Chapter 6 Gastrointestinal and digestive physiology
The main function of the gastrointestinal tract is the provision of the body’s nutritional requirements. This involves the mechanical propulsion of food along the gastrointestinal tract, its digestion (the breakdown of long-chain or complex food molecules into simpler units) and absorption of the products of digestion into the blood. Various exocrine secretions are involved in digestion and absorption, while the liver is important for the metabolic processing of the absorbed materials. These features will be considered in turn after a discussion of the nature and regulation of our daily diet.
6.1 Nutrition and appetite
Nutritional requirements
These are difficult to define since different individuals have different requirements. A daily requirement figure appropriate for most of the population (e.g., 97.5%) is normally used. Our diet has to provide adequate energy for body metabolism and a supply of amino acids for the maintenance of functional and structural proteins. Energy may be derived from carbohydrate, fat or protein (Section 4.8), but some amino acids cannot be synthesized in the body and these essential amino acids must be supplied from digested protein. Thus, basic dietary requirements are usually specified in terms of total energy and protein needs. This equates to 12.6 MJ (3000 kcal) of energy and 46 g of protein per day for a young adult male with a moderate workload, but these values may be affected by many factors.
Vitamin and mineral requirements may also be specified but with even less certainty than energy needs. The dietary requirements of the vitamins folate and B12 and of the mineral iron are of particular clinical interest since deficiencies of these are relatively common and can lead to haemoglobin deficiency, i.e., anaemia (Section 2.3). The recommended daily requirements of folate (200 μg) and B12 (2 μg) are similar in adult men and women. Women have a higher iron requirement, at 15 mg day−1 compared with 10 mg for men. This reflects increased iron loss resulting from menstruation each month.
It may be that other aspects of the diet, e.g., fibre and lipid content, are also important for health. Studies to test such ideas unambiguously are, however, extremely difficult to design and carry out.
Control of eating
Following sustained growth during childhood and adolescence, body weight remains remarkably stable over many years of adulthood. This stability can only be achieved by matching energy intake to energy use. If the food we eat contains more energy than we need then the excess has to be stored, mainly in the form of fat, and weight increases. To maintain a stable weight, therefore, food intake has to be controlled. This is coordinated by the hunger centre and the satiety centre in the hypothalamus (Fig. 89). Following a meal, distension of the stomach and increased levels of circulating nutrients stimulate the satiety centre which inhibits feeding, while hunger develops as these inputs wane. Fat stores also release a protein hormone called leptin which acts on the hypothalamus to inhibit eating. This provides a feedback system tending to regulate the total lipid content (and thus the weight) of the body. Emotional factors also affect the hypothalamic centres, e.g., anxiety can increase or decrease appetite, and eating disorders, such as anorexia nervosa or bulimia, may reflect abnormalities in central nervous control of their activity.
Obesity is generally defined as a body mass index (BMI) of more than 30 kg m−2, where:
Obesity is a serious health problem since it is associated with an increased risk of diabetes mellitus, hypertension, cardiac and joint disease. Although hypothyroidism causes weight gain by decreasing metabolism, most obese people have a normal or slightly increased basal metabolic rate. Abnormal feedback control of lipid store mass is another possible explanation but leptin levels are increased in obesity in proportion with fat content, so if there is reduced negative feedback it must reflect a diminished response to leptin in the hypothalamus. This remains under study but the fact that the number of seriously overweight people in Western society has increased dramatically over the last few decades suggests that an environmental factor is important, with our increasingly sedentary lifestyle being a likely candidate.
6.2 Gastrointestinal motility
Food has to be propelled through the gastrointestinal tract from mouth to anus. The time taken for this to occur is referred to as the transit time. This can vary from less than 20 hours to over 140 hours and much of this variation appears to depend on the fibre content of the diet (i.e., the amount of indigestible carbohydrate present). A high-fibre diet is usually associated with a short transit time as well as a large fecal mass.
