsprung's      disease is   an    ncommon
     2. Anorectal manometry is used to evaluate            developmental disorder (incidence is 1 in 5000)
        the function of both the internal and              resulting in constipation.
        external anal sphincters. Failure of               The male to female ratio is 3.8:1 and there is no
        relaxation of the internal sphincter on            racial predilection. A family history is present in 7%
        rectal distention suggests Hirschsprung's          of cases and increases to 21% for pancolonic
        disease. Failure to relax the anus during          involvement. Children (3–10%) with Down
        Valsalva's maneuver defines rectal                 syndrome carry added risk for Hirschsprung disease.
                                                           In approximately 80% of patients, the aganglionic
                                                           segment is limited to the rectosigmoid area, but the
                                                           entire colon may be involved.

 Zyady Pediatrics                                                                    Gastrointestinal Disorders
PATHOGENESIS                                                            GASTROINTESTINAL
 Multiple theories are currently under consideration                      HEMORRHAGE
 including: failure of the progenitor cells, which are
 destined to become the ganglion cells of the                 Bleeding from the GIT is a common and,
 submucosal and myenteric plexuses, to complete               potentially, life-threatening condition in infants and
 their distal bowel migration in the colon; failure of        children. Usually, a careful history and physical
 differentiation of progenitor cells; or regression of        examination, as well as consideration of the patient's
 progenitor cells. As a result, the abnormally                age, will suggest the most likely causes. However,
 innervated distal colon remains tonically                    attempts to make a specific diagnosis should occur
 contracted and obstructs the flow of feces.                  only after the patient's cardiovascular status has been
                                                              adequately stabilized.
 1. In most cases, the onset of symptoms occurs
    in the first month, and the diagnosis is made               The diagnostic approach in the patient who has
    in the first 3 mo. The neonate classically has              suspected GI bleeding involves 3 sequential steps.
    delayed passage of meconium and then shows
                                                                A. Did the patient actually bleed?
    evidence of obstruction with poor feeding,
    bilious vomiting, and abdominal distention.                     Food coloring can turn emesis and stools red,
    Bloody diarrhea, sepsis, shock are possible.                    and bismuth and iron may make stools black.
 2. In older child, FTT and persistent abdominal                    Confirmation of the presence of heme protein
    distention may be seen, as well as intermittent                 is accomplished with a guaiac test.
    bouts of intestinal obstruction. Enterocolitis
                                                                B. Did the bleeding originate in the upper or
    with bloody diarrhea may also occur.
                                                                   lower tract?
DIAGNOSIS                                                           Hematemesis suggests a site proximal to the
                                                                    ligament of Treitz. If the picture is unclear,
 A. Rectal examination may reveal a narrowed
                                                                    gastric aspiration should be performed. A
    high-pressure zone in continuity with the
                                                                    gastric aspirate positive for blood is highly
    sphincter, and stool may not be palpable.                       specific for upper tract bleeding. A negative
 B. Plain X-R may show gaseous distention of                        aspirate suggests lower tract bleeding but
    proximal bowel but no gas or feces in rectum.                   cannot exclude an upper tract source that has
                                                                    stopped bleeding or a duodenal lesion with no
 C. Barium enema may demonstrate a transition                       reflux of blood back into the stomach.
    zone between the narrowed abnormal distal
    segment and dilated normal proximal bowel.                  C. What is the specific source of the bleeding?
 D. Anal manometry demonstrates failure of the                      1. Endoscopy is the most sensitive and
    internal anal sphincter to automatically relax                     specific technique to evaluate GI
    with balloon distention of the rectum.                             bleeding.
 E. A rectal biopsy revealing no ganglion cells                          −   Upper enoscopy should be the first
    and hypertrophied nerve trunks is necessary                              test     in   patients    who     have
    for the diagnosis. Staining of these biopsy                              hematemesis or melena. Eighty
    specimens for acetylcholinesterase activity                              percent of UGI bleeding sites can be
    will show prominently stained nerve fibers in                            identified. In addition to identifying
    both the lamina propria mucosae and lamina                               the lesion and documenting the
    muscularis mucosae of the colon.                                         activity of bleeding, endoscopy
                                                                             provides potential therapy, including
TREATMENT                                                                    sclerotherapy and coagulation.
 Initial treatment is usually a diverting colostomy.                     −   Sigmoidoscopy should be the first
 Subsequently, at 6 months or 1 year of age, the                             diagnostic study in patients who have
 aganglionic segment is removed, and remaining                               suspected        colonic         bleeding.
 colon is anastomosed to the anorectal region. In                            Abnormal colonic mucosa will
 older children, the preliminary colostomy may not                           immediately alert the clinician to an
 be required. In patients who have short-segment                             infectious or inflammatory process
 Hirschsprung's disease, an anorectal myomectomy                             (e.g., ulcerative colitis) or possibly
 may provide symptomatic improvement.                                        identify structural lesion (e.g., polyp).

Zyady Pediatrics                                                              Gastrointestinal Disorders
       −   If inspection of the entire colon is
           indicated, colonoscopy may be
           performed.                                       1. Cardiovascular resuscitation.
       −   Intraoperative endoscopy is reserved                a- With massive bleeding, whole blood (or a
           for those patients who continue to                     combination of packed cells and FFP)
           have significant bleeding when                         should be given to maintain intravascular
           extensive endoscopic and radiologic                    volume. Once bleeding has stopped,
           test findings are negative and a small                 packed cells alone may be given.
           bowel source of bleeding is
                                                               b- Vitamin K; platelets; and plasma should
           suspected. In this procedure, a
                                                                  be given as needed to correct any
           laparotomy is performed and the
           bowel is telescoped over the
           endoscope. The cause of obscure                  2. Treatment of upper tract lesions
           small intestinal bleeding can be
                                                               a- Mucosal lesions of the upper tract should
           identified in 80% of patients.
                                                                  be treated with antacids, H2-receptor
   2. Radiologic evaluation                                       antagonists, or proton pump inhibitors.
       −   A plain abdominal X-R may exclude                   b- Esophageal varices may be treated with a
           bowel obstruction.                                     variety of techniques, including:
       −   Barium studies are contraindicated in                   −   Octreotide is a synthetic analogue of
           the actively bleeding child because                         somatostatin that will decrease
           they are usually insensitive and will                       splanchnic blood flow.
           make      other     diagnostic   testing
                                                                   −   Vasopressin infusion decreases portal
           difficult. A barium or air contrast
                                                                       preload pressure and therefore
           enema may be the first diagnostic test
                                                                       decreases variceal blood flow.
           if intussusception is suspected.
                                                                   −   Sclerotherapy    permits      variceal
       −   Bleeding scans, involving injection of
                                                                       obliteration by direct variceal
           Tc 99m pertechnetate-labeled RBCs,
                                                                       injection of a sclerosant solution.
           may detect very slow rates of
                                                                       Endoscopic placement of elastic
           bleeding (0.l cc/min). Tc 99m
                                                                       bands around varices is now
           pertechnetate injected intravenously
                                                                       performed in some pediatric patients.
           may detect ectopic gastric mucosa in
           the case of Meckel's diverticulum.                      −   TIPS is an angiographic technique in
                                                                       which a stent is placed within the
       −   Angiography may be used to detect
                                                                       liver through hepatic parenchyma to
           bleeding sites in more difficult cases
                                                                       connect intrahepatic branches of the
           and requires a higher bleeding rate
                                                                       portal vein and hepatic veins.
           (0.5 cc/min).
                                                                   −   Surgery to decompress the portal
       −   Enteroclysis involves the intubation
                                                                       system can be performed.
           of the jejunum, the gradual
           instillation of barium, air or                   3. Treatment of lower tract lesions depends
           methylcellulose, and evaluation of the              on the cause (e.g., surgery is used for
           mucosal surface of the bowel through                Meckel's diverticulum).
           fluoroscopy. This technique may
           identify the site of small bowel
           bleeding in 5% to 10% of patients.

 Zyady Pediatrics                                                                   Gastrointestinal Disorders

        DISORDERS OF THE ORAL                                  DECIDUOUS AND PRIMARY TEETH
               CAVITY                                       Most infants are born without teeth.
                                                            Natal teeth are present at birth, are usu            ally
  EFFECTS OF SYSTEMIC DISEASE ON                            supernumerary, and may be poorly attached. Usually
         THE ORAL CAVITY                                    no treatment is necessary, but these sometimes need
1. Medications taken for a variety of conditions            to be removed by a dentist if they are causing
   may cause oral abnormalities.                            difficulties with feeding or injuries to the tongue.

    −    Drugs with anticholinergic properties              Next table presents the ages when normal deciduous
         diminish saliva production and increase the        teeth are acquired. The lower central incisors are the
         risk of dental caries.                             first to erupt, followed by the upper central incisors,
    −    Tetracyclines taken before the eruption of         lateral incisors, first molars, and bicuspids. Delayed
         the permanent teeth stain the enamel.              eruption may occur                          i
                                                                                           in associaton with
    −    Excessive fluoride in vitamin preparations         hypopituitarism,      hypothyroidism,    osteopetrosis,
         or in water can result in mottled teeth.           Gaucher disease, Down syndrome, cleidocranial
    −    Gingival hypertrophy may be caused by              dysplasia, and rickets.
         cyclosporine, phenytoin, and CCBs.                 Deciduous teeth begin to be replaced by the
2. GER can lead to enamel erosion and caries.               permanent teeth at around age 6 years. The sequence
                                                            of replacement is similar to that of the appearance of
3. Neonatal hyperbilirubinemia can result in                deciduous teeth.
   bluish black discoloration of deciduous teeth.
4. RF is associated with mottled enamel of the
   permanent teeth.                                                              Primary, Age           Permanent,
5. Congenital       syphilis   causes      marked                                    (mo)                Age (yr)
   abnormalities in the shape of teeth, especially
   incisors and molars.                                                         Upper      Lower       Upper     Lower
6. CD and Behçet are associated with oral ulcers.           Central incisor      6±2         7±2         7-8       6-7
7. Candidiasis    is    seen    commonly        with
   immunodeficiency disorders and diabetes.                 Lateral incisor      9±2         7±2         8-9       7-8
8. Abnormal pigmentation of the lips and buccal             Cuspids              18 ± 2     16 ± 2     11-12       9-10
   mucosa is seen with Peutz-Jeghers syndrome
   and Addison disease.
                                                            1st bicuspids          -           -       10-11      10-12
9. Leukemic infiltrates result in gum hyperplasia
   and bleeding; treatment of neoplastic conditions         2nd bicuspids          -           -       10-12      11-12
   can cause severe mucositis.
                                                            1st molars           14 ± 4     12 ± 4       6-7       6-7
10. Some tumors, including lymphoma, may
    present as mass lesions of the buccal cavity.
                                                            2nd molars           24 ± 4     20 ± 4     12-13      11-13
11. Osteogenesis imperfecta is associated with
    abnormal dentin and risk of caries.                     3rd molars             -           -       17-21      17-21
12. Children   with    ectodermal      dysplasias
    commonly have malformed or missing teeth.
13. Pierre Robin syndrome is associated with
    micrognathia and cleft palate.
14. Disorders resulting in facial dysmorphism
    can have a profound effect on dental occlusion
    and mandibular function. Examples include
    mandibulofacial dysostosis, Crouzon syndrome,
    conditions associated with dwarfism, and others.

