(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 GI system In general, there is considerable redundancy of control systems as well as excess capacity for nutrient digestion and uptake This served us well in ancient times when food sources 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 U.S National Institutes of Diabetes, Digestive and Kidney Diseases found that on an annual basis, for every 100 U.S residents, there were 35 ambulatory care visits and nearly five 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 physiological principles, as will be stressed in this section This page intentionally left blank Overview of Gastrointestinal Function & Regulation OB J E C TIVES ■ After studying this chapter, you should be able to: ■ ■ ■ ■ ■ C H A P T E R 25 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 means of muscle rings known as sphincters, that 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 lumen is a single layer of columnar epithelial cells This 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 is functionally divided into segments, by 455 456 SECTION IV Gastrointestinal Physiology Lumen Epithelium Basement memdrane Mucosa Lamina propria Muscularis mucosa Submucosa Circular muscle Myenteric plexus Muscularis propria Longitudinal muscle Mesothelium (Serosa) FIGURE 251 Organization of the wall of the intestine into functional layers (Adapted from Yamada: Textbook of Gasteronenterology, 4th ed, pp 151–165 Copyright LWW, 2003.) 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 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 CHAPTER 25 Overview of Gastrointestinal Function & Regulation Simple columnar epithelium Lacteal Villus Capillary network Goblet cells 457 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 classical experiments of Pavlov where dogs were conditioned to salivate in 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 (see Clinical Box 25–1) Intestinal crypt ANATOMIC CONSIDERATIONS Lymph vessel Arteriole Venule FIGURE 252 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 McGraw-Hill, 2008.) Na+ and Cl− are extracted and K+ and bicarbonate are added Because the ducts are relatively impermeable to water, the loss 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 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 on a common chamber (gastric pit) that opens in turn on 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 ORIGIN & REGULATION OF GASTRIC SECRETION The stomach also adds a significant volume of digestive juices to the meal Like salivary secretion, the stomach actually 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 458 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 253 Regulation of salivary secretion by the parasympathetic nervous system ACh, acetylcholine Saliva is also produced by the sublingual glands (not depicted), but these are a minor contributor to both resting and stimulated salivary flows (Adapted from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 2006.) 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 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 antiinflammatory 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 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 CHAPTER 25 Overview of Gastrointestinal Function & Regulation 459 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 Mucous neck cells (stem cell compartment) Parietal cells (acid, intrinsic factor secretion) Antrum (secretes mucus, pepsinogen, and gastrin) FIGURE 254 Anatomy of the stomach The principal secretions of the body and antrum are listed in parentheses ECL cell (histamine secretion) (Reproduced with permission from Widmaier EP, Raff H, Strang KT: Vander‘s Human Physiology: The Mechanisms of Body Function, 11th ed McGraw-Hill, 2008.) that is released by G cells in the antrum of the stomach both in 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 (ECL cells) that are located in the gland, and release histamine Histamine is also a trigger of parietal cell secretion, via binding to H2 histamine receptors Finally, parietal and chief cells can also be stimulated by acetylcholine, released from enteric nerve endings in the fundus During the cephalic phase of gastric secretion, secretion is predominantly activated 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 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 Chief cells (pepsinogen secretion) FIGURE 255 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 (Adapted from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 2006.) 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 pumps are TABLE 251 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 460 SECTION IV Gastrointestinal Physiology FUNDUS ANTRUM Peptides/amino acids GRP H+ G cell ACh H+ − Parietal cell D cell P SST Gastrin Chief cell ACh ? ? Histamine ACh Circulation ECL cell Nerve ending FIGURE 256 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 ECL cells and parietal cells ECL cells release histamine, which also acts on parietal cells Acetylcholine (ACh), released from nerves, is an agonist 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 known as canali- IC MV M IC M TV G M IC IC FIGURE 257 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 (Based on the work 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.) 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 from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 2006.) culi, 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 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 as we will see are later used to neutralize gastric acidity once its function is complete (Figure 25–9) 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 morphological 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 histamine antagonists that are widely used therapies for adverse effects of excessive gastric secretion, such as reflux) Gastric secretion adds about 2.5 L per day to the intestinal contents However, despite their substantial volume and fine control, gastric secretions are dispensable for the full CHAPTER 25 Overview of Gastrointestinal Function & Regulation Resting 461 Secreting Canaliculus H+, K+ ATPase Tubulovesicle Ca++ M3 CCK−B ACh CCK−B M3 Ca++ cAMP Gastrin H2 H2 Histamine FIGURE 258 Parietal cell receptors and schematic representation of the morphological 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 from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 2006.) 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) Lumen Blood Stream Na+, K+ ATPase 2K+ Potassium channel 3Na+ H2O + CO2 C.A.II H+ HCO3− K+ + Na+ NHE-1 + H , K ATPase H+ + HCO3− H+ Cl− HCO3− Cl− ClC exchanger Chloride channel Apical FIGURE 259 Ion transport proteins of parietal cells Protons are generated in the cytoplasm via the action of carbonic anhydrase II (C.A 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 Cl−/HCO3− Basolateral basolateral membrane is considered a “housekeeping” transporter that maintains intracellular pH in the face of cellular metabolism during the unstimulated state (Adapted from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 2006.) 462 SECTION IV Gastrointestinal Physiology TABLE 252 Principal digestive enzymes.a Source Enzyme Activator Substrate Catalytic Function or Products Salivary glands Salivary α-amylase Cl− Starch Hydrolyzes 1:4α linkages, producing α-limit dextrins, maltotriose, and maltose Stomach Pepsins (pepsinogens) HCl Proteins and polypeptides Cleave peptide bonds adjacent to aromatic amino acids Triglycerides Fatty acids and glycerol Gastric lipase Exocrine pancreas Trypsin (trypsinogen) Enteropeptidase Proteins and polypeptides Cleave peptide bonds on carboxyl side of basic amino acids (arginine or lysine) Chymotrypsins (chymotrypsinogens) Trypsin Proteins and polypeptides Cleave peptide bonds on carboxyl side of aromatic amino acids Elastase (proelastase) Trypsin Elastin, some other proteins Cleaves bonds on carboxyl side of aliphatic amino acids Carboxypeptidase A (procarboxypeptidase A) Trypsin Proteins and polypeptides Cleave carboxyl terminal amino acids that have aromatic or branched aliphatic side chains Carboxypeptidase B (procarboxypeptidase B) Trypsin Proteins and polypeptides Cleave carboxyl terminal amino acids that have basic side chains Colipase (procolipase) Trypsin Fat droplets Binds pancreatic lipase to oil droplet in the presence of bile acids Pancreatic lipase … Triglycerides Monoglycerides and fatty acids Cholesteryl ester hydrolase … Cholesteryl esters Cholesterol Starch Same as salivary α-amylase … RNA Nucleotides … DNA Nucleotides Phospholipids Fatty acids, lysophospholipids Pancreatic α-amylase Ribonuclease Deoxyribonuclease Phospholipase A2 (pro-phospholipase A2) Intestinal mucosa Cytoplasm of mucosal cells Trypsin Enteropeptidase … Trypsinogen Trypsin Aminopeptidases … Polypeptides Cleave amino terminal amino acid from peptide Carboxypeptidases … Polypeptides Cleave carboxyl terminal amino acid from peptide Endopeptidases … Polypeptides Cleave between residues in midportion of peptide Dipeptidases … Dipeptides Two amino acids Maltase … Maltose, maltotriose Glucose Lactase … Lactose Galactose and glucose Sucraseb … Sucrose; also maltotriose and maltose Fructose and glucose Isomaltaseb … α-limit dextrins, maltose maltotriose Glucose Nuclease and related enzymes … Nucleic acids Pentoses and purine and pyrimidine bases Various peptidases … Di-, tri-, and tetrapeptides Amino acids a Corresponding proenzymes, where relevant, are shown in parentheses b Cl− Sucrase and isomaltase are separate subunits of a single protein 738 INDEX Insulin, 431, 436, 481 anabolic effect of, 436 biosynthesis & secretion, 433 deficiency acidosis, 439 cholesterol metabolism, 440 coma, 439–440 fat metabolism in diabetes, 439 glucose tolerance, 437–438 hyperglycemia effects, 438 intracellular glucose, effects, 438 protein metabolism, changes, 438–439 deficiency, effects of, 440 effect on Na, K ATPase pump activity, 53 effects of, 433, 434 glucose transporters, 434 hypoglycemic, 436 preparations, 434–435 relation to potassium, 435–436 insulin-like activity in blood, 433 and insulin-like growth factors comparison of, 329 structure of, 328 intracellular responses, 436 mechanism of action