2 Colonic and Anorectal Physiology
Abstract
This chapter will focus on colonic physiology, including function, microflora, and propulsion and storage, and anorectal physiology, including anal continence, investigative techniques, and clinical applications.
2.1 Colonic Physiology
The colon is the final conduit of the digestive tract in which digestive material is stored. Another major function of the large bowel is the absorption of water and salt. The absorption of sodium and chloride is balanced with the secretion of potassium and bicarbonate. This interaction is essential for the maintenance of electrolyte homeostasis. By absorbing most of the water and salt presented to it, the colon responds to body requirements and plays an essential role in protecting the body against dehydration and electrolyte depletion. The absorptive capability enables the colon to reduce the volume of fluid material received from the small bowel and to transform it into a semisolid mass suitable for defecation. The propulsion of feces toward the rectum and the storage of this material between defecations are the result of complex and poorly understood patterns of motility. Other functions of the large bowel include digestion of carbohydrate and protein residues and secretion of mucus.
2.1.1 Functions
Absorption
Physiologic control of intestinal ion transport involves an integrated system of neural, endocrine, and paracrine components. 1 Endogenous mediators, including neurotransmitters and peptides, act on enterocytes through membrane receptors coupled to energy-requiring “pumps” or “channels” through which ions flow passively in response to electrochemical gradients.
In healthy individuals, the colon absorbs water, sodium, and chloride, while secreting potassium and bicarbonate. It receives approximately 1,500 mL of fluid material from the ileum over a 24-hour period. From this input, the large bowel absorbs approximately 1,350 mL of water, 200 mmol of sodium, 150 mmol of chloride, and 60 mmol of bicarbonate. 2 It has been estimated that the colon possesses enough reserve capacity to absorb an additional 3.5 to 4.5 L of ileal effluent, a feature that allows the large bowel to compensate for impaired absorption in the small intestine. 3 Several factors that determine colonic absorption include the volume, composition, and rate of flow of luminal fluid. The success of whole gut irrigation capitalizes on this principle. The absorptive capacity is not homogeneous throughout the large intestine due to significant differences in the colonic segments. It has been shown that more salt and water are absorbed from the right colon than from the distal colon. 3 Thus, a right hemicolectomy is more likely to result in diarrhea than is a left hemicolectomy. Whenever ileocecal flow exceeds the capacity of the colon to absorb fluid and electrolytes, an increase in fecal water excretion (diarrhea) will ensue.
Most electrolytes cannot cross the phospholipid membrane of colonic epithelial cells by simple diffusion. Passing this membrane is only possible using distinct membrane proteins, which act like channels, carriers, and pumps. These proteins are required to facilitate and to speed up the transport across the apical membrane. This transport is passive because it is not energy dependent and because the flow is down the concentration gradient.
Absorption of Salt
The average concentration of sodium in the fluid chyme accepted by the colon from the terminal ileum is 130 to 135 mmol/L and in the stool is approximately 40 mmol/L. When the luminal concentration of sodium is high, more is absorbed; no absorption occurs when the luminal concentration is below 15 to 25 mmol/L. 4 In this way, there is a linear relationship between the luminal concentration of sodium and sodium absorption. The bulk of sodium absorption is electroneutral in exchange for intracellular hydrogen. This electroneutral absorption is facilitated by Na+/H+ exchange proteins. To date, three types of Na+/H+ exchangers (NHE) have been identified in the colon. NHE3 is the most prominent one. In addition to the electroneutral pathway, the distal colon also exhibits an electrogenic way to enhance the sodium uptake. This electrogenic absorption is facilitated by proteins in the apical membrane, which act like an ion-specific channel, belonging to the family of epithelial Na+ channels (ENaCs). These ENaC proteins are inhibited by the diuretic amiloride and stimulated by mineralocorticoids. A small proportion of sodium is absorbed with the help of a sodium–glucose linked transporter. This membrane protein acts like a carrier and couples sodium and glucose. The transport of sodium across the apical membrane with the aid of all these distinct proteins is driven by the downhill electrochemical gradient and the negative membrane voltage. The electrochemical gradient is generated by the Na+, K+-ATPase at the basolateral membrane, which acts as a pump. This pump is stimulated by mineralocorticoids and has an electrogenic effect, extruding three Na+ ions in exchange for two K+ ions, and thereby maintaining relatively low intracellular Na+ and high intracellular K+ concentrations compared with concentrations of these electrolytes in the extracellular environment. The Na+/K+ pump results in a negative intracellular voltage. Across the colonic mucosa, there is an electrical potential difference of approximately 20 to 60 mV. 2 The basolateral membrane of the mucosal cell is electrically positive, whereas the apical membrane along the luminal border is electrically negative (▶ Fig. 2.1). 5 , 6 Sodium absorption is also stimulated by short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate, which are produced by bacterial fermentation. 7 , 8 , 9 The absorption of sodium is closely linked to the absorption of chloride. This anion either moves through the paracellular pathway or enters the epithelial cell through its apical membrane (▶ Fig. 2.1). The transcellular absorption of chloride is electroneutral in exchange for intracellular bicarbonate 10 and is facilitated by Cl−/HCO3 − exchange proteins. The absorption of chloride is also driven by a concentration gradient and is increased by a low luminal pH. Chloride concentrations are high in ileal effluent but fall markedly during passage through the large intestine. Although the transport of salt across the colonic mucosal layer is characterized by net absorption, salt can also move backward into the colonic lumen through cellular and paracellular pathways. After basolateral uptake, the cellular pathway ends with apical excretion of chloride through Cl− channels. The most important one is cystic fibrosis transmembrane conductance regulator. In patients with cystic fibrosis, this apical membrane protein does not function properly, resulting in impaired secretion of both Cl− and HCO3 −. 11
Absorption of Water
Like the small bowel, the colon also absorbs water by simple diffusion. This process does not require membrane proteins and is driven by the osmotic gradient across the colonic mucosa, generated by the absorption of sodium. Water is transported through both paracellular and cellular pathways. Like salt, water also can move backward into the colonic lumen (▶ Fig. 2.1). Water cannot be absorbed if the colonic lumen contains a high concentration of inabsorbable, osmotically active solutes. Any water that remains in the colon will simply be excreted as watery diarrhea. The most common cause of this so-called osmotic diarrhea is lactose intolerance. Lactose must be cleaved into its component monosaccharides by lactase before their absorption. In the absence of lactase, osmotically active lactose cannot be absorbed and remains in the intestinal lumen, thus interfering with water resorption.
