The digestive system is the collective name used to describe the alimentary canal, its accessory organs and a variety of digestive processes that take place at different levels in the canal to prepare food eaten in the diet for absorption. The alimentary canal begins at the mouth, passes through the thorax, abdomen and pelvis and ends at the anus (Fig. 12.1). It has a general structure which is modified at different levels to provide for the processes occurring at each level (Fig. 12.2). The digestive processes gradually break down the foods eaten until they are in a form suitable for absorption. For example, meat, even when cooked, is chemically too complex to be absorbed from the alimentary canal. Digestion releases its constituents: amino acids, mineral salts, fat and vitamins. Digestive enzymes (p. 24) that effect these changes are secreted into the canal by specialised glands, some of which are in the walls of the canal and some outside the canal, but with ducts leading into it.
Figure 12.1 The digestive system.
Figure 12.2 General structure of the alimentary canal.
After absorption, nutrients are used to synthesise body constituents. They provide the raw materials for the manufacture of new cells, hormones and enzymes, and the energy needed for these and other processes and for the disposal of waste materials.
The activities in the digestive system can be grouped under five main headings.
This is the taking of food into the alimentary tract, i.e. eating and drinking.
This mixes and moves the contents along the alimentary tract.
This consists of:
• mechanical breakdown of food by, e.g. mastication (chewing)
• chemical digestion of food into small molecules by enzymes present in secretions produced by glands and accessory organs of the digestive system.
This is the process by which digested food substances pass through the walls of some organs of the alimentary canal into the blood and lymph capillaries for circulation and use by body cells.
Food substances that have been eaten but cannot be digested and absorbed are excreted from the alimentary canal as faeces by the process of defaecation.
The fate of absorbed nutrients and how they are used by the body is then explored. In the final section disorders of the digestive system are considered.
Organs of the digestive system (Fig. 12.1)
After studying this section, you should be able to:
identify the main organs of the alimentary canal
list the accessory organs of digestion.
Also known as the gastrointestinal (GI) tract, this is a long tube through which food passes. It commences at the mouth and terminates at the anus, and the various parts are given separate names, although structurally they are remarkably similar. The parts are:
• small intestine
• large intestine
• rectum and anal canal.
Various secretions are poured into the alimentary tract, some by glands in the lining membrane of the organs, e.g. gastric juice secreted by glands in the lining of the stomach, and some by glands situated outside the tract. The latter are the accessory organs of digestion and their secretions pass through ducts to enter the tract. They consist of:
• three pairs of salivary glands
• the pancreas
• the liver and biliary tract.
The organs and glands are linked physiologically as well as anatomically in that digestion and absorption occur in stages, each stage being dependent upon the previous stage or stages.
Basic structure of the alimentary canal (Fig. 12.2)
After studying this section, you should be able to:
describe the distribution of the peritoneum
explain the function of smooth muscle in the walls of the alimentary canal
discuss the structures of the alimentary mucosa
outline the nerve supply of the alimentary canal.
The layers of the walls of the alimentary canal follow a consistent pattern from the oesophagus onwards. This basic structure does not apply so obviously to the mouth and the pharynx, which are considered later in the chapter.
In the organs from the oesophagus onwards, modifications of structure are found which are associated with specific functions. The basic structure is described here and any modifications in structure and function are described in the appropriate section.
The walls of the alimentary tract are formed by four layers of tissue:
• adventitia or serosa – outer covering
• muscle layer
• mucosa – lining.
Adventitia or serosa
This is the outermost layer. In the thorax it consists of loose fibrous tissue and in the abdomen the organs are covered by a serous membrane (serosa) called peritoneum.
The peritoneum is the largest serous membrane of the body (Fig. 12.3A). It is a closed sac, containing a small amount of serous fluid, within the abdominal cavity. It is richly supplied with blood and lymph vessels, and contains many lymph nodes. It provides a physical barrier to local spread of infection, and can isolate an infective focus such as appendicitis, preventing involvement of other abdominal structures. It has two layers:
• the parietal peritoneum, which lines the abdominal wall
• the visceral peritoneum, which covers the organs (viscera) within the abdominal and pelvic cavities.
Figure 12.3 A. The peritoneal cavity (gold), the abdominal organs of the digestive system and the pelvic organs. B. The greater omentum.
The arrangement of the peritoneum is such that the organs are invaginated (pushed into itself forming a pouch) into the closed sac from below, behind and above so that they are at least partly covered by the visceral layer, and attached securely within the abdominal cavity. This means that:
• pelvic organs are covered only on their superior surface
• the stomach and intestines, deeply invaginated from behind, are almost completely surrounded by peritoneum and have a double fold (the mesentery) that attaches them to the posterior abdominal wall. The fold of peritoneum enclosing the stomach extends beyond the greater curvature of the stomach, and hangs down in front of the abdominal organs like an apron (Fig. 12.3B). This is the greater omentum, and it stores fat, which provides both insulation and a long-term energy store
• the pancreas, spleen, kidneys and adrenal glands are invaginated from behind but only their anterior surfaces are covered and are therefore retroperitoneal (lie behind the peritoneum)
• the liver is invaginated from above and is almost completely covered by peritoneum, which attaches it to the inferior surface of the diaphragm
• the main blood vessels and nerves pass close to the posterior abdominal wall and send branches to the organs between folds of peritoneum.
The parietal peritoneum lines the anterior abdominal wall.
The two layers of peritoneum are actually in contact, and friction between them is prevented by the presence of serous fluid secreted by the peritoneal cells, thus the peritoneal cavity is only a potential cavity. A similar arrangement is seen with the membranes covering the lungs, the pleura (p. 243). In the male, the peritoneal cavity is completely closed but in the female the uterine tubes open into it and the ovaries are the only structures inside (Ch. 18).
With some exceptions this consists of two layers of smooth (involuntary) muscle. The muscle fibres of the outer layer are arranged longitudinally, and those of the inner layer encircle the wall of the tube. Between these two muscle layers are blood vessels, lymph vessels and a plexus (network) of sympathetic and parasympathetic nerves, called the myenteric plexus (Auerbach’s plexus, Fig. 12.2). These nerves supply the adjacent smooth muscle and blood vessels.
Contraction and relaxation of these muscle layers occurs in waves, which push the contents of the tract onwards. This type of contraction of smooth muscle is called peristalsis (Fig. 12.4) and is under the influence of sympathetic and parasympathetic nerves. Muscle contraction also mixes food with the digestive juices. Onward movement of the contents of the tract is controlled at various points by sphincters, which are thickened rings of circular muscle. Contraction of sphincters regulates forward movement. They also act as valves, preventing backflow in the tract. This control allows time for digestion and absorption to take place.
Figure 12.4 Movement of a bolus by peristalsis.
This layer consists of loose areolar connective tissue containing collagen and some elastic fibres, which binds the muscle layer to the mucosa. Within it are plexuses of blood vessels and nerves, lymph vessels and varying amounts of lymphoid tissue. The blood vessels are arterioles, venules and capillaries. The nerve plexus is the submucosal plexus (Meissner’s plexus, Fig. 12.2), containing sympathetic and parasympathetic nerves that supply the mucosal lining.
This consists of three layers of tissue:
• mucous membrane formed by columnar epithelium is the innermost layer, and has three main functions: protection, secretion and absorption
• lamina propria consisting of loose connective tissue, which supports the blood vessels that nourish the inner epithelial layer, and varying amounts of lymphoid tissue that has a protective function
• muscularis mucosa, a thin outer layer of smooth muscle that provides involutions of the mucosa layer, e.g. gastric glands (p. 291), villi (p. 294).
In parts of the tract that are subject to great wear and tear or mechanical injury, this layer consists of stratified squamous epithelium with mucus-secreting glands just below the surface. In areas where the food is already soft and moist and where secretion of digestive juices and absorption occur, the mucous membrane consists of columnar epithelial cells interspersed with mucus-secreting goblet cells (Fig. 12.5). Mucus lubricates the walls of the tract and protects them from the damaging effects of digestive enzymes. Below the surface in the regions lined with columnar epithelium are collections of specialised cells, or glands, which release their secretions into the lumen of the tract. The secretions include:
• saliva from the salivary glands
• gastric juice from the gastric glands
• intestinal juice from the intestinal glands
• pancreatic juice from the pancreas
• bile from the liver.
Figure 12.5 Columnar epithelium with a goblet cell. A. Diagram. B. Coloured transmission electron micrograph of a section through a goblet cell (pink and blue) of the small intestine.
These are digestive juices and most contain enzymes that chemically break down food. Under the epithelial lining are varying amounts of lymphoid tissue that provide protection against ingested microbes.
The alimentary canal and its related accessory organs are supplied by nerves from both divisions of the autonomic nervous system, i.e. both parasympathetic and sympathetic parts (Fig. 12.6). Their actions are antagonistic and one has a greater influence than the other, according to body needs, at any particular time. When digestion is required, this is normally through increased activity of the parasympathetic nervous system.
Figure 12.6 Autonomic nerve supply to the digestive system. Parasympathetic – blue; sympathetic – red.
The parasympathetic supply
One pair of cranial nerves, the vagus nerves, supplies most of the alimentary canal and the accessory organs. Sacral nerves supply the most distal part of the tract. The effects of parasympathetic stimulation are:
• increased muscular activity, especially peristalsis, through increased activity of the myenteric plexus
• increased glandular secretion, through increased activity of the submucosal plexus (Fig. 12.2).
The sympathetic supply
This is provided by numerous nerves that emerge from the spinal cord in the thoracic and lumbar regions. These form plexuses (ganglia) in the thorax, abdomen and pelvis, from which nerves pass to the organs of the alimentary tract. The effects of sympathetic stimulation are to:
• decrease muscular activity, especially peristalsis, because there is less stimulation of the myenteric plexus
• decrease glandular secretion, as stimulation of the submucosal plexus is reduced.
Mouth (Fig. 12.7)
Figure 12.7 Structures seen in the widely open mouth.
After studying this section, you should be able to:
list the principal structures associated with the mouth
describe the structure of the mouth
describe the structure and function of the tongue
describe the structure and function of the teeth
outline the arrangement of normal primary and secondary dentition.
The mouth or oral cavity is bounded by muscles and bones:
Anteriorly – by the lips
Posteriorly – it is continuous with the oropharynx
Laterally – by the muscles of the cheeks
Superiorly – by the bony hard palate and muscular soft palate
Inferiorly – by the muscular tongue and the soft tissues of the floor of the mouth.
The oral cavity is lined throughout with mucous membrane, consisting of stratified squamous epithelium containing small mucus-secreting glands.
The part of the mouth between the gums and the cheeks is the vestibule and the remainder of the cavity is the oral cavity. The mucous membrane lining of the cheeks and the lips is reflected onto the gums or alveolar ridges and is continuous with the skin of the face.
The palate forms the roof of the mouth and is divided into the anterior hard palate and the posterior soft palate (Fig. 12.1). The hard palate is formed by the maxilla and the palatine bones. The soft palate is muscular, curves downwards from the posterior end of the hard palate and blends with the walls of the pharynx at the sides.
The uvula is a curved fold of muscle covered with mucous membrane, hanging down from the middle of the free border of the soft palate. Originating from the upper end of the uvula are four folds of mucous membrane, two passing downwards at each side to form membranous arches. The posterior folds, one on each side, are the palatopharyngeal arches and the two anterior folds are the palatoglossal arches. On each side, between the arches, is a collection of lymphoid tissue called the palatine tonsil.
The tongue is a voluntary muscular structure that occupies the floor of the mouth. It is attached by its base to the hyoid bone (see Fig. 10.4, p. 236) and by a fold of its mucous membrane covering, called the frenulum, to the floor of the mouth (Fig. 12.8). The superior surface consists of stratified squamous epithelium, with numerous papillae (little projections). Many of these contain sensory receptors (specialised nerve endings) for the sense of taste in the taste buds (see Fig. 8.25, p. 201). There are several types of papilla; however no clear relationship between these and discrimination of different tastes has been found.
Figure 12.8 The inferior surface of the tongue.
The main arterial blood supply to the tongue is by the lingual branch of the external carotid artery. Venous drainage is by the lingual vein, which joins the internal jugular vein.
The nerves involved are:
• the hypoglossal nerves (12th cranial nerves), which supply the voluntary muscle
• the lingual branch of the mandibular nerves, which arise from the 5th cranial nerves, are the nerves of somatic (ordinary) sensation, i.e. pain, temperature and touch
• the facial and glossopharyngeal nerves (7th and 9th cranial nerves), the nerves of taste.
Functions of the tongue
The tongue plays an important part in:
• chewing (mastication)
• swallowing (deglutition)
• speech (p. 240)
• taste (p. 200).
Nerve endings of the sense of taste are present in the papillae and widely distributed in the epithelium of the tongue, soft palate, pharynx and epiglottis.
The teeth are embedded in the alveoli or sockets of the alveolar ridges of the mandible and the maxilla (Fig. 12.9). Babies are born with two sets, or dentitions, the temporary or deciduous teeth and the permanent teeth (Fig. 12.10). At birth the teeth of both dentitions are present, in immature form, in the mandible and maxilla.
Figure 12.9 The permanent teeth and the jaw bones.
Figure 12.10 The roof of the mouth. A. The deciduous teeth – viewed from below. B. The permanent teeth – viewed from below.
There are 20 temporary teeth, 10 in each jaw. They begin to erupt when the child is about 6 months old, and should all be present by 24 months (Table 12.1).
Table 12.1Deciduous and permanent dentitions
The permanent teeth begin to replace the deciduous teeth in the 6th year of age and this dentition, consisting of 32 teeth, is usually complete by the 21st year.
Functions of the teeth
Teeth have different shapes depending on their functions. Incisors and canine teeth are the cutting teeth and are used for biting off pieces of food, whereas the premolar and molar teeth, with broad, flat surfaces, are used for grinding or chewing food (Fig. 12.11).
Figure 12.11 The shapes of the permanent teeth.
Structure of a tooth (Fig. 12.12)
Although the shapes of the different teeth vary, the structure is the same and consists of:
• the crown – the part that protrudes from the gum
• the root – the part embedded in the bone
• the neck – the slightly narrowed region where the crown merges with the root.
Figure 12.12 A section of a tooth.
In the centre of the tooth is the pulp cavity containing blood vessels, lymph vessels and nerves, and surrounding this is a hard ivory-like substance called dentine. Outside the dentine of the crown is a thin layer of very hard substance, the enamel. The root of the tooth, on the other hand, is covered with a substance resembling bone, called cement, which secures the tooth in its socket. Blood vessels and nerves pass to the tooth through a small foramen (hole) at the apex of each root.
Most of the arterial blood supply to the teeth is by branches of the maxillary arteries. The venous drainage is by a number of veins which empty into the internal jugular veins.
The nerve supply to the upper teeth is by branches of the maxillary nerves and to the lower teeth by branches of the mandibular nerves. These are both branches of the trigeminal nerves (5th cranial nerves) (see p. 166).
Salivary glands (Fig. 12.13)
Figure 12.13 A. The position of the salivary glands. B. Enlargement of part of a gland.
After studying this section, you should be able to:
describe the structure and the function of the principal salivary glands
explain the role of saliva in digestion.
Salivary glands release their secretions into ducts that lead to the mouth. There are three main pairs: the parotid glands, the submandibular glands and the sublingual glands. There are also numerous smaller salivary glands scattered around the mouth.
These are situated one on each side of the face just below the external acoustic meatus (see Fig. 8.1, p. 186). Each gland has a parotid duct opening into the mouth at the level of the second upper molar tooth.
These lie one on each side of the face under the angle of the jaw. The two submandibular ducts open on the floor of the mouth, one on each side of the frenulum of the tongue.
These glands lie under the mucous membrane of the floor of the mouth in front of the submandibular glands. They have numerous small ducts that open into the floor of the mouth.
Structure of the salivary glands
The glands are all surrounded by a fibrous capsule. They consist of a number of lobules made up of small acini lined with secretory cells (Fig. 12.13B). The secretions are poured into ductules that join up to form larger ducts leading into the mouth.
Arterial supply is by various branches from the external carotid arteries and venous drainage is into the external jugular veins.
