Megacolon

Megacolon describes the condition of prolonged dilation of the large bowel. It may contribute to or result from chronic constipation. In the absence of defining criteria, it is a diagnosis of radiographic and functional assessment with systematic elimination of potential underlying causes.

Only a small population presents with primary megacolon. The majority of patients who present with megacolon can be classified according to their primary disease: obstructive versus non-obstructive (colonic inertia). The various etiologies determine appropriate treatment (Table 39-1).

Anatomy

The large intestine is that portion of the intestinal tract that is aboral to the ileum, is separated by the muscular ileocolic sphincter, and concludes at the rectum. At its proximal extent lies the cecum, a spiral diverticulum just wider in diameter than the ileum. From the ileocolic junction, the colon tracks cranially for a short distance and is relatively fixed in position by the mesocolon in the right caudal abdomen. The transverse colon travels the width of the abdomen to the descending colon; the large bowel joins the rectum at the pelvic inlet [1]. The junction between colon and rectum is ill defined and can be described as the abdominopelvic boundary, the 7th lumbar vertebra, or the point at which the cranial rectal artery dives below the seromuscular layer [2].

The histologic anatomy of the colon consists of four layers: serosa, muscularis (longitudinal and circular), submucosa, and muscosa [3]. The serosa maintains no externally distinct property, whereas the mucosa is lined by a single layer of tall columnar epithelial cells [3]. In this portion of the gastrointestinal tract, the crypts of Lieberkühn maintain mature epithelial cells at the tip, while the proliferative epithelial cells are neighbored by the glandular cells at the base [1]. Goblet cells are abundant in the colon; their increased concentration allows space for a minimal amount of lamina propria and provides the histologic boundary from the ileum [3]. The submucosa houses the vascular supply and lymphatic system in loose connective tissue that also suspends the nervous supply [1]. As the rectum becomes a distinct structure, lymph nodules become more apparent.

The vascular supply to the large intestine is divided. The ileocolic junction to the midportion is supplied by branches of the cranial mesenteric artery as the ileocolic, midcolic, and right colic arteries. The caudal mesenteric artery, as the left colic artery, supplies the descending colon and cranial rectum. The venous system is established through the middle colic and ileocolic veins into the caudal mesenteric vein, leading to the portal vein.

All aspects of colonic innervation are maintained within the autonomic nervous system; this can be separated into intrinsic and extrinsic components. The intrinsic nervous supply coordinates global gastrointestinal movement. It is composed of the submucosal (Meissner's) and the myenteric (intramuscular, Auerbach's) plexuses that are linked in reflex circuits [4]. The intrinsic nervous system regulates secretion and absorption, vascular tone, and motility. Enteric primary afferent neurons transmit information about stretch or tension, although some communicate chemical or mechanical stimuli. These cells then stimulate others within their class to produce coordinated responses [5]. The arc is completed by effector nerve endings controlling secretory and smooth motor units [4]. Excitatory and inhibitory motor neurons produce coordinated events resulting in defecation. The interstitial cells of Cajal have been credited with controlling the rate of peristaltic waves [5]. Extrinsic innervation is supplied by parasympathetic (cholinergic) fibers, which stimulate muscle activity, whereas sympathetic (adrenergic) fibers inhibit.

Physiology

Motility

Motility is influenced by integrating cellular excitability, chemical control, and nervous input. The complex cellular events result in segmental and propulsive muscular contractions. In combination with interneuron stimulation of proximal contraction and distal relaxation, aboral movement ensues while mixing ingesta [5]. Evacuation of the colon by mass contractile movements originates in the distal segment of the colon. Colonic motility is also influenced by neurotransmitters, such as substance P, vasoactive intestinal polypeptide, somatostatin, and cholecystokinin [6].

The ileocolonic junction permits a bolus of ingesta to enter the proximal segment of the colon; this ensures regulated filling and prevention of reflux [1]. Emptying of the proximal colon is controlled through the perception of tone in the presence of fatty acids as well as the volume and consistency of ingesta: both trigger waves of contraction [5]. Propagating waves are triggered more frequently in the proximal colon than in the distal, and they begin to dampen about midcolon [5]. This explains infrequent daily defecations when compared with the extensive movement of stool in the colon. Conversely, more frequent segmental contractions occur in the distal colon.

Defecation, as studied in humans, is a process that begins nearly an hour prior to the expulsion of feces [5]. Propagating waves increase in number in the distal colon, with a dramatic increase within 15 minutes, producing a conscious sensation. Sequentially, oral initiation of these waves results in a full distal colon and stimulation of the anorectal phase [5]. Stool and gas stretch the rectal wall and trigger the rectoanal inhibitory complex, allowing relaxation of the rectum and the involuntary internal anal sphincter. When the external anal sphincter is relaxed voluntarily, a coordinated muscle event assists the passage of feces [5]. Suppression of defecation results in storage of stool in the rectum (accommodation).