Secretion
Bicarbonate
As described earlier, chloride is absorbed in exchange for intracellular bicarbonate. This process is facilitated by Cl−/HCO3 − exchange proteins located in the apical membrane. The fact that chloride in the colonic lumen facilitates the secretion of bicarbonate is clinically evident in patients with ureterosigmoidostomy, who may develop hyperchloremia and secrete excessive amounts of bicarbonate. 12 Besides this Cl−-dependent process, there are two other pathways involved in the secretion of bicarbonate. One is through the apical Cl− channels, mediated by cyclic adenosine monophosphate (cAMP). The other pathway is by exchange with SCFAs. The resulting net secretion of bicarbonate ions into the lumen aids in neutralization of the acids generated by microbial fermentation in the large bowel. 11 , 13
Potassium
Potassium may be absorbed or secreted, depending on the luminal concentration. It is absorbed if the concentration exceeds 15 mEq/L, and is secreted if it falls below this value. Since luminal K+ concentration is usually less than 15 mEq/L, net secretion normally occurs. 5 Potassium moves into the colonic lumen through both cellular and paracellular pathways (▶ Fig. 2.1). In the past, it was thought that this transport was mainly passive, along an electrochemical gradient. At present, it has become clear that colonic epithelial cells also contain membrane proteins, which act as channels to facilitate the uptake and excretion of potassium at their basolateral and apical membrane, respectively. 3 , 11 Because the distal colon is relatively impermeable to potassium, the luminal concentration may increase by the continued absorption of water. It has been suggested that there may be active secretion of potassium in the human rectum. 8 The presence of potassium in fecal bacteria and colonic mucus, as well as from desquamated cells, also may contribute to the high concentration (50–90 mmol/L) of potassium in human stool. 7 , 9
Urea
Urea is another constituent of the fluid secreted into the colonic lumen. Of the urea synthesized by the liver, about 6 to 9 g/day (20%) is metabolized in the digestive tract, mainly in the colon. 2 Because the maximum amount of urea entering the colon from the ileum is about 0.4 g/day, 14 the bulk of urea hydrolyzed in the large bowel by bacterial ureases must be secreted into the lumen. The metabolism of urea in the colon gives rise to 200 to 300 mL of ammonia each day. Since only a small amount of ammonia (1–3 mmol) can be found in the feces, most must be absorbed across the colonic mucosa. Although the production of ammonia in the large bowel can be abolished by neomycin, the absorption of ammonia is not affected by this antibiotic.
Ammonia
Ammonia absorption probably occurs by passive coupled nonionic diffusion in which bicarbonate and ammonium ions form ammonia and carbon dioxide. 2 The nonionized ammonia can freely diffuse across the colonic mucosa. This process is partially influenced by the pH of the luminal contents; as the luminal pH falls, the absorption of ammonia decreases. 2 Although urea is the most important source of ammonia, the ammonia in the colon also may be derived from dietary nitrogen, epithelial cells, and bacterial debris.
Mucus
Mucus is another product secreted into the colonic lumen. Throughout the entire length of the large bowel, the epithelium contains a large number of mucus-secreting cells, and it has been shown that nerve fibers come close to these goblet cells. Stimulation of the pelvic nerves increases mucus secretion from the colonic mucosa, as has been confirmed histologically. There is evidence for such a nerve-mediated secretion of mucus in the large bowel. 15 The colon is able to absorb amino acids and fatty acids, but only by passive mechanisms. Bile acids also can be reabsorbed.
Digestion
A little recognized function of the colon is the role it plays in digestion. Digestion of food begins in the stomach and is almost accomplished when transit to the end of the small intestine is complete. However, a small amount of protein and carbohydrate is not digested during transit through the small bowel. The colon plays a role in salvaging calories from malabsorbed sugars and dietary fiber. 16 In the colon, some of the protein residues are fermented by anaerobic bacteria into products such as indole, skatole (b-methylindole), phenol, cresol, and hydrogen sulfide, which create the characteristic odor of feces. The carbohydrate residues are broken down by anaerobic bacteria into SCFAs such as acetic 60%, propionic 20%, and butyric acid 15%. 17 It has been estimated that 100 mmol of volatile fatty acids are produced for each 20 g of dietary fiber consumed.
Most of these SCFAs, which constitute the major fecal anion in humans, 18 are absorbed in a concentration-dependent way. Their absorption is associated with the appearance of bicarbonate in the lumen, which in turn stimulates the absorption of sodium and water. 1 Other end products of fiber fermentation are hydrogen and methane. About 70% of colonic mucosal energy supply is derived from SCFAs originating in the lumen. 17 The functions of the colonocytes, mainly dependent on the absorption and oxidation of SCFAs, include cellular respiration, cell turnover, absorption, and numerous enzyme activities. Furthermore, SCFAs are used by the colonocytes not only as a source of energy but also as substrates for gluconeogenesis, lipogenesis, protein synthesis, and mucin production.
Propulsion and Storage
The main functions of colonic and anorectal motor activity are to absorb water, to store fecal wastes, and to eliminate them in a socially acceptable manner. 19 The first is achieved by colonic segmentation and motor activity that propels colonic material forward and backward over relatively short distances. The second is facilitated by colonic and rectal compliance and accommodation, whereas the third is regulated by the coordination of anorectal and pelvic floor mechanisms with behavioral and cognitive responses. 19
Distinct patterns of mechanical activity are required for the normal propulsion and storage of colonic contents. The rate and volume of material moved along a viscus also is related to the pressure differential, the diameter of the tube, and the viscosity of the material. Observation of transit does not necessarily reflect the contractile activity responsible for transit. Although the investigation of colonic motility in vivo has proved to be difficult because of the relative inaccessibility of the colon, new data have been revealed through the use of modern recording techniques. This information provides a better understanding of normal colonic motility in humans.
Assessment and Control of Motility
Radiologic Evaluation
Early efforts to investigate colonic motility involved radiographic studies in which the colon was filled with barium from either above or below. These studies could demonstrate only organized movements of the colon, represented by changes in contour, and were not helpful in the detailed examination of colonic motility. Moreover, the well-known side effects of radiation have limited the possibilities of radiologic observations, even with such sophisticated techniques as time-lapse cinematography. 20
At the beginning of the 20th century, radiographic studies revealed three types of colonic motility: retrograde movement, segmental nonpropulsive movement, and mass movement. Retrograde movements were identified as contractions originating in the transverse colon and traveling toward the cecum. 21 , 22 Later, studies with cinematography also demonstrated a retrograde transportation of colonic contents. 23 These retrograde movements are believed to delay the transit in the right colon, resulting in greater exposure of colonic contents to the mucosa to allow sufficient absorption of salt and water. 24
Segmental nonpropulsive movements are the type more frequently observed during radiologic investigation. These segmental movements are caused by localized, simultaneous contractions of longitudinal and circular muscles, isolating short segments of the colon from one another. Adjacent segments alternately contract, pushing the colonic contents either anterograde or retrograde over a short distance. 20 Although segmental movements occur mainly in the right colon, they also have been observed in the descending colon and the sigmoid colon. Like retrograde movements, segmental contractions also might slow colonic transit.
The third type of colonic motility identified from radiographic observations is mass movement, for the first time described by Hertz. 25 It occurs three or four times a day, primarily in the transverse and descending colon, but it also occurs in the sigmoid colon during defecation. Colonic contents are propelled by mass movement over a long distance at a rate of approximately 0.5–1cm/s. 26 , 27 Using a microtransducer placed via a sigmoid colostomy, Garcia et al 28 recorded activity over a 24-hour period. They documented a series of contractions and spiking potentials averaging 5.6 minutes, following which a “big contraction” appeared with mean pressure values of 127 mm Hg and mean electric values of 10.6 mV. The duration of this phenomenon averaged 24.93 seconds and corresponded to an observed intense evacuation via the colostomy. They assumed that this electropressure phenomenon represents the mass movement.
Radiologic assessment can demonstrate only changes in contour. For detailed examination of colonic motility, other techniques must be employed, such as isotope scintigraphy, the measurement of intracolonic pressure, the investigation of colonic and rectal wall contractility with barostat balloons, and the examination of myoelectrical activity of colonic smooth muscle.
