(BQ) Part 2 book Review of medical physiology presents the following contents: Gastrointestinal function, circulation, respiration, formation and excretion of urine, essay questions, and multiple choice questions.
SECTION V Gastrointestinal Function Digestion & Absorption 25 cocalyx is an unstirred layer similar to the layer adjacent to other biologic membranes (see Chapter 1) Solutes must diffuse across this layer to reach the mucosal cells The mucous coat overlying the cells also constitutes a significant barrier to diffusion Most substances pass from the intestinal lumen into the enterocytes and then out of the enterocytes to the interstitial fluid The processes responsible for movement across the luminal cell membrane are often quite different from those responsible for movement across the basal and lateral cell membranes to the interstitial fluid The dynamics of transport in all parts of the body are considered in Chapter INTRODUCTION The gastrointestinal system is the portal through which nutritive substances, vitamins, minerals, and fluids enter the body Proteins, fats, and complex carbohydrates are broken down into absorbable units (digested), principally in the small intestine The products of digestion and the vitamins, minerals, and water cross the mucosa and enter the lymph or the blood (absorption) The digestive and absorptive processes are the subject of this chapter The details of the functions of the various parts of the gastrointestinal system are considered in Chapter 26 Digestion of the major foodstuffs is an orderly process involving the action of a large number of digestive enzymes ( Table 25–1) Enzymes from the salivary and lingual glands attack carbohydrates and fats; enzymes from the stomach attack proteins and fats; and enzymes from the exocrine portion of the pancreas attack carbohydrates, proteins, lipids, DNA, and RNA Other enzymes that complete the digestive process are found in the luminal membranes and the cytoplasm of the cells that line the small intestine The action of the enzymes is aided by the hydrochloric acid secreted by the stomach and the bile secreted by the liver The mucosal cells in the small intestine are called enterocytes In the small intestine they have a brush border made up of numerous microvilli lining their apical surface (see Figure 26–28) This border is rich in enzymes It is lined on its luminal side by a layer that is rich in neutral and amino sugars, the glycocalyx The membranes of the mucosal cells contain glycoprotein enzymes that hydrolyze carbohydrates and peptides, and the glycocalyx is made up in part of the carbohydrate portions of these glycoproteins that extend into the intestinal lumen Next to the brush border and gly- CARBOHYDRATES Digestion The principal dietary carbohydrates are polysaccharides, disaccharides, and monosaccharides Starches (glucose polymers) and their derivatives are the only polysaccharides that are digested to any degree in the human gastrointestinal tract In glycogen, the glucose molecules are mostly in long chains (glucose molecules in 1:4α linkage), but some chain branching is produced by 1:6α linkages; (see Figure 17–11) Amylopectin, which constitutes 80–90% of dietary starch, is similar but less branched, whereas amylose is a straight chain with only 1:4α linkages Glycogen is found in animals, whereas amylose and amylopectin are of plant origin The disaccharides lactose (milk sugar) and sucrose (table sugar) are also ingested, along with the monosaccharides fructose and glucose In the mouth, starch is attacked by salivary α-amylase However, the optimal pH for this enzyme is 6.7, and its action is inhibited by the acidic gastric juice 467 Table 25–1 Principal digestive enzymes The corresponding proenzymes are shown in parentheses Source Enzyme Salivary glands Salivary α-amylase Lingual glands Lingual lipase Stomach Pepsins (pepsinogens) Activator − Cl HCl Gastric lipase Exocrine pancreas Catalytic Function or Products Starch Hydrolyzes 1:4α linkages, producing α-limit dextrins, maltotriose, and maltose Triglycerides Fatty acids plus 1,2-diacylglycerols Proteins and polypeptides Cleave peptide bonds adjacent to aromatic amino acids Triglycerides Fatty acids and glycerol 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 Facilitates exposure of active site of pancreatic lipase Pancreatic lipase Triglycerides Monoglycerides and fatty acids Cholesteryl esters Cholesterol Bile salt-acid lipase Intestinal mucosa Substrate Cholesteryl ester hydrolase Cholesteryl esters Cholesterol Pancreatic α-amylase Cl− Starch Same as salivary α-amylase Ribonuclease RNA Nucleotides Deoxyribonuclease DNA Nucleotides Phospholipase A2 (prophospholipase A2) Trypsin Phospholipids Fatty acids, lysophospholipids 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, α-dextrins Glucose (continued) DIGESTION & ABSORPTION / 469 Table 25–1 Principal digestive enzymes The corresponding proenzymes are shown in parentheses (continued) Source Intestinal mucosa (continued) Cytoplasm of mucosal cells Enzyme Activator Substrate Catalytic Function or Products Lactase Lactose Galactose and glucose Sucrasea Sucrose; also maltotriose and maltose Fructose and glucose α-Dextrinasea α-Dextrins, maltose, maltotriose Glucose Trehalase Trehalose Glucose Nuclease and related enzymes Nucleic acids Pentoses and purine and pyrimidine bases Various peptidases Di-, tri-, and tetrapeptides Amino acids Sucrase and α-dextrinase are separate subunits of a single protein a when food enters the stomach In the small intestine, both the salivary and the pancreatic α-amylase also acts on the ingested polysaccharides Both the salivary and the pancreatic α-amylases hydrolyze 1:4α linkages but spare 1:6α linkages, terminal 1:4α linkages, and the 1:4α linkages next to branching points Consequently, the end products of α-amylase digestion are oligosaccharides: the disaccharide maltose; the trisaccharide maltotriose; some slightly larger polymers with glucose in 1:4α linkage; and ␣-dextrins, polymers of glucose containing an average of about eight glucose molecules with 1:6α linkages (Figure 25–1) The oligosaccharidases responsible for the further digestion of the starch derivatives are located in the outer portion of the brush border, the membrane of the microvilli of the small intestine (Figure 25–2) Some of these enzymes have more than one substrate ␣-Dextrinase, which is also known as isomaltase, is mainly responsible for hydrolysis of 1:6α linkages Along with maltase and sucrase, it also breaks down maltotriose and maltose Sucrase and α-dextrinase are initially synthesized as a single glycoprotein chain which is inserted into the brush border membrane It is then hydrolyzed by pancreatic proteases into sucrase and isomaltase subunits Sucrase hydrolyzes sucrose into a molecule of glucose and a molecule of fructose In addition, two disaccharidases are present in the brush border: lactase, which hydrolyzes lactose to glucose and galactose, and trehalase, which hydrolyzes trehalose, a 1:1α-linked dimer of glucose, into two glucose molecules Deficiency of one or more of the brush border oligosaccharidases may cause diarrhea, bloating, and flatulence after ingestion of sugar The diarrhea is due to the increased number of osmotically active oligosaccharide molecules that remain in the intestinal lumen, causing the volume of the intestinal contents to increase In the colon, bacteria break down some of the oligosaccharides, further increasing the number of osmotically active particles The bloating and flatulence are due to the production of gas (CO2 and H2) from disaccharide residues in the lower small intestine and colon Lactase is of interest because, in most mammals and in many races of humans, intestinal lactase activity is high at birth, then declines to low levels during childhood and adulthood The low lactase levels are associated with intolerance to milk (lactose intolerance) Most Europeans and their American descendants retain their intestinal lactase activity in adulthood; the incidence of lactase deficiency in northern and western Europeans is only about 15% However, the incidence in blacks, American Indians, Orientals, and Mediterranean populations is 70–100% Milk intolerance can be ameliorated by administration of commercial lactase preparations, but this is expensive Yogurt is better tolerated than milk in intolerant individuals because it contains its own bacterial lactase 470 CHAPTER 25 / G G An α-dextrin G G G G G G Maltotriose G G Maltose Ga G Lactose F G Sucrose Figure 25–1 Principal end products of carbohydrate digestion in the intestinal lumen Each circle represents a hexose molecule G, glucose; F, fructose; Ga, galactose Absorption Hexoses and pentoses are rapidly absorbed across the wall of the small intestine (Table 25–2) Essentially all of the hexoses are removed before the remains of a meal reach the terminal part of the ileum The sugar molecules pass from the mucosal cells to the blood in the capillaries draining into the portal vein The transport of most hexoses is uniquely affected by the amount of Na+ in the intestinal lumen; a high Luminal digestion Starch Amylase concentration of Na+ on the mucosal surface of the cells facilitates and a low concentration inhibits sugar influx into the epithelial cells This is because glucose and Na+ share the same cotransporter, or symport, the sodium-dependent glucose transporter (SGLT, Na+glucose cotransporter) The members of this family of transporters, SGLT and SGLT 2, resemble the glucose transporters responsible for facilitated diffusion (see Chapter 19) in that they cross the cell membrane 12 times and have their COOH and NH2 terminals on the cytoplasmic side of the membrane However, there is no homology to the GLUT series of transporters SGLT and SGLT are also responsible for glucose transport out of the renal tubules (see Chapter 38) Since the intracellular Na+ concentration is low in intestinal cells as it is in other cells, Na+ moves into the cell along its concentration gradient Glucose moves with the Na+ and is released in the cell (Figure 25–3) The Na+ is transported into the lateral intercellular spaces, and the glucose is transported by GLUT into the interstitium and thence to the capillaries Thus, glucose transport is an example of secondary active transport (see Chapter 1); the energy for glucose transport is provided indirectly, by the active transport of Na+ out of the cell This maintains the concentration gradient across the luminal border of the cell, so that more Na+ and consequently more glucose enter When the Na+/glucose cotransporter is congenitally defective, the resulting glucose/galactose malabsorption causes severe diarrhea that is often fatal if glucose and galactose are not promptly removed from the diet The use of glucose and its polymers to retain Na+ in diarrheal disease is discussed below Membrane digestion α-Dextrinase Maltase Sucrase α-Dextrins 95 Maltotriose 50 25 25 Maltose 50 25 25 Trehalase 100 Lactose Lactase 100 Sucrose Sucrase 100 Trehalose Product Glucose Galactose Fructose Figure 25–2 Substrate specificities of the enzymes involved in carbohydrate digestion, and the hexoses that are the final products Numbers are percentages of each substrate cleaved by a particular enzyme Note that trehalase, lactase, and sucrase are solely responsible for the breakdown of trehalose, lactose, and sucrose respectively, but that α-dextrins, maltotriose, and maltose are substrates for several enzymes (Reproduced, with permission, from Johnson LR [editor]: Essential Medical Physiology, Raven, 1992.) DIGESTION & ABSORPTION / 471 Table 25–2 Normal transport of substances by the intestine and location of maximum absorption or secretion.a Small Intestine Absorption of: Upper Sugars (glucose, galactose, etc) Amino acids Water-soluble and fat-soluble vitamins except vitamin B12 Betaine, dimethylglycine, sarcosine Antibodies in newborns Pyrimidines (thymine and uracil) Long-chain fatty acid absorption and conversion to triglyceride Bile salts Vitamin B12 Na+ K+ Ca2+ Fe2+ Cl− SO42− ++ ++ +++ + + + +++ + +++ + +++ +++ +++ ++ b Mid Lower Colon +++ +++ ++ ++ ++ + ++ + + ++ + ++ + ++ + ++ ++ ++ +++ ? + +++ +++ +++ + + + + 0 0 ? ? ? 