Ebook Ganong''s review of medical physiology (25th edition): Part 2

(BQ) Part 2 book Ganong''s review of medical physiology presents the following contents: Gastrointestinal physiology, respiratory physiology, cardiovascular physiology, renal physiology. Invite you to consult.

SECTION IV Gastrointestinal Physiology For unicellular organisms that exist in a sea of nutrients, it is possible to satisfy nutritional requirements simply with the activity of membrane transport proteins that permit the uptake of specific molecules into the cytosol However, for multicellular organisms, including humans, the challenges of delivering nutrients to appropriate sites in the body are significantly greater, particularly if the organisms are terrestrial Further, most of the food we eat is in the form of macromolecules, and even when these are digested to their component monomers, most of the end products are water-soluble and not readily cross cell membranes (a notable exception are the constituents of dietary lipids) Thus, the gastrointestinal system has evolved to permit nutrient acquisition and assimilation into the body, while prohibiting the uptake of undesirable substances (toxins and microbial products, as well as microbes themselves) The latter situation is complicated by the fact that the intestine maintains a lifelong relationship with a rich microbial ecosystem residing in its lumen, a relationship that is largely mutually beneficial if the microbes are excluded from the systemic compartment The intestine is a continuous tube that extends from mouth to anus and is formally contiguous with the external environment A single cell layer of columnar epithelial cells comprises the semipermeable barrier across which controlled uptake of nutrients takes place Various glandular structures empty into the intestinal lumen at points along its length, providing for digestion of food components, signaling to distal segments, and regulation of the microbiota There are also important motility functions that move the intestinal contents and resulting waste products along the length of the gut, and a rich innervation that regulates motility, secretion and nutrient uptake, in many cases in a manner that is independent of the central nervous system There is also a large number of endocrine cells that release hormones that work together with neurotransmitters to coordinate overall regulation of the gastrointestinal system In general, there is a considerable redundancy of control systems as well as excess capacity for nutrient digestion and uptake This served humans well in ancient times when food sources Barrett_CH25_p451-474.indd 451 were scarce but may now contribute to the modern epidemic of obesity The liver, while playing important roles in whole body metabolism, is usually considered a part of the gastrointestinal system for two main reasons First, it provides for excretion from the body of lipid-soluble waste products that cannot enter the urine These are secreted into the bile and thence into the intestine to be excreted with the feces Second, the blood flow draining the intestine is arranged such that substances that are absorbed pass first through the liver, allowing for the removal and metabolism of any toxins that have inadvertently been taken up, as well as clearance of particulates, such as small numbers of enteric bacteria In this section, the function of the gastrointestinal system and liver will be considered, and the ways in which the various segments communicate to provide an integrated response to a mixed meal (proteins, carbohydrates, and lipids) The relevance of gastrointestinal physiology for the development of digestive diseases will also be considered While many are rarely life-threatening (with some notable exceptions, such as specific cancers) digestive diseases represent a substantial burden in terms of morbidity and lost productivity A 2009 report of the US National Institutes of Diabetes, Digestive and Kidney Diseases found that on an annual basis, for every 100 US residents, there were 35 ambulatory care visits and nearly overnight hospital stays that involved a gastrointestinal diagnosis Digestive diseases also appear to be increasing in this population (although mortality, principally from cancers, is thankfully in decline) On the other hand, digestive diseases, and in particular infectious diarrhea, remain important causes of mortality in developing countries where clean sources of food and water cannot be assured In any event, the burden of digestive diseases provides an important impetus for gaining a full understanding of gastrointestinal physiology, since it is a failure of such physiology that most often leads to disease Conversely, an understanding of specific digestive conditions can often illuminate physiologic principles, as will be stressed in this section 6/27/15 4:34 PM This page intentionally left blank Overview of Gastrointestinal Function & Regulation O B J EC T IVES After studying this chapter, you should be able to: 25 C H A P T E R ■■ Understand the functional significance of the gastrointestinal system, and in ■■ ■■ ■■ ■■ ■■ particular, its roles in nutrient assimilation, excretion, and immunity Describe the structure of the gastrointestinal tract, the glands that drain into it, and its subdivision into functional segments List the major gastrointestinal secretions, their components, and the stimuli that regulate their production Describe water balance in the gastrointestinal tract and explain how the level of luminal fluidity is adjusted to allow for digestion and absorption Identify the major hormones, other peptides, and key neurotransmitters of the gastrointestinal system Describe the special features of the enteric nervous system and the splanchnic circulation INTRODUCTION The primary function of the gastrointestinal tract is to serve as a portal whereby nutrients and water can be absorbed into the body In fulfilling this function, the meal is mixed with a variety of secretions that arise from both the gastrointestinal tract itself and organs that drain into it, such as the pancreas, gallbladder, and salivary glands Likewise, the intestine displays a variety of motility patterns that serve to mix the meal with digestive secretions and move it along the length of the gastrointestinal tract Ultimately, residues of the meal that cannot be absorbed, along with cellular debris, are expelled from the body All of these functions are tightly regulated in concert with the ingestion of meals Thus, the gastrointestinal system has evolved a large number of regulatory mechanisms that act both locally and over long distances to coordinate the function of the gut and the organs that drain into it STRUCTURAL CONSIDERATIONS is functionally divided into segments by means of muscle rings known as sphincters, which restrict the flow of intestinal contents to optimize digestion and absorption These sphincters include the upper and lower esophageal sphincters, the pylorus that retards emptying of the stomach, the ileocecal valve that retains colonic contents (including large numbers of bacteria) in the large intestine, and the inner and outer anal sphincters After toilet training, the latter permits delaying the elimination of wastes until a time when it is socially convenient The intestine is composed of functional layers (Figure 25–1) Immediately adjacent to nutrients in the The parts of the gastrointestinal tract that are encountered by the meal or its residues include, in order, the mouth, esophagus, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, and anus Throughout the length of the intestine, glandular structures deliver secretions into the lumen, particularly in the stomach and mouth Also important in the process of digestion are secretions from the pancreas and the biliary system of the liver The intestine itself also has a very substantial surface area, which is important for its absorptive function The intestinal tract 453 Barrett_CH25_p451-474.indd 453 6/27/15 4:34 PM 454 SECTION IV  Gastrointestinal Physiology Lumen Epithelium Basement membrane Mucosa Lamina propria Muscularis mucosa Submucosa Circular muscle Myenteric plexus Muscularis propria Longitudinal muscle Mesothelium (serosa) FIGURE 25–1  Organization of the wall of the intestine into functional layers (Adapted with permission from Yamada T: Textbook of Gastroenterology, 4th ed New York, NY: Lippincott Williams & Wilkins; 2003.) lumen is a single layer of columnar epithelial cells This represents the barrier that nutrients must traverse to enter the body Below the epithelium is a layer of loose connective tissue known as the lamina propria, which in turn is surrounded by concentric layers of smooth muscle, oriented circumferentially and then longitudinally to the axis of the gut (the circular and longitudinal muscle layers, respectively) The intestine is also amply supplied with blood vessels, nerve endings, and lymphatics, which are all important in its function The epithelium of the intestine is also further specialized in a way that maximizes the surface area available for nutrient absorption Throughout the small intestine, it is folded up into fingerlike projections called villi (Figure 25–2) Between the villi are infoldings known as crypts Stem cells that give rise to both crypt and villus epithelial cells reside toward the base of the crypts and are responsible for completely renewing the epithelium every few days or so Indeed, the gastrointestinal epithelium is one of the most rapidly dividing tissues in the body Daughter cells undergo several rounds of cell division in the crypts then migrate out onto the villi, where they are eventually shed and lost in the stool The villus epithelial cells are also notable for the extensive microvilli that characterize their apical membranes These microvilli are endowed with a dense glycocalyx (the brush border) that probably protects the cells to some extent from the effects of digestive enzymes Some digestive enzymes are also actually part of the brush border, being membrane-bound proteins These so-called “brush border hydrolases” perform the final steps of digestion for specific nutrients Barrett_CH25_p451-474.indd 454 GASTROINTESTINAL SECRETIONS SALIVARY SECRETION The first secretion encountered when food is ingested is saliva Saliva is produced by three pairs of salivary glands (the parotid, submandibular, and sublingual glands) that drain into the oral cavity It has a number of organic constituents that serve to initiate digestion (particularly of starch, mediated by amylase) and which also protect the oral cavity from bacteria (such as immunoglobulin A and lysozyme) Saliva also serves to lubricate the food bolus (aided by mucins) Secretions of the three glands differ in their relative proportion of proteinaceous and mucinous components, which results from the relative number of serous and mucous salivary acinar cells, respectively Saliva is also hypotonic compared with plasma and alkaline; the latter feature is important to neutralize any gastric secretions that reflux into the esophagus The salivary glands consist of blind end pieces (acini) that produce the primary secretion containing the organic constituents dissolved in a fluid that is essentially identical in its composition to plasma The salivary glands are actually extremely active when maximally stimulated, secreting their own weight in saliva every minute To accomplish this, they are richly endowed with surrounding blood vessels that dilate when salivary secretion is initiated The composition of the saliva is then modified as it flows from the acini out into ducts that eventually coalesce and deliver the saliva into the mouth Na+ and Cl− are extracted and K+ and bicarbonate are added Because the ducts are relatively impermeable to water, the loss 6/27/15 4:34 PM CHAPTER 25  Overview of Gastrointestinal Function & Regulation 455 Simple columnar epithelium Lacteal Villus Capillary network Goblet cells Intestinal crypt Lymph vessel Arteriole Venule FIGURE 25–2  The structure of intestinal villi and crypts The epithelial layer also contains scattered endocrine cells and intraepithelial lymphocytes The crypt base contains Paneth cells, which secrete antimicrobial peptides, as well as the stem cells that provide for continual turnover of the crypt and villus epithelium The epithelium turns over every 3–5 days in healthy adult humans (Reproduced with permission from Fox SI: Human Physiology, 10th ed New York, NY: McGraw-Hill; 2008.) of NaCl renders the saliva hypotonic, particularly at low secretion rates As the rate of secretion increases, there is less time for NaCl to be extracted and the tonicity of the saliva rises, but it always stays somewhat hypotonic with respect to plasma Overall, the three pairs of salivary glands that drain into the mouth supply 1000–1500 mL of saliva per day Salivary secretion is almost entirely controlled by neural influences, with the parasympathetic branch of the autonomic nervous system playing the most prominent role (Figure 25–3) Sympathetic input slightly modifies the composition of saliva (particularly by increasing proteinaceous content), but has little influence on volume Secretion is triggered by reflexes that are stimulated by the physical act of chewing, but is actually initiated even before the meal is taken into the mouth as a result of central triggers that are prompted by thinking about, seeing, or smelling food Indeed, salivary secretion can readily be conditioned, as in the