Motility Requirements of Different Organs

Motility refers to spontaneous motion/movement, be it of a single cell moving through tissue or medium, or material moving inside hollow organs, e.g., the gastrointestinal tract, cardiovascular system, bladder, and uterus. In all cases, the cell or organ itself generates the force for motion. Cell motility results in its translocation or deformation of its membrane; organ motility results in mixing/turnover, propulsion, or both of the luminal contents. However, the rates of propulsion and the extent of mixing/turning-over vary among organs. Correspondingly, the modes of force generation differ among these organs. For the cardiovascular system, the primary movement is rapid and continuous blood circulation through a closed loop system. A single pump—the heart—performs this function by generating rhythmic phasic contractions (RPCs) sequentially in its four chambers. Myogenic mechanisms regulate the frequency and force of these contractions; circulating hormones and autonomic nerves may modulate them. Although numerous cell types and nutrients enter and leave the blood stream, blood consistency remains stable, and vigorous mixing movements are not required. The urinary bladder function requires storage until voluntary voiding. Tonic bladder smooth muscle contraction accompanied by centrally regulated sphincter relaxation accomplishes this function. The consistency of urine is also more or less constant.

The motility function of the gastrointestinal tract differs markedly from those of the cardiovascular system and the urinary bladder. First, the consistency and nature of ingested meals varies widely from liquid to solid. Second, numerous endocrine and exocrine secretions occur as the ingested meal moves through the gastrointestinal tract. These secretions digest the complex molecules in the meal into simpler molecules so they can be absorbed by the epithelial cells. The gut motility function requires thorough mixing of secretions with the ingested meal for complete digestion. In addition, the digesta needs frequent turnover to expose all of it uniformly to the epithelial surface for efficient absorption. Third, digestion and absorption are relatively slow processes, which require much slower but steady propulsion of digesta than that required by blood or urine. Therefore, the motility function of the gastrointestinal tract requires both mixing/turning over and propulsion of luminal contents. The propulsion of digesta generally occurs in irregular incremental steps, rather than in a continuous stream, as in cardiovascular circulation and bladder emptying. Further, digestive and absorptive functions are not constant throughout the gastrointestinal tract. The intensity of mixing/turning over and the rates of propulsion vary among the organs of the gastrointestinal tract, and in fact, in different parts of the same organ.

Little or no absorption of nutrients occurs in the esophagus, which is primarily a conduit for rapid transfer of the swallowed bolus from the upper esophageal sphincter to the gastric fundus without significant mixing/turning over. It takes less than 15 seconds for this transfer over about a 30-cm length of human esophagus.

The stomach secretes hydrochloric acid and pepsinogen for bacteriocidal action and protein digestion, respectively. Therefore, it requires mixing of these secretions with the meal, followed by slow and regulated emptying at a rate that does not overwhelm the digestive and absorptive capacity of the small intestine. Rapid gastric emptying results in malabsorption, while too-slow emptying may result in feelings of fullness, bloating, and nausea accompanied by weight loss. Accordingly, the motility function of the stomach is to store food temporarily in the gastric fundus, transfer it gradually to the corpus and the antrum, mix it with secretions, and triturate it in preparation for digestion in the small intestine. Coordinated motility of the antrum, pylorus, and duodenum empties the meal in small squirts into the small intestine. Hormonal, enteric neuronal, and extrinsic neuronal feedbacks stimulated by the nutrients entering the small intestine and sensory cells that monitor the state of digestion continuously modulate the gastric motility function for an optimal rate of gastric emptying. It takes about 15 to 30 minutes—called the lag phase of gastric emptying—for the stomach to begin emptying a solid meal into the small intestine. The lag phase is absent or short for liquid meals, which do not require trituration. The total gastric emptying time depends on the nutritional contents of the meal (carbohydrates, proteins, fat) and on meal viscosity.

Endocrine, pancreatic, and biliary secretions enter the proximal small intestine in response to meal ingestion. Most digestion and absorption of nutrients occurs in the proximal half of the small intestine. The bile acids are absorbed in the terminal ileum. Small intestinal motility intensively mixes the exocrine and endocrine secretions with the meal and at the same time spreads the mixture rapidly over the proximal half so that the entire absorptive surface is available for absorption of nutrients. The absorption rate of the bile acids is slower than that of the nutrients. As a result, the mixing function intensifies in the distal small intestine, while the propulsion rate slows. It takes about two hours for the head of an average meal to reach the ileocecal sphincter. The total small intestinal transit time depends on the nutritional content of the meal.