Composition of saliva
Saliva is the combined secretions from the salivary glands and the small mucus-secreting glands of the oral mucosa. About 1.5 litres of saliva is produced daily and it consists of:
• mineral salts
• a digestive enzyme: salivary amylase
• blood-clotting factors.
Secretion of saliva
Secretion of saliva is under autonomic nerve control. Parasympathetic stimulation causes profuse secretion of watery saliva with a relatively low content of enzymes and other organic substances. Sympathetic stimulation results in secretion of small amounts of saliva rich in organic material, especially from the submandibular glands. Reflex secretion occurs when there is food in the mouth and the reflex can easily become conditioned so that the sight, smell and even the thought of food stimulates the flow of saliva.
Functions of saliva
Chemical digestion of polysaccharides
Saliva contains the enzyme amylase that begins the breakdown of complex sugars, including starches, reducing them to the disaccharide maltose. The optimum pH for the action of salivary amylase is 6.8 (slightly acid). Salivary pH ranges from 5.8 to 7.4 depending on the rate of flow; the higher the flow rate, the higher is the pH. Enzyme action continues during swallowing until terminated by the strongly acidic pH (1.5 to 1.8) of the gastric juices, which degrades the amylase.
Lubrication of food
The high water content means that dry food entering the mouth is moistened and lubricated by saliva before it can be made into a bolus ready for swallowing.
Cleaning and lubricating the mouth
An adequate flow of saliva is necessary to clean the mouth, and to keep it soft, moist and pliable. It helps to prevent damage to the mucous membrane by rough or abrasive food.
Lysozyme, immunoglobulins and clotting factors present in saliva combat invading microbes.
The taste buds are stimulated only by chemical substances in solution and therefore dry foods only stimulate the sense of taste after thorough mixing with saliva. The senses of taste and smell are closely linked and involved in the enjoyment, or otherwise, of food (see Ch. 8).
After studying this section, you should be able to:
describe the structure of the pharynx.
The pharynx is divided for descriptive purpose into three parts, the nasopharynx, oropharynx and laryngopharynx (see p. 236). The nasopharynx is important in respiration. The oropharynx and laryngopharynx are passages common to both the respiratory and the digestive systems. Food passes from the oral cavity into the pharynx then to the oesophagus below, with which it is continuous. The walls of the pharynx consist of three layers of tissue.
The lining membrane (mucosa) is stratified squamous epithelium, continuous with the lining of the mouth at one end and the oesophagus at the other. Stratified epithelial tissue provides a lining well suited to the wear and tear of swallowing.
The middle layer consists of connective tissue which becomes thinner towards the lower end and contains blood and lymph vessels and nerves.
The outer layer consists of a number of involuntary muscles that are involved in swallowing. When food reaches the pharynx swallowing is no longer under voluntary control.
The blood supply to the pharynx is by several branches of the facial arteries. Venous drainage is into the facial veins and the internal jugular veins.
This is from the pharyngeal plexus and consists of parasympathetic and sympathetic nerves. Parasympathetic supply is mainly by the glossopharyngeal and vagus nerves and sympathetic from the cervical ganglia.
Oesophagus (Fig. 12.14)
Figure 12.14 The oesophagus and some related structures.
After studying this section, you should be able to:
describe the location of the oesophagus
outline the structure of the oesophagus
explain the mechanisms involved in swallowing, and the route taken by a bolus.
The oesophagus is about 25 cm long and about 2 cm in diameter and lies in the median plane in the thorax in front of the vertebral column behind the trachea and the heart. It is continuous with the pharynx above and just below the diaphragm it joins the stomach. It passes between muscle fibres of the diaphragm behind the central tendon at the level of the 10th thoracic vertebra. Immediately the oesophagus has passed through the diaphragm it curves upwards before opening into the stomach. This sharp angle is believed to be one of the factors that prevents the regurgitation (backflow) of gastric contents into the oesophagus. The upper and lower ends of the oesophagus are closed by sphincters. The upper cricopharyngeal or upper oesphageal sphincter prevents air passing into the oesophagus during inspiration and the aspiration of oesophageal contents. The cardiac or lower oesophageal sphincter prevents the reflux of acid gastric contents into the oesophagus. There is no thickening of the circular muscle in this area and this sphincter is therefore ‘physiological’, i.e. this region can act as a sphincter without the presence of the anatomical features. When intra-abdominal pressure is raised, e.g. during inspiration and defaecation, the tone of the lower oesophageal sphincter increases. There is an added pinching effect by the contracting muscle fibres of the diaphragm.
Structure of the oesophagus
There are four layers of tissue as shown in Figure 12.2. As the oesophagus is almost entirely in the thorax the outer covering, the adventitia, consists of elastic fibrous tissue that attaches the oesophagus to the surrounding structures. The proximal third is lined by stratified squamous epithelium and the distal third by columnar epithelium. The middle third is lined by a mixture of the two.
The thoracic region is supplied mainly by the paired oesophageal arteries, branches from the thoracic aorta. The abdominal region is supplied by branches from the inferior phrenic arteries and the left gastric branch of the coeliac artery.
From the thoracic region venous drainage is into the azygos and hemiazygos veins. The abdominal part drains into the left gastric vein. There is a venous plexus at the distal end that links the upward and downward venous drainage, i.e. the general and portal circulations.
Functions of the mouth, pharynx and oesophagus
Formation of a bolus
When food is taken into the mouth it is chewed (masticated) by the teeth and moved round the mouth by the tongue and muscles of the cheeks (Fig. 12.15). It is mixed with saliva and formed into a soft mass or bolus ready for swallowing. The length of time that food remains in the mouth depends, to a large extent, on the consistency of the food. Some foods need to be chewed longer than others before the individual feels that the bolus is ready for swallowing.
Figure 12.15 The muscles used in chewing.
Swallowing (deglutition) (Fig. 12.16)
This occurs in three stages after chewing is complete and the bolus has been formed. It is initiated voluntarily but completed by a reflex (involuntary) action.
1. The mouth is closed and the voluntary muscles of the tongue and cheeks push the bolus backwards into the pharynx.
2. The muscles of the pharynx are stimulated by a reflex action initiated in the walls of the oropharynx and coordinated in the medulla and lower pons in the brain stem. Involuntary contraction of these muscles propels the bolus down into the oesophagus. All other routes that the bolus could take are closed. The soft palate rises up and closes off the nasopharynx; the tongue and the pharyngeal folds block the way back into the mouth; and the larynx is lifted up and forward so that its opening is occluded by the overhanging epiglottis preventing entry into the airway (trachea).
3. The presence of the bolus in the pharynx stimulates a wave of peristalsis that propels the bolus through the oesophagus to the stomach.
Figure 12.16 Section of the face and neck showing the positions of structures during swallowing.
Peristaltic waves pass along the oesophagus only after swallowing begins (see Fig. 12.4). Otherwise the walls are relaxed. Ahead of a peristaltic wave, the cardiac sphincter guarding the entrance to the stomach relaxes to allow the descending bolus to pass into the stomach. Usually, constriction of the cardiac sphincter prevents reflux of gastric acid into the oesophagus. Other factors preventing gastric reflux include:
• the attachment of the stomach to the diaphragm by the peritoneum
• the maintenance of an acute angle between the oesophagus and the fundus of the stomach, i.e. an acute cardio-oesophageal angle
• increased tone of the cardiac sphincter when intra-abdominal pressure is increased and the pinching effect of diaphragm muscle fibres.
The walls of the oesophagus are lubricated by mucus which assists the passage of the bolus during the peristaltic contraction of the muscular wall.
After studying this section, you should be able to:
describe the location of the stomach with reference to surrounding structures
explain the physiological significance of the layers of the stomach wall
discuss the digestive functions of the stomach.
The stomach is a J-shaped dilated portion of the alimentary tract situated in the epigastric, umbilical and left hypochondriac regions of the abdominal cavity.
Organs associated with the stomach (Fig. 12.17)
Anteriorly – left lobe of liver and anterior abdominal wall
Posteriorly – abdominal aorta, pancreas, spleen, left kidney and adrenal gland
Superiorly – diaphragm, oesophagus and left lobe of liver
Inferiorly – transverse colon and small intestine
To the left – diaphragm and spleen
To the right – liver and duodenum.
Figure 12.17 The stomach and its associated structures.
Structure of the stomach (Fig. 12.18)
The stomach is continuous with the oesophagus at the cardiac sphincter and with the duodenum at the pyloric sphincter. It has two curvatures. The lesser curvature is short, lies on the posterior surface of the stomach and is the downward continuation of the posterior wall of the oesophagus. Just before the pyloric sphincter it curves upwards to complete the J shape. Where the oesophagus joins the stomach the anterior region angles acutely upwards, curves downwards forming the greater curvature and then slightly upwards towards the pyloric sphincter.
Figure 12.18 Longitudinal section of the stomach.
The stomach is divided into three regions: the fundus, the body and the pylorus. At the distal end of the pylorus is the pyloric sphincter, guarding the opening between the stomach and the duodenum. When the stomach is inactive the pyloric sphincter is relaxed and open, and when the stomach contains food the sphincter is closed.
Walls of the stomach
The four layers of tissue that comprise the basic structure of the alimentary canal (Fig. 12.2) are found in the stomach but with some modifications.
(Fig. 12.19). This consists of three layers of smooth muscle fibres:
• an outer layer of longitudinal fibres
• a middle layer of circular fibres
• an inner layer of oblique fibres.
Figure 12.19 The muscle fibres of the stomach wall. Sections have been removed to show the three layers.
In this respect, the stomach is different from other regions of the alimentary tract as it has three layers of muscle instead of two.
This arrangement allows for the churning motion characteristic of gastric activity, as well as peristaltic movement. Circular muscle is strongest in the pylorus and pyloric sphincter.
When the stomach is empty the mucous membrane lining is thrown into longitudinal folds or rugae, and when full the rugae are ‘ironed out’ and the surface has a smooth, velvety appearance. Numerous gastric glands are situated below the surface in the mucous membrane and open on to it (Fig. 12.20). They consist of specialised cells that secrete gastric juice into the stomach.
Figure 12.20 Coloured scanning electron micrograph of the mucous membrane lining the stomach showing the entrance to a gastric gland.
Arterial supply to the stomach is by the left gastric artery, a branch of the coeliac artery, the right gastric artery and the gastroepiploic arteries. Venous drainage is through veins of corresponding names into the portal vein. Figures 5.44 and 5.46 (pp. 101 and 103) show these vessels.
Gastric juice and functions of the stomach
Stomach size varies with the volume of food it contains, which may be 1.5 litres or more in an adult. When a meal has been eaten the food accumulates in the stomach in layers, the last part of the meal remaining in the fundus for some time. Mixing with the gastric juice takes place gradually and it may be some time before the food is sufficiently acidified to stop the action of salivary amylase.
The activity of gastric muscle consists of a churning movement that breaks down the bolus and mixes it with gastric juice, and peristaltic waves that propel the stomach contents towards the pylorus. When the stomach is active the pyloric sphincter closes. Strong peristaltic contraction of the pylorus forces chyme, gastric contents after they are sufficiently liquefied, through the pyloric sphincter into the duodenum in small spurts. Parasympathetic stimulation increases the motility of the stomach and secretion of gastric juice; sympathetic stimulation has the opposite effect.
About 2 litres of gastric juice are secreted daily by specialised secretory glands in the mucosa (Fig. 12.21). It consists of:
• mucus secreted by mucous neck cells in the glands and surface mucous cells on the stomach surface
• inactive enzyme precursors: pepsinogens secreted by chief cells in the glands.
Figure 12.21 Structure of the gastric mucosa showing gastric glands. A. Diagram. B. Stained section of the pyloric region of the stomach (magnified x 150).
Functions of gastric juice
• Water further liquefies the food swallowed.
• Hydrochloric acid:
– acidifies the food and stops the action of salivary amylase
– kills ingested microbes
– provides the acid environment needed for effective digestion by pepsins.
• Pepsinogens are activated to pepsins by hydrochloric acid and by pepsins already present in the stomach. These enzymes begin the digestion of proteins, breaking them into smaller molecules. Pepsins act most effectively at a very low pH, between 1.5 and 3.5.
• Intrinsic factor (a protein) is necessary for the absorption of vitamin B12 from the ileum.
• Mucus prevents mechanical injury to the stomach wall by lubricating the contents. It prevents chemical injury by acting as a barrier between the stomach wall and the corrosive gastric juice. Hydrochloric acid is present in potentially damaging concentrations and pepsins would digest the gastric tissues.
Secretion of gastric juice
There is always a small quantity of gastric juice present in the stomach, even when it contains no food. This is known as fasting juice. Secretion reaches its maximum level about 1 hour after a meal then declines to the fasting level after about 4 hours.
There are three phases of secretion of gastric juice (Fig. 12.22).
Figure 12.22 The three phases of secretion of gastric juice.
1 Cephalic phase
This flow of juice occurs before food reaches the stomach and is due to reflex stimulation of the vagus (parasympathetic) nerves initiated by the sight, smell or taste of food. When the vagus nerves have been cut (vagotomy), this phase of gastric secretion stops. Sympathetic stimulation, e.g. during emotional states, also inhibits gastric activity.
2 Gastric phase
When stimulated by the presence of food the enteroendocrine cells in the pylorus (Fig. 12.21) and duodenum secrete gastrin, a hormone which passes directly into the circulating blood. Gastrin, circulating in the blood which supplies the stomach, stimulates the gastric glands to produce more gastric juice. In this way secretion of digestive juice is continued after completion of a meal and the end of the cephalic phase. Gastrin secretion is suppressed when the pH in the pylorus falls to about 1.5.
3 Intestinal phase
When the partially digested contents of the stomach reach the small intestine, two hormones, secretin and cholecystokinin, are produced by endocrine cells in the intestinal mucosa. They slow down the secretion of gastric juice and reduce gastric motility. By slowing the emptying rate of the stomach, the chyme in the duodenum becomes more thoroughly mixed with bile and pancreatic juice. This phase of gastric secretion is most marked following a meal with a high fat content.
The rate at which the stomach empties depends largely on the type of food eaten. A carbohydrate meal leaves the stomach in 2 to 3 hours, a protein meal remains longer and a fatty meal remains in the stomach longest.
Functions of the stomach
• temporary storage allowing time for the digestive enzymes, pepsins, to act
• chemical digestion – pepsins convert proteins to polypeptides
• mechanical breakdown – the three smooth muscle layers enable the stomach to act as a churn, gastric juice is added and the contents are liquefied to chyme. Gastric motility and secretion are increased by parasympathetic nerve stimulation
• limited absorption of water, alcohol and some lipid-soluble drugs
• non-specific defence against microbes – provided by hydrochloric acid in gastric juice. Vomiting may occur in response to ingestion of gastric irritants, e.g. microbes or chemicals
• preparation of iron for absorption further along the tract – the acid environment of the stomach solubilises iron salts, which is required before iron can be absorbed
• production and secretion of intrinsic factor needed for absorption of vitamin B12 in the terminal ileum
• regulation of the passage of gastric contents into the duodenum. When the chyme is sufficiently acidified and liquefied, the pylorus forces small jets of gastric contents through the pyloric sphincter into the duodenum. The sphincter is normally closed, preventing backflow of chyme into the stomach
• secretion of the hormone gastrin (see above).
Small intestine (Figs 12.23 and 12.24)
Figure 12.23 The duodenum and its associated structures.
Figure 12.24 The jejunum and ileum and their related structures.
After studying this section, you should be able to:
describe the location of the small intestine, with reference to surrounding structures
sketch a villus, labelling its component parts
discuss the digestive functions of the small intestine and its secretions
explain how nutrients are absorbed in the small intestine.
The small intestine is continuous with the stomach at the pyloric sphincter. The small intestine is a little over 5 metres long and leads into the large intestine at the ileocaecal valve. It lies in the abdominal cavity surrounded by the large intestine. In the small intestine the chemical digestion of food is completed and absorption of most nutrients takes place.
The small intestine comprises three continuous parts.
The duodenum is about 25 cm long and curves around the head of the pancreas. Secretions from the gall bladder and pancreas merge in a common structure – the hepatopancreatic ampulla – and enter the duodenum at the duodenal papilla. The duodenal papilla is guarded by a ring of smooth muscle, the hepatopancreatic sphincter (of Oddi) (see Fig. 12.38).
