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movements are associated with the superimposition of trains of action potentials on the BER.


Vomiting (or emeus) is the sudden and forceful oral expulsion of the contents of the stomach and sometimes the duodenum. It is frequently preceded by anorexia (loss of appetite) and nausea (a feeling of sickness). Immediately before vomiting it is common to experience characteristic autonomic responses, such as copious watery salivation (waterbrash), vasoconstriction with pallor, sweating, dizziness, and tachycardia. Retching often precedes vomiting. Respiration is inhibited during the process of vomit­ing. The larynx is closed and the soft palate rises to close off the nasopharynx and prevent the inhalation of vomited material (vomitus). The stomach and pyloric sphincter relax and contraction of the duodenum reverses the normal pressure gradient so that intestinal contents are allowed to enter the stomach (a process sometimes referred to as reverse peristalsis). The diaphragm and abdominal wall then contract powerfully, the gastro-esophageal sphincter relaxes, and the pylorus closes. The resulting rise in intragastric pressure causes the expulsion of the gastric contents.

The vomiting reflex is coordinated by the dorsal portion of the reticular formation of the medulla, which lies close to the respiratory and cardiovascular control areas of the brainstem. Afferent impulses arrive at this region from many parts of the body, including the pharynx and other areas of the GI tract, viscera such as the liver, gallbladder, urinary bladder, uterus and kidneys, the cerebral cortex, and the semicircular canals of the ears (giving rise to motion sickness). Furthermore, a variety of chemical agents, including anesthetics, opiates, and digitalis, appear to trigger vomiting by stimulating receptors in the floor of the fourth ventricle. The motor impulses responsible for the action of vomiting are transmitted from the vomiting 'center' via the trigeminal, facial, glossopharyngeal, vagus, and hypoglossal nerves (cranial nerves V, VII, IX, X, and XII).

Although vomiting is, generally, a protective mechanism whereby potentially toxic substances are removed from the body, prolonged vomiting can lead to a state of metabolic alkalosis due to the continued loss of acid from the stomach (see Chapter 29).

Absorption by the stomach

Very little absorption occurs in the stomach. Ethyl alcohol is the only water-soluble substance absorbed in significant amounts and even this can only be absorbed because its lipid solubility enables it to diffuse readily through the plasma membranes of the gastric mucosal cells. Certain organic substances which are un-ionized, and therefore relatively fat soluble, at the acidic pH of the stomach, may be absorbed here. An example is aspirin which has a pK^ of 3-5 so that it remains largely un-ionized in the stomach. Molecules of aspirin diffuse through the mucosal barrier into the intracellular comparrment in which the pH is closer to neutral. The aspirin molecules become ionized and are therefore unable to diffuse back into the gastric lumen but are absorbed into the circulation.


  1. The stomach stores food, mixes it with gastric juice, and breaks it into
    smaller pieces. Eventually semiliquid chyme is formed. The stomach
    then delivers chyme to the duodenum in a controlled fashion.

  2. The stomach is able to store large amounts of food since intragastric
    pressure rises little despite significant distension.

3.The fasting stomach shows only weak contractile activity. After a meal peristaltic contractions begin, increasing in power as they approach the antrum where mixing is most vigorous. Peristalsis is the mechanical consequence of the basic electrical rhythm (BER) or slow-wave rhythm of the gastric smooth muscle. Gastric motility is enhanced by mechanical distension and gastrin.

4. The stomach normally empties at a rate compatible with full diges­
tion and absorption by the small intestine. Many factors contribute to
this regulation. Distension of the stomach increases the rate of emp­
tying. The presence in the chyme of fats, proteins, high acidity, and
hypertonicity all delay the rate of emptying.

5. Vomiting is a protective mechanism whereby noxious or potentially
toxic substances are expelled from the GI tract. The vomiting reflex
is coordinated in the medulla of the brain. Prolonged vomiting can
cause metabolic alkalosis through the loss of gastric acid.

