Motor and sensory functions of colon are regulated by nervous system of bowel and include extrinsic and intrinsic innervation. Intrinsic nervous system consists of myentric, submucosal and mucosal nerve plexi. Myenteric plexus regulates the smooth muscle functions that are responsible for motility whereas, submucosal plexus is responsible of ion transport and absorption. Extrinsic nervous system is composed of parasympathetic and sympathetic autonomic innervations. While right colon innervation is carried out by parasympathetic nerves that are carried by vagus nerve, transverse colon, left colon and rectum innervation is accomplished by sacral parasympathetic nerves (S₂-S₄) that enter from distal colon. Sympathetic nerves reach the bowel along with superior and inferior mesenteric arteries and result in tonic sympathetic effects (₉).

They usually express excitatory properties for sphincter muscles and inhibitory for non-sphincterics. Symphatic system affects the bowel by α2 receptors. Clonidine –a α2 receptor agonist- increases the compliance of the colon by decreasing its tonus. Yohimbine - a α2 receptor antagonist- has a reverse effect to clonidine. The α1 and β receptors have no effects to the colonic tonus (₁₀). The functions of enteric and extrinsic neurons are regulated by some neurotransmitters that are released from between the neurons. There include noradrenalin, acetylcholine, opioids, serotonin, somatostatin, CCK, substance-P, VIP, and neuropeptide-Y (₁₁). It has been shown that, while cholecystokinin stimulates pancreatic secretions maximally, it has no effect on colonic tonus or phasic activity (₁₁).

Atropine decreases the colonic tonus (₁₂). There are five subtypes of serotonin receptors. These have important effects on the regulation of motor activity and sensory innervation of colon. 5-HT₃ antagonists (e.g., ondansetrone) delay the orocaecal and colonic passage along with inhibiting colonic tonus and compliance. 5-HT₄ receptor agonists stimulate acetylcholine secretion, thus display prokinetic activity (₁₃). A somatostatin analogue octreotide decreases the postprandial colonic tonus, particularly decreasing motility in descending colon and rectum in a fashion that is paradoxical to the gastrocolic reflex (₁₄). Several neuropeptides show abnormal segmental distribution in the colons that are resected in constipated patients (₁₅).

Injury of autonomic nerves after trauma may progress to infections, degeneration of neurons and neuropathies, disturbances in secretory motor and sensory functions and usually results in constipation. In the patients that have spinal cord injury above the sacral segment, proximal and distal colonic transport time increases due to loss of control. Colonic motility rate and tonus are normal and the response to feeding is little or none (₁₆).

Spinal cord lesions that include sacral segments or injury in the efferent nerves that emerge from these segments result in the loss of rectosigmoidal neural innervation and anal sphincteric control. In the patients with such lesions, left colon loses its constrictor ability, rectal tonus and sensitivity decreases and those results in colonic dilatation and fecal impaction (₁₆). Parkinson's disease and multiple sclerosis are often associated with constipation. There is a decrease in the number of dopamine containing neurons in Parkinson's disease. Lewy bodies have been found in the neurons of myenteric plexus (₁₇). In addition to that, there is a relaxation defect in the skeletal muscles of pelvic floor. As shown in a study, constipation which is the most common symptom of the disease is seen in 43% of patients of multiple sclerosis (₁₈). It has been proposed that, the slow colonic transit time and lack of postprandial motor response seen in the colon of multiple sclerosis patients result from the disturbance in parasympathetic control of colon in spinal cord injuries. There is constipation secondary to autonomic dysfunction in diabetes mellitus (DM). In a large group that consists of diabetic patients, constipation rate in patients with diabetic neuropathy is 22% whereas; the rate is 9.2% in the group of diabetic patients without neuropathy. However, comparison with the control group fails to show a big difference (₁₉). In a study carried out by Feldman et al, constipation is seen more frequently in insulin dependent DM when compared to insulin independent DM. Altomore et al performed a study in 23 patients that have low transit rate without obstruction and irritable bowel syndrome and it shows sympathetic disorders in postganglionic tests in 70% of constipated patients and 8% of control group (₂₀).

