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REVIEW
Received: 3 June 2011 / Accepted: 23 January 2012 / Published online: 26 February 2012
Springer Science+Business Media, LLC 2012
Abstract Human defecation involves integrated and bases. However, although continence is ultimately depen-
coordinated sensorimotor functions, orchestrated by cen- dent upon sphincteric function (as long as anal pressure is
tral, spinal, peripheral (somatic and visceral), and enteric greater than rectal pressure, continence is maintained),
neural activities, acting on a morphologically intact gas- defecation appears to be a much more complex process.
trointestinal tract (including the final common path, the Disordered defecation and incontinence are both associated
pelvic floor, and anal sphincters). The multiple factors that with significant economic and personal burdens [1].
ultimately result in defecation are best appreciated by Rational directed management of the individual consti-
describing four temporally and physiologically fairly dis- pated patient is suboptimal [2], primarily because our
tinct phases. This article details our current understanding understanding of defecation is incomplete; this may reside
of normal defecation, including recent advances, but in a combination of lack of appropriate investigative tools,
importantly identifies those areas where knowledge or over-reliance on acceptance of various mechanisms
consensus is still lacking. Appreciation of normal physi- believed to contribute to defecation through received wis-
ology is central to directed treatment of constipation and dom, lack of focused research, and lack of consensus over
also of fecal incontinence, which are prevalent in the what constitutes ‘‘normal.’’ This review describes con-
general population and cause significant morbidity. temporary understanding of the processes involved in
defecation in humans and identifies gaps in our knowledge.
Keywords Defecation Rectal evacuation Such understanding is fundamental to the definition/clas-
Physiology of defecation Rectal sensorimotor function sification and management of patients presenting with
Colonic motor activity symptoms of constipation characterized by evacuatory
dysfunction.
Introduction
Frequency of Normal Defecation
Continence and defecation are inextricably linked, with
common anatomical, physiological, and neurological Infrequency of defecation is often used to define consti-
pation. A community questionnaire survey involving more
than 1,800 volunteers found that the most common bowel
S. Palit P. J. Lunniss S. M. Scott pattern was once a day in both sexes, but this pattern was
Academic Surgical Unit (GI Physiology Unit), Barts and the
present in only 40% of men and 33% of women [3];
London School of Medicine and Dentistry, Blizard Institute,
Queen Mary University, London, UK another 7% of men and 4% of women had a regular twice
or thrice daily bowel habit [3]. Inquiring the bowel
S. Palit (&) symptoms of 1,455 healthy adults, Connell et al. [4] found
GI Physiology Unit, Royal London Hospital, Wingate Institute
that over 99% had between three motions per day to three
of Neurogastroenterology, 26 Ashfield Street,
London E1 2AJ, UK motions per week. Similar findings were reported by Hardy
e-mail: s.palit@qmul.ac.uk et al., in a study involving 440 nurses [5]. Based on these
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1446 Dig Dis Sci (2012) 57:1445–1464
studies, it is generally accepted that in adults the ‘‘normal’’ rectum gradually hardens and becomes more difficult to
frequency ranges between a maximum of three times per evacuate causing a vicious cycle that can ultimately lead to
day to a minimum of three times per week [6]. However, chronic rectal distension [29]. Ignoring the defecatory urge
less than three motions per week has been considered may be a conscious decision or an unconscious automatic
normal if this is not associated with discomfort [7]. It is habit of the child resulting from altered or diminished brain
important to note that patients’ perception of what is processing of urge sensations due to loss of attention [30].
‘‘normal’’ and what is constipation can differ from their Such ‘‘conditioning’’ behavior has also been reported in
clinicians [8, 9]. While clinicians usually define constipa- adults [31], many of whom display toilet avoidance behavior
tion by decreased stool frequency, patients tend to define it due to pain, or to the lack of the ‘‘sanctum’’ of one’s private
in terms of disordered function (e.g. need to strain), and lavatory [32]. In a seminal study, Klauser et al. compared
passage of hard stool [10]. frequency of defecation and colonic transit in 12 healthy
In children, the frequency of bowel movements male volunteers during a 2-week study where 1 week of
decreases with age; the decline occurs during the first normal defecation and 1 week of voluntary suppression of
3 years and is most rapid from the first months postpartum defecation followed each other in a randomized order [33].
[11]. By the age of 4, bowel frequency is equivalent to that Voluntary suppression of defecation led to decrease in stool
of adults [12]. The average frequency of defecation in frequency, stool volume, and increases in total colonic and
children is 6.3 ± 1.3 times per week (range, 4–9 per week) recto-sigmoid transit times, a finding which suggests that
[13]. The frequency of high amplitude propagating con- constipation can be ‘‘learned’’ [33].
tractions (HAPCs), which have been linked to colonic mass Appropriate toilet training also appears necessary for
movements (see below), is significantly higher in young normal defecation. Improper training has been implicated as
children when compared to children older than 4 years of a cause of constipation in children. Studies have shown that
age [14]; this correlates with the increased number of toilet training is now initiated at an older age than it was in
bowel movements observed in young children [14]. the past [34]. In the 1940s, toilet training usually started
before 18 months of age, whereas today, training often starts
between 21 and 36 months, and only 40–60% children
Factors Influencing Evacuation complete toilet training by the age of 3 [35, 36]. One study
reported that girls develop toileting skills earlier than boys
Influence of Psycho-Behavioral Factors and Voluntary [37]. Lack of successful toilet training by 42 months of age
Suppression of Defecation is associated with toileting refusal behavior [36].
Toilet training is initiated and completed significantly
There is now increasing recognition that a variety of psycho- earlier in urban areas as compared to rural areas [38]. Race
behavioral factors can affect gastrointestinal function. and income are independent predictors of the age at which
Influence of psychological trait on bowel habit has long been parents believe they should initiate toilet training; Cauca-
appreciated [15], and several studies have shown that the sians and higher income group parents are more likely to
incidence of constipation is higher in patients with psycho- start toilet training at a later stage as compared to other
logical impairment [16–18] or a history of traumatic life races and lower income groups [39]. Parents play a key role
events including sexual and physical abuse [19, 20]. The in toilet training; they need to provide the direction,
influence of mental state, such as short-term anxiety and motivation, and positive reinforcement in addition to set-
stress, also impact on bowel habit. Furthermore, it is well ting aside time and having patience during the process [40].
known that stool ‘‘withholding’’ behavior, often triggered by
an instinct to avoid painful evacuation, is one of the main Influence of Posture on Defecation
causes of defecatory dysfunction in children [21–23]. Two
separate studies have reported that up to 97% of constipated The defecatory position that a subject assumes is dictated
children display stool withholding behavior [24, 25]. Other by a number of factors, including the type of toilet avail-
associated findings were the presence of a rectal/abdominal able (if available), physical and mental ability, and cultural
mass and a history of earlier painful defecation [21, 24, 25]. factors. In Western countries, sitting on a toilet seat
There is evidence that constipation and painful defecation (commode) is common, whereas in Africa and Asia
not only precede toileting refusal [26], but also help in squatting is the preferred position.
maintaining this behavior [27, 28], which manifests as Using defecography (simulated defecation of a neostool
‘‘retentive posturing’’ where toddlers hold an erect posture under continuous fluoroscopic screening), it has been
and forcefully contract their gluteal and pelvic floor mus- demonstrated that the anorectal angle becomes more obtuse
culature [24] until the defecatory urge disappears due to (opens up) with increasing hip flexion, making evacuation
rectal accommodation. It is hypothesized that stool in the easier [41]. In a study which compared the time and sense
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Dig Dis Sci (2012) 57:1445–1464 1447
of satisfactory rectal emptying in three postures (sitting on to stool form, frequency of defecation is poorly correlated
a Western standard commode; sitting on a similar com- with whole gut or colonic transit [47, 51], in that true slow
mode with a 10 cm stool under the subjects’ feet, effec- transit is usually associated with infrequency, but frequent
tively lowering the height of the commode; and in the bowel actions does not imply fast transit, i.e. a constipated
squatting posture), it was found that evacuation was patient may revisit the toilet repeatedly [52]. Likewise, in
quickest and afforded a more complete sense of bowel children, stool frequency has been shown to correlate with
emptying in the squatting posture and was most difficult on total gastrointestinal transit time, but not all children with
the standard Western type commode [42]. As expected, prolonged transit have reduced bowel frequency [13].
other studies have shown that evacuation is also easier Very few studies have compared the effect of stool
when sitting compared to lying [43, 44]. The latter of these volume or form on evacuation. Bannister et al. demon-
studies also showed, perhaps not surprisingly, that com- strated that evacuation of small hard spheres mimicking
pared to the sitting posture, the frequency of dyssynergia pellet-like stool required more effort (measured as longer
(uncoordinated pelvic floor activity) during evacuation was time and higher intrarectal pressures) than the expulsion of
greater when lying down [44]. a compressible 50 ml balloon, used as a surrogate of soft
stool [53]. In a more recent study [44], only 4% of subjects
Influence of Colonic Transit, Volume, and Consistency were unable to expel a silicone stool-substitute in the sit-
of Stool ting position, while 16% were unable to expel a 50 cc
balloon. Moreover, balloon expulsion time was signifi-
Stool volume and consistency are directly related to gas- cantly longer than expulsion of the stool substitute.
trointestinal (GI) transit time [45]. Co-ordinated colonic
motor activity drives transit, and hence the rate at which Influence of Diet and Intraluminal Contents
colonic contents are delivered to the rectum, as well as the
physical and chemical nature of the feces itself. Ingestion of a meal is regarded as the most potent physi-
As a general rule (though not absolute), loose stools are ological stimulus influencing colonic/gastrointestinal tran-
associated with rapid GI/colonic transit [46, 47] whereas sit and motor activity. A meal-induced increase in colonic
constipation may be associated with slow GI transit and motor activity is more pronounced in the transverse/
reduced motility [48]. Degen and Phillips, who assessed descending colon than the recto-sigmoid colon [54–56].
transit in 32 healthy volunteers with scintigraphy and Studies performed around 30 years ago showed that overall
radio-opaque markers [45], concluded that hard stools colonic response to a meal is excitatory and follows a
correlated significantly with slower intraluminal movement biphasic pattern, with a first peak of activity seen within the
and loose stool with faster transit. Other studies have first 10–50 min and a second peak occurring within 70 and
reported that constipation may be associated with greater 90 min of having a meal [57–59]. A fatty meal stimulates
levels of (uncoordinated) contractile activity in the pelvic colonic motor activity [54, 57, 58, 60] to a greater extent
colon in comparison to patients with diarrhoea [49]. Intu- than a carbohydrate-rich [54, 58] or a protein-rich meal
itively, reduced colonic motor activity, and hence delayed [58]. However, fatty meals also stimulate retrograde colo-
transit should allow greater water absorption from intra- nic activity which may result in a net decrease in colonic
luminal contents, desiccating the stool, and reducing vol- transit [54]. The stimulatory effect of a carbohydrate-rich
ume, resulting in harder motions that are more difficult to meal has a more rapid onset than that of a fatty meal [54]
expel. In a study investigating constipated children, Ben- but is shorter lived. Ingestion of a protein and amino acid-
ninga et al. found a significant association between the rich meal actually inhibits colonic motor activity [58, 59].
