Rheology of human faeces and pathophysiology of defaecation.

BACKGROUND: Rectal evacuation involves multiple mechanisms that are not completely understood. The aim of this study was to quantify the rheologic property, i.e., yield stress, which governs the ease of deformation of a range of faeces of differing consistency and understand its influence on the pathophysiology of defaecation. METHODS: Yield stresses of faeces of differing consistencies and Bristol scores were determined by the Vane test. We then explored the effects of this property on ease of defecation using a simple static model of the recto-anal junction based on the laws of flow for yield stress pastes and checked the conclusions by X-ray defaecography experience. RESULTS: The yield stress of faeces increased exponentially with their solid content, from 20 to 8000 Pa. The static model of the recto-anal junction showed that evacuation of faeces of normal consistency and yield stress is possible with moderate dilatation of the anal canal, whilst the evacuation of faeces with higher yield stress requires greater dilatation of the anal canal. X-ray defaecography showed that such increases occurred in vivo. CONCLUSIONS: The diameter of the recto-anal junction is increased to enable the passage of feces with high yield stress. The finite limits to such dilation likely contribute to fecal impaction. Hence, difficulties in defaecation may result either from unduly high yield stress or pathologies of reflex recto-anal dilatation or a combination of the two.

Deconstructing the physical processes of digestion: reductionist approaches may provide greater understanding.

I provide a broad overview of the physical factors that govern intestinal digestion i.e. the admixture of food particles in digesta with secreted enzymes and the subsequent mass transfer of liberated nutrients from the surfaces of particles to the gut wall, with a view to outlining the quantitative work that is required to determine the relative importance of these factors in the digestion of particular foods. I first discuss what is known of the mechanical forces generated by contraction of the walls of the various segments of the gut and the level of diffusive, and advective mixing that it generates within the lumen. I then discuss the particular physical effects that may limit the digestion of solid, physically and/or chemically homogenous and heterogeneous food particles, notably capillarity, porosity, poro-elastic flow and compaction and their likely effects on diffusive and convective mass transfer at particulate surfaces. Similarly, I discuss mucins and morphology on mass transfer of nutrients to the gut wall i.e. the mucosa.

Spatiotemporal analysis of spontaneous myogenic contractions in the urinary bladder of the rabbit: timing and patterns reflect reported electrophysiology.

The dynamics of propagating myogenic contractions in the wall of the resting ex vivo urinary bladder of the rabbit were characterized by spatiotemporal maps and related to cyclic variation in intravesical pressure (Pves). Patches of propagating contractions (PPCs) enlarged and involuted in near synchrony with peaks in Pves [mean 3.85 ± 0.3 cycles per minute (cpm)] and were preceded by regions of stretch. The maximum area of the bladder undergoing contraction (55.28 ± 2.65%) and the sizes of individual PPCs (42.61 ± 1.65 mm2) coincided with the peak in Pves PPCs originated and propagated within temporary patch domains (TPDs) and comprised groups of nearly synchronous cyclic propagating individual contractions (PICs). The TPDs were located principally along the vertical axis of the anterior surface of the bladder. The sites of origin of PICs within PPCs were inconsistent, consecutive contractions often propagating in opposite directions along linear maps of strain rate. Similar patterns of movement occurred in areas of the anterior bladder wall that had been stripped of mucosa. Pves varied cyclically with area of contraction and with the indices of aggregation of PPCs, indicating that they grew by peripheral enlargement and collision without annihilation. The synchronization of PICs within PPCs was sometimes lost, uncoordinated PICs then occurring irregularly (between 4 and 20 cpm) having little effect on Pves We postulate that the formation and involution of PPCs within a TPD resulted from cyclic variation in excitation that increased the incidence and distance over which component PICs propagated.

The first of the viscoceuticals? A shear thickening gum induces gastric satiety in rats.

