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Sarna SK. Colonic Motility: From Bench Side to Bedside. San Rafael (CA): Morgan & Claypool Life Sciences; 2010.

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Colonic Motility: From Bench Side to Bedside.

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Colonic Motility in Health

Methods of Recording Human Colonic Motor Activity and Analysis of Data

Silastic tubes containing side holes or solid-state transducers are widely used methods of recording human colonic motor activity. In spite of some limitations [28, 194], these methods have yielded highly useful information that is the basis of our current understanding of human colonic motor activity in health and in motility disorders. Most investigators position these tubes in the colon via the anus after colon cleansing, which alters colonic motility to some degree [38, 149, 195, 196]. However, similar effects of cleansing in controls and in patients minimize the errors in interpreting differences in findings. These methods do not record contractions that fail to occlude the lumen up to the diameter of the recording tube. However, for the colon, the non-luminal-occluding contractions have a relatively minor impact on propulsion. This limitation does not apply to GMCs, which by definition always occlude the lumen.

Colonic motor patterns are one of the most variable and unpredictable phenomena in organisms. The frequency, amplitude, and timing of all three types of contractions are variable at any given location in the colon. Overall, motor activity shows diurnal variation. Gender affects the intensity and pattern of colonic contractions. Psychological stress and physical exercise alter the motor activity and function. Together, the limitations of recording methods, heterogeneous groups of normal subjects, and unpredictable variability account for the often-conflicting findings in clinical studies. An ideal study design will include a single gender with an age difference between individuals of no more than 10 years and a solid-state transducer recording from the entire length of the colon for a minimum of 24 hours.

A computer program is needed to quantitate colonic motor activity as area under contractions (AUC). However, this number does not indicate propagation of contractions essential for propulsion. Transit time might be faster if the overall increase in colonic motor activity includes a higher frequency of propagating contractions or the mean distance of contractions increases. On the other hand, transit time may be slower if an increase in AUC is accompanied by an impairment in propagation of contractions. However, an increase in AUC might indicate a higher level of mixing/turning over of the fecal material.

Most studies define propagation as sequential occurrence of contractions over at least three adjacent recording locations, the minimum requirement. However, the distances between the recording sites vary among studies. The requirement that a contraction must propagate over at least 20 cm (about 20% of the length of the colon) will better distinguish mass movements by GMCs from slower propulsion by short-duration and long-duration RPCs. The currently used criteria (that any contraction that appears at three sequential recording sites, traveling within a wide velocity range of 0.2 to 12 cm/sec [38, 195] or any velocity greater than 0.5 cm/sec [28], is a propagating contraction) are too lenient. Using this wide range of velocity overestimates the antegrade or retrograde propagation of both types of RPCs. RPCs occur randomly at adjacent locations in the colon; the wide velocity range will include the chance occurrence of randomly occurring contractions as propagated contractions. This criterion might also give a false sense of retrograde propagation. The concept of retrograde propulsion arose from radiological observations of back and forth movements of contrast material, which is caused by bidirectional displacement of luminal contents by a strong contraction at a given location.

Take-home Message

Colonic motor activity is highly variable. Clinical study designs have come a long way from early studies, which reported data from a short distal segment of the colon recorded for one or two hours. Tighter study designs, including better stratification of patient groups, would further improve consistency between studies. No doubt, stricter designs of clinical studies are not always feasible.

Correlation between Colonic Contractions and Propulsion

GMCs are the best-defined contractions in the human colon due to the lack of any ambiguity in recording them. The average frequency of GMCs in the human colon is about 6 to 10 per 24 hours, mean amplitude about 115 mmHg, mean duration about 20 seconds, and they propagate distally at a speed of about 1 cm/sec [28, 195, 197]. The definition of colonic GMCs must include amplitude of at least 100 mmHg. The calculated length of segment contracted concurrently by a GMC is about 20 cm (duration of contraction x speed of propagation). Most GMCs originate in the proximal colon and propagate a mean distance of about 45 cm [195]. Most GMCs, therefore, produce mass movements from the ascending colon to the transverse or descending colon. Only those GMCs that originate in the sigmoid colon or proximal to it and propagate up to the rectum produce the urge to defecate or act of defecation.