presence of a palpable rectal mass and a colonic transit Likewise, alcohol has been shown to have an inhibitory
time of[100 h [50]; these children suffered from nocturnal effect on recto-sigmoid motility [61, 62]. Patients in whom
‘‘overflow’’ fecal soiling. Conversely, increased and co- the colonic intraluminal contents have a high osmotic load
ordinated motor activity can deliver larger quantities of (e.g. bile salt malabsorption, lactose intolerance, etc.) have
more liquid fecal material into the rectum, which may a rapid colonic transit [63]. It should be noted that the
overpower the continence mechanism. In constipated effect of dietary components on colonic motor functions
patients, stool form correlates well with whole gut [47] and using contemporary methodologies (pancolonic manome-
colonic transit [51]. In constipated subjects, a mean Bristol try/scintigraphy) has not been reproduced.
stool form [47] of \3 (indicating hard stools, ranging from Although it is generally agreed that an increase in die-
pellet-like or ‘‘nuts,’’ to sausage- or snake-like, with cracks tary fibre intake is beneficial for constipation [64–66], there
on its surface) is specific and sensitive for the diagnoses of have been concerns about the adverse effects of a high fibre
delayed whole gut and colonic transit [51]. This relation- diet in children, including a resultant lowering of calorie
ship may be absent in healthy individuals [51]. In contrast intake [67–69], increased fecal energy loss [66, 69], and
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1448 Dig Dis Sci (2012) 57:1445–1464
decreased bioavailability of minerals [70]. Dietary fibre access to sanitation [94, 95]. Cultural and lifestyle fac-
intake can also lead to excessive gas formation resulting in tors are likely to have major influence, but obviously are
abdominal bloating and cramping, though it has been more difficult to study.
reported that if fibre content in diet is increased gradually Circulating hormones (like somatostatin) and humoral
rather than acutely, excessive gas formation can be reduced factors (like substance P, vasoactive intestinal peptide,
[71]. peptide YY, cholecystokinin, etc.) are also known to be
important as they can influence gastrointestinal motility
Influence of Age and Gender that underscores efficient defecation [101–106]. Sec-
ondary constipation is a well known consequence of
Age and gender are also known to effect evacuation [72]; systemic disorders including diabetes, hypothyroidism,
epidemiological studies indicate that the incidence of hypercalcemia, several form of myopathies and neurop-
constipation is characterized by two peaks—one during athies, etc.
early childhood and the second after the age of 60–65 (see Additionally, in patients with intractable constipation a
below). In childhood constipation, one study has shown reduction in the number of interstitial cells of Cajal [107–
that half of the affected children develop constipation 110], which are regarded as intestinal pacemakers [111,
within the first year of their life [73], with transition from 112], morphological changes or reduction in number of
breast milk to formula feeding being proposed as the ganglia and/or glial cells [110, 113, 114], and an abnormal
possible cause [74]. Other studies have reported a peak nerve fibre density in the circular muscle layer [115] have
incidence between 3 and 5 years [75–78]. The second all been identified. The mechanistic significance of such
peak, occurring in geriatric patients [9, 79], has been var- findings is however unclear.
iously attributed to aging with consequent loss of tissue
elasticity [80], increased evidence of neuropathy with age
Gaps in Our Knowledge
[81], pelvic floor weakness and laxity [81], reduced
mobility, polypharmacy [82], etc.
• The precise influence of psychobehavioral factors,
With regard to gender, incidence of childhood consti-
particularly according to underlying subject state or
pation is reported to be similar between boys and girls [13,
trait;
83, 84], or slightly higher in boys [85]. However in adults,
• The force vectors that are endowed by changes in
constipation is much more common in women [3, 9, 79,
posture, and that positively influence evacuatory
86]. It is not clear why this change occurs. However,
efficiency;
gender specific differences in pathophysiologic mecha-
• Why colonic transit is longer in females;
nisms and the increased incidence of constipation in
• The influence of diet on colonic motor function using
association with pregnancy and delivery have been impli-
contemporary methodologies;
cated [85]. Colonic transit time is faster in males compared
• Why there is no gender specific difference in the
to females [87, 88], and females are also more likely to
prevalence of constipation in children, yet constipation
pass hard stools [3, 45], perhaps making them more sus-
is more prevalent in adult women.
ceptible to constipation [3]. Increased perineal descent,
reflecting a less supportive pelvic floor (likely a conse-
quence of parity), has been noted in elderly females com-
pared to younger females, and there is a decreased ability The Phases of Defecation
among both sexes to evacuate 18-mm spheres with
advancing age [80]. Other possible causes for a female The multiple factors that ultimately result in defecation
preponderance in the adult population include the influence are best appreciated by describing four temporally and
of female hormones [3], the menstrual cycle [96–99], physiologically fairly distinct phases: (1) the basal phase,
parity and childbirth, pelvic floor function [100], and pelvic (2) a pre-defecatory phase, leading to generation of a
surgery (e.g. hysterectomy) [89], but for the sake of brevity defecatory urge, (3) the expulsive phase, during which
will not be addressed in further detail. evacuation occurs, and finally, (4) termination of defe-
cation (Fig. 1).
Other Influences
The Basal Phase
There are several other important factors relating to
ability to defecate, not least intact cognition [90] and Prior to the events that specifically lead up to defecation, a
mobility [91, 92], as evidenced by studies of the insti- comprehension of normal colo-rectal motor functions, in
tutionalized [93], as well as fluid intake [90, 92], and the absence of a desire to defecate, requires description.
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Dig Dis Sci (2012) 57:1445–1464 1449
Colonic Motor Activity colonic activity [122] and exhibit reduced colonic respon-
ses to food [122–125], as well as lacking spatio-temporal
Colonic functions relevant to normal defecation include: organization of colonic contractile patterns [126].
absorption of water from intraluminal contents, net ante- Colonic motor functions can simplistically be subdi-
grade propulsion of colonic contents at an adequate rate, vided into ‘‘transit’’ (i.e. intra-luminal movement), mea-
and temporary storage of feces until convenient to expel sured clinically either by radio-opaque marker studies,
them. After delivery of chyme from the terminal ileum into colonic scintigraphy, or more recently by wireless tele-
the caecum, luminal contents are transported distally while metric capsule methods [127–129], or ‘‘contractile activi-
gradual desiccation and mixing occurs, making them pro- ties,’’ the sum of which underlies the shift in intra-luminal
gressively more solid [116]. This transport is facilitated by content. This is best measured by intraluminal manometry
complex colonic motility patterns. [116]. Although colonic manometry remains a research
Colonic motor activity shows a circadian pattern, in that tool in adults, it been used to influence clinical manage-
it increases after awakening [117] and is higher during the ment in highly selected pediatric cases [130–133].
day compared to the night [117–120]. Colonic activity also From transit studies the upper limit of normal colonic
increases after meals (see above) [117, 120, 121]. Patients transit time has been determined to be around 72 h in
with constipation may lack the nocturnal suppression of adults [134]. Colonic transit is faster in children [12], being
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1450 Dig Dis Sci (2012) 57:1445–1464
reported as less than 57 h [13, 135–137]. ‘‘Slow transit’’ originate anywhere in the colon, they do so mostly in the
refers to a clinical condition likely resulting from ineffec- proximal colon and then migrate distally for a variable
tive colonic propulsion. Abnormalities of colonic transit distance [117, 120, 121, 147]. The distance of propagation
are often expressed as segmental (right colonic, left colonic correlates with the proximity of the site of origin to the
or recto-sigmoid delay) or pan colonic in nature [138–140]. caecum [120, 121, 147]. One study found that only a third
Colonic motor activity is characterized by brief (phasic) of the HAPSs reached the anus, the remainder terminating
contractions and also sustained (tonic) contractions (best at the rectosigmoid region [117]. HAPSs are often tem-
measured with a barostat) [127]. Phasic contractions are porally associated with defecation [117, 148, 151] or
further classified as propagating or non-propagating con- passing flatus [117]. They help in propulsion of the fecal
tractions, or sequences, based on whether or not they bolus [147] and are the manometric equivalent of ‘‘mass
propagate along the colon. Non-propagated contractions movements’’ noted radiologically (i.e. a rapid shift of a
appear to be the most common event and can occur as considerable volume of intraluminal content) [152, 153].
isolated, seemingly random contractions or in ‘‘bursts’’ Frequency of HAPSs is often reduced in patients with
[116, 118]. They have a frequency of between 2 and 4 constipation [122–125, 140, 151, 154, 155], and this is the
cycles per minute [141] and an amplitude of between 5 and most consistent motor abnormality described is such
50 mm Hg [117]. The duration of these contractions can patients.
either be short (\15 s) or long (15–60 s) [116, 142, 143]. The majority of the colonic propagated activity is
‘‘Bursts’’ of non-propagated pressure activity, lasting 3 min characterized by low amplitude propagated sequences
or more can also occur [116]. These contractions can either (PSs; or low amplitude propagated contractions: LAPCs).
be rhythmic (occurring at frequencies of 2–3 cycles/min or These typically have amplitude \50 mmHg [156], occur
6–8 cycles/min) or arrhythmic [116, 118]. As a caveat, it 40–120 times in a 24 h period [117, 147, 157], and prop-
should be noted however, that the majority of colonic agate for distances \22.5 cm [121]. Studying the relation
manometries have been performed with recording sites between frequency of PSs and constipation, some authors
spaced 10 cm or more apart. A recent study using high have found a reduced frequency in obstructed defecation
resolution manometry with 1 cm sensor spacing indicates [122] and slow transit constipation [155]; others have
that manometric pressure patterns often propagate for less found no difference [151]. In healthy individuals, propa-
than 10 cm [144], which indicates propagated activity may gating sequences display a spatio-temporal or ‘‘regional
have been previously ‘‘mislabeled’’ as non-propagated linkage’’ (where two consecutive PSs, originating from
[141]. Although the role of non-propagated activity in different colonic regions overlap) [120, 158]. The signifi-
luminal transport is not fully understood [141], it is thought cance of this finding lies in the fact that although a single
to aid mixing of intraluminal contents by local propulsion PS does not span the entire length of the colon, a series of
[145, 146] and retropulsion [147] of the fecal bolus. ‘‘regionally linked’’ PSs can. This linkage has been found
Propagated colonic activity can be retrograde (oral to be absent in patients with constipation [126, 158].