The digesta enters the colon as fluid. The colon absorbs most of the water and electrolytes for conservation and reduction of fecal mass. The colonic mucosa is tighter and its absorption rate slower than that of the small intestine. Therefore, it requires extensive turning over of its contents and a very slow net distal propulsion to absorb electrolytes and water. It takes over 24 hours for the digesta to move from the ileocecal sphincter to the rectum, a length of about one meter. In addition, the sigmoid colon and rectum serve as temporary storage for feces prior to defecation at a convenient and safe time. Although the colonic transit is ultraslow, ultrarapid propulsion accomplishes defecation in a short period.

Overall, propulsion rates slowdown as the ingested meal travels distally over the gastrointestinal tract, while the mixing/turning-over movements intensify. Such varied motility functions cannot be achieved by a single pump located at the beginning of the gastrointestinal tract, as in the cardiovascular system, or by individual pumps located at the beginning of each gut organ. Instead, smooth muscle cells at each location throughout the gut generate independent contractions. Through various enteric neural and myogenic regulatory mechanisms, these contractions organize as propagating and nonpropagating contractions of varying amplitudes and durations in response to sensory signals generated by local and distant conditions within the gut, to produce variable intensities of mixing/turning over and propulsion rates of the ingested meal.

How Gut Contractions Mix/Turn Over and Propel Digesta

It is obvious that a single type of contraction, such as the more-or-less-constant-amplitude rhythmic phasic contractions of the cardiac muscle or the intermittent tonic contractions of the urinary bladder, could not perform the complex and varied motility functions of the gut. The propulsion of digesta in the gut does not occur by creating a pressure differential between adjacent organs or between the oral and anal ends of a short segment. Instead, the digesta is propelled when the contractions propagate, similar to propulsion by a peristaltic pump, where each stroke of the piston propels. The efficacies of mixing/turning over and propulsion depend on the spatiotemporal characteristics of contractions.

The temporal characteristics of gut contractions include frequency, amplitude, and duration, whereas the spatial characteristics include direction of propagation, distance of propagation, and velocity of propagation. These spatiotemporal characteristics of contractions determine whether they (1) propel, (2) produce back and forth movements to mix, stir, and turn over the fecal material, or (3) do both [1–5].

Each smooth muscle cell in the gut wall generates independent contractions. However, communication between adjacent smooth muscle cells through gap junctions and neuronal networks in the myenteric and submucosal plexi coordinates contractions spatially to varying degrees in different parts of the gut. This coordination allows some contractions to occur sequentially at adjacent locations to various distances in the gut (propagating contractions), while others do not propagate or propagate over very short distances (nonpropagating contractions). Input from the cholinergic excitatory motor neurons and the excitation-contraction coupling in smooth muscle cells (see later) determine the amplitudes of propagating and nonpropagating contractions. The amplitude of a contraction and its distance of propagation together determine the distance a single bolus of digesta is propelled by each propagating contraction.

Figure 1A illustrates a contraction beginning at a proximal location and propagating in the anal direction. This contraction is strong to occlude the lumen. As a result, it propels the digesta trapped ahead of it up to the distance of its propagation, at the same time causing modest mixing. The speed of propulsion of the bolus of digesta is nearly the same as the velocity of propagation of the contraction. The frequency of propagated contractions determines the total volume of digesta propelled per unit of time. The lumen-occluding propagating contractions occur frequently in the gastric antrum and in the proximal small intestine. The contraction in Figure 1B also propagates, but it is not strong enough to occlude the lumen. A part of the digesta escapes through the luminal opening as the contraction propagates and is left behind to cause mixing. This type of contraction is less propulsive than that in Figure 1A; however, it produces more mixing. This type of contraction occurs in the gastric corpus and mid small intestine. The contractions in Figure 1C occur randomly at adjacent locations; some occlude the lumen, while others do not. These nonpropagating contractions produce back and forth movements of the digesta, causing intense mixing/turning over with slow net distal propulsion. These types of contractions occur predominantly in the terminal ileum and the colon. The contraction shown in Figure 1D is also a lumen-occluding propagating contraction like that in Figure 1A. However, this contraction is much stronger in amplitude and longer in duration, and it propagates uninterrupted over several-fold longer distances than the one in Figure 1A. Such contractions are ultrapropulsive. They cause mass movements, such as those during defecation.

FIGURE 1

The role of different spatiotemporal patterns of contractions in mixing and propulsion in the gut. (A) A lumen-occluding contraction that propagates in the anal direction propels the digesta ahead of it up to the distance of its propagation. The gastric (more...)

