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Understanding Pathophysiology 5th Edition Huether Test Bank

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  • ISBN-10 ‏ : ‎ 0323078915
  • ISBN-13 ‏ : ‎ 978-0323078917
  • Author:  Sue E. Huether

Learn the essential concepts of pathophysiology and stay up to date on treatments, manifestations, and mechanisms of disease with Understanding Pathophysiology, 5th Edition. Filled with vibrant illustrations and complemented by online resources that bring pathophysiology concepts to life, this easy-to-read text delivers the latest, most accurate information on the disease process across the lifespan, giving you the fundamental knowledge you need to move forward in your nursing education.

 

Table of Content:

  1. PART I Basic Concepts of Pathophysiology
  2. UNIT 1 The Cell
  3. Interactive Review – Unit 1
  4. Chapter 1 Cellular Biology
  5. Prokaryotes and Eukaryotes
  6. Cellular Functions
  7. FIGURE 1-1 Typical Components of a Eukaryotic Cell and Structure of the Cytoplasm. A, Components of a eukaryotic cell. B, The drawing is approximately to scale and emphasizes the crowding in the cytoplasm. Only the macromolecules are shown: RNAs are shown in blue, ribosomes in green, and proteins in pink. Enzymes and other macromolecules diffuse relatively slowly in the cytoplasm, in part because they interact with many other macromolecules; small molecules, by contrast, diffuse nearly as rapidly as they do in water.
  8. Structure and Function of Cellular Components
  9. Nucleus
  10. Cytoplasmic Organelles
  11. QUICK CHECK 1-1
  12. Plasma Membranes
  13. Membrane Composition
  14. Lipids
  15. Proteins
  16. FIGURE 1-2 The Nucleus. The nucleus is composed of a double membrane, called a nuclear envelope, that encloses the fluid-filled interior, called nucleoplasm. The chromosomes are suspended in the nucleoplasm (illustrated here much larger than actual size to show the tightly packed DNA strands). Swelling at one or more points of the chromosome, shown in A, occurs at a nucleolus where genes are being copied into RNA. The nuclear envelope is studded with pores. B, The pores are visible as dimples in this freeze-etch of a nuclear envelope. C, Histone-folding DNA in chromosomes.
  17. FIGURE 1-3 Structure of a Phospholipid Molecule. A, Each phospholipid molecule consists of a phosphate functional group and two fatty acid chains attached to a glycerol molecule. B, The fatty acid chains and glycerol form nonpolar, hydrophobic “tails,” and the phosphate functional group forms the polar, hydrophilic “head” of the phospholipid molecule. When placed in water, the hydrophobic tails of the molecule face inward, away from the water, and the hydrophilic head faces outward, toward the water.
  18. TABLE 1-1 PRINCIPAL CYTOPLASMIC ORGANELLES
  19. TABLE 1-2 PLASMA MEMBRANE FUNCTIONS
  20. FIGURE 1-4 Functions of Plasma Membrane Proteins. The plasma membrane proteins illustrated here show a variety of functions performed by the different types of plasma membranes.
  21. Carbohydrates
  22. Fluid Mosaic Model
  23. FIGURE 1-5 Fluid Mosaic Model. Schematic, three-dimensional view of the fluid mosaic model of membrane structure. The lipid bilayer provides the basic structure and serves as a relatively impermeable barrier to most water-soluble molecules.
  24. Cellular Receptors
  25. FIGURE 1-6 Cellular Receptors. (A) 1, Plasma membrane receptor for a ligand (here, a hormone molecule) on the surface of an integral protein. A neurotransmitter can exert its effect on a postsynaptic cell by means of two fundamentally different types of receptor proteins: 2, channel-linked receptors, and 3, non–channel-linked receptors. Channel-linked receptors are also known as ligand-gated channels. (B) Example of ligand-receptor interaction. Insulin-like growth factor 1 (IGF-1) is a ligand and binds to the insulin-like growth factor 1 receptor (IGF-1R). With binding at the cell membrane the intracellular signaling pathway is activated, causing translation of new proteins to act as intracellular communicators. This pathway is important for cancer growth. Researchers are developing pharmacologic strategies to reduce signaling at and downstream of the insulin-like growth factor 1 receptor (IGF-1R), hoping this will lead to compounds useful in cancer treatment.
  26. Cell-to-Cell Adhesions
  27. Extracellular Matrix
  28. FIGURE 1-7 Extracellular Matrix. Tissues are not just cells but also extracellular space. The extracellular space is an intricate network of macromolecules called the extracellular matrix (ECM). The macromolecules that constitute the ECM are secreted locally (by mostly fibroblasts) and assembled into a meshwork in close association with the surface of the cell that produced them. Two main classes of macromolecules include proteoglycans, which are bound to polysaccharide chains called glycosaminoglycans, and fibrous proteins (e.g., collagen, elastin, fibronectin, and laminin), which have structural and adhesive properties. Together the proteoglycan molecules form a gel-like ground substance in which the fibrous proteins are embedded. The gel permits rapid diffusion of nutrients, metabolites, and hormones between the blood and the tissue cells. Matrix proteins modulate cell-matrix interactions including normal tissue remodeling (which can become abnormal, for example, with chronic inflammation). Disruptions of this balance result in serious diseases such as arthritis, tumor growth, and others.
  29. FIGURE 1-8 Fibroblasts in Connective Tissue. This micrograph shows tissue from the cornea of a rat. The extracellular matrix surrounds the fibroblasts (F).
  30. Specialized Cell Junctions
  31. Cellular Communication and Signal Transduction
  32. FIGURE 1-9 Junctional Complex. A, Schematic drawing of a belt desmosome between epithelial cells. This junction, also called the zonula adherens, encircles each of the interacting cells. The spot desmosomes and hemidesmosomes, like the belt desmosomes, are adhering junctions. This tight junction is an impermeable junction that holds cells together but seals them in such a way that molecules cannot leak between them. The gap junction, as a communicating junction, mediates the passage of small molecules from one interacting cell to the other. B, Electron micrograph of desmosomes.
  33. FIGURE 1-10 Cellular Communication. Three primary ways in which cells communicate with one another.
  34. FIGURE 1-11 Primary Modes of Chemical Signaling. Five forms of signaling mediated by secreted molecules. Hormones, paracrines, neurotransmitters, and neurohormones are all intercellular messengers that accomplish communication between cells. Autocrines bind to receptors on the same cell. Not all neurotransmitters act in the strictly synaptic mode shown; some act in a contact-dependent mode as local chemical mediators that influence multiple target cells in the area.
  35. FIGURE 1-12 Schematic of a Signal Transduction Pathway. Like a telephone receiver that converts an electrical signal into a sound signal, a cell converts an extracellular signal, A, into an intracellular signal, B. C, An extracellular signal molecule (ligand) bonds to a receptor protein located on the plasma membrane, where it is transduced into an intracellular signal. This process initiates a signaling cascade that relays the signal into the cell interior, amplifying and distributing it en route. Amplification is often achieved by stimulating enzymes. Steps in the cascade can be modulated by other events in the cell. D, Different cell behaviors rely on multiple extracellular signals.
  36. TABLE 1-3 CLASSES OF PLASMA MEMBRANE RECEPTORS
  37. Cellular Metabolism
  38. Role of Adenosine Triphosphate
  39. Food and Production of Cellular Energy
  40. Oxidative Phosphorylation
  41. FIGURE 1-13 Three Phases of Catabolism, Which Lead From Food to Waste Products. These reactions produce adenosine triphosphate (ATP), which is used to power other processes in the cell.
  42. FIGURE 1-14 Glycolysis. Each of the numbered reactions is catalyzed by a different enzyme. At step 4, a six-carbon carbohydrate is metabolized to two three-carbon carbohydrates, so that the number of molecules at every step after this is doubled. Reactions 5 and 6 are responsible for the net synthesis of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) molecules.
  43. Membrane Transport: Cellular Intake and Output
  44. FIGURE 1-15 What Happens to Pyruvate, the Product of Glycolysis? In the presence of oxygen, pyruvate is oxidized to acetyl coenzyme A (CoA) and enters the citric acid cycle. In the absence of oxygen, pyruvate instead is reduced, accepting the electrons extracted during glycolysis and carried by reduced nicotinamide adenine dinucleotide (NADH). When pyruvate is reduced directly, as it is in muscles, the product is lactic acid. When CO2 is first removed from pyruvate and the remainder is reduced, as it is in yeasts, the resulting product is ethanol.
  45. Movement of Water and Solutes
  46. Passive Transport: Diffusion, Filtration, and Osmosis
  47. Diffusion
  48. Filtration: hydrostatic pressure
  49. FIGURE 1-16 Passive Diffusion of Solute Molecules Across the Plasma Membrane. Oxygen, nitrogen, water, urea, glycerol, and carbon dioxide can diffuse readily down the concentration gradient. Macromolecules are too large to diffuse through pores in the plasma membrane. Ions may be repelled if the pores contain substances with identical charges. If the pores are lined with cations, for example, other cations will have difficulty diffusing because the positive charges will repel one another. Diffusion can still occur, but it occurs more slowly.
  50. Osmosis
  51. FIGURE 1-17 Hydrostatic Pressure and Oncotic Pressure in Plasma. 1, Hydrostatic pressure in plasma. 2, Oncotic pressure exerted by proteins in the plasma usually tends to pull water into the circulatory system. 3, Individuals with low protein levels (e.g., starvation) are unable to maintain a normal oncotic pressure; therefore water is not reabsorbed into the circulation and, instead, causes body edema.
  52. FIGURE 1-18 Tonicity. Tonicity is important, especially for red blood cell function.
  53. QUICK CHECK 1-2
  54. Mediated and Active Transport
  55. Mediated transport
  56. FIGURE 1-19 Conformational Change Model of Mediated Transport (Facilitated Diffusion). The transporter protein has two states: “ping” and “pong.” In the ping state, sites for molecules of a specific solute are exposed on the outside of the bilayer. In the pong state, the sites are exposed to the inner side of the bilayer.
  57. FIGURE 1-20 Channel Mode of Mediated Transport (Facilitated Diffusion). A channel protein forms a water-filled pore across the bilayer through which specific ions can diffuse.
  58. FIGURE 1-21 Mediated Transport. Illustration shows simultaneous movement of a single solute molecule in one direction (uniport), of two different solute molecules in one direction (symport), and of two different solute molecules in opposite directions (antiport).
  59. FIGURE 1-22 Active Transport and the Sodium-Potassium Pump. Three Na+ ions bind to sodium-binding sites on the carrier’s inner face. At the same time, an energy-containing adenosine triphosphate (ATP) molecule produced by the cell’s mitochondria binds to the carrier. The ATP dissociates, transferring its stored energy to the carrier. The carrier then changes shape, releases the three Na+ ions to the outside of the cell, and attracts two potassium (K+) ions to its potassium-binding sites. The carrier then returns to its original shape, releasing the two K+ ions and the remnant of the ATP molecule to the inside of the cell. The carrier is now ready for another pumping cycle.
  60. BOX 1-1 NEW UNDERSTANDINGS ABOUT ATP
  61. Active Transport of Na+ and K+
  62. Transport by Vesicle Formation
  63. Endocytosis and Exocytosis
  64. FIGURE 1-23 Endocytosis and Exocytosis. A, Endocytosis and fusion with lysosome and exocytosis. B, Electron micrograph of exocytosis.
  65. TABLE 1-4 MAJOR TRANSPORT SYSTEMS IN MAMMALIAN CELLS
  66. BOX 1-2 THE NEW ENDOCYTIC MATRIX
  67. FIGURE 1-24 Ligand Internalization by Means of Receptor-Mediated Endocytosis. A, The ligand attaches to its surface receptor (through the bristle coat or clathrin coat) and, through receptor-mediated endocytosis, enters the cell. The ingested material fuses with a lysosome and is processed by hydrolytic lysosomal enzymes. Processed molecules can then be transferred to other cellular components. B, Electron micrograph of a coated pit showing different sizes of filaments of the cytoskeleton (×82,000).
  68. Receptor-Mediated Endocytosis
  69. Caveolae
  70. Movement of Electrical Impulses: Membrane Potentials
  71. FIGURE 1-25 Sodium-Potassium Pump and Propagation of an Action Potential. A, Concentration difference of sodium (Na+) and potassium (K+) intracellularly and extracellularly. The direction of active transport by the sodium-potassium pump is also shown. B, The top diagram represents the polarized state of a neuronal membrane when at rest. The lower diagrams represent changes in sodium and potassium membrane permeabilities with depolarization and repolarization.
  72. QUICK CHECK 1-3
  73. Cellular Reproduction: the Cell Cycle
  74. FIGURE 1-26 Interphase and the Phases of Mitosis. A, The G1/S checkpoint is to “check” for cell size, nutrients, growth factors, and DNA damage. See text for resting phases. The G2/M checkpoint checks for cell size and DNA replication. B, The orderly progression through the phases of the cell cycle is regulated by cyclins (so-called because levels rise and fall) and cyclin-dependent protein kinases (CDKs) and their inhibitors. When cyclins are complexed with CDKs, cell cycle events are triggered.
  75. Phases of Mitosis and Cytokinesis
  76. Rates of Cellular Division
  77. Growth Factors
  78. TABLE 1-5 EXAMPLES OF GROWTH FACTORS AND THEIR ACTIONS
  79. Tissues
  80. Tissue Formation
  81. Types of Tissues
  82. QUICK CHECK 1-4
  83. FIGURE 1-27 How Growth Factors Stimulate Cell Proliferation. A, Resting cell. With the absence of growth factors, the retinoblastoma (Rb) protein is not phosphorylated; thus it holds the gene regulatory proteins in an inactive state. The gene regulatory proteins are required to stimulate the transcription of genes needed for cell proliferation. B, Proliferating cell. Growth factors bind to the cell surface receptors and activate intracellular signaling pathways, leading to activation of intracellular proteins. These intracellular proteins phosphorylate and thereby inactivate the Rb protein. The gene regulatory proteins are now free to activate the transcription of genes, leading to cell proliferation.
  84. BOX 1-3 CHARACTERISTICS OF EPITHELIAL TISSUES
  85. Simple Squamous Epithelial Cell. Photomicrograph of simple squamous epithelial cell in parietal wall of Bowman’s capsule in kidney.
  86. Cornified Stratified Squamous Epithelium. Diagram of stratified squamous epithelium of skin.
  87. Stratified Squamous Transitional Epithelium. Photomicrograph of stratified squamous transitional epithelium of urinary bladder.
  88. Simple Cuboidal Epithelium. Photomicrograph of simple cuboidal epithelium of pancreatic duct.
  89. Simple Columnar Epithelium. Photomicrograph of simple columnar epithelium.
  90. Pseudostratified Ciliated Columnar Epithelium. Photomicrograph of pseudostratified ciliated columnar epithelium of trachea.
  91. BOX 1-4 CONNECTIVE TISSUES
  92. Loose Areolar Connective Tissue.
  93. Dense, Irregular Connective Tissue.
  94. Dense, Regular (White Fibrous) Connective Tissue.
  95. Elastic Connective Tissue.
  96. Adipose Tissue. A, Fat storage areas—distribution of fat in male and female bodies. B, Photomicrograph of adipose tissue.
  97. Cartilage. A, Hyaline cartilage. B, Elastic cartilage. C, Fibrous cartilage.
  98. Bone.
  99. BOX 1-5 MUSCLE TISSUES
  100. Skeletal (Striated) Muscle.
  101. Cardiac Muscle.
  102. Smooth (Visceral) Muscle.
  103. DID YOU UNDERSTAND?
  104. Cellular Functions
  105. Structure and Function of Cellular Components
  106. Cell-to-Cell Adhesions
  107. Cellular Communication and Signal Transduction
  108. Cellular Metabolism
  109. Membrane Transport: Cellular Intake and Output
  110. Cellular Reproduction: The Cell Cycle
  111. Tissues
  112. KEY TERMS
  113. References
  114. Chapter 2 Genes and Genetic Diseases
  115. FIGURE 2-1 Successive Enlargements from a Human to the Genetic Material.
  116. DNA, RNA, and Proteins: Heredity at the Molecular Level
  117. Definitions
  118. Composition and Structure of DNA
  119. DNA as the Genetic Code
  120. FIGURE 2-2 Watson-Crick Model of the DNA Molecule. The DNA structure illustrated here is based on that published by James Watson (left) and Francis Crick (photograph, right) in 1953. Note that each side of the DNA molecule consists of alternating sugar and phosphate groups. Each sugar group is bonded to the sugar group opposite it by a pair of nitrogenous bases (adenine-thymine or cytosine-guanine). The sequence of these pairs constitutes a genetic code that determines the structure and function of a cell.
  121. Replication of DNA
  122. FIGURE 2-3 Replication of DNA. The two chains of the double helix separate, and each chain serves as the template for a new complementary chain.
  123. FIGURE 2-4 Base Pair Substitution. Missense mutations (A) produce a single amino acid change, whereas nonsense mutations (B) produce a stop codon in the mRNA. Stop codons terminate translation of the polypeptide.
  124. Mutation
  125. FIGURE 2-5 Frameshift Mutations. Frameshift mutations result from the addition or deletion of a number of bases that is not a multiple of three. This mutation alters all of the codons downstream from the site of insertion or deletion.
  126. From Genes to Proteins
  127. Transcription
  128. Gene Splicing
  129. Translation
  130. FIGURE 2-6 General Scheme of Ribonucleic Acid (RNA) Transcription. A, Transcription of messenger RNA (mRNA). A DNA molecule “unzips” in the region of the gene to be transcribed. RNA nucleotides already present in the nucleus temporarily attach themselves to exposed DNA bases along one strand of the unzipped DNA molecule according to the principle of complementary pairing. As the RNA nucleotides attach to the exposed DNA, they bind to each other and form a chainlike RNA strand called a messenger RNA (mRNA) molecule. Notice that the new mRNA strand is an exact copy of the base sequence on the opposite side of the DNA molecule. As in all metabolic processes, the formation of mRNA is controlled by an enzyme—in this case, the enzyme is called RNA polymeraseB, Editing of an mRNA transcript.
  131. Chromosomes
  132. FIGURE 2-7 Protein Synthesis.
  133. FIGURE 2-8 From Molecular Parts to the Whole Somatic Cell.
  134. FIGURE 2-9 Phases of Meiosis and Comparison to Mitosis
  135. Chromosome Aberrations and Associated Diseases
  136. Polyploidy
  137. FIGURE 2-10 Karyotype of Chromosomes. A, Human karyotype. B, Homologous chromosomes and sister chromatids.
  138. FIGURE 2-11 Structure of Chromosomes. A, Human chromosomes 2, 5, and 13. Each is replicated and consists of two chromatids. Chromosome 2 is a metacentric chromosome because the centromere is close to the middle; chromosome 5 is submetacentric because the centromere is set off from the middle; chromosome 13 is acrocentric because the centromere is at or very near the end. B, During mitosis, the centromere divides and the chromosomes move to opposite poles of the cell. At the time of centromere division, the chromatids are designated as chromosomes.
  139. Aneuploidy
  140. Autosomal aneuploidy
  141. FIGURE 2-12 Nondisjunction. Nondisjunction causes aneuploidy when chromosomes or sister chromatids fail to divide properly.
  142. Sex chromosome aneuploidy
  143. FIGURE 2-13 Child With Down Syndrome.
  144. FIGURE 2-14 Down Syndrome Increases With Maternal Age. Rate is per 1000 live births related to maternal age.
  145. TABLE 2-1 CHARACTERISTICS OF VARIOUS CHROMOSOME DISORDERS
  146. Abnormalities of Chromosome Structure
  147. Deletions
  148. FIGURE 2-15 Turner Syndrome. A, A sex chromosome is missing, and the person’s chromosomes are 45,X. Characteristic signs are short stature, female genitalia, webbed neck, shieldlike chest with underdeveloped breasts and widely spaced nipples, and imperfectly developed ovaries. B, As this karyotype shows, Turner syndrome results from monosomy of sex chromosomes (genotype XO).
  149. Duplications
  150. FIGURE 2-16 Klinefelter Syndrome. This young man exhibits many characteristics of Klinefelter syndrome: small testes, some development of the breasts, sparse body hair, and long limbs. This syndrome results from the presence of two or more X chromosomes with one Y chromosome (genotypes XXY or XXXY, for example).
  151. FIGURE 2-17 Abnormalities of Chromosome Structure. A, Deletion occurs when a chromosome segment is lost. B, Normal crossing over. C, The generation of duplication and deletion through unequal crossing over.
  152. Inversions
  153. Translocations
  154. FIGURE 2-18 Normal and Abnormal Chromosome Translocation. A, Normal chromosomes and reciprocal translocation. B, Pairing at meiosis. C, Consequences of translocation in gametes; unbalanced gametes result in zygotes that are partially trisomic and partially monosomic and consequently develop abnormally.
  155. Fragile sites
  156. QUICK CHECK 2-1
  157. Elements of Formal Genetics
  158. Phenotype and Genotype
  159. FIGURE 2-19 Symbols Commonly Used in Pedigrees.
  160. Dominance and Recessiveness
  161. Transmission of Genetic Diseases
  162. FIGURE 2-20 Punnett Square and Autosomal Dominant Traits. A, Punnett square for the mating of two individuals with an autosomal dominant gene. Here both parents are affected by the trait. B, Punnett square for the mating of a normal individual with a carrier for an autosomal dominant gene.