propagation) or antegrade (aboral propagation). Retrograde The sigmoid colon primarily exhibits cyclical bursts of
colonic activity is thought to be less frequent than ante- contractions (though they occur throughout the rest of the
grade activity [117, 122] and appears mostly confined to colon also), called motor complexes (MC) or ‘‘periodic
the proximal colon [147]. The frequency of retrograde colonic motor activity’’; these may be important in mod-
propagated activity may be higher in patients with consti- ulating the delivery of fecal material into the rectum. These
pation than in healthy individuals [122] indicating that the MCs typically have amplitudes of 15–60 mm Hg, last
ratio between retrograde and propagated contractile activ- 3–30 min, and recur at 80–90 min intervals [159]. By
ity may be an important pathophysiological mechanism of conventional manometry, up to 70% of these are non-
delayed colonic transit. propagating, approximately 18% propagate aborally, and
Among propagated sequences, there are sets of propa- 15% migrate orally [117]. Another feature of the sigmoid is
gated pressure waves that are distinct by virtue of their that when distended, it contracts, with concomitant relax-
elevated amplitude. These waves, known as high amplitude ation of the recto-sigmoid junction; this mechanism likely
propagated sequences (HAPSs; or contractions: HAPCs) facilitates progression of feces into the rectum [160]. The
have been widely and variously defined [116, 148], but presence of a sphincter between the sigmoid and the rectum
typically have amplitudes [100 mmHg [147, 149, 150]. In (the recto-sigmoid sphincter of O’Beirne) [161] has long
adults, HAPCs occur, on average, 5–6 times a day (range been debated. Although the evidence of a convincing
2–24) [116], whereas the frequency of HAPCs is signifi- anatomical sphincter is lacking, a high-pressure zone with
cantly greater in children younger than 4 years of age [14], unique contractile properties (in response to sigmoid and
which likely correlates to the increased number of bowel rectal distension/contraction) has been shown in the distal
movements in infants/toddlers. Although HAPCs can sigmoid, which supports the idea of a physiological
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Dig Dis Sci (2012) 57:1445–1464 1451
sphincter [161–164]. The role of the recto-sigmoid junction The anal canal is normally closed by the tonic activity of
in normal defecation is still unclear. However, it is inter- the internal and external anal sphincters, together with the
esting to note that many severely constipated patients have anal cushions. The internal anal sphincter (IAS) is chiefly
an empty rectum on rectal examination [165, 166]. responsible for continence at rest [180], and is predomi-
nantly composed of slow-twitch, fatigue-resistant smooth
Rectal Motor Activity muscles. Electromyographic study of the IAS demonstrates
a constant activity at rest [181–183], which is unaffected
Rectal motor activity, like the sigmoid, is characterized by by respiration or administration of a general anaesthesia
recurrent motor complexes. The frequency of rectal MCs [184]. The contribution of the IAS to anal canal tone is
appears unaffected by meal intake [117]. The role of these debated, but has been reported as being as much as 85% at
motor activities is not fully understood [141]. However, rest, 65% during constant rectal distension, and 40% after
rectal MCs are seen to propagate in a retrograde direction sudden rectal distension [185]. Other studies estimate a
[167]; it has thus been postulated they help to keep the lesser influence, in that approximately 55% of resting anal
rectum empty by acting as a ‘‘braking mechanism’’ to tone is due to IAS activity [186]. The external anal
untimely flow of colonic contents [167]. It has been pro- sphincter is also in a state of constant tonic activity at rest
posed that MC activity may be used as a marker of enteric [187], and this generates approximately 30% of the basal
neuromotor function as their presence is independent of resting anal tone [186]. The anal vascular cushions,
intact extrinsic innervation [116, 159, 168]. In healthy including the superior hemorrhoidal plexus, contribute to
volunteers, during the basal phase, the rectum remains approximately 15% of the resting anal tone [186], but
mostly empty [169] or can contain a variable amount of importantly provide the ‘‘hermetic seal’’ which cannot be
feces without conscious awareness [170]. achieved by sphincteric muscle tone alone.
Integral to the dynamic nature of anal canal activity is
Pelvic Floor and Puborectalis Activity the intermittent, transient relaxation of the internal anal
sphincter, which allows descent of distal rectal contents
At rest, the levator ani, the puborectalis, and the external anal into the upper anal canal, endowing a subconscious or
sphincter remain in a state of continuous contraction. This conscious perception of their physical nature. This so-
reflex is known as the postural reflex [171] and it helps to called sampling reflex occurs approximately seven times
support the weight of the pelvic viscera. The reflex is main- per hour [188] in healthy control subjects, but less fre-
tained through the lower lumbar and sacral spinal cord [171]. quently in patients with incontinence [189]. This reflex can
In relation to defecation, among the pelvic floor mus- be reproduced under laboratory conditions, where rectal
cles, the puborectalis is probably the most relevant. It distension causes reflex relaxation of the internal anal
originates from the posterior surfaces of the pubis, passes sphincter (in this case know as the ‘‘recto-anal inhibitory
around the anorectal junction inferolaterally, and decus- reflex’’: RAIR), as well as contraction of the external anal
sates with its fibers from the opposite side to form a sling sphincter.
behind the anorectal junction. The puborectalis derives its In vivo, the consequence of the sampling reflex is a drop
nerve supply from direct branches of the anterior roots of in upper anal canal pressure, so that rectal pressure
S3 and S4 [63, 172–174]. becomes greater than or equal to mid anal pressure [188].
At rest, the contractile traction of puborectalis maintains Lower anal canal pressure, however, remains virtually
the anorectal angle (angle between the long axis of the unchanged [190], and overall, maximal intra-anal pressure
rectum and the long axis of the anal canal) at approxi- remains higher than intra-rectal pressure to preserve con-
mately 90 [175]. While this angulation helps in preser- tinence [191]. The net effect of this pressure change is to
vation of continence [176], increased acuity has been briefly expose the anal sensory area to the rectal contents so
related to obstructed defecation [177, 178]. that sampling can occur [188, 190]. The reflex is controlled
by the enteric nervous system [180, 192, 193], with a
Anal Canal Activity degree of regulation from the sacral cord [192], and is
absent in patients suffering from Hirschsprung’s disease
At rest, the anal canal remains closed to preserve conti- [194].
nence. The anal sphincter complex is extremely dynamic The anal canal epithelium is lined by highly sensitive
and is influenced by a variety of reflexes and modulation by nerve endings derived from sensory, motor and autonomic
higher centers in such a way that rather than acting as a nerves, in addition to the enteric nervous system [63]. The
passive barrier, it provides an airtight seal at all times anal sensory area contains specialized sensory end organs,
except when the subject wants to pass flatus or defecate including Krause end bulbs, Golgi Mazzoni bodies, genital
[179]. corpuscles, Meisnner’s corpuscles, and Pacinian corpuscles
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1452 Dig Dis Sci (2012) 57:1445–1464
[195]. It is important to note, however, that this informa- propagated sequence, of which 62% were associated with
tion was derived from studies performed over 50 years ago, HAPSs [121]. This study also showed that propagated
using techniques which may now be regarded as outdated. sequences were more likely to result in urge during the 1 h
Few other data are available. Slowly adapting afferents that pre-expulsive phase (as compared to the basal phase), and
remain silent in basal conditions, but are sensitive to cir- that sequences that propagated further were more likely to
cumferential stretch, exist in the IAS of guinea pigs [196]. result in an urge. During the pre-expulsive phase, propa-
Lynn et al. also demonstrated that in guinea pigs, rectal gated sequences often start as unperceived colonic con-
nerve axons to the IAS predominantly end in extensive tractions in the proximal colon, and migrate distally while
varicose arrays within the circular muscle [196]. Mecha- increasing in amplitude to become a ‘‘full blown’’ HAPS,
notransduction sites were strongly associated to these that is then associated with an urge to defecate [148]. It is
varicose arrays [196]. feasible that increased colonic activity seen during the pre-
expulsive phase leads to movement of colonic contents
distally, which in turn stimulates distal colonic afferents (or
Gaps in Our Knowledge
indeed perhaps rectal) [148], possibly by distension,
resulting in sensory perception. However, balloon disten-
• Manometric methods for studying pancolonic motor
sion of the colon in healthy individuals typically results in a
activity have thus far been suboptimal. The use of high
colicky or ‘‘windy’’ pain rather than the usual defecatory
resolution manometry may unravel the complexity of
urge [198, 199]. Goligher et al. reported that performing
motor activities present in the human large intestine;
balloon distension of the terminal colonic segment in
• The physiological function of motor complex activity;
patients with colostomies typically resulted in periumbili-
• The existence or not of a true recto-sigmoid sphincter
cal or suprapubic pain rather than the typical ‘‘rectal-type’’
and how this regulates movement into the rectum;
sensation associated with an urge to defecate [199].
• The contributions of feedback reflexes to normal (and
abnormal) motor functions;
Role of the Rectum, the Pelvic Floor, and the Extra-Rectal
• Characterization of human anal sensory receptors and
Tissues
afferent pathways.
The rectum is regarded as the primary site of origin of the
The Pre-Expulsive Phase defecatory urge. Gradual distension of the rectum produces
a graded sensory response starting with an initial awareness
During this phase, specific motor events occur, which of filling [200]. With continued distension, this is followed
culminate in an awareness by the subject of an urge to by a constant sensation (likened to the desire to pass wind)
defecate, the ‘‘call to stool.’’ that is replaced by a sustained urge to defecate, and finally
by a sense of discomfort and an intense urge to defecate as
Origin of the Defecatory Urge the maximal tolerable volume/pressure is reached [201–
203]. Rectal-type sensation similar to a desire to defecate
In order to achieve normal defecation, the importance of a can be elicited by distension of the bowel up to 15 cm from
defecatory urge cannot be overemphasized. The voluntary the anal verge, whereas distension above this level typi-
process involved in defecation starts with a sensation of cally leads to a colonic-type sensation similar to wind pain
‘‘call to stool.’’ Although our knowledge on the origin of or suprapubic pain [199]. In patients with residual rectum
this urge has increased significantly in the last few decades, following colectomy (and colorectal anastamosis), balloon
the precise location of the receptors responsible and con- distension below the suture line results in a normal defe-
tribution of the organs involved are still debated. It is likely catory urge [199]. In another surgical study, following a
that the colon, rectum, anus, extra-rectal tissue, and the unique procedure in which the anorectum was mobilized
puborectalis may all contribute to varying degrees (see on its neurovascular pedicle and transposed to the anterior
below). abdominal wall to preserve intestinal length in patients
with short bowel syndrome, balloon distension through an
Role of the Colon abdominal wall stoma provoked sensation of pelvic filling
[204].
In healthy subjects, there is a close relationship between In support of an extra-rectal origin of urge sensation, it
HAPSs and urge to evacuate, a relationship that is often has been shown that defecatory desire can be provoked by
absent in patients with constipation [197]. In one study in stimulating nerve endings and stretch receptors in pelvic
volunteers, it was shown that out of 27 instances of per- floor muscles including the puborectalis, and from struc-
ceived urge to defecate, 26 were associated with a tures adjacent to the rectum [205]. It has also been shown
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1454 Dig Dis Sci (2012) 57:1445–1464
functioning of rectal afferent nerves and normal rectal wall Our understanding of the morphology of visceral affer-
biomechanical properties appear critically important for ent nerve endings potentially responsible for generation of
perception of rectal fullness and ultimately a defecatory rectal sensation is far from complete [243], and most of our
urge [222]. It is postulated that habitual suppression of the knowledge is based on animal studies. In the myenteric
defecatory urge may lead to attenuation of the call to stool ganglia of the guinea pig rectum, specialized nerve termi-
resulting in rectal fecal impaction and secondary dilation, nals with branched, flattened lamellar endings, called rectal
potentially culminating in a megarectum [223–226]. Nev- intraganglionic laminar endings (rIGLEs), have been
ertheless, the clinical importance of impaired peripheral identified as mechanotransduction sites of low threshold,
sensations in children has been questioned [30]. Although stretch-sensitive mechanoreceptors [244, 245]. Their den-
earlier studies reported that larger rectal distension vol- sity decreases significantly proximally along the distal gut
umes were needed to trigger rectal sensation in constipated [244]. Functionally, rIGLEs are probably independent of
children [227, 228], more recent studies found no differ- the enteric nervous system since they have been shown to
ence in sensory function in children with functional con- function normally in the rectums of piebald lethal mice
stipation when compared to healthy volunteers [229, 230], devoid of any enteric ganglia [246]. In addition, medium-
although rectal compliance (stretch response to an imposed to-high threshold mechanoreceptors sensitive to local
force) was greater (i.e. the rectum was more lax) in con- compression and stretch are present in close association
stipated individuals. Alternatively, megarectum may be with intramural and extramural blood vessels of major
secondary to other disordered neuromuscular dysfunctions viscera including the colon [247].