classic experiments of Pavlov where dogs were conditioned to salivate in Barrett_CH25_p451-474.indd 455 response to a ringing bell by associating this stimulus with a meal Salivary secretion is also prompted by nausea but inhibited by fear or during sleep Saliva performs a number of important functions: it facilitates swallowing, keeps the mouth moist, serves as a solvent for the molecules that stimulate the taste buds, aids speech by facilitating movements of the lips and tongue, and keeps the mouth and teeth clean The saliva also has some antibacterial action, and patients with deficient salivation (xerostomia) have a higher than normal incidence of dental caries The buffers in saliva help maintain the oral pH at about 7.0 GASTRIC SECRETION Food is stored in the stomach; mixed with acid, mucus, and pepsin; and released at a controlled, steady rate into the duodenum (Clinical Box 25–1) 6/27/15 4:35 PM 456 SECTION IV  Gastrointestinal Physiology Smell Taste Sound Sight Higher centers Parotid gland ACh Otic ganglion Pressure in mouth Parasympathetics Submandibular gland ACh Submandibular ganglion Increased salivary secretion via effects on • Acinar secretion • Vasodilatation Salivatory nucleus of medulla − Sleep Fatigue Fear FIGURE 25–3  Regulation of salivary secretion by the parasympathetic nervous system ACh, acetylcholine Saliva is also produced by the sublingual glands (not depicted), but these are the minor contributors to both resting and stimulated salivary flows (Adapted with permission from Barrett KE: Gastrointestinal Physiology New York, NY: McGraw-Hill; 2006.) ANATOMIC CONSIDERATIONS The gross anatomy of the stomach is shown in Figure 25–4 The gastric mucosa contains many deep glands In the cardia and the pyloric region, the glands secrete mucus In the body of the stomach, including the fundus, the glands also contain parietal (oxyntic) cells, which secrete hydrochloric acid and intrinsic factor, and chief (zymogen, peptic) cells, which secrete pepsinogens (Figure 25–5) These secretions mix with mucus secreted by the cells in the necks of the glands Several of the glands open onto a common chamber (gastric pit) that opens in turn onto the surface of the mucosa Mucus is also secreted along with HCO3− by mucus cells on the surface of the epithelium between glands The stomach has a very rich blood and lymphatic supply Its parasympathetic nerve supply comes from the vagi and its sympathetic supply from the celiac plexus CLINICAL BOX 25–1 Peptic Ulcer Disease Gastric and duodenal ulceration in humans is related primarily to a breakdown of the barrier that normally prevents irritation and autodigestion of the mucosa by the gastric secretions Infection with the bacterium Helicobacter pylori disrupts this barrier, as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the production of prostaglandins and consequently decrease mucus and HCO3− secretion The NSAIDs are widely used to combat pain and treat arthritis An additional cause of ulceration is prolonged excess secretion of acid An example of this is the ulcers that occur in the Zollinger–Ellison syndrome This syndrome is seen in patients with gastrinomas These tumors can occur in the stomach and duodenum, but most of them are found in the pancreas Barrett_CH25_p451-474.indd 456 The gastrin causes prolonged hypersecretion of acid, and severe ulcers are produced THERAPEUTIC HIGHLIGHTS Gastric and duodenal ulcers can be given a chance to heal by inhibition of acid secretion with drugs such as omeprazole and related drugs that inhibit H+–K+ ATPase (“proton pump inhibitors”) If present, H pylori can be eradicated with antibiotics, and NSAID-induced ulcers can be treated by stopping the NSAID or, when this is not advisable, by treatment with the prostaglandin agonist misoprostol Gastrinomas can sometimes be removed surgically 6/27/15 4:35 PM CHAPTER 25  Overview of Gastrointestinal Function & Regulation 457 Acid, intrinsic factor, pepsinogen Fundus Esophagus Mucus layer Lower esophageal sphincter Body (secretes mucus, pepsinogen, and HCI) Duodenum Surface mucous cells (mucus, trefoil peptide, bicarbonate secretion) Cell migration Pyloric sphincter Antrum (secretes mucus, pepsinogen, and gastrin) Parietal cells (acid, intrinsic factor secretion) FIGURE 25–4  Anatomy of the stomach The principal secretions of the body and antrum are listed in parentheses (Reproduced ECL cell (histamine secretion) with permission from Widmaier EP, Raff H, Strang KT: Vander’s Human Physiology: The Mechanisms of Body Function, 11th ed New York, NY: McGraw-Hill; 2008.) ORIGIN & REGULATION OF GASTRIC SECRETION The stomach also adds a significant volume of digestive juices to the meal Like salivary secretion, the stomach readies itself to receive the meal before it is actually taken in, during the so-called cephalic phase that can be influenced by food preferences Subsequently, there is a gastric phase of secretion that is quantitatively the most significant, and finally an intestinal phase once the meal has left the stomach Each phase is closely regulated by both local and distant triggers The gastric secretions (Table 25–1) arise from glands in the wall of the stomach that drain into its lumen, and also from the surface cells that secrete primarily mucus and bicarbonate to protect the stomach from digesting itself, as well as substances known as trefoil peptides that stabilize the mucusbicarbonate layer The glandular secretions of the stomach differ in different regions of the organ The most characteristic secretions derive from the glands in the fundus or body of the stomach These contain the distinctive parietal cells, which secrete hydrochloric acid and intrinsic factor; and chief cells, which produce pepsinogens and gastric lipase (Figure 25–5) The acid secreted by parietal cells serves to sterilize the meal and also to begin the hydrolysis of dietary macromolecules Intrinsic factor is important for the later absorption of vitamin B12, or cobalamin Pepsinogen is the precursor of pepsin, which initiates protein digestion Lipase similarly begins the digestion of dietary fats There are three primary stimuli of gastric secretion, each with a specific role to play in matching the rate of secretion to functional requirements (Figure 25–6) Gastrin is a hormone that is released by G cells in the antrum of the stomach both in Barrett_CH25_p451-474.indd 457 Mucous neck cells (stem cell compartment) Chief cells (pepsinogen secretion) FIGURE 25–5  Structure of a gastric gland from the fundus or body of the stomach These acid- and pepsinogen-producing glands are referred to as “oxyntic” glands in some sources Similarly, some sources refer to parietal cells as oxyntic cells ECL, enterochromaffinlike (Adapted with permission from Barrett KE: Gastrointestinal Physiology New York, NY: McGraw-Hill; 2006.) response to a specific neurotransmitter released from enteric nerve endings, known as gastrin-releasing peptide (GRP) or bombesin, and also in response to the presence of oligopeptides in the gastric lumen Gastrin is then carried through the bloodstream to the fundic glands, where it binds to receptors not only on parietal (and likely, chief cells) to activate secretion, but also on so-called enterochromaffin-like cells TABLE 25–1  Contents of normal gastric juice (fasting state) Cations: Na+, K+, Mg2+, H+ (pH approximately 3.0) Anions: Cl−, HPO42−, SO42− Pepsins Lipase Mucus Intrinsic factor 6/27/15 4:35 PM 458 SECTION IV  Gastrointestinal Physiology ANTRUM FUNDUS Peptides/amino acids GRP H+ − H+ G cell ACh Parietal cell D cell P SST Gastrin Chief cell ACh ? ? Histamine ACh Circulation ECL cell Nerve ending FIGURE 25–6  Regulation of gastric acid and pepsin secretion by soluble mediators and neural input Gastrin is released from G cells in the antrum in response to gastrin releasing peptide (GRP) and travels through the circulation to influence the activity of enterochromaffin-like (ECL) cells and parietal cells ECL cells release histamine, which also acts on parietal cells Acetylcholine (ACh), released from nerves, is an agonist for ECL cells, chief cells, and parietal cells Other specific agonists of the chief cell are not well understood Gastrin release is negatively regulated by luminal acidity via the release of somatostatin from antral D cells P, pepsinogen (Adapted with permission from Barrett KE: Gastrointestinal Physiology New York, NY: McGraw-Hill; 2006.) (ECL cells) that are located in the gland, and release histamine Histamine is also a trigger of parietal cell secretion, via binding to H2-receptors Finally, parietal and chief cells can also be stimulated by acetylcholine, released from enteric nerve endings in the fundus Gastric secretion that occurs during the cephalic phase is defined as being activated predominantly by vagal input that originates from the brain region known as the dorsal vagal complex, which coordinates input from higher centers Vagal outflow to the stomach then releases GRP and acetylcholine, thereby initiating secretory function However, before the meal enters the stomach, there are few additional triggers and thus the amount of secretion is limited Once the meal is swallowed, on the other hand, meal constituents trigger substantial release of gastrin and the physical presence of the meal also distends the stomach and activates stretch receptors, which provoke a “vago-vagal” as well as local reflexes that further amplify secretion during the gastric phase The presence of the meal also buffers gastric acidity that would otherwise serve as a feedback inhibitory signal to shut off secretion secondary to the release of somatostatin, which inhibits both G and ECL cells as well as secretion by parietal cells themselves (Figure 25–6) This probably represents a key mechanism whereby gastric secretion is terminated after the meal moves from the stomach into the small intestine Gastric parietal cells are highly specialized for their unusual task of secreting concentrated acid (Figure 25–7) The cells are packed with mitochondria that supply energy to drive the apical H+,K+-ATPase, or proton pump, that moves H+ ions out of the parietal cell against a concentration gradient of more than a million-fold At rest, the proton Barrett_CH25_p451-474.indd 458 pumps are sequestered within the parietal cell in a series of membrane compartments known as tubulovesicles When the parietal cell begins to secrete, on the other hand, these vesicles fuse with invaginations of the apical membrane IC MV M IC M TV G IC M IC FIGURE 25–7  Composite diagram of a parietal cell, showing the resting state (lower left) and the active state (upper right) The resting cell has intracellular canaliculi (IC), which open on the apical membrane of the cell, and many tubulovesicular structures (TV) in the cytoplasm When the cell is activated, the TVs fuse with the cell membrane and microvilli (MV) project into the canaliculi, so the area of cell membrane in contact with gastric lumen is greatly increased M, mitochondrion; G, Golgi apparatus (Reproduced with pemission of Ito S, Schofield GC: Studies on the depletion and accumulation of microvilli and changes in the tubulovesicular compartment of mouse parietal cells in relation to gastric acid secretion J Cell Biol 1974; Nov; 63(2 Pt 1):364–382.) 6/27/15 4:35 PM CHAPTER 25  Overview of Gastrointestinal Function & Regulation Resting 459 Secreting Canaliculus H+, K+ ATPase Tubulovesicle M3 M3 Ca2+ cAMP ACh CCK-B Ca2+ CCK-B Gastrin H2 H2 Histamine FIGURE 25–8  Parietal cell receptors and schematic representation of the morphologic changes depicted in Figure 25–7 Amplification of the apical surface area is accompanied by an increased density of H+, K+–ATPase molecules at this site Note that acetylcholine (ACh) and gastrin signal via calcium, whereas histamine signals via cAMP (Adapted with permission from Barrett KE: Gastrointestinal Physiology New York, NY: McGraw-Hill; 2006.) counterion for HCl secretion (Figure 25–9) The secretion of protons is also accompanied by the release of equivalent numbers of bicarbonate ions into the bloodstream, which are later used to neutralize gastric acidity once its function is complete (Figure 25–9) known as canaliculi, thereby substantially amplifying the apical membrane area and positioning the proton pumps to begin acid secretion (Figure 25–8) The apical membrane also contains potassium channels, which supply the K+ ions to be exchanged for H+, and Cl− channels that supply the Apical Cl– H+ K+ H+, K+ ATPase CIC Carbonic anhydrase II ATP Lumen K+ K+ channel ADP H+ + HCO3– H2O + CO2 ADP Cl–/HCO3– exchanger HCO3– Cl– Basolateral NHE-1 Na+ H+ ATP Na+, K+ ATPase 2K+ 3Na+ Bloodstream FIGURE 25–9  Ion transport proteins of parietal cells Protons are generated in the cytoplasm via the action of carbonic anhydrase II Bicarbonate ions are exported from the basolateral pole of the cell either by vesicular fusion or via a chloride/bicarbonate exchanger The sodium/hydrogen exchanger, NHE1, on the basolateral membrane is considered a “housekeeping” transporter that maintains intracellular pH in the face of cellular metabolism during the unstimulated state Barrett_CH25_p451-474.indd 459 6/27/15 4:35 PM 460 SECTION IV  Gastrointestinal Physiology The three agonists of the parietal cell—gastrin, histamine, and acetylcholine—each bind to distinct receptors on the basolateral membrane (Figure 25–8) Gastrin and acetylcholine promote secretion by elevating cytosolic free calcium concentrations, whereas histamine increases intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) The net effects of these second messengers are the transport and morphologic changes described above However, it is important to be aware that the two distinct pathways for activation are synergistic, with a greater than additive effect on secretion rates when histamine plus gastrin or acetylcholine, or all three, are present simultaneously The physiologic significance of this synergism is that high rates of secretion can be stimulated with relatively small changes in availability of each of the stimuli Synergism is also therapeutically significant because secretion can be markedly inhibited by blocking the action of only one of the triggers (most commonly that of histamine, via H2-antagonists that are widely used therapies for adverse effects of excessive gastric secretion, such as reflux) Gastric secretion adds about 2.5 L/day to the intestinal contents However, despite their substantial volume and fine control, gastric secretions are dispensable for the full digestion and absorption of a meal, with the exception of cobalamin absorption This illustrates an important facet of gastrointestinal physiology, namely that digestive and absorptive capacities are markedly in excess of normal requirements On the other hand, if gastric secretion is chronically reduced, individuals may display increased susceptibility to infections acquired via the oral route PANCREATIC SECRETION The pancreatic juice contains enzymes that are of major importance in digestion (see Table 25–2) Its secretion is controlled in part by a reflex mechanism and in part by the gastrointestinal hormones secretin and cholecystokinin (CCK) ANATOMIC CONSIDERATIONS The portion of the pancreas that secretes pancreatic juice is a compound alveolar gland resembling the salivary glands Granules containing the digestive enzymes (zymogen granules) are formed in the cell and discharged by exocytosis (see Chapter 2) from the apexes of the cells into the lumens of the pancreatic ducts (Figure 25–10) The small duct radicles coalesce into a single duct (pancreatic duct of Wirsung), which usually joins the bile duct to form the ampulla of the bile duct (also known as the ampulla of Vater) (Figure 25–11) The ampulla opens through the duodenal papilla, and its orifice is encircled by the sphincter of Oddi Some individuals have an accessory pancreatic duct (duct of Santorini) that enters the duodenum more proximally Barrett_CH25_p451-474.indd 460 Endocrine cells of pancreas Exocrine cells (secrete enzymes) Duct cells (secrete bicarbonate) FIGURE 25–10  Structure of the pancreas (Reproduced with permission from Widmaier EP, Raff H, Strang KT: Vander’s Human Physiology: The Mechanisms of Body Function, 11th ed New York, NY: McGraw-Hill; 2008.) COMPOSITION OF PANCREATIC JUICE The pancreatic juice is alkaline (Table 25–3) and has a high HCO3− content (approximately 113 mEq/L vs 24 mEq/L in plasma) About 1500 mL of pancreatic juice is secreted per day Bile and intestinal juices are also neutral or alkaline, and these three secretions neutralize the gastric acid, raising the pH of the duodenal contents to 6.0–7.0 By the time the chyme reaches the jejunum, its pH is nearly neutral, but the intestinal contents are rarely alkaline The pancreatic juice also contains a range of digestive enzymes, but most of these are released in inactive forms and only activated when they reach the intestinal lumen (see Chapter 26) The enzymes are activated following proteolytic cleavage by trypsin, itself a pancreatic protease that is released as an inactive precursor (trypsinogen) The potential danger of the release into the pancreas of a small amount of trypsin is apparent; the resulting chain reaction would produce active enzymes Right hepatic duct Cystic duct Gallbladder Left hepatic duct Common hepatic duct Bile duct Pancreas Accessory pancreatic duct Ampulla of bile duct Duodenum Pancreatic duct FIGURE 25–11  Connections of the ducts of the gallbladder, liver, and pancreas (Adapted with permission from Bell GH, Emslie-Smith D, Paterson CR: Textbook of Physiology and Biochemistry, 9th ed Churchill Livingstone, 1976.) 6/27/15 4:35 PM 736 INDEX Insulin, 429, 434, 479 (Cont’d.) glucose transporters, 432 hypoglycemic, 434 preparations, 432–433 relation to potassium, 433–434 insulin-like activity in blood, 431 and insulin-like growth factors comparison of, 327 structure of, 326 intracellular responses, 434 mechanism of action receptors, 434–435 metabolism, 431 principal actions of, 432 sensitivity, 333 structure/species specificity, 430–431 Insulin-dependent diabetes mellitus, 447 Insulin excess compensatory mechanisms, 438–439 symptoms, 438 Insulin-glucagon molar ratios, 444 Insulinoma, 446 Insulin receptors, 434–434 Insulin secretion, 440 factors affecting, 439 regulation of, 439 autonomic nerves, effect of, 441 B cell responses, long-term changes, 441–442 cAMP, 440–441 hypoglycemic agents, 440 intestinal hormones, 441 plasma glucose level, effects of, 439–40 protein/fat derivatives, 440 Insulin-sensitive tissues, endosomes in, 433 Insulin sensitizers, 305 Integrins, 40 Intention tremor, 252 Intercalated cells, 672 Intercalated disks, 112 Intercellular communication by chemical mediators, 53–54 types of, 52–53 Intercellular connections, 41 in mucosa of small intestine, 41 Interleukins, 71, 72, 74 Intermediary metabolism, actions of glucocorticoids on, 363 Intermediate-density lipoproteins, 28 Intermediate filaments, 38, 39 Internalization, 53 Internal urethral sphincter, 692 Internodal atrial pathways, 519 Interstitial cells of Cajal, 496 Interstitial fluid, 3, Interstitial fluid volume edema, 582 elephantiasis, 582 lymphedema, 582 precapillary constriction, 582 promoting factors, 582 Intestinal epithelial cells, disposition of short peptides in, 481 Intestinal fluid/electrolyte transport, 464–466 Intestinal lumen, 475 Intestinal mucosa lipid digestion and passage in, 482 Barrett_Index_p721-756.indd 736 Intestinal smooth muscle effects of agents on membrane potential of, 116–117 Intestinal villi, 455 Intestine epithelium of, 454 functional layers, 454 substances, normal transport of, 458 Intracellular canaliculi, 458 Intracellular fluid, 3, Intracellular H+ concentration, defense of, 713–718 Intracranial hematoma, 284 Intrafusal muscle fibers, 229 Intrahepatic portal vein radicles, 509 Intrahypothalamic system, 308 Intramembranous bone formation, 383 Intrauterine devices, 409 Intravenous immunoglobulin, Lambert–Eaton Syndrome treatment, 132 Intrinsic depression, 546 Inverse stretch reflex definition of, 232 in Golgi tendon organ, 232, 233 muscle tone and, 233 pathways responsible for, 231 Invertebrates, body temperature of, 316 In vitro fertilization, 412 Iodide transport across thyrocytes, 339 Iodine homeostasis and thyroid hormones, 338–339 Ion channels activation by chemical messengers, 53 multiunit structure of, 48–49 pore formation in, 49, 50 pore-forming subunits of, 50 regulation of gating in, 48 spatial distribution of, 93 Ion distribution and fluxes, 103 Ionotropic glutamate receptors properties of, 141, 142 subtypes of, 141–142 Ionotropic receptors, 138 salt and sour tastes triggered by, 224 Ion transport proteins of parietal cells, 459 IOP, 179 IPSP See Inhibitory postsynaptic potential IRDS See Infant respiratory distress syndrome Iron absorption of, 483–484 intestinal absorption of, 484 Iron uptake, disorders of, 485 Irritant receptors, 662 IRV See Inspiratory reserve volume Ischemic hypoxia, 651 Ischemic/stagnant hypoxia, 647 Ishihara charts, 193 Islet cell hormones effects of, 444 pancreatic, organization of, 445 pancreatic polypeptide, 445 somatostatin, 444–445 Islet cell structure, 430 human, 430 rat pancreas, 430 Isocapnic buffering, 666 Isohydric principle, Isomaltase, 476 Isometric contractions, 105 Isotonic contractions, 105 muscle preparation arranged for recording, 107 Isotonic muscle contractions, 487 Isotonic solutions, Isovolumetric ventricular contraction, 538 Isovolumetric ventricular relaxation, 539 Itch, 161, 162 IUDs See Intrauterine devices J JAK-STAT pathway, signal transduction via, 61, 63 JAK2-STAT pathways, 324 Janus tyrosine kinases, 61, 63 Jaundice bilirubin, 511 obstructive, 514 JG cells See Juxtaglomerular cells Junctional potentials, 133 Juvenile diabetes, 447 Juxtacrine communication, 52 Juxtaglomerular apparatus, 672 Juxtaglomerular cells, 703 Juxtamedullary nephrons, 672 K Kainate receptors, 141 Kallmann syndrome, 316 Karyotype, 390 Kaspar Hauser syndrome, 332 Kayser-Fleischer rings, 246 KCC1 See Potassium/chloride cotransporter K+ channels, 49, 50 K+ depletion, 441 Ketoacidosis, 27 Ketone bodies formation and metabolism of, 26, 27 health problems due to, 27 Ketosis, 437 Ketosteroids, 362 17-Ketosteroids, 362 Kidneys acid–base balance maintenance, 709 ammonia production, 712 autoregulation, 676 countercurrent exchangers in, 687 distal tubule of, 465 metabolically produced acid loads, 714 proximal tubular cells secretion of acid, 710 Kinesin, 39, 89 Kinins active factor, 597 angiotensin-converting enzyme, 596 bradykinin receptors, 597 formation of, 596–597 kallikreins, 596–597 lysylbradykinin, 596–597 Kinocilium, 202 Klinefelter syndrome, 395 Knee jerk reflex, 229 6/29/15 3:54 PM INDEX Kölliker-Fuse nuclei, 656 Krebs cycle See Citric acid cycle Kupffer cells, 508, 510 Kussmaul breathing, 437, 659 L Labyrinth See Inner ear Lacis cells, 703 Lactase, 476 Lactation, 414–415 breasts, development of, 414 initiation of, 414 menstrual cycles, effect, 414–415 milk, secretion/ejection of, 414 Lactic acidosis, 438, 547 Lactose, 476 brush border digestion, 478 Lactose intolerance, treatment for, 477 Lactotropes, 322 Lambert–Eaton Syndrome, 132 Lamellar bodies, 623 Language areas in categorical hemisphere concerned with, 292 physiology of, 292–293 Language-based activity active areas of brain during, 284 Language disorders aphasias, 293 stuttering, 293 Large-molecule transmitters, 138 calcitonin gene-related peptide, 154 CCK receptors, 154 gastrointestinal hormones, 154 neuropeptide Y, 154 opioid peptides, 153–154 oxytocin, 154 somatostatin, 154 substance P, 153 vasopressin, 154 Laron dwarfism, 332 Lateral brain stem pathway, 240 Lateral intercellular spaces, 672, 680 L channels, 521 LDL, 28 L-dopa, 332 Leader sequence, 18, 43, 44 Leaky epithelium, 679 Learning associative, 285 and cerebellum, 251 definition of, 283 nonassociative, 285 and synaptic plasticity, 286 Left and right planum temporale in brain, 209 Left ventricular ejection time, 540 Length–tension relationship in cardiac muscle, 114–115 human triceps muscle, 107 sliding filament mechanism of muscle contraction and, 107 Leptin, 397 LES See Lower esophageal sphincter Lesions of representational and categorical hemispheres, 291 Leukemia inhibitory factor, 96 Barrett_Index_p721-756.indd 737 Levodopa, 142, 149 for MSA treatment, 256 for Parkinson disease treatment, 247 Lewy bodies, 247 Leydig cells, 392, 425 interstitial cells of, 417 LH See Luteinizing hormone LHRH, 314 Lidocaine, for chronic pain, 166 LIF, 96 Light adaptation, 194 Light microscope, hypothetical cell seen with, 34 Light therapy, 279 Linear acceleration, responses to, 211–212 Lipid breakdown during exercise, 109 Lipid digestion intestinal mucosa, 482 intracellular handling of, 482 Lipids, 481–483 biologically important, 25 in cells, 26, 27 fat absorption, 482–483 fat digestion, 481–482 fatty acids See Fatty acids plasma, 26, 28 short-chain fatty acids, 483 steatorrhea, 482 transport of, 26, 28 Lipoproteins, 28 Liver acinus, concept of, 509 bile synthesis in, 507 biliary system bile formation, 513 biliary secretion, regulation of, 513 cholecystectomy, effects of, 513–514 gallbladder, functions of, 513 gallbladder, visualizing, 514 blood, detoxifies, 510 blood percolates, 507 excretion ammonia metabolism, 512 substances, 512 functional anatomy, 507–509 functions of, 509–511 bile, 510–511 bilirubin metabolism/excretion, 511 glucuronyl transferase system, 512 jaundice, 511 metabolism/detoxification, 509–510 plasma proteins synthesis, 510 glucose buffer function of, 510 hepatic circulation, 509 metabolically produced acid loads, 714 schematic anatomy of, 508 transport/metabolic functions of, 507 Local anesthetics and nerve fibers, 95 Local current flow, in axon, 93 Local injury, 81–82 Localized cortical lesions, 294 Local response of membrane, 93 Long QT syndrome, 114 Long-term depression, 286–287 Long-term learned responses, 286 Long-term memory, 285 recalling of, 288 storage in neocortex, 288 737 Long-term potentiation in NMDA receptor, 286 in Schaffer collaterals in hippocampus, 287 Loop of Henle, 672 operation, 686 Loops of Henle, 683–684 Loss-of-function receptor mutations, 63, 64 Lou Gehrig disease, 240 Lovastatin, 29 Low-density lipoproteins, 28 Lower esophageal sphincter, 498 Lower motor neurons, 238 damage to, 240 Lown-Ganong-Levine syndrome, 532 LTP See Long-term potentiation Lung airway conduction, 622, 623 alveolar air, 634 alveolar airway, 623–624 alveolocapillary membrane, diffusion across, 634–635 anatomy, 621–627 biologically active substances metabolism, 637 blood and lymph in, 626–627 blood flow, 632 bronchi, 623 capacities, 628–629 complexity, 619 compliance of, 629–632 diffusing capacity, 635 endocrine functions, 637–638 gas exchange in, 634–635 gas transport in, 639–652 metabolic functions, 637–638 parenchyma See Alveolar airway partial pressures, 633–934 perfusion, 636 pleura, 626–627 pressure-volume curves in, 629–630, 631 receptors, 662 respiratory muscles, 624–626 respiratory system, 634 