Hirshsprung's disease is a disorder characterized as the lack of ganglions in myenteric and submucosal plexi. First symptoms are identified on birth and rarely on newborn or early childhood. Agangliosis start from anal verge and expand proximally. Hirshsprung's disease is documented in deficiency of nerve growth facto in colon muscle layer. Idiopathic megacolon and megarectum can be congenital or acquired. However the role of the defect in enteric nervous system is insignificant. In megacolon, dilated segment and normal phasic contractions are present but colonic tonus is decreased (₂₁). In a study Gattuso et al conducted on 30 patients with megacolon or megarectum; longitudal, circular and muscularis mucosa fibrosis and significant dilatation in megarectum histological specimens due to smooth muscle hypertrophy is documented. Even a decrease in neural tissue density in megarectum specimens is present but these are not observed in idiopathic megacolon (₂₂).

Chagas disease is caused by Trypanozoma cruzi, an agent that the destructs the enteric plexus with infection. The disease is characteristically presents with constipation. Krishnonurty et al showed a decrease in number, and a disorder in structure of argirophilic neurons, found in the resected colon material of constipated patients (₂₃).

Schouteen et al, who study the neuropathogenic changes in patients with idiopathic low passage constipation, documented the decrease or complete absence of neurofliaments in myenteric plexus. Destructive effects of laxatives on enteric neurons are not clearly understood. In a study of Milner et al, it has been shown that, no changes occur in colonic structure and neuropeptide levels with chronic use of laxatives (₂₄). Another study conducted documented that, no increase in the argirophilic dye absorption occurs, although argirophilic neurons decrease (₂₅). Recent studies focus on Cajal cells, an interstitial cell type. It's been assumed that the Cajal cells play an important role in regulation of intrinsic electrical activity and electromechanic connections in bowel. The studies show that the distribution of Cajal cells in different colonic localizations and the volume in the myenteric plexus of resected colon decrease in idiopathic slow transit constipation (₂₆).

Normal passage time from mouth to caecum is approximately 6 hours. Regional passage time with radioopaque substance is approximately 12 hours each for right colon, left colon and sigmoid colon. In general, colonic transit time is 36 hours (₁₃). Bowel transit time is affected by several factors. Previously it has been told that, ileocolic junction regulates the bowel transit time. However, the studies conducted on patients with right hemicolectomy showed that, despite the loss of ileocolic sphincter, there is no significant change in bowel passage time. Diet, calorie intake, water influx in colon, distal obstruction affects colonic transit time. As the fiber content of diet increases, colonic transit time decreases, defecation frequency increases and the feces gains a softer nature. When calorie intake is decreased, colonic transit slows down, but is back to normal once normal calorie intake is established (₂₇).

There are three types of contraction pattern were described. These are segmentation, driving movements and mass movements. Segmental activities are formed by the contraction of isolated circular smooth muscle fragments. This kind of activity is not driving. The result of segmentation is an obstacle for the luminal content trying to move to distal segments. Increase in segmentation results in constipation. Colonic segmentation increases as a response to meals and decreases in sleep. Segmental activities are decreased by atropine, 5-HT3, PGE₂ and bradikinin. Drugs like Prostigmine and cholecystokinin increase the segmental activity (₁₀). There is no response to the intravenous infusion of invivo PGF₂, but PGE₂ inhibits the segmental activity (₂₈).

Documentation of driving activity in colon is harder than in esophagus and small intestine. Such activities are formed by the systematic contractions of circular muscles. This occurs in small intervals in colon. On the contrary, mass movements are high amplitude contractions that are not frequent. These movements push the luminal content to the distal and are related to defecation. Recent studies show a decrease in the frequency and number of high amplitude waves in patients with slow passage constipation, idiopathic constipation and normal passage constipation (₂₉). However, absence of postprandial early motor response is documented in patients with slow passage (₃₀).

