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Colonic Physiology
Ursula M. Szmulowicz and Tracy L. Hull

The human colon is a dynamic organ, involved in a vast array an axis comprised of the superior mesenteric artery, as
of functions, including the absorption of water and electro- viewed from the front. Although the cranial limb of the her-
lytes, the salvage of unabsorbed nutrients, and the transport niated primary intestinal loop – the future small intestine –
of luminal contents as feces. While not an organ essential for continues to elongate and organize into loops, the caudal
life, the colon still plays a major role in maintaining the over- limb – the proximal colon – remains mainly unaltered, its
all health of the human body. Understanding these physio- only adjustment involving the development of a cecal bud,
logic principles is integral to the successful treatment – both a bulge from its antimesenteric border.3 In the tenth week of
medical and surgical – of colonic disease. gestation, the herniated intestine commences its return to the
abdominal cavity, in the process completing an additional
180° counterclockwise rotation to finalize the disposition of
Embryology the embryonic proximal jejunum on the left and the primitive
colon on the right.2 The cecum – the last component to reen-
The embryology of the colon informs its anatomy. In the third ter the abdomen – initially is located in the right upper quad-
and fourth weeks of gestation, the primitive intestine arises rant but then migrates inferiorly to the right iliac fossa as the
from the cephalocaudal and lateral folding of the dorsal sur- dorsal mesentery suspending the ascending colon shortens
face of the endoderm-lined yolk sac, forming a straight tube and then recedes.4 As the cecal bud descends, the appendix
situated posteriorly in the embryo.1–3 Although the mucosa appears as a narrow diverticulum.2–7 The loss of the dorsal
originates from the endoderm of the yolk sac, the muscular mesentery of the ascending and descending colon produces
wall, connective tissue, and serosa have a mesodermal etiol- their retroperitoneal fixation, absent in the cecum, transverse
ogy.4 By the fourth week of gestation, the gut tube develops colon, and sigmoid colon.2
into three distinct regions: the foregut, midgut, and hindgut.4
The midgut begins immediately distal to the confluence
of the common bile duct and the duodenum, extending to Innervation
include the proximal two-thirds of the transverse colon. At
the midgut, the primitive intestine maintains its connection Colonic innervation emanates from two sources: the extrinsic
to the yolk sac via the vitelline duct; failure of the vitelline and the intrinsic nerves. Extrinsic innervation involves the
duct to obliterate ultimately results in a Meckel’s diverticu- sympathetic and parasympathetic nerves of the autonomic
lum or a vitelline cyst or fistula.2,5 The hindgut reaches from nervous system, which are responsible for colonic motility
the distal third of the transverse colon to the anal canal proxi- and sensation. Intrinsic innervation arises from the poorly
mal to the dentate line. The midgut receives its vascular understood enteric nervous system.
supply from the superior mesenteric artery and the hindgut The parasympathetic nerves primarily exert an excitatory
from the inferior mesenteric artery.6 affect upon colonic motility. The main parasympathetic neu-
The colon gains its ultimate position by means of a series rotransmitters include acetylcholine and tachykinins such
of rotations of the embryonic gut. During the fifth week of as substance P. The parasympathetic supply to the proximal
gestation, the midgut, particularly the future ileum, rapidly colon originates from the posterior division of the vagus
enlarges beyond the capacity of the abdominal cavity, cul- nerve – the tenth cranial nerve.8,9 These parasympathetic
minating in its physiologic herniation through the umbilicus fibers reach the colon by following the branches of the supe-
in the sixth week.1 While exteriorized, this hairpin-shaped rior mesenteric artery: the ileocolic and middle colic arter-
primary intestinal loop rotates 90° counterclockwise around ies. The distal colon, however, receives its parasympathetic

D.E. Beck et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery: Second Edition, 23
DOI 10.1007/978-1-4419-1584-9_2, © Springer Science+Business Media, LLC 2011
24 U.M. Szmulowicz and T.L. Hull

input from the second to fourth sacral nerves, with the third with the ventral spinal ramus, after which it is distributed to
sacral nerve the most dominant.8,9 These pelvic splanchnic the sweat glands and arrector pili muscles of the body wall
nerves – the nervi erigentes – emerge from the lateral horns and to the smooth muscle of the blood vessels throughout
of S2–4.8,9 After exiting the spinal column, the preganglionic the body.18 Yet, most preganglionic fibers – those innervat-
parasympathetic fibers travel superiorly and laterally, deep ing the abdominopelvic viscera – pass through the sympa-
to the peritoneum, to join the inferior hypogastric plexus, thetic trunk without synapsing, instead proceeding to the
located on the anterolateral pelvic wall, adjacent to the lat- interconnected collateral (preaortic or prevertebral) ganglia
eral ligaments at the level of the lower third of the rectum.10 that lie anterior to the aorta at its junction with its main vas-
From the inferior hypogastric plexus, these parasympathetic cular branches as part of a specific splanchnic (“visceral”)
fibers are distributed to the pelvic organs and to the distal nerve: the greater (T5–T9 or 10), lesser (T10–T11), least
colon as far proximal as the splenic flexure.11 The pregangli- (T12), or lumbar (L1–2) splanchnic nerves.12,17,19 While
onic parasympathetic fibers ultimately synapse in the bowel the midgut receives its sympathetic input from the lesser
wall at the ganglia within the myenteric plexus of Auerbach splanchnic nerve, the hindgut is supplied by the lumbar
and Meissner’s plexus.12 splanchnic nerve.18 Once these preganglionic fibers synapse
Unlike the parasympathetic nerves, the sympathetic sys- at a collateral ganglion, the postganglionic fibers follow the
tem effects a tonic inhibition of the nonsphincteric colonic vasculature to the intestine, concluding in the enteric gan-
muscle and, thus, of colonic peristalsis.11 Additionally, glia.20 Some of the postganglionic fibers terminate instead
sympathetic fibers prevent epithelial secretion and reduce on intestinal epithelial cells, whereby intestinal secretion is
splanchnic blood flow.9 However, the sympathetic supply is inhibited.20 The midgut derivatives are primarily innervated
excitatory to sphincter muscles, particularly to the ileocecal by postganglionic fibers from the superior mesenteric gan-
junction and the internal anal sphincter.9,11,13 The primary glion and the hindgut structures, from the inferior mesen-
sympathetic neurotransmitter is norepinephrine.8,11 The teric ganglion, although commingling between the ganglia
inhibition of colonic tone, although not fully understood, is common.8
is believed to be mediated via a2 adrenergic receptors.14 In The intrinsic innervation of the colon – the enteric
one study in humans, the a2 agonist clonidine was  deter- ­nervous system – is uniquely able to mediate reflex behavior
mined to decrease fasting colonic tone, while the a2 independent of input from the brain or spinal cord.21 This
antagonist yohimbine increased it.15 Stimulation of  the  a2 intrinsic network regulates the majority of colonic motil-
adrenoreceptor also blocked the release of acetylcholine ity.9 However, the activity of the enteric nervous system is
from the hyperpolarized parasympathetic neurons in the impacted by the extrinsic nerves: the sympathetic, parasym-
myenteric and pelvic plexi, thus arresting parasympathetic pathetic, and visceral afferent nerves.8,11 This “little brain”
function.11,15 In contrast, the in  vivo administration of the employs the same modulators and neuro transmitters pres-
a1 agonist phenylephrine and the b2 agonist ritodrine at the ent in the central nervous system, including the excitatory
highest acceptable dosages had no impact upon colonic acetylcholine, substance P, and neurokinin A and the inhibi-
tone.15 Yet, in an in vitro study, agonists of the b1, b2, and tory nitric oxide, adenosine triphosphate (ATP), vasoactive
b3 colonic adrenoceptors relaxed the human taenia coli; the intestinal polypeptide (VIP), and pituitary adenyl cyclase-
circular muscular tone maximally diminished after treat- activating peptide.9,13,21,22 The enteric nervous system acts
ment with the b1 agonist.16 through many different types of neurons, with their cell bod-
The preganglionic sympathetic effector cells are derived ies amassed within neuronal plexi positioned either between
from the intermediolateral cell column (lateral horns) of the the circular and longitudinal muscles (the myenteric plexus
thoracic (T1–12) and, in particular, the lumbar spine (L1–2 of Auerbach) or in the submucosal layer.9 The submucosal
or 3–4). The sympathetic nerve fibers leave the spinal col- plexi are comprised of Meissner’s plexus, situated adjacent
umn via the ventral spinal nerve roots (rami). These myeli- to the mucosa, and Schabadasch’s plexus, which lies near
nated preganglionic fibers then exit from the ventral spinal the circular muscle.9 Notably, the number of neurons in the
nerve root as a white ramus communicans (“communicat- enteric nervous system greatly exceeds that of the entire
ing branches”) to merge with the paired sympathetic trunks autonomic nervous system.9 The myenteric plexus directs
(paravertebral ganglia), found along the entire length of the smooth muscle function while the submucosal plexus modu-
vertebral column. Once it has joined a sympathetic trunk, the lates mucosal ion transport and absorptive functions.11 More-
preganglionic sympathetic nerve fiber either immediately over, the enteric network influences blood flow to the colon.20
synapses at that ganglion or it ascends or descends along Control of colonic motor function via the enteric nervous
the trunk before synapsing at another vertebral level, from system remains poorly understood at this time. However, a
the first cervical vertebra to the first coccygeal vertebra, reflex arc is initiated by a mechanical (e.g., stretch), chemi-
along the sympathetic trunk.17 A single preganglionic fiber cal, or other noxious stimulus, which activates an enteric
synapses with 30 or more postganglionic fibers.8 After syn- primary afferent neuron; the impulse is carried to an enteric
apsing, the unmyelinated postganglionic fibers depart the motor neuron – the effector cell – via an enteric interneuron,
sympathetic trunk as a gray ramus communicans, reuniting producing an excitatory or inhibitory effect.9,20
2. Colonic Physiology 25