  163. Autosomal Dominant Inheritance
  164. Characteristics of Pedigrees
  165. FIGURE 2-21 Pedigree Illustrating the Inheritance Pattern of Postaxial Polydactyly, an Autosomal Dominant Disorder. Affected individuals are represented by shading.
  166. Recurrence Risks
  167. Delayed Age of Onset
  168. FIGURE 2-22 Pedigree for Retinoblastoma Showing Incomplete Penetrance. Female with marked arrow in line II must be heterozygous, but she does not express the trait.
  169. Penetrance and Expressivity
  170. FIGURE 2-23 Neurofibromatosis. Tumors. The most common is sessile or pedunculated. Early tumors are soft, dome-shaped papules or nodules that have a distinctive violaceous hue. Most are benign.
  171. Epigenetics and Genomic Imprinting
  172. FIGURE 2-24 Epigenetic Modifications. Because DNA is a long molecule, it needs packaging to fit in the tiny nucleus. Packaging involves coiling of the DNA in a “left-handed” spiral around spools, made of four pairs of proteins individually known as histones and collectively as the histone octamer. The entire spool is called a nucleosome (also see Figure 1-2). Nucleosomes are organized into chromatin, the repeating building blocks of a chromosome. Histone modifications are correlated with methylation, are reversible, and occur at multiple sites. Methylation occurs at the 5 position of cytosine and provides a “footprint” or signature as a unique epigenetic alteration (red). When genes are expressed, chromatin is open or active; however, when chromatin is condensed because of methylation and histone modification, genes are inactivated.
  173. Autosomal Recessive Inheritance
  174. Characteristics of Pedigrees
  175. FIGURE 2-25 Pedigree for Cystic Fibrosis. Cystic fibrosis is an autosomal recessive disorder. The double bar denotes a consanguineous mating. Because cystic fibrosis is relatively common in European populations, most cases do not involve consanguinity.
  176. Recurrence Risks
  177. Consanguinity
  178. FIGURE 2-26 Punnett Square for the Mating of Heterozygous Carriers Typical of Most Cases of Recessive Disease.
  179. X-Linked Inheritance
  180. X Inactivation
  181. FIGURE 2-27 The X Inactivation Process. The maternal (m) and paternal (p) X chromosomes are both active in the zygote and in early embryonic cells. X inactivation then takes place, resulting in cells having either an active paternal X or an active maternal X. Females are thus X chromosome mosaics, as shown in the tissue sample at the bottom of the page.
  182. Sex Determination
  183. FIGURE 2-28 Distal Short Arms of the X and Y Chromosomes Exchange Material During Meiosis in the Male. The region of the Y chromosome in which this crossover occurs is called the pseudoautosomal region. The SRY gene, which triggers the process leading to male gonadal differentiation, is located just outside the pseudoautosomal region. Occasionally, the crossover occurs on the centromeric side of the SRY gene, causing it to lie on an X chromosome instead of a Y chromosome. An offspring receiving this X chromosome will be an XX male, and an offspring receiving the Y chromosome will be an XY female.
  184. QUICK CHECK 2-2
  185. Characteristics of Pedigrees
  186. Recurrence Risks
  187. Sex-Limited and Sex-Influenced Traits
  188. FIGURE 2-29 Punnett Square and X-Linked Recessive Traits. A, Punnett square for the mating of a normal male (XHY) and a female carrier of an X-linked recessive gene (XHXh). B, Punnett square for the mating of a normal female (XHXH) with a male affected by an X-linked recessive disease (XhY). C, Punnett square for the mating of a female who carries an X-linked recessive gene (XHXh) with a male who is affected with the disease caused by the gene (XhY).
  189. Evaluation of Pedigrees
  190. Linkage Analysis and Gene Mapping
  191. Classic Pedigree Analysis
  192. FIGURE 2-30 Genetic Results of Crossing Over. A, No crossing over. B, Crossing over with recombination. C, Double crossing over, resulting in no recombination.
  193. Complete Human Gene Map: Prospects and Benefits
  194. HEALTH ALERT
  195. FIGURE 2-31 Example of Diseases: A Gene Map. ADA, Adenosine deaminase; ALD, adrenoleukodystrophy; PKU, phenylketonuria.
  196. Multifactorial Inheritance
  197. FIGURE 2-32 Multifactorial Inheritance. Analysis of mode of inheritance for grain color in wheat. The trait is controlled by three independently assorted gene loci.
  198. FIGURE 2-33 Threshold of Liability for Pyloric Stenosis in Males and Females.
  199. BOX 2-1 CRITERIA USED TO DEFINE MULTIFACTORIAL DISEASES
  200. QUICK CHECK 2-3
  201. DID YOU UNDERSTAND?
  202. DNA, RNA, and Proteins: Heredity at the Molecular Level
  203. Chromosomes
  204. Elements of Formal Genetics
  205. Transmission of Genetic Diseases
  206. Linkage Analysis and Gene Mapping
  207. Multifactorial Inheritance
  208. KEY TERMS
  209. References
  210. Chapter 3 Altered Cellular and Tissue Biology
  211. Cellular Adaptation
  212. FIGURE 3-1 Adaptive and Dysplastic Alterations in Simple Cuboidal Epithelial Cells.
  213. Atrophy
  214. FIGURE 3-2 Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic cerebrovascular disease, resulting in reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the surface of the brain.
  215. Hypertrophy
  216. Hyperplasia
  217. FIGURE 3-3 Hypertrophy of Cardiac Muscle in Response to Valve Disease. A, Transverse slices of a normal heart and a heart with hypertrophy of the left ventricle (L, normal thickness of left ventricular wall; T, thickened wall from heart in which severe narrowing of aortic valve caused resistance to systolic ventricular emptying). B, Histology of cardiac muscle from the normal heart. C, Histology of cardiac muscle from a hypertrophied heart.
  218. Dysplasia: Not a True Adaptive Change
  219. FIGURE 3-4 Hyperplasia of the Prostate With Secondary Thickening of the Obstructed Urinary Bladder. The enlarged prostate is seen protruding into the lumen of the bladder, which appears trabeculated. These “trabeculae” result from hypertrophy and hyperplasia of smooth muscle cells that occur in response to increased intravesical pressure caused by urinary obstruction.
  220. Metaplasia
  221. Cellular Injury
  222. FIGURE 3-5 Reversible Changes in Cells Lining the Bronchi.
  223. FIGURE 3-6 Stages of Cellular Adaptation, Injury, and Death. The normal cell responds to physiologic and pathologic stresses by adapting (atrophy, hypertrophy, hyperplasia, metaplasia). Cell injury occurs if the adaptive responses are exceeded or compromised by injurious agents, stress, and mutations. The injury is reversible if it is mild or transient, but if the stimulus persists the cell suffers irreversible injury and eventually death.
  224. TABLE 3-1 TYPES OF PROGRESSIVE CELL INJURY AND RESPONSES
  225. General Mechanisms of Cell Injury
  226. Hypoxic Injury
  227. FIGURE 3-7 Hypoxic Injury Induced by Ischemia. A, Consequences of decreased oxygen delivery or ischemia with decreased ATP. The structural and physiologic changes are reversible if oxygen is delivered quickly. Significant decreases in ATP result in cell death, mostly by necrosis. B, Mitochondrial damage can result in changes in membrane permeability, loss of membrane potential, and decreased ATP. Between the outer and inner membranes of the mitochondria are proteins that can activate the cell’s suicide pathways, called apoptosis. C, Calcium ions are critical mediators of cell injury. Calcium ions are usually maintained at low concentrations in the cell’s cytoplasm; thus ischemia and certain toxins can initially cause an increase in the release of Ca++ from intracellular stores and later an increased movement (influx) across the plasma membrane.
  228. TABLE 3-2 COMMON THEMES IN CELL INJURY AND CELL DEATH
  229. FIGURE 3-8 Hypoxia and Inflammation. Shown is a simplified drawing of clinical conditions characterized by tissue hypoxia that causes inflammatory changes (left) and inflammatory diseases that ultimately lead to hypoxia (right). These diseases and conditions are discussed in more detail in their respective chapters.
  230. FIGURE 3-9 Reperfusion Injury. Without oxygen, or anoxia, the cells display hypoxic injury and become swollen. With reoxygenation, reperfusion injury increases because of the formation of reactive oxygen radicals that can cause cell necrosis.
  231. HEALTH ALERT
  232. QUICK CHECK 3-1
  233. Free Radicals and Reactive Oxygen Species—Oxidative Stress
  234. Chemical Injury
  235. Mechanisms
  236. FIGURE 3-10 Generation of Reactive Oxygen Species and Antioxidant Mechanisms in Biologic Systems. Free radicals are generated within cells in several ways, including from normal respiration; absorption of radiant energy; activation of leukocytes during inflammation; metabolism of chemicals or drugs; transition metals, such as iron (Fe+++) or copper (Cu+), where the metals donate or accept electrons as in the Fenton reaction; nitric oxide (NO) generated by endothelial cells (not shown); and reperfusion injury. Ubiquinone (coenzyme Q), a lipophilic molecule, transfers electrons in the inner membrane of mitochondria, ultimately enabling their interaction with oxygen (O2) and hydrogen (H2) to yield water (H2O). In so doing, the transport allows free energy change and the synthesis of 1 mole of adenosine triphosphate (ATP). With the transport of electrons, free radicals are generated within the mitochondria. Reactive oxygen species (O2·−, H2O2, OH·) act as physiologic modulators of some mitochondrial functions but may also cause cell damage. O2 is converted to superoxide (O2·−) by oxidative enzymes in the mitochondria, endoplasmic reticulum (ER), plasma membrane, peroxisomes, and cytosol. O2 is converted to H2O2 by superoxide dismutase (SOD) and further to OH· by the Cu/Fe Fenton reaction. Superoxide catalyzes the reduction of Fe++ to Fe+++, thus increasing OH· formation by the Fenton reaction. H2O2 is also derived from oxidases in peroxisomes. The three reactive oxygen species (H2O2, OH·, and O2·−) cause free radical damage to lipids (peroxidation of the membrane), proteins (ion pump damage), and DNA (impaired protein synthesis). The major antioxidant enzymes include SOD, catalase, and glutathione peroxidase.
  237. TABLE 3-3 Biologically Relevant Free Radicals
  238. BOX 3-1 DISEASES AND DISORDERS LINKED TO OXYGEN-DERIVED FREE RADICALS
  239. TABLE 3-4 METHODS CONTRIBUTING TO INACTIVATION OR TERMINATION OF FREE RADICALS
  240. Chemical Agents Including Drugs
  241. FIGURE 3-11 Human Exposure to Pollutants. Pollutants contained in air, water, and soil are absorbed through the lungs, gastrointestinal tract, and skin. In the body they may act at the site of absorption but are generally transported through the bloodstream to various organs where they can be stored or metabolized. Metabolism of xenobiotics may result in the formation of water-soluble compounds that are excreted, or a toxic metabolite may be created by activation of the agent.
  242. FIGURE 3-12 Chemical Injury of Liver Cells Induced by Carbon Tetrachloride (CCl4) Poisoning. Light blue boxes are mechanisms unique to chemical injury, purple boxes involve hypoxic injury, and green boxes are clinical manifestations.
  243. TABLE 3-5 COMMON DRUGS OF ABUSE
  244. Lead
  245. FIGURE 3-13 Acetaminophen Metabolism and Toxicity. CYP2E1, a cytochrome; NAPQI, toxic byproduct; GSH, glutathione.
  246. TABLE 3-6 SOCIAL OR STREET DRUGS AND THEIR EFFECTS
  247. TABLE 3-7 COMMON SOURCES OF LEAD EXPOSURE
  248. Carbon Monoxide
  249. Ethanol
  250. FIGURE 3-14 Major Pathways of ADH Metabolism of Alcohol in the Liver.
  251. FIGURE 3-15 Fetal Alcohol Syndrome. When alcohol enters the fetal blood, the potential result can cause tragic congenital abnormalities, such as microcephaly (“small head”), low birth weight, and cardiovascular defects, as well as developmental disabilities, such as physical and mental retardation, and even death. Note the small head, thinned upper lip, small eye openings (palpebral fissures), epicanthal folds, and receded upper jaw (retrognathia) typical of fetal alcohol syndrome.
  252. FIGURE 3-16 Alcoholic Hepatitis. Chicken-wire fibrosis extending between hepatocytes (Mallory trichrome stain).
  253. Mercury
  254. QUICK CHECK 3-2
  255. Unintentional and Intentional Injuries
  256. TABLE 3-8 MAJOR SOURCES OF MERCURY EXPOSURE AND HEALTH EFFECTS
  257. BOX 3-2 CLASSIFICATION OF PREVENTABLE ADVERSE EVENTS IN PRIMARY CARE
  258. Asphyxial Injuries
  259. Suffocation
  260. Strangulation
  261. HEALTH ALERT
  262. Chemical Asphyxiants
  263. Drowning
  264. TABLE 3-9 UNINTENTIONAL AND INTENTIONAL INJURIES
  265. TABLE 3-10 MECHANISMS OF CELLULAR INJURY
  266. BOX 3-3 RECOMMENDATIONS TO AVOID MEDICAL ERRORS
  267. What can you do? Be Involved in Your Healthcare.
  268. Medicines
  269. Hospital Stays
  270. Surgery
  271. Other Steps You Can Take
  272. QUICK CHECK 3-3
  273. Infectious Injury
  274. Immunologic and Inflammatory Injury
  275. Manifestations of Cellular Injury: Accumulations
  276. FIGURE 3-17 Mechanisms of Intracellular Accumulations.
  277. Water
  278. FIGURE 3-18 The Process of Oncosis (Formerly Referred to as “Hydropic Degeneration”). ATP, Adenosine triphosphate.
  279. Lipids and Carbohydrates
  280. FIGURE 3-19 Fatty Liver. The liver appears yellow.
  281. Glycogen
  282. Proteins
  283. Pigments
  284. Melanin
  285. Hemoproteins
  286. FIGURE 3-20 Hemosiderin Accumulation Is Noted as the Color Changes in a “Black Eye.”
  287. Calcium
  288. FIGURE 3-21 Free Cytosolic Calcium: A Destructive Agent. Normally, calcium is removed from the cytosol by adenosine triphosphate (ATP)-dependent calcium pumps. In normal cells, calcium is bound to buffering proteins, such as calbindin or paralbumin, and is contained in the endoplasmic reticulum and the mitochondria. If there is abnormal permeability of calcium-ion channels, direct damage to membranes, or depletion of ATP (i.e., hypoxic injury), calcium increases in the cytosol. If the free calcium cannot be buffered or pumped out of cells, uncontrolled enzyme activation takes place, causing further damage. Uncontrolled entry of calcium into the cytosol is an important final common pathway in many causes of cell death.
  289. FIGURE 3-22 Aortic Valve Calcification. A, This calcified aortic valve is an example of dystrophic calcification. B, This algorithm shows the dystrophic mechanism of calcification.
  290. Urate
  291. Systemic Manifestations
  292. TABLE 3-11 SYSTEMIC MANIFESTATIONS OF CELLULAR INJURY
  293. FIGURE 3-23 Schematic Illustration of the Morphologic Changes in Cell Injury Culminating in Necrosis or Apoptosis. Myelin figures come from degenerating cellular membranes and are noted within the cytoplasm or extracellularly.
  294. Cellular Death
  295. Necrosis
  296. FIGURE 3-24 Coagulative Necrosis. A wedge-shaped kidney infarct (yellow).
  297. TABLE 3-12 FEATURES OF NECROSIS AND APOPTOSIS
  298. FIGURE 3-25 Liquefactive Necrosis of the Brain. The area of infarction is softened as a result of liquefaction necrosis.
  299. FIGURE 3-26 Caseous Necrosis. Tuberculosis of the lung, with a large area of caseous necrosis containing yellow-white and cheesy debris.
  300. FIGURE 3-27 Fat Necrosis of Pancreas. Interlobular adipocytes are necrotic; acute inflammatory cells surround these.
  301. Apoptosis
  302. FIGURE 3-28 Gangrene, a Complication of Necrosis. In certain circumstances, necrotic tissue will be invaded by putrefactive organisms that are both saccharolytic and proteolytic. Foul-smelling gases are produced, and the tissue becomes green or black as a result of breakdown of hemoglobin. Obstruction of the blood supply to the bowel almost inevitably is followed by gangrene.
  303. FIGURE 3-29 Necrosis and Apoptosis in Liver Cells. Necrosis is caused by exogenous injury whereby cells are swollen and have nuclear changes in ruptured cell membrane. Apoptosis is single cell death. It is genetically programmed (suicide genes) and depends on energy. Apoptotic bodies contain part of the nucleus and cytoplasmic organelles, which are ultimately engulfed by macrophages or adjacent cells. RER, Rough endoplasmic reticulum.
  304. Autophagy
  305. FIGURE 3-30 Mechanisms of Apoptosis. The two pathways of apoptosis differ in their induction and regulation, and both culminate in the activation of “executioner” caspases. The induction of apoptosis by the mitochondrial pathway involves the Bcl-2 family, which causes leakage of mitochondrial proteins. The regulators of the death receptor pathway involve the proteases, called caspases.
  306. FIGURE 3-31 Autophagy. Cellular stresses, such as nutrient deprivation, activate autophagy genes that create vacuoles in which cellular organelles are sequestered and then degraded following fusion of the vesicles with lysosomes. The digested materials are recycled to provide nutrients for the cell.
  307. QUICK CHECK 3-4
  308. Aging & Altered Cellular and Tissue Biology
  309. FIGURE 3-32 Microinsults.
  310. TABLE 3-13 THEORIES OF AGING
  311. Normal Life Span and Life Expectancy
  312. TABLE 3-14 BIOLOGY OF AGING
  313. Degenerative Extracellular Changes
  314. HEALTH ALERT
  315. FIGURE 3-33 Some Biological Changes Associated With Aging. Insets show proportion of remaining functions in the organs of a person in late adulthood compared with a 20-year-old.
  316. Cellular Aging
  317. Tissue and Systemic Aging
  318. Frailty
  319. Somatic Death
  320. QUICK CHECK 3-5
  321. DID YOU UNDERSTAND?
  322. Cellular Adaptation
  323. Cellular Injury
  324. Manifestations of Cellular Injury
  325. Cellular Death
  326. Aging and Altered Cellular and Tissue Biology
  327. Somatic Death
  328. KEY TERMS
  329. References
  330. Chapter 4 Fluids and Electrolytes, Acids and Bases
  331. Distribution of Body Fluids
  332. TABLE 4-1 TOTAL BODY WATER (%) IN RELATION TO BODY WEIGHT*
  333. TABLE 4-2 DISTRIBUTION OF BODY WATER (70-KG MAN)
  334. Maturation and the Distribution of Body Fluids
  335. Water Movement Between Plasma and Interstitial Fluid
  336. TABLE 4-3 NORMAL WATER GAINS AND LOSSES (70-KG MAN)
  337. PEDIATRIC CONSIDERATIONS
  338. Newborn Infants
  339. Children and Adolescents
  340. GERIATRIC CONSIDERATIONS
  341. Water Movement Between ICF and ECF
  342. Alterations in Water Movement
  343. Edema
  344. Pathophysiology
  345. FIGURE 4-1 Net Filtration—Fluid Movement Between Plasma and Interstitial Space. The movement of fluid between the vascular, interstitial spaces and the lymphatics is the result of net filtration of fluid across the semipermeable capillary membrane. Capillary hydrostatic pressure is the primary force for fluid movement out of the arteriolar end of the capillary and into the interstitial space. At the venous end, capillary oncotic pressure (from plasma proteins) attracts water back into the vascular space. Interstitial hydrostatic pressure promotes the movement of fluid and proteins into the lymphatics. Osmotic pressure accounts for the movement of fluid between the interstitial space and the intracellular space. Normally, intracellular and extracellular fluid osmotic pressures are equal (280 to 294 mOsm) and water is equally distributed between the interstitial and intracellular compartments.
  346. FIGURE 4-2 Mechanisms of Edema Formation. H2O, Water; Na+, sodium ion.
  347. Clinical Manifestations
  348. Evaluation and Treatment
  349. FIGURE 4-3 Pitting Edema.
  350. QUICK CHECK 4-1
  351. TABLE 4-4 REPRESENTATIVE DISTRIBUTION OF ELECTROLYTES IN BODY COMPARTMENTS
  352. Sodium, Chloride, and Water Balance
  353. Sodium and Chloride Balance
  354. FIGURE 4-4 The Renin-Angiotensin-Aldosterone System. (1) Renal juxtaglomerular cells sense decrease in blood pressure and release renin; (2) renin activates angiotensinogen to angiotensin I; (3) angiotensin I is converted to angiotensin II via angiotensin-converting enzyme (ACE) in the lung capillaries; (4) angiotensin II promotes vasoconstriction and stimulates aldosterone secretion from the adrenal cortex, resulting in renal sodium and water retention, potassium excretion, and an increase in blood pressure; (5) aldosterone causes increased reabsorption of sodium and water retention.
