Guyton & Hall Textbook Ch. 61 PDF

UNIT XII Gastrointestinal Physiology effective in emptying the large bowel all the way from the Bibliography splenic flexure of the colon to the anus. Browning KN, Travagli RA: Central nervous system control of gastro- Defecation signals entering the spinal cord initia...

UNIT XII Gastrointestinal Physiology effective in emptying the large bowel all the way from the Bibliography splenic flexure of the colon to the anus. Browning KN, Travagli RA: Central nervous system control of gastro- Defecation signals entering the spinal cord initiate intestinal motility and secretion and modulation of gastrointestinal other effects, such as taking a deep breath, closure of the functions. Compr Physiol 4:1339, 2014. glottis, and contraction of the abdominal wall muscles to Camilleri M: Physiological underpinnings of irritable bowel syndrome: force the fecal contents of the colon downward, and at the neurohormonal mechanisms. J Physiol 592:2967, 2014. Farré R, Tack J: Food and symptom generation in functional gas- same time they cause the pelvic floor to relax downward trointestinal disorders: physiological aspects. Am J Gastroenterol and pull outward on the anal ring to evaginate the feces. 108:698, 2013. When it becomes convenient for the person to defe- Ford AC, Lacy BE, Talley NJ: Irritable bowel syndrome. N Engl J Med cate, the defecation reflexes can purposely be activated by 376:2566, 2017. taking a deep breath to move the diaphragm downward Furness JB: The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 9:286, 2012. and then contracting the abdominal muscles to increase Gracie DJ, Hamlin PJ, Ford AC: The influence of the brain-gut axis the pressure in the abdomen, thus forcing fecal contents in inflammatory bowel disease and possible implications for treat- into the rectum to cause new reflexes. Reflexes initiated in ment. Lancet Gastroenterol Hepatol 4:632, 2019. this way are almost never as effective as those that arise Hockley JRF, Smith ESJ, Bulmer DC: Human visceral nociception: find- naturally, and thus people who too often inhibit their ings from translational studies in human tissue. Am J Physiol Gas- trointest Liver Physiol 315:G464, 2018. natural reflexes are likely to become severely constipated. Huizinga JD, Lammers WJ: Gut peristalsis is governed by a multitude In newborns and in some people with transected spinal of cooperating mechanisms. Am J Physiol Gastrointest Liver Physiol cords, the defecation reflexes cause automatic emptying 296:G1, 2009. of the lower bowel at inconvenient times during the day Kumral D, Zfass AM: Gut movements: a review of the physiology of because of lack of conscious control exercised through gastrointestinal transit. Dig Dis Sci 63:2500, 2018. Lang IM, Medda BK, Shaker R: Characterization and mechanism of voluntary contraction or relaxation of the external anal the esophago-esophageal contractile reflex of the striated mus- sphincter.␣ cle esophagus. Am J Physiol Gastrointest Liver Physiol 317:G304, 2019. Mittal RK: Regulation and dysregulation of esophageal peristalsis by OTHER AUTONOMIC REFLEXES THAT the integrated function of circular and longitudinal muscle lay- AFFECT BOWEL ACTIVITY ers in health and disease. Am J Physiol Gastrointest Liver Physiol 311:G431, 2016. Aside from the duodenocolic, gastrocolic, gastroileal, Ouyang A, Regan J, McMahon BP: Physiology of the upper segment, enterogastric, and defecation reflexes that have been dis- body, and lower segment of the esophagus. Ann N Y Acad Sci cussed in this chapter, several other important nervous 1300:261, 2013. reflexes also can affect the overall degree of bowel activ- Sanders KM, Ward SM, Koh SD: Interstitial cells: regulators of smooth muscle function. Physiol Rev 94:859, 2014. ity. They are the peritoneointestinal reflex, renointestinal Spencer NJ, Dinning PG, Brookes SJ, Costa M: Insights into the mech- reflex, and vesicointestinal reflex. anisms underlying colonic motor patterns. J Physiol 594:4099, The peritoneointestinal reflex results from irritation of 2016. the peritoneum; it strongly inhibits the excitatory enteric Szarka LA, Camilleri M: Methods for measurement of gastric motility. nerves and thereby can cause intestinal paralysis, espe- Am J Physiol Gastrointest Liver Physiol 296:G461, 2009. cially in patients with peritonitis. The renointestinal and vesicointestinal reflexes inhibit intestinal activity as a result of kidney or bladder irritation, respectively. 806  CHAPTER 65 UNIT XII Secretory Functions of the Alimentary Tract Throughout the gastrointestinal tract, secretory glands Fourth, also associated with the alimentary tract are subserve two primary functions: (1) digestive enzymes several complex glands—the salivary glands, pancreas, are secreted in most areas of the alimentary tract, from and liver—that provide secretions for digestion or emul- the mouth to the distal end of the ileum; and (2) mucous sification of food. The liver has a highly specialized struc- glands located from the mouth to the anus provide mucus ture that is discussed in Chapter 71. The salivary glands for lubrication and protection of all parts of the alimen- and the pancreas are compound acinous glands of the tary tract. type shown in Figure 65-2. These glands lie outside the Most digestive secretions are formed in response to walls of the alimentary tract and, in this aspect, they differ the presence of food in the alimentary tract, and the from all other alimentary glands. They contain millions of quantity secreted in each segment of the tract is usually acini lined with secreting glandular cells; these acini feed the amount needed for proper digestion. Furthermore, into a system of ducts that finally empty into the alimen- in some portions of the gastrointestinal tract, even the tary tract.␣ types of enzymes and other constituents of the secre- tions are varied in accordance with the types of food BASIC MECHANISMS OF STIMULATION OF present. In this chapter we describe the different alimen- THE ALIMENTARY TRACT GLANDS tary secretions, their functions, and regulation of their production. Contact of Food With Gut Epithelium Activates the Enteric Nervous System and Stimulates Secretion GENERAL PRINCIPLES OF ALIMENTARY The presence of food in a particular segment of the gastro- TRACT SECRETION intestinal tract usually stimulates the glands of that region and adjacent regions to secrete moderate to large quanti- TYPES OF ALIMENTARY TRACT GLANDS ties of juices. Part of this local effect, especially the secre- Several types of glands provide the different types of tion of mucus by mucous cells, results from direct contact alimentary tract secretions. First, on the surface of the stimulation of the surface glandular cells by the food. epithelium in most parts of the gastrointestinal tract are billions of single-cell mucous glands called simply mucous Nerve Endoplasmic Golgi cells or sometimes goblet cells because they look like gob- Capillary fiber reticulum apparatus lets. They function mainly in response to local irritation of the epithelium: They extrude mucus directly onto the Secretion epithelial surface to act as a lubricant that also protects the surfaces from excoriation and digestion. Second, many surface areas of the gastrointestinal tract are lined by pits that represent invaginations of the epi- thelium into the submucosa. In the small intestine, these pits, called crypts of Lieberkühn, are deep and contain specialized secretory cells. One of these cells is shown in Figure 65-1. Third, in the stomach and upper duodenum are large numbers of deep tubular glands. A typical tubular gland Basement Mitochondria Ribosomes Zymogen can be seen in Figure 65-4, which shows an acid- and membrane granules pepsinogen-secreting gland of the stomach (oxyntic Figure 65-1. Typical function of a glandular cell for formation and gland). secretion of enzymes and other secretory substances. 