Which of the following is not a digestive function

78.9.1.3.1 Digestive Dysfunction

Impaired digestive function during intestinal inflammation could have significant consequences for nutritional status, particularly in chronic diseases of the small intestine, such as Crohn’s disease. Deficits in digestive function could be ascribed to a loss of brush border enzyme activity caused by decreased surface area of the small intestine. However, the recent literature is surprisingly sparse regarding the effects of inflammation on digestive enzyme activities. In earlier studies of rats infected with the nematode N. brasiliensis, villous atrophy was associated with decreased activities of digestive enzymes.252 In rabbits infected with Yersinia enterocolitica, decreased brush border enzyme activities were associated with decreased brush border surface area.253 The effect was more persistent in the jejunum and more transient in the ileum. Exposure of the rat small intestine to ionizing radiation causes a decrease in brush border peptidases secondary to release of the enzymes into the lumen, where they retain their activity.254 In studies of human biopsies, disaccharidase activity was decreased in inflamed proximal duodenum, and the degree of deficit is proportional to the severity of inflammation.255 In ileal Crohn’s disease, activities of lysophospholipase and disaccharidases were decreased in inflamed regions and, interestingly, also in non-involved areas of ileum, albeit to a lesser extent.256 More recent studies have begun to investigate the mechanisms underlying inflammation-induced changes in the expression of digestive enzymes. In the human intestinal epithelial cell line Caco-2, IL-6 and IFN-γ both caused a decrease in sucrase-isomaltase gene expression, whereas TNF-α caused an increase and IL-1β had no effect.257 This was not a generalized effect on all digestive enzymes because expression of lactase was not affected by these cytokines. Decreases in sucrase-isomaltase expression were also observed in Crohn’s disease.257 More studies are warranted to further examine the mechanisms underlying altered digestive enzyme expression in inflamed gut and to determine the importance of this functional deficit in the nutrient malabsorption characteristic of chronic inflammatory intestinal diseases.

Digestive Dysfunction

Impaired digestive function during intestinal inflammation could have significant consequences for nutritional status, particularly in chronic diseases of the small intestine, such as Crohn's disease. Deficits in digestive function could be ascribed to a loss of brush-border enzyme activity caused by decreased functional surface area of the small intestine. However, the recent literature is surprisingly sparse regarding the effects of inflammation on digestive enzyme activities. In earlier studies of rats infected with the nematode Nippostrongylus brasiliensis, villous atrophy was associated with decreased activities of digestive enzymes (182). In rabbits infected with Yersinia enterocolitica, decreased brush-border enzyme activities were associated with decreased brush-border surface area (183). The effect was more persistent in the jejunum and more transient in the ileum. Exposure of the rat small intestine to ionizing radiation causes a decrease in brush-border peptidases secondary to release of the enzymes into the lumen, where they retain their activity (184). In studies of human biopsies, disaccha-ridase activity was decreased in inflamed proximal duodenum, with the degree of deficit being proportional to the severity of inflammation (185). In ileal Crohn's disease, activities of lysophospholipase and disaccharidases were decreased in inflamed regions and, interestingly, also in noninvolved areas of ileum, albeit to a lesser extent (186).

More recent studies have begun to investigate the mechanisms underlying inflammation-induced changes in the expression of digestive enzymes. In the human intestinal epithelial cell line Caco-2, IL-6 and IFN-γ both cause a decrease in sucrase-isomaltase gene expression, whereas TNF-α caused an increase and IL-1β had no effect (187). This was not a generalized effect on all digestive enzymes because expression of lactase was not affected by these cytokines. Decreases in sucrase-isomaltase expression were also observed in Crohn's disease (187). More studies are warranted to further examine the mechanisms underlying altered digestive enzyme expression in inflamed gut and to determine the importance of this functional deficit in the nutrient malabsorption characteristic of chronic inflammatory intestinal diseases.

Large Intestine (Da Chang)

The digestive function of the Large Intestine, as described in TCM, is very similar to that understood in Western medicine. In some Chinese texts it is described as ‘passing and changing’, referring to what happens to the faecal matter. However, many of the normal functions of the Large Intestine are also ascribed to the Spleen. The most important action is the reception of food and drink from the Small Intestine, and the reabsorption of a proportion of the fluid. The remainder goes to make up the faeces and is excreted.