  355. FIGURE 4-5 The Atrial Natriuretic Hormone (ANH) System. GFR, Glomerular filtration rate; Na+, sodium ion.
  356. Water Balance
  357. FIGURE 4-6 The Antidiuretic Hormone (ADH) System.
  358. TABLE 4-5 WATER AND SOLUTE IMBALANCES
  359. QUICK CHECK 4-2
  360. Alterations in Sodium, Water, and Chloride Balance
  361. FIGURE 4-7 Effects of Alterations in Extracellular Sodium Concentration in RBC, Body Cell, and Neuron. A, Hypotonic Alteration: Decrease in ECF sodium (Na) concentration (hyponatremia) results in ICF osmotic attraction of water with swelling and potential bursting of cells. B, Isotonic Alteration: Normal concentration of sodium in the ECF and no change in shifts of fluid in or out of cells. C, Hypertonic Alteration: An increase in ECF sodium concentration (hypernatremia) results in osmotic attraction of water out of cells with cell shrinkage. RBC, Red blood cell.
  362. Isotonic Alterations
  363. Hypertonic Alterations
  364. Hypernatremia
  365. Pathophysiology
  366. HEALTH ALERT
  367. Clinical Manifestations
  368. Evaluation and Treatment
  369. Water Deficit
  370. Pathophysiology
  371. Clinical Manifestations
  372. Evaluation and Treatment
  373. Hypotonic Alterations
  374. Hyponatremia
  375. Pathophysiology
  376. Clinical Manifestations
  377. Evaluation and Treatment
  378. Water Excess
  379. Pathophysiology
  380. Clinical Manifestations
  381. Evaluation and Treatment
  382. QUICK CHECK 4-3
  383. Alterations in Potassium and other Electrolytes
  384. Potassium
  385. Hypokalemia
  386. Pathophysiology
  387. Clinical Manifestations
  388. FIGURE 4-8 Electrocardiogram Changes With Potassium Imbalance.
  389. TABLE 4-6 CLINICAL MANIFESTATIONS OF POTASSIUM LEVEL ALTERATIONS
  390. Evaluation and Treatment
  391. Hyperkalemia
  392. Pathophysiology
  393. Clinical Manifestations
  394. Evaluation and Treatment
  395. QUICK CHECK 4-4
  396. Other Electrolytes—Calcium, Magnesium, and Phosphate
  397. Acid-Base Balance
  398. Hydrogen Ion and pH
  399. TABLE 4-7 ALTERATIONS IN OTHER BODY ELECTROLYTES
  400. Buffer Systems
  401. Carbonic Acid–Bicarbonate Buffering
  402. TABLE 4-8 PH OF BODY FLUIDS
  403. Protein Buffering
  404. Renal Buffering
  405. Acid-Base Imbalances
  406. Metabolic Acidosis
  407. FIGURE 4-9 Integration of pH Control Mechanisms. Elevated carbon dioxide (CO2) levels result in increased formation of carbonic acid (H2CO3) in red blood cells. The resulting increase in hydrogen ions (H+), coupled with elevated CO2 levels, results in HHbCO2 and an increase in respiratory rate and secretion of H+ by the kidneys, thus helping to regulate the pH of body fluids.
  408. TABLE 4-9 BUFFER SYSTEMS
  409. Metabolic Alkalosis
  410. FIGURE 4-10 Davenport Diagram: Classic Working Diagram for Studying Primary Uncompensated Acid-Base Imbalance. The point ⊗ represents a normal pH value (7.4) and normal values for the partial pressure of arterial carbon dioxide (PaCO2 = 40 mm Hg) and the bicarbonate concentration (HCO3− = 24 mEq/L). Note that as the Paco2 increases toward 60 mm Hg (A) the pH decreases (respiratory acidosis), and that as it decreases toward 20 mm Hg (B) the pH increases (respiratory alkalosis). Metabolic acidosis develops as the concentration of HCO3− decreases (C), and metabolic alkalosis develops as the concentration of HCO3− increases (D).
  411. TABLE 4-10 CAUSES OF METABOLIC ACIDOSIS
  412. FIGURE 4-11 Metabolic Acidosis.
  413. FIGURE 4-12 Metabolic Alkalosis.
  414. Respiratory Acidosis
  415. FIGURE 4-13 Respiratory Acidosis.
  416. Respiratory Alkalosis
  417. FIGURE 4-14 Respiratory Alkalosis.
  418. QUICK CHECK 4-5
  419. DID YOU UNDERSTAND?
  420. Distribution of Body Fluids
  421. Alterations in Water Movement
  422. Sodium, Chloride, and Water Balance
  423. Alterations in Sodium, Water, and Chloride Balance
  424. Alterations in Potassium and Other Electrolytes
  425. Acid-Base Balance
  426. KEY TERMS
  427. References
  428. UNIT 2 Mechanisms of Self-Defense
  429. Interactive Review – Unit 2
  430. Chapter 5 Innate Immunity: Inflammation and Wound Healing
  431. Human Defense Mechanisms
  432. TABLE 5-1 OVERVIEW OF HUMAN DEFENSES
  433. Innate Immunity
  434. First Line of Defense: Physical and Biochemical Barriers and Normal Flora
  435. Physical Barriers
  436. Epithelial Cell–Derived Chemicals
  437. FIGURE 5-1 The Closed Barrier. The digestive, respiratory, and genitourinary tracts and skin form closed barriers between the internal organs and the environment.
  438. Normal Flora
  439. QUICK CHECK 5-1
  440. Second Line of Defense: Inflammation
  441. FIGURE 5-2 The Major Local Changes in the Process of Inflammation. Compared to the normal circulation, inflammation is characterized by (1) dilation of the blood vessels and increased blood flow, leading to erythema and warmth; (2) increased vascular permeability with leakage of plasma from the vessels, leading to edema; and (3) movement of leukocytes from the vessels into the site of injury.
  442. FIGURE 5-3 Acute Inflammatory Response. Inflammation is usually initiated by cellular injury and may be complicated by infection. Mast cell degranulation, the activation of three plasma systems, and the release of subcellular components from the damaged cells occur as a consequence. These systems are interdependent, so that induction of one (e.g., mast cell degranulation) can result in the induction of the other two. The result is the development of the characteristic microscopic and clinical hallmarks of inflammation. The figure numbers refer to additional figures in which more detailed information may be found on that portion of the response.
  443. QUICK CHECK 5-2
  444. Plasma Protein Systems and Inflammation
  445. Complement System
  446. FIGURE 5-4 Plasma Protein Systems in Inflammation: Complement, Clotting, and Kinin Systems. Each plasma protein system consists of a family of proteins that are activated in sequence to create potent biologic effects. The complement system can be activated by three mechanisms, each of which results in proteolytic activation of C3. The fragments of C3 activation, C3a and C3b, are major components of inflammation. C3a is a potent anaphylatoxin, which induces degranulation of mast cells. C3b can bind to the surface or cells, such as bacteria, and either serve as an opsonin for phagocytosis or proteolytically activate the next component of the complement cascade, C5. The smaller fragment of C5 activation is C5a, a powerful anaphylatoxin, and is also chemotactic for neutrophils, attracting them to the site of inflammation. The larger fragment, C5b, activates the components of the membrane attack complex (C5-C9), which damage the bacterial membrane and kill the bacteria. The clotting system can be activated by the tissue factor (extrinsic) pathway and the contact activation (intrinsic) pathway. All routes of clotting initiation lead to activation of factor X and thrombin. Thrombin is an enzyme that proteolytically activates fibrinogen to form fibrin and small fibrinopeptides (FPs). Fibrin polymerizes to form a clot, and the FPs are highly active as chemotactic factors and causing increased vascular permeability. The XIIa produced by the clotting system can also be activated by kallikrein of the kinin system (red arrow). Prekallikrein is enzymatically converted to kininogen, which activates bradykinin. Bradykinin functions similar to histamine and increases vascular permeability. Bradykinin can also stimulate nerve endings to cause pain. TF, tissue factor; FPs, Fibrinopeptides.
  447. Clotting System
  448. Kinin System
  449. Control and Interaction of Plasma Protein Systems
  450. QUICK CHECK 5-3
  451. FIGURE 5-5 Cellular Components of the Blood. Cells in the blood can be classified as red blood cells (erythrocytes), cellular fragments (platelets), or white blood cells (leukocytes). Leukocytes consist of lymphocytes, monocytes, and granulocytes (neutrophils, eosinophils, basophils).
  452. Cellular Components of Inflammation
  453. Cellular Receptors
  454. FIGURE 5-6 Principal Mediators of Inflammatory Processes. C3b, Large fragment produced from complement component C3; C5a, small fragment produced from complement component C5; ECF-A, eosinophil chemotactic factor of anaphylaxis; FGF, fibroblast growth factor; IFN, interferon; IgG, immunoglobulin G (predominant class of antibody in the blood); IL, interleukin; MCF, monocyte chemotactic factor; NCF, neutrophil chemotactic factor; PAF, platelet-activating factor; TGF, T-cell growth factor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.
  455. FIGURE 5-7 The Action of Interferon. See text for details.
  456. Mast Cells and Basophils
  457. Degranulation
  458. FIGURE 5-8 Mast Cell and Mast Cell Degranulation and Synthesis of Biologic Mediators During Inflammation. (A) Colorized photomicrograph of mast cell; dense red granules contain histamine and other biologically active substances. Among these are histamine, which is a major initiator of vascular changes, and a variety of chemotactic factors. (B) Mast cell degranulation (left) and synthesis (right). Histamine and biologically active substances are released immediately after stimulation of mast cells. Other substances are synthesized in response to mast cell stimulation. These include lipid-based molecules that originate from plasma membrane phospholipids as a result of the action of phospholipase A2. These include platelet-activating factor and a variety of prostaglandins and leukotrienes.
  459. FIGURE 5-9 Effects of Histamine Through H1 and H2 Receptors. The effects depend on (1) the density and affinity of H1 or H2 receptors on the target cell and (2) the identity of the target cell. ATP, Adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate.
  460. Synthesis of Mediators
  461. Endothelium
  462. Platelets
  463. Phagocytes
  464. Neutrophils
  465. Monocytes and Macrophages
  466. FIGURE 5-10 Process of Phagocytosis. The process that results in phagocytosis is characterized by three interrelated steps: adherence and diapedesis, tissue invasion by chemotaxis, and phagocytosis. A, Adherence, margination, diapedesis, and chemotaxis. The primary phagocyte in the blood is the neutrophil, which usually moves freely within the vessel (1). At sites of inflammation, the neutrophil progressively develops increased adherence to the endothelium, leading to accumulation along the vessel wall (margination or pavementing) (2). At sites of endothelial cell retraction the neutrophil exits the blood by means of diapedesis (3)Chemotaxis. In the tissues, the neutrophil detects chemotactic factor gradients through surface receptors (1) and migrates towards higher concentrations of the factors (2). The high concentration of chemotactic factors at the site of inflammation immobilizes the neutrophil (3)B, Specific receptors for recognition and attachment. C, Phagocytosis. Opsonized microorganisms bind to the surface of a phagocyte through specific receptors (1). The microorganism is ingested into a phagocytic vacuole, or phagosome (2). Lysosomes fuse with the phagosome, resulting in the formation of a phagolysosome (3). During this process the microorganism is exposed to products of the lysosomes, including a variety of enzymes and products of the hexose-monophosphate shunt (e.g., H2O2, O2−). The microorganism is killed and digested (4)Ab, Antibody; AbR, antibody receptor; C3b, complement component C3b; C3bR, complement C3b receptor; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor.
  467. Eosinophils
  468. Dendritic Cells and T Lymphocytes
  469. Phagocytosis
  470. FIGURE 5-11 Steps in Phagocytosis. These scanning electron micrographs show examples of the progressive steps in phagocytosis. A, A leukocyte undergoes chemotactic movement (in direction of arrow) by extending a filopodium (upper left) from the trailing body of the cell. B, Engulfment of red blood cells by a macrophage (M) that attaches to the red blood cells (R)C, An extension of the macrophage membrane (P; pseudopod) starts to enclose the red cell. D, The red blood cells are almost totally engulfed by the macrophage.
  471. QUICK CHECK 5-4
  472. Acute and Chronic Inflammation
  473. Local Manifestations of Acute Inflammation
  474. Systemic Manifestations of Acute Inflammation
  475. Fever
  476. Leukocytosis
  477. TABLE 5-2 CIRCULATING LEVELS OF ACUTE-PHASE REACTANTS DURING INFLAMMATION
  478. Plasma Protein Synthesis
  479. Chronic Inflammation
  480. FIGURE 5-12 The Chronic Inflammatory Response. Inflammation usually becomes chronic because of the persistence of an infection, an antigen, or a foreign body in the wound. Chronic inflammation is characterized by the persistence of many of the processes of acute inflammation. In addition, large amounts of neutrophil degranulation and death, the activation of lymphocytes, and the concurrent activation of fibroblasts result in the release of mediators that induce the infiltration of more lymphocytes and monocytes/macrophages and the beginning of wound healing and tissue repair. For more detailed information on each portion of the response, see the figures referenced in this illustration.
  481. FIGURE 5-13 Tuberculous Granuloma. A central area of amorphous caseous necrosis (C) is surrounded by a zone of lymphocytes (L) and enlarged epithelioid cells (E). Activated macrophages frequently fuse to form multinucleated cells (Langhans giant cells). In tuberculoid granulomas the nuclei of the giant cells move to the cellular margins in a horseshoe-like formation.
  482. QUICK CHECK 5-5
  483. Wound Healing
  484. FIGURE 5-14 Wound Healing by Primary and Secondary Intention and Phases of Wound Healing. Phases of wound healing (coagulation, inflammation, proliferation, remodeling, and maturation) and steps in wound healing by primary intention (left) and secondary intention (right). Note large amounts of granulation tissue and wound contraction in healing by secondary intention.
  485. Phase I: Inflammation
  486. Phase II: Proliferation and New Tissue Formation
  487. FIGURE 5-15 Time Course of Cells Infiltrating a Wound. Neutrophils and macrophages are the predominant cells that infiltrate a wound during inflammation. Lymphocytes appear later and peak at day 7. Fibroblasts are the predominant cells during the proliferative and remodeling phases of the healing process.
  488. Phase III: Remodeling and Maturation
  489. Dysfunctional Wound Healing
  490. Wound Disruption
  491. FIGURE 5-16 Hypertrophic Scar and Keloid Scar Formation. Hypertrophic scar (A) and keloid scar (B) caused by excessive synthesis of collagen at suture sites.
  492. Impaired Contraction
  493. QUICK CHECK 5-6
  494. PEDIATRIC CONSIDERATIONS
  495. GERIATRIC CONSIDERATIONS
  496. DID YOU UNDERSTAND?
  497. Human Defense Mechanisms
  498. Physical and Mechanical Barriers
  499. Biochemical Barriers
  500. The Inflammatory Process
  501. Plasma Protein Systems
  502. Cellular Components of Inflammation
  503. Cellular Products
  504. Mast Cell
  505. Endothelium and Platelets
  506. Phagocytes
  507. Local Manifestations of Acute Inflammation
  508. Systemic Manifestations of Acute Inflammation
  509. Chronic Inflammation
  510. Wound Healing
  511. PEDIATRIC CONSIDERATIONS: Age-Related Factors Affecting Innate Immunity in the Newborn Child
  512. GERIATRIC CONSIDERATIONS: Age-Related Factors Affecting Innate Immunity in the Elderly
  513. KEY TERMS
  514. References
  515. Chapter 6 Adaptive Immunity
  516. Third Line of Defense: Adaptive Immunity
  517. FIGURE 6-1 Lymphocytes. A scanning electron micrograph showing lymphocytes (yellow, like cotton candy), red blood cells, and platelets.
  518. TABLE 6-1 CLINICAL USE OF ANTIGEN OR ANTIBODY
  519. Humoral and Cellular Immunity
  520. Active and Passive Immunity
  521. FIGURE 6-2 Lymphoid Tissues: Sites of B Cell and T Cell Differentiation. Immature lymphocytes migrate through central (primary) lymphoid tissues: the bone marrow (central lymphoid tissue for B lymphocytes) and the thymus (central lymphoid tissue for T lymphocytes). Mature lymphocytes later reside in the T and B lymphocyte–rich areas of the peripheral (secondary) lymphoid tissues.
  522. Antigens and Immunogens
  523. FIGURE 6-3 Overview of the Immune Response. The immune response can be separated into two phases: the generation of clonal diversity and clonal selection. During the generation of clonal diversity, lymphoid stem cells from the bone marrow migrate to the central lymphoid organs (the thymus or regions of the bone marrow), where they undergo a series of cellular division and differentiation stages resulting in either immunocompetent T cells from the thymus or immunocompetent B cells from the bone marrow. These cells are still naïve in that they have never encountered foreign antigen. The immunocompetent cells enter the circulation and migrate to the secondary lymphoid organs (e.g., spleen and lymph nodes), where they establish residence in B and T cell–rich areas. The clonal selection phase is initiated by exposure to foreign antigen. The antigen is usually processed by antigen-presenting cells (APCs) for presentation to T-helper cells (Th cells). The intercellular cooperation among APCs, Th cells, and immunocompetent T and B cells results in a second stage of cellular proliferation and differentiation. Because antigen has “selected” those T and B cells with compatible antigen receptors, only a small population of T and B cells undergo this process at one time. The result is an active cellular immunity or humoral immunity, or both. Cellular immunity is mediated by a population of effector T cells that can kill targets (T-cytotoxic cells) or regulate the immune response (T-regulatory cells), as well as a population of memory cells (T-memory cells) that can respond more quickly to a second challenge with the same antigen. Humoral immunity is mediated by a population of soluble proteins (antibodies) produced by plasma cells and by a population of memory B cells that can produce more antibody rapidly to a second challenge with the same antigen.
  524. QUICK CHECK 6-1
  525. Humoral Immune Response
  526. Antibodies
  527. Classes of Immunoglobulins
  528. FIGURE 6-4 Structure of Different Immunoglobulins. Secretory IgA, IgD, IgE, IgG, and IgM. The black circles attached to each molecule represent carbohydrate residues.
  529. FIGURE 6-5 Molecular Structure of an Antibody and Other Antigen-Binding Molecules. Antigen-binding molecules include antibody and cell-surface receptors. A, The typical antibody molecule consists of two identical heavy chains and two identical light chains connected by interchain disulfide bonds (— between chains in the figure). Each heavy chain is divided into three regions with relatively constant amino acid sequences (CH1, CH2, and CH3) and a region with a variable amino acid sequence (VH). Each light chain is divided into a constant region (CL) and a variable region (VL). The hinge region (Hi) provides flexibility in some classes of antibody. Within each variable region are three highly variable complementary-determining regions (CDR1, CDR2, CDR3) separated by relatively constant framework regions (FRs). B, Fragmentation of the antibody molecule by limited digestion with the enzyme papain has identified three important portions of the molecule: an Fc fragment (crystalline fragment that binds complement and Fc receptors) and two identical Fab fragments (antigen-binding fragments). C, A molecular model of a typical antibody molecule; the light chains are the strands of red spheres (each represents an individual amino acid). As the antibody folds, the CDRs are placed in proximity to form the antigen-binding site. D, The antigen receptor on the surface of B cells (BCR complex) is a monomeric antibody with a structure similar to that of circulating antibody, with an additional transmembrane region (TM) that anchors the molecule to the cell surface. The active BCR complex contains molecules (Igα and Igβ) that are responsible for intracellular signaling after the receptor has bound antigen. E, The T cell receptor (TCR) consists of an α and a β chain joined by a disulfide bond. Each chain consists of a constant region (Cα and Cβ) and a variable region (Vα and Vβ). Each variable region contains CDRs and FRs in a structure similar to that of antibody. The active TCR is associated with several molecules that are responsible for intracellular signaling. These include CD3, which is a complex of γ (gamma), ε (epsilon), and δ (delta) subunits and a complex of two ζ (zeta) molecules. The ζ molecules are attached to a cytoplasmic protein kinase (ZAP70) that is critical to intracellular signaling.
  530. TABLE 6-2 PROPERTIES OF IMMUNOGLOBULINS
  531. Molecular Structure
  532. Antigen-Antibody Binding
  533. FIGURE 6-6 Antigenic Determinants (Epitopes). Generic examples of epitopes on protein (A) and polysaccharide (B) molecules are shown. In A, an antigenic protein may have multiple different epitopes (epitopes 1 and 2) that react with different antibodies. Each sphere represents an amino acid with the red spheres representing epitope 1 and the yellow spheres representing epitope 2. Individual epitopes may consist of eight or nine amino acids. In B, a polysaccharide is constructed of a backbone with branched side chains. Each sphere represents an individual carbohydrate with the red spheres representing the carbohydrates that form the epitope. In this example, two identical epitopes are shown that would bind two identical antibodies. In C, this ribbon model of an antibody shows the heavy chains in blue and the light chains in red. Green represents antigen molecules bound to each antigen-binding site.