We examined the effect of gavage of 4 ml of a viscous shear-thickening polysaccharide solution (15% w/w) extracted from the fronds of the mamaku tree fern (Cythea medullaris) in reducing appetite and delaying gastric emptying in twenty six Sprague Dawley rats. After two weeks habituation to a pelleted chow, the rats were gavaged on alternate days with either the mamaku extract or with the same volume of deionised water for a total of five times over a period of two weeks. The body mass and food intake of each rat were determined daily and the weights of their stomach contents determined on euthanasia two hours after the final gavage. The rats gavaged with the mamaku gum consumed significantly lower quantities of chow on the day of gavage. The weights of the stomach contents of rats two hours after gavage with mamaku extract were significantly greater than those following gavage with water. The failure of the rats dosed with mamaku to lose body weight likely resulted from the overall adverse effect of gavage on food intake, the limited numbers of doses of the gum and the rebound hyperphagia on days when the rats were not gavaged. Together the results indicate that gavage with mamaku gum delayed gastric emptying with respect to that of rats dosed with water and supressed appetite for 12-24 hours after dosage.

Continuous wavelet analysis of postprandial EGGs suggests sustained gastric slow waves may be slow to develop in infants with colic.

BACKGROUND: Electrogastrography in conjunction with Fast Fourier transform has limited success in detecting low grade abnormalities in gastric electrophysiological activity owing to the non-stationarity of the signal. Analysis by continuous wavelet transform is suitable for non-stationary signals and was used to analyse EGG activity in babies with and without colic. METHODS: Thirty minute postprandial EGG recordings were obtained from 23 sleeping breast-fed infants with clinically validated recurrent colic and 26 breast-fed non-colicky infants. Continuous wavelet transform analysis (CWT) identified three principal frequency components. The mean, standard deviation, and the number of frequency maxima that fell below one standard deviation from the mean were determined for each infant and each frequency. KEY RESULTS: Three component frequencies in the ranges 1.4-2.5 cpm, 2.5-4.0 cpm, and 4.0-15 cpm were found in all EGGs. Pairwise comparisons of the characteristics of each of the frequency ranges by univariate analyses showed significant differences between colicky and non-colicky subjects only in the number of maxima in the mid range of frequencies that lay below one standard deviation from the mean. However, CWT based on all frequencies allowed discrimination of the EGGS of colicky from non-colicky babies on a basis of number of frequency maxima below one standard deviation from the mean in the midrange of frequencies and in the mean and standard deviation in the low range of frequencies that was likely a harmonic of the midrange. CONCLUSIONS & INFERENCES: CWT allowed distinction of EGG signals from colicky and healthy babies. The results indicate that colic may result from tardiness in the establishment of coherent propagation of the gastric slow wave in colicky babies.

Advanced spatiotemporal mapping methods give new insights into the coordination of contractile activity in the stomach of the rat.

We used spatiotemporal mapping of strain rate to determine the direction of propagation and amplitudes of the longitudinal and circumferential components of antrocorporal (AC) contractions and fundal contractions in the rat stomach maintained ex vivo and containing a volume of fluid that was within its normal functional capacity. In the region of the greater curvature the longitudinal and circular components of AC contractions propagated synchronously at right angles to the arciform geometric axis of the stomach. However, the configuration of AC contractions was U shaped, neither the circular nor the longitudinal component of contractions being evident in the upper proximal corpus. Similarly, in the distal upper antrum of some preparations, circumferential components propagated more rapidly than longitudinal components. Ongoing "high-frequency, low-amplitude myogenic contractions" were identified in the upper proximal gastric corpus and on the anterior and posterior wall of the fundus. The amplitudes of these contractions were modulated in the occluded stomach by low-frequency pressure waves that occurred spontaneously. Hence the characteristics of phasic contractions vary regionally in the antrum and corpus and a previously undescribed high-frequency contractile component was identified in the proximal corpus and fundus, the latter being modulated in synchrony with cyclic variation in intrafundal pressure in the occluded fundus.

A method for assessing real time rates of dissolution and absorption of carbohydrate and other food matrices in human subjects.