General features of gut motility
The propulsion of gastrointestinal contents depends on the contractile activity of the gastrointestinal smooth muscle, which is generally organized as an inner circular and an outer longitudinal layer in the intestinal wall (Fig. 90). The electrical activity in this muscle consists of spontaneous waves of depolarization lasting several seconds, which are known as slow waves (Fig. 91). These may have action potential spikes superimposed on their peaks. The electrical activity in smooth muscle is dependent on Ca2+, rather than Na+ as is the case in nerves and striated muscle. The frequency of the slow waves varies in different parts of the gastrointestinal tract, with average values of about 3 min−1 in the stomach, 12 min−1 in the upper small intestine, falling to 9 min−1 in the terminal ileum. Slow waves excite spontaneous contractility, which is modified by the action of nerves, hormones and local factors such as chemical stimulation and mechanical stretch. Nervous control comes both from extrinsic autonomic nerves and intrinsic nerves, with the latter forming the myenteric and submucosal nerve plexuses within the wall of the gut itself.
Mouth and oesophagus
Chewing is essentially a voluntary activity involving the skeletal muscles of the mouth and jaw. It has the effect of:
Swallowing is divided into three phases. During the oral phase, a bolus of food is forced backwards voluntarily with the tongue until pressure on the pharyngeal wall initiates the swallowing reflex (Fig. 92). This reflex cannot subsequently be interrupted and is coordinated by the swallowing centre in the medulla oblongata. During the pharyngeal phase the soft palate is deflected upwards, sealing off the nasal passages from the pharynx. Muscle contraction pulls the larynx upwards, the glottis closes and the epiglottis deflects the food posteriorly, away from the laryngeal opening. These events protect against aspiration of food into the airways. A travelling wave of constriction (a peristaltic wave) drives the food through the relaxed oesophageal sphincters and along the oesophagus itself in the oesophageal phase of swallowing. The reflex is controlled via both somatic nerves, supplying the striated muscle in the pharynx, larynx and upper oesophagus, and parasympathetic nerves innervating smooth muscle in the mid and lower oesophagus. These nerves stimulate contraction of most of the muscles involved, but nerves also stimulate relaxation of the oesophageal sphincters.
Box 20 Clinical note: Hiatus hernia
Between meals, a functional sphincter at the lower end of the oesophagus protects it from damage caused by entry of gastric acid. This is assisted by the acute angle of entry between the oesophagus and stomach, which produces a functional flap valve (Fig. 93). Protection is diminished in a condition known as hiatus hernia, in which the gastro-oesophageal junction lies above the diaphragm. One of the main symptoms of this condition is pain (heartburn), which is made worse on bending or lifting. This is caused by acid reflux into the lower oesophagus.
Stomach
From the mechanical point of view, the stomach has two functions.
Mechanical activity in the stomach consists of regular, peristaltic waves generated within the stomach muscle at a rate of about 3 min−1. These spread from the body to the antrum, where the strongest contractions occur (Fig. 94). As the contractions reach the pylorus, the pyloric sphincter closes and prevents excessive emptying into the small intestine. So, although each wave forces some chyme into the duodenum, the bulk is mixed back into the body of the stomach.

Fig. 94 Mechanical mixing in the stomach is promoted by gastric peristaltic waves and pyloric contraction.
Regulation of gastric motility
Regulatory factors influence the strength of gastric contraction more than its frequency. Factors which increase contractility tend to accelerate gastric emptying.
During a meal gastric contractility is stimulated by mechanical distension and increased parasympathetic nervous activity as well as by the hormone gastrin, which is secreted by the G cells in the gastric mucosa.
The presence of acid or fat in the duodenum slows gastric emptying, thus allowing time for pH neutralization and intestinal lipid absorption. This effect may be mediated by release of the hormones cholecystokinin and secretin from the small intestine in response to chyme.
Increased sympathetic nervous activity inhibits gastric motility, e.g., during heavy exercise or following blood loss.
Small intestine
Three patterns of contractile activity are commonly seen in the small intestine.
Large intestine
The colon normally maintains a slow rate of segmentation (2–4 contractions h−1). Three to four times a day, however, the large bowel undergoes a contraction known as a mass movement. This is a synchronized and sustained contraction of the circular muscle which does not travel as a peristaltic wave would. It often occurs immediately after a meal, possibly triggered by the gastrin-dependent gastrocolic reflex.