  534. FIGURE 6-7 Direct and Indirect Functions of Antibody. Protective activities of antibodies can be direct (through the action of antibody alone) or indirect (requiring activation of other components of the innate immune response, usually through the Fc region). Direct means include neutralization of viruses or bacterial toxins before they bind to receptors on the surface of the host’s cells. Indirect means include activation of the classical complement pathway through C1, resulting in formation of the membrane-attack complex (MAC), or increased phagocytosis of bacteria opsonized with antibody and complement components bound to appropriate surface receptors (FcR and C3bR).
  535. Function of Antibodies
  536. Direct effects
  537. BOX 6-1 MONOCLONAL ANTIBODIES
  538. FIGURE 6-8 Immunologic Mechanisms That Activate the Inflammatory Response. Immunologic factors may activate inflammation through three mechanisms: (1) IgE can bind to the surface of a mast cell and, after binding antigen, induce the cell’s degranulation; (2) antigen and antibody can activate the complement system, releasing anaphylatoxins and chemotactic factors, especially C5a, that result in mast cell degranulation and neutrophil chemotaxis; and (3) antigen may also react with T lymphocytes, resulting in the production of lymphokines that may contribute to the development of either acute or chronic inflammation.
  539. Indirect effects
  540. IgE
  541. FIGURE 6-9 IgE Function. (1) Soluble antigens from a parasitic infection cause production of IgE antibody by B cells. (2) Secreted IgE binds to IgE-specific receptors on the mast cell. (3) Additional soluble parasite antigen cross-links the IgE on the mast cell surface, (4) leading to mast cell degranulation and release of many proinflammatory products, including eosinophil chemotactic factor of anaphylaxis (ECF-A). (5) ECF-A attracts eosinophils from the circulation. (6) The eosinophil attaches to the surface of the parasite and releases potent lysosomal enzymes that damage microorganisms.
  542. FIGURE 6-10 Secretory Immune System. A, Lymphocytes from the mucosal-associated lymphoid tissues circulate throughout the body in a pattern separate from other lymphocytes. For example, lymphocytes from the gut-associated lymphoid tissue circulate through the regional lymph nodes, the thoracic duct, and the blood and return to other mucosal-associated lymphoid tissues rather than to lymphoid tissue of the systemic immune system. B, Lymphoid tissue associated with mucous membranes is called mucosal-associated lymphoid tissue (MALT).
  543. Secretory Immune System
  544. Cell-Mediated Immunity
  545. T Lymphocytes
  546. Immune Response: Collaboration of B Cells and T Cells
  547. Generation of Clonal Diversity
  548. Development of B Lymphocytes
  549. TABLE 6-3 GENERATION OF CLONAL DIVERSITY VS. CLONAL SELECTION
  550. Development of T Lymphocytes
  551. QUICK CHECK 6-2
  552. Clonal Selection
  553. FIGURE 6-11 Summary of Adaptive Immunity This simplified flowchart summarizes an example of adaptive immune responses when exposed to a microbial antigen.
  554. FIGURE 6-12 Primary and Secondary Immune Responses. The initial administration of antigen induces a primary response during which IgM is initially produced, followed by IgG. Another administration of the antigen induces the secondary response in which IgM is transiently produced and larger amounts of IgG are produced over a longer period of time.
  555. Primary and Secondary Immune Responses
  556. Cellular Interactions in the Immune Response
  557. B cell receptor for antigen
  558. FIGURE 6-13 Activation of a B Cell by a T Cell–Independent Antigen. Molecules containing repeating identical antigenic determinants may interact simultaneously with several receptors on the surface of the B cell and induce the proliferation and production of immunoglobulins. Because Th2 cells do not participate, class switch does not occur and the resultant antibody response is IgM.
  559. FIGURE 6-14 Antigen-Presenting Molecules. Two sets of molecules are primarily responsible for antigen presentation: MHC class I and MHC class II. The MHC molecules are encoded from the major histocompatibility complex on chromosome 6. This region contains information for the α chains of three principal class I molecules, called HLA-A, HLA-B, and HLA-C. These will be discussed in more detail in Chapter 7. Each of the MHC class I α chains forms a complex with β2-microglobulin, which is encoded by a gene on chromosome 15. The MHC class I molecules present small peptide antigens (eight or nine amino acids in length) in a pocket formed by the α1 and α2 domains of the α chain. The conformation of the molecule is stabilized by β2-microglobulin as well as by intrachain disulfide bonds. The α and β chains of class II molecules are also encoded in the MHC region. The principal class II molecules are HLA-DR, HLA-DP, and HLA-DQ. The MHC class II molecules present peptide antigens in a pocket formed by the α1 domain of the α chain and the β1 domain of the β chain. Both MHC class I and class II molecules are anchored to the plasma membrane by hydrophobic regions on the ends of the α and β chains.
  560. Antigen processing and presentation
  561. Antigen-presenting molecules
  562. FIGURE 6-15 Antigen Processing. Antigen processing and presentation are required for initiation of most immune responses. Foreign antigen may be either endogenous (cytoplasmic protein) or exogenous (e.g., bacterium). Endogenous antigenic peptides are transported into the endoplasmic reticulum (ER) (1), where the MHC molecules are being assembled. In the ER, antigenic peptides bind to the α chains of the MHC class I molecule (2), and the complex is transported to the cell surface (3). The α and β chains of the MHC class II molecules are also being assembled in the endoplasmic reticulum (4), but the antigen-binding site is blocked by a small molecule (invariant chain) to prevent interactions with endogenous antigenic peptides. The MHC class II–invariant chain complex is transported to phagolysosomes (5) where exogenous antigenic fragments have been produced as a result of phagocytosis (6). In the phagolysosomes, the invariant chain is digested and replaced by exogenous antigenic peptides (7), after which the MHC class II–antigen complex is inserted into the cell membrane (8).
  563. FIGURE 6-16 Dendritic Cells and Cell-Mediated Immunity. A, Dendritic cells are phagocytic antigen-presenting cells (APCs) found in the skin, mucosa, and lymphoid tissues. B, Dendritic cells (Langerhans cells) are marked by the blue stain in the epidermis. C, Dendritic cells capturing microbial antigens from epithelia and transporting them to regional lymph nodes. The T cells are then activated to proliferate and to differentiate into effector and memory cells, which migrate to sites of infection and promote various functions in cell-mediated immunity.
  564. T cell receptor for antigen
  565. CD molecules
  566. T-helper lymphocytes
  567. FIGURE 6-17 Development of T Cell Subsets. The most important step in clonal selection is the production of populations of T-helper (Th) cells (Th1, Th2, and Th17) and T-regulatory (Treg) cells that are necessary for the development of cellular and humoral immune responses. In this model, APCs (1) (probably multiple populations) may influence whether a precursor Th cell (Thp cell) (2) will differentiate into a Th1, Th2, Th17, or Treg cell (3). Differentiation of the Thp cell is initiated by three signaling events. The antigen signal is produced by the interaction of the T cell receptor (TCR) and CD4 with antigen presented by MHC class II molecules. A set of co-stimulatory signals is produced from interactions between adhesion molecules (not shown). A third signal is produced by the interactions of cytokines (particularly interleukin-1 [IL-1]) with appropriate cytokine receptors (IL-1R) on the Thp cell. The Thp cell up-regulates IL-2 production and expression of the IL-2 receptor (IL-2R), which acts in an autocrine fashion to accelerate Thp cell differentiation and proliferation. Commitment to a particular phenotype results from the relative concentrations of other cytokines. IL-12 and IFN-γ produced by some populations of APCs favor differentiation into the Th1 cell phenotype; IL-4, which is produced by a variety of cells, favors differentiation into the Th2 cell phenotype; IL-6 and TGF-β (T cell growth factor) facilitate differentiation into Th17 cells; IL-2 and TGF-β induce differentiation into Treg cells. The Th1 cell is characterized by the production of cytokines that assist in the differentiation of T-cytotoxic (Tc) cells, leading to cellular immunity, whereas the Th2 cell produces cytokines that favor B cell differentiation and humoral immunity. Th1 and Th2 cells affect each other through the production of inhibitory cytokines: IFN-γ will inhibit development of Th2 cells, and IL-4 will inhibit the development of Th1 cells. Th17 cells produce cytokines that affect phagocytes and increase inflammation. Treg cells produce immunosuppressive cytokines that prevent the immune response from being excessive. APC, Antigen-presenting cell; IFN, interferon; MHC, major histocompatibility complex; TGF, transforming growth factor.
  568. T cell clonal selection: the cellular immune response
  569. Superantigens
  570. FIGURE 6-18 Tc Cell Clonal Selection. The immunocompetent Tc cell can react with antigen but cannot yet kill target cells. During clonal selection, this cell reacts with antigen presented by MHC class I molecules on the surface of a virally infected or cancerous abnormal cell. (1) The antigen–MHC class I complex is recognized simultaneously by the T cell receptor (TCR), which binds to antigen, and CD8, which binds to the MHC class I molecule. (2) A separate signal is provided by cytokines, particularly IL-2 from Th1 cells. (3) In response to these signals, the Tc cell develops into an effector Tc cell with the ability to kill abnormal cells.
  571. B cell clonal selection: the humoral immune response
  572. FIGURE 6-19 Superantigens. The T cell receptor (TCR) and major histocompatibility complex (MHC) class II molecule are normally held together by processed antigen. Superantigens, such as some bacterial exotoxins, bind directly to the variable region of the TCR β chain and the MHC class II molecule. Each superantigen activates sets of Vβ chains independently of the antigen specificity of the TCR.
  573. Memory cells
  574. T Lymphocyte Functions
  575. T-Cytotoxic Lymphocytes
  576. FIGURE 6-20 Bc Cell Clonal Selection. Immunocompetent B cells undergo proliferation and differentiation into antibody-secreting plasma cells. Multiple signals are necessary (1). The B cell itself can directly bind soluble antigen through the B cell receptor (BCR) and act as an antigen processing cell. Antigen is internalized, processed (2), and presented (3) to the TCR on a Th2 cell by MHC class II molecules (4). A cytokine signal is provided by the Th2 cell cytokines (e.g., IL-4) that react with the B cell (5). The B cell differentiates into plasma cells that secrete antibody (6).
  577. FIGURE 6-21 Cellular Killing Mechanisms. Several cells have the capacity to kill abnormal (e.g., virally infected, cancerous) target cells. (1) T-cytotoxic (Tc) cells recognized endogenous antigen presented by MHC class I molecules. The Tc cell mobilizes multiple killing mechanisms that induce apoptosis of the target cell. (2) Natural killer (NK) cells identify and kill target cells through receptors that recognize abnormal surface changes. NK cells specifically kill targets that do not express surface MHC class I molecules. (3) Several cells, including macrophages and NK cells, can kill by antibody-dependent cellular cytotoxicity (ADCC). IgG antibodies bind to foreign antigen on the target cell, and cells involved in ADCC bind IgG through Fc receptors (FcR) and initiate killing. The insert is a scanning electron microscopic view of Tc cells (L) attacking a much larger tumor cell (Tu).
  578. T Cells That Activate Macrophages
  579. T-Regulatory Lymphocytes
  580. QUICK CHECK 6-3
  581. PEDIATRIC CONSIDERATIONS
  582. Antibody Levels in Umbilical Cord Blood and in Neonatal Circulation. Early in gestation, maternal IgG begins active transport across the placenta and enters the fetal circulation. At birth, the fetal circulation may contain nearly adult levels of IgG, which is almost exclusively from the maternal source. The fetal immune system has the capacity to produce IgM and small amounts of IgA before birth (not shown). After delivery, maternal IgG is rapidly destroyed and neonatal IgG production increases.
  583. GERIATRIC CONSIDERATIONS
  584. DID YOU UNDERSTAND?
  585. Third Line of Defense: Adaptive Immunity
  586. Antigens and Immunogens
  587. Humoral Immune Response
  588. Cell-Mediated Immunity
  589. Immune Response: B Cells and T Cells Together
  590. Pediatric considerations: Age-Related Factors Affecting Mechanisms of Self-Defense in the Newborn Child
  591. Geriatric considerations: Age-Related Factors Affecting Mechanisms of Self-Defense in the Elderly
  592. KEY TERMS
  593. References
  594. Chapter 7 Infection and Defects in Mechanisms of Defense
  595. Infection
  596. HEALTH ALERT
  597. Microorganisms and Humans: A Dynamic Relationship
  598. TABLE 7-1 NORMAL INDIGENOUS FLORA OF THE HUMAN BODY
  599. BOX 7-1 THE MANY RELATIONSHIPS BETWEEN HUMANS AND MICROORGANISMS
  600. TABLE 7-2 CLASSES OF ORGANISMS INFECTIOUS TO HUMANS
  601. Classes of Infectious Microorganisms
  602. TABLE 7-3 EXAMPLES OF MICROOrGANISMS THAT CAUSE TISSUE DAMAGE
  603. TABLE 7-4 EXAMPLES OF MECHANISMS USED BY PATHOGENS TO RESIST THE IMMUNE SYSTEM
  604. Pathogenic Defense Mechanisms
  605. Infection and Injury
  606. Bacterial Disease
  607. FIGURE 7-1 General Structure of Bacteria. A, The structure of the bacterial cell wall determines its staining characteristics with gram stain. A gram-positive bacterium has a thick layer of peptidoglycan (left). A gram-negative bacterium has a thick peptidoglycan layer and an outer membrane (right)B, Example of a gram-positive (darkly stained microorganisms, arrow) group A Streptococcus. This microorganism consists of cocci that frequently form chains. C, Example of a gram-negative (pink microorganisms, arrow) Neisseria meningitides in cerebrospinal fluid. Neisseria form complexes of two cocci (diplococci).
  608. TABLE 7-5 EXAMPLES OF COMMON BACTERIAL INFECTIONS
  609. Viral Disease
  610. Viral replication
  611. FIGURE 7-2 Stages of Viral Infection of a Host Cell. The virion (1) becomes attached to the cell’s plasma membrane by absorption; (2) releases enzymes that weaken the membrane and allow it to penetrate the cell; (3) uncoats itself; (4) replicates; and (5) matures and escapes from the cell by budding from the plasma membrane. The infection then can spread to other host cells.
  612. Cellular effects of viruses
  613. TABLE 7-6 EXAMPLES OF HUMAN DISEASES CAUSED BY SPECIFIC VIRUSES
  614. Fungal Disease
  615. FIGURE 7-3 Morphology of Fungi. (A) Fungi may be either mold or yeast forms, or dimorphic. (B) Photograph showing Candida albicans with both the mycelial and the yeast forms. (C) Oral infection with C. albicans (candidiasis, i.e., thrush). (D) Gram stain of sputum showing that clinical isolates of C. albicans present as chains of elongated budding yeasts (× 1000).
  616. TABLE 7-7 COMMON PATHOGENIC FUNGI
  617. Parasitic Disease
  618. TABLE 7-8 EXAMPLES OF PARASITES THAT ARE IMPORTANT IN HUMANS
  619. Clinical Manifestations of Infection
  620. Countermeasures Against Pathogenic Defenses
  621. TABLE 7-9 REDUCTION IN VACCINE-PREVENTABLE DISEASES IN THE UNITED STATES
  622. Antimicrobials
  623. TABLE 7-10 CHEMICALS OR ANTIMICROBIALS IDENTIFIED THAT PREVENT GROWTH OF OR DESTROY MICROORGANISMS
  624. HEALTH ALERT
  625. Vaccines
  626. QUICK CHECK 7-1
  627. Deficiencies in Immunity
  628. Initial Clinical Presentation
  629. Primary (Congenital) Immune Deficiencies
  630. TABLE 7-11 EXAMPLES OF PRIMARY IMMUNE DEFICIENCIES
  631. B Lymphocyte Deficiencies
  632. T Lymphocyte Deficiencies
  633. Combined Deficiencies
  634. FIGURE 7-4 Facial Anomalies Associated With DiGeorge Syndrome. Note the wide-set eyes, low-set ears, and shortened structure of the upper lip.
  635. Complement Deficiencies
  636. Phagocytic Deficiencies
  637. Secondary (Acquired) Immune Deficiencies
  638. Evaluation and Care of Those With Immune Deficiency
  639. BOX 7-2 SOME CONDITIONS KNOWN TO BE ASSOCIATED WITH ACQUIRED IMMUNE DEFICIENCIES
  640. Normal Physiologic Conditions
  641. Psychologic Stress
  642. Dietary Insufficiencies
  643. Malignancies
  644. Physical Trauma
  645. Medical Treatments
  646. Other Diseases or Genetic Syndromes
  647. TABLE 7-12 LABORATORY EVALUATION OF IMMUNE DEFICIENCIES
  648. Replacement Therapies for Immune Deficiencies
  649. FIGURE 7-5 The Structure and Genetic Map of HIV-1. The HIV-1 virion consists of a core of two identical strands of viral RNA molecules of viral enzymes (reverse transcriptase [RT], protease [PR], integrase [IN]) encoated in a core capsid structure consisting primarily of the structural viral protein p24. The capsid is further encased in a matrix consisting primarily of viral protein p17. The outer surface is an envelope consisting of the plasma membrane of the cell from which the virus budded (lipid bilayer) and two viral glycoproteins: a transmembrane glycoprotein, gp41, and a noncovalently attached surface protein, gp120. The HIV-1 genome contains regions that encode the structural proteins (gag), the viral enzymes (pol), and the envelope proteins (env). The genome of complex retroviruses, like HIV-1, often contains a variety of small regions that regulate expression of the virus.
  650. Acquired Immunodeficiency Syndrome (AIDS)
  651. Epidemiology of AIDS
  652. Pathogenesis of AIDS
  653. Clinical Manifestations of AIDS
  654. HEALTH ALERT
  655. High Risk (in descending order of risk)
  656. Some Risk (in descending order of risk)
  657. Some Risk (depending on situation, intactness of mucous membranes, etc.)
  658. No Risk
  659. Unresolved Issues
  660. FIGURE 7-6 Life Cycle and Possible Sites of Therapeutic Intervention of Human Immunodeficiency Virus (HIV). The HIV virion consists of a core of two identical strands of viral RNA encoated in a protein structure with viral proteins gp41 and gp120 on its surface (envelope). HIV infection begins when a virion binds to CD4 and chemokine co-receptors on a susceptible cell and follows the process described here. The provirus may remain latent in the cell’s DNA until it is activated (e.g., by cytokines). The HIV life cycle is susceptible to blockage at several sites (see the text for further information), including entrance inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors.
  661. FIGURE 7-7 Typical Progression from HIV Infection to AIDS in Untreated Persons. A, Clinical progression begins within weeks after infection; the person may experience symptoms of acute HIV syndrome. During this early period, the virus progressively infects T cells and other cells and spreads to the lymphoid organs, with a sharp decrease in the number of circulating CD4+ T cells. During a period of clinical latency, the virus replicates and T cell destruction continues, although the person is generally asymptomatic. The individual may develop HIV-related disease (constitutional symptoms)—a variety of symptoms of acute viral infection that do not involve opportunistic infections or malignancies. When the number of CD4+ cells is critically suppressed, the individual becomes susceptible to a variety of opportunistic infections and cancers with a diagnosis of AIDS. The length of time for progression from HIV infection to AIDS may vary considerably from person to person. B, Laboratory tests are changing throughout infection. Antibody and Tc cell (cytotoxic T lymphocytes [CTLs]) levels change during the progression to AIDS. During the initial phase antibodies against HIV-1 are not yet detectable (window period), but viral products, including proteins and RNA, and infectious virus may be detectable in the blood a few weeks after infection. Most antibodies against HIV are not detectable in the early phase. During the latent phase of infection antibody levels against p24 and other viral proteins, as well as HIV-specific CTLs, increase, and then remain constant until the development of AIDS.
  662. BOX 7-3 AIDS-DEFINING OPPORTUNISTIC INFECTIONS AND NEOPLASMS FOUND IN INDIVIDUALS WITH HIV INFECTION
  663. Infections
  664. Protozoal and Helminthic Infections
  665. Fungal Infections
  666. Bacterial Infections
  667. Viral Infections
  668. Neoplasms
  669. Treatment and Prevention of AIDS
  670. FIGURE 7-8 Clinical Symptoms of AIDS. A, Severe weight loss and anorexia. B, Kaposi sarcoma lesions. C, Perianal lesions of herpes simplex infection. D, Deterioration of vision from cytomegalovirus retinitis leading to areas of infection, which can lead to blindness.
  671. Pediatric AIDS and Central Nervous System Involvement
  672. HEALTH ALERT
  673. QUICK CHECK 7-2
  674. Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
  675. TABLE 7-13 RELATIVE INCIDENCE AND EXAMPLES OF HYPERSENSITIVITY DISEASES*
  676. TABLE 7-14 EXAMPLES OF AUTOIMMUNE DISORDERS
  677. Mechanisms of Hypersensitivity
  678. Type I: IgE-Mediated Hypersensitivity Reactions
  679. Mechanisms of IgE-mediated hypersensitivity
  680. Clinical manifestations of IgE-mediated hypersensitivity
  681. FIGURE 7-9 Mechanism of Type I, IgE-Mediated Reactions. First exposure to an allergen leads to antigen processing and presentation of antigen by an antigen-presenting cell (APC) to B lymphocytes, which is under the direction of T-helper 2 (Th2) cells. Th2 cells produce specific cytokines (e.g., IL-4, IL-13, and others) that favor maturation of the B lymphocytes into plasma cells that secrete IgE. The IgE is adsorbed to the surface of the mast cell by binding with IgE-specific Fc receptors. When an adequate amount of IgE is bound the mast cell is sensitized. During a reexposure, the allergen cross-links the surface-bound IgE and causes degranulation of the mast cell. Contents of the mast cell granules, primarily histamine, induce local edema, smooth muscle contraction, mucous secretion, and other characteristics of an acute inflammatory reaction.
