Common Gastrointestinal Disorders - Nepal Medicos Times

Common Gastrointestinal Disorders

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Et. Mainly idiopathic, but some factors have been incriminated e.g.:-  Maternal drug exposure e.g. Phenobarbital.  Syndrome/malformation complex e.g. chromosomal aneuploidy & holoprosencephaly.  Genetic factors; because there are families in which a cleft lip or palate, or both is inherited in a dominant fashion (van der Woude syndrome).
C.M. Male>Female. It varys in severity & may be unilateral or bilateral. Cx.
Feeding difficulty is the immediate problem.  Malposition of teeth → abnormal dentition.  Recurrent otitis media → hearing loss.  Speech defects due to hypernasal quality for certain sounds.  Cosmetic effects. Rx.  Feeding should be with special nipple contain plastic obturator.  Surgical closure of a cleft lip is usually performed by 3 mo of age,
when the infant is medically stable.  Surgical closure of a cleft palate is individualized, but should be done before 1 yr (if medically stable) to enhance normal speech development. Otherwise, if surgery is deferred beyond the 3rd yr, a
contoured speech bulb can be used for intelligible speech. Velopharyngeal Incompetence
Et. It is mainly due to cleft palate, but may occur with osseous or
neuromuscular abnormalities e.g. velocardiofacial syndrome. Path. It is due to inability to form an effective seal between oropharynx (soft palate) & nasopharynx during swallowing → recurrent OM with loss of liquid through the nose while drinking when head is down; it also
cause inability of phonation → hypernasal speech and inability to blow. Rx. It may need surgery. Note: Adenoid usually produces hyponasal speech but in these patients adenoidectomy may precipitate overt hypernasal speech.
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It is the most frequent congenital anomaly of the esophagus. Half of
patients usually have other abnormalities e.g. VATER/VACTERL associations as well as tracheomalacia (which improve as the child grow). Path. EA with distal TEF is the most common type (85%). Other abnormalities are uncommon e.g. double blind (8%), H-type (4%). C.M. Maternal polyhydramnios may suggest EA. A newborn with EA is
typically has frothing & bubbling at mouth and nose after birth as well as episodes of coughing, cyanosis, and respiratory distress. Feeding exacerbates these symptoms, causes regurgitation, and may precipitate aspiration. Inability to pass a NG tube in a newborn is suggestive of EA. H-type fistula may present later in life as chronic respiratory problems, e.g. refractory bronchospasm and recurrent aspiration pneumonias. Inv. Plain X- ray: may reveal a coiled feeding tube in the esophageal pouch. Air-distended stomach indicates the presence of coexisting TEF; whereas airless, scaphoid abdomen may indicate EA without TEF.  Esophagogram by using gastrographine injected under pressure can
demonstrate EA +/_ TEF. Note: Barium should not be used because it is toxic to the lung if aspirated. Endoscopy can show the orifice of TEF by observing the methylene blue dye in the esophagus during its injection into the endotracheal tube combined with forced inspiration.  Bronchoscopy can also show the orifice of TEF.
Rx.  Maintain patent airway and prevent aspiration by continuous suction
of secretions from mouth & nose then put the newborn in a prone position to prevent aspiration.  Use antibiotics to prevent consequent pneumonia.  Ambu bag, ETT & mechanical ventilation are better to be avoided
because it may worsen distention of abdominal viscera.  Surgical ligation of the TEF and primary end-to-end anastomosis of the
esophagus are performed when feasible.
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Cxs of surgery include: anastomotic leak, re-fistulization, and anastomotic stricture. GERD is a major problem resulting from intrinsic
abnormalities of esophageal function & delayed gastric emptying. In premature or complicated infant, a primary closure may be delayed by temporizing with fistula ligation and gastrostomy tube placement. Laryngotracheoesophageal Clefts
Et. It is uncommon anomalies result when the septum between
esophagus and trachea fails to fully develop → common channel defect between them. C.M. Strider, choking, cyanosis, aspiration of feedings, and recurrent chest infections. Inv. Contrast radiography or direct Endoscopy. Rx. Surgical repair.
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GERD is the most common esophageal disorder in children of all ages.
Although it occasionally physiological, but it become pathological when
it more frequent, more prolonged, or associated with Cxs. Natural history: Infant reflux becomes evident in the 1st few months of
life (peaks at ≈ 4 mo) and resolves in most by 1 yr and nearly all by 2 yr.
GERD in older children tend to be chronic, waxing and waning, and
usually do not completely resolve in about half of them. Et. Transient relaxation of the lower esophageal sphincter (LES) is the
primary mechanism for GERD. It is aggravated by:-  Esophagitis due to GERD itself → vicious cycle.  Gastric distention e.g. postprandial, abnormal gastric emptying, or air swallowing.  Factors that intra-abdominal pressure e.g. increased movement, straining, obesity, large-volume or hyperosmolar meals, and increased
respiratory effort (coughing, wheezing).  Positions that place LES below air-fluid interface in the stomach.  Genetic predisposition has been proposed for GERD. C.M. Infantile reflux manifests as postprandial regurgitation +/_ signs of esophagitis e.g. irritability, arching, choking, gagging, & feeding aversion. Some infants presents with Cxs e.g. FTT or respiratory symptoms e.g. obstructive apnea, strider, or wheezing.  Older children may have regurgitation during the preschool years with complaints of abdominal and chest pain supervenes in later childhood and adolescence.  Occasional children present with neck contortions (arching, turning of head) designated "Sandifer syndrome".
Esophageal; include: esophagitis, stricture, and "Barrett" esophagus
which is a metaplastic transformation of the normal esophageal
squamous epithelium into intestinal columnar epithelium, it may be a
precursor for adenocarcinoma although it is rare in children.
Extra-esophageal (respiratory) or (atypical); include: Obstructive
Apnea due to laryngospasm; Strider, if infant is anatomically
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predisposed e.g. laryngomalacia; Reflux laryngitis due to laryngeal edema or vocal cord nodule, both → hoarseness, voice fatigue, throat clearing & chronic cough; other Cxs include: pharyngitis, sinusitis, otitis
media, and sensation of globus.  Nutritional; FTT which may need nutritional support by Enteral (nasogastric or nasojejunal, or percutaneous gastric or jejunal) or
Parenteral feedings.
Dental erosions; especially on the lingual surface of teeth; it the most common oral lesion of GERD.
Note: Asthma co-occurs with GERD in about half of children & factors that suggest the presence of GERD with asthma are: symptoms of reflux disease, refractory or steroid-dependent asthma, and those with nocturnal worsening of asthma.
Inv. Empirical antireflux therapy is a cost-effective strategy for diagnosis
by a trial of high-dose proton pump inhibitor.  Barium contrast study for upper GIT to exclude other anatomical
abnormalities.  Esophageal pH monitoring is better done by dual or 2 probes (proximal & distal), whereas single probe is mainly used to assess the
efficacy of acid suppression during treatment & to evaluate atypical GERD symptoms.
Intraluminal impedance test to diagnose non-acid reflux.  Esophageal manometry to evaluate dysmotility, especially before surgery.
Radionucleotide scintigraphy may demonstrate delayed gastric emptying and aspiration.
Endoscopy is diagnostic for erosive esophagitis & Cxs e.g. strictures or
Barrett esophagus. Esophageal biopsies may diagnose histologic reflux esophagitis in the absence of erosions; it also excludes allergic and
infectious causes as well as it can be used therapeutically to dilate
reflux-induced strictures.
Laryngotracheobronchoscopy evaluates visible airway signs that are associated with extraesophageal GERD. Bronchoalveolar lavage may also permit diagnosis of silent aspiration (during swallowing or reflux)
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with subsequent quantification of lipid-laden macrophages in the airway.
D.Dx. Hiatus hernia, pyloric stenosis, intestinal obstruction (especially malrotation with intermittent volvulus), milk and other food allergies, nonesophageal inflammatory diseases, infections, inborn errors of metabolism, hydronephrosis, increased intracranial pressure, rumination, and bulimia. Rx. Dietary measures for infants include small volume & frequent feeding. Thickening of formula with tablespoonfull of rice for each oz
of formula. Short trial of hypoallergenic diet can be used to exclude milk or soy protein allergy at all ages.
Positioning; prone position (when the infant is awake and observed) or upright carried position can be used to minimize reflux.
Older children should avoid acidic or reflux-inducing foods and beverages, weight reduction for obese patients and elimination of smoke exposure. They may benefit from left side position and head elevation during sleep.
Pharmacotherapy include:-  Antacids provide rapid but transient relief of symptoms.  Antihistamine (H2) blockers e.g. cimetidine, famotidine, nizatidine, and ranitidine are the first line of treatment for mild-to-moderate
reflux esophagitis.  Proton pump inhibitors e.g. omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole are used for severe and erosive esophagitis; they are provide the most potent antireflux effect.  Prokinetic agents e.g. metoclopramide, domperidone, bethanechol, and erythromycin can increase LES pressure and some will improve
gastric emptying or esophageal clearance, but unfortunately none
affect the frequency of transient LES relaxation as well as chronic use of metoclopramide (for >3 mo) has been associated with tardive
Surgery e.g. fundoplication or pyloroplasty is effective therapy for intractable GERD that are not responding to conservative therapy or
associated with Cxs .
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Et. Ingestion of an Alkali agents produce severe, deep liquefactive necrosis, and because they are tasteless, they more commonly ingested than acids. Acidic agents are bitter, so less consumed; they produce coagulative necrosis which somewhat protective thick eschar. Volatile
acids can result in respiratory symptoms. C.M. Vomiting, drooling, strider, refusal to drink, oral burns, dysphagia, and abdominal pain. Male>Female.
Note: Absence of oropharyngeal lesions does not exclude the possibility of
significant esophago-gastric injury. Cx. Necrosis, esophagitis, perforation & stricture formation (which occur especially when there is circumferential ulcerations), white plaques, and
sloughing of mucosa. Rx. 1- Dilution with water or milk is recommended & removal of contaminated clothes. Neutralization, induced emesis, and gastric
lavage are contraindicated.
2- If symptoms are present, oral fluids or solids should be withheld.
3- Upper Endoscopy is recommended for rapid identification of tissue damage and must be undertaken in all symptomatic children within
12-24 hr of ingestion. 4- Stricture formation can be treated by dilatation & stenting and in
some severe cases, surgical resection with colon or small bowel
interposition. 5- Use of corticosteroids & prophylactic antibiotic are controversial.