18.8 The small intestine

Chyme, produced by the chemical and mechanical actions of the stomach, is emptied into the duodenum where it is mixed with secretions from the liver and exocrine pancreas as well as from the small intestine itself. The small intestine is the major site of both digestion and absorption in the GI tract. In life the small intestine is a tube about 4 m long with a diameter of about 2.5 cm and is divided into three segments: the duodenum, jejunum, and ileum. The duodenum is about 25 cm long (literally 'duo-denum' means 12 finger-widths). The ducts which deliver bile and pancreatic secretions unite close to the duodenum at the hepato-pancreatic ampulla, which opens into the duodenum at the major duodenal papilla. The sphincter of Oddi controls the entry of bile and pancreatic juice into the small intestine. The jejunum is about 1.5 m long and extends from the duodenum to the ileum, a coiled tube about 2.5 m in length.

Special histologic characteristics of the small intestine

The small intestine is exquisitely adapted for nutrienr absorp­tion, particularly in the proximal portion. It presents a huge surface area (estimated at around 200 m2) borh by means of irs length and by structural modifications of its wall. The mucosa and submucosa, particularly of the jejunum, are thrown into deep folds called circular folds (Fig. 18.15a) which, because of their shape, force chyme to spiral as it passes through the lumen. This spiraling slows down the rate of passage of chyme and facil­itates mixing with intestinal juices, thereby optimizing con­ditions for digestion and absorption. Peyer'spatches, large isolated


18 The gut and nutrition

clusters of lymph nodules similar to the tonsils, are found in the wall of the ileum. They form part of the collection of small lymphoid tissues of the GI and respiratory tracts referred to as the mucosa-associated lymphatic tissue (MALT).

The folded surface of the small intestine is covered with finger-like projections or villi, about 1 mm high (Fig. 18.15b), the surface of which is formed chiefly by columnar absorptive epithelial cells (enterocytes) bound by tight junctions at their apical surfaces. The mucosal surface of these cells consists of many tiny processes or microvilli (roughly 1.0/Ltm long and 0.1 fim in diameter) which constitute the brush border. This increases the surface area of the small intestine still further.

The villi themselves differ in appearance throughout the small intestine. They are broad in the duodenum, slender and leaf-like in the jejunum, and shorter, more finger-like in the ileum. Within each villus is a modified lymph vessel (lacteal) opening into the local lymphatic circulation, blood vessels, some smooth muscle (which enables the villus to alter its length), and connective tissue.

The blood vessels of the villi have a countercurrent arrange­ment. A single unbranched arterial vessel runs up the central core of the lamina propria of the villus. At the tip it branches extensively to form a capillary network that collects into veins at the base.

Between the villi are simple tubular glands, 0.3-0.5 mm deep, called crypts of Lieberkuhn. They are found throughout the small intestine but are most numerous in the mucosa of the proximal small intestine. A variety of cell types are found here, the most abundant of which are undifferentiated cells which pro­liferate to replace lost enterocytes (see below).

A number of different types of endocrine and paracrine cells have also been identified in the crypts and on the villi. These cells have been shown to produce somatostatin (D-cells), secretin (S-cells), neurotensin (N-cells), CCK, and 5-hydroxytryptamine (5HT). CCK and secretin are secreted by cells in the wall of the duodenum in response to the presence of fat digestion products and acid, respectively. In addition to the crypts of Lieberkuhn, the duodenum (but not the jejunum or ileum) also contains submucosal Brunner's glands.

The epithelium of the small intestine is self-renewing

The small intestine has a very rapid rate of cell turnover. In humans, the entire epithelium is renewed every 6 days. This rapid turnover is important because the epithelial cells are sens­itive to hypoxia and to other irritants. Epithelial cells are formed by the mitotic proliferation of a population of undifferentiated stem cells within the crypts. These new cells then migrate upwards towards the tip of the villus from where they are shed into the lumen of the intestine. As the cells migrate and leave the crypts they become fully mature and the brush-border enzymes develop. The rate at which cells proliferate can be altered by a number of factors. Starvation and prolonged intra-

Fig. 18.15 Structural characteristics of the small intestine, (a) A section of ileum, showing circular folds and a lymph nodule (Peyer's patch), (b) A schematic view of an intestinal villus in longitudinal section.