807 UNIT XII Gastrointestinal Physiology Regulation of Glandular Secretion by Hormones. In Primary secretion: the stomach and intestine, several different gastrointes- 1. Ptyalin 2. Mucus tinal hormones help regulate the volume and composi- 3. Extracellular fluid tion of the secretions. These hormones are liberated from the gastrointestinal mucosa in response to the presence of food in the lumen of the gut. The hormones are then absorbed into the blood and carried to the glands, where they stimulate secretion. This type of stimulation is par- Na+ active absorption Cl− passive absorption ticularly valuable to increase the output of gastric juice K+ active secretion and pancreatic juice when food enters the stomach or HCO3− secretion duodenum. Chemically, the gastrointestinal hormones are poly- peptides or polypeptide derivatives and will be discussed in more detail later.␣ Saliva Figure 65-2. Formation and secretion of saliva by a submandibular BASIC MECHANISM OF SECRETION BY salivary gland. GLANDULAR CELLS Secretion of Organic Substances. Although all the ba- sic mechanisms by which glandular cells function are not In addition, local epithelial stimulation also activates known, experimental evidence points to the following the enteric nervous system of the gut wall. The types of principles of secretion, as shown in Figure 65-1. stimuli that activate this system are (1) tactile stimulation, 1. The nutrient material needed for formation of the (2) chemical irritation, and (3) distention of the gut wall. secretion must first diffuse or be actively transport- The resulting nervous reflexes stimulate the mucous cells ed by the blood in the capillaries into the base of the on the gut epithelial surface and the deep glands in the gut glandular cell. wall to increase their secretion.␣ 2. Many mitochondria located inside the glandular cell Autonomic Stimulation of Secretion near its base use oxidative energy to form adenosine triphosphate (ATP). Parasympathetic Stimulation Increases Alimentary 3. Energy from the ATP, along with appropriate sub- Tract Glandular Secretion Rate. Stimulation of the strates provided by the nutrients, is then used to parasympathetic nerves to the alimentary tract almost synthesize the organic secretory substances; this invariably increases the rates of alimentary glandular se- synthesis occurs almost entirely in the endoplasmic cretion. This increased secretion rate is especially true of reticulum and Golgi complex of the glandular cell. the glands in the upper portion of the tract (innervated by Ribosomes adherent to the reticulum are specifi- the glossopharyngeal and vagus parasympathetic nerves) cally responsible for formation of proteins that are such as the salivary glands, esophageal glands, gastric secreted. glands, pancreas, and Brunner's glands in the duodenum. 4. The secretory materials are transported through It is also true of some glands in the distal portion of the the tubules of the endoplasmic reticulum, passing large intestine, which are innervated by pelvic parasym- in about 20 minutes all the way to the vesicles of the pathetic nerves. Secretion in the remainder of the small Golgi complex. intestine and in the first two-thirds of the large intestine 5. In the Golgi complex, the materials are modified, occurs mainly in response to local neural and hormonal added to, concentrated, and discharged into the cy- stimuli in each segment of the gut.␣ toplasm in the form of secretory vesicles, which are Sympathetic Stimulation Has a Dual Effect on Ali- stored in the apical ends of the secretory cells. mentary Tract Glandular Secretion Rate. Stimulation of 6. These vesicles remain stored until nervous or hor- the sympathetic nerves going to the gastrointestinal tract monal control signals cause the cells to extrude the causes a slight to moderate increase in secretion by some vesicular contents through the cells' surface. This of the local glands. However, sympathetic stimulation also action probably occurs in the following way. The constricts the blood vessels that supply the glands. There- hormone binds to its receptor and, through one of fore, sympathetic stimulation can have a dual effect: (1) several possible cell signaling mechanisms, increas- sympathetic stimulation alone usually slightly increases es the cell membrane permeability to calcium ions. secretion, and (2) if parasympathetic or hormonal stimu- Calcium enters the cell and causes many of the vesi- lation is already causing copious secretion by the glands, cles to fuse with the apical cell membrane. The api- superimposed sympathetic stimulation usually reduces cal cell membrane then breaks open, thus empty- secretion, sometimes significantly, mainly because of va- ing the vesicles to the exterior; this process is called soconstrictive reduction of the blood supply.␣ exocytosis.␣ 808  Chapter 65 Secretory Functions of the Alimentary Tract Water and Electrolyte Secretion. A second necessity Table 65-1 Daily Alimentary Tract Secretions Juices for glandular secretion is secretion of sufficient water Type of Secretion Daily Volume (ml) pH and electrolytes to go along with the organic substances. Saliva 1000 6.0–7.0 Secretion by the salivary glands, discussed in more de- tail later, provides an example of how nervous stimula- Gastric secretion 1500 1.0–3.5 UNIT XII tion causes water and salts to pass through the glandular Pancreatic secretion 1000 8.0–8.3 cells in great profusion, washing the organic substances Bile 1000 7.8 through the secretory border of the cells at the same time. Small intestine secretion 1800 7.5–8.0 Hormones acting on the cell membrane of some glan- Brunner's gland secretion 200 8.0–8.9 dular cells also cause secretory effects similar to those Large intestinal secretion 200 7.5–8.0 caused by nervous stimulation.␣ Total 6700 Lubricating and Protective Properties of Mucus in the Gastrointestinal Tract secretion that contains mucin for lubricating and for sur- Mucus is a thick secretion composed mainly of water, face protective purposes. electrolytes, and a mixture of several glycoproteins that are composed of large polysaccharides bound with much The parotid glands secrete almost entirely the serous smaller quantities of protein. Mucus is slightly different in type of secretion, whereas the submandibular and sub- different parts of the gastrointestinal tract, but in all lo- lingual glands secrete both serous secretion and mucus. cations it has several important characteristics that make The buccal glands secrete only mucus. Saliva has a pH it both an excellent lubricant and a protectant for the gut between 6.0 and 7.0, which is a favorable range for the wall: digestive action of ptyalin.