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It is most common between 6 mo & 3 yr of age as well as those with mental retardation. Coins, small toy items & button batteries are most commonly ingested. Food impactions occationally occur if there is underlying structural anomaly or motility disorder. Lodgment of the FB usually occur at upper or lower esophageal sphinicter or at the level of aortic arch. C.M. At least 30% of children with esophageal FB may be totally asymptomatic!, but many have an initial bout of choking, gagging, and
coughing may be followed by excessive salivation, dysphagia, food
refusal, emesis, or pain in the neck, throat, or sternal notch regions. Respiratory symptoms e.g. strider, wheezing, cyanosis, or dyspnea may be encountered if FB impinges on the larynx or the posterior
membranous tracheal wall. Cervical swelling, erythema, or subcutaneous
crepitations suggest perforation of oropharynx or proximal esophagus.
Inv. Plain X-ray may reveal the object if it radiopaque. It usually lie in coronal plain in A-P view.  Barium contrast may be helpful in the occasional asymptomatic patient with negative plain films.  Endoscopy is both diagnostic & therapeutic. Rx. Assess risk for airway compromise and in cases of suspected airway perforation obtain chest CT scan and surgical consultation.  Asymptomatic blunt objects and coins can be observed for up to 24 hr in anticipation of passage into the stomach. Otherwise they should be removed by Rigid Endoscope.
Meat impactions can be observed for up to 12 hr. Sometimes glucagon
can facilitate passage of distal esophageal food boluses by decreasing the LES pressure!.
Button batteries (especially lithium batteries) are the most dangerous one & must be expediently removed because they can cause esophageal perforation within minutes!.  Foley catheter sometimes can be used to remove FB by passage it beyond the coin under fluoroscopy.  Bougienage of esophageal coins toward the stomach may be used in
selected uncomplicated cases.
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Once in the stomach, 95% of all ingested FBs will pass without difficulty through the remainder of the GIT (although with delay) because most objects will pass within 4-6 days, but some for up to 3-4 wk!. Batteries beyond the duodenum pass per rectum in 85% within 72 hr. Water-
absorbing polymer balls (e.g. beads) can expand to about 400 times its starting size, so may → intestinal obstruction. Perforations are rare (<1%) of all objects ingested; it tend to occur in
areas of physiologic sphincters, acute angulation, congenital gut malformations, or areas of previous bowel surgery. Inv. Abdominal plain X-ray or contrast study. Rx.
Conservative Rx is indicated for most FBs. Parents should be instructed to continue a regular diet and to observe the stools for the object; cathartics should be avoided.  Objects that should be removed endoscopically include: large or
lithium batteries, magnets & lead-based FB. Long or sharp objects (e.g. safety pins) are also better to be removed, otherwise they should be
monitored radiologically & parents must be instructed to report any sign of bleeding or perforation immediately to the physician e.g. abdominal pain, vomiting, persistent fever, hematemesis, or melena.
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It is an accumulation of exogenous material in the stomach or intestine. They include:-  Trichobezoars: composed of patient's own hair, especially found in females with underlying personality problems.  Phytobezoars: composed of a combination of plant and animal material.  Lactobezoars: mainly found in premature infants & attributed to the high casein or calcium content of some premature formulas. Note: Swallowing of the chewing gum can occasionally form a bezoar.
C.M. Patient usually presented with symptoms of gastric outlet or partial
intestinal obstruction e.g. vomiting, anorexia, weight loss and severe halitosis. Some have features of chronic gastritis. Inv. Abdominal plain X-ray, contrast study, US, or CT scan. Rx. Bezoars in the stomach usually can be removed endoscopically; if unsuccessful, surgical intervention may be needed. Coca-Cola has been
used as a dissolution therapy for gastric phytobezoar. Lactobezoars
usually resolve when feeding is withheld for 1-2 days.
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Epid. HPS is more common in whites than blacks, Male>Female, offspring of a mother (and to a lesser extent a father) who had HPS,
monozygotic than dizygotic twins; it is rare in Asians. HPS may be associated with other congenital defects & syndromes e.g. TEF, hypoplasia or agenesis of the inferior labial frenulum, eosinophilic
gastroenteritis, Apert synd, Zellweger synd, Trisomy 18, Smith-Lemli-
Opitz synd, and Cornelia de Lange synd. Et. The cause of HPS is unknown, although many factors have been implicated e.g. use of erythromycin in neonates. HPS is usually not present at birth, i.e. it is not a congenital disorder!. C.M.
Hx. Non-bilious vomiting is the initial symptom of HPS. It usually starts
after 3 wk of age, although it may develop as early as 1st wk of life and
as late as 5th mo. The vomiting may be initially projectile but usually progressive,
occurring immediately after feeding causing malnutrition, the infant is hungry and wants to feed again. There also may be hx of little stool. As vomiting continues → progressive loss of fluid & (HCl) acid →
hypochloremic metabolic alkalosis. HPS usually causes prolonged
indirect hyperbilirubinia "Icteropyloric syndrome".
Ex. The pyloric mass is firm, movable, olive shaped, ≈ 2 cm in length; it is best palpated from the left side, during feeding or after vomiting; it located in the right upper quadrant of abdomen. After feeding, there may be a visible gastric peristalsis. Inv. US of abdomen show ↑ pyloric thickness ≈ 4 mm or an overall pyloric length 14 mm.  Contrast studies (Ba meal) show huge gastric distention, elongated pyloric channel, a bulge of the pyloric muscle into the antrum "shoulder sign", and parallel streaks of barium seen in the narrowed channel
“double tract sign”.
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D.Dx. Duodenal stenosis, GERD, hiatal hernia, gastroenteritis, cong adrenal hyperplasia, inborn errors of metabolism, & feeding mismanagement. Rx.
Preoperative Rehydration is essential & directed toward correcting fluid and electrolyte losses and acid-base balance. IVF therapy is begun with 0.45–0.9% saline, in 5–10% dextrose, with addition of KCl 30–50
mEq/L. Fluid therapy should be continued until the infant is rehydrated and the serum bicarbonate concentration is <30 mEq/dL (which is essential to prevent postoperative apnea); this can be accomplished within 24 hr.  Surgery: by pyloromyotomy (Ramstedt procedure).
Postoperative vomiting occurs in half the infants and is thought to be secondary to edema of the pylorus at the incision site; however, in most cases, feedings can be initiated within 12–24 hr after surgery;
otherwise, Endoscopic balloon dilation has been successful in infants with persistent vomiting secondary to incomplete pyloromyotomy.
Laparoscopic technique (without surgery) is equally successful.  Conservative Rx by nasodudodenal feedings or atropine sulfate (as pyloric muscle relaxant) before feedings is advisable in patients who are not good surgical candidates.
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Motility Disorders of the Intestine
Causes of non-mechanical obstruction or "pseudo-obstruction" include: Chronic intestinal pseudo-obstruction; Functional constipation; Hirschsprung disease; intestinal neuronal dysplasia; hypothyroidism; scleroderma; diabetic neuropathy; amyloidosis; porphyria; angioneurotic edema; mitochondrial disorders; hypokalemia; opiates; lead toxicity; and radiation. Causes of mechanical obstruction include: intussusception; adhesions; FB ingestion...etc. CHRONIC INTESTINAL PSEUDO-OBSTRUCTION Et. It can occur as a primary disease or secondary to a large number of conditions that can transiently or permanently alter bowel motility. The
most common primary cause is Ogilvie syndrome (acute pseudoobstruction of the colon); whereas the most common secondary cause is gastroenteritis. Path. It represents a wide spectrum of pathologic disorders including abnormalities of the nerves (intestinal neuropathy) or musculature
(intestinal myopathy) of the gut. It either involve the entire GIT or limited to a certain region e.g. stomach or colon. Urinary tract involvement occurs in ≈ 40% of cases with intestinal myopathy.
C.M. These are group of disorders characterized by wax and wane of signs and symptoms of intestinal obstruction in the absence of anatomical lesion, which include: abdominal pain & distention, vomiting, and
constipation (although some has diarrhea!) as well as growth failure. Inv. Plain abdominal radiographs show air-fluid levels in small intestine.  Contrast studies show slow passage of barium.  Motility studies are usually abnormal (except anorectal motility).  Intestinal biopsy is usually abnormal. Rx. Nutritional support by oral or parenteral nutrition.  Prokinetic agents e.g. erythromycin, metoclopramide, & domperidone have some benefit especially for those with gastroparesis.  Antibiotics +/_ probiotics orally & octereotide are given to treat bacterial overgrowth.  If these measures are failed, surgery is indicated.
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FUNCTIONAL (IDIOPATHIC) CONSTIPATION It is defined as delay or difficulty in defecation due to intentional or
subconscious fecal withholding that has been present for 2 wk. It
typically starts after the neonatal period (usually above 2 yr), i.e. it is an acquired rather than congenital disorder. Dietary changes, coercive or inappropriately early toilet training, or school entrance may play a role. C.M.
Hx. Typical behavior of withholding stool is contracting the gluteal muscles by stiffening the legs during passage of painful bowel
movements. Therefore, child is voluntarily trys withholding feces to
avoid this painful stimulus. Parents may misinterpret these activities as straining because it may be associated with fecal soiling & encopresis (due to constipation with overflow incontinence). FTT, weight loss, abdominal pain & distention, vomiting may also present. Ex. Large volume of stool palpated in the suprapubic area; rectal exam
demonstrates normal anal tone & dilated rectal vault filled with stool. Cx. Retentive constipation anal irritation and often anal fissure with bleeding; rarely toxic megacolon may occur. Urinary tract symptoms may also occur as a sequence of constipation e.g. urine retention, overflow incontinence, megacystis, and UTI.
Inv.  First exclude other causes of constipation e.g. spinal cord lesions (by X-
ray of spine); or hypothyroidism...etc.  Barium enema in functional constipation may show acquired mega-
rectosigmoid.  Rectal motility studies can demonstrate a pattern of paradoxical contraction of the external anal sphincter during defecation. Rx. 1. Patient & family education is essential about the pathophysiology of disease. 2. Regular bowel training program is often helpful, including sitting on the toilet for 5–10 min after meals. 3. If an impaction is present on the initial exam, enema is indicated. 4. Maintenance medications of stool softeners e.g. polyethylene glycol, glycerin (orally or rectaly), lactulose, or mineral oil. Bowel stimulants
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e.g. senna or bisacodyl also can be used for short-term but prolonged use should be avoided.
Maintenance medications are generally continued until a regular bowel
pattern has been established and the associated pain during defecation is abolished.