Fluid balance affects GIS transit. Approximately 9 liters of fluid reaches the bowel with oral intake and endogenous secretions. Small intestines transport approximately 1.5 liters of fluid to colon, most of it is reabsorbed there and maximally 200 ml of water is expelled with feces. Preston et al documented the increase in motilin, pancreatic polypeptide, and gastrin secretions in response to water injection in constipated patients. The motility increase associated with this forms the basis of antegrade enema technique (₃₁). Sjolund et al showed the decrease in basal and postprandial motilin levels (₃₂).

In addition this, van der Sjip et al documented that, there is no change in the levels of neurotensin, motilin, gastrin, pancreatic polypeptide secreted from upper GIS to circulation and fluctuations in somatostatin levels (₃₃). Immunoreactive serotonin receptor levels are found in lower concentrations in circular muscles and muscularis mucosa of patients with colonic inertia. There is positive relationship between serotonin receptor levels in circular muscle and colonic transit time (₁₂).

• Simple Constipation: Average Frequency or hard passage of feces. Symptoms are intermittent and minimally disturbing. Response to conservative treatment (intake of fiber) is good (39).

• Secondary Constipation: It occurs secondarily to local or systemic diseases. For example, during the course of mechanical obstruction, adverse drug effects (narcotic analgesics, NSAIDs, some chemotherapeutics, calcium channel blockers, antiarythmics), hypothyroidism, hypercalcemia, some neurological diseases (multiple sclerosis, Parkinson's Disease), some psychiatric disorders (depression, anorexia nervosa)

• Chronic Idiopathic Constipation (CIC): It consists of colonic inertia and pelvic exit obstructions that are not related with any organic cause (paradoxical contraction of puborectal muscle). 4 main pathologies are observed in CIC:

• • Colonic inertia (retardation of colon passage)

  • Pelvic exit obstructions

  • Colonic inertia + pelvic exit obstructions

  • Irritable bowel disease

Colon contents leave the colon in at most 72 hours in normal population (₄₀). Prolongation of this period shows retardation in colon passage. This condition is defined as colonic inertia and actually occurs as a result of autonomic nerve pathologies (degenerations of Aurebach and Meissner plexi appear in gastrin, motilin, pancreatic polypeptide, glucagons and other peptide deficiencies). Colonic inertia can be segmental or diffuse. Involvement of other hollow organs is defined so, any surgical treatment will be useless in those patients (₄₁). It has been proposed that genetic factors (Ret oncogene) may be involved in development of colonic inertia (₄₂). Megacolon (diameter of colon exceeds 8 cm in ascending colon; 6 cm in descending colon and haustrations are lost) causes CIC.

PEO is encountered under different names in literature: Puborectal syndrome, spastic pelvic floor syndrome, anismus, nonrelaxing puborectal muscle syndrome, rectoanal dysnergy, immotile perineum, paradoxical puborectal contraction, pelvic floor dysnergy. In normal defecation, pelvic floor muscles, puborectal muscle and sphincters relax simultaneously. However in PEO, puborectal muscle and external sphincter exhibit disorganized contractions instead oh relaxation by some reason and prevent defecation (₄₃).

Due to this contraction of puborectal muscle, the anorectal angle (the angle that is between the line drawn through the center of anal canal and lines drawn from the posterior wall of rectum or according to another definition; the angle that is between the line drawn through the center of anal canal and lines drawn from the middle of inferior rectum) that should have widened cannot widen (₄₄). Since anorectal line is not straightened enough and anorectal ring cannot relax, contents of rectum cannot be expulsed to the anal canal. Addition to this, the conditions like internal sphincter being hypertonic, rectum wall contraction disorder and reduction in rectal awareness may prevent defecation (₄₅).

Perineal Looseness can cause PEO too. Some claim that, exerting too much force or vaginal labor traumas may cause pudental nerve injury that may result in perineal looseness (₄₆).