␣ 1. Mucus has adherent qualities that make it adhere tightly to the food or other particles and to spread as a thin film Secretion of Ions in Saliva. Saliva contains especially over the surfaces. large quantities of K+ and HCO3−. Conversely, the con- 2. It has sufficient body that it coats the wall of the gut and centrations of both Na+ and Cl− are several times less in prevents actual contact of most food particles with the saliva than in plasma. One can understand these special mucosa. concentrations of ions in the saliva from the following de- 3. Mucus has a low resistance for slippage, so the particles scription of the mechanism for secretion of saliva. can slide along the epithelium with great ease. Figure 65-2 shows secretion by the submandibular 4. Mucus causes fecal particles to adhere to one another to gland, a typical compound gland that contains acini and form the feces that are expelled during a bowel move- salivary ducts. Salivary secretion is a two-stage operation. ment. The first stage involves the acini, and the second stage 5. Mucus is strongly resistant to digestion by the gastroin- testinal enzymes. involves the salivary ducts. The acini secrete a primary 6. The glycoproteins of mucus have amphoteric properties, secretion that contains ptyalin and/or mucin in a solu- which means that they are capable of buffering small tion of ions with concentrations not greatly different from amounts of either acids or alkalies; also, mucus often those of typical extracellular fluid. As the primary secre- contains moderate quantities of HCO3−, which specifi- tion flows through the ducts, two major active transport cally neutralize acids. processes take place that markedly modify the ionic com- Thus, mucus has the ability to allow easy slippage of position of the fluid in the saliva. food along the gastrointestinal tract and to prevent exco- First, Na+ is actively reabsorbed from all the salivary riative or chemical damage to the epithelium. A person be- ducts and K+ is actively secreted in exchange for Na+. comes acutely aware of the lubricating qualities of mucus Therefore, Na+ concentration of the saliva becomes greatly when the salivary glands fail to secrete saliva, because then reduced, whereas K+ concentration becomes increased. it is difficult to swallow solid food even when it is eaten along with large amounts of water.␣ However, there is excess Na+ reabsorption compared with K+ secretion, which creates electrical negativity of about −70 millivolts in the salivary ducts; this negativity SECRETION OF SALIVA in turn causes Cl− to be reabsorbed passively. Therefore, Cl− concentration in the salivary fluid falls to a very low Saliva Contains a Serous Secretion and a Mucus Se- level, matching the ductal decrease in Na+ concentration. cretion. The principal glands of salivation are the parotid, Second, HCO3− is secreted by the ductal epithelium submandibular, and sublingual glands; in addition, there into the lumen of the duct. This secretion is at least partly are many tiny buccal glands. Daily secretion of saliva nor- caused by passive exchange of bicarbonate for Cl−, but it mally ranges between 800 and 1500 ml, as shown by the may also result partly from an active secretory process. average value of 1000 ml in Table 65-1. The net result of these transport processes is that under Saliva contains two major types of protein secretion: resting conditions, the concentrations of Na+ and Cl− in (1) a serous secretion that contains ptyalin (an α-amylase), saliva are only about 15 mEq/L each, about one-seventh which is an enzyme for digesting starches, and (2) mucus to one-tenth their concentrations in plasma. Conversely, 809 UNIT XII Gastrointestinal Physiology K+ concentration is about 30 mEq/L, seven times as great Superior and inferior salivatory nuclei as in plasma, and HCO3− concentration is 50 to 70 mEq/L, Tractus Submandibular about two to three times that of plasma. solitarius gland Submandibular During maximal salivation, the salivary ionic concentra- ganglion tions change considerably because the formation rate of pri- mary secretion by the acini can increase as much as 20-fold. Facial This acinar secretion then flows through the ducts so rapidly nerve that the ductal reconditioning of the secretion is consider- Chorda ably reduced. Therefore, when copious quantities of saliva tympani Sublingual are being secreted, the sodium chloride concentration is gland about one-half or two-thirds that of plasma, and potassium concentration rises to only four times that of plasma.␣ Parotid gland Function of Saliva for Oral Hygiene. Under basal awake Glossopharyngeal Otic ganglion conditions, about 0.5 ml of saliva, almost entirely of the mu- nerve cous type, is secreted each minute; however, during sleep, little secretion occurs. This secretion plays an exceedingly important role for maintaining healthy oral tissues. The mouth is loaded with pathogenic bacteria that can easily Tongue Taste stimuli destroy tissues and cause dental caries. Saliva helps prevent the deteriorative processes in several ways: Figure 65-3. Parasympathetic nervous regulation of salivary secretion. 1. The flow of saliva helps wash away pathogenic bacte- ria, as well as food particles that provide their metabolic support. when a person smells or eats favorite foods, salivation 2. Saliva contains several factors that destroy bacteria. is greater than when food that is disliked is smelled or One of these is thiocyanate ions and another is several eaten. The appetite area of the brain, which partially proteolytic enzymes—most important, lysozyme—that regulates these effects, is located in proximity to the (a) attack the bacteria, (b) aid thiocyanate ions in enter- parasympathetic centers of the anterior hypothalamus, ing the bacteria where these ions in turn become bacte- and it functions to a great extent in response to signals ricidal, and (c) digest food particles, thus helping further from the taste and smell areas of the cerebral cortex or to remove the bacterial metabolic support. amygdala. 3. Saliva often contains significant amounts of antibodies Salivation also occurs in response to reflexes origi- that can destroy oral bacteria, including some that cause nating in the stomach and upper small intestines—par- dental caries. In the absence of salivation, oral tissues often become ulcerated and otherwise infected, and ticularly when irritating foods are swallowed or when a caries of the teeth can become rampant.␣ person is nauseated because of some gastrointestinal abnormality. The saliva, when swallowed, helps to remove the irritating factor in the gastrointestinal tract by diluting NERVOUS REGULATION OF SALIVARY or neutralizing the irritant substances. SECRETION Sympathetic stimulation can also increase salivation Figure 65-3 shows the parasympathetic nervous path- a slight amount—much less so than parasympathetic ways for regulating salivation and demonstrates that the stimulation. Also, the saliva formed in response to sym- salivary glands are controlled mainly by parasympathetic pathetic activity is thicker compared to saliva produced nervous signals all the way from the superior and inferior during increased parasympathetic activity. The sympa- salivatory nuclei in the brain stem. thetic nerves originate from the superior cervical ganglia The salivatory nuclei are located approximately at and travel along the surfaces of the blood vessel walls to the juncture of the medulla and pons and are excited the salivary glands. by both taste and tactile stimuli from the tongue and A secondary factor that also affects salivary secre- other areas of the mouth and pharynx. Many taste tion is the blood supply to the glands because secretion stimuli, especially the sour taste (caused by acids), always requires adequate nutrients from the blood. The elicit copious secretion of saliva—often 8 to 20 times parasympathetic nerve signals that induce copious saliva- the basal rate of secretion. Also, certain tactile stimuli, tion also moderately dilate the blood vessels. In addition, such as the presence of smooth objects in the mouth salivation directly dilates the blood vessels, thus provid- (e.g., a pebble), cause marked salivation, whereas rough ing increased salivatory gland nutrition as needed by the objects cause less salivation and occasionally even secreting cells. Part of this additional vasodilator effect inhibit salivation. is caused by kallikrein secreted by the activated salivary Salivation can also be stimulated or inhibited by ner- cells, which in turn acts as an enzyme to split one of the vous signals arriving in the salivatory nuclei from higher blood proteins, an α2-globulin, to form bradykinin, a centers of the central nervous system. For example, strong vasodilator. 