(Congenital Aganglionic Megacolon)
Epid. HD is the most common cause of lower intestinal obstruction in
neonates, Male>Female. It may be associated with other congenital syndromes or defects e.g. Down, Smith-Lemli-Opitz, Waardenburg, Cartilage-hair hypoplasia, and Congenital hypoventilation syndromes and many other abnormalities; it is uncommon in premature infants. Path. Absence of ganglion cells in the bowel wall; although it is mainly limited to the rectosigmoid (75%), it may extend proximally and involve the entire colon in 10% of cases. C.M. Hx. It should be suspected in any full-term infant with delayed passage of meconium >48 hr after birth (because 99% of full-term infants pass meconium within 48 hr of birth), although some infants with HD pass meconium normally but subsequently present with chronic
constipation. Less common presentation is FTT with hypoproteinemia (due to protein-losing enteropathy). Breast-fed infants may not suffer as severe a disease as formula-fed infants. Ex. Abdominal exam reveal distention with large fecal mass is palpable in the left lower abdomen; rectal exam reveal normal anal tone with empty rectum, rectal exam is usually followed by an explosive passage
of foul-smelling feces and gas. Cx. Enterocolitis due to stasis that allows proliferation of bacteria, e.g. Clostridium difficile, Staphylococcus aureus, anaerobes, coliforms, with associated sepsis and signs of bowel obstruction. D.Dx. In neonates, HD must be differentiated from; meconium plug syndrome, meconium ileus, and intestinal atresia. In older patients, it must be differentiated from: functional constipation & other causes of non- mechanical obstruction including Currarino triad (anorectal
malformations, sacral bone anomalies, and presacral anomaly).
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Inv. Ba-enema should be done after the 2nd wk of life without preparation. It may show a Transition zone between normal dilated proximal colon and a smaller-caliber obstructed distal colon (except when the entire colon is affected). If only the rectosigmoid is affected, picture is similar
to those with functional constipation. Ba retention also helpful in Dx.  Rectal suction biopsies are the procedure of choice; it should be performed no closer than 2 cm from the dentate line. It also can be done intraoperatively. The biopsy shows absence of both Meissner & Auerbach plexuses, hypertrophied nerve bundles, & high concentration of acetylcholinesterase.  Anorectal manometry measures the pressure of the internal anal
sphincter response to a balloon distended in the rectum; it shows either failure to relax or "paradoxical" rise in its pressure. Note: In ultrashort-segment Hirschsprung disease, also called "anal achalasia", the aganglionic segment is limited to the internal sphincter. The
clinical symptoms are similar to those of children with functional constipation. Ganglion cells are present on rectal suction biopsy, but the anorectal manometry is abnormal. Rx. Surgery. INTESTINAL NEURONAL DYSPLASIA
It may be associated with Hirschsprung disease or others conditions with
similar manifestations to that of Hirschsprung disease, but instead of absence of intestinal ganglion cells, it demonstrates absent (or
hypoplasia) of the sympathetic innervation of myenteric and submucosal
plexuses (Type A), or dysplastic submucosal plexus with giant ganglia and
thickened nerve fibers (Type B) which account for >95% of cases. It is either segmental or involve the entire intestinal tract. Rx. Same as that for functional constipation and, if unsuccessful, surgery.
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ILEUS It is failure of gut peristalsis without evidence of mechanical obstruction. Et. Abdominal surgery; especially if followed by narcotic administration.  Infections e.g. peritonitis, gastroenteritis, pneumonia.  Metabolic abnormalities e.g. uremia, hypokalemia, hypercalcemia, hypermagnesemia, or acidosis.  Drugs e.g. antimotility agents, opiates, or vincristine. C.M. Nausea, vomiting, feeding intolerance, abdominal distention with associated pain, and delayed passage of stool and bowel gas. Bowel sounds are minimal or absent. Inv. Abdominal radiographs demonstrate multiple air–fluid levels
throughout the abdomen. Rx. Correction of the underlying abnormality e.g. electrolytes disturbances (especially hypokalemia). Nasogastric tube decompression to reduce emesis. Th use of antiemetics is controversial. Pg. Ileus after abdominal surgery generally resolves within 72 hr.
ADHESIONS These are a common cause of postoperative small bowel mechanical obstruction after abdominal surgery at any time after the 2nd postoperative week. The majority are due to single fibrous bands of tissues. C.M. Features of mechanical obstruction & bowel sounds are initially hyperactive but then disappear. Rx. Nothing by mouth, NGT decompression, IV fluids (add Potassium if hypokalemia is present), and antibiotics; if unsuccessful, surgery.
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It is the most common cause of intestinal obstruction between 5 mo & 6 yr of age; it is rare in neonates, 60% <1 yr; Male>Female. Et. Most cases are idiopathic (90%). The condition may complicate otitis
media, gastroenteritis, Henoch-Schonlein purpura, Cystic fibrosis, or URTI (especially adenovirus type C). It is postulated that gastrointestinal
infection or the introduction of new food proteins results in swollen
Peyer patches in the terminal ileum which may predispose to
intussusception. In 5% of cases, recognizable causes for the intussusception are found, e.g. Meckel diverticulum, intestinal polyp, neurofibroma, intestinal
duplication, hemangioma, or malignant conditions e.g. lymphoma. Path. Intussusceptions occurs when upper portion of the bowel
"intussusceptum" is invaginates into the lower portion "intussuscipiens", pulling its mesentery along with it into the enveloping loop. Constriction of the mesentery obstructs venous return; engorgement of the intussusceptum follows, with edema, and bleeding from the mucosa leads to bloody stool which sometimes contain mucus. They mostly ileo-colic, less commonly ceco-colic, and rarely exclusively ileo-ileal. Most intussusceptions do not strangulate the bowel within the 1st 24 hr, but eventually may result into intestinal gangrene & shock. C.M. Hx. In typical cases, a previously well child develop sudden onset of severe paroxysmal colicky pain that recurs at frequent intervals and is accompanied by loud cries and straining efforts with legs and knees flexed. The infant may be normal between the paroxysms.
If the intussusception is not reduced, the infant becomes progressively weaker & lethargic. Eventually, shock-like state with fever develops. Vomiting occurs in most cases and is usually more frequent in early phase, but later, the vomitus becomes bile stained. The stool gradually ↓
in amount & it is of normal appearance initially but 60% of infants pass stool containing a red blood and mucus called "currant jelly stool".
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Ex. Palpation of the abdomen usually reveals a slightly tender sausage-
shaped mass in 70% of patient, sometimes ill defined, which may increase in size and firmness during a paroxysm of pain and is most often in the right upper abdomen. Abdominal distention and tenderness develop as intestinal obstruction becomes more evident. On rectal exam, bloody mucus on the finger after its withdrawal. Cx. Intestinal infarction, perforation, peritonitis, and death. Inv. Clinical Hx & Ex is the most valuable for diagnosis.
Plain abdominal X-ray may show a density in the area of intussusception.  US of abdomen may show a tubular mass in longitudinal view and a
target appearance in transverse view.  Contrast enemas demonstrate a filling defect or cupping in the head of the contrast media, the coiled-spring sign.
D.Dx. It may be difficult to diagnose intussusception in a child who
already has gastroenteritis; but a change in the pattern of illness, character of pain, nature of vomiting, and the onset of rectal bleeding should alert the physician. Rx. Reduction of an acute intussusception is an emergency procedure
and should be performed immediately after diagnosis.
lleo-colic & colico-colic intussusceptions can be reduced either by: Hydrostatic reduction (by barium or saline) or Air reduction under fluoroscopic or ultrasonic guidance. The success rate of reduction is ≈ 80% in the 1st 48 hr of intussusceptions, whereas it ≈ 50% if symptoms are present > 48 hr.
The risk of bowel perforation with hydrostatic reduction is ≈ 1%, whereas with Air reduction ≈ 0.1%. Reduction should not be attempted but surgical reduction is indicated in the presence of: refractory shock, suspected bowel necrosis or
perforation, peritonitis, and multiple recurrences (suspected lead point).  Ileo-ileal intussusceptions usually follow bowel surgery, with HSP, or
idiopathic; it usually resolves spontaneously; otherwise it cannot be
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reduced by the above procedures and require manual operative
reduction or resection. Pg. Although intussusceptions may be reduced spontaneously; it is usually fatal if untreated in infants. The chances of recovery are directly related to the duration of intussusception before reduction. The
mortality rate rapidly rises after the 2nd day of symptoms.
Most recurrences occur within 72 hr of the reduction; recurrence rate after hydrostatic or air reduction is ≈ 10% and after surgical reduction <5%, whereas none has recurred after surgical resection. Corticosteroids may ↓ the frequency of recurrence of intussusceptions.
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The diarrhea is defined as excessive loss of fluid and electrolyte in the
stool. Acute diarrhea is defined as sudden onset of excessively loose stools >10 mL/kg/day in infants or >200 g/24 hr in older children. Et. There are many causes of diarrhea including bacterial, viral, & parasitic pathogens, as well as noninfectious causes e.g. toxins &
chemicals. Infectious causes are mainly acquired by feco-oral route through ingestion of contaminated food or water. The most common viral agent in diarrhea is rotavirus, whereas the most common bacterial agents are Salmonella, Shigella, & E. coli.
Bacterial dysentery mean diarrhea that contain blood and leukocytes in
stool and associated with abdominal cramps, tenesmus, and fever. It mainly caused by: Salmonella, Shigella, enteroinvasive E. coli,
Campylobacter jejuni, Yersinia enterocolitica, and Vibrio parahaemolyticus.
Risk factors for gastroenteritis include: young age, immune deficiency, measles, malnutrition, lack of exclusive or predominant breast-feeding, poverty, poor environmental hygiene, and development indices of the
country. In addition children with vit A or zinc deficiency have increased
risk of mortality from diarrhea. Path. Enteropathogens elicit either:-  Inflammatory diarrhea; produced by direct invasion of bacteria or
production of cytotoxins → effusion of fluid, protein, and cells
(erythrocytes, leukocytes) which enter the intestinal lumen.  Non-inflammatory diarrhea; produced either by: enterotoxin
produced by some bacteria, destruction of villi (surface of cells) by viruses, adherence of parasites, or adherence and/or translocation of bacteria. Note: Normally, the epithelial cells at the tip of villus are continually renewed every 4–5 days. Cx.
Death in GE is due to either severe dehydration or malnutrition which can cause persistent diarrhea, PEM, or secondary infection.  Extraintestinal Manifestations (mainly with bacterial pathogens) e.g. Systemic spread with focal infections; Reactive arthritis; Guillain-Barre
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syndrome; Glomerulonephritis; IgA nephropathy; HUS; Hemolytic
anemia; & Erythema nodosum.  Clinical evaluation of diarrhea:-
1. Assess the degree of dehydration by the following:-  Mild dehydration (<5% in infant; <3% in older child):-
N or ↑ pulse; ↓ urine output; thirsty; normal physical findings.
Moderate dehydration (5-10% in infant; 3-6% in older child):-
Tachycardia; little or no urine output; irritable/lethargic; sunken eyes and fontanel; ↓ tears; dry mucous membranes; mild delay in elasticity (skin turgor); delayed capillary refill (>1.5 sec); cool and pale.