Colonic Function The short-chain fatty acids occupy an integral position

in colonic health. More than 95% of the short-chain fatty
acids are created in and are immediately appropriated by the
Salvage, Metabolism, and Storage
colon, with very little excreted in the feces.25,27,32 An aver-
Although digestion and absorption primarily take place in age of 400 mmol/day, with a range of 150–600 mmol/day,
the stomach and small intestine, the colon still plays a major of short-chain fatty acids are produced in the colon.33,34 This
role in these operations. The colon processes various com- reclamation of undigested matter in the colon as short-chain
plex carbohydrates and, to a lesser extent, proteins that prove fatty acids provides 5–15% of the total caloric needs of an
resistant to digestion and absorption in the more proximal individual.27 These weak acids – the preeminent colonic
intestine.23,24 Unlike the small intestine, the colon salvages anions – mainly remain dissociated in the colonic lumen
nutrients from these products via fermentation. Fermentation until absorbed either in exchange for bicarbonate via a SCFA/
occurs by means of the saccarolytic and proteolytic members HCO3− transport channel; by an active transport mechanism
of the over 400 species of bacteria, the majority of which are such as the sodium-coupled monocarboxylate transporter
obligate anaerobes, present within the colon.25 Approximately (SMCT1) or the monocarboxylate transporter isoform 1
10% of ingested carbohydrates enter the cecum as undigested (MCT1); or by diffusion in their lipid soluble form.27 The
material.11 Among the diverse end products of the bacterial sodium-coupled monocarboxylate transporter facilitates the
fermentation of complex carbohydrates – mainly the soluble conservation of sodium, chloride, and water in the colon.27
plant residues (fiber) – are the short-chain fatty acids, repre- Furthermore, the short-chain fatty acids are incorporated as
sented principally by butyrate (15%), propionate (25%), and the basic elements for mucin synthesis, lipogenesis, gluco-
acetate (60%).26 Ingestion of a diet higher in complex carbo- neogenesis, and protein production. In particular, propionate
hydrates, beans, resistant starches, and soluble fiber leads to combines with other three-carbon compounds in the liver to
a greater output of short-chain fatty acids than that of insol- participate in gluconeogenesis. Acetate is used by the liver
uble fibers. The composition of the bacterial microenviron- as a component to fashion longer-chain fatty acids and by the
ment also influences the amount of synthesized short-chain muscle as sustenance.23,24
fatty acids.11,27 The nondigestible carbohydrate inulin – an Although the least abundant of the short-chain fatty acids,
extract of chicory – has been studied as a prebiotic, a food butyrate has the greatest import in colonic homeostasis. This
that selectively alters the admixture of the colonic bacterial short-chain fatty acid acts as the primary energy source for
flora; although its addition to the diet increased the proportion the colonocyte, supplying 70–90% of its energy require-
of beneficial bifidobacteria in the feces in various studies, its ments; these epithelial cells receive their nourishment solely
impact – whether healthful or harmful – upon other bacterial from luminal substrates, not from the bloodstream.20,23,24
species could not be well gauged.28 Bacterial fermentation of Of the short-chain fatty acids, butyrate best promotes the
the complex carbohydrates primarily transpires in the ascend- absorption of water, sodium, and chloride from the colon,
ing and proximal transverse colon. In contrast, the undigested acting as an antidiarrheal agent.27 This short-chain fatty acid
dietary proteins that reach the colon, as well as proteins from also advances colonic cell proliferation and differentiation,
mucous and sloughed epithelial cells, are fermented in the repair, and immune function.11,27,35 Butyrate has been shown
distal colon, primarily because the carbohydrates – the pre- to influence colon carcinogenesis: studies have revealed that
ferred nutrient of most bacteria – were previously exhausted in fewer butyrate transporters were present in human colonic
the proximal colon; the concentration of the short-chain fatty adenocarcinomas, resulting in a decrease in the utilization
acids produced in the distal colon is 30% less than in the prox- of the trophic butyrate in the malignant cells.27 Moreover,
imal colon.27,29,30 However, a diet that includes prebiotics such in vitro studies of cancer cell lines identified apoptosis, non-
as inulin results in a greater degree of saccarolytic fermenta- proliferation, and differentiation after the administration of
tion in the distal colon due to the greater availability of these butyrate.27 One method by which butyrate modulates gene
slowly fermentable, highly polymerized carbohydrates.27 The expression and, thus, cancer growth likely arises from its
fermented proteins are converted into short-chain fatty acids, ability to suppress histone deacetylase, thus encouraging the
branched chain fatty acids, and amines. In addition, the bacte- union of various transcription factors with nuclear DNA; to
rial fermentation of undigested proteins generates ammonia, modify intracellular kinase signaling; and to inhibit nuclear
phenols, indoles, and sulfurs; these possibly toxic substances factor-kB.27
are considered potential etiologic agents for such diseases as In the colon, many metabolic processes are influenced
colon cancer and ulcerative colitis.27 Some of these proteolytic by functional food components. These foods – the pre- and
metabolites become a nitrogen source for bacterial growth.29,31 probiotics – alter the colonic microenvironment, adding
The residual products of the bacterial fermentation of com- to the impact of environmental factors and genetics.33 As
plex carbohydrates and proteins are absorbed or, like carbon previously discussed, prebiotics – primarily nondigestable
dioxide, hydrogen, and methane, passed with the feces.28 The oligosaccharides (NDOs) – are slowly fermentable foods
dietary fats that reach the colon likely are not recovered in the that selectively propagate microbial proliferation and/or
colon but are expelled with the stool.25 ­activity.36 These products are completely metabolized in the
26 U.M. Szmulowicz and T.L. Hull