 Zyady Pediatrics                                                                Gastrointestinal Disorders

              DENT AL CARIES                                         CLEFT LIP AND PALATE
ETIOLOGY                                                    EPIDEMIOLOGY
 Dental caries, commonly referred to as "cavities,"          Cleft lip and palate occur separately or together
 occur as a result of interactions between the tooth         and affect approximately 1 in 700 infants. It is
 enamel, dietary carbohydrates, and oral flora.              more common in Asians (1 : 500) and least
 There is increased susceptibility if the enamel is          common in Africans (1 : 2500). Clefting occurs
 abnormal or hypoplastic. Bacteria (Streptococcus            with two possible patterns: isolated soft tissue
 mutans) that can adhere to and colonize the teeth,          cleft palate or cleft lip with or without associated
 survive at low pH, and produce acids during                 clefts of the hard palate. Isolated cleft palate is
 fermentation of carbohydrates cause dental caries.          associated with a higher risk of other congenital
                                                             malformations. The combined cleft lip/palate type
 The diet has a significant role. A classic example
                                                             has a male predominance.
 is "bottle mouth," or baby bottle caries. This
 condition results from the practice of allowing an
 infant to have a bottle in the mouth for prolonged
 periods, especially during sleep, and with sweet            1. There is a strong genetic component; the risk
 beverages or milk in the bottle. This practice                 is higher in children with affected first-degree
 allows bacteria to have continuous substrate for               relatives. Monozygotic twins are affected with
 acid production and can result in destruction of               only 60% concordance, suggesting other
 multiple teeth, especially the upper incisors.                 nongenomic factors.
 Sticky sweet foods, such as many candies, also
                                                             2. Environmental factors during gestation also
 offer a mechanism for prolonged presence of
 carbohydrate at the surface of the tooth.                      increase risk, including drugs (phenytoin,
                                                                valproic acid, thalidomide), maternal alcohol
                                                                and tobacco use, dioxins and other herbicides,
                                                                and possibly high altitude.
 Risk of caries is associated with lack of dental
                                                             3. Chromosomal          and     nonchromosomal
 care and poor socioeconomic st tus and    a
                                                                syndromes are associated with clefting as are
 predictably is greatest in developing countries.
                                                                specific genes in some families.
 Treatment of caries is with dental restorative
 surgery. The carious portion is removed and filled         MANIFESTATIONS
 with silver amalgam or plastic. If the damage is
                                                             Cleft lip can be UL or BL and associated with
 severe, a protective crown may be required;
                                                             cleft palate and defects of the alveolar ridge and
 extraction of the tooth may be necessary when not
 salvageable.                                                dentition. When present, palatal defects allow
                                                             direct communication between the nasal and oral
                                                             cavities, creating problems with speech and
                                                             swallowing. Feeding is a significant problem.
 1. Avoiding inappropriate use of bottles and
    excessive sweets is a commonsense remedy                TREATMENT
    for baby bottle caries.
                                                             Management includes squeeze-bottle feedings,
 2. Oral hygiene offers some protection, but                 special nipples, nipples with attached shields to
    young children (<8 years old) do not have the            seal the palate, and gastrostomy in severe cases.
    ability to brush their own teeth adequately;
                                                             Surgical closure of the cleft lip is usually done by
    brushing should be done by the parents.
                                                             3 months of age. Closure of the palate follows,
 3. Fluoride supplementation of water supplies to            usually before 1 year of age. Missing teeth are
    a concentration of 1 ppm is highly effective in          replaced by prostheses. Cosmetic results are often
    reducing dental caries. Excessive fluoride               good, but depend on the severity of the defect.
    supplementation causes fluorosis, a largely
    cosmetic defect of chalky white marks and               COMPLICATIONS
    brown staining of the teeth.
                                                             Speech is nasal as a result of the cleft palate.
                                                             Surgical treatment is effective, but sometimes
                                                             does not restore palatal function completely.
                                                             Speech therapy may help. Frequent episodes of
                                                             otitis media are common, as are defects of teeth
                                                             and the alveolar ridge.

 Zyady Pediatrics                                                                  Gastrointestinal Disorders

DISORDERS OF THE ESOPHAGUS                                        Complication                   Symptom

     GASTROESOPHAGEAL REFLUX                                     1- Peptic            Heartburn, excessive crying,
                                                                    esophagitis       dysphagia, failure to thrive,
GER is a common disorder encountered in pediatric                                     hematemesis, anemia,
practice. Some degree of gastroesophageal reflux
occurs in the majority of infants; this "physiologic"            2- Esophageal        Dysphagia,       vomiting        of
GER is considered a developmental variation in GI                   stricture         undigested food, drooling
motility that resolves as the infant matures. All
pediatricians and parents have witnessed the                     3- Barrett's         Similar to esophagitis or stricture,
regurgitation of small amounts of formula by healthy                esophagus         can lead to adenocarcinoma of
babies after feedings.                                              (metaplastic      esophagus
                                                                 4- FTT               Anorexia, excessive vomiting
  1. Low resting tone of the LES is associated
     with reflux. However, LES pressure is normal
                                                                 5- Aspiration        Apnea,       cyanosis,    choking,
     in the majority of patients who have GER.
                                                                                      laryngitis, pneumonia
     Transient relaxation of the LES has been
     shown to be the most important factor
                                                                 6- Broncho-          Cough,       nocturnal      cough,
     allowing GER.                                                                    wheezing
  2. Delayed gastric emptying (found in a
     subgroup of GER patients)                                   7- Rumination        Gagging, mouthing, reswallowing
  3. Impaired esophageal motility (decreased
     esophageal clearance of refluxate)                      DIAGNOSIS
  4. Gastric distention and increased intragastric            The diagnosis of GER is based on the history,
     or intra-abdominal pressure                              physical examination, and exclusion of anatomic
  5. Loss of extrinsic mechanical factors at the              abnormalities that may predispose to the clinical
     LES, including the crural diaphragm and the              features of reflux. The following tests are
     cardioesophageal angle of His (oblique angle             necessary only when the diagnosis is in doubt.
     of esophagus as it enters the stomach)                   A. Barium swallow is the best test for
  6. Underlying diseases or conditions associated                eliminating other anatomic causes of
     with gastroesophageal reflux include:                       vomiting, but high false-positive and false-
                                                                 negative rates limit its usefulness as a
      −   Progressive       systemic      sclerosis              diagnostic tool for GER.
      −   Mixed connective tissue disease                     B. Overnight esophageal pH monitoring is the
      −   Cystic fibrosis                                        "gold standard" for assessing. This study is
      −   Neuromuscular disease (cerebral palsy,                 most useful when trying to ass        ociate
          myopathy)                                              symptoms with GER (chronic cough, apnea).
      −   Tracheoesophageal fistula                           C. Radionuclide scans evaluate GER by adding
                                                                 technetium 99m to formula or a meal and
MANIFESTATIONS                                                   scanning the stomach to measure gastric
  1. Vomiting may occur immediately or hours                     emptying. Subsequent scanning of the lung
     after a feeding. The vomiting is usually                    fields can be useful in demonstrating reflux
     effortless and painless, consisting of small                with aspiration.
     amounts of curdled formula.                              D. Esophageal manometry is used to measure
      In the older child, a tendency to vomit easily,            resting LES pressure in addition to esophageal
      heartburn, dysphagia, halitosis, and loss of               motility, which makes this rnodality useful to
      dental enamel may occur.                                   diagnose motility problems such as achalasia.
      The vomiting is always nonbilious and rarely            E. Endoscopy is useful to visualize the
      contains blood.                                            esophageal mucosa, and biopsy allows
                                                                 histologic confirmation of esophagitis, even if
  2. Complications. Persistent GER can lead to a                 the mucosa appears grossly normal. Biopsies
     number of complications.                                    of the stomach and duodenum screen for other
                                                                 disease such as H pylori and allergy.
 Zyady Pediatrics                                                                  Gastrointestinal Disorders
TREATMENT                                                    PHARMACOLOGIC THERAPY FOR GER
 1. Conservative therapy. Most infants who
    have "benign" GER can be treated                               Class                     Mechanism
    conservatively with simple measures while
    awaiting maturation of UGI motility.                      Antacid             Neutralizes gastric acid

     a- Positioning: Infant seats and similar                 H2-receptor         Blocks histamine receptor
        devices have been shown to increase GER               antagonists
        by increasing intra-abdominal pressure.                                   on parietal cell
        For sleep, infants should be placed on
        their side; elevating the head of the bed             Proton     pump Blocks H+-K*-ATPase             pump in
        20 degrees may decrease reflux.                       inhibitors      parietal cell membrane
     b- Dietary changes                                       Prokinetic          Increases LES       tone,   promotes
         1. Size and frequency of meals         :             agents              gastric emptying
            Frequent, smaller feedings of formula
            thickened with 1-2 tsp/oz of cereal
            may aid infants who have GER.                                      ACHALASIA
         2. Fatty foods, chocolate, caffeine-                Primary disorders of esophageal motility (other than
            containing liquids, and NSAIDs may               those contributing to GER) are rare. The most
            aggravate reflux and should be                   common of these is achalasia, which is a disorder of
            avoided.                                         unknown cause characterized by a hypertonic LES
         3. Empiric infant formula changes                   that fails to relax adequately with swallowing.
            should be discouraged as they may
            lead to false impressions of food                MANIFESTATIONS
            allergy. Cow's milk and soy protein                Most children are > 5 years of age at the time of
            allergy are distinct entities (often with          presentation, although the disorder has been
            associated symptoms such as diarrhea               reported in infants.
            and poor weight gain, and a history or
            family history of atopy). If suspected,            1. Dysphagia for both solid and liquid foods is
            then a reasonable trial with a protein-               the cardinal symptom.
            hydrolysate formula may be tried to                2. Other symptoms include regurgitation of
            see if symptoms improve. If not,                      undigested food, weight loss, substernal pain,
            regular formula should be restarted.                  and respiratory symptoms such as nocturnal
 2. Medication. Drug therapy should be reserved                   cough due to aspiration.
    for   patients  who    have     complicated,
    symptomatic GER (Table).                                 DIAGNOSIS

 3. Surgery is indicated for patients who have                 A. Barium swallow demonstrates a widened,
    failed medical therapy, patients who have life-               tortuous esophagus with a narrowed distal
    threatening     or      severely      debiliating
                                               t                  "beak." Sometimes, even on plain radiograph,
    complications, and selected patients who have                 an air-fluid level in esophagus may be seen.
    esophageal stricture or Barrett's esophagus.               B. Esophageal manometry is necessary to
     Procedure. Surgical procedures are designed                  document lack of peristalsis, an abnormally
     to re-establish competence of the lower                      high LES pressure, and incomplete LES
     esophageal junction. The most commonly                       relaxation with swallowing.
     used procedure is the Nissen fundoplication,              C. Endoscopy is used to exclude other causes of
     during which part of the gastric fundus is                   distal esophageal disease.
     wrapped around the distal esophagus to create
     a high-pressure zone to resist GER.                     TREATMENT
                                                               Although medical therapy (i.e., CCBs) may
                                                               occasionally improve symptoms, disruption of the
                                                               LES by pneumatic dilatation or surgery (Heller's
                                                               myotomy) is usually required. Endoscopy and
                                                               injection of the LES with botulinum toxin to
                                                               paralyze the muscle is undergoing trials.

 Zyady Pediatrics                                                               Gastrointestinal Disorders
     STRUCTURAL ABNORMALITIES                                           FOREIGN BODIES
1. Tracheoesophageal fistula (see neonatology)
2. Congenital strictures usually occur at the
                                                            Young children often place nonfood items in their
   junction of the middle and distal thirds of the
                                                            mouths. When these items are swallowed, they
   esophagus and result in dysphagia. This lesion
                                                            may become lodged in the upper esophagus at the
   must be differentiated from the more common
                                                            thoracic inlet. The most common objects are
   peptic stricture due to GER or caustic
   ingestions. Congenital webs have a similar               coins. Smaller coins may pass harmlessly into the
   presentation. Diagnosis is made by barium                stomach, where they rarely cause symptoms.
   studies and endoscopy; treatment involves                Children with a prior history of esophageal atresia
   dilatation and, if necessary, surgery.                   or with poor motility secondary to GER are more
                                                            prone to food impactions, which seldom occur in
             CAUSTIC AGENTS                                 the normal esophagus.