Severe dehydration (>10% in infant; >6% in older child):-
Peripheral pulses either rapid and weak or absent; ↓ BP; no urine output; very sunken eyes and fontanel; no tears; parched mucous membranes; delayed elasticity (poor skin turgor); very delayed capillary refill (>3 sec); cold and mottled; limp, depressed consciousness.
Note: Many of these signs are, unfortunately, unreliable in patients with severe malnutrition, especially skin fold "turger" due to loss of skin fat.
2. Obtain appropriate contact or exposure hx. 3. Clinically determine the etiology of diarrhea for institution of prompt antibiotic therapy, if indicated. To determine the location of inflammation; nausea and vomiting usually indicate infection in the stomach and upper intestine. Periumbilical pain and large watery diarrhea are indicative of involvement of the small intestine. Severe abdominal pain and tenesmus
are indicative of involvement of the large intestine and rectum. Inv. GSE: Look for mucus, blood, fecal leukocytes, or parasites.  Stool cultures should be obtained early in the course of diseas. It is usually indicated in the following 4 conditions: bloody diarrhea,
chronic diarrhea, immunosuppression, & outbreaks of HUS.  Blood tests e.g. CBP, blood culture, serologic tests, & PCR are sometimes used for specific pathogens.  Recently, multiplexed nucleic acid technology can detect many gastrointestinal pathogens.
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Rx. It include: initial rehydration, replacement of ongoing losses, nutrition, & other therapies. 1. Initial Rehydration: according to the degree of dehydration as follows:-  No or Minimal dehydration; No need.  Mild to Moderate dehydration; ORS (50 – 100) ml/kg over 3–4 hr.  Severe dehydration; Shoot of Normal Saline (NS) or Ringer Lactate (RL), 20 ml/kg over 20 min that can be repeated until perfusion and
mental status improve; then shift to Glucose Saline (1/
2) twice
maintenance fluid rates or ORS 100 ml/kg over 4 hr.  Important Notes on Rehydration:- Indications of IV fluid therapy include: severe dehydration, age <6 mo, prematurity, chronic illness, high fever, bloody diarrhea, persistent vomiting, poor urine output, and depressed level of consciousness.  RL should be avoided in patient with isolated vomiting due to the presence of lactate (which converted in liver to bicarbonate) which worsens the alkalosis; whereas Ringer alone is not contraindicated.
 Average loss of electrolytes in diarrhea (in mEq/L); Sodium: 55, Potassium: 25, Bicarbonate: 15. Thus appropriate replacement fluid:- D5% 0.2 NS + 20 mEq/L KCl + 20 mEq/L sodium bicarbonate.  Average loss of electrolytes in vomiting (in mEq/L); Sodium: 60, Potassium: 10, Chloride: 90. Thus appropriate replacement fluid:- NS + 10 mEq/L KCl. Calculation of 24-hr fluid need is as follows:- Deficit + Maintainance - Initial boluses (shoots).
Deficits = percentage of dehydration × body weight. Maintainance = 1st 10 kg (100 ml/kg), 2nd 10 kg (50 ml/kg), and 3rd 10 kg (20 ml/kg).  Sources of water loss (in the absence of gastroenteritis): urine (60%), insensible losses, skin and lungs (≈35%), & stool (5%).
 During rehydration, always recheck for disappearance of signs of dehydration (see above) as well as check the signs of overhydration e.g. edema & pulmonary congestion.  Be careful during management of patient with hyper- or hyponatremic dehydration (by measuring serum Na) through appropriate choice of
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fluid type and rate of administration because these types of dehydration are dangerous & should be corrected slowly (see later).
2.Replacement of ongoing losses:- No or Minimal dehydration; for patients <10 kg, give ≈10 ml/kg of ORS for each diarrheal stool or vomiting episode; for patients >10 kg, give
≈20 ml/kg.  Mild to Moderate dehydration; same as above.  Severe dehydration; Same as above, but if patient is unable to drink, administer ORS through NG tube or by IV Glucose Saline (1/
4) with addition of 20 mEq/L KCl after urination. Oral Rehydration Therapy:- ORS is generally better than IV fluid Rx, it should be given slowly when there is vomiting, then ↑ gradually as tolerated orally or by NG tube.  The most commonly used ORS by WHO is that which contains:- Carbohydrate 13.5 g/L, Na 75 mmol/L, K 20 mmol/L, Cl 65 mmol/L,
Base 10 mmol/L & Osmolality 245 mosm/L.
Note: ORS with lower osmolality can be more effective in reducing stool output. Cereal-based oral rehydration fluids can be prepared at home which also can be advantageous for malnourished children.  Home remedies e.g. decarbonated soda beverages, fruit juices, and tea are not suitable for rehydration or maintenance therapy because they have inappropriately high osmolalities and low sodium concentrations. 3. Nutrition:-
For all degrees of dehydration, continue breast-feeding or resume age-
appropriate normal diet after initial hydration. Diet selection in acute diarrhea include any type of food (because coupled transport of sodium to glucose & amino acids is largely unaffected) except fatty food as its absorption is affected by diarrhea. Although acute diarrheal episodes usually do not cause lactose intolerance, it is prudent to lactose load in the diet by addition of cereals to milk or replacement of milk with yogurt. Rarely, patient may develop cow's milk protein intolerance which may need replacement with specialized formula.
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4. Additional therapies:- Antibiotic Rx if timely used in select cases, it may reduce the duration and severity of diarrhea and prevent Cxs, but it should weighted against
bacterial resistance. Nitazoxanide, an anti-infective agent, has been
effective in the treatment of wide variety of pathogens. Zinc supplementation can ↓ duration and severity of diarrhea. It recommend for all children with acute diarrhea in at risk areas for 10–
14 days during and after diarrhea orally in dose 10 mg/day for infants
<6 mo and 20 mg/day for those >6 mo.
Vit A supplementation may reduces diarrhea-specific mortality.  Antimotility agents are contraindicated in children with dysentry and probably have no role in Rx of acute watery diarrhea.  Antiemetic agents are of little value and potentially associated with serious SE. Ondansetron is effective & less toxic, it can be given as oral
or sublingual tablet.  Probiotics (see later).
Pv. It can be accomplished by; Improving case Rx & tracing the source;
Promotion of exclusive breast-feeding in the first 4-6 mo of age; Breastfeeding should continue for up to 2 yr; Improved complementary feeding practices; Improved water and sanitary facilities; Promotion of personal and domestic hygiene; Rotavirus immunization; and Vit A supplementation.
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Probiotics are living microorganisms that have a beneficial effect on the host. They include: Lactobacilli, Bifidobacteria, and the yeast Saccharomyces boulardii.
Prebiotics include materials that enhance the proliferation and
development of probiotic microorganisms.
Synbiotics = Probiotics + Prebiotics.  Probiotics must fulfill the following criteria to be beneficial:-
Of human source, nonpathogenic (safe); resist gastric, bile, & pancreatic
digestion; adhere to and colonize the enterocytes. Moreover, it should produce antimicrobial substances, have favorable immuno-modulation properties & have the ability to influence metabolic activities.  Clinical uses & trials of Probiotics:-
Acute infectious diarrhea; Antibiotic-associated diarrhea; Necrotizing enterocolitis; Lactase deficiency; Celiac disease; Food protein
hypersensitivity; Helicobacter pylori infection; as well as other
conditions.  SE & rational use of Probiotics:-  They may cause mild gastrointestinal complaints e.g. diarrhea, flatulence, and change of bowel habit.  May cause bacteremia or fungemia with endocarditis, especially those
who suffer from immune deficiency or cardiac anomalies.  Probiotics may be unsafe in immunodeficient patient or < 4 mo of age.  Immune response may be induced against probiotics by enterocytes.  Potential transfer of virulence and/or resistance factors to antibiotics
from probiotics to the commensal gut flora.  Lactobacilli may potentially contribute to dental caries.  Probiotics sometimes of no effect or lose their effect when mixed with another one.
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Specific Types of Dehydration:-
Isotonic dehydration is the most common type of dehydration in gastroenteritis, but occationally, hypo- or hypernatremic dehydration may occur which require special attention during rehydration. However, even children with mild to moderate hypo- or hypernatremic
dehydration can be managed safely with ORS.
Hyponatremic Dehydration
It occurs when serum Na <135 mEq/L. Et. Child with diarrhea who is taking large quantities of low-salt fluid
(e.g. water, fruit juice, or diluted formula), diarrhea with high sodium content (e.g. cholera), or in infants <6 mo of age when caregivers offer water to their infant as a supplement or during hot weather. Note: Infants <6 mo should not be given water to drink; infants between 6 and 12 mo should not receive more than 1-2 ounces. If the infant appears thirsty, the mother should offer breastfeed or formula to the child. Path. Hyponatremia → ↓ osmolality of the extracellular space → shift of water from the extracellular space to the intracellular space → swelling of cells and the most dangerous are brain cells → ↑ intracranial pressure
→ ↓ cerebral blood flow. C.M. The degree of dehydration is usually overestimated (due to rapid
depletion of intravascular fluid). Acute, severe hyponatremia can cause brainstem herniation and apnea. Other neurologic symptoms
include: anorexia, nausea, emesis, malaise, lethargy, confusion, agitation, headache, reduced reflexes, seizures, and coma. Hyponatremia can also
cause muscle cramps, weakness, and rhabdomyolysis. Some patients may have hypothermia and Cheyne-Stokes respirations. Rx. The initial goal in treating hyponatremia is correction of intravascular volume depletion with isotonic fluid (NS or RL). An overly rapid correction (>12 mEq/L over the first 24 hr) or overcorrection
(serum Na >135 mEq/L) is associated with increased risk of Central Pontine Myelinolysis, especially if the patient has prolonged hyponatremia.
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However, most patients with hyponatremic dehydration do well with the same basic strategy that is outlined in patients with isotonic
dehydration (see above). Patients with neurologic symptoms (e.g. seizures) as a result of hyponatremia need to receive acute infusion of hypertonic saline (3%),
4 mL/kg to raise serum Na concentration rapidly. Hypernatremic Dehydration It is the most dangerous form of dehydration that occur when serum Na > 145-150 mEq/L. Et. It commonly occur in any patient with diarrhea (including neonates)
associated with poor oral intake due to anorexia or emesis, or the fluid
loss is replaced with a concentrated formula.