Isotope Scintigraphy
Although evacuation proctography and isotope proctography with radiolabeled material inserted into the rectum allow the description of rectal emptying, neither technique provides any information about transport of colonic contents during defecation. Colorectal scintigraphy after oral intake of isotopes is a physiological technique and allows accurate assessment of colorectal transport during defecation. Utilizing this technique, Krogh and co-workers observed an almost complete emptying of the rectosigmoid, the descending colon, and part of the transverse colon after normal defecation. 29
Measurement of Intracolonic Pressure
Pressure activity of the large bowel has been intensively studied with many different devices, including water- or air-filled balloons, perfused catheters, radiotelemetry capsules, and microtransducers. The measurement of intracolonic pressure presents special problems. First, the colonic contents may interfere with recording by changing the basal physiologic state of the colon or plugging or displacing the recording device. Second, problems of retrograde introduction of recording devices and difficulty in maintaining them at a constant site may be encountered.
Initially, manometric recordings were limited to the rectum and distal sigmoid colon. Most studies were static and manometry was performed with a retrogradely placed assembly in the prepared left hemicolon. To avoid the potential perturbation of motor patterns by colonic cleansing and to permit ambulation, several authors have adopted an antegrade approach via nasocolonic intubation of the unprepared colon. To capture all the relevant activity throughout the entire colon with sufficient spatial resolution, it is necessary to use an assembly with multiple, closely spaced recording sites. 30 Initially, the manometric devices, designed for this purpose, contained a maximum of about 16 recording sites. In order to obtain recordings from the entire length of the colon, the sensors were spaced at intervals of 7 cm or more. Recently, it has been shown that sensor spacing above 2 cm results in misinterpretation of the frequency and polarity of propagating pressure waves. 31 Studies utilizing manometric devices with sensor spacing of 7 cm or more are actually based on low-resolution manometry. This technique has revealed two major pressure wave patterns. The first wave pattern is a very distinctive pattern of high-amplitude propagating sequences (HAPS). Most of these pressure waves with a high amplitude (> 100 mm Hg) arise in the cecum and ascending colon, especially after awaking and after a meal. The other pressure wave pattern, detected by this low-resolution manometry, is difficult to classify and is usually defined as segmental or nonpropagating activity. Recently, Dinning et al introduced high-resolution fiber-optic manometry. 32 The device, utilized in their study, contained 72 sensors spaced at 1-cm intervals. After mechanical bowel preparation, the catheter was introduced with a colonoscope and fastened to the mucosa of the ascending colon with endoclips. An abdominal X-ray was performed to verify the correct placement of the catheter (▶ Fig. 2.2).
Manometric recordings were obtained from 10 healthy individuals. The authors were able to identify five distinct motor patterns:
High-amplitude propagating sequences. These HAPS occurred in all subjects, started in the proximal colon, and always propagated in an antegrade direction. HAPS represented only 1 to 2% of all detected pressure events. They had a high amplitude (> 116 mm Hg) and their average extent of propagation was 33 ± 12 cm, with a mean velocity of 0.4 ± 0.1 cm per second (▶ Fig. 2.3).
Cyclic motor patterns. These patterns are characterized by repetitive propagating pressure events with a cyclic frequency of two to six per minute and an amplitude of 23.1 ± 21.4 mm Hg. These pressure events propagated both antegrade and retrograde with an average extent of < 7 cm. They occurred in all patients and represented almost 70% of all detected activity in the colon. Although observed in all colonic segments, most cyclic motor patterns were identified in the sigmoid colon (▶ Fig. 2.4).
Short single motor patterns. These patterns are characterized by single pressure events, separated by intervals of more than 1 minute, when they occurred repetitively. These pressure events had an amplitude of 58.1 ± 26.7 mm Hg and propagated both antegrade and retrograde with an average extent of < 7 cm. They were observed in all subjects and represented almost a quarter of detected pressure events.
Long single motor events. These are also characterized by single pressure events, separated by intervals of more than 1 minute, when they occurred repetitively. In contrast to short single motor events, they propagated only in antegrade direction, over a longer distance and with a greater velocity. These pressure events were detected in 7 of the 10 subjects.
Retrograde slowly propagating motor pattern. This pattern was observed in only two patients. This pattern started in the sigmoid colon and propagated backward into the transverse colon.
After a meal, HAPS appeared in 5 of 10 subjects. Apart from these HAPS, the major effect of ingesting a meal was a significant increase in cyclic retrograde motor patterns, especially in the sigmoid colon. According to the authors, the relative scarcity of HAPS (not detected in the fasting state and observed in only five subjects after ingesting a meal) may have been influenced by the study protocol. The recordings started within an hour of catheter placement in a prepared and empty colon and stopped 4 hours later. It has been shown that HAPS are more abundant in an unprepared colon. It seems likely that colonic distension due to large volumes of fecal material triggers the activation of HAPS.
Simultaneous assessment of isotope movement and intracolonic pressure changes has revealed that HAPS represent the manometric equivalent of propulsive mass movements and that fewer than 5% of these pressure events reach the rectum. 33 In contrast to earlier reports, more recent work has revealed that HAPS do not display regional variation in conduction velocity. 30 They can be activated by mechanical colonic distension and by intraluminal chemical stimulation with agents such as glycerol, bisacodyl, oleic acid, chenodeoxycholic acid, and SCFAs. It has been shown that neostigmine, which can be used to relieve distension in acute colonic pseudo-obstruction, also induces HAPS. 34 Colonic distension and chemical stimulation act on underlying enteric circuits. Because HAPS increase upon awakening and appear rapidly after a meal, it seems likely that extrinsic neural input is also important. Crowell et al 35 found that 41% of these pressure waves occur in the hour before defecation. The relationship between high-amplitude pressure waves and defecation has been confirmed by others. 36 , 37 Bampton et al studied the spatial and temporal organization of pressure patterns throughout the unprepared colon during spontaneous defecation. 38 , 39 They were able to demonstrate a preexpulsive phase commencing up to 1 hour before stool expulsion. This phase is characterized by a distinctive biphasic spatial and temporal pattern with an early and a late component. The early component is characterized by an array of antegrade propagating sequences. The site of their origin migrates distally with each subsequent sequence. The late component, in the 15 minutes before stool expulsion, is characterized by an array of antegrade propagating sequences. The site of their origin migrates proximally with each subsequent sequence. The amplitude of the pressure waves, occurring in this late phase, increases significantly. Many of them are real high-amplitude pressure waves. They are associated with an increasing sensation of urge to defecate. Some of the last propagating sequences, prior to stool expulsion, commence in the ascending colon (▶ Fig. 2.5). This latter finding illustrates that the entire colon is involved in the process of defecation. Hirabayashi et al investigated colorectal motility in adult mongrel dogs before and during spontaneous defecation with the help of force strain gauge transducers implanted in the proximal, distal, and sigmoid colon, as well as in the rectum and the anal canal. During defecation, giant contractions were detected, running from the distal colon into the rectum. It seems likely that these giant contractions are the myoelectric equivalent of the high-amplitude pressure waves. 40