colon into short-chain fatty acids, energy, and lactic acid, ensue due to the greater concentrations of short-chain fatty
leaving no nondigestable oligosaccharides in the stool.33 In acids to which the transverse colon is exposed following a
contrast, probiotics represent active bacterial cultures that right hemicolectomy, producing such changes as an increase
benefit the host by replenishing the colonic microenviron- in water and sodium retention.30
ment.37 Synbiotics combine the action of pre- and probiot-
ics.33 Investigations of these functional foods have focused
Transport of Water and Electrolytes
on the lactobacilli and bifidobacteria, the growth of which
transforms the colonic milieu, augmenting the immune func- Among its roles in preserving intestinal homeostasis, the
tion of the gut-associated lymphoid tissue (GALT).31,33 The colon is also integral to water and electrolyte transport.
effect of these supplements is thought to be attributable to an The colon maintains an appropriate hydration and electro-
increased production of butyrate, changes in mucin produc- lyte balance by means of the absorption and secretion of
tion, or interference in the binding of pathogenic bacteria to intestinal water and electrolytes. The mucosal surface area
the colonic mucosa.27,38 Prebiotics are particularly associated available for these processes amounts to approximately
with an elevation of the concentration of short-chain fatty 2,000 cm2.30 While the surface epithelial cells in the colon
acids.33 To combat the rising incidence of antibiotic-resistant are primarily responsible for absorption, the crypt cells are
bacteria in hospitals, the World Health Organization has involved in fluid secretion; however, crypt cells have been
recommended the use of microbial interference therapies – found to some degree to contribute to absorption.11,30,46 After
nonpathogenic bacteria that eradicate pathogens – such as the liquid effluent from the small intestine has traversed
probiotics.34 Currently, probiotics are prescribed in cases of the colon, fluid and electrolyte absorption and secretion as
disturbed microbial balance, such as antibiotic-associated well as bacterial activity produce about 200 g of solid feces
diarrhea. In the future, pre- and probiotics may become per day.20
important supplements regularly administered to patients to The colon is extremely efficient at conserving intestinal
promote health and to prevent illness. These functional foods water.13 Water is passively absorbed along an osmotic gradi-
further present the possibility of reducing the potential of ent, enabled by a luminal sodium concentration lower than
carcinogens to form cancers.31,38 that of the epithelial cells; as such, the salvage of intestinal
While the colon is one organ, it demonstrates regional water relies upon sodium conservation.11,30 Normally, the
differences. As noted, the proximal and distal colon have colon is presented with 1.5–2 L of water daily, as compared
different embryological origins, derived from the mid- and to the 9–10 L that pass through the small intestine; of this
hindgut, respectively. In appearance, the proximal colon amount, 1.5–2 L are ingested, with the remainder originat-
is more saccular and the distal colon, more tubular.39 The ing from salivary, biliary, pancreatic, and intestinal secre-
short-chain fatty acids are principally synthesized in the tions.24,30 Approximately 90% of this water is reclaimed by
more acidic environment of the proximal colon. The proxi- the colon, leaving 100–150 mL in the feces.20 The absorption
mal colon serves as a reservoir, in contrast to the distal colon, of water primarily follows a paracellular pathway, although
which mainly performs as a conduit.40 Yet, this truism is a transcellular route involves various protein channels: aqua-
­disputed by studies in which radiopaque markers were deter- porins 3, 4, 5, 8, and 9.20 The ascending colon demonstrates
mined to have the same dwell time of approximately 11 h in the greatest absorptive capability, as the chyme resides within
the proximal, distal, and middle colonic segments, suggest- this segment the longest, thus maximizing its contact with
ing that the proximal colon does not preferentially operate the mucosa. As a consequence, diarrhea more consistently
as a receptacle for stool.9 Also, the character of the lumi- ensues after a right, as opposed to a left, hemicolectomy.
nal contents impacts transit times. Large volumes of liquid Fluid retention is promoted by the antidiuretic hormone.43
quickly pass through the ascending colon but remain within When challenged, the proximal colon, with the additional
the transverse colon for as long as 20–40  h; in contrast, a contribution of the sigmoid colon and rectosigmoid, is able
solid meal is retained by the cecum and ascending colon for to save a further 5–6 L of intestinal water daily.47–49 Yet this
longer periods than a liquid diet.9,41,42 The salvage of water facility is contingent upon the composition, rate of flow (less
and electrolytes is primarily accorded to the proximal colon, than 1–2 mL/min), and amount of the effluent. In the case
although the distal colon and rectum contribute to this task, that the absorptive capacity of the colon is exceeded, diar-
albeit to a lesser extent.43,44 In the event that a large amount of rhea results. Fluid secretion in the colon only transpires in
chyme is delivered to the colon, the distal colon and rectum the presence of diverse secretagogues, such as laxatives,
may assist in the absorption of enough fluid to produce a bacterial endotoxins, hormones (e.g., VIP), and endogenous
solid stool.41 The regional heterogeneity of the colon exhib- substances (e.g., bile acids).43
its adaptability. After a right hemicolectomy, the transverse The colon is essential to the recovery of sodium. Under
colon adjusts to become a neo-proximal colon; 6 months normal conditions, the colon principally absorbs sodium and
after the surgery, the progress of an ingested isotope from chloride but secretes bicarbonate and potassium. The liquid
the small intestine through the shortened colon returns to chyme delivered to the colon contains 130–140 mmol/L of
the preoperative baseline.45 The assumption of this role may sodium whereas the concentration in stool is 40  mmol/L;
2. Colonic Physiology 27

approximately 95% of the sodium transported into the colon microorganisms into ammonia, which is then passively
is conserved.29,43 If required, the colon is able to increase its absorbed by the surface epithelial cells.29,43 Ammonia is also
salvage of sodium to 800 mmol/L/day.43 The normal colon derived from dietary nitrogen, the sloughed mucosal lining,
can prevent hyponatremia even despite a diet containing as and bacterial waste. Only 1–3 mmol of ammonia is excreted
little as 1 mEq of sodium daily; in contrast, the absence of with the feces. The majority of the ammonia that reaches
a colon encourages dehydration and hyponatremia.43 The the colon is returned via the enterohepatic circulation to the
transport mechanisms for sodium absorption, located on liver, where it is refashioned into urea.30
the luminal surface of the epithelial cells, vary throughout the
colon: a Na+/H+ exchange channel in the proximal colon and
an electrogenic sodium-specific channel (ENaC) in the distal Colonic Motility
colon and rectum.20 The Na+/H+ exchange channels (NHE 2
and 3) are coupled to the Cl−-HCO3− exchange channels.20 Methodology to Measure Colonic Transit
The activity of the electrogenic sodium-specific channel in
Although altered motility is thought to play a major role
the distal colon and rectum is requisite for the desiccation
in various gastrointestinal disorders, surprisingly little is
of stool.20 These two types of transport channel allow for
known about the subject. This lack of understanding arises
the passive diffusion of sodium into the colonic epithelial
in part from the inaccessibility of the colon, particularly
cells along an electrochemical gradient, consisting of a low
the proximal colon, for direct study. Bowel questionnaires
intracellular sodium concentration (<15 mM) and a negative
have been used to gain insight into colonic motility; how-
intracellular electrical potential difference as compared to
ever, interestingly, stool frequency – or the recollection of
the lumen.30 This favorable electrochemical gradient is cre-
the patient of their stool frequency – and colorectal transit
ated by the active extrusion of sodium via the Na+/K+ ATPase
time, which represents 75% of total intestinal transit time,
pump on the basolateral membrane of the epithelial cell:
are poorly related.41,53,54 Early evaluations using barium were
three sodium ions are expelled in exchange for two potas-
also unable to achieve a precise measurement of colonic
sium ions.20,30 Aldosterone, a mineralocorticoid secreted
motility.55 The initial techniques to determine colonic motil-
by the adrenal gland in response to sodium depletion and
ity began with the calculation of colonic transit time.
dehydration, enhances fluid and sodium absorption in the
colon.46,50 The absorption of sodium is further promoted by
Radiopaque Markers
somatostatin, a2-adrenergic agents (e.g., clonidine), and the
short-chain fatty acids.11,24 One of the first methods to gauge colonic transit time
Like sodium, chloride is recovered from the colonic lumen. involves radiopaque markers. This study, proposed by Hin-
In the proximal colon, chloride is traded for bicarbonate ton and colleagues in 1969 to assess severe constipation, fol-
via the Cl−-HCO3− exchange channel found on the luminal lows the passage of the markers over sequential abdominal
surface of the epithelial cells; the activity of this channel is radiographs.11,56 Total and regional colonic transit times are
linked to the Na+/H+ exchange protein.20,29 However, chloride reflected by the number and the location of the markers.11
also is absorbed through a Cl−-HCO3− exchange channel that For men, the average total colonic transit is 30.7 h (SD 3.0)
is not associated with sodium.20 Chloride absorption is sup- and for women, 38.3  h (SD 2.9).55 Currently, the commer-
ported by an acidic luminal milieu; consequentially, the con- cially available SitzmarksTM (Konsyl Pharmaceuticals, Eas-
comitant secretion of bicarbonate neutralizes organic acids ton, MD) are composed of a gelatin capsule containing 24
within the colonic lumen.24,43 The transport mechanism for radioopaque PVC O-rings. Various protocols for the exami-
bicarbonate secretion is poorly understood. Yet, bicarbon- nation exist, all of which require the cessation of all laxatives
ate, responsible for the alkalinity of the feces, is the primary 48 h prior to swallowing the markers. In one approach that
electrolyte wasted in diarrhea.20 focuses on total colonic transit, 5 days after taking the cap-
Potassium transport is primarily a passive process, follow- sule, an abdominal radiograph is obtained. A normal study
ing the movement of sodium across cell membranes. However, demonstrates evacuation of 80% of the markers. The reten-
active potassium secretion occurs in the proximal colon and tion of more than 20% of the markers suggests slow transit
active absorption in the distal colon.11,20 The H+/K+ ATPase constipation. Some physicians give a single capsule on Sun-
actively conveys potassium into the epithelial cells of the dis- day evening and obtain abdominal X-rays on days 1, 3, and
tal colon and rectum.20 A potassium channel is believed to 5. The film on the first day provides evidence that gastric
facilitate active secretion in the proximal colon.20 Potassium and small motility are grossly normal if all the markers are
secretion, combined with potassium derived from bacteria in the colon.
and colonic mucous, may explain the relatively high concen- In order to localize the markers to specific segments of the
tration of this electrolyte – 50–90 mmol/L – in stool.51,52 colon – right, left, and pelvis – another technique requires
The colon contributes to the metabolism of urea. that the patient consume one capsule, after which abdomi-
Approximately 0.4–1 g of urea enters the colon in the small nal radiographs are performed every other day until all 24
bowel effluent daily.43 The urea is converted by the colonic markers have been expelled. As an alternative, patients
28 U.M. Szmulowicz and T.L. Hull