  682. TABLE 7-15 IMMUNOLOGIC MECHANISMS OF TISSUE DESTRUCTION
  683. Evaluation and treatment of IgE hypersensitivity
  684. FIGURE 7-10 Type I Hypersensitivity Reactions. Manifestations of allergic reactions as a result of type I hypersensitivity include pruritus, angioedema (swelling caused by exudation), edema of the larynx, urticaria (hives), bronchospasm (constriction of airways in the lungs), hypotension (low blood pressure), and dysrhythmias (irregular heartbeat) because of anaphylactic shock, and gastrointestinal cramping caused by inflammation of the gastrointestinal mucosa. Photographic inserts show a diffuse allergic-like eye and skin reaction on an individual. The skin lesions have raised edges and develop within minutes or hours, with resolution occurring after about 12 hours.
  685. TABLE 7-16 CAUSES OF CLINICAL ALLERGIC REACTIONS
  686. Type II: Tissue-Specific Hypersensitivity Reactions
  687. Type III: Immune Complex–Mediated Hypersensitivity Reactions
  688. Mechanisms of type III hypersensitivity
  689. Immune complex disease
  690. FIGURE 7-11 Mechanisms of Type II, Tissue-Specific Reactions. Antigens on the target cell bind with antibody and are destroyed or prevented from functioning by one of the following mechanisms: (A) complement-mediated lysis (an erythrocyte target is illustrated here); (B) clearance (phagocytosis) by macrophages in the tissue; (C) neutrophil-mediated immune destruction; (D) antibody-dependent cell-mediated cytotoxicity (ADCC) (apoptosis of target cells is induced by natural killer [NK] cells by two mechanisms: by the release of granzymes and perforin, which is a molecule that creates pores in the plasma membrane, and enzymes [granzymes] that enter the target through the perforin pores; by the interactions of Fas ligand [FasL; a molecule similar to TNF-α] on the surface of NK cells with Fas [the receptor for FasL] on the surface of target cells); or (E) modulation or blocking of the normal function of receptors by antireceptor antibody. This example of mechanism (E) depicts myasthenia gravis in which acetylcholine receptor antibodies block acetylcholine from attaching to its receptors on the motor end-plates of skeletal muscle, thereby impairing neuromuscular transmission and causing muscle weakness. C1, Complement component C1; C3b, complement fragment produced from C3, which acts as an opsonin; C5a, complement fragment produced from C5, which acts as a chemotactic factor for neutrophils; Fcγ receptor, cellular receptor for the Fc portion of IgG; FcR, Fc receptor.
  691. FIGURE 7-12 Mechanism of Type III, Immune Complex–Mediated Reactions. Immune complexes form in the blood from circulating antigen and antibody. Both small and large immune complexes are removed successfully from the circulation and do not cause tissue damage. Intermediate-sized complexes are deposited in certain target tissues in which the circulation is slow or filtration of the blood occurs. The complexes activate the complement cascade through C1 and generate fragments including C5a and C3b. C5a is chemotactic for neutrophils, which migrate into the inflamed area and attach to the IgG and C3b in the immune complexes. The neutrophils attempt unsuccessfully to phagocytose the tissue and in the process release a variety of degradative enzymes that destroy the healthy tissues. Fcγ receptor is the cellular receptor for the Fc portion of IgG.
  692. Type IV: Cell-Mediated Hypersensitivity Reactions
  693. FIGURE 7-13 Mechanism of Type IV, Cell-Mediated Reactions. Antigens from target cells stimulate T cells to differentiate into T-cytotoxic cells (Tc cells), which have direct cytotoxic activity, and T-helper cells (Th1 cells) involved in delayed hypersensitivity. The Th1 cells produce lymphokines (especially interferon-γ [IFNγ]) that activate the macrophage through specific receptors (e.g., IFNγ receptor [IFNγR]). The macrophages can attach to targets and release enzymes and reactive oxygen species that are responsible for most of the tissue destruction.
  694. FIGURE 7-14 Development of Allergic Contact Dermatitis. A, The development of allergy to poison ivy. The first (primary) contact with allergen sensitizes (produces reactive T cells) the individual but does not produce a rash (dermatitis). Secondary contact activates a type IV cell-mediated reaction that causes dermatitis. B, Contact dermatitis caused by a delayed hypersensitivity reaction leading to vesicles and scaling at the sites of contact.
  695. QUICK CHECK 7-3
  696. Antigenic Targets of Hypersensitivity Reactions
  697. Allergy
  698. Allergens
  699. Allergic disease: bee sting allergy
  700. Autoimmunity
  701. Breakdown of tolerance
  702. Autoimmune disease: systemic lupus erythematosus
  703. Alloimmunity
  704. Alloantigens
  705. Alloimmune disease: transfusion reactions
  706. ABO system
  707. Rh system
  708. Alloimmune disease: transplant rejection
  709. Major histocompatibility complex
  710. FIGURE 7-15 ABO Blood Types. This figure shows the relationship of antigens and antibodies associated with the ABO blood groups. The surfaces of erythrocytes of individuals with blood group O have a core carbohydrate that is present on cells of all ABO blood groups (H antigen). The sera of blood group O individuals contain IgM antibodies against both A and B carbohydrates. In individuals of the blood group A, some of the H antigens have been modified into A antigens. The sera of these individuals have IgM antibodies against the B antigen. In individuals with blood group B, some of the H antigens have been modified into B antigens. These individuals have IgM antibodies against the A antigen in their sera. In individuals of the blood group AB, some of the H antigens have been modified into both the A and B antigens. These individuals do not have antibody to either A or B antigens.
  711. FIGURE 7-16 Human Leukocyte Antigens (HLAs). The major histocompatibility complex (MHC) is located on chromosome 6 and contains genes that code for class I antigens, class II antigens, and class III proteins (i.e., complement proteins and cytokines).
  712. Transplantation
  713. FIGURE 7-17 Inheritance of HLA. HLA alleles are inherited in a co-dominant fashion; both maternal and paternal antigens are expressed. Specific HLA alleles are commonly given numbers to indicate different antigens. In this example, the mother has linked genes for HLA-A3 and HLA-B12 on one chromosome 6 and genes for HLA-A10 and HLA-B5 on the second chromosome 6. The father has HLA-A28 and HLA-B7 on one chromosome and HLA-A1 and HLA-B35 on the second chromosome. The children from this pairing may have one of four possible combinations of maternal and paternal HLA.
  714. Transplant rejection
  715. QUICK CHECK 7-4
  716. DID YOU UNDERSTAND?
  717. Infection
  718. Deficiencies in Immunity
  719. Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
  720. KEY TERMS
  721. References
  722. Chapter 8 Stress and Disease
  723. Historical Background and General Concepts
  724. FIGURE 8-1 Physiologic and Behavioral Stress Responses. Stress processes arise from bidirectional communication patterns between the brain and other physiologic systems (autonomic, immune, neural, and endocrine). Importantly, these bidirectional mechanisms are protective, promoting short-term adaptation (allostasis). Chronic stress mechanisms, however, can lead to long-term dysregulation and promote behavioral responses and physiologic responses that lead to stress-induced disorders/diseases (allostatic load), compromising health.
  725. FIGURE 8-2 The Alarm Reaction. The alarm reaction includes increased secretion of glucocorticoids (cortisol) by the adrenal cortex and increased secretion of epinephrine and small amounts of norepinephrine from the adrenal medulla. The response to the release of cortisol and sympathetic nerve activation is summarized in Figure 8-3. ACTH, Adrenocorticotropic hormone.
  726. FIGURE 8-3 The Stress Response.
  727. FIGURE 8-4 Hypothalamic-Pituitary-Adrenal (HPA) Axis. The response to stress begins in the brain. The hypothalamus is the control center in the brain for many hormones including corticotropin-releasing hormone (CRH).
  728. Stress Overview: Multiple mediators and systems
  729. TABLE 8-1 EXAMPLES OF STRESS-RELATED DISEASES AND CONDITIONS
  730. FIGURE 8-5 Stress Interactions Are Nonlinear and Complex. Nonlinearity means that when one mediator is increased or decreased, the subsequent compensatory changes in other mediators depend on time and level of change, causing multiple interacting variables. The inevitable consequences from adapting to daily life over time include changes in behavioral responses. For example, these changes include sleeping patterns, smoking, alcohol consumption, physical activity, and social interactions. These behavioral patterns are a part of the allostatic overload with chronic elevations in cortisol level, sympathetic activity, and levels of proinflammatory cytokines, and a decrease in parasympathetic activity.
  731. QUICK CHECK 8-1
  732. The Stress Response
  733. Neuroendocrine Regulation
  734. Catecholamines
  735. TABLE 8-2 PHYSIOLOGIC EFFECTS OF CATECHOLAMINES*
  736. Glucocorticoids: Cortisol
  737. HEALTH ALERT
  738. TABLE 8-3 PHYSIOLOGIC EFFECTS OF CORTISOL
  739. HEALTH ALERT
  740. Stress, Inflammation, Obesity, and Type 2 Diabetes. The induction of reactive oxygen species (ROS) generation and inflammation through the proinflammatory transcription factor, NF-κβ, activates most proinflammatory genes. Macronutrient intake, obesity, free fatty acids, infection, smoking, psychologic stress, and genetic factors increase the production of ROS. Interference with insulin signaling (insulin resistance) leads to hyperglycemia and proinflammatory changes. Proinflammatory changes increase levels of TNF-α and IL-6, and also lead to the inhibition of insulin signaling and insulin resistance. Inflammation in pancreatic β cells leads to β cell dysfunction, which in combination with insulin resistance leads to type 2 diabetes. CRP, C-reactive protein.
  741. FIGURE 8-6 Effect of Corticotropin-Releasing Hormone (CRH)–Mast Cell–Histamine Axis, Cortisol, and Catecholamines on the Th1/Th2 Balance—Innate and Adaptive Immunity. Adaptive immunity provides protection against multicellular parasites, extracellular bacteria, some viruses, soluble toxins, and allergens. Innate immunity provides protection against intracellular bacteria, fungi, protozoa, and several viruses. Type 1 cytokines or proinflammatory cytokines include IL-12, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Type 2 cytokines or anti-inflammatory cytokines include IL-10 and IL-4. Solid lines (black) represent stimulation, whereas dashed lines (blue) represent inhibition (i.e., Th1 and Th2 are mutually inhibitory, IL-12 and IFN-γ inhibit Th2, and vice versa; IL-4 and IL-10 inhibit Th1 responses). Stress and CRH modulate inflammatory/immune and allergic responses by stimulating cortisol (glucocorticoid), catecholamines, and peripheral (immune) CRH secretion and by changing the production of regulatory cytokines and histamines. CRH (peripheral, immune), corticotropin-releasing hormone; NE, norepinephrine; Th, helper T cell; IL, interleukin; Tc, cytotoxic T cell; NK, natural killer cell; dashed lines, decreased (inhibited); solid lines, increased (stimulation).
  742. Parasympathetic System
  743. Other Hormones
  744. TABLE 8-4 OTHER HORMONES THAT INFLUENCE THE STRESS RESPONSE
  745. Role of the Immune System
  746. FIGURE 8-7 Nervous System/Endocrine System/Immune System Interactions. Interconnections or pathways of communication among the immune, nervous, and endocrine systems.
  747. Stress, Personality, Coping, and Illness
  748. HEALTH ALERT
  749. Myocardial Ischemia
  750. Left Ventricular Dysfunction
  751. Ventricular Dysrhythmias
  752. HEALTH ALERT
  753. Coping
  754. FIGURE 8-8 Health Outcome Determination in Stressful Life Situations Is Moderated by Numerous Factors. Whether a life-challenged individual experiences distress or illness depends on the subject’s appraisal of the event and the coping strategies used during the stressful period. Models (A) and (B) reflect possible outcomes in stressed healthy and symptomatic individuals. Model (C) illustrates the dynamic clinical setting in which the diagnosis of a serious illness and subsequent medical interventions may be perceived as stressful challenges and have potentially detrimental influences on physical outcome.
  755. GERIATRIC CONSIDERATIONS
  756. QUICK CHECK 8-2
  757. DID YOU UNDERSTAND?
  758. Concepts of Stress
  759. The Stress Response
  760. Stress, Personality, Coping, and Illness
  761. GERIATRIC CONSIDERATIONS: Aging & The Stress-Age Syndrome
  762. KEY TERMS
  763. References
  764. UNIT 3 Cellular Proliferation: Cancer
  765. Interactive Review – Unit 3
  766. Chapter 9 Biology, Clinical Manifestations, and Treatment of Cancer
  767. Cancer Terminology and Characteristics
  768. TABLE 9-1 CHARACTERISTICS OF BENIGN VERSUS MALIGNANT TUMORS
  769. Tumor Classification and Nomenclature
  770. Benign and Malignant
  771. Carcinoma in Situ
  772. Classification of Tumors—Classic Histology and Modern Genetics
  773. FIGURE 9-1 Loss of Cellular and Tissue Differentiation During the Development of Cancer. The cells of a benign neoplasm (B) resemble those of the normal colonic epithelium (A), in that they are columnar and have an orderly arrangement. Loss of some degree of differentiation is evident in that the neoplastic cells do not show much mucin vacuolization. Cells of the well-differentiated malignant neoplasm (C) of the colon have a haphazard arrangement, and although gland lumina are formed they are architecturally abnormal and irregular. Nuclei vary in shape and size, especially when compared with (A). Cells in the poorly-differentiated malignant neoplasm (D) have an even more haphazard arrangement, with very poor formation of gland lumina. Nuclei show greater variation in shape and size compared with the well-differentiated malignant neoplasm in (C). Cells in anaplastic malignant neoplasms (E) bear no relation to the normal epithelium, with no recognizable gland formation. Tremendous variation is found in the size of cells and their nuclei, with very intense staining (hyperchromatic nuclei). Not knowing the site of origin makes it impossible to classify this tumor by microscopic appearance alone. Well-differentiated tumors often resemble their cell of origin, as shown in the example of a benign tumor of smooth muscles (F).
  774. FIGURE 9-2 Progression from Normal to Neoplasm in the Uterine Cervix. A sequence of cellular and tissue changes progressing from low-grade to high-grade intraepithelial neoplasms (also called carcinoma in situ) and then to invasive cancer is seen often in the development of cancer. In this example of the early stages of cervical neoplastic changes, the presence of anaplastic cells and loss of normal tissue architecture signify the development of cancer. The high rate of cell division and the presence of local mutagens and inflammatory mediators all contribute to the accumulation of genetic abnormalities that lead to cancer.
  775. BOX 9-1 TYPES OF GENETIC LESIONS IN CANCER
  776. Tumor Markers
  777. FIGURE 9-3 Molecular Markers Aid in Cancer Classification and Treatment Choices. A, Cancers can be classified based on gene expression patterns. In this breast cancer study, gene expression was measured in tumors from 115 patients. Each row is a different gene, and each column is a different patient sample. Red denotes high gene expression; green signifies low gene expression. Using this molecular subtyping method, breast cancer can be subdivided into at least four molecular subtypes—luminal A, luminal B, HER2, and basal. The group on the far right is normal breast tissue. B, Molecular classification predicts overall survival. In this group of women, breast cancer molecular subtypes were determined by gene expression profiles in a group of women with similar stage tumors, as in (A). The molecular subtype is a good predictor of response to chemotherapy and survival. This molecular subtyping method can help select the best therapy for women.
  778. QUICK CHECK 9-1
  779. TABLE 9-2 EXAMPLES OF TUMOR MARKERS
  780. The Biology of Cancer Cells
  781. Cancer Cells in the Laboratory
  782. The Genetic Basis of Cancer
  783. Cancer-Causing Mutations in Genes
  784. FIGURE 9-4 Cancerous Cells Show Abnormal Growth in the Laboratory. Cancer cells, unlike most normal cells (A), usually continue to grow and accumulate on top of one another after they have formed a confluent monolayer in culture (loss of contact inhibition) and (B) can grow without being attached to a surface, called anchorage independence.
  785. FIGURE 9-5 Clonal Proliferation Model of Neoplastic Progression in the Colon. During clonal proliferation, progressively altered populations of colon cells (colonocytes) arise over time. As genetic and epigenetic changes occur, different subclones (indicated by different color cells) coexist for a time. Clones that grow the fastest out-compete other clones, producing even more malignant, and abnormal-appearing, growths. The sequential accumulation of mutations has been well studied in the progression from a normal colon cell to a benign intestinal polyp to a malignant colon cancer. One of the earliest mutations in colon cancer is loss of the tumor-suppressor gene APC. Additional mutations (often in the oncogene RAS), activation of COX-2, and loss of the tumor suppressors DCC and TP53 occur as the lesion progresses from a benign polyp to an invasive carcinoma. APC, Adenomatous polyposis coli; COX-2, cyclooxygenase-2; DCC, deleted in colon cancer; TP53, p53 gene.
  786. Clonal selection
  787. FIGURE 9-6 Marked Increases in Cancer With Age. The incidence of cancer increases exponentially with advancing age. For example, this graph depicts the number of cases of colon cancer diagnosed per 100,000 women in England and Wales in 1 year. Similar data are seen for other cancers, and in men as well. These data suggest that stepwise accumulation of genetic and epigenetic alterations over time increases the risk of developing cancer. The slope of the curve predicts that five to seven mutations must accumulate before full-blown cancer develops.
  788. TABLE 9-3 COMPARISON OF CANCER GENE TYPES
  789. Oncogenes and Tumor-Suppressor Genes: Accelerators and Brakes
  790. Passengers and drivers
  791. What are the driver mutations?
  792. QUICK CHECK 9-2
  793. What Types of Changes in Genes Actually Occur in Cancer?
  794. Mutation of normal genes into oncogenes
  795. Point mutations
  796. Chromosome translocations and copy number variation
  797. FIGURE 9-7 Many Growth Factors Signal Through the RAS Protein. When a normal cell is stimulated through a growth factor receptor, inactive (GDP-bound) RAS is activated to a GTP-bound state. Activated RAS sends growth signals to the nucleus through cytoplasmic kinases, starting with the activation of kinase RAF. The mutant RAS protein is permanently activated because of its inability to hydrolyze GTP, leading to continual stimulation of the cell without any external trigger. GAP, GTPase-activating protein; GDP, guanosine diphosphate; GTP, guanosine triphosphate; MAPK, mitogen-activated protein kinase.
  798. FIGURE 9-8 Oncogene Activation Mechanisms. Cellular genes may become cancerous oncogenes as a result of (A) point mutations that alter one or a few nucleotide base pairs, causing the production of a protein that is activated as a result of the altered sequence (e.g., RAS); (B) amplification of the cellular gene, resulting in higher levels of protein expression (e.g., MYCN in neuroblastoma); or (C) chromosomal translocations that either (1) lead to the juxtaposition of a strong promoter, causing increased protein expression (MYC in Burkitt lymphoma), or (2) produce a novel fusion protein that is derived from gene fragments normally present on different chromosomes (BCR-ABL in chronic myeloid leukemia).
  799. FIGURE 9-9 N-myc Gene Amplification in Neuroblastoma. The N-myc gene is detected in human neuroblastoma cells using a technique called FISH (fluorescent in situ hybridization). (A) A single pair of N-myc genes are detected in normal cells and in low-grade neuroblastoma. (B) Multiple, amplified copies of the N-myc gene are detected in some cases of neuroblastoma. Amplification of the N-myc gene is strongly associated with a poor prognosis in childhood neuroblastoma.
  800. Gene amplification
  801. Tumor-suppressor genes
  802. TABLE 9-4 SOME FAMILIAL CANCER SYNDROMES CAUSED BY TUMOR-SUPPRESSOR GENE FUNCTION LOSS
  803. QUICK CHECK 9-3
  804. Loss of heterozygosity
  805. FIGURE 9-10 Silencing Tumor-Suppressor Genes. Tumor-suppressor genes can be deactivated by a variety of mechanisms. (A) In this example, the first hit is a point mutation in a tumor-suppressor gene (white box), followed by either epigenetic silencing or chromosome loss of the second allele (red box). (B) Genes can normally be silenced by a variety of interacting processes including DNA methylation, histone modification, nucleosomal remodeling, and microRNA changes (not shown). A number of cellular enzymes contribute to these modifications, including DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and complex nucleosomal remodeling factors (NURFs). Gene silencing is essential for normal development and differentiation. (C) Histone modification and promoter methylation regulate gene expression. Genes are transcribed when chromatin is modified by addition of acetyl (Ac) groups to specific lysine groups in histones. Gene expression can be turned off when specific acetyl groups are removed (by HDACs) or when the CpG-rich promoter regions of genes are modified by direct DNA methylation (by DNA methyltransferase). In addition, small endogenous RNA molecules (microRNAs or miRNA) can bind to mRNA and reduce gene expression. (D) Changes in promoter methylation turn cancer genes off and on. Oncogenes can be turned on by promoter hypomethylation, and tumor-suppressor genes can be turned off by promoter hypermethylation. Each of these changes can produce selective growth and survival advantages for the cancer cell. TF, Transcription factor; Me, methylation.