810  Chapter 65 Secretory Functions of the Alimentary Tract Esophageal Secretion Gastric pit Esophageal secretions are entirely mucous and mainly pro- Mucus layer vide lubrication for swallowing. The main body of the es- ophagus is lined with many simple mucous glands. At the gastric end and to a lesser extent in the initial portion of UNIT XII the esophagus, many compound mucous glands can also be found. The mucus secreted by the compound glands in the Surface upper esophagus prevents mucosal excoriation by newly epithelium entering food, whereas the compound glands located near the esophagogastric junction protect the esophageal wall from digestion by acidic gastric juices that often reflux from the stomach back into the lower esophagus. Despite Mucous this protection, a peptic ulcer at times can still occur at the neck cells gastric end of the esophagus.␣ Oxyntic GASTRIC SECRETION (parietal) cells In addition to mucus-secreting cells that line the entire surface of the stomach, the stomach mucosa has two ECL cell important types of tubular glands—oxyntic glands (also called gastric glands) and pyloric glands. The oxyntic (acid-forming) glands secrete hydrochloric acid, pepsino- gen, intrinsic factor, and mucus. The pyloric glands secrete Peptic mainly mucus for protection of the pyloric mucosa from (chief) cells the stomach acid. They also secrete the hormone gastrin. The oxyntic glands are located on the inside surfaces of the body and fundus of the stomach—the proximal 80% of the stomach. The pyloric glands are located in the antral portion of the stomach—the distal 20% of the stomach. Figure 65-4. Gastric (oxyntic) gland from the body of the stomach. ECL, Enterochromaffin-like cells. Secretions From the Gastric (Oxyntic) Glands A typical stomach oxyntic gland is shown in Figure 65-4. It is composed of three main types of cells: (1) mucous Mucous neck cells, which secrete mainly mucus; (2) peptic (or chief) neck cells cells, which secrete large quantities of pepsinogen; and (3) parietal (or oxyntic) cells, which secrete hydrochloric acid and intrinsic factor. Oxyntic glands also contain some additional cells types, including the enterochromaffin-like (ECL) cells that secrete histamine. Oxyntic Secretion of hydrochloric acid by the parietal cells (parietal) cell Secretion involves special mechanisms, as follows. Basic Mechanism of Hydrochloric Acid Secretion. Canaliculi When stimulated, the parietal cells secrete an acid so- lution that contains about 160 mmol/L of hydrochloric acid, which is nearly isotonic with the body fluids. The pH of this acid is about 0.8, demonstrating its extreme acid- ity. At this pH, the H+ concentration is about 3 million times that of the arterial blood. To concentrate the H+ this tremendous amount requires more than 1500 calories of Figure 65-5. Schematic anatomy of the canaliculi in a parietal (ox- energy/L of gastric juice. At the same time that H+ is se- yntic) cell. creted, HCO3− diffuses into the blood so that gastric ve- nous blood has a higher pH than arterial blood when the stomach is secreting acid. canaliculi. The hydrochloric acid is formed at the villus- Figure 65-5 shows schematically the functional struc- like projections inside these canaliculi and is then con- ture of a parietal cell (also called an oxyntic cell), dem- ducted through the canaliculi to the secretory end of the onstrating that it contains large branching intracellular cell. 811 UNIT XII Gastrointestinal Physiology Interstitial Parietal cell Lumen of Thus, the final secretion from the canaliculus con- fluid canaliculus tains water, hydrochloric acid at a concentration of about 150 to 160 mEq/L, potassium chloride at a CO2 CO2 concentration of 15 mEq/L, and a small amount of sodium chloride. HCO3– HCO3– CO2 + To produce a concentration of H+ as great as that H+ (155 mEq/L) OH– + H+ Cl– Cl– found in gastric juice requires minimal backleak into the ATP mucosa of the secreted acid. A major part of the stomach's H2O ability to prevent backleak of acid can be attributed to the K+ K+ K+ K+ (15 mEq/L) gastric barrier due to the formation of alkaline mucus and ATP to tight junctions between epithelia cells, as described later. If this barrier is damaged by toxic substances, such Na+ Na+ Na+ (3 mEq/L) as occurs with excessive use of aspirin or alcohol, the secreted acid does leak down an electrochemical gradient Cl– Cl– Cl– Cl– (173 mEq/L) into the mucosa, causing stomach mucosal damage.␣ (Osmosis) H2O H2O The Basic Factors That Stimulate Gastric Secretion Are Acetylcholine, Gastrin, and Histamine. Acetylcho- line released by parasympathetic stimulation excites se- Figure 65-6. Postulated mechanism for secretion of hydrochloric cretion of pepsinogen by peptic cells, hydrochloric acid by acid. (The points labeled “ATP” [adenosine triphosphate] indicate active pumps, and the dashed lines represent free diffusion and parietal cells, and mucus by mucous cells. In comparison, osmosis.) both gastrin and histamine strongly stimulate acid secre- tion by parietal cells but have little effect on the other cells.␣ The main driving force for hydrochloric acid secretion Secretion and Activation of Pepsinogen. Several by the parietal cells is a hydrogen-potassium pump (H+-K+ slightly different types of pepsinogen are secreted by the adenosine triphosphatase [ATPase]). The chemical mech- peptic and mucous cells of the gastric glands, but all the anism of hydrochloric acid formation is shown in Figure pepsinogens perform the same basic functions. 65-6 and consists of the following steps: When pepsinogen is first secreted, it has no digestive 1. Water inside the parietal cell becomes dissociated activity. However, as soon as it comes in contact with into H+ and hydroxide (OH−) in the cell cytoplasm. hydrochloric acid, it is activated to form active pepsin. In The H+ is then actively secreted into the canaliculus this process, the pepsinogen molecule, having a molecu- in exchange for K+, an active exchange process that lar weight of about 42,500, is split to form a pepsin mol- is catalyzed by H+-K+ ATPase. Potassium ions trans- ecule, having a molecular weight of about 35,000. ported into the cell by the Na+-K+ ATPase pump on Pepsin functions as an active proteolytic enzyme in a the basolateral (extracellular) side of the membrane highly acidic medium (optimum pH, 1.8–3.5), but above tend to leak into the lumen but are recycled back a pH of about 5 it has almost no proteolytic activity and into the cell by the H+-K+ ATPase. The basolateral becomes completely inactivated in a short time. Hydro- Na+-K+ ATPase creates low intracellular Na+, which chloric acid is as necessary as pepsin for protein digestion contributes to Na+ reabsorption from the lumen of in the stomach, as discussed in Chapter 66.