As previously mentioned, the cyclic motor pattern is by far the most common colonic motor pattern. This pattern is characterized by short-extent and low-amplitude contractions with a cyclic frequency of 2 to 6 per minute. In the past, this activity was classified as nonpropagating, based on low-resolution manometry with sensors spaced at intervals of 7 cm or more. However, since the introduction of high-resolution manometry, it has become clear that these cyclic contractions propagate both antegrade and retrograde with an average extent of < 7 cm. Although these contractions occur in all regions of the colon, they are most prevalent in the sigmoid and the rectum. In this region of the colon, these complexes have a predominant retrograde direction. Based on this finding, it has been suggested that they resist anally directed flow and assist in the maintenance of continence and control of defecation. 32 Like HAPS, this type of activity is also suppressed during the night and increases after awakening. Ingesting a meal results in a rapid and large increase in cyclic retrograde propagating contractions, whereas the cyclic antegrade propagating contractions show no change after a meal. Retrograde transport is a major component of normal colonic physiology. It has been postulated that the cyclic retrograde propagating contractions contribute to this retrograde transport, thereby acting as a gatekeeper to keep the rectum empty. It has been suggested that reduction or absence of these contractions may contribute to fecal incontinence. It has been shown that sacral nerve stimulation is associated with an increase in cyclic retrograde patterns. This intriguing finding may explain some of the symptomatic improvement obtained with this type of treatment. 41 The cyclic retrograde motor patterns in the rectum are most likely the same as the rectal motor complexes, as described by Kumar et al. 42 All colonic motor activity is reduced during sleep. Another potent inhibitor of colonic activity is rectal distension. This rectocolonic inhibitory reflex prevents further passage of stool to a loaded rectum and is presumed to be mediated by long colocolonic pathways. 43
Using low-resolution manometry, some workers were able to demonstrate that constipated subjects display significantly fewer high-amplitude contractions than healthy volunteers. 44 , 45 , 46 During the last decade, numerous studies, based on high-resolution manometry, have revealed that slow transit constipation is indeed associated with abnormal colonic motility. It has been convincingly demonstrated that the large bowel of patients with slow transit constipation exhibit little or no HAPS. In these patients, the normal increase of HAPS after a meal is lacking. Almost all patients with slow transit constipation exhibit normal cyclic propagating pressure events in the fasting state. However, the huge increase in the postprandial retrograde propagating cyclic motor pattern, normally seen in healthy subjects, is completely absent in patients with slow transit constipation. Based on this finding, it has been suggested that this phenomenon is due to attenuated neural input to the colon. 47 Similar abnormalities have been observed in children with intractable constipation. 48 Recently, Dinning et al conducted an intriguing study in patients with slow transit constipation before and after subtotal colectomy. Prior to the operation, abnormal colonic motility was recorded in vivo, as described above. Once the colon was removed, ex vivo manometric recordings were obtained with the colonic specimen in an organ bath. Regular propagating motor patterns were recorded at approximately 1 per minute. This activity did not differ from control colon tissue obtained from patients undergoing a low anterior resection. Since the deficits in colonic motility are not apparent ex vivo, the authors suggest that extrinsic parasympathetic input to the colon plays a role in the pathophysiology of slow transit constipation. 49
Contractile Activity
It has been reported that barostat balloons have the potential to explore variations in the contractile state of the colonic and rectal wall. Barostat balloons are infinitely compliant plastic bags. The barostat assembly moves air in and out to maintain a constant preset pressure in the balloon. Changes in tone are reflected by changes in bag volume. A significant reduction of bag volume has been documented immediately after the ingestion of food, indicating a sustained increase in colonic tone in the postprandial period. During overnight sleep, colonic tone decreases. 50 , 51 The increase in colonic tone in response to feeding shows remarkable regional differences. Assessing the contractile activity in the transverse and sigmoid colon using a barostat assembly, Ford et al 52 found that the mean increase in colonic tone after the ingestion of food was significantly greater in the transverse than in the sigmoid colon. The contractile responses in the human colon are mediated by a 5HT3 mechanism. 53 It has been reported that hypocapnic hyperventilation produces an increase in colonic tone. This finding suggests that autonomic mechanisms are also involved in the control of the contractile state of the large bowel. 54 Grotz et al 55 reported that changes in rectal wall contractility in response to feeding, to a cholinergic agonist, and to a smooth muscle relaxant are decreased in constipated patients. Gosselink and Schouten 56 used a barostat assembly to investigate the tonic response of the rectum to a meal in healthy volunteers and in 60 women with obstructed defecation. Total colonic transit time was normal in 30 patients and prolonged in the other 30. Following the meal, all controls showed a significant increase in rectal tone. A similar response was found in the patients with a normal colonic transit time. In the patients with a prolonged colonic transit, the increase in rectal tone was significantly lower. In the past, it has been stated that intracolonic barostat balloons are more sensitive than manometric probes in the detection of nonoccluding contractions. Using a combined barostat–manometry assembly, von der Ohe et al 53 found a significant decrease of bag volume consistent with an increment in colonic tone after the ingestion of a 1,000-kcal meal. This response was not associated with concomitant changes in intracolonic pressure. In addition, they also reported that the barostat balloon measurements indicated 70% more phasic events than the manometric side holes located 2 cm proximal to 7 cm distal to the balloon. However, it should be mentioned that the manometric assembly, used in this and other studies, only provided low-resolution recordings. It seems likely that the modern high-resolution techniques are more suitable for detailed examination of colonic motility.
Myoelectrical Activity
The electrical activity of smooth muscle cells of the colon is characterized by cyclical depolarization and repolarization of their membrane, resulting in slow wave potentials. The frequency of these slow wave potentials varies between 3 and 12 cycles per minute. This basic electrical rhythm is generated by the interstitial cells of Cajal (ICC), in particular the subpopulations of these cells which are located within the myenteric plexus and along the submucosal surface of the circular muscle layer. 57 Experimental studies have revealed that slow waves are absent in animals lacking ICC. Based on these and other studies, it is now abundantly clear that ICC act as pacemakers. Within the ICC, fluctuations in intracellular calcium concentrations appear responsible for the spontaneous changes in membrane polarization. The slow waves generated by ICC conduct passively into neighboring smooth muscle cells. Thereafter, they sweep over many other smooth muscle cells. Slow waves are the manifestation of incomplete depolarization. The baseline membrane potential of smooth muscle cells is usually −70 to −60 millivolts (mV). Under resting conditions, the membrane potential exhibits spontaneous fluctuations, varying between 20 and 30 mV. Complete depolarization (0 mV) cannot be achieved with these small fluctuations. The membrane potential can only come closer to zero mV if the smooth muscle cell is sensitized by excitatory molecules. These substances elevate the baseline membrane potential (bring it closer to zero) and make the cell more excitable. When the membrane potential exceeds the threshold value, Ca 2 + channels are opened. The inward flow of Ca 2 + produces a further upward depolarization resulting in action potentials and subsequent contraction of the smooth muscle cell. The frequency of these contractions is equal to or less than the frequency of the slow waves (▶ Fig. 2.6). Because spike potentials cannot occur without slow waves, these spontaneous fluctuations in membrane potential are a prerequisite for contraction of smooth muscle cells. Because these cells are electrically interconnected by gap junctions, the electrical signal responsible for contraction can spread readily from cell to cell. The smooth muscle cells of the colon are arranged in fibers. These fibers are grouped together in bundles. Because fibers and bundles also make connections with one another by gap junctions, the smooth muscle of the colon functions as a syncytium. Because of this syncytial arrangement, an action potential elicited at any point spreads in all directions. The distance depends on the excitability of the smooth muscle, which is regulated by excitatory and inhibitory substances derived from the enteric nervous system (ENS) and from the endocrine/paracrine system. As mentioned above, excitatory substances, such as acetylcholine, elicit smooth muscle cell contraction by elevating the baseline membrane potential, whereas inhibitory substances, such as norepinephrine, inhibit contraction by lowering the baseline. The complex interaction between smooth muscle cells, ENS, and endocrine/paracrine system is also essential for the synchronization of contractions. This is an important aspect of myoelectrical activity. For example, the circular muscle layer of the colon can only act appropriately when all smooth muscle cells in the corresponding section of the circumference contract simultaneously. Therefore, slow waves pass simultaneously over the entire circumference of the circular muscle layer. If that area has been sensitized by an excitatory regulatory molecule, the entire circumference of circular muscle will contract in synchrony.