About two thirds of the propagating RPCs in the colon do not propel luminal contents, and one-third of the rest propel only partially [38]. The ability of a propagating RPC to propel fecal material increases with its amplitude. Therefore, most RPCs likely do not occlude the lumen of the colon, or they do not occur at uniform amplitude around the circumference to generate a uniform ringlike lumen-occluding contraction. Given that the amplitudes of RPCs are highly variable, the amplitude of a propagating RPC is highly likely to drop below a critical threshold before it reaches its maximum distance of propagation, reducing the distance and effectiveness of propulsion (see Figure 20). These factors make propulsion by RPCs highly ineffective. The lack of a strong correlation between propagating RPCs and propulsion show that colonic RPCs predominantly cause mixing and turning over of luminal contents and produce markedly slow propulsion. The long- duration contractions propagate better than the short-duration contractions and likely produce slow net propulsion over short distances [38].

The measurements of area under contractions show that the sum of all contractile activity increases steadily from the cecum to the sigmoid colon [38]. By contrast, the frequency of propagating RPCs and their mean distance of propagation decrease from the cecum to the sigmoid colon. The relatively intense RPC activity in the ascending and transverse colons results in intensive mixing/turning over of the newly arrived liquid digesta from the ileum [198, 199]. Inefficient propulsion by RPCs allows longer contact time of the newly arrived digesta to absorb water and electrolytes in these segments of the colon. As the fecal material moves to the sigmoid colon, the need for frequent turnover decreases, and so does the activity of RPCs. In fact, the RPCs would be less effective in mixing/turning over the semisolid to solid feces in the sigmoid colon anyway. These patterns of RPCs explain the slower transit in the ascending and transverse colons [199].

Take-home Messages

  1. Colonic propulsion occurs primarily by GMCs.
  2. RPCs in the colon are highly disorganized spatially and variable in amplitude from one contraction to the next, requiring computer-based analysis to quantitate the area under contractions and mean propagation distances.
  3. The RPCs primarily turn over fecal material for uniform exposure to the absorptive mucosal surface. Total RPC activity decreases from the ascending to the sigmoid colon.

Diurnal Variations of Human Colonic Motor Activity

The overall colonic motor activity, (area under contractions; AUC) as well as the frequency of GMCs, exhibit diurnal variation [28, 34, 154, 197, 200202] (Figure 27). The overall activity reduces by about half throughout the colon in females and males during sleep. The reduction is less in the rectosigmoid colon of male subjects [28]. The frequency of GMCs reduces by about 80% during sleep [203]—the nocturnal GMCs occur primarily in the ascending colon [200]. The reduction in the frequency of propagated RPCs relates to the depth of sleep [200]. However, the propagating RPCs or even GMCs in the ascending colon appear transiently during nocturnal arousal from deep sleep and during the REM stage of sleep.

FIGURE 27. Twenty-four-hour profile of the area under contractions (AUC) and the total number of contractions in healthy humans.

FIGURE 27

Twenty-four-hour profile of the area under contractions (AUC) and the total number of contractions in healthy humans. Both parameters increased after ingestion of a 1000-kCal meal at 6:00 PM, on waking up in the morning, and after 400-kCal breakfast. (more...)

An obvious reason for depression of colonic motor activity during sleep is to slow down fecal transit, which prevents awakening at night for bowel movement. The motor activity of the upper gut also decreases during sleep [204]. Respiratory and cardiovascular functions are similarly correlated with sleep stages [205207].