0 +++ Sec ? ? + ? Amount of absorption is graded + to +++ Sec, secreted when luminal K+ is low Upper small intestine refers primarily to jejunum, although the duodenum is similar in most cases studied (with the notable exception that the duodenum secretes HCO3− and shows little net absorption or secretion of NaCl) a b The glucose mechanism also transports galactose Fructose utilizes a different mechanism Its absorption is independent of Na+ or the transport of glucose and galactose; it is transported instead by facilitated diffusion from the intestinal lumen into the enterocytes by GLUT and out of the enterocytes into the interstitium by GLUT Some fructose is converted to glucose in the mucosal cells Pentoses are absorbed by simple diffusion Insulin has little effect on intestinal transport of sugars In this respect, intestinal absorption resembles glucose reabsorption in the proximal convoluted tubules of the kidneys (see Chapter 38); neither process requires phosphorylation, and both are essentially normal in diabetes but are depressed by the drug phlorhizin The maximal rate of glucose absorption from the intestine is about 120 g/h PROTEINS & NUCLEIC ACIDS Protein Digestion Protein digestion begins in the stomach, where pepsins cleave some of the peptide linkages Like many of the other enzymes concerned with protein digestion, pepsins are secreted in the form of inactive precursors (proenzymes) and activated in the gastrointestinal tract The pepsin precursors are called pepsinogens and are activated by gastric hydrochloric acid Human gas- tric mucosa contains a number of related pepsinogens, which can be divided into two immunohistochemically distinct groups, pepsinogen I and pepsinogen II Pepsinogen I is found only in acid-secreting regions, whereas pepsinogen II is also found in the pyloric region Maximal acid secretion correlates with pepsinogen I levels Pepsins hydrolyze the bonds between aromatic amino acids such as phenylalanine or tyrosine and a second amino acid, so the products of peptic digestion are polypeptides of very diverse sizes A gelatinase that liquefies gelatin is also found in the stomach Chymosin, a milk-clotting gastric enzyme also known as rennin, is found in the stomachs of young animals but is probably absent in humans Because pepsins have a pH optimum of 1.6–3.2, their action is terminated when the gastric contents are mixed with the alkaline pancreatic juice in the duodenum and jejunum The pH of the intestinal contents in the duodenal cap is 2.0–4.0, but in the rest of the duodenum it is about 6.5 In the small intestine, the polypeptides formed by digestion in the stomach are further digested by the powerful proteolytic enzymes of the pancreas and intestinal mucosa Trypsin, the chymotrypsins, and elastase act at interior peptide bonds in the peptide molecules and are called endopeptidases The formation of the active endopeptidases from their inactive precursors 472 / CHAPTER 25 Brush border ECF GI lumen Intercellular space Na+ ATPase ATP ADP 2Na+ Na+ SGLT Glucose Glucose GLUT Figure 25–3 Mechanism for glucose transport across intestinal epithelium Glucose transport into the intestinal cell is coupled to Na+ transport, utilizing the cotransporter SGLT Na+ is then actively transported out of the cell, and glucose enters the interstitium by facilitated diffusion via GLUT From there, it diffuses into the blood is discussed in Chapter 26 The carboxypeptidases of the pancreas are exopeptidases that hydrolyze the amino acids at the carboxyl and amino ends of the polypeptides Some free amino acids are liberated in the intestinal lumen, but others are liberated at the cell surface by the aminopeptidases, carboxypeptidases, endopeptidases, and dipeptidases in the brush border of the mucosal cells Some di- and tripeptides are actively transported into the intestinal cells and hydrolyzed by intracellular peptidases, with the amino acids entering the bloodstream Thus, the final digestion to amino acids occurs in three locations: the intestinal lumen, the brush border, and the cytoplasm of the mucosal cells Absorption At least seven different transport systems transport amino acids into enterocytes Five of these require Na+ and cotransport amino acids and Na+ in a fashion similar to the cotransport of Na+ and glucose (Figure 25–3) Two of these five also require Cl– In two systems, transport is independent of Na+ The di- and tripeptides are transported into enterocytes by a system that requires H+ instead of Na+ There is very little absorption of larger peptides In the enterocytes, amino acids released from the peptides by intra- cellular hydrolysis plus the amino acids absorbed from the intestinal lumen and brush border are transported out of the enterocytes along their basolateral borders by at least five transport systems From there, they enter the hepatic portal blood Two of these systems are dependent on Na+, and three are not Significant amounts of small peptides also enter the portal blood Absorption of amino acids is rapid in the duodenum and jejunum but slow in the ileum Approximately 50% of the digested protein comes from ingested food, 25% from proteins in digestive juices, and 25% from desquamated mucosal cells Only 2–5% of the protein in the small intestine escapes digestion and absorption Some of this is eventually digested by bacterial action in the colon Almost all of the protein in the stools is not of dietary origin but comes from bacteria and cellular debris Evidence suggests that the peptidase activities of the brush border and the mucosal cell cytoplasm are increased by resection of part of the ileum and that they are independently altered in starvation Thus, these enzymes appear to be subject to homeostatic regulation In humans, a congenital defect in the mechanism that transports neutral amino acids in the intestine and renal tubules causes Hartnup disease A congenital defect in the transport of basic amino acids causes cystinuria In infants, moderate amounts of undigested proteins are also absorbed The protein antibodies in maternal colostrum are largely secretory immunoglobulins (IgAs), the production of which is increased in the breast in late pregnancy They cross the mammary epithelium by transcytosis and enter the circulation of the infant from the intestine, providing passive immunity against infections Absorption is by endocytosis and subsequent exocytosis Protein absorption declines with age, but adults still absorb small quantities Foreign proteins that enter the circulation provoke the formation of antibodies, and the antigen–antibody reaction occurring on subsequent entry of more of the same protein may cause allergic symptoms Thus, absorption of proteins from the intestine may explain the occurrence of allergic symptoms after eating certain foods The incidence of food allergy in children is said to be as high as 8% Certain foods are more allergenic than others Crustaceans, mollusks, and fish are common offenders, and allergic responses to legumes, cows’ milk, and egg white are also relatively frequent Absorption of protein antigens, particularly bacterial and viral proteins, takes place in large microfold cells or M cells, specialized intestinal epithelial cells that overlie aggregates of lymphoid tissue (Peyer’s patches) These cells pass the antigens to the lymphoid cells, and lymphocytes are activated The activated lymphoblasts enter the circulation, but they later return to the intesti- DIGESTION & ABSORPTION nal mucosa and other epithelia, where they secrete IgA in response to subsequent exposures to the same antigen This secretory immunity is an important defense mechanism It is discussed in more detail in Chapter 27 Nucleic Acids Nucleic acids are split into nucleotides in the intestine by the pancreatic nucleases, and the nucleotides are split into the nucleosides and phosphoric acid by enzymes that appear to be located on the luminal surfaces of the mucosal cells The nucleosides are then split into their constituent sugars and purine and pyrimidine bases The bases are absorbed by active transport LIPIDS Fat Digestion A lingual lipase is secreted by Ebner’s glands on the dorsal surface of the tongue, and the stomach also secretes a lipase (Table 25–1) The gastric lipase is of little importance except in pancreatic insufficiency, but lingual lipase is active in the stomach and can digest as much as 30% of dietary triglyceride Most fat digestion begins in the duodenum, pancreatic lipase being one of the most important enzymes involved This enzyme hydrolyzes the 1- and 3-bonds of the triglycerides (triacylglycerols) with relative ease but acts on the 2-bonds at a very low rate, so the principal products of its action are free fatty acids and 2-monoglycerides (2-monoacylglycerols) It acts on fats that have been emulsified Its activity is facilitated when an amphipathic helix that covers the active site like a lid is bent back Colipase, a protein with a molecular weight of about 11,000, is also secreted in the pancreatic juice, and when this molecule binds to the COOH-terminal domain of the pancreatic lipase, opening of the lid is facilitated Colipase is secreted in an inactive proform (Table 25–1) and is activated in the intestinal lumen by trypsin Another pancreatic lipase that is activated by bile salts has been characterized This 100,000-kDa bile salt-activated lipase represents about 4% of the total protein in pancreatic juice In adults, pancreatic lipase is 10–60 times more active, but unlike pancreatic lipase, bile salt-activated lipase catalyzes the hydrolysis of cholesterol esters, esters of fat-soluble vitamins, and phospholipids, as well as triglycerides A very similar enzyme is found in human milk Most of the dietary cholesterol is in the form of cholesteryl esters, and cholesteryl ester hydrolase also hydrolyzes these esters in the intestinal lumen / 473 Fats are relatively insoluble, which limits their ability to cross the unstirred layer and reach the surface of the mucosal cells However, they are finely emulsified in the small intestine by the detergent action of bile salts, lecithin, and monoglycerides When the concentration of bile salts in the intestine is high, as it is after contraction of the gallbladder, lipids and bile salts interact spontaneously to form micelles (Figure 25–4) These cylindrical aggregates, which are discussed in more detail in Chapter 26, take up lipids, and although their lipid concentration varies, they generally contain fatty acids, monoglycerides, and cholesterol in their hydrophobic centers Micellar formation further solubilizes the lipids and provides a mechanism for their transport to the enterocytes Thus, the micelles move down their concentration gradient through the unstirred layer to the brush border of the mucosal cells The lipids diffuse out of the micelles, and a saturated aqueous solution of the lipids is maintained in contact with the brush border of the mucosal cells (Figure 25–4) BULK SOLUTION OF INTESTINAL CONTENTS Dietary triglyceride ion S rpt B so e of b c a FA resen UNSTIRRED p n i LAYER FA in ab abso se rp nc tio eo n fB S Pancreatic lipase Mucosa Figure 25–4 Lipid digestion and passage to intestinal mucosa Fatty acids (FA) are liberated by the action of pancreatic lipase on dietary triglycerides and, in the presence of bile salts (BS), form micelles (the circular structures), which diffuse through the unstirred layer to the mucosal surface (Reproduced, with permission, from Thomson ABR: Intestinal absorption of lipids: Influence of the unstirred water layer and bile acid micelle In: Disturbances in Lipid and Lipoprotein Metabolism Dietschy JM, Gotto AM Jr, Ontko JA [editors] American Physiological Society, 1978.) / CHAPTER 25 Steatorrhea cause of steatorrhea is defective reabsorption of bile salts in the distal ileum (see Chapter 26) Pancreatectomized animals and patients with diseases that destroy the exocrine portion of the pancreas have fatty, bulky, clay-colored stools (steatorrhea) because of the impaired digestion and absorption of fat The steatorrhea is due mostly to the lipase deficiency However, acid inhibits the lipase, and the lack of alkaline secretion from the pancreas also contributes by lowering the pH of the intestine contents In some cases, hypersecretion of gastric acid can cause steatorrhea Another Fat Absorption Traditionally, lipids were thought to enter the enterocytes by passive diffusion, but some evidence suggests that carriers are involved Inside the cells, the lipids are rapidly esterified, maintaining a favorable concentration gradient from the lumen into the cells (Figure 25–5) O Lumen Unstirred layer OH Glucose OH OPO3 Glycerol 3-phosphate O OH O MICELLE R C OH Fatty acid O C R OH 2-Monoglyceride Fatty acid: CoA ligase MGT R C S CoA Fatty acyl CoA *O O O O C R O C R OPO3 Phosphatidic acid O O C R O O O C R OH 1,2-Diglyceride DGT O C R DGT O C R Triglyceride O C R OH 1,2-Diglyceride Glycerophospholipids ★ ★★ ★★ ★★ Mucosal cell ★ ★★ ★ ★ ★★ ★★ ★ ★★ O C R R ★ 474 To lymph Figure 25–5 Lipid absorption Triglycerides are formed in the mucosal cells from monoglycerides and fatty acids Some of the glycerides also come from glucose via phosphatidic acid The triglycerides are then converted to chylomicrons and released by exocytosis From the extracellular space, they enter the lymph Heavy arrows indicate major pathways *, reaction inhibited by monoglyceride; MGT, monoacylglycerol acyltransferase; DGT, diacylglycerol