Rejy Joseph, MD and Robin D. Rothstein, MD
What is the migrating motor complex (MMC)?
The migrating motor complex is a cyclical pattern of gastrointestinal motility occurring during the fasting period that consists of three phases that repeat every 90 to 120 minutes. Phase I is a period of absent motor activity (motor quiescence) lasting 40 to 70 minutes. Phase II lasts 20 to 30 minutes and is characterized by irregular motor activity. Phase III consists of a 5- to 10-minute period of intense lumen-occluding contractions that begin in the body of the stomach and sequentially propagate aborally through the small intestine.
What physical finding is usually present in a scleroderma patient with gastrointestinal dysmotility?
What complications may occur in a scleroderma patient with small bowel involvement?
Malabsorption, pseudo-obstruction, pneumatosis cystoides intestinalis, bacterial overgrowth, and malnutrition.
True/False: The abnormalities in small bowel motility that may occur in scleroderma occur secondary to a myopathic process.
False. Both myopathic and neuropathic abnormalities are responsible. The neurologic changes typically occur first followed by myopathic alterations.
Subcutaneous octreotide has been used to manage small bowel motor complications of scleroderma. What is a common long-term complication of this therapy?
The development of biliary sludge and gallstones.
What effect does low dose octreotide have on small bowel motility as detected by intestinal manometry?
Stimulates phase III of the migrating motor complex. However, higher doses of octreotide actually inhibit gastrointestinal motility.
What developmental abnormality of the gastrointestinal tract may occur in children with familial pseudo-obstruction syndromes?
Intestinal malrotation or nonrotation.
In general, surgery is not performed in patients with chronic idiopathic intestinal pseudo-obstruction; however, surgery may be considered in certain circumstances. What surgical procedures are occasionally performed in these patients?
Placement of venting gastrostomy and/or jejunostomy tubes, ileostomy or colostomy, and intestinal transplantation.
What complication of gut dysmotility is associated with an increased risk of spontaneous bacterial peritonitis in patients with end-stage liver disease?
Small bowel dysmotility is associated with bacterial overgrowth that may lead to bacterial translocation resulting in systemic infection.
A 36-year-old man with short bowel syndrome as a result of vascular injury during an exploratory laparotomy presents with persistent foul-smelling diarrhea despite various dietary maneuvers and antidiarrheal agents. What small intestinal condition is likely to be responsible for the diarrhea?
Small intestinal bacterial overgrowth.
The use of proton pump inhibitors may further increase what complication in patients with chronic intestinal pseudo-obstruction?
Small intestinal bacterial overgrowth. While the hypochlorhydria caused by potent antisecretory agents does not generally result in clinically significant bacterial overgrowth (with clinically significant types of bacteria) in otherwise healthy individuals, it may in patients with chronic intestinal pseudo-obstruction.
List some causes of mechanical obstruction that may occur in patients with chronic intestinal pseudo-obstruction.
Adhesions from prior surgery or bezoars related to hypomotility.
What endocrine conditions may cause small intestinal dysmotility?
Diabetes mellitus, hypothyroidism, hyper- and hypoparathyroidism, and adrenal insufficiency.
When should antibiotics be considered for use in cases of chronic intestinal pseudo-obstruction?
Antibiotics may be considered if there is bacterial overgrowth and can be used on a rotational schedule to delay/prevent the development of antibiotic resistance.
What are nonendocrine causes of pseudo-obstruction?
Amyloidosis, paraneoplastic syndrome, connective tissue diseases (scleroderma), degenerative neuropathies, viral diseases, radiotherapy, and medications.
What medications are associated with the development of chronic intestinal pseudo-obstruction?
Narcotics, tricyclic antidepressants, phenothiazines, ganglionic blockers, calcium-channel blockers, and anti-Parkinson’s medications are a few of the more common medications associated with this condition.
What clinical tests are available to diagnose intestinal dysmotility?
First and foremost, it is essential to rule out mechanical obstruction. Nuclear scintigraphy may be used to evaluate transit through the stomach, small intestine, and colon. Stationary or ambulatory small bowel manometry may be performed using a water-perfused or solid-state catheter.
What features on small bowel manometry suggest myopathic or neuropathic causes of chronic intestinal pseudo-obstruction?
In myopathy, there are low amplitude contractions and in neuropathic conditions, there is organizational disarray of the phase III complex (intrinsic neuropathy) or fed pattern (extrinsic neuropathy).
Why is it important to differentiate mechanical obstruction from pseudo-obstruction and how is this best accomplished?