␣ the canaliculus. Thus, most of the K+ and Na+ in the Secretion of Intrinsic Factor by Parietal Cells. The canaliculus is reabsorbed into the cell cytoplasm, substance intrinsic factor, which is essential for vitamin and H+ takes their place in the canaliculus. B12 absorption in the ileum, is secreted by the parietal 2. The pumping of H+ out of the cell by the H+-K+ AT- cells along with the secretion of hydrochloric acid. When Pase permits OH− to accumulate and form HCO3− the acid-producing parietal cells of the stomach are de- from CO2, either formed during metabolism in the stroyed, which frequently occurs in persons with chronic cell or while entering the cell from the blood. This gastritis, not only does achlorhydria (lack of stomach acid reaction is catalyzed by carbonic anhydrase. The secretion) develop, but pernicious anemia also often de- HCO3− is then transported across the basolateral velops because of failure of red blood cell maturation in membrane into the extracellular fluid in exchange the absence of vitamin B12 stimulation of the bone mar- for Cl− ions, which enter the cell and are secreted row. This condition is discussed in Chapter 33.␣ through chloride channels into the canaliculus, giv- ing a strong solution of hydrochloric acid in the PYLORIC GLANDS SECRETE MUCUS AND canaliculus. The hydrochloric acid is then secreted GASTRIN outward through the open end of the canaliculus into the lumen of the gland. The pyloric glands are structurally similar to the oxyntic 3. Water passes into the canaliculus by osmosis be- glands but contain few peptic cells and almost no pari- cause of extra ions secreted into the canaliculus. etal cells. Instead, they contain mostly mucous cells that 812  Chapter 65 Secretory Functions of the Alimentary Tract are identical with the mucous neck cells of the oxyntic end of the stomach. Gastrin is a large polypeptide se- glands. These cells secrete a small amount of pepsinogen, creted in two forms—a large form called G-34, which as discussed earlier, and an especially large amount of thin contains 34 amino acids, and a smaller form, G-17, which mucus that helps to lubricate food movement, as well as contains 17 amino acids. Although both of these forms to protect the stomach wall from digestion by the gastric are important, the smaller form is more abundant. UNIT XII enzymes. The pyloric glands also secrete the hormone When meats or other foods containing protein reach gastrin, which plays a key role in controlling gastric secre- the antral end of the stomach, some of the proteins from tion, as we discuss shortly.␣ these foods have a special stimulatory effect on the gas- trin cells in the pyloric glands to cause release of gastrin SURFACE MUCOUS CELLS into the blood to be transported to the ECL cells of the The entire surface of the stomach mucosa between glands stomach. The vigorous mixing of the gastric juices trans- has a continuous layer of a special type of mucous cells ports the gastrin rapidly to the ECL cells in the body of called simply “surface mucous cells.” They secrete large the stomach, causing release of histamine directly into the quantities of viscid mucus that coats the stomach mucosa deep oxyntic glands. The histamine then acts quickly to with a gel layer of mucus often more than 1 millimeter stimulate gastric hydrochloric acid secretion.␣ thick, thus providing a major shell of protection for the REGULATION OF PEPSINOGEN SECRETION stomach wall, as well as contributing to lubrication of food transport. Stimulation of pepsinogen secretion by the peptic cells in Another characteristic of this mucus is that it is alka- the oxyntic glands occurs in response to two main types line. Therefore, the normal underlying stomach wall is not of signals: (1) acetylcholine released from the vagus nerves directly exposed to the highly acidic, proteolytic stomach or from the gastric enteric nervous plexus, and (2) acid secretion. Even the slightest contact with food or any in the stomach. The acid probably does not stimulate the irritation of the mucosa directly stimulates the surface peptic cells directly but instead elicits additional enteric mucous cells to secrete additional quantities of this thick, nervous reflexes that support the original nervous signals alkaline, viscid mucus.␣ to the peptic cells. Therefore, the rate of secretion of pep- sinogen, the precursor of the enzyme pepsin that causes protein digestion, is strongly influenced by the amount of STIMULATION OF GASTRIC ACID acid in the stomach. In people who have lost the ability to SECRETION secrete normal amounts of acid, secretion of pepsinogen Parietal Cells of the Oxyntic Glands Are the Only is also decreased, even though the peptic cells may other- Cells That Secrete Hydrochloric Acid. As noted earlier wise appear to be normal. in the chapter, the acidity of the fluid secreted by the pa- rietal cells of the oxyntic glands can be great, with pH as Phases of Gastric Secretion low as 0.8. However, secretion of this acid is under con- Gastric secretion is said to occur in three “phases” (as tinuous control by both endocrine and nervous signals. shown in Figure 65-7): a cephalic phase, a gastric phase, Furthermore, parietal cells operate in close association and an intestinal phase. with another type of cell called enterochromaffin-like cells Cephalic Phase. The cephalic phase of gastric secre- (ECL cells), the primary function of which is to secrete tion occurs even before food enters the stomach, especial- histamine. ly while it is being eaten. It results from the sight, smell, The ECL cells lie in the deep recesses of the oxyntic thought, or taste of food, and the greater the appetite, the glands and therefore release histamine in direct contact more intense is the stimulation. Neurogenic signals that with the parietal cells of the glands. The formation and cause the cephalic phase of gastric secretion originate in the cerebral cortex and in the appetite centers of the amyg- secretion rates of hydrochloric acid by the parietal cells dala and hypothalamus. They are transmitted through the are directly related to the amount of histamine secreted dorsal motor nuclei of the vagi and thence through the va- by the ECL cells. In turn, the ECL cells are stimulated gus nerves to the stomach. This phase of secretion normally to secrete histamine by the hormone gastrin, which is accounts for about 30% of the gastric secretion associated formed almost entirely in the antral portion of the stom- with eating a meal.␣ ach mucosa in response to proteins in the foods being Gastric Phase. Once food enters the stomach, it ex- digested. The ECL cells may also be stimulated by hor- cites the following: (1) long vagovagal reflexes from the mones secreted by the enteric nervous system of the stomach to the brain and back to the stomach; (2) lo- stomach wall. We will first discuss the gastrin mechanism cal enteric reflexes; and (3) the gastrin mechanism, all for control of the ECL cells and their subsequent control of which cause secretion of gastric juice during several of parietal cell secretion of hydrochloric acid.