Sigmoidocel is the descent of sigmoid colon to Douglas pouch in patient with deep pouches. It's a defecographic finding rather than a clinical finding.

Rectal Intusseption is another defecographic finding that can cause PEO. It's the overlapping of entire rectum wall layers from proximal to distal (₄₃). Some researchers accept the overlapping of rectum mucosa for more than 3 mm as rectal intusseption (₄₇). In a study conducted in 209 patients that have PEO, defecography showed 23% Rectocel, 10% rectal intusseption, 8% Sigmoidocel, 63% perineal looseness (₄₈). In addition to this, diseases like rectal prolepses, rectocel, and anal stenosis may cause PEO too.

It's essential to discern whether the constipation is related to a systemic disease or not. If there are symptoms that suggest a systemic disease in the history physical examination, these must be consulted with the related departments.

After that step, any organic cause related to colon and rectum must be eliminated (e.g. tumors). Appearance of constipated that is not present before in middle aged or elder patients, suggest malignancy. It should be kept in mind that, in a patient who has chronic idiopathic constipation since his youth can develop malignancy. Namely, malignancy must be eliminated in a patient with constipation. The gold standard is the endoscopic examination. In general rectosigmoidoscopy is sufficient in patients who are under 40. However, if the patient is over 40, colonoscopy must be performed fist. Another benefit of Endoscopy is that it also documents the benign formations related with chronic idiopathic constipation (megacolon, rectal ulcer).

Colon examination using double contrast enema, provides valuable information about the morphological structure of colon (colon length, presence of segmental or total megacolon, conditions of haustrations). However, colon X-rays in constipated patients are usually normal.

Studies are carried out to see if chronic idiopathic constipation is caused by colonic inertia or by pelvic exit obstruction or by combination of both. For this purpose, colonic passage time, defecography, EMG, balloon extraction test, and anorectal manometric studies are used.

It shows the passage time of colonic content. The patient ingest a gelatin capsule that is filled with a definite number of radioopaque rings and opens in terminal ileum It is based on the fact of whether it is eliminated from the body within 72 hours or not. Another method used practically is the consumption of sitz-marks (a capsule that contains 24 radioopaque substances) in one time and evaluation with a direct abdominal X-ray after 3 days. In patients whose constipation is a result of colonic inertia, at least 8 or more opaque substances must be visualized. If the 3 ^rd day X-ray couldn't be taken, it is taken on 5 ^th day, and in normal population, 80% of radioopaque substance must be eliminated (₄₉). Another approach is the observation of the journey of radioopaque rings with X-rays taken on the same hour for 5 days consecutively and it is thought to be more sensitive despite the fact that it has more x-ray shots. In the X-rays, the radioopaque substance may be seen as diffused completely or collected in a fashion that suggests segmental obstruction. On the other way, in the patients with pelvic exit obstruction, opaque substances are not encountered in colon but gathered in the pelvis, in rectum area (₄₀). For the patients who have prolonged colonic passage time and who are candidates of a surgical treatment, examination of upper GIS motor function prior to the surgery (by upper GIS manometry, nuclear gastric emptying test, hydrogen breath test) is essential (₄₁).

It is used to document pelvis exit obstruction. Since it will show the defecation procedure step by step, the causes of pelvic exit pathologies can also be detected. Anismus, rectocel, rectal intusseption, Sigmoidocel, megarectum can be shown with this test. In the defecographic findings for anismus, anorectal angle does not increase. Normally, the angle should increase more than 5% (₄₄,₄₈).

It's very valuable in the diagnosis of anismus. Bipolar needle or surface electrodes are used. Electrodes are placed on posterior middle line 12 mm distal to anal verge for puborectal muscle and to laterals for external sphincters (₄₀). After the electrodes are applied to puborectal muscle, electrical activity of the muscle is recorded during the contraction, relaxation and exertion of force periods of the patient. Normally the activity increases in contraction phase and completely decreased during exertion of force. In anismus patients, activity increases in exertion of force period. Even though EMG and defecography are not superior to each other for the diagnosis of anismus, the diagnostic value increases two folds when they are combined (₄₄).