The Large Intestine is the final part of the digestive system and will reflect any imbalances occurring in the other organs of digestion in terms of quantity or quality.

Deficient Yang energy in the Spleen is also called Deficient Energy in the Large Intestine because both tend to result in the same symptoms. This means that the Large Intestine is part of the fluid balance mechanism of the body. The Large Intestine is linked to the Lung both interiorly and exteriorly via the meridians and can therefore have an influence on the Lung/Kidney water cycle. The Lung is said to disperse water while the Large Intestine absorbs it. Equally the Lung takes in air while the Large Intestine discharges gas. If there is Heat in the Lung the faeces will be dry and if the function of the Lung is weak the faeces tend to be loose. Simple stagnation of food in the Large Intestine or constipation can give rise to a degree of breathlessness.

If the Large Intestine is functioning poorly the mind becomes unclear and muddled. It is as though the failure to eliminate the waste leaves feelings of staleness and lifelessness. Many neurological patients suffering from constipation will describe the effect of it in just this way, as will those suffering from a drug-induced constipation. Optimum functioning of the body requires elimination of that which is no longer of use, both physically and psychologically.

Small Intestine

The ultimate digestive function of the small intestine requires intestinal epithelium to secrete digestive enzymes and to provide sufficient surface area to absorb nutrients. Therefore, it is important to understand the development of the cellular differentiation as well as overall intestinal length.

As previously mentioned, the hedgehog signaling pathway is also important in endodermal and mesodermal differentiation in small intestinal development. In addition, the genes encoding for the transcription factors Sox9, Sox17, and SRY have been shown to be essential in endoderm differentiation, whereas the Hox family of transcription factors are involved in mesodermal differentiation (de Santa Barbara et al, 2003).

After differentiation, the intestinal villous and crypt development is under the control of several growth factors that are secreted in autocrine, paracrine, endocrine, and exocrine pathways (Ménard, 2004). Glucagon-like peptide 1 and 2 are secreted by intestinal neurons and L cells, respectively, and are associated with increased intestinal length (Sigalet et al, 2004). Clinical trials in adults are underway administering glucagon-like peptide 2 in patients with short bowel syndrome and may eventually show promise in pediatric patients with intestinal failure.

The small intestine is well developed after its extracorporeal migration into the umbilical cord. Rapid epithelial proliferation occludes the small-intestinal lumen early in development, but the lumen becomes patent at 12 weeks’ gestation. There is a gradual development of digestive function that is not fully complete until 34 weeks’ gestation, thus posing additional problems regarding administering enteral nutrition to premature infants.

Small Intestine

The ultimate digestive function of the small intestine requires intestinal epithelium to secrete digestive enzymes and to provide sufficient surface area to absorb nutrients. Therefore it is important to understand the development of the cellular differentiation as well as overall intestinal length.

As previously mentioned, the hedgehog signaling pathway is also important in endodermal and mesodermal differentiation in small-intestinal development. In addition, the genes Sox9, Sox17, and SRY that encode the corresponding transcription factors have been shown to be essential in endoderm differentiation, whereas the Hox family of transcription factor genes are involved in mesodermal differentiation (de Santa Barbara et al., 2003).

After differentiation, the intestinal villous and crypt development is under the control of several growth factors that are secreted in autocrine, paracrine, endocrine, and exocrine pathways (Ménard, 2004). Glucagon-like peptide 1 and 2 are secreted by intestinal neurons and L cells, respectively, and are associated with increased intestinal length (Sigalet et al., 2004). Clinical trials in adults are under way administering glucagon-like peptide 2 in patients with short bowel syndrome and may eventually show promise in pediatric patients with intestinal failure. Preclinical experiments show promise that trophic factors, including glucagon-like peptide 2, insulin-like growth factor, and epidermal growth factor, may be beneficial as therapies in neonatal and pediatric short bowel syndrome (Lim et al., 2016). New advances in the generation of intestinal organoids have brought a new dimension to understanding the molecules responsible for intestinal development and in vitro tissue engineering (Clevers et al., 2014).