acyltransferase DIGESTION & ABSORPTION Short-Chain Fatty Acids in the Colon Increasing attention is being focused on short-chain fatty acids (SCFAs) that are produced in the colon and absorbed from it SCFAs are two- to five-carbon weak acids that have an average normal concentration of about 80 mmol/L in the lumen About 60% of this total is acetate, 25% propionate, and 15% butyrate They are formed by the action of colonic bacteria (see Chapter 26) on complex carbohydrates, resistant starches, and other components of the dietary fiber, ie, the material that escapes digestion in the upper gastrointestinal tract and enters the colon Absorbed SCFAs are metabolized and make a significant contribution to the total caloric intake In addi- 475 100 80 % fat absorbed The rate of uptake of bile salts by the jejunal mucosa is low, and for the most part the bile salts remain in the intestinal lumen, where they are available for the formation of new micelles The fate of the fatty acids in enterocytes depends on their size Fatty acids containing less than 10–12 carbon atoms are water-soluble enough that they pass through the enterocyte unmodified and are actively transported into the portal blood They circulate as free (unesterified) fatty acids The fatty acids containing more than 10–12 carbon atoms are too insoluble for this They are reesterified to triglycerides in the enterocytes In addition, some of the absorbed cholesterol is esterified The triglycerides and cholesteryl esters are then coated with a layer of protein, cholesterol, and phospholipid to form chylomicrons These leave the cell and enter the lymphatics (Figure 25–5) In mucosal cells, most of the triglyceride is formed by the acylation of the absorbed 2-monoglycerides, primarily in the smooth endoplasmic reticulum However, some of the triglyceride is formed from glycerophosphate, which in turn is a product of glucose catabolism Glycerophosphate is also converted into glycerophospholipids that participate in chylomicron formation The acylation of glycerophosphate and the formation of lipoproteins occur in the rough endoplasmic reticulum Carbohydrate moieties are added to the proteins in the Golgi apparatus, and the finished chylomicrons are extruded by exocytosis from the basal or lateral aspects of the cell Absorption of long-chain fatty acids is greatest in the upper parts of the small intestine, but appreciable amounts are also absorbed in the ileum (Figure 25–6) On a moderate fat intake, 95% or more of the ingested fat is absorbed The processes involved in fat absorption are not fully mature at birth, and infants fail to absorb 10–15% of ingested fat Thus, they are more susceptible to the ill effects of disease processes that reduce fat absorption / 60 40 500-mL meal 30 g fat 20 Duodenum 50 100 150 200 cm from nose 250 300 Figure 25–6 Fat absorption, based on measurement after a fat meal in humans The double-headed arrow identifies the duodenum (Redrawn and reproduced, with permission, from Davenport HW: Physiology of the Digestive Tract, 2nd ed Year Book, 1966.) tion, they exert a trophic effect on the colonic epithelial cells, combat inflammation, and are absorbed in part by exchange for H+, helping to maintain acid–base equilibrium A family of anion exchangers are present in the colonic epithelial cells SCFAs also promote the absorption of Na+, although the exact mechanism for coupled Na+–SCFA absorption is unsettled Absorption of Cholesterol & Other Sterols Cholesterol is readily absorbed from the small intestine if bile, fatty acids, and pancreatic juice are present Closely related sterols of plant origin are poorly absorbed Almost all the absorbed cholesterol is incorporated into chylomicrons that enter the circulation via the lymphatics, as noted above Nonabsorbable plant sterols such as those found in soybeans reduce the absorption of cholesterol, probably by competing with cholesterol for esterification with fatty acids ABSORPTION OF WATER & ELECTROLYTES Water, Sodium, Potassium, & Chloride Overall water balance in the gastrointestinal tract is summarized in Table 25–3 The intestines are presented each day with about 2000 mL of ingested fluid plus 7000 mL of secretions from the mucosa of the gastrointestinal tract and associated glands Ninety-eight percent of this fluid is reabsorbed, with a daily fluid loss of only 200 mL in the stools Only small amounts of water move across the gastric mucosa, but water moves 476 / CHAPTER 25 Table 25–3 Daily water turnover (mL) in the gastrointestinal tract Ingested Endogenous secretions Salivary glands Stomach Bile Pancreas Intestine Lumen IF 2000 7000 1500 2500 500 1500 1000 7000 Total Input K+ 2Cl− Na+ cAMP Cl− channel mV Paracellular path CI− Na+ −40 mV ∼ K+ K+ + 10 mV Na+ 9000 Data from Moore EW: Physiology of Intestinal Water and Electrolyte Absorption, American Gastroenterological Society, 1976 Figure 25–7 Movement of ions across enterocytes in the small intestine Cl– enters the enterocyte from the interstial fluid (IF) via the Na+–K+–2Cl– cotransporter on its basolateral surface and is secreted into the intestinal lumen via Cl– channels, some of which are activated by cyclic AMP K+ recycles to the IF via basolateral K+ channels (Reproduced, with permission, from Field M, Roa MC, Chang EB: Intestinal electrolyte transport and diarrheal disease N Engl J Med 1989;321:800.) in both directions across the mucosa of the small and large intestines in response to osmotic gradients Some Na+ diffuses into or out of the small intestine depending on the concentration gradient Because the luminal membranes of all enterocytes in the small intestine and colon are permeable to Na+ and their basolateral membranes contain Na+–K+ ATPase, Na+ is also actively absorbed throughout the small and large intestines In the small intestine, secondary active transport of Na+ is important in bringing about absorption of glucose, some amino acids (see above), and other substances Conversely, the presence of glucose in the intestinal lumen facilitates the reabsorption of Na+ This is the physiologic basis for the treatment of Na+ and water loss in diarrhea by oral administration of solutions containing NaCl and glucose Cereals containing carbohydrates are also useful in the treatment of diarrhea This type of treatment has even proved to be beneficial in the treatment of cholera, a disease associated with very severe and, if untreated, frequently fatal diarrhea Cl– normally enters enterocytes from the interstitial fluid via Na+–K+–2Cl– cotransporters in their basolateral membranes (Figure 25–7), and the Cl– is then secreted into the intestinal lumen via channels that are regulated by various protein kinases One of these is activated by protein kinase A and hence by cAMP The cAMP concentration is increased in cholera The cholera bacillus stays in the intestinal lumen, but it produces a toxin which binds to GM-1 ganglioside recep- tors, and this permits part of the A subunit (A1 peptide) of the toxin to enter the cell The A1 peptide binds adenosine diphosphate ribose to the α subunit of Gs, inhibiting its GTPase activity (see Chapter 1) Therefore, the constitutively activated G protein produces prolonged stimulation of adenylyl cyclase and a marked increase in the intracellular cAMP concentration In addition to increased Cl– secretion, the function of the mucosal carrier for Na+ is reduced, thus reducing NaCl absorption The resultant increase in electrolyte and water content of the intestinal contents causes the diarrhea However, Na+–K+ ATPase and the Na+/glucose cotransporter are unaffected, so coupled reabsorption of glucose and Na+ bypasses the defect Water moves into or out of the intestine until the osmotic pressure of the intestinal contents equals that of the plasma The osmolality of the duodenal contents may be hypertonic or hypotonic, depending on the meal ingested, but by the time the meal enters the jejunum, its osmolality is close to that of plasma This osmolality is maintained throughout the rest of the small intestine; the osmotically active particles produced by digestion are removed by absorption, and water moves passively out of the gut along the osmotic gradient thus generated In the colon, Na+ is pumped out and water moves passively with it, again along the osmotic gradient Saline cathartics such as magnesium sulfate are poorly absorbed salts that retain their osmotic equivalent of water in the intestine, thus increasing intestinal volume and consequently exerting a laxative effect Reabsorbed Jejunum Ileum Colon Balance in stool 8800 5500 2000 1300 8800 200 INDEX Small motor nerve system (γ efferent system), 130f, 131 control of discharge of, 133 effects of discharge of, 132–133, 132f movement control and, 210 Smell, 122t, 185–188 See also under Olfactory abnormalities of, 188 adaptation and, 188 discrimination and, 186–187 loss of sense of, in Kallmann’s syndrome, 250 memory and, 188 nasal pain fibers and, 188 odorant-binding proteins in, 187 olfactory bulbs in, 185, 186f olfactory cortex in, 185–186 receptors for in olfactory mucous membrane, 185, 186f signal transduction and, 187 in vomeronasal organ, 187–188 signal transduction in, 187 sniffing and, 185, 188 thresholds for, 186–187, 187t vomeronasal organ in, 187–188 Smoking, emphysema and, 689 Smooth (agranular) endoplasmic reticulum, 9f, 18 Smooth muscle, 65, 82–84 denervation hypersensitivity in, 119 morphology of, 82 multiunit, 82, 84 nerve endings in, 118–119, 119f plasticity of, 84 types of, 82 vascular, 580, 581f visceral (unitary), 82, 82–84 See also Visceral (unitary) smooth muscle Smooth pursuit movements, 169, 169f SMS See Stiff-man syndrome SNAP-25, 87, 88f SNAREs, 27, 28 Sneezing, 232, 678 Snellen charts, for visual acuity assessment, 167 Sniffing, in olfaction, 185, 188 SOCCs See Store-operated calcium channels SOCS3 (suppressor of cytokine signaling-3), anorexiant effects of leptin and, 239 SOD See Superoxide dismutase SOD-1 gene, defective, in amyotrophic lateral sclerosis, 203, 518 Sodium See also Sodium channels absorption of, 476, 476f in amino acid transport, 472 concentration of, ECG affected by changes in, 563 conductance of during action potential, 59, 59f dietary, 313 aldosterone secretion affected by, 379, 380f, 723 hypertension and, 641 distribution of, 8t, 30f changes in during action potential in cardiac muscle, 78, 80f, 548 in neurons, 59 resting membrane potential and, 59 in skeletal muscle, 68, 69t edema and, 594, 726 equilibrium potential for, 8, 8t excretion/tubular reabsorption of, 709, 710t, 711f, 723–724, 723t, 724f abnormal, 726 adrenocortical steroids/mineralocorticoids affecting, 375–376, 376, 376–377, 376f, 376t, 381, 723, 724f aldosterone affecting, 375–376, 376f, 380, 723, 724f angiotensin II affecting, 456, 723 in Bartter’s syndrome, 715 estrogens affecting, 442 extracellular volume and, 723, 729–730, 730f mechanisms of, 723, 723t natriuretic hormones affecting, 460 regulation of, 723–724, 723t, 724f renal nerves in regulation of, 704, 705t glucose transport and, 470–471, 472f in kidneys, 711 in hypertension, 641 loss of, in congenital adrenal hyperplasia, 366 in neuromuscular transmission, 117 plasma levels of, 699t aldosterone and, 375–376, 376f, 379 in plasma osmolality, in renin secretion regulation, 458 retention of, 726 estrogens affecting, 442 extracellular volume defense and, 729–730, 730f in hypovolemic shock, 638 secondary active transport of, 35, 35f size of, 32t urinary levels of, 699t Sodium-bile salt cotransporter, 502 Sodium channels, 32–33, 34f amiloride-inhibitable, 33 in cardiac muscle, 78, 548 epithelial (ENaCs) See Epithelial sodium channels in neurons changes in during action potential, 59 distribution of, 59–60 inactivated state of, 59 photoreceptor potentials and, 157, 157f / 899 in touch sensation, 141 Sodium current, in cardiac muscle, 78, 80f, 548 Sodium-dependent glucose cotransporters (SGLT), 337, 338t, 470, 472f in tubular reabsorption of glucose, 711 Sodium-hydrogen exchange in hydrogen secretion, 720, 720f in sodium reabsorption/excretion, 709, 710t Sodium-potassium-activated adenosine triphosphatase See Na+-K+ ATPase Sodium-potassium-chloride cotransporter, 476 in cerebral capillaries, 615 in loop of Henle, 713 diuretic mechanism of action and, 724, 725t in sodium reabsorption/excretion, 709, 710t Sodium-potassium pump See Na+-K+ ATPase Solitary lymphatic nodules, 505 Soluble N-ethylmalemite-sensitive factor attachment receptors (SNAREs), 27, 28 Solutes concentration of, units for measuring, 3–4 in osmosis, renal handling of, 710t Solutions ideal, normality of, tonicity of, Solvents, in osmosis, Soma (cell body), neuron, 52f, 53 Somatic angiotensin-converting enzyme, 455, 456f Somatic chromosomes (autosomes), 411, 412, 413f nondisjunction of, 414–416, 418f Somatic motor activity See Movement Somatic sensory area I, 139, 140f effects