Strong alkali solutions (e.g., lye) used as drain          MANIFESTATIONS
cleaners are most dangerous. Less damaging are
ammonia cleaning solutions, bleaches, and                   Some children are asymptomatic, but most exhibit
dishwasher detergents. Acids tend to cause more             some degree of drooling, food refusal, or chest
damage to the stomach than to the esophagus. The            discomfort. Older children usually can point to the
absence of oral burns or dysphagia does not predict         region of the chest where they feel the object to be
the presence or degree of esophageal damage from            lodged.
ingestion of caustic agents.                                Respiratory symptoms tend to be minimal, but
                                                            cough may be present, especially when the
MANIFESTATIONS                                              esophagus is completely blocked by a large object,
  1. Acute. There may be burns of the hands, face,          such as a piece of meat, which presses on the
     oral cavity; local pain; drooling; dysphagia,          trachea.
     stridor, or dyspnea; abdominal and chest pain;
     and shock if there is mediastinal penetration.        DIAGNOSIS
  2. Chronic. Stricture formation may develop 2-4           Plain chest and abdominal radiographs should be
     weeks after ingestion and cause dysphagia.             taken when foreign body ingestion is suspected.
                                                            Metallic objects are easily visualized. A plastic
DIAGNOSIS                                                   object often can be seen if the child is given a
                                                            small amount of dilute x-ray contrast material to
  A. CXR: can detect evidence of perforation and            drink, although endoscopy is probably safer and
     mediastinitis.                                         more definitive.
  B. Endoscopy should be performed within 24
     hours under general anesthesia to document            TREATMENT
     esophagitis or gastritis.                              Endoscopy is ultimately necessary in most cases
  C. Barium swallow can be performed 1-2 weeks              to remove an esophageal foreign body.
     after ingestion and sequentially thereafter to         Whenever objects that may threaten the airway are
     detect and note progression of stricture.              being recovered, endoscopy should be performed
                                                            with endotracheal intubation and under general
TREATMENT                                                   anesthesia.
  No attempt should be made to induce vomiting or
  to neutralize the caustic agent. The use of              COMPLICATIONS
  corticosteroids to prevent stricture has not been         Sharp objects may lacerate or perforate the
  proved to be efficacious. These agents are                esophagus; smooth objects present for a long time
  contraindicated if there has been perforation.            also may result in perforation. Corrosive objects,
  1. IVFs are necessary. The cardiorespiratory              such as zinc-containing pennies and disc batteries,
     status should be monitored carefully.                  can cause considerable local tissue injury and
                                                            esophageal perforation.
  2. Antibiotics may be administered, particularly
     if there is suspicion of perforation.
  3. Repetitive esophageal dilatation or      even
     reconstructive surgery may be needed.

 Zyady Pediatrics                                                                    Gastrointestinal Disorders

  DISORDERS OF THE STOM ACH                                                       GASTRITIS
                                                              H. pylori is strongly associated with gastritis and
             PYLORIC STENOSIS                                 PUD in both adults and children. Other causes of
                                                              gastritis include allergies, aspirin, alcohol, NSAIDs,
Pyloric stenosis is an acquired condition caused by
                                                              ingestion of corrosive agents, vasculitis, Crohn's
hypertrophy and spasm of the pyloric muscle,
                                                              disease, eosinophilic gastritis, viral infection,
resulting in gastric outlet obstruction. Pyloric
                                                              Menetrier's disease, bile reflux, and irradiation.
stenosis is an important cause of gastric outlet
obstruction in approximately 1 in every 500 infants.
It frequently affects more than one child in a family,
with a male-to-female ratio of 5:1.                             Clinical features include abdominal pain and
                                                                tenderness (usually epigastric), nausea, vomiting,
MANIFESTATIONS                                                  and, occasionally, overt bleeding.
  Symptoms usually begin between 2 and 4 weeks
  of age, although in 5% of patients they are present
  shortly after birth.                                          Diagnosis of gastritis may be difficult because a
                                                                barium study of the stomach is usually
  1. Projectile nonbilious vomiting is the
                                                                unrevealing in this disorder. If the clinical picture
     cardinal feature. The vomited material never
                                                                warrants investigation (i.e., if there is severe pain,
     contains bile because gastric outlet obstruction
                                                                bleeding, or persistent vomiting), endoscopy can
     is proximal to the duodenum. This feature
                                                                be performed. Antral gastritis with nodularity is
     differentiates pyloric stenosis from most other
                                                                frequently seen with H. pylori infection.
     obstructive lesions of early childhood.
                                                                A. Rapid urease test on biopsy tissue can be
  2. Constipation and poor weight gain may be
                                                                   performed to identify H. pylori
     observed when the diagnosis is delayed.
                                                                B. Serologic studies may also reveal exposure to
  3. Although metabolic alkalosis is commonly
                                                                   H. pylori.
     seen secondary to the persistent vomiting,
     normal serum electrolyte levels never exclude              C. Carbon 13-labeled urea breath test is being
     a diagnosis of pyloric stenosis.                              used in some centers for the diagnosis of
                                                                   active H. pylori infection in children.
  A. Palpation of a firm, mobile, nontender, olive-
     shaped mass in the right hypochondrium or                  1. If the gastritis is secondary to ingestion of
     epigastrium in the appropriate clinical setting               aspirin or another drug, that medication
     confirms the diagnosis.                                       should be discontinued and a brief (1- to 2-
                                                                   week) course of antacids or an H 2-receptor
  B. Visible peristaltic waves traveling from left to
                                                                   blocker should be initiated.
     right across the abdomen may be seen.
                                                                2. If H. pylori is identified, treatment with a
  C. If a pyloric mass cannot be palpated, US
                                                                   combination of a proton pump inhibitor and
     evaluation should be performed.
                                                                   two antiobiotics (e.g., amoxicillin and
  D. Barium upper GI series also may be obtained                   clarithromycin) for 2 weeks should be given
     whenever doubt about the diagnosis exists;                    when a peptic ulcer has been documented
     this shows a "string sign" caused by barium                   endoscopically. In the absence of ulcers,
     moving through an elongated, constricted                      treatment for H. pylori should be considered
     pyloric channel                                               on an individual basis.
                                                                3. If significant idiopathic gastritis is found
                                                                   grossly or on biopsy, a minimum 6-week
  Treatment includes IV fluid and electrolyte                      course of an H2-receptor blocker is indicated.
  resuscitation     followed        by          i
  pyloromyotomy. Before surgery, dehydration and
  hypochloremic alkalosis must be corrected.
  For pyloromyotomy, a small incision is made,
  usually directly over the pylorus or at the
  umbilicus, and the pyloric muscle is incised
  longitudinally to release the constriction. Care is
  taken not to cut into the mucosa itself.
 Zyady Pediatrics                                                                   Gastrointestinal Disorders
          PEPTIC ULCER DISEASE                                 TREATMENT
In children < 6 years of age, ulcers are found with             If the ulcer is thought to be secondary to an
equal frequency in boys and girls; a gastric location           underlying illness, the predisposing factors must
is as common as a duodenal one; and a precipitating             be addressed. The management of the ulcer itself
event (e.g., drugs, stress) is common. In children > 6          has historically been directed against gastric acid,
years of age, ulcers are most frequently found in               either through neutralization (via antacids) or
boys and are more common in the duodenum.                       suppression of secretion (via H2-receptor
                                                                blockers). The goal of either modality is the
RISK FACTORS                                                    maintenance of gastric pH at or above 5.
                                                                Sucralfate can be beneficial by binding to
  1. Helicobacter pylori infection                              ulcerated areas and possibly having cytoprotective
  2. Drugs                                                      effects. Documented H. pylori infection should be
     − NSAIDs, including aspirin                                treated as discussed previously.
     − Tobacco use
     − Potassium supplements                                       Medications
  3. Family history                                                 1. Antacids. In the acutely ill patient,
  4. Sepsis                                                            antacids can be administered at a dose of
  5. Head trauma                                                       0.5 mL/kg every 1-2 hours.
  6. Burn injury
  7. Hypotension                                                    2. H2-receptor blockers. Ranitidine (2-3
                                                                       mg/kg every 12 hours orally, 1-1.5 mg/kg
MANIFESTATIONS                                                         every 12 hours iv) and cimetidine (10
                                                                       mg/kg every 6 hours orally or iv) have
  1. In neonates, bleeding and perforation from a                      been used in the pediatric population.
     gastric ulcer are usually the first indications                   Because ranitidine does not inhibit the
     that an ulcer is present. These infants usually                   cytochrome P-450 hepatic enzyme system
     have other underlying problems, such as                           as does cimetidine, its use may be
     sepsis or respiratory distress. Rarely, peptic                    preferred when additional medications are
     ulceration may be observed in otherwise                           being used.
     healthy-appearing neonates.
                                                                   Duration of therapy. A minimum 6-week
  2. Older infants and toddlers frequently vomit                    course of therapy is recommended. Thirty to
     and eat poorly. Bleeding is also common and                    fifty percent of children who have primary
     is seen with equal frequency in primary                        peptic ulcers suffer at least one recurrence.
     (idiopathic) and secondary (e.g., stress) ulcers.              The recurrence rate is especially high in
  3. In older children, pain becomes a more                         adolescents.
     important feature and may persist for some                    Dietary       restrictions       probably    are
     time before the child receives medical                         unnecessary,       although      elimination  of
     attention. Although many patients have                         substances that increase gastric acid secretion
     "classic" ulcer pain relieved by eating, it is not             (e.g., alcohol, caffeine) is advisable.
     uncommon for some children to claim that
     eating makes their pain worse. Nocturnal
     awakening may be present. Either overt or
     occult bleeding is seen in approximately half
     of school-age children who have ulcer disease.

  Endoscopic evaluation of the upper GIT is
  preferred because of its superior sensitivity in
  detecting pathology compared with contrast
  radiography. Endoscopy also allows for tissue
  biopsy and evaluation of patterns of inflammation
  (e.g., allergic versus peptic) and possible infection
  (e.g., H. pylorl).