␣ hours while food remains in the stomach. The gastric phase of secretion accounts for about 60% of the to- Stimulation of Acid Secretion by Gastrin. Gastrin is tal gastric secretion associated with eating a meal and a hormone secreted by gastrin cells, also called G cells. therefore accounts for most of the total daily gastric se- These cells are located in the pyloric glands in the distal cretion of about 1500 ml.␣ 813 UNIT XII Gastrointestinal Physiology Vagal center of medulla Cephalic phase via vagus Parasympathetics excite pepsin and acid production Food Secretory fiber Gastric phase: 1. Local nervous Afferent Vagus Local nerve secretory reflexes fibers trunk plexus 2. Vagal reflexes 3. Gastrin-histamine stimulation Circulatory system Gastrin Intestinal phase: 1. Nervous mechanisms Figure 65-7. Phases of gastric se- 2. Hormonal mechanisms cretion and their regulation. Small bowel Intestinal Phase. The presence of food in the upper por- inhibitory hormones usually also reduce stomach motility tion of the small intestine, particularly in the duodenum, at the same time that they reduce gastric secretion, as dis- will continue to cause stomach secretion of small amounts cussed in Chapter 64. of gastric juice, probably partly because of small amounts Gastric Secretion During the Interdigestive Period. The of gastrin released by the duodenal mucosa. This secretion stomach secretes a few milliliters of gastric juice each hour accounts for about 10% of the acid response to a meal.␣ during the “interdigestive period,” when little or no digestion is occurring anywhere in the gut. The secretion that does Inhibition of Gastric Secretion by Other Intestinal Factors occur is usually almost entirely of the nonoxyntic type, com- Although intestinal chyme slightly stimulates gastric secre- posed mainly of mucus but little pepsin and almost no acid. tion during the early intestinal phase of stomach secretion, Emotional stimuli may increase interdigestive gastric it paradoxically inhibits gastric secretion at other times. secretion (which is highly peptic and acidic) to 50 ml or This inhibition results from at least two influences. more per hour, in much the same way that the cephalic 1. The presence of food in the small intestine initiates a phase of gastric secretion excites secretion at the onset of reverse enterogastric reflex, transmitted through the my- a meal. This increase of secretion in response to emotional enteric nervous system and extrinsic sympathetic and stimuli may contribute to the development of peptic ulcers, vagus nerves, that inhibits stomach secretion. This re- as discussed in Chapter 67.␣ flex can be initiated by (a) distending the small bowel, (b) the presence of acid in the upper intestine, (c) the Chemical Composition of Gastrin and Other Gastroin- testinal Hormones presence of protein breakdown products, or (d) irrita- tion of the mucosa. This reflex is part of the complex Gastrin, cholecystokinin (CCK), and secretin are all large poly- mechanism discussed in Chapter 64 for slowing stom- peptides with approximate molecular weights of 2000, 4200, ach emptying when the intestines are already filled. and 3400, respectively. The terminal five amino acids in the 2. The presence of acid, fat, protein breakdown products, gastrin and CCK molecular chains are the same. The function- hyperosmotic or hypo-osmotic fluids, or any irritat- al activity of gastrin resides in the terminal four amino acids, ing factor in the upper small intestine causes release of and the activity for CCK resides in the terminal eight amino several intestinal hormones. One of these hormones is acids. All the amino acids in the secretin molecule are essential. secretin, which is especially important for control of pan- A synthetic gastrin, pentagastrin, is composed of the creatic secretion. However, secretin opposes stomach se- terminal four amino acids of natural gastrin plus the amino cretion. Three other hormones—glucose-dependent insu- acid alanine, has all the same physiological properties as the linotropic peptide (gastric inhibitory peptide), vasoactive natural gastrin.␣ intestinal polypeptide, and somatostatin—also have slight to moderate effects in inhibiting gastric secretion. The purpose of intestinal factors that inhibit gastric se- PANCREATIC SECRETION cretion is presumably to slow passage of chyme from the The pancreas, which lies parallel to and beneath the stom- stomach when the small intestine is already filled or already ach (illustrated in Figure 65-10), is a large compound overactive. In fact, the enterogastric inhibitory reflexes plus 814  Chapter 65 Secretory Functions of the Alimentary Tract gland, and most of its internal structure is similar to that contact with the mucosa. Trypsinogen also can be auto- of the salivary glands shown in Figure 65-2. The pancre- catalytically activated by trypsin that has already been atic digestive enzymes are secreted by pancreatic acini, formed from previously secreted trypsinogen. Chymo- and large volumes of sodium bicarbonate solution are trypsinogen is activated by trypsin to form chymotryp- secreted by the small ductules and larger ducts leading sin, and procarboxypolypeptidase is activated in a similar UNIT XII from the acini. The combined product of enzymes and manner. sodium bicarbonate then flows through a long pancreatic Secretion of Trypsin Inhibitor Prevents Digestion of duct that normally joins the hepatic duct immediately the Pancreas. It is important that the proteolytic en- before it empties into the duodenum through the papilla zymes of the pancreatic juice not become activated until of Vater, surrounded by the sphincter of Oddi. after they have been secreted into the intestine because Pancreatic juice is secreted most abundantly in the trypsin and the other enzymes would digest the pan- response to the presence of chyme in the upper portions creas. Fortunately, the same cells that secrete proteolytic of the small intestine, and the characteristics of pancre- enzymes into the acini of the pancreas simultaneously se- atic juice are determined to some extent by the types of crete another substance called trypsin inhibitor. This sub- food in the chyme. The pancreas also secretes insulin, stance, which is formed in the cytoplasm of the glandular but it is not secreted by the same pancreatic tissue that cells, prevents activation of trypsin inside the secretory secretes intestinal pancreatic juice. Instead, insulin is cells and in the acini and ducts of the pancreas. In addi- secreted directly into the blood—not into the intestine— tion, because it is trypsin that activates the other pancre- by the islets of Langerhans that occur in islet patches atic proteolytic enzymes, trypsin inhibitor prevents acti- throughout the pancreas. These structures are discussed vation of the other enzymes as well. in Chapter 79. When the pancreas becomes severely damaged or when a duct becomes blocked, large quantities of pancre- PANCREATIC DIGESTIVE ENZYMES atic secretion sometimes become pooled in the damaged areas of the pancreas. Under these conditions, the effect Pancreatic secretion contains multiple enzymes for of trypsin inhibitor is often overwhelmed, in which case digesting all of the three major types of food—proteins, the pancreatic secretions rapidly become activated and carbohydrates, and fats. It also contains large quantities of can literally digest the entire pancreas within a few hours, HCO3−, which play an important role in neutralizing the giving rise to the condition called acute pancreatitis. This acidity of the chyme emptied from the stomach into the condition is sometimes lethal because of accompanying duodenum. circulatory shock; even if it is not lethal, it usually leads to The most important of the pancreatic enzymes for a lifetime of pancreatic insufficiency.