Most of our knowledge regarding the electrophysiological characteristics of the colon is based on in vitro studies and on studies conducted in animal models. In vivo studies are difficult to perform. The technique most often described for the in vivo investigation of large bowel myoelectrical activity uses monopolar or bipolar electrodes mounted on intraluminal tubes. After introduction of the tube into the colon, the electrodes are clipped to the mucosa or attached to the mucosal surface by suction. Alternatively, the electrodes can be implanted under the serosal coat. Some researchers have used silver/silver chloride electrodes placed on the skin of the abdominal wall and overlying the large bowel. With this technique, only the frequency and regularity of the colonic slow waves can be determined. 58
The in vivo investigation of large bowel myoelectrical activity poses many problems. First, it is very difficult with intraluminal recording techniques to obtain a continuous and stable contact between electrode and mucosal surface and to eliminate the effects of colonic contents and/or transit. Second, none of the recording devices is capable of measuring all the activity actually generated. Serosal electrodes record a greater number of spike potentials and a higher proportion of the longitudinal muscle activity than do mucosal electrodes. 59 Third, it is not possible to differentiate between the myoelectrical activity generated by the two muscle layers. Finally, the reliability of the recording techniques and the comparability of methods have yet to be evaluated. Differences in recording techniques undoubtedly account for the conflicting results reported in the literature. Although in vivo studies are inappropriate to unravel all details of colonic myoelectrical activity in humans, they are not futile. Using in vivo techniques, for example, it has been shown that slow waves could be recorded in a continuous manner. 60 Furthermore, two types of slow wave activity have been described: slow waves with a low frequency of 3 to 4 cpm and slow waves with a higher frequency of 6 to 12 cpm, the latter being more common. 58 , 61 , 62 In recent years, in vitro studies have revealed that slow waves with a higher frequency are generated by ICC located within the myenteric plexus, whereas slow waves with a lower frequency arise in ICC along the submucosal surface of the circular muscle layer. 57 , 63 Using in vivo studies, spike potentials can be recorded as short spike bursts (SSBs), lasting only a few seconds, and as long spike bursts (LSBs), which last approximately 30 seconds. 64 SSBs are related to low-frequency slow waves 59 and are associated with low-amplitude contractions. 64 LSBs are related to high-frequency slow waves, which appear in bursts and are likely to represent the electrical control activity of the longitudinal muscle and also periodically the circular muscle. 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 The LSBs are associated with high-amplitude contractions. 64
It has been postulated that abnormal slow wave activity, as well as changing ratios of SSBs to LSBs, might reflect colonic dysfunction. Myoelectrical investigation of rectosigmoid activity in cases of irritable bowel syndrome has revealed an increased incidence of low-frequency slow waves. 66 , 67 Furthermore, increased SSBs were found in patients with predominantly constipation-type bowel activity, whereas in patients with predominantly diarrhea-type activity, a considerable decrease in SSB frequency, and LSB frequency to a lesser extent, could be demonstrated. 64 An increased incidence of SSBs also was found in patients with slow-transit constipation, whereas a short colonic transit time (as in patients with diarrhea) seems to be correlated with a preponderance of LSBs (▶ Fig. 2.7). 68 , 69
Neurogenic Control of Motility
Colonic motility is controlled by extrinsic and intrinsic neuronal systems. Considering the influence of these systems, it must be remembered that they are acting on a background of fluctuating intrinsic changes in smooth muscle cell membrane excitability. 70 The extrinsic system consists of preganglionic parasympathetic neurons and postganglionic sympathetic neurons. The intrinsic (or enteric) nervous system may be defined as that system of neurons in which the cell body is within the wall of the colon. The extrinsic innervation of the colon is described in Chapter 1. The pathways are summarized in ▶ Fig. 2.8 and ▶ Fig. 2.9.
The ENS plays a major role in the regulation of secretion, motility, immune function, and inflammation in the small and large bowels. 71 The intrinsic nervous system of the colon consists of a number of interconnected plexuses. Within these networks, small groups of nerve cell bodies or enteric ganglia can be seen.
The 80 to 100 million enteric neurons can be classified into functionally distinct subpopulations, including intrinsic primary afferent neurons (IPANs), interneurons, motor neurons, secretomotor and vasomotor neurons. The enteric nerve cells are organized in two main plexuses, the myenteric plexus of Auerbach and the submucosal plexus of Meissner. Within the myenteric plexus, there is an abundant network of separate cells, first described by Cajal. These cells, now commonly referred to as ICC, are neither neurons nor Schwann cells. 72 In the colon, the ICC are also situated within the circular and longitudinal smooth muscle layers and along the submucosal surface of the circular muscle layer. These cells are connected not only with each other, but also with neurons and smooth muscle cells. The main function of ICC is the generation of the autorhythmicity of the circular muscle. They also serve as conductors of excitable events and may be mediators of enteric neurotransmission. 71 Recently, another class of interstitial cells has been described. These fibroblastlike cells have a similar distribution to the ICC and exhibit platelet-derived growth factor receptor α (PDGFRα). These cells are now referred to as PDGFRα + cells. There is growing evidence that these cells play an important role as mediators of purinergic neurotransmission. 57 The interstitial cells (Cajal and PDGFRα) are both interconnected and electrically coupled to neighboring smooth muscle cells through low-resistance gap junctions. They also make synapselike contacts with enteric nerves. The smooth muscle cells, the ICC, and the PDGFRα+ cells form an integrated system, referred to as the SIP syncytium (▶ Fig. 2.10).
Studies with the aid of zinc-iodide osmium-impregnated colon have revealed that the structural organization of the ENS is far more complex than previously thought. 73 In the mucosal plexus, fine nerve fibers were evident in the connective tissue of the lamina propria among the tubular glands, close to the glandular epithelium and encircling their fundus like a nest to form the interglandular, periglandular, and subglandular networks, respectively. No ganglia were found in the mucosal plexus. The muscularis mucosae plexus appeared as a fine felt made up of a nonganglionated nervous network in which nerve bundles ran mostly parallel to the long axes of the smooth muscle cells. Ganglia of the submucosal plexus appeared arranged along three different planes. The innermost network was composed of small-sized, regularly arranged ganglia in a single row immediately below the muscularis mucosae. Nerve strands from these ganglia ran toward the mucosal plexus and the middle part of the submucosa. A second series of ganglia was deeply located, often at the same level as the large blood vessels, and a third was closely opposed to the circular muscle layer. Nerve strands connected all these ganglia to each other. The intramuscular nerve fiber bundles run parallel to the long axes of the smooth muscle cells and form the nonganglionated circular and longitudinal muscular plexuses, respectively. Large-caliber nerve fibers pass through the serosa and penetrate the longitudinal muscle layer. The subserosal plexus at all colonic levels except the sigmoid has no ganglia, and all nerve fibers are amyelinated.