18.9 Motility of the small intestine


venous feeding, for example, cause atrophy of the cells and a reduction in proliferation.

Secretion of fluid and enzymes by the small intestine

Cells of the crypts are responsible for the secretion of 2—3 liters each day of isotonic fluid. Secretion occurs as a result of trans-cellular chloride movement from the interstitial fluid to the lumen, followed by paracellular movement of sodium and water. The principal stimulant of fluid secretion is distension of the intestine by acidic or hypertonic chyme.

It was once believed that the intestinal juice (or succus entericus) contained most of the enzymes required for the com­plete digestion of food. It has now been established, however, that the only enzymes derived from the small intestine itself (rather than the pancreas) are the brush-border enzymes. The prin­cipal brush-border enzymes are disaccharidases (maltase, sucrase, etc.), peptidases, and phosphatases. One of the duodenal brush-border peptidases, enteropeptidase (commonly called entero-kinase), breaks down pancreatic trypsinogen to activate it.

Children under 4 years of age also express the enzyme lactase, which promotes the digestion of lactose (milk sugar). Lactose intolerance is caused by a lack of this enzyme, which results in diarrhea and discomfort if large amounts of this sugar are ingested since undigested lactose cannot be absorbed. The enzyme is less active in older individuals.

In the duodenum, the Brunner's glands secrete a bicarbonate-rich alkaline fluid containing mucus which, together with the secretions of the crypts, protects the duodenal mucosa from mechanical damage and erosion by the acid and pepsin contained within chyme arriving from the stomach. Although the glands

secrete spontaneously when acid chyme enters the duodenum, their secretion may be further stimulated by vagal activity, endogenous prostaglandins, and the hormones gastrin, secretin, and CCK. Sympathetic stimulation, however, causes a marked decrease in the rate of mucus production, leaving the duodenum more susceptible to erosion. Indeed, three-quarters of peptic ulcers occur in this region of the gut, many of which are related to stress. Table 18.1 lists the major hormones, electrolytes, and enzymes produced by the small intestine.


  1. The small intestine is the major site of both digestion and absorption
    in the GI tract. Here chyme is mixed with bile, pancreatic juice, and
    the intestinal secretions.

  2. The small intestine provides a huge surface area for nutrient absorp­
    tion. The folded mucosal surface is covered with projections called
    villi. The brush-border membranes of the mucosal epithelial cells
    house enzymes. Between the villi lie simple tubular glands, the
    crypts of Lieberkiihn. The epithelia of both vilii and cryps contain
    many different cell types, including mucus-secreting goblet cells,
    phagocytic cells, and endocrine cells.

  3. The small intestinal epithelium is self-renewing, replacing itself
    completely every 6 days or so. Loss of cells at the tips of the villi
    releases enzymes from the brush border of the enterocytes into the
    intestinal lumen. One of these, enterokinase, activates pancreatic
    trypsin which then activates other proteolytic enzymes.

  4. Crypt cells secrete 2—3 liters of isotonic fluid each day. Chloride is
    transported out of the cells and sodium and water follow passively by
    the paracellular route. In the duodenum, Brunner's glands contribute
    to the secretion of alkaline fluid which helps to protect the epithe­
    lium from the corrosive effects of acidic chyme arriving from the
    stomach. Secretion is stimulated by vagal neurons and by CCK,
    secretin, gastrin, and endogenous prostaglandins.

Table 18.1 The secretions of the small intestine (a) Hormones

Hormone Cells of origin

Cholecystokinin (CCK) I-cells Neurotensin M-cells Secretin S-cells Serotonin (5HT) Enterocbromaffin cells Somatostacin D-cells

(b) Other secretory products

^ Secretory product Source

Lysozyme Paneth cells of crypts Mucus Goblet cells Isotonic fluid (2—3 1 day"1) Crypts Alkaline fluid Brunner's glands (duodenum only)

18.9 Motility of the small intestine

Typically, chyme traverses the length of the small intestine in 3-5 hours (although under certain conditions it may take as long as 10 hours). The rate of movement is normally such that the last part of one meal is leaving the ileum as the next meal enters the stomach. The most important types of movement in the small intestine are segmentation and peristalsis, described in Section 18.2. Segmentation is of great importance in mixing the chyme with the digestive enzymes present in the small intestine and in facilitating the absorption of the products of digestion. The villi and microvilli of the intestinal mucosa also exhibit mixing movements.