of lesions in, 141 in pain sensation, 142 Somatic sensory area II, 139, 140, 140f effects of lesions in, 141 in pain sensation, 142 Somatomammotropin, human chorionic (hCS) See Human chorionic somatomammotropin Somatomedin C See Insulin-like growth factor I Somatomedins, 400–402, 403f, 404t Somatostatin (growth-inhibiting hormone/GIH), 95t, 113, 114f, 247, 248f, 249–250, 333, 350–351, 487 in appetite/food intake control, 238t, 240 900 / INDEX Somatostatin (cont.) D cell secretion of, 333, 350, 487 in hypothalamic control of growth hormone, 236t, 249f, 403, 405f insulin secretion affected by, 113, 350–351 interactions of with other islet hormones, 351, 351f locations of, 95t, 113 neurons secreting, 250f receptors for, 113, 351 structure of, 249f Somatostatin 14, 113, 114f, 350–351, 487 Somatostatin 28, 113, 114f, 350–351, 487 Somatostatinomas, 351 Somatosympathetic reflex, 605 Somatotropes, 396, 397t tumors of G protein/G protein receptor mutation and, 47–48, 48t gigantism/acromegaly caused by, 409 Somatotropin See Growth hormone Somnambulism (sleepwalking), 201 Sound decibel scale for, 177–178, 178t localization of, 182 transmission of, 178, 179f Sound waves, 176–178, 177f, 178f conduction of, 179 traveling, 179–180, 179f Sounds of Korotkoff, 583, 589 Sour taste, sensation of, 189 receptors for, 190, 190f SP-A/SP-B/SP-C/SP-D, in surfactant formation, 656 SP/NKA (substance P/neurokinin A) gene, 111, 112t Space motion sickness, 184, 632 Space travel disuse osteoporosis and, 387 effects of zero gravity and, 632 Spasm (muscle) deep pain and, 143 in spinal animal/human, 209 visceral pain and, 144–145 Spastic (hypertonic) muscle, 134 Spastic neurogenic bladder, 728 Spastic paralysis, 203 Spatial orientation, 184 Spatial summation of excitatory postsynaptic potentials, 89, 89f of inhibitory postsynaptic potentials, 90 SPCA (factor VII), 540t, 541t deficiency of, 545t Special senses, 121–122, 122t See also under Sensory Specialization, complementary, of cerebral hemispheres, 272–273 Specific cholinesterase See also Acetylcholinesterase Specific dynamic action of food, 281 Specific sensory relay nuclei, 192 Spectrin, 14f, 533 Speech, scanning, 222 Sperm See Spermatozoa Sperm count infertility and, 427 temperature and, 427 Spermatic arteries and veins, 424 Spermatids, 425, 426f Spermatocytes, 425, 425f, 426f Spermatogenesis, 424, 425, 426f temperature affecting, 427 Spermatogonia (germ cells), 424, 425, 425f, 426f Spermatozoa (sperms), 425, 426f antibodies against, 428 development of, 425–427, 426f in fertilization, 448, 448f motility of, 425–426 receptor for, in fertilization, 426–427 transport of, oxytocin affecting, 247–248 Spermicides, 447t Spermiogenesis, 426f Spherocytosis, hereditary (congenital hemolytic icterus), 533 Sphincters anal, 510–511, 510f, 511f autonomic nerve impulses affecting, 226 bladder, autonomic nerve impulses and catecholamines affecting, 228t esophageal, lower, 490, 490f motor disorders and, 490–491 extrinsic, 490 gastric, autonomic nerve impulses and catecholamines affecting, 228t intestinal, autonomic nerve impulses and catecholamines affecting, 228t intrinsic, 490 iris, autonomic nerve impulses and catecholamines affecting, 227t of Oddi, 500, 503 precapillary, 577, 579f constriction of, in white reaction, 625 urethral, 726 Sphygmomanometer, 589, 589f Spike potential, 55, 56f basic electrical rhythm and, 481, 481f changes in excitability during, 56–57, 57f in visceral smooth muscle, 82 Spinal animal/human, 135, 209 withdrawal reflex in, 135, 209 Spinal cord central excitatory and inhibitory states and, 137 injury/transection of bladder affected by, 209, 728 complications of, 208–209 denervation hypersensitivity and, 120 respiratory control and, 653 spinal reflexes after, 208 spinal shock after, 207–208 withdrawal reflex and, 135, 209 postsynaptic inhibition in, 91, 92f, 111 Spinal fluid See Cerebrospinal fluid Spinal integration, 207–210 Spinal reflexes defecation as, 511 in ejaculation, 428 motor integration and, 207t after spinal cord injury/transection, 208, 209–210 Spinal shock, 207–208 Spinnbarkeit, 437 Spinobulbar muscular atrophy, trinucleotide repeat expansion in, 215t Spinocerebellar ataxia, trinucleotide repeat expansion in, 215t Spinocerebellar tracts, dorsal and ventral, 221t Spinocerebellum, 202, 220–221, 221f See also Cerebellum Spiral arteries, of endometrium, 436, 437f Spiral ganglion, 173, 173f Spiral valves, 500 Spirometry/spirometer, 281, 281f Spironolactone, 725t Splanchnic circulation, 623–625, 624f in hypovolemic shock, 638 reservoir function of, 625 Splay, 711, 712f Spleen, 533–534 capsule of, autonomic nerve impulses and catecholamines affecting, 228t contraction of, in shock, 638 platelets in, 531 reservoir function of, 625 Spliceosomes, 22 “Split-brain animal,” intercortical transfer of memory and, 268 Splitting, of heart sound, 569 Spongy (trabecular) bone, 384–385, 384f “Spray” endings, in proprioception, 142 Sprue, celiac (gluten enteropathy), 507 Squint (strabismus), 156 SRP See Signal recognition particle SRY (sex-determining region of Y chromosome), 411 SS14 See Somatostatin 14 SS28 See Somatostatin 28 SSTR1 through SSTR5, 113 insulin secretion and, 113, 351 ST interval, 551t ST segment, 550, 550f changes in, in myocardial infarction, 561, 561t, 562f INDEX Stable factor (factor VII), 540t, 541t deficiency of, 545t Stagnant (ischemic) hypoxia, 683, 690–691 See also Hypoxia in hypovolemic shock, 638 “Staircase” phenomenon (treppe), 72 Standard bicarbonate, in Siggaard-Andersen curve nomogram, 737, 737f Standard deviation of sample, 812 Standard error of mean, 812–813 Standard limb leads, for ECG, 550, 551 Standard metabolic rate See Basal (standard) metabolic rate Standing, compensation for effects of, 630–631, 631f Stapedius muscle, 171 Stapes, 171, 172f in hearing, 178, 179f StAR (steroidogenic acute regulatory) protein, 365 Starches, digestion of, 467–469, 470f Starling forces, capillary filtration and, 592, 592f Starling’s law of the heart, 80, 81f, 572 Starvation, 298 carbohydrate metabolism and, 290–291, 298 catch-up growth and, 406–407 cellular lipids in, 300 glucagon secretion affected by, 350 ketosis in, 298 response to, 298 thyroid hormone metabolism affected by, 323, 323f STAT (signal transducer and activator of transcription) proteins, 46, 47f, 400 Static fusiform axons, 131 Static reflexes, 207 Static response, 131, 134f Statins, 306 Statistical evaluation of data, 811–814 Stearic acid, 299t Steatorrhea, 474, 507 Stellate cells, in cerebellum, 219f, 220 Stellate ganglia, 223 Stem cell factor (SCF), 517f, 519, 520t Stem cells hematopoietic, 515–516, 519 totipotential, 516 Stenosis, valvular, murmurs and, 569, 570t Stereocilia, 175, 175f tip links joining, 176, 176f Stereognosis, 147 impaired (astereognosis), 147, 273 Steroid factor-1, 366 Steroid feedback in ovarian function control, 445–446, 446f in testicular function control, 432–433, 432f Steroid hormone-binding globulin, 541t Steroid hormones, 356 See also Glucocorticoids; Mineralocorticoids adrenal secretion of, 356, 358, 358f aggressive behavior and, 260 biosynthesis of, 362f, 363f, 364–366, 364f, 365t enzyme deficiencies affecting, 365–366, 366f fetoplacental unit producing, 450, 450f mechanism of action of, 37, 38–39, 38f neuroactive, 115 nongenomic actions of, 39 rapidity of action of, 39 receptors for, 39, 39f sex See Sex hormones/steroids structure of, 361, 361f synthetic, 363, 364t Steroidogenic acute regulatory (StAR) protein, 365 Sterols, 298, 299t See also Cholesterol absorption of, 475 STH (somatotropin) See Growth hormone Stiff-man syndrome, glutamate decarboxylase autoimmunity in, 110 Stimulus adequate, 121, 137 arousal value of, 267 conditioned, 267, 268, 268f intensity discrimination and, 126, 126f irradiation of, 135 maximal, 60 nociceptive, withdrawal reflex and, 135–136 supramaximal, 60 unconditioned, 267, 268, 268f Stimulus artifact, 55, 55f Stokes-Adams syndrome, 555 Stomach, 491–497 See also under Gastric anatomy of, 491, 491f autonomic nerve impulses and catecholamines affecting, 228t digestive enzymes of, 468t fat digestion in, 473 gastrointestinal hormone distribution in, 484f iron absorption and, 477 length of, 505t miscellaneous functions of, 496–497, 496f protein digestion in, 471 resection of, 496–497 intrinsic factor deficiency and, 496 malabsorption and, 496–497 Stool (feces), 509, 509t acholic, 509 bile pigments in, 501 pH of, 509 rectal distention with, defecation and, 510–511, 510f / 901 Stop codons, 24 Store-operated calcium channels, 40 Strabismus, 156, 169–170 Strangeness, sense of, 270–271 Stratum basale, 436 Stratum functionale, 436 Streamline (laminar) flow, 569, 582–583, 583f Strength–duration curve, 56 Streptokinase, for myocardial infarction, 544 Stress, ACTH/glucocorticoids in, 370, 374, 374f Stress analgesia, 145 Stress proteins, 39 Stretch receptors atrial, 607 baroreceptors as, 605 in bladder, 727 left ventricular, 608 postsynaptic inhibition in spinal cord and, 91 Stretch reflex, 129–134, 130f, 132f, 133f, 134f, 135f, 208t afferent fiber central connections and, 131 cerebellar stimulation affecting, 221 clinical examples of, 129–130 clonus and, 134 corticospinal and corticobulbar system affecting, 206 gamma efferent discharge and control of, 133 effects of, 132–133, 132f inverse (autogenic inhibition), 133–134, 133f, 134f, 135f lengthening reaction and, 134 muscle spindle function and, 131, 132f muscle spindle structure and, 130–131, 130f muscle tone and, 134 reaction time for, 131 reciprocal innervation and, 133 in spinal animal/human, 209 supraspinal regulation of, 210, 210f thyroid hormones affecting, 325 Stretch stimulus peristalsis and, 480 visceral smooth muscle affected by, 83, 83f Stria vascularis, 173f Striae, in Cushing’s syndrome, 371 Striations in cardiac muscle, 78, 79f in skeletal muscle, 65–67, 66f, 67f Striatum, 213, 213t, 214, 214f fetal, transplantation of for Huntington’s disease, 215 for Parkinson’s disease, 217 implicit memory and, 269 Striosomes, 214 Stroke, 620 excitotoxins and, 109, 620 902 / INDEX Stroke volume, 571 cardiac output affected by, 571–572 exercise affecting, 574, 575f, 575t, 633, 634f gravity affecting, 631f myocardial contractility affecting, 573–574, 574f Structural lipids, 300 Strychnine, glycine activity affected by, 111 Stuart-Prower factor (factor X), 540t, 541t, 542f, 543 deficiency of, 545t Student’s t test, 813 Stuttering, 275 Subcommissural organ, 615f, 616 Subfornical organ, 615, 615f, 616 angiotensin II affecting, 456, 616 thirst regulation and, 241, 626 Subliminal fringe, 94 Sublingual glands, 489t Submandibular (submaxillary) glands, 488f, 489t Submucosa, 479, 480f Submucous (Meissner’s) plexus, 479, 480f Substance P, 95t, 111–112, 112t, 483t, 487 axon reflex and, 603, 625–626 capillary permeability/vasodilation affected by, 593, 602–603 locations of, 95t, 111–112, 484f, 487 in pain sensation, 142 in peristalsis, 480 structure of, 112, 483t Substance P/neurokinin A (SP/NKA) gene, 111, 112t Substantia gelatinosa, 138 Substantia nigra, 213, 213f, 213t dopaminergic neuron loss in, in Parkinson’s disease, 216, 216f, 217 Subthalamic nucleus (body of Luys), 213, 213f, 213t, 214f surgical lesions in, for Parkinson’s disease, 217 Succinate dehydrogenase-ubiquinone oxidoreductase, 11 Sucking (open) pneumothorax, 688 Sucrase, 469, 469t, 470f Sucrose, 467, 470f size of, 32t Sucrose space, Sudden infant death syndrome, 693–694 Sulfates, urinary, 294 Sulfokinase, adrenal, 365 Sulfonylureas, 346 Summation, in synaptic transmission, 93–94, 93f of excitatory postsynaptic potentials, 89, 89f, 94 of inhibitory postsynaptic potentials, 90 Summation of contractions, 71–72, 72f Sunday morning paralysis, 61 Superfemale (XXX pattern), 416, 418f, 418t Superior colliculi, 169 Superior ganglia, 223, 225f Superior peduncle (brachium conjunctivum), 217, 217f, 218f Superoxide dismutase, 518 aging and, 49 in amyotrophic lateral sclerosis, 203, 518 Supersensitivity See Denervation hypersensitivity Supplementary motor area, 204, 204f, 205–206 Supporting reactions negative, 208t positive (magnet), 208t, 209 Suppression scotoma, 170 Suppressor of cytokine signaling-3 (SOCS3), anorexiant effects of leptin and, 239 Suppressor strip, 212 Suprachiasmatic nuclei, 234f, 235 Supramaximal stimulus, 60 Supraoptic crest See Organum vasculosum of lamina terminalis Supraventricular tachycardia, 558 Surface tension, alveolar, 654, 656f surfactant and, 655–657 Surfactant, 655–657, 656f deficiency of in atelectasis, 657, 688 in infant respiratory distress syndrome, 656 glucocorticoids affecting maturation of, 657 Surgical shock, 640 Sustaining collateral, 119, 119f Sustentacular cells hair cells supported by, 175 in otolithic organ (macula), 173 in taste buds, 188, 188f Swallowing, 232, 489–490 fainting caused by (deglutition syncope), 640 lower esophageal sphincter activity