Types of Gut Contractions

Gut smooth muscle cells generate three distinct types of contractions which together achieve the complex and varied mixing and propulsive functions of the gut: (1) rhythmic phasic contractions (RPCs), (2) ultrapropulsive contractions (UPCs), and (3) tonic contractions (TCs). A gut smooth muscle cell can generate concurrently all three types of contractions.

Ultrapropulsive Contractions

UPCs (Figure 1D) are of two types: giant migrating contractions (GMCs) and retrograde giant contractions (RGCs). These contractions are several-fold larger in amplitude and longer in duration than RPCs (Figure 2). The GMCs rapidly propagate (~1 cm/sec) in the anal direction over very long distances [6]. The RGCs originate in the mid small intestine and rapidly propagate (~10 cm/sec) in the oral direction up to the antrum [7] (Figure 3). Both types of giant contractions produce mass movements, i.e., rapid propulsion of luminal contents over long segments of the gut. The rapid transit caused by GMCs and RGCs does not allow much contact time between the digesta and the mucosal surface, precluding any digestion or absorption during the mass movement.

FIGURE 2

Record showing a small intestinal GMC starting in the middle of a migrating motor complex, propagating in the anal direction at the strain gauge transducer SG6—implanted surgically at 255 cm from the pylorus. Note the much larger amplitude and (more...)

FIGURE 3

Record showing an RGC starting at strain gauge transducer Jej-IL3 located at 46% of the length of the small bowel from the pylorus. Note the larger amplitude and longer duration of RGC and its rapid propagation to the antrum (~10 cm/sec). Retching and (more...)

GMCs are more effective than RPCs in propulsion because of the marked differences in the spatiotemporal characteristics of these two types of contractions.

1. Propagating RPCs are not always strong enough to occlude the lumen. However, the amplitude of GMCs is twofold to threefold larger than that of the largest RPCs [6], and therefore, GMCs invariably occlude the lumen.
2. GMCs last several-fold longer than RPCs, helping them easily overcome any resistance in the propulsion of luminal contents.
3. A propagating RPC usually propagates a few centimeters at a time. By contrast, a GMC propagates over appreciable distances and often to the end of the organ in which it originates [6].

In humans and most nonrodent species, GMCs occur spontaneously in the small intestine and the colon [6, 8–10]. In the distal small intestine, they occur primarily in the fasting state after digestion is complete. However, in the colon, they occur in the fasting and the postprandial state. In the esophagus, a swallow stimulates a GMC that propagates in the anal direction. It strongly compresses the esophageal wall, relaxing the lower esophageal sphincter by descending inhibition to let the bolus pass through (Figure 4) [11]. Reflux of gastric contents also can stimulate GMCs in the distal esophagus to clear the esophagus rapidly (secondary peristalsis).

FIGURE 4

A voluntary swallow stimulates a GMC in the proximal human esophagus, which propagates in the anal direction and induces descending inhibition of the lower esophageal tone to let the swallowed bolus pass through without resistance. A manometric catheter, (more...)

Species such as rodents, guinea pigs, and rabbits defecate compacted pellets instead of the formed stools produced by higher species such as humans and dogs. These pellets form in the midcolon, proximal to which the fecal material is thick fluid. Since colonic RPCs are not powerful enough to propel hard pellets effectively, the colons in these species generate predominantly GMCs [12–18]. GMCs in the rat colon occur at a frequency of about 17 to 45/hour [12] and in the mouse colon at about 15 to 25/hour [15] (Figure 5). However, unlike in human and canine colons, most GMCs in the rodent colon do not always propagate or propagate only over short distances and hence are responsible for the gradual distal propulsion of the pellets [12].

FIGURE 5

Colonic motor activity in an intact conscious rat. The colon generated primarily GMCs. Arrow shows tiny RPCs. C = colonic strain gauge transducer. The number after C indicates the distance in cm of the transducer from the cecum. (Reproduced with permission (more...)

Tonic Contractions

The circular smooth muscle cells of the sphincters (the lower esophageal sphincter and the internal anal sphincter) and organ junctions (the pylorus and ileocecal junction) in the gut generate a sustained tonic contraction, which keeps their lumen partially or completely closed to prevent reflux. Activation of enteric inhibitory neurons reduces this tone to allow the passage of luminal contents in the distal direction.