The ENS functions semi-autonomously. It receives preganglionic fibers from the parasympathetic system and postganglionic fibers from the sympathetic system. The parasympathetic and sympathetic fibers that synapse on neurons within the ENS appear to play a modulatory role, as indicated by the observation that deprivation of input from both autonomic nerve systems does not abolish colonic activity. The ENS also receives sensory input from the luminal side of the colonic wall. Three groups of neurons can be distinguished in the ENS: (1) sensory neurons, (2) interneurons, and (3) motor neurons. The sensory neurons are divided into two groups: IPANs with their cell bodies within the colonic wall and extrinsic primary afferent neurons (EPANs) with their cell bodies outside the colonic wall. The sensory neurons function as a surveillance network. The IPANs transmit sensory information directly to the motor neurons in the same plane or indirectly through an ascending or descending chain of interneurons. 74 The sensory neurons play an important role in local reflex pathways, monitoring the chemical nature of the colonic contents as well as the tension in the wall of the large bowel. For example, localized radial distention of the colon evokes an ascending excitatory reflex (i.e., contraction of the circular muscle on the proximal side) and a descending inhibitory reflex (i.e., relaxation of the circular muscle on the distal side) (▶ Fig. 2.11). 70 These reflexes also can be elicited by mechanical and chemical irritation of the mucosa. Some of the sensory neurons for these reflexes have their endings in the mucosa (▶ Fig. 2.12). The interneurons form a relay system, linking information between enteric neurons. 70 They project more than 10 mm in oral, aboral, and circumferential directions. Interneurons are interconnected with each other and are arranged in chains, enabling the transmission of signals over longer distances. Descending interneurons are more numerous than ascending interneurons. Interneurons synapse on motor neurons. The ascending interneurons are mainly cholinergic, whereas the descending interneurons release a wide variety of neurotransmitters. 75 The most important enteric neurons are the motor neurons, of which different groups can be distinguished: excitatory motor, inhibitory motor, secretomotor, and vasomotor. 70 The motor neurons, innervating the longitudinal and circular muscles and the muscularis mucosae, are either excitatory or inhibitory. By releasing neurotransmitters that provoke muscle contraction or relaxation, they play an important role in controlling colonic motility (▶ Fig. 2.11). The main neurotransmitters of the excitatory motor neurons are acetylcholine and substance P, of which acetylcholine is the most important one. The receptors for acetylcholine on colonic smooth muscle cells are of the muscarinic subtype. They are blocked by muscarinic antagonists such as atropine and scopolamine, but not by nicotinic antagonists. 70 The receptors for acetylcholine also have been found on the membrane of myenteric ganglion cells. Therefore, acetylcholine might have a direct as well as an indirect effect on colonic motility. Inhibitory motor neurons of the ENS are nonadrenergic and noncholinergic (NANC). The cell bodies of these inhibitory neurons are located in the myenteric plexus (▶ Fig. 2.12). They predominantly supply the circular muscle and to a lesser extent the longitudinal muscle. The neurotransmitters of the inhibitory NANC neurons are nitric oxide (NO), vasoactive intestinal polypeptide (VIP), adenosine triphosphate, and possibly pituitary adenylate cyclase–activating polypeptide, gamma aminobutyric acid (GABA), neuropeptide Y, and carbon monoxide. 76 In the past, NANC neurons have been called purinergic, based on the signaling by adenosine triphosphate and peptidergic, based on the signaling by vasoactive intestinal peptide. 70 , 77 The inhibitory motor neurons are involved in the mediation of the descending inhibitory phase of the peristaltic reflex (▶ Fig. 2.11 and ▶ Fig. 2.12). 70 The secretomotor and vasomotor neurons, which have their cell bodies in the submucosal plexus, control epithelial transport (mainly secretion) and local blood flow, respectively. These neurons are driven by the IPANs. Chemical and mechanical stimuli result in a release of local mediators, such as 5-hydroxytryptamine (serotonin). These mediators activate the IPANs, which, in turn, stimulate the secretomotor and vasomotor neurons by releasing acetylcholine and vasoactive intestinal peptide. 78 The secretomotor neurons are either cholinergic or noncholinergic. The cholinergic neurons release acetylcholine as transmitter, whereas the noncholinergic neurons utilize nitric oxide and vasoactive intestinal peptide for their signal transmission (▶ Fig. 2.12). It has been reported that the number of colonic neurons declines with age, with the exception of the NANC neurons. 79 , 80 This finding might be an explanation for the higher incidence of constipation among older people.
2.2 Hormonal Control of Motility
Colonic function is affected by an extensive endocrine system. Approximately 15 different gastrointestinal hormones have been identified. 81 These gut hormones are synthesized in endocrine and paracrine cells. Many of these substances also are found in enteric neurons; therefore, they are potential neurotransmitters. The pharmacokinetics, catabolism, and release of these hormones are very complex, and their exact role in the regulation of large bowel motor activity is undetermined. The role of only a few hormones, such as gastrin and cholecystokinin, is known. These hormones are synthesized and released in the upper part of the gastrointestinal tract. Because they can reach the colon through the bloodstream, they might be able to control colonic motility.
Investigators have shown that spike potential activity of the colon does increase following the administration of gastrin and pentagastrin. 61 , 82 However, the gastrocolic reflex (i.e., increased colonic motility during and after a meal) is unlikely to be due to gastrin, because this reflex is still present in patients with total gastrectomy and because plasma levels of gastrin peak much later than the postprandial increase in colonic motility. 83 More likely, cholecystokinin is the mediator of this postprandial colonic activity. Cholecystokinin is a well-known colonic stimulant, increasing colonic spike activity at physiologic concentrations and in a dose-dependent manner. 84
Other upper gastrointestinal hormones such as glucagon and somatostatin have inhibitory effects. 82 It has been reported that secretin also inhibits colonic motility, 85 but this effect could not be demonstrated by others. 61 Therefore, it is not clear whether secretin has an inhibitory effect or no effect at all on colonic motility. Present knowledge indicates that these hormones play their major role in the control of secretion and absorption.
2.2.1 Pharmacologic Influence
In a study of the effects of morphine and the opiate antagonist naloxone on human colonic transit, Kaufman et al 86 found that morphine significantly delayed transit in the cecum and ascending colon and decreased the number of bowel movements per 48 hours. Naloxone accelerated transit in the transverse colon and rectosigmoid colon but had no effect on the number of bowel movements per 48 hours. These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit. Of immediate practical significance is the fact that it thus may be inadvisable to prescribe morphine as a postoperative analgesic following colonic operations.
