Chronic intestinal pseudo-obstruction comprises a group of disorders characterized by signs and symptoms of intestinal obstruction in the absence of an anatomic lesion. Pseudo-obstruction can occur as a primary disease or be secondary to a large number of conditions that can transiently or permanently alter bowel motility. Pseudo-obstruction represents a wide spectrum of pathologic disorders from abnormal myoelectric activity to abnormalities of the nerves (intestinal neuropathy) or musculature (intestinal myopathy) of the gut. The organs involved can include the entire gastrointestinal tract or be limited to certain components, such as the stomach or colon. The distinctive pathologic abnormalities are considered together because of their clinical similarities.

Most congenital forms of pseudo-obstruction occur sporadically. A few clusters of autosomal dominant or recessive patients have been reported as having cases associated with abnormal gut muscle or nerves. Patients with autosomal dominant forms of pseudo-obstruction have variable expressions of the disease. Acquired pseudo-obstruction can follow episodes of acute gastroenteritis, presumably resulting in injury to the myenteric plexus.

In congenital pseudo-obstruction, abnormalities of the muscle or nerves can be demonstrated in most cases. In muscular disease, the outer longitudinal muscle layer is replaced by fibrous material. In neuronal disease, there may be disorganized ganglia, hypoganglionosis, or hyperganglionosis. Abnormalities in the interstitial cells of Cajal (potential gut pacemaker) have been demonstrated in some children and mitochondrial defects have been found in others. Genetic defects have been identified in the transcription factor SOX10, the DNA polymerase gamma gene (POLG), and a locus on chromosome 8.

Constipation is defined by a delay or difficulty in defecation present for 2 weeks or longer and significant to cause distress to the patient. Another approach to the definition is noted in Table 324-2. Functional constipation, also known as idiopathic constipation or fecal withholding, can usually be differentiated from constipation secondary to organic causes on the basis of a history and physical examination (Chapter 21.4). Unlike anorectal malformations and Hirschsprung disease, functional constipation typically starts after the neonatal period. Usually, there is an intentional or subconscious withholding of stool. An acute episode usually precedes the chronic course. The acute episode may be a dietary change from human milk to cow’s milk, secondary to the change in protein:carbohydrate ratio or an allergy to cow’s milk. The stool becomes firm, smaller, and difficult to pass, resulting in anal irritation and often an anal fissure. In toddlers, coercive or inappropriately early toilet training is a factor that can initiate a pattern of stool retention. In older children, retentive constipation can develop after entering a situation that makes stooling inconvenient such as school. Because the passage of bowel movements is painful, voluntary withholding of feces to avoid the painful stimulus develops.

When children have the urge to defecate, typical behaviors include contracting the gluteal muscles by stiffening the legs while lying down, holding onto furniture while standing, or squatting quietly in corners, waiting for the call to stool to pass. The urge to defecate passes as the rectum accommodates to its contents. A vicious cycle of retention develops as increasingly larger volumes of stool need to be expelled. Caregivers might misinterpret these activities as straining, but it is withholding behavior. In functional constipation, daytime encopresis is common, and some children have a history of blood in the stool noted with the passage of a large bowel movement. Findings suggestive of underlying pathology include failure to thrive, weight loss, abdominal pain, vomiting, or persistent anal fissure or fistula.

The physical examination often demonstrates a large volume of stool palpated in the suprapubic area; rectal examination demonstrates a dilated rectal vault filled with guaiac-negative stool. The presence of a hair tuft over the spine or spinal dimple, or failure to elicit a cremasteric reflex or anal wink suggests spinal pathology. A tethered cord is suggested by decreased or absent lower leg reflexes. Spinal cord lesions can occur with overlying skin anomalies. Urinary tract symptoms include recurrent urinary tract infection and enuresis. Children with no evidence of abnormalities on physical examination rarely require radiologic evaluation.