The small intestine is well developed after its extracorporeal migration into the umbilical cord. Rapid epithelial proliferation occludes the small-intestinal lumen early in development, but the lumen becomes patent at 12 weeks' gestation. There is a gradual development of digestive function that is not fully complete until 34 weeks' gestation, thus posing additional problems regarding the administration of enteral nutrition to premature infants.

Bile Acid Functions

In addition to digestive functions, lipid metabolism, and molecular signaling, bile acids have regulatory effects on bile flow, hepatocyte cellular function, and regeneration. In the colon, bile salts promote propulsive motility, and in higher concentrations, they induce secretion. An antimicrobial effect in the intestine has been reported and may limit bacterial overgrowth. On a cellular level, bile acids can induce reactive oxygen and nitrogen species, DNA damage, and apoptosis.7 Their accumulation within hepatocytes initiates ligand-dependent and/or ligand-independent death receptor oligomerization and modulates these signaling pathways, resulting in a strong sensitization of hepatocytes to death receptor–mediated apoptosis.8 The functions of bile acids at various stages of the enterohepatic circulation are described schematically in Figure 3-1.

COORDINATION OF SECRETION AND MOTILITY

All aspects of digestive function are under the regulatory influence of extrinsic and intrinsic neurons. Because the initial hypothesis that intestinal propulsion was driven by local neuronal reflexes within the intestine, much of the subsequent work focused on the myenteric plexus, a predominant player in driving peristalsis. However, more recent work has clearly demonstrated that autonomous reflexes also exist in the submucosal plexus (52). Even though the myenteric plexus strongly influences submucous functions in vitro, mucosal-submucous preparations devoid of myenteric plexus still have intact neural reflex pathways regulating secretion. Furthermore, reflex-evoked dilation of arterioles and mucosal secretion from enterocytes are confined strictly within submucosal neurons.

Endocrine cells or mast cells can act as sensory cells that are triggered to release mediators on mechanical or chemical stimulation. Neurons that are in proximity may be triggered by applied force or by chemicals to regulate the release of 5-HT from enterochromaffin cells. Mediators released from these sensory cells may affect enterochromaffin cells in an autocrine (direct) manner or adjacent epithelial cells in a paracrine (indirect) manner, or they may affect these cells indirectly through their actions on neurons in proximity (neurocrine). There has been limited progress in understanding the complex regulation of 5-HT release in tissue studies because of the potential interference from mediators released from other cells. By far, most of our information on sensory signaling is centered on 5-HT release and its activation of IPANs (2,11).

Mucosal reflexes initiated by stroking or touch of the mucosa, balloon distention, and distortion of the mucosal surface cells and activation of enterochromaffin cells, alterations in luminal pH, nutrients, or nitrogen puffs on the mucosa all lead to secretion. Myenteric IPANs have their cell bodies in the myenteric plexus and a sensory process projecting to the mucosa. Intracellular recordings from myenteric AH/IPANs proved that mucosal stimulation causes excitation of these neurons that regulate motility. Submucous IPANs are presumed to respond to sensory stimulation, and this can be inferred from studies done in myenteric IPANs. It is not technically feasible to record mechanosensory responses in submucous IPANs because of their short afferent projections to the mucosal lining. Coordinated activity of neurons in submucous and myenteric plexuses is orchestrated, and appropriate secretion and vasomotor responses are triggered during normal or pathophysiologic circumstances.