The patient is put in left lateral supine position and a balloon filled with 50 -60 ml of warm water in front of a 2mm catheter is placed just above the anorectal junction by pulling. The patient is asked to extract the balloon by exerting force after a resting period of 3-4 minutes. Normal people can perform this without any difficulty while it's difficult for constipated patients (₄₀,₄₄). Fleshman et al found out that 9 patients out of 21 diagnosed with anismus failed to extract the balloon. Thus, they reported that defecography has a false positive diagnostic value and balloon extraction test performed in defecation position is more specific (₅₀).

It is performed to measure the pressures formed by pelvic floor and anal sphincters. Some pressure abnormalities may be seen in CIC. Anal resting pressures may be elevated. Relaxation amplitude may be decreased or totally lost in rectoanal inhibitor reflex (RAIR). RAIR is especially lost in adult Hirschsprung's Disease and megarectum (₅₁). Another advantage of anorectal manometry is that, it's important in the postoperative evaluation of total colectomy and iliorectal anastomoses.

Additionally there are tests like pudental nerve terminal motor permeability, rectal sensation and perinometer.

As a result, it's important to conduct these tests to expose the causes of CIC and to plan the treatment. All of the tests should be carried out as shown in the algorithm below (Figure 1).

Figure 2

Figure 1: Algorithm in the diagnosis of constipation

In constipation due to colonic inertia, the diets of patients are regulated. Simple laxatives and enema are used. Exercises conducted. Intake of substances like cellulose that increase the amount of fiber rich feces, fruits and vegetables, meals cooked with olive oil and large amounts of fluid is advised. The number and amplitude of colonic movements that are seen in adults in the morning and after the meals, are decreased CIC. Benzofuran group drugs are suggested to increase such movements in these patients. (₃₆). Additionally, osmotic agents that increase the inflow of fluid to the bowel lumen like magnesium hydroxide, polyethyleneglicol, laxatives and enemas are used (₃₇,₅₁).

In conditions where conservative treatment fails, surgery may be considered only if all the tests identify the source of CIC as colonic inertia. Careful and selective approach must be used before decision for surgery is made. If surgery is based on the anorectal physiological studies, satisfactory results can be obtained. Motility disorder in remaining parts of GIS should be clearly eliminated. Psychiatric conditions of the patients should be evaluated carefully. Patients must be informed about the surgical procedure, its complications and possible results (increase in the number of defecation, softening of fecal content, abdominal pain, incontinence).In general, defecation in every 15 days constitutes a surgical indication, although there is no definite agreement on the time period.

The most distinguished method for surgical treatment is Total colectomy and ileo-rectal anastomosis. Postoperative results show variation. Ghosh et al documented that, in 21 patients with CIC, who underwent colectomy and ileo-rectal anastomosis, presented with abdominal pain, swelling, sense of urgent defecation and forced defecation more frequently than the control group (15 patients who had total colectomy for other purposes). Additionally, 71% of the patients who had this operation experienced brid ileus in later period (p<0.01). However, different values are obtained in different studies. A first few cases that are operated laparoscopically in our clinic, are satisfactory.

Also, it's disturbing that; of these patients, 68% had esophageal motor dysfunction, 19% had delayed gastric emptying, 10% had increased small intestinal passage time, 54% had urodynamic abnormalities and 14% had abnormal results in autonomic function tests (₅₂).

Piuta et al conducted a study to emphasize the importance of diagnostic tests and total colectomy.71% of the patients had successful results, 21% had no improvement in life quality and 8% had no benefits from the treatment. Psychiatric disorders or afferent nervous system disorders have been identified in all of the patients who had no benefit from the treatment (₅₃).

Beck et al performed abdominal total colectomy to 14 patients and reported that all the patients have satisfactory results (₅₄).