In refractory patients (intractable constipation), specialized testing should be considered to rule out conditions such as hypothyroidism, hypocalcemia, lead toxicity, celiac disease, and allergy testing. Colonic transit studies using radio-opaque markers or scintigraphy techniques may be useful. Selected children can benefit from MRI of the spine to identify an intraspinal process, motility studies to identify underlying myopathic or neuropathic bowel abnormalities, or a barium enema to identify structural abnormalities. Anorectal motility studies can demonstrate a pattern of paradoxical contraction of the external anal sphincter during defecation, which can be treated by behavior modification. Colonic motility can guide therapy in refractory cases, demonstrating segmental problems that might require surgical intervention.

Therapy for functional constipation includes patient education, relief of impaction, and softening of the stool (Chapter 21.4). The parents must understand that soiling associated with overflow incontinence is associated with loss of normal sensation and not a willful act. A regular bowel training program, including sitting on the toilet for 5-10 min after meals and keeping track of the frequency of bowel movements, is often helpful in establishing a regular bowel habit. If an impaction is present on the initial physical examination, an enema is usually required to clear the impaction while bowel softeners are started as maintenance medications. Typical regimens include the use of polyethylene glycol preparations, lactulose, or mineral oil. Prolonged use of stimulants such as senna or bisacodyl should be avoided. Children with behavioral problems that are interfering with successful treatment might benefit from a referral to a mental heath care provider. Maintenance therapy is generally continued until a regular bowel pattern has been established and the association of pain with the passage of stool is abolished. Children with spinal problems can be successfully managed with low volumes of fluid through a cecostomy or sigmoid tube.

Hirschsprung disease, or congenital aganglionic megacolon, is a developmental disorder (neurocristopathy) of the enteric nervous system, characterized by the absence of ganglion cells in the submucosal and myenteric plexus. It is the most common cause of lower intestinal obstruction in neonates, with an overall incidence of 1 in 5,000 live births. The male:female ratio for Hirschprung disease is 4 : 1 for short-segment disease and closer to 1 : 1 as the length of the involved segment increase. Prematurity is uncommon.

There is an increased familial incidence in long-segment disease. Hirschsprung disease may be associated with other congenital defects, including Down, Goldberg-Shprintzen, Smith-Lemli-Opitz, Shah-Waardenburg, cartilage-hair hypoplasia, and congenital hypoventilation (Ondine’s curse) syndromes and urogenital or cardiovascular abnormalities. Hirschsprung disease has been seen in association with microcephaly, mental retardation, abnormal facies, autism, cleft palate, hydrocephalus, and micrognathia.

Clinical Manifestations

Hirschsprung disease is usually diagnosed in the neonatal period secondary to a distended abdomen, failure to pass meconium, and/or bilious emesis or aspirates with feeding intolerance. In 99% of healthy full-term infants, meconium is passed within 48 hr of birth. Hirschsprung disease should be suspected in any full-term infant (the disease is unusual in preterm infants) with delayed passage of stool. Some neonates pass meconium normally but subsequently present with a history of chronic constipation. Failure to thrive with hypoproteinemia from protein-losing enteropathy is a less common presentation because Hirschsprung disease is usually recognized early in the course of the illness. Breast-fed infants might not suffer disease as severe as formula-fed infants.

Failure to pass stool leads to dilatation of the proximal bowel and abdominal distention. As the bowel dilates, intraluminal pressure increases, resulting in decreased blood flow and deterioration of the mucosal barrier. Stasis allows proliferation of bacteria, which can lead to enterocolitis (Clostridium difficile, Staphylococcus aureus, anaerobes, coliforms) with associated diarrhea, abdominal tenderness, sepsis and signs of bowel obstruction. Early recognition of Hirschsprung disease before the onset of enterocolitis is essential in reducing morbidity and mortality.