ingest single capsules on three successive days, with only In one trial, the results from the capsule approach correlated
one abdominal radiograph done on day 4 of the study so as well with those acquired from the radiopaque markers, with a
to minimize radiation exposure.57 The number of markers similar sensitivity and specificity in detecting abnormal tran-
present equals the colonic transit time in hours. To better sit in those patients with constipation.59 The capsule is able
determine the distribution of the markers, some centers use to gauge phasic colonic contractions but not colonic motor
capsules holding markers of different shape on each of the patterns.62 This costly procedure is not widely employed but
3 days. An accumulation of the markers in the rectosigmoid is attractive in that radiation exposure is avoided and patient
indicates a dyssynergic defecation pattern.58 The reliability compliance is facilitated.59
of the technique is affected by patient compliance as well as
by differences in the interpretation of the results.59 Techniques to Record Colonic Motility
Colonic motility remains a constantly evolving field of
study. The techniques by which colonic motility are gauged
Some centers favor the more expensive colonic scintigra- rely upon the monitoring of electrical activity or of intralu-
phy over the radiopaque marker method to measure colonic minal pressure, using surface electrodes or a manometry
transit. As with the marker study, the protocols are not stan- or barostat apparatus, respectively.11 This indirect assess-
dardized among institutions. Although patients refrain from ment of colonic motility has been hindered by the instru-
taking laxatives or opiates 24 h before the test, a normal diet ments available for its measurement, the colonic anatomy,
is maintained throughout the study. The isotope is positioned and the need for prolonged readings. Recordings are usu-
in the cecum by the ingestion of a delayed release capsule or ally obtained over 6 h in the laboratory and over 24 h in an
by orocecal intubation.11 The delayed release capsule, coated ambulatory setting due to the long colonic transit time, espe-
with the pH-sensitive polymer methacrylate, is comprised of cially as compared to the small intestine.62 Also, the meth-
activated charcoal or polystyrene pellets labeled with either ods suffer from an absence of standardization. Although
In or 99mTc. The coating dissolves at the pH of 7.2–7.4 evaluations of colonic motility had initially focused upon
found in the distal ileum, after which the radioactive mate- the easily accessed distal colon, subsequent trials have indi-
rial is delivered into the colon.40,60 Images are taken with a cated that this segment is not representative of the proximal
gamma camera at specified intervals, usually at 4, 24, and colon. Yet, placement of the intraluminal devices is difficult,
48 h after consumption of the isotope, although this can be requiring either oral or nasal intubation or colonoscopy; fur-
performed as frequently as twice daily.11,61 Segmental transit thermore, application of the surface electrodes demands sur-
is usually determined for the ascending, transverse, descend- gery. Additionally, the necessity to purge the colon of stool
ing, and rectosigmoid regions of the colon. The proportion of may impact the results, producing an increase in the number
the counts is calculated in each section and then multiplied of high amplitude propagated contractions, although these
by a weighing factor: 0 for the cecum, 1 for the ascending findings are conflicting.63,64 Determinations of colonic pres-
colon, 2 for the transverse colon, 3 for the descending colon, sure are further influenced by artifact from extrinsic forces
4 for the rectosigmoid colon, and 5 for stool.60 The results are such as cough, straining, and sneezing.62 Thus, most of these
expressed as the geometric center of the isotope mass at any approaches rest in the researchers’ domain and have not
given time point, with a low count indicating that the isotope been assimilated into the standard clinical armamentarium.
is close to the cecum and a higher count that it has progressed However, significant progress is being gained with these
more distally.11,61 For clinical use, the total percentage of tools to understand the physiology and pathophysiology of
retained isotope as compared to normal data appears to be colonic motility.
the most convenient reporting system. Scintigraphy corre-
lates well with the radiopaque technique in assessing colonic Manometry
transit, with a similar sensitivity in diagnosing patients with
Colonic manometry has been the more frequently employed
slow transit constipation.60 The total exposure to radiation
method to measure phasic (brief) colonic contractions. How-
is also equivalent.11 Due to its greater costs, in most cases
ever, few centers utilize this technique in regular practice.
scintigraphy serves as a research instrument.
In this procedure, a flexible catheter – either a solid-state or a
water-perfused catheter system – is inserted into the colon. It
Wireless Motility Capsule
is argued that the water-perfused system increases the amount
The wireless motility capsule has been proposed as an alter- of fluid in the colon, thus altering the results. However, the
native method to determine colonic transit time. This tech- solid-state catheters are fragile, expensive, and sensitive to
nique, already proven for the study of gastroparesis, uses a corrosive damage from colonic irritants.65 However, this
capsule containing miniature pressure, temperature, and pH nonperfused system is more convenient and portable, allow-
measurement devices. The capsule is ingested, after which ing for long-term and ambulatory recordings.66 The validity
continuous recordings are obtained in an ambulatory setting, of the readings depends upon the proper placement of the
with the data captured over 5 days via a wireless instrument.59 catheter. As noted, the introduction of the catheter occurs
2. Colonic Physiology 29

via an oral or nasal route, confirmed with fluoroscopy, or by Electrodes

colonoscopy. With endoscopy, the catheter is either carried
Electrodes have also been applied for the study of colonic
along with the colonoscope in a piggyback fashion, grasped
motility. These devices record the myoelectrical signals
by biopsy forceps, or is threaded over a guidewire, deposited
from the colon that result in muscular activity.74,75 The elec-
via the colonoscope, under fluoroscopic guidance. The tip
trodes are placed on the serosal surface via surgery or on the
of the catheter is stationed as far proximal as the transverse
mucosa by colonoscopy. The technique is seldom used due
colon; with direct colonoscopic deployment, the proximal
to ethical concerns.
transverse colon is reached in all subjects, with the probe
remaining in position in greater than 80% of cases.65,67–69 To
adhere to more physiologic conditions, unprepared colons Peristalsis
are currently advocated, despite the impediment presented
by the retained stool to the retrograde placement of the Peristalsis represents the alternating waves of contraction
catheters; in some cases, enemas are instead used. Also, and relaxation of the circular muscles of the colon wall.
to prevent data artifact, minimal air is insufflated via the Fecal material is propelled antegrade through the colon by
colonoscope and as much aspirated as possible during its the contraction of the circular muscle proximal but the relax-
withdrawal. The patients are often asked to maintain a diary ation of the muscle distal to it, i.e., descending inhibition.11
to mark events such as bowel movements, flatus, and meals. During peristaltic activity, the saccular haustra – the product
Manometry is well able to detect the changes in intraluminal of circular muscle contraction – recede and then reform, first
pressure after eating or the administration of a colonic stimu- proximal to and subsequently at the level of the transferred
lant (e.g., bisacodyl). However, these variations in pressure material, again giving rise to colonic segmentation.9,41,76 The
do not consistently correspond to contractions: in a study contribution of the longitudinal smooth muscle to colonic
of colonic motility, the simultaneous use of manometry and activity is unknown.9 The average rate of antegrade colonic
colonoscopy indicated that a majority of pressure fluctua- transit is approximately 1  cm/h.9 The peristaltic reflex is
tions perceived by the catheter reflected colonic relaxation, thought to be initiated by luminal distention and, possibly,
not contraction.70 Furthermore, manometry does not reliably by chemical stimuli, which stimulate the enteric sensory
identify all contractions, some of which are not associated neurons; ultimately, the enteric motor neurons – the effec-
with an appreciable pressure deflection.9,70 An investigation tor cells – are activated via the intermediary of the enteric
comparing the barostat with manometry suggested that the interneurons.11 The interneurons may also directly detect
measurements obtained from manometry are also affected changes in smooth muscle length.77 The primary neurotrans-
by the luminal diameter in which the tip of the device lies.70 mitters involved in the peristaltic reflex include the excitatory
However, unlike the barostat, manometry recognizes pat- acetylcholine and the inhibitory nitric oxide and adenosine
terns of motor activity due to the multiple recording sites triphosphate (ATP).11 Although the enteric nervous network
along the catheter.62 primarily controls peristalsis, the extrinsic nervous system
modifies the reflex, with the sympathetic nerves suppressing
and the parasympathetic nerves promoting motility, espe-
cially during defecation. Interestingly, the parasympathetic
The colonic barostat device addresses the inability of manom- nerves also assist in the synchronization of descending inhi-
etry to record colonic tone, i.e., sustained contractions. As bition. The antegrade movement of the fecal bolus is further
with manometry, it is utilized clinically in few centers. The dependent upon the radius of the colonic segment, the con-
instrument includes a compressible polyethylene balloon, sistency of the feces, and the pressure differential between
placed within the colonic lumen, that is attached via tub- segments.
ing to a barostat – a cylinder containing a piston.11 The bal- Colonic motility adheres to several patterns. Generally,
loon is maintained at a low constant pressure such that it is contractions vary between tonic and phasic. The poorly
continuously in close contact with the colon wall in a single understood tonic contractions are sustained events of slow
location.71 Contraction of the colon constricts the balloon, onset, not necessarily inciting an elevation of the intralu-
reducing its volume by forcing air into the barostat; in con- minal pressure.76 Bassotti et  al. further classify the briefer
trast, colonic relaxation produces an increase in the volume phasic contractile episodes as high and low amplitude propa-
of the balloon so as to sustain a constant pressure.11 Changes gated contractions and as segmental contractions.71,78
in the volume of the balloon reflect colonic tone, although High amplitude propagated contractions – also known
phasic contractions are also assessed.72,73 However, patterns as migrating long spike bursts, large bowel peristalsis, and
of colonic activity cannot be distinguished as measurements giant migrating contractions – function to transport large
are obtained in only one site.62 Unlike the manometry tech- volumes of feces over long distances.71,78,79 These con-
nique, the barostat system is capable of detecting contrac- tractions are believed to be the manometric equivalent
tions that do not produce a significant pressure change, even of mass movement – first identified on radiographic studies
in colonic segments wider than 5.6 cm.11 of the colon – whereby colonic contents are projected
30 U.M. Szmulowicz and T.L. Hull