receptors, 436–437 metabolism, 433 principal actions of, 434 sensitivity, 335 structure/species specificity, 432–433 Insulin-dependent diabetes mellitus, 449 Insulin excess compensatory mechanisms, 440–441 symptoms, 440 Insulin–glucagon molar ratios, 445 Insulinoma, 448 Insulin receptors, 436 Insulin secretion, 442 factors affecting, 441 regulation of, 441 autonomic nerves, effect of, 442–443 B cell responses, long-term changes, 443 cyclic amp, 442 hypoglycemic agents, 442 intestinal hormones, 443 plasma glucose level, effects of, 441–442 protein/fat derivatives, 442 Insulin-sensitive tissues, endosomes in, 435 Insulin sensitizers, 305 Integrins, 42 Intention tremor, 252 Intercalated cells, 674 Intercalated disks, 110 Intercellular communication by chemical mediators., 54–55 types of, 54 Intercellular connections, 43 in mucosa of small intestine, 43 Interleukins as multi-CSF, 70 Intermediary metabolism, actions of glucocorticoids on, 365 Intermediate-density lipo-proteins, 29 Intermediate filaments, 41 Internalization, 55 Internal urethral sphincter, 694 Internodal atrial pathways, 521 Interstitial cells of Cajal, 498 Interstitial fluid, 3, Interstitial fluid volume edema, 584 elephantiasis, 585 lymphedema, 585 precapillary constriction, 584 promoting factors, 584, 585 Intestinal epithelial cells, disposition of, 482 Intestinal fluid/electrolyte transport, 466–468 Intestinal lumen, 477 Intestinal mucosa lipid digestion and passage in, 484 Intestinal smooth muscle effects of agents on membrane potential of, 115 Intestinal villi, 457 Intestine epithelium of, 456 functional layers, 456 substances, normal transport of, 459 Intracellular canaliculi, 460 Intracellular fluid, 3, Intracellular H+ concentration, defense of, 714–718 Intracranial hematoma, 284 Intrafusal muscle fibers, 229 Intrahepatic portal vein radicles, 511 Intrahypothalamic system, 308 Intramembranous bone formation, 385 Intrauterine devices, 412 Intravenous immunoglobulin, Lambert–Eaton Syndrome treatment, 130 Intrinsic depression, 550 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, 414 Iodide transport across thyrocytes, 341 Iodine homeostasis and thyroid hormones, 340–341 Ion channels activation by chemical messengers, 55 multiunit structure of, 51 pore formation in, 51 poreforming subunits of, 52 regulation of gating in, 50 spatial distribution of, 91 Ion distribution and fluxes, 102 Ionotropic glutamate receptors properties of, 140 subtypes of, 139–140 Ionotropic receptors, 136 Ionotropic receptors, salt and sour tastes triggered by, 223 Ion transport proteins of parietal cells, 461 IOP, 179 IPSP See Inhibitory postsynaptic potential IRDS See Infant respiratory distress syndrome Iron absorption of, 486 intestinal absorption of, 486 Iron uptake, disorders of, 486 Irritant receptors, 664 IRV See Inspiratory reserve volume Ischemic hypoxia, 653 Ischemic/stagnant hypoxia, 649 Ishihara charts, 193 Islet cell hormones effects of, 446 pancreatic, organization of, 446–447 pancreatic polypeptide, 446 somatostatin, 446 Islet cell structure, 432 human, cell types, 432 human pancreatic islet electronmicrograph of, 432 rat pancreas islet of Langerhans, 432 Isocapnic buffering, 668 Isohydric principle, Isomaltase, 478 Isometric contractions, 104 Isotonic contractions, 104 muscle preparation arranged for recording, 106 Isotonic muscle contractions, 488 Isotonic solutions, Isovolumetric ventricular contraction, 540 Isovolumetric ventricular relaxation, 541 Itch, 159, 160 IUDs See Intrauterine devices J JAK2–STAT pathways, 326 JAK–STAT pathways, signal transduction via, 63, 64 Janus tyrosine kinases, 63 Jaundice bilirubin, 514 obstructive, 517 JG cells See Juxtaglomerular cells Junctional potentials, 130 Juvenile diabetes, 449 Juxtacrine communication, 54 Juxtaglomerular apparatus, 674 Juxtaglomerular cells, 705 Juxtamedullary nephrons, 674 K Kainate receptors, 141 Kallmann syndrome, 316 Karyotype, 392 Kaspar Hauser syndrome, 334 Kayser–Fleischer rings, 246 KCC1 See Potassium/chloride cotransporter K+ channels, 51 K+ depletion, 443 Ketoacidosis, 28 Ketone bodies formation and metabolism of, 27, 28 health problems due to, 28 Ketosis, 439 Ketosteroids, 364 17-Ketosteroids, 364 Kidneys acid–base balance maintenance, 711 ammonia production, 713 autoregulation, 678 INDEX countercurrent exchangers in, 689 distal tubule of, 466 metabolically produced acid loads, 715 proximal tubular cells secretion of acid, 712 Kinesin, 41 Kinins active factor, 598–599 angiotensin-converting enzyme, 598 bradykinin receptors, 599 formation of, 598 kallikreins, 598 lysylbradykinin, 598 Kinocilium, 202 Klinefelter syndrome, 397 Knee jerk reflex, 229 Kölliker–Fuse nuclei, 658 Krebs cycle See Citric acid cycle Kupffer cells, 510 Kupffer cells, 512 Kussmaul breathing, 439, 661 L Labyrinth See Inner ear Lacis cells, 705 Lactase, 478 Lactation, 416–417 breasts, development of, 416 gynecomastia, 417 initiation of, 416–417 menstrual cycles, effect, 417 milk, secretion/ejection of, 416 Lactic acidosis, 440, 548 Lactose, 478 brush border digestion, 480 Lactose intolerance, treatment for, 479 Lactotropes, 324 Lambert–Eaton Syndrome, 130 Lamellar bodies, 624 Language areas in categorical hemisphere concerned with, 293 physiology of, 292–293 Language-based activity active areas of brain during, 284 Language disorders aphasias, 293 stuttering, 294 Large-molecule transmitters, 136 calcitonin gene-related peptide, 151 CCK receptors, 151 gastrointestinal hormones, 151 neuropeptide Y, 151 opioid peptides, 150 oxytocin, 151 somatostatin, 150, 151 substance P, 150 vasopressin, 151 Laron dwarfism, 334 Lateral brain stem pathway, 240–241 Lateral intercellular spaces, 674, 682 L channels, 523 LDL, 29 L-Dopa, 334 Leader sequence, 20 Leaky epithelium, 681 Learning associative, 284, 285 and cerebellum, 251, 252 definition of, 283 nonassociative, 285 and synaptic plasticity, 286 Left and right planum temporale in brain, 209 Left ventricular ejection time, 542 Length–tension relationship in cardiac muscle, 112, 113 human triceps muscle, 107 sliding filament mechanism of muscle contraction and, 105 Leptin, 399 LES See Lower esophageal sphincter Lesions of representational and categorical hemispheres, 291 Leukemia inhibitory factor, 95 Levodopa, 140 for MSA treatment, 256 for Parkinson disease treatment, 247 Lewy bodies, 248 Leydig cells, 394, 426 interstitial cells of, 419 LH See Luteinizing hormone LHRH, 314 Lidocaine for chronic pain, 164 LIF, 95 Light adaptation, 194 Light microscope, hypothetical cell seen with, 36 Light therapy, 279 Linear acceleration, responses to, 211–212 Lipid breakdown during exercise, 106–107 Lipid digestion intestinal mucosa, 484 intracellular handling of, 484 Lipids, 483–485 biologically important, 26 in cells, 27, 28 fat absorption, 484–485 fat digestion, 483–484 fatty acids See Fatty acids plasma, 29 short-chain fatty acids, 485 steatorrhea, 484 transport of, 29 Lipoproteins, 29 Liver acinus, concept of, 511 bile synthesis in, 509 biliary system bile formation, 514–516 biliary secretion, regulation of, 516 cholecystectomy, effects of, 516 gallbladder, functions of, 516 gallbladder, visualizing, 516–517 blood, detoxifies, 512 blood percolates, 509 excretion ammonia metabolism, 514 substances, 514 functional anatomy, 509–510 functions of, 511 bile, 512–513 bilirubin metabolism/excretion, 513 glucuronyl transferase system, 514 jaundice, 514 739 metabolism/detoxification, 512 plasma proteins synthesis, 512 glucose buffer function of, 512 hepatic circulation, 510–511 metabolically produced acid loads, 715 principal functions of, 511 roles in, 512 schematic anatomy of, 510 transport/metabolic functions of, 509 Local anesthetics and nerve fibers, 93 Local-circuit interneurons, 171 Local current flow, in axon, 91 Local injury, 80 Localized cortical lesions, 294 Local response of membrane, 90 Long QT syndrome, 113 Long-term depression, 286 Long-term learned responses, 285 Long-term memory, 285 recalling of, 289 storage in neocortex, 288 Long-term potentiation in NMDA receptor, 286 in Schaffer collaterals in hippocampus, 287 Loop of Henle, 674 operation, 688 Loops of Henle, 685–686 Loss-of-function receptor mutations, 64 Lou Gehrig disease, 240 Lovastatin, 30 Low-density lipoproteins, 29 Lower esophageal sphincter, 500 Lower motor neurons, 239 damage to, 240 Lown–Ganong–Levine syndrome, 534 LTP See Long-term potentiation Lung airway conduction, 621–622, 624 alveolar air, 634–635 alveolar airway, 624–625 alveolocapillary membrane, diffusion across, 635 anatomy, 621–627 biologically active substances metabolism, 638 blood and lymph in, 627 blood flow, 632–633 bronchi, 623 capacities, 629 complexity, 619 compliance of, 629–632 diffusing capacity, 635 endocrine functions, 638 gas exchange in, 634–635 gas transport in, 641–655 metabolic functions, 638 parenchyma See also Alveolar airway partial pressures, 634 perfusion, 636 pleura, 626–627 Po2 and Pco2 values in, 642 pressure–volume curves in, 630, 631 receptors, 664 respiratory muscles, 626 respiratory system, 635 respiratory tract, regions of, 621 responses mediated by receptors in, 664 ventilation, 632–633, 636 740 INDEX Lung volume, 629 Luteal cells, 401 Luteinizing hormone, 304 actions of, 333 constituents of, 332 episodic secretion of, 411 half-life of, 332 receptors for, 333 Luteinizing hormone-releasing hormone, 314 Luteolysis, 411 LVET See Left ventricular ejection time Lymphatic circulation functions of, 584 lymphatics draining, 584 lymphatic vessels, 584 Lymphatic organs, glucocorticoids effects on, 366 Lymph node, anatomy of, 69 Lymphocytes, 473 in bloodstream, 69 during fetal development, 69 Lysergic acid diethylamide, 149 Lysine vasopressin, 311 Lyso-PC damages cell membranes, 463 Lysosomal diseases, 39 Lysosomes definition of, 39 enzymes found in, 39 M Machado-Joseph disease, 252 Macroglia, 83–84 Macrophages, 69 Macrosomia, 446 Macula, 180 Macula densa, 674, 684, 705 Macular sparing, 191 Maculopathy, 181 Magnocellular neurons, electrical activity of, 312 Major depressive disorder, 149 Major histocompatibility complex, 491 Major histocompatibility complex (MHC) genes, 75 Major proglucagon fragment, 443 Malabsorption, 491 Malabsorption syndrome, 491 Male contraception, 423 Male menopause See Andropause Male pseudohermaphroditism, 397, 398 