Colonic motor activity, including the frequency of GMCs, significantly increases upon awakening in the morning, which sometimes induces the urge to defecate followed by defecation [28, 34, 197]. The stimulus for increase of motor activity during nocturnal arousals, the REM stage of sleep, and awakening in the morning comes from the CNS via the autonomic neurons, but we do not know the precise mechanisms. It is likely that central activity stimulates the parasympathetic neurons to activate the enteric cholinergic excitatory neurons. The enteric neurons may have accumulated ChAT or ACh in vesicles during low activity in sleep to mount a robust contractile response during nocturnal arousal, REM, or awakening in the morning.

Take-home Messages

  1. Colonic motor activity, including RPCs and GMCs, exhibits diurnal variation to slow down transit during sleep.
  2. Colonic motor activity increases sharply on awakening, which may result in the urge to defecate.

Gastrocolonic Reflex/Response

The increase in colonic motor activity following a meal—especially in the morning when the sigmoid colon and rectum are likely full—is a primitive reflex to prod the colon to empty in preparation for the entry of new digesta [22, 43, 44, 208211]. Most clinical and animal studies show that this response occurs in the whole colon and lasts less than 2 hours [212, 213]. A pronounced increase in sigmoid motor activity—particularly when it includes GMCs—induces an urge to defecate. Infants and newborns display this reflex prominently. Adults may adapt to ignore it.

Studies on experimental animals suggest that the vago-vagal reflex mediates the gastrocolonic response to ingestion of a meal [214, 215]. Electrical stimulation of efferent thoracic vagal fibers stimulates colonic motor activity [216]. The efferent vagal neurons synapse on enteric neurons to enhance the release of ACh, which in turn stimulates excitation-contraction coupling in circular smooth muscle cells to contract them. Clinical studies show that cholinergic receptor antagonists, interference with calcium mobilization by octylonium bromide, or calcium channel blockers (nifedipine and verapamil) block the gastrocolonic response to eating a meal [42, 43, 217, 218], which confirms the roles of cholinergic excitatory motor neurons and excitation-contraction coupling in gastrocolonic response.

The ingestion of a regular meal containing fat releases cholecystokinin (CCK) from endocrine cells in the duodenum and jejunum. However, systemic administration of CCK-8 [22] or cerulean—an analog of CCK-8—to attain its plasma levels within the range achieved by ingestion of a 1000 kCal meal has no significant effect on colonic motor activity in any part of the human colon [208]. In addition, the inhibition of CCK-1 receptors by loxiglumide [208] or dexloxiglumide [219] does not block the gastrocolonic response to ingestion of a meal or transient increase in colonic propulsion, respectively. Therefore, the postprandial physiologic concentrations of CCK in healthy subjects do not affect colonic motor activity or function. However, pharmacologic doses of CCK-8 stimulate colonic motor activity [208]. The safe administration of CCK-8 in humans makes it a useful tool to investigate the potential loci of defect in regulatory mechanisms in motility disorders. CCK acts on presynaptic neurons to release ACh [22], which stimulates contractions. A defect in the motor response to CCK suggests a possible impairment in ACh synthesis/release and/or a defect in excitation-contraction coupling in smooth muscle cells (see Figures 10 and 11).

The evaluation of gastrocolonic response is an effective tool to investigate abnormalities in the release of ACh and excitation-contraction coupling in colonic motility disorders. However, this test cannot pinpoint whether the abnormal response is due to a defect in the synthesis/release of ACh or in the cell-signaling pathways of excitation-contraction coupling. The increase of contractile activity in the sigmoid colon by the short-acting cholinesterase inhibitor edrophonium chloride is greater than in the rest of the colon, suggesting that it might contain a greater number of ChAT-containing neurons or that these neurons may express higher levels of ChAT [220].

Take-home Messages

  1. The ingestion of a meal (~1000 kCal) enhances colonic motor activity for about two hours.
  2. Vago-vagal reflex mediates the gastrocolonic response. Efferent vagal nerves stimulate the enteric cholinergic neurons to enhance the release of ACh, resulting in an increase of colonic motor activity.
  3. The physiological increase of plasma CCK does not contribute to the gastrocolonic response. However, pharmacological doses of CCK increase colonic contractions by releasing ACh from the enteric motor neurons.