We prepared pasta of differing physical dimensions but identical chemical composition that contained two monosaccharide probes (lactulose and mannitol) that are absorbed passively and promptly excreted in urine. We showed that the rates of their liberation from the pasta under simulated gastric and small intestinal conditions largely depended upon the rate of digestion of the starchy matrix. We showed, in 20 female subjects, that excretion of mannitol was slower from the pasta with the larger particle size. Hence, after consumption of either the powdered pasta or the simple solution of probe sugars, the mass of mannitol excreted between 1 and 2½ hours was greater than that excreted between 2½ and 4 hours. However these masses did not differ significantly after consumption of the pasta pellets. These differences were not reflected in the concurrent patterns of variation in either serum glucose or insulin taken over 120 minutes, their levels being similar for pasta pellets and powder with their peak values occurring synchronously during the first hour. Hence feeding test foods impregnated with lactulose and mannitol probes provided a reproducible and practical means of assessing the timing of digestion of the carbohydrate matrix and showed that this was more protracted than suggested by post prandial glucose levels. Further, the transit times calculated on a basis of the ratios of the two marker sugars could identify that the prolongation of digestion of larger particles was not accompanied by retention of digesta in particular segments of the gut.

Flow and mixing by small intestine villi.

Flow and mixing in the small intestine are multi-scale processes. Flows at the scale of the villi (finger-like structures of ≈500 µm length) are poorly understood. We developed a three-dimensional lattice-Boltzmann model to gain insight into the effects of villous movements and the rheology of digesta on flow, mixing and absorption of nutrients at the periphery of the intestinal lumen. Our model simulated the hydrodynamic consequences of villi movements that resulted from folding of the mucosa during longitudinal contractions. We found that cyclic approximation and separation of groups of villi generated laminar eddies at the edges of the group and augmented mass transfers in the radial direction between the inter-villous space and the intestinal lumen which improved the absorption of nutrients and mixing at the periphery of the lumen. This augmentation was greater with highly diffusible nutrients and with high levels of shear-thinning (pseudoplasticity) of the fluid. We compared our results with bulk flows simulations done by previous workers and concluded that villous movements during longitudinal contractions is a major radial mixing mechanism in the small intestine and increases mixing and absorption around the mucosa despite adverse rheology.

A review of mixing and propulsion of chyme in the small intestine: fresh insights from new methods.

The small intestine is a convoluted flexible tube of inconstant form and capacity through which chyme is propelled and mixed by varying patterns of contraction. These inconstancies have prevented quantitative comparisons of the manner in which contractile activity engenders mixing of contained chyme. Recent quantitative work based on spatiotemporal mapping of intestinal contractions, macro- and micro-rheology, particle image velocimetry and real-time modelling has provided new insights into this process. Evidence indicates that the speeds and patterns of the various types of small intestinal contraction are insufficient to secure optimal mixing and enzymatic digestion over a minimal length of intestine. Hence particulate substrates and soluble nutrients become dispersed along the length of the lumen. Mixing within the lumen is not turbulent but results from localised folding and kneading of the contents by contractions but is augmented by the inconstant spatial disposition of the contractions and their component contractile processes. The latter include inconstancies in the sites of commencement and the directions of propagation of contraction in component groups of smooth muscle cells and in the coordination of the radial and circular components of smooth muscle contraction. Evidence suggests there is ongoing augmentation of mixing at the periphery of the lumen, during both the post-prandial and inter-meal periods, to promote flow around and between adjacent villi. This results largely from folding of the relatively inelastic mucosa during repeated radial and longitudinal muscular contraction, causing chyme to be displaced by periodic crowding and separation of the tips of the relatively rigid villi. Further, micro-rheological studies indicate that such peripheral mixing may extend to the apices of enterocytes owing to discontinuities in the mobile mucus layer that covers the ileal mucosa.

Survival implications of the development of behavioural responsiveness and awareness in different groups of mammalian young.

