Chronic Megacolon
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Megacolon, as well as megarectum, is a descriptive term. It denotes dilatation of the colon that is not caused by mechanical obstruction. [1, 2] Although the definition of megacolon has varied in the literature, most researchers use the measurement of greater than 12 cm for the cecum as the standard. Because the diameter of the large intestine varies, the following definitions would also be considered: greater than 6.5 cm in the rectosigmoid region and greater than 8 cm for the ascending colon.
Megacolon can be divided into the following 3 categories:
Acute megacolon (pseudo-obstruction)
Chronic megacolon, which includes congenital, acquired, and idiopathic causes
This article is devoted to chronic (noncongenital) megacolon.
The pathophysiology of chronic megacolon is incompletely understood. It likely represents an amalgam of primary disorders involving muscular and nervous systems of the intestine. Much basic science work has been performed in this area.
For example, with respect to the large bowel reacting to its luminal contents, fatty acids appear to reduce the volume of the proximal large bowel. Opiate narcotics, on the other hand, reduce the propensity of the colon to constrict.
Control of colonic contractility is through a complex interaction of intrinsic colonic nerves, splanchnic nervous control, and central nervous system input. The final common pathway of intrinsic nervous control of colonic motility is via postganglionic nerves: stimulatory cholinergic nerves and inhibitory nitric oxide-releasing nerves. Evidence suggests that excessive production of nitric oxide may be the mechanism for toxic megacolon in ulcerative colitis; as yet, there is no evidence for a possible role of nitric oxide in chronic megacolon unrelated to inflammatory bowel disease.
Studies in mouse models and in children with chronic colonic pseudo-obstruction show abnormalities involving the number and function of the interstitial cells of Cajal (intestinal pacemaker cells). Inherited disorders likely involve abnormal maturation and function of these cells, whereas acquired disorders demonstrate decreased numbers of them.
Animal studies show that the splanchnic nerves can dramatically affect colonic motility, both to contract and relax the colon. Extrinsic adrenergic nerves seem mainly to act by reducing acetylcholine release from intrinsic postganglionic nerves, although a direct action on smooth muscle cells cannot be excluded. At this time, the respective roles of the intrinsic and splanchnic nerves in inducing megacolon have yet to be clarified.
Wallukat et al reported their experience in distinguishing distinct patterns of autoantibodies against G-protein-coupled receptors in Chagas cardiomyopathy and megacolon. [3] The investigators measured beta1-autobodies, beta2-autoantibodies, and muscarinergic2 autoantibodies, generally considered to be involved in the pathogenesis of Chagas cardiomyopathy and megacolon, from asymptomatic Chagas patients and those with cardiomyopathy and/or megacolon.
Autoantibodies were found in almost all patients with Chagas cardiomyopathy and/or megacolon; beta1 autoantibodies and muscarinergic2 autoantibodies were predominant in those with Chagas cardiomyopathy, whereas beta2 autoantibodies and muscarinergic2 autoantibodies were predominant in those with Chagas megacolon. [3] Of the 34% of asymptomatic patients who demonstrated similar patterns of autoantibodies, 84% of these individuals also had levels of beta1 autoantibody that are typical for Chags cardiomyopathy, which the authors stated mirrored the epidemiologic situation in Latin America: clinical manifestations develop in approximately 30% of Chagas patients and cardiomyopathy in about 90% of them. [3]
Wallukat et al concluded that measuring the levels of beta1-autobodies, beta2-autoantibodies, and muscarinergic2 autoantibodies may be useful for potentially identifying patients at high risk of developing life-threatening complications of Chagas disease, but they cautioned further studies are needed. [3]
In another study, Sanchez-Mejias et al examined the potential roles of the EDNRB and EDN3 genes in the pathogenesis of Hirschsprung disease in 196 Spanish patients. [4] The investigators found several novel mutations in both genes as well as a truncating mutation in alternative isoform of EDNRB. In addition, an overrepresentation of a specific EDN3 haplotype was present in affected patients compared with control subjects. [4]
Sanchez-Mejias indicated their findings suggest “the isoform EDNRB Delta 3 might be playing an essential role in the formation of enteric nervous system” and “based on the haplotype distribution, EDN3 might be considered as a common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion.” [4]
Some experts believe it is common practice to separate the disorders associated with chronic megacolon into the following: (1) colonic inertia (eg, generalized delayed transit), and (2) rectosphincteric dyssynergy (eg, functional outlet obstruction).