distally in seconds.40,67,80,81 The high amplitude propagated however, in the rectosigmoid region, a slower interval of 3
contractions transpire between 2 and 24 times a day, with an cycles per minute is preeminent, possibly giving rise to a
average of approximately five to six times a day.62,71 These physiologic sphincter to aid in continence.9,78,83
contractions, with an amplitude of 100–200 mmHg (average Unlike other mammals, humans possess a colon in which
of 100 mmHg), persist for 20–30 s.62,71 The contraction usu- cyclic motility is absent.78 The human rectum, however, does
ally begins in the proximal colon and is transmitted distally display such cyclic activity, the rectal motor complex. The
for 15 cm or longer, with the velocity gradually increasing to rectal motor complex is comprised of phasic contractions
as fast as 1 cm/s as the impulse moves caudad.11 A contrac- with amplitude of more than 5  mmHg. These phasic con-
tion that starts in the proximal colon is conveyed farther than tractions appear at a cycle of 2–3 per minute, with each per-
that commencing in the distal colon: 50 cm from the cecum sisting for approximately 3 min. Yet, the interlude between
and 20 cm from the sigmoid colon.9 More than 95% of these these contractions ranges from 10 to 260 min. This phasic
contractions proceed antegrade; however, only one-third of activity in the rectum and, potentially, the rectosigmoid may
these contractions result in the transit of fecal material.11,71,78 contribute to fecal continence, as it is correlated with an ele-
Moreover, not all instances of defecation, particularly those vated anal canal pressure; this role is further suggested by
involving liquid stool, are incited by a high amplitude the greater prominence of this activity at night.
propagated contraction.78 High amplitude propagated con-
tractions are considered the probable origin of the pressure
Cellular Basis of Motility
spikes that occur upon morning waking (35%) and after
meals (50%).71 The urge to defecate is likely attributable Colonic motor activity is driven and coordinated by the
to these contractions.71 Borborigmy is thought also to arise interstitial cells of Cajal, the intestinal pacemaker cells.84 In
from high amplitude propagated contractions.78 The impe- the absence of these cells, the intestinal smooth muscle is
tus for these contractions is incompletely comprehended. inactive.85 The interstitial cells of Cajal arise from smooth
These contractions are elicited by cholinergic medications muscle precursor cells; that is, the cells are of mesenchy-
(e.g., neostigmine), eating, colonic distention, short-chain mal, not neuronal, origin.86 These cells are classified by their
fatty acids, and laxatives (e.g., bisacodyl).11 However, only location as ICCMY – in the myenteric plexus, between the
in 50% of cases does colonic distention produce propagat- muscular layers; ICCSM – in the submucosal surface of the
ing activity.78 In patients with constipation, high amplitude circular muscle; and ICCIM – within the circular and longi-
propagated contractions are decreased in number, ampli- tudinal muscles.87 The interstitial cells of Cajal are linked
tude, extent, and speed. to the individual smooth muscle cells via intracellular gap
The low amplitude propagated contractions are still junctions; the similarly coupled smooth muscle cells func-
less understood. These contractions (5–40  mmHg) – also tion as a single unit, a syncytium.9 The gap junctions allow
referred to as long spike bursts – last for 3 s.71 As with the for the passage of current – predominantly slow waves  –
high amplitude propagated contractions, these contractions from the interstitial cells of Cajal to the smooth muscle
are strongly related to meals and the sleep-wake cycle. There syncytium, leading to its depolarization.86 The interstitial
may be an association with the passage of flatus and, in par- cells of Cajal are believed to be mechanosensitive, able to
ticular, liquid stool.82,83 Similar to the high amplitude propa- transduce stretch stimulus from the distended colonic lumen
gated contractions, these contractions are likely provoked by into electrical activity.88 The ICCSM – the primary pacemaker
colonic distention.71 The mechanisms by which these two cells – ­continuously generate high amplitude slow waves, at
propagated contractions are regulated remain unclear. How- a frequency of 2–4 per minute, within the circular muscle
ever, propulsive activity depends upon a functional enteric layer.9 Unlike the other types of interstitial cells of Cajal, the
nervous system.71 ICCSM are present only within the colon, solely in its proxi-
Segmental contractions, presenting singly or in rhythmic mal portion.86 A slow wave of sufficient charge produces a
or arrhythmic bursts, account for the majority of colonic smooth muscle action potential, allowing for an influx of
activity, particularly at rest.78 These contractions appear calcium into the smooth muscle cells via the L-type calcium
with an amplitude of 5–50 mmHg.71 Found primarily in the channels and, thus, a brief contraction.76 The amplitude of the
ascending and transverse colon, this activity produces local- slow waves is greatest at the submucosal surface of the circu-
ized contractions of the circular and longitudinal muscles, in lar muscle, diminishing while traveling through the muscular
effect segregating the haustrae.71 These segmental contrac- wall.89 Slow waves migrate antegrade and retrograde along
tions, the correlate of myoelectical short spike bursts, result short segments of the colon, rapidly in the circumferential
in the slow, sequential antegrade or retrograde movement of and slowly in the longitudinal axis; as waves of different
colonic contents among the haustra, allowing for mixing of inception meet, their propagation ceases, giving rise to non-
the material.13 Additionally, contact with the mucosal sur- propulsive mixing activity.9,85 A second pacemaker site may
face is maximized, which permits the absorption of intestinal involve the ICCMY. In addition to the slow waves, the ICCMY
water and electrolytes.71 Only 6% of segmental contractions may initiate low amplitude myenteric potential oscillations
are rhythmic, with a frequency of 2–8 cycles per minute; (MPOs) at a frequency of 12–20 per minute, which are
2. Colonic Physiology 31