[231–233]. Whether idiopathic megarectum is a primary or It has been shown that rectal sensation is preserved after
secondary phenomenon is unknown [223], but it is likely bilateral pudendal nerve block [185, 248]. However, low
that psychological [234], behavioral, and neurophysio- spinal anaesthesia (L5–S1) abolishes rectal sensation,
logical factors may all play a part [223]. which is then perceived only as a vague abdominal dis-
In consideration of the perception of rectal filling, it has comfort at higher levels of rectal filling. Rectal sensation,
been postulated that in vivo, the incoming fecal bolus, likely including abdominal discomfort, is fully abolished by high
transported by PS activity, deforms the rectal wall, altering spinal anaesthesia (T6–T12) [249]. This shows that the
stress and strain, and thus activating mechanoreceptors that sacral outflow plays a key role in the perception of rectal
then induce reflex rectal contractions [235, 236]. The sensation while the thoracolumbar outflow has a lesser role.
amplitude of the rectal contraction increases with higher It has also been shown that the sense of rectal distension is
rectal volumes [191]. It has been proposed in some studies impaired in patients with bilateral excision of sacral nerve
that rectal sensation does not occur unless accompanied by roots (preserving S1–2 bilaterally) [250]. The importance
rectal contractions [201, 237]. Furthermore, the duration of of the lower sacral cord and the S3 nerve root in particular
rectal contractile activity correlates well to the duration of is emphasized by the preservation of bowel and bladder
rectal sensation [201]. Reduced rectal contractility has been function by preserving at least one S3 nerve root during
reported in constipated patients [165, 238]. Rectal sensation, sacral resection [251].
and by implication contraction of the rectum, is also an Current neuroanatomical thinking indicates that spinal
important determinant of reflex external anal sphincter con- afferents travel in parallel with the sympathetic and sacral
traction [201], and hence maintenance of continence [239]. parasympathetic pathways from the rectum, in nerves
In order to evaluate whether volume, pressure or weight passing in the lateral ligaments, through the pelvic plexus
of rectal contents provides the main trigger for rectal sen- and the pelvic splanchnic nerves (nervi erigentes) to reach
sation, Broens et al. compared the sensation generated by the sacral segments of the spinal cord, with the majority of
inflating a rectal balloon with 60 ml of air, water, and the sensory information entering the S3 and S4 nerve roots
mercury [202]. The study demonstrated a constant rela- [250, 251]. However, a proportion of rectal sensory infor-
tionship between level of rectal sensation and the pressure mation is conveyed via lumbar afferents which run from
in the rectal balloon. Sensation levels were independent of the inferior mesenteric ganglion into the hypogastric
both the weight and the volume of the rectal contents. They nerves, down through the pelvic ganglia, entering the rec-
concluded that rectal sensation is sensitive to intrarectal tum via the rectal nerves. This pathway is probably
pressure changes which triggers tension-activated stretch responsible for the perception of abdominal discomfort
receptors [202]. However more recent studies suggest that associated with rectal distension [249].
rectal wall deformation rather than intrarectal pressure is Integrity of afferent neuronal pathways can be assessed
the direct stimulus, since mechanoreceptors are stimulated using cerebral evoked potentials [252, 253] whereas
by circumferential strain and shearing forces that cause efferent pathways can be evaluated using motor evoked
deformations in rectal wall morphology [240–242], which potentials [254]; alterations have been suggested in patients
may be secondary to intraluminal pressure changes [242]. with colorectal dysfunction. By measuring cerebral evoked
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123
1456 Dig Dis Sci (2012) 57:1445–1464
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Dig Dis Sci (2012) 57:1445–1464 1457
Internal anal sphincter relaxation occurs involuntarily in abdominal pressure during coughing, but relaxation to
response to rectal distension and the relaxation is propor- the same stimulus during evacuation;
tional to the intra-rectal pressure [180, 182]. After assum- • Modeling of the colo-recto-anal force vectors generated
ing a posture convenient for defecation, the subject strains during evacuation;
by contracting the abdominal muscles and diaphragm • How ‘‘full’’ opening of the anal canal is effected—
against a closed glottis (Valsalva maneuver). This is passive stretching, active relaxation or both;
associated with relaxation of the external anal sphincter. It • The relative contributions of voluntary and involuntary
has been suggested that the levator plate (that inserts into components to active defecation, and whether these
the posterior aspect of the rectum) and the longitudinal simply reflect behavioral differences (e.g. responding
muscles of the anus contract simultaneously during evac- appropriately to the call to stool, or going by routine).
uation. The resultant force vector is directed posteriorly
and downwards resulting in the opening of the anorectal
angle [284] (Fig. 3). This is facilitated by contraction of the Termination of Defecation
pubococcygeus muscle that ‘‘splints’’ the perineal body,
effectively tensing the anterior wall of the anal canal, This phase begins under semi-voluntary control (the
allowing only the posterior wall to move backwards [284]. sense of complete rectal emptying, with cessation of
Contraction of the conjoint longitudinal muscles of the those maneuvers aimed at increasing intra-pelvic pres-
anus also causes flattening of the anal vascular cushions sure), and thence by involuntary contraction of the
[285] and shortening of the anal canal [141]. The incoming external anal sphincter and pelvic floor, which closes the
fecal bolus possibly further flattens the vascular cushions anal canal and reverses the pressure gradient towards the
by direct compression [285]. All these changes, occurring rectum. When traction is applied to the anus and then
simultaneously, decrease the anal canal pressure to a value released (likened in vivo to passage of stool), the
lower than the intrarectal pressure resulting in a pressure external sphincter shows a momentary increase in
gradient from the rectum to the outside. Expulsion occurs activity that tends to close the canal. This reflex is
and continues due to high intra-rectal pressure, augmented known as the ‘‘closing reflex’’ [141, 171, 174, 287] and
by straining. It has been postulated that once defecation is important at the end of defecation to provide the
starts, sensory input from the anus maintains the propulsive internal sphincter, which is no longer inhibited by rectal
activity until the rectum is empty [101, 286]. This is distension, time to recover its tone [287]. This reflex
probably due to a spinal reflex since rectal emptying, once seems to be cortically modulated since it is impaired in
initiated, is nearly complete even in patients with spinal patients with spinal injury [171]. Once straining ceases
injury [286]. and intra-abdominal pressure falls, the postural reflex in
the pelvic floor is reactivated [171], resulting in con-
Gaps in Our Knowledge traction of the puborectalis which increases its traction
on the anorectal junction, returning the angle to its basal
• The contribution of colonic and rectal contractile state. Simultaneous relaxation of the conjoint longitudi-
activities to fecal expulsion; nal muscle elongates the anal canal and allows the anal
• Mechanism of modulation of the postural reflex, with cushions to passively distend, resulting in full closure of
pelvic floor contraction in response to increased intra- the anal canal.
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Dig Dis Sci (2012) 57:1445–1464 1459
35. Schum TR, McAuliffe TL, Simms MD, Walter JA, Lewis M, 56. Rao SS, Welcher K, Zimmerman B, Stumbo P. Is coffee a
Pupp R. Factors associated with toilet training in the 1990s. colonic stimulant? Eur J Gastroenterol Hepatol. 1998;10:
Ambul Pediatr. 2001;1:79–86. 113–118.
36. Taubman B. Toilet training and toileting refusal for stool only: a 57. Snape WJ, Wright SH, Battle WM, Cohen S. The gastrocolic
prospective study. Pediatrics. 1997;99:54–58. response: evidence for a neural mechanism. Gastroenterology.
37. Schum TR, Kolb TM, McAuliffe TL, Simms MD, Underhill RL, 1979;77:1235–1240.
Lewis M. Sequential acquisition of toilet-training skills: a 58. Wright SH, Snape WJ, Battle W, Cohen S, London RL. Effect of
descriptive study of gender and age differences in normal chil- dietary components on gastrocolonic response. Am J Physiol.
dren. Pediatrics. 2002;109:E48. 1980;238:G228–G232.
38. Aziz S, Moiz Fakih HA, Di Lorenzo C. Bowel habits and toilet 59. Battle WM, Cohen S, Snape WJ Jr. Inhibition of postprandial
training in rural and urban dwelling children in a developing colonic motility after ingestion of an amino acid mixture. Dig
country. J Pediatr. 2011;158:784–788. doi:10.1016/j.jpeds. Dis Sci. 1980;25:647–652.
2010.11.024. 60. Renny A, Snape WJ Jr, Sun EA, London R, Cohen S. Role of
39. Horn IB, Brenner R, Rao M, Cheng TL. Beliefs about the cholecystokinin in the gastrocolonic response to a fat meal.
appropriate age for initiating toilet training: are there racial and Gastroenterology. 1983;85:17–21.
socioeconomic differences? J Pediatr. 2006;149:165–168. doi: 61. Berenson MM, Avner DL. Alcohol inhibition of rectosigmoid
10.1016/j.jpeds.2006.03.004. motility in humans. Digestion. 1981;22:210–215.
40. Gorski PA. Toilet training guidelines: parents–the role of the 62. Bouchoucha M, Nalpas B, Berger M, Cugnenc PH, Barbier JP.
parents in toilet training. Pediatrics. 1999;103:1362–1363. Recovery from disturbed colonic transit time after alcohol
41. Tagart RE. The anal canal and rectum: their varying relationship withdrawal. Dis Colon Rectum. 1991;34:111–114.
and its effect on anal continence. Dis Colon Rectum. 1966;9: 63. Rao SS. Pathophysiology of adult fecal incontinence. Gastro-
449–452. enterology. 2004;126:S14–S22.
42. Sikirov D. Comparison of straining during defecation in three 64. Loening-Baucke V, Miele E, Staiano A. Fiber (glucomannan) is
positions: results and implications for human health. Dig Dis beneficial in the treatment of childhood constipation. Pediatrics.
Sci. 2003;48:1201–1205. 2004;113:e259–e264.
43. Barnes PR, Lennard-Jones JE. Balloon expulsion from the 65. Castillejo G, Bullo M, Anguera A, Escribano J, Salas-Salvado J.
rectum in constipation of different types. Gut. 1985;26: A controlled, randomized, double-blind trial to evaluate the
1049–1052. effect of a supplement of cocoa husk that is rich in dietary fiber
44. Rao SS, Kavlock R, Rao S. Influence of body position and stool on colonic transit in constipated pediatric patients. Pediatrics.
characteristics on defecation in humans. Am J Gastroenterol. 2006;118:e641–e648. doi:10.1542/peds.2006-0090.
2006;101:2790–2796. doi:10.1111/j.1572-0241.2006.00827.x. 66. Williams CL, Bollella M. Is a high-fiber diet safe for children?
45. Degen LP, Phillips SF. How well does stool form reflect colonic Pediatrics. 1995;96:1014–1019.
transit? Gut. 1996;39:109–113. 67. Heaton KW. Food fibre as an obstacle to energy intake. Lancet.
46. Davies GJ, Crowder M, Reid B, Dickerson JW. Bowel function 1973;2:1418–1421.
measurements of individuals with different eating patterns. Gut. 68. Levine AS, Tallman JR, Grace MK, Parker SA, Billington CJ,
1986;27:164–169. Levitt MD. Effect of breakfast cereals on short-term food intake.
47. O’Donnell LJ, Virjee J, Heaton KW. Detection of pseudodiar- Am J Clin Nutr. 1989;50:1303–1307.
rhoea by simple clinical assessment of intestinal transit rate. 69. Stevens J, Levitsky DA, VanSoest PJ, Robertson JB, Kalkwarf
BMJ. 1990;300:439–440. HJ, Roe DA. Effect of psyllium gum and wheat bran on spon-
48. Bharucha AE. Lower gastrointestinal functions. Neurogastro- taneous energy intake. Am J Clin Nutr. 1987;46:812–817.
enterol Motil. 2008;20:103–113. doi:10.1111/j.1365-2982.2008. 70. Haghshenass M, Mahloudij M, Reinhold JG, Mohammadi N.