The smooth muscle cells in the major organs also generate a basal tone that maintains their resting shape in length and diameter. The ingestion of a meal increases the tone of circular muscle cells in the small intestine and the colon, which narrows the lumen to varying degrees but does not occlude it [19–21] (Figure 6). The amplitude and duration of increase in tone depend upon the volume and caloric intake of food [20]. The generation of tone by itself does not cause major mixing/turnover or propulsion; however, it narrows the lumen to accentuate the motility function of RPCs. With a narrower lumen, weaker RPCs, such as those shown in Figure 1B, might occlude the lumen to enhance their effectiveness in propulsion and/or mixing/turning over.

FIGURE 6

Increase of circular muscle tone in the human transverse and sigmoid colon after ingestion of a meal. A barostat recorded the tone. The increase of tone reduces the volume inside the balloon to maintain it at a constant pressure. The increase of postprandial (more...)

Descending Inhibition

Due to their strong lumen-occluding amplitude and long distances of uninterrupted propagation, GMCs propel a large bolus of digesta in the segment over which they propagate. The bolus accumulates in size as the GMC propagates, causing distension of the receiving segment. In healthy subjects, the distal segment relaxes its tone and inhibits its ongoing RPCs (Figure 7), thus accommodating the large bolus without generating resistance against propulsion. This is called descending inhibition [8–10, 22]. It is stimulated by strong compression of the gut wall by a GMC, stimulating in turn descending interneurons which themselves connect to inhibitory motor neurons projecting into smooth muscle cells [9, 23]. The descending inhibition also relaxes the tone of the sphincters—the lower esophageal sphincter and internal anal sphincter—for easy passage of the large bolus through them [10, 11].

FIGURE 7

GMCs induce descending inhibition in the colon. A GMC originated at the location of strain gauge transducer C5 (5 cm distal to the ileocecal junction) and propagated in the anal direction up to the location of transducer C26 (26 cm distal to the ileocecal (more...)

Bayliss and Starling [24] initially used the term peristalsis to describe a contraction that begins above a local luminal stimulus and propagates distally while producing descending inhibition of spontaneous contractions and relaxation of tone ahead of it. As noted above, GMCs meet these conditions [6, 8–10] but not RPCs [1, 3, 25]. Note that RPCs do not induce descending inhibition (Figure 7), because they do not strongly compress the gut wall, and they do not propagate over long distances to accumulate a large bolus. Instead, they propel digesta in small amounts over short distances, which may fill the receiving segment and shift luminal contents back and forth but does not distend it. The original term “peristalsis”, therefore, applies only to GMCs.

Composition of Three Types of Contractions in Gut Organs

The composition of the three types of contractions differs among the gut organs to meet their spe- cific requirements of motility function, that is, the rate of propulsion and intensity of mixing/turning over. The esophageal muscles generate predominantly GMCs that rapidly propel the swallowed bolus from the pharyngeal sphincter into the stomach without any mixing, because no digestion/absorption occurs in this organ. The gastric fundus serves as a temporary reservoir to hold the ingested meal. It relaxes (adaptive relaxation) to accommodate the large volume of ingested meal. Thereafter, it generates a slowly rising tonic contraction that gradually transfers the meal to the corpus, where the mixing and propulsive movements begin [5]. The gastric corpus and antrum generate primarily RPCs to mix the ingested meal with acid and pepsinogen secretions. The amplitude of a gastric RPC increases as it propagates from the corpus to the antrum. Under appropriate antropyloroduodenal coordination, a small bolus of the ingested meal empties into the duodenum with each propagating gastric RPC.

The small intestine generates all three types of contractions. Its tone increases after a meal to narrow the lumen [21]. Intestinal RPCs cause mixing/turnover and slow net distal propulsion of the digesta. The percentage of small intestinal postprandial RPCs that propagate and the mean distance of their propagation decrease from the duodenum to the terminal ileum, which accounts for the decrease in propulsion rate and the intensification of mixing/turning over from the duodenum to the ileum [1, 2, 25, 26]. In healthy individuals, the few GMCs in the small intestine occur in the terminal ileum to empty rapidly any material refluxed from the proximal colon to the terminal ileum [27].