Chronic accommodation and retention of stool can result in megarectum and exacerbation of perineal hernia. Anal continence is the result of appropriate rectal capacity in the presence of sphincter coordination and reflexes. Normal reflexes and sphincter mechanism are insufficient, in the absence of an adequate reservoir, to maintain continence.

Absorption and Secretion

The majority of absorption occurs in the proximal half of the colon (absorbing colon); the distal portion serves to store feces prior to expulsion (storage colon). The majority of metabolite digestion and absorption for the body occurs in the small intestine; colonic bacteria complete this locally in the large intestine. Products of this metabolism, such as short-chain fatty acids, are rapidly absorbed by epithelial cells [1]. Short-chain fatty acids, specifically butyrate, provide energy to mucosal cells; deprivation leads to compromised colonic mucosal health [1]. Bacteria also digest dietary fiber; the remainder is fermented. Both processes allow the colon to take up carbohydrates inaccessible to the small intestine.

Water absorption is a passive process with the exchange of sodium. By means of Na+/K+ ATPase, sodium is actively pumped into the colonic epithelium. This action is preserved through the high sensitivity of tight junctions that prevent back-diffusion in this region of the bowel [6]. Because it has a higher electrical gradient than does the small intestine, the colonic epithelium permits diffusion across the apical membrane [1]. This activity is enhanced by glucocorticoids, mineralocorticoids, and catecholamines.

Bicarbonate is secreted in exchange for the absorption of chloride [6]. This assists in the neutralization of acidic bacterial byproducts. The gradient created by the exchange of sodium and chloride into the colonic epithelia allows water to follow passively.

Potassium exchange can occur in both directions [6]. Again, the potential difference generated is greater in the colon; a net secretion of potassium occurs, assisted by active conductance on the apical membrane [1]. Mucus is the predominant secretory product serving to lubricate formed feces, thereby facilitating defecation while protecting the mucosa.

Bacteria of the colon contribute to the production of nutrients in addition to aiding further digestion. Cellulose breakdown is of particular importance to herbivores. Vitamin K production by bacteria is essential to the support of the clotting cascade [7].

Pathophysiology

Feces can be retained for several days in the normal dog and cat without permanent damage to the distal colon. Prolonged retention can derange the absorptive process such that the feces become more dehydrated and, therefore, firmer with time [8]. These concretions are painful to pass and can become impossible to eliminate (obstipation). When retention is severe and prolonged, irreversible changes in colonic motility can lead to colonic inertia. Significant distention in excess of three to four months is speculated to produce such effects.

Animals can demonstrate variable presenting signs. Central nervous system depression, anorexia, and weakness have been attributed to toxins absorbed by the compromised mucosa [8]. Abdominal pain and distention can result from the excessive amount of feces within the abdominal colon. Vomiting occurs secondary to the obstructive nature of colonic impaction, the effect of toxins on the chemoreceptor trigger zone, or vagal stimulation of intestinal distention.8 Diarrhea may be observed as fluid bowel contents can pass about the solidified feces. Mucosal irritation by the mechanical obstruction results in increased mucus secretion by goblet cells and often exudation of blood. This produces a watery, mucoid, and potentially, bloody diarrhea. Common presenting complaints can include lethargy, anorexia, vomiting, tenesmus, weight loss, and diarrhea [8].

Idiopathic Megacolon

Affecting middle-aged to older cats with few exceptions, idiopathic megacolon has an unknown etiology. Described as progressive intractable constipation, histologic evaluation does not identify abnormality in animals as it does in its human analog. Hirschprung's disease (HD), described as aganglionosis of the distal large intestine, is often identified early in children owing to associated clinical features [9]. Important features of HD, characterized as a process of slow-transit constipation, are decreased ganglionic density and decreased concentration of Cajal cells [10]. These directly affect the motility of the distal large intestine and the production of a normal defecation reflex.

In the absence of histologic abnormalities, feline idiopathic megacolon (FIM) is attributed to inappropriate intrinsic or extrinsic innervation of the colon. Washabau and Stalis demonstrated the presence of myenteric neurons in colonic smooth muscle in cats with FIM as well as the neurons hyposensitivity to stimulation [11]. They postulated that the disorder is limited to the intrinsic nervous system in the absence of lower urinary tract signs [11].

Many owners are not intimately aware of their animal's defecation habits and, so do not identify unusual behavior early in the disease. Most cats present with prolonged and, therefore, severe disease. FIM is an exclusionary diagnosis made through the elimination of other predisposing causes of constipation (i.e., renal insufficiency) by blood work, urinalysis, and imaging studies. The results of blood work can be consistent with prerenal azotemia and electrolyte abnormalities compatible with metabolic acidemia in cases of severe, prolonged constipation. Abdominal radiographs demonstrate fecal distention in the colon with all causes of megacolon. Radiographs should be scrutinized for pelvic fracture malunions, distortions in the spine, and extramural compression. This can be supplemented by abdominal ultrasound and computed tomography for confirmation of soft tissue and bony obstructive etiologies, respectively. Rectal examination, colonoscopy, and contrast radiography can also assist in the systematic exclusion of causes.