␣ digesting proteins are trypsin, chymotrypsin, and car- boxypolypeptidase. By far the most abundant of these is SECRETION OF BICARBONATE IONS trypsin. Trypsin and chymotrypsin split whole and partially Although the enzymes of the pancreatic juice are secreted digested proteins into peptides of various sizes but do not entirely by the acini of the pancreatic glands, the other cause release of individual amino acids. However, car- two important components of pancreatic juice, HCO3− boxypolypeptidase splits some peptides into individual and water, are secreted mainly by the epithelial cells of amino acids, thus completing digestion of some proteins the ductules and ducts that lead from the acini. When all the way to the amino acid state. the pancreas is stimulated to secrete copious quantities The pancreatic enzyme for digesting carbohydrates is of pancreatic juice, the HCO3− concentration can rise pancreatic amylase, which hydrolyzes starches, glycogen, to as high as 145 mEq/L, a value about five times that of and most other carbohydrates (except cellulose) to form HCO3− in the plasma. This high concentration provides a mostly disaccharides and a few trisaccharides. large quantity of alkali in the pancreatic juice that serves The main enzymes for fat digestion are the follow- to neutralize the hydrochloric acid emptied into the duo- ing: (1) pancreatic lipase, which is capable of hydrolyzing denum from the stomach. neutral fat into fatty acids and monoglycerides; (2) cho- The basic steps in the cellular mechanism for secreting lesterol esterase, which causes hydrolysis of cholesterol sodium bicarbonate solution into the pancreatic ductules esters; and (3) phospholipase, which splits fatty acids from and ducts, shown in Figure 65-8, are as follows: phospholipids. 1. Carbon dioxide diffuses to the interior of the cell When first synthesized in the pancreatic cells, the from the blood and, under the influence of carbonic proteolytic digestive enzymes are in their enzymatically anhydrase, combines with water to form carbonic inactive forms—trypsinogen, chymotrypsinogen, and pro- acid (H2CO3). The carbonic acid dissociates into carboxypolypeptidase. They become activated only after HCO3− and H+. Additional HCO3− enters the cell they are secreted into the intestinal tract. Trypsinogen through the basolateral membrane by co-transport is activated by an enzyme called enterokinase, which is with Na+. The HCO3− is then exchanged for Cl− by secreted by the intestinal mucosa when chyme comes in secondary active transport through the luminal 815 UNIT XII Gastrointestinal Physiology Blood Interstitial Pancreatic duct cell Lumen 3. Secretin, which is also secreted by the duodenal and fluid jejunal mucosa when highly acidic food enters the small intestine Na+ Na+ Cl– Cl– The first two of these stimuli, acetylcholine and CCK, HCO3– HCO3– stimulate the acinar cells of the pancreas, causing produc- H2O Cl– Cl– tion of large quantities of pancreatic digestive enzymes but CO2 CA HCO3– HCO3– relatively small quantities of water and electrolytes to go + with the enzymes. Without the water, most of the enzymes H+ H+ remain temporarily stored in the acini and ducts until more Na+ Na+ fluid secretion comes along to wash them into the duode- num. Secretin, in contrast to the first two basic stimuli, Na+ stimulates secretion of large quantities of water solution of ATP sodium bicarbonate by the pancreatic ductal epithelium. K+ K+ Multiplicative Effects of Different Stimuli. When all the different stimuli of pancreatic secretion occur at once, K+ K+ the total secretion is far greater than the sum of the se- cretions caused by each one separately. Therefore, the Na+, H2O Na+, H2O various stimuli are said to “multiply,” or “potentiate,” one another. Thus, pancreatic secretion normally results from the combined effects of the multiple basic stimuli, not Figure 65-8. Secretion of isosmotic sodium bicarbonate solution by the pancreatic ductules and ducts. ATP, Adenosine triphosphate; CA, from one alone.␣ carbonic anhydrase. Phases of Pancreatic Secretion Pancreatic secretion, as with gastric secretion, occurs in border of the cell into the lumen of the duct. The three phases: the cephalic phase, the gastric phase, and Cl− that enters the cell is recycled back into the lu- the intestinal phase. Their characteristics are described in men by special chloride channels. the following sections. 2. The H+ formed by dissociation of carbonic acid in- side the cell is exchanged for Na+ through the baso- Cephalic and Gastric Phases. During the cephalic phase lateral membrane of the cell by secondary active of pancreatic secretion, the same nervous signals from transport. Sodium ions also enter the cell by co- the brain that cause secretion in the stomach also cause transport with HCO3− across the basolateral mem- acetylcholine release by the vagal nerve endings in the brane. Sodium ions are then transported across the pancreas. This signaling causes moderate amounts of en- luminal border into the pancreatic duct lumen. The zymes to be secreted into the pancreatic acini, accounting negative voltage of the lumen also pulls the positive- for about 20% of the total secretion of pancreatic enzymes ly charged Na+ across the tight junctions between after a meal. However, little of the secretion flows im- the cells. mediately through the pancreatic ducts into the intestine 3. The overall movement of Na + and HCO 3− from because only small amounts of water and electrolytes are the blood into the duct lumen creates an os- secreted along with the enzymes. motic pressure gradient that causes osmosis of During the gastric phase, the nervous stimulation of water also into the pancreatic duct, thus form- enzyme secretion continues, accounting for another ing an almost completely isosmotic bicarbonate 5% to 10% of pancreatic enzymes secreted after a meal. solution.␣ However, again, only small amounts reach the duodenum because of continued lack of significant fluid secretion.␣ REGULATION OF PANCREATIC SECRETION Intestinal Phase. After chyme leaves the stomach and Basic Stimuli That Cause Pancreatic enters the small intestine, pancreatic secretion becomes Secretion copious, mainly in response to the hormone secretin.