Treatment of the two conditions is significantly different. Barium contrast studies, including small bowel follow-through or enteroclysis, may indicate a transition point. The latter is the more sensitive of the two. CT enterography is also useful and has generally superseded barium contrast studies in the diagnosis of bowel obstruction. Small bowel manometry may also be helpful as patterns suggestive of mechanical obstruction have been described and include simultaneous or rapidly propagating clustered contractions and/or high amplitude, prolonged, or giant contractions.
What tumors and associated autoantibodies occur with paraneoplastic visceral neuropathy?
The most common tumor causing paraneoplastic visceral neuropathy is small cell cancer of the lung, which may also be associated with a generalized sensory neuropathy. Histologically, there may be degeneration of neurons and a lymphoplasmacytic infiltration in the bowel, but no evidence of tumor. Associated antibodies that can be detected in the serum are anti-Hu, aka ANNA-1 (type 1 antineuronal nuclear antibody).
What tests are useful for the diagnosis of bacterial overgrowth and what are their potential shortcomings?
Culture of small intestinal aspirate is the gold standard in the diagnosis of bacterial overgrowth; however, both false positives (contamination) and false negatives (difficulties in culturing anerobes) may occur. Alternatively, a 14C-xylose breath test, which measures expired CO2 production, can be used. However, it requires the use of radiolabeled material and is not widely available. Hydrogen breath testing using either glucose or lactulose as a substrate is also widely available and does not involve radiation; however, its sensitivity and specificity have been questioned.
What are the shortcomings of hydrogen breath tests?
Interpretation may be difficult in some cases when there are altered transit times. In these cases, the hydrogen peak occurring from SIBO may be difficult to discriminate from the normal peak from colonic bacteria. False negative results occur in patients with low bacterial counts or those who do not have hydrogen-generating bacteria (8%–20%).
What findings are suggestive of small bowel bacterial overgrowth on the breath hydrogen test?
An increase in breath hydrogen (usually > 20 ppm) expired during the first 2 hours of ingestion of substrate or an elevation of the fasting breath hydrogen (also usually > 20 ppm). The classical double-peak described in the lactulose hydrogen breath test is infrequently seen and does not appear to reliably distinguish small bowel bacterial overgrowth.
What measures could improve the reliability of breath testing for bacterial overgrowth?
Certain foods (bread, pasta, fiber) should be avoided prior to testing as they cause prolonged hydrogen secretion. Cigarette smoking or vigorous physical exercise may also affect hydrogen secretion and needs to be avoided for 2 hours prior to testing. Oral bacteria may lead to an early hydrogen peak; thus, pretest mouthwashing with an antiseptic should be considered.
What disturbances in small bowel motility may be seen in amyloidosis?
Dysmotility seems to correlate with the degree of amyloid deposition in the gut. Small bowel loops may be dilated and transit can be delayed. Small bowel motility studies may reveal findings consistent with either a myopathic or a neuropathic disturbance.
What small bowel motility abnormalities have been described in irritable bowel syndrome?
Most studies do not indicate any specific abnormality; however, some patients have discrete clustered contractions in the duodenum and jejunum that are associated with symptoms.
What is the utility of a full-thickness intestinal biopsy in a patient with suspected pseudo-obstruction?
To completely evaluate the neuromuscular apparatus of the gut, a full-thickness intestinal biopsy with special stains for muscle, nerves, and connective tissue can be obtained. The clinical utility of this information, however, remains unclear and opportunities to obtain this tissue are infrequently encountered.
What factors play a role in the pathophysiology of ileus?
The lack of intestinal activity is most likely related to increased sympathetic inhibitory activity (imbalance of autonomic nervous system) and a resultant loss of normal coordination of activity. Nitric oxide, vasoactive intestinal polypeptide, and possibly substance P act as inhibitory neurotransmitters in the gut and may also play a role. Finally, decreases in motilin and increases in the inhibitory factor’s calcitonin gene-related peptide and corticotropin-releasing factor have also been implicated in the pathophysiology of ileus.
• • • SUGGESTED READINGS • • •
Stanghellini V, Cogliandro RF, de Giorgio R, Barbara G, Salvioli B, Corinaldesi R. Chronic intestinal pseudo-obstruction: manifestations, natural history and management. Neurogastroenterol Motil. 2007;19(6):440-452.
Millar AJ, Gupte G, Sharif K. Intestinal transplantation for motility disorders. Semin Pediatr Surg. 2009;18(4):258-262.
Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010;16(24):2978-2990.