The peristaltic waves rarely travel more than about 10 cm and are known as 'short-range' peristaltic contractions. Exceptions to this are the so-called 'housekeeper contractions' described later. Waves of peristalsis are initiated by distension of the small intestine.

^ 412

18 The gut and nutrition

Segmentation and peristalsis are

inherent properties of the intestinal

smooth muscle

The basic electrical rhythm of the small intestine is independent of extrinsic innervation and both segmentation and peristaltic contractions are inherent properties of the intestinal smooth muscle. However, the excitability of the smooth muscle and the strength of its contraction can be modified by extrinsic nerves as well as by the variety of hormones utilized as neurotransmitters by the intramural plexuses. Parasympathetic stimulation increases the excitability of the smooth muscle, while sympa­thetic stimulation depresses it. These autonomic effects are exerted principally via the enteric nerve plexuses.

Extrinsic nerves play a role in certain long-range intestinal reflexes. These include the so-called ileo-gastric and gastro-ileal reflexes, which describe the reflex interactions that operate between the stomach and the terminal ileum. The ileo-gastric reflex refers to the reduction in gastric motility that occurs in response to distension of the ileum. The gastro-ileal reflex describes the increase in motility of the terminal ileum (particu­larly in segmentation) that occurs whenever there is an increase in secretory and/or motor activity of the stomach. Both of these will have the overall effect of matching emptying of the small intestine with the arrival of chyme in the duodenum.

Movements of the villi of the mucosa contribute to absorption and mixing

The intestinal villi show piston-like contraction and relaxation movements which are thought to facilitate the removal of the digestion products of fats from the lacteals (the lymphatic vessels which course through the villi). One possible sequence of events is that when the villus is relaxed, absorption takes place via intercellular channels. As the villus contracts, these intercellular channels are cut off and the absorbed material is forced into more distal parts of the lymphatic system. This is sometimes referred to as 'milking' the lacteals. Strands of smooth muscle within the lamina propria are thought to give rise to these pumping movements.

The villi also show pendular (swaying) movements which may contribute to the mixing of chyme within the intestinal lumen. These movements are enhanced by the presence of amino acids and fatty acids within the intestinal lumen.

Patterns of motility in the small intestine during fasting

The patterns of contractility described above relate to the behavior of the small intestine following a meal. During periods of fasting, or once a meal has been processed, the smooth muscle of the small intestine shows a different characteristic pattern in which segmentation movements wane and waves of peristalsis, initiated at the duodenal end, sweep slowly along the length of

the small intestine. Individual waves travel up to 70 cm before dying out and the entire wave of contraction takes 1-2 hours to travel the length of the small intestine. The electrical activity that underlies this contractile behavior is known as the migrating motility complex (MMC) and is repeated every 70—90 minutes. The purpose of these waves of peristalsis appears to be to sweep out the last remains of the digested meal, together with bacteria and other debris, into the large intestine. For this reason, the contractions are sometimes called 'housekeeper contractions'.

The mechanisms that initiate and control the MMC are not understood. Both vagal and hormonal mechanisms (particularly another gut hormone, motilin) have been implicated.

The ileo-cecal sphincter controls the emptying of the small intestine

The first part of the large intestine is called the cecum and the junc­tion between the terminal ileum and the cecum is the ileo-cecal sphincter. This normally regulates the rate of entry of chyme into the large intestine to ensure that water and electrolytes are fully absorbed from it in the colon. Its activity is governed by the neurons of the intramural plexuses. The sphincter is normally closed, but short-range peristaltic contractions of the terminal ileum cause the sphincter to relax and allow a small amount of chyme to pass through. The long-range reflexes ensure that the rate of emptying is matched to the ability of the colon to deal with the volume of chyme delivered. After a meal, for example, ileal empty­ing is enhanced through the operation of the gastro-ileal reflex.


l.The rate at which chyme moves through the small intestine is carefully controlled to ensure adequate time for the completion of digestion and absorption. Two types of movement are inherent properties of the intestinal smooth muscle: segmentation is respons­ible for the mixing of chyme with enzymes and for exposing it to the absorptive mucosal surface; peristaltic contractions propel chyme along towards the ileo-cecal valve.