 Zyady Pediatrics                                                                   Gastrointestinal Disorders

      INFLAMMATORY BOWEL                                       3. Symptoms can be subtle in CD. Small bowel
                                                                  involvement in CD is associated with loss of
          DISEASE (IBD)                                           appetite, crampy postprandial pain, poor
                                                                  growth, delayed puberty, anemia. Severe CD
EPIDEMIOLOGY                                                      may cause partial or complete small bowel
                                                                  obstruction. Perineal abnormalities, including
 The peak incidence of IBD in children is in the                  skin tags and fistulas, are another feature
 second decade of life. The incidence of IBD is                   distinguishing     CD     from    UC.       Oth er
 increasing, especially in industrialized countries,              extraintestinal manifestations of CD include
 for reasons that are unclear. IBD is uncommon in                 arthritis, erythema nodosum, uveitis or iritis.
 tropical and Third World countries.
                                                              LABORATORY AND IMAGING STUDIES
                                                               A. Blood tests should include CBC, ESR, and
 1. Genetic factors play a role in susceptibility:                CRP and possibly serologic tests for IBD
     −   Significantly higher risk if there is a                  (Table 129-2). Anemia and elevated platelet
         family history of IBD. Having a first-                   counts are typical.
         degree relative with IBD increases the                B. Testing for abnormal serum antibodies can
         risk about 30-fold.                                      be helpful in diagnosing IBD and in
     −   Susceptibility has been linked to some                   discriminating between the colitis of CD and
         HLA subtypes, and linkage analysis has                   UC. Because there is overlap between CD and
         identified multiple other susceptibility                 UC, none of these tests can discriminate
         loci on several chromosomes.                             absolutely between the two conditions.
     −   It is more common in Jewish than in other                 1. Atypical     perinuclear  staining    by
         ethnic populations.                                          antineutrophil cytoplasmic antibody is
                                                                      found in about 66% of UC patients and in
 2. Environmental factors also seem to play a                         only a few CD cases.
    role because there is often nonconcordance
    among monozygotic twins. The environmental                     2. Anti-Saccharomyces cerevisiae antibody
    agents responsible have not been identified. It                   is present in most CD patients and is
    is possible that viral infections can initiate the                uncommon in UC. Another IBD-specific
    inflammatory process. Dietary triggers are                        antibody is anti-OmpC, directed against
    unproven. Smoking doubles the risk of CD                          an E coli membrane protein.
    and halves the risk for UC.                                C. Imaging
MANIFESTATIONS                                                     1. Upper GI series with small bowel
                                                                      follow-through is needed to detect small
 Clinical manifestations depend on the region of                      bowel involvement.
 involvement. UC involves only the colon, whereas
 CD can include the entire gut from mouth to anus.                 2. Upper endoscopy cannot evaluate the
                                                                      jejunum and ileum, but is more sensitive
 1. Colitis from either condition results in                          than contrast studies in identifying
    diarrhea, blood, and mucus in the stool;                          proximal CD involvement.
    urgency; and tenesmus, a sensation of
    incomplete emptying after defecation. When                     3. Colonoscopy is preferred over contrast
    colitis is severe, the child often awakens from                   enema because biopsy specimens can be
    sleep to pass stool. Toxic megacolon is a life-                   obtained and because visual features can
    threatening complication characterized by                         be diagnostic.
    fever, abdominal distention and pain,                              Findings in UC include diffuse carpeting
    massively dilated colon, anemia, and low                           of distal or entire colon with tiny ulcers
    serum albumin owing to fecal protein losses.                       and loss of haustral folds. Within the
 2. Extraintestinal manifestations of UC occur                         involved segment, no skip areas.
    in a few patients and may include primary                          In CD, ulcerations tend to be much larger
    sclerosing cholangitis, arthritis, uveitis, and                    with a linear, branching, or aphthous
    pyoderma gangrenosum.                                              appearance; skip areas are present.
                                                                   4. The capsule endoscope, a swallowed
                                                                      device that can visualize the entire small
                                                                      bowel, is potentially useful to visualize
                                                                      subtle small bowel disease.
 Zyady Pediatrics                                                                Gastrointestinal Disorders

                                              Ulcerative Colitis                 Crohn's Disease

   Location                              −    Colon only                     −   Mouth to anus
                                         −    Proctitis                      −   60% ileocolonic
                                         −    Left sided                     −   30% Small bowel
                                         −    Pancolitis                     −   10% Colonic

   Histology                             −    Mucosal inflammation           −   Transmural inflammation
                                         −    Diffuse involvement            −   Skip areas
                                         −    Crypt abscesses                −   Aphthoid lesions
                                         −    Crypt distortion               −   Granuloma

   Clinical features
     1.   Rectal bleeding                −    Usual                          −   Sometimes
     2.   Abdominal mass                 −    Rare                           −   Common
     3.   Perianal disease               −    Rare                           −   Common
     4.   Ileal involvement              −    None                           −   Common
     5.   Strictures                     −    Unusual                        −   Common
     6.   Fistula                        −    Very rare                      −   Common
     7.   Risk of cancer                 −    Greatly increased              −   Increased

   Extraintestinal manifestations (%)
     1.   Osteopenia at onset            −    No                             −   Common
     2.   Nephrolithiasis                −    No                             −   Common
     3.   Uveitis                        −    Less common                    −   Common
     4.   Arthritis                      −    Less common                    −   Common
     5.   Erythema nodosum               −    Less common                    −   Common
     6.   Autoimmune hepatitis           −    Common                         −   Rare
     7.   Sclerosing cholangitis         −    Common                         −   Rare
     8.   Venous thrombosis              −    Common                         −   Less common

TREATMENT                                                   B. Crohn Disease
 A. Ulcerative Colitis                                            1. Inflammation in CD typically responds
                                                                     less well to aminosalicylates; oral or IV
    1. Aminosalicylate       drugs deliver 5-                        steroids are more important in inducing
       aminosalicylic acid (5-ASA) to distal gut.                    remission.
       Because it is rapidly absorbed, pure 5-
       ASA must be specially packaged in                          2. To avoid the need for repetitive steroid
       coated capsules or pills or taken as a                        therapy, immunosuppressive        drugs,
       suppository to be effective in the colon.                     usually either azathioprine or 6-
       Other aminosalicylates (sulfasalazine,                        mercaptopurine, are started soon after
       olsalazine, and balsalazide) use 5-ASA                        diagnosis.
       covalently linked to a carrier molecule.                   3. CD that is difficult to control also may be
    2. When aminosalicylates alone cannot                            treated with methotrexate or with agents
       control the disease, steroid therapy may                      that block the action of tumor necrosis
       be required to induce remission.                              factor-α. Infliximab is the most effective
                                                                     such drug; thalidomide also blocks tumor
    3. An immunosuppressive drug, such as 6-
                                                                     necrosis factor action, but its use must be
       mercaptopurine or azathioprine, is useful                     supervised because of teratogenicity.
       to spare excessive steroid use. More
       potent immunosuppressives, such as                         4. As with UC, surgery is sometimes
       cyclosporine, are under investigation.                        necessary, usually because of obstructive
                                                                     symptoms, abscess, or severe, unremitting
    4. Surgical colectomy with ileoanal                              symptoms. Because surgery is n         ot
       anastomosis is an option for unresponsive
                                                                     curative in CD, its use must be limited,
       severe disease or electively to end chronic                   and the length of bowel resection must be
       symptoms and to reduce risk of cancer.                        minimized.
 Zyady Pediatrics                                                                 Gastrointestinal Disorders

            LIVER DISEASE                                    NEONAT AL OBSTRUCTIVE JAUNDICE
GENERAL PRINCIPLES                                          Direct hyperbilirubinemia in the neonate is never
                                                            logic," and therefore should always be investigated.
 Certain unique of aspects liver disease in infancy         Direct hyperbilirubinemia is defined as a direct
 and childhood must be considered before specific           bilirubin > 2 mg/dL or > 20% of the total bilirubin.
 hepatic disorders can be evaluated.
    Estimation of liver size. In healthy children <        ETIOLOGY
     2 years of age, both the liver and spleen are            Direct hyperbilirubinemia in the neonate is a
     usually palpable below the costal margins due            medical emergency and must be expeditiously
     to the relatively large size of these organs at          investigated to avoid permanent liver damage. The
     this age. In older children, standards have              key distinction in the neonatal period is between
     been established for liver span as measured by           intrahepatic and extrahepatic causes. Extrahepatic
     percussion in the midclavicular line.                    causes require prompt surgical therapy to relieve
    Reaction to hepatic injury in infancy.                   obstruction and reconstitute bile flow from liver.
     Jaundice is the most important manifestation             A. Exlrahepalic Causes
     of a variety of hepatic insults in infancy.
     Hypoglycemia occurs early in the course of                   1.   Biliary atresia
     hepatic injury.                                              2.   Choledochal cyst
                                                                  3.   Common duct stenosis, stone
    Key elements of the history                                  4.   Obstructing tumor
     1. The family history is important in the                    5.   Bile/mucus plug
        consideration of metabolic liver disease.                 6.   Spontaneous perforation of common duct

     2. Illness or exposure during pregnancy may              B. Intrahepatic Causes
        suggest a vertically transmitted (i.e., from              1. Infeclious
        mother to infant) infectious cause of
        hepatitis.                                                     −   TORCH
                                                                       −   Coxsackie, Echovirus, EBV, HBV
     3. A dietary history is crucial in the                            −   Syphilis
        diagnosis of hepatic disease resulting                         −   UTI
        from the failure to metabolize galactose
        or fructose.                                              2. Metabolic
                                                                       −   Galactosemia
    Diagnostic       tests.    Increased     serum
     transaminase levels reflect hepatocyte injury,                    −   Hereditary fructose intolerance
     not liver function. Blood glucose and albumin                     −   Cystic fibrosis
                                                                       −   α l-antitrypsin deficiency
     levels as well as prothrombin time are indirect
                                                                       −   Niemann-Pick disease
     measures of function. The serum ALP level is
     usually elevated in children who have                             −   Gaucher's disease
                                                                       −   Glycogen storage disease
     obstructive or inflammatory hepatic lesions.
     However, in infancy and adolescence, serum                   3. Miscellaneous
     alkaline phosphatase levels from bone are
                                                                       −   Neonatal hepatitis
     normally elevated compared to adult values.
                                                                       −   AlagiIle syndrome
     Thus other enzymes, such as "γ-glutamyl
                                                                       −   Byler disease
     transpeptidase, GGT), which is liver specific,
     are more useful.                                                  −   ZeIIweger syndrome
                                                                       −   Trisomy (17, 18, 21 )
                                                                       −   Hypopituitarism
                                                                       −   Hepatic hemangiomatosis
                                                                       −   TPN-induced cholestasis

 Zyady Pediatrics                                                                  Gastrointestinal Disorders
 A. Tests for specific causes of cholestasis
                                                              Cholestasis is caused by many different disorders,
     1. Serum level tests, including total and                the common characteristic of which is cholestatic
        direct bilirubin; aminotransferases and               jaundice. Clinical features of several of the most
        GGT; CBC; titers of toxoplasmosis,                    common causes are given.
        rubella, CMV, and HSV; VDRL; HbsAg;
                                                              The jaundice of extrahepatic biliary atresia
        α l-antitrypsin level and phenotyping;
                                                              (biliary atresia) usually is not evident immediately
        amino acids; blood culture (if clinically
                                                              at birth, but develops in the first week or two of
        indicated); albumin; PT; and PTT.
                                                              life. The reason is that extrahepatic bile ducts are
     2. Urine tests, including urinalysis, urine              usually present at birth, but are then destroyed by
        culture, and organic and amino acids                  an idiopathic inflammatory process. Aside from
                                                              jaundice, these infants do not initially appear ill.
     3. Sweat test
                                                              The liver injury progresses rapidly to cirrhosis;
     4. Abdominal US to rule out a choledochal                symptoms       of     portal      hypertension  with
        cyst or common duct stone                             splenomegaly, ascites, muscle wasting, and poor
                                                              weight gain are evident by a few months of age. If
     5. Radionuclide   biliary imaging to
                                                              surgical drainage is not performed successfully
        document patency of the extrahepatic
                                                              early in the course (ideally by 2 months),
        biliary system
                                                              progression to liver failure is inevitable.
     6. Liver biopsy
                                                              Neonatal hepatitis is characterized by an ill-
 B. Differentiation   of     intrahepatic        and          appearing infant with an enlarged liver and
    extrahepatic idiopathic causes.                           jaundice. There is no specific diagnostic test, but if
                                                              liver biopsy is performed, the presence of
     1. Often, the tests for neonatal cholestasis
                                                              hepatocyte giant cells is characteristic. CMV and
        reveal no specific cause. However,
                                                              syphilis must be ruled out. He           patobiliary
        neonatal hepatitis and biliary atresia are
                                                              scintigraphy typically shows slow hepatic uptake
        the most common causes of persistent
                                                              with eventual excretion of isotope into the
        direct jaundice. No serum test (including
                                                              intestine. These infants have a good prognosis
        aminotransferases, GGT, bilirubin, α-
                                                              overall, with spontaneous resolution occurring in
        fetoprotein)       reliably     distinguishes
        between these two entities. Further testing
        is directed at differentiating between these          α1-Antitrypsin deficiency presents with clinical
        two entities, including percutaneous liver            findings indistinguishable from neonatal hepatitis.
        biopsy, which can reliably differentiate              Only 20% of all infants with the genetic defect
        more than 90% of the time.                            exhibit neonatal cholestasis. Of these affected
                                                              infants, about 30% go on to have severe chronic
     2. Ultimately, it may be necessary to
                                                              liver disease resulting in cirrhosis and liver failure.
        perform a laparotomy and intraoperative
                                                              α1-Antitrypsin deficiency is the leading metabolic
        cholangiography to accurately delineate
                                                              disorder requiring liver transplantation.
        the presence or absence of the
        extrahepatic biliary system. Transhepatic             Alagille syndrome is characterized by chronic
        cholangiograms or ERCP for neonates is                cholestasis with the unique liver biopsy finding of
        available in some centers.                            paucity of bile ducts in the p         ortal triads.
                                                              Associated abnormalities in some (syndromic)
                                                              types include peripheral pulmonic stenosis or
                                                              other cardiac anomalies; hypertelorism; unusual
                                                              facies with deep-set eyes, prominent forehead, and
                                                              a pointed chin; butterfly vertebrae; and a defect of
                                                              the limbus (posterior embryotoxon). Cholestasis is
                                                              variable but is usually lifelong and associated with
                                                              hypercholesterolemia       and    severe    pruritus.
                                                              Progression to end-stage liver disease is
                                                              uncommon. Liver transplantation sometimes is
                                                              performed electively to relieve severe and
                                                              uncontrollable pruritus.