Mass movements force the colonic contents into the rectum, distending it and thereby initiating the defecation reflex (Fig. 96). The sensory output from stretch receptors in the rectal walls stimulates parasympathetic nerves in the sacral spinal cord which, in turn, increase the contraction of the colon while relaxing the smooth muscle of the internal anal sphincter. Somatic nerves to the striated muscle of the external anal sphincter are inhibited, allowing it to relax. Rectal distension also gives rise to a conscious awareness of the urge to defecate and in the early years of life we learn to respond to this by voluntarily contracting the external anal sphincter. This allows us to control defecation (faecal continence). When appropriate, however, the external sphincter is allowed to relax and defecation proceeds. Expulsion is often assisted by using the abdominal muscles and diaphragm to increase intra-abdominal pressure. This is referred to as abdominal straining.
6.3 Digestion and secretion
Digestion is the term given to the processes whereby the complex molecules in food are broken down into simpler subunits which can be absorbed from the gut and metabolized in the body. This largely depends on a variety of secretions produced by the gastrointestinal tract and associated organs. The whole of the gut is lined by exocrine glands and cells, secreting a total volume of about 7–8 L into the lumen each day. Each secretion is a mixture of aqueous and organic components. The aqueous component is derived from the extracellular fluid surrounding the secretory cells but differs from plasma because of modifications caused by the actions of a variety of ion pumps and carriers. Since different secretory cells contain different pumps, the composition of the aqueous component varies from gland to gland. Also, in glands with ducts, the secretion may be further modified by the duct epithelium (e.g., salivary glands and pancreas; Fig. 98). Digestive secretions usually also have an organic component, often in the form of one or more digestive enzymes manufactured by the secretory cells.
Box 21 Clinical note: Abnormal gastrointestinal motility
Vomiting
Vomiting is a complex set of motor functions coordinated by the vomiting centre in the medulla oblongata. The area postrema in the medulla oblongata is particularly implicated as a chemoreceptor zone which can trigger vomiting. The inputs stimulating this centre, and the resulting motor effects, are summarized in Fig. 97. Vomiting is usually associated with the sensation of nausea and is often preceded by sweating, pallor and an elevated heart rate. These are typical signs of sympathetic nervous activity. Although vomiting is preceded by reverse or antiperistalsis which can drive intestinal contents back into the stomach, the vomiting act is generated by an increase in abdominal pressure, which compresses the relatively relaxed stomach. There is little or no contribution from gastric contraction. In vomiting, NaCl, water and H+ are all lost, so that dehydration and alkalosis may result.
Diarrhoea
Diarrhoea is an increased frequency of defecation. It is commonly caused by:
In contrast to vomiting, diarrhoea does not involve coordination by regulatory centres in the brain. Diarrhoea causes loss of K+ and HCO3 −, both of which are secreted by the colon. Hypokalaemia (K+ deficiency) and acidosis may result, although dehydration (loss of NaCl and water) is the main consequence. Diarrhoea and vomiting caused by infected food and water are among the most common causes of infant death in the developing nations of the world.
Constipation
Infrequent or difficult defecation is a common complaint, particularly in the elderly. The underlying cause is often inadequate fibre (roughage) in the diet so that only a small volume of dietary residue enters the large intestine. Rectal stretch is reduced under these conditions so the major sensory stimulus for the defecation reflex is lost. Slow passage through the large intestine also favours increased water absorption leading to further compaction of the faeces. Treatment usually involves the prescription of high-fibre foods and supplements. Constipation may also arise due to repeated voluntary inhibition of the defecation reflex, e.g., in those suffering from a condition such as an anal fissure, which makes defecation painful. This can eventually cause the reflex itself to wane, leading to a more prolonged constipated state.
The overall activity of each gland is controlled by a combination of local and distant factors acting through nerves (nervous control), blood-borne hormones (endocrine control) and locally secreted chemicals (paracrine control).
Saliva
Saliva is secreted by the parotid, submandibular, sublingual and buccal salivary glands. The aqueous component is formed by primary secretion of a solution similar to extracellular fluid. This is modified as it passes along the gland ducts, with removal of Na+ and Cl−, and addition of K+ and HCO3 −. Bicarbonate makes saliva alkaline and helps buffer the acid in food, protecting against dental caries. The main organic components of saliva are:
Secretion of saliva is reflexly stimulated via the salivary nuclei in the medulla oblongata in response to:
The efferent limb of the reflex is parasympathetic and follows cranial nerves VII and IX to reach the glands. Parasympathetic stimulation favours a rapid flow of enzyme-rich saliva. Drugs which block parasympathetic neurotransmission produce a dry mouth by inhibiting salivation.