conveyed to the circular and longitudinal smooth muscle.9 carbohydrates; in contrast, proteins inhibit motor function.71
The MPOs possibly are the source of propagating contrac- The colonic response to eating includes two phases: an ini-
tions.9 Moreover, the ICCMY synchronize the activity of the tial stimulation of the gastro-duodenal wall mechano- and
circular and longitudinal layers of the smooth muscle.86 As chemoreceptors and a subsequent activation of receptors
opposed to the ICCSM, the ICCMY are widespread throughout in the colonic wall.71 The means by which the gastrocolic
the colon.86 The etiology of the intrinsic electrical activity of reflex arises is unclear but may involve cholecystokinin,
the ICCMY and ICCSM is uncertain but may involve calcium gastrin, serotoninergic input, or cholinergic stimuli. How-
regulated nonselective cation channels or large-conductance ever, cholecystokinin antagonists do not block the reflex;
chloride channels; the oscillations from the interstitial cells also, infusions of high dose cholecystokinin have no effect
of Cajal remain even the absence of extrinsic neural input.9 upon colonic activity although pancreatic exocrine secre-
The ICCIM are thought to mediate such extrinsic input – from tion and gallbladder contraction are maximally stimulated.92
the enteric and autonomic neural networks – upon smooth Interestingly, the colonic motor response to eating persists
muscle function; the release of acetylcholine and nitric oxide following a gastrectomy or spinal injury; yet, the colon must
from excitatory and inhibitory neurons, respectively, results be in continuity for the reflex to take place.71
in alterations in the activity of the ICCIM.9,88 Furthermore, the Stress, both physical and emotional, also influences
ICCIM appear to augment the slow waves and MPOs from colonic function. One study found that psychological stress
the ICCSM and ICCMY , respectively, as they are transmitted induced a significant increase in propagating contractions,
along the smooth muscle syncytium.9 Much still remains to both in their frequency and amplitude, throughout the colon,
be elucidated about the cellular basis of colonic motility. even in the absence of an appreciable autonomic response.93
Despite the withdrawal of the stressor, the augmented motor
activity endured.93 In contrast, physical stress, consisting of
Characteristics of Colonic Motility in Health exposures to extremes of temperature, precipitated a signifi-
Manometry studies have demonstrated a noncyclical pattern cant elevation in the frequency and amplitude of simultane-
of colonic activity.11 The variations in colonic activity are ous contractions, which ceased immediately after the activity
mirrored by changes in colonic tone.83 The human colon fol- stopped.93 In some trials, low and high amplitude propagated
lows a circadian rhythm in which sleep is associated with its contractions are stimulated by acute physical exercise.71,94
relaxation and, thus, with a marked diminution of its pressure
activity.65,90 However, as previously noted, the rectum and
rectosigmoid display continued phasic activity during the Defecation
night. Immediately after morning waking, a two- to three-
fold increase in colonic pressure activity – likely due to high The process of defecation involves the entire colon, not
amplitude propagated contractions – occurs, inciting an urge solely the anus and rectum. As already described, the
to defecate in some cases. A similar rise in colonic activity majority of colonic activity – the segmental contractions –
transpires during brief night-time arousals or during REM serve to retain fecal material so as to promote the salvage
sleep.71 The mechanism by which the colon rapidly responds of intestinal water and electrolytes. However, periodically,
to these alterations in wakefulness is unknown. During the colonic activity shifts in order to foster the expulsion of
day, the transverse and descending colon reveal more pres- stool. Approximately 1 h prior to the act of defecation, an
sure activity than the rectosigmoid colon. Moreover, less involuntary preexpulsive phase is initiated, in which the
activity is seen in the transverse and descending colon of frequency and amplitude of antegrade nonpropagating and,
women, as compared to men.65 particularly, propagating contractions steadily increase
Oral intake also impacts colonic activity. Within 1–3 min throughout the whole colon.95 The early component of the
of the initial bites of a meal, long before the food reaches preexpulsive phase – the first 15–60 min – is characterized
the colon, segmental contractions begin in the proximal and by propagating contractions that initially arise from the
distal colon, persisting for 2–3  h.65,91 This colonic motor proximal colon but subsequently from the distal colon; this
response to eating, or gastrocolic reflex, also features a initial sequence is thought to transport stool into the distal
concomitant increase in the colonic smooth muscle tone, colon, thus stimulating distal colonic afferent nerves, which
especially in the proximal colon, often affiliated with high in turn provoke further propagating sequences.9,95 During
amplitude propagated contractions.39,41,71 The colon exhibits the late phase, consisting of the last 15  min, the point of
regional differences in its response to a meal: the proximal origin of these contractions reverses from the distal to the
colon evinces a swifter but briefer duration of contractile proximal colon.9,95 Scintigraphic studies reveal that, in one
activity than the distal colon.71 Although infrequently identi- bowel movement, 20% of the ascending colon can be emp-
fied during scintigraphic studies, retrograde propulsion most tied; other evaluations indicate that nearly the entire colon
commonly appears after meals as well as during morning may be evacuated of stool in a single defecatory action.9,96
waking.65 Colonic motility is instigated by a higher calorie A number of investigations identified antegrade high ampli-
meal (more than 500  kcal), fat, and, to a lesser degree, tude propagated contractions in close temporal relation to
32 U.M. Szmulowicz and T.L. Hull

defecation; yet, not all of these contractions necessarily The modulation of visceral sensation occurs through
­precede or end in ­defecation.78,97,98 However, at least one s­ everal methods. Enteroenteric reflexes mediated by the
high amplitude propagated contraction of very high ampli- spinal cord produce variations in the smooth muscle tone,
tude usually coincides with the urge to defecate.95 While the leading to changes in the activation of the nerve endings
early activity is unnoticed, the late phase is often associated in the intestine or mesentery.100 The perception of visceral
with the urge to defecate that occurs prior to the voluntary pain is influenced by descending noradrenergic and seroton-
act of fecal evacuation.95 ergic pathways that emanate from the reticular formation,
hypothalamus, and frontal cortex. These fibers project to the
dorsal horn of the spinal cord, where they modify noxious
Colonic Sensation input from the visceral afferent nerves.13 This mechanism
likely explains the experience of wounded soldiers who feel
Colonic sensation has proved a complicated, poorly under- no pain in the midst of battle.101 The intersection of visceral
stood topic. The normal physiologic processes of the healthy spinal afferent nerves with somatic afferent nerves in the
colon are largely unnoticed, with only fullness and an urge dorsal horn of the spinal cord produces the phenomenon
to defecate consciously perceptible.11 The colon itself con- of referred pain, in which visceral sensation is consciously
tains no specialized sensory end organs.41 However, naked recognized as somatic pain, located in a dermatome of the
nerve endings lie within the serosa, muscularis propria, and same embryologic origin as the visceral structure: T8–T12
mucosa of the colon while Pacinian corpuscles are found for the midgut and T12–L2 for the hindgut.8,13,101 In addition,
in the mesentery.9 Afferent nerve fibers reach the central visceral afferent nerves from the colon relay information via
nervous system via parasympathetic pathways and spinal collaterals to the reticular formation and thalamus, which
afferent nerves, both of which display mechano- and chemo- induce alterations in affect, appetite, pulse, and blood pres-
sensitivity.99 The parasympathetic fibers convey sensory sure through autonomic, hypothalamic, and limbic system
information from the proximal colon via the vagus nerve connections.13,102
to cell bodies in the nodose and jugular ganglia and, from
the distal colon, by the pelvic splanchnic nerves.13,41,99 The
precise role of the parasympathetic afferent fibers remains
unknown but likely involves unconscious reflex sensation,
Disturbances in Colonic Physiology
not painful stimuli.9 Sensory input from the colon is chiefly
Physiology of Constipation
detected by spinal afferent neurons, primarily by those with
their cell bodies within the lumbar dorsal root ganglia.8,9,99 Constipation is a common complaint, with a prevalence of
These lumbar spinal afferent nerves travel with the sym- 2–28% among Western populations.103 This disorder refers
pathetic fibers within the lumbar splanchnic nerves from to infrequent bowel movements (fewer than three per week);
the colon by way of the inferior mesenteric ganglia.9 The hard or lumpy stools; incomplete evacuation; a sensation
lumbar spinal afferent fibers conclude in sensory endings of anorectal obstruction; the need for manual maneuvers
throughout the entire large intestine, whereby pain, colorec- to facilitate defecation; and/or excessive straining.104 Indi-
tal distention, mesenteric traction, and noxious mucosal viduals with constipation are an incredibly heterogeneous
stimuli are discerned.9 In contrast, the sacral spinal affer- group. Distinct subtypes of constipation exist, each requir-
ents, with their cell bodies in the sacral dorsal root ganglia ing different treatment modalities; however, even within
of S2–4, are thought to be concerned with a sensation of these subtypes, there may be wide variability in the clinical
rectal fullness and an urge to defecate.9 These sacral spi- presentation and pathophysiologic etiology. The causes for
nal afferent fibers are borne along with the parasympathetic constipation range from dietary, pharmacologic, structural,
pelvic splanchnic nerves.8 to systemic.
Visceral pain sensation is carried by rapidly conducting Many people become constipated due to dietary and life-
Ad fibers or by unmyelinated C fibers.11 The Ad fibers are style neglect. In the USA, fiber intake is overall low. Two
associated with the more localized “discriminative” pain, primary roles of the colon, solidifying liquid chyme into
which persists for as long as the stimulus, and the C fibers stool and defecation, are dependent upon adequate dietary
in the diffuse “affective-motivational” pain, which contin- fiber: dietary fiber “normalizes” large bowel function.105,106 In
ues beyond the duration of the catalyst.11 Sensory informa- particular, the bulkier stool produced by fiber supplementation
tion is transported to the brain along the spinothalamic and stimulates propulsive activity, thus decreasing colonic transit
spinoreticular tracts as well as by the dorsal column of the time.103 The recommendation for adequate fiber intake ranges
spinal cord.11 The spinothalamic tracts specifically transmit from 20 to 35  g/day for adults.107 For an individual on a
sensation from the Ad and C fibers to the somatosensory cor- 1,500–2,000 kcal/day diet, in order to include 15 g of fiber,
tex via the lateral thalamic nuclei or to the frontal, parietal, 11 servings of refined grains and 5 servings of fruits and
and limbic regions by means of the medial thalamic nuclei, vegetables must be consumed.105 Fiber is classified as either
respectively.11 soluble or insoluble, acting by differing mechanisms to
2. Colonic Physiology 33