Figure 12.38 Direction of the flow of bile from the liver to the duodenum.
The jejunum is the middle section of the small intestine and is about 2 metres long.
The ileum, or terminal section, is about 3 metres long and ends at the ileocaecal valve, which controls the flow of material from the ileum to the caecum, the first part of the large intestine, and prevents regurgitation.
Structure of the small intestine
The walls of the small intestine are composed of the four layers of tissue shown in Figure 12.2. Some modifications of the peritoneum and mucosa (mucous membrane lining) are described below.
A double layer of peritoneum called the mesentery attaches the jejunum and ileum to the posterior abdominal wall (see Fig. 12.3A). The attachment is quite short in comparison with the length of the small intestine, therefore it is fan shaped. The large blood vessels and nerves lie on the posterior abdominal wall and the branches to the small intestine pass between the two layers of the mesentery.
The surface area of the small intestine mucosa is greatly increased by permanent circular folds, villi and microvilli.
The permanent circular folds, unlike the rugae of the stomach, are not smoothed out when the small intestine is distended (Fig. 12.25). They promote mixing of chyme as it passes along.
Figure 12.25 Section of a small piece of small intestine (opened out), showing the permanent circular folds.
The villi are tiny finger-like projections of the mucosal layer into the intestinal lumen, about 0.5 to 1 mm long (Fig. 12.26). Their walls consist of columnar epithelial cells, or enterocytes, with tiny microvilli(1 μm long) on their free border. Goblet cells (see also Fig. 12.5) that secrete mucus are interspersed between the enterocytes. These epithelial cells enclose a network of blood and lymph capillaries. The lymph capillaries are called lacteals because absorbed fat gives the lymph a milky appearance. Absorption and some final stages of digestion of nutrients take place in the enterocytes before entering the blood and lymph capillaries.
Figure 12.26 A. A highly magnified diagram of one complete villus in the small intestine. B. Coloured scanning electron micrograph showing many villi.
The intestinal glands are simple tubular glands situated below the surface between the villi. The cells of the glands migrate upwards to form the walls of the villi replacing those at the tips as they are rubbed off by the intestinal contents. The entire epithelium is replaced every 3 to 5 days. During migration, the cells form digestive enzymes that lodge in the microvilli and, together with intestinal juice, complete the chemical digestion of carbohydrates, protein and fats.
Numerous lymph nodes are found in the mucosa at irregular intervals throughout the length of the small intestine. The smaller ones are known as solitary lymphatic follicles, and about 20 or 30 larger nodes situated towards the distal end of the ileum are called aggregated lymphatic follicles (Peyer’s patches, Fig. 12.25). These lymphatic tissues, packed with defensive cells, are strategically placed to neutralise ingested antigens (Ch. 15).
The superior mesenteric artery supplies the whole of the small intestine, and venous drainage is by the superior mesenteric vein that joins other veins to form the portal vein (see Figs 5.45 and 5.46, pp. 102 and 103). The portal vein contains a high concentration of absorbed nutrients and this blood passes through the liver before entering the hepatic veins and, ultimately, into the inferior vena cava (see Fig. 12.36).
Figure 12.36 Scheme of blood flow through the liver.
About 1500 ml of intestinal juice are secreted daily by the glands of the small intestine. It consists of:
• mineral salts.
The pH of intestinal juice is usually between 7.8 and 8.0.
Functions of the small intestine
The functions are:
• onward movement of its contents by peristalsis, which is increased by parasympathetic stimulation
• secretion of intestinal juice, also increased by parasympathetic stimulation
• completion of chemical digestion of carbohydrates, protein and fats in the enterocytes of the villi
• protection against infection by microbes that have survived the antimicrobial action of the hydrochloric acid in the stomach, by the solitary lymph follicles and aggregated lymph follicles
• secretion of the hormones cholecystokinin (CCK) and secretin
• absorption of nutrients.
Chemical digestion in the small intestine
When acid chyme passes into the small intestine it is mixed with pancreatic juice, bile and intestinal juice, and is in contact with the enterocytes of the villi. In the small intestine digestion of all the nutrients is completed:
• carbohydrates are broken down to monosaccharides
• proteins are broken down to amino acids
• fats are broken down to fatty acids and glycerol.
Pancreatic juice is secreted by the exocrine pancreas (p. 300) and enters the duodenum at the duodenal papilla. It consists of:
• mineral salts
– nucleases that digest DNA and RNA
• inactive enzyme precursors including:
Pancreatic juice is alkaline (pH 8) because it contains significant quantities of bicarbonate ions, which are alkaline in solution. When acid stomach contents enter the duodenum they are mixed with pancreatic juice and bile and the pH is raised to between 6 and 8. This is the pH at which the pancreatic enzymes, amylase and lipase, act most effectively.
Digestion of proteins
Trypsinogen and chymotrypsinogen are inactive enzyme precursors activated by enterokinase, an enzyme in the microvilli, which converts them into the active proteolytic enzymes trypsin and chymotrypsin. These enzymes convert polypeptides to tripeptides, dipeptides and amino acids. It is important that they are produced as inactive precursors and are activated only upon arrival in the duodenum, otherwise they would digest the pancreas.
Digestion of carbohydrates
Pancreatic amylase converts all digestible polysaccharides (starches) not acted upon by salivary amylase to disaccharides.
Digestion of fats
Lipase converts fats to fatty acids and glycerol. To aid the action of lipase, bile salts emulsify fats, i.e. reduce the size of the globules, increasing their surface area.
Control of secretion
The secretion of pancreatic juice is stimulated by secretin and CCK, produced by endocrine cells in the walls of the duodenum. The presence in the duodenum of acid chyme from the stomach stimulates the production of these hormones (see Fig. 12.22).
Bile, secreted by the liver, is unable to enter the duodenum when the hepatopancreatic sphincter is closed; therefore it passes from the hepatic duct along the cystic duct to the gall bladder where it is stored (see Fig. 12.38).
Bile has a pH of around 8 and between 500 and 1000 ml are secreted daily. It consists of:
• mineral salts
• bile salts
• bile pigments, mainly bilirubin
• The bile salts emulsify fats in the small intestine.
• Fatty acids are insoluble in water, which makes them very difficult to absorb through the intestinal wall. Bile salts make cholesterol and fatty acids soluble, enabling both these and fat-soluble vitamins (i.e. vitamins A, D, E and K) to be readily absorbed.
• The bile pigment, bilirubin, is a waste product of the breakdown of erythrocytes and is excreted in the bile rather than in the urine because of its low solubility in water. Bilirubin is altered by microbes in the large intestine. Some of the resultant urobilinogen, which is highly water-soluble, is reabsorbed and then excreted in the urine, but most is converted to stercobilin and excreted in the faeces (see Fig. 12.37).
• Stercobilin colours and deodorises the faeces.
Release from the gall bladder
After a meal, the duodenum secretes the hormones secretin and CCK during the intestinal phase of gastric secretion (p. 292). They stimulate contraction of the gall bladder and relaxation of the hepatopancreatic sphincter, enabling the bile and pancreatic juice to pass through the duodenal papilla into the duodenum together. Secretion is markedly increased when chyme entering the duodenum contains a high proportion of fat.
The principal constituents of intestinal secretions are water, mucus and mineral salts.
Most of the digestive enzymes in the small intestine are contained in the enterocytes of the walls of the villi. Digestion of carbohydrate, protein and fat is completed by direct contact between these nutrients and the microvilli and within the enterocytes. The enzymes that complete chemical digestion of food at the surface of the enterocytes are:
• sucrase, maltase and lactase.
Chemical digestion associated with enterocytes
Alkaline intestinal juice (pH 7.8 to 8.0) assists in raising the pH of the intestinal contents to between 6.5 and 7.5.
Enterokinase activates pancreatic peptidases such as trypsin which convert some polypeptides to amino acids and some to smaller peptides. The final stage of breakdown of all peptides to amino acids takes place at the surface of the enterocytes.
Lipase completes the digestion of emulsified fats to fatty acids and glycerol in the intestine.
Sucrase, maltase and lactase complete the digestion of carbohydrates by converting disaccharides such as sucrose, maltose and lactose to monosaccharides at the surface of the enterocytes.
Control of secretion
Mechanical stimulation of the intestinal glands by chyme is believed to be the main stimulus for the secretion of intestinal juice, although the hormone secretin may also be involved.
Absorption of nutrients (Fig. 12.27)
Absorption of nutrients from the small intestine through the enterocytes occurs by several processes, including diffusion, osmosis, facilitated diffusion and active transport. Water moves by osmosis, small fat-soluble substances, e.g. fatty acids and glycerol, are able to diffuse through cell membranes while others are generally transported inside the villi by other mechanisms.
Figure 12.27 The absorption of nutrients into villi.
Monosaccharides and amino acids pass into the capillaries in the villi. Fatty acids and glycerol enter into the lacteals where they are transported along lymphatic vessels and enter the circulation at the thoracic duct (Ch. 6).
Some proteins are absorbed unchanged, e.g. antibodies present in breast milk and oral vaccines, such as poliomyelitis vaccine. The extent of protein absorption is believed to be limited.
Other nutrients such as vitamins, mineral salts and water are also absorbed from the small intestine into the blood capillaries. Fat-soluble vitamins are absorbed into the lacteals along with fatty acids and glycerol. Vitamin B12combines with intrinsic factor in the stomach and is actively absorbed in the terminal ileum.
The surface area through which absorption takes place in the small intestine is greatly increased by the circular folds of mucous membrane and by the very large number of villi and microvilli present (Fig. 12.26). It has been calculated that the surface area of the small intestine is about five times that of the whole body.
Large amounts of fluid enter the alimentary tract each day (Fig. 12.28). Of this, only about 1500 ml is not absorbed by the small intestine, and passes into the large intestine.
Figure 12.28 Average volumes of fluid ingested, secreted, absorbed and eliminated from the gastrointestinal tract daily.
Large intestine, rectum and anal canal
After studying this section, you should be able to:
identify the different sections of the large intestine
describe the structure and functions of the large intestine, the rectum and the anal canal.
The large intestine is about 1.5 metres long, beginning at the caecum in the right iliac fossa and terminating at the rectum and anal canal deep in the pelvis. Its lumen is about 6.5 cm in diameter, larger than that of the small intestine. It forms an arch round the coiled-up small intestine (Fig. 12.29).
Figure 12.29 The parts of the large intestine and their positions.
For descriptive purposes the large intestine is divided into the caecum, colon, sigmoid colon, rectum and anal canal.
This is the first part of the large intestine (Fig. 12.30). It is a dilated region which has a blind end inferiorly and is continuous with the ascending colon superiorly. Just below the junction of the two the ileocaecal valve opens from the ileum. The vermiform appendix is a fine tube, closed at one end, which leads from the caecum. It is usually about 8 to 9 cm long and has the same structure as the walls of the large intestine but contains more lymphoid tissue.
Figure 12.30 Interior of the caecum.
The colon has four parts which have the same structure and functions.
The ascending colon
This passes upwards from the caecum to the level of the liver where it curves acutely to the left at the hepatic flexure to become the transverse colon.
The transverse colon
This is a loop of colon that extends across the abdominal cavity in front of the duodenum and the stomach to the area of the spleen where it forms the splenic flexure and curves acutely downwards to become the descending colon.
The descending colon
This passes down the left side of the abdominal cavity then curves towards the midline. After it enters the true pelvis it is known as the sigmoid colon.
The sigmoid colon
This part describes an S-shaped curve in the pelvis that continues downwards to become the rectum.
This is a slightly dilated section of the large intestine about 13 cm long. It leads from the sigmoid colon and terminates in the anal canal.
The anal canal
This is a short passage about 3.8 cm long in the adult and leads from the rectum to the exterior. Two sphincter muscles control the anus; the internal sphincter, consisting of smooth muscle, is under the control of the autonomic nervous system and the external sphincter, formed by skeletal muscle, is under voluntary control (Fig. 12.31).
Figure 12.31 Arrangement of muscle fibres in the large intestine, rectum and anus. Sections have been removed to show the layers.
The four layers of tissue described in the basic structure of the gastrointestinal tract (Fig. 12.2) are present in the caecum, colon, the rectum and the anal canal. The arrangement of the longitudinal muscle fibres is modified in the caecum and colon. They do not form a smooth continuous layer of tissue but are instead collected into three bands, called taeniae coli, situated at regular intervals round the caecum and colon. They stop at the junction of the sigmoid colon and the rectum. As these bands of muscle tissue are slightly shorter than the total length of the caecum and colon they give it a sacculated or puckered appearance (Fig. 12.31).
The longitudinal muscle fibres spread out as in the basic structure and completely surround the rectum and the anal canal. The anal sphincters are formed by thickening of the circular muscle layer.
In the submucosal layer there is more lymphoid tissue than in any other part of the alimentary tract, providing non-specific defence against invasion by resident and other potentially harmful microbes.
In the mucosal lining of the colon and the upper region of the rectum are large numbers of mucus-secreting goblet cells (see Fig. 12.5B) within simple tubular glands. They are not present beyond the junction between the rectum and the anal canal.
The lining membrane of the anal canal consists of stratified squamous epithelium continuous with the mucous membrane lining of the rectum above and which merges with the skin beyond the external anal sphincter. In the upper section of the anal canal the mucous membrane is arranged in 6 to 10 vertical folds, the anal columns. Each column contains a terminal branch of the superior rectal artery and vein.
Arterial supply is mainly by the superior and inferior mesenteric arteries (see Fig. 5.45, p. 102). The superior mesenteric artery supplies the caecum, ascending and most of the transverse colon. The inferior mesenteric artery supplies the remainder of the colon and the proximal part of the rectum. The middle and inferior rectal arteries, branches of the internal iliac arteries, supply the distal section of the rectum and the anus.
Venous drainage is mainly by the superior and inferior mesenteric veins which drain blood from the parts supplied by arteries of the same names. These veins join the splenic and gastric veins to form the portal vein (see Fig. 5.47, p. 103). Veins draining the distal part of the rectum and the anus join the internal iliac veins, meaning that blood from this region returns directly to the inferior cava, bypassing the portal circulation.
Functions of the large intestine, rectum and anal canal
The contents of the ileum which pass through the ileocaecal valve into the caecum are fluid, even though a large amount of water has been absorbed in the small intestine. In the large intestine absorption of water, by osmosis, continues until the familiar semisolid consistency of faeces is achieved. Mineral salts, vitamins and some drugs are also absorbed into the blood capillaries from the large intestine.
The large intestine is heavily colonised by certain types of bacteria, which synthesise vitamin K and folic acid. They include Escherichia coli, Enterobacter aerogenes, Streptococcus faecalis and Clostridium perfringens. These microbes are commensals, i.e. normally harmless, in humans. However, they may become pathogenic if transferred to another part of the body, e.g. E. coli may cause cystitis if it gains access to the urinary bladder.
Gases in the bowel consist of some of the constituents of air, mainly nitrogen, swallowed with food and drink and as a feature of some anxiety states. Hydrogen, carbon dioxide and methane are produced by bacterial fermentation of unabsorbed nutrients, especially carbohydrate. Gases pass out of the bowel as flatus (wind).
Large numbers of microbes are present in the faeces.
The large intestine does not exhibit peristaltic movement as in other parts of the digestive tract. Only at fairly long intervals (about twice an hour) does a wave of strong peristalsis sweep along the transverse colon forcing its contents into the descending and sigmoid colons. This is known as mass movement and it is often precipitated by the entry of food into the stomach. This combination of stimulus and response is called the gastrocolic reflex.
Usually the rectum is empty, but when a mass movement forces the contents of the sigmoid colon into the rectum the nerve endings in its walls are stimulated by stretch. In the infant, defaecation occurs by reflex (involuntary) action. However, during the second or third year of life the ability to override the defaecation reflex is learned. In practical terms this acquired voluntary control means that the brain can inhibit the reflex until such time as it is convenient to defaecate. The external anal sphincter is under conscious control through the pudendal nerve. Thus defaecation involves involuntary contraction of the muscle of the rectum and relaxation of the internal anal sphincter. Contraction of the abdominal muscles and lowering of the diaphragm increase the intra-abdominal pressure (Valsalva’s manoeuvre) and so assist the process of defaecation. When defaecation is voluntarily postponed the need to defaecate tends to fade until the next mass movement occurs and the reflex is initiated again. Repeated suppression of the reflex may lead to constipation (hard faeces) as more water is absorbed.