01111.x. Iron-deficiency anemia in an Iranian population associated with
49. Connell AM. The motility of the pelvic colon. II. Paradoxical high intakes of iron. Am J Clin Nutr. 1972;25:1143–1146.
motility in diarrhoea and constipation. Gut. 1962;3:342–348. 71. Anderson JW, Smith BM, Gustafson NJ. Health benefits and
50. Benninga MA, Buller HA, Tytgat GN, Akkermans LM, Bossuyt practical aspects of high-fiber diets. Am J Clin Nutr. 1994;59:
PM, Taminiau JA. Colonic transit time in constipated children: 1242S–1247S.
does pediatric slow-transit constipation exist? J Pediatr Gas- 72. Mugie SM, Benninga MA, Di Lorenzo C. Epidemiology of
troenterol Nutr. 1996;23:241–251. constipation in children and adults: a systematic review. Best
51. Saad RJ, Rao SS, Koch KL, et al. Do stool form and frequency Pract Res Clin Gastroenterol. 2011;25:3–18. doi:10.1016/j.bpg.
correlate with whole-gut and colonic transit? Results from a 2010.12.010.
multicenter study in constipated individuals and healthy con- 73. Del Ciampo IR, Galvao LC, Del Ciampo LA, Fernandes MI.
trols. Am J Gastroenterol. 2010;105:403–411. doi:10.1038/ajg. Prevalence of chronic constipation in children at a primary
2009.612. health care unit. J Pediatr (Rio J). 2002;78:497–502.
52. Dinning PG, Hunt L, Lubowski DZ, Kalantar JS, Cook IJ, Jones 74. Iacono G, Merolla R, D’Amico D, et al. Gastrointestinal
MP. The impact of laxative use upon symptoms in patients with symptoms in infancy: a population-based prospective study. Dig
proven slow transit constipation. BMC Gastroenterol. Liver Dis. 2005;37:432–438. doi:10.1016/j.dld.2005.01.009.
2011;11:121. doi:10.1186/1471-230X-11-121. 75. Loening-Baucke V. Prevalence, symptoms and outcome of
53. Bannister JJ, Davison P, Timms JM, Gibbons C, Read NW. constipation in infants and toddlers. J Pediatr. 2005;146:
Effect of stool size and consistency on defecation. Gut. 1987; 359–363. doi:10.1016/j.jpeds.2004.10.046.
28:1246–1250. 76. Issenman RM, Hewson S, Pirhonen D, Taylor W, Tirosh A. Are
54. Rao SS, Kavelock R, Beaty J, Ackerson K, Stumbo P. Effects of chronic digestive complaints the result of abnormal dietary
fat and carbohydrate meals on colonic motor response. Gut. patterns? Diet and digestive complaints in children at 22 and
2000;46:205–211. 40 months of age. Am J Dis Child. 1987;141:679–682.
55. Ford MJ, Camilleri M, Wiste JA, Hanson RB. Differences in 77. Ip KS, Lee WT, Chan JS, Young BW. A community-based
colonic tone and phasic response to a meal in the transverse and study of the prevalence of constipation in young children and the
sigmoid human colon. Gut. 1995;37:264–269. role of dietary fibre. Hong Kong Med J. 2005;11:431–436.
123
1460 Dig Dis Sci (2012) 57:1445–1464
78. van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology cycle and orocaecal transit in normal and constipated women.
of childhood constipation: a systematic review. Am J Gastro- Gut. 1989;30:30–34.
enterol. 2006;101:2401–2409. doi:10.1111/j.1572-0241.2006. 100. Kepenekci I, Keskinkilic B, Akinsu F, et al. Prevalence of pelvic
00771.x. floor disorders in the female population and the impact of age,
79. Sonnenberg A, Koch TR. Epidemiology of constipation in the mode of delivery, and parity. Dis Colon Rectum. 2011;54:85–94.
United States. Dis Colon Rectum. 1989;32:1–8. doi:10.1007/DCR.0b013e3181fd2356.
80. Bannister JJ, Abouzekry L, Read NW. Effect of aging on ano- 101. McCrea GL, Miaskowski C, Stotts NA, Macera L, Varma MG.
rectal function. Gut. 1987;28:353–357. Pathophysiology of constipation in the older adult. World J
81. Bartolo DC, Jarratt JA, Read NW. The use of conventional Gastroenterol. 2008;14:2631–2638.
electromyography to assess external sphincter neuropathy in 102. Goyal RK, Hirano I. The enteric nervous system. N Engl J Med.
man. J Neurol Neurosurg Psychiatry. 1983;46:1115–1118. 1996;334:1106–1115. doi:10.1056/NEJM199604253341707.
82. Chatoor D, Emmnauel A. Constipation and evacuation disor- 103. Tzavella K, Riepl RL, Klauser AG, Voderholzer WA, Schindl-
ders. Best Pract Res Clin Gastroenterol. 2009;23:517–530. doi: beck NE, Muller-Lissner SA. Decreased substance P levels in
10.1016/j.bpg.2009.05.001. rectal biopsies from patients with slow transit constipation. Eur
83. Sonnenberg A, Koch TR. Physician visits in the United States J Gastroenterol Hepatol. 1996;8:1207–1211.
for constipation: 1958 to 1986. Dig Dis Sci. 1989;34:606–611. 104. Battle WM, Snape WJ Jr, Alavi A, Cohen S, Braunstein S.
84. de Araujo Sant’Anna AM, Calcado AC. Constipation in school- Colonic dysfunction in diabetes mellitus. Gastroenterology.
aged children at public schools in Rio de Janeiro, Brazil. J 1980;79:1217–1221.
Pediatr Gastroenterol Nutr. 1999;29:190–193. 105. El-Salhy M, Norrgard O, Spinnell S. Abnormal colonic endo-
85. van Ginkel R, Reitsma JB, Buller HA, van Wijk MP, Taminiau crine cells in patients with chronic idiopathic slow-transit con-
JA, Benninga MA. Childhood constipation: longitudinal follow- stipation. Scand J Gastroenterol. 1999;34:1007–1011.
up beyond puberty. Gastroenterology. 2003;125:357–363. 106. Cortesini C, Cianchi F, Infantino A, Lise M. Nitric oxide syn-
86. Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of thase and VIP distribution in enteric nervous system in idio-
constipation (EPOC) study in the United States: relation of pathic chronic constipation. Dig Dis Sci. 1995;40:2450–2455.
clinical subtypes to sociodemographic features. Am J Gastro- 107. He CL, Burgart L, Wang L, et al. Decreased interstitial cell of
enterol. 1999;94:3530–3540. doi:10.1111/j.1572-0241.1999. Cajal volume in patients with slow-transit constipation. Gas-
01642.x. troenterology. 2000;118:14–21.
87. Meier R, Beglinger C, Dederding J, et al. Influence of age, 108. Hasler WL. Is constipation caused by a loss of colonic inter-
gender, hormonal status and smoking habits on colonic transit stitial cells of Cajal? Gastroenterology. 2003;125(1):264–265;
time. Neurogastroenterol Motil. 1995;7:235–238. discussion 265–266.
88. Degen LP, Phillips SF. Variability of gastrointestinal transit in 109. Sabri M, Barksdale E, Di Lorenzo C. Constipation and lack of
healthy women and men. Gut. 1996;39:299–305. colonic interstitial cells of Cajal. Dig Dis Sci. 2003;48:849–853.
89. Johanson JF, Sonnenberg A, Koch TR. Clinical epidemiology of 110. Wedel T, Spiegler J, Soellner S, et al. Enteric nerves and
chronic constipation. J Clin Gastroenterol. 1989;11:525–536. interstitial cells of Cajal are altered in patients with slow-transit
90. Veugelers R, Benninga MA, Calis EA, et al. Prevalence and constipation and megacolon. Gastroenterology. 2002;123:
clinical presentation of constipation in children with severe 1459–1467.
generalized cerebral palsy. Dev Med Child Neurol. 111. Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen
2010;52:e216–e221. doi:10.1111/j.1469-8749.2010.03701.x. HB, Bernstein A. W/kit gene required for interstitial cells of
91. Dukas L, Willett WC, Giovannucci EL. Association between Cajal and for intestinal pacemaker activity. Nature. 1995;373:
physical activity, fiber intake, and other lifestyle variables and 347–349. doi:10.1038/373347a0.
constipation in a study of women. Am J Gastroenterol. 112. Ward SM, Sanders KM. Physiology and pathophysiology of the
2003;98:1790–1796. doi:10.1111/j.1572-0241.2003.07591.x. interstitial cell of Cajal: from bench to bedside. I. Functional
92. Chien LY, Liou YM, Chang P. Low defaecation frequency in development and plasticity of interstitial cells of Cajal networks.
Taiwanese adolescents: association with dietary intake, physical Am J Physiol Gastrointest Liver Physiol. 2001;281:G602–G611.
activity and sedentary behaviour. J Paediatr Child Health. 113. Bassotti G, Villanacci V, Maurer CA, et al. The role of glial
2011;47:381–386. doi:10.1111/j.1440-1754.2010.01990.x. cells and apoptosis of enteric neurones in the neuropathology of
93. Kinnunen O. Study of constipation in a geriatric hospital, day intractable slow transit constipation. Gut. 2006;55:41–46. doi:
hospital, old people’s home and at home. Aging (Milano). 1991; 10.1136/gut.2005.073197.
3:161–170. 114. Wedel T, Roblick UJ, Ott V, et al. Oligoneuronal hypogangli-
94. Lundblad B, Hellstrom AL. Perceptions of school toilets as a onosis in patients with idiopathic slow-transit constipation. Dis
cause for irregular toilet habits among schoolchildren aged 6 to Colon Rectum. 2002;45:54–62.
16 years. J Sch Health. 2005;75:125–128. 115. Hutson JM, Catto-Smith T, Gibb S, et al. Chronic constipation:
95. Vernon S, Lundblad B, Hellstrom AL. Children’s experiences of no longer stuck! Characterization of colonic dysmotility as a
school toilets present a risk to their physical and psychological new disorder in children. J Pediatr Surg. 2004;39:795–799.
health. Child Care Health Dev. 2003;29:47–53. 116. Scott SM. Manometric techniques for the evaluation of colonic
96. Fukuda S, Matsuzaka M, Takahashi I, et al. Bowel habits before motor activity: current status. Neurogastroenterol Motil. 2003;
and during menses in Japanese women of climacteric age: a 15:483–513.
population based study. Tohoku J Exp Med. 2005;206:99–104. 117. Rao SS, Sadeghi P, Beaty J, Kavlock R, Ackerson K. Ambu-
97. Celik AF, Turna H, Pamuk GE, Pamuk ON. How prevalent are latory 24-h colonic manometry in healthy humans. Am J Physiol
alterations in bowel habits during menses? Dis Colon Rectum. Gastrointest Liver Physiol. 2001;280:G629–G639.
2001;44:300–301. 118. Narducci F, Bassotti G, Gaburri M, Morelli A. Twenty four hour
98. Hinds JP, Stoney B, Wald A. Does gender or the menstrual cycle manometric recording of colonic motor activity in healthy man.
affect colonic transit? Am J Gastroenterol. 1989;84:123–126. Gut. 1987;28:17–25.