  806. Turning off genes without mutation
  807. Epigenetic silencing
  808. MicroRNAs, oncomirs, and non–coding RNAs
  809. Guardians of the Genome
  810. QUICK CHECK 9-4
  811. Genetics and Cancer-Prone Families
  812. Types of Genes Misregulated in Cancer
  813. Alterations in Progrowth and Antigrowth Signals
  814. FIGURE 9-11 A Familial Colon Cancer Pedigree. Darkened symbols represent individuals diagnosed with colon cancer. One of the individuals in the first generation must have carried a mutation in the APC gene. Squares, Males; circles, females; filled circles, diagnosed with colon cancer.
  815. FIGURE 9-12 The Hallmarks of Cancer. Cancers acquire alterations in specific pathways during their evolution. The six key pathways that must be altered are shown at the top of the circle, and supporting pathways are shown at the bottom of the circle. Mutation in key genes often alters several pathways; for example, p53 mutations alter both angiogenesis and evasion of apoptosis. = Inhibits.
  816. Angiogenesis
  817. QUICK CHECK 9-5
  818. Telomeres and Unlimited Replicative Potential
  819. FIGURE 9-13 Tumor-Induced Angiogenesis. Malignant tumors secrete angiogenic factors and tissue-remodeling matrix metalloproteinases (MMPs) that actively induce formation of new blood vessels. New blood vessels are formed from both local endothelial cells and circulating precursor cells recruited from the bone marrow. Circulating platelets can also release regulatory proteins into the tumor. bFGF and bFGFR, Basic fibroblast growth factor and its receptor, respectively; MMPs, matrix metalloproteases; PDGF and PDGFR, platelet-derived growth factor and its receptor, respectively; VEGF and VEGFR, vascular endothelial growth factor and its receptor, respectively.
  820. Cancer Metabolism
  821. FIGURE 9-14 Control of Immortality: Telomeres and Telomerase Normal adult somatic cells cannot divide indefinitely because the ends of their chromosomes are capped by telomeres. In the absence of the telomerase enzyme, telomeres become progressively shorter with each division until, when they are critically short, they signal to the cell to stop dividing. In germ cells, adult stem cells, and cancer cells the telomerase gene is “switched on,” producing an enzyme that rebuilds the telomeres. Thus, like germ cells, the cancer cell becomes immortal and able to divide indefinitely without losing its telomeres.
  822. Oncogene Addiction
  823. FIGURE 9-15 Cancers Have Altered Metabolism. Normal tissues use oxidative phosphorylation (OXPHOS) to turn glucose into CO2 and energy (in the form of ATP). Cancers take a different approach; even in the presence of oxygen, they do not use OXPHOS. Instead, they consume large quantities of glucose to make cellular building blocks, supporting rapid proliferation.
  824. FIGURE 9-16 The Intense Glucose Requirement of Cancer Aids in Diagnosis. This 54-year-old woman had a non–small cell lung cancer (NSCLC) surgically removed. Five years later, these images were obtained. The positron emission tomography (PET) scan using 18F-deoxyglucose shows metastatic lesions in the brain, right shoulder, and mediastinal and cervical lymph nodes as well as the liver, left pelvis, and proximal femur. (Left) PET whole-body image. (Right) Representative coronal image from the whole-body FDG-PET/CT–fused image of the same patient. The fused image consists of the CT image with the metabolic information superimposed in color. The pattern of distribution is most likely from the primary tumor to the large mediastinal lymph nodes, followed by lymphatic spread to cervical lymph nodes. Blood-borne dissemination produced the bone, brain, and liver metastases. Normally, only the heart, brain, and bladder show a strong signal on PET scan. CT, Computed tomography; FDG, fluorodeoxyglucose.
  825. Cancer Stem Cells
  826. FIGURE 9-17 The Concept of Cancer Stem Cells. (A) Only rare cells within a cancer can initiate cancer regrowth. In laboratory experiments it takes as many as 100,000 breast cancer cells injected into a mouse mammary fat pad to form a new cancer. If the breast cancer cells are sorted, one rare subtype (shown here in red) is much more proficient at forming new cancers. (B) Conventional chemotherapy can destroy the bulk of a cancer. However, if the cancer stem cells (red cells) are not destroyed, the cancer may regrow. If therapies can be devised that kill the cancer stem cells, then durable long-term responses may be achieved.
  827. QUICK CHECK 9-6
  828. Stroma-Cancer Interactions
  829. FIGURE 9-18 Cancers Live in a Complex Microenvironment. Neoplastic cells produce angiogenic factors (cytokines and chemokines) that are mitogenic or chemoattractants, or both, for numerous types of stromal cells, including fibroblasts, bone marrow–derived cells (BMDCs), macrophages, mesenchymal stem cells (MSCs), and other inflammatory and immune cells. In return, these activated stroma cells secrete additional proteolytic enzymes and growth factors that stimulate the cancer cells and promote new blood vessel growth. This stromal reaction, which in the normal situation promotes wound healing, now stimulates tumor growth and promotes metastatic dissemination.
  830. Inflammation, Immunity, and Cancer
  831. The Immune System Protects Us Against Viral-Associated Cancers
  832. TABLE 9-5 CHRONIC INFLAMMATORY CONDITIONS AND INFECTIOUS AGENTS ASSOCIATED WITH NEOPLASMS
  833. Viral Causes of Cancer
  834. Bacterial Cause of Cancer
  835. QUICK CHECK 9-7
  836. Cancer Invasion and Metastasis
  837. FIGURE 9-19 Cancer Metastasis Requires a Complex Series of Events. Cancer cells must gain access to blood and lymphatic vessels, survive the trip to distant locations, move back into the tissues, and initiate a new tumor. Because each of these steps is required, the successful metastatic cell is rare compared with the huge numbers of cancer cells at the primary site. Consequently, metastasis usually only occurs late in cancer evolution.
  838. Very Few Cells in a Cancer Have the Ability to Metastasize
  839. Clinical Manifestations and Treatment of Cancer
  840. Clinical Manifestations of Cancer
  841. Diagnosis and Staging
  842. HEALTH ALERT
  843. TABLE 9-6 OBTAINING TISSUE—THE BIOPSY
  844. Paraneoplastic Syndromes
  845. FIGURE 9-20 Tumor Staging by the TNM System. Example of staging for breast cancer.
  846. TABLE 9-7 PARANEOPLASTIC SYNDROMES
  847. Pain
  848. Fatigue
  849. Cachexia
  850. FIGURE 9-21 Cachexia. This severe form of malnutrition results in wasting and extensive loss of adipose tissue.
  851. Anemia
  852. Leukopenia and Thrombocytopenia
  853. Infection
  854. TABLE 9-8 FACTORS PREDISPOSING INDIVIDUALS WITH CANCER TO INFECTION
  855. Gastrointestinal Tract
  856. Hair and Skin
  857. Treatment of Cancer
  858. Chemotherapy
  859. TABLE 9-9 EXAMPLES OF MOLECULAR-ERA ANTICANCER DRUGS
  860. Radiation Therapy
  861. Surgery
  862. QUICK CHECK 9-8
  863. DID YOU UNDERSTAND?
  864. Cancer Terminology and Characteristics
  865. The Biology of Cancer Cells
  866. Cancer Invasion and Metastasis
  867. Clinical Manifestations and Treatment of Cancer
  868. KEY TERMS
  869. References
  870. Chapter 10 Cancer Epidemiology
  871. Genes, Environmental-Lifestyle Factors, and Risk Factors
  872. TABLE 10-1 SUMMARY OF ENVIRONMENTAL AND OCCUPATIONAL LINKS WITH CANCER
  873. BOX 10-1 ESTABLISHED ENVIRONMENTAL-LIFESTYLE FACTORS AND RISK OF CANCER
  874. QUICK CHECK 10-1
  875. Epigenetics and Genetics
  876. FIGURE 10-1 Epigenetics, Genetics, Environment, and Cancer. Epigenetic mechanisms are affected by many factors and processes including development in utero and during childhood, diet, environmental chemicals, radiation, drugs/pharmaceuticals, and aging. DNA methylation occurs when methyl groups, an epigenetic factor found in some dietary sources, for example, can tag DNA and activate or repress genes. Histones are proteins around which DNA can wind for compaction and gene regulation. Histone modification occurs when the binding of epigenetic factors to histone “tails” alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated. All of these factors and processes can have an effect on and influence people’s health, possibly resulting in cancer, autoimmune disease, mental disorders, diabetes, and other diseases.
  877. TABLE 10-2 ESTIMATED NEW U.S. CANCER CASES AND DEATHS BY GENDER, 2010*
  878. TABLE 10-3 DIFFERENCES BETWEEN MULTIGENERATIONAL AND TRANSGENERATIONAL PHENOTYPES
  879. FIGURE 10-2 Fetal Vulnerability to External and Internal Environments. The fetus is particularly vulnerable to changes in the external and internal environments, which can have immediate and lifelong consequences. Such environmentally induced changes can occur at multiple levels, including molecular and behavioral. Ultimately these alterations may be epigenetic, inducing mitotically heritable alterations in gene expression without changing the DNA.
  880. TABLE 10-4 SOMATIC VERSUS GERM CELL INHERITANCE
  881. In Utero and Early Life Conditions
  882. QUICK CHECK 10-2
  883. Tobacco Use
  884. Diet
  885. FIGURE 10-3 Dietary Factors, DNA Methylation, and Cancer. Certain dietary factors (see Table 10-5) may supply methyl groups (+CH3) that can be donated through S-adenosylmethonine (SAM) to many acceptors in the cell (DNA, proteins, lipids, and metabolites). Donation and removal (demethylation) are affected by numerous enzymes, including DNA methyltransferase (DNMT). Increased DNMT activity occurs in many tumor cells. Hypermethylation can inhibit or silence tumor-suppressor genes (see Chapter 9) and DNA methylation inhibitors as anticancer agents and can block DNMT, thus reactivating tumor-suppressor genes. DNA hypomethylation can reactivate and mutate genes, including cancer-causing oncogenes. SAH, S-Adenosylhomocysteine.
  886. FIGURE 10-4 Methylation of a Gene Region and Its Effect on Gene Transcription. (A) (Green circles) Unmethylated cytosine guanine dinuceotide (CpG) sites (a) and (black circles) methylated CpG sites. Methylation of exons (b, c) does not block gene transcription. Mosaic methylation of promoter CpG island also does not block transcription (d). However, dense methylation of promoter CpG islands completely blocks transcription, and is often associated with hypomethylation of downstream regions (e). (B) DNA methylation in normal and cancer cells. DNA methylation in normal cells (1). A hypomethylated promoter is related to gene expression. DNA methylation in cancer cells (2). Aberrant DNA hypermethylation in the promoter leads to gene silencing (muting) and tumor development. The DNA methylation process is catalyzed by the enymes DNA methyltransferases (DNMTs) by adding a methyl group (CH3) to the 5-position of the cystosine ring of CpG dinucleotides. (Green circles) Unmethylated cytosine guanine dinucleotide (CpG) sites; (black circles) hypermethylated CpG sites.
  887. TABLE 10-5 RELATIONSHIP OF DIETARY FACTORS TO RISK OF MAJOR CANCERS*
  888. Obesity
  889. NUTRITION & DISEASE
  890. Increase
  891. Decrease
  892. BOX 10-2 DIET AND CANCER KEY POINTS
  893. HEALTH ALERT
  894. FIGURE 10-5 Weight and Risk of Dying from Cancer. A, As a man’s body mass index (BMI) rises above the normal range (18.5 to 24.9), his risk of dying of colorectal, esophageal, kidney, and other cancers also rises. For example, the risk of dying from colorectal cancer is 10% higher for men who are overweight (BMI 25 to 29.9) than for men of normal or lower BMI. For the most obese men (BMI 35 or higher) the risk is almost double (84%). B, As a woman’s BMI rises above the normal range (18.5 to 24.9), her risk of dying of breast, kidney, uterine, and other cancers rises. For example, the risk of dying of breast cancer is 34% higher for women who are overweight. For the most obese women (BMI >40), the risk of dying from breast cancer is double. The risk of kidney cancer is almost five times higher, and the risk of uterine cancer is six times higher.
  895. TABLE 10-6 WHO CLASSIFICATION OF BODY MASS INDEX (BMI)
  896. Alcohol Consumption
  897. FIGURE 10-6 Energy Balance, Lipid Metabolism, and Insulin Sensitivity and Tumor Development. In obesity, increased release from adipose tissue of free fatty acids (FFAs), tumor necrosis factor-alpha (TNF-α), and resistin and decreased release of adiponectin lead to insulin resistance and compensatory chronic hyperinsulinemia. Increased insulin levels ultimately lead to decreased liver synthesis and blood levels of insulin-like growth factor binding protein-1 (IGFBP1) and, theoretically, also decreased IGFBP1 synthesis locally in other tissues. Increased fasting levels of insulin in plasma are also correlated with decreased levels of IGFBP2 in the blood, leading to increased levels of bioavailable IGF-1. Insulin and IGF-1 signal through the insulin receptor (IR) and IGF-1 receptor (IGF1R) to stimulate cellular proliferation and inhibit apoptosis in many tissue types. These effects could promote tumor development.
  898. Ionizing Radiation
  899. FIGURE 10-7 Pie Chart Showing Sources of Exposure to Ionizing Radiation. Percent contribution of various sources of exposure to the total collective effective dose (1,870,000 person-Sv) and the total effective dose per individual in the U.S. population (6.2 mSv) for 2006. Percent values have been rounded to the nearest 1%, except those <1%. Sv, Sievert.
  900. Radiation-Induced Cancer
  901. FIGURE 10-8 NCRP estimates that 67 million CT scans (compared to 3 million in 1980), 18 million nuclear medicine procedures, and 17 million interventional fluoroscopy procedures, and 18 million nuclear medicine procedures were performed in the U.S. in 2006.
  902. FIGURE 10-9 Free Radicals. Free radicals formed by water nearby and around DNA cause indirect effects. These effects have a short life of single free radicals. Oxygen can modify the reaction, enabling longer lifetimes of oxidative free radicals.
  903. HEALTH ALERT
  904. HEALTH ALERT
  905. NCRP estimates that 67 million CT scans (compared to 3 million in 1980), 18 million nuclear medicine procedures, and 17 million interventional fluoroscopy procedures, and 18 million nuclear medicine procedures were performed in the U.S. in 2006.
  906. Median Effective Radiation Dose for Each Type of CT Study
  907. FIGURE 10-10 Bystander Response Mechanism. Inflammatory cytokines are strongly increased after exposure to ionizing radiation or oxidants. Membrane-associated cytokines, such as tumor necrosis factor-alpha (TNFα), activate intracellular kinases (messengers), which release nuclear factor κβ (NF-κβ). NF-κβ enters the nucleus and promotes transcription of cyclooxygenase-2 (COX-2) and induces nitric oxide synthase (iNOS) genes, which stimulate production of nitric oxide (NO). Mitochondrial damage promotes the production of hydrogen peroxide that easily crosses plasma membranes and is subjected to antioxidant removal. Activation of COX-2 provides a continuous supply of reactive radicals and cytokines propagating bystander signals through gap junctions or medium. H2O2, Hydrogen peroxide; IL, interleukin; OH, hydroxyl radical; ONOO, peroxynitrite anion; PG-E2, prostaglandin E2; ROS, reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor; Trail, TNF-related apoptosis-inducing ligand.
  908. BOX 10-3 THEORETIC MODELS TO UNDERSTAND LOW-DOSE RADIATION
  909. Theoretic Models for Estimating Risk of Low-Dose Ionizing Radiation. Collective population dose is expressed as a person-rem (roentgen equivalent, man). Estimating a collective dose then enables an application of a “constant risk factor” to obtain a statistical estimate of the number of additional cancers (above background radiation) resulting from that exposure. These computations apply to low doses—low-dose rates only (A). Many propose the best fit is the linear no-threshold (LNT) model (B). The most common alternative to the LNT model is the linear-quadratic model. The quadratic term is the square of the dose. The linear term is equal to zero (C). The threshold model is a threshold below which there is no increase in cancer risk. Proponents of this model argue that because some toxic chemicals/materials exhibit such thresholds, radiation must also have a threshold. Their arguments are related to repair of the radiation damage caused by lower doses of radiation (D). Some evidence exists that low levels of radiation produce a higher level of risk per unit dose, which is called the supralinear model.
  910. TABLE 10-7 CANCER INCIDENCE AND FATALITY (BEIR VII) ESTIMATES OF LOW-LEVEL RADIATION PER GENDER*
  911. Carcinogenesis: Genomic Instability
  912. FIGURE 10-11 Models of the Responses of Clonogenic Cells to Ionizing Radiation. Mutations and/or chromosomal aberrations are shown as filled circles and apparently normal cells as open circles. A, If a cell faithfully repairs DNA damage, then its clonal descendants will appear normal. B, If a cell is directly mutated by radiation, then all of its descendants will express the same mutation. C, Radiation-induced genomic instability is characterized by nonclonal effects in descendant cells.
  913. Gap junction intercellular communication
  914. Ultraviolet Radiation
  915. FIGURE 10-12 Theoretic Scheme of Multistep Skin Carcinogenesis. Ultraviolet radiation (UVR), inflammation, and xenobiotics (see p. 262) lead to oxidative stress, resulting in direct DNA damage, protein oxidation, lipid peroxidation, and apoptosis. The protective mechanisms shown in red include apoptosis, DNA repair, and antioxidants. DMBA, Dimethylbenz[a]anthracene; ROS, reactive oxygen species; UVA, ultraviolet A; UVB, ultraviolet B.
  916. Electromagnetic Radiation
  917. FIGURE 10-13 Electromagnetic radiation from a cell phone can penetrate the skull. EMR from a cell phone can penetrate the skull and deposit energy 4 to 6 cm into the brain.132 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.
  918. QUICK CHECK 10-3
  919. Sexual and Reproductive Behavior: Human Papillomaviruses
  920. HEALTH ALERT
  921. Other Viruses and Microorganisms
  922. Physical Activity
  923. Chemicals and Occupational Hazards as Carcinogens
  924. Air Pollution
  925. BOX 10-4 KNOWN CARCINOGENIC AGENTS CLASSIFIED BY THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC)
  926. Agents or Group of Agents
  927. Mixtures
  928. Exposure Circumstances
  929. BOX 10-5 PROBABLE CARCINOGENIC AGENTS CLASSIFIED BY THE IARC
  930. Agents and Group of Agents
  931. Mixtures
  932. Exposure Circumstances
  933. BOX 10-6 NOTABLE OUTDOOR POLLUTANTS
  934. QUICK CHECK 10-4
  935. DID YOU UNDERSTAND?
  936. Genes, Environmental-Lifestyle Factors, and Risk Factors
  937. Epigenetics and Genetics
  938. Tobacco Use
  939. Diet
  940. Obesity
  941. Alcohol Consumption
  942. Ionizing Radiation (IR)
  943. Ultraviolet Radiation (UVR)
  944. Electromagnetic Radiation (EMR)
  945. Sexual and Reproductive Behavior
  946. Physical Activity
  947. Chemicals and Occupational Hazards
  948. KEY TERMS
  949. References
  950. Chapter 11 Cancer in Children
  951. Incidence and Types of Childhood Cancer
  952. TABLE 11-1 CHILDHOOD AGE-ADJUSTED INVASIVE CANCER INCIDENCE RATES BY PRIMARY SITE AND AGE, UNITED STATES*
  953. Etiology
  954. Genetic Factors
  955. TABLE 11-2 CHILDHOOD AGE-ADJUSTED CANCER INCIDENCE RATES FOR CHILDREN UP TO 19 YEARS OF AGE BY PRIMARY SITE AND RACE AND ETHNICITY, UNITED STATES*
  956. TABLE 11-3 CONGENITAL FACTORS ASSOCIATED WITH CHILDHOOD CANCER
  957. TABLE 11-4 SELECTED ONCOGENES AND TUMOR-SUPPRESSOR GENES ASSOCIATED WITH CHILDHOOD CANCER
  958. TABLE 11-5 DRUGS THAT MAY INCREASE RISK OF CHILDHOOD CANCER
  959. Environmental Factors
  960. Prenatal Exposure
  961. Childhood Exposure
  962. HEALTH ALERT
  963. Prognosis
  964. QUICK CHECK 11-1
  965. DID YOU UNDERSTAND?
  966. Incidence and Types of Childhood Cancers
  967. Etiology
  968. Prognosis
  969. KEY TERMS
  970. References
  971. PART II Body Systems and Diseases
  972. UNIT 4 The Neurologic System
  973. Interactive Review – Unit 4
  974. Chapter 12 Structure and Function of the Neurologic System
  975. Overview and Organization of the Nervous System
  976. Cells of the Nervous System
  977. The Neuron
  978. FIGURE 12-1 Neuron With Composite Parts. Multipolar neuron: neuron with multiple extensions from the cell body.
  979. FIGURE 12-2 Neuronal Transmission and Synaptic Cleft. Electrical impulse travels along axon of first neuron to synapse. Chemical transmitter is secreted into synaptic space to depolarize membrane (dendrite or cell body) of next neuron in pathway. Cell A represents pseudounipolar cell; cell B represents multipolar cell.