 Zyady Pediatrics                                                                 Gastrointestinal Disorders
 A. Neonatal hepatitis. The treatment for
    neonatal hepatitis and other causes of                     Neonatal hepatitis
    prolonged      intrahepatic cholestasis is                  In most patients, the cholestasis resolves over
    supportive, including:                                      the first year of life with no sequelae.
    1. Administration of ursodeoxycholic acid, a                A few infants develop progressive liver
       secondary bile acid, to increase bile flow               disease and cirrhosis, with its complication of
       and reduce hypercholesterolemia.                         ascites, portal hypertension, esophageal
                                                                varices, and liver failure. These children may
    2. Supplementation of fat-soluble vitamins
       (A, D, E, K).                                            be candidates for liver transplantation.

    3. Supplementation of the diet with medium-                Biliary atresia
       chain triglycerides that do not require bile             Without surgical correction, biliary cirrhosis
       acids for assimilation.                                  and its complications supervene, and most
    4. Use of cholestyramine, a bile acid-                      patients die in the first 2 years of life.
       binding resin, and antihistamines to treat               After successful portoenterostomy and with
       pruritus.                                                normalization of serum bilirubin levels, the 5-
 B. Biliary atresia                                             year survival rate is 60-90%. Patients may
                                                                continue to do well, but many eventually
    1. Surgical management. In most patients,                   develop cirrhosis, especially if the course
       a portoenterostomy must be created                       includes recurrent cholangitis.
       between the cut surface of the liver at the
       porta hepatis and the bowel (Kasai                       Liver transplantation is available for patients
       procedure). Successful drainage of the                   with biliary atresia who fail corrective
       biliary tract occurs most frequently when                surgery. The 5-year survival rate for liver
       the operation is performed before the                    transplantation recipients who have biliary
       infant is 60 days old. Complications of                  atresia is now > 70%.
       surgery include failure to establish bile
       flow, loss of bile flow due to further
       injury to bile ducts, and ascending
    2. Medical management. See above for
       previously     described    treatment of
       cholestasis, with the addition of
       prophylactic antibiotics (trimethoprim-
       sulfamethoxazole), to help prevent
       cholangitis. Cholangitis is aggressively
       treated with intravenous antibiotics.

 Zyady Pediatrics                                                                Gastrointestinal Disorders

                     Hepatitis A        Hepatitis B        Hepatitis C         Hepatitis D        Hepatitis E

Features             RNA                DNA                RNA                 Defective RNA      RNA

Age group            Primarily young    All ages           All ages            All ages           Primarily 15-40

Onset                Abrupt             Insidious          Insidious           Insidious          Abrupt

Incubation           21-42 days         50-180 days        42-56 days          Variable           30-45 days

 Feces                        +                -                   -                  -                    +
 Food                         +                -                   -                  -                    +
 Semen                        -                +                   ?                  +                    -
 Saliva                       -                +                   +                  +                    -
 Transfusion                  -                +                   +                  +                    -
 Dialysis                     -                +                   +                  +                    -
 Sexual                       +                +                   +                  +                    -
 Mother/infant                -                +                   +                  +                    -

Prevalence           5%-10%             >2%                0.6%                1-10% of HBV       Rare

 Anorexia            Common             Common             Common              Common             Common
 Nausea, vomit       Common             Common             Common              Uncommon           Common
 Fever               Common             Uncommon           Uncommon            Uncommon           Common
 Arthritis/rash      Rare               Common             Rare                Rare               Rare

 Severity            Mild               Mild-severe        Intermediate        Mild-severe        Mild-severe
 Mortality           < 1%               1-3%               1-3%                1-3%               High
 Chr hepatitis       No                 Yes                Yes                 Yes                No
 Chr carrier         No                 Yes                Yes                 Yes                No
 Cancer              No                 Yes                Yes                 ?                  No

MANIFESTATIONS                                              2. HBV. A prodrome of malaise, fatigue, low-
 1. HAV. Most cases are self-limited, but rare                 grade fever, and arthralgias is followed by
    cases can manifest as fulminant liver failure.             jaundice, pruritus, nausea, and vomiting.
    In young children, the illness is mild, either                In some cases, the prodromal i lness   l
    asymptomatic or manifesting with malaise and                  resembles serum sickness, with prominent
    vomiting, but usually without jaundice.                       migrating polyarticular arthritis, urticaria,
    Between the ages of 6-14, jaundice is evident                 macropapular rash, and glomerulonephritis.
    in 50% of cases. After the age of 14 years, 70-               Prodromal symptoms subside as active
    80% of cases present with jaundice. In this                   hepatitis begins.
    older age group, headache, fever, and malaise
    are followed by jaundice that persists for a                  As with HAV, young children may not
    few weeks. Symptoms tend to diminish as the                   develop clinical hepatitis. The incidence of
    jaundice peaks, heralding recovery.                           chronic infection is inversely proportional to
                                                                  age. Infants infected in the perinatal period
                                                                  usually develop chronic illness. In older
                                                                  children and adults, the incidence of chronic
                                                                  infection is < 10%.

 Zyady Pediatrics                                                                   Gastrointestinal Disorders
 3. HCV. Clinical manifestations are often absent              D. Hepatitis D (delta hepatitis)
    early in the course, with fatigue, jaundice, and
                                                                   1. Delta antigen in the serum is only briefly
    other signs of liver injury occurring later.
                                                                      detectable (first 2 weeks of the disease).
     In contrast to other viral hepatitides, hepatitis                Antibodies to delta virus (anti-HDV)
     C becomes chronic in about 80% of cases.                         become detectable in > 90% of patients
     The chronic infection is characterized by slow                   within 3-8 weeks of infection with acute
     progression to cirrhosis in about 20% of cases,                  hepatitis D.
     generally occurring over 30 years. A higher
                                                                   2. The highest titers of anti-HDV are found
     incidence and more rapid progression are seen
                                                                      in patients who have chronic hepatitis D.
     with concurrent liver injury caused by HIV,
     HBV, alcohol, and fatty liver.
                                                              UNDERSTANDING SEROLOGY IN VIRAL HEPATITIS
                                                                   Marker                       Meaning
 Typically, children with acute viral hepatitis have
 elevated serum levels of aminotransferases with or            Anti-HAV (IgM)      Recent hepatitis A infection
 without icterus. In severe cases, hepatic synthetic
 function may be affected, with resulting                      HbsAg               Infection with HBV (acute/ chronic)
 prolongation of the PT.                                       anti-HBs            Clinical recovery (protective)
 A. Hepatitis A virus. The diagnosis of acute                  anti-HBc            Active HBV infection
    hepatitis A is established by the finding of
                                                               HBeAg               Active infection, high infectivity.
    hepatitis A antibodies of the immunoglobulin
    M (IgM) class (IgM antibody is present for 1               anti-HBe            Resolving infection
    to 3 months; IgG antibody is longer lasting).              HBV DNA             Active infection (high infectivity)
    Anti-HAV IgG may represent past, not
    present, infection.                                        HCV RNA             Confirms infection with HCV

 B. Hepatitis B virus.                                         anti-HCV            Acute/chr infection (not protective)

     1. The standard marker for hepatitis B is the             HD Ag               Acute HDV infection
        presence of HBsAg. The presence of                     anti-HDV            Exposure to HDV;
        antibodies directed against HBsAg (anti-
        HBs) usually indicates immunity.
     2. IgG antibodies directed against hepatitis
        B core antigen (anti-HBc) may indicate                 No specific therapy exists for acute viral hepatitis.
        acute infection, chronic infection, or past            Strict bed rest is not necessary, but vigorous
        infection. IgM antibodies against HBcAg                activity should be avoided.
        (anti-HBc IgM) are more indicative of
                                                               Supportive care with IV fluids is occasionally
        acute infection.
                                                               necessary with severe symptoms. In fulminant
     3. Hepatitis B e antigen (HBeAg) is marker                cases, multisystem support is provided.
        of viral replication and infectivity and
        chronic infection if it is present for > 2
        months. It almost guarantees transmission
        of hepatitis B virus from mother to infant
        when appropriate prophylaxis is absent.
 C. Hepatitis C virus.
     1. Reverse PCR to detect HCV RNA in the
        serum or liver is the most sensitive
        marker of infection with HCV.
     2. Anti-HCV antibody. With the newer
        assays (second- and third-generation),
        HCV infection can usually be detected
        within 3 months of the time of exposure.
        Anti-HCV antibody persists in chronic
        hepatitis C but eventually disappears after
        recovery from acute hepatitis C.

 Zyady Pediatrics                                                                  Gastrointestinal Disorders