This paper focuses on the development of behaviours that are critical for the survival of newborn and juvenile mammals of veterinary and wider biological interest. It provides an updated, integrated and comparative analysis of how postnatal maturation of sensory, motor and perceptual capacities support and constrain behavioural interactions between mammalian young and the mother, any littermates and the environment. Young that are neurologically exceptionally immature, moderately immature and mature at birth are compared, and include, for example, marsupial joeys, rodent pups and ruminant offspring. Mothers in these three groups exhibit distinctive patterns of birthing and postnatal care behaviours. To secure survival of the young, maternal care must compensate for behavioural inadequacies imposed by the limited sensory capacities the young possess at each stage. These sensory capacities develop in a predictable sequence in most mammals such that before birth the sequence progresses to an extent that parallels the degree of neurological maturity reached at birth. The extent of neurological maturity is likewise reflected in how long it takes after birth for the necessary brain circuit connectivity to develop sufficiently to support cortically based cognitive modulation of behaviour. This takes several months, days-to-weeks or minutes-to-hours in young that are, respectively, neurologically exceptionally immature, moderately immature, or mature at birth. Once achieved, cognitive awareness confers a high degree of behavioural flexibility that allows the young to respond more effectively to the unpredictability of their postnatal environments. It is shown that the onset of this cognitively based flexibility in the young of each group coincides with their first exposure to a variable environment that requires such behavioural flexibility.

Spatiotemporal organization of standing postprandial contractions in the distal ileum of the anesthetized pig.

BACKGROUND: Spatiotemporal (ST) mapping has mainly been applied to ex vivo preparations of the gut. We report the results of ST mapping of the spontaneous and remifentanil-induced motility of circular and longitudinal muscles of the distal ileum in the postprandial anaesthetized pig. METHODS: Spatiotemporal maps of strain rate were derived from image sequences of an exteriorized loop of ileum on a superfusion tray at laparotomy. Parameters were obtained by direct measurement from these maps, and by auto- and cross-correlation of map segments. KEY RESULTS: Localized domains of standing longitudinal and circular activity that alternated between neighboring domains occurred spontaneously and both were promptly extinguished following intraluminal dosage with lidocaine. Longitudinal or circular contractions within a domain typically occurred at times that would coincide with every second or third cycle of the slow wave but propagated within the domain at a rate consistent with that reported within spike patches. Shortly after intravenous administration of remifentanil, longitudinal and circular contractions at the reported slow wave frequency propagated over longer distances at a high speed before slowing to a rate similar to that reported for slow waves. CONCLUSIONS & INFERENCES: ST mapping based on cross-correlation is a robust tool for the analysis of intestinal movement and minimizing movement artefacts. We propose that the ST pattern of standing longitudinal and circular contractions arises from variation in the refractory period of smooth muscle, and hence, in its response to successive slow waves with neural stimuli influencing the former and having a mainly permissive role.

Gastrointestinal tone; its genesis and contribution to the physical processes of digestion.

BACKGROUND: Myogenic tone has long been recognised as an important component of gastrointestinal motility. Recent work has clarified the cellular mechanisms that engender tone and the neurogenic and mechanical stimuli that modulate it but has also highlighted cellular and regional specialisation in these mechanisms within the GI tract. Smooth muscle in all segments of the gut has the capability of latching, i.e. can generate ongoing specific rather than tetanic tone. This is likely modulated by both direct and indirect input from agonists such as acetylcholine and mechanoreceptors, the latter originating in ICC-IM, smooth muscle cells or elements of the ENS. Tonic contraction can occur in the absence of phasic contractions or concurrent with them, and it can modulate wall compliance and the capacity of particular segments, thereby affecting the level of on-flow and mixing, both luminal and adjacent to the mucosa. PURPOSE: The review seeks to provide an overview of our understanding of the mechanism by which tone is generated and maintained, highlighting its modulation by neurogenic and mechanical stimuli, its mechanical consequences in the walls of the various segments of the gastrointestinal tract and its contribution to flow and mixing of contained digesta.

Mucosal microfolds augment mixing at the wall of the distal ileum of the brushtail possum.

BACKGROUND: Recent work suggests that mixing in the small intestine takes place in central luminal and peripheral compartments. However, while movements of villi have been described, the mechanisms by which peripheral mixing are engendered remain unclear. METHODS: We examined the disposition and movement of mucosa and associated villi during contractions of the everted terminal ileum of the brushtail possum. We then simulated the effect of these movements on peripheral mixing. KEY RESULTS: Compression of the intestinal mucosa by phasic longitudinal or radial contractions created short-lived microfolds, which were of similar scale to the attached villi. The packing density of the villous tips increased in the concavities and decreased on the crests of these microfolds. Simulations showed that these caused liquid digesta to be expelled from, or drawn into, intervillous spaces, significantly augmenting peripheral, but not bulk, luminal mixing. CONCLUSIONS & INFERENCES: We describe a mechanism by which peripheral mixing may be engendered by mucosal microfolds without requiring the coordinated contraction of individual villi or groups of villi.