  1. Segmentation is characterized by closely spaced contractions of the
    circular smooth muscle, the frequency of which coincides with the
    rate of slow-wave activity in each part of the gut. Peristaltic con­
    tractions are less frequent and usually propel chyme only short

  2. The motility of the intestinal smooth muscle is influenced by both
    intrinsic and extrinsic neurons and the neurotransmitters of the intra­
    mural plexuses. Parasympathetic activity enhances intestinal motility.

  3. The intestinal villi exhibit both piston-like contractions and swaying,
    pendular movements. The latter may contribute to the mixing
    of chyme, while the former serve to facilitate the removal of fatty
    digestion products from the lacteals of the villi.

  4. In the fasting intestine, segmentation wanes and periodic bursts
    of peristaltic activity are seen in which the contents of the gut are
    swept long distances along the tfact. These are called 'housekeeper'

18.10 The exocrine functions of the pancreas


18.10 The exocrine functions of the pancreas

The pancreas performs two distinct functions—acting as an endocrine gland, secreting the hormones insulin and glucagon, into the bloodstream, and as an accessory digestive (exocrine) organ, secreting an enzyme-rich fluid into the GI tract. The endocrine role of the pancreas is discussed fully in Chapter 27. Only its exocrine function will be described here.

Gross and fine structure of the pancreas

The pancreas lies deep to the stomach and extends across the abdomen for about 20 cm. The tail of the pancreas lies close to the spleen, while its head is encircled by the duodenum. Its anatomic situation is illustrated in Fig. 18.1.

A schematic representation of the structure of the exocrine pancreas is shown in Fig. 18.16. It is similar to the salivary glands, being made up of lobules consisting of acinar cells which secrete enzymes and fluid into a system of microscopic (inter­calated) ducts lined with epithelial cells which also secrete fluid. These drain into larger intralobular ducts which, in turn, empty into interlobular ducts and finally the main pancreatic duct, which extends from left to right through the pancreas itself. In

Fig. 18.16 (a) A schematic representation of the structure of the exocrine pancreas, (b) A summary of the sites of action and effects of secretin, cholecystokinin, and acetylcholine on the secretion of the acinar and duct cells of the exocrine pancreas.

most people, the main pancreatic duct fuses with the bile duct before emptying into the duodenum. There is also a smaller pan­creatic duct (duct of Santorini) which drains directly into the duodenum. Acinar cells occupy more than 80 per cent of the total pancreatic volume and duct cells about 4 per cent. The islet cells occupy about 2-3 per cent of the gland and the remainder is connective tissue, blood vessels, etc.

The pancreas is supplied by branches of the celiac and superior mesenteric arteries and its venous drainage is via the portal vein. It is innervated by preganglionic parasympathetic vagal fibers which synapse with cholinergic postganglionic fibers within the pancreas. Pancreatic blood vessels receive sympathetic innervation from the celiac and superior mesenteric plexuses.

The composition of pancreatic juice

Pancreatic juice has two major components—an aqueous com­ponent and an enzyme component—the relative proportions of which may vary according to various stimuli. Between 200 and 800 ml of alkaline fluid are secreted each day. This is rich in bicarbonate with a pH of about 8 and, together with the intesti­nal secretions, helps to neutralize the acidic chyme as it arrives in the duodenum. All the major enzymes Aeeded to complete the digestion of fats, proteins, and carbohydrates are contained within the enzymic component of the pancreatic juice.