Defecation

Perfect defecation means painless and complete evacuation of the rectum and part of the sigmoid and descending colons in a short period after receiving a few minutes of warning. Under resting conditions, tonic contraction of the internal anal sphincter (regulated by myogenic mechanisms) and tonic contractions of the external anal sphincter and puborectalis muscle (regulated by central mechanisms) maintain continence. Defecation is a three-step process. (1) Issue a warning of impending defecation to allow subjects to find a safe and convenient place. (2) Relax the anal sphincters and puborectalis muscle for resistance-free passage of stool. (3) Induce a mass movement to accomplish defecation in a reasonably short period. The following considerations explain the defecation process.

  1. RPCs play little role in evacuation during defecation. Propulsion by this type of contraction is very sluggish in the colon. The distal colon would require several hours to empty solely by RPCs; this is not acceptable. In addition, RPCs do not produce descending inhibition to relax the internal anal sphincter. However, RPCs may gradually fill up the rectum. The rectum accommodates slow filling without sending sensory signals to the higher centers. In this case, the urge to defecate may occur after a long delay when rectal filling exceeds its accommodative capacity.
  2. GMCs play a critical role in normal defecation: they rapidly propel luminal contents over long distances to provide the force for expulsion of feces within a short period. Usually, a group of GMCs begins in the ascending or the descending colon, but they stop short of the rectum (Figure 28) [36]. These predefecation GMCs bring the fecal material to the descending/sigmoid colon and rapidly fill up the rectum. The internal and external anal sphincters remain closed (Figure 29). The filling of the rectum, with the internal and external anal sphincters closed, distends the rectum, which sends the signal for urge to defecate to the CNS via the visceral sensory nerves [8, 36]. Rapid distension of a balloon in the rectum mimics this urge to defecate [221]. There is generally a window of up to about 15 minutes to evacuate after the initial warning.
  3. The assumption of squatting or sitting position straightens the anorectal angle to allow easy passage of the feces (Figure 29).
  4. The sensory mechanisms in the upper anal canal sense the fecal contents as gas, liquid, or solid [222].
  5. During the final phase of defecation, a GMC or GMCs propagate up to the rectum, pushing feces into the anal canal. These GMCs produce descending inhibition of the internal anal sphincter via the enteric interneurons and inhibitory motor neurons (see section on descending inhibition), which relaxes the internal anal sphincter [223]. The puborectalis muscle and external anal sphincters relax under voluntary control (Figure 29), further straightening the anorectal angle with perineal descent to allow expulsion of feces. This sequence may repeat a few times for complete evacuation as far up as the middle colon. The pressure in the external anal sphincter returns to baseline to resume continence.
FIGURE 28. Spontaneous GMCs in the colon associated with urges to defecate and defecation.

FIGURE 28

Spontaneous GMCs in the colon associated with urges to defecate and defecation. The first three GMCs (shown by upward arrows) started near the splenic flexure and terminated in the sigmoid colon. The second and third GMCs caused urges to defecate. The (more...)

FIGURE 29. Pelvic floor function during defecation.

FIGURE 29

Pelvic floor function during defecation. (A) At rest, the closure of internal and external sphincters as well as the acute anal-rectal angle maintains continence. (B) The squatting position and voluntary relaxation of the puborectalis muscle and external (more...)

Valsalva maneuver (straining) during the final phase of defecation increases intra-abdominal pressure to squeeze the rectum and aid in the expulsion of feces, much like squeezing toothpaste. However, in the absence of GMCs, the Valsalva maneuver by itself causes imperfect defecation. First, it empties primarily the stools in the rectum, causing small volume of fecal expulsion. Second, compression of the rectum by increase in abdominal pressure does not induce descending inhibition; only distension or a strong contraction, such as a GMC, produces descending inhibition.