Neurologic diseases include the following:
Chagas disease
Parkinson disease
Myotonic dystrophy
Diabetic neuropathy
Spinal cord injury
Paraneoplastic neuropathy
Amyloidosis
Systemic diseases include the following:
Scleroderma
Dermatomyositis/polymyositis
Systemic lupus erythematosus
Mixed connective tissue disease
Metabolic diseases include the following:
Hypothyroidism
Hypokalemia
Porphyria
Pheochromocytoma
Medication-induced conditions can cause acquired megacolon.
Idiopathic include the following:
Nonfamilial visceral neuropathy (sporadic hollow visceral neuropathy or chronic idiopathic intestinal pseudo-obstruction)
Results from damage to the myenteric plexus from drugs or viral infections
The most common nonmechanical cause of acquired megacolon is infection with T cruzi (Chagas disease). [2] This infection results in the destruction of the enteric nervous system. [5, 6, 7] Although this disease was originally confined to South America, recent estimates indicate that 350,000 people in the United States are seropositive, one third of whom are thought to have chronic Chagas disease.
Enteric neuropathies include the following:
Hirschsprung disease (congenital aganglionosis) [2, 8] : It is caused by a single gene mutation of the RET proto-oncogene on band 10q11.2. The defect occurs in 1 in 5000 live births. Some cases are familial, with an overall incidence of 3.6% among siblings of index cases.
Waardenburg-Shah syndrome (piebaldism, neural deafness, megacolon)
Multiple endocrine neoplasia type 2A (MEN 2A) or 2B (MEN 2B)
Visceral myopathies include the following:
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) – Only type III involves marked dilatation of the colon
Oculogastrointestinal neuropathy (OGIN)
Idiopathic
In the newborn period, an unrecognized imperforate anus may be the cause of megacolon.
No large-scale studies have been conducted to determine prevalence/incidence of acquired megacolon.
The most common cause of megacolon worldwide is infection with Trypanosoma cruzi (Chagas disease).
Race has not been documented to play a role in megacolon.
The frequency of acquired megacolon is equally distributed between the sexes. The congenital megacolon, Hirschsprung disease, predominantly occurs in males.
Although clinically chronic megacolon can occur in any age group, inherited types usually present in young patients, and acquired types usually present in older patients.
Prognosis is related to the severity of the megacolon and the severity of the patient’s comorbid diseases.
Although some patients cannot be managed on any type of bowel program and quickly require surgery, other patients may be maintained on a strict bowel program. No detailed longitudinal studies, however, have been performed to assess strict prognostic associations or indicators.
Mortality/morbidity
No large-scale studies have been conducted to determine prevalence/incidence of acquired megacolon. However, once present, the approximate risk of a spontaneous perforation from nontoxic megacolon is 3%.
The most dangerous complication is perforation, which rarely occurs. Perforation is generally due to overdistention of the bowel or to stercoral ulcer. If the etiology is overdistention, perforation typically occurs in the cecum. Stercoral ulcers typically occur in the sigmoid/rectosigmoid region.
Education of the patient with regard to the strict bowel program is essential to management. Maintaining effective management requires extensive effort and discipline from both the health care provider and the patient. To this end, educating the patient about the entire process is crucial.
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David Manuel, MD Affiliate Faculty, Department of Medicine, Loyola University Health System; Gastroenterologist, Digestive Health Center
David Manuel, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Crohn’s and Colitis Foundation of America
Disclosure: Nothing to disclose.
Michael H Piper, MD Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne State University School of Medicine; Consulting Staff, Digestive Health Associates, PLC
Michael H Piper, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, Michigan State Medical Society
Disclosure: Nothing to disclose.
Roberto M Gamarra, MD Consulting Gastroenterologist, Digestive Health Associates, PLC
Roberto M Gamarra, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Crohn’s and Colitis Foundation of America
Disclosure: Nothing to disclose.
Clifford Y Ko, MD, MS Professor, Department of Surgery, University of California, Los Angeles, David Geffen School of Medicine
Clifford Y Ko, MD, MS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society of Colon and Rectal Surgeons, Association for Academic Surgery, California Medical Association, New York Academy of Sciences
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Douglas M Heuman, MD, FACP, FACG, AGAF Chief of Hepatology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center; Professor, Department of Internal Medicine, Division of Gastroenterology, Virginia Commonwealth University School of Medicine
Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, American Gastroenterological Association
Disclosure: Received grant/research funds from Novartis for other; Received grant/research funds from Bayer for other; Received grant/research funds from Otsuka for none; Received grant/research funds from Bristol Myers Squibb for other; Received none from Scynexis for none; Received grant/research funds from Salix for other; Received grant/research funds from MannKind for other.
BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine
BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Terence David Lewis, MBBS, MBBS
Terence David Lewis, MBBS, MBBS is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, Sigma Xi
Disclosure: Nothing to disclose.
Chronic Megacolon
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