Few studies have explored the integrative activity of the enteric nervous system in the coordination of secretion and motility (53–55). Two complementary techniques are being used to study coordination. Secretion is monitored by Isc current analysis of chloride secretion responses of whole-thickness colonic segments set up as flat sheets in Ussing chambers. Smooth muscle responses are monitored by either mini strain-gauge recordings of intestinal smooth muscle tension or sonomicrometric analysis of motion and change in muscle length (54). Dimaprit was used to activate histamine H2 receptors to identify neural circuits and transmitters involved in the coordination of secretion and muscle contraction. Dimaprit, acting on H2 receptors, was shown previously to induce a cyclical secretory response (1.6–1.8 cycles per 5 minutes) that was coordinated with changes in tension (55). Cyclical secretion and large-amplitude contractions (LACs) were abolished by the H2 receptor blocker cimetidine, or with tetrodotoxin blockade. Secretion and muscle contraction become uncoupled after severing the neural connections between submucous and myenteric plexuses. The stereotypical secretory response is initiated in the submucous plexus because it persists after removing the myenteric plexus. These studies illustrate that a neural program activated by histamine via submucous neurons is important in flushing out the lumen, and they support the notion that the submucous plexus is capable of autonomous control of muscle contractions, and presumably motility, and coordination of secretory and motility functions. Mucosal stroking experiments provided proof that purinergic activation of P2Y1R contributes to the coordination response.

Sonomicrometry uses tiny 1-mm diameter piezoelectric crystals to transmit and receive ultrasound waves and estimates motion with high spatial and temporal resolution. Isc was recorded simultaneously with muscle length by piezoelectric crystals fixed on the serosal surface 3 to 6 mm apart in the circular or longitudinal direction for monitoring responses in the two muscle layers, or alternatively, muscle tension was recorded by strain gauges sutured flush with the serosal surface.

Our coordination studies give proof that sonomicrometry is an excellent complementary method to mini strain-gauge recordings of muscle responses. Data indicated that inhibitory adenosine A1Rs modulate the histamine H2–mediated stereotypic pattern of cyclical secretion and motility with either technique. In these studies, dimaprit caused cyclical increases in Isc of 170 ± 23 μA/cm2 at frequencies of 1.2 cycles per 5 minutes. Cyclical changes in Isc were coordinated with LACs measured by sonomicrometry as intercrystal distance of 221 ± 35 μm (equivalent to 66% of the peak carbachol response of 335 ± 56 μm; n = 4). In strain-gauge coordination studies, dimaprit caused LACs of 1.4 ± 0.4 g tension in association with large increases in Isc of 116 ± 51 μA/cm2. The A1R agonist 2-chloro-N6-cyclopentyladenosine (CCPA) reduced or abolished cyclical Isc and LACs with either technique. Coordination of Isc and LACs was lost after CCPA. The adenosine A1R antagonist 8-cyclopentyltheophylline reversed the effects of the A1R agonist with both recording approaches.

Importance of Fiber to Gastrointestinal Tract Health

Fiber is important for digestive function. It provides bulk in the lower intestinal tract, retains water in the fecal matter, and aids in the passage of digesta through the gut. These are some of the positive benefits of insoluble fiber, most of which are largely due to its physical properties. A lack of fiber in the diet can result in constipation, poor stool formation, and compromised gut motility.

Fiber also may contribute to intestinal health due to its biochemical properties. Both soluble and insoluble fiber will be fermented by symbiotic microflora in the gut. The resulting short-chain fatty acids (e.g. butyrate, acetate, and propionate) will be absorbed by the colonic epithelium and will stimulate colonic blood flow and enhance absorption of fluid and electrolytes (Topping and Clifton, 2001). Butyrate is a preferred fuel for colonic epithelial cells, and appears to contribute to colon health (Topping and Clifton, 2001; Wong et al., 2006). Fiber fermentation products may contribute in a variety of ways to intestinal health.

In the wild, many primates feed on gums, a soluble fiber. This is especially true for the small-bodied callitrichid primates. The common marmoset (Callithrix jacchus) feeds extensively on gum in its native Brazil, which raises questions about the nutritional or physiological reasons to feed marmosets gum in captivity.