Gastric secretion
Relevant structure
The inner surface of the stomach is thrown into a series of visible folds, known as rugae, which increase the surface area of the gastric mucosa. The mucosal surface consists of a flat layer of mucus-secreting, columnar epithelial cells, but this is interrupted by multiple gastric pits, each of which leads down into a number of tubular exocrine glands (Fig. 99). The mucosal cells lining the gastric glands are the source of the gastric secretions, with a number of specialist cells producing separate components. The upper one-third to half is lined by mucus-secreting cells. The other two types of exocrine cell, which line the deeper regions of the gastric pits, are the acid-secreting parietal cells (or oxyntic cells) and the smaller, more numerous, cuboidal chief cells, which secrete the enzyme precursor pepsinogen. The gastric mucosa also contains cells which produce chemicals capable of stimulating acid secretion. The G cells produce the peptide hormone gastrin, while the enterochromaffin-like cells secrete histamine, which acts as a paracrine signal stimulating acid secretion in adjacent parietal cells.
Components of gastric secretion
Gastric acid
The parietal cells secrete HCl. This produces a pH of 2–3 within the stomach itself. Active transport of H+ in exchange for K+ by an ATP-dependent proton pump (H+/K+ ATPase) in the cell membrane facing the gastric lumen (the luminal membrane) is the central mechanism involved (Fig. 100). Proton production in the cell depends on dissociation of carbonic acid formed by the reaction of CO2 with H2O in a reaction catalysed by the enzyme carbonic anhydrase (Section 4). This also produces HCO3 −, which is transported out of the parietal cell and into the blood. Because of this, gastric venous blood is more alkaline than systemic arterial blood.
Intrinsic factor
This is also secreted by parietal cells and binds to vitamin B12, allowing it to be absorbed in the terminal ileum.
Pepsinogen
Pepsinogen is an enzyme precursor secreted by the chief cells. Its release is stimulated in parallel with acid secretion and pepsinogen is activated to pepsin by acid digestion in the stomach. Pepsin is an acid protease, i.e., it breaks dietary protein into peptides and amino acids at acid pH. Pepsin also promotes its own formation by breaking down pepsinogen.
Mucus
Mucus is secreted by the mucus cells of the gastric pits and the surface cells between the pits. This forms an acid-resistant layer over the stomach mucosa, the effectiveness of which is enhanced by the fact that HCO3 − is secreted into the mucus, making it alkaline. As a result, the epithelial surface remains close to neutral while acid permeates through the mucin to the stomach lumen.
Control of acid secretion
Acid secretion is stimulated in three phases during a meal.
The cephalic phase
This depends on higher centres in the brain acting via the vagus nerve (parasympathetic). It is initiated by the thought, smell, sight or anticipation of food.
The gastric phase
This begins when food enters the stomach. Ingested food molecules, particularly proteins, stimulate both the intrinsic gastric nerves and release of the peptide hormone gastrin. This is secreted into the blood by G cells in the mucosa of the gastric antrum and acts as the main endocrine stimulus to gastric secretion.
The intestinal phase
This starts when chyme enters the intestine and probably depends on gastrin secretion from cells in the mucosa of the duodenum and small intestine.
Parietal cell stimulation
At the level of the parietal cell itself, acid secretion can be stimulated by acetylcholine from parasympathetic and intrinsic nerves and by circulating gastrin. There is also paracrine regulation based on the stimulatory effect of histamine, secreted by cells in the gastric mucosa, which acts on H2 receptors on the parietal cells.
Box 22 Clinical note: Peptic ulceration
An ulcer is a break in the mucosal epithelium and when this occurs in the stomach or duodenum it is referred to as a peptic ulcer. One of the main causes is believed to be mucosal damage by gastric acid but infection with the bacterium Helicobacter pylori may also contribute in many cases. Current drug treatments aim to neutralize or decrease acid secretion or increase mucosal protection. This may be combined with antibiotics to eradicate H. pylori, if present.