respiratory tract, regions of, 621 responses mediated by receptors in, 662 ventilation, 632, 636 Lung volume, 628–629 Luteal cells, 399 Luteinizing hormone, 304 actions of, 333 constituents of, 330–331 episodic secretion of, 408 half-life of, 331 receptors for, 333 Luteinizing hormone–releasing hormone, 314 Luteolysis, 409 LVET See Left ventricular ejection time Lymphatic circulation functions of, 581–582 lymphatics draining, 581–582 lymphatic vessels, 581–582 Lymphatic organs, glucocorticoids effects on, 364 Lymph node, anatomy of, 69 Lymphocytes, 472 in bloodstream, 69 during fetal development, 69, 70 Lysergic acid diethylamide, 152 6/29/15 3:54 PM 738 INDEX Lysine vasopressin, 311 Lyso-PC, 462 Lysosomal diseases, 37 Lysosomes definition of, 37 enzymes found in, 37 M Machado–Joseph disease, 252 Macroglia, 85–86 Macrophages, 67, 69 Macrosomia, 444 Macula, 180 Macula densa, 672, 682, 703 Macular sparing, 190–191 Maculopathy, 181 Magnocellular neurons, electrical activity of, 312 Major depressive disorder, 152 Major histocompatibility complex, 489 Major histocompatibility complex (MHC) genes, 76 Major proglucagon fragment, 442 Malabsorption, 489 Malabsorption syndrome, 489 Male contraception, 421 Male menopause See Andropause Male pseudohermaphroditism, 395, 396 Male reproductive system, 417 anatomical features of, 418 embryology of brain development, 393–394 differentiation of, 392 genitalia, 391–393 gonad development, 391 gametogenesis or ejaculation blood-testis barrier, 417–418 ejaculation, 421 erection, 420–421 prostate-specific antigen (PSA), 421 semen, 420 spermatogonia, 418–419 spermatozoa, development of, 419–420 temperature, effect of, 420 structure, 417 testes, endocrine function of actions, 422–423 anabolic effects, 423 estrogens, testicular production of, 424–425 inhibins, 425 mechanism of action, 423–424 secondary sex characteristics, 423 secretion, 422 steroid feedback, 425–426 testosterone, chemistry/biosynthesis of, 421–422 transport/metabolism, 422 testicular function, abnormalities of androgen-secreting tumors, 426 cryptorchidism, 426 hormones and cancer, 426 male hypogonadism, 426 Male secondary sex characteristics, 423 Malignancy, humoral hypercalcemia of, 382 Malignant hyperthermia, 106, 320 Maltase, 476 Maltose, 476 Barrett_Index_p721-756.indd 738 Maltotriose, 476 Mammalian nerve fibers, 94 Mammalian skeletal muscle, 100 electrical and mechanical responses of, 103 Mammalian spinal motor neurons, ion concentration inside and outside, Mammotropes, 322 Manubrium, 200 MAOIs, 152 Masculinization, 372 Masking, 205 Mass action contraction, 502 Mass discharge in stressful situations, 265 Mast cells, 67, 68–69, 153 Mastication, 497 Maximal voluntary ventilation, 629 Maximum metabolic rate, 488 McCune-Albright syndrome, 411 M cells See Microfold cells MDMA, 152 Mechanoreceptors, 159 hair cells as, 202 Medial brain stem pathways, 239 medial tracts involved in, 239–240 Medial temporal lobe and hippocampus, 288 Median eminence, 309 Medullary chemoreceptors, 659 Medullary control basic pathways, 587, 588 factors affecting activity of RVLM, 587, 589 factors affecting heart rate, 587, 590 heart rate by vagus nerves, 587, 589 intermediolateral gray column, 587 rostral ventrolateral medulla, 587 somatosympathetic reflex, 587 Medullary hormones, structure and function of, 353–354 Medullary reticulospinal tracts and posture, 239 Meiosis, 15 Meissner corpuscles, 160 Meissner plexus, 472 Melanophore, 323 Melanopsin, 185 Melanotropins biosynthesis, 323 physiological functions, 323 Melatonin secretion of, 278 and sleep–wake state, 279–280 synthesis, diurnal rhythms of compounds in, 280 Memantine, 142 for Alzheimer disease treatment, 289 Membrane polarization, abnormalities of, 532 Membrane potential extracellular Ca2+ concentration and, 91–92 genesis of, 9–10, 90 resting, 90 from separation of positive and negative charges, sequential feedback control in, 91–92 of smooth muscle, 115–116 subthreshold stimuli effect on, 92 upstroke in, 90 Membrane transport proteins aquaporins, 47 carriers, 48 uniports, 48 Membranous labyrinth, 200 Memory and brain, link between, 285 episodic, 284 explicit or declarative, 283 forms of, 285 implicit, 284 intercortical transfer of, 287 long-term, 285 neural basis of, 286 procedural, 284 semantic, 284 short-term, 285 working, 288 Memory B cells, 70, 77 Memory T cells, 70 Menarche, 396 Menopause, 398–399 Menorrhagia, 410 Menstrual cycle anovulatory cycles, 401–402 basal body temperature and plasma hormone concentrations, 403 breasts, cyclical changes, 402 changes during intercourse, 402 estrous cycle, 403–404 indicators of ovulation, 402–403 normal menstruation, 401 ovarian cycle, 399–400 ovarian vs uterine changes, 401 uterine cervix, cyclical changes, 402 uterine cycle, 400–401 vaginal cycle, 402 Menstrual cycle ovulation, 402–403 Menstruation, 399 Mentation, 348 Merkel cells, 160 Mesangial cells, 671 relaxation of, 678 Mesocortical system, 150 Metabolic acidosis, 645–646 acid–base paths, 646 Metabolic alkalosis, 5, 645 Metabolic myopathies, 102 Metabolic rate, 487 and body weight, 488 factors affecting, 488 Metabolic syndrome, 448 Metabotropic glutamate receptors activation of, 143 subtypes of, 143 Metabotropic receptors, 138 Metahypophysial diabetes, 441 Metathyroid diabetes, 441 Methemoglobin, 651 3,4-Methylenedioxymethamphetamine, 152 Mexiletine, 166 mGluR See Metabotropic glutamate receptors MHC See Major histocompatibility complex Micelles, 463, 482 Microfilaments, 38 composition of, 39 structure of, 39 Microfold cells, 481 Microglia, 85, 167 6/29/15 3:54 PM INDEX MicroRNAs, 17 Microscopy techniques, cellular constituents examination by, 33 Microsomes, 34 Microtubule-organizing centers, 40 Microtubules composition of, 38 drugs affecting, 38–39 structures of, 38–39 Microvilli, 458 Micturition, 669 Midcollicular decerebrate cats, decerebrate rigidity in, 241–242 Middle cerebellar peduncle, 248 Middle ear functions of, 199–200 medial view of, 201 structures of, 199–200 Mifepristone (RU 486), 407 Migrating motor complex, 496–497 Milk ejection reflex, 313 Mineralocorticoids, 351 aldosterone See Aldosterone mechanism of action of, 368–369 relation to glucocorticoid receptors, 369 secondary effects of excess, 370 Miotics, 187 MIS See Müllerian inhibiting substance Mitochondria components involved in oxidative phosphorylation in, 36 functions, 36 genome, 36 Mitochondrial diseases, 36, 37 Mitochondrial DNA, 36 diseases caused by abnormalities in, 45 Mitochondrial genome and nuclear genome, interaction between, 36 Mitochondrial membrane proton transport across inner and outer lamellas of inner, 11 Mitogen-activated protein (MAP) kinase cascade, 54 Mitosis, 15 Molecular building blocks deoxyribonucleic acid, 12–15 mitosis and meiosis, 15 nucleosides, nucleotides, and nucleic acids, 12 ribonucleic acids, 15–17 Molecular medicine, 45 Molecular motors dyneins, 39 kinesin, 39 myosin, 39–40 Molecular weight of substance, Moles, Mongolism See Down syndrome Monoamine oxidase inhibitors, 152 Monoamines adrenoceptors, 149–150 ATP, 153 catecholamines, 148–149 dopamine, 150 epinephrine, 147 histamine, 153 noradrenergic synapses, 150 norepinephrine, 147 Barrett_Index_p721-756.indd 739 secreted at synaptic junctions, 142 serotonergic receptors, 152 serotonergic synapses, 152–153 serotonin, 151–152 Monocular and binocular visual fields, 195 Monocytes activated by cytokines, 69 Monogenic forms of deafness, 210 Monosynaptic reflexes, 229 Mood disorders, 152 Morphological changes, parietal cell receptors and schematic representation of, 459 Mosaicism, 394 Motilin, 471 Motivation and addiction, 174 Motor axons, branching of, 130 Motor cortex See also Primary motor cortex axons of neurons from, 238 somatotopic organization for, 238 and voluntary movement plasticity, 238 posterior parietal cortex, 238 premotor cortex, 238 primary motor cortex, 237 supplementary motor area, 237–238 Motor homunculus, 237 Motor neurons, inputs converging on, 227 Motor neuron with myelinated axon, 86 Motor pathways, general principles of central organization of, 235–236 Motor system, divisions of, 238 Motor unit, 110 Movement, corticospinal and corticobulbar system role in, 239 MPGF See Major proglucagon fragment MRF See Müllerian regression factor mRNA transcription, 15, 16 MRP-2 See Multidrug resistance protein MSH See α-Melanocyte-stimulating hormone MTOCs, 40 Mucosa irritation, 500 Mucosal cells, 483 Mucosal immune system, 472–473 Müllerian inhibiting substance, 390 Müllerian regression factor, 392 Multidrug resistance protein 2, 511 Multiple sclerosis, 88, 89 Multiple system atrophy, 256 Multiunit smooth muscle, chemical mediators effect on, 116–117 Murmurs, 542 Muscarinic cholinergic receptors, 146, 147, 259 Muscarinic poisoning, 263 Muscle, contractile element of, 545 Muscle channelopathies, 106 Muscle fibers, 99 classification of, 108 depolarization of, 103, 104 electrical response to repeated stimulation, 105 isometric tension of, 107 length and tension, link between, 107–108 in motor unit, 110 sarcotubular system of See Sarcotubular system Muscle rigor, 109 Muscles, control of corticobulbar tract, 238–239 739 corticospinal tracts, 238 movement and, 239 Muscle spindle afferents, dynamic and static responses of, 231 discharge, effect of conditions on, 231 essential elements of, 229 function of, 230–231 loading, 230–231 mammalian, 230 motor nerve supply, 229, 230 sensory endings in, 229 Muscle tone, 232–233 Muscle twitch, 103 Muscle weakness by autoimmune attack, 132 myasthenia gravis, 132 Muscular dystrophy, 102 Mushroom poisoning, 263 MV See Microvilli MVV See Maximal voluntary ventilation Myasthenia, 106 Myasthenia gravis, 106, 132 Mycetism, 263 Myelinated axons conduction in, 93 depolarization in, 93 Myelin sheath, 88 defects, adverse neurological consequences of, 88 nodes of Ranvier and, 88 Myenteric plexus, 472 Myocardial fibers, 520 Myocardial hibernation, 546 Myocardial infarction, 532–534, 612 Myoepithelial cells, contraction of, 313 Myoglobin, 641 dissociation curves, comparison of, 642 Myopia, 187–188 Myosin, 39–40 power stroke in skeletal muscle, 104 in skeletal muscle, 101 Myotatic reflex See Inverse stretch reflex Myotonia dystrophy, 106 Myxedema See Hypothyroidism N N, N-dimethyltryptamine, 152 Na, K ATPase See Sodium–potassium adenosine triphosphatase (Na, K ATPase) Na, K ATPase-inhibiting factor, 706 Na+ channels, 49, 50 inactivated state, 90 NAD+ See Nicotinamide adenine dinucleotide NADH generation in citric acid cycle, 22 NADP+, 11 NADPH oxidase activation, 68 Na+ excretion, steroids affecting, 369 Na+/I– symporter, 339 Narcolepsy, 276 Natalizumab for MS treatment, 88 Natriuretic hormones, 704–706 actions, 705 Natriuretic peptide receptors, 705 Natural killer cells, 69, 73 Nearsightedness, 187–188 6/29/15 3:54 PM 740 INDEX NEAT See Nonexercise activity thermogenesis Negative feedback inhibition of spinal motor neuron, 129 Neocortex interneurons, 270–271 pyramidal cells, 270–271 Neostigmine, myasthenia gravis treatment by, 132 Nephrogenic diabetes insipidus, 698 Nephron, 671–672 diagram, 672 Nerve cells excitability during IPSP, 125 excitation and conduction antidromic conduction, 94 electrotonic potentials, 93 firing level, 93 ionic fluxes, 90–91 local response, 93 orthodromic conduction, 94 resting membrane potential, 90 Nerve fibers, 94–95 local anesthetics effect on, 95 susceptibility to conduction block, 95 type and functions of, 94–95 Nerve impulses See Action potentials Nerve supply to smooth muscle, 117–118 Nervi erigentes, 421 Nervous system, actions of glucocorticoids on, 363 Neural communication, 52 Neural control mechanisms, 311 Neural control of adrenal medullary secretion, 356 Neural hormones, 311 Neural mechanisms of color vision, 194 Neural pathways, 189–190, 501 Neurogenesis, 287 Neuroglycopenic symptoms, 438 Neuroleptic drugs, 246 Neurological exam, 164, 165 Neuromodulators, 137, 145 Neuromuscular junction, 121 diseases of, 132 structure of, 130 Neuromuscular transmission events at neuromuscular junctions, 131 events occurring during, 130–131 neuromuscular junction, 130 Neuronal growth, factors affecting, 96 Neurons axonal transport, 89 classification of, 85 components of, 87–88 factor enhancing growth of, 96 important zones of, 87 myelinated, 86, 88 threshold, to stimulation changes, 91, 93 types of, 87 unmyelinated, 88 Neuropathic pain, 165, 166 Neuropeptide Y, 154, 264 Neuropeptide YY, 445 Neurophysin, 311 Neurosecretion, 311 Neurotransmitters, 137, 139 Neurotrophins Barrett_Index_p721-756.indd 740 function of, 95–96 receptors for, 95–96 for SCI treatment, 235 Neutral fat, 26 Neutrophils, 72 average half-life of, 67–68 NHE See Sodium/hydrogen exchanger Nicotinamide adenine dinucleotide, 11 Nicotinamide adenine dinucleotide phosphate, 11 Nicotinic acetylcholine-gated ion channel, threedimensional model of, 147 Nicotinic cholinergic receptors, 134, 146 actions of acetylcholine on, 259 Nicotinic receptors, 134 NIDDM See Non-insulin-dependent diabetes mellitus Nigrostriatal projection, 244 Nigrostriatal system, 150 NIHL, 210 Nipples, stimulation of, 312 NIS See Na+/I– symporter Nitric oxide produced in endothelial cells, 117 synthesis of, 154 Nitric oxide synthase, 421 NK cells See Natural killer cells NMDA receptor antagonists, 142 for chronic pain, 166 NMDA receptors activation of, 167 changes and LTP, 286 diagrammatic representation of, 144 in neurons, 143 properties of, 141, 142 N-methyl-D-aspartate receptors See NMDA receptors NO See Nitric oxide Nociceptive pathways, transmission in, 172 