and, 490 medullary control of, 232 Sweat glands, autonomic nerve impulses and catecholamines affecting, 228t Sweating, in heat loss, 253, 635 Sweet taste, sensation of, 189 receptors for, 190, 190f Symbionts, in gastrointestinal tract, 509 Sympathectomy blood vessel dilation caused by, 602 denervation hypersensitivity and, 120 Sympathetic division of autonomic nervous system, 223, 224f, 225f blood vessels innervated by, 602–603, 602f brown fat innervated by, 301 cardiac innervation by, 549 cerebral circulation affected by, 617–618, 618f in defecation, 510 drugs and toxins affecting, 230t gastrointestinal system innervated by, 479–480 in glucagon secretion, 349–350 in insulin secretion, 346–347 myocardial contractility and, 573, 574f renal circulation affected by, 702, 704 in renin secretion regulation, 458 in salivary secretion, 489 vasoactive actions of, 602–603, 603–604, 603t, 604f visceral pain sensation and, 143, 144f Sympathetic dystrophy, reflex, 146 Sympathetic ganglia, 223, 224f drugs and toxins affecting, 230t postsynaptic potentials in, 90, 224–226, 226t transmission in, 224–226, 226t Sympathetic vasodilator system, 602, 609–610 Symports/symporters, 32 See also specific type and Cotransporters Na+-I¯ (iodide pump), 319 Synapses, 85, 86f, 87f chemical, 85, 94 See also Chemical transmission pre- and postsynaptic structure and function and, 86–88, 87f electrical, 85, 91 en passant, 118 “immunologic,” 527 inhibition and facilitation at, 91–94, 92f, 93f types of, 85, 86f, 87f Synaptic communication See Synaptic transmission Synaptic delay, 89–90 Synaptic knobs (terminal buttons/axon telodendria), 51, 52f, 85, 86f facilitation by, 89 Synaptic plasticity, learning and, 116, 117f Synaptic potentials, 54 Synaptic transmission, 36, 36f, 85, 85–116 chemical, 85 neurotransmitter systems in, 85 electrical, 85, 91 functional anatomy related to, 85–88, 86f, 87f, 88f inhibition and facilitation of, 91–94, 92f, 93f plasticity and learning in, 116, 117f postsynaptic electrical events in, 88–91, 89f, 90f, 91f Synaptic vesicles, 86–88, 87f, 88f Synaptic zones, rod and cone, 150, 152f INDEX Synaptobrevin, 87, 88f Synchronization, in sleep, 195 Synchronizing zone, medullary, 198–199 Syncope, 640 See also Fainting Syncytiotrophoblast, 448 Syndrome of inappropriate hypersecretion of antidiuretic hormone (SIADH), 246–247 Syndrome X (metabolic syndrome), 347–348 Syndromic deafness, 183 Syntaxin, 87, 88f Synthetic senses, 147 Synthetic steroids, 363, 364t estrogens, 442–443 α-Synuclein, in Parkinson’s disease, 217 Systemic (major) circulation, 515, 577, 578f exercise affecting, 633–634, 634f, 634t Systole, 547 antral, 494 atrial, 547, 565, 566f, 567f blood flow changes during, 587, 587f, 595 coronary artery, 621–622, 621f length of, 566–568, 568t total electromechanical, 568 ventricular, 547, 565, 566f, 567f Systolic dysfunction, end-diastolic volume affected by, 573, 573f Systolic heart failure, 643 Systolic murmurs, 569, 570, 570t Systolic pressure, 565, 587, 588f See also Blood pressure age affecting, 590, 590f exercise affecting, 633, 634f T2R receptor family, in bitter taste sensation, 190, 190f T3 See Triiodothyronine T4 See Thyroxine T cell receptors, 527, 527f genetic basis of diversity and, 529–530 in transplant rejection, 530–531, 530t T cells See T lymphocytes αβ T cells, 525, 527, 527f γδ T cells, 525, 527 T channels, in cardiac muscle, 78, 548, 549f T (tense) configuration, 666 T helper cells (TH1), 525 T helper cells (TH2), 525 in B cell activation, 527, 528f T lymphocytes, 521, 525 development of, 517f in HIV infection, 531 immune system disorders and, 531, 531f memory, 525, 525–526, 525f receptors for, 527, 527f genetic basis of diversity and, 529–530 in transplant rejection, 530–531, 530f t-PA See Tissue-type plasminogen activator t-SNARES/t-snare proteins, 27, 28, 87 T system in cardiac muscle, 78, 79f in skeletal muscle, 66f, 67–68 in contraction, 69, 70, 70t, 71f t test, Student’s, 813 T wave, 550, 550f, 551 Tabes dorsalis, bladder affected in, 728 Tac antigen, 522 Tachycardia, 554, 556 atrial, 556–557, 557f paroxysmal, 556 atrial, with block, 557 nodal, 558 supraventricular, 558 ventricular, 558, 558f in shock, 637 Tachykinins, 95t, 112–113, 112t locations of, 95t pulmonary circulation affected by, 664t receptors for, ligands for, 42t Tachypnea, 684 in pulmonary embolism, 694 Tacrolimus (FK-506), for transplant rejection, 530, 530f Tamoxifen, 443, 453 Tamponade, cardiac, 641 Tandem repeats, 19 Tangent screen, for visual field assessment, 168 Taste, 122t, 188–191 abnormalities of, 191 after-effects and, 191 discrimination and, 190–191 flavor and, 191 modalities of, 189 pathways in, 189, 189f receptors for, 188–189, 188f, 189–190, 190f sense organs for (taste buds), 188–189, 188f, 189f signal transduction in, 189–190 thresholds for, 190–191, 190t variations in, 191 Taste buds, 188–189, 188f, 189f TATA box, 22, 22f Tau protein, in Alzheimer’s disease, 271 Taxol See Paclitaxel TBG See Thyroxine-binding globulin TBPA (thyroxine-binding prealbumin) See Transthyretin TBW See Total body water Technetium 99m stannous pyrophosphate, for coronary blood flow measurement, 622 α-Tectin, deafness caused by mutant forms of, 183 Tectocerebellar tract, 221t Tectorial membrane, 172f, 173, 173f / 903 Teeth chewing and, 488 grinding (bruxism), 199 Tegmental system, lateral, 262f, 263 Teleceptors, 121 Telodendria, axon (terminal buttons/synaptic knobs), 51, 52f, 85, 86f facilitation by, 89 Telomerase, 20 aging and, 20, 49 Telomeres, 20 Temperature See also Body temperature appetite/food intake affected by, 240 cutaneous vessels affected by, 253, 254, 625–626 exercise and, 252, 634–635, 634f heat loss mechanisms affected by, 252–253, 252t metabolic rate/metabolism affected by, 252, 252f, 281 oxygen-hemoglobin dissociation curve affected by, 667, 667f, 668f regulation of, 236t, 251–255, 252f, 252t, 254t, 255t See also Thermoregulation scrotal/testicular, 251, 427 sensation of, 122t, 142 pathways for, 139f, 142 receptors for, 138, 139f, 142 of skin, heat loss and, 253 spermatogenesis affected by, 427 vasoconstriction caused by, 598 vasodilation caused by, 597 Temperature threshold, thermoregulating responses and, 254 Temporal association area, 272, 272f Temporal lobe, 272f in face recognition, 275, 275f medial, in memory, 269–270, 270f Temporal (ventral) pathway, in vision, 163 Temporal summation of excitatory postsynaptic potentials, 89, 89f of inhibitory postsynaptic potentials, 90 Teniae coli, 508, 508f Tense (T) configuration, 666 Tension cardiac muscle contraction and, 80–81, 81f, 572–573, 573, 574f skeletal muscle contraction and, 72–73, 73f vessel wall, distending pressure and (law of Laplace), 576, 586, 586f visceral smooth muscle contraction and, 84 Tension pneumothorax, 688 Tensor tympani muscle, 171 Terminal bronchioles, 648f 904 / INDEX Terminal buttons (synaptic knobs/axon telodendria), 51, 52f, 85, 86f facilitation by, 89 Terminal cisterns, in skeletal muscle, 68 Tertiary adrenal insufficiency, 381 Tertiary structure of protein, 292 Testes development of, 414, 415f estrogens produced by, 431 function of abnormalities of, 433 control of, 431–433, 432f endocrine, 428–431, 429f, 429t, 430t, 431f See also Testosterone inhibins affecting, 432, 432f steroid feedback and, 432–433, 432f rete, 424f estrogen receptors in, 425 structure of, 424, 424f temperature and, 427 tumors of cryptorchidism and, 433 functioning, 433 undescended (cryptorchidism), 433 Testicular descent, abnormalities of, 433 Testicular feminizing syndrome, 418 Testosterone, 411 See also Androgens actions/effects of, 368–369, 429–430, 431f anabolic, 430 mechanisms of, 430–431 age affecting levels of, 418, 419f binding of, 429, 429t, 430 chemistry and biosynthesis of, 428, 429f genital development and, 414, 417, 417f gonadal development and, 411 pubertal changes in levels of, 418, 419f receptor for, 430, 431f secondary sex characteristics and, 430, 430t secretion of, 428 menstrual cycle and, 441t sexual behavior affected by, 257 transport and metabolism of, 429, 429f, 429t Testotoxicosis, G protein/G protein receptor mutation and, 47, 48t Tetanus (tetanic contraction) in multiunit smooth muscle, 84 in skeletal muscle, 72, 72f Tetanus toxin, 87 Tetany hypocalcemic, 382, 392, 392f hypocapnia and, 692 Tetrahydrobiopterin in catecholamine biosynthesis, 102, 102f deficiency of, in phenylketonuria, 103 ∆9-Tetrahydrocannabinol (THC), receptors for, 114–115 Tetraploid cells, 20 TGF See Transforming growth factor TGFα See Transforming growth factor alpha TGFβ See Transforming growth factor beta TH1 cells, 525 TH2 cells, 525 in B cell activation, 527, 528f Thalamic fasciculus, 213 Thalamic nuclei, 192 Thalamocortical oscillations, 197, 198f Thalamus, 192 basal ganglia relationship and, 213, 214f in memory, 270 Thalassemias, 535 Thallium 201, for coronary blood flow measurement, 622 THC See ∆9-Tetrahydrocannabinol Thebesian veins, 620f, 621 Theca interna, 434, 435f estrogen biosynthesis in, 438, 440f Thelarche, 419 Theophylline, as diuretic, mechanism of action of, 725t Thermal gradient, 253 Thermodilution, for cardiac output measurement, 571 Thermodynamics, first law of, 282 Thermogenesis nonexercise activity (NEAT), 311 thyroid hormone, 327 Thermoreceptors, 138, 139f, 142 Thermoregulation, 251–255, 252f, 252t, 254t, 255t afferents in, 254 blood flow in skin and, 253, 254, 625 exercise and, 252, 634–635, 634f fever and, 254–255, 255f heat loss and, 252–253, 252t heat production and, 252, 252t hypothalamus in, 236t, 251–255, 252f, 252t, 254t, 255t hypothermia and, 255 mechanisms of, 253–254, 254t progesterone in, 444 thyroid hormones and, 254 UCP in, 254, 301–302 Thermostatic hypothesis, appetite/for food intake regulation, 238 Theta rhythm, EEG, 195 Thiamine (vitamin B1), 314t requirements/RDAs for, 312t Thiazide diuretics, 724, 725t Thiazolidinediones, 12, 346 Thick filaments, in skeletal muscle, 65, 66f, 67, 67f in contraction, 69, 70t Thin filaments, in skeletal muscle, 65, 66f, 67, 67f in contraction, 69, 70t in dystrophin-glycoprotein complex, 68, 68f Thiocyanates, in goitrogens, 332 Thiorphan, ANP levels affected by, 462 Thiourylenes, 330–331, 331f Third-degree (complete) heart block, 555, 555f implanted pacemaker for, 556 Third heart sound, 567f, 569 Thirst, 240–242 defense of tonicity and, 729, 730f hemorrhage and, 241, 241f, 638 regulation of angiotensin II in, 241, 241f hypothalamus in, 236t, 240–242, 241f Thoracic pump, 595 Thorel, internodal tract of, 547 Thoroughfare vessel, 577 3β-hydroxysteroid dehydrogenase, 362f, 364, 365t deficiency of, 365 Threshold, 55, 55f, 57f auditory, 177, 178, 178f changes in during electrotonic and action potentials, 56–57, 57f olfactory, 186–187, 187t age affecting, 188 taste, 190–191, 190t temperature, thermoregulating responses and, 254 two-point, 147 visual, 167 Threshold intensity, 56 Thrombasthenic purpura, 532 Thrombin, 542f, 543, 543f binding of to thrombomodulin, 543, 543f Thrombocytopenic purpura, 532 Thrombocytosis, 531, 532 Thrombolytic therapy for myocardial infarction, 544 for stroke, 620 Thrombomodulin, 543, 543f Thromboplastin (factor III), 540t tissue, 542f, 543 Thrombopoietin, 520t, 532 Thrombosis, 545 stroke and, 620 thrombocytosis and, 532 Thromboxane A2, 308, 308f, 600 in cardiovascular regulation, 600 receptor for, G protein/G protein receptor mutation and, 48t Thromboxane B2, 308f Thromboxanes, 308, 308f, 310t pulmonary circulation affected by, 664t Thrombus See also Thrombosis mural, 545 Thymus glucocorticoids affecting, 370 INDEX T lymphocyte development and, 517f, 525, 525f Thyroglobulin, 319, 320f antibodies to, 329 Thyroglossal duct, 317 Thyroid-binding proteins, 321–322, 321t estrogens affecting, 322, 322t fluctuations in concentrations of, 322, 322t Thyroid gland, 317–332 anatomy of, 317, 318f calcitonin produced by, 393–394, 394f disorders of, 328–330 See also Hyperthyroidism; Hypothyroidism hormones secreted by See Thyroid hormones thyroid-stimulating hormone affecting, 326–327 Thyroid hormone thermogenesis, 327 Thyroid hormones See also Thyroxine; Triiodothyronine calcium metabolism affected by, 395 calorigenic action of, 323, 324, 324f, 324t effects secondary to, 324–325 carbohydrate metabolism affected by, 326, 352 cardiovascular system affected by, 324t, 325 catecholamine relation and, 325–326 chemistry of, 317, 318f cholesterol levels/metabolism affected by, 306, 324t, 326 clinical correlates of imbalances of, 328–332, 328f, 329f, 329t, 331f, 332f See also Hyperthyroidism; Hypothyroidism deiodination of, 320 fluctuations in, 323, 323f in diabetes, 347, 352 effects of, 323–326, 324t formation and secretion of, 317–320, 318f, 319f, 320f regulation of, 326–328, 327f control mechanisms in, 327–328, 327f secretion, 319–320, 320f synthesis, 319, 320f antithyroid drugs affecting, 330–331 growth affected by, 326, 406, 406f, 407f