  980. FIGURE 12-3 Types of Neuroglial Cells. Neuroglia of the CNS: A, Astrocytes attached to the outside of a capillary blood vessel in the brain. B, A phagocytic microglial cell. C, Ciliated ependymal cells forming a sheet that usually lines fluid cavities in the brain. D, An oligodendrocyte with processes that wrap around nerve fibers in the CNS to form myelin sheaths. Neuroglia of the peripheral nervous system (PNS): E, A Schwann cell supporting a bundle of nerve fibers in the PNS. F, Another type of Schwann cell encircling a peripheral nerve fiber to form a thick myelin sheath. G, Satellite cells, another type of Schwann cell, surround and support cell bodies of neurons in the PNS.
  981. Neuroglia and Schwann Cells
  982. TABLE 12-1 SUPPORT CELLS OF THE NERVOUS SYSTEM
  983. Nerve Injury and Regeneration
  984. The Nerve Impulse
  985. FIGURE 12-4 Repair of a Peripheral Nerve Fiber. When cut, a damaged motor axon can regrow to its distal connection only if the Schwann cells remain intact (to form a guiding tunnel) and if scar tissue does not block its way.
  986. QUICK CHECK 12-1
  987. Synapses
  988. TABLE 12-2 SUBSTANCES THAT ARE NEUROTRANSMITTERS OR NEUROMODULATORS
  989. Neurotransmitters
  990. HEALTH ALERT
  991. QUICK CHECK 12-2
  992. The Central Nervous System
  993. The Brain
  994. FIGURE 12-5 Reticular Activating System. System consists of nuclei in the brain stem reticular formation plus fibers that conduct to the nuclei from below and fibers that conduct from the nuclei to widespread areas of the cerebral cortex. Functioning of the reticular activating system is essential for consciousness.
  995. TABLE 12-3 DIVISIONS OF THE CENTRAL NERVOUS SYSTEM
  996. Forebrain
  997. Telencephalon
  998. FIGURE 12-6 The Cerebral Hemispheres. A, Left hemisphere of cerebrum, lateral view. B, Functional areas of the cerebral cortex, midsagittal view. C, Functional areas of the cerebral cortex, lateral view.
  999. FIGURE 12-7 Primary Somatic Sensory (A) and Motor (B) Areas of the Cortex. This illustration shows which parts of the body are “mapped” to specific cortical areas. The exaggerated face indicates that more cortical area is devoted to processing information to and from the many receptors and motor units of the face than for the leg or arm, for example.
  1000. FIGURE 12-8 Examples of Somatic Motor and Sensory Pathways. A, Motor: pyramidal pathway illustrated by the lateral corticospinal tract and extrapyramidal pathways illustrated by the rubrospinal and reticulospinal tracts. B, Sensory: pathways of the medial lemniscal system that conducts information about discriminating touch and kinesthesis and the spinothalamic pathway that conducts information about pain and temperature.
  1001. FIGURE 12-9 Basal Nuclei. A, The basal nuclei seen through the cortex of the left cerebral hemisphere. B, The basal nuclei seen in a frontal (coronal) section of the brain.
  1002. Diencephalon
  1003. BOX 12-1 FUNCTIONS OF THE HYPOTHALAMUS
  1004. Midbrain
  1005. Mesencephalon
  1006. Hindbrain
  1007. Metencephalon
  1008. Myelencephalon
  1009. QUICK CHECK 12-3
  1010. The Spinal Cord
  1011. FIGURE 12-10 Spinal Cord Within Vertebral Canal and Exiting Spinal Nerves. A, Posterior view of brain stem and spinal cord in situ with spinal nerves and plexus. B, Lateral view of brain stem and spinal cord. C, Enlargement of caudal area showing termination of spinal cord (conus medullaris) and group of nerve fibers constituting the cauda equina.
  1012. FIGURE 12-11 Coverings of the Spinal Cord. The dura mater is shown in natural color. Note how it extends to cover the spinal nerve roots and nerves. The arachnoid is highlighted in blue and the pia mater in pink.
  1013. FIGURE 12-12 Major Tracts of the Spinal Cord. The major ascending (sensory) tracts, shown only on the left here, are highlighted in blue. The major descending (motor) tracts, shown only on the right, are highlighted in red.
  1014. FIGURE 12-13 Cross Section of Spinal Cord Showing Simple Reflex Arc.
  1015. FIGURE 12-14 Neuromuscular Junction. This figure shows how the distal end of a motor neuron fiber forms a synapse, or “chemical junction,” with an adjacent muscle fiber. Neurotransmitters (specifically, acetylcholine) are released from the neuron’s synaptic vesicles and diffuse across the synaptic cleft. There they stimulate receptors in the motor end-plate region of the sarcolemma.
  1016. Motor Pathways
  1017. Sensory Pathways
  1018. Protective Structures of the Central Nervous System
  1019. Cranium
  1020. Meninges
  1021. FIGURE 12-15 Flow of Cerebrospinal Fluid and Meninges of the Brain. A, The fluid produced by filtration of blood by the choroid plexus of each ventricle flows inferiorly through the lateral ventricles, interventricular foramen, third ventricle, cerebral aqueduct, fourth ventricle, and subarachnoid space to the blood. B, Meninges of the brain in relation to CSF and venous blood flow.
  1022. TABLE 12-4 COMPOSITION OF CEREBROSPINAL FLUID
  1023. Cerebrospinal Fluid and the Ventricular System
  1024. FIGURE 12-16 Vertebral Column. A, Right lateral view. B, Anterior view.
  1025. FIGURE 12-17 A, Lumbar Vertebra, Superior View; B, Intervertebral Disk.
  1026. Vertebral Column
  1027. QUICK CHECK 12-4
  1028. FIGURE 12-18 Major Arteries of the Head and Neck.
  1029. Blood Supply of the Central Nervous System
  1030. Blood Supply to the Brain
  1031. FIGURE 12-19 Arteries at the Base of the Brain. The arteries that compose the circle of Willis are the two anterior cerebral arteries, joined to each other by the anterior communicating artery and two short segments of the internal carotids, off of which the posterior communicating arteries connect to the posterior cerebral arteries.
  1032. FIGURE 12-20 Areas of the Brain Affected by Occlusion of the Anterior, Middle, and Posterior Cerebral Artery Branches. A, Inferior view. B, Lateral view.
  1033. TABLE 12-5 ARTERIAL SYSTEMS SUPPLYING THE BRAIN
  1034. Blood-Brain Barrier
  1035. Blood Supply to the Spinal Cord
  1036. The Peripheral Nervous System
  1037. FIGURE 12-21 Large Veins of the Head. Deep veins and dural sinuses are projected on the skull. Note two superficial veins in the face are tributaries that send blood through emissary veins in the skull foramen into deep veins inside the skull terminating in the internal jugular vein.
  1038. FIGURE 12-22 Blood-Brain Barrier. Cell membranes with tight junctions create a physical barrier between capillary blood and the cytoplasm of astrocytes.
  1039. FIGURE 12-23 Arteries of the Spinal Cord. A, Arteries of cervical cord exposed from the rear. B, Arteries of spinal cord diagrammatically shown in horizontal section.
  1040. QUICK CHECK 12-5
  1041. The Autonomic Nervous System
  1042. FIGURE 12-24 Cranial and Peripheral Nerves. A, Ventral surface of the brain showing attachment of the cranial nerves. B, Peripheral nerve trunk and coverings.
  1043. FIGURE 12-25 Locations of Neurotransmitters and Receptors of the Autonomic Nervous System. In all pathways, preganglionic fibers are cholinergic, secreting acetylcholine (Ach), which stimulates nicotinic receptors in the postganglionic neuron. Most sympathetic postganglionic fibers are adrenergic, A, secreting norepinephrine (NE), thus stimulating α- or β-adrenergic receptors. A few sympathetic postganglionic fibers are cholinergic, stimulating muscarinic receptors in effector cells, B, all parasympathetic postganglionic fibers are cholinergic, C, stimulating muscarinic receptors in effector cells.
  1044. TABLE 12-6 THE CRANIAL NERVES
  1045. Anatomy of the Sympathetic Nervous System
  1046. FIGURE 12-26 Sympathetic Division of the Autonomic Nervous System. CG, Celiac ganglion; CiG, ciliary ganglion; IMG, inferior mesenteric ganglion; OG, otic ganglion; PP, pelvic plexus; SCG, superior cervical ganglion; SG, submandibular ganglion; SMG, superior mesenteric ganglion; SpG, sphenopalatine ganglion.
  1047. Anatomy of the Parasympathetic Nervous System
  1048. Neurotransmitters and Neuroreceptors
  1049. FIGURE 12-27 Parasympathetic Division of the Autonomic Nervous System. CiG, Ciliary ganglion; OG, otic ganglion; PN, pelvic nerve; PP, pelvic plexus; SG, submandibular ganglion; SpG, sphenopalatine ganglion; VN, vagus nerve.
  1050. FIGURE 12-28 The Autonomic Nervous System and the Type of Neurotransmitters Secreted by Preganglionic and Postganglionic Fibers. Note that all preganglionic fibers are cholinergic (Ach). A somatic nerve is used for comparison.
  1051. FIGURE 12-29 Some Important Functions of the Sympathetic Nervous System. A, Regulation of vasomotor tone. B, Regulation of strenuous muscular exercise (“fight or flight” response).
  1052. TABLE 12-7 ACTIONS OF AUTONOMIC NERVOUS SYSTEM NEURORECEPTORS
  1053. Functions of the Autonomic Nervous System
  1054. QUICK CHECK 12-6
  1055. GERIATRIC CONSIDERATIONS
  1056. Structural Changes With Aging
  1057. Cellular Changes With Aging
  1058. Cerebrovascular Changes With Aging
  1059. Functional Changes With Aging
  1060. DID YOU UNDERSTAND?
  1061. Overview and Organization of the Nervous System
  1062. Cells of the Nervous System
  1063. The Nerve Impulse
  1064. The Central Nervous System
  1065. The Peripheral Nervous System
  1066. The Autonomic Nervous System
  1067. GERIATRIC CONSIDERATIONS: Aging & the Nervous System
  1068. KEY TERMS
  1069. References
  1070. Chapter 13 Pain, Temperature, Sleep, and Sensory Function
  1071. Pain
  1072. The Experience of Pain
  1073. Evolution of Pain Theories
  1074. Neuroanatomy of Pain
  1075. FIGURE 13-1 Gate Control Theory of Pain. Schematic diagram of the gate control theory of pain mechanism. Large A-beta (Aβ) fiber non-nociceptor impulses (i.e., mechanical and thermal) activate inhibitory interneuron in spinal cord dorsal horn and decrease pain transmission (close pain gate). Small fiber impulses block the inhibitory interneuron and promote pain transmission (open pain gate).
  1076. TABLE 13-1 STIMULI THAT ACTIVATE NOCICEPTORS (PAIN RECEPTORS)
  1077. Neuromodulation of Pain
  1078. FIGURE 13-2 Transmission of Pain Sensations. The Aδ and C fibers synapse in the laminae of the dorsal horn, crossover to the contralateral spinothalamic tract, and then ascend to synapse in the midbrain through the neospinothalamic and paleospinothalamic tracts. Impulses are then conducted to the sensory cortex.
  1079. FIGURE 13-3 Descending Pathway and Endorphin Response. Endorphin receptors are located close to known pain receptors in the periphery and ascending and descending pain pathways.
  1080. Clinical Descriptions of Pain
  1081. FIGURE 13-4 Sites of Referred Pain. A, Anterior view. B, Posterior view.
  1082. BOX 13-1 CATEGORIES OF PAIN
  1083. Pain Threshold and Pain Tolerance
  1084. TABLE 13-2 COMPARISON OF ACUTE AND CHRONIC PAIN
  1085. TABLE 13-3 COMMON CHRONIC PAIN CONDITIONS
  1086. QUICK CHECK 13-1
  1087. TABLE 13-4 PAIN PERCEPTION IN INFANTS, CHILDREN, AND ELDERLY PERSONS
  1088. Temperature Regulation
  1089. Control of Body Temperature
  1090. Temperature Regulation in Infants and Elderly Persons
  1091. Pathogenesis of Fever
  1092. TABLE 13-5 MECHANISMS OF HEAT PRODUCTION AND HEAT LOSS
  1093. Benefits of Fever
  1094. Disorders of Temperature Regulation
  1095. Hyperthermia
  1096. FIGURE 13-5 Production of Fever. Pathogens release exogenous pyrogens and activate monocytes/macrophages and other inflammatory cells that secrete endogenous pyrogenic cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon (IFN), which promote the synthesis and secretion of prostaglandin E2 (PGE2) in the anterior hypothalamus. PGE2 increases the thermostatic set point, and the autonomic nervous system is stimulated, resulting in shivering, muscle contraction, peripheral vasoconstriction, and the production of fever.
  1097. BOX 13-2 EFFECTS OF FEVER AT THE EXTREMES OF AGE
  1098. Elderly Persons
  1099. Children
  1100. Hypothermia
  1101. Trauma and Temperature
  1102. QUICK CHECK 13-2
  1103. Sleep
  1104. BOX 13-3 DEFINING CHARACTERISTICS OF HYPOTHERMIA
  1105. Accidental Hypothermia
  1106. Therapeutic Hypothermia
  1107. Sleep Disorders
  1108. Common Dyssomnias
  1109. Insomnia
  1110. Sleep disordered breathing and hypersomnia
  1111. BOX 13-4 SLEEP CHARACTERISTICS OF INFANTS AND ELDERLY PERSONS
  1112. Infants
  1113. Elderly Persons
  1114. Disorders of the sleep-wake schedule
  1115. Common Parasomnias
  1116. QUICK CHECK 13-3
  1117. The Special Senses
  1118. Vision
  1119. The Eye and Its External Structures
  1120. FIGURE 13-6 Internal Anatomy of the Eye.
  1121. Visual Dysfunction
  1122. Alterations in ocular movements
  1123. FIGURE 13-7 Extrinsic Muscles of the Right Eye.
  1124. FIGURE 13-8 Lacrimal Apparatus. Fluid produced by lacrimal glands (tears) streams across the eye surface, enters the canals, and then passes through the nasolacrimal duct to enter the nose.
  1125. Alterations in visual acuity
  1126. TABLE 13-6 CHANGES IN THE EYE CAUSED BY AGING
  1127. TABLE 13-7 CAUSES OF VISUAL ACUITY CHANGES
  1128. Alterations in accommodation
  1129. Alterations in refraction
  1130. FIGURE 13-9 Alterations in Refraction. A, Myopic eye. Parallel rays of light are brought to a focus in front of the retina. B, Hyperopic eye. Parallel rays of light come to a focus behind the retina in the unaccommodative eye. C, Simple myopic astigmatism. The vertical bundle of rays is focused on the retina; the horizontal rays are focused in front of the retina.
  1131. Alterations in color vision
  1132. Neurologic disorders causing visual dysfunction
  1133. External Eye Structure Disorders
  1134. FIGURE 13-10 Visual Pathways and Defects.
  1135. Hearing
  1136. The Normal Ear
  1137. FIGURE 13-11 The Ear. External, middle, and inner ears. (Anatomic structures are not drawn to scale.)
  1138. FIGURE 13-12 The Inner Ear. A, The bony labyrinth (orange) is the hard outer wall of the entire inner ear and includes the semicircular canals, vestibule, and cochlea. Within the bony labyrinth is the membranous labyrinth (purple), which is surrounded by perilymph and filled with endolymph. Each ampulla in the vestibule contains a crista ampullaris that detects changes in head position and sends sensory impulses through the vestibular nerve to the brain. B, The inset shows a section of the membranous cochlea. Hair cells in the organ of Corti detect sound and send the information through the cochlear nerve. The vestibular and cochlear nerves join to form the eighth cranial nerve.
  1139. Auditory Dysfunction
  1140. GERIATRIC CONSIDERATIONS
  1141. Conductive hearing loss
  1142. Sensorineural hearing loss
  1143. Mixed and functional hearing loss
  1144. Ménière disease
  1145. Ear Infections
  1146. Otitis externa
  1147. Otitis media
  1148. FIGURE 13-13 Olfaction. Midsagittal section of the nasal area shows the location of major olfactory sensory structures.
  1149. Olfaction and Taste
  1150. GERIATRIC CONSIDERATIONS
  1151. Olfactory and Taste Dysfunctions
  1152. QUICK CHECK 13-4
  1153. Somatosensory Function
  1154. Touch
  1155. Proprioception
  1156. QUICK CHECK 13-5
  1157. DID YOU UNDERSTAND?
  1158. Pain
  1159. Temperature Regulation
  1160. Sleep
  1161. The Special Senses
  1162. Somatosensory Function
  1163. KEY TERMS
  1164. Retinal Detachment (see video)
  1165. References
  1166. Chapter 14 Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function
  1167. Alterations In Cognitive Systems
  1168. Alterations in Arousal
  1169. Pathophysiology
  1170. TABLE 14-1 CLINICAL MANIFESTATIONS OF METABOLIC AND STRUCTURAL CAUSES OF ALTERED AROUSAL
  1171. Clinical Manifestations and Evaluation
  1172. TABLE 14-2 DIFFERENTIAL CHARACTERISTICS OF STATES CAUSING ALTERED AROUSAL
  1173. FIGURE 14-1 Abnormal Respiratory Patterns With Corresponding Level of Central Nervous System Activity.
  1174. FIGURE 14-2 Pupils at Different Levels of Consciousness.
  1175. TABLE 14-3 LEVELS OF ALTERED CONSCIOUSNESS
  1176. TABLE 14-4 PATTERNS OF BREATHING
  1177. FIGURE 14-3 Test for Oculocephalic Reflex Response (Doll’s Eyes Phenomenon). A, Normal response—eyes turn together to side opposite from turn of head. B, Abnormal response—eyes do not turn in conjugate manner. C, Absent response—eyes move in direction of head movement (brain stem injury).
  1178. QUICK CHECK 14-1
  1179. Outcomes of Alterations in Arousal
  1180. FIGURE 14-4 Test for Oculovestibular Reflex (Caloric Ice Water Test). A, Ice water is injected into the ear canal. Normal response—conjugate eye movements. B, Abnormal response—dysconjugate or asymmetric eye movements. C, Absent response—no eye movements.
  1181. FIGURE 14-5 Pathologic Reflexes. A, Grasp reflex. B, Snout reflex. C, Palmomental reflex. D, Suck reflex.
  1182. TABLE 14-5 ABNORMAL MOTOR RESPONSES WITH DECREASED RESPONSIVENESS
  1183. FIGURE 14-6 Decorticate and Decerebrate Responses. A, Decorticate response. Flexion of arms, wrists, and fingers with adduction in upper extremities. Extension, internal rotation, and plantar flexion in lower extremities. Both sides. B, Decerebrate response. All four extremities in rigid extension, with hyperpronation of forearms and plantar extension of feet. C, Decorticate response on right side of body and decerebrate response on left side of body.
  1184. BOX 14-1 Criteria for Brain Death
  1185. Alterations in Awareness
  1186. HEALTH ALERT
  1187. Pathophysiology
  1188. Clinical Manifestations
  1189. Evaluation and treatment
  1190. TABLE 14-6 CLINICAL MANIFESTATIONS OF ALTERATIONS IN ATTENTION AND MEMORY
  1191. Seizure Disorders
  1192. Conditions Associated With Seizure Disorders
  1193. Types of seizure disorders
  1194. TABLE 14-7 CAUSES OF RECURRENT SEIZURES IN DIFFERENT AGE GROUPS
  1195. Clinical Manifestations
  1196. TABLE 14-8 INTERNATIONAL CLASSIFICATION OF EPILEPTIC SEIZURES
  1197. Evaluation and treatment
  1198. QUICK CHECK 14-2
  1199. FIGURE 14-7 Right Cortical, Subcortical, and Brain Stem Areas of the Brain Mediating Cognitive Function.
  1200. TABLE 14-9 TERMINOLOGY APPLIED TO A SEIZURE DISORDER
  1201. Data Processing Deficits
  1202. Agnosia
  1203. Dysphasia
  1204. Acute Confusional States
  1205. Pathophysiology
  1206. Clinical Manifestations
  1207. Evaluation and treatment
  1208. QUICK CHECK 14-3
  1209. Dementia
  1210. Pathophysiology
  1211. TABLE 14-10 MAJOR TYPES OF DYSPHASIA
  1212. Clinical Manifestations
  1213. Evaluation and treatment
  1214. TABLE 14-11 EXAMPLES OF LANGUAGE DISTURBANCES
  1215. TABLE 14-12 DIFFERENCES BETWEEN ORGANIC AND FUNCTIONAL CONFUSION
  1216. Alzheimer Disease
  1217. TABLE 14-13 COMPARISON OF DELIRIUM AND DEMENTIA
  1218. Pathophysiology
  1219. Clinical Manifestations
  1220. FIGURE 14-8 Common Pathologic Findings in Alzheimer Disease. The middle panel represents coronal slices through the left brain.