Path. Hypernatremia → ↑ osmolality of the extracellular space → shift of
water from the intracellular to the extracellular space which mainly affect the brain cells → brain shrinkage and tearing blood vessels within the
brain. The movement of water from the intracellular to the extracellular space during hypernatremic dehydration partially protects the intravascular volume. Therefore, the signs of dehydration are often underestimated, i.e. there is a delay in medical attention till more profound dehydration occurs. C.M. Patients with hypernatremic dehydration are often lethargic, but restless & irritable when touched. Some infants have a high-pitched
cry and hyperpnea; alert patients are very thirsty. Hypernatremia may cause fever and hyperreflexia. More severe neurologic symptoms may develop if cerebral bleeding or thrombosis occurs. Pinched abdominal skin of hypernatremic infant has a “doughy” feel, probably due to intracellular water loss. Hypernatremia usually associated with hyperglycemia and mild hypocalcemia; the cause is unknown.
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Brain hemorrhage is the most devastating consequence of hypernatremia. It include: subarachnoid, subdural, and parenchymal
hemorrhages. CSF protein is often elevated.  Thrombotic Cxs include: stroke, dural sinus thrombosis, peripheral
thrombosis, and renal vein thrombosis.  Central pontine (or extrapontine) myelinolysis can also occur in
children with hypernatremic dehydration. Rx. Idiogenic osmoles are generated within the brain during hypernatremia to increase the osmolality within brain cells providing protection against their shrinkage. They dissipate slowly during the
correction of hypernatremia; therefore, if rapid lowering of the
extracellular osmolality during the correction of hypernatremia, an osmotic gradient may be created that causes water movement from the
extracellular space into the brain cells → cerebral edema with features similar to those of hyponatremic dehydration (see above). To minimize the risk of cerebral edema, serum Na concentration should not decrease >12 mEq/L every 24 hr. The deficits may need to be
corrected slowly according to the degree of hypernatremia as follows:- 145-157 mEq/L: 24 hr (1 day), 158-170 mEq/L: 48 hr (2 days), 171-
183 mEq/L: 72 hr (3 days), 184-196 mEq/L: 84 hr (3.5 days). RL should not be used during initial resuscitation because it is more hypotonic than NS and may cause too rapid decrease in serum Na concentration. G.S. 1/
2 is appropriate as a maintainance fluid. During therapy, patient should be discouraged to take free water or
diluted formula but ORS may be a good choice. serum Na should be assessed frequently. If patient develop convulsion due to cerebral edema during therapy, use hypertonic saline (3%) 4 mL/kg to raise serum Na concentration rapidly.
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Chronic diarrhea is defined as loose or watery stools >3 times a day for >2 wk. It also called persistent or protracted diarrhea. It is a common problem in the developing countries.
Note: Awakening at night to pass stool is often a sign of an organic cause of diarrhea. Path. The mechanisms of diarrhea are generally divided into secretory and osmotic, but often diarrhea is the result of both mechanisms. Osmotic Diarrhea occurs whenever digestion or absorption is impaired as in the following:-  Malabsorption of water-soluble nutrients (congenital or acquired) e.g. glucose or galactose malabsorption.  Disaccharidase deficiencies (congenital or acquired) e.g. lactase or
sucrase deficiency.  Excessive intake of carbonated fluids or non-absorbable solutes e.g. sorbitol, lactulose, or Mg OH.  Intestinal damage e.g. enteric infection.  Reduced functional absorptive surface e.g. celiac disease.  Secretory Diarrhea is usually due to activation of the intracellular mediators e.g. cAMP, cGMP & calcium by; bacterial toxins, hormones,
neurotransmitters, & other substances that eventually stimulate active chloride secretion from the crypt cells and inhibit the neutral coupled sodium chloride absorption. The Differentiation between: Osmotic & Secretory Diarrhea:-  Volume of stool Small Large  Response to fasting Diarrhea stops Diarrhea continues  Reducing substances Positive Negative  Stool pH <5 >6  Stool Na <70 mEq/L >70 mEq/L  2 [Na+K] of stool < stool osmolarity > stool osmolarity  Ion gap ≥ 100 mOsm/kg < 100 mOsm/kg
Note: Sucrose is not a reducing agent unless after addition of HCl to the stool sample before adding reducing agent.
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Mutational Defects of Ion Transport Proteins include:- Congenital defects of sodium-hydrogen exchange, chloride-bicarbonate
exchange, and sodium–bile acid transport proteins are also result in
secretory diarrhea that is evident at birth & usually presented with FTT during the neonatal period with hx of polyhydramnios in the
mother. The defect in chloride-bicarbonate exchange is most common → congenital chloride diarrhea & hypochloremic metabolic alkalosis.  Alteration in Intestinal Motility; these include: malnutrition, scleroderma, intestinal pseudo-obstruction syndromes, and diabetes
mellitus → hypomotility → bacterial overgrowth → deconjugation of bile salts → ↑ cAMP → secretory diarrhea. Reduction in Anatomic Surface Area e.g. Short bowel syndrome &
Celiac disease → loss of fluids, electrolytes, macronutrients, and micronutrients osmotic diarrhea. Et. of chronic diarrhea (in general):-  INTRA-LUMINAL FACTORS include:-  Pancreatic disorders e.g. Cystic fibrosis, Chronic pancreatitis,
Shwachman-Diamond syndrome.  Bile acid disorders e.g. Chronic cholestasis, Terminal ileum resection, Bacterial overgrowth  Intestinal disorders e.g. All causes of Osmotic Diarrhea.
MUCOSAL FACTORS include:-  Altered mucosal integrity e.g. Infections, Infestations, Cow's milk and soy protein intolerance.  Altered immune function e.g. Autoimmune enteropathy, AIDS.  Altered function e.g. Defects in Cl/HCO3, Na+/H+, bile acids, acrodermatitis enteropathica.  Altered digestive function e.g. Enterokinase deficiency.  Altered surface area e.g. Celiac disease, Postenteritis syndrome, Microvillus inclusion disease.  Altered secretory function e.g. Enterotoxin-producing bacteria, Tumors Secreting vasoactive peptides  Altered anatomic structures e.g. Hirschsprung disease, Partial small
bowel obstruction.
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Common causes of chronic diarrhea (according to age):- NEONATES: Microvillus inclusion disease, Cong short bowel synd, Cong chloride diarrhea, & other causes of cong diarrhea syndromes. Note: Breast fed neonate & young infant normally has numerous loose stools per day, especially when the infant begin to fed (due to gastro-colic reflex), this may be confused with diarrhea. INFANTS: Postenteritis malabsorption syndrome, Cow's milk/soy protein intolerance, Secondary disaccharidase deficiencies, & Cystic
fibrosis.  CHILDREN: Chronic nonspecific diarrhea, Secondary disaccharidase deficiencies, Giardiasis, Postenteritis malabsorption syndrome, Celiac
disease, & Cystic fibrosis.  ADOLESCENTS: Irritable bowel syndrome, Inflammatory bowel disease, Giardiasis, & Lactose intolerance.  Specific Causes of Chronic Diarrhea:- Enteric Infections are by far the most common cause of chronic
diarrhea in developing and developed countries. The sequential infections with the same or different pathogen may be responsible for prolonged symptoms. Entero-adherent Escherichia coli &
Cryptosporidium parvum have been implicated in chronic diarrhea in
developing countries. In developed countries chronic infectious diarrhea usually runs a benign course and the etiology is often viral e.g. rotavirus or norovirus. CMV & Clostridium difficile are emerging agents of severe diarrhea in children that may become chronic.  Postenteritis Syndrome is a clinical-pathologic condition in which small intestinal mucosal damage persists after acute gastroenteritis. Sensitization to food antigens, secondary disaccharidase deficiency, or an infection or reinfection with an enteric
pathogen is responsible for postenteritis syndrome. A change of the gut microflora and/or antibiotic therapy may also contribute to postenteritis diarrhea.  Food Allergy: It is a common cause of chronic diarrhea (see chapter 2). Chronic Nonspecific Diarrhea (Functional diarrhea) (Toddler's diarrhea) usually occur in children <4 yr of age; whereas Irritable Bowel Syndrome usually occur in children ≥5 yr. Both are the most
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benign etiology of diarrhea. Both conditions are now considered the same with a slightly different age presentation.
Et. Ingestion of significant amounts of carbonated fluids or fruit juices. C.M. The hallmark of chronic nonspecific diarrhea is abdominal pain & diarrhea associated with normal weight growth in well-appearing subjects. In younger children diarrhea is often watery, sometimes containing undigested food particles; it usually more severe in the morning. Rx. Carbonated fluids or fruit juices should be reduced because they usually contain sorbitol (nonabsorbable sugar) & fructose. If the child's fluid intake is >150 ml/kg/day, then it should be <90 ml/kg/day, i.e., a
diet based on the “4 F” principles (↓ fructose & fluids, ↑ fat & fiber) +/_ probiotics is beneficial. In older children, irritable bowel syndrome is often associated with abdominal pain which may be related to anxiety, depression, or other psychologic disturbances.  Intractable Diarrhea Syndrome is the most severe etiology of diarrhea that includes a number of heterogeneous conditions →
permanent defect in the structure or function of intestine → progressive
or irreversible intestinal failure that require parenteral nutrition
for survival. The main causes of intractable diarrhea include: structural enterocyte defects, disorders of intestinal motility, immune-based disorders, short gut, and multiple food intolerance.  Phenotypic Diarrhea (Syndromic diarrhea) (tricho-hepato-enteric syndrome) is a rare disease that may be due to AR transmission presenting with facial dysmorphism, woolly hair, severe diarrhea, and
malabsorption; half of patients have liver disease.  Congenital Diarrheal Diseases e.g. microvillus inclusion disease, intestinal epithelial dysplasia & others are also rare disorders (see the
text for more details). Evaluation of patient with chronic diarrhea:- Personal and family history may provide specific clues that may suggest congenital, allergic, or inflammatory etiology. A previous
episode of acute gastroenteritis suggests postenteritis syndrome; the
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association of diarrhea with specific food may indicate food allergy; hx of polyhydramnios may suggest congenital diarrhea syndromes or, cystic fibrosis. The presence of eczema, asthma or family hx of atopy is
usually associated with allergic disorders. Specific extraintestinal
manifestations might suggest hormone-secreting tumors or an autoimmune disease.
Clinical examination should include general and nutritional status evaluation. Dehydration, marasmus, or kwashiorkor require prompt supportive interventions to stabilize the patient. Caloric intake should be quantitatively determined and the relationship between weight modifications and energy intake should be carefully considered.  Anthropometric evaluation is an essential step to evaluate “if, since
when, and how much” diarrhea has affected body weight. It includes evaluation of weight and height curves and of the weight for height index to determine the impact of diarrhea on growth. Weight is generally impaired before height, but with time, linear growth also becomes affected, and both parameters may be equally abnormal in the
long term. Assessment of body composition may be performed by measuring mid-arm circumference and triceps skinfold thickness.
Biochemical markers can assist in grading malnutrition. The half -life
of serum proteins can differentiate between short-term and long-term malnutrition.