iodine metabolism and, 317–319, 319f mechanisms of action of, 37, 38–39, 38f, 38t, 323–324, 324f metabolism of, 322–323, 323f Na+/I¯ symporter (iodide pump) and, 319 Na+-K+ ATPase activity affected by, 34 nervous system affected by, 324t, 325 for nonthyroidal diseases, 332 plasma protein binding and, 321–322, 321t fluctuations in, 322, 322t receptors for, 323 thyroid resistance in abnormalities of, 330 resistance to, 330 skeletal muscle affected by, 324t, 326 transport of, 321–322, 321f, 321t, 322t Thyroid isthmus, 317 Thyroid peroxidase, 319 antibodies to, 329 Thyroid-stimulating hormone (thyrotropin/TSH), 248, 248f, 326–328, 327f, 396 actions of, 248f cells secreting, 396, 397t chemistry of, 326, 327f fluctuations in binding and, 322, 322t half life of, 326 in hyperthyroidism, 329 hypothalamus in regulation of, 236t, 249f, 327, 327f in hypothyroidism, 328 metabolism of, 326, 327f pituitary gland in regulation of, 326, 327, 327f plasma levels of, 326, 327f in thyroid hormone resistance, 330 receptors for, 327 antibodies to, 329 G protein/G protein receptor mutation and, 47, 48t structure of, 397 suppression of, 332 in thermoregulation, 254 thyroid gland affected by, 326–327 in thyroid hormone resistance, 330 tumors secreting, 410 Thyroid storm, 325–326 Thyroiditis, Hashimoto’s, 329–330 Thyrotoxic myopathy, 326 Thyrotoxicosis See Hyperthyroidism Thyrotropes, 396, 397t Thyrotropin See Thyroid-stimulating hormone Thyrotropin-releasing hormone (TRH), 95t, 247, 248f, 249 in hypothalamic control of TSH, 236t, 249, 249f, 326, 327, 327f locations of, 95t neurons secreting, 249, 250f prolactin secretion affected by, 249, 423, 423t structure of, 249f Thyroxine (T4), 317, 318f See also Thyroid hormones calorigenic action of, 324, 324f effects secondary to, 324–325 chemistry of, 317, 318f deiodination of, 322–324 fluctuations in, 323, 323f / 905 distribution of, 321, 321f iodine metabolism and, 317–319, 319f mechanism of action of, 323–324, 324f metabolism of, 322–323, 323f plasma levels of, 321, 321f plasma protein binding and, 321–322, 321t fluctuations in, 322, 322t receptors for, 323 resistance to effects of, 330 secretion of, 319–320, 320f regulation of, 326–328, 327f supplemental, 328, 332 synthesis of, 319, 320f transport of, 321–322, 321f, 321t Thyroxine-binding globulin, 321, 321t, 541t affinity of for thyroid hormone, 321, 321t estrogens affecting, 322, 322t fluctuations in concentrations of, 322 Thyroxine-binding prealbumin See Transthyretin Tickle, sensation of, 147 Tidal volume, 651, 652f in dead space calculation, 659 Tight junctions (zonula occludens), 16, 16f Timbre of sound, 177 Time constant, for inhibitory postsynaptic potentials, 90, 90f Timed vital capacity (FEV1), 651–652, 652f Tip links, 176, 176f Tissue conductance, in heat loss, 253 Tissue factor pathway inhibitor (TFI), 542f, 543 Tissue kallikrein, 601, 601f Tissue macrophages/tissue macrophage system, 517f, 519, 519f Tissue renin-angiotensin system, 456–457 Tissue thromboplastin, 542f, 543 Tissue transplantation, 530–531, 530f Tissue-type plasminogen activator (t-PA), 543, 543f clinical use of, 544 for myocardial infarction, 544 for stroke, 620 Tissues See also specific type oxygen delivery to, 666 exercise affecting, 683 Titin, 67 Titratable acidity, 721 TLRs See Toll-like receptors Tm See Transport maximum TmG See Transport maximum (Tm), for glucose TNF See Tumor necrosis factor α-Tocopherol/α-tocopherol transfer protein, 313 Tolazamide, 346 Tolbutamide, 346 906 / INDEX Tolerance (drug), morphine causing, 146 Tolerance (immune), 530 Toll-like receptors, 524 Toll receptor protein, 524 Tone (tonus), muscle, 134 during sleep, 196 of visceral smooth muscle, 82 Tongue, taste buds in, 188f, 189 Tonic-clonic (grand mal) seizures, 201 Tonic contractions, 506 Tonic labyrinthine reflexes, 208t, 211 Tonic neck reflexes, 208t, 211 Tonic (slowly adapting) receptors, 124 respiratory responses mediated by, 678, 679t Tonicity, See also Osmolality defense of, 729, 730f Tonsils, 664 Tonus (tone), muscle, 134 during sleep, 196 of visceral smooth muscle, 82 Tooth-grinding (bruxism), 199 Torsades des pointes, 558, 559f Total blood volume, 1, Total body water, age and sex affecting, 3, 3t Total (physiologic) dead space, 659, 659–660 Total electromechanical systole, 568 Total tension, skeletal muscle, 72–73, 73f Totipotential stem cells, 516 Touch-pressure sensation, 122t, 123, 141–142 See also Cutaneous sensation adaptation and, 124 pathways for, 139f, 141–142 in spatial orientation, 184 TPα/TPβ receptors, 310t TPH1 gene, serotonin production and, 106 TPL See Tissue thromboplastin TQ segment changes, in myocardial infarction, 561, 561t TRα1 and 2, 323 TRβ and 2, 323 thyroid hormone resistance and, 330 TR3 See Reverse triiodothyronine Trabecular (spongy) bone, 384–385, 384f Trace elements, 313, 313t Trachea, 649 Tractus solitarius, nucleus of See Nucleus of tractus solitarius Trail endings, 130f, 131 Tranquilizers, 261 trans Golgi, 27 Transaminases, 294, 295f Transamination, amino acid, 293f, 294, 294f, 295f Transcellular fluids, Transcobalamin II, 496 Transcortin (corticosteroid-binding globulin), 366, 367 Transcription, 21, 21f, 23f, 24 stimulation of, 38–39, 38f Transcription factors, 22 in hypoxia, 683 Transcytosis (vesicular transport), 27–28, 28f, 30, 36, 577 Transducin, 158, 158f, 159, 159f cone (Gt2), 159 rod (Gt1), 158 Transduction See Signal transduction Transfer RNA (tRNA), 21, 21f, 24 Transferrin, 477, 478f, 541t, 636f Transforming growth factor (TGF), 63 Transforming growth factor-α (TGF-α), in juxtacrine communication, 37 Transforming growth factor-β (TGF-β), 523t receptors binding, 46 Transfusion autologous, 538 for shock, 641 Transfusion reactions, 538 Transient receptor potential (TRP) subfamily, 123 Transit time, in small intestine and colon, 508 Translation, 21, 21f, 23f, 24 Translocases, in fatty acid metabolism, 298 Translocon, 24–25, 25f Transmitters See also specific type and Neurotransmitters autonomic pharmacology and, 230–231, 230t chemistry of, 94, 95–96t denervation hypersensitivity to, 119–120 “false,” 231 quantal release of in neuromuscular transmission, 117–118 reuptake of, 97–98 Transmural pressure, 586 Transplant rejection, 530–531, 530f absence of with “fetal graft,” 449 Transplantation, tissue, 530–531, 530f Transport See also specific substance and Diffusion across capillary wall, 35–36, 577–578, 579f across cell membranes, 28–35 across epithelia, 35 active, 32 secondary, 35, 35f axoplasmic (axoplasmic flow), 53–54 vesicular (transcytosis), 27–28, 28f, 30, 36 Transport maximum (Tm), 709 for glucose (TmG), 290 Transport proteins, 30–32 See also Cotransporters ATP-binding-cassette (ABC), 25, 27f in cholesterol transport, 305 in neurotransmitter reuptake, 97–98, 99f Transposition, chromosomal, aberrant sexual differentiation and, 417 Transthyretin (thyroxine-binding prealbumin), 321, 321t, 541t affinity of for thyroid hormone, 321, 321t Traube-Hering waves, 609 Traumatic shock, 639 Traveling waves, 179–180, 179f Trefoil peptides, 491–492 Trehalase, 469, 469t, 470f Trehalose, 469, 470f Treitz, ligament of, 505 Tremor intention, 222 in Parkinson’s disease, 216 physiologic, 131 Treppe, 72 TRH See Thyrotropin-releasing hormone Triacylglycerols See Triglycerides Triads, in sarcotubular system, 68 Triamterene, 725t Tricarboxylic acid cycle See Citric acid cycle Trichromats, 165 Tricuspid valve disease, murmurs in, 570t Trifascicular block, 556 Triglycerides (triacylglycerols), 298, 299t absorption of, 475 in diabetes, 342 digestion of, 473, 473f Trigone, autonomic nerve impulses and catecholamines affecting, 228t Triiodothyronine (T3), 317, 318f See also Thyroid hormones calorigenic action of, 324, 324f effects secondary to, 324–325 cardiovascular effects of, 325 chemistry of, 317, 318f deiodination of, 322–323 fluctuations in, 323, 323f iodine metabolism and, 317–319, 319f mechanism of action of, 323–324, 324f metabolism of, 322–323, 323f plasma levels of, 321 plasma protein binding and, 321–322, 321t fluctuations in, 322, 322t receptors for, 39, 39f, 323 resistance to effects of, 330 reverse (RT3) See Reverse triiodothyronine secretion of, 319–320, 320f regulation of, 326–328, 327f synthesis of, 319, 320f transport of, 321–322, 321t Trinucleotide repeat diseases, 27, 215–216, 215t Triple response, 625–626, 625f Triplets, in genetic code, 24 INDEX Trisomy 21 (Dwon’s syndrome), 417 Tritanomaly, 165 Tritanopia, 165 Trk receptors, 62, 62t tRNA (transfer RNA), 21, 21f, 24 Troglitazone, 346 Trophic action, of gastrin, 485 Tropic hormones, 396 Tropomyosin in red blood cells, 14f in skeletal muscle, 65, 67, 67f in contraction, 69, 71f isoforms of, 74 in smooth muscle, 82 Troponin, 40 in skeletal muscle, 65, 67, 67f in contraction, 69, 70t, 71f isoforms of, 74 Troponin C calbindin-D proteins and, 388–389 in skeletal muscle, 65, 67 in contraction, 69, 70t, 71f Troponin I in myocardial infarction, 623 in skeletal muscle, 65, 67 in contraction, 69, 71f Troponin T in myocardial infarction, 623 in skeletal muscle, 65, 67, 71f Trousseau’s sign, 392, 392f TRP subfamily See Transient receptor potential (TRP) subfamily True cholinesterase, 100 See also Acetylcholinesterase True hermaphroditism, 416, 418t True plasma, pH of, 730 Trypsin/trypsinogen, 468t, 471, 497–498, 498f Tryptophan, in serotonin biosynthesis, 106, 106f, 107f Tryptophan hydroxylase, 106, 106f TSH See Thyroid-stimulating hormone Tubal ligation, 447t Tuberoinfundibular system, 262f, 263, 264f Tubular function, 708–713, 708f, 710t See also Tubular reabsorption; Tubular secretion Tubular maximum See Transport maximum Tubular myelin, in surfactant formation, 656, 656f Tubular reabsorption, 699, 708, 710t See also specific substance mechanisms of, 709, 711f Tubular secretion, 699, 708, 710t, 712 mechanisms of, 709 PAH transport and, 712 α-Tubulin, in microtubules, 13, 14f β-Tubulin, in microtubules, 13, 14f γ-Tubulin in centrosomes, 15 in microtubules, 13 Tubuloglomerular feedback, 712–713, 713f Tufted cells, in olfactory bulbs, 185, 186f Tumor marker, hCG as, 449 Tumor necrosis factor α, 523t fever and, 255 insulin resistance and, 348t mast cell release of, 518 thyroid growth affected by, 327 apoptosis and, 26 β, 523t Tumor suppressor genes, 27 Tuning fork tests, 182, 182t Turbulent blood flow, 583, 583f heart murmurs and, 569 Korotkoff sounds and, 583, 589 Turner’s syndrome (gonadal dysgenesis), 407, 414 delayed/absent puberty and, 421 TV (tidal volume), 651, 652f in dead space calculation, 659 21β-hydroxylase (CYP21A2/P450c21), 362f, 364, 365t deficiency of, 366 26S proteasomes, 25, 297 Twitch in multiunit smooth muscle, 84 in skeletal muscle, 68–69, 69f Two-point discrimination/threshold, 147 Tympanic membrane (eardrum), 171, 172f in hearing, 178–179, 179f secondary, 171 Tympanic reflex, 179 Type I alveolar cells, 649, 650f Type diabetes (insulin-dependent diabetes mellitus/IDDM), 354 See also Diabetes mellitus Type I medullary interstitial cells, 702 Type I vitamin D-resistant rickets, 389 Type II alveolar cells (granular pneumocytes), 649 surfactant produced by, 656, 656f Type diabetes (non-insulin-dependent diabetes mellitus/NIDDM), 354 See also Diabetes mellitus obesity/metabolic syndrome and, 311, 347–348, 354 Type II vitamin D-resistant rickets, 389 Tyrosine in catecholamine biosynthesis, 102, 102f in thyroid hormone synthesis, 319, 320f antithyroid drugs affecting, 330–331 Tyrosine hydroxylase, in catecholamine biosynthesis, 102, 102f Tyrosine kinases, 38t, 44, 45, 46, 46f in angiogenesis, 581 Tyrosine phosphatases, 44, 46f / 907 u-PA See Urokinase-type plasminogen activator U wave, 550, 550f Ubiquinone-cytochrome c oxidoreductase, 11 Ubiquitin, 25, 297 Ubiquitination, 297 in Parkinson’s disease, 217 UCP 1, 301–302 in thermoregulation, 254, 301–302 UCP 2, 301–302 UCP 3, 301–302 UDP-glucuronosyltransferase (glucuronyl transferase system), 367, 368f, 503 in bilirubin metabolism and excretion, 502, 502f UDPG See Uridine diphosphoglucose UDPGA See Uridine diphosphoglucuronic acid UFA See Free fatty acids Ulcers decubitus, 208 peptic, 496 Ultimobranchial bodies, 393 Ultrasound (ultrasonography), gallbladder, 504 Umami (taste modality), 189 receptors for, 190, 190f Umbilical artery, 626f, 628, 628f Umbilical vein, 626f, 628, 628f Uncompensated metabolic acidosis, 734, 735f Uncompensated respiratory acidosis/alkalosis, 734, 734f Unconditioned stimulus, 267, 268, 268f Underwater diving, hazards of, 694–695, 694t Undescended testes (cryptorchidism), 433 Unilateral inattention and neglect, 273 Unipolar ECG, 550 Unipolar EEG, 194 Unipolar (V) leads, for ECG, 551, 551f Uniports, 32 Unitary smooth muscle See Visceral (unitary) smooth muscle “Universal donors”/”universal recipients,” 538 Unmyelinated neurons, 51 Unstirred layer, 467 Up-regulation, 37 Upper motor neurons, 203 Urea blood-brain barrier penetration by, 614f formation