Chronic Megacolon

Updated: Mar 28, 2016
  • Author: David Manuel, MD; Chief Editor: BS Anand, MD  more...
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Overview

Background

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:

This article is devoted to chronic (noncongenital) megacolon.

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Pathophysiology

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).

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Etiology

Causes of acquired megacolon

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.

Causes of congenital megacolon

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.

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Epidemiology

United States data

No large-scale studies have been conducted to determine prevalence/incidence of acquired megacolon.

International data

The most common cause of megacolon worldwide is infection with Trypanosoma cruzi (Chagas disease).

Race-, sex-, and age-related demographics

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.

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Prognosis

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%.

Complications

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.

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Patient Education

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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