Inv. Stepwise diagnostic work-up for children with chronic diarrhea include:- Step 1:- Intestinal microbiology e.g. Stool cultures, Microscopy for parasites, PCR for viruses, Stool electrolytes, H2 breath test.  Screening test for celiac disease by Antitissue Transglutaminase Ab.  Tests for food allergy e.g. skin prick test, food elimination & challenge.  Abdominal US may detect liver and pancreatic abnormalities or an increase in distal ileal wall thickness that suggests IBS.
Noninvasive tests for intestinal function (e.g. ↑ fecal calprotectin or lactoferrin indicate intestinal inflammation), pancreatic function, sweat test for CF.
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Step 2:- Intestinal Biopsy e.g. Standard jejunal/colonic histology,
Morphometry, Periodic Acid–Schiff (PAS) staining, Electron microscopy. Step 3:- Special investigations e.g. Intestinal immunohistochemistry, Anti-
enterocyte antibodies, Serum chromogranin and catecholamines, Autoantibodies, 75Se-homocholic acid–taurine measurement, Brush border enzymatic activities, Motility and electrophysiological studies. Rx. Chronic diarrhea associated with impaired nutritional status should always be considered a serious disease, and Rx should be started
promptly including; nutritional rehabilitation, elimination diet, and
drugs. Drug Rx includes therapies for specific etiologies and
interventions aimed at counteracting fluid secretion and/or promoting restoration of disrupted intestinal epithelium.  General supportive measures; e.g. replacement of fluid and
electrolyte losses is the most important early intervention because death in most instances is caused by dehydration.
Nutritional rehabilitation is often essential and is based on clinical
and biochemical assessment. In moderate to severe malnutrition, caloric intake may be progressively increased to ≥ 50% above the recommended dietary allowances & the intestinal absorptive capacity should be monitored by digestive function tests. In children with steatorrhea, medium chain triglycerides may be the main source of lipids. Lactose-free diet should be started in all children with chronic diarrhea (as recommended by WHO). Lactose is generally replaced by maltodextrin or a combination of complex carbohydrates. Semi-elemental or elemental diets have the double purpose of overcoming food intolerance (which may be the primary cause of chronic diarrhea) and facilitating nutrient absorption. The sequence of elimination should be graded from less to more restricted diets e.g. cow's milk protein hydrolysate to amino-acid–based formula (depending on the child's situation). However in severely compromised
infants it may be convenient to start with amino-acid–based feeding.
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Clinical nutrition includes enteral or parenteral nutrition. Enteral nutrition may be delivered via nasogastric or gastrostomy tube and is
indicated in a child who cannot be fed through the oral route (due to a
primary intestinal diseases or extreme weakness). In extreme wasting, enteral nutrition might not be sufficient, and parenteral nutrition is
required.  Micronutrient & vitamin supplementation are part of nutritional
rehabilitation and prevent further problems, especially among malnourished children in developing countries. Zinc supplementation is an important factor in both prevention and therapy of chronic diarrhea, because it promotes ion absorption, restores epithelial proliferation, and stimulates immune response. Vit A supplementation is also
recommended.  Drug therapy includes anti-infectious drugs, immune suppression, and
drugs that can inhibit fluid loss and promote cell growth. Specific antibiotics should be prescribed if a bacterial agent is detected. Empirical antibiotic therapy may be used in children with small bowel bacterial overgrowth or with suspected bacterial diarrhea e.g. TMP-SMZ, metronidazole, albendazole, or nitazoxanide (which have a broad spectrum of activity against many pathogens). In
Rotavirus-induced severe and protracted diarrhea, oral administration of human immunoglobulins (300 mg/kg) should be considered. In selected conditions e.g. autoimmune enteropathy, immune suppression may be considered. Rx may also directed at modifying specific pathophysiologic processes e.g. severe ion secretion may be reduced by pro-absorptive agents e.g. Racecadotril, an enkephalinase inhibitor. In diarrhea due to
neuroendocrine tumors, microvillus inclusion disease, and enterotoxin-
induced severe diarrhea, a trial with Octreotide, a somatostatin analog, may be considered. Zinc & Growth Hormone can promote enterocyte growth and ion absorption and may be effective when intestinal atrophy is associated
with ion secretion.  When the above measures are failed, the only options may be either parenteral nutrition or intestinal transplantation.
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Et. Causes of malabsorption are similar to those of chronic diarrhea; however, it can be classified according to the following:-  Malabsorption due to generalized mucosal defect:- Food-induced enteropathy e.g. Celiac disease, Cow's milk and other protein-sensitive enteropathies.  Congenital bowel mucosal defects e.g. Microvillous inclusion disease,
Tufting enteropathy.  Protein-losing enteropathy e.g. Lymphangiectasia, Disorders causing bowel mucosal inflammation.  Infection induced e.g. Parasitic infections (especially Giardiasis),
Bacterial overgrowth, Tropical sprue, Postinfectious enteropathy.  Immunodeficiency disorders e.g. Congenital or Acquired
immunodeficiency disorders, AIDS, Immunosuppressive therapy.  Autoimmune enteropathy.
Miscellaneous e.g. Immunoproliferative small intestinal disease, Short bowel syndrome, Chronic malnutrition, Radiation enteritis.  Malabsorption due to predominant nutrient malabsorption:- Carbohydrate malabsorption e.g. Lactose malabsorption, Congenital
lactase deficiency, Congenital sucrase-isomaltase deficiency.  Fat malabsorption e.g. Pancreatic exocrine insufficiency, Cystic fibrosis,
Shwachman-Diamond syndrome, Chronic pancreatitis, Protein-calorie
malnutrition, Liver and biliary disorders, Bile acid synthetic defects,
Abetalipoproteinemia.  Amino acid malabsorption e.g. Lysinuric protein intolerance (defect in dibasic amino acid transport), Hartnup disease (defect in free neutral amino acids), Blue diaper syndrome (isolated tryptophan malabsorption).  Mineral and Vitamin malabsorption e.g. Congenital chloride diarrhea,
Congenital sodium absorption defect, Acrodermatitis enteropathica (zinc malabsorption), Menke disease (copper malabsorption), Folate malabsorption, Vit B12 malabsorption.  Drug-induced malabsorption e.g. Sulfasalazine : folic acid, Phenytoin : calcium, Cholestyramine : calcium & fat.
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Clinical approach to child with suspected malabsorption:- The common presenting features of malabsorption are diarrhea, abdominal distention & FTT. Many patients have good appetite, but others have anorexia. There are some clues in the History may indicate the etiology of malabsorption e.g.:-  Oncet of diarrhea early in life → cong defect.  Onset of symptoms after introduction of particular food →
malabsorption of that food.  Explosive watery diarrhea → carbohydrate malabsorption.  Loose, bulky stools → celiac disease.  Pasty and yellowish offensive stool → exocrine pancreatic insufficiency.  Green stool with undigested food → rapid intestinal transit.  Clay-like (acholic) stool → obstructive jaundice. There are some clues in the Examination may indicate the etiology of malabsorption e.g.:-  Generalized edema → protein-losing enteropathy.  Clubbing → cystic fibrosis or celiac disease.  Perianal excoriation and gaseous abdominal distention →
carbohydrate malabsorption.  Perianal and circumoral rash → acrodermatitis enteropathica.  Abnormal hair → Menkes syndrome.  Typical facial features diagnostic of the Johannson-Blizzard syndrome. Inv.
Tests for Carbohydrate malabsorption:- 1. Test for reducing substances in the stool is suggestive if > ++. 2. Breath Hydrogen Test; patient should be fast overnight & on no antibiotics, then given the suspected sugar (lactose or sucrose) as an oral solution; in malabsorption, the sugar is not digested or absorbed in the small bowel, passes to the colon, and is metabolized by the normal
bacteria flora → ↑ breath hydrogen > 20 ppm. 3. Small bowel mucosal biopsies; can directly measure mucosal disaccharidases.
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Tests for Fat malabsorption:- 1. GSE show fat globules, but remember normally absorption of fat in the
child > full-term > premature. 2. Stool collection (for 3 days) for fecal fat estimation is definitive but cumbersome test. 3. Acid Steatocrit test is simple, rapid & reliable test. 4. Estimation of fat-soluble vitamins (A, D & E) serum levels; vit K can
be estimated by measuring PT. 5. Duodenal fluid aspirate for evaluation of bile acid levels.  Test for Gastrointestinal Protein Loss:- There is no test for food protein malabsorption, but the only test for protein loss from GIT is the estimation of α1-antitrypsin in stool which
is an endogenous protein present in the plasma and secreted in the
intestine during any condition associated with protein-losing enteropathy; it resist digestion thus it considered as screening test for these conditions.  Tests for Pancreatic Exocrine Function:- 1. Serum Trypsinogen concentration is reduced in pancreatic
insufficiency. It is a screening test, although it may ↑ in early stages of cystic fibrosis. 2. Fecal Elastase-1 estimation is sensitive but not specific test because it may be false-positive in intestinal villous atrophy & diarrhea. 3. Duodenal fluid aspirate for bicarbonate, trypsinogen, and lipase after stimulation with secretin and cholecystokinin. 4. Urine or Breath concentration of substances that reduced in pancreatic
insufficiency.  Tests for Intestinal Mucosal Disorders:- 1. Small bowel mucosal biopsies; for histologic exam, measuring mucosal disaccharidases activities, duodenal aspirates to measure pancreatic enzyme concentration, quantitative bacterial cultures, or
other infections e.g. Giardia. 2. Imaging procedures including plain radiographs, barium contrast studies, & US may show dilated intestinal loops, but usually not specific.
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CELIAC DISEASE (Gluten-Sensitive Enteropathy)
Epid. CD is a common disease that found in at least 1% of population.
The concordance in monozygotic twins approachs 100%. HLA that associated with CD are DQ2 & DQ8.
Path. CD is an immune-mediated enteropathy caused by permanent sensitivity to gluten in genetically susceptible individuals, although environmental factors also play a role. Gluten protein is found in wheat, rye, barley & (infrequently) oat, it reacts with transglutaminase enzyme
in the gut and it is a potent inducer of T-cell lines. C.M.