Constituents of faeces
The faeces consist of a semisolid brown mass. The brown colour is due to the presence of stercobilin (p. 296 and Fig. 12.37).
Figure 12.37 Fate of bilirubin from breakdown of worn-out erythrocytes.
Even though absorption of water takes place in the small and large intestines, water still makes up about 60 to 70% of the weight of the faeces. The remainder consists of:
• fibre (indigestible cellular plant and animal material)
• dead and live microbes
• epithelial cells shed from the walls of the tract
• fatty acids
• mucus secreted by the epithelial lining of the large intestine.
Mucus helps to lubricate the faeces and an adequate amount of dietary non-starch polysaccharide (NSP, fibre and previously known as roughage) ensures that the contents of the large intestine are sufficiently bulky to stimulate defaecation.
Pancreas (Fig. 12.32)
Figure 12.32 The pancreas in relation to the duodenum and biliary tract; part of the anterior wall of the duodenum has been removed.
After studying this section, you should be able to:
differentiate between the structures and functions of the exocrine and endocrine pancreas.
The pancreas is a pale grey gland weighing about 60 grams. It is about 12 to 15 cm long and is situated in the epigastric and left hypochondriac regions of the abdominal cavity (see Figs 3.34 and 3.35, p. 47). It consists of a broad head, a body and a narrow tail. The head lies in the curve of the duodenum, the body behind the stomach and the tail lies in front of the left kidney and just reaches the spleen. The abdominal aorta and the inferior vena cava lie behind the gland.
The pancreas is both an exocrine and endocrine gland.
The exocrine pancreas
This consists of a large number of lobules made up of small acini, the walls of which consist of secretory cells. Each lobule is drained by a tiny duct and these unite eventually to form the pancreatic duct, which extends the whole length of the gland and opens into the duodenum. Just before entering the duodenum the pancreatic duct joins the common bile duct to form the hepatopancreatic ampulla. The duodenal opening of the ampulla is controlled by the hepatopancreatic sphincter (of Oddi) at the duodenal papilla.
The function of the exocrine pancreas is to produce pancreatic juice containing enzymes that digest carbohydrates, proteins and fats (p. 295). As in the alimentary tract, parasympathetic stimulation increases the secretion of pancreatic juice and sympathetic stimulation depresses it.
The endocrine pancreas
Distributed throughout the gland are groups of specialised cells called the pancreatic islets (of Langerhans). The islets have no ducts so the hormones diffuse directly into the blood. The endocrine pancreas secretes the hormones insulin and glucagon, which are principally concerned with control of blood glucose levels (see Ch. 9).
The splenic and mesenteric arteries supply the pancreas, and venous drainage is by veins of the same names that join other veins to form the portal vein.
After studying this section, you should be able to:
describe the location of the liver in the abdominal cavity
describe the structure of a liver lobule
list the functions of the liver.
The liver is the largest gland in the body, weighing between 1 and 2.3 kg. It is situated in the upper part of the abdominal cavity occupying the greater part of the right hypochondriac region, part of the epigastric region and extending into the left hypochondriac region. Its upper and anterior surfaces are smooth and curved to fit the under surface of the diaphragm (Fig. 12.33); its posterior surface is irregular in outline (Fig. 12.34).
Figure 12.33 The liver: anterior view.
Figure 12.34 The liver, turned up to show the posterior surface.
Organs associated with the liver
Superiorly and anteriorly – diaphragm and anterior abdominal wall
Inferiorly – stomach, bile ducts, duodenum, hepatic flexure of the colon, right kidney and adrenal gland
Posteriorly – oesophagus, inferior vena cava, aorta, gall bladder, vertebral column and diaphragm
Laterally – lower ribs and diaphragm.
The liver is enclosed in a thin inelastic capsule and incompletely covered by a layer of peritoneum. Folds of peritoneum form supporting ligaments attaching the liver to the inferior surface of the diaphragm. It is held in position partly by these ligaments and partly by the pressure of the organs in the abdominal cavity.
The liver has four lobes. The two most obvious are the large right lobe and the smaller, wedge-shaped, left lobe. The other two, the caudate and quadrate lobes, are areas on the posterior surface (Fig. 12.34).
The portal fissure
This is the name given to the region on the posterior surface of the liver where various structures enter and leave the gland.
The portal vein enters, carrying blood from the stomach, spleen, pancreas and the small and large intestines.
The hepatic artery enters, carrying arterial blood. It is a branch from the coeliac artery, which is a branch from the abdominal aorta.
Nerve fibres, sympathetic and parasympathetic, enter here.
The right and left hepatic ducts leave, carrying bile from the liver to the gall bladder.
Lymph vessels leave the liver, draining some lymph to abdominal and some to thoracic nodes.
Blood supply (see Figs 5.44 and 5.46)
The hepatic artery and the portal vein take blood to the liver (see Fig. 12.36). Venous return is by a variable number of hepatic veins that leave the posterior surface and immediately enter the inferior vena cava just below the diaphragm.
The lobes of the liver are made up of tiny functional units, called lobules, which are just visible to the naked eye (Fig. 12.35A). Liver lobules are hexagonal in outline and are formed by cubical-shaped cells, the hepatocytes, arranged in pairs of columns radiating from a central vein. Between two pairs of columns of cells are sinusoids (blood vessels with incomplete walls, Ch. 5) containing a mixture of blood from the tiny branches of the portal vein and hepatic artery (Fig. 12.35B). This arrangement allows the arterial blood and portal venous blood (with a high concentration of nutrients) to mix and come into close contact with the liver cells. Amongst the cells lining the sinusoids are hepatic macrophages (Kupffer cells) whose function is to ingest and destroy worn out blood cells and any foreign particles present in the blood flowing through the liver.
Figure 12.35 A. A magnified transverse section of a liver lobule. B. Direction of the flow of blood and bile in a liver lobule.
Blood drains from the sinusoids into central or centrilobular veins. These then join with veins from other lobules, forming larger veins, until eventually they become the hepatic veins, which leave the liver and empty into the inferior vena cava. Figure 12.36 shows the system of blood flow through the liver. One of the functions of the liver is to secrete bile. In Figure 12.35B it is seen that bile canaliculi run between the columns of liver cells. This means that each column of hepatocytes has a blood sinusoid on one side and a bile canaliculus on the other. The canaliculi join up to form larger bile canals until eventually they form the right and left hepatic ducts, which drain bile from the liver.
Lymphoid tissue and a system of lymph vessels are also present in each lobule.
Functions of the liver
The liver is an extremely active organ. Those functions already described are only mentioned here.
The liver has an important role in maintaining plasma glucose levels. After a meal when levels rise, glucose is converted to glycogen for storage under the influence of the hormone insulin. Later, when glucose levels fall, the hormone glucagon stimulates conversion of glycogen into glucose again, keeping levels within the normal range (see Fig 12.39).
Figure 12.39 Summary of the source, distribution and use of glucose.
Stored fat can be converted to a form in which it can be used by the tissues to provide energy (see Fig. 12.44).
Figure 12.44 Summary of the fates of the three main energy sources in the central metabolic pathways.
Deamination of amino acids
• removes the nitrogenous portion from the amino acids not required for the formation of new protein; urea is formed from this nitrogenous portion which is excreted in urine
• breaks down nucleic acids (genetic material, see p. 24 and Ch. 17) to form uric acid, which is excreted in the urine.
Removes the nitrogenous portion of amino acids and attaches it to other carbohydrate molecules forming new non-essential amino acids (see Fig. 12.42).
Figure 12.42 The fate of amino acids in the body.
Synthesis of plasma proteins
and most blood clotting factors from amino acids.
Breakdown of erythrocytes and defence against microbes
This is carried out by phagocytic hepatic macrophages (Kupffer cells) in the sinusoids (breakdown of red blood cells also takes place in the spleen and bone marrow).
Detoxification of drugs and toxic substances
These include ethanol (alcohol) and toxins produced by, e.g., microbes. Some drugs are extensively inactivated by the liver and are not very effective when given by mouth (orally), e.g. glyceryl trinitrate. This is because after absorption from the alimentary tract, they travel in the blood to the liver where they are largely metabolised so that levels in the blood leaving the liver are inadequate to achieve therapeutic effects. This is known as ‘first pass metabolism’.
Inactivation of hormones
These include insulin, glucagon, cortisol, aldosterone, thyroid and sex hormones.
Production of heat
The liver uses a considerable amount of energy, has a high metabolic rate and produces a great deal of heat. It is the main heat-producing organ of the body.
Secretion of bile
The hepatocytes synthesise the constituents of bile from the mixed arterial and venous blood in the sinusoids. These include bile salts, bile pigments and cholesterol.
Stored substances include:
• glycogen (see p. 307)
• fat-soluble vitamins: A, D, E, K
• iron, copper
• some water-soluble vitamins, e.g. vitamin B12.
Composition of bile
Between 500 and 1000 ml of bile are secreted by the liver daily. Bile consists of:
• mineral salts
• bile pigments, mainly bilirubin
• bile salts, which are derived from the primary bile acids, cholic acid and chenodeoxycholic acid
The bile acids, cholic and chenodeoxycholic acid, are synthesised by hepatocytes from cholesterol, then secreted into bile as sodium or potassium salts. In the small intestine they emulsify fats, aiding their digestion. In the terminal ileum most of the bile salts are reabsorbed and return to the liver in the portal vein. This enterohepatic circulation, or recycling of bile salts, ensures that large amounts of bile salts enter the small intestine daily from a relatively small bile acid pool (Fig. 12.37).
Bilirubin is one of the products of haemolysis of erythrocytes by hepatic macrophages (Kupffer cells) in the liver and by other macrophages in the spleen and bone marrow. Bilirubin is insoluble in water and is carried in the blood bound to albumin. In hepatocytes it is conjugated (combined) with glucuronic acid and becomes water-soluble enough to be excreted in bile. Bacteria in the intestine change the form of bilirubin and most is excreted as stercobilin in the faeces. A small amount is reabsorbed and excreted in urine as urobilinogen (Fig. 12.37). Jaundice is yellow pigmentation of the tissues, seen in the skin and conjunctiva, caused by excess blood bilirubin (p. 326).
After studying this section, you should be able to:
describe the route taken by bile from the liver, to the gall bladder, and then to the duodenum
outline the structure and functions of the gall bladder.
Bile ducts (Fig. 12.38)
The right and left hepatic ducts join to form the common hepatic duct just outside the portal fissure. The hepatic duct passes downwards for about 3 cm where it is joined by the cystic duct from the gall bladder. The cystic and hepatic ducts merge forming the common bile duct, which passes downwards behind the head of the pancreas. This is joined by the main pancreatic duct at the hepatopancreatic ampulla and the opening into the duodenum, at the duodenal papilla, is controlled by the hepatopancreatic sphincter (of Oddi). The common bile duct is about 7.5 cm long and has a diameter of about 6 mm.
The walls of the bile ducts have the same layers of tissue as those described in the basic structure of the alimentary canal (Fig. 12.2). In the cystic duct the mucous membrane lining is arranged in irregular circular folds, which have the effect of a spiral valve. Bile passes through the cystic duct twice – once on its way into the gall bladder and again when it is expelled from the gall bladder into the common bile duct and then on to the duodenum.
The gall bladder is a pear-shaped sac attached to the posterior surface of the liver by connective tissue. It has a fundus or expanded end, a body or main part and a neck, which is continuous with the cystic duct.
The wall of the gall bladder has the same layers of tissue as those described in the basic structure of the alimentary canal, with some modifications.
This covers only the inferior surface because the upper surface of the gall bladder is in direct contact with the liver and held in place by the visceral peritoneum that covers the liver.
There is an additional layer of oblique muscle fibres.
This displays small rugae when the gall bladder is empty that disappear when it is distended with bile.
The cystic artery, a branch of the hepatic artery, supplies blood to the gall bladder. Blood is drained away by the cystic vein that joins the portal vein.
Functions of the gall bladder
• reservoir for bile
• concentration of the bile by up to 10- or 15-fold, by absorption of water through the walls of the gall bladder
• release of stored bile.
When the muscle wall of the gall bladder contracts, bile passes through the bile ducts to the duodenum. Contraction is stimulated by:
• the hormone cholecystokinin (CCK), secreted by the duodenum
• the presence of fat and acid chyme in the duodenum.
Relaxation of the hepatopancreatic sphincter (of Oddi) is caused by CCK and is a reflex response to contraction of the gall bladder.
Summary of digestion and absorption of nutrients
After studying this section, you should be able to:
list the principal digestive enzymes, their sites of action, their substrates and their products
describe the sites of absorption of the main nutrient groups.
Table 12.2 summarises the main digestive processes of the principal nutrient groups, the locations where these processes occur and the enzymes involved.
Table 12.2Summary showing the sites of digestion and absorption of nutrients
After studying this section, you should be able to:
discuss general principles of metabolism, including anabolism, catabolism, units of energy and metabolic rate
compare and contrast the metabolic rates of the body’s main energy sources (carbohydrate, protein and fat)
describe in simple terms the central metabolic pathways; glycolysis, citric acid cycle and oxidative phosphorylation.
Metabolism constitutes all the chemical reactions that occur in the body, using nutrients to:
• provide energy by chemical oxidation of nutrients
• make new or replacement body substances.
Two types of process are involved:
This process breaks down large molecules into smaller ones releasing chemical energy, which is stored as adenosine triphosphate (ATP), and heat. Heat is used to maintain core body temperature at the optimum level for chemical activity (36.8°C). Excess heat is lost, mainly through the skin (Ch. 14).
This is building up, or synthesis, of large molecules from smaller ones and requires a source of energy, usually ATP.
Anabolism and catabolism usually involve a series of chemical reactions, known as metabolic pathways. These consist of ‘small steps’ that permit controlled, efficient and gradual transfer of energy from ATP rather than large intracellular ‘explosions’. Metabolic pathways are switched on and off by hormones, providing control of metabolism and meeting individual requirements.
Both processes occur continually in all cells, maintaining an energy balance. Very active tissues, such as muscle or liver, need a large energy supply to support their requirements.
The energy produced in the body may be measured and expressed in units of work (joules) or units of heat (kilocalories).
A kilocalorie (kcal) is the amount of heat required to raise the temperature of 1 litre of water by 1 degree Celsius (1°C). On a daily basis, the body’s collective metabolic processes generate a total of about 3 million kilocalories.
1 kcal = 4184 joules (J) = 4.184 kilojoules (kJ)
The nutritional value of carbohydrates, protein and fats eaten in the diet may be expressed in kilojoules per gram or kcal per gram.
1 gram of carbohydrate provides 17 kilojoules (4 kcal)
1 gram of protein provides 17 kilojoules (4 kcal)
1 gram of fat provides 38 kilojoules (9 kcal)
Chapter 11 provides examples of foods providing these nutrients.
Body weight remains constant when energy intake is equal to energy use. When intake exceeds requirement, body weight increases. Conversely, body weight decreases when nutrient intake does not meet energy requirements.
The metabolic rate is the rate at which energy is released from the fuel molecules inside cells. As most of the processes involved require oxygen and produce carbon dioxide as waste, the metabolic rate can be estimated by measuring oxygen uptake or carbon dioxide excretion.
The basal metabolic rate (BMR) is the rate of metabolism when the individual is at rest in a warm environment and is in the postabsorptive state, i.e. has not had a meal for at least 12 hours. In this state the release of energy is sufficient to meet only the essential needs of vital organs, such as the heart, lungs, nervous system and kidneys. The postabsorptive state is important because the intake of food, especially protein, increases metabolic rate. Some of the many different factors that affect metabolic rate are shown in Table 12.3.
Table 12.3 Factors affecting metabolic rate
Effect on metabolic rate
Gradually reduced with age
Higher in men than women
Relatively higher in larger people
Pregnancy, menstruation, lactation
Ingestion of food
Muscular activity, physical exertion
Elevated body temperature (fever)
Excess thyroid hormones
Most foods contain a mixture of different amounts of carbohydrate, protein, fat, minerals, vitamins, fibre (non-starch polysaccharide) and water. Carbohydrates, proteins and fats are the sources of energy and they are obtained from the variety of food eaten in the diet (see Ch. 11).