An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum (Trichosurus vulpecula).

Multiple particle-tracking techniques were used to quantify the thermally driven motion of ensembles of naked polystyrene (0.5 µm diameter) microbeads in order to determine the microrheological characteristics around the gut mucosa. The microbeads were introduced into living ex vivo preparations of the wall of the terminal ileum and proximal colon of the brushtail possum (Trichosurus vulpecula). The fluid environment surrounding both the ileal villi and colonic mucosa was heterogeneous; probably comprising discrete viscoelastic regions suspended in a continuous Newtonian fluid of viscosity close to water. Neither the viscosity of the continuous phase, the elastic modulus (G') nor the sizes of viscoelastic regions varied significantly between areas within 20 µm and areas more than 20 µm from the villous mucosa nor from the tip to the sides of the villous mucosa. The viscosity of the continuous phase at distances further than 20 µm from the colonic mucosa was greater than that at the same distance from the ileal villous mucosa. Furthermore, the estimated sizes of viscoelastic regions were significantly greater in the colon than in the ileum. These findings validate the sensitivity of the method and call into question previous hypotheses that a contiguous layer of mucus envelops all intestinal mucosa and restricts diffusive mass transfer. Our findings suggest that, in the terminal ileum and colon at least, mixing and mass transfer are governed by more complex dynamics than were previously assumed, perhaps with gel filtration by viscoelastic regions that are suspended in a Newtonian fluid.

Spatiotemporal mapping of the muscular activity of the gizzard of the chicken (Gallus domesticus).

We report the results of spatiotemporal mapping of the spontaneous actions of component muscles of the gizzard and associated structures in ex vivo preparations with combined superfusion and vascular perfusion. Ongoing spontaneous contraction of cranial and caudal thin muscles occurred at a frequency of 2.2 ± 0.1 cycles per minute. Contractions of M. tenuis craniodorsalis with mean duration of 2.8 ± 0.2 s commenced ventrally adjacent to the distal limit of the proventriculus and progressed dorsally at 2.02 ± 0.03 mm•s(-1) in a concerted front. Near simultaneous contraction of M. tenuis caudoventralis of mean duration of contraction of 4.7 ± 0.7 s commenced dorsally and progressed ventrally at a similar rate (2.1 ± 0.1 mm•s(-1)) and in a similar manner. Contraction of the caudoventralis preceded that of craniodorsalis (mean 1.1 ± 0.15 s). Contraction of the 2 tenuis muscles was synchronous with the first component peak of the cyclic increase in lumen pressure and with distension of the crassus musculature. Contraction of the M. crassus caudodorsalis muscle coincided with the second component peak and was followed by distension of the tenuis musculature. The latter commenced before the relaxation of the tenuis muscles. Contractions of the crassus muscle propagated rapidly at right angles to the orientation of the muscle fibers at a faster velocity than that of the tenuis musculature. The durations of the component peaks in lumen pressure indicated that the duration of crassus contraction was similar to that of the tenuis musculature.

The effect of aspirin and smoking on urinary excretion profiles of lactulose and mannitol in young women: toward a dynamic, aspirin augmented, test of gut mucosal permeability.