increase stool weight. Soluble fibers such as oat bran provide decrease in the frequency as well as the amplitude of high
rapidly fermentable material to the proximal colon, which amplitude propagated contractions is demonstrated in slow
allows for sustained bacterial growth.108 The consequent transit constipation, leading to reduced colonic propulsive
higher bacterial content of the stool results in the greater activity.41,64,71,114,115 Furthermore, the preexpulsive phase of
fecal mass.108 In an average bowel movement, 50% of the the defecatory process is depressed.103 Conflicting results
stool weight consists of bacteria.103 Also, soluble fibers cause have been obtained from investigations into excessive, dis-
a rise in the excretion of lipid and fat, further boosting stool organized rectosigmoid phasic activity – a “brake” to ante-
weight.108 In contrast, poorly fermentable insoluble fibers such grade propulsion – as a factor in slow transit constipation.60,64
as wheat bran, cellulose, and lignin augment stool weight by Histological evaluations reveal a marked decrease in the pop-
providing more undigested plant material for evacuation.108 ulation of myenteric plexus neurons; however, of the neu-
One gram of wheat bran generates 2.7  g of stool.103 Wheat rons present in the myenteric plexus, those that produce the
bran also promotes fat excretion, but not to the extent of oat potent inhibitory neurotransmitter nitric oxide are vastly pre-
bran.108 The outcomes of fiber supplementation as a treatment dominant, especially as compared to controls.116 Slow tran-
for constipation have yielded conflicting data. sit constipation also features a significant reduction in the
Constipation may be seen more commonly in sedentary interstitial cells of Cajal either throughout the colon or solely
individuals. The Nurses Health Study suggested that those in the sigmoid colon.84,117,118 Moreover, the morphology of
women who engaged in daily strenuous activity were 44% the existing cells is seen to be strikingly abnormal, demon-
less likely to experience constipation than those who exer- strating few dendrites and an irregular surface.103 Colonic
cised less than once a week.109 During exercise, phasic and transit studies of slow transit constipation reveal retention of
propagating motor activity is diminished in the colon, with the more than 20% of the radiopaque markers 5 days after their
effect more pronounced with more vigorous effort; however, ­ingestion.103
after the physical exertion is completed, an increase in the
frequency and amplitude of the propagating pressure waves
is demonstrated, possibly due to the restoration of parasym- Obstructed Defecation
pathetic input.68 This postexercise pattern may precipitate
the propulsion of feces.68 During or after exercise, individu- Obstructed defecation usually results from abnormalities in
als often report an urge to defecate or defecation itself.109 In pelvic as opposed to colonic function. Typically, this disor-
fact, abdominal cramps and diarrhea are frequently related der is associated with failure of the puborectalis muscle to
by runners.110,111 However, in a small study of the impact of relax during defecation, producing a functional – not a phys-
regular exercise – 1 h a day, 5 days a week – upon chronic ical – obstruction.11 Anatomic abnormalities also causing
idiopathic constipation, there was no symptomatic improve- obstructed defecation include rectocele, enterocele, excessive
ment in the eight subjects after 4 weeks of increased activ- perineal descent, and rectal intussusception. These patients
ity.112 Moreover, a small study examining colonic transit in report inordinate straining, incomplete evacuation, painful
otherwise sedentary men after mild exercise, consisting of defecation, infrequent bowel movements, and digital anal
1 h of walking on a treadmill for 3 days/week, showed no disimpaction.103 Among the diagnostic tests for obstructed
significant difference in the passage of radiopaque markers defecation are anorectal manometry or electromyelography,
as compared to baseline.113 balloon expulsion, barium defecography, and dynamic MRI.
Idiopathic slow transit constipation involves ineffectual A defecogram may identify retention of 50–100% of the
colonic propulsion, resulting in a measurable delay in the instilled barium in the rectum of patients with obstructive
movement of fecal material through the colon. The sever- defecation.58 Colonic transit studies in these patients dem-
ity of the presentation is variable, with the most intractable onstrate collection of six or more radiopaque markers in the
cases referred to as colonic inertia. These patients with slow distal colon, indicating partial evacuation of the rectum.58,119
transit constipation, usually women, have fewer than one Two-thirds of patients with obstructive defecation may dis-
bowel movement per week, often in association with abdom- play a concurrent pattern of slow transit constipation.58
inal pain, a lack of an urge to defecate, malaise, fatigue, or Obstructed defecation rarely arises from a colonic
bloating.103 Little benefit is gained from dietary fiber sup- source – a sigmoidocele. In this variant, a redundant sigmoid
plementation, which, conversely, may cause worsened con- colon descends into the rectovaginal pouch (of Douglas)
stipation, or from laxatives.103 The symptoms often arise during defecation, impinging upon the rectum during
during puberty and steadily deteriorate over time.103 Retarded attempted evacuation.120 In one study of 463 patients with
colonic transit in these individuals is either pan-colonic or constipation, fecal incontinence, or chronic idiopathic
segmental.60 Slow transit constipation is consistently affili- rectal pain, a sigmoidocele was diagnosed on defecography
ated with a blunted colonic motor response to eating (i.e., in 5.2%.120 Defecography is the primary method of diagnosis
gastrocolic reflex), including both propulsive and segmental of a sigmoidocele. The severity of a sigmoidocele is
contractions.60,64,83 In contrast, in patients with colonic iner- determined by the extent of its decline into the pelvis, as
tia, there is no colonic response to a meal.103 A  significant ­compared to the pubococcygeal and ischiococcygeal lines.120
34 U.M. Szmulowicz and T.L. Hull