Hx. Typical presentation usually within 1st 2 yr of life after introduction of gluten in the diet; it include one or more of the following:- FTT, diarrhea, vomiting, irritability, anorexia (or sometimes
appetite), abdominal pain & distention, loose, bulky & foul-smell stools, and rarely rectal prolapse. Ex. growth parameters, muscle wasting & hypotonia, abdominal distention, edema, & rarely finger clubbing. Extraintestinal manifestations & associations with CD include:-  Iron-deficiency anemia (it is the most common which not respond to
iron therapy), dental enamel hypoplasia of permanent teeth,
osteopenia/osteoporosis, short stature, delayed puberty, hepatitis,
arthritis, epilepsy, headache, depression, ataxia, & myelopathy.  Autoimmunity e.g. DM type 1, Thyroiditis, Addison disease, Biliary cirrhosis, Dermatitis herpetiformis, & IgA deficiency.  Syndromes e.g. Turner, Down, & William.  Malignancy (if untreated) e.g. Adenocarcinoma & NHL of the small intestine. Inv. Anti-tissue Transglutaminase2 IgA antibody & Anti-endomysium IgA antibody are 10-fold increase compared to the general population; they are highly sensitive & specific tests, but measurement of serum IgA concentration is mandatory to exclude false-negative results if CD is
associated with IgA-deficiency, which if present, do Anti-tissue
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transglutaminase IgG antibody (instead of IgA), Anti-endomysium IgG,
or Antibodies against gliadin-derived deamidated peptides (D-AGA).
Small Intestinal Biopsy is the definitive test for CD, but since mucosal
involvement is usually patchy, so multiple biopsies must be obtained.
Histologic changes include: partial or total villous atrophy, crypt elongation, ↑ number & mitotic index of lymphocytes. Because there are a lot of conditions which can produce similar histological changes, therefore 2 biopsies are required to diagnose CD: Initial biopsy at presentation and the 2nd to document healing on gluten withdrawal from the diet, although this may not be required
when there is a good clinical & biochemical response to the gluten-free diet, as well as gluten challenge is currently not considered mandatory except in situations when there is doubt about the initial diagnosis.  Genetic Tests; the absence of HLA DQ2 and/or DQ8 have a strong negative predictive value for diagnosis of CD, whereas their presence have very weak positive predictive value. Rx. The only treatment for CD is life-long gluten-free diet which require
exclusion of wheat, barley, & rye as well as unpurified oat. After gluten withdrawal, there should be rapid remission of symptoms (within 1 wk). Levels of tissue transglutaminases should also ↓ after 6
mo of gluten withdrawal, it can be used to monitor compliance with gluten-free diet.  Clinical Patterns of CD; It can be divided into following 4 variants:-  Symptomatic; when the classic features are present (see above).
Silent; when there are no apparent symptoms in spite of histologic evidence of villous atrophy, these mostly identified during serologic screening of high risk groups.  Potential; denote subjects with positive CD serology but without evidence of altered jejunal histology, although they may be
symptomatic.  Latent; denote subjects who have a normal histology, but at some other time, have shown a gluten-sensitive enteropathy.
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There are at least 5 hepatotropic viruses: HAV, HBV, HCV, HDV, & HEV. All are RNA (except HBV is DNA).  Transmission of the viruses as follow:-  Fecal-oral; only A & E.  Parenteral, Sexual & Perinatal; ALL except A & E (although A can rarely transmitted parenterally).
Chronic infection is mainly caused by; B, C, D.  FHF is mainly caused by; B, D, E. Common biochemical profiles of viral hepatitis:-
Cytopathic injury (injury of liver cells) → ↑ ALT & AST.
Cholestasis → ↑ of TSB (mainly direct), ALP, GGT (γ-glutamyl trans-
peptidase), 5′-nucleotidase, and Bile acids in the serum & urine.  Altered synthetic function (due to liver failure) → ↑ PT, PTT, & INR, hypoalbuminemia, hypoglycemia, hyperammonemia, & lactic acidosis. Note: The above tests are considered liver function tests (LFT). Hepatitis A It is the most prevalent & highly contagious virus that usually causes acute and benign hepatitis. C.M. I.P. ≈ 3 wk. It usually cause anicteric illness with symptoms indistinguishable from those of viral gastroenteritis especially in young children, whereas in older children & adolescents it can cause acute febrile illness with abrupt onset of anorexia, nausea, vomiting, malaise followed by jaundice. The typical duration of illness is 1-2 wk.
There is usually tender hepatomegaly +/_ regional LAP, splenomegaly or BM hypoplasia. Other organs are rarely affected. Inv. Liver Function Tests (LFT).  PCR; for viral RNA in blood.  Serology of HAV:-  Acute infection: Anti-HAV IgM, remain for 4-6 mo.  Past infection (recovery) & Post-vaccination: Anti-HAV IgG, detected within 8 wk & remain life-long.
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Cx. There are only 2 uncommon Cxs:-  Acute Liver Failure; it mainly occur in older adolescents & adults, patient with underlying liver disorders, or in immunocompromised
patients.  Prolonged Cholestatic Syndrome; which waxes and wanes over
several months. It may cause pruritus and fat malabsorption, but eventually resolve without sequelae. Rx. There is no specific therapy for HAV. Supportive treatment consists
of IV hydration (as needed). Prolonged cholestasic synd can be treated
with antipruritic agents and fat-soluble vitamins. Pg. Excellent for most cases, however serial monitoring for early signs of ALF is important. HAV usually do not cause chronic infection. Pv.
Isolation with careful handwashing. HAV is highly contagious for 2 wk before and ≈ 1 wk after the onset of jaundice, thus patients should be
excluded from school during this period.  Vaccination can be given to the high risk group e.g. children >1 yr
during outbreak of HAV infection, individuals at occupational risk of exposure & patients with chronic liver disease or immune disorder. HA vaccine is given in 2 doses, 6-12 mo apart.  Immunoglobulin by IM injection is only used for postexposure Px. Hepatitis B It is common & most dangerous one because it usually associated with Cxs. It unlike other hepatotropic viruses in that it is mainly non-
cytopathogenic virus that causes injury predominantly by immune-
mediated processes. C.M. I.P. is between 6 wk-6 mo (mean 4 mo). Many acute cases of HBV infection in children are asymptomatic, whereas in others it gives symptoms similar to that of HAV infection but may be more severe that
may cause ALF or FHF in 1-5% of cases. In a few children, the illness may be preceded by a serum sickness–like prodrome marked by arthralgia or skin rash.
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PCR, for viral DNA in blood.  Serology of HBV:-  Active infection (acute or chronic): HBe Ag.
Acute infection: HBs Ag, anti-HBc IgM.
Chronic infection: HBs Ag, anti-HBc IgG.
Past infection (recovery): anti-HBs, anti-HBc IgG.  Post-vaccination: anti-HBs only (because vaccine donot contain c Ag). Note: Anti-HBc Ab is the most valuable single serologic marker for HBV infection because it present early in the disease & continue during the"window period" when both HBs Ag & anti-HBs are absent. Cx.
ALF or FHF; especially when there is super-infection or co-infection with HDV.
Extrahepatic diseases; by circulating immune complexes which may result in membranous glomerulonephritis, polymyalgia rheumatica, vasculitis, aplastic anemia, and Guillain-Barre syndrome.  Chronic HBV infection; it defined as +ve HBs Ag for >6 mo. The incidence is inversely correlated with the age of acquisition, i.e. infants
<1 yr ≈ 90%, younger children between 1-5 yr ≈ 30% & older children >5 yr ≈ 5%.
Chronic HBV infection can be divided into 3 phases; immune tolerant
(chronic carrier state), immune-active (associated with serious Cxs) &
Cxs of chronic infection include: Liver Cirrhosis, End-Stage Liver
Disease (ESLD), or Hepatocellular Carcinoma (HCC). Rx. Most uncomplicated acute HBV infection can be treated with supportive measures similar HAV.  ALF & FHF therapy will be discussed later. Chronic HBV infection, especially the immune-active phase, can be treated with Interferon-α-2b or Peginterferon-α2 (given once weekly) As well as several antiviral agents e.g. Lamivudine (approved for
children >2yr), Adefovir, Tenofevir ( >12yr), & Entecavir ( >16yr).
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SE of Interferon are anemia, neutropenia, retinal changes, influenza-like symptoms, and autoimmune disorders.
The goal of therapy is cessation of active replication which is indicated
by seroconversion of HBe Ag anti-HBe Ab or by undetectable viral DNA by PCR (which is more difficult). Pv.
 HBV is present in high concentrations in blood, serum, and serous exudates, in moderate concentrations in saliva, vaginal fluid, and semen & least amount in the breast milk. Therefore, HBV is usually not spread
by breast-feeding, kissing, hugging, or sharing water & utensils; thus neither isolation nor exclusion from school is required.
Vaccination against HBV should be given to all neonates as well as to
high risk group e.g. individuals at occupational risk of exposure, IV acquisition of drugs or blood products, acupuncture or tattoos, sexual
contact, institutional care, and intimate contact with carriers. There are 2 types of vaccines, both given at 0, 1-2, 6 mo apart.  Hepatitis B Immunoglobulin (HBIG) is only used for postexposure Px
because it provides a temporary protection (3–6 mo).  Schedule of immunization of newborn:- All newborn >2 kg & the mother is HBs Ag –ve, give vaccine at birth, 1-
2 mo & 6-18 mo apart.  If newborn <2 kg (or medically unstable) & the mother is HBs Ag –ve, the 1st dose of vaccine can be delayed upto 2 mo of age.  If the mother is HBs Ag +ve, there is high probability of perinatal transmission (especially when she also HBe Ag +ve), this may result in
high probability of chronic infection in the newborn. Therefore, if HBV
DNA viral load in the maternal blood >200,000 IU/mL, then these
mothers should receive antiviral e.g. telbivudine, lamivudine, or
tenofovir during the 3rd trimester, as well as the newborns should be
given HBIG within 12 hr after birth along with vaccination at normal schedule; 0, 1, 6 mo. Then after 9-18 mo of life, infant should be re-
evaluated to detect HBV infection by checking HBs Ag & anti-HBs
antibodies:-  If the result is positive for anti-HBs → the child is immune.
 If the result is positive for HBs Ag only → the parent should be
counseled and the child evaluated by pediatric gastroenterologist.
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 If the result is negative for both HBs Ag & anti-HBs → 2nd complete
hepatitis B vaccine series should be administered, followed by testing for anti-HBs to determine if subsequent doses are needed. Hepatitis C It has marked genetic heterogeneity that permits it to escape the host immune system. C.M. I.P. is ≈ 8 wk. Acute HCV infection cause an acute illness which typically the least severe of all hepatotropic virus infections and the
onset tends to be insidious.
Cx. HCV is the most likely of all hepatotropic virus to cause chronic
infection with a sequelae similar to those of HBV, i.e. cirrhosis, ESLD or
HCC, as well as it may cause small vessel vasculitis.