99. Turnbull GK, Thompson DG, Day S, Martin J, Walker E, 119. Christensen J. The response of the colon to eating. Am J Clin
Lennard-Jones JE. Relationships between symptoms, menstrual Nutr. 1985;42:1025–1032.
123
Dig Dis Sci (2012) 57:1445–1464 1461
120. Dinning PG, Zarate N, Szczesniak MM, et al. Bowel preparation colonic transit time in children. J Pediatr Gastroenterol Nutr.
affects the amplitude and spatiotemporal organization of colonic 1991;13(1):42–45.
propagating sequences. Neurogastroenterol Motil. 2010;22:633- 136. Zaslavsky C, da Silveira TR, Maguilnik I. Total and segmental
e176. doi:10.1111/j.1365-2982.2010.01480.x. colonic transit time with radio-opaque markers in adolescents
121. Bampton P, Dinning P, Kennedy M, Lubowski D, Cook I. with functional constipation. J Pediatr Gastroenterol Nutr.
Prolonged multi-point recording of colonic manometry in the 1998;27:138–142.
unprepared human colon: providing insight into potentially 137. Gutierrez C, Marco A, Nogales A, Tebar R. Total and segmental
relevant pressure wave parameters. Am J Gastroenterol. colonic transit time and anorectal manometry in children with
2001;96:1838–1848. doi:10.1111/j.1572-0241.2001.03924.x. chronic idiopathic constipation. J Pediatr Gastroenterol Nutr.
122. Dinning PG, Szczesniak MM, Cook IJ. Twenty-four hour spatio- 2002;35:31–38.
temporal mapping of colonic propagating sequences provides 138. Stivland T, Camilleri M, Vassallo M, et al. Scintigraphic mea-
pathophysiological insight into constipation. Neurogastroenterol surement of regional gut transit in idiopathic constipation.
Motil. 2008;20:1017–1021. doi:10.1111/j.1365-2982.2008.01147.x. Gastroenterology. 1991;101:107–115.
123. Rao SS, Sadeghi P, Beaty J, Kavlock R. Ambulatory 24-hour 139. Diamant NE, Kamm MA, Wald A, Whitehead WE. AGA
colonic manometry in slow-transit constipation. Am J Gastroenterol. technical review on anorectal testing techniques. Gastroenter-
2004;99:2405–2416. doi:10.1111/j.1572-0241.2004.40453.x. ology. 1999;116:735–760.
124. Herve S, Savoye G, Behbahani A, Leroi AM, Denis P, Ducrotte 140. Dinning PG, Smith TK, Scott SM. Pathophysiology of colonic
P. Results of 24-h manometric recording of colonic motor causes of chronic constipation. Neurogastroenterol Motil.
activity with endoluminal instillation of bisacodyl in patients 2009;21:20–30. doi:10.1111/j.1365-2982.2009.01401.x.
with severe chronic slow transit constipation. Neurogastroen- 141. Brookes SJ, Dinning PG, Gladman MA. Neuroanatomy and
terol Motil. 2004;16:397–402. doi:10.1111/j.1365-2982.2004. physiology of colorectal function and defaecation: from basic
00535.x. science to human clinical studies. Neurogastroenterol Motil.
125. Leroi AM, Lalaude O, Antonietti M, et al. Prolonged stationary 2009;21:9–19. doi:10.1111/j.1365-2982.2009.01400.x.
colonic motility recording in seven patients with severe consti- 142. Sarna SK. Physiology and pathophysiology of colonic motor
pation secondary to antidepressants. Neurogastroenterol Motil. activity (1). Dig Dis Sci. 1991;36:827–862.
2000;12:149–154. 143. Spriggs EA, Code CF, Bargen JA, Curtiss RK, Hightower NC Jr.
126. Dinning PG, Zarate N, Hunt LM, et al. Pancolonic spatiotem- Motility of the pelvic colon and rectum of normal persons and
poral mapping reveals regional deficiencies in, and disorgani- patients with ulcerative colitis. Gastroenterology. 1951;19:
zation of colonic propagating pressure waves in severe 480–491.
constipation. Neurogastroenterol Motil. 2010;22:e340–e349. 144. Dinning PG, Arkwright JW, Szczesniak MM, et al. High-reso-
doi:10.1111/j.1365-2982.2010.01597.x. lution colonic manometry: have we been incorrectly labeling
127. Camilleri M, Bharucha AE, di Lorenzo C, et al. American colonic motor patterns? Gastroenterology. 2009;136:A-224.
Neurogastroenterology and Motility Society consensus state- 145. Garcia-Olmo D, Garcia-Picazo D, Lopez-Fando J. Correlation
ment on intraluminal measurement of gastrointestinal and between pressure changes and solid transport in the human left
colonic motility in clinical practice. Neurogastroenterol Motil. colon. Int J Colorectal Dis. 1994;9:87–91.
2008;20:1269–1282. doi:10.1111/j.1365-2982.2008.01230.x. 146. Bassotti G, de Roberto G, Castellani D, Sediari L, Morelli A.
128. Rao SS, Camilleri M, Hasler WL, et al. Evaluation of gastro- Normal aspects of colorectal motility and abnormalities in slow
intestinal transit in clinical practice: position paper of the transit constipation. World J Gastroenterol. 2005;11:2691–2696.
American and European Neurogastroenterology and Motility 147. Cook IJ, Furukawa Y, Panagopoulos V, Collins PJ, Dent J.
Societies. Neurogastroenterol Motil. 2011;23:8–23. doi:10.11 Relationships between spatial patterns of colonic pressure and
11/j.1365-2982.2010.01612.x. individual movements of content. Am J Physiol Gastrointest
129. Dinning PG, Di Lorenzo C. Colonic dysmotility in constipation. Liver Physiol. 2000;278:G329–G341.
Best Pract Res Clin Gastroenterol. 2011;25:89–101. doi:10.10 148. Bampton PA, Dinning PG, Kennedy ML, Lubowski DZ,
16/j.bpg.2010.12.006. deCarle D, Cook IJ. Spatial and temporal organization of pres-
130. Martin MJ, Steele SR, Noel JM, Weichmann D, Azarow KS. sure patterns throughout the unprepared colon during sponta-
Total colonic manometry as a guide for surgical management of neous defecation. Am J Gastroenterol. 2000;95:1027–1035. doi:
functional colonic obstruction: preliminary results. J Pediatr 10.1111/j.1572-0241.2000.01839.x.
Surg. 2001;36:1757–1763. doi:10.1053/jpsu.2001.28815. 149. Bharucha AE. Constipation. Best Pract Res Clin Gastroenterol.
131. Di Lorenzo C, Flores AF, Reddy SN, Hyman PE. Use of colonic 2007;21:709–731.
manometry to differentiate causes of intractable constipation in 150. Bassotti G, Gaburri M. Manometric investigation of high-
children. J Pediatr. 1992;120:690–695. amplitude propagated contractile activity of the human colon.
132. Pensabene L, Youssef NN, Griffiths JM, Di Lorenzo C. Colonic Am J Physiol. 1988;255:G660–G664.
manometry in children with defecatory disorders. Role in 151. Bassotti G, Chistolini F, Nzepa F, Morelli A. Colonic propulsive
diagnosis and management. Am J Gastroenterol. 2003;98 impairment in intractable slow-transit constipation. Arch Surg.
(5):1052–1057. doi:10.1111/j.1572-0241.2003.07412.x. 2003;138:1302–1304. doi:10.1001/archsurg.138.12.1302.
133. Rudolph CD, Winter HS. NASPGN guidelines for training in 152. Torsoli A, Ramorino ML, Ammaturo MV, Capurso L, Paoluzi P,
pediatric gastroenterology. NASPGN executive council, NAS- Anzini F. Mass movements and intracolonic pressures. Am J Dig
PGN training and education committee. J Pediatr Gastroenterol Dis. 1971;16:693–696.
Nutr. 1999;29:S1–S26. 153. Ritchie JA, Truelove SC, Ardan GM, Tuckey MS. Propulsion
134. Spanish Group for the Study of Digestive Motility. Measure- and retropulsion of normal colonic contents. Am J Dig Dis.
ment of colonic transit time (total and segmental) with radi- 1971;16:697–704.
opaque markers. National reference values obtained in 192 154. Bassotti G, Gaburri M, Imbimbo BP, et al. Colonic mass
healthy subjects. Spanish group for the study of digestive movements in idiopathic chronic constipation. Gut. 1988;29:
motility. Gastroenterol Hepatol. 1998;21:71–75. 1173–1179.
135. Bautista Casasnovas A, Varela Cives R, Villanueva Jeremias A, 155. Hagger R, Kumar D, Benson M, Grundy A. Colonic motor
Castro-Gago M, Cadranel S, Tojo Sierra R. Measurement of activity in slow-transit idiopathic constipation as identified by
123
1462 Dig Dis Sci (2012) 57:1445–1464
24-h pancolonic ambulatory manometry. Neurogastroenterol 178. Bartolo DC, Roe AM, Virjee J, Mortensen NJ. Evacuation
Motil. 2003;15:515–522. proctography in obstructed defaecation and rectal intussuscep-
156. Bassotti G, Germani U, Morelli A. Human colonic motility: tion. Br J Surg. 1985;72:S111–S116.
physiological aspects. Int J Colorectal Dis. 1995;10:173–180. 179. Lunniss PJ, Scott SM. Imaging of the anal sphincter. In: Sultan
157. Bassotti G, Clementi M, Antonelli E, Pelli MA, Tonini M. Low- AH, Thakar R, Fenner DE, eds. Pathophysiology of Anal
amplitude propagated contractile waves: a relevant propulsive Incontinence. London: Springer; 2007.
mechanism of human colon. Dig Liver Dis. 2001;33:36–40. 180. Frenckner B. Function of the anal sphincters in spinal man. Gut.
158. Dinning PG, Szczesniak MM, Cook IJ. Spatio-temporal analysis 1975;16:638–644.
reveals aberrant linkage among sequential propagating pressure 181. Hancock BD. Measurement of anal pressure and motility. Gut.
wave sequences in patients with symptomatically defined 1976;17:645–651.
obstructed defecation. Neurogastroenterol Motil. 2009;21:945- 182. Ustach TJ, Tobon F, Hambrecht T, Bass DD, Schuster MM.
e75. doi:10.1111/j.1365-2982.2009.01323.x. Electrophysiological aspects of human sphincter function. J Clin
159. Kumar D, Williams NS, Waldron D, Wingate DL. Prolonged Invest. 1970;49:41–48. doi:10.1172/JCI106220.
manometric recording of anorectal motor activity in ambulant 183. Pedersen IK, Christiansen J. A study of the physiological vari-
human subjects: evidence of periodic activity. Gut. 1989;30: ation in anal manometry. Br J Surg. 1989;76:69–70.
1007–1011. 184. Wankling WJ, Brown BH, Collins CD, Duthie HL. Basal elec-
160. Shafik A. Sigmoido-rectal junction reflex: role in the defecation trical activity in the anal canal in man. Gut. 1968;9:457–460.
mechanism. Clin Anat. 1996;9:391–394. doi:10.1002/(SICI) 185. Frenckner B, Euler CV. Influence of pudendal block on the
1098-2353(1996)9:6\391:AID-CA6[3.0.CO;2-E. function of the anal sphincters. Gut. 1975;16:482–489.