BACKGROUND: We explored the temporal dynamics of the lactulose mannitol test and the influence of a single dose of aspirin. METHODS: Twenty healthy female volunteers each received 600 mg aspirin or placebo in random sequence and were subsequently dosed with 10 g lactulose and 5 g mannitol, their urine collected every half hour for 6h. KEY RESULTS: The lactulose:mannitol ratios (LMR) of urine samples collected over the entire 6-h period were significantly higher than those collected in the first 3 h. Greater quantities of mannitol were excreted over the first than the subsequent 3 h. A similar pattern of temporal variation in mannitol excretion was found in smokers and non-smokers and was maintained following administration of a single 600 mg dose of aspirin. The rates at which lactulose was excreted were relatively constant over the entire 6 h period of collection, but mean levels were increased over the entire 6 h following the administration of aspirin. The effect of aspirin did not differ significantly between smokers and non-smokers. CONCLUSIONS & INFERENCES: While the LMR test is sufficiently sensitive to reproducibly detect the increase in intestinal permeability resulting from a single 600 mg oral dose of aspirin, the temporal patterns of excretion of mannitol and lactulose differ both in the presence and absence of aspirin. Hence, variation in sampling period and in method of dosage are likely to influence the result and it is preferable to examine the patterns of absorption of component sugars separately with due regard to the method of dosage.

A comparison of the organization of longitudinal and circular contractions during pendular and segmental activity in the duodenum of the rat and guinea pig.

BACKGROUND: Little is known of the spatiotemporal organization of pendular duodenal contractions. METHODS: We used longitudinal and radial spatiotemporal mapping to examine and compare pendular and segmental contractile activity in the proximal duodenum of the rat and guinea pig when the lumen was perfused with saline or micellar decanoic acid. KEY RESULTS: Isolated phasic longitudinal contractions occurred along the rat duodenum with a frequency of 36 ± 2 cpm and strain rate amplitude of 26.8 ± 8.0% s(-1). These contractions occurred at fixed locations along the duodenum forming columns on the longitudinal strain rate map. The strain rate activity had local maxima at 4-6 points spaced at 7.7 ± 4.0 mm intervals along the duodenum and were uncoordinated between neighboring domains. Similarly disposed, less distinct, longitudinal contractions occurred in the guinea pig duodenum at a frequency of 25.2 ± 6.6 cpm with amplitude 6.8 ± 3.6% s(-1) but these were generally accompanied by numerous circular contractions that were distributed over 4-5 fixed locations and occurred with a frequency of 9 ± 3 cpm. Isolated static circular muscle contractions also occurred but at a lower rate in the rat than the guinea pig. Both types of contractions propagated after dosage with tetrodotoxin, lidocaine, atropine, or apamin. CONCLUSIONS & INFERENCES: Localized contractions during segmental and pendular activity had some features of the spike patches that are normally associated with slow wave propagation. However, the commencement of propagation following administration of neural blocking agents and cholinergic inhibitors indicates their localization is maintained by inhibitory elements of the enteric nervous system.

Identification of multiple compartments present during the mastication of solid food.

The particle size distributions (PSDs) of two portion sizes (2g and 4g) of five foods (cake, cereal bar, muesli bar, cooked pasta and peanuts) after human mastication were determined. The PSD of the expectorated bolus and residual 'debris' rinsed from the mouth were each determined by wet sieving. There were significant differences in the PSD between food types, between portion sizes in the debris fraction and between the bolus and debris fractions. The latter suggests the existence of a two compartment system where particles are comminuted in at least one compartment within the oral cavity.

Changes in the viscoelastic behaviour of the rumenal digesta mat of sheep fed on pasture or chaffed lucerne hay.

We examined the changes in the physical properties of the digesta mat over a period of 24 h after cessation of feeding, in sheep that had been maintained on pasture or fed chaffed lucerne hay. The dry matter content of the digesta mat declined at similar rates in both dietary groups, although it was generally higher in sheep fed lucerne. Median particle size declined in the digesta mats of both dietary groups at similar rates in samples taken after 8 h, but median particle size was significantly greater in sheep fed chopped lucerne hay than in those fed grass. Thus, particles were not reduced to a common size suggesting that factors in addition to particle size governed the rate of breakdown of the rumen mat. The relationship between the elastic and loss moduli was of a consistent pattern in all samples taken from the rumen mat indicating that it behaved as a weak gel. The elastic and loss moduli of the digesta mats of sheep that had been fed pasture or chopped lucerne hay converged to similar values after 12 h and declined broadly at similar rates after this. The relationship between these two moduli and the dry matter content of the rumen mat were of similar curvilinear form for sheep on both diets. These findings suggest that the rate of breakdown of the rumen mat is more likely to be governed by its composite behaviour than by the size of the constituent particles.