Intestinal Motility Disorders

The phrase "intestinal motility disorders" applies to abnormal intestinal contractions, such as spasms and intestinal paralysis, and is used to describe a variety of disorders in which the gut has lost its ability to coordinate muscular activity because of endogenous or exogenous causes. ^{[1, 2, 3]} Intestinal motility disorders can be categorized as upper gastrointestinal (GI) or lower GI motility disorders.

Upper GI motility disorders include the following ^[4] :

• Achalasia: Loss of esophageal peristalsis, with failure of the lower esophageal sphincter (LES) to relax
• Gastroesophageal reflux disease (GERD): Reflux of gastric contents from the stomach into the esophagus, causing symptoms or resulting in mucosal damage
• Gastroparesis: Delayed gastric emptying without evidence of mechanical obstruction, resulting in upper GI symptoms such as nausea, vomiting, early satiety, and abdominal pain
• Biliary dyskinesia: Gallbladder motility disorder that results in abdominal pain in the absence of gallsones, sludge, or microlithiasis

Lower GI motility disorders include the folllowing ^{[4, 5]} :

• Irritable bowel syndrome (diarrhea-predominant, constipation-predominant, and mixed): Chronic abdominal pain with change in bowel habits (according to Rome criteria) without an organic cause or the symptoms
• Colonic inertia: Delayed passage of stool through the colon without abnormalities in the defecation process, which results in constipation
• Intestinal pseudo-obstruction (Ogilvie syndrome): Acute severe colonic dilatation without an anatomic obstruction or process
• Pelvic floor dyssynergia: A functional obstruction from impaired relaxation of the puborectalis muscle, the external anal sphincter, or both, resulting in a decrease in the anorectal angle and causing difficulty in evacuation of stool
• Hirschsprung disease: Also known as congenital aganglionic megacolon, in which the distal section of the colon that is missing ganglion cells fails to relax, causing a functional obstruction
• Fecal incontinence: Involuntary leakage of stool

Upper intestinal motlity disorders may manifest as the following:

• Abdominal distention

• Severe abdominal colicky pain

• GERD

• Intractable or recurrent nausea or vomiting

Lower intestinal motility disorders may manifest as the following:

• Recurrent obstruction

• Severe abdominal colicky pain

• Severe constipation

• Diarrhea

• Stool incontinence

Coordinated movements of the stomach and intestines are required to digest and propel intestinal contents along the digestive tract. The complex patterns of contraction and relaxation necessary for proper motility of the gastrointestinal (GI) tract are generated in the nerves and muscles within the GI walls.

Every day, at any time, many factors can influence GI motility (eg, physical exercise, emotional distress). The pathogenesis of primary intestinal motility disorders probably is multifactorial, but neither biochemical abnormality nor structural abnormality has been demonstrated commonly, except in some forms of intestinal pseudo-obstruction. More recently, there is evidence that low-grade mucosal inflammation and immune activation (particularly with mast cell involvement) in association with impaired epithelial barrier function and aberrant neuronal sensitivity may play a role in functional GI disorders. ^[6]

Although the overall structural organization is similar throughout the digestive tract, each part has distinct motor activities. The musculature of the digestive tract has either extrinsic innervation (both sympathetic and parasympathetic) or intrinsic innervation (Auerbach plexus or myenteric plexus).

Intrinsic innervation is fundamental to coordinating GI motor activity. A neural network branching between longitudinal and circular muscle layers of the GI tract constitutes intrinsic innervation. Another nervous intrinsic plexus in the GI tract (Meissner plexus or submucosal plexus) helps to modify mucosal absorption and secretion without influencing motility.

Random, unorganized motor activity with occasional peristaltic and antiperistaltic complexes occurs during feeding, and this allows gastric remixing of foods. After this, another motor activity occurs, which is more regular, and this begins the peristaltic waves (ie, contractions of the circular musculature of the small intestine) that allow progression of undigested food through the intestines.

These events happen because the gastric pacemaker area, which originates electric slow waves with a frequency of 3 cycles per minute, occurs at the junction between the body and the antrum of the stomach. These electric waves, called migrating myoelectric complexes, determine the frequency of muscular contractions in the antral and pyloric areas through electromechanical coupling.

Migrating myoelectric complexes regulate gastric emptying and move gastric contents distally. Every 90 minutes, a cluster of migrating myoelectric complexes arises in the stomach and migrates distally beyond the ileum. Vagal function and the release of nitric oxide, vasoactive intestinal polypeptide, motilin, and nutrients of the meal and other enterohormones also affect GI motility.