Male reproductive system, 419 anatomical features of, 420 embryonic differentiation of, 394 gametogenesis or ejaculation blood–testis barrier, 419–420 ejaculation, 423 erection, 422–423 prostate specific antigen (PSA), 423 semen, 422 spermatogonia, 420–421 spermatozoa, development of, 421–422 temperature, effect of, 422 structure, 419 testes, endocrine function of actions, 424–425 anabolic effects, 425 estrogens, testicular production of, 426–427 inhibins, 427 mechanism of action, 425–426 secondary sex characteristics, 425 secretion, 424 steroid feedback, 427 testosterone, chemistry/biosynthesis of, 423–424 transport/metabolism, 424 testicular function, abnormalities of androgen-secreting tumors, 428 cryptorchidism, 428 hormones and cancer, 428 male hypogonadism, 428 Male secondary sex characteristics, 425 Malignancy, humoral hypercalcemia of, 384 Malignant hyperthermia, 105, 320 Maltase, 478 Maltose, 478 Maltotriose, 478 Mammalian nerve fibers, 92 Mammalian skeletal muscle, 98 electrical and mechanical responses of, 102 Mammalian spinal motor neurons, ion concentration inside and outside, 10 Mammotropes, 324 Manubrium, 199 MAOIs, 149 Masculinization, 374 Masking, 205 Mass action contraction, 505 Mass discharge in stressful situations, 265 Mast cells, 68 Mastication, 500 Maximal voluntary ventilation, 629 Maximum metabolic rate, 490 McCune–Albright syndrome, 413 M cells See Microfold cells MDMA, 149 Mechanoreceptors, 157 hair cells as, 202 Medial brain stem pathways, 239, 241 medial tracts involved in, 240 Medial temporal lobe and hippocampus, 288 Median eminence, 309 Medullary chemoreceptors, 661 Medullary control basic pathways, 589, 590 factors affecting activity of RVLM, 589, 591 factors affecting heart rate, 589, 592 heart rate by vagus nerves, 589, 591 intermediolateral gray column, 589 rostral ventrolateral medulla, 589 somatosympathetic reflex, 589 Medullary hormones, structure and function of, 355–356 Medullary reticulospinal tracts and posture, 240 Meiosis, 14 Meissner’s corpuscles, 158 Meissner’s plexus, 473 Melanophore, 325 Melanopsin, 185 Melanotropins biosynthesis, 325 physiological functions, 325 Melatonin secretion of, 278 and sleep-wake state, 280 synthesis, diurnal rhythms of compounds in, 280 Memantine, 140 for Alzheimer disease treatment, 289 Membrane polarization, abnormalities of, 534 Membrane potential extracellular Ca2+ concentration and, 89 genesis of, 10 resting, 88 from separation of positive and negative charges, 88 sequential feedback control in, 88–89 of smooth muscle, 114 subthreshold stimuli effect on, 90 upstroke in, 88 Membrane transport proteins aquaporins, 50 carriers, 50 uniports, 51 Membranous labyrinth, 200 Memory and brain, link between, 285 episodic, 284 explicit or declarative, 283, 284 forms of, 285 implicit, 284 intercortical transfer of, 286–287 long-term, 285 neural basis of, 285–286 procedural, 284 semantic, 284 short-term, 285 working, 288 Memory B cells, 70 Memory T cells, 69–70 Menarche, 398 Menopause, 400 Menorrhagia, 413 Menstrual cycle anovulatory cycles, 404 basal body temperature and plasma hormone concentrations, 405 breasts, cyclical changes, 404 changes during intercourse, 404–405 estrous cycle, 406 indicators of ovulation, 405–406 normal menstruation, 404 ovarian cycle, 401–402 ovarian vs uterine changes, 403 uterine cervix, cyclical changes, 404 uterine cycle, 402–404 vaginal cycle, 404 Menstrual cycle ovulation, 405 Menstruation, 401 Mentation, 349 Merkel cells, 158 Mesangial cells, 673 relaxation of, 680 Mesocortical system, 147 Metabolic acidosis, 647–648 acid–base paths, 648 Metabolic alkalosis, 647–648 Metabolic myopathies, 100 INDEX Metabolic rate, 488 and body weight, 490 factors affecting, 489 Metabolic syndrome, 449–450 Metabotropic glutamate receptors activation of, 141 subtypes of, 141 Metabotropic receptors, 136 Metahypophysial diabetes, 443 Metathyroid diabetes, 443 Methemoglobin, 653 3, 4-Methylenedioxymethamphetamine, 149 Mexiletine, 164 mGluR See Metabotropic glutamate receptors MHC See Major histocompatibility complex Micelles, 465, 483 Microfilaments, 40 composition of, 41 structure of, 41 Microfold cells, 483 Microglia, 83 microRNAs, 16 Microscopy techniques, cellular constituents examination by, 35 Microsomes, 36 Microtubule-organizing centers, 42 Microtubules composition of, 40 drugs affecting, 40, 41 structures of, 40 Microvilli, 460 Micturition, 671 Midcollicular decerebrate cats, decerebrate rigidity in, 242 Middle cerebellar peduncle, 248 Middle ear functions of, 199 medial view of, 201 structures of, 200 Mifepristone (RU 486), 410 Migrating motor complex, 498 Migrating motor complexes, 499 Milk ejection reflex, 313 Mineralocorticoids, 353 aldosterone See Aldosterone mechanism of action of, 370–371 relation to glucocorticoid receptors, 371 secondary effects of excess, 372 Miotics, 187 MIS See Müllerian inhibiting substance Mitochondria components involved in oxidative phosphorylation in, 38 functions, 38 genome, 38 Mitochondrial diseases, 39 Mitochondrial DNA, 38 diseases caused by abnormalities in, 47 Mitochondrial genome and nuclear genome, interaction between, 38 Mitochondrial membrane proton transport across inner and outer lamellas of inner, 12 Mitogen activated protein (MAP) kinase cascade, 56 Mitosis, 14 Molecular building blocks deoxyribonucleic acid, 14 mitosis and meiosis, 14 nucleosides, nucleotides, and nucleic acids, 12–13 ribonucleic acids, 14–16 Molecular medicine, 47 Molecular motors dyneins, 41 kinesin, 41 myosin, 41, 42 Molecular weight of substance, Moles, Mongolism See Down syndrome Monoamine oxidase inhibitors, 149 Monoamines adrenoceptors, 146–147 ATP, 149–150 catecholamines, 145–146 dopamine, 147, 148 epinephrine, 145 histamine, 149–150 noradrenergic synapses, 147 norepinephrine, 145 secreted at synaptic junctions, 140 serotonergic receptors, 148, 149 serotonergic synapses, 149 serotonin, 148 Monocular and binocular visual fields, 195 Monocytes activated by cytokines, 69 Monogenic forms of deafness, 210 Monosynaptic reflexes, 229 Mood disorder, 149 Morphological changes, parietal cell receptors and schematic representation of, 461 Mosaicism, 396 Motilin, 472 Motivation and addiction, 172 Motor axons, branching of, 128 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, 236–238 supplementary motor area, 238 Motor homunculus, 237 Motor neurons, inputs converging on, 227 Motor neuron with myelinated axon, 84 Motor pathways, general principles of central organization of, 236 Motor system, division of, 239 Motor unit, 108, 109 Movement, corticospinal and corticobulbar system role in, 239 MPGF See Major proglucagon fragment MRF See Müllerian regression factor mRNA transcription, 16, 18 MRP-2 See Multidrug resistance protein MSH See α−Melanocyte-stimulating hormone MTOCs, 42 Mucosa irritation, 502 Mucosal cells, 484 Mucosal immune system, 473 Müllerian inhibiting substance, 392 741 Müllerian regression factor, 394 Multidrug resistance protein 2, 513 Multiple sclerosis, 86 Multiple system atrophy, 256 Multiunit smooth muscle, chemical mediators effect on, 115 Murmurs, 544 Muscarinic cholinergic receptors, 144, 145 Muscarinic poisoning, 263 Muscarinic receptors, 259 Muscle channelopathies, 105 Muscle, contractile element of, 547 Muscle fibers, 97 classification of, 106, 107 depolarization of, 103 electrical response to repeated stimulation, 104 isometric tension of, 106 length and tension, link between, 105 in motor unit, 109 sarcotubular system of See Sarcotubular system Muscle rigor, 108 Muscles, control of corticobulbar tract, 239 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, 233 Muscle twitch, 102 Muscle weakness by autoimmune attack, 130 myasthenia gravis, 129 Muscular dystrophy, 100 Mushroom poisoning, 263 MV See Microvilli MVV See Maximal voluntary ventilation Myasthenia, 105 Myasthenia gravis, 129 Mycetism, 263 Myelinated axons conduction in, 91 depolarization in, 91 Myelin sheath, 85 defects, adverse neurological consequences of, 86 nodes of Ranvier and, 86 Myenteric plexus, 473 Myocardial fibers, 522 Myocardial hibernation, 550 Myocardial infarctions, 537 Myoepithelial cells, contraction of, 313 Myoglobin, 643 dissociation curves, comparison of, 644 Myopia, 187, 188 Myosin, 41, 42 power stroke in skeletal muscle, 102–103 in skeletal muscle, 99 Myotatic reflex See Inverse stretch reflex Myotonia dystrophy, 105 Myxedema See Hypothyroidism 742 INDEX N Na+ channels, 51 inactivated state, 88 NaCl osmotic pressure, NAD+ See Nicotinamide adenine dinucleotide NADH generation in citric acid cycle, 23 NADP+, 11–12 NADPH oxidase activation, 68 NA+ excretion, steroids affecting, 371 Na+/I–symporter, 341 Na, K ATPase cell volume and pressure dependance on, Narcolepsy, 276 Natalizumab for MS treatment, 86 Natriuretic hormones, 706–708 actions, 707 Na, K ATPase-inhibiting factor, 708 natriuretic peptide receptors, 707–708 secretion/metabolism, 707–708 structure, 706–707 Natriuretic peptide, 707 Natriuretic peptide receptors, 707 diagrammatic representation of, 708 Nearsightedness, 187, 188 NEAT See Nonexercise activity thermogenesis Negative feedback inhibition of spinal motor neuron, 127 Neocortex interneurons, 270, 271 pyramidal cells, 270–271 Neostigmine, myasthenia gravis treatment by, 129 Nephrogenic diabetes insipidus, 700 Nephron, 673–674 diagram, 674 Nerve cells excitability during IPSP, 123 excitation and conduction antidromic conduction, 91–92 electrotonic potentials, 90 firing level, 90 ionic fluxes, 88–89 local response, 90 orthodromic conduction, 91–92 resting membrane potential, 87–88 Nerve fibers local anesthetics effect on, 93 susceptibility to conduction block, 93 type and functions of, 92–93 Nerve impulses See Action potentials Nerve supply to smooth muscle, 116 Nervi erigentes, 422 Nervous system, actions of glucocorticoids on, 365 Neural communication, 54 Neural control mechanisms, 311 Neural control of adrenal medullary secretion, 358 Neural hormones, 311 Neural mechanisms of color vision, 194 Neural pathways, 189–190, 503 Neurogenesis, 287 Neuroglycopenic symptoms, 440 Neuroleptic drugs, 246 Neurological exam, 162, 163 Neuromodulators, 143 Neuromuscular junction, 119 diseases of, 129–130 structure of, 128 Neuromuscular transmission events at, 128 events occurring during, 127–129 neuromuscular