of, 294, 296f plasma levels of, 294, 699t in plasma osmolality, renal handling of, 710t, 718 size of, 32t starvation affecting excretion of, 298 urinary levels of, 699t, 718 in water excretion, 718 908 / INDEX Urea cycle, 294, 296f Urea nitrogen blood See Blood urea nitrogen excretion of, in starvation, 298 Urea transporters, 718 Uremia, 725–726 Cheyne-Stokes respiration in, 693 in hypovolemic shock, 638 Ureters autonomic nerve impulses and catecholamines affecting, 228t bladder filling and, 726 Urethral sphincters, 726 Uric acid, 297, 297f in gout, 297 renal handling of, 297, 710t starvation affecting excretion of, 298 Uridine, as transmitter, 114 Uridine diphosphogalactose, 291 Uridine diphosphoglucose (UDPG), 288, 289f, 291 Uridine diphosphoglucuronic acid (UDPGA), in bilirubin metabolism and excretion, 502, 502f Uridine triphosphate (UTP), 96t Urinary bladder See Bladder Urinary incontinence, overflow, 728 Urinary sulfates, 294 Urination See Micturition Urine acidification of, 720–723, 720f, 721f albumin in, 707, 725 buffers in, 721 casts in, 724 concentration of, 713–714, 713t in collecting ducts, 716 defects in, 725 glomerular filtration rate and, 719 fate of hydrogen in, 720, 721f formation and excretion of, 699–728 See also Micturition; Renal function glucose in See Glycosuria increase in volume of (diuresis), 725 osmotic, 718–719, 719f, 725 in diabetes, 341, 343, 343f, 719 water, 718 osmolality of, 716 pH of, 722 hydrogen/renal acid secretion and, 720, 721f, 722–723 implications of changes in, 722–723 protein in, glomerular capillary permeability and, 706–707 sodium levels in, 699t vasopressin affecting volume/concentration of, 244, 713t Urine flow, in calculating glomerular filtration rate, 705–706 Urogastrone (epidermal growth factor), thyroid gland affected by, 327 Urogenital slit, 414, 415f, 416f Urokinase-type plasminogen activator (u-PA), 543, 543f Uropepsinogen, 492 Urotensin-II, vasoconstriction caused by, 602 US See Unconditioned stimulus UT-A, 718 UT-B, 718 Uterine cervix cyclic changes in, 437 at parturition, 450, 451f Uterine circulation, 626f, 627 Uterine contractions, in parturition, 451 Uterine cycle, 435–436, 436f Uterine tubes fertilization in, 448 ligation of, for contraception, 447t Uterus autonomic nerve impulses and catecholamines affecting, 228t blood flow in, 626f, 627 estrogens affecting, 441 oxytocin affecting, 247–248 progesterone affecting, 443–444 UTP (uridine triphosphate), 96t Utricle, 173 linear acceleration affecting, 184 Utropin, in muscular dystrophy, 77 V1 area (visual cortex), 149, 151f, 152f, 161–163, 161f, 162f, 163f, 164f, 164t pathways to, 149, 151f, 160–161, 161f V2–8 areas, in vision, 163, 164f, 164t V (unipolar) leads, for ECG, 551, 551f V segment, of immunoglobulin chain, 528, 528f genetic basis of diversity and, 529–530 v-SNAREs/v-snare proteins, 27, 28, 87 V1A vasopressin receptors, 243, 244 V1B/V3 vasopressin receptors, 243, 244 V2 vasopressin receptors, 243, 244 antagonists of, as diuretics, 725t defects of in nephrogenic diabetes insipidus, 47, 48t, 247, 716 V3 vasopressin receptors See V1B/V3 vasopressin receptors v wave, of venous pressure tracing, 567f, 569, 595 VAChT, 100 Vagal stimulation bile secretion affected by, 503 gastric secretion affected by, 494 in respiration, 671–672, 678 salivary secretion affected b, 489 Vagal tone, in cardiovascular regulation, 603 Vaginal cycle, 437 Valium See Diazepam Vallate papillae, taste buds in, 188f, 189 Valsalva maneuver, in baroreceptor evaluation, 608, 609f Valves heart, murmurs in disorders of, 569–570, 570t venous, 580 incompetent, varicose veins caused by, 595 Valvulae conniventes, 505 Valvular heart disease, murmurs in, 569–570, 570t Valvular regurgitation (insufficiency), murmurs and, 569, 570t Valvular stenosis, murmurs and, 569, 570t Vanillins, 143 Vanilloid receptor-1 (VR1), 123, 142, 143 in pain sensation, 123, 142, 143 in temperature sensation, 123, 142 Vanillylmandelic acid (3-methoxy-4-hydroxymandelic acid/VMA), 103, 104f, 358, 359 Vaporization, heat loss and, 252t, 253 Variable segment, of immunoglobulin chain, 528, 528f genetic basis of diversity and, 529–530 Variance, analysis of, 813 Variation, biologic, 812 Varicose veins, 595 Varicosities, on postganglionic neurons, 118, 119f Vas deferens, 424, 424f ligation of (vasectomy), 428, 447t Vasa recta, 702, 703f as countercurrent exchangers, 716, 717, 718f Vascular endothelial growth factor (VEGF), 581 in corpus luteum growth, 434 Vascular hindrance, 585 Vascular reactivity, glucocorticoids affecting, 369 Vascular resistance See also Resistance cerebral, gravity affecting, 630 flow and pressure and, 581–582, 588–589, 589f pulmonary hypertension and, 641, 641–642, 694 Vascular smooth muscle, 580, 581f Vasculogenesis, 581 Vasectomy, 428, 447t Vasoactive intestinal peptide (VIP), 96t, 113–114, 483t, 486–487 bronchodilation caused by, 224, 650, 654 cholinergic release of, 224, 226 gastrointestinal circulation affected by, 480 locations of, 96t, 113–114, 484f, 486 lower esophageal sphincter affected by, 490 pulmonary circulation affected by, 664t in salivary secretion, 489 INDEX tumors secreting, 486–487, 488 vasodilation caused by, 226, 602 Vasoconstriction, 597, 597–598 angiotensin II causing, 456 blood vessel injury causing, 532, 542, 542f, 597–598 chemoreceptor stimulation causing, 609 coronary, neural mediators of, 622–623 of cutaneous blood vessels, 626–627 cold causing, 254, 626–627 dopamine causing, 361 endothelins causing, 599, 600 in hemostasis, 542, 542f hepatic artery, 614 hormones causing, 601–602 in hypocapnia, 692 in hypovolemic shock, 637–638 neural regulatory mechanisms in, 602–603, 603t sympathetic input in, 602–603, 602f, 603t thromboxane A2 in, 600 turbulence and, 583, 583f vasomotor control and, 603–604, 603f vasopressin causing, 244 Vasodilation, 597 adrenomedullin causing, 601 calcitonin gene-related peptide causing, 114 coronary chemical mediators of, 622 neural mediators of, 622–623 of cutaneous blood vessels, 626–627 in temperature regulation, 253 dopamine causing, 361 endothelial factors affecting, 598–599 hormones causing, 600–601, 600f, 601f hypercapnia causing, 609 kinins causing, 600–601 lung inflation causing, 605 metabolic changes causing, 597 muscle blood flow in exercise and, 633 natriuretic hormones causing, 460 neural regulatory mechanisms in, 602–603, 603t nitric oxide causing, 598–599 prostacyclin in, 598 sympathetic input and, 602–603, 603t, 609–610 vasomotor control and, 603f, 604 Vasodilator metabolites, 597 coronary blood flow affected by, 622 muscle blood flow in exercise and, 633 uterine blood flow in pregnancy and, 627 Vasodilator system, sympathetic, 602, 609–610 Vasogenic (distributive/low-resistance) shock, 636, 637t, 640 Vasomotor area/center, 603–604 afferents to, 604–605, 605t in blood pressure control, 603–604, 603f, 604–605, 604f in cardiovascular function control, 603–604, 603f, 604f, 605f in cerebral circulation control, 617–618 stimulation of chemoreceptor, 608–609 direct, 609 in hypovolemic shock, 638 Vasopressin, 95t, 113, 242, 242f, 396, 604 actions/effects of, 244, 604 biosynthesis/intraneuronal transport/secretion of, 242, 243f, 250f angiotensin II affecting, 456 clinical implications and, 246–247 defense of extracellular volume and, 729, 730f hemorrhage and, 244, 245–246, 638 hypothalamus in, 233, 236t by magnocellular neurons, 242–243, 244f miscellaneous stimuli in, 245t, 246 osmotic stimuli in, 245, 245f outside pituitary gland, 243 volume effects in, 245–246, 245t, 246f, 729, 730f deficiency of, 247, 716 in diabetes insipidus, 247, 716 half-life of, 244 hypersecretion of, 246–247 in hypovolemic shock, 638 locations of, 95t, 113, 243 metabolism of, 244 pulmonary circulation affected by, 664t receptors for, 243 antagonists of, as diuretics, 725t defects of in nephrogenic diabetes insipidus, 47, 48t, 247, 716 in renin secretion regulation, 458 synthetic agonists and antagonists of, 244 tonicity regulated by, 729, 730f vasoconstriction caused by, 244, 604 in water metabolism, 244, 713t, 714f, 716 Vasovagal attacks, 640 Vater, ampulla of, 497, 498f VC See Vital capacity Vectorcardiography (vectorcardiogram), 553 VEGF See Vascular endothelial growth factor Veins, 578t, 580, 587f See also specific named vein and under Venous autonomic nerve impulses and catecholamines affecting, 227t as capacitance vessels, 586 / 909 changes in caliber of (venoconstriction/venodilation), 597 See also Vasoconstriction; Vasodilation injury and, 598 innervation of, 602, 602f pressure in, 567f, 569, 587f, 595 See also Venous pressure valves in, 580 incompetent, varicose veins caused by, 595 varicose, 595 Velocity of air flow, 649 of circulation in arteries and arterioles, 587, 587f average, 583f, 584, 584f in capillaries, 587f, 590–592 critical, 583, 589 measurement of, 582, 582f in veins, 587f, 595 of muscle contraction, 73 Vena cava, 578t velocity and blood flow in, 587f Venae comitantes, in thermoregulation, 254 Venoconstriction, 597, 602 in hypovolemic shock, 638 vasomotor control of, 604 Venodilation, 597 Venous circulation, 595–596 Venous occlusion plethysmography, 582 Venous pressure, 567f, 569, 587f, 595 central, 595 measurement of, 596 gravity affecting, 588f, 595, 630, 631f hepatic, 624 jugular (in head), 567f, 569, 595 measurement of, 596 peripheral gravity affecting, 588f, 595 measurement of, 596 portal, 624 Venous return, exercise affecting, 634 Venous-to-arterial shunts, 688 Venous valves, 580 incompetent, varicose veins caused by, 595 Ventilation See also under Pulmonary and Breathing; Lungs acid-base balance changes affecting, 675–676 altitude affecting, 684–686, 685f, 686f alveolar, 659, 659t exercise affecting, 681–683, 682f maximal voluntary, 652, 652f mechanical, 695–696 menstrual cycle affecting, 678 pulmonary (respiratory minute volume), 652, 652f regional differences in, 658, 658f gravity and, 662, 662f uneven, 658–660, 659f 910 / INDEX Ventilation-perfusion imbalance, hypoxia caused by, 686t, 687–688, 687f Ventilation/perfusion ratios, 662–663, 663f Ventral cochlear nuclei, 174, 174f Ventral (anterior) corticospinal tract, 204, 204f damage to, 206 Ventral noradrenergic bundle, 262f, 263 Ventral (temporal) pathway, in vision, 163 Ventral spinocerebellar tract, 221t Ventral tegmentum, in motivation, 260, 260t Ventral thalamus, 192 Ventricles, cardiac autonomic nerve impulses and catecholamines affecting, 227t conduction speed in, 549t contraction of (ventricular systole), 547, 565, 566f, 567f Ventricular arrhythmias, 557–558, 558f myocardial infarction and, 561–563 Ventricular contraction, isovolumetric (isovolumic/isometric), 565, 566f, 567f Ventricular ejection, 565, 566f, 567f, 568 Ventricular extrasystole (premature beats), 556, 557–558, 558f Ventricular fibrillation, 558, 559f cardiopulmonary resuscitation for management of, 558–559, 559f, 560f electronic defibrillators for management of, 558–559, 559f Ventricular filling, 568 Ventricular relaxation, isovolumetric, 565–566, 566f, 567f Ventricular systole, 547, 565, 566f, 567f Ventricular tachycardia, paroxysmal, 558, 558f Ventricular volume end-diastolic, 565 factors affecting, 573, 573f end-systolic, 565 Venules, 578t, 579f, 580 pressure in, 587f, 595 Verbal system, 269 Vermis, 217, 218f Vertebral arteries, 611 Vertebral fractures, osteoporosis and, 386–387 Vertigo, 184 Very low density lipoproteins (VLDL), 302t, 303, 304f in diabetes, 343 Vesicles, synaptic, 86–88, 87f, 88f Vesicular GABA transporter (VGAT), 98, 109 Vesicular monoamine transporters (VMAT), 97–98, 99f Vesicular transport (transcytosis), 27–28, 28f, 30, 36, 577 Vestibular division of eighth cranial nerve, 173, 174, 174f Vestibular eye movements, 169, 169f Vestibular function, 183–184, 183f See also Equilibrium hair cells in, 175–176, 175f, 177f Vestibular ganglion, 174, 174f Vestibular nuclei, 174, 174f in rotational acceleration, 184 Vestibular pathways, 174–175, 174f Vestibular placing reaction, 212 Vestibulocerebellar tract, 221t Vestibulocerebellum (flocculonodular lobe), 220, 221, 221f in motion sickness, 184, 221 Vestibulo-ocular reflex, 184 plasticity of, 269 VGAT, 98, 109 Viagra See Sildenafil Vibratory sensation/sensibility, 141, 147 Villi arachnoid, 612–613 placental, 626f, 627–628 small intestinal, 505, 505f Vinblastine, microtubule assembly affected by, 13 Violence, rage and, 260 Vioxx See Rofecoxib VIP See Vasoactive intestinal peptide VIPomas, 486–487 Virilization, enzyme deficiency causing, 365, 366, 366f Visceral function autonomic nerve impulses and catecholamines affecting, 226, 227t central regulation of, 232–255 See also Hypothalamus; Medulla, oblongata Visceral pain, 121 muscle spasm and rigidity and, 144–145 pathways for sensation of, 143–144, 144f referred, 145, 145f stimulation of pain fibers and, 144 Visceral responses conditioning of (biofeedback), 268 respiratory components