PREVENTION                                                              FULMINANT HEPATITIS
 A. Hepatitis A. Family members, children, and               FHF is defined as severe liver disease with onset of
    staff exposed at day care centers, as well as            hepatic encephalopathy within 8 weeks after initial
    their sexual contacts, should receive immune             symptoms, in the absence of chronic liver disease.
    globulin (0.02 mL/kg) within 2 weeks of
    contact. A vaccine is now available and is               ETIOLOGY
    effective in preventing infection with hepatitis
    A in endemic areas.                                        1. Viral infection: Acute viral hepatitis accounts
                                                                  for > 80% of FHF. Drugs and toxins are the
 B. Hepatitis B                                                   second common etiology.
     1. Hepatitis B immune globulin (HBIG).                        a- HAV is the most common cause of
        People who have had sexual, or mucosal                        reported fulminant hepatitis in children
        exposure should receive HBIG (0.06                            from underdeveloped countries.
        mL/kg) plus full vaccination. The dose of                  b- HBV is uncommon cause but is usually
        HBIG should be repeated in 1 month.                           seen in infants of HBsAg-positive, anti-
     2. Hepatitis B vaccine is a recombinant                          HBe-positive mothers.
        vaccine with few side effects. It is given                 c- HDV may convert a chronic persistent
        as 3 doses, 1 and 6 months following the                      hepatitis B to fulminant hepatitis.
        first dose. The vaccine is now                             d- HEV is particularly virulent in pregnant
        recommended for all infants, family                           women, causing FHF in 20% of patients.
        contacts of chronic carriers, and other                    e- Other important viral causes in infancy
        high-risk populations. These populations                      include HSV, CMV, EBV and echovirus.
        include all health care workers engaged in             2. Autoimmune chronic active hepalitis,
        patient care or contact with laboratory                   especially the type 2 form (positive anti-
        specimens from patients, residents, and                   liver/kidney microsomal antibodies)
        staff of institutions where retarded
        individuals; seronegative homosexual                   3. Metabolic causes.
        men; IV drug abusers; dialysis patients;
                                                                   a- Ttyrosinemia, galactosemia, hereditary
        and recipients of high-risk blood products
                                                                      fructose         intolerance,         neonatal
        (e.g., hemophiliacs) are cared for.
                                                                      hemochromatosis,          α      l-antitrypsin
     3. Prophylaxis in infanls. All infants                           deficiency,       Zellweger         syndrome ,
        should be immunized against hepatitis B.                      disorders of fatty acid oxidation, and bile
        Infants of women who are serum HBsAg-                         acid synthetic defects in the neonate may
        positive in the third trimeste of  r                          lead to fulminant hepatic failure in infants
        pregnancy, should also receive 0.5 mL                         or young children.
        HBIG within 12 hours of birth and start                    b- Wilson's disease, α-antitrypsin deficiency,
        the vaccine series. With the proper and                       cystic fibrosis, Niemann-Pick disease, and
        timely administration of HBIG and                             glycogen storage disease (type IV) may
        hepatitis B vaccine, 90% of the cases of                      lead to this condition in the older child.
        chronic HBV infection that would have
                                                               4. Hepalotoxic drugs can cause fulminant
        resulted from perinatal transmission can
                                                                  hepatitis by overdosage (acetaminophen);
        be prevented.
                                                                  through genetic proclivity to slow metabolism
     4. Booster doses. Antibodies to HBsAg                        (isoniazid); or through an idiosyncratic
        (anti-HBs) that are generated by exposure                 reaction to a normal dose (hal thane,  o
        to the vaccine appear to diminish with                    phenytoin). In some patients, valproic acid is
        time. Long-term studies of children and                   converted to toxic metabolites that disrupt
        adults indicate protection against chronic                various intramitochondrial pathways, which
        HBV infection for 10 years or more, even                  results in hyperammonemia, hypoglycemia,
        though anti-HBs concentrations may                        and hepatic steatosis and failure.
        become low. At present, routine booster
                                                               5. Plant toxins have also been implicated (e.g.,
        doses of vaccine are not recommended,
                                                                  Amanita phalloides mushrooms).
        except for people continuously exposed to
        hepatitis B (e.g., health care workers) and            6. Infiltrative      diseases         (leukemia,
        immunocompromised          patients    [e.g.,             hemophagocytic lymphohistiocytosis,)
        hemodialysis patients, those who have
                                                               7. Reye's syndrome
        HIV infection].
                                                               8. Cryptogenic
 Zyady Pediatrics                                                               Gastrointestinal Disorders
MANIFESTATIONS                                            STAGES OF HEPATIC ENCEPHALOPATHY
 Liver failure is a multisystem disorder with              1. Stage I
 complex interactions among the liver, kidneys,
                                                               −     Agitated
 vascular structures, gut, CNS, and immune
                                                               −     Obeys age-appropriate commands
                                                               −     Normal reflexes
 1. Early symptoms include anorexia and fever,
                                                           2. Stage II
    progressive jaundice, mental status changes.
                                                               −     Confused and lethargic
 2. Hepatic encephalopathy is characterized by
                                                               −     May not obey commands
    varying degrees of impairment (Table).
                                                               −     Hyperreflexic
 3. Respiratory compromise occurs as severity                  −     Asterixis present
    of the failure increases and requires early
                                                           3. Stage III
    institution of ventilatory support.
                                                               −     Sleepy but arousable
 4. Renal function is impaired, and frank RF, or
                                                               −     Motor response to pain
    hepatorenal syndrome may occur. This
                                                               −     Hyperventilation
    syndrome is characterized by low urine
                                                               −     Hyperreflexic
    output, azotemia, and low urine sodium.
                                                               −     Asterixis present
 5. Increased risk of infection.
                                                           4. Stage IV
 6. Hypoglycemia resulting from impaired
                                                               −     Unconscious, not arousable
    glycogenolysis and gluconeogenesis must be.
                                                               −     Unresponsive to pain
 7. Ascites        develops       secondary to                 −     Irregular respirations
    hypoalbuminemia and disordered regulation                  −     Hyperreflexic
    of fluid and electrolyte homeostasis.                      −     Pupil response sluggish
 8. Esophageal varices may cause significant               5. Stage V
    hemorrhage, whereas hypersplenism from
                                                               −     Unconscious
    portal    hypertension  may      produce
                                                               −     Flaccid muscle tone
                                                               −     Apneic
                                                               −     Hypoactive reflexes
INVESTIGATIONS                                                 −     Pupils fixed
 A. Blood tests: There is hyperbilirubinaemia,
    high serum aminotransferases and low levels           TREATMENT
    of coagulation factors. Aminotransferases are
                                                           Management must be carried out in ICU at a liver
    not useful indicators of the course of the
                                                           transplant center. Treatment is supportive; the
    disease as they tend to fall along with the
                                                           definitive lifesaving therapy is transplantation.
    albumin with progressive liver damage.
                                                           Children have undergone transplantation with a
 B. Ultrasound will define liver size and any              70% survival rate. This compares with the 30%
    evidence of underlying liver pathology.                survival rate with conservative management.
 C. Liver biopsy may be indicated to ascertain                                 −   Avoid sedatives
    the nature and degree of injury and estimate                               −   Neomycin via nasogastric tube
    the likelihood of recovery. In the presence of                             −   Lactulose via nasogastric tube
    coagulopathy, biopsy must be done using a                                  −   Enemas if constipated
    transjugular or surgical approach.                                         −   Protein restriction
                                                                               −   Ventilation (stage III/IV)
 D. Tests to follow the severity of liver injury                               −   FFP only if active bleeding
    and to monitor the response to therapy.                Coagulopathy
                                                                               −   Platelet transfusions as required
     1. Coagulation tests and serum albumin are                                −   Restrict fluid (60% maintenance)
        used to follow hepatic synthetic function.                             −   Restrict Na (0.5-1 mEq/kg/day)
        In addition to monitoring PT and PTT,                                  −   Monitor CVP
        many centers measure factor V serially as                              −   Maintain adequate intravascular
                                                           Renal failure
        a sensitive index of synthetic function.                                   volume, give albumin if low
                                                                               −   Diuretics
     2. Renal function tests, electrolytes, serum                              −   Dialysis or hemofiltration
        ammonia, blood counts, and urinalysis                                  −   Exchange transfusion
        also should be followed.                                               −   Liver transplantation

 Zyady Pediatrics                                                                Gastrointestinal Disorders
            CHRONIC HEPATITIS                                MANIFESTATIONS
Chronic hepatitis can be defined as an inflammatory           Patients with chronic persistent hepatitis usually
process of the liver lasting > 6 months. Chronic              have symptoms similar to acute hepatitis, such as
hepatitis has been differentiated on the basis of             fever, malaise, anorexia, and abdominal pain.
pathology into chronic persistent hepatitis and               The presentation in chronic active hepatitis is
chronic active hepatitis.                                     more severe, with:
  A. Chronic persistent hepatitis is defined by an            1. Jaundice, hepatosplenomegaly,       and      right
     inflammatory reaction limited to the portal                 upper quadrant abdominal pain.
     zone, with little or no fibrosis.
                                                              2. Ascites.
  B. Chronic active hepatitis is defined by an
     inflammatory reaction that is not limited to the         3. Digital clubbing.
     portal area and periportal fibrosis.                     4. Cutaneous stigmata of chronic liver disease
Patients with chronic persistent hepatitis have an               (spider angioma, prominent abdominal wall
improved chance of complete resolution and                       venous pattern).
decreased progression to chronic active hepatitis.            5. Arthritis or glomerulonephritis may occur.
Although this distinction may be important for
progression of disease and prognosis, chronic                INVESTIGATIONS
hepatitis is now more commonly grouped on the
basis of underlying cause.                                    A. General chemistry panel.
                                                                  1. The serum bilirubin level is elevated but
ETIOLOGY                                                             is usually < 5 mg/dL.
  1. Infectious. Chronic HBV is still the most                    2. The serum levels of aminotransferases are
     common cause of chronic liver disease. In the                   typically elevated at least 10-fold.
     United States, chronic HCV is now more
     common. Co-infection with other viruses such                 3. Of the plasma proteins, serum albumin is
     as HCV/HBV and HBV/HIV may also lead to                         low, and gamma globulin is elevated.
     chronic liver disease. Other viral causes                    4. The ESR is likewise elevated.
     include: EBV and CMV.
                                                              B. Evaluation for an underlying cause:
  2. Autoimmune hepatitis is believed to be the
     result of either a primary or secondary defect               1. Serologic tests for hepatitis A, B, C, D;
     in T-cell function that leads to injury. Often                  CMV; and EBV are helpful. About 25%
     these patients are initially s      een with                    of patients have detectable levels of
     hypergammaglobulinemia. Because there is                        serum HBsAg. It is important to test for
     no specific histopathology, other causes of                     anti-HCV or HCV RNA in the serum to
     chronic hepatitis must be rule         d out.                   rule out hepatitis C as a cause.
     Autoimmune hepatitis may be classified on                    2. Further     evaluation   for    metabolic/
     the basis of antibodies.                                        autoimmune disease includes: α 1-
      a- Type I (antinuclear, anti-smooth muscle                     antitrypsin; ceruloplasmin; 24-hour urine
         antibody -positive) tends to be more                        copper collection; sweat chloride testing;
         common and occurs in older patients.                        and autoantibodies (antinuclear antibody,
                                                                     anti-smooth muscle antibody, and anti-
      b- Type II [anti-liver/kidney microsomal                       LKM antibody).
         (LKM) antibody positive] is le          ss
         common; it occurs in younger patients                C. An ultrasound is often performed to evaluate
         and has a poorer response to treatment.                 the underlying anatomy of the liver.

      c- Type III with soluble liver antigen (now             D. Hypersplenism may result in               anemia,
         designated anti SLP/LP) but this group                  leukopenia, and thrombocytopenia.
         behaves as type I.
  3. Metabolic/genetic. Wilson's disease, α 1-
     antitrypsin deficiency, cystic fibrosis
  4. Toxins/drugs

 Zyady Pediatrics                                                                Gastrointestinal Disorders
                                                             2. Autoimmune hepatitis is treated with
                                                                immunosuppression. Prednisone is usually the
 1. Viral hepatitis.                                            first-line medication and is tapered very
                                                                gradually in association with close monitoring
     a- Hepatitis B                                             of liver function. In patients unable to be
         Treatment with recombinant INF-α results               weaned from prednisone, azothioprine may be
         in a disappearance of viral markers of                 helpful. Cyclosporine may be helpful in cases
         replication, infectivity, normalization of             of       treatment    failure    with     other
         levels of aminotransferases, and improved              immunosuppressants. In one recent series,
         liver histology in 50% of patients. Long-              immunosuppressant therapy was able to be
         term follow-up reveals that some of these              stopped in 19% of patients after a median of 3
         patients relapse after therapy, but about              years of treatment.
         one third of treated patients achieve a             3. Liver transplantation may be necessary for
         sustained response. Usual dosage is 10                 patients in whom cirrhosis develops, with its
         million units/m 2 (up to 10 million units)             attendant complications (portal hypertension,
         given SC, 3 times a weeks for 6 months.                esophageal varices, ascites, liver failure).
         Side effects include fever, fatigue,
         headaches, muscle aches, neutropenia,
         and thrombocytopenia.                                 PRIMARY SCLEROSING CHOLANGITIS
         Although not yet routinely used in                Primary sclerosing cholangitis occurs by itself or
         pediatric patients, lamivudine has shown          more often in association with UC. It may be
         great promise in the treatment of chronic         accompanied by evidence of autoimmune hepatitis;
         hepatitis B. In a recent study lamivudine         when this occurs, overlap syndrome is diagnosed.
         led to a sustained improvement of levels          Antineutrophil cytoplasmic antibody is present in
         of aminotransferases in 68% of patients.          many cases.
         Side effects were similar to those of INF-
         α and included headache, cough, diarrhea,         Diagnosis is by liver biopsy and cholangiography,
         malaise, and fatigue.                             generally performed as ERCP. These studies show
                                                           inflammation and fibrosis surrounding bile ducts in
     b- Hepatitis C                                        biopsy specimens and varying degrees of segmental
                                                           stricturing of larger bile ducts by cholangiography.
         For patients who have hepatitis C, the
         initial response is equivalent, but the           Treatment consists of ursodiol administration,
         relapse rate is very high. Patients who           which seems to slow progression and improves
         have the highest risk for progressing to          indices of hepatic injury; dilation of major biliary
         cirrhosis may best benefit from INF-α             strictures during ERCP; and liver transplantation for
         therapy. This includes patients who have          end-stage liver disease.
         persistently elevated aminotransferase
         levels, positive HCV RNA, and moderate
         inflammation or necrosis on biopsy. The
         usual recommended treatment regimen is
         3 million units/m 2 (maximum 3 million
         units), three times a week for 12 months.
         This longer treatment course does not
         appear to improve the initial response of
         40-50%, but increases the sustained
         response to 20-30% from 10-20% with a
         6-month course.
         Ribavirin, when used in combination with
         INF-α for a 6-month course, leads to
         improved sustained response rates
         compared to those seen with INF-α
         alone. The most common side effect is a
         reversible hemolytic anemia, with a
         decrease in Hb by 10-20% of baseline.