Take-home Messages

  1. GMCs in the sigmoid colon fill up the rectum while the anal sphincters are closed, causing an urge to defecate.
  2. Subsequent GMCs that propagate up to the rectum produce descending inhibition, which relaxes the internal anal sphincter.
  3. The puborectalis muscle and external anal sphincter relax under voluntary control while GMC expels the feces.
  4. Fecal expulsion by Valsalva maneuver requires straining to push feces through the anal sphincters due to the lack of adequate descending inhibition.

What Causes the Random Generation of GMCs?

While we do not know the complete answer, a number of observations and pharmacological experiments provide significant clues to the generation of GMCs.

  1. Voluntary actions do not generate GMCs. However, the incidence of GMCs decreases during sleep, and GMCs do not occur under anesthesia. By contrast, the probability of occurrence of GMC increases after a meal or on awakening in the morning. Finally, intracerebroventricular (ICV) administration of thyrotrpophin releasing hormone by a cannula in the left ventricle stimulates a colonic GMC (Figure 30A). Taken together, the activation of neurons in the lower brain stimulates colonic GMCs, but this action is not under voluntary control.
  2. S2 and S3 sacral nerve stimulation increases the frequency of GMCs twofold throughout the colon (Figure 30B) [224]. The central stimulation of GMC likely works through the parasympathetic outflow.
  3. The stimulation of mucosal nerve endings by bisacodyl, a mucosal irritant contact laxative, stimulates colonic GMCs [225227]. We do not know whether bisacodyl stimulates intrinsic sensory neurons or the extrinsic sensory neurons (vago-vagal reflex) to stimulate GMCs. Regardless, each pathway as well as sacral nerve stimulation and central stimulation by thyrotrophin-releasing hormone converge on the enteric motor neurons to release ACh. Supramaximal accumulation of ACh at the neuromuscular junction activates excitation-contraction coupling in circular muscle cells to stimulate GMCs (see earlier section on GMCs). Neostigmine and edrophonium chloride stimulate GMCs also by accumulation of ACh at the neuromuscular junction [8, 134, 220] (Figure 31).
  4. Fermentation by anaerobic bacteria breaks down undigested carbohydrates into short-chain fatty acids. The infusion of short-chain fatty acids into the human ileum results in abdominal cramping and an urge to defecate [228]. The investigators did not record colonic motility in this study, but these symptoms are typical of colonic GMCs. However, they found that ileal infusion of volatile fatty acids in dogs stimulates GMCs that propagate right up to the terminal ileum and presumably into the colon to generate the urge to defecate [229] (Figure 32A). Animal studies in rats show that colonic infusion of short-chain fatty acids indeed stimulates GMCs in the proximal colon that propagate all the way to the distal colon [230] (Figure 32B). Short-chain fatty acids in the colon stimulate the release of 5-HT from the enterochromafin cells. 5-HT acts on 5-HT3 receptors on vagal afferents neurons to stimulate vago-vagal reflex. The efferent vagal nerves synapse on nicotinic receptors on enteric motor neurons to release ACh, which stimulates GMCs [230].
  5. The stimulation of GMCs by short-chain fatty acids can be blocked by 1) mucosal application of lidocane, which desensitizes nerve endings, 2) intraluminal application of 5-HT3 receptor antagonist, 3) bilateral vagotomy, or 4) intravenous administration of hexamethonium or atropine. These findings suggest that short-chain fatty acids use the vago-vagal reflex, rather than the intrinsic neuronal reflex involving ISNs and interneurons, to stimulate GMCs.
  6. Perfusion of long-chain oleic acid—a common dietary constituent—in the ascending colon stimulates GMCs that start near the cecum and propagate in the anal direction (Figure 33). The GMCs accelerate colonic transit, associate with abdominal cramping, and induce defecation [231]. This model mimics steatorrhea. Control infusions of saline have no effect.
  7. Strenuous physical exercise after a meal stimulates GMCs [232]. The ingestion of a meal increases colonic motor activity. Most of the postprandial increase in motor activity is of nonpropagating RPCs because the patients lie in bed during this test for manometric recording. However, if patients are mobile after a meal, the frequency of GMC increases, producing mass movements [233]. Taken together, somatic activity in the postprandial state promotes the stimulation of colonic GMCs (mass movements).
  8. Excessive absorbable or nonabsorbable fluids in the colon––including those secreted from the small intestine by oral laxatives—stimulate GMCs [149, 234, 235].
FIGURE 30. Central stimulation of GMCs.