Hirschsprung disease in older patients must be distinguished from other causes of abdominal distention and chronic constipation (Table 324-3 and Fig. 324-1). The history often reveals constipation starting in infancy that has responded poorly to medical management. Fecal incontinence, fecal urgency, and stool-withholding behaviors are usually not present. The abdomen is tympanitic and distended, with a large fecal mass palpable in the left lower abdomen. Rectal examination demonstrates a normally placed anus that easily allows entry of the finger but feels snug. The rectum is usually empty of feces, and when the finger is removed, there may be an explosive discharge of foul-smelling feces and gas. The stools, when passed, can consist of small pellets, be ribbon-like, or have a fluid consistency, unlike the large stools seen in patients with functional constipation. Intermittent attacks of intestinal obstruction from retained feces may be associated with pain and fever. Urinary retention with enlarged balder or hydronephrosis can occur secondary to urinary compression.

Table 324-3 DISTINGUISHING FEATURES OF HIRSCHSPRUNG DISEASE AND FUNCTIONAL CONSTIPATION

VARIABLE	FUNCTIONAL	HIRSCHSPRUNG DISEASE
HISTORY
Onset of constipation	After 2 yr of age	At birth
Encopresis	Common	Very rare
Failure to thrive	Uncommon	Possible
Enterocolitis	None	Possible
Forced bowel training	Usual	None
EXAMINATION
Abdominal distention	Uncommon	Common
Poor weight gain	Rare	Common
Rectum	Filled with stool	Empty
Rectal Examination	Stool in rectum	Explosive passage of stool
Malnutrition	None	Possible
INVESTIGATIONS
Anorectal manometry	Relaxation of internal anal sphincter	Failure of internal anal sphincter relaxation
Rectal biopsy	Normal	No ganglion cells, increased acetylcholinesterase staining
Barium enema	Massive amounts of stool, no transition zone	Transition zone, delayed evacuation (>24 hr)

Figure 324-1 Barium enema in a 14 yr old boy with severe constipation. The enormous dilatation of the rectum and distal colon is typical of acquired functional megacolon.

In neonates, Hirschsprung disease must be differentiated from meconium plug syndrome, meconium ileus, and intestinal atresia. In older patients, the Currarino triad must be considered, which includes anorectal malformations (ectopic anus, anal stenosis, imperforate anus), sacral bone anomalies (hypoplasia, poor segmentation), and presacral anomaly (anterior meningoceles, teratoma, cyst).

Diagnosis

Rectal suction biopsy is the gold standard for diagnosing Hirschsprung disease. The biopsy material should contain an adequate amount of submucosa to evaluate for the presence of ganglion cells. To avoid obtaining biopsies in the normal area of hypoganglionosis, which ranges from 3 to 17 mm in length, the suction rectal biopsy should be obtained no closer than 2 cm above the dentate line. The biopsy specimen should be stained for acetylcholinesterase to facilitate interpretation. Patients with aganglionosis demonstrate a large number of hypertrophied nerve bundles that stain positively for acetylcholinesterase with an absence of ganglion cells.

Anorectal manometry measures the pressure of the internal anal sphincter while a balloon is distended in the rectum. In normal patients, rectal distention initiates relaxation of the internal anal sphincter in response to rectal distention with a balloon. In patients with Hirschsprung disease, the internal anal sphincter fails to relax in response to rectal distention. Although the sensitivity and specificity can vary widely, in experienced hands, the test can be quite sensitive. The test, however, can be technically difficult to perform in young infants. A normal response in the course of manometric evaluation precludes a diagnosis of Hirschsprung disease; an equivocal or paradoxical response requires a repeat motility or rectal biopsy.