Pancreatic secretion
The pancreatic secretions pass from the secretory cells, which are arranged in grape-like clumps termed acini, down branch ducts to the main pancreatic duct, which fuses with the common bile duct before opening into the duodenum (Fig. 101). The secretion is alkaline; therefore, it neutralizes the gastric acid entering the duodenum. The balance between H+ secretion in the stomach and HCO3 − secretion by the pancreas ensures that there is normally no overall change in arterial plasma pH following a meal. Pancreatic secretions sampled close to the acini contain the highest concentrations of HCO3 −, but as these secretions pass along the pancreatic ducts there is absorption of HCO3 − in exchange for Cl−, and pH falls.
The pancreatic acini elaborate and secrete enzymes relevant to the digestion of each main food type.
Proteases and peptidases are secreted from the pancreas as inactive precursors (e.g., chymotrypsinogen, trypsinogen and procarboxypeptidase) which are only activated (to chymotrypsin, trypsin and carboxypeptidase) by enzymic degradation in the small intestine. Activation is catalysed by enterokinase, an enzyme secreted by the intestinal mucosa. Secretion in inactive form and the presence of trypsin inhibitor prevent autodigestion of the pancreas. The active enzymes catalyse the production of short peptides from proteins in the diet. This is adequate for normal protein digestion even in the absence of any gastric pepsin activity.
Pancreatic amylase digests carbohydrate under alkaline conditions, releasing oligosaccharides.
Lipase and cholesterol esterase produce monoglycerides, free fatty acids and cholesterol from triglycerides and cholesterol esters. Lipid digestion also depends on the emulsifying action of bile salts.
Control of pancreatic secretion
Pancreatic secretion is most strongly stimulated by food entering the small intestine, which triggers release of two intestinal peptide hormones.
Acid in the duodenum stimulates endocrine release of secretin which causes secretion of a large volume of HCO3 −-rich fluid.
Food molecules, particularly proteins and lipids, promote release of cholecystokinin, which activates enzyme production and secretion.
Parasympathetic nerve stimulation produces a scanty pancreatic secretion which is enzyme rich. This probably contributes to the cephalic and gastric phases of pancreatic secretion, which precede entry of food to the intestine (intestinal phase).
Bile
The aqueous component of bile contains NaHCO3. The main organic components are:
This mixture is secreted into the bile canaliculi by the hepatocytes of the liver (see Fig. 113) and then stored and concentrated in the gallbladder (Fig. 101). Following a meal, the gallbladder is stimulated to contract by cholecystokinin, and bile is expelled through the common bile duct into the duodenum.
Bile salts
Bile salts have a steroid nucleus which is usually conjugated with an amino acid. This makes them amphipathic (part water soluble, part fat soluble), allowing them to stabilize fatty emulsions in aqueous conditions. As a result, dietary lipids form an intestinal emulsion of microscopic fat droplets, each droplet being held in its watery environment by a surface coat of bile salt. The bile salt molecules orient themselves with their fat-soluble side towards the lipid core of the emulsified droplets and their water-soluble aspect in contact with the external solution.
Bile salts are important in both the digestion and absorption of lipid.
Emulsification is necessary for efficient fat digestion since it maintains a large surface area for lipase action. This relies on the stabilizing effect of the bile salts. In their absence, the triglycerides would simply form a fatty layer floating on the surface, like an oil slick on water, and the rate of digestion would be insignificant.
Lipid absorption requires bile salts to stabilize the fatty acids and monoglycerides released by lipases in the form of even smaller molecular aggregates known as micelles. The products of lipid digestion diffuse out of these to be absorbed by the cells of the mucosal epithelium (Section 6.4).
Enterohepatic recirculation of bile salts
Bile salts are reabsorbed in the small intestine, both by passive diffusion and by an active transport system located in the lower end of the ileum (the terminal ileum). Over 80% of the secreted bile salts are absorbed back into the blood in this way and as they pass through the liver they can be resecreted back into bile (Fig. 102). This reabsorption–secretion cycle is referred to as the enterohepatic recirculation of bile salts; it minimizes the amount of bile salt synthesis required.

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