While  third degree sigmoidoceles likely benefit from a has been ­implicated in the pathogenesis of IBS: infusion of
s­ igmoid ­colectomy, the significance and optimal manage- cholecystokinin induces typical symptoms of irritable bowel
ment of first and second degree sigmoidoceles are not fully syndrome.129,130 However, in a randomized trial, the CCK-1
understood.120 The clinician should also be cognizant of con- receptor antagonist dexloxiglumide led to no amelioration
comitant pelvic floor disorders in these patients. in IBS symptomology; moreover, overall colonic transit was
unchanged, although emptying of the ascending colon was
delayed.130 However, a pilot study of a similar CCK-1 receptor
Irritable Bowel Syndrome antagonist, loxiglumide, yielded some improvement in IBS
symptoms.131 A randomized trial of neurotrophin-3, a protein
Irritable bowel syndrome (IBS) is a functional disorder with growth factor integral to the development of the enteric ner-
multiple manifestations: constipation-predominant (IBS-C), vous system, in constipated patients revealed more frequent
diarrhea-predominant (IBS-D), and mixed (IBS-A). Irritable spontaneous bowel movements, a more rapid colonic transit
bowel syndrome is characterized by altered bowel habits and time, and a reduction in associated symptoms.132 Approxi-
chronic, recurring abdominal pain directly related to defe- mately one-third of subjects experienced transient injection
cation, in the absence of an anatomic abnormality.54 Extra- site reactions after subcutaneous administration.132
colonic complaints include lower back pain, lethargy, nausea, Diarrhea-predominant irritable bowel syndrome is
urinary symptoms, dyspareunia, and dysmenorrhea.121 The encountered in approximately one-third of patients with IBS.
etiology of irritable bowel syndrome is unclear but is believed The majority of men with irritable bowel syndrome experi-
to involve visceral hypersensitivity to intraluminal stimuli.54 ence the diarrhea-predominant type. This subtype is often
Aberrant motility, inflammation, anomalies in extrinsic auto- affiliated with urgency and fecal incontinence.121 IBS-D may
nomic innervation, abnormal brain–gut interaction, and the follow an episode of acute gastroenteritis, pelvic surgery, or
role of psychosocial factors have also been extensively inves- emotional stress.11 Some patients with IBS-D display accel-
tigated. Hormonal factors may be involved, as symptoms are erated proximal colonic transit, with an increased frequency
often increased perimenstrually; however, the complaints of high and low amplitude propagated contractions.11,78 Addi-
persist even in the absence of menses.122 The treatment of IBS tionally, the colonic motor response to eating is enhanced in
is based on the nature and severity of symptoms. ­Education, a proportion of these patients, resulting in an intense urge
reassurance, and the elimination of foods that incite the typi- to defecate and abdominal pain immediately after meals.11
cal complaints are the initial interventions. In some patients, Rectal hypersensitivity is also a feature in some of these
fiber supplementation exacerbates the IBS.121 For those who patients.11 Antispasmodics such as hyoscine are prescribed
do not respond to conservative measures, medication is con- for those with abdominal pain and bloating, especially after
sidered. However, the pharmacologic therapy of IBS-A has meals. Low-dose tricyclic antidepressants (e.g., amitrip-
not been well studied. tyline) are added when the pain is more constant and even
In approximately one-third of patients with irritable disabling; these medications function not as mood stabiliz-
bowel syndrome, constipation is the main feature (IBS-C). ers but instead act directly on the gut and central pain pro-
Women are primarily affected by IBS-C. The majority of cessing.121,124,133 Loperamide is an antidiarrheal agent safe for
these patients demonstrate normal colonic transit and motil- long-term use.121 Diarrhea is effectively addressed by selec-
ity patterns, although there is a possible overlap with slow tive serotonin 5-HT3 antagonists such as Alosetron. This
transit constipation.123 Tegaserod, an agonist of the 5-HT4 drug was initially FDA approved in March 2000, only to be
receptor that is involved in the metabolism of serotonin, retracted due to reports of ischemic colitis, severe constipa-
showed promise as a treatment of IBS-C but was withdrawn tion, and even death.134 In June 2002, it was adopted solely
by the Food and Drug Administration in 2007 due to a high for women with chronic, severe IBS-D.135 However, the
incidence of myocardial infarction, stroke, and unstable medication may only be supplied by physicians participat-
angina.124,125 In some studies, probiotics such as Lactoba- ing in the Prometheus Prescribing Program, after the patient
cillus and Bifidobacterium produce variable degrees of signs a patient–physician agreement.135 Further investigation
alleviation of IBS symptoms such as pain.126 Lubiprostone into these novel pharmaceuticals for IBS is required.
(Amitiza®, Sucampo Pharmaceuticals, Inc., Bethesda, MD),
a prostaglandin E1 analog, activates type 2 chloride chan-
nels on the apical membrane of colonic epithelial cells.127,128 Ogilvie’s Syndrome
This medication promotes intestinal fluid secretion and,
indirectly, colonic motility in patients with IBS-C.128 Stud- Ogilvie’s syndrome, initially described in 1948, is also
ies of lubiprostone revealed significant improvement in stool known as acute colonic pseudo-obstruction. This disorder
frequency and consistency, abdominal discomfort and pain, is characterized by an imbalance of autonomic innervation
straining, and bloating.128 Cholecystokinin, found in elevated to the colon: the inhibitory sympathetic input exceeds that
levels in the plasma and sigmoid colon of IBS-C patients, of the excitatory parasympathetic nerves.136 A massively
2. Colonic Physiology 35

dilated colon – particularly the proximal colon – results synthase inhibitors (e.g., nitro-l-arginine methyl ester), and
from the consequent suppression of peristaltic activity.136 somatostatin analogs (e.g., octreotide).136 Surgical treat-
The ­specific source for the initial motor disturbance that ment – a cecostomy tube or a subtotal colectomy – is a final
allows for this scenario is unknown.136 One hypothesis option if less invasive techniques are unsuccessful. Even in
ascribes this functional obstruction to impairment of the a nonemergent setting, surgery has a 30% mortality rate.136
pelvic (parasympathetic) splanchnic nerves supplying the However, failure to decompress the colon may yield cecal
distal colon, ­giving rise to an atonic segment, lacking peri- ischemia and/or perforation in 14–40% of cases; the mortality
staltic function.136 Acute colonic pseudo-obstruction has of these patients increases to 40–50%.136
been reported ­concurrent with infectious or inflammatory
(e.g., acute pancreatitis), cardiovascular (e.g., myocardial
infarction), metabolic (e.g., hypokalemia), postoperative Implications of Colonic Physiology
(e.g., spinal or pelvic surgery), posttraumatic, neurologic for the Surgeon
(e.g., Alzheimer’s disease), respiratory (e.g., pneumonia),
and neoplastic causes (e.g., metastatic disease); drugs (e.g., Why is an understanding of colonic physiology important for
antidepressants); and old age.136 As indicated by the law the surgeon? Knowledge of the embryologic development of
of LaPlace (wall stress = [(transmural pressure) × (radius)]/ the colon is essential when considering nerve preservation,
wall thickness), the cecum is at greatest risk of perforation vascular supply, and resection margins during colectomies.
in light of its thin wall and large diameter.137 Despite symp- The poorly understood topic of colonic motility impacts
toms and signs consistent with a large bowel obstruction, no surgeons, particularly in the phenomenon of postoperative
mechanical blockade is present. The management of Ogil- ileus. In a murine model of postoperative ileus, a reduction
vie’s syndrome begins with eliminating the presence of a in the number of interstitial cells of Cajal was evident on
physical obstruction with a water-soluble contrast enema. both sides of the colonic anastomosis within hours of the sur-
In the majority of cases, colonic dilatation responds to con- gery; as a consequence, fewer slow waves were identified in
servative therapy, including nasogastric decompression, that particular segment, possibly giving rise to postoperative
­correction of fluid and electrolyte abnormalities, cessation ileus.88 Various disorders of colonic motility may stem from
of antimotility medications such as opiates, and remedy of abnormalities of the interstitial cells of Cajal. These cells are
the underlying illness.138 In the absence of peritoneal signs significantly depleted in the colons of patients with diver-
or a cecal diameter greater than 12 cm on radiographic stud- ticulosis and with slow transit constipation.141 As basic sci-
ies, conservative measures may be continued for 48–72 h. ence research advances, the surgeon ultimately will be called
This approach is associated with a 14% mortality rate.136 upon to evaluate and apply novel pharmaceuticals to reduce
The colon may also be mechanically decompressed via the impact of postoperative ileus as well as to treat other dis-
colonoscopy, although, in one study, this difficult procedure orders of colonic motility. Surgeons also will invariably be
in an unprepared colon was affiliated with a 1.7% morbid- consulted to assess the suitability of surgical management
ity and a 3.4% mortality rate; yet, colonoscopic decom- for abnormalities of colonic motility such as colonic inertia
pression was successful in 79.3% of cases, albeit with a and intractable constipation.
recurrence in 20% of patients.139 Pharmacologic treatment The resection of a portion or the entirety of the colon can
has become the mainstay of management for acute colonic have profound functional ramifications for the patient. Prior
pseudo-obstruction if conservative measures fail. Neostig- to a colectomy, the surgeon optimally should discuss these
mine (2–2.5 mg IV over 1–60 min), an acetylcholinesterase possible outcomes with the patient. Postoperatively, the phys-
inhibitor, provides a surfeit of acetylcholine to the enteric iologic consequences of a colectomy must be managed. For
neurons and the neuromuscular junctions, thus inducing instance, a patient with a new ileostomy requires counseling
propagating contractions, specifically high amplitude prop- regarding adequate fluid and salt intake to compensate for
agating contractions, and the prompt evacuation of stool the loss of the colon. Furthermore, defecatory ­dysfunction –
and flatus.62,138,140 In a double-blind randomized trial, the frequent bowel movements, urgency, or soiling – may occur
initial clinical response to neostigmine was 91%, as com- after a low anterior resection. Subsequent to the procedure,
pared to 0% among those receiving a placebo; colonic dis- injury of the parasympathetic pelvic splanchnic nerves due
tention recurred in two patients (18%) given neostigmine, to dissection around the inferior mesenteric artery may pro-
ultimately requiring a subtotal colectomy in one patient.138 duce a denervated colonic segment with an increased colonic
Administration of neostigmine may produce bradycardia, transit time and a greater proportion of nonpropagating con-
abdominal pain, vomiting, and excessive salivation.138 Alter- tractions.142 The neorectum demonstrates a decline in com-
native, less-studied pharmacologic treatments are comprised pliance postoperatively, although the maximum tolerated
of 5-HT4 receptor agonists (e.g., cisapride), motilin receptor volume returns to normal 6 months later.143 Yet, the volume
agonists (e.g., erythromycin), muscarinic receptor agonists needed to elicit the recto-anal inhibitory reflex is persistently
(e.g., bethanechol), neurotrophins (e.g., NT-3), nitric oxide reduced even 1 year after surgery.143
36 U.M. Szmulowicz and T.L. Hull

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