␣ Three basic stimuli are important in causing pancreatic Secretin Stimulates Copious Secretion of Bicarbonate secretion: Ions, Which Neutralizes Acidic Stomach Chyme. Se- 1. Acetylcholine, which is released from the parasym- cretin is a polypeptide containing 27 amino acids (with pathetic vagus nerve endings and from other cho- a molecular weight of ≈3400). It is present in an inactive linergic nerves in the enteric nervous system form, prosecretin, in the S cells in the mucosa of the duo- 2. Cholecystokinin (CCK), which is secreted by the du- denum and jejunum. When acid chyme with a pH less odenal and upper jejunal mucosa when food enters than 4.5 to 5.0 enters the duodenum from the stomach, it the small intestine causes duodenal mucosal release and activation of secre- 816  Chapter 65 Secretory Functions of the Alimentary Tract tin, which is then absorbed into the blood. The one truly Water and potent constituent of chyme that causes secretin release is NaHCO3 hydrochloric acid from the stomach. Enzymes Secretin in turn causes the pancreas to secrete large Rate of pancreatic secretion quantities of fluid containing a high concentration of UNIT XII HCO3− (up to 145 mEq/L) but a low concentration of Cl−. The secretin mechanism is especially important for two reasons. First, secretin begins to be released from the mucosa of the small intestine when the pH of the duode- nal contents falls below 4.5 to 5.0, and its release increases greatly as the pH falls to 3.0. This mechanism immediately causes copious secretion of pancreatic juice that contains abundant amounts of sodium bicarbonate. The net result is then the following reaction in the duodenum: HCI Soap Peptone HCl + NaHCO3 → NaCl + H2 CO3 Figure 65-9. Sodium bicarbonate (NaHCO3), water, and enzyme se- The carbonic acid then immediately dissociates into cretion by the pancreas, caused by the presence of acid (HCl), fat CO2 and water. The CO2 is absorbed into the blood and (soap), or peptone solutions in the duodenum. expired through the lungs, thus leaving a neutral solu- tion of sodium chloride in the duodenum. In this way, the acid contents that are emptied into the duodenum from Acid from stomach releases secretin from the stomach become neutralized, and thus further peptic wall of duodenum; digestive activity by the gastric juices in the duodenum fats and amino acids is immediately blocked. Because the mucosa of the small cause release of cholecystokinin intestine cannot withstand the digestive action of acid Common gastric juice, this protective mechanism is essential to bile duct prevent the development of duodenal ulcers, as discussed in Chapter 67. Bicarbonate ion secretion by the pancreas provides Vagal an appropriate pH for action of the pancreatic digestive stimulation releases enzymes, which function optimally in a slightly alkaline enzymes or neutral medium, at a pH of 7.0 to 8.0. Fortunately, into acini the pH of the sodium bicarbonate secretion averages 8.0.␣ Secretin causes copious secretion Cholecystokinin Contributes to Control of Diges- of pancreatic fluid tive Enzyme Secretion by the Pancreas. The presence and bicarbonate; of food in the upper small intestine also causes a second cholecystokinin Secretin and cholecystokinin causes secretion hormone, CCK, a polypeptide containing 33 amino ac- absorbed into blood stream of enzymes ids, to be released from yet another group of cells, the I cells, in the mucosa of the duodenum and upper jejunum. Figure 65-10. Regulation of pancreatic secretion. This release of CCK results especially from the presence of proteoses and peptones (products of partial protein di- to soap (a fat); and (3) intense digestive enzyme secre- gestion) and long-chain fatty acids in the chyme coming tion (when peptones enter the duodenum) stimulated by from the stomach. CCK. CCK, like secretin, passes via the blood to the pan- Figure 65-10 summarizes the more important fac- creas, but instead of causing sodium bicarbonate secre- tors that regulate pancreatic secretion. The total amount tion, it mainly causes secretion of much more pancreatic secreted each day is about 1 liter.␣ digestive enzymes by the acinar cells. This effect is similar to that caused by vagal stimulation but is even more pro- BILE SECRETION BY THE LIVER nounced, accounting for 70% to 80% of the total secretion of the pancreatic digestive enzymes after a meal. One of the many functions of the liver is to secrete bile, The differences between the pancreatic stimulatory normally between 600 and 1000 ml/day. Bile serves two effects of secretin and CCK are shown in Figure 65-9, important functions. which demonstrates the following: (1) intense sodium First, bile plays an important role in fat digestion and bicarbonate secretion in response to acid in the duode- absorption, not because of any enzymes in the bile that num, stimulated by secretin; (2) a dual effect in response cause fat digestion, but because bile acids perform two 817 UNIT XII Gastrointestinal Physiology Bile acids via blood stimulate Vagal stimulation causes weak parenchymal secretion contraction of gallbladder Liver Stomach Secretin via blood stream stimulates liver ductal secretion Acid Bile stored and concentrated up to 15 times in gallbladder Pancreas Sphincter Duodenum of Oddi Cholecystokinin via blood stream causes: 1. Gallbladder contraction Figure 65-11. Liver secretion and gall- 2. Relaxation of sphincter of Oddi bladder emptying. functions: (1) they help emulsify large fat particles of the by epithelial cells that line the ductules and ducts. This food into many minute particles, the surface of which can second secretion sometimes increases the total quantity then be attacked by lipase enzymes secreted in pancreatic of bile by as much as 100%. The second secretion is stimu- juice, and (2) they aid in absorption of digested fat end lated especially by secretin, which causes release of addi- products through the intestinal mucosal membrane. tional quantities of HCO3− to supplement the HCO3− in Second, bile serves as a means for excretion of several pancreatic secretion (for neutralizing acid that empties important waste products from the blood. These waste into the duodenum from the stomach). products include in particular bilirubin, an end product of The Gallbladder Stores and Concentrates Bile. Bile is hemoglobin destruction, and excesses of cholesterol. secreted continually by the liver cells, but most of it is PHYSIOLOGIC ANATOMY OF BILIARY normally stored in the gallbladder until it is needed in the SECRETION duodenum. The maximum volume that the gallbladder can hold is only 30 to 60 ml. Nevertheless, as much as 12 Bile is secreted in two stages by the liver: hours of bile secretion (usually ≈450 ml) can be stored in 1. The initial portion is secreted by the principal func- the gallbladder because water, sodium, chloride, and most tional cells of the liver, the hepatocytes.This initial other small electrolytes are continually absorbed through secretion contains large amounts of bile acids, the gallbladder mucosa, concentrating the remaining bile cholesterol, and other organic constituents. It is constituents that contain the bile salts, cholesterol, leci- secreted into minute bile canaliculi that originate thin, and bilirubin. between the hepatic cells (see Figure 71-1). Most of this gallbladder absorption is caused by active 2. Next, the bile flows in the canaliculi toward the in- transport of sodium through the gallbladder epithelium, terlobular septa, where the canaliculi empty into and this transport is followed by secondary absorption of terminal bile ducts and then into progressively Cl−, water, and most other diffusible constituents. Bile is larger ducts, finally reaching the hepatic duct and normally concentrated in this way about 5-fold, but it can common bile duct. From these ducts the bile either be concentrated up to a maximum of 20-fold.␣ empties directly into the duodenum or is diverted for minutes up to several hours through the cystic Composition of Bile. Table 65-2 lists the composition of duct into the gallbladder, shown in Figure 65-11. bile when it is first secreted by the liver and then after it has In its course through the bile ducts, a second portion of been concentrated in the gallbladder. By far the most abun- liver secretion is added to the initial bile. This additional dant substances secreted in the bile are bile salts, which ac- secretion is a watery solution of Na+ and HCO3− secreted count for about one-half of the total solutes also in the bile. 818