Nociceptive stimuli, 162 Nociceptors, 159 impulse transmitted from, 161 types of, 160 Nocturia, 690 Noise-induced hearing loss, 210 Nonadrenergic, noncholinergic transmitters, 264 chemical transmission at autonomic junctions, 264 Nonassociative learning, 285 Nonconstitutive pathway, 46 Nonconvulsive generalized seizure, 277 Nonexercise activity thermogenesis, 486 Non-insulin-dependent diabetes mellitus, 435 Nonionic diffusion, 8, 712 Nonpathogenic bacteria, 472 Nonsteroidal anti-inflammatory drugs axonal growth after injury and, 97 for chronic pain, 165, 166 pharmacology of, 30 Nonsuppressible insulin-like activity, 431 Noradrenergic and cholinergic postganglionic nerve fibers, effects of stimulation of, 264 Noradrenergic fibers, 520 Noradrenergic neurons, 147 Noradrenergic neurotransmission, 259–261, 264 Noradrenergic synapses, 150 pharmacology of, 148, 150 Norepinephrine, 147, 598 action on heteroreceptor, 138 biosynthesis, 353 biosynthesis and release, 148 catabolism of, 149 chemical transmission at autonomic junctions, 259 chemistry of, 138 effect on intestinal smooth muscle, 117 effect on unitary smooth muscle, 117–118 and epinephrine levels in human venous blood, 354 metabolic effects of, 355–356 as neuromodulator, 147 pharmacology of, 141 plasma levels, 353 reuptake of, 139 secretion of, 147 Norepinephrine-secreting neurons, 147 Norepinephrine transporter, 139, 149 Normal human pancreatic juice, composition of, 462 Normal sinus rhythm, 527 Normal trabecular bone vs trabecular bone, 386 NOS See Nitric oxide synthase NPR See Natriuretic peptide receptors NPY See Neuropeptide Y NSAIDs See Nonsteroidal anti-inflammatory drugs NSILA See Nonsuppressible insulin-like activity NSR See Normal sinus rhythm Nuclear cholescintigraphy, 514 Nuclear factor kappa B, 54 and inflammatory response, 81 Nuclear membrane, 34, 43 Nuclear pore complexes, 43 Nucleic acids, 12, 481 basic structure of, 13 Nucleoli, 34, 43 Nucleosides, nitrogen-containing base of, 12 Nucleotides, 12 basic structure of, 13 Nucleus chromosomes in, 42 composition of, 42–43 interior of, 43 nucleolus, 43 nucleosomes in, 42 Nucleus of the tractus solitarius, 697 Nutrients, intake of, 484–486 Nutrition caloric intake/distribution, 489–490 dietary components, essential, 489 mineral requirements, 490 vitamins, 490–492 Nutritional principles, 487–489 Nutrition and growth physiology, 329 Nyctalopia, 183 Nystagmus, 212, 252 O OATP See Organic anion transporting polypeptide Obesity, 448, 486 Obstructive sleep apnea, 276 Occlusion and fractionation, 234 6/29/15 3:54 PM INDEX Ocular dominance columns, 191–192 Oculocardiac reflex, 530 Odorant-binding proteins, 220 Odorant receptor, signal transduction in, 219–220 Odorant receptors, 219–220 Odorants, 220 Odor detection, abnormalities in, 221 Odor detection threshold, 220 Odor-producing molecules, 220 Olfaction See Smell Olfactory bulbs, neural circuits in, 218 Olfactory cortex diagram of, 219 five regions of, 218–219 Olfactory discrimination, 220 Olfactory epithelium nasal cavity, 219 olfactory bulbs and, 218 olfactory sensory neurons in, 217 axons of, 218 dendrite of, 217 location of, 217 structure of, 218 Olfactory pathway, 219 Olfactory system, adaptation in, 221 Oligodendrocytes, 85–86 Olivocochlear bundle, 207 Oncogenes, 45 Oncotic pressure, 52 Ondine’s curse, 663 Open-angle glaucoma, 179 OPG See Osteoprotegerin Opioid peptides, 153–154 Opioids for chronic pain, 165, 166 nociceptive transmission and, 172, 173 Opsin, 183, 184 Optic pathways, effect of lesions in, 190–191 Optics principles, image-formation, 185–186 Optometric vision therapy, 187 Oral glucose tolerance test, 435, 436 Oral temperature, 316 Orexin, 486 Organic anion transporting polypeptide, 511 Organophosphates, 262 Orthodromic and antidromic conduction, 94 Orthograde transport, 89 Orthostatic hypotension, 256 Osmolal concentration of plasma, Osmolal concentration of substance in fluid, Osmolarity, Osmole, Osmoreceptors, 310 Osmosis definition, 6–7 diagrammatic representation of, Osmotically active substances, Osmotic diuresis, 686–687 Osmotic pressure, 678 factors influencing, nonionizing compound, Ossicular conduction, 206 Osteoblasts, 385 Osteoclast resorbing bone, 385 Osteolytic hypercalcemia, 382 Osteomalacia, 378 Barrett_Index_p721-756.indd 741 Osteons, 383 Osteopetrosis, 386 Osteoporosis, 365, 387 involutional, 386 Osteoprotegerin, 385 Otoliths, 201 Outer hair cells, functions of, 207 Ovarian agenesis, 395 Ovarian function, control of, 408–410 contraception, 409–410 control of cycle, 409 feedback effects, 408–409 hypothalamic components, 408 reflex ovulation, 409 Ovarian function, menstrual abnormalities of, 410 Ovarian hormones actions, 407 breasts, effects on, 405 central nervous system, effects on, 405 chemistry, biosynthesis, 404 endocrine organs, effects on, 405 female genitalia, effects on, 404–405 female secondary sex characteristics, 405 mechanism of action, 406, 407 progesterone, 407 relaxin, 407–408 secretion, 404, 406–407 synthetic and environmental estrogens, 406 Ovarian hyperstimulation syndrome, 331 Overflow incontinence, 693 Ovulation, 399, 402–403 Oxidation, 11 Oxidative deamination of amino acids, 19 Oxidative phosphorylation, 11 enzyme complexes responsible for, 36 mitochondrial components involved in, 36 Oxygen administration, 652 potential toxicity, 652 Oxygenated hemoglobin, comparative titration curves for, 644 Oxygenation reaction, 640 Oxygen debt, 109, 665 Oxygen delivery to tissues, 639 Oxygen-hemoglobin dissociation curve, 640 temperature and pH, effects of, 641 Oxygen transport, 639–641 Oxyphil cells, 379 Oxytocin, 154, 311 action on uterine musculature, 313 physiologic effects, 313 Oxytocin-containing neurons, discharge of, 313 Oxytocin receptors, 413 Oxytocin-secreting neurons, stimulation of, 312 P Pacemaker cells pre-Bötzinger complex, 656 Pacemaker potential, 521 Pacinian corpuscles, 160, 164 generator potential in, 163 Paclitaxel, 38–39 PAH See p-Aminohippuric acid Pain acute, 165 741 chronic, 165 classification of, 165 deep and visceral, 167 definition, 165 hyperalgesia and allodynia, 165–167 referred, 168 vs sensations, 165 Pain transmission, modulation of gray and brainstem role in, 173 information processing in dorsal horn, 172–173 stress-induced analgesia, 173–174 Pallesthesia, 164 p-Aminohippuric acid, 675 PAMs See Pulmonary alveolar macrophages Pancreas structure, 460 Pancreatic α-amylase, 476 Pancreatic β cells, 305 Pancreatic digestive enzymes, 460, 462 Pancreatic duct cells, ion transport pathways in, 462, 463 Pancreatic endopeptidases, 480 Pancreatic juice alkaline, 460 composition of, 462 enzymes, 460, 461 regulation of, 462 Pancreatic polypeptide, 429 Pancreatic proteases, 479 Pancreatic secretion, 460, 461 Pancreatitis, acute, 462 Paracellular pathway, 679 Paracrine communication, 52 Paracrine fashion, 467 Paracrines, 467 Paradoxical sleep See Rapid eye movement sleep Parafollicular cells, 382 Paraganglia, 352 Parageusia, 224 Parallel fibers, 249 Parasomnias, 276 Parasympathetic activation, 265 Parasympathetic cholinergic noradrenergic discharge, 265 Parasympathetic innervations, 265 Parasympathetic nervous system, 257–259 cell bodies in, 258–259 cranial nerve nuclei, 259 organization of, 258 parasympathetic sacral outflow, 259 salivary secretion, regulation of, 455, 456 Parathyroidectomy, effects of, 380 Parathyroid excess, diseases of, 381 Parathyroid glands actions, 380 anatomy, 379 malignancy, hypercalcemia of, 382 mechanism of action, 380–381 parathyroid hormone–related protein, 382 PTH, synthesis/metabolism of, 379–380 regulation of secretion, 381–382 Parathyroid hormone, 375, 380 signal transduction pathways, 381 Parathyroid hormone–related protein, 382 effects of, 380 Paraventricular neurons, 308 Paravertebral ganglia, 257 6/29/15 3:54 PM 742 INDEX Parietal cell, agonists of, 460 Parietal cell, composite diagram of, 459 Parkinson disease, 142 basal ganglia-thalamocortical circuitry in, 248 familial cases of, 247 hypokinetic features of, 245 lead pipe rigidity in, 245 pathogenesis of movement disorders in, 245–246, 248 prevalence of, 247 in sporadic idiopathic form, 247 symptoms, 247 treatment of, 247, 248 Paroxysmal atrial tachycardia with block, 529 Paroxysmal ventricular tachycardia, 530 Partial pressures, 633–934 Partial seizures, 276 Parturition, 413 Parvocellular pathway, 190 Patch clamping, 47 Patchy ventilation-perfusion imbalance, 649 Pattern recognition receptors, 73–74 pAVP See Plasma vasopressin PB See Barometric pressure PC See Phosphatidylcholine Pegaptanib sodium, 181 Pendred syndrome, 210 Penicillin G and silibinin for muscarinic poisoning treatment, 263 Pepsins, 479 PepT1 See Peptide transporter Peptic ulcer disease, 456 Peptide bonds, formation of, 17–18 Peptide hormones, 299 precursors for, 300 Peptides, 17 Peptide transporter 1, 480 Peptide YY structure, 471 Periaqueductal gray, 173 Pericytes, 671 Perilymph, ionic composition of, 204 Perinuclear cisterns, 43 Periodic breathing, 664 in disease, 665 Periodic limb movement disorder, 276 Periosteum, 384 Peripheral chemoreceptor reflex hemorrhage, 593 Mayer waves, 593 Traube-Hering waves, 593 vasoconstriction, 593 Peripheral nerve damage, 97 Peripheral nerves composition of, 94 sensitivity to hypoxia and anesthetics, 95 Peripheral proteins, 34 in cell membrane, 34 Peristalsis, 502 Peritubular capillaries, 672 Permeability, 677 Permissive effects of glucocorticoids, 363 Peroxisome proliferator-activated receptor γ, 440 Peroxisome proliferator-activated receptors, 38 Peroxisomes, 34, 38 Pertussis toxin effect on cAMP, 60 for peripheral nerve injury treatment, 97 Barrett_Index_p721-756.indd 742 p53 gene mutation, 45 PGES expression See Prostaglandin synthase expression PGH2, 29 pH, 640–641 definition, 4–5 effects on oxygen-hemoglobin dissociation curve, 641 proton concentration and, Phagocytic function, disorders of, 72 Phagocytosis, 46, 68 Phantom limb pain, 171 Pharynx, food movement, 498 Phasic bursting, 312, 313 Phenobarbital, 145 Phenylephrine, 263 Phenylketonuria, 149 Phenytoin, 277 Pheochromocytomas, 356 Phlorhizin, 681 “Phosphate timer,” 54 Phosphatidylcholine, 462, 513 Phosphatidylinositol metabolism in cell membranes, 59 Phosphodiesterase, 59, 117 Phospholipid bilayer, organization of, 35 Phospholipids, 25 Phosphorus magnetic resonance, 713 Phosphorus metabolism, 376 Phosphorylcreatine, 108 Photoreceptor mechanism, 182 Photoreceptor potentials, ionic basis of, 182 Photoreceptors, 159 receptor potentials of, 182 rod and cone, 180, 181 sequence of events in, 183–184 Phototransduction in rods and cones, sequence of events involved in, 183–184 Physiochemical disturbances, 89 Physiological tremor, 231 Physostigmine, muscarinic poisoning treatment by, 263 Piebaldism, 323–324 Pigment abnormalities, 323–324 Pinocytosis, 46 Pituitary gland anatomy of, 322 anterior See Anterior pituitary gland anterior and intermediate lobes of, 308 diagrammatic outline of formation of, 322 functions of, 321 histology of, 322 hypothalamus relation to, 308, 309 Pituitary insufficiency causes of, 334 effects of, 333–334 PKU, 149 Placenta circulation, 614, 615 fetal adrenal cortex, interactions, 413 Planum temporale, 291 Plasma carriers for hormones, 301 dopamine levels, 354 glucose homeostasis, 24 glucose level, 20 factors determining level of, 23–24 nonelectrolytes of, osmolal concentration of, 7–8 Plasma erythropoietin levels, 706 Plasma glucose homeostasis, 436 level, 438, 439 Plasma growth hormone, 330 Plasma hormone concentrations, changes, 397 Plasma K+ level, correlation of, 534 Plasma lipids, 26, 28 Plasma membrane See Cell membrane Plasma osmolality and changes in ECF volume in thirst, 310 plasma vasopressin, relation between, 696 and thirst, link between, 310 Plasma osmolality and disease, Plasma proteins afibrinogenemia, 564 hypoproteinemia, 564 origin of, 563–564 physiologic functions, 563 Plasma renin activity, 701–702 Plasma renin concentration, 702 Plasma testosterone, human male, 396 Plasma vasopressin, 697 mean arterial blood pressure, relation between, 697 plasma osmolality, relation between, 696 Plasticity cortical, 171 of motor cortex, 238 of smooth muscle, 118 synaptic, 143 Platelet-activating factor, 79 Platelets ADP receptors in human, 79 aggregation, 79 clotting factors and PDGF in, 79 cytoplasm of, 79 production, regulation of, 81 response to tissue injury, 79 wound healing role, 79 Pleural cavity, 626 connective fibers, 626 parietal pleura, 626 pleural space, 626 pressure in, 628 visceral pleura, 626 PLMD, 276 PMS See Premenstrual syndrome Pneumotaxic center, 656 Podocytes, 671 Poikilothermic animals, 316 Point mutations, 14 Poly(A) tail, 15 Polydipsia, 698 Polymodal nociceptors, 160 Polypeptides, 17 Polypeptide YY, 445 Polysynaptic reflexes, 229, 234 Polyuria, 690, 698 POMC See Proopiomelanocortin Pontine reticulospinal tracts and posture, 239 Pontogeniculo-occipital (PGO) spikes, 275 Portal hypophysial vessels, 309 Positive feedback loop, 90 Posterior lobe hormones, synthesis of, 311 6/29/15 3:54 PM INDEX Posterior parietal cortex, 238 Posterior pituitary glands, hormones of biosynthesis of, 311 intraneuronal transport of, 311 secretion of, 311–312 vasopressin and oxytocin, 311 Postextrasystolic potentiation, 546 Postganglionic autonomic neurons, 133 Postganglionic neurons, 256 Postsynaptic density, 122, 143 Postsynaptic inhibition, 128 Postsynaptic membrane, receptors concentrated in clusters on, 138 Postsynaptic neurons action potential generation in, 126–127 action potential in See Postsynaptic potentials PSD on membrane