In practice, GMCs can start anywhere in the small intestine and propagate uninterruptedly to the terminal ileum. In extreme cases of rapid propulsion, a GMC may begin in the distal small intestine and propagate uninterruptedly all the way to the anal sphincter to expel the entire contents of the distal small intestine and the colon within a few minutes. The small intestine also generates RGCs, which rapidly retropel the contents of the proximal half of the small intestine into the stomach in preparation for vomiting [7]. RGCs occur in response to ingestion of a noxious substance or in response to a central stimulus. RGCs invariably start in the mid small intestine and propagate uninterruptedly to the antrum. RGCs may not start distal to the mid small intestine, probably due to regurgitation of unpleasant digesta in the distal small intestine and because it may be just as easy to rapidly expel the digesta from these locations via the colon by GMCs. In contrast to the stomach and the small intestine, the colon generates only RPCs, GMCs, and TCs. The following section discusses the roles of these types of contractions in colonic motility function.

Functions and Spatiotemporal Characteristics of Colonic Contractions

The colon is the final major organ in the gastrointestinal tract. Its motility function has a major impact on the frequency and timing of defecation as well as on the consistency and shape of stools. These variables differ markedly between species. For example, both humans and dogs normally defecate once or twice a day and have formed feces. On the other hand, rodents and guinea pigs—used frequently in experimental studies—defecate frequently and produce pellets. Consequently, the composition of the above three types of colonic contractions differs between species. In addition, the spatiotemporal characteristics of the same type of contraction differ in the colons of different species. For example, GMCs occur only a few times a day in human and dog colons, but in rodent colons, these contractions occur frequently but irregularly [12–18]. It is, therefore, crucial to identify the type of contraction to evaluate colonic motor function and investigate its mechanisms of regulation by species. Failure to do so would make it difficult to extrapolate the findings from animal models to human colonic motility function in health and disease and may lead to contradictory results because the regulatory mechanisms of different types of colonic contractions differ. For example, slow waves regulate the maximum frequency and timing of RPCs, but they do not regulate these characteristics in GMCs and TCs.

The colon wall, like the rest of the gut, has two outer muscle layers: the circular muscle layer and the longitudinal muscle layer. In humans, the longitudinal muscle layer is bundled into three-taenia coli with a thin longitudinal muscle coat over the rest of the surface. In other species, such as dogs, the longitudinal muscle layer is a thin uniform coat around the circumference. The contractions of the circular muscle cells partially or completely occlude the lumen, and hence, they are effective in mixing, turning over, and propulsion as they propagate. Contractions of the longitudinal muscle shorten the length of the colon, which has minimal effect on mixing and propulsive functions. For this reason, the following sections do not discuss longitudinal muscle contractions.

Colonic Rhythmic Phasic Contractions

The spatiotemporal characteristics of RPCs, which cause the postprandial function of mixing/turnover and net distal propulsion, differ between organs. For example, the maximum frequency of contractions in the human stomach is about 3 times per minute, in the duodenum about 12 times per minute, which decreases to about 6 to 8 times per minute in the ileum. The digesta in the stomach and the small intestine is largely fluid. By contrast, the fluid contents of the ascending colon gradually become semisolid to solid in the sigmoid colon as water is absorbed. To meet the challenge of turning over and slowly propelling the semisolid to solid contents, the colon generates two types of RPCs, short-duration RPCs (2 to 3 seconds in duration) and long-duration RPCs (15 to 20 seconds) [29–31] (Figure 8). The short-duration contractions show little or no propagation, and their amplitudes vary considerably. The long-duration contractions may propagate over short distances [29]. The longer duration of long-duration RPCs enables them to turn over and propel the semisolid to solid contents more effectively. The frequency of short-duration RPCs in the human colon is about 3 to 12 times per minute; that of long-duration RPCs is about 0.5 to 2 times per minute. Short-duration RPCs occur more frequently, while long-duration RPCs occur in bursts generally lasting a few minutes [29, 30]. The variability in the frequency of colonic RPCs is much greater than that of gastric and small intestinal RPCs. Together, colonic RPCs are highly disorganized in space and vary widely in amplitude and duration, making them effective in turning over of fecal material with a very slow rate of propulsion. Different mechanisms regulate these two types of phasic contractions, as discussed later.

FIGURE 8

Short- and long-duration contractions in canine and human colons. The top tracing shows short-duration RPCs in the dog colon. The second tracing shows long-duration RPCs. The third tracing from the top shows three long-duration RPCs followed by a series (more...)

The rodent colon also generates RPCs, but their amplitude in the intact conscious state is very small when recorded by strain gauge transducers [12, 15, 18]. The feces, already semisolid in the proximal rat colon, form discrete hard pellets in the middle and distal colons. The small-amplitude RPCs are unlikely to affect significantly the mixing or propulsion of these contents. Instead, the rodent colon generates frequent GMCs [12, 13, 32], as discussed in the next section.