 Zyady Pediatrics                                                                 Gastrointestinal Disorders

       METABOLIC LIVER DISEASE                               DIAGNOSIS
The metabolic diseases affecting liver function are           A. There are low serum levels of α1AT (usually
numerous and varied in presentation. For example, α              < 100 mg/dL, The normal range is 2-4 g/L)
l-antitrypsin deficiency can occur in neonates as                and an abnormal protein phenotype (PiZZ).
cholestasis and in older children as cirrhosis. The           B. Liver biopsy shows characteristic PAS-
remainder of this section focuses on two metabolic               positive,     diastase-resistant    eosinophilic
liver diseases of particular importance to the                   cytoplasmic       granules       in         rtal
pediatrician: namely, α l-antitrypsin deficiency and             hepatocytes. These can be shown to be α1AT
Wilson's disease.                                                using specific antiserum. Fibrosis and
                                                                 cirrhosis can be present.
                                                              Cigarette smoking accelerates the onset of lung
  α1AT is a serum protease inhibitor synthesized in           disease and should be avoided. In patients who
  the liver. Co-dominant alleles dictate the type and         have liver disease and poor synthetic function,
  concentration of α1AT inherited.                            liver transplantation has been successful with 1-
  The gene is located on chromosome 14. The                   year survival of 80%. However, the progression to
  genetic variants of α1AT are characterized by their         liver dysfunction may be gradual, and some
  electrophoretic mobilities as medium (M), slow              patients do not require transplantation unless
  (S) or very slow (Z). The normal genotype is                deterioration is present.
  protease inhibitor MM (PiMM), the homozygote
  for Z is PiZZ, and the heterozygotes are PiMZ and
  PiSZ. S and Z variants are due to a single amino
  acid replacement of glutamic acid at positions 264
  and 342 of the polypeptide, respectively. This
  results in decreased synthesis and secretion of the
  protein by the liver.
  How this causes liver disease is uncertain. It is
  postulated that the failure of secretion of the
  abnormal protein leads to an accumulation in the
  liver, causing liver damage.
  About 1 child in 5000 in Britain is born with the
  homozygous deficiency.

  The majority of patients with clinical disease are
  homozygotes        with      a    PiZZ  phenotype.
  Heterozygotes (e.g. PiSZ or PiMZ) may develop
  liver disease, but the risk is small.
  1. Some may present in childhood and a few
     require transplantation. About 5-10% of PiZZ
     patients have neonatal cholestasis. Jaundice
     resolves in most cases. Occasionally, severe
     disease causes death in the first year of life.
  2. About 10-15% of adult patients will develop
     cirrhosis, usually over the age of 50 years.
     About 5% of patients die of their liver disease.
  3. About 75% of adult patients will have
     respiratory problems (emphysema). Patients
     are usually, but not always, cigarette smokers

 Zyady Pediatrics                                                                   Gastrointestinal Disorders

               WILSON'S DISEASE                                DIAGNOSIS
Wilson's disease is a treatable autosomal recessive             A. Serum copper and ceruloplasmin are
disorder, which is the result of a mutation in a gene              usually reduced but can be normal. The
that maps to chromosome 13 (at 14q21 ) and appears                 ceruloplasmin level is usually < 20 mg/dL in
to encode a copper-binding, membrane-spanning                      95% of patients who are heterozygous for
protein. This diagnosis needs to be considered in the              Wilson's disease, but it may be low in other
differential diagnosis of any liver disease in children            disorders as well.
5 or older.                                                     B. Urinary copper is usually increased (100-
                                                                   1000 mg in 24 hours; normal levels < 40 mg
PATHOGENESIS                                                       in 24 hours).
  Organ damage occurs as the result of toxicity from            C. Liver biopsy. The diagnosis depends on
  copper deposition. Although levels of the copper-                measurement of the amount of copper in the
  binding protein, ceruloplasmin, are low in 95% of                liver, although high levels of copper are also
  patients, the exact mechanism underlying Wilson's                found in the liver in chronic cholestasis.
  disease is not known.                                            Quantification of liver copper by biopsy
                                                                   demonstrates levels > 250 ug/g by dry weight.
                                                                D. Genetic analysis is limited as already > 200
  Wilson's disease has many unusual modes of                       mutations have been identified at the ATP7B
  presentation, so there is often a delay in diagnosis.            locus located on chromosome 13.
  1. Liver disease is the primary mode of
     presentation in pediatric patients, but it is             TREATMENT
     rarely clinically evident before 5 years of age.           1. Dietary restrictions. Chocolate, nuts, liver,
     The presentation may include an episode of                    shellfish, mushrooms, and other foods rich in
     acute hepatitis, fulminant hepatitis, chronic                 copper should be avoided.
     hepatitis, or cirrhosis.
                                                                2. Life-long treatment with chelating agents is
  2. Neurologic      symptoms       (e.g.,   tremor,               necessary.     Such     agents      include D-
     dysarthria, loss of fine motor control, chorea,               penicillamine, trientine (if penicillamine is not
     ataxia, seizures) usually occur in young                      tolerated), and oral zinc (to reduce intestinal
     adulthood. Psychiatric symptoms can be                        copper absorption and help maintain negative
     very striking, leading to a diagnosis of                      copper balance).
     obsessive-compulsive disorder, schizophrenia,
     manic-depressive disorder, or antisocial                       Serious side-effects of D-penicillamine occur
     behavior.                                                      in 10% and include skin rashes, leucopenia
                                                                    and renal damage.
  3. Coombs-negative hemolytic anemia occurs.
                                                                3. All siblings and children of patients should be
  4. There is renal involvement, usually a                         screened and treatment given even in the
     Fanconi-like syndrome.                                        asymptomatic if there is evidence of copper
  5. Corneal deposition of copper causes the                       accumulation
     formation of the pathognomonic Kayser-
     Fleischer rings (a slit lamp may be required to           PROGNOSIS
     see them).                                                 The prognosis is excellent with early treatment.
                                                                Neurological damage is, however, permanent and
                                                                fulminant hepatitis continues to be associated with
                                                                a poor prognosis.

 Zyady Pediatrics                                                                   Gastrointestinal Disorders

         LIVER TRANSPLANT ATION                               LONG-TERM        COMPLICATIONS          OF        LIVER
                                                              TRANSPLANTATION         AND                     CHRONIC
Liver transplantation has become the accepted                 IMMUNOSUPPRESSION INCLUDE:
therapy for end-stage liver disease and metabolic
liver disease in children. With the use of reduced-            1. Growth impairment if high                doses   of
size grafts and living related donors, organs are more            corticosteroids are required.
readily available for the smaller pediatric patient.           2. Nephrotoxicity and hypertension.
MAJOR INDICATIONS IN CHILDREN:                                 3. Biliary strictures, obstruction, or leak.
  1. Biliary atresia (particularly after           an          4. Susceptibility to infection, including viral
     unsuccessful Kasai procedure).                               (e.g., EBV, CMV, and HSV); Pneumocystis
  2. α1AT deficiency.                                             carinii; bacterial; and fungal infections
  3. Wilson's disease.                                         5. Chronic rejection. This process occurs in
  4. Tyrosinemia                                                  10% of transplantation cases and leads to
  5. Other inborn errors of metabolism.                           progressive   cholestasis   and     decreased
  6. Cryptogenic cirrhosis                                        numbers of bile ducts. Retransplantation may
  7. Chronic hepatitis.                                           be required.
  8. Fulminant hepatitis.
                                                               6. Lymphoproliferative disease. A potentially
  Chronic     immunosuppression        with    FK506              fatal disorder associated with the intensity of
  (Prograf; Fuji- sawa), cyclosporine, prednisone,                immunosuppression and EBV infection (either
  and azathioprine is necessary to prevent rejection.             primary or reactivation). Treatment includes
                                                                  decreasing immunosuppression and antivirals
PROGNOSIS                                                         (ganciclovir/acyclovir).
  One-year survival rates are nearly 90% and five-
  year survival rates are approximately 80%.
  Children < 12 months of age experience a
  significantly poorer prognosis.

  1. Primary allograft nonfunction
  2. Acute cellular rejection.
  3. Vascular thrombosis (especially the hepatic
     artery in children).
  4. Biliary complications such as anastomotic
     stricture with primary biliary reconstruction,
     bile leak after removal of the T-tube, ischemic
     injury to bile duct, and recurrent cholangitis.

 Zyady Pediatrics                                                               Gastrointestinal Disorders

 DISORDERS OF THE PANCREAS                                       Therapy (see respiratory section):
                                                                   1. Pancreatic extracts given before meals
       PANCREAT IC INSUFFICIENCY                                      to supplement enzyme activity.
                                                                   2. A balanced but high-caloric diet.
            CYSTIC FIBROSIS (CF)                             2. Pancreatitis may occur in some patients who
CF is the major cause of pancreatic insufficiency in            retain some pancreatic exocrine function.
the United States, Canada, and western Europe. The
general aspects of cystic fibrosis and its pulmonary          OTHER CONDITIONS ASSOCIATED WITH
complications are discussed in respiratory section.           PANCREATIC INSUFFICIENCY INCLUDE
The following discussion focuses on pancreatic
insufficiency and other GI manifestations of cystic          1. Malnutrition, which is the most common
fibrosis.                                                       cause of childhood pancreatic insufficiency
PANCREATIC DISEASE DUE TO CF                                 2. Shwachman-Diamond syndrome (pancreatic
  1. Pancreatic insufficiency. Of patients who                  insufficiency and bone marrow dysfunction).
     have cystic fibrosis, 85- 90% have evidence of          3. Pearson syndrome.
     exocrine pancreatic dysfunction.
                                                             4. Johanson-Blizzard syndrome.
      Pathogenesis. The pancreas seems to be
      affected in utero. Decreased ductal water flow         5. Isolated pancreatic enzyme defects.
      is present because of decreased anion
      secretion by CF cells, which leads to a rise in
      the protein concentration of the pancreatic
      ducts. This in turn causes microprecipitation
      of protein and plugging of the ductal lumens.
      Later, exocrine pancreatic elements are
      replaced by fibrous tissue and fat.
      Clinical features
        1. Malnutrition and FTT may begin in the
           first few months of life.
        2. Steatorrhea occurs, and stools are
           bulky, foul-smelling, and pale and
           greasy in appearance.
        3. Complications due to malabsorption of
           fat-soluble vitamins or calcium may
           occur (e.g., hemorrhagic diathesis,
           rickets, neurologic abnormalities).
      Diagnosis of pancreatic insufficiency is
      made on the basis of the following:
        A. Quantitative determination of fecal fat
        B. Serum levels of pancreatic trypsinogen
           (increased before the age of 8 years, but
           then subnormal).
        C. Duodenal          intubation         and
           cholecystokinin-secretin stimulation to
           assay    enzymes      and    bicarbonate
           produced by the pancreas (gold
        D. Bentiromide       (N-benzoyI-L-tyrosyl-
           para-aminobenzoic acid) test. After oral
           administration of bentiromide, plasma
           para-aminobenzoic acid levels are low
           in patients who have steatorrhea.