of, 143 synaptic endings, 122 Postsynaptic potentials excitatory and inhibitory, 123–125 slow EPSPs and IPSPs, 125 temporal and spatial summation of, 127–128 Posttetanic potentiation, 286 Posttranscriptional modification of polypeptide chain, 18–19 of pre-mRNA, 15–16 reactions in, 18 Posture maintenance brain stem pathways involved in lateral, 240 medial, 239–240 Posture-regulating systems decerebration, 241–243 decortication, 243 Potassium/chloride cotransporter, 465 Potassium ions active transport of, 51 changes in membrane conductance of, 90–91 concentration difference and sodium ions, 91–92 equilibrium potential for, in mammalian spinal motor neurons, and membrane potential, 9, 91 molecular size of, 48 in skeletal muscle, 103 Potential difference, 90 See also membrane potential Power stroke of myosin in skeletal muscle, 104 ΠΠΑΡγ See Peroxisome proliferator-activated receptor γ PPARs, 38 PRA See Plasma renin activity Pralidoxime, 262 PRC See Plasma renin concentration pre-Bötzinger complex, 656 pacemaker cells in, 656 p75 receptors, 96 Precocious/delayed puberty delayed/absent puberty, 398 menopause, 398–399 sexual precocity, 397–398 Precocious pseudopuberty, 397 Precocious sexual development classification of, 397 Precursor proteins, 425 Prednisone for Lambert–Eaton Syndrome treatment, 132 Barrett_Index_p721-756.indd 743 for MS treatment, 88 for myasthenia gravis treatment, 132 Preejection period (PEP), 540 Preganglionic neurons, 256 Pregnancy endocrine changes, 412 fertilization & implantation, 411–412 fetal graft, 411 fetoplacental unit, 413 human chorionic gonadotropin, 412 human chorionic somatomammotropin, 412 infertility, 411–412 parturition, 413 placental hormones, 412–413 uterine blood flow, 614 Pregnenolone, 358 Premature beat, heart, 529 Prematurity, retinopathy of, 652 Premenopausal women, 483 Premenstrual syndrome, 410 Premotor cortex, 238 pre-mRNA, posttranscriptional modification of, 15–16 Preproenkephalin, 355 Prepro-oxyphysin, 311, 312 Prepropressophysin, 311 PreproPTH, 379 Prestin, 207 Presynaptic inhibition comparison of neurons producing, 128 effects on action potential and Ca2+ current, 129 and facilitation, 128 Presynaptic nerve terminals, 87 small synaptic vesicle cycle in, 124 Presynaptic receptor, 138 PRH, 315 Primary adrenal insufficiency, 373 Primary ciliary dyskinesia, 40 Primary colors, 193 Primary evoked potential, 271 Primary hyperaldosteronism, 372 Primary motor cortex, 237 cell organization in, 237 imaging techniques for mapping, 237 location of, 237 motor homunculus and, 237 Primary plexus, 309 Primary somatosensory cortex, 169 Primary structure of proteins, 18 Primary visual cortex, 191–192 connections to sensory areas, 192 distribution in human brain, 192 layers in, 191 nerve cells in, 191 ocular dominance columns in, 191–192 orientation columns in, 191 responses of neurons in, 191 visual projections from, 192 Primordial follicles, 398 Principal cells, 672 Principal digestive enzymes, 461 Proarrhythmic, 532 Proenzymes, 479 Progesterone, biosynthesis of, 407 Programmed cell death See Apoptosis Progressive motility, 420 743 Prolactin actions of, 331–332 components of, 331 functions of, 321 half-life of, 331 secretion, regulation of, 332–333 Prolactin-inhibiting hormone, 315 Prolactin-releasing hormone, 315 Proliferative phase, 401 Proopiomelanocortin, 486 biosynthesis, 323 Proprioceptors, 159 Prorenin, 700 Prosopagnosia, 294 Prostacyclin, 594 Prostaglandin H2, 29 Prostaglandins, 420 pharmacology of, 29 synthesis of, 30 Prostaglandin synthase expression, 672 Prostate, 417 Prostate-specific antigen, 421 Protease-activated receptor-2 (PAR-2) activation, 162 Protein degradation and production, balance between, 19 and ubiquitination, 19 Protein digestion, 479–480 Protein folding, 18 Protein kinases, 53–54 in cancer, 54 in mammalian cell signaling, 54 Protein linkages to membrane lipids, 35 Protein processing, cellular structures involved in, 44 Protein-rich food, 500 Proteins, 489–490, 643 amino acids found in, 18 composition of, 17–18 embedded in cell membrane, 34, 35 in skeletal muscle, 99–100 structure of, 18 ubiquitination of, 19 Protein synthesis activation of, 54–55 definition of, 18 in endoplasmic reticulum, 18 initiation of, 18 mechanism of, 18 quality control in, 44–45 RNA role in, 16–17 Protein translation and rough endoplasmic reticulum, 43 Protodiastole, 538 Proton transport, 11 Proto-oncogenes, 45 Protopathic pain, 161 Protoplasmic astrocytes, 86 Proximal convoluted tubule, 671 Proximal tubule Na+ reabsorption mechanism, 680–681 solutes reabsorption, 681 PRRs, 73–74 PSA See Prostate specific antigen PSD See Postsynaptic density Pseudocholinesterase, 145 Pseudohypoparathyroidism, 63, 381 6/29/15 3:54 PM 744 INDEX Psilocin, 152 Psychosocial dwarfism, 332 PTH See Parathyroid hormone PTHrP See Parathyroid hormone–related protein Puberty, 396 control of onset, 396–397 precocious and delayed, 397–398 Pulmonary alveolar macrophages, 624 Pulmonary arteries/veins, 636–637 Pulmonary chemoreflex, 662 Pulmonary circulation, 627, 628, 635–638 flow, 635 gravity, 635–636 pressure, 635 pulmonary blood vessels, 635 regulation of pulmonary blood flow, 636–637 ventilation/perfusion ratios, 636 volume, 635 Pulmonary fibrosis, 630, 631 Pulmonary hypertension, 636 Pulse, 540 Pulse oximeter, 628 Pupillary light reflexes, 188–189 Purines compounds containing, 12 ring structure of, 12 Purkinje cells, 249 output of, 250 Purkinje fibers, 520, 522 Purkinje system, 519 Pyramidal neurons, 270–271 Pyridostigmine, 262 for myasthenia gravis treatment, 132 Pyrimidines catabolism of, 12 compounds containing, 12 ring structure of, 12 Q QRS vector, 526 Quality control, 44–45 Quantitating respiratory phenomena, 628–629 lung volumes and capacities, 628–629 Quaternary structure of protein, 18 R Radiation, 317 Rafts and caveolae, 46 Raloxifene, 406 Ramelteon, 279 Ranibizumab, 181 RANKL See Receptor activator for nuclear factor kappa beta ligand Rapid auditory processing theory, 292 Rapid eye movement sleep, 273, 664 EEG waves during, 274 PET scans of, 275 phasic potentials, 275 rapid movements of eyes, 275 Rapidly adapting receptors, 662 RAS, 271 Rasagiline for MSA treatment, 256 Rayleigh match, 193 Barrett_Index_p721-756.indd 744 Raynaud disease, 264 Raynaud phenomenon, 264 Rebound phenomenon, 252 Receptive relaxation, 499 Receptor activator for nuclear factor kappa beta ligand, 385 Receptor adaption, 164 Receptor–ligand interaction, 53 Receptor potential, 163 Receptors See also specific receptors desensitization, 139 G-protein–coupled See G-protein–coupled receptors and G-protein diseases, 63, 64 ionotropic, 138 metabotropic, 138 for neurotransmitters and neuromodulators, 138, 141 on nociceptive unmyelinated nerve terminals, 162 on postsynaptic membrane, 138 presynaptic, 138 proteins as, 35 rapidly adapting, 164 slowly adapting, 164 and transmitters, 138, 139 Reciprocal innervation, 232, 655 Recovery heat, 110 Recruitment of motor units, 234 Rectum distention of, 504 responses to distention of, 504 Red blood cells characteristics, 555, 557 fibrin fibrils, 557 formation and destruction, 555, 557 5α-Reductase deficiency, 395 Reduction, 11 Referred pain, 168 Reflex arc activity in, 228 components of, 228 monosynaptic reflexes, 229 polysynaptic reflexes, 229 Reflexes general properties, 228 and semireflex thermoregulatory responses, 318 spinal integration of, 234–235 stimulus for, 228 Reflex ovulation, 409 Reflex sympathetic dystrophy, 166 Refraction, 186 Refractive power, 186 Refractory period, neuron, 93 Regulatory elements, of gene, 14 Relaxation volume, 629 Relaxed (R) configuration, 640 Relaxin, 326, 407–408 REM sleep See Rapid eye movement sleep Renal circulation, 674–676 Renal failure, acute, 547 Renal function, 671–691 abnormal Na+ handling, 691 acidosis, 691 adrenocortical steroids effects, 690 aquaporins, 683 bladder, 691–693 bladder emptying, 691–692 bladder filling, 691 blood flow, 674–675 blood vessels, 672–673 capillary bed size, 678 capsule, 673 collecting ducts, 684–685 concentrating ability, 690–691 countercurrent mechanism, 685–686 deafferentation effects, 693 denervation effects, 693 diluting ability, 690–691 disordered renal function effects, 690–691 distal tubule, 684 diuretics, 689–690 filtration fraction, 678 free water clearance, 688 functional anatomy, 671–674 glomerular filtration, 676–679 glomerular filtration rate (GFR), 676–677 glomerular filtration rate (GFR), changes in, 678 glomerular filtration rate (GFR), control of, 677 glomerulotubular balance, 682–683 glucose reabsorption, 680–681 glucose transport mechanism, 681 humoral effects, 688–689 hydrostatic pressure, 678 K+ excretion, regulation, 689 loop of Henle, 683–684 lymphatics, 673 Na+ excretion, regulation, 688–689 Na+ reabsorption, 679–680 nephron, 671–672 osmotic diuresis, 686–687 osmotic pressure, 678 oxygen consumption, 676 PAH transport, 681–682 permeability, 677 proximal tubule, 683 reflex control, 692–693 regional blood flow, 676 renal blood flow autoregulation, 676 renal blood flow regulation, 675 renal circulation, 674–676 renal nerves functions, 675–676 renal vessels innervation, 673–674 renal vessels pressure, 675 secondary active transport, additional examples, 681 spinal cord transection effects, 693 tubular function, 679–688 tubular reabsorption & secretion mechanisms, 679 tubuloglomerular feedback, 682–683 urea role, 686 uremia, 691 urine concentration relation, 687–688 water diuresis, 689 water excretion, regulation, 89 water intoxication, 689 water transport, 683 Renal glucose transport, 681 Renal H+ secretion, 709–713 ammonia secretion, 712 6/29/15 3:54 PM INDEX bicarbonate excretion, 713 body fluids principal buffers, 714 factors affecting acid secretion, 712 Na–H exchanger, 709 pH changes, 712 pH of body fluids, 714 reaction with buffers, 711–712 in urine, 712–713 Renal hypertension, 704 Renal interstitial pressure, 673 Renal medullary interstitial cells, 672 Renal physiology, 669 Renal plasma clearance, 676–677 Renal plasma flow, 674 Renal principal cell, 689 Renal threshold, 680 Renal tubular acidosis, 691 Renin and aldosterone secretion, 370–371 Renin-angiotensin system, 700–704 angiotensin-converting enzyme & angiotensin II, 700–701 metabolism of, 701–702 receptors, 702–703 angiotensinogen, 700 angiotensins, actions of, 702 pharmacologic manipulation of, 701 renin, 700 renin secretion, regulation of, 703–704 summary of, 699 tissue renin-angiotensin systems, 702 Renin secretion conditions, 704 factors, 703 regulation of, 703–704 Renin substrate, 700 amino terminal end of, 701 Renorenal reflex, 674 Replication, 15 Representational and categorical hemispheres, lesions of, 291 Reproductive abnormalities, 411 Reserpine, 150 Residual volume, 629 Respiration, 619 acid–base balance, ventilatory responses to changes in, 659 airway resistance, 630 alveolar surface tension, surfactant role, 630–631 baroreceptor stimulation, respiratory effects of, 663 blood flow, 632 brain stem, chemoreceptors in, 659 breath holding, 661–662 breathing, work of, 632 carotid & aortic bodies, 658–659 chemical control, 657 chemical control of breathing, 657–662 chest wall, 629–632 compliance of lungs, chest wall, 629–632 control systems, 655–656 CO2 response, H+ effect, 661 CO2 response curve, hypoxia effects on, 661 coughing & sneezing, 662 dead space, 632–633 exercise effects, 664–666 Barrett_Index_p721-756.indd 745 expiration, 628 inspiration, 628 lung capacities, 628–629 lungs, responses mediated by receptors in, 662 lung volumes, 628–629 medullary systems, 656 movement in, 626 muscles, 624–626 neural control of breathing, 655–656 nonchemical influences on, 662–664 oxygen deficiency, ventilatory response to, 660–661 pontine & vagal influences, 656 pressure-volume curves in, 629–630, 631 proprioceptors, afferents from, 662–663 quantitating phenomena, 628–629 regulation of, 655–656 regulation of respiratory activity, 656–657 respiratory abnormalities, 664 sleep, effects of, 664 uneven ventilation, 632–633 ventilation, 632 ventilatory responses to CO2, 660 visceral reflexes, respiratory components of, 663 Respiration at birth, 616 Respiratory acidosis, 645, 659, 712, 715 Respiratory alkalosis, 645, 659 Respiratory burst, 68 Respiratory center, stimuli affecting, 657 Respiratory compensation, 646, 715 Respiratory control pattern generator, 656 Respiratory enzyme pathway, 109 Respiratory exchange ratio, 487 Respiratory minute volume, 629 Respiratory muscles, 624–626, 632 Respiratory quotient, 487–488 Respiratory system, 634 partial pressures of gases, 634 pressure-volume curve, 629–630, 631 Respiratory tract alveolar airway, 621 conducting airway, 621 regions of, 621 upper airway, 621 Resting heat, 110 Resting membrane potential, 90 of cardiac muscle, 113 of hair cells, 204 Reticular activating system, 271 Reticuloendothelial system, 69 Reticulospinal tracts, 239 Retina blood vessels, 180 layers, 178 melanopsin, 184 neural components of extrafoveal portion of, 179 pigment epithelium, 180 potential changes initiating action potentials in, 182 receptor layer of, 180 visual information processing in, 185 Retinal, 183 Retinal ganglion cells projections to right lateral geniculate body, 190 745 response to light focused on receptive fields, 185 types of, 190 Retinohypothalamic fibers, 278 Retinoid X receptor, 346 Retrograde amnesia, 286 Retrograde transport, 89 Retrolental fibroplasia, 652 Reuptake catecholamines, 149 definition of, 139 of norepinephrine, 139 Rhodopsin, 183 structure of, 183 Ribonucleic acids and DNA, difference between, 15 