Central metabolic pathways
Much of the metabolic effort of cells is concerned with energy production to fuel cellular activities. Certain common pathways are central to this function. Fuel molecules enter these central energy-producing pathways and in a series of steps, during which a series of intermediate molecules are formed and energy is released, these fuel molecules are chemically broken down. The end results of these processes are energy production and carbon dioxide and water (called metabolic water) formation. Much of the energy is stored as ATP, although some is lost as heat. The carbon dioxide is excreted through the lungs.
The preferred fuel molecule is glucose, but alternatives should glucose be unavailable include amino acids, fatty acids, glycerol and occasionally nucleic acids. Each of these may enter the central energy-producing pathways and be converted to energy, carbon dioxide and water. There are three central metabolic pathways (see Fig. 12.44):
• the citric acid (Krebs) cycle
• oxidative phosphorylation.
Products from glycolysis enter the citric acid cycle, and products from the citric acid cycle proceed to oxidative phosphorylation. The fates of the different fuel molecules entering the central metabolic pathways are discussed in the following sections.
Erythrocytes and neurones can use only glucose for fuel and therefore maintenance of blood glucose levels is needed to provide a constant energy source to these cells. Most other cells can also use other sources of fuel.
Digested carbohydrate, mainly glucose, is absorbed into the blood capillaries of the villi of the small intestine. It is transported by the portal circulation to the liver, where it is dealt with in several ways (Fig. 12.39):
• Glucose may be oxidised to provide the chemical energy, in the form of ATP, necessary for the considerable metabolic activity which takes place in the liver (p. 301).
• Some glucose may remain in the circulating blood to maintain the normal blood glucose of about 3.5 to 8 millimoles per litre (mmol/l) (63 to 144 mg/100 ml).
• Some glucose, if in excess of the above requirements, may be converted to the insoluble polysaccharide, glycogen, in the liver and in skeletal muscles. The hormone insulin is needed for this change to take place. The formation of glycogen inside cells is a means of storing carbohydrate without upsetting the osmotic equilibrium. Before it can be used to maintain blood levels or to provide ATP it must be broken down again into its constituent glucose units. Liver glycogen constitutes a store of glucose used for liver activity and to maintain the blood glucose level. Muscle glycogen stores provide the glucose requirement of muscle activity. Glucagon, adrenaline (epinephrine) and thyroxine are the main hormones associated with the breakdown of glycogen to glucose. These processes can be summarised:
• Carbohydrate in excess of that required to maintain the blood glucose level and glycogen stores in the tissues is converted to fat and stored in the fat depots.
All body cells require energy to carry out their metabolic processes including multiplication for replacement of worn out cells, contraction of muscle fibres and synthesis of secretions produced by glands. The oxidation of carbohydrate and fat provides most of the energy required by the body. When glycogen stores are low and more glucose is needed, the body can make glucose from non-carbohydrate sources, e.g. amino acids, glycerol. This is called gluconeogenesis (formation of new glucose).
Carbohydrate and energy release (Fig. 12.40)
Glucose is broken down in the body releasing energy, carbon dioxide and metabolic water. Catabolism of glucose occurs in a series of steps with a little energy being released at each stage. The total number of ATP molecules which may be generated from the complete breakdown of one molecule of glucose is 38, but for this to be achieved the process must occur in the presence of oxygen (aerobically). In the absence of oxygen (anaerobically) this number is greatly reduced; the process is therefore much less efficient.
Figure 12.40 Oxidation of glucose.
Aerobic respiration (catabolism)
Aerobic catabolism of glucose can occur only if the oxygen supply is adequate, and is the process by which energy is released during prolonged, manageable exercise. When exercise levels become very intense, the energy requirements of muscles outstrip the oxygen supply, and anaerobic breakdown then occurs. Such high levels of activity can be sustained for only short periods, because there is accumulation of wastes (mainly lactic acid) and reduced efficiency of the energy production process.
The first stage of glucose catabolism is glycolysis. This is an anaerobic process that takes place in the cytoplasm of the cell. Through a number of intermediate steps one glucose molecule is converted to two molecules of pyruvic acid, with the net production of two molecules of ATP. The remainder of the considerable energy stores locked up in the original molecule of glucose is released only if there is enough oxygen to allow the pyruvic acid molecules to enter the biochemical roundabout called the citric acid cycle (Fig. 12.40). This takes place in the mitochondria of the cell and is oxygen dependent. For every two molecules of pyruvic acid entering the citric acid cycle, a further two molecules of ATP are formed but this is still far short of the maximum possible 38 ATP molecules. The remaining 34 molecules of ATP come from the third energy-generating process, oxidative phosphorylation, a process dependent on hydrogen atoms released during earlier stages of glucose breakdown. Oxidative phosphorylation, like the citric acid cycle, can occur only in the presence of oxygen and takes place in the mitochondria.
When oxygen levels in the cell are low, the molecule of glucose still undergoes glycolysis and is split into two molecules of pyruvic acid, because glycolysis is an anaerobic process. However, the pyruvic acid does not enter the citric acid cycle or progress to oxidative phosphorylation; instead it is converted anaerobically to lactic acid. Build-up of lactic acid causes the pain and cramps of overexercised muscles. When oxygen levels are restored, lactic acid is reconverted to pyruvic acid, which may then enter the citric acid cycle.
Fate of the end products of carbohydrate metabolism
Some of the lactic acid produced by anaerobic catabolism of glucose may be oxidised in the cells to carbon dioxide and water but first it must be changed back to pyruvic acid. If complete oxidation does not take place, lactic acid passes to the liver in the circulating blood where it is converted to glucose and may then take any of the pathways open to glucose (Fig. 12.39).
This is excreted from the body as a gas by the lungs.
This is added to the considerable amount of water already present in the body; excess is excreted as urine by the kidneys.
Dietary protein consists of a number of amino acids. About 20 amino acids have been named and nine of these are described as essential because they cannot be synthesised in the body. The others are non-essential amino acids because they can be synthesised by many tissues. The enzymes involved in this process are called transaminases. Digestion breaks down dietary protein into its constituent amino acids in preparation for absorption into the blood capillaries of the villi in the wall of the small intestine. Amino acids are transported in the portal circulation to the liver and then into the general circulation, thus making them available to all the cells and tissues of the body. Different cells choose from those available the particular amino acids required for building or repairing their specific type of tissue and for synthesising their secretions, e.g. antibodies, enzymes or hormones.
Amino acids not required for building and repairing body tissues cannot be stored and are broken down in the liver (see deamination below).
Amino acid pool (Fig. 12.41)
A small pool of amino acids is maintained within the body. This is the source from which the different cells of the body draw the amino acids they need to synthesise their own materials, e.g. new cells, secretions such as enzymes, hormones and plasma proteins.
Figure 12.41 Sources and use of amino acids in the body.
Sources of amino acids
These are derived from dietary protein.
These are obtained from the breakdown of body proteins. In adults, about 80 to 100 g of protein are broken down and replaced each day. The entire intestinal mucosa is replaced about every 5 days.
Loss of amino acids
Amino acids not needed by the body are broken down, or deaminated, mainly in the liver. The nitrogenous part, the amino group (NH2), is converted to ammonia (NH3) and then combined with carbon dioxide forming urea, which is excreted in the urine. The remaining part is used to provide energy, as glucose by gluconeogenesis, or stored as fat, if in excess of immediate requirements.
The faeces contain a considerable amount of protein consisting of cells shed from the lining of the alimentary tract.
Endogenous and exogenous amino acids are mixed in the ‘pool’ and the body is said to be in nitrogen balance when the rate of removal from the pool is equal to the additions to it. Unlike carbohydrates, the body has no capacity for the storage of amino acids except for this relatively small pool. Figure 12.42 depicts what happens to amino acids in the body.
Amino acids and energy release (see Fig. 12.44)
Proteins, in the form of amino acids, are potential fuel molecules that are used by the body only when other energy sources are low, e.g. in starvation. To supply the amino acids for use as fuel, in extreme situations, the body breaks down muscle, its main protein source. Some amino acids can be converted directly to glucose, which enters glycolysis. Other amino acids are changed to intermediate compounds of the central metabolic pathways, e.g. acetyl coenzyme A or oxaloacetic acid, and therefore enter the system at a later stage.
Fat metabolism (Fig. 12.43)
Fat is synthesised from excess dietary carbohydrates and proteins, and stored in the fat depots, i.e. under the skin, in the omentum or around the kidneys.
Figure 12.43 Sources, distribution and use of fats in the body.
Fats that have been digested and absorbed as fatty acids and glycerol into the lacteals are transported via the cisterna chyli and the thoracic duct to the bloodstream and so, by a circuitous route, to the liver. Fatty acids and glycerol circulating in the blood are used by the cells of organs and glands to provide energy and in the synthesis of some of their secretions. In the liver some fatty acids and glycerol are used to provide energy and heat, and some are recombined forming triglycerides, the form in which fat is stored. A triglyceride consists of three fatty acids chemically combined with a glycerol molecule (see Fig. 2.9, p. 24). When required, triglycerides are converted back to fatty acids and glycerol and used to provide energy. The end products of fat metabolism are energy, heat, carbon dioxide and water.
Fatty acids and energy release
When body tissues are deprived of glucose, as occurs in prolonged fasting, starvation, energy-restricted diets or during strenuous exercise, the body uses alternative energy sources, mainly fat stores. Fatty acids may be converted to acetyl coenzyme A, and enter the energy production pathway in that form. One consequence of this is accumulation of ketone bodies, which are produced in the liver from acetyl coenzyme A when levels are too high for processing through the citric acid cycle (see Fig. 12.44). Ketone bodies then enter the blood and can be used by other body tissues, including the brain (which is usually glucose dependent) as a source of fuel. However, at high concentrations, ketone bodies are toxic, particularly to the brain. Ketone bodies include acetone and some weak organic acids. Normally levels are low because they are used as soon as they are produced. When production exceeds use, in the situations mentioned above, levels rise causing ketosis. Ketosis is associated with acidosis, which can lead to coma or even death if severe. Excretion of excess ketone bodies is via:
• the urine (ketonuria)
• the lungs, giving the breath a characteristic sweet smell of acetone or ‘pear drops’.
In ketosis, compensation is required to maintain acid– base balance. This is achieved by buffer systems that excrete excess acid (hydrogen ions) by the lungs, through hyperventilation, or kidneys. In health, ketosis is self-limiting and ketone body production stops when fasting or exercise ceases. Ketoacidosis is associated with uncontrolled type 1 diabetes mellitus (p. 227).
Glycerol and energy release (Fig. 12.44)
The body converts glycerol from the degradation of fats into one of the intermediary compounds produced during glycolysis, and in this form it enters the central metabolic pathways.
Diseases of the mouth
After studying this section, you should be able to:
discuss the main inflammatory and infectious conditions of the mouth
outline the sites and effects of oral squamous cell carcinoma
distinguish between cleft lip and cleft palate, including describing the anatomical abnormalities involved.
Inflammatory and infectious conditions
Injury may be caused to tissues in and around the mouth by food and other ingested substances, if they are corrosive, abrasive or excessively hot or cold. Corrosive chemicals are the most likely to cause serious tissue damage and acute inflammation. The mouth contains a large number and variety of micro-organisms. The antibacterial action of saliva helps to limit their growth, but the presence of plaque and residual foodstuffs, especially sugars, in the mouth can promote infection. Inflammation of the mouth is known as stomatitis, and inflammation of the gums as gingivitis.
Thrush (oral candidiasis)
This acute fungal infection of the epithelium of the mouth is caused by the yeast Candida albicans, which grows in white patches on the tongue and oral mucosa. In adults it causes opportunistic infection mainly in debilitated people and in those whose immunity is lowered by, e.g., steroids, antibiotics or cytotoxic drugs. In babies it may be a severe infection, sometimes causing epidemics in nurseries by cross-infection. It occurs most commonly in bottle-fed babies. Chronic thrush may develop, affecting the roof of the mouth in people who wear dentures. The fungus survives in fine grooves on the upper surface of the denture and repeatedly reinfects the oral mucosa.
Painful cracks develop in folds of tissue at the corners of the mouth, usually in elderly debilitated people, especially if they do not wear their dentures and the folds remain moist. Common causal organisms are Candida albicans and Staphylococcus aureus.
Dietary deficiency of iron and B group vitamins predispose to this condition.
This is inflammation of the gums, which may be acute or chronic.
This is a rare condition previously known as Vincent’s infection, in which there is severe inflammation that mainly affects the gums. It is caused by two commensal organisms acting together, Borrelia vincentiand a fusiform bacillus. Both organisms may be present in the mouth but only cause the condition in the presence of malnutrition, debilitating disease, poor oral hygiene or injury caused by previous infection.
This common inflammatory condition occurs in response to accumulation of bacterial plaque around the teeth. It causes bleeding gums and gradually destroys the tissues that support the teeth, which eventually loosen and may fall out.
Aphthous stomatitis (recurrent oral ulceration)
This common condition features extremely painful ulcers that occur singly or in crops inside the mouth. The cause is unknown.
Acute herpetic gingivostomatitis
Inflammation of the mouth and gums is caused by Herpes simplex virus and is the most common oral virus infection. It is characterised by extensive and very painful ulceration.
Secondary or recurrent herpes lesions (cold sores)
Lesions, caused by Herpes simplex virus, occur round the nose and on the lips. After an outbreak the viruses remain dormant within the cells. Later outbreaks, usually at the same site, are precipitated by a variety of stimuli including exposure to UV rays (strong sunlight) and impaired immune response in, for example, old age.
Tumours of the mouth
Squamous cell carcinoma
This is the most common type of malignant tumour in the mouth. It affects mainly elderly people and carries a poor prognosis. The usual sites are the lower lip and the edge of the tongue. Ulceration occurs frequently and there is early spread to surrounding tissues and cervical lymph nodes.
Cleft palate and cleft lip (harelip)
During embryonic development, the roof of the mouth (hard palate) develops as two separate (right and left) halves; this occurs from the lips anteriorly to the uvula posteriorly. Before birth, these two halves normally fuse along the midline. If fusion is incomplete, a cleft (division) occurs, which may be very minor, or it may be substantial. Cleft lip (Fig. 12.45B) ranges from a minor notch in the upper lip to a more extensive condition when the lip is completely split in one or two places and the nose is involved. In cleft palate, there is a gap between the two halves of the palate, which creates a channel of communication between the mouth and the nasal cavity (Fig. 12.45C). Factors believed to play a causative part in these conditions include genetic abnormalities, and fetal exposure to factors such as hypoxia, certain drugs or poor nutrition, between weeks 7 and 10 of pregnancy.
Figure 12.45 Cleft lip and cleft palate: A. Normal hard palate. B. Cleft lip. C. Cleft palate.
Drinking, eating and development of speech cannot take place normally until the defect has been surgically repaired.
Tooth decay starts with discolouration and then formation of cavities (caries). It arises when bacteria present in plaque on the teeth act on sugars forming acid, which may eventually destroy the hard parts of the teeth. The condition can be prevented by good oral hygiene.
Diseases of the pharynx
See tonsillitis and diphtheria (p. 254).
Diseases of salivary glands
After studying this section, you should be able to:
outline the pathophysiology of mumps
explain the nature of salivary calculi
describe the most common tumours of the salivary glands.
This is an acute inflammatory condition of the salivary glands, especially the parotids. It is caused by the mumps virus, one of the parainfluenza group. The virus is inhaled in infected droplets and, during the 18- to 21-day incubation period, viruses multiply elsewhere in the body before spreading to the salivary glands. The virus is present in saliva for about 7 days before and after symptoms appear so the infection may spread to others during this 2-week period. Viruses also occasionally spread to:
• the pancreas, causing pancreatitis
• the testes, causing orchitis (testicular inflammation) after puberty and sometimes atrophy of the glands and sterility
• the brain, causing meningitis (see Ch. 7) or meningoencephalitis.
In developed countries, children are usually vaccinated against mumps in their preschool years.