 Zyady Pediatrics                                                                     Gastrointestinal Disorders
                PANCREAT ITIS
                                                                 Acute pancreatitis can be difficult to diagnose.
             ACUTE PANCREATITIS                                  A. Elevations in total serum amylase or lipase
Exocrine pancreas produces numerous proteolytic                     support the diagnosis. Nonspecific elevations
enzymes, including trypsin, chymotrypsin, and                       of the enzymes are common, however. As
carboxypeptidase. These are produced as inactive                    acute pancreatitis progresses, the amylase
proenzymes to protect the panc            reas from                 level tends to decline faster than lipase,
autodigestion. Trypsin is activated after leaving the               making the latter a good choice for diagnostic
pancreas by enterokinase, an intestinal brush border                testing late in the course. Enzyme levels are
enzyme. After activation, trypsin cleaves other                     not 100% sensitive or specific
proteolytic proenzymes into their active states.                 B. Serial measurement of lab tests is important
Protease inhibitors found in pancreatic juice inhibit               to monitor for complications. At diagnosis,
early activation of trypsin. Pancreatitis occurs when               baseline CBC, CRP, electrolyte, BUN,
digestive enzymes are activated inside the pancreas,                creatinine, glucose, calcium, and phosphorus
causing injury.                                                     should be obtained. These should be measured
                                                                    at least daily, along with amylase and lipase.
                                                                 C. Imaging studies are important for diagnosis.
  Triggers for acute pancreatitis differ between                    Edema is present in all but the mildest cases.
  adults and children. In the adult, most episodes are              US is capable of detecting this edema. If
  related to alcohol or gallstones. In children, most               overlying bowel gas obscures the pancreas, a
  cases are idiopathic. Some cases are caused by:                   CT scan allows complete visualization of the
                                                                    gland. CT scans should be done with oral and
  1. Abdominal trauma (also surgery & ERCP).
                                                                    IV contrast agents to facilitate interpretation.
  2. Penetrating duodenal ulcer.                                    US and CT also can be used to monitor for the
                                                                    development of pseudocysts. The other
  3. Biliary obstruction: stones, parasites, tumors.
                                                                    important reason to perform imaging early in
  4. Structural anomalies: choledochal             cyst,            the course is to rule out gallstones.
     pancreas divisum, biliary stenosis.
  5. Infections (e.g., mumps and other viruses).

  6. Drugs (e.g., L-asparaginase, azathioprine).                 There are no proven specific therapies for acute
  7. Systemic diseases (e.g., collagen vascular
     disease, H-S purpura, HUS, Kawasaki disease,                1. If a predisposing etiology is found, such as a
     IBD, hyperlipidemia, hypercalcemia).                           gallstone obstructing the sphincter of Oddi,
                                                                    this should be specifically treated.
  8. Metabolic abnormalities (organic acidemias).
                                                                 2. Otherwise, the old maxim of "rest the gland"
  9. Cystic fibrosis.                                               is accomplished by NPO, use of an acid-
                                                                    blocking drug, and nasogastric suction.
                                                                 3. Pain relief should be provided, avoiding
  1. Relatively rapid onset of pain, usually in the                 morphine because of its tendency to cause
     epigastric region. The pain may radiate to the                 spasm of the sphincter of Oddi. Meperidine is
     back and is always aggravated by eating. The                   the traditional narcotic of choice.
     patient moves frequently to find a position of
                                                                 4. Fluid resuscitation is necessary because of
     comfort. Nausea and vomiting occur in most
     cases. Pain is typically continuous and quite                  vomiting and third space losses.
     severe, usually requiring narcotics.                        5. Nutritional support should be provided early
                                                                    because the patient may be NPO for extended
  2. Severe pancreatitis can lead to hemorrhage,
     visible as ecchymoses in flanks (Grey Turner                   periods. Feedings administered downstream
                                                                    from the duodenum via a nasojejunal tube are
     sign) or periumbilical region (Cullen sign).
                                                                    generally well tolerated. If this is not possible,
  3. Rupture of a minor pancreatic duct can lead to                 parenteral nutrition is an option.
     a pancreatic pseudocyst, characterized by
                                                                 6. Antibiotics should be considered if the patient
     persistent pain and tenderness and a palpable
                                                                    is febrile, has extensive pancreatic necrosis, or
     mass. With necrosis and fluid collections,
                                                                    has laboratory evidence of infection. A broad-
     patients experiencing severe pancreatitis are
                                                                    spectrum antibiotic, such as imipenem, is
     prone to infectious complications.
                                                                    considered the best choice.
 Zyady Pediatrics                                                                 Gastrointestinal Disorders
                                                              A. Laboratory diagnosis of chronic pancreatitis
  1.   Hypocalcemia.
                                                                 is similar to acute pancreatitis. Diagnostic
  2.   Hyperglycemia.                                            testing for the etiology of chronic pancreatitis
                                                                 should include genetic testing for hereditary
  3.   Pseudocyst formation, which occurs in 5% of
                                                                 pancreatitis and cystic fibrosis and sweat
       patients and is heralded by an epigastric mass
                                                                 chloride determination.
       and recurrent pain (pseudocysts are easily
       detected and monitored by US).                         B. Monitoring also should include looking for
                                                                 consequences of chronic injury, including DM
  4. Peritonitis.
                                                                 and compromise of the pancreatic and biliary
                                                              C. Pancreatic and biliary imaging has been
Chronic pancreatitis is defined as recurrent or                  accomplished by ERCP. ERCP offers the
persistent attacks of pancreatitis, which have                   possibility of therapeutic intervention to
resulted in irreversible morphologic changes in                  remove gallstones, dilate strictures, and place
pancreatic structure. These include scarring of the              stents to enhance flow of pancreatic juice.
ducts with irregular areas of narrowing and dilation             MRCP is an alternative to ERCP. Plain
(beading), fibrosis of parenchyma, and loss of acinar            abdominal x-rays may show calcifications.
and islet tissue. Pancreatic exocrine insufficiency
and diabetes mellitus may result from unremitting            TREATMENT
chronic pancreatitis. Most patients have discrete             1. Treatment is largely supportive.
attacks of acute symptoms occurring repeatedly, but
chronic pain may be present.                                  2. Potential but unproven therapies include the
                                                                 use of:
ETIOLOGY AND EPIDEMIOLOGY                                         −   Daily pancreatic enzyme supplements
  The causes of chronic pancreatitis include                      −   Daily antioxidant therapy
  hereditary pancreatitis and milder phenotypes of                −   Low-fat diets
  cystic fibrosis associated with pancreatic                      −   Octreotide (somatostatin) to abort early
  sufficiency.                                                        attacks
  Familial disease is caused by one of several                3. Interventional ERCP to dilate large strictures
  known mutations in the trypsinogen gene. These                 and remove stones and surgical pancreatic
  mutations obliterate auto-digestion sites on the               drainage procedures to decompress dilated
  trypsin molecule, inhibiting feedback inhibition of            pancreatic ducts by creating a side-to-side
  trypsin digestion. Genetic testing is readily                  pancreatico-jejunostomy may have some
  available for these mutations.                                 value.

  1. Children with chronic pancreatitis initially
     present with recurring attacks of acute
     pancreatitis. Injury to the pancreatic ducts
     predisposes these children to continued
     attacks owing to scarring of small and large
     pancreatic ducts, stasis of pa         ncreatic
     secretions, stone formation, and inflammation.
     Chronic pain is a serious problem in most
     affected individuals. These patients have
     many episodes; many do not req             uire
  2. Loss of pancreatic exocrine and endocrine
     tissue over time can lead to exocrine and
     endocrine deficiency. More than 90% of the
     pancreatic mass must be destroyed before
     exocrine deficiency becomes clinically
     apparent; this is a late complication that does
     not occur in all cases.

 Zyady Pediatrics                                                                 Gastrointestinal Disorders

                PERITONITIS                                  INVESTIGATIONS
The peritoneum consists of a single layer of                  Blood tests should focus on identifying the nature
mesothelial cells that covers all intra-abdominal             of the inflammation and its underlying cause.
organs. The portion that covers the abdominal wall
                                                              A. An elevated WBC count, ESR, and CRP
is derived from the underlying somatic structures
                                                                 suggest infection. In children > 5 years,
and is innervated by somatic nerves. The portion
                                                                 appendicitis is the leading cause.
covering the viscera is derived from visceral
mesoderm and is innervated by non-myelinated                  B. Total serum protein, albumin, and urinalysis
visceral afferents.                                              should be ordered to rule out nephrotic
                                                              C. Liver function tests should be performed to
  Inflammation of the peritoneum, or peritonitis,                rule out chronic liver disease causing ascites.
  usually is caused by infection, but may result from
                                                              D. The best way to diagnose suspected peritonitis
  exogenous irritants introduced by penetrating
                                                                 is to sample the peritoneal fluid with a needle
  injuries or surgical procedures, radiation, and
                                                                 or catheter (paracentesis). Peritoneal fluid in
  endogenous irritants, such as meconium.
                                                                 SBP has a high neutrophil count of > 250
  Infectious peritonitis can be an acute complication            cells/mm3. Other tests that should be run on
  of intestinal inflammation and perforation, as in              the peritoneal fluid include amylase (to rule
  appendicitis, or it can occur secondary to                     out pancreatic ascites), culture, albumin, and
  contamination of preexisting ascites associated                lactate dehydrogenase concentration. For
  with renal, cardiac, or hepatic disease. In this               culture, a large sample of fluid should be
  setting, when there is no other intra-abdominal                placed into aerobic and anaerobic blood
  source, it is referred to as spontaneous bacterial             culture bottles immediately on obtaining the
  peritonitis. SBP is usually due to pneumococcus                sample.
  and less often to E. coli.
                                                              E. As discussed before, appendicitis may be
                                                                 identified by US or CT scan. When other
MANIFESTATIONS                                                   intra-abdominal emergencies are suspected,
  Peritonitis is characterized on examination by                 such as midgut volvulus, meconium ileus,
  marked      abdominal       tenderness.   Rebound              peptic disease, or any other c          ondition
  tenderness also generally is quite pronounced. The             predisposing to intestinal perforation, specific
  patient tends to move very little owing to intense             testing should be performed.
  peritoneal irritation and pain.
  Fever is not always present, and absence of fever
  should not be regarded as contradictory to the              1. Peritonitis caused by an intra-abdominal
  diagnosis. Patients who are taking corticosteroids             surgical process, such as appendicitis or a
  for an underlying condition, such as nephrotic                 penetrating wound, must be man         aged
  syndrome, are likely to have little fever and                  surgically.
  reduced tenderness.
                                                              2. SBP should be treated with a broad-spectrum
                                                                 antibiotic with good coverage of resistant
                                                                 pneumococcus     and      enteric    bacteria.
                                                                 Cefotaxime is generally effective as initial
                                                                 therapy while awaiting culture and sensitivity
                                                              3. Anaerobic coverage with metronidazole
                                                                 should be added whenever a perforated viscus
                                                                 is suspected.