An unprepared contrast enema is most likely to aid in the diagnosis in children older than 1 mo because the proximal ganglionic segment might not be significantly dilated in the first few weeks of life. Classic findings are based on the presence of an abrupt narrow transition zone between the normal dilated proximal colon and a smaller-caliber obstructed distal aganglionic segment. In the absence of this finding, it is imperative to compare the diameter of the rectum to that of the sigmoid colon, because a rectal diameter that is the same as or smaller than the sigmoid colon suggests Hirschsprung disease. Radiologic evaluation should be performed without preparation to prevent transient dilatation of the aganglionic segment. As many as 10% of newborns with Hirschsprung disease have a normal contrast study. Twenty-four hour delayed films are helpful in showing retained contrast (Fig. 324-2). If significant barium is still present in the colon, it increases the suspicion of Hirschsprung disease even if a transition zone is not identified. Barium enema examination is useful in determining the extent of aganglionosis before surgery and in evaluating other diseases that manifest as lower bowel obstruction in a neonate. Full-thickness rectal biopsies can be performed at the time of surgery to confirm the diagnosis and level of involvement.

Figure 324-2 Lateral view of a barium enema in a 3 yr old girl with Hirschsprung disease. The aganglionic distal segment is narrow, with distended normal ganglionic bowel above it.

Intestinal neuronal dysplasia (IND) describes different quantitative (hypo- or hyperganglionosis) and qualitative (immature or heterotropic ganglion cells) abnormalities of the myenteric and/or submucous plexus. The typical histology is that of hyperganglionosis and giant ganglia. Type A occurs very rarely and is characterized by congenital aplasia or hypoplasia of the sympathetic innervation. Patients present early in the neonatal period with episodes of intestinal obstruction, diarrhea, and bloody stools. Type B, which accounts for >95% of cases, is characterized by malformation of the parasympathetic submucous and myenteric plexus with giant ganglia and thickened nerve fibers, increased acetylcholinesterase staining, and isolated ganglion cells in the lamina propria. IND type B mimics Hirschsprung disease, and patients present with chronic constipation.

Clinical manifestations include abdominal distention, constipation, and enterocolitis. Various lengths of bowel may be affected from segmental to the entire intestinal tract. IND has been observed in an isolated form and proximal to an aganglionic segment. Other intra- and extraintestinal manifestations are present in patients with IND. It has been reported in all age groups, most commonly in infancy, but is also seen in adults who have had constipation not dating back to childhood.

Associated diseases and conditions include Hirschsprung disease, prematurity, small left colon syndrome, and meconium plug syndrome. Studies have identified a deficiency in substance P in patients with IND. No mutations in the coding regions of the RET, GDNF, EDNRB, or EDN3 genes have been identified.

Management includes that for functional constipation and, if unsuccessful, surgery is indicated.

Superior mesenteric artery syndrome results from compression of the 3rd duodenal segment by the artery against the aorta. Weight loss from malnutrition or catabolic states can cause mesenteric fat depletion, which collapses the duodenum within a narrowed aortomesenteric angle. Other etiologies include extra-abdominal compression (e.g., body cast) and mesenteric tension, as can occur from ileo-anal pouch anastomosis.

Symptoms include intermittent epigastric pain, anorexia, nausea, and vomiting. Associated factors include thin body habitus, prolonged bed rest, abdominal surgery, and exaggerated lumbar lordosis. Onset can be within weeks of a trigger, but some patients have chronic symptoms that evade diagnosis. A classic example is an underweight adolescent who begins vomiting 1-2 wk following scoliosis surgery.

The diagnosis is established radiologically by demonstrating a duodenal cutoff just right of midline along with proximal duodenal dilatation, with or without gastric dilatation. Although the upper gastrointestinal series remains a mainstay, modalities including CT, MR angiography, or ultrasound may be more appropriate if there is concern for other etiologies like malignancy. Upper endoscopy should be considered to rule out intraluminal pathology.

Treatment focuses on obstructive relief and nutritional rehabilitation. Lateral or prone positioning can shift the duodenum away from obstructing structures and allow resumption of oral intake. In such cases, prokinetic agents such as metoclopramide may be helpful. If repositioning is unsuccessful, patients require nasojejunal enteral nutrition past the obstruction or, if this is not tolerated, total parenteral nutrition. Rarely, patients with refractory courses require surgery to bypass the obstruction.