Knowles and Martin attempted to define a novel classification for intestinal motility disorders, ^[7] in which these conditions are categorized as well-defined entities, entities with a variable dysfunction-symptom relation, questionable entities, and entities associated with behavioral disorders.

Well-defined entities in the Knowles-Martin classification include the following:

• Delayed colonic transit: Slow transit constipation (eg, enteric neuropathy, enteric myopathy, Parkinson disease, endocrine disorders, spinal injury); the impairment of gastric motility in Parkinson disease patients, particularly in those with motor complications (42%), may be due in part to the effect of L-dopa on gastric dopaminergic receptors ^[8] ; in patients with spina bifida and spinal cord injuries, altered histology of the enteric nervous system as well as myenteric plexus neuronal loss and decreased nerve fiber density may play a major role in intestinal motility ^[9]

• Dilated colon (diffuse or segmental) - Ogilvie syndrome, megacolon

• Absent rectoanal inhibitory reflex: Hirschsprung disease

Entities with a variable dysfunction-symptom relation include the following:

• Abnormally low anal canal pressure fecal incontinence (eg, diabetes mellitus, spinal injury)

Questionable entities include the following:

• Accelerated transit bile salts

• Short bowel

• Rare endocrine and metabolic disorders

Entities associated with behavioral disorders include the following:

• Impaired pelvic floor relaxation, prolonged storage in the rectosigmoid, outlet delay, anismus

• Avoidance of defecation, functional fecal retention (eg, poor pelvic floor training, poor diet, fear of pain, learned suppression)

Causes of intestinal motility disorders appear to be multifactorial, and only a few have been detected.

Achalasia

Studies on primary achalasia suggest it is primarily an autoimmune disorder. Worldwide, the most common cause of secondary achalasia is Trypanosoma cruzi infection (Chagas disease); another cause is iatrogenic (ie, surgical error in forming fundoplication or gastric banding). ^[10] Systemic diseases that infiltrate the lower esophageal sphincter can cause a pseudoachalasia, such as tumors of the gastroesophageal junction or gastric cardia and amyloidosis.

Gastroesophageal reflux disease

Many different factors can attribute to gastroesophageal reflux disease (GERD). These include but are not limited to transient lower esophageal relaxations, weak lower esophageal sphincter, delayed gastric emptying, increased gastric acid production, hiatal hernia, and obesity. ^[11]

Gastroparesis

The most common etiologies of gastroparesis noted in tertiary care centers include idiopathic (36%), diabetes mellitus (29%), and postsurgical (13%). ^[12] Less common etiologies include postviral and opioid-induced gastroparesis. Rare causes include paraneoplastic syndrome, Parkinson disease, amyloidosis, and scleroderma.

Biliary dyskinesia

The exact etiology of biliary dyskinesia is unknown.

Irritable bowel syndrome

The causes of irritable bowel syndrome (IBS) remain unknown. According to some reports, the small intestine and colon of patients with IBS are more sensitive and reactive to mild stimuli than usual. IBS may be related to the immature status of muscles and nerves in the intestinal wall of affected persons.

Colonic inertia

The underlying etiology of colonic inertia appears to be dysfunction of the enteric nerve plexus. It has been suggested that patients have a decreased number or complete absence of interstitial cells of Cajal. ^[13]

Intestinal pseudo-obstruction (Ogilvie syndrome)

The exact etiology of acute colonic pseudo-obstruction is unknown. It has been hypothesized that a dysregulation of nerve impulses in the enteric nervous system results in a large bowel obstruction without an actual physical obstruction. The inciting event is most commonly postsurgical, cardiopulmonary conditions, metabolic disorders, and trauma, among many other reported causes. ^[14]

Pelvic floor dyssynergia

Pelvic floor dyssynergia and pelvic floor dysfunction are caused by impaired relaxation of the external anal sphincter, impaired relaxation of the puborectalis muscle, or decreased propulsion of stool through the colon. Similar to other motility disorders, there is an underlying dysfunction of nerve conduction. Defecation specifically involves coordination of the enteric, parasympathetic, and sympathetic nervous systems.