Calculi (stones) are formed in the salivary glands by the crystallisation of mineral salts in saliva. They may partially or completely block the ducts, leading to inflammation and swelling of the gland, a predisposition to infection and, in time, atrophy. The causes are not known.
Tumours of the salivary glands
Mixed tumours (pleomorphic salivary adenoma)
This benign tumour consists of epithelial and connective tissue cells and occurs mainly in the parotid gland. It is the most common tumour of the salivary glands. A second tumour may develop in the same gland several years after the first has been removed and it occasionally undergoes malignant change.
Malignant tumours most commonly affect the parotid glands. Some forms have a tendency to infiltrate nerves in the surrounding tissues, causing severe pain. Lymph spread is to the cervical nodes.
Diseases of the oesophagus
After studying this section, you should be able to:
explain how oesophageal varices develop
discuss the main inflammatory conditions of the oesophagus
describe the main oesophageal tumours
define oesophageal atresia and tracheo-oesophageal fistula.
Oesophageal varices (Fig. 12.46)
In conditions such as cirrhosis (p. 325) or venous thrombosis, blood flow into the liver via the portal vein is impeded and blood pressure within the portal system rises (portal hypertension). This forces blood from the portal vein into anastomotic veins, which redirect (shunt) blood into the systemic venous circulation, bypassing the liver. Fifty per cent or more of the portal blood may be shunted into anastomotic veins, leading to rising pressure in these veins too. One route taken by the shunted blood is into veins of the distal oesophagus, which become distended and weakened by the abnormally high volume of blood. Varices (localised dilations of veins) develop when the weakest regions of the vessel wall bulge outwards into the lumen of the oesophagus, and, being thin walled and fragile, they are easily eroded or traumatised by swallowed food. Bleeding may be slight, but chronic, leading to iron deficiency anaemia (p. 66); however, sudden rupture can cause life-threatening haemorrhage.
Figure 12.46 Oesophageal varices.
Inflammatory and infectious conditions
This arises after caustic materials are swallowed and also if immunocompromised people acquire severe fungal infections, typically candidiasis (p. 311), or viral infections, e.g. Herpes simplex. Dysphagia(difficulty in swallowing) is usually present. Following severe injury, healing causes fibrosis, and there is a risk of oesophageal stricture developing later, as the fibrous tissue shrinks.
This condition, the commonest cause of indigestion (or ‘heartburn’), is caused by persistent regurgitation of acidic gastric juice into the oesophagus, causing irritation, inflammation and painful ulceration. Haemorrhage occurs when blood vessels are eroded. Persistent reflux leads to chronic inflammation and if damage is extensive, secondary healing with fibrosis occurs. Shrinkage of mature fibrous tissue may cause stricture of the oesophagus. This condition sometimes gives rise to Barrett’s oesophagus (see below). Reflux of gastric contents is associated with:
• increase in the intra-abdominal pressure, e.g. in pregnancy, constipation and obesity
• high acid content of gastric juice
• low levels of secretion of the hormone gastrin, leading to reduced sphincter action at the lower end of the oesophagus
• the presence of hiatus hernia (p. 321).
This condition develops after long-standing reflux oesophagitis. Columnar cells resembling those found in the stomach replace the squamous epithelium of the lower oesophagus and this is a premalignant state carrying an increased risk of subsequent malignancy.
This problem tends to occur in young adults. Peristalsis of the lower oesophagus is impaired and the lower oesophageal sphincter fails to relax during swallowing, causing dysphagia, regurgitation of gastric contents and aspiration pneumonia. The oesophagus becomes dilated and the muscle layer hypertrophies. Autonomic nerve supply to the oesophageal muscle is abnormal, but the cause is not known.
Tumours of the oesophagus
Benign tumours are rare, accounting for only 5% of oesophageal tumours.
These occur more often in males than females. They are most common in the lower oesophagus but can arise at any level. Both types of tumour, described below, tend to begin as an ulcer that spreads round the circumference causing a stricture that results in dysphagia. By the time of diagnosis, local spread has usually occurred and the prognosis is very poor.
Squamous carcinoma usually affects the middle third and is associated with some dietary deficiencies, regular consumption of very hot food, tannic acid (in tea and sorghum) and possibly viruses. The worldwide incidence varies considerably. In developed countries, long-term alcohol consumption and cigarette smoking are also implicated.
Adenocarcinoma develops from Barrett’s oesophagus (see above).
The most common congenital abnormalities of the oesophagus are:
• oesophageal atresia, in which the lumen is narrow or blocked
• tracheo-oesophageal fistula, in which there is an opening (fistula) between the oesophagus and the trachea through which milk or regurgitated gastric contents are aspirated.
One or both abnormalities may be present. The causes are unknown.
Diseases of the stomach
After studying this section, you should be able to:
compare the main features of chronic and acute gastritis
discuss the pathophysiology of peptic ulcer disease
describe the main tumours of the stomach and their consequences
define the term congenital pyloric stenosis.
Inflammation of the stomach can be an acute or chronic condition.
This is usually a response to irritant drugs or alcohol. The drugs most commonly implicated are non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, even at low doses, although many others may also be involved. Other causes include the initial response to Helicobacter pylori infection (see below) and severe physiological stress, e.g. in extensive burns and multiple organ failure.
There are varying degrees of severity. Mild cases can be asymptomatic or may present with nausea and vomiting associated with inflammatory changes of the gastric mucosa. Erosions can also occur, which are characterised by tissue loss affecting the superficial layers of the gastric mucosa. In more serious cases, there are multiple erosions, which may result in life-threatening haemorrhage causing haematemesis(vomiting of frank blood or black ‘coffee grounds’ when there has been time for digestion of blood to occur) and melaena (passing black tarry faeces), especially in elderly people.
The outcome depends on the extent of the damage. In many cases recovery is uneventful after the cause is removed. Where there has been extensive tissue damage, healing is by fibrosis causing reduced elasticity and peristalsis.
Chronic gastritis is a milder longer-lasting condition. It is usually associated with Helicobacter pylori but is sometimes due to autoimmune disease or chemical injury. It is more common in later life.
The microbe Helicobacter pylori can survive in the gastric mucosa and is commonly associated with gastric conditions, especially chronic gastritis and peptic ulcer disease.
Autoimmune chronic gastritis
This is a progressive disease. Destructive inflammatory changes that begin on the surface of the mucous membrane may extend to affect its whole thickness, including the gastric glands. When this stage is reached, secretion of hydrochloric acid and intrinsic factor are markedly reduced. The antigens are the gastric parietal cells and the intrinsic factor they secrete. When these cells are destroyed as a result of this abnormal autoimmune condition, the inflammation subsides. The initial causes of the autoimmunity are not known but there is a familial predisposition and an association with thyroid disorders. Secondary consequences include:
• pernicious anaemia due to lack of intrinsic factor (p. 67)
• increased risk of cancer of the stomach.
Ulceration involves the full thickness of the gastrointestinal mucosa (Fig. 12.47). It is caused by disruption of the normal balance between the corrosive effect of gastric juice and the protective effect of mucus on the gastric epithelial cells. It may be viewed as an extension of the gastric erosions found in acute gastritis. The most common sites for ulcers are the stomach and the first few centimetres of the duodenum. More rarely they occur in the oesophagus and round the anastomosis of the stomach and small intestine, following gastrectomy. The underlying causes are not known but, if gastric mucosal protection is impaired, the epithelium can be exposed to gastric acid causing the initial cell damage that leads to ulceration. The main protective mechanisms are: a good blood supply, adequate mucus secretion and efficient epithelial cell replacement.
Figure 12.47 Peptic ulceration: a large duodenal ulcer.
Reduced blood flow and ischaemia may be caused by excessive cigarette smoking and severe stress, either physical or mental. In stressful situations the accompanying sympathetic activity causes constriction of the blood vessels supplying the alimentary tract.
Secretion of mucus
The composition and the amount of mucus may be altered, e.g.:
• by regular and prolonged use of aspirin and other anti-inflammatory drugs
• by the reflux of bile acids and salts
• in chronic gastritis.
Epithelial cell replacement
There is normally a rapid turnover of gastric and intestinal epithelial cells. This may be reduced:
• by raised levels of steroid hormones, e.g. in response to stress or when they are used as drugs
• in chronic gastritis
• by irradiation and the use of cytotoxic drugs.
In peptic ulcer disease, the alimentary tract is commonly colonised by the bacterium Helicobacter pylori, a causative agent in this disorder.
Acute peptic ulcers
These lesions involve tissue to the depth of the submucosa and may be single or multiple. They are found in many sites in the stomach and in the first few centimetres of the duodenum. Their development is often associated with acute gastritis, severe stress, e.g. severe illness, shock, burns, severe emotional disturbance and following surgery. Healing without the formation of fibrous tissue usually occurs when the stressor is removed, although haemorrhage, which may be life-threatening, can be a complication.
Chronic peptic ulcers
These ulcers penetrate through the epithelial and muscle layers of the stomach wall and may include the adjacent pancreas or liver. In the majority of cases they occur singly in the pylorus of the stomach and in the duodenum. Occasionally there are two ulcers facing each other in the duodenum, called kissing ulcers. Helicobacter pylori is found in 90% of people with duodenal ulcers and 70% of those with gastric ulcers. The remaining gastric ulcers are almost entirely due to non-steroidal anti-inflammatory drugs (NSAIDs). Smoking predisposes to peptic ulceration and delays healing. Healing occurs with the formation of fibrous tissue and subsequent shrinkage may cause:
• stricture of the lumen of the stomach
• gastric outflow obstruction or stenosis of the pyloric sphincter
• adhesions to adjacent structures, e.g. pancreas, liver, transverse colon.
Complications of peptic ulcers
When a major artery is eroded a serious and possibly life-threatening haemorrhage may occur, causing shock (p. 111), haematemesis and/or melaena.
Chronic persistent low level bleeding from an ulcer may lead to development of iron deficiency anaemia (p. 66).
When an ulcer erodes through the full thickness of the wall of the stomach or duodenum their contents enter the peritoneal cavity, causing acute peritonitis (p. 317).
Infected inflammatory material may collect under the diaphragm, forming a subphrenic abscess (Fig. 12.48) and the infection may spread through the diaphragm to the pleural cavity.
Gastric outflow obstruction
Also known as pyloric stenosis, fibrous tissue formed as an ulcer in the pyloric region heals, causes narrowing of the pylorus that obstructs outflow from the stomach and results in persistent vomiting.
Development of a malignant tumour
This is frequently associated with chronic gastritis caused by Helicobacter pylori.
Tumours of the stomach
Benign tumours of the stomach occur rarely.
This is a common malignancy that occurs more frequently in men than women. The causes have not been established, but there appears to be a strong link with Helicobacter pylori infection, dietary factors and some, as yet unknown, environmental factors. The local growth of the tumour gradually destroys the normal tissue so that achlorhydria (reduced hydrochloric acid secretion) and pernicious anaemia are frequently secondary features. As the tumour grows, the surface may ulcerate and become infected, especially when achlorhydria develops.
This condition carries a poor prognosis because spread has often already occurred prior to diagnosis. Commonly tumour fragments have been spread in the blood through the hepatic portal vein to the liver where they lodge and cause metastases. Local spread is to adjacent organs, e.g. the oesophagus, duodenum and pancreas. Transmission to the peritoneal cavity may occur when the outermost layer, the serosa, is affected. Lymphatic spread is also common, initially to nearby nodes and later to more distant ones.
Congenital pyloric stenosis
In this condition there is spasmodic constriction of the pyloric sphincter, characteristic projectile vomiting and failure to put on weight. In an attempt to overcome the spasms, hypertrophy of the muscle of the pylorus develops, causing obstruction of the pylorus 2 to 3 weeks after birth. The cause is not known but there is a familial tendency and it is more common in boys.
Diseases of the intestines
After studying this section, you should be able to:
describe appendicitis and its consequences
discuss the principal infectious disease of the intestines
compare and contrast the features of Crohn’s disease and ulcerative colitis
distinguish between diverticulitis and diverticulosis
describe the main tumours of the intestines
describe the abnormalities present in hernia, volvulus and intussusception
list the main causes of intestinal obstruction
compare the causes and outcomes of primary and secondary malabsorption.
Diseases of the small and large intestines are described together because they have certain characteristics in common and some conditions affect both.
The lumen of the appendix is very small and there is little room for swelling when it becomes inflamed. The initial cause of inflammation is not always clear. Microbial infection is commonly superimposed on obstruction by, for example, hard faecal matter (faecoliths), kinking or a foreign body. Inflammatory exudate, with fibrin and phagocytes, causes swelling and ulceration of the mucous membrane lining. In the initial stages, the pain of appendicitis is usually located in the central area of the abdomen. After a few hours, the pain shifts and is localised to the region above the appendix (the right iliac fossa). In mild cases the inflammation subsides and healing takes place. In more severe cases microbial growth progresses, leading to suppuration, abscess formation and further congestion. The rising pressure inside the appendix occludes first the veins, then the arteries and ischaemia develops, followed by gangrene and rupture.
Complications of appendicitis
The peritoneum becomes acutely inflamed, the blood vessels dilate and excess serous fluid is secreted. It occurs as a complication of appendicitis when:
• microbes spread through the wall of the appendix and infect the peritoneum
• an appendix abscess ruptures and pus enters the peritoneal cavity
• the appendix becomes gangrenous and ruptures, discharging its contents into the peritoneal cavity.
The most common are:
• subphrenic abscess, between the liver and diaphragm, from which infection may spread upwards to the pleura, pericardium and mediastinal structures
• pelvic abscess from which infection may spread to adjacent structures (Fig. 12.48).
Figure 12.48 Abscess formation; complication of appendicitis.
When healing takes place fibrous tissue forms and later shrinkage may cause:
• stricture or obstruction of the bowel
• limitation of the movement of a loop of bowel, which may twist around the adhesion causing a type of bowel obstruction called a volvulus (p. 322).
Microbial diseases (Fig. 12.49)
The incidence of the diseases in this section varies considerably but they represent a major cause of morbidity and mortality worldwide. Public health measures including clean, safe drinking water and effective sewage disposal, and safe food hygiene practices greatly reduce the spread of these conditions, many of which are highly contagious. Meticulous handwashing after defaecation and contact between the hands and any potentially contaminated material is essential, especially in healthcare facilities. Contamination of drinking water results in diarrhoeal diseases that are a major cause of infant death in developing countries.
Figure 12.49 The routes of excretion of microbes in typhoid and paratyphoid (enteric) fever.
This type of enteritis is caused by the bacterium Salmonella typhi, ingested in contaminated food and water. As humans are its only host, it is acquired from an individual who is either suffering from the disease or is a carrier.
After infection, there is an incubation period of about 14 days before signs of the disease appear. During this period the microbes invade lymphoid tissue in the walls of the small and large intestines, especially the aggregated lymph follicles (Peyer’s patches) and solitary lymph nodes. The microbes then enter the blood vessels and spread to the liver, spleen and gall bladder. In the bacteraemic period acute inflammation develops with necrosis of intestinal lymphoid tissue and ulceration of overlying mucosa. The spleen becomes enlarged and red spots are typically seen on the skin, especially of the chest and back.
Without treatment, severe, and often fatal, illness is common 2 weeks after the onset of illness. Complications due to spread of microbes during the bacteraemic phase include pneumonia, meningitis and typhoid cholecystitis in which microbes multiply in the gall bladder and are secreted in the bile, reinfecting the intestine (Fig. 12.49). Bacterial toxins can cause disorders of the heart (myocarditis, Ch. 5) and kidneys (nephritis, Ch.13). In the bowel, ulcers may perforate a blood vessel wall resulting in haemorrhage or erode the intestinal wall causing acute peritonitis.
A few individuals (up to 5%) may become carriers where there is asymptomatic but chronic infection of the gall bladder. Continued release of microbes into the bile leads to indefinite infection of the faeces; much less often the urinary system is also involved and microbes are released into the urine. Carriers may transmit the infection to others.
This disease is caused by Salmonella paratyphi A or B spread in the same way as typhoid fever, by the faecal–oral route. The infection, causing inflammation of the intestinal mucosa, is usually confined to the ileum although the duration is shorter and the symptoms less severe than typhoid fever. Other parts of the body are not usually affected but occasionally people become carriers (Fig 12.49).