PCR; for viral RNA in blood is very sensitive & specific for HCV as it can detect the virus within days of infection. It also useful in monitoring for the response to Rx.  Serology; anti-HCV is neither protective nor confirmatory Ab because it has many false +ve & -ve results.  LFT; ALT & AST are typically fluctuating in HCV infection which does not correlate with the degree of hepatic damage.  Liver biopsy is the only mean to assess the degree of hepatic damage e.g. hepatic fibrosis (which may be required before Rx). Rx. It is usually restricted to adults; however, Peg-interferon & Ribavirin are the most effective therapy for HCV type 2 & 3 (but not type 1).
The goal of Rx is to achieve sustained viral response which defined by the absence of viremia for 6 mo after stopping the medications. Pv. There is neither vaccine nor Ig specific for HCV; however, the
immunization against HAV and HBV will prevent super-infection with this virus which ↑ risk of severe liver damage. Pg. Children with HCV are generally do better than adults, but patients
should be screened annually for HCC by US & α-FP.
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Hepatitis D
It is defective virus that requires HBV for infection, either as coinfection
or super-infection. It has similar manifestations to other hepatotropic viruses but more severe that may cause ALF or chronic
Inv. Anti-HDV IgM for acute & Anti-HDV IgG for chronic or past
infection. Rx. Similar to that of HBV. Pv. Immunization against HBV. Hepatitis E It is similar to HAV in many aspects but it more severe & mainly affect adolescents & adults with high mortality among pregnant women. It can occur as epidemics. It can cause ALF but not chronic illness. I.P. of ≈ 6 wk.
Inv. Anti-HEV IgM for acute & Anti-HEV IgG for past infection. PCR for
viral RNA also can be detected in the blood or stool. Rx. Similar to that of HAV. Pv. Vaccination of high risk groups.
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(Acute Liver Failure) Et. Idiopathic form accounts for 40-50% of cases in children. Otherwise, the most common cause of FHF are Hepatitis viruses as well as to other viruses e.g. EBV, HSV, CMV. Other causes include: autoimmune hepatitis, hepato-toxic drugs, chemicals, ischemia or hypoxia & metabolic
disorders. Path. FHF is a clinical syndrome resulting from massive necrosis of hepatocytes or from severe functional impairment in the synthetic, excretory, and detoxifying functions of liver. C.M. FHF can be the presenting feature of liver disease or it can
complicate a previously known liver disease. Hx. Progressive jaundice, fever, anorexia, fetor hepaticus, vomiting, and
abdominal pain. Ex. Hemorrhagic diathesis, ascites, the liver may be enlarged initially, but rapid ↓ in liver size without clinical improvement is an ominous sign.  CNS manifestations in FHF (Hepatic Encephalopathy) usually pass into 4 stages:- Stage 1: Lethargy, euphoria, reversal of day-night sleeping. Stage 2: Drowsiness, inappropriate behavior, agitation, asterixis. Stage 3: Stupor but arousable, hyper-reflexia, Babiniski +ve, asterixis. Stage 4: Coma, flaccidity, areflexia, no asterixis. Pathogenesis of HE is due to ↓ hepatic clearance of substances that is normally metabolized by the liver → ↑ serum ammonia (although it can occur with
normal level of ammonia), ↑ false neurotransmitters, ↑ amines, ↑ γ-
aminobutyric acid (GABA) receptor activity, or ↑ circulating levels of endogenous benzodiazepine-like compounds. Inv.
TSB; ↑ direct & indirect bilirubin levels.  Aminotransferase levels (ALT & AST) are initially very high, but then ↓
as the patient deteriorates.  PT, PTT, & INR are prolonged, even after vit K administration.
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Metabolic disturbances, especially hypoglycemia & hyperammonemia, also hypokalemia, hyponatremia, metabolic acidosis, & respiratory alkalosis.  Definition (Criteria) of FHF involve 2 conditions:- 1. Biochemical evidence of acute liver injury (usually <8 wk duration), i.e. no evidence of chronic liver disease. 2. Hepatic-based coagulopathy defined as either; presence of clinical
hepatic encephalopathy + PT >15 sec or INR >1.5 (not corrected by vit K), or PT >20 sec or INR >2 regardless of presence of clinical hepatic
encephalopathy. Rx. It includes admission to the ICU with continuous monitoring of vital
signs. Identifiable causes of FHF should recieve specific Rx, otherwise therapy of FHF is mainly supportive.
The following factors should be controlled because they may precipitate
or aggravate HE:- 1. Glucose & electrolytes disturbances; correct or prevent hypoglycemia
and hyponatremia. Parenteral supplementation of calcium, magnesium and phosphorus may be required.
2. Hypovolemia should be corrected by cautious infusions of isotonic fluids and blood products to prevent hypervolemia due to renal dysfunction (Hepatorenal syndrome). Hemofiltration can be used to
treat fluid overload & ARF. 3. Cerebral edema can be managed by ET intubation & hyperventilation, especially in patient with advanced coma (because corticosteroids & mannitol are ineffective). 4. Avoided sedation, in contrast, Flumazenil (benzodiazepine antidote) &
N-Acetylcysteine (acetaminophen antidote) can be given. 5. Hyperammonemia can be treated by or eliminate protein intake
and use of purgatives e.g. Lactulose, a nonabsorbable disaccharide, is
metabolized to organic acids by colonic bacteria. It given in a dose 10-
50 ml every 2-4 hr, orally or by NG tube that is sufficient to cause several acidic, loose bowel motions, or it can be diluted with water &
given as retention enema every 6 hr. Lactulose is probably lowers blood
ammonia levels through decreasing microbial ammonia production and through trapping of ammonia in acidic intestinal contents.
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Non-absorbable Antibiotics e.g. rifaximin or neomycin, orally or
rectally are more effective in reduction of enteric bacteria that responsible for ammonia production. 6. Costipation should be treated by Lactulose as above. 7. Coagulopathy must be treated by administration of vit K, FFP,
cryoprecipitate, factor 8, or platelets. Plasmapheresis may also
8. GIT bleeding can be prevented by prophylactic use of proton pump inhibitors. 9. Infection should be monitored closely anywhere in the body & treated aggressively. The most common organisms in FHF are Staph. aureus & Staph. epidermidis.
10. Other methods of management of FHF include:-  Temporary liver support continues to be evaluated as a bridge for liver transplantation or regeneration. Liver support is either by liver dialysis
with albumin-containing dialysate, or by biologic devices involve liver
cell lines or porcine hepatocytes.  Liver transplantation can be lifesaving in advanced stages of hepatic
coma. It is done either as orthotopic or reduced-size allografts from a
living donor. Pg. It depends on the cause of FHF & stage of HE. It is most favorable with acetaminophen poisoning & viral hepatitis
(especially HAV), whereas it is most severe with the idiopathic form
which may be complicated with aplastic anemia (≈ 10%) which usually fatal. The overall mortality with supportive care alone exceeds 60%, but patients who recover usually do not develop cirrhosis or chronic liver
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(Hepatolenticular Degeneration) Et. WD is an AR disease due to genetic mutation on chromosome 13 which encodes a copper transporting protein. Path. The copper transporting P-type ATPase (ATP7B) is mainly present in liver, it has 2 functions; excretion of copper in the bile and
incorporation of copper into the ceruloplasmin. Therefore, absence of this enzyme result in accumulation of cupper in the liver which when
become overloaded, it redistribute to the other organs → toxic effects. C.M. The age of onset has very wide range according to the degree of mutation, as early as 2–3 yr & as late as 80 yr of age. Forms of Wilsonian hepatic disease include: asymptomatic
hepatomegaly +/_ splenomegaly, subacute or chronic hepatitis, and
fulminant hepatic failure (which mainly affect female patients!). Chronic liver disease may be present as; cryptogenic cirrhosis, portal
hypertension, ascites, edema, variceal bleeding, or other effects of hepatic
dysfunction e.g. delayed puberty, amenorrhea, coagulation defect…etc.
The younger the patient (especially <5 yr), the more likely hepatic
manifestations will be the predominant (as above), whereas after 20 yr, neurologic manifestations will predominate e.g. behavioral changes, deterioration in school performance, intention tremor, dysarthria, dystonia, or lack of motor coordination. Kayser-Fleischer ring of iris is
always present in patients with neurologic symptoms. Psychiatric
manifestations include: depression, anxiety, or psychosis. Coombs-negative hemolytic anemia may be the initial manifestation of WD which usually correspond with the release of large amounts of copper from damaged hepatocytes. This also may cause Fanconi
syndrome +/_ progressive RF. Unusual manifestations of WD include: arthritis, cardiomyopathy, and endocrinopathies (especially hypoparathyroidism). Note: WD should be considered in any child or adolescent present with: unexplained acute or chronic liver disease, neurologic symptoms of unknown cause, acute hemolysis, psychiatric illnesses, behavioral changes, Fanconi syndrome, or bone disease with a tendency to familial patterns.
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Inv. · Serum Ceruloplasmin level (<20 mg/dL) due to its shorter half-life
because of failure of copper to incorporate into ceruloplasmin. Note: Ceruloplasmin level may be falsely in acute inflammation and in states
of elevated estrogen level. · Serum Copper level may be in early disease, whereas urinary copper
excretion is >100 μg/day. In equivocal cases, it can be accentuated by chelation with d-penicillamine. · Liver biopsy is of value in determining the extent and severity of liver
disease and for measuring the hepatic copper content (>250 μg/g dry wt) unless patient develop liver cirrhosis, because it will be unreliable. · Kayser-Fleischer rings demonstration requires a slit-lamp examination by an ophthalmologist. · Family members may also require screening by all the above tests (except liver biopsy); as well as by genetic screening e.g. linkage analysis or direct DNA mutation analysis. Rx. Once Dx has been made, Rx needs to be life long by the following:- · Restrict diet with high copper e.g. liver, shellfish, nuts, & chocolate. · Copper-chelating agents include: D-penicillamine or Trientine (Trien) (TETA), both orally in dose 20 mg/kg/day ÷ 2. Ammonium tetrathio-molybdate is mainly used for those with neurologic disease. SE of D-Penicillamine: 10-50% of patients initially treated with penicillamine for neurologic symptoms have worsening of their condition. Others may develop hypersensitivity reactions (Goodpasture synd, SLE, polymyositis),
aplastic anemia, nephrosis, and vitamin B6 & zinc deficiency. · Zinc, orally 25 mg × 3 daily is able to impair gastrointestinal absorption of copper. It can be used as adjuvant or maintenance therapy as well as a primary therapy in presymptomatic persons. · Antioxidants (vit E & curcumin) may also have a role as adjunctive Rx. · Liver transplantation is curative for WD. Pg. WD is fatal in untreated patients. The response to Rx is depend on the time of initiation of therapy and individual response to chelation. Early Rx can result in marked improvement of hepatic & neurologic
symptoms as well as disappearance of Kayser-Fleischer rings. Pv. WD expression can be prevented in asymptomatic siblings by early institution of chelation or zinc therapy.