Severity of dehydration and metabolic derangement must be addressed prior to intervention. Obstipation can then be the focus of treatment by the administration of stool softeners and enemas. Manual evacuation of stool should be performed gently in the anesthetized patient to minimize further mechanical trauma to already compromised mucosa. As the translocation of bacteria and toxins is a concern, administration of prophylactic antibiotics is recommended. Medical management includes high-fiber diet, stool softeners, bulk laxatives, prokinetic agents, and intermittent enemas. When aggressive medical therapy is unsuccessful, surgery can be considered.

Surgical management by subtotal colectomy is the treatment of choice. The surgeon must identify the objectives of colectomy when assessing the need to excise the ileocolic junction. Although removal of the ileocolic junction may produce looser stools, preservation may allow affected colonic tissue to remain. A survey of 22 cats undergoing subtotal or total colectomy demonstrated significantly looser stools in the group with total colectomy [12]. Recurrence of constipation occurred at comparable rates in the two populations, suggesting that the colonic tissue associated with the sphincter is insufficient to produce significant complications [12]. Removal of the ileocolic sphincter will likely allow some degree of recto-ileo reflux. Thus, preservation of the ileocolic junction has been recommended as surgical management of FIM. Initially, diarrhea is observed, but completely resolves or progresses to semi-formed stool in a period of weeks to months. The ileum and rectum are credited with the absorptive and reservoir capabilities that allow function to normalize with time [13]. Gregory et al. evaluated the enteric functions of cats that had undergone colectomy; they found minimal differences between surgically-treated and untreated cats [13]. Serum concentrations of electrolytes remained within the normal limits. Trends in fecal concentrations of sodium and potassium were higher and lower, respectively, but not statistically significant; this was directly attributed to the removal of the proximal colon [13].

Megacolon Secondary to Neurologic or Medical Disease

Disruption of the nervous supply of the large intestine can contribute to decreased or complete absence of colonic motility. Interruption of the appropriate signals can interfere with the normal defecation reflex and lead to constipation and megacolon. Removal of the affected colon may provide a satisfactory result when reflex mechanisms remain intact.

Manx cats have demonstrated abnormalities in their sacral spinal cord, producing urinary and fecal incontinence [14]. These abnormalities are manifested in bony structural deformities as well. Surgical intervention is not recommended owing to co-morbidities.

Megacolon secondary to autonomic ganglioneuritis was reported in a dog with a 6-week history of constipation and tenesmus [15]. Neurologic exam revealed only generalized muscle weakness. Histopathology demonstrated moderate lymphoplasmacytic infiltrates of the autonomic ganglia. The muscularis was normal, while the mucosa was edematous and mildly congested. The etiology of the neuritis was never identified [15].

Constipation has been observed with poorly managed metabolic disease, potentiating the development of megacolon if the constipation is frequent and prolonged. Although not described in veterinary literature, toxic megacolon has been documented in humans [16,17]. Other neurologic and medical etiologies of megacolon have also been reported (Table 39-1).

Outlet Obstruction

Megacolon has been described secondary to a variety of processes physically obstructive to the outflow tract of the colon. Pelvic fracture malunion is one of the most common causes of secondary megacolon in the cat and the dog. Neoplasia, primary to the colon (intramural) or of adjacent tissue (extramural), can cause obstruction at a critical size. Altered anatomy, such as perineal hernia and anal or rectal atresia can result in constipation and then megacolon. In rare cases, foreign body or inappropriate nutrition can lead to obstruction of outflow.

Any disease process resulting in a prolonged, severe distention can result in permanent changes to colonic smooth muscle function [18]. Reduced motility or inertia can be particularly difficult to treat.

Clinical signs of outflow obstruction mimic those of idiopathic megacolon; therefore, diagnosis should place special importance on a thorough rectal examination. Following identification of the underlying obstruction, treatment is focused on surgical correction of the cause. Invasive procedures such as hemipelvectomy or pelvic reconstruction may be required to correct intrapelvic abnormalities. Schrader evaluated six animals with pelvic malunion and determined that surgical correction by pelvic osteotomy was successful in those animals whose clinical signs were less than six weeks in duration [19]. Clinical signs exceeding six weeks resulted in colonic inertia and, when obstipated, these animals were not managed successfully by pelvic reconstruction or ostectomy [19]. Removal of the ileocolic sphincter, in the subset of cats with megacolon secondary to pelvic malunion, is offered as a means to produce loose stools and minimize the intensity of continued medical management [20]. This population remains at risk of recurrent constipation despite total colectomy and may warrant continued medical management.