of, 680 Visceral sensation, 121 See also Smell; Taste; Visceral pain cortical lesions affecting, 141 cortical plasticity and, 140–141 cortical representation and, 139–140, 140f pathways for, 138–141, 139f, 140f Visceral (unitary) smooth muscle, 82, 82–84 autonomic nerve impulses and catecholamines affecting, 83, 83f, 84, 227t contraction of, 82–84, 82f, 83f, 83t molecular basis of, 82–83 electrical and mechanical activity of, 82 function of nerve supply to, 84 length/tension relationship and (plasticity), 84 stimulation of, 82f, 83, 83f Viscosity of blood, resistance and, 585, 585f Vision, 122t, 148–170 See also under Visual accommodation in, 153–154, 154f anatomic considerations in, 148–152, 149f binocular, 167f, 168 color, 163–166, 164f See also Color vision cortical areas concerned with, 163, 163f, 164t See also Visual cortex critical fusion frequency and, 167 cyclic GMP in, 159, 159f dark adaptation and, 166–167, 166f double (diplopia), 168 eye muscles/eye movements and, 152, 153f, 168–170, 169f image-forming mechanism in, 152–156, 154f, 155f, 156f See also Retina defects of, 155–156, 156f light adaptation and, 167 light intensity and, 152, 155, 157 near point of, 154, 155f pathways in, 149, 151f, 152f, 160–163, 161f, 162f, 163f, 164f, 164t lesions of, 168 photopic, cones in, 152 processing in retina and, 160 receptors in (photoreceptors/rods and cones), 148, 150–152, 150f, 152f, 153f, 156–160, 157f, 158f, 159f, 160f See also Photoreceptors rhodopsin in, 158–159, 158f scotopic (night), rods in, 152 vitamin A/vitamin A deficiency and, 167, 313t Visual acuity, 167 strabismus affecting, 170 Visual angle, 155 Visual cortex, 149, 151f, 152f, 161–163, 161f, 162f, 163f, 164f, 164t pathways to, 149, 151f, 160–161, 161f Visual field defects, 151f, 168 Visual fields, 167–168, 167f frontal, 149 Visual fusion, 168 critical frequency of, 167 Visual pathways, 149, 151f, 152f, 160–163, 161f, 162f, 163f, 164f, 164t lesions of, 168 Visual processing, in retina, 160 INDEX Visual purple (rhodopsin), 158–159, 158f gene for, 165 mutation in, 48t structure of receptor for, 43f Visual receptors (photoreceptors/rods and cones), 148, 150–152, 150f, 152f, 153f, 156–160, 157f, 158f, 159f, 160f See also Photoreceptors Visual threshold, 167 Visuospatial relations, hemispheric specialization and, 273 Visuospatial system, 269 Vital capacity, 651, 652f timed (FEV1), 651–652, 652f Vital centers, medullary, 232 Vitamin A, 313, 313t deficiency of, 313t eye/vision affected by, 167, 313t excess of, 316 in photosensitive compounds, 157, 158 requirements/RDAs for, 312t Vitamin B1 (thiamine), 314t requirements/RDAs for, 312t Vitamin B2 (riboflavin), 314t requirements/RDAs for, 312t Vitamin B6 (pyridoxine), 314t requirements/RDAs for, 312t Vitamin B12 (cyanocobalamin), 315t, 496, 496f absorption of, 477 coronary artery disease and, 623 deficiency of, 313, 315t, 496 requirements/RDAs for, 312t, 313 Vitamin C, 315t requirements/RDAs for, 312t Vitamin D, 313, 315t, 387–389 actions of, 388–389 mechanisms of, 388 chemistry of, 387–388, 388f deficiency of, 315t, 389 excess of, 316 regulation of synthesis of, 389, 389f requirements/RDAs for, 312t Vitamin D3 (cholecalciferol), 387–388, 388f Vitamin D-binding protein, 388 Vitamin D-resistant rickets, 389 Vitamin E, 313, 315t deficiency of, 315t requirements/RDAs for, 312t Vitamin K, 315t anticoagulants affecting, 544 deficiency of, 315t, 545 excess of, 316 intestinal bacteria producing, 509 requirements/RDAs for, 312t Vitamins, 313–316, 313–315t absorption of, 477–478 eye/vision affected by deficiency of, 167 requirements/RDAs for, 312t thyroid hormones affecting, 324 Vitiligo, 398 Vitreous (vitreous humor), 148, 149f VLDL See Very low density lipoproteins VMA See Vanillylmandelic acid VMAT1, 97–98, 99f VMAT2, 97–98, 99f VO2max See Maximal oxygen consumption Voiding reflex, 727–728, 728 Volley effect, 180 Voltage-gated ion channels, 31 Volume conductor, body as, 58 ECG and, 549–550 Volume of distribution, Voluntary movement, control of See Movement, control of Vomeronasal organ, 187–188 Vomiting, 232 See also Nausea area postrema and, 616 5-HT receptors and, 107, 233 medullary control of, 232, 232–233, 233f Vomiting center, 232, 233f von Willebrand disease, 545 von Willebrand factor, 532, 544–545 VOR See Vestibulo-ocular reflex VR1 receptor, 123, 142, 143 in pain sensation, 123, 142, 143 in temperature sensation, 123, 142 VRL-1 receptor, 123, 142, 143 in pain sensation, 123, 143 in temperature sensation, 123, 142, 143 Vulnerable period, 558 Walking, body mechanics and, 77 Wallerian degeneration, 53–54, 119, 119f Warfarin, 544 Warm-blooded species, 251 Warm shock See Distributive (vasogenic/ low-resistance) shock Warmth, sensation of, 122t, 123 Water absorption of, 475–477, 476t in colon, 476, 476t, 508 distribution of in body, 1, 2f as diuretic, mechanism of action of, 725t excretion/metabolism/loss of, 710t, 713–720, 713t, 714f, 715t in adrenal insufficiency, 370, 376–377, 381 aquaporins in, 714 countercurrent mechanism in, 716–718, 717f, 718f dehydration and, 729, 730f estrogens affecting, 442 “free water clearance” and, 719–720 glucocorticoids affecting, 370 insensible, 253 loop of Henle and, 714–715, 714f, 715t pituitary insufficiency affecting, 408–409 / 911 progesterone affecting, 444 renal tubules and, 714, 714f, 715, 715t urea in, 718 vasopressin affecting, 244, 713t, 714f, 716 intake of angiotensin II affecting, 241, 241f, 456 diuresis and, 718 excessive (water intoxication), 718 in adrenal insufficiency, 370, 381 hypothalamus in regulation of, 236t, 240–242, 241f renal handling of, 710t, 713–720, 713t retention of in edema, 594, 726 extracellular volume defense and, 729, 730f size of, 32t vaporization of, heat loss and, 253 Water balance, 710t, 713–720, 713t, 714f in gastrointestinal tract, 476, 476t hypothalamic regulation and, 236t, 240–242, 241f Water channels, vasopressin-responsive See Aquaporins Water diuresis, 718 Water-hammer pulse, 568 Water intoxication, 718 in adrenal insufficiency, 370, 381 Water vapor, partial pressures affected by, 647, 684–685 Waterfall effect, 662 WBCs See White blood cells Weakness (paresis), 203 Weaning, from respirator, 696 Weber-Fechner law, 126 Weber test, 182, 182t Weight See Body weight Weightlessness See Zero gravity Wenckebach, internodal tract of, 547 Wenckebach phenomenon, 555, 555f Werner’s syndrome, 49 Wernicke’s area, 272f, 273, 274, 274f lesion of in aphasia, 274, 274t Wheal, 625 White blood cells (leukocytes), 516–520, 516t See also specific type development of, 518f, 519 glucocorticoids affecting, 370, 370t polymorphonuclear (PMNs/granulocytes), 516, 516t, 517f glucocorticoids affecting, 370t “White coat hypertension,” 590 White (type II/fast) muscles, 73, 73t twitch duration of, 69 White rami communicantes, 223, 224f White reaction, 590, 625 Whole cell recording (whole cell patch clamp), 31, 31f 912 / INDEX Willis, circle of, 611 Wilson’s disease, 214, 313 Windkessel effect, 587 Windkessel vessels, 587 Wirsung, pancreatic duct of, 497, 497f, 498f Withdrawal bleeding, estrogen therapy and, 441 Withdrawal method of contraception, 447t Withdrawal reflex, 134–136, 136f fractionation and occlusion and, 136 importance of, 135–136 local sign in, 136, 136f pain eliciting, 143 in spinal animal/human, 135, 209 Wolff–Chaikoff effect, 331 Wolff-Parkinson-White syndrome (accelerated AV conduction), 559–560, 560f Wolffian duct system, 414, 415f testosterone-receptor complexes affecting, 430, 431f Work of breathing, 657–658, 657f, 657t, 658f Working memory, 267, 269 encoding, 269 hippocampus and medial temporal cortex in, 269–270, 270f Wound healing, 635f, 636 See also Inflammatory response X chromosome, 411–412, 411f, 412, 413f cone pigment genes on, 165 defects of in color blindness, 165–166 inactivation of, 412–413, 413f X-inactivation center, 412 X-linked color blindness, 165–166 Xanthine oxidase, inhibition of in treatment of gout, 297f, 298 Xanthines as diuretics, mechanism of action of, 725t inotropic effect of, 574 Xenon coronary blood flow studied with, 622, 622f pulmonary ventilation and perfusion patterns studied with, 659, 663 Xerostomia, 489 XO pattern, 414, 418f, 418t See also Gonadal dysgenesis XX pattern, 411, 412f males with, 417 XX/XY mosaicism, 416 XXX pattern (superfemale), 416, 418f, 418t XXY pattern (seminiferous tubule dysgenesis/Klinefelter’s syndrome), 414–416, 418f, 418t XY pattern, 412, 412f females with, 417 Y chromosome, 411–412, 412, 412f, 413f Yawning, 680 Yellow marrow, 515 YO pattern, 416, 418f Young-Helmholtz theory, of color vision, 163–164, 164f Z lines in cardiac muscle, 78 in skeletal muscle, 65, 66f, 67f Zaroxolyn See Metolazone Zero gravity (weightlessness), effects of, 632 Zeta (ζ) chains, fetal hemoglobin, 535, 535f Zinc deficiency of, 313 requirements/RDAs for, 312t Zinc finger motif, 23, 23f Zollinger-Ellison syndrome, 496 calcitonin levels in, 394 Zona fasciculata, 356, 357, 357f hormone biosynthesis in, 362f, 364, 365 Zona glomerulosa, 356, 357, 357f in cortical regeneration, 357 hormone biosynthesis in, 363f, 364–365 Zona pellucida, 448, 448f Zona reticularis, 356, 357, 357f hormone biosynthesis in, 362f, 364, 365 Zonula adherens, 16, 16f Zonula occludens (tight junctions), 16, 16f Zonule (lens ligament), 148, 149f in accommodation, 154 ZP3 Zygote, 17 Zymogen (chief) cells, gastric, 491, 491f, 492 Zymogen granules gastric, 492 pancreatic, 497, 497f salivary, 488, 488f Ranges of Normal Values in Human Whole Blood (B), Plasma (P), or Serum (S)a Normal Value (Varies With Procedure Used) Determination Acetoacetate plus acetone (S) Aldosterone (supine) (P) Alpha-amino nitrogen (P) Aminotransferases Alanine aminotransferase Aspartate aminotransferase Ammonia (B) Amylase (S) Ascorbic acid (B) Bilirubin (S) Traditional Units SI Units 0.3–2.0 mg/dL 3.0–10 ng/dL 3.0–5.5 mg/dL 3–20 mg/L 83–227 pmol/L 2.1–3.9 mmol/L 3–48 units/L 0–55 units/L 12–55 µmol/L 53–123 units/L 0.4–1.5 mg/dL (fasting) Conjugated (direct): up to 0.4 mg/dL Total (conjugated plus free): up to 1.0 mg/dL 12–55 µmol/L 884–2050 nmol ⋅ s−1/L 23–85 µmol/L Up to µmol/L Up to 17 µmol/L Calcium (S) Carbon dioxide content (S) Carotenoids (S) Ceruloplasmin (S) Chloride (S) Cholesterol (S) Cholesteryl esters (S) 8.5–10.5 mg/dL; 4.3–5.3 meq/L 24–30 meq/L 0.8–4.0 µg/mL 23–43 mg/dL 100–108 meq/L < 200 mg/dL 60–70% of total cholesterol 2.1–2.6 mmol/L 24–30 mmol/L 1.5–7.4 µmol/L 240–430 mg/L 100–108 mmol/L < 5.17 mmol/L Copper (total) (S) Cortisol (P) (AM, fasting) Creatinine (P) Glucose, fasting (P) Iron (S) Lactic acid (B) 70–155 µg/dL 5–25 µg/dL 0.6–1.5 mg/dL 70–110 mg/dL 50–150 µg/dL 0.5–2.2 meq/L 11.0–24.4 µmol/L 0.14–0.69 µmol/L 53–133 µmol/L 3.9–6.1 mmol/L 9.0–26.9 µmol/L 0.5–2.2 mmol/L Lipase (S) Lipids, total (S) Magnesium (S) Osmolality (S) PCO2 (arterial) (B) Pepsinogen (P) 3–19 units/L 450–1000 mg/dL 1.4–2.0 meq/L 280–296 mosm/kg H2O 35–45 mm Hg 200–425 units/mL 4.5–10 g/L 0.7–1.0 mmol/L 280–296 mmol/kg H2O 4.7–6.0 kPa pH (B) Phenylalanine (S) Phosphatase, acid (S) 7.35–7.45 0–2 mg/dL Males: 0–0.8 sigma unit/mL Females: 0.01–0.56 sigma unit/mL 13–39 units/L (adults) 9–16 mg/dL as lipid phosphorus 2.6–4.5 mg/dL (infants in first year: up to 6.0 mg/dL) 0.22–0.65 µmol ⋅ s−1/L 2.9–5.2 mmol/L 0.84–1.45 mmol/L PO2 (arterial) (B) Potassium (S) Protein Total (S) Albumin (S) Globulin (S) Pyruvic acid (P) 75–100 mm Hg 3.5–5.0 meq/L 10.0–13.3 kPa 3.5–5.0 mmol/L 6.0–8.0 g/dL 3.1–4.3 g/dL 2.6–4.1 g/dL 0–0.11 meq/L 60–80 g/L 31–43 g/L 26–41 g/L 0–110 µmol/L Sodium (S) Urea nitrogen (S) Uric acid (S) Women Men 135–145 meq/L 8–25 mg/dL 135–145 mmol/L 2.9–8.9 mmol/L 2.3–6.6 mg/dL 3.6–8.5 mg/dL 137–393 µmol/L 214–506 µmol/L Phosphatase, alkaline (S) Phospholipids (S) Phosphorus, inorganic (S) 0–120 µmol/L a Based in part on Kratz A, et al Laboratory reference values N Engl J Med 2004;351:1548 See also Table 27–1: Normal values for cellular elements in human blood; and Table 32–2: Concentrations of various substances in human CSF and plasma Ranges vary somewhat from one laboratory to another depending on the details of the methods used, and specific values should be considered in the context of the range of values for the laboratory that made the determination Download more eBooks here: http://avaxhm.com/blogs/ChrisRedfield ... H3C CH2CH2CONH2 B N CN Co + NH2COCH2 N CH3 N D C CH3 CH2 C CH3 CH2CH2CONH2 C CH3 CH2 CH3 CH O CHCH2 NH O − O N P O O HO H H N CH3 CH3 H O HO CH2 H Figure 26 –15 Cyanocobalamin (vitamin B 12) Empiric... of cyanocobalamin is very rare, apparently because the minimum daily requirements are quite low and the vitamin is found in most foods of animal origin CH3 CH2CH2CONH2 C NH2COCH2 CH3 CH2CONH2... CHAPTER 25 Brush border Intestinal lumen Heme Enterocyte HT Blood Heme HO2 Fe3+ reductase Fe2+ Hp Fe2+ DMT1 Fe2+ Fe2+ Fe3+- ferritin Shed FP Fe2+ Fe3+ Fe3+−TF Figure 25 –8 Absorption of iron Fe3+