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

Learning objectives

At the end of this section you should be able to:

• list the main requirements of a healthy diet

• describe the mechanisms responsible for weight control.

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.

• Increased physical activity requires a higher energy intake.

• Pregnancy and lactation increase energy and protein needs in women.

• Age is an important factor. Total dietary requirements increase from birth to young adulthood. When the effect of increasing size is eliminated by expressing energy needs in MJ kg⁻¹ of body mass, however, values fall throughout life, from birth onwards.

• Disease states can also have dramatic effects, e.g., hyperthyroidism increases metabolic rate (Section 8.3) and, therefore, increases the required energy intake.

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.

Fig. 89 Summary of factors controlling appetite.

Box 19 Clinical note: Obesity

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.

Fig. 90 Transverse section of intestinal wall showing the main structural features.

Fig. 91 Spontaneous electrical slow waves and action potential spikes. The frequency is typical of stomach.

Mouth and oesophagus

Chewing is essentially a voluntary activity involving the skeletal muscles of the mouth and jaw. It has the effect of:

• reducing the risk of choking by breaking up large lumps of food

• mixing food with saliva and mucus, thus lubricating it prior to swallowing

• decreasing the particle size of the food, allowing it to be more easily mixed and digested in the stomach and intestine.

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.

Fig. 92 Main structural and functional elements involved in the three phases of swallowing.

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.

Fig. 93 The gastro-oesophageal junction in a normal stomach and in hiatus hernia.

Stomach

From the mechanical point of view, the stomach has two functions.

• It is a reservoir for food during meals, a function assisted by parasympathetically mediated relaxation of gastric muscle during swallowing (receptive relaxation).

• It is a mixing chamber, which churns food into semiliquid chyme and then dispenses it into the duodenum in relatively small volumes in the period following a meal.

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.

• The spontaneous mechanical activity in intestinal smooth muscle mainly consists of segmentation (Fig. 95). In segmentation there is no travelling wave of contraction. Instead, the muscle contracts simultaneously at regular intervals along the gut wall, thus dividing the lumen of the gut into a series of discontinuous segments and displacing the gut contents. The muscle then relaxes again before contracting at adjacent sites, once more pushing the chyme sideways in both directions. This mixes the intestinal contents and promotes efficient digestion and absorption. The frequency of contraction decreases as one moves distally from the duodenum (12 min⁻¹) to the ileum (9 min⁻¹). The force of contraction is increased in response to parasympathetic stimulation and decreased by sympathetic nerves and circulating catecholamines.

• The main propulsive force in the small intestine comes from localized waves of peristalsis. Unlike those in the oesophagus or stomach, these only travel a few centimetres along the small intestine before dying out and so the progress of intestinal contents is slow, particularly immediately after the ingestion of a meal. This helps to ensure that there is adequate time for digestion and absorption.

• In the fasted state, i.e., several hours after a meal when absorption is essentially complete, more strongly propulsive migratory motor complexes develop. These help sweep the intestinal residue into the large intestine via the ileocaecal valve. Eating suppresses this form of activity, however, with a return to segmentation.

Fig. 95 Mechanical activity in the small intestine. (A) Segmentation. (B) Localized peristaltic waves.

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.

Fig. 96 Summary of the defecation reflex. Both excitatory (+) and inhibitory (−) connections are involved.

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.

Fig. 98 The principles of exocrine secretion.

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.

Fig. 97 The inputs and outputs leading to vomiting.

Diarrhoea

Diarrhoea is an increased frequency of defecation. It is commonly caused by:

• increased bowel motility in response to inflammation, e.g., because of a bowel infection

• failure to absorb nutrient molecules from the intestinal lumen, leading to osmotic retention of excess fluid in the intestine

• excess secretion by the intestinal mucosa, e.g., in response to bacterial toxins.

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:

• mucus, for lubrication in eating and speech

• amylase, which digests starch at alkaline pH

• lysozyme, which has antibacterial actions and protects against oral infection.

Secretion of saliva is reflexly stimulated via the salivary nuclei in the medulla oblongata in response to:

• stimulation of chemoreceptors and mechanoreceptors in the mouth

• activity in higher centres of the CNS, e.g., smelling, or thinking about food.

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.

Fig. 99 A tubular gastric gland. Several glands open into each gastric pit. The surface epithelium secretes protective mucus and HCO₃ ⁻.

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.

Fig. 100 Summary of the mechanism of HCl secretion in a gastric parietal cell. CA, carbonic anhydrase.

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.

Fig. 101 The anatomy of the main pancreatic and biliary ducts.

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:

• the bile salts or acids

• the bile pigments

• lecithin

• cholesterol.

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.