161. Ballantyne GH. Rectosigmoid sphincter of O’Beirne. Dis Colon 186. Lestar B, Penninckx F, Kerremans R. The composition of anal
Rectum. 1986;29:525–531. basal pressure. An in vivo and in vitro study in man. Int J
162. Wadhwa RP, Mistry FP, Bhatia SJ, Abraham P. Existence of a Colorectal Dis. 1989;4:118–122.
high pressure zone at the rectosigmoid junction in normal Indian 187. Floyd WF, Walls EW. Electromyography of the sphincter ani
men. Dis Colon Rectum. 1996;39:1122–1125. externus in man. J Physiol. 1953;121:49P–50P.
163. Shafik A, Doss S, Asaad S, Ali YA. Rectosigmoid junction: 188. Miller R, Lewis GT, Bartolo DC, Cervero F, Mortensen NJ.
anatomical, histological, and radiological studies with special Sensory discrimination and dynamic activity in the anorectum:
reference to a sphincteric function. Int J Colorectal Dis. 1999; evidence using a new ambulatory technique. Br J Surg.
14:237–244. 1988;75:1003–1007.
164. Shafik A. A study of the effect of distension of the rectosigmoid 189. Miller R, Bartolo DC, Cervero F, Mortensen NJ. Anorectal
junction on the rectum and anal canal with evidence of a rec- sampling: a comparison of normal and incontinent patients. Br J
tosigmoid-rectal reflex. J Surg Res. 1999;82:73–77. doi: Surg. 1988;75:44–47.
10.1006/jsre.1998.5517. 190. Duthie HL, Bennett RC. The relation of sensation in the anal
165. Waldron D, Bowes KL, Kingma YJ, Cote KR. Colonic and canal to the functional anal sphincter: a possible factor in anal
anorectal motility in young women with severe idiopathic con- continence. Gut. 1963;4:179–182.
stipation. Gastroenterology. 1988;95:1388–1394. 191. Haynes WG, Read NW. Ano-rectal activity in man during rectal
166. Waldron DJ, Kumar D, Hallan RI, Wingate DL, Williams NS. infusion of saline: a dynamic assessment of the anal continence
Evidence for motor neuropathy and reduced filling of the rectum mechanism. J Physiol. 1982;330:45–56.
in chronic intractable constipation. Gut. 1990;31:1284–1288. 192. Meunier P, Mollard P. Control of the internal anal sphincter
167. Rao S, Welcher K. Periodic rectal motor activity: the intrinsic (manometric study with human subjects). Pflugers Arch.
colonic gatekeeper? Am J Gastroenterol. 1996;91:890–897. 1977;370:233–239.
168. Spencer NJ. Control of migrating motor activity in the colon. 193. Beuret-Blanquart F, Weber J, Gouverneur JP, Demangeon S,
Curr Opin Pharmacol. 2001;1:604–610. Denis P. Colonic transit time and anorectal manometric anom-
169. Truelove SC. Movements of the large intestine. Physiol Rev. alies in 19 patients with complete transection of the spinal cord.
1966;46:457–512. J Auton Nerv Syst. 1990;30:199–207.
170. Halls J. Bowel content shift during normal defaecation. Proc R 194. Meunier P, Marechal JM, Mollard P. Accuracy of the mano-
Soc Med. 1965;58:859–860. metric diagnosis of Hirschsprung’s disease. J Pediatr Surg.
171. Porter NH. A physiological study of the pelvic floor in rectal 1978;13:411–415.
prolapse. Ann R Coll Surg Engl. 1962;31:379–404. 195. Duthie HL, Gairns FW. Sensory nerve-endings and sensation in
172. Snooks SJ, Swash M. The innervation of the muscles of conti- the anal region of man. Br J Surg. 1960;47:585–595. doi:
nence. Ann R Coll Surg Engl. 1986;68:45–49. 10.1002/bjs.18004720602.
173. Madoff RD, Parker SC, Varma MG, Lowry AC. Faecal incon- 196. Lynn PA, Brookes SJ. Function and morphology correlates of
tinence in adults. Lancet. 2004;364:621–632. doi: rectal nerve mechanoreceptors innervating the guinea pig
10.1016/S0140-6736(04)16856-6. internal anal sphincter. Neurogastroenterol Motil. 2011;23:
174. Bajwa A, Emmanuel A. The physiology of continence and 88–95, e9. doi:10.1111/j.1365-2982.2010.01593.x.
evacuation. Best Pract Res Clin Gastroenterol. 2009;23: 197. Dinning PG, Bampton PA, Andre J, et al. Abnormal predefe-
477–485. doi:10.1016/j.bpg.2009.06.002. catory colonic motor patterns define constipation in obstructed
175. Mahieu P, Pringot J, Bodart P. Defecography: I. Description of a defecation. Gastroenterology. 2004;127:49–56.
new procedure and results in normal patients. Gastrointest 198. Ford MJ, Camilleri M, Zinsmeister AR, Hanson RB. Psycho-
Radiol. 1984;9:247–251. sensory modulation of colonic sensation in the human transverse
176. Bartolo DC, Read NW, Jarratt JA, Read MG, Donnelly TC, and sigmoid colon. Gastroenterology. 1995;109:1772–1780.
Johnson AG. Differences in anal sphincter function and clinical 199. Goligher J, Hughes E. Sensibility of the rectum and colon. Its
presentation in patients with pelvic floor descent. Gastroenter- role in the mechanism of anal continence. Lancet. 1951;1:
ology. 1983;85:68–75. 543–547.
177. Bannister JJ, Timms JM, Barfield LJ, Donnelly TC, Read NW. 200. Meunier P, Mollard P, Marechal JM. Physiopathology of meg-
Physiological studies in young women with chronic constipa- arectum: the association of megarectum with encopresis. Gut.
tion. Int J Colorectal Dis. 1986;1:175–182. 1976;17:224–227.
123
Dig Dis Sci (2012) 57:1445–1464 1463
201. Sun WM, Read NW, Miner PB. Relation between rectal sen- behavioural retraining including biofeedback. Colorectal Dis.
sation and anal function in normal subjects and patients with 2002;4:477–482.
faecal incontinence. Gut. 1990;31:1056–1061. 224. Harraf F, Schmulson M, Saba L, et al. Subtypes of constipation
202. Broens PM, Penninckx FM, Lestar B, Kerremans RP. The predominant irritable bowel syndrome based on rectal percep-
trigger for rectal filling sensation. Int J Colorectal Dis. tion. Gut. 1998;43:388–394.
1994;9:1–4. 225. Di Lorenzo C, Benninga MA. Pathophysiology of pediatric fecal
203. Broens P, Penninckx F. Filling sensations after restorative incontinence. Gastroenterology. 2004;126:S33–S40.
proctocolectomy. Acta Chir Belg. 2002;102:20–23. 226. Mertz H, Naliboff B, Mayer E. Physiology of refractory chronic
204. Williams NS, Corry DG, Abercrombie JF, Powell-Tuck J. constipation. Am J Gastroenterol. 1999;94:609–615. doi:
Transposition of the anorectum to the abdominal wall. Br J 10.1111/j.1572-0241.1999.922_a.x.
Surg. 1996;83:1739–1740. 227. Meunier P, Marechal JM, de Beaujeu MJ. Rectoanal pressures
205. Scharli AF, Kiesewetter WB. Defecation and continence: some and rectal sensitivity studies in chronic childhood constipation.
new concepts. Dis Colon Rectum. 1970;13:81–107. Gastroenterology. 1979;77:330–336.
206. Lembo T, Munakata J, Mertz H, et al. Evidence for the hyper- 228. Molnar D, Taitz LS, Urwin OM, Wales JK. Anorectal
sensitivity of lumbar splanchnic afferents in irritable bowel manometry results in defecation disorders. Arch Dis Child.
syndrome. Gastroenterology. 1994;107:1686–1696. 1983;58:257–261.
207. Lane RH, Parks AG. Function of the anal sphincters following 229. van den Berg MM, Voskuijl WP, Boeckxstaens GE, Benninga
colo-anal anastomosis. Br J Surg. 1977;64:596–599. MA. Rectal compliance and rectal sensation in constipated
208. Simonsen OS, Stolf NA, Aun F, Raia A, Habr-Gama A. Rectal adolescents, recovered adolescents and healthy volunteers. Gut.
sphincter reconstruction in perineal colostomies after abdomi- 2008;57:599–603. doi:10.1136/gut.2007.125690.
noperineal resection for cancer. Br J Surg. 1976;63:389–391. 230. Voskuijl WP, van Ginkel R, Benninga MA, Hart GA, Taminiau
209. Abercrombie JF, Rogers J, Williams NS. Total anorectal JA, Boeckxstaens GE. New insight into rectal function in
reconstruction results in complete anorectal sensory loss. Br J pediatric defecation disorders: disturbed rectal compliance is an
Surg. 1996;83:57–59. essential mechanism in pediatric constipation. J Pediatr.
210. Shouler P, Keighley MR. Changes in colorectal function in 2006;148:62–67. doi:10.1016/j.jpeds.2005.08.061.
severe idiopathic chronic constipation. Gastroenterology. 1986; 231. Lunniss P, Gladman M, Benninga M, Rao S. Pathophysiology of
90:414–420. evacuation disorders. Neurogastroenterol Motil. 2009;21:31–40.
211. De Medici A, Badiali D, Corazziari E, Bausano G, Anzini F. 232. Gattuso JM, Kamm MA, Talbot JC. Pathology of idiopathic
Rectal sensitivity in chronic constipation. Dig Dis Sci. 1989; megarectum and megacolon. Gut. 1997;41:252–257.
34:747–753. 233. Gattuso JM, Smith VV, Kamm MA. Altered contractile proteins
212. Meunier P. Physiologic study of the terminal digestive tract in and neural innervation in idiopathic megarectum and megaco-
chronic painful constipation. Gut. 1986;27:1018–1024. lon. Histopathology. 1998;33:34–38.
213. Baldi F, Ferrarini F, Corinaldesi R, et al. Function of the internal 234. Ringel Y, Whitehead WE, Toner BB, et al. Sexual and physical
anal sphincter and rectal sensitivity in idiopathic constipation. abuse are not associated with rectal hypersensitivity in patients
Digestion. 1982;24:14–22. with irritable bowel syndrome. Gut. 2004;53:838–842.
214. Wald A, Tunuguntla AK. Anorectal sensorimotor dysfunction in 235. Denny-Brown D, Robertson E. An investigation of the nervous
fecal incontinence and diabetes mellitus. Modification with control of defecation. Brain. 1935;58:256–307.
biofeedback therapy. N Engl J Med. 1984;310:1282–1287. doi: 236. White JC, Verlot MG, Ehrentheil O. Neurogenic disturbances of
10.1056/nejm198405173102003. the colon and their investigation by the colonmetrogram: a
215. Lubowski DZ, Nicholls RJ. Faecal incontinence associated with preliminary report. Ann Surg. 1940;112:1042–1057.
reduced pelvic sensation. Br J Surg. 1988;75:1086–1088. 237. Corsetti M, Gevers AM, Caenepeel P, Tack J. The role of ten-
216. Hoffmann B, Timmcke A, Gathright JJ, Hicks T, Opelka F, sion receptors in colonic mechanosensitivity in humans. Gut.
Beck D. Fecal seepage and soiling: a problem of rectal sensa- 2004;53:1787–1793. doi:10.1136/gut.2004.038786.
tion. Dis Colon Rectum. 1995;38:746–748. 238. Vasudevan SP, Gladman MA, Swash M, Lunniss PJ, Scott SM.