production from DNA, 15 role in protein synthesis, 15 types of, 15 Ribosomes, 34, 44 Rickets, 378 Rigor mortis, 109 Riluzole, 142 for ALS treatment, 240 Rituximab for MS treatment, 88 RMICs See Renal medullary interstitial cells RMV See Respiratory minute volume RNA See Ribonucleic acids Rod photoreceptor components of, 180 Rod receptor potential, 182 Rods density along horizontal meridian, 182 photosensitive pigment in, 183 schematic diagram of, 181 sequence of events involved in phototransduction in, 183–184 Rotational acceleration, responses to, 210–211 Rough endoplasmic reticulum and protein translation, 43 RPF See Renal plasma flow RQ See Respiratory quotient Rubrospinal tract, 240 Ruffini corpuscles, 160 RV See Residual volume Ryanodine receptor, 104 S Saline cathartics, 466 Saliva, 454 Salivary α-amylase, 476 Salivary glands, 454 Salivary secretion, 454–455 regulation of, 456 Saltatory conduction, 94 Salt-sensitive taste, 224 SA node See Sinoatrial node Sarcomere, 101 Sarcotubular system components of, 101–102 T system and, 101–102 Satiety factor, 486 SBP, 301 Scala tympani, 200 Scala vestibuli, 200 6/29/15 3:54 PM 746 INDEX SCFAs See Short-chain fatty acids Schizophrenia, 150 Schwann cells, 86, 97 SCI, 235 Sclera, 177 SDA See Specific dynamic action Sealing zone, 385 Secondary active transport, 51 Secondary adrenal insufficiency, 373 Secondary hyperaldosteronism, 372 Secondary sex characteristics, 423 Secondary structure of protein spatial arrangement, 18 β-Sheets, 18 Second messengers cyclic AMP, 59–60 diacylglycerol as, 58, 59 effect on aldosterone secretion, 373 effect on Na, K ATPase pump activity, 51 inositol trisphosphate as, 57–58 intracellular Ca2+ as, 55 phosphorylation and, 53–54 in regulation of aldosterone secretion, 373 short-term changes in cell function by, 53 Secretin, 460 Secretory immunity, 78, 481 Segmentation contractions, 502 Seizures EEG activity during, 277 genetic mutations and, 277 partial/generalized, 276 treatment of, 277–278 types of, 276–277 Selectins, 40, 68 Selective dorsal rhizotomy, CP treatment by, 236 Selective estrogen receptor modulators, 406 Semantic memory, 284 Semen, 420 Seminiferous epithelium, 419 Seminiferous tubule dysgenesis, 395 Seminiferous tubules, 417 Senile dementia, 289 Sensitization and habituation, 286 Sensorineural and conduction deafness, tests for comparing, 211 Sensorineural hearing loss, 209 Sensory association area, 170 Sensory coding definition, 163 duration, 161, 164–165 intensity of sensation, 161, 164 location, 161, 163–164 modality, 161, 163 neurological exam, 164, 165 Sensory homunculus, 170 Sensory modalities, 159, 160 Sensory nerve fibers, numerical classification of, 95 Sensory receptors in ear, 202 as transducers, 159 Serial electrocardiographic patterns, diagrammatic illustration of, 533 SERMs See Selective estrogen receptor modulators Serotonergic receptors, 152 classes of, 152 Barrett_Index_p721-756.indd 746 functions of, 152, 154 pharmacology of, 152 Serotonergic synapses, 152 Serotonin, 501 biosynthesis, 151–152 chemistry of, 138, 139 pharmacology of, 141 synthesis of, 141 Serotonin reuptake inhibitors, 152 Serpentine receptors See G-protein–coupled receptors Sertoli cells, 417 Serum dehydroepiandrosterone sulfate (DHEAS), changes in, 362 Seven-helix receptors See G-protein–coupled receptors Sex chromosomes, defects, 396 Sex chromosomes, nondisjunction of, 394 Sex determination, diagrammatic summary of, 394 Sex differentiation disorders, 395 Sex hormone–binding globulin, 301 Sex hormones, 389, 417 Sex steroid-binding globulin, 422 Sex steroids in women, 405 Sexual excitement, 402 SFO See Subfornical organ SGLT See Sodium-dependent glucose transporter SHBG, 301 Shock, 547 hypovolemic, 547 low-resistance, 547 obstructive, 547 treatment of, 547 Short-chain fatty acids, 483 “Short-circuit” conductance, 26 Short gut syndrome, 489 Short-term memory, 285 Shy-Drager syndrome, 256 SIADH See Syndrome of “inappropriate” hypersecretion of antidiuretic hormone Sickle cell anemia, 560 Sick sinus syndrome, 527 Siggaard–Andersen curve nomogram, 716–717 Signal hypothesis, 19 Signal peptide, 18, 43, 44 Signal recognition particle, 18–19 Signal transduction in odorant receptor, 219–220 in taste receptors, 222–224 via JAK-STAT pathway, 61–62, 63 Sinemet for Parkinson disease treatment, 247 Single-breath N2 curve, 633 Sinoatrial node, 519 membrane potential of, 521 Sinus arrhythmia, 527 in young/old man, 527 Sinus bradycardia, 527 Skeletal muscles actin and myosin arrangement in, 101 body movements and, 111 contractile mechanism in, 99–100 contraction of See Contraction, muscular cross-striations in, 101 denervation of, 110 electrical characteristics, 102–103 ion distribution and fluxes in, 103 length–tension relation in, 107–108 mammalian, 100 mechanical efficiency of, 109 in middle ear, 200 motor unit, 109 muscle fibers in, 99 pathway linking CNS to, 256 proteins in, 99–100 relaxation of, 264–265 strength of, 111 Skin coloration, control of, 323–324 Sleep effects of, 664 importance of, 275 Sleep apnea, obstructive, 665 Sleep disorders, 276 Sleep stages distribution of, 275 NREM sleep, 273–274 REM sleep, 273 EEG waves during, 274 PET scans of, 275 phasic potentials, 275 rapid movements of eyes, 275 Sleep–wake cycle, 272–273 alpha rhythm, 273 beta rhythm, 273 EEG and muscle activity during, 274 sleep stages, 273–274 thalamocortical loops and, 273 Sleep–wake state melatonin and, 279–280 neurochemical mechanisms promoting, 278 GABA, 278, 279 histamine, 278, 279 melatonin, 279–280 midbrain reticular formation, 278 RAS neurons, reciprocal activity, 278, 279 transitions between, 278 Sleepwalking, 276 Slowly adapting receptors, 662 Small-conductance calcium-activated potassium (SK) channels, 240 Small G-proteins, 44, 56 Small intestine chloride secretion in, 466 intestinal motility, 502 transit time, 503–504 Small-molecule neurotransmitters biosynthesis of, 139 excitatory and inhibitory amino acids acetylcholine, 145 acetylcholine receptors, 146–147 cholinergic receptors, 146–147 GABA, 144–145 glutamate, 140–144 glycine, 145 monoamines adrenoceptors, 149–150 ATP, 153 catecholamines, 148–149 dopamine, 150 epinephrine, 147 histamine, 153 noradrenergic synapses, 150 norepinephrine, 147 6/29/15 3:54 PM INDEX secreted at synaptic junctions, 142 serotonergic receptors, 152 serotonergic synapses, 152–153 serotonin, 151–152 with neuropeptides, 138 Smell adaptation and, 221 classification of, 217 odorant-binding proteins and, 220 odorant receptors and, 219–220 odor detection threshold, 220 olfactory cortex function in See Olfactory cortex olfactory epithelium See Olfactory epithelium signal transduction and, 219–220 Smooth muscle contraction of calmodulin-dependent myosin light chain kinase activity, 116 Ca2+ role in, 116 chemical mediators effect on, 116–117 sequence of events in, 116 drugs acting on, 117 effects of agents on membrane potential of, 116–117 electrical activity of, 115–116 force generation of, 118 mechanical activity of, 115–116 nerve endings in, 132 nerve supply to, 117–118 overexcitation in airways, 117 plasticity of, 118 postganglionic autonomic neurons on, 133 relaxation of cellular mechanisms linked with, 117 skeletal and cardiac muscle, comparison of, 115 striations in, 114 types of, 115 of uterus, oxytocin effect on, 313 Sneezing, 662 SOCCs, 55 Sodium-dependent glucose transporter, 478 Sodium/hydrogen exchanger, 465 Sodium ions active transport of, 51 changes in membrane conductance of, 90–91 concentration difference and potassium ions, 91–92 in mammalian spinal motor neurons, molecular size of, 48 in skeletal muscle, 103 Sodium–potassium adenosine triphosphatase (Na, K ATPase) in active transport, 48, 51 α and β subunits of, 49–51 ATP hydrolysis by, 49 cell volume and pressure dependence on, 8–9 electrogenic pump, 49 heterodimer, 49 ion binding sites, 51 regulation of, 51 structure of, 49 Solutes, normal clearance values of, 677 Somatic cell division, 15 Somatic chromosomes, 390 Somatic motor activity, 227 Barrett_Index_p721-756.indd 747 Somatic nervous system, 257 Somatomedins polypeptide growth factors, 325 principal circulating, 325–326 relaxin isoforms, 326 Somatomotor nervous system and ANS, difference between, 264 Somatosensory pathways, 168 cortical plasticity, 171 dorsal column pathway, 164, 168–170 effects of CNS lesions, 172 ventrolateral spinothalamic tract, 170–171 Somatostatin, 154, 429, 471 for acromegaly, 326 Somatotopic organization, 168–170 Somatotropes, 322 Somnambulism, 276 Sound definition of, 204 localization, 208–209 loudness and pitch of, 205 transmission of, 205–206 Sound frequencies audible to humans, 205 Sound waves amplitude of, 205 characteristics of, 204 conduction of, 205–206 definition of, 204 SP See Surfactant protein Spastic CP, 236 Spastic neurogenic bladder, 693 Spatial summation, 127–128 Specific dynamic action, 488 Specific ionic composition, defense of, 706 Spermatogenesis, 417, 420 Spermatogonia, 418 Spermatozoon, ejaculation of, 420 Spherical follicle, 337–338 Sphincter of Oddi, 508 Sphincters, 453 Spinal cord, transection of, 235 Spinal cord injury, 234 Spinal cord stimulation, 171 Spinal motor neuron, 110 negative feedback inhibition of, 129 Spinal reflex, 228 Spinal shock, 234 Spinnbarkeit, 402 Spinocerebellum, 250 Spiny stellate cells, 271 Splanchnic circulation See also Gastrointestinal circulation schematic of, 473 SRP, 18–19 SSRIs, 152 Standard limb leads, 522, 524 StAR protein See Steroidogenic acute regulatory protein Stellate cells, 249 Stem cells, factors stimulating production of, 71 Stenosis, 542 Stereocilia, 202 Stereognosis, 164 Steroid binding proteins, 301 Steroid biosynthesis, 358–359 enzyme deficiencies effect on, 359–360 intracellular pathway of, 354 747 precursor of, 358 Steroid hormones, thyroid and, difference between, 300 Steroidogenic acute regulatory protein in adrenals and gonads, 360 functions of, 300 regulation of steroid biosynthesis by, 301 Steroid-secreting cells, structures of, 354 Sterols, 25 Stokes–Adams syndrome, 528 Stomach, 499–501 acid-secreting cells of, 468 anatomy of, 457 gastrointestinal motility, 500 regulation of, 500 glandular secretions of, 457 small intestine intestinal motility, 502 vomiting, 500–501 Store-operated Ca2+ channels, 55 Strabismus, 187 Strangeness and familiarity, 289 Stratum functionale, 401 Strength-duration curve, 92 Stress, glucocorticoids effects on, 364 Stress-induced analgesia, 173 Stretch reflexes, 229 pathways responsible for, 231 reciprocal innervation and, 232 Stretch reflex-inverse stretch reflex sequence, 233 Striations in cardiac muscle, 111–112 Striations in skeletal muscle identification by letters, 101 thick filaments, 101 thin filaments, 101 Stroke volume, 544 Structural lipids, 26 Subcortical structures and navigation in humans, 294 Subfornical organ, 702 Submucous plexus, 472 Substance P, 138, 153, 161, 472 Substantia nigra, 243 Sucrose, 476 Sugars, intestinal transport of, 479 Superior cerebellar peduncle, 248 Superior colliculi, 196 Supplementary motor area, 237–238 Suppressor strip, 242 Suprachiasmatic nuclei (SCN), circadian activity of, 278 Surface tension, 623–624 Surfactant, 623–624, 631 Surfactant protein, 622, 631 Surgical approach for acromegaly and gigantism, 326 for Parkinson disease treatment, 247 Swallowing, 498 Sweet-responsive receptors, 224 Sweet taste, 224 Sympathetic activation, 265 Sympathetic innervations, 265 Sympathetic nervous system sympathetic preganglionic and postganglionic fiber projection in, 257 as thoracolumbar division of CNS, 256–257 Sympathetic noradrenergic discharge, 265 6/29/15 3:54 PM 748 INDEX Sympathetic paravertebral ganglion, 257 Sympathetic preganglionic and postganglionic fibers projection of, 257 Sympathomimetic drugs, Horner syndrome treatment by, 263 Sympathomimetics, 150 Symport, 478 Synapses anatomic structure of, 122 cell-to-cell communication via, 121 in cerebral and cerebellar cortex, 122 facilitation at, 128 inhibition at in cerebellum, 130 inhibitory systems for, 129–130 postsynaptic and presynaptic, 128 on motor neuron, 122 transmission of action potential, 121 Synaptic delay, 124 Synaptic elements, functions of, 122–123 Synaptic junctions, electrical transmission at, 125 Synaptic knob, 87 electron micrograph of, 122 Synaptic physiology, 140 Synaptic plasticity and learning, 286 Synaptic transmission, 121 Synaptic vesicles docking and fusion in nerve endings, 124 kinds of, 122 neurotransmitter storage in, 137 transport along axon, 122–123 Synaptobrevin, 123 cleavage by botulinum toxin, 125 Synaptosome-associated protein (SNAP-25) cleavage by botulinum toxin, 125 Syncope, 592 Syncytiotrophoblast, 411 Syndrome of “inappropriate” hypersecretion of antidiuretic hormone, 698 Syndromic deafness, 210 Syntrophins, 102 Systemic response to injury, 82 System mediating acquired immunity, 70, 71 Systolic dysfunction, 546 effect of, 548 Systolic failure, 538 Systolic pressure, 537 T T3 See Triiodothyronine T4 See Thyroxine Tabes dorsalis, 693 Tachycardia, 527 Tachycardias, 527 Tachypnea, 647 Tactile agnosia, 164 Tamoxifen, 302, 406, 415 Tardive dyskinesia, 246 Taste classification of, 217 reactions and contrast phenomena, 224–225 sense organ for See Taste buds Taste buds basal cells, 221, 222 Barrett_Index_p721-756.indd 748 fungiform papillae, 222 innervation, 221 in papillae of human tongue, 222 types of, 221 Taste detection, abnormalities in, 224 Taste modalities receptors for, 222–224 types of, 222–223 Taste pathways, 222, 223 Taste receptors signal transduction in, 222–224 types