junction, 127 Neuronal growth, factors affecting, 94–95 Neurons axonal transport, 86–87 classification of, 85 components of, 84, 85 factor enhancing growth of, 94–95 important zones of, 85 myelinated, 85 threshold, to stimulation changes, 90–91 types of, 85 unmyelinated, 86 Neuropathic pain, 164 Neuropeptide Y, 151, 264 Neuropeptide YY, 446 Neurophysin, 311 Neurosecretion, 311 Neurotransmitters, reuptake of, 137 Neurotrophins function of, 94 receptors for, 93, 94 for SCI treatment, 235 Neutral fat, 27 Neutrophils, average half-life of, 67 NHE See Sodium/hydrogen exchanger Nicotinamide adenine dinucleotide, 12 Nicotinamide adenine dinucleotide phosphate, 11–12 Nicotinic acetylcholine-gated ion channel, threedimensional model of, 144 Nicotinic cholinergic receptors, 144 actions of acetylcholine on, 259 Nicotinic receptors, 130 NIDDM See Non-insulin-dependent diabetes mellitus Nigrostriatal projection, 244 Nigrostriatal system, 147 NIHL, 210 Nipples, stimulation of, 312 NIS See Na+/I–symporter Nitric oxide produced in endothelial cells, 116 synthesis of, 151 Nitric oxide synthase, 422 NMDA receptor antagonists, 140 for chronic pain, 164 NMDA receptors changes and LTP, 286 diagrammatic representation of, 141 in neurons, 141 properties of, 140 N-methyl-D-aspartate receptors See NMDA receptors N, N-dimethyltryptamine, 149 NO See Nitric oxide Nociceptive pathways, transmission in, 170 Nociceptive stimuli, 160 Nociceptors impulse transmitted from, 159 types of, 158 Nocturia, 692 Noise-induced hearing loss, 210 Nonadrenergic, noncholinergic transmitters, 264 chemical transmission at autonomic junctions, 264 Nonassociative learning, 285 Nonconstitutive pathway, 48 Nonconvulsive generalized seizure, 277 Nonepinephrine, 146–147 Nonexercise activity thermogenesis, 488 Non-insulin-dependent diabetes mellitus, 437 Nonionic diffusion, 8, 713 Nonpathogenic bacteria, 473 Nonsteroidal anti-inflammatory drugs axonal regeneration prevention by, 94 for chronic pain, 164 Nonsuppressible insulin-like activity, 443 Noradrenergic and cholinergic postganglionic nerve fibers, effects of stimulation of, 264 Noradrenergic fibers, 522 Noradrenergic neurons, 145 Noradrenergic neurotansmission, 260, 261, 264 Noradrenergic synapses, 147 pharmacology of, 147 Norepinephrine, 145, 599 action on heteroreceptor, 136 biosynthesis, 355 catabolism of, 146 chemical transmission at autonomic junctions, 259 effect on intestinal smooth muscle, 115 effect on unitary smooth muscle, 116 and epinephrine levels in human venous blood, 356 metabolic effects of, 357–358 as neuromodulator, 145 plasma levels, 355 reuptake of, 137 secretion of, 145 Norepinephrine-secreting neurons, 145 Norepinephrine transporter, 137 Normal human pancreatic juice, composition of, 463 Normal sinus rhythm, 529 Normal trabecular bone vs trabecular bone, 388 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, 516 Nuclear factor-κΒ and inflammatory response, 80 Nuclear membrane, 45 Nuclear pore complexes, 45 Nucleic acids, 483 basic structure of, 15 Nucleoli, 45 Nucleosides, nitrogen-containing base of, 12 Nucleotides, 12 basic structure of, 15 Nucleus chromosomes in, 44 composition of, 44 interior of, 45 nucleolus, 45 nucleosomes in, 44 INDEX Nucleus of the tractus solitarius, 699 Nutrients, intake of, 486–487 Nutrition caloric intake/distribution, 490–492 dietary components, essential, 490 mineral requirements, 492 vitamins, 492–494 Nutritional principles, 487–490 Nutrition and growth physiology, 331 Nyctalopia, 183 Nyeloperoxidase, 68 Nystagmus, 212, 252 O OATP See Organic anion transporting polypeptide Obesity, 449–450, 488 Obstructive sleep apnea, 276 Occlusion and fractionation, 234 Ocular dominance columns, 191–192 Oculocardiac reflex, 532 Odorant-binding proteins, 221 Odorant receptors, 219–220 Odorant receptor, signal transduction in, 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, 83–84 Olivocochlear bundle, 207 Oncogenes, 47 Oncotic pressure, 54 Ondine’s curse, 665 Open-angle glaucoma, 179 OPG See Osteoprotegerin Opioid peptides, 150 Opioids, nociceptive transmission and, 171 Opsin, 183, 184 Optic pathways, effect of lesions in, 190–191 Optics principles, image-formation, 186 Optometric vision therapy, 187 Oral glucose tolerance test, 437, 438 Oral temperature, 317 Orexin, 487 Organic anion transporting polypeptide, 513 Organophosphates, 262 Orthodromic and antidromic conduction, 91–92 Orthograde transport, 87 Orthostatic hypotension, 256 Osmolal concentration of plasma, Osmolal concentration of substance in fluid, Osmolarity, Osmole, Osmoreceptors, 310 Osmosis definition, diagrammatic representation of, Osmotically active substances, Osmotic diuresis, 689–690 Osmotic pressure, 680 factors influencing, nonionizing compound, Ossicular conduction, 206 Osteoblasts, 386 Osteoclast resorbing bone, 387 Osteolytic hypercalcemia, 384 Osteomalacia, 380 Osteons, 385 Osteopetrosis, 388 Osteoporosis, 367, 389 involutional, 388 Osteoprotegerin, 387 Otoliths, 201 Outer hair cells, functions of, 207 Ovarian agenesis, 397 Ovarian function, control of, 410–412 contraception, 412 control of cycle, 411–412 feedback effects, 411 hypothalamic components, 410–411 reflex ovulation, 412 Ovarian function, menstrual bnormalities of, 412–413 Ovarian hormones actions, 409 breasts, effects on, 408 central nervous system, effects on, 408 chemistry, biosynthesis, 406–407 endocrine organs, effects on, 407–408 female genitalia, effects on, 407 female secondary sex characteristics, 408 mechanism of action, 408, 410 progesterone, 409 relaxin, 410 secretion, 407, 409 synthetic and environmental estrogens, 408–409 Ovarian hyperstimulation syndrome, 333 Overflow incontinence, 695 Ovulation, 401 Oxidation, 11 Oxidative deamination of amino acids, 21 Oxidative phosphorylation, 12 enzyme complexes responsible for, 38 mitochondrial components involved in, 38 Oxygen administration, 654 potential toxicity, 654 Oxygenated hemoglobin, comparative titration curves for, 646 Oxygenation reaction, 642 Oxygen debt, 107–108, 667 Oxygen delivery to tissues, 641 Oxygen–hemoglobin dissociation curve, 642 temperature and pH, effects of, 643 Oxygen transport, 641–644 Oxyphil cells, 381 743 Oxytocin, 151, 311 action on uterine musculature, 313 physiologic effects, 313 Oxytocin-containing neurons, discharge of, 313 Oxytocin receptors, 416 Oxytocin-secreting neurons, stimulation of, 312 P Pacemaker cells pre-Bötzinger complex, 658 Pacemaker potential, 523 Pacinian corpuscle, generator potential in, 161 Pacinian corpuscles, 158 Paclitaxel, 41 PAH See p-Aminohippuric acid Pain chronic, 164 classification of, 164 deep and visceral, 165–166 definition, 163 hyperalgesia and allodynia, 164–165 referred, 166 vs sensations, 163 Pain transmission, modulation of gray and brainstem role in, 172, 173 information processing in dorsal horn, 170–172 stress-induced analgesia, 173 Pallesthesia, 162 p-Aminohippuric acid, 676 PAMs See Pulmonary alveolar macrophages Pancreas structure, 463 Pancreatic α-amylase hydrolyze, 478 Pancreatic β cells, 305 Pancreatic digestive enzymes, 463 Pancreatic duct cells, ion transport pathways in, 464 Pancreatic endopeptidases, 482 Pancreatic juice alkaline, 463 composition of, 463 contains enzymes, 461 regulation of, 464 Pancreatic polypeptide, 431 Pancreatic proteases, 481 Pancreatic secretion, 461–462 Pancreatitis, acute, 463 Paracellular pathway, 681 Paracrine communication, 54 Paracrine fashion, 468 Paracrines, 468 Paradoxical sleep See REM sleep Parafollicular cells, 384 Paraganglia, 354 Parageusia, 225 Parallel fibers, 249 Parasomnias, 276 Parasympathetic activation, 265 Parasympathetic cholinergic noradrenergic discharge, 265 Parasympathetic innervations, 265 Parasympathetic nervous system, 257 cell bodies in, 259 cranial nerve nuclei, 259 organization of, 258 parasympathetic sacral outflow, 259 salivary secretion, regulation of, 458 744 INDEX Parathyroidectomy, effects of, 382 Parathyroid excess, diseases of, 383 Parathyroid glands actions, 382 anatomy, 381 malignancy, hypercalcemia of, 384 mechanism of action, 382–383 parathyroid hormonerelated protein, 384 PTH, synthesis/metabolism of, 381–382 regulation of secretion, 383 Parathyroid hormone, 377, 382 signal transduction pathways, 378 Parathyroid hormonerelated protein, 384 effects of, 381 Paraventricular neurons, 308 Paravertebral ganglia, 257 Parietal cell, composite diagram of, 460 Parietal cell—gastrin, agonists of, 460 Parkinson disease basal ganglia-thalamocortical circuitry in, 248 familial cases of, 248 hypokinetic features of, 245 lead pipe rigidity in, 248 pathogenesis of movement disorders in, 248 prevalence of, 247 in sporadic idiopathic form, 247 symptoms, 247 treatment of, 247 Paroxysmal atrial tachycardia with block, 531 Paroxysmal ventricular tachycardia, 532 Partial pressures, 634 Partial seizures, 276 Parturition, 416 Parvocellular pathway, 190 Patch clamping, 49 Patchy ventilation–perfusion imbalance, 651 Pattern recognition receptors, 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 hydrolyze, 481 PepT1 See Peptide transporter Peptic ulcer disease, 458 Peptide bonds, formation of, 19 Peptide hormones, 299 precursors for, 300 Peptides, 18 Peptide transporter 1, 482 Peptide YY structure, 472 Periaqueductal gray, 172 Pericytes, 673 Perilymph, ionic composition of, 205 Perinuclear cisterns, 45 Periodic breathing, 666 in disease, 667 Periodic limb movement disorder, 276 Periosteum, 386 Peripheral chemoreceptor reflex hemorrhage, 595 Mayer waves, 595 Traube–Hering waves, 595 vasoconstriction, 595 Peripheral nerve damage, 94 Peripheral nerves composition of, 92 sensitivity to hypoxia and anesthetics, 93 Peripheral proteins, 37 in cell membrane, 36, 37 Peristalsis, 504 Peritubular capillaries, 674 Permeability, 679 Permissive effects of glucocorticoids, 365 Peroxisome proliferator-activated receptor γ, 442 Peroxisome proliferator-activated receptors, 40 Peroxisomes, 40 Pertussis toxin effect on cAMP, 62 p53 gene mutation, 47 PGES expression See Prostaglandin synthase expression PGH2, 30 pH, 643 definition, effects on oxygen–hemoglobin dissociation curve, 643 proton concentration and, Phagocytic function, disorders of, 71 Phagocytosis, 48 Phantom limb pain, 169 Pharynx, food movement, 500 Phasic bursting, 312, 313 Phenobarbital, 143 Phenylephrine, 263 