217. Hancke E, Schurholz M. Impaired rectal sensation in idiopathic 2006 Joint international society meeting in neurogastroenterol-
faecal incontinence. Int J Colorectal Dis. 1987;2:146–148. ogy and GI motility. Neurogastroenterol Motil. 2006;18:
218. Farthing MJ, Lennard-Jones JE. Sensibility of the rectum to 663–798. doi:10.1111/j.1365-2982.2006.00826.x.
distension and the anorectal distension reflex in ulcerative 239. Read MG, Read NW. Role of anorectal sensation in preserving
colitis. Gut. 1978;19:64–69. continence. Gut. 1982;23:345–347.
219. Williams NS, Ogunbiyi OA, Scott SM, Fajobi O, Lunniss PJ. 240. Gregersen H, Kassab G. Biomechanics of the gastrointestinal
Rectal augmentation and stimulated gracilis anal neosphincter: a tract. Neurogastroenterol Motil. 1996;8:277–297.
new approach in the management of fecal urgency and incon- 241. Gladman MA, Aziz Q, Scott SM, Williams NS, Lunniss PJ.
tinence. Dis Colon Rectum. 2001;44:192–198. Rectal hyposensitivity: pathophysiological mechanisms. Neu-
220. Chan CL, Scott SM, Williams NS, Lunniss PJ. Rectal hyper- rogastroenterol Motil. 2009;21(5):508–516, e4-5. doi:10.1111/
sensitivity worsens stool frequency, urgency, and lifestyle in j.1365-2982.2008.01216.x.
patients with urge fecal incontinence. Dis Colon Rectum. 242. Petersen P, Gao C, Arendt-Nielsen L, Gregersen H, Drewes AM.
2005;48:134–140. Pain intensity and biomechanical responses during ramp-con-
221. Sun WM, Donnelly TC, Read NW. Utility of a combined test of trolled distension of the human rectum. Dig Dis Sci. 2003;
anorectal manometry, electromyography, and sensation in 48:1310–1316.
determining the mechanism of ‘idiopathic’ faecal incontinence. 243. Zagorodnyuk VP, Brookes SJ, Spencer NJ. Structure-function
Gut. 1992;33:807–813. relationship of sensory endings in the gut and bladder. Auton
222. Gladman MA, Lunniss PJ, Scott SM, Swash M. Rectal hypo- Neurosci. 2010;153:3–11. doi:10.1016/j.autneu.2009.07.018.
sensitivity. Am J Gastroenterol. 2006;101:1140–1151. doi: 244. Lynn PA, Olsson C, Zagorodnyuk V, Costa M, Brookes SJ.
10.1111/j.1572-0241.2006.00604.x. Rectal intraganglionic laminar endings are transduction sites of
223. Mimura T, Nicholls T, Storrie JB, Kamm MA. Treatment of extrinsic mechanoreceptors in the guinea pig rectum. Gastro-
constipation in adults associated with idiopathic megarectum by enterology. 2003;125:786–794.
123
1464 Dig Dis Sci (2012) 57:1445–1464
245. Olsson C, Costa M, Brookes SJ. Neurochemical characterization 265. Broens P, Vanbeckevoort D, Bellon E, Penninckx F. Combined
of extrinsic innervation of the guinea pig rectum. J Comp radiologic and manometric study of rectal filling sensation. Dis
Neurol. 2004;470:357–371. doi:10.1002/cne.20000. Colon Rectum. 2002;45:1016–1022.
246. Spencer NJ, Kerrin A, Zagorodnyuk VP, et al. Identification of 266. Lubowski D, Meagher A, Smart R, Butler S. Scintigraphic
functional intramuscular rectal mechanoreceptors in aganglionic assessment of colonic function during defaecation. Int J Colo-
rectal smooth muscle from piebald lethal mice. Am J Physiol rectal Dis. 1995;10:91–93.
Gastrointest Liver Physiol. 2008;294:G855–G867. doi:10.1152/ 267. Herbst F, Kamm MA, Morris GP, Britton K, Woloszko J,
ajpgi.00502.2007. Nicholls RJ. Gastrointestinal transit and prolonged ambulatory
247. Song X, Chen BN, Zagorodnyuk VP, et al. Identification of colonic motility in health and faecal incontinence. Gut. 1997;41:
medium/high-threshold extrinsic mechanosensitive afferent 381–389.
nerves to the gastrointestinal tract. Gastroenterology. 268. Kamm MA, van der Sijp JR, Lennard-Jones JE. Colorectal and
2009;137:274–284, 284 e1. doi:10.1053/j.gastro.2009.02.061. anal motility during defaecation. Lancet. 1992;339:820.
248. Chan CL, Ponsford S, Scott SM, Swash M, Lunniss PJ. Con- 269. Rao SS, Kuo B, McCallum RW, et al. Investigation of colonic
tribution of the pudendal nerve to sensation of the distal rectum. and whole gut transit with wireless motility capsule and radio-
Br J Surg. 2005;92:859–865. doi:10.1002/bjs.4877. opaque markers in constipation. Clin Gastroenterol Hepatol.
249. Frenckner B, Ihre T. Influence of autonomic nerves on the 2009 (Epub ahead of print). doi:10.1016/j.cgh.2009.01.017.
internal anal sphincter in man. Gut. 1976;17:306–312. 270. Bharucha AE, Wald A, Enck P, Rao S. Functional anorectal
250. Gunterberg B, Kewenter J, Petersen I, Stener B. Anorectal disorders. Gastroenterology. 2006;130:1510–1518.
function after major resections of the sacrum with bilateral or 271. MacDonald A, Paterson PJ, Baxter JN, Finlay IG. Relationship
unilateral sacrifice of sacral nerves. Br J Surg. 1976;63:546–554. between intra-abdominal and intrarectal pressure in the proc-
251. Todd LT Jr, Yaszemski MJ, Currier BL, Fuchs B, Kim CW, Sim tometrogram. Br J Surg. 1993;80:1070–1071.
FH. Bowel and bladder function after major sacral resection. 272. Ito T, Sakakibara R, Uchiyama T, Zhi L, Yamamoto T, Hattori
Clin Orthop Relat Res. 2002;397:36–39. T. Videomanometry of the pelvic organs: a comparison of the
252. Garvin B, Lovely L, Tsodikov A, Minecan D, Hong S, Wiley normal lower urinary and gastrointestinal tracts. Int J Urol.
JW. Cortical and spinal evoked potential response to electrical 2006;13:29–35. doi:10.1111/j.1442-2042.2006.01224.x.
stimulation in human rectum. World J Gastroenterol. 2010; 273. Bharucha AE. Pelvic floor: anatomy and function. Neurogas-
16:5440–5446. troenterol Motil. 2006;18:507–519. doi:10.1111/j.1365-
253. Loening-Baucke V, Yamada T. Cerebral potentials evoked by 2982.2006.00803.x.
rectal distention in humans. Electroencephalogr Clin Neuro- 274. Enck P, Vodusek DB. Electromyography of pelvic floor mus-
physiol. 1993;88:447–452. cles. J Electromyogr Kinesiol. 2006;16:568–577. doi:10.1016/
254. Remes-Troche JM, Tantiphlachiva K, Attaluri A, et al. A bi- j.jelekin.2006.08.007.
directional assessment of the human brain-anorectal axis. Neu- 275. Panu R, Bo Minelli L, Sanna L, et al. Comparative study of
rogastroenterol Motil. 2011;23:240–248, e117-8. doi: sensitive and vegetative innervation of external and internal anal
10.1111/j.1365-2982.2010.01619.x. sphincter muscles in different mammals. Ital J Anat Embryol.
255. Loening-Baucke V, Yamada T. Is the afferent pathway from the 1995;100:147–158.
rectum impaired in children with chronic constipation and 276. Rao SSC, Mudipalli RS, Stessman M, Zimmerman B. Investi-
encopresis? Gastroenterology. 1995;109:397–403. gation of the utility of colorectal function tests and Rome II
256. Hobday DI, Hobson AR, Sarkar S, Furlong PL, Thompson DG, criteria in dyssynergic defecation (Anismus). Neurogastroen-
Aziz Q. Cortical processing of human gut sensation: an evoked terol Motil. 2004;16:589–596.
potential study. Am J Physiol Gastrointest Liver Physiol. 277. Rasmussen OO. Anorectal function. Dis Colon Rectum.
2002;283:G335–G339. doi:10.1152/ajpgi.00230.2001. 1994;37:386–403.
257. Gladman MA, Dvorkin LS, Lunniss PJ, Williams NS, Scott SM. 278. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Me-
Rectal hyposensitivity: a disorder of the rectal wall or the arin F, Spiller RC. Functional bowel disorders. Gastroenterology.
afferent pathway? An assessment using the barostat. Am J 2006;130:1480–1491. doi:10.1053/j.gastro.2005.11.061.
Gastroenterol. 2005;100:106–114. doi:10.1111/j.1572-0241. 279. Rasquin-Weber A, Hyman PE, Cucchiara S, et al. Childhood
2005.40021.x. functional gastrointestinal disorders. Gut. 1999;45:II60–II68.
258. Liao D, Lelic D, Gao F, Drewes AM, Gregersen H. Biome- 280. Loening-Baucke VA, Cruikshank BM. Abnormal defecation
chanical functional and sensory modelling of the gastrointestinal dynamics in chronically constipated children with encopresis. J
tract. Philos Transact A Math Phys Eng Sci. 2008;366: Pediatr. 1986;108:562–566.
3281–3299. doi:10.1098/rsta.2008.0091. 281. Loening-Baucke V. Factors determining outcome in children with
259. Gladman M. Rectal Hyposensitivity: Clinical and Physiological chronic constipation and faecal soiling. Gut. 1989;30:999–1006.
Studies. London: Queen Mary, University of London; 2005. 282. Wald A, Chandra R, Gabel S, Chiponis D. Evaluation of bio-
260. Madoff RD, Orrom WJ, Rothenberger DA, Goldberg SM. feedback in childhood encopresis. J Pediatr Gastroenterol Nutr.
Rectal compliance: a critical reappraisal. Int J Colorectal Dis. 1987;6:554–558.
1990;5:37–40. 283. Loening-Baucke V. Balloon defecation as a predictor of out-
261. Dall F, Jørgensen C, Houe D, Gregersen H, Djurhuus J. Bio- come in children with functional constipation and encopresis. J
mechanical wall properties of the human rectum. A study with Pediatr. 1996;128:336–340.
impedance planimetry. Gut. 1993;34:1581–1586. 284. Petros PE, Swash M. The musculoelastic theory of anorectal
262. Musial F, Crowell MD. Rectal adaptation to distention: impli- function and dysfunction. Pelviperineology. 2008;27:89–93.
cations for the determination of perception thresholds. Physiol 285. Loder PB, Kamm MA, Nicholls RJ, Phillips RK. Haemorrhoids:
Behav. 1995;58:1145–1148. pathology, pathophysiology and aetiology. Br J Surg.
263. Chan CL, Scott SM, Knowles CH, Lunniss PJ. Exaggerated 1994;81:946–954.
rectal adaptation—another cause of outlet obstruction. Colo- 286. Lynch AC, Anthony A, Dobbs BR, Frizelle FA. Anorectal physi-
rectal Dis. 2001;3:141–142. ology following spinal cord injury. Spinal Cord. 2000;38:573–580.
264. Wester C, Brubaker L. Normal pelvic floor physiology. Obstet 287. Nyam DC. The current understanding of continence and defe-
Gynecol Clin North Am. 1998;25:707–722, v. cation. Singapore Med J. 1998;39:132–136.
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