Other Salmonella infections
Salmonella typhimurium and S. enteritidis are the most common microbes in this group. Generally the effects are confined to the gastrointestinal tract, unlike the infections above. In addition to humans their hosts are domestic animals and birds. The microbes may be present in meat, poultry, eggs and milk, causing infection if cooking does not achieve sterilisation. Mice and rats also carry the organisms and may contaminate food before or after cooking.
Enteritis is usually short lived and accompanied by acute abdominal pain and diarrhoea, causing dehydration and electrolyte imbalance. Sometimes vomiting is present. In children and debilitated elderly people the infection may be severe or even fatal.
Escherichia coli (E. coli) food poisoning
Common sources of these bacteria include undercooked meat and unpasteurised milk; adequate cooking kills E. coli. The severity of the disease depends on the type of E. coli responsible; some types are more virulent than others. Outbreaks of E. coli food poisoning can cause fatalities, particularly in young and elderly people.
Staphylococcal food poisoning
After eating contaminated food, Staphylococcus aureus releases toxins that cause acute gastroenteritis (rather than the microbe itself causing the condition). Although cooking kills the bacteria, the toxin is heat resistant.
There is usually short-term acute inflammation with violent vomiting and diarrhoea, causing dehydration and electrolyte imbalance. In most cases complete recovery occurs within 24 hours.
Clostridium perfringens food poisoning
These microbes, although normally present in the intestines of humans and animals, cause food poisoning when ingested in large numbers. Meat may be contaminated at any stage between slaughter and the consumer. Outbreaks of food poisoning are associated with large-scale cooking, e.g. in institutions. Slow cooling after cooking and/or slow reheating allow microbial multiplication. When they reach the intestines, the bacteria release a toxin that causes diarrhoea and abdominal pain.
The microbe Clostridium difficile is already present in the large intestine, but after antibiotic therapy many other commensal intestinal bacteria die. This allows Cl. difficile to take over and multiply, releasing toxins that damage the mucosa of the large intestine and causing profound diarrhoea. Significant inflammation of the large intestine (colitis), which is often fatal in elderly and debilitated people, may occur as a complication.
Campylobacter food poisoning
These Gram-negative bacilli are a common cause of gastroenteritis accompanied by fever, acute pain and sometimes bleeding. They affect mainly young adults and children under 5 years. The microbes are present in the intestines of birds and animals, and are spread in undercooked poultry and meat. They may also be spread in water and milk. Pets, such as cats and dogs, may be a source of infection. There is an association with Guillain-Barré syndrome (Ch. 7).
Cholera is caused by Vibrio cholerae and is spread by contaminated water, faeces, vomit, food, hands and fomites. The only known hosts are humans. In some infected people, known as subclinical carriers, no symptoms occur, although these people can transmit the condition to others while their infection remains. A very powerful toxin is released by the bacteria, which stimulates the intestinal glands to secrete large quantities of water, bicarbonate and chloride. This leads to persistent diarrhoea, severe dehydration and electrolyte imbalance, and may cause death due to hypovolaemic shock.
This infection of the large intestine is caused by bacteria of the Shigella group. The severity of the condition depends on the organisms involved. In the UK it is usually a relatively mild condition caused by Shigella sonnei. Shigella dysenteriae causes the most severe type of infection and it occurs mainly in tropical countries. Children and elderly debilitated adults are particularly susceptible. The only host is humans and the organisms are spread by faecal contamination of food, drink, hands and fomites.
The intestinal mucosa becomes inflamed, ulcerated and oedematous with excess mucus secretion. In severe infections, the acute diarrhoea, containing blood and excess mucus, causes dehydration, electrolyte imbalance and anaemia. When healing occurs the mucous membrane is fully restored.
Amoebic dysentery (amoebiasis)
This disease is caused by Entamoeba histolytica. The only known hosts are humans and it is spread by faecal contamination of food, water, hands and fomites. Although many infected people do not develop symptoms they may become asymptomatic carriers. Within the colon, the amoebae grow, divide and invade the mucosal cells, causing inflammation. Without treatment the condition frequently becomes chronic with mild, intermittent diarrhoea and abdominal pain. This may progress with ulceration of the colon accompanied by persistent and debilitating diarrhoea that contains mucus and blood. Complications are unusual but include severe haemorrhage from ulcers and liver abscesses.
Several viruses, including rotavirus and norovirus, are known to cause vomiting and/or diarrhoea. Rotavirus is a major cause of diarrhoea in young children. It is easily spread in healthcare facilities. Norovirus, also known as the ‘winter vomiting virus’, is responsible for outbreaks that commonly occur in winter causing short-lived and self-limiting enteritis with vomiting as the main symptom. It spreads easily in families and in child and healthcare facilities. Spread is by the faecal–oral route but airborne transmission by inhalation may also occur.
Inflammatory bowel disease (IBD)
This term includes Crohn’s disease and ulcerative colitis. A comparison of the main features is shown in Table 12.4. Their aetiology is unknown but is thought to involve environmental and immune factors in genetically susceptible individuals. Both conditions typically have a pattern of relapse and remission.
Table 12.4 Comparison of the main features of Crohn’s disease and ulcerative colitis
Usually between 20 and 40 years of age (mean 26 years); both sexes affected equally; smokers at higher risk
Usually between 20 and 40 years of age (mean 34 years); more women affected than men; smoking not a risk factor
Main sites of lesions
Anywhere in digestive tract from mouth to anus; common in terminal ileum
Rectum always involved, with variable spread along colon
Entire thickness of the wall inflamed and thickened tissue; ulcers and fistulae common
Only mucosa involved
Nature of lesions
‘Skip’ lesions, i.e. diseased areas interspersed with regions of normal tissue; ulcers and fistulae common
Continuous lesion; mucosa is red and inflamed
In severe cases, surgery may improve condition, but relapse rate very high, slightly increased risk of cancer
Surgical removal of entire colon cures the condition, significantly increased risk of cancer
This chronic inflammatory condition of the alimentary tract, also known as regional ileitis, usually occurs in young adults. The terminal ileum and the rectum are most commonly affected but the disease may affect any part of the tract. There is chronic patchy inflammation with oedema of the full thickness of the intestinal wall, causing partial obstruction of the lumen, sometimes described as skip lesions. There are periods of remission of varying duration. The main symptoms are diarrhoea, abdominal pain and weight loss. Complications include:
• secondary infections, occurring when inflamed areas ulcerate
• fibrous adhesions and subsequent intestinal obstruction caused by the healing process
• fistulae between intestinal lesions and adjacent structures, e.g. loops of bowel, surface of the skin (p. 361)
• perianal fistulae, fissures and skin tags
• cancer of the small or large intestine.
This is a chronic inflammatory disease of the mucosa of the colon and rectum, which may ulcerate and become infected. It usually occurs in young adults and begins in the rectum and sigmoid colon. From there it may spread proximally to involve a variable proportion of the colon and, sometimes, the entire colon. The main symptom is bloody diarrhoea. There are periods of remission lasting weeks, months or years. Individuals may develop other systemic problems affecting, for example, the joints (ankylosing spondylitis, p. 423), skin and liver. In long-standing cases, cancer sometimes develops.
Toxic megacolon is an acute complication where the colon loses its muscle tone and dilates. There is a high risk of electrolyte imbalance, perforation and hypovolaemic shock, which may be fatal if untreated.
Diverticula are small pouches of mucosa that protrude (herniate) into the peritoneal cavity through the circular muscle fibres of the colon between the taeniae coli (Fig. 12.50). The walls consist of mucous membrane with a covering of visceral peritoneum. They occur at the weakest points of the intestinal wall, i.e. where the blood vessels enter, most commonly in the sigmoid colon.
Figure 12.50 Diverticular disease; cross-section of bowel showing one diverticulum.
The causes of diverticulosis (presence of diverticuli) are not known but it is associated with deficiency of dietary fibre. In Western countries, diverticulosis is fairly common after the age of 60 but diverticulitis affects only a small proportion.
Diverticulitis arises when faeces impact in the diverticula and the walls become inflamed and oedematous as secondary infection develops. This reduces the blood supply causing ischaemic pain. Occasionally, rupture occurs resulting in peritonitis (p. 317).
Tumours of the small and large intestines
Benign and malignant tumours of the small intestine are rare, especially compared with their occurrence in the stomach, large intestine and rectum.
Benign neoplasms may form a broad-based mass or polyp, i.e. develop a pedicle. Occasionally polyps twist upon themselves, causing ischaemia, necrosis and possibly gangrene. Malignant changes may occur in adenomas, which are mostly found in the large intestine. The incidence is high in developed countries.
This is the most common malignancy of the alimentary tract in Western countries and as a cause of cancer-related death is second only to lung cancer in the UK. The tumours are adenocarcinomas with about half arising in the rectum, one-third in the sigmoid colon and the remainder elsewhere in the colon.
The tumour may be:
• a soft polypoid mass, projecting into the lumen of the colon or rectum with a tendency to ulceration, infection and bleeding
• a hard fibrous mass encircling the colon, causing narrowing of the lumen and, eventually, obstruction.
The most important predisposing factor for colorectal cancer is thought to be diet. In cultures eating a high-fibre, low-fat diet, the disease is virtually unknown, whereas in Western countries, where large quantities of red meat and saturated animal fat and insufficient fibre are eaten, the disease is much more common. Slow movement of bowel contents may result in conversion of unknown substances present into carcinogenic agents. Genetic factors are also implicated. Predisposing diseases include ulcerative colitis and some benign tumours (usually adenomas).
Local spread of intestinal tumours occurs early but may not be evident until there is severe ulceration and haemorrhage or obstruction. Spread can be outwards through the wall into the peritoneal cavity and adjacent structures.
Lymph-spread metastases occur in mesenteric lymph nodes, the peritoneum and other abdominal and pelvic organs. Pressure caused by enlarged lymph nodes may cause obstruction or damage other structures.
Blood-spread metastases are most common in the liver, brain and bones.
A hernia is a protrusion of an organ or part of an organ through a weak point or aperture in the surrounding structures. In those affecting the digestive system, a piece of bowel protrudes through a weak point in either the musculature of the anterior abdominal wall or an existing opening (Fig. 12.51A). It occurs when there are intermittent increases in intra-abdominal pressure, most commonly in men who lift heavy loads at work. The underlying causes of the abdominal wall weakness are unknown. Outcomes include:
• spontaneous reduction, i.e. the loop of bowel slips back to its correct place when the intra-abdominal pressure returns to normal
• manual reduction, i.e. by applying gentle pressure over the abdominal swelling
• strangulation (Fig. 12.51B), when reduction is not possible and the venous drainage from the herniated loop of bowel is obstructed, causing congestion, ischaemia and gangrene. In addition there is intestinal obstruction (p. 322).
Figure 12.51 Hernias: A. Common sites of herniation. B. Strangulated hernia formation. C. Hiatus hernia.
Sites of hernias (Fig. 12.51A)
The weak point is the inguinal canal, which contains the spermatic cord in the male and the round ligament in the female. It occurs more commonly in males than in females.
The weak point is the femoral canal through which the femoral artery, vein and lymph vessels pass from the pelvis to the thigh.
The weak point is the umbilicus where the umbilical blood vessels from the placenta entered the fetus before birth.
This is caused by repeated stretching of fibrous tissue formed after previous abdominal surgery.
This is the protrusion of a part of the fundus of the stomach through the oesophageal opening in the diaphragm (Fig. 12.51C). Although often asymptomatic, irritation of the oesophagus only occurs when there is reflux of acid gastric juice, especially when the individual lies flat or bends down. The long-term effects may be oesophagitis, fibrosis and narrowing of the oesophagus, causing dysphagia. Strangulation does not occur.
Rolling hiatus hernia
An abnormally large opening in the diaphragm allows a pouch of stomach to ‘roll’ upwards into the thorax beside the oesophagus. This is associated with obesity and increased intra-abdominal pressure.
Sliding hiatus hernia
Part of the stomach is pulled upwards into the thorax. The abnormality may be caused by shrinkage of fibrous tissue formed during healing of a previous oesophageal injury. The sliding movement of the stomach in the oesophageal opening is due to shortening of the oesophagus by muscular contraction during swallowing.
A loop of bowel may herniate through the epiploic foramen (of Winslow, Fig. 12.3A), the opening in the lesser omentum that separates the greater and lesser peritoneal sacs.
Congenital diaphragmatic hernia
Incomplete formation of the diaphragm, usually on the left side, allows abdominal organs such as the stomach and loops of intestine into the thoracic cavity, preventing normal development of the fetal lungs.
This occurs when a loop of bowel twists occluding its lumen resulting in obstruction. It is usually accompanied by strangulation, where there is interruption of the blood supply causing gangrene. It occurs in parts of the intestine that are attached to the posterior abdominal wall by a long double fold of visceral peritoneum, the mesentery. The most common site in adults is the sigmoid colon and in children the small intestine. Predisposing factors include:
• an unusually long mesentery
• heavy loading of the sigmoid colon with faeces
• a slight twist of a loop of bowel, causing gas and fluid to accumulate and promote further twisting
• adhesions formed following surgery or peritonitis.
In this condition a length of intestine is invaginated into itself causing intestinal obstruction (Fig. 12.52). It occurs most commonly in children when a piece of terminal ileum is pushed through the ileocaecal valve. The overlying mucosa bulges into the lumen, creating a partial obstruction and a rise in pressure inside the intestine proximal to the swelling. Strong peristaltic waves develop in an attempt to overcome the partial obstruction. These push the swollen piece of bowel into the lumen of the section immediately distal to it, creating the intussusception. The pressure on the veins in the invaginated portion is increased, causing congestion, further swelling, ischaemia and possibly gangrene. Complete intestinal obstruction may occur. In adults tumours that bulge into the lumen, e.g. polyps, together with the strong peristalsis, may be the cause.
Figure 12.52 Intussusception.
This is not a disease in itself. The following is a summary of the effects and main causes of obstruction with some examples.
Mechanical causes of obstruction
• constriction or blockage of the intestine by, for example, strangulated hernia, intussusception, volvulus, peritoneal adhesions; partial obstruction (narrowing of the lumen) may suddenly become complete
• stenosis and thickening of the intestinal wall, e.g. in diverticulosis, Crohn’s disease and malignant tumours; there is usually a gradual progression from partial to complete obstruction
• obstruction by, for example, a large gallstone or a tumour growing into the lumen
• pressure on the intestine from outside, e.g. a large tumour in any pelvic or abdominal organ, such as a uterine fibroid; this is most likely to occur inside the confined space of the bony pelvis.
Neurological causes of obstruction
Partial or complete loss of peristaltic activity produces the effects of obstruction. Paralytic ileus is the most common form. The mechanisms are not clear but there are well-recognised predisposing conditions including major surgery requiring considerable handling of the intestines and peritonitis.
Secretion of water and electrolytes continues although intestinal mobility is lost and absorption impaired. This causes distension and electrolyte imbalance, leading to hypovolaemic shock.
Vascular causes of obstruction
When the blood supply to a segment of bowel is cut off, ischaemia is followed by infarction and gangrene. The damaged bowel becomes unable to function. The causes may be:
• atheromatous changes in the blood vessel walls, with thrombosis (p. 113)
• embolism (p. 113)
• mechanical obstruction of the bowel, e.g. strangulated hernia (p. 321).
Effects of intestinal obstruction
Symptoms include abdominal pain, vomiting and constipation. When the upper gastrointestinal tract is affected vomiting may be profuse, although it may be absent in lower bowel obstruction. There are neither bowel sounds present nor passing of flatus (wind) as peristalsis ceases. Without treatment, irrespective of the cause, this condition is fatal.
Impaired absorption of nutrients and water from the intestines is not a disease in itself, but the result of abnormal changes in one or more of the following:
• villi in the small intestine, e.g. coeliac disease, tropical sprue (see below)
• digestion of food
• absorption or transport of nutrients from the small intestine.
Intestinal conditions that impair normal digestion and/or absorption and transport of nutrients include:
• extensive resection of the small intestine
• ‘blind loop syndrome’ where there is microbial overgrowth in a blind end of intestine following surgery
• lymphatic obstruction by diseased or absent (following surgical excision) lymph nodes.