Phenylketonuria, 146 Phenytoin, 277 Pheochromocytomas, 358 Phlorhizin, 683 “Phosphate timer,” 56 Phosphatidylcholine, 463, 514 Phosphatidylinositol metabolism in cell membranes, 61 Phosphodiesterase, 116 Phospholipid bilayer, organization of, 37 Phospholipids, 26 Phosphorus magnetic resonance, 714 Phosphorus metabolism, 379 Phosphorylcreatine, 106 Photoreceptor mechanism, 182 Photoreceptor potentials, ionic basis of, 183 Photoreceptors, 157 receptor potentials of, 182 rod and cone, 180, 181 sequence of events in, 184 Phototransduction in rods and cones, sequence of events involved in, 184 Physicochemical disturbances, 87 Physiological tremor, 231 Physostigmine, muscarinic poisoning treatment by, 263 Piebaldism, 325–326 Pigment abnormalities, 325–326 Pinocytosis, 48 Pituitary gland anatomy of, 324 anterior See Anterior pituitary gland anterior and intermediate lobes of, 308 diagrammatic outline of formation of, 324 functions of, 323 histology of, 324 hypothalamus relation to, 308, 309 Pituitary insufficiency causes of, 336 effects of, 335–336 PKU, 146 Placenta circulation, 614 fetal adrenal cortex, interactions, 415 Planum temporale, 292 Plasma carriers for hormones, 301 dopamine levels, 356 glucose homeostasis, 25 glucose level, 22 factors determining, 24–25 nonelectrolytes of, osmolal concentration of, Plasma erythropoietin levels, 709 Plasma glucose homeostasis, 438 Plasma glucose level, 440, 441 Plasma growth hormone, 332 Plasma hormone concentrations, changes, 399 Plasma K+ level, correlation of, 536 Plasma lipids, 29 Plasma membrane See Cell membrane Plasma osmolality and changes in ECF volume in thirst, 310 plasma vasopressin, relation between, 698 and thirst, link between, 310 Plasma osmolality and disease, Plasma proteins afibrinogenemia, 565 hypoproteinemia, 565 origin of, 565 physiologic functions, 565, 566 Plasma renin activity, 704 Plasma renin concentration, 704 Plasma testosterone, human male, 398 Plasma vasopressin, 699 relation between, 698 mean arterial blood pressure, 699 Plasticity of motor cortex, 238 Platelet-activating factor, 80 Platelets ADP receptors in human, 79 aggregation, 80 clotting factors and PDGF in, 78, 79 cytoplasm of, 78 production, regulation of, 80 response to tissue injury, 78 wound healing role, 79 Pleural cavity, 626 connective fibers, 627 parietal pleura, 626 pleural space, 627 pressure in, 628 visceral pleura, 626, 627 PLMD, 276 PMS See Premenstrual syndrome Pneumotaxic center, 658 p75NTR receptors, 93, 94 Podocytes, 673 Poikilothermic animals, 316 Point mutations, 14 Poly(A) tail, 16 Polydipsia, 700 Polymodal nociceptors, 158 INDEX Polypeptides, 18 Polypeptide YY, 446 Polysynaptic connections between afferent and efferent neurons in spinal cord, 234 Polysynaptic reflex, 234 Polysynaptic reflexes, 229 Polyuria, 692, 700 POMC See Pro-opiomelanocortin Pontine reticulospinal tracts and posture, 240 Pontogeniculo-occipital (PGO) spikes, 275 Portal hypophysial vessels, 309 Positive feedback loop, 88 Posterior lobe hormones, synthesis of, 311 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, 548 Postganglionic autonomic neurons, 131 Postganglionic neurons, 256 Postsynaptic density, 120, 141 Postsynaptic inhibition, 126 Postsynaptic membrane, receptors concentrated in clusters on, 136 Postsynaptic neurons action potential generation in, 124–125 action potential in See Postsynaptic potentials PSD on membrane of, 141 synaptic endings, 120 Postsynaptic potentials excitatory and inhibitory, 121–123 slow EPSPs and IPSPs, 123 temporal and spatial summation of, 125 Posttetanic potentiation, 286 Posttranscriptional modification of polypeptide chain, 20 of pre-mRNA, 16 reactions in, 20 Posture maintenance brain stem pathways involved in lateral, 240–241 medial, 239–240 Posture-regulating systems decerebration, 241–243 decortication, 243 Potassium/chloride cotransporter, 466 Potassium ions active transport of, 53, 54 changes in membrane conductance of, 88 concentration difference and sodium ions, 88 equilibrium potential for, 10 in mammalian spinal motor neurons, 10 and membrane potential, 10 Power stroke of myosin in skeletal muscle, 102–103 ΠΠΑΡγ See Peroxisome proliferator-activated receptor γ PPARs, 40 PRA See Plasma renin activity Pralidoxime, 262 PRC See Plasma renin concentration pre-Bötzinger complex, 658 pacemaker cells in, 658 Precocious/delayed puberty delayed/absent puberty, 400 menopause, 400–401 sexual precocity, 399–400 Precocious pseudopuberty, 399 Precocious sexual development classification of, 399 Precursor proteins, 427 Prednisone for Lambert–Eaton Syndrome treatment, 130 for MS treatment, 86 for myasthenia gravis treatment, 129 Preejection period (PEP), 542 Preganglionic neurons, 256 Pregnancy endocrine changes, 414 fertilization & implantation, 413–414 fetal graft, 414 fetoplacental unit, 415 human chorionic gonadotropin, 414 human chorionic somatomammotropin, 415 infertility, 414 parturition, 415–416 placental hormones, 415 Pregnenolone, 360 Premature beat, heart, 531 Prematurity, retinopathy of, 654 Premenopausal women, 485 Premenstrual syndrome, 413 Premotor cortex, 238 pre-mRNA, posttranscriptional modification of, 16 Preproenkephalin, 357 Prepro-oxyphysin, 311, 312 Prepropressophysin, 311 PreproPTH, 381 Prestin, 207 Presynaptic inhibition comparison of neurons producing, 126 effects on action potential and Ca2+ current, 127 and facilitation, 126 Presynaptic nerve terminals, small synaptic vesicle cycle in, 122 Presynaptic receptor, 136 PRH, 314 Primary adrenal insufficiency, 375 Primary ciliary dyskinesia, 42 Primary colors, 193 Primary evoked potential, 271 Primary hyperaldosteronism, 374 Primary messengers, 56 Primary motor cortex, 236–238 cell organization in, 237 imaging techniques for mapping, 237–238 location of, 236–237 motor homunculus and, 237 Primary plexus, 309 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, 400 Principal cells, 674 Principal digestive enzymes, 462 Proarrhythmic, 534 Proenzymes, 481 Progesterone, biosynthesis of, 409 Programmed cell death See Apoptosis Progressive motility, 422 Prolactin actions of, 333, 334 components of, 333 functions of, 323 half-life of, 333 secretion, regulation of, 334–335 Prolactin-inhibiting hormone, 314 Prolactin-releasing hormone, 314 Proliferative phase, 403 Proopiomelanocortin biosynthesis, 325 Pro-opiomelanocortin, 487 biosynthesis, 325 Proprioceptors, 157 Prorenin, 702 Prosopagnosia, 294 Prostacyclin, 596 Prostaglandin H2, 30 Prostaglandins, 422 pharmacology of, 31 synthesis of, 30 Prostaglandin synthase expression, 674 Prostate, 419 Prostate specific antigen, 423 Protease-activated receptor-2 (PAR-2) activation, 160 Protein degradation and production, balance between, 20–21 and ubiquitination, 20–21 Protein digestion, 481–482 Protein folding, 20 Protein kinases, 56 in cancer, 57 in mammalian cell signaling, 56 Protein linkages to membrane lipids, 37 Protein processing, cellular structures involved in, 46 Protein-rich food, 502 Proteins, 491, 645 amino acids found in, 19 composition of, 18 embedded in cell membrane, 36, 37 in skeletal muscle, 97 structure of, 18–19 ubiquitination of, 20 Protein synthesis activation of, 56 definition of, 19 in endoplasmic reticulum, 20 initiation of, 20 mechanism of, 19–20 RNA role in, 16, 19–20 Protein transferrin, 485 Protein translation and rough endoplasmic reticulum, 45 Protodiastole, 540 Proton transport, 12 Proto-oncogenes, 47 Protopathic pain, 159 745 746 INDEX Protoplasmic astrocytes, 84 Proximal convoluted tubule, 673 Proximal tubule Na+ reabsorption mechanism, 682 solutes reabsorption, 683 PRRs, 74 PSA See Prostate specific antigen PSD See Postsynaptic density Pseudocholinesterase, 144 Pseudohypoparathyroidism, 64, 383 Psilocin, 149 Psychosocial dwarfism, 334 PTH See Parathyroid hormone PTHrP See Parathyroid hormonerelated protein Puberty, 398 control of onset, 398–399 Pulmonary alveolar macrophages, 625 Pulmonary arteries/veins, 637 Pulmonary chemoreflex, 664 Pulmonary circulation, 627, 628, 636–638 flow, 636 gravity, 636 pressure, 636 pulmonary blood vessels, 636 pulmonary reservoir, $603 regulation of pulmonary blood flow, 637–638 ventilation/perfusion ratios, 636–637 volume, 636 Pulmonary fibrosis, 631 Pulmonary hypertension, 637 Pulse, 542 Pulse oximeter, 629 Pupillary light reflexes, 188 Purine adenosine triphosphate, 473 Purines compounds containing, 13 ring structures of, 12 Purkinje cells, 249 output of, 250 Purkinje fibers, 522, 524 Purkinje system, 521 Pyramidal neurons, 270–271 Pyridostigmine, 262 for myasthenia gravis treatment, 129 Pyrimidines catabolism of, 13 compounds containing, 13 ring structures of, 12 Q QRS vector, 528 Quality control, 46–47 Quantitating respiratory phenomena, 628–629 lung volumes and capacities, 629 Quaternary structure, 19 R Radiation, 318 Rafts and caveolae, 49 Ralfinamide, 164 Raloxifene, 409 Ramelteon, 279 Ranibizumab, 181 RANKL See Receptor activator for nuclear factor kappa beta ligand Rapid auditory processing theory, 292 Rapid eye movement sleep, 273, 666 EEG waves during, 274 PET scans of, 275 phasic potentials, 275 rapid movements of eyes, 275 Rapidly adapting receptors, 664 RAS, 271 Rasagiline for MSA treatment, 256 Rayleigh match, 194 Raynaud disease, 264 Raynaud phenomenon, 264 Rebound phenomenon, 252 Receptive relaxation, 502 Receptor activator for nuclear factor kappa beta ligand, 387 Receptor–ligand interaction, 55 Receptors See also Specific receptors desensitization, 137 G protein-coupled, 136 and G protein diseases, 64 ionotropic, 136 metabotropic, 136 for neurotransmitters and neuromodulators, 136, 139 on nociceptive unmyelinated nerve terminals, 160 on postsynaptic membrane, 136 presynaptic, 136 and transmitters, 136, 137 Reciprocal innervation, 232, 657 Recovery heat, 108 Recruitment of motor units, 234 Rectum distention of, 506 responses to distention of, 506 Red blood cells characteristics, 557, 559 fibrin fibrils, 557, 559 formation and destruction, 557, 559 5α-Reductase deficiency, 397 Reduction, 11 Referred pain, 166 Reflex arc activity in, 228 components of, 228 monosynaptic reflexes, 229 polysynaptic reflexes, 229 Reflexes general properties, 228 and semireflex thermoregulatory responses, 318–319 spinal integration of, 234–236 stimulus for, 228 Reflex ovulation, 412 Reflex sympathetic