2.3 Microflora
2.3.1 Common Microflora
The bacterial population of the gastrointestinal tract is a complex collection of aerobic and anaerobic microorganisms. Distal to the ileocecal valve, the bacterial concentrations increase sharply, rising to 10 11 to 10 12 colony-forming units (cfu) per milliliter. Nearly one-third of the fecal dry weight consists of viable bacteria, with as many as 10 11 to 10 12 microorganisms present per gram of feces. 87 , 88 Stephen and Cummings 88 reported that bacteria comprise 55% of the total fecal solids. Anaerobic bacteria outnumber aerobes by a factor of 10 2 to 10 4 . Typically, Bacteroides species are present in numbers of 10 10 to 10 12 /g of feces, and Escherichia coli are present in numbers of 10 8 to 10 10 /g of feces. The predominant isolates are listed in ▶ Table 2.1. 89 Dunn 90 has summarized the microbial flora that are found in conventional ileostomies and ileal reservoirs (▶ Table 2.2). 90
Organism | Concentration (cfu/mL) |
Aerobic or facultative organisms | |
Streptococci | |
Microorganisms | |
Enterobacteria | |
Staphylococci | |
Lactobacilli | |
Fungi | |
Anaerobic bacteria | |
Bacteroides spp. | |
Bifidobacterium spp. | |
Streptococci a | |
Clostridium spp. | |
Eubacterium spp. | |
a Includes Peptostreptococcus and Peptococcus. 89 | |
Organisms | Aerobes | Anaerobes | |
Upper small intestine | 0–105 | 0–105 | Few |
Lower small intestine | 104–109 | 104–109 | 104–109 |
Conventional ileostomy | |||
Upper small intestine | 0–105 | 0–105 | Few |
Lower small intestine | 107–109 | 104–1,010 | 104–1,011 |
Continent ileostomy | |||
Upper small intestine | 0–105 | 0–105 | Few |
Lower small intestine | 107–109 | 103–1,010 | 106–1,010 |
Ileal ileoanal reservoir | |||
Upper small intestine | 103–105 | 103–105 | 102–104 |
Lower small intestine | 106–1,011 | 106–1,011 | 107–1,011 |
It is self-evident that the nature of colonic bacteria is of paramount importance to the surgeon. Knowledge of the type of resident bacteria serves as a useful guide to the rational selection of appropriate antibiotic therapy, both in the prophylactic and therapeutic settings.
2.3.2 Microflora Activity
Guarner and Malagelada conducted an extensive review of gut flora in health and disease in which they summarize the major functions of the gut microflora, including metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonized host against invasion by alien microbes. 91 Much of the following information has been derived from their comprehensive review. Gut microflora might also be an essential factor in certain pathologic disorders including multisystem organ failure, colon carcinoma, and inflammatory bowel diseases. Several hundred grams of bacteria living within the colonic lumen affect host homeostasis. Some of these bacteria are potential pathogens and can be a source of infection and sepsis when the integrity of the bowel barrier is physically or functionally breached. Bacteria are also useful in promotion of human health. The constant interaction between the host and its microbial guests can infer important health benefits to the human host. Probiotics and prebiotics are known to have a role in the prevention or treatment of some diseases.
2.3.3 Metabolic Functions
A major metabolic function of the colonic microflora is the fermentation of nondigestible dietary residue, which is a major source of energy in the colon. Nondigestible carbohydrates include large polysaccharides (resistant starches, cellulose, hemicellulose, pectins, and gums), some oligosaccharides that escape digestion, and unabsorbed sugars and alcohols. The metabolic end point is generation of SCFAs. Anaerobic metabolism of peptides and proteins (putrefaction) by the microflora also produces SCFAs but, at the same time, it generates a series of potentially toxic substances including ammonia, amines, phenols, thiols, and indoles. Available proteins include elastin and collagen from dietary sources, pancreatic enzymes, sloughed epithelial cells, and lysed bacteria. Substrate availability in the human adult colon is about 20 to 60 g carbohydrates and 5 to 10 g protein per day.
Colonic microorganisms also play a part in vitamin synthesis and in absorption of calcium, magnesium, and iron. Absorption of ions in the cecum is improved by carbohydrate fermentation and production of SCFAs, especially acetate, propionate, and butyrate. All of these fatty acids have important functions in host physiology. Butyrate is almost completely consumed by the colonic epithelium, and it is a major source of energy for colonocytes. Acetate and propionate are found in portal blood and are eventually metabolized by the liver (propionate) or peripheral tissues, particularly muscle (acetate). Acetate and propionate might also have a role as modulators of glucose metabolism: absorption of these SCFAs would result in lower glycemic responses to oral glucose or standard meal—a response consistent with an ameliorated sensitivity to insulin. Foods with a high proportion of nondigestible carbohydrates have a low glycemic index. Vitamin K is produced by intestinal microorganisms. 89
The enterohepatic circulation of many compounds depends on flora that produce bacterial enzymes, such as B-glucuronidase and sulfatase. Some of the endogenous and exogenous substances that undergo an enterohepatic circulation include bilirubin, bile acids, estrogens, cholesterol, digoxin, rifampin, morphine, colchicine, and diethylstilbestrol. 92 The main role of anaerobes appears to be the provision of catabolic enzymes for organic compounds that cannot be digested by enzymes of eukaryotic origin. They are needed for the catabolism of cholesterol, bile acids, and steroid hormones; they hydrolyze a number of flavonoid glycosides to anticarcinogens; and they detoxify certain carcinogens. 93
2.3.4 Trophic Functions
All three SCFAs stimulate epithelial cell proliferation and differentiation in the large and small intestine in vivo in rats. A role for SCFAs in prevention of some human pathological states such as chronic ulcerative colitis and colonic carcinogenesis has been long suspected, although conclusive evidence is still lacking. 91 SCFAs butyrate, propionate, and acetate produced during fiber fermentation promote colonic differentiation and can reverse or suppress neoplastic progression. Basson et al 94 sought to identify candidate genes responsible for SCFA activity on colonocytes and to compare the relative activities of independent SCFAs. A total of 30,000 individual genetic sequences were analyzed for differential expression among the three SCFAs. More than 1,000 gene fragments were identified as being substantially modulated in expression by butyrate. Butyrate tended to have the most pronounced effects and acetate the least.
2.3.5 Host Immunity Functions
The intestinal mucosa is the main interface between the immune system and the external environment. 91 Gut-associated lymphoid tissues contain the largest pool of immunocompetent cells in the human body. The dialogue between host and bacteria at the mucosal interface seems to play a part in development of a competent immune system. The immune response to microbes relies on innate and adaptive components, such as immunoglobulin secretion. Most bacteria in human feces are coated with specific IgA units. Innate responses are mediated not only by white blood cells such as neutrophils and macrophages that can phagocytose and kill pathogens, but also by intestinal epithelial cells, which coordinate host responses by synthesizing a wide range of inflammatory mediators and transmitting signals to underlying cells in the mucosa. The innate immune system has to discriminate between potential pathogens from commensal bacteria, with the use of a restricted number of preformed receptors. The system allows immediate recognition of bacteria to rapidly respond to an eventual challenge.