of, 222 Taste threshold definition of, 224 and intensity discrimination, 224–225 of substances, 224 Taxol, 38–39 TBG concentration and thyroid hormones, 342 TBI, 284 T cell receptors, 76–77 T cells activation in acquired immunity, 71, 76–77 CD8 and CD4 proteins on, 76 maturation, sites of congenital blockade of, 81 polypeptides of circulating, 76 types of, 69–70 T channels, 521 Temperature, 640 effects on oxygen-hemoglobin dissociation curve, 641 Temperature regulation, 316–320 mechanisms for, 318–319 Temporal lobe memory, 285 Temporal summation, 127–128 Tenotomy, CP treatment by, 236 Tense (T) configuration, 640 Tertiary adrenal insufficiency, 373 Tertiary structure of protein, 18 Testes, endocrine function of actions, 422–423 anabolic effects, 423 estrogens, testicular production of, 424–425 inhibins, 425 mechanism of action, 423–424 secondary sex characteristics, 423 secretion, 422 steroid feedback, 425–426 testosterone, chemistry/biosynthesis of, 421–422 transport/metabolism, 422 Testicular descent, 426 Testicular feminizing syndrome, 395 Testicular function, abnormalities of androgen-secreting tumors, 426 cryptorchidism, 426 hormones and cancer, 426 male hypogonadism, 426 Testosterone, 417, 423–424 biosynthesis of, 421–422 17-ketosteroid metabolites of, 422 schematic diagram of, 423 Testosterone-receptor, 424 Testosterone secretion rate, 422 Testotoxicosis, 63 Tetanic contraction, 105 Tetanus, 105, 107 Tetanus toxins, 125 Tetanus toxoid vaccine, 125 Tetrabenazine, 246 TG See Triglycerides TGF-α, 52 TGF-β, 74 Thalamic pain syndrome, 172 Thalamocortical loops, 273 Thalamostriatal pathway, 244 Thalamus division of, 269 functions of, 269 sensory relay nuclei, 270 ventral anterior and ventral lateral nuclei, 270 Theca interna, 399 Theca interna cells, interactions, 404 Thermal gradient, 317 Thermal nociceptors, 160 Thermodilution, 543 Thermoreceptors, 159 threshold for activation of, 162 Thermoregulatory responses in humans, 318–319 Thiazolidinediones, 440 Thioridazine, 181 Thioureylenes, hyperthyroidism treatment by, 345 Thirst, 310 Thrombocytopenic purpura, 81 Thrombopoietin, 81 Thromboxane A2, 594 Thymectomy, myasthenia gravis treatment by, 132 Thymidine–adenine–thymidine–adenine (TATA) sequence, 14 Thyrocytes basolateral membranes of, 339 iodide transport across, 339 Thyroglossal duct, 337 Thyroid cell, 338 Thyroid gland anatomy of, 337–338 histology of, 338 lobes of, 337 spherical follicle, 337–338 Thyroid growth, factors affecting, 343 Thyroid hormones, 383 biological activity of, 338 calorigenic action of, 346–347 effect on Na, K ATPase pump activity, 51 fluctuations in deiodination, 342 iodine homeostasis and, 338–339 mechanism of action of, 345–346 metabolism of, 342 physiologic effects on, 345, 346 brain, 348 carbohydrate metabolism, 348 cardiovascular system, 347–348 catecholamines, 348 cholesterol metabolism, 348 nervous system, 348 normal growth, 348 skeletal muscle, 348 secretion, regulation of, 343–345 steroids and, difference between, 300 synthesis and secretion, 339–341 transport of, 341–342 6/29/15 3:54 PM INDEX Thyroid-stimulating hormone chemistry and metabolism of, 343 deficiency, 334 effect on thyroid, 343 secretion in cold, 318 Thyroid-stimulating immunoglobulins, 305 Thyrotropin-releasing hormone, 314 functions of, 315 Thyroxine, 338 calorigenic effect of, 346–347 mechanism of action of, 345–346 metabolism of, 342 plasma level in adults, 341 protein binding, 341 Tibialis muscular dystrophy, 102 Tickle, 161, 162 Tidal volume, 628 Tight junctions, 41 Tip links, 202 schematic representation of, 203 Tissue conductance, 318 Tissue macrophage system, 69 Titin in skeletal muscle, 101, 102 Titratable acid, 711 Tizanidine, ALS treatment by, 240 TLRs, 73 Toll-like receptors, 73 Tonic-clonic seizure, 277 Tonic contractions, 502 Tonicity, 7–8 Tonicity, defense of, 695 clinical implications, 698 metabolism, 696 synthetic agonists/antagonists, 698 vasopressin, effects of, 696 vasopressin receptors, 695 vasopressin secretion control of, 696–697 stimuli, variety of, 698 volume effects on, 697–698 Topiramate, 277 for alcohol addiction, 174 for chronic pain, 166 Torsades de pointes, 530 Total blood volume, Total body calcium, 386 Total lung capacity, 629 Trabecular bone, structure of, 384 Transamination reactions, citric acid cycle in, 19, 20 Transcellular fluids, Transcription, 15–16, 54 activation of, 54 definition, 15 diagrammatic outline of, 16 into pre-mRNA, 15–16 Transcytosis, 52 Transducin, 184 Transepithelial transport, 51 Transferrin, 484 Transforming growth factor alpha, 52 Transforming growth factor beta, 74 Transient receptor potential channels, 161 Transient sleep disorders, 279 Translation See Protein synthesis Transmembrane proteins in cell membrane, 34, 35 Barrett_Index_p721-756.indd 749 signal peptide, 18 in tight junctions, 41 Transmitter chemistry of, 138–139 endogenous cannabinoids, 155 hypersensitivity of postsynaptic structure to, 134 nitric oxide, 154 quantal release of, 131 receptors and, 138, 139 Transport proteins, 47, 680 See also Membrane transport proteins Traumatic brain injury, 284 Traveling waves movement in cochlea, 206–207 schematic representation of, 206 TR genes, 345–346 TRH See Thyrotropin-releasing hormone TRH-secreting neurons, 315 Triacylglycerols, 25 Tricarboxylic acid cycle See Citric acid cycle Trichromats, 193 Tricyclic antidepressants, 150 Triglyceride, 483 Triglycerides (TGs), 25 Triiodothyronine, 338 calorigenic effect of, 346–347 mechanism of action of, 345–346 metabolism of, 342 plasma level in adults, 341 protein binding, 341 Trinucleotide repeat diseases, 45, 245 tRNA-amino acid-adenylate complex, 18 tRNA for amino acids, 18 Troglitazone (Rezulin), 440 Trophic action, 468 Tropic hormones, 321 Tropomyosin in skeletal muscle, 101 Troponin, 56, 100 Trousseau sign, 380 TRP channels, 161 True hermaphroditism, 394 Tryptophan hydroxylase in CNS, 151 TSH See Thyroid-stimulating hormone TSH receptor, 343 TSIs, 305 T tubule, 104, 106 Tubular function, 679–688 Tubular myelin, 623 Tubular reabsorption, 669 Tubular secretion, 669 Tubuloglomerular feedback, 682 Tumor suppressor genes (p53 gene), 45 Turner syndrome See Ovarian agenesis Turnover rate of endogenous proteins, 17 Two-point threshold test, 164 Tympanic membrane, 199 movements of, 206 Type diabetes mellitus, 305 Type diabetes mellitus, 305 Typical depression, 152 Tyrosine kinase activity, 434 Tyrosine kinase associated (Trk) receptors, 96 Tyrosine kinases, diagrammatic representation of, 61 Tyrosine phosphatases, diagrammatic representation of, 61 749 U Ubiquitination definition, 19 and protein degradation, 19 of proteins, 19 Ultrasonography, 514 Umami taste, 224 Uncal herniation, 243 Uncompensated metabolic acidosis, 645 Uncompensated respiratory alkalosis, 645 Unconditioned stimulus, 288 Unipolar electrocardiographic leads, 524 Unipolar recording, 522 Uniports, 48 Units for measuring concentration of solutes, Upper motor neuron lesion, 233 Upper motor neurons, 238, 240 damage to, 240 Urea, 686 Urea cycle, 512 Urea formation enzymes involved in, 19–20 in liver, 20 precursor for, 19 Uremia, 547 Uric acid, 12, 13 excretion on purine-free diet, 12 synthesis and breakdown of, 12 Urinary pH changes implications of, 712 Urine, 714 Urotensin-II, 598 US, 288 Uterine circulation, 614 Uterine musculature sensitivity to oxytocin, 313 V Vagal outflow, 458 Valproate, 277 Valsalva maneuver bradycardia, 591 diagram of response to straining, 591, 592 heart rate, 593 hyperaldosteronism, 593 intrathoracic pressure, 591 tachycardia, 591 Vasa recta, 672 Vascular endothelial growth factor, 399 Vascular link between hypothalamus and anterior pituitary, 308, 309 Vascular reactivity, 363 Vascular smooth muscle contraction and relaxation, 567–568 latch-bridge mechanism, 567 Vas deferens, 417 Vasectomy, 421 Vasoactive intestinal polypeptide, 264, 497, 514 Vasopressin, 138, 154, 304, 683, 696 physiologic effects, 313 Vasopressin, effects of, 696 Vasopressin escape, 698 Vasopressin receptors, 313, 695 Vasopressin-secreting neurons stimulation of, 312 in suprachiasmatic nuclei, 313 6/29/15 3:54 PM 750 INDEX Vasopressin secretion control of, 696–697 osmotic pressure and, 695 stimuli, variety of, 698 stimuli affecting, summary of, 696 volume effects on, 697–698 Vasospasm, 401 VEGF See Vascular endothelial growth factor Venous circulation, 580–581 Venous pressure and flow, 580 air embolism, 581 effects of heartbeat, 580 muscle pump, 580 thoracic pump, 580–581 venous pressure measurement, 581 Venous-to-arterial shunts, 649 Ventilation, 632 alveolar, variations effect in respiratory rate, 633 uneven, 632–633 Ventilation/blood flow comparison, 650 Ventilation-perfusion imbalance, 649–650 Ventilation/perfusion ratio, 636 Ventricle, left, normal pressure-volume loop of, 540 Ventricular ejection, 538 Ventricular fibrillation, 530 Ventricular muscle, comparison of, 521 Ventricular premature beats, 530 Ventricular systole, 519, 537 start of, 538 Ventrolateral spinothalamic tract, 170–171 Venules and veins, 570 Vertebrates, body temperature of, 316 Very low-density lipoproteins, 28 Very low density lipoproteins, 490 Vesicle transport and coat complex, 47 Vesicular monoamine transporter, 139, 149 Vesicular traffic, 44 small G-proteins of Rab family and, 47 Vessels brain capillaries, 602 cerebral ischemia, 601 cerebrospinal fluid, 602 circle of Willis, 601 paravertebral veins, 601 relation of fibrous astrocyte, 602 transport across cerebral capillaries, 602 vertebral arteries, 601 Vestibular labyrinth, 212 Vestibular system ampullary responses to rotation, 211 division of, 209 responses to linear acceleration, 211–212 responses to rotational acceleration, 210–211 spatial orientation, 212 vestibular apparatus, 209 vestibular nuclei, 209 Vestibulocerebellar output, 250–251 Vestibulocerebellum, 250 Vestibulospinal tracts, medial and lateral, 239–240 Vibratory sensibility, 164 Villus sampling, chorionic, 395 VIP See Vasoactive intestinal polypeptide Barrett_Index_p721-756.indd 750 VIPomas See VIP-secreting tumors VIP-secreting tumors, 471 Virilization, 360 Visceral and deep pain, 167 Visceral reflexes, respiratory components of, 663 Visceral sensation, 171 Visual acuity, 181 Visual fields, 194–195 Visual function binocular vision, 194–195 critical fusion frequency, 194 dark adaptation, 194 eye movements, 195–196 superior colliculi, 196 visual fields, 194–195 Visual information processing, 185 Visual pathways, 207–208 Visual pathways and cortex, responses in cortical areas concerned with vision, 192–193 effect of lesions, 190–191 neural pathways, 189–190 primary visual cortex, 191–192 Visual projection areas in human brain, 192 Vital lung capacity, 629 Vitamin A deficiency, 183 Vitamin D formation and hydroxylation of, 377–378 metabolites of, 377–378 Vitamin D-binding protein (DBP), 375 Vitamins, 490 human nutrition, 490–492 Vitamins, absorption of, 483 Vitiligo, 324 VLDL See Very low density lipoproteins VMAT, 139, 149 Voltage-gated Ca2+ channels Ca2+ influx by, 104–105 in cardiac myocytes, 113 Voltage-gated K+ channels, 48–49 feedback control in, 91, 92 opening and closing of, 90–91 sequential feedback control in, action potential, 91–92 Voltage-gated Na+ channels feedback control in, 91, 92 response to depolarizing stimulus, 90–91 sequential feedback control in, action potential, 91–92 spatial distribution of, 93 Volume conductor, 522 Voluntary movement brain stem pathways involved in lateral, 240 medial, 239–240 control of, 237 corticospinal and corticobulbar system role in, 239 Vomeronasal organ, 219 Vomiting, 500–501 neural pathways, 501 von Willebrand factor, 79 VPB See Ventricular premature beats Vulnerable period, 530 W Warmth receptors, 162 Waterfall effect, 636 Water-hammer pulse, 540 Water intake factors influencing, 310 plasma osmolality and changes in ECF volume effect on, 310 psychologic and social factors effect on, 311 Water metabolism, actions of glucocorticoids on, 364 Water metabolism and pituitary insufficiency, 333–334 Water molecule dipole moment, hydrogen bond network in, molecular weight of, 48 Weak acid, buffering capacity of, Weak base, buffering capacity of, Wenckebach phenomenon, 528 Wernicke area, 207 White blood cells cells grow, 554–557 cellular elements, 555 production of, 71 White fat depots, 26 White rami communicans, 257 Whole body ammonia homeostasis, 512 Wilson disease, 246 Withdrawal reflex, importance of, 234 Wolff-Chaikoff effect, 344 Wolff-Parkinson-White syndrome, 531, 532 Working memory, 285, 288 Wound healing, 82 X X chromosomes, 390 Xerophthalmia, 183 Xerostomia, 455 Y Yawning, 663 Y chromosomes, 390 Young–Helmholtz theory of color vision, 193 Z Ziconotide for chronic pain, 166 Zinc deficiency, 490 Zollinger–Ellison syndrome, 382 Zolpidem, 279 Zona fasciculata, 352 Zona glomerulosa, 352 Zona pellucida, 411 Zona reticularis, 352 Zonula adherens, 41 Zonula occludens, 41 Zymogen granules, 460 6/29/15 3:54 PM ... absorption of fats Barrett_CH25_p451-474.indd 4 62 120 90 (HCO3−) 60 (CI−) 30 (Amylase) (K+) 20 −10 +10 +20 +30 +40 Time (min) Volume of secretion (mL) 0.3 0 .2 17.7 15 .2 5.1 0.6 FIGURE 25 – 12 Effect of. .. Paterson CR: Textbook of Physiology and Biochemistry, 9th ed Churchill Livingstone, 1976.) 6 /27 /15 4:35 PM CHAPTER 25   Overview of Gastrointestinal Function & Regulation 461 TABLE 25 2 Principal digestive... 6 /27 /15 4:35 PM 4 62 SECTION IV  Gastrointestinal Physiology TABLE 25 –3  Composition of normal human pancreatic juice Secretin 12. 5 units/kg IV 150 Cations: Na+, K+, Ca2+, Mg2+ (pH approximately