dystrophy, 164 Refraction, 186 Refractive power, 186 Refractory period, 91 Regulatory elements, 14 Relaxation volume, 630 Relaxed (R) configuration, 642 Relaxin, 328 REM sleep See Rapid eye movement sleep Renal circulation, 676 Renal failure, acute, 548 Renal function, 673–693 abnormal Na+ handling, 693 acidosis, 693 adrenocortical steroids effects, 690–691 aquaporins, 685 bladder, 693–695 bladder emptying, 693–694 bladder filling, 693 blood flow, 676–677 blood vessels, 674–675 capillary bed size, 679–680 capsule, 675 collecting ducts, 686–687 countercurrent mechanism, 687–688 deafferentation effects, 695 denervation effects, 695 diluting ability, 692–693 disordered renal function effects, 692–693 distal tubule, 686 diuretics, 692 filtration fraction, 681 free water clearance, 690 functional anatomy, 673–676 glomerular filtration, 678–681 glomerular filtration rate (GFR), 678–679 glomerular filtration rate (GFR) changes in, 680–681 glomerular filtration rate (GFR) control of, 679 glomerulotubular balance, 684–685 glucose reabsorption, 682–683 glucose transport mechanism, 683 humoral effects, 691 hydrostatic pressure, 680 K+ excretion, regulation, 691–692 loop of Henle, 685–686 loss of concentrating, 692–693 lymphatics, 675 Na+ excretion, regulation, 690–691 Na+ reabsorption, 681–682 nephron, 673–674 osmotic diuresis, 689–690 osmotic pressure, 680 oxygen consumption, 678 PAH transport, 683–684 permeability, 679 proximal tubule, 685 reflex control, 694–695 regional blood flow, 678 renal blood flow autoregulation, 678 renal blood flow regulation, 677 renal circulation, 676–678 renal nerves functions, 677–678 renal vessels innervation, 675–676 renal vessels pressure, 677 secondary active transport, additional examples, 683 spinal cord transection effects, 695 tubular function, 681–690 tubular reabsorption & secretion mechanisms, 681 tubuloglomerular feedback, 684–685 urea role, 688–689 uremia, 693 urine concentration relation, 690 water diuresis, 691 INDEX water excretion, regulation, 691 water intoxication, 691 water transport, 685 Renal glucose transport, 683 Renal H+ secretion, 711–714 ammonia secretion, 713 bicarbonate excretion, 714 body fluids principal buffers, 716 factors affecting acid secretion, 714 fate of, 712 fate of H+ in urine, 712 Na–H exchanger, 711 pH changes, 713 pH of body fluids, 715 reaction with buffers, 712–713 Renal hypertension, 706 Renal interstitial pressure, 675 Renal medullary interstitial cells, 674 Renal physiology, 671 Renal plasma clearance, 678 Renal plasma flow, 676 Renal principal cell, 691 Renal threshold, 682 Renal tubular acidosis, 693 Renin and aldosterone secretion, 372–373 Renin–angiotensin system, 702–706 angiotensin-converting enzyme & angiotensin II, 702–703 metabolism of, 704 receptors, 704–705 angiotensinogen, 702 angiotensins, actions of, 704 pharmacologic manipulation of, 703 renin, 702 renin secretion, regulation of, 705–706 summary of, 701 tissue renin-angiotensin systems, 704 Renin secretion conditions, 706 factors, 706 regulation of, 705–706 Renin substrate, 702 amino terminal end of, 703 Renorenal reflex, 676 Replication, 14 Representational and categorical hemispheres, lesions of, 291 Reproductive abnormalities, 413 Reserpine, 147 Residual volume, 629 Respiration, 619 acid-base balance, ventilatory responses to changes in, 661–662 airway resistance, 631 alveolar surface tension, surfactant role, 631–632 baroreceptor stimulation, respiratory effects of, 665 blood flow, 632–633 brain stem, chemoreceptors in, 661 breath holding, 663 breathing, work of, 632 carotid & aortic bodies, 660–661 chemical control, 659 chemical control of breathing, 659–663 chest wall, 629–632 compliance of lungs, chest wall, 629–632 control systems, 657–658 CO2 response curve, hypoxia effects on, 662–663 CO2 response, H+ effect, 663 coughing & sneezing, 664 dead space, 633–634 exercise effects, 666–669 expiration, 627–628 inspiration, 627–628 lung capacities, 629 lungs, responses mediated by receptors in, 664 lung volumes, 629 medullary systems, 658 movement in, 626 muscles, 626 neural control of breathing, 657–658 nonchemical influences on, 664–666 oxygen deficiency, ventilatory response to, 662 pontine & vagal influences, 658 pressure–volume curves in, 631 proprioceptors, afferents from, 664–665 quantitating phenomena, 628–629 regulation of, 657–669 regulation of respiratory activity, 658–659 respiratory abnormalities, 666 respiratory muscles, 626 sleep, effects of, 665–666 uneven ventilation, 633–634 ventilation, 632–633 ventilatory responses to CO, 662 visceral reflexes, respiratory components of, 665 Respiration at birth, 615–616 Respiratory acidosis, 647, 662, 714, 716 Respiratory alkalosis, 647, 662 Respiratory burst, 68 Respiratory center, stimuli affecting, 659 Respiratory compensation, 648–649, 716 Respiratory control pattern generator, 658 Respiratory enzyme pathway, 107 Respiratory exchange ratio, 489 Respiratory minute volume, 629 Respiratory muscles, 626, 632 Respiratory quotient, 489 Respiratory system, 635 partial pressures of gases, 635 pressure-volume curve, 630, 631 Respiratory tract alveolar airway, 621 conducting airway, 621 regions of, 621 upper airway, 621 Resting heat, 108 Resting membrane potential, 87–88 of cardiac muscle, 110 of hair cells, 203 Reticular activating system, 271 Reticuloendothelial system, 69 Reticulospinal tracts, 240 Retina blood vessels, 180 layers, 178 melanopsin, 185 neural components of extrafoveal portion of, 178, 179 pigment epithelium, 180 747 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 response to light focused on receptive fields, 185 types of, 190 Retinohypothalamic fibers, 278 Retinoid X receptor, 348 Retrograde amnesia, 286 Retrograde transport, 87 Retrolental fibroplasia, 654 Reuptake catecholamines, 146 definition of, 137 of norepinephrine, 137 R-flurbiprofen, Alzheimer disease treatment by, 289 Rhodopsin, 183 structure of, 184 Ribonucleic acids and DNA, difference between, 14 production from DNA, 16 role in protein synthesis, 16 types of, 16 Ribosomes, 46 Rickets, 380 Rigor mortis, 108 Riluzole, 140 for ALS treatment, 240 Rituximab for MS treatment, 86 RMICs See Renal medullary interstitial cells RMV See Respiratory minute volume RNA See Ribonucleic acids Rod photoreceptor components of, 180 Rod receptor potential, 182–183 Rods density along horizontal meridian, 182 photosensitive pigment in, 183 schematic diagram of, 182 sequence of events involved in phototransduction in, 184 Rotational acceleration, responses to, 211 Rough endoplasmic reticulum and protein translation, 45 RPF See Renal plasma flow RQ See Respiratory quotient Rubrospinal tract, 240 Ruffini corpuscles, 158 RV See Residual volume Ryanodine receptor, 103 S Saline cathartics, 468 Saliva, 456 Salivary α-amylase, 478 Salivary glands, 456 Salivary secretion, 456–457 regulation of, 458 Saltatory conduction, 91 748 INDEX Salt-sensitive taste, 223 SA node See Sinoatrial node Sarcomere, 99 Sarcotubular system components of, 100, 101 T system and, 101 Satiety factor, 487 SBP, 302 Scala tympani, 200 Scala vestibuli, 200 SCFAs See Short-chain fatty acids Schizophrenia, 147 Schwann cells, 83–84 SCI, 235 Sclera, 177 SDA See Specific dynamic action Sealing zone, 387 Secondary active transport, 53–54 Secondary adrenal insufficiency, 375 Secondary hyperaldosteronism, 374 Secondary sex characteristics, 425 Secondary structure of proteins β-sheets, 18–19 spatial arrangement, 18 Second messengers cyclic AMP, 60–61 diacylglycerol as, 60–61 effect on aldosterone secretion, 375 effect on Na, K ATPase pump activity, 53 inositol trisphosphate as, 59–60 intracellular Ca2+ as, 56–58 phosphorylation and, 55–56 in regulation of aldosterone secretion, 375 short-term changes in cell function by, 55 Secretory immunity, 78, 483 Segmentation contractions, 504 Seizures EEG activity during, 277, 278 genetic mutations and, 277 partial/generalized, 276 treatment of, 277, 278 types of, 276–277 Selectins, 42, 68 Selective dorsal rhizotomy, CP treatment by, 236 Selective estrogen receptor modulators, 409 Semantic memory, 284 Semen, 422 Seminiferous epithelium, 421 Seminiferous tubule dysgenesis, 397 Seminiferous tubules, 419 Senile dementia, 289 Sensitization and habituation, 286 Sensorineural and conduction deafness, tests for comparing, 211 Sensorineural hearing loss, 209 Sensory association area, 169 Sensory coding definition, 161 intensity of sensation, 162, 163 location, 162 modality, 161–162 neurological exam, 163 Sensory homunculus, 168 Sensory modalities, 157, 158 Sensory nerve fibers, numerical classification of, 92 Sensory receptors in ear, 202 as transducers, 157 Serial electrocardiographic patterns, diagrammatic illustration of, 535 SERMs See Selective estrogen receptor modulators Serotonergic receptors, 148, 149 classes of, 148 functions of, 148, 149 pharmacology of, 149 Serotonergic synapses, 149 Serotonin, 148, 504 Serotonin reuptake inhibitors, 149 Serpentine receptors See G protein-coupled receptors Sertoli cells, 419 Serum dehydroepiandrosterone sulfate (DHEAS), changes in, 364 Seven-helix receptors See G protein-coupled receptors Sex chromosomes, defects, 398 Sex chromosomes, nondisjunction of, 396 Sex determination, diagrammatic summary of, 396 Sex differentiation disorders, 397 Sex hormone-binding globulin, 302 Sex hormones, 391, 419 Sex steroid-binding globulin, 424 Sex steroids in women, 407 Sexual excitement, 405 SFO See Subfornical organ SGLT See Sodium-dependent glucose transporter SHBG, 302 Shock, 548 hypovolemic, 548 low-resistance, 548 obstructive, 548 treatment of, 548 Short-chain fatty acids, 485 “Short-circuit” conductance, 27 Short gut syndrome, 491 Short-term memory, 285 Shy–Drager syndrome, 256 SIADH See Syndrome of “inappropriate” hypersecretion of antidiuretic hormone Sick sinus syndrome, 529 Siggaard–Andersen curve nomogram, 717 Signal hypothesis, 20 Signal peptide, 20 Signal recognition particle, 20 Signal transduction in odorant receptor, 219–220 in taste receptors, 223–224 via JAK–STAT pathway, 63, 64 Sinemet for Parkinson disease treatment, 247 Single-breath N2 curve, 633 Sinoatrial node, 521 membrane potential of, 523 Sinus arrhythmia, 529 in young/old man, 529 Sinus bradycardia, 529 Skeletal muscles actin and myosin arrangement in, 99 body movements and, 110 