Rantis et al applied conservative medical treatment to 51 patients with CIC. 35% of patients had no successful results so, to a total of 12 suitable patients (24%), total colectomy (5 patients), anterior resection with rectopexy (3 patients), colostomy (2 patients), sigmoidectomy (1 patients with volvulus), abdominoperineal resection (1 patient) are performed. Among these patients 84& had successful results (₅₅).

Gregory et al performed subtotal colectomy to 112 patients and were successful in 67%. Among these patients, %21 had incontinence, %46 had occasional diarrhea, and 4% had abdominal pain. Diarrhea and incontinence is seen more frequently in patients who had ileo-rectal anastomosis than the patients who ileo-sigmoid anastomosis. However this result is not statistically significant. Again there is no difference between anastomose level and the quality of life. The patients who have permanent ileostomies, have significantly lower scores of life quality (₅₆).

In another study conducted by Christian et al, subtotal colectomy was performed to 12 patients and success was achieved in 10 of them. One of the patients, who had unsuccessful results, later developed narcotic dependency. The other had normal preoperative defecography and high rectum compliance and because of this, he underwent proctotectomy and ileo-anal pouch anastomosis later and the operation was satisfactory. 3 patients had abdominal pain, 2 patients had diarrhea and 1 patient had incontinence as complication (₅₇).

Platell et al performed either total colectomy and ileo-rectal anastomosis or subtotal colectomy and caeco-rectal anastomosis to 96 patients. Postoperatively, 3.1% developed anastomose leak, 11.5% had pelvic abscess with 2.1% mortality rate. 81.6% of patients had symptomatic improvement, 51.2% had exertion difficulties, 50.65 had anal incontinence, 55.2% had abdominal pain, and 75.9% had abdominal swelling complaints. 35.6% of the patients later developed brid ileus and operated again. 9.2% of them had developed ileostomy requirement (₅₃).

You et al performed different types of segmental colectomies to 10 patients. Improvement was observed in all the patients in the postoperative 3 month period and 3 patients developed the constipation symptoms again after 2 years. Subtotal colectomy + ileo-rectal anastomose is performed to those patients and they were improved (₅₈). This study had showed the sufficiency of segmental colectomy.

Rivera et al opened percutaneous caecostomy to 12 pediatric patients with anorectal abnormalities and spina bifida, and achieved successful palliation (₅₉).

Pinho et al performed anorectal myectomy to 63 patients. Spontaneous rectal emptying is achieved only in 11 patients and 44 had failed. Incontinence was observed in 6 patients (₆₀).

Eccersiey et al performed irrigation to 11 patients from sigmoidostomy thru a canal. Also, irrigation is performed to 10 patients from transverse colon thru a canal. Abdominal swelling was observed in all the patients in transverse colon group but successful emptying was achieved. 3 patients from sigmoid group had benefit (₆₁).

Additionally patients who are cured with complete laparoscopic total colectomy + ileo-rectal anastomosis are reported (₆₂,₆₃).

It's a physiotherapeutic method used to regain the function of defecation and muscles of anorectal region in constipated patients with diagnosis of pelvic exit obstruction. After there patients are connected to the EMG or manometer with electrodes or perfusion catheters, they perform the contraction and relaxation maneuvers in a specific order and they relearn the working condition of the muscles via the images they obtain on the monitor. These exercises are conducted as 1-3 sessions per week for duration of 4-6 weeks (₆₄). The patient is informed about regional anatomy, how the muscles work, and the mechanism of defecation before they start the therapy. The success rate of the treatment with such method is 31-100% (₆₅).

Inhibition of puborectal muscle contractions are based on paralyzing the muscle by injection of Botulinum-A toxin. It has no lasting efficiency. (₆₆)

It can be performed as partial or complete myotomy in anismus. The technique is abandoned due to postoperative failure and development of incontinence (₅₁). Surgeons in Anatolia region may still perform this technique.

It was once performed in patients with pelvic exit obstruction but it is abandoned since it has no benefits.