^ The aqueous component of pancreatic juice

This is formed almost entirely by the columnar epithelial cells which line the ducts. Resting secretion is chiefly from the inter­calated and intralobular ducts but during stimulation, the inter­lobular ducts also secrete pancreatic fluid. Duct cells secrete a slightly hypertonic fluid rich in bicarbonate ions and with sodium and potassium concentrations similar to those of plasma.

Precise details of the ionic mechanisms underlying the secre­tion of the alkaline fluid have not been clarified. A possible sequence of events is illustrated in Fig. 18.17. Hydrogen ions are transported out of the cell into the interstitial fluid and thence to the plasma in exchange for either sodium or potassium ions. Bicarbonate ions are then transported out of the duct cell across its luminal membrane in exchange for chloride or via an anion channel in the luminal membrane. Sodium diffuses from the interstitial fluid to the duct lumen via a paracellular pathway to maintain electroneutrality. Water follows osmotically, moving transcellularly or paracellularly into the duct lumen.

Secretion of the aqueous component of pancreatic juice appears to be regulated by cyclic AMP which increases the time for which the apical membrane anion channels are open and stimulates the activity of the proton pumps in the basolateral membrane.

The ionic composition of the pancreatic fluid depends upon its rate of secretion, as shown in Fig. 18.18. As it flows along the ducts, the primary secretion of the ductal epithelial cells under­goes modification. Bicarbonate ions are reabsorbed from the fluid in exchange for chloride ions. The result of this is that, at low


18 The gut and nutrition

Fig. 18.17 The ionic movements underlying the secretion of an alkaline fluid by duct cells of the exocrine pancreas.

Fig. 18.18 The electrolyte composition of rabbit pancreatic juice as a function of the rate of secretion. The greater the rate of secretion, the higher the bicarbonate concentration.

flow rates, fluid levels of bicarbonate are much lower (down to 20-30 mM) than at high flow rates, when the fluid spends little time in the ducts and is therefore scarcely altered. At maximal flow rates the bicarbonate concentration of human pancreatic juice is around 140 mM. It may be seen from Fig. 18.18 that as the bicarbonate concentration falls, chloride levels rise correspondingly.

The enzyme components of pancreatic juice

Pancreatic juice contains a wide array of digestive enzymes, including proteolytic, amylolytic, and lipolytic agents as well as many others such as ribonuclease, deoxyribonuclease, and elas-tases. A list of the principal enzymes and their actions is given in Table 18.2.

^ Proteolytic enzymes of the pancreas

Proteolytic enzymes including trypsin, a number of chymotrypsins, and carboxypeptidases are stored within the acinar cells as zymogen granules. They are secreted in this inactive form (trypsinogen, chymotrypsinogens, and procarboxypeptidases) and are activated inside the lumen of the small intestine. In this way the pancreas, like the stomach, avoids self-digestion. Activation of trypsino­gen may occur spontaneously, in response to the alkaline envi­ronment of the small intestine, and in response to enterokinase (enteropeptidase), one of the brush-border enzymes. Chymot­rypsinogens are then activated by trypsin itself. Trypsin and chymotrypsins are endopolypeptidases which hydrolyze peptide bonds within protein molecules to release some free amino acids and polypeptides of varying size. Carboxypeptidases (activated by trypsin), elastase, and aminopeptidases are then able to digest these further.

Table 18.2 The enzymes of the small intestine

Enzyme Zymogen Activator Action

Trypsin Trypsinogen Enterokinase Cleaves internal peptide bonds Chymotrypsin Chymotrypsinogen Trypsin Cleaves internal peptide bonds Elastase Proelastase Trypsin Cleaves internal peptide bonds Carboxypeptidase Procarboxypeptidase Trypsin Attacks peptides at C-terminal end Amylase Digests starch to maltose and oligosaccharides Lipase Cleaves glycerides, liberating fatty acids and glycerol Colipase Procolipase Trypsin Binds to micelles to anchor lipase to lipid Phospholipase A2 Prophospholipase Trypsin Cleaves Fatty acids from phospholipids Cholesterol esterase Trypsin Releases esterified cholesterol RNAase Cleaves RNA into short fragments DNAase Cleaves DMA into short fragments

^ 18.10 The exocrine functions of the pancreas
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