This disease is the main cause of malabsorption in Western countries. It is due to an abnormal, genetically determined immunological reaction to the protein gluten, present in wheat. When it is removed from the diet, recovery is complete. There is marked villous atrophy, especially in the jejunum, and malabsorption characterised by the passage of loose, pale-coloured, fatty stools (steatorrhoea).
There may be abnormal immune reaction to other antigens. Atrophy of the spleen is common and malignant lymphoma of the small intestine is a rarer consequence. It often presents in infants after weaning but can affect people of any age.
This disease is endemic in subtropical and tropical countries except Africa. After visiting an endemic area most travellers suffering from sprue recover, but others may not develop symptoms until months or even years later.
There is partial villous atrophy with malabsorption, chronic diarrhoea, severe wasting and pernicious anaemia due to deficient absorption of vitamin B12 and folic acid. The cause is unknown but it may be that bacterial growth in the small intestine is a factor.
Diseases of the pancreas
After studying this section, you should be able to:
compare and contrast the causes and effects of acute and chronic pancreatitis
outline the main pancreatic tumours and their consequences.
Proteolytic enzymes produced by the pancreas are secreted in inactive forms, which are not activated until they reach the intestine; this protects the pancreas from digestion by its own enzymes. If these precursor enzymes are activated while still in the pancreas, pancreatitis results. The severity of the disease is directly related to the amount of pancreatic tissue destroyed.
Mild forms are more common and damage only those cells near the ducts. Recovery is usually complete.
Severe forms cause widespread damage with necrosis and haemorrhage. Common complications include infection, suppuration, and local venous thrombosis. Pancreatic enzymes, especially amylase, enter and circulate in the blood, causing similar damage to other structures. In severe cases there is a high mortality rate.
The causes of acute pancreatitis are not clear but known predisposing factors are gallstones and alcoholism. Other associated conditions include:
• cancer of the ampulla or head of pancreas
• viral infections, notably mumps
• kidney and liver transplantation
• severe hypothermia
• drugs, e.g. corticosteroids, some cytotoxic agents.
This is either due to repeated attacks of acute pancreatitis or may arise gradually without evidence of pancreatic disease. It is more common in men and is frequently associated with fibrosis and distortion of the main pancreatic duct. There is intestinal malabsorption when pancreatic secretions are reduced and diabetes mellitus (p. 227) occurs when severe damage affects the β-islet cells (see Ch. 9).
Protein material secreted by the acinar cells blocks the tiny acinar ducts. This eventually leads to the formation of encapsulated cysts which are a feature of acute and chronic pancreatitis.
The most common cause in the Western world is excessive chronic alcohol consumption. In developing countries dietary factors and malnutrition have been implicated. It is also associated with cystic fibrosis.
Cystic fibrosis (see p. 258)
Tumours of the pancreas
Benign tumours are very rare.
These are relatively common and affect up to twice as many men as women. They occur most frequently in the head of the pancreas, obstructing the flow of bile and pancreatic juice into the duodenum. Jaundice, sometimes accompanied by itching, develops. Weight loss is the result of impaired digestion and absorption of fat, although anorexia and metabolic effects of the tumour may also play a role. Tumours in the body and tail of the gland rarely cause symptoms until the disease is advanced. Irrespective of the site, metastases are often recognised before the primary tumour and the prognosis is generally poor. There is an association with cigarette smoking, diabetes mellitus and possibly chronic pancreatitis.
Diseases of the liver
After studying this section, you should be able to:
compare and contrast the causes, forms and effects of chronic and acute hepatitis
describe the main non-viral inflammatory conditions of the liver
discuss the causes and consequences of liver failure
describe the main liver tumours.
New liver cells develop only when needed to replace damaged cells. Capacity for regeneration is considerable and damage is usually extensive before it is evident. The effects of disease or toxic agents are seen when:
• regeneration of hepatocytes (liver cells) does not keep pace with damage, leading to hepatocellular failure
• there is a gradual replacement of damaged cells by fibrous tissue, leading to portal hypertension.
In most liver disease both conditions are present.
Areas of necrosis develop as groups of hepatocytes die and the eventual outcome depends on the size and number of these areas. Causes of the damage may be a variety of conditions, including:
• viral infections
• toxic substances
• circulatory disturbances.
Viral infections are the commonest cause of acute liver injury and different types are recognised. The types are distinguished serologically, i.e. by the antibodies produced to combat the infection. The severity of the ensuing disease caused by the different virus types varies considerably, but the pattern is similar. The viruses enter the liver cells, causing degenerative changes. An inflammatory reaction ensues, accompanied by production of an exudate containing lymphocytes, plasma cells and granulocytes. There is reactive hyperplasia of the hepatic macrophages (Kupffer cells) in the walls of the sinusoids.
As groups of cells die, necrotic areas of varying sizes develop, phagocytes remove the necrotic material and the lobules collapse. The basic lobule framework (Fig. 12.35) becomes distorted and blood vessels develop kinks. These changes interfere with the circulation of blood to the remaining hepatocytes and the resultant hypoxia causes further damage. Fibrous tissue develops in the damaged area, and adjacent hepatocytes proliferate. The effect of these changes on the overall functioning of the liver depends on the size of the necrotic areas, the amount of fibrous tissue formed and the extent to which the blood and bile channels are distorted.
Previously known as ‘infectious hepatitis’, this type affects mainly children, causing a mild illness. Infection is spread by hands, food, water and fomites contaminated by infected faeces. The incubation period is 15 to 40 days and the viruses are excreted in the faeces for 7 to 14 days before clinical symptoms appear and for about 7 days after. Symptoms may include general malaise followed by a period of jaundice (p. 327) that is accompanied by passing of dark urine and pale faeces. Antibodies develop and confer lifelong immunity after recovery. Subclinical disease may occur but not carriers.
Previously known as ‘serum hepatitis’, infection occurs at any age, but mostly in adults. The incubation period is 50 to 180 days. The virus enters the blood and is spread by blood and blood products. People at greatest risk of infection are those who come in contact with blood and blood products in the course of their work, e.g. health-care workers. The virus is also spread by body fluids, i.e. saliva, semen, vaginal secretions, and from mother to fetus (vertical transmission). Others at risk include IV drug users and men who have sex with men. Antibodies are formed and immunity persists after recovery. Infection usually leads to severe illness lasting 2 to 6 weeks, often followed by a protracted convalescence. Carriers may, or may not, have had clinical disease. Type B virus may cause massive liver necrosis and death. In less severe cases recovery may be complete. In chronic hepatitis (see opposite) that may develop, live viruses continue to circulate in the blood and other body fluids. The condition is thought to predispose to liver cancer.
This virus is spread by blood and blood products, which accounts for the infection of many people with haemophilia. In countries, including the UK, where blood donors are now screened for the virus this route of transmission is now rare. It is prevalent in IV drug users. The infection is very frequently asymptomatic as a carrier state occurs. Infection is usually diagnosed later in life when cirrhosis (see opposite) or chronic liver failure becomes evident.
Many drugs undergo chemical change in the liver before excretion in bile or by other organs. They may damage the liver cells in their original form or while in various intermediate stages. Some substances always cause liver damage (predictably toxic) while others only do so when hypersensitivity to normal doses develops (unpredictably toxic). In both types the extent of the damage depends on the size of the dose and/or the duration of exposure (Box 12.1).
Box 12.1 Some hepatotoxic substances
Predictable group (dose related)
Unpredictable group (individual idiosyncrasy)
The intensely active hepatocytes are particularly vulnerable to damage by hypoxia, which is usually due to impaired blood supply caused by:
• fibrosis in the liver following inflammation
• compression of the portal vein, hepatic artery or vein by a tumour
• acute general circulatory failure and shock
• venous congestion caused by acute or chronic right-sided heart failure (Ch. 5).
This is defined as any form of hepatitis which persists for more than 6 months. It may be caused by viruses, alcohol or drugs, but sometimes the cause is unknown.
Mild, persistent inflammation may follow acute viral hepatitis. There is usually little or no fibrosis.
There may be continuing progressive inflammation with cell necrosis and the formation of fibrous tissue that may lead to cirrhosis of the liver. There is distortion of the liver blood vessels and hypoxia, leading to further hepatocyte damage. This condition is commonly associated with Types B and C viral hepatitis, some forms of autoimmunity and unpredictable (idiosyncratic) drug reactions.
Cirrhosis of the liver
This is the result of long-term injury caused by a variety of agents. The most common causes are:
• excessive alcohol consumption
• hepatitis B and C virus infections
• recurrent obstruction of the biliary tract.
As the inflammation subsides, destroyed liver tissue is replaced by fibrous tissue. There is hyperplasia of hepatocytes adjacent to damaged areas, in an attempt to compensate for the destroyed cells. This leads to the formation of nodules consisting of hepatocytes confined within sheets of fibrous tissue.
As the condition progresses portal hypertension develops, leading to congestion in the organs drained by the tributaries of the portal vein, to ascites and to the development of oesophageal varices (p. 313).
Liver failure may occur when hyperplasia is unable to keep pace with cell destruction, and there is increased risk of liver cancer developing.
This occurs when liver function is markedly impaired. It can be acute or chronic and may be the outcome of a wide variety of disorders, e.g.:
• acute viral hepatitis
• extensive necrosis due to poisoning, e.g. some drug overdoses, hepatotoxic chemicals, adverse drug reactions
• cirrhosis of the liver.
Liver failure has serious effects on other parts of the body.
The cells affected are the astrocytes in the brain. The condition is characterised by apathy, disorientation, muscular rigidity and confusion, progressing to coma. Several factors may be involved, e.g.:
• nitrogenous bacterial metabolites absorbed from the colon, which are normally detoxified in the liver, reach the brain via the blood
• other metabolites, normally present in trace amounts, e.g. ammonia, may reach toxic concentrations and change the permeability of the cerebral blood vessels and the effectiveness of the blood–brain barrier
• hypoxia and electrolyte imbalance.
Blood coagulation defects
The liver fails to synthesise substances needed for blood clotting, i.e. prothrombin, fibrinogen and factors II, V, VII, IX and X. Purpura, bruising and bleeding may occur.
Oliguria and renal failure
Portal hypertension may cause the development of oesophageal varices (p. 313). If these rupture, bleeding may lead to a fall in blood pressure sufficient to reduce the renal blood flow, causing progressive oliguria and renal failure.
Oedema and ascites
These may be caused by the combination of two factors:
• portal hypertension raises the capillary hydrostatic pressure in the organs drained by the tributaries of the portal vein (see Fig. 5.46, p. 103)
• diminished production of serum albumin and clotting factors reduces the plasma osmotic pressure.
Together these changes cause the movement of excess fluid into the interstitial spaces where it causes oedema. Eventually free fluid accumulates in the peritoneal cavity and the resultant ascites may be severe.
The following factors may cause jaundice as liver failure develops:
• inability of the hepatocytes to conjugate and excrete bilirubin
• obstruction to the movement of bile through the bile channels by fibrous tissue that has distorted the structural framework of liver lobules.
Tumours of the liver
Benign tumours are very rare.
Cancer of the liver is frequently associated with cirrhosis but the relationship between them is not clear. It may be that both cirrhosis and cancer are caused by the same agents or that the carcinogenic action of an agent is promoted by cirrhotic changes. Malignancy sometimes develops following acute hepatitis caused by Types B and C viruses. The most common sites of metastases are the abdominal lymph nodes, the peritoneum and the lungs.
Secondary malignant tumours (metastases) in the liver are more common than primary liver tumours. They usually spread there from primary tumours in the gastrointestinal tract, the lungs and the breast. They tend to grow rapidly and are often the cause of death.
Diseases of the gall bladder and bile ducts
After studying this section, you should be able to:
describe the causes and consequences of gallstones
compare and contrast acute and chronic cholecystitis
briefly outline the common sites and consequences of biliary tract tumours
discuss the main causes and effects of jaundice.
Gallstones consist of deposits of the constituents of bile, most commonly cholesterol. Many small stones or one or more large stones may form but they do not necessarily produce symptoms. Predisposing factors include:
• changes in the composition of bile that affect the solubility of its constituents
• high blood cholesterol levels
• diabetes mellitus
• female gender
• several pregnancies in young women, especially when accompanied by obesity.
This is acute inflammation of the gall bladder usually associated with gallstones, and occurs when a gallstone becomes impacted (stuck) in the cystic duct, often after a fatty meal. Strong peristaltic contractions of the smooth muscle in the wall of the cystic duct that occur in an attempt to move the stone onwards result in biliary colic, severe acute pain in the right hypochondrium. This does not cause jaundice because bile from the liver can still pass directly into the duodenum. Bile is unable to leave the gall bladder and an inflammatory reaction follows. This may be complicated by bacterial infection and distension of the gall bladder, which carries the risk of perforation and peritonitis.
The onset is usually insidious, sometimes following repeated acute attacks. Gallstones are invariably present and there may be accompanying biliary colic. Pain is due to the spasmodic contraction of muscle, causing ischaemia when the gall bladder is packed with gallstones. There is usually secondary infection with suppuration. Ulceration of the tissues between the gall bladder and the duodenum or colon may occur with fistula formation and, later, fibrous adhesions.
This is inflammation of bile ducts in which there is partial or complete obstruction by gallstones. Complete obstruction of the common bile duct causes acute cholangitis, which is typically accompanied by biliary colic, fever and jaundice (because the flow of bile into the duodenum is blocked). In practice, not all of these symptoms are usually present. This situation predisposes to secondary infection which can spread upwards in the biliary tree to the liver (ascending cholangitis) causing liver abscesses.
Tumours of the biliary tract
Benign tumours are rare.
These are relatively rare and gallstones are nearly always present. Local spread to the liver, the pancreas and other adjacent organs is common. Lymph and blood spread lead to widespread metastases. The tumour has often spread by the time of diagnosis and, therefore, the prognosis is poor.
This is not a disease in itself, but yellowing of the skin and mucous membrane is a sign of abnormal bilirubin metabolism and excretion. Bilirubin, produced from the breakdown of haemoglobin, is normally conjugated in the liver and excreted in the bile (Fig. 12.37). Conjugation, the process of adding certain groups to the bilirubin molecule, makes it water-soluble and greatly enhances its removal from the blood, an essential step in excretion.
Unconjugated bilirubin, which is fat-soluble, has a toxic effect on brain cells. However, it is unable to cross the blood–brain barrier until the plasma level rises above 340 μmol/l, but when it does it may cause neurological damage, seizures (fits) and mental impairment. Serum bilirubin may rise to 40 to 50 μmol/l before the yellow coloration of jaundice is evident in the skin and conjunctiva (normal 3 to 13 μmol/l). Jaundice is often accompanied by pruritus (itching) caused by the irritating effects of bile salts on the skin.
Jaundice develops when there is an abnormality of bilirubin processing and the different types are considered below.
Types of jaundice
Whatever stage in bilirubin processing is affected, the end result is rising blood bilirubin levels.
This is due to increased haemolysis of red blood cells (see Fig. 12.37 and p. 59) that results in production of excess bilirubin. Because the excess bilirubin is unconjugated it cannot be excreted in the urine, which therefore remains normal in colour.
Neonatal haemolytic jaundice occurs in many babies, especially in those born prematurely where the normal high haemolysis is coupled with shortage of conjugating enzymes in the hepatocytes of the still immature liver.
This is the result of damage to the liver itself by, e.g.:
• viral hepatitis (p. 324)
• toxic substances, such as drugs
• amoebiasis (amoebic dysentery) (p. 319)
• cirrhosis (p. 325).
Excess bilirubin accumulates in the liver. Because it is mainly in the conjugated form, it is water-soluble and excreted in the urine making it dark in colour.
Causes of obstruction to the flow of bile in the biliary tract include:
• gallstones in the common bile duct
• tumour of the head of the pancreas
• fibrosis of the bile ducts, following cholangitis or injury by the passage of gallstones.
In this situation excess bilirubin is also conjugated and is therefore excreted in the urine. The effects of raised serum bilirubin include:
• pruritus (itching)
• pale faeces due to absence of stercobilin (p. 296)
• dark urine due to the presence of increased amounts of bilirubin.
For a range of self-assessment exercises on the topcs in this chapter, visitwww.rossandwilson.com.