Gums are incomplete foods, providing mainly energy in the form of fermentable soluble fiber and minerals (Power, 2010). Gums have been suggested to serve as important calcium sources for galagos (Bearder and Martin, 1980) and marmosets and other callitrichids (Garber, 1984) in the wild. The levels of calcium in gums that have been assayed range from below 0.5% to around 1% on a dry matter basis. These are fairly high levels for wild foods, but most manufactured primate diets contain 0.8–1.2% calcium on a dry matter basis. If feeding gum reduces consumption of the nutritionally complete feed that should form the base of the diet, then calcium intake may not be increased. In contrast, substituting gum for fruit may indeed increase calcium consumption. However, that increase will come at the expense of decreasing the consumption of vitamins in fruit. At present, there are no demonstrated nutritional reasons for including gum in the diet of captive, gum-feeding primates. There are hypothetical advantages, such as providing a fermentable substrate that would increase butyrate production in the colon to enhance colonic health (Wong et al., 2006). However, some starches and pectins in captive callitrichid diets probably already reach the colon to be fermented, providing a source of butyrate. Gum added to the diets of common and pygmy marmosets appeared to slow the passage rate of digesta (Power, 1991; Power and Oftedal, 1996). Whether a slower passage rate of digesta would have any positive health benefits in captivity is unknown. Based on the lack of evidence that gum has a nutritional purpose in captive callitrichid diets, it should be treated as an enrichment food. Gum arabic syrup has been used successfully as an enrichment device for marmosets (McGrew et al., 1986).

Esophageal Transport

The esophagus has no direct digestive function. The esophageal mucosa secretes low amounts of mucus that contains no enzymes but serves to facilitate the bolus transport and to protect the esophageal mucosa against acid and other aggressive components of gastroesophageal refluxate such as pepsin and potentially pancreatic enzymes. The main function of the esophagus is to transport ingested material to the stomach. During swallowing, coordinated activities of lingual and pharyngeal muscles transport the bolus toward the upper esophageal sphincter whereas the nasopharynx and larynx need to be occluded. The upper esophageal sphincter relaxes briefly in order to allow entrance of the bolus into the esophagus. Within seconds, it closes again and the bolus is then propelled downward through the tubular part of the esophagus which is formed by striated muscles in the upper third and by smooth muscles in the lower parts. At each time during the peristaltic wave, a segment several centimeters in length is contracted. The food bolus is always pushed several centimeters ahead of the zone of maximal contractility that is located in the middle of the contracted segment. In the distal part of the tubular esophagus, intraluminal pressure may rise physiologically to up to 180 mmHg. Normal propagation velocity of the peristaltic wave ranges from 2 to 8 cm s–1. The lower esophageal sphincter, which normally maintains a resting pressure of about 15–30 mmHg that serves to prevent reflux of gastric contents, relaxes before the peristaltic wave arrives and, thus, lets the bolus pass into the stomach.

Phlegm-Damp and food

Poor eating habits or poor digestive function allows accumulation of Phlegm-Damp. A diet which is unlikely to create Damp is one which has few fatty rich foods and includes foods which help to mobilize fluids and break up congestion. Herbal digestives are often taken by Chinese people after a meal to help to avoid Damp accumulating, e.g., hawthorn flakes after eating heavy meats. Where there is already evidence of internal Phlegm-Damp (weight gain), reducing intake of fatty meats, dairy products, sweets (especially chocolate and ice cream), bread, and fried foods is important. Dairy products are one of the main dietary culprits for many Westerners, milk and cheese being such a popular part of the diet in countries like Australia, New Zealand, UK, France, and America. It is well known by nutritionists that adult Caucasians often lose the capacity to digest the components of dairy (specifically lactose) as they mature, and in the case of many Asians, that capacity was not there even in childhood. Some studies relate the inability to digest dairy products (or galactose, a sugar found only in milk) or overconsumption of dairy products, to impaired ovarian function.6 High levels of galactose appear to be toxic to ovarian germ cells and trials have been done to examine its association with premature ovarian failure.7

However, for women who can digest lactose and galactose and who do not have a tendency to Phlegm-Damp, then milk or dairy products can be an important source of protein and calcium.

In a case where infertility is related to Phlegm-Damp in the lower Jiao, a diet based on aromatic rice (and some millet and barley) with the addition of broad beans, chick peas and, especially, adzuki beans, will support the Spleen and drain Damp.8

The Clinical Handbook of Internal Medicine, Vol. 2, Chapter 26, provides more in depth discussion of diets for different constitutions with appropriate food inclusions or exclusions.9