contractile mechanism in, 97 contraction of See Contraction, muscular cross-striations in, 98–100 denervation of, 108 electrical characteristics, 101, 102 ion distribution and fluxes in, 102 length-tension relation in, 105 mammalian, 98 mechanical efficiency of, 108 in middle ear, 200 motor unit, 108, 109 muscle fibers in, 97 pathway linking CNS to, 256 proteins in, 97, 100 relaxation of, 264–265 strength of, 110 Skin coloration, control of, 325–326 Skin disorder, connexin mutations and, 45 Sleep effects of, 665–666 importance of, 275 Sleep apnea, obstructive, 667 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 alpha rhythm, 273 beta rhythm, 273 EEG and muscle activity during, 274 sleep stages, 273 thalamocortical loops and, 273 Sleep-wake state melatonin and, 280 neurochemical mechanisms promoting, 278 GABA, 280 histamine, 280 melatonin, 280 midbrain reticular formation, 279 RAS neurons, reciprocal activity, 279–280 transitions between, 278 Sleepwalking, 276 Slowly adapting receptors, 664 Small-conductance calcium-activated potassium (SK) channels, 240 Small G proteins, 58 Small intestine chloride secretion in, 467 intestinal motility, 504 transit time, 505–506 Small-molecule neurotransmitters biosynthesis of, 137 excitatory and inhibitory amino acids acetylcholine, 144 acetylcholine receptors, 144–145 cholinergic receptor, 145 GABA, 142–143 glutamate, 138–142 glycine, 143 monoamines adrenoceptors, 146–147 ATP, 149–150 INDEX catecholamines, 145–146 dopamine, 147, 148 epinephrine, 145 histamine, 149–150 noradrenergic synapses, 147 norepinephrine, 145 serotonergic receptors, 148, 149 serotonergic synapses, 149 serotonin, 148 with neuropeptides, 136 Smell adaptation and, 221 classification of, 217 odorant-binding proteins and, 221 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, 115 Ca2+ role in, 114–115 chemical mediators effect on, 115 sequence of events in, 115 drugs acting on, 116 effects of agents on membrane potential of, 115 electrical activity of, 114 force generation of, 116 mechanical activity of, 114 nerve endings in, 130 nerve supply to, 116 overexcitation in airways, 116 plasticity of, 116 postganglionic autonomic neurons on, 131 relaxation of cellular mechanisms linked with, 115 skeletal and cardiac muscle, comparison of, 114 striations in, 114 types of, 114 of uterus, oxytocin effect on, 313 Sneezing, 664 SOCCs, 57 Sodium-dependent glucose transporter, 480 Sodium/hydrogen exchanger, 466 Sodium ions active transport of, 53, 54 changes in membrane conductance of, 88 concentration difference and potassium ions, 88 in mammalian spinal motor neurons, 10 Sodium–potassium adenosine triphosphatase (Na, K ATPase) ATP hydrolysis by, 51 α and β subunits of, 51–53 electrogenic pump, 51 heterodimer, 51, 52 ion binding sites, 53 regulation of, 53 Solutes, normal clearance values of, 679 Somatic cell division, 14 Somatic chromosomes, 392 Somatic motor activity, 227 Somatic nervous system, 257 Somatomedins polypeptide growth factors, 327 principal circulating, 327, 328 relaxin isoforms, 328 Somatomotor nervous system and ANS, difference between, 264 Somatosensory pathways, 166 cortical plasticity, 169, 170 dorsal column pathway, 167–169 effects of CNS lesions, 170 ventrolateral spinothalamic tract, 169 Somatostatin, 150, 151, 431, 472 for acromegaly, 328 Somatostatin inhibits, 472 Somatotopic organization, 167–169 Somatotropes, 324 Somnambulism, 276 Sound definition of, 203 localization, 209 loudness and pitch of, 203 transmission of, 206 Sound frequencies audible to humans, 205 Sound waves amplitude of, 205 characteristics of, 205 conduction of, 206 definition of, 203 SP See Surfactant protein Spastic CP, 236 Spastic neurogenic bladder, 695 Spatial summation, 125 Specific dynamic action, 489 Specific ionic composition, defense of, 708–709 Spermatogenesis, 419, 422 Spermatogonia, 420 Spermatozoon, ejaculation of, 422 Spherical follicle, 340 Sphincter of Oddi, 510 Sphincters, 455 Spinal cord injury, 235 Spinal cord stimulation, 169 Spinal cord, transection of, 235 Spinal motor neuron, 109 negative feedback inhibition of, 127 Spinal reflex, 228 Spinal shock, 235 Spinnbarkeit, 404 Spinocerebellum, 250 Spiny stellate cells, 271 Splanchnic circulation See also Gastrointestinal circulation schematic of, 474 SRP, 20 SSRIs, 149 Standard limb leads, 524, 526 StAR protein See Steroidogenic acute regulatory protein Stellate cells, 249 Stem cells, factors stimulating production of, 70 Stenosis, 544 Stereoagnosia, 162 Stereocilia, 202 Stereognosis, 162 749 Steroid binding proteins, 302 Steroidogenic acute regulatory protein in adrenals and gonads, 362 functions of, 300 regulation of steroid biosynthesis by, 301 Steroids biosynthesis, 360–361 enzyme deficiencies effect on, 361–362 intracellular pathway of, 356 precursor of, 360 Steroid-secreting cells, structures of, 356 Steroids hormones, thyroid and, difference between, 300 Sterols, 26 Stokes–Adams syndrome, 530 Stomach, 502–504 acid-secreting cells of, 469 anatomy of, 459 gastrointestinal motility, 502 regulation of, 502 glandular secretions of, 458 small intestine intestinal motility, 504 vomiting, 502–504 Store-operated Ca2+ channels, 57 Strabismus, 187 Strangeness and familiarity, 289 Stratum functionale, 403 Strength–duration curve, 89 Stress, glucocorticoids effects on, 366 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, 110 Striations in skeletal muscle identification by letters, 98–99 thick filaments, 99 thin filaments, 99–100 Stroke volume, 546 Structural lipids, 27 Subcortical structures and navigation in humans, 294 Subfornical organ, 704 Submucous plexus, 473 Substance P, 150, 473 Substantia nigra, 244 Sucrose, 478 Sugars, intestinal transport of, 481 Superior cerebellar peduncle, 248 Superior colliculi, 196 Supplementary motor area, 238 Suppressor strip, 243 Suprachiasmatic nuclei (SCN), circadian activity of, 278 Surface tension, 624 Surfactant, 624, 632 Surfactant protein, 623, 632 Surgical approach for acromegaly and gigantism, 328 for Parkinson disease treatment, 247 Swallowing, 500 Sweet-responsive receptors, 224 Sweet taste, 223–224 Sympathetic activation, 265 Sympathetic innervations, 265 750 INDEX Sympathetic nervous system sympathetic preganglionic and postganglionic fiber projection in, 257 as thoracolumbar division of CNS, 256 Sympathetic noradrenergic discharge, 265 Sympathetic paravertebral ganglion, 257 Sympathetic preganglionic and postganglionic fibers projection of, 257 Sympathomimetic drugs, Horner syndrome treatment by, 263 Sympathomimetics, 147 Symport, 480 Synapses anatomic structure of, 120 cell-to-cell communication via, 119 in cerebral and cerebellar cortex, 120 facilitation at, 126 inhibition at in cerebellum, 127 inhibitory systems for, 126–127 postsynaptic and presynaptic, 126 on motor neuron, 120 transmission of action potential, 119 Synaptic delay, 122 Synaptic elements, functions of, 120–121 Synaptic junctions, electrical transmission at, 123 Synaptic knob, electronmicrograph of, 120 Synaptic physiology, 138 Synaptic plasticity and learning, 286 Synaptic transmission, 119 Synaptic vesicle docking and fusion in nerve endings, 122 Synaptic vesicles kinds of, 120 transport along axon, 120–121 Synaptobrevin cleavage by botulinum toxin, 123 Synaptosome-associated protein (SNAP-25) cleavage by botulinum toxin, 123 Syncytiotrophoblast, 414 Syndrome of “inappropriate” hypersecretion of antidiuretic hormone, 700 Syndromic deafness, 210 Syntrophins, 101 Systemic response to injury, 80–81 System mediating acquired immunity, 69, 70 Systolic dysfunction, 547 effect of, 549 Systolic failure, 540 Systolic pressure, 539 T T3 See Triiodothyronine T4 See Thyroxine Tabes dorsalis, 695 Tachycardia, 529 Tachycardias, 529 Tachypnea, 649 Tactile agnosia, 162 Tamoxifen, 302, 409, 417 Tardive dyskinesia, 246 Taste classification of, 217 reactions and contrast phenomena, 224 sense organ for See Taste buds Taste buds basal cells, 221, 222 fungiform papillae, 222 innervation, 221 in papillae of human tongue, 222 types of, 221 Taste detection, abnormalities in, 225 Taste modalities receptors for, 223–224 types of, 222–223 Taste pathways, 222, 223 Taste receptors signal transduction in, 223–224 types of, 223 Taste threshold definition of, 224 and intensity discrimination, 224 of substances, 224 Taxol, 41 TBG concentration and thyroid hormones, 344 TBI, 284 T cell receptors heterodimers, 76 MHC protein–peptide complexes and, 76 T cells activation in acquired immunity, 71, 74 CD8 and CD4 proteins on, 76 maturation, sites of congenital blockade of, 80 polypeptides of circulating, 76 types of, 69 T channels, 523 Temperature, 643 effects on oxygen–hemoglobin dissociation curve, 643 Temperature regulation, 316–320 mechanisms for, 318–319 Temporal lobe memory, 285 Temporal summation, 125 Tenotomy, CP treatment by, 236 Tense (T) configuration, 642 Tertiary adrenal insufficiency, 375 Tertiary structure of protein, 19 Testes, endocrine function of actions, 424–425 anabolic effects, 425 estrogens, testicular production of, 426–427 inhibins, 427 mechanism of action, 425–426 secondary sex characteristics, 425 secretion, 424 steroid feedback, 427 testosterone, chemistry/biosynthesis of, 423–424 transport/metabolism, 424 Testicular descent, 428 Testicular feminizing syndrome, 397 Testicular function, abnormalities of androgen-secreting tumors, 428 cryptorchidism, 428 hormones and cancer, 428 male hypogonadism, 428 Testosterone, 419, 425 biosynthesis of, 424 17-ketosteroid metabolites of, 425 schematic diagram of, 426 Testosterone–receptor, 426 Testosterone secretion rate, 424 Testotoxicosis, 64 Tetanic contraction, 104–105 Tetanus, 106 Tetanus toxins and botulinum, 123 Tetanus toxoid vaccine, 123 Tetrabenazine, 246 TG See Triglyceride TGFα, 54 Thalamic pain syndrome, 170 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, 401 Theca interna cells, interactions, 407 Thermal gradient, 318 Thermal nociceptors, 158 Thermodilution, 545 Thermoreceptors, 157 threshold for activation of, 161 Thermoregulatory responses in humans, 318–319 Thiazolidinediones, 442 Thioridazine, 181 Thioureylenes, hyperthyroidism treatment by, 347 Thirst, 310 Thrombocytopenic purpura, 80 Thrombopoietin, 80 Thromboxane A2, 596 Thymectomy, myasthenia gravis treatment by, 129 Thymidine–adenine–thymidine–adenine (TATA) sequence, 14 Thyrocytes basolateral membranes of, 341 iodide transport across, 341 Thyroglossal duct, 339 Thyroid cell, 340 Thyroid gland anatomy of, 339–340 histology of, 340 lobes of, 339 spherical follicle, 340 Thyroid growth, factors affecting, 345 Thyroid hormones, 385 biological activity of, 340 calorigenic action of, 348–349 effect on Na, K ATPase pump activity, 53 fluctuations in deiodination, 344–345 iodine homeostasis and, 340–341 mechanism of action of, 347–348 metabolism of, 344–345 physiologic effects on, 347 brain, 349 cardiovascular system, 349 catecholamines, 350 nervous system, 349–350 normal growth, 350 skeletal muscle, 350 secretion, regulation of, 345–347 steroids and, difference between, 300 synthesis and secretion, 341–343 transport of, 343–344 INDEX Thyroid-stimulating hormone chemistry and metabolism of, 345 deficiency, 336 effect on thyroid, 345 secretion in cold, 319 Thyroid-stimulating immunoglobulins, 306 Thyrotropin-releasing hormone, 314 functions of, 315 Thyroxine, 340 calorigenic effect of, 348 mechanism of action of, 347–348 metabolism of, 344 plasma level in adults, 343 protein binding, 343–344 Tibialis muscular dystrophy, 100 Tickle, 159, 160 Tidal volume, 629 Tight junctions, 43 Tip links, 202 schematic representation of, 204 Tissue conductance, 318 Tissue macrophage system, 69 Tissues, Po2 and Pco2 values in, 642 Titin in skeletal muscle, 100 Titratable acid, 712 Tizanidine, ALS treatment by, 240 TLRs, 74 Toll-like receptors, 74 Tonic-clonic seizure, 277 Tonic contractions, 504 Tonicity, Tonicity, defense of, 697 clinical implications, 700 metabolism, 698 synthetic agonists/antagonists, 700 vasopressin, effects of, 698 vasopressin receptors, 697–698 vasopressin secretion control of, 698–699 stimuli, variety of, 700 volume effects on, 699–700 Topiramate, 277 for chronic pain, 164 Torsade de pointes, 532 Total blood volume, Total body calcium, 388 Total lung capacity, 629 Trabecular bone, structure of, 386 Transamination reactions, citric acid cycle in, 21 Transcellular fluids, Transcription activation of, 56 definition, 16 diagrammatic outline of, 18 into pre-mRNA, 16 Transcytosis, 54 Transducin, 184 Transepithelial transport, 53 Transforming growth factor alpha, 54 Transient receptor potential channels, 159 Transient sleep disorders, 279 Translation See Protein synthesis Transmembrane proteins in cell membrane, 36, 37 signal peptide, 20 in tight junctions, 43 Transmitter chemistry of, 136–137 endogenous cannabinoids, 151–152 hypersensitivity of postsynaptic structure to, 131 nitric oxide, 151 quantal release of, 129 receptors and, 136, 137 Transport proteins, 682 See also Membrane transport proteins Traumatic brain injury, 284 Traveling waves movement in cochlea, 206 schematic representation of, 207 TR genes, 347–348 TRH See Thyrotropin-releasing hormone TRH-secreting neurons, 315 Triacylglycerols, 26 Tricarboxylic acid cycle See Citric acid cycle Trichromats, 193, 194 Tricyclic antidepressants, 147 Triglyceride, 484 Triglycerides, 26 Triiodothyronine, 340 calorigenic effect of, 348 mechanism of action of, 347–348 metabolism of, 344 plasma level in adults, 343 protein binding, 343–344 Trinucleotide repeat diseases, 47, 245 tRNA–amino acid–adenylate complex, 19 tRNA for amino acids, 19 Troglitazone (Rezulin), 442 Trophic action, 469 Tropic hormones, 323 Tropomyosin in skeletal muscle, 100 Troponin, 57 Trousseau’s sign, 382 TRP channels, 159 True hermaphroditism, 396 Tryptophan hydroxylase in CNS, 148 TSH See Thyroid-stimulating hormone TSH receptor, 345 TSIs, 306 T tubule, 104 Tubular function, 681 Tubular myelin, 624 Tubular reabsorption, 671 Tubular secretion, 671 Tubuloglomerular feedback, 684 Tumor suppressor genes (p53 gene), 47 Turner syndrome See Ovarian agenesis Turnover rate of endogenous proteins, 17 Two-point threshold test, 162 Tympanic membrane, 199 movements of, 206 Type diabetes mellitus, 305 Type diabetes mellitus, 305 Typical depression, 149 Tyrosine kinase activity, 436 Tyrosine kinase associated (Trk) receptors, 93–94 Tyrosine kinases, diagrammatic representation of, 63 Tyrosine phosphatases, diagrammatic representation of, 63 751 U Ubiquitination definition, 20 and protein degradation, 20–21 of proteins, 20 Ultrasonography, 516 Umami taste, 224 Uncal herniation, 243 Uncompensated metabolic acidosis, 648 Uncompensated respiratory alkalosis, 647 Unconditioned stimulus, 287 Unipolar electrocardiographic leads, 526 Unipolar recording, 524 Uniports, 51 Units for measuring concentration of solutes, Uper motor neuron lesion, 233 Upper motor neurons, 239, 240 damage to, 240 Urea, 688–689 Urea cycle, 515 Urea formation enzymes involved in, 21 in liver, 21 precursor for, 21 Uremia, 548 Uric acid excretion on purine-free diet, 13 synthesis and breakdown of, 13 Urinary pH changes implications of, 714 Urine, 715 Urotensin-II, 599 US, 287 Uterine circulation, 614 Uterine musculature sensitivity to oxytocin, 313 V Vagal outflow, 459 Valproate, 277 Valsalva maneuver bradycardia, 593 diagram of response to straining, 593, 594 heart rate, 595 hyperaldosteronism, 595 intrathoracic pressure, 593 tachycardia, 593 Vasa recta, 674 Vascular endothelial growth factor, 401 Vascular link between hypothalamus and anterior pituitary, 308, 309 Vascular reactivity, 365 Vascular smooth muscle contraction and relaxation, 569, 570 latch-bridge mechanism, 569 Vas deferens, 419 Vasectomy, 423 Vasoactive intestinal polypeptide, 264, 497, 516 Vasopressin, 151, 303, 685, 698 physiologic effects, 313 Vasopressin, effects of, 698 Vasopressin escape, 700 Vasopressin receptors, 313, 697–698 Vasopressin-secreting neurons stimulation of, 312 in suprachiasmatic nuclei, 313 752 INDEX Vasopressin secretion control of, 698–699 osmotic pressure of, 697 stimuli affecting, summary of, 698 stimuli, variety of, 700 volume effects on, 699–700 Vasospasm, 403 VEGF See Vascular endothelial growth factor Venous circulation, 582 Venous pressure and flow, 582 air embolism, 583 effects of heartbeat, 583 muscle pump, 583 thoracic pump, 583 venous pressure measurement, 583–584 Venous-to-arterial shunts, 651 Ventilation, 632–633 alveolar, variations effect in respiratory rate, 633 intrapleural pressures effect, 633 uneven, 633–634 Ventilation/blood flow comparison, 652 Ventilation-perfusion imbalance, 651–652 Ventilation/perfusion ratio, 636, 637 Ventricle, left, normal pressure–volume loop of, 542 Ventricular ejection, 540 Ventricular fibrillation, 532 Ventricular muscle, comparison of, 523 Ventricular premature beats, 532 Ventricular systole, 521, 539 start of, 540 Ventrolateral spinothalamic tract, 169 Venules and veins, 572 Vertebrates, body temperature of, 316 Very low density lipoprotein, 29 Very low density lipoproteins, 29, 492 Vesicle transport and coat complex, 49 Vesicular monoamine transporter, 137 Vesicular traffic, 46 small G proteins of Rab family and, 49 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, 211 spatial orientation, 212 vestibular apparatus, 209 vestibular nuclei, 209 Vestibulocerebellar output, 250–251 Vestibulocerebellum, 250 Vestibulospinal tracts, medial and lateral, 240 Vibratory sensibility, 162 Villus sampling, chorionic, 397 VIP See Vasoactive intestinal polypeptide VIPomas See VIP-secreting tumors VIP-secreting tumors, 472 Virilization, 362 Visceral and deep pain, 165–166 Visceral reflexes, respiratory components of, 665 Visceral sensation, 169 Visual acuity, 181 Visual fields, 195 Visual function binocular vision, 195 critical fusion frequency, 194–195 dark adaptation, 194 eye movements, 195–196 superior colliculi, 196 visual fields, 195 Visual information processing, 185 Visual pathways, 207–209 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, 193 Vital lung capacity, 629 Vitamin A deficiency, 183 Vitamin D formation and hydroxylation of, 379 metabolite of, 379–381 Vitamin D-binding protein (DBP), 379 Vitamins, 492 human nutrition, 493–494 Vitamins, absorption of, 485 Vitiligo, 326 VLDL See Very low density lipoprotein VMAT, 137 Voltage-gated Ca2+ channels Ca2+ influx by, 103 in cardiac myocytes, 110, 111 Voltage-gated K+ channels, 51 feedback control in, 90 opening and closing of, 88 sequential feedback control in, action potential, 88–89 Voltage-gated Na+ channels feedback control in, 90 reponse to depolarizing stimulus, 88 sequential feedback control in, action potential, 88–89 spatial distribution of, 91 Volume conductor, 524 Voluntary movement brain stem pathways involved in lateral, 240–241 medial, 239–240 control of, 237 corticospinal and corticobulbar system role in, 239 Vomeronasal organ, 219 Vomiting, 502 neural pathways, 503 Von Willebrand factor, 79 VPB See Ventricular premature beats Vulnerable period, 533 W Warmth receptors, 161 Water dipole moment, hydrogen bond network in, Waterfall effect, 636 Water-hammer pulse, 542 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, 365–366 Water metabolism and pituitary insufficiency, 335–336 Weak acid, buffering capacity of, Weak base, buffering capacity of, Wenckebach phenomenon, 530 Wernicke’s area, 208 White blood cells cells grow, 556–558 cellular elements, 556, 557 production of, 70 White fat depots, 27 White rami communicans, 257 Whole body ammonia homeostasis, 515 Wilson disease, 246 Withdrawal reflex, importance of, 234 Wolff–Chaikoff effect, 346 Wolff–Parkinson–White syndrome, 533, 534 Working memory, 285, 288 Wound healing, 81 X X chromosomes, 392 Xerophthalmia, 183 Xerostomia, 457 Y Yawning, 665 Y chromosomes, 392 Young–Helmholtz theory of color vision, 193 Z Ziconotide, chronic pain by, 164 Zinc deficiency, 492 Zollinger–Ellison syndrome, 384 Zolpidem, 279 Zona fasciculata, 354 Zona glomerulosa, 354 Zona pellucida, 413 Zona reticularis, 354 Zonula adherens, 43 Zonula occludens, 43 Zymogen granules, 463 ... or smell of food 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 a single dose of secretin... SO 42 , HPO 42 Digestive enzymes (see Table 25 –1; 95% of protein in juice) Other proteins 464 SECTION IV Gastrointestinal Physiology REGULATION OF THE SECRETION OF PANCREATIC JUICE Secretin 12. 5... the face of cellular metabolism during the unstimulated state (Adapted from Barrett KE: Gastrointestinal Physiology McGraw-Hill, 20 06.) 4 62 SECTION IV Gastrointestinal Physiology TABLE 25 2 Principal