Hirschsprung disease

Hirschsprung disease is a congenital disorder that results from absence of ganglion cells in a portion of the colon, most commonly the rectosigmoid colon. This is caused by a failure of neural crest cells to migrate during fetal development. Several genetic mutations have also been found to be associated with Hirschsprung disease. ^[15]

Fecal incontinence

Aging, dementia, stroke, Parkinson disease, spinal cord injuries, rectal tears during birthing, diabetes, surgical complications, and neuromuscular disorders (eg, myasthenia gravis) may cause fecal incontinence.

Occasionally, fecal incontinence may occur after ingestion of certain foods. Sugars, insoluble fibers, and starches (except rice) are broken down in the intestines, forming a variable amount of gas that must be expelled. Most people who have lactase deficiency cannot digest lactose, a sugar common in several foods (eg, milk, cakes). People who have lactose deficiency may experience uncontrolled liquid diarrhea after lactose ingestion.

Constipation

Constipation commonly has several causes, either primary or secondary. The most frequent of these are the following:

• Diet that is very poor in fiber and high in animal fats and refined sugars

• Pregnancy

• Psychological constipation related to lifestyle changes (eg, travel, a new job, or divorce), in which the patient ignores the urge to defecate

• Hypothyroidism

• Electrolyte imbalance, especially if it involves Ca⁺⁺ or K⁺

• Tumors producing mechanical compression on an intestinal tract, either internally or externally

• Nervous system injuries

• Intoxication from lead, mercury, phosphorus, or arsenic

• Constipation also may be secondary to rhagades (anal fissures) and piles.

Genetic factors

In a retrospective study investigating the association between mitochondrial disorders and chronic intestinal pseudo-obstruction (CIP) in 80 patients, Amiot et al determined that 15 patients (19% of the study cohort) had mitochondrial defects, including mutations in the thymidine phosphorylase gene (5 patients), the DNA polymerase-gamma gene (5 patients), and tRNA(leu(UUR)) (2 patients); 3 of the patients had no identifiable genetic defects. ^[16] Extradigestive symptoms occurred in all 15 patients.

Unlike other CIP patients, patients in whom the condition was associated with a mitochondrial defect tend to require frequent and long-term parenteral nutrition. ^[16] Because of the frequent occurrence of digestive and neurologic complications, these patients also had a high incidence of premature death. The authors suggested that mitochondrial defects are an important cause of CIP and recommended that CIP patients be tested for such defects, particularly those with severe CIP who experience associated neurologic symptoms.

According to some epidemiologic reports, as many as 30 million Americans have intestinal motility disorders. Available data from the medical literature indicate that worldwide, 30%-45% of all gastrointestinal conditions are referable to intestinal motility disorders.

When intestinal motility disorders are idiopathic and not related to either malignancies or systemic diseases, morbidity is minimal and mortality from complications is low (1%-1.5%); complications usually occur in patients with intestinal pseudo-obstruction.

Persons of any age group may be affected, depending on the specific intestinal motility disorder. For example, IBS occurs more frequently in people aged 20-40 years, whereas intestinal pseudo-obstruction may occur in either newborns or elderly patients. Most patients are female, with a female-to-male ratio of 2.8:1. Primary intestinal motility disorders are most common in white persons and are usually thought to be related to diet.

Primary intestinal motility disorders or disorders that are not secondary to malignancy or debilitating pathology have a good prognosis. According to many reports, the prognosis is excellent for patients with irritable bowel syndrome and mild fecal incontinence.

The prognosis is worse for patients with intestinal pseudo-obstruction, which has a high mortality.

Complications

Complications of intestinal motility disorders vary greatly, depending on the specific type of disorder under consideration.

Intestinal pseudo-obstruction is often associated with a high mortality (15%-30%), in most cases due to delayed diagnosis.

Constipation may have a severe complication, impaction. If this condition is not recognized early, the patient may die. Impaction is the collection of dry and hardened feces in the rectum or colon. Symptoms of impaction may be similar to those of constipation or may be unrelated to the gastrointestinal system.

If abdominal distention occurs, movements of the diaphragm are compromised and cause insufficient aeration with subsequent hypoxia and left ventricular dysfunction. In addition, hypoxia can precipitate angina or tachycardia. When a vasovagal response begins, the patient may have hypotension. Patients with impaction may experience vomiting, diarrhea, and resultant dehydration. They may present in an acutely confused and disoriented state, with tachycardia, fever, and altered blood pressure.

Irritable bowel syndrome is not usually associated with complications. Fecal incontinence may cause psychological problems in affected patients.