2.3.6 Protective Functions
Anaerobes are usually seen as destructive creatures without any redeeming virtues. Resident bacteria are a crucial line of resistance to colonization by exogenous microbes and, therefore, are highly relevant in prevention of invasion of tissues by pathogens. 91 Colonization resistance also applies to opportunistic bacteria that are present in the gut but have restrictive growth. Use of antibiotics can disrupt the ecological balance and allow overgrowth of species with potential pathogenicity such as toxigenic Clostridium difficile, associated with pseudomembranous colitis. Benefits we derive from anaerobes include their probable function in restraining growth of C. difficile in human carriers. 93
2.3.7 Bacterial Translocation
The passage of viable bacteria from the gastrointestinal tract through the epithelial mucosa is called bacterial translocation. Translocation of endotoxins from viable or dead bacteria in very small amounts probably constitutes a physiologically important boost to the reticuloendothelial system, especially to the Kupffer cells in the liver. However, dysfunction of the gut mucosal barrier can result in the translocation of many viable microorganisms, usually belonging to gram-negative aerobic genera (Escherichia, Proteus, Klebsiella). After crossing the epithelial barrier, bacteria can travel via the lymph to extraintestinal sites, such as the mesenteric lymph nodes, liver, and spleen. Subsequently, enteric bacteria can disseminate throughout the body producing sepsis, shock, multisystem organ failure, or death of the host. 91
The three primary mechanisms in promotion of bacterial translocation in animals are overgrowth of bacteria in the small intestine, increased permeability of the intestinal mucosal barrier, and deficiencies in host immune defenses. Bacterial translocation can occur in human beings during various disease processes. Indigenous gastrointestinal bacteria have been cultured directly from the mesenteric lymph nodes of patients undergoing laparotomy. Data suggest that the baseline rate of positive mesenteric lymph node culture could approach 5% in otherwise healthy people. However, in disorders such as multisystem organ failure, acute severe pancreatitis, advanced liver cirrhosis, intestinal obstruction, and inflammatory bowel diseases, rates of positive culture are much higher (16–50%). 91
2.3.8 Colon Carcinogenesis
Intestinal bacteria could play a part in the initiation of colon carcinoma through production of carcinogens, cocarcinogens, or procarcinogens. In healthy people, diets rich in fat and meat but poor in vegetables increase the fecal excretion of N-nitroso compounds, a group of genotoxic substances that are known initiators and promoters of colon carcinoma. Such diets also increase the genotoxic potential of human fecal water. Another group of carcinogens of dietary origin are the heterocyclic aromatic amines that are formed in meat when it is cooked. Some intestinal microorganisms strongly increase damage to DNA in colon cells induced by heterocyclic amines, whereas other intestinal bacteria can uptake and detoxify such compounds. 91 Bacteria of the Bacteroides and Clostridium genera increase the incidence and growth rate of colonic neoplasms induced in animals, whereas other genera such as lactobacillus and bifidobacteria prevent carcinogenesis. Although the evidence is not conclusive, colonic flora seem to be an environmental factor that modulates risk of colonic carcinoma in human beings. 91
2.3.9 Role in Inflammatory Bowel Diseases
Resident bacterial flora have been suggested to be an essential factor in driving the inflammatory process in human inflammatory bowel diseases. In patients with Crohn’s disease, intestinal T lymphocytes are hyperactive against bacterial antigens. 91 Patients with Crohn’s disease or ulcerative colitis have increased intestinal mucosal secretion of IgG-type antibodies against a broad spectrum of commensal bacteria. Patients with inflammatory bowel diseases have higher amounts of bacteria attached to their epithelial surfaces than do healthy people. Unrestrained activation of the intestinal immune system by elements of the flora could be a key event in the pathophysiology of inflammatory bowel disease. Some patients with Crohn’s disease (17–25%) have mutations in the NOD2/CARD15 gene, which regulates host responses to bacteria. 94 , 95
In inflammatory bowel diseases in human beings, direct interaction of commensal microflora with the intestinal mucosa stimulates inflammatory activity in the gut lesions. Fecal stream diversion has been shown to prevent recurrence of Crohn’s disease, whereas infusion of intestinal contents to the excluded ileal segments reactivated mucosal lesions. 96 In ulcerative colitis, short-term treatment with an enteric-coated preparation of broad-spectrum antibiotics rapidly reduced mucosal release of cytokines and eicosanoids and was more effective in reduction of inflammatory activity than were intravenous steroids. 97 However, antibiotics have limited effectiveness in clinical management of inflammatory bowel disease, since induction of antibiotic-resistant strains substantially impairs sustained effects.
2.3.10 Probiotics and Prebiotics
Bacteria can be used to improve human health. A bacterium that provides specific health benefits when consumed as a food component or supplement would be called a probiotic. Oral probiotics are living microorganisms that upon ingestion in specific numbers exert health benefits beyond those of inherent basic nutrition. 91 According to this definition, probiotics do not necessarily colonize the human intestine. Prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating growth, or activity, or both, of one or a restricted number of bacteria in the colon. For example, coadministration of probiotics to patients on antibiotics significantly reduced antibiotic-associated diarrhea 98 , 99 and can be used to prevent such antibiotic-associated diarrhea. 100 Examples of such bacteria include various strains of lactobacillus GG, Bifidobacterium bifidum, and Streptococcus thermophilus.
Probiotics and prebiotics have been shown to prevent colon carcinoma in several animals, but their role in reduction of risk of colon carcinoma in human beings is not established. 101 However, probiotics have been shown to reduce the fecal activity of enzymes known to produce genotoxic compounds that act as initiators of carcinoma in human beings. 91
2.4 Intestinal Gas
Intestinal gas may be endogenous or exogenous. Five gases—nitrogen, oxygen, carbon dioxide, hydrogen, and methane—make up 99% of all the gas in the gut. Only nitrogen and oxygen are found in the atmosphere and therefore can be swallowed. Hydrogen, methane, and carbon dioxide are produced by bacterial fermentation of carbohydrates and proteins in the colon. Approximately one-third of the human population produces methane. Small amounts of hydrogen sulfide are also produced. Levitt, 102 in his extensive studies of this subject, found that patients who complain of excessive flatus almost invariably have high concentrations of hydrogen and carbon dioxide. Hydrogen is cleared by the lungs. Since carbon dioxide is a result of fermentation, therapy consists of diet manipulation with a decrease in the amount of carbohydrate, especially lactose, wheat, and potatoes.
The most dramatic and important point for the surgeon regarding intestinal gas is the fact that explosions may occur during electrocautery in the colon. Because both hydrogen and methane are explosive, intestinal gases should be aspirated before electrocautery is used.
2.5 Anorectal Physiology
During the last decades, detailed investigations have given us a better understanding of anorectal physiology. The methods that are used for the systematic and fundamental study of anorectal physiology include anorectal manometry, defecography, continence tests, electromyography of the anal sphincters and the pelvic floor, and nerve stimulation tests. Moreover, combining proctography with simultaneous pressure recordings and electromyographic measurements permits these investigations to present a more dynamic and physiologic account of the state of the anorectal region. Modern imaging techniques furnish a clearer picture of the mechanisms of anal continence and defecation and demonstrate pathophysiologic abnormalities in patients with disorders of continence and defecation.
2.5.1 Anal Continence
It is difficult to give a clear definition of anal continence. Complete control or complete lack of control is easy to define; however, while varying degrees of lack of control of flatus and fecal soiling may seem like major disabilities to some patients, other less fastidious individuals may be unconcerned by them. Maintaining anal continence is a complex matter because it is controlled by local reflex mechanisms as well as by conscious will. Normal continence depends on a highly integrated series of complicated events. Stool volume and consistency are important because patients who have weakened mechanisms may be continent for a firm stool but incontinent for liquid feces. Also significant is the rate of delivery of feces into the rectum, which emphasizes the reservoir function of the rectum. Other important factors include the sphincteric component, sensory receptors, mechanical factors, and the corpus cavernosum of the anus (see Box 2.1).
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