FIGURE 30

Central stimulation of GMCs. (A) An intracerebroventricular administration of thyrotrophin-releasing hormone stimulated a GMC in the dog colon. (B) Electrical stimulation of the S3 sacral nerve increased the daily frequency of GMCs in a patient with slow-transit (more...)

FIGURE 31. Stimulation of GMCs in canine colon by intravenous administration of 30 µg/kg neostigmine, a cholinesterase inhibitor.

FIGURE 31

Stimulation of GMCs in canine colon by intravenous administration of 30 µg/kg neostigmine, a cholinesterase inhibitor. Neostigmine stimulated a series of GMCs, three of which (connected by solid lines) resulted in defecations. SG = strain gauge (more...)

FIGURE 32. Intraluminal administration of volatile fatty acids (VFA) stimulates GMCs.

FIGURE 32

Intraluminal administration of volatile fatty acids (VFA) stimulates GMCs. (A) Intraluminal administration of short-chain fatty acids in an isolated loop of ileum and colon with intact extrinsic innervations stimulated a GMC that propagated to the ileocolonic (more...)

FIGURE 33. Perfusion of oleic acid into the ascending colon stimulates GMCs that start near the cecum and propagate in the anal direction.

FIGURE 33

Perfusion of oleic acid into the ascending colon stimulates GMCs that start near the cecum and propagate in the anal direction. (Reproduced with permission from Spiller et al. and Phillips, SF, Gastroenterology, 91: 100–107, 1986 [231].)

Take-home Messages

  1. Vagovagal reflex may play a prominent role in the generation of colonic GMCs.
  2. Short-chain fatty acids generated by bacterial fermentation of carbohydrates in the ascending colon may be a major dietary source of stimulation of GMCs in the colon. This works well because fermentation produces short-chain fatty acids with delay, which allows time for absorption of water and electrolytes in the ascending colon before a GMC propels them by mass movement.
  3. Malabsorption of fats is also a dietary source of stimulation of colonic GMCs.
  4. The release of 5-HT in the colon utilizes vago-vagal reflex, rather than the enteric reflexes, to stimulate GMCs.
  5. Several physiological stimuli, such as somatic activity, stimulate GMCs when ingestion of a meal has primed the vago-vagal reflex.

Anorectal Motor Activity

Anorectal motor activity plays a critical role in maintaining continence. Findings from several studies using the manometric method of recording show marked variations in details, such as amplitudes, durations, and frequencies of contractions as well as in the effects of meal ingestion and sleep on these parameters [236244]. The following points represent consensus related to anorectal motor function.

  1. The resting anal pressure (about 70 mmHg) is greater than the resting rectal pressure (about 30 to 40 mmHg). This gradient is helpful in maintaining continence.
  2. The rectum generates periodic bursts of contractions: rectal motor complex (RMC) (Figure 34). Each burst of contractions lasts about 5 to 10 minutes during the awake state and recurs at a frequency of about 0.5/hour. RMCs may occur more frequently in the distal rectum than in the mid or proximal rectum. The contractions occur at a frequency of about 2 to 3 cycles per minute.
  3. Most parameters of RMCs decrease during sleep and increase after a meal. We do not understand the roles of RMCs in maintaining continence.
  4. The anal canal shows transient spontaneous relaxations that relate loosely to contractions in the rectum.
FIGURE 34. Rectal motor complexes in the mid and lower rectums.

FIGURE 34

Rectal motor complexes in the mid and lower rectums. (Reproduced with permission from Ronholt et al. and Chritiansen, J, Dis Colon Rectum, 42:1551–1558, 1999 [237].)

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