  1221. TABLE 14-14 CLINICAL MANIFESTATIONS OF THE MAJOR DEGENERATIVE DEMENTIAS
  1222. Evaluation and treatment
  1223. HEALTH ALERT
  1224. TABLE 14-15 PROGRESSION OF ALZHEIMER DISEASE
  1225. Frontotemporal Dementia
  1226. Alterations in Cerebral Hemodynamics
  1227. Increased Intracranial Pressure
  1228. FIGURE 14-9 Clinical Correlates of Compensated and Uncompensated Phases of Intracranial Hypertension.
  1229. FIGURE 14-10 Herniation. Herniations can occur both above and below the tentorial membrane. Suprateneorial: 1, uncal (transtentorial); 2, central 3, cinculate 4, transcalvarial; infratentorial:5, upward, 6, cerebellar tonsillar.
  1230. Cerebral Edema
  1231. BOX 14-2 Herniation Syndrome
  1232. Supratentorial Herniation
  1233. Infratentorial Herniation
  1234. Hydrocephalus
  1235. FIGURE 14-11 Brain Edema. Intercellular lakes of high protein content fluid. (Hematoxylin-eosin stain; ×90.)
  1236. TABLE 14-16 TYPES OF HYDROCEPHALUS
  1237. Pathophysiology
  1238. Clinical Manifestations
  1239. Evaluation and treatment
  1240. QUICK CHECK 14-4
  1241. Alterations in Neuromotor Function
  1242. Alterations in Muscle Tone
  1243. Hypotonia
  1244. TABLE 14-17 ALTERATIONS IN MUSCLE TONE
  1245. Hypertonia
  1246. Alterations in Movement
  1247. FIGURE 14-12 Paroxysm of Left-Sided Hemifacial Spasm.
  1248. Paresis/Paralysis
  1249. FIGURE 14-13 Dystonic Posturing of the Hand and Foot.
  1250. FIGURE 14-14 Spasmodic Torticollis. A characteristic head posture.
  1251. TABLE 14-18 UPPER AND LOWER MOTOR NEURON SIGNS AND SYMPTOMS
  1252. Upper Motor Neuron Syndromes
  1253. FIGURE 14-15 Motor Function Syndromes. Disturbances in motor function are classified pathologically along upper and lower motor neuron structures. It should be noted that the same pathologic condition occurs at more than one site in an upper motor neuron (above right). A few pathologic conditions involve both upper and lower motor neuron structures, as in amyotrophic lateral sclerosis, for example. Other lesion sites include myoneural junction and primary muscle, making it possible to classify conditions as neuromuscular and muscular, respectively.
  1254. FIGURE 14-16 Structures of the Upper Motor Neuron, or Pyramidal, System. Pyramidal system fibers are shown to originate primarily in cells in precentral gyrus of motor cortex; to converge at internal capsule; to descend to form central third of cerebral peduncle; to descend further through pons, where small fibers supply cranial nerve motor nuclei along the way; to form pyramids at medulla, where most of the fibers decussate; and then to continue to descend in lateral column of white matter of spinal cord. A few fibers descend without crossing at medulla level (see Figure 12-8).
  1255. Lower Motor Neuron Syndromes
  1256. FIGURE 14-17 Structures Composing Lower Motor Neuron, Including Motor (Efferent) and Sensory (Afferent) Elements. (Top) Anterior horn cell (in anterior gray column of spinal cord and its axon), terminating in motor end-plate as it innervates extrafusal muscle fibers in quadriceps muscle. (Detailed enlargement) Sensory and motor elements of gamma loop system. Gamma efferent fibers shown innervating the muscle spindle (sensory receptor of skeletal muscle). Contraction of muscle spindle fibers stretches central portion of the spindle and causes the gamma afferent spindle fiber to transmit impulse centrally to cord. Muscle spindle gamma afferent fibers in turn synapse on the anterior horn cell and impulses are transmitted by way of alpha efferent fibers to skeletal (extrafusal) muscle, causing it to contract. Muscle spindle discharge is interrupted by active contraction of skeletal muscle fibers.
  1257. Amyotrophies
  1258. Hyperkinesia
  1259. Huntington Disease
  1260. HEALTH ALERT
  1261. Pathophysiology
  1262. TABLE 14-19 TYPES OF HYPERKINESIA AND TREMOR
  1263. Clinical Manifestations
  1264. Evaluation and treatment
  1265. Hypokinesia
  1266. Akinesia and bradykinesia
  1267. Loss of associated movement
  1268. Parkinson Disease
  1269. Pathophysiology
  1270. Clinical Manifestations
  1271. FIGURE 14-18 Pathophysiology of Parkinson Disease.
  1272. FIGURE 14-19 Stooped Posture of Parkinson Disease.
  1273. Evaluation and treatment
  1274. Alterations in Complex Motor Performance
  1275. Disorders of Posture (Stance)
  1276. Disorders of Gait
  1277. Disorders of Expression
  1278. FIGURE 14-20 Pathways Disrupted in Dyspraxias. Formulation of the idea of the motor act is thought to originate in the region of the supramarginal gyrus in the inferior left parietal lobe. This area is connected via associational pathways to the left premotor cortex. The left premotor cortex is connected through the corpus callosum to the right premotor and motor areas. An injury that interrupts the pathways between the left supramarginal gyrus and the premotor region produces a dyspraxia that involves the entire body. An injury that disrupts the callosal pathways produces a dyspraxia of the left side of the body only.
  1279. Extrapyramidal Motor Syndromes
  1280. QUICK CHECK 14-5
  1281. TABLE 14-20 PYRAMIDAL VS. EXTRAPYRAMIDAL MOTOR SYNDROME
  1282. DID YOU UNDERSTAND?
  1283. Alterations in Cognitive Systems
  1284. Alterations in Cerebral Hemodynamics
  1285. Alterations in Neuromotor Function
  1286. Alterations in Tone
  1287. Alterations in Movement
  1288. Alterations in Complex Motor Performance
  1289. Extrapyramidal Motor Syndromes
  1290. KEY TERMS
  1291. Generalized seizure (see video)
  1292. Alzheimer disease (see video)
  1293. Parkinson disease (see video)
  1294. References
  1295. Chapter 15 Disorders of the Central and Peripheral Nervous Systems and Neuromuscular Junction
  1296. Central Nervous System Disorders
  1297. Traumatic Brain and Spinal Cord Injury
  1298. Brain Trauma
  1299. TABLE 15-1 CAUSES OF BRAIN INJURIES
  1300. TABLE 15-2 SEVERITY OF TRAUMA RELATED TO TRAUMA STATE INDUCED AND ONSET AND PERSISTENCE OF CLINICAL MANIFESTATIONS
  1301. TABLE 15-3 CATEGORIES OF DIFFUSE BRAIN INJURY
  1302. Primary brain injury
  1303. Focal brain injury
  1304. FIGURE 15-1 Coup and Contrecoup Head Injury After Blunt Trauma. 1, Coup injury: impact against object; a, site of impact and direct trauma to brain; b, shearing of subdural veins; c, trauma to base of brain. 2, Contrecoup injury: impact within skull; a, site of impact from brain hitting opposite side of skull; b, shearing forces through brain. These injuries occur in one continuous motion—the head strikes the wall (coup) and then rebounds (contrecoup).
  1305. FIGURE 15-2 Brain Hematomas.
  1306. Diffuse brain injury
  1307. Secondary brain trauma
  1308. QUICK CHECK 14-1
  1309. Spinal Cord Trauma
  1310. Pathophysiology
  1311. FIGURE 15-3 Hyperextension Injuries of the Spine. Hyperextension injuries of the spine can result in fracture or nonfracture injuries with spinal cord damage.
  1312. FIGURE 15-4 Flexion Injury of the Spine. Hyperflexion produces translation (subluxation) of vertebrae that compromises the central canal and compresses spinal cord parenchyma or vascular structures.
  1313. FIGURE 15-5 Axial Compression Injuries of the Spine. In axial compression injuries of the spine, the spinal cord is contused directly by retropulsion of bone or disk material into the spinal canal.
  1314. FIGURE 15-6 Flexion-Rotation Injuries of the Spine.
  1315. TABLE 15-4 MECHANISMS OF VERTEBRAL INJURY INVOLVING BONE, LIGAMENTS, AND JOINTS
  1316. TABLE 15-5 SPINAL CORD INJURIES
  1317. Clinical Manifestations
  1318. TABLE 15-6 CLINICAL MANIFESTATIONS OF SPINAL CORD INJURY
  1319. FIGURE 15-7 Autonomic Hyperreflexia. A, Normal response pathway. B, Autonomic dysreflexia pathway. SA, Sinoatrial.
  1320. Evaluation and Treatment
  1321. Degenerative Disorders of the Spine
  1322. Degenerative Joint Disease (DJD)
  1323. Degenerative disk disease
  1324. Spondylolysis
  1325. Spondylolisthesis
  1326. Spinal stenosis
  1327. Low Back Pain
  1328. FIGURE 15-8 Herniated Nucleus Pulposus.
  1329. Pathogenesis
  1330. Evaluation and Treatment
  1331. Herniated Intervertebral Disk
  1332. Pathophysiology
  1333. Clinical Manifestations
  1334. FIGURE 15-9 Clinical Features of a Herniated Nucleus Pulposus.
  1335. Evaluation and Treatment
  1336. Cerebrovascular Disorders
  1337. Cerebrovascular Accidents (Stroke Syndromes)
  1338. Thrombotic stroke
  1339. Embolic stroke
  1340. Hemorrhagic stroke
  1341. Lacunar stroke
  1342. Pathophysiology
  1343. Cerebral infarction
  1344. Cerebral hemorrhage
  1345. Clinical Manifestations
  1346. Evaluation and Treatment
  1347. Intracranial Aneurysm
  1348. Pathophysiology
  1349. FIGURE 15-10 Types of Aneurysms.
  1350. FIGURE 15-11 Berry Aneurysm, Angiogram. In this lateral view with contrast filling a portion of the cerebral arterial circulation can be seen a berry aneurysm (arrow) involving the middle cerebral artery of the circle of Willis at the base of the brain.
  1351. Clinical Manifestations
  1352. Evaluation and Treatment
  1353. Vascular Malformation
  1354. Pathophysiology
  1355. Clinical Manifestations
  1356. Evaluation and Treatment
  1357. Subarachnoid Hemorrhage
  1358. Pathophysiology
  1359. Clinical Manifestations
  1360. Evaluation and Treatment
  1361. QUICK CHECK 14-2
  1362. TABLE 15-7 SUBARACHNOID HEMORRHAGE CLASSIFICATION SCALE
  1363. Headache
  1364. Migraine
  1365. TABLE 15-8 CHARACTERISTICS OF COMMON HEADACHES
  1366. Cluster Headache
  1367. Tension-type headache
  1368. Infection and Inflammation of the Central Nervous System
  1369. FIGURE 15-12 Viral Infection in the Central Nervous System (CNS). Viruses infect specific cell types within the CNS depending on the particular properties of the virus together with individual cell membrane proteins expressed on permissive cell types. Normally the brain is protected from circulating pathogens and toxins by the blood-brain barrier. CMV, Cytomegalovirus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV-1, human T cell lymphotropic virus (causes T cell leukemia); JCV, John Cunningham virus (a polyomavirus causing progressive multifocal leukoencephalopathy); SSPE, subacute sclerosing panencephalitis; VZV, varicella-zoster virus.
  1370. Meningitis
  1371. Pathophysiology
  1372. Clinical Manifestations
  1373. Evaluation and Treatment
  1374. Brain or Spinal Cord Abscess
  1375. Pathophysiology
  1376. Clinical Manifestations
  1377. FIGURE 15-13 Brain Abscess. Early brain abscess appearing as a poorly demarcated area (arrow) of cerebritis at the gray-white junction.
  1378. Evaluation and Treatment
  1379. Encephalitis
  1380. Pathophysiology
  1381. Clinical Manifestations
  1382. TABLE 15-9 CLASSIFICATION AND CHARACTERISTICS OF ARBOVIRUSES CAUSING ENCEPHALITIS
  1383. HEALTH ALERT
  1384. Evaluation and Treatment
  1385. Neurologic Complications of AIDS
  1386. Human immunodeficiency virus–associated dementia (HIV encephalopathy)
  1387. HIV myelopathy
  1388. HIV peripheral neuropathy
  1389. Aseptic viral meningitis
  1390. Opportunistic infections
  1391. CNS neoplasms
  1392. Other CNS complications
  1393. Demyelinating Degenerative Disorders
  1394. Multiple Sclerosis
  1395. Pathophysiology
  1396. FIGURE 15-14 Pathogenesis of Multiple Sclerosis.
  1397. Clinical Manifestations
  1398. Evaluation and Treatment
  1399. HEALTH ALERT
  1400. Amyotrophic Lateral Sclerosis
  1401. Pathophysiology
  1402. Clinical Manifestations
  1403. Evaluation and Treatment
  1404. TABLE 15-10 PERIPHERAL NERVOUS SYSTEM DISORDERS
  1405. QUICK CHECK 14-3
  1406. Peripheral Nervous System and Neuromuscular Junction Disorders
  1407. Peripheral Nervous System Disorders
  1408. Neuromuscular Junction Disorders
  1409. Myasthenia Gravis
  1410. Pathophysiology
  1411. Clinical Manifestations
  1412. Evaluation and Treatment
  1413. QUICK CHECK 14-4
  1414. Tumors of the Central Nervous System
  1415. Cranial Tumors
  1416. Primary Brain (Intracerebral) Tumors
  1417. FIGURE 15-15 Common Sites of Intracranial Tumors.
  1418. FIGURE 15-16 Origin of Clinical Manifestations Associated With an Intracranial Neoplasm.
  1419. TABLE 15-11 BRAIN AND SPINAL CORD TUMORS
  1420. TABLE 15-12 CLASSIFICATION SYSTEMS FOR ASTROCYTOMAS
  1421. Astrocytoma
  1422. HEALTH ALERT
  1423. Oligodendroglioma
  1424. Ependymoma
  1425. Primary Extracerebral Tumors
  1426. Meningioma
  1427. Nerve sheath tumors
  1428. Metastatic carcinoma
  1429. Spinal Cord Tumors
  1430. Pathophysiology
  1431. Clinical Manifestations
  1432. Evaluation and Treatment
  1433. QUICK CHECK 14-5
  1434. DID YOU UNDERSTAND?
  1435. Central Nervous System Disorders
  1436. Demyelinating Degenerative Disorders
  1437. Peripheral Nervous System and Neuromuscular Junction Disorders
  1438. Tumors of the Central Nervous System
  1439. KEY TERMS
  1440. Epidural hematoma (see video)
  1441. Embolic stroke (see video)
  1442. Cerebral Infarction (see video)
  1443. Arteriovenous malformation (AVM) (see video)
  1444. Subarachnoid hemorrhage (see video)
  1445. Meningitis (see video)
  1446. Brain abscess (see video)
  1447. Guillain-Barré syndrome (see video)
  1448. References
  1449. Chapter 16 Alterations of Neurologic Function in Children
  1450. Normal Growth and Development of the Nervous System
  1451. HEALTH ALERT
  1452. Structural Malformations
  1453. Defects of Neural Tube Closure
  1454. FIGURE 16-1 Cranial Sutures and Fontanelles in Infancy. Fibrous union of suture lines and interlocking of serrated edges (occurs by 6 months; solid union requires approximately 12 years).
  1455. FIGURE 16-2 Disorders Associated With Specific Stages of Embryonic Development.
  1456. TABLE 16-1 REFLEXES OF INFANCY
  1457. FIGURE 16-3 Normal Spine, Meningocele, and Myelomeningocele. Diagram showing section through normal spine (A), meningocele (B), and myelomeningocele (C).
  1458. Clinical Manifestations
  1459. TABLE 16-2 FUNCTIONAL ALTERATIONS IN MYELODYSPLASIA RELATED TO LEVEL OF LESION
  1460. FIGURE 16-4 Normal Brain and Arnold-Chiari II Malformation. A, Diagram of normal brain. B, Diagram of Arnold-Chiari II malformation with downward displacement of cerebellar tonsils and medulla through foramen magnum causing compression and obstruction to flow of CSF.
  1461. Malformations of the Axial Skeleton
  1462. Spina Bifida
  1463. Cranial Deformities
  1464. FIGURE 16-5 Normal and Abnormal Head Configurations. Normal skull: Bones separated by membranous seams until sutures gradually close. Microcephaly and craniostenosis: Microcephaly is head circumference more than 2 standard deviations below the mean for age, gender, race, and gestation and reflects a small brain; craniosynostosis is premature closure of sutures. Scaphocephaly or dolichocephaly (frequency 56%): Premature closure of sagittal suture, resulting in restricted lateral growth. Brachycephaly: Premature closure of coronal suture, resulting in excessive lateral growth. Oxycephaly or acrocephaly (frequency 5.8% to 12%): Premature closure of all coronal and sagittal sutures, resulting in accelerated upward growth and small head circumference. Plagiocephaly (frequency 13%): Unilateral premature closure of coronal suture, resulting in asymmetric growth.
  1465. TABLE 16-3 CAUSES OF MICROCEPHALY
  1466. QUICK CHECK 16-1
  1467. Encephalopathies
  1468. Static Encephalopathies
  1469. Inherited Metabolic Disorders of the Central Nervous System
  1470. FIGURE 16-6 Metabolic Error and Consequences in Phenylketonuria.
  1471. TABLE 16-4 INHERITED METABOLIC DISORDERS OF THE CENTRAL NERVOUS SYSTEM
  1472. Defects in Amino Acid Metabolism
  1473. Phenylketonuria
  1474. Defects in Lipid Metabolism
  1475. TABLE 16-5 MAJOR TYPES OF SEIZURE DISORDERS FOUND IN CHILDREN
  1476. QUICK CHECK 16-2
  1477. Seizure Disorders
  1478. Epilepsy
  1479. Acute Encephalopathies
  1480. Reye Syndrome
  1481. Intoxications of the Central Nervous System
  1482. Meningitis
  1483. Bacterial meningitis
  1484. TABLE 16-6 COMMONLY INGESTED POISONS
  1485. Viral meningitis
  1486. Cerebrovascular Disease in Children
  1487. Tumors
  1488. Brain Tumors
  1489. FIGURE 16-7 Location of Brain Tumors in Children.
  1490. TABLE 16-7 BRAIN TUMORS IN CHILDREN
  1491. TABLE 16-8 TREATMENT STRATEGIES FOR CHILDHOOD BRAIN TUMORS
  1492. BOX 16-1 Clinical Manifestations of Brain Tumors
  1493. Headache
  1494. Vomiting
  1495. Neuromuscular Changes
  1496. Behavioral Changes
  1497. Cranial Nerve Neuropathy
  1498. Vital Sign Disturbances
  1499. Other Signs
  1500. Embryonal Tumors
  1501. Neuroblastoma
  1502. FIGURE 16-8 Retinoblastoma. The tumor occupies a large portion of the inside of the eye bulbus.
  1503. Retinoblastoma
  1504. FIGURE 16-9 The Two-Mutation Model of Retinoblastoma Development. In inherited retinoblastoma, the first mutation is transmitted through the germline of an affected parent. The second mutation occurs somatically in a retinal cell, leading to development of the tumor. In sporadic retinoblastoma, development of a tumor requires two somatic mutations.
  1505. QUICK CHECK 16-3
  1506. DID YOU UNDERSTAND?
  1507. Normal Growth and Development of the Nervous System
  1508. Structural Malformations
  1509. Encephalopathies
  1510. Cerebrovascular Disease in Children
  1511. Tumors
  1512. Key Terms
  1513. References
  1514. UNIT 5 The Endocrine System
  1515. Interactive Review – Unit 5
  1516. Chapter 17 Mechanisms of Hormonal Regulation
  1517. Mechanisms of Hormonal Regulation
  1518. Regulation of Hormone Release
  1519. FIGURE 17-1 Principal Endocrine Glands.
  1520. TABLE 17-1 STRUCTURAL CATEGORIES OF HORMONES
  1521. Hormone Transport
  1522. Mechanisms of Hormone Action
  1523. FIGURE 17-2 Feedback Loops. A, Endocrine feedback loops involving the hypothalamus-pituitary gland and end organs; in this example, the thyroid gland is illustrated (endocrine regulation). B, General model for control and negative feedback to hypothalamic-pituitary target organ systems. Negative feedback regulation is possible at three levels: target organ (ultra-short feedback), anterior pituitary (short feedback), and hypothalamus (long feedback). TRH, Thyroid-releasing hormone; TSH, thyroid-stimulating hormone; T3, triiodothyronine; T4, tetraiodothyronine (thyroxine).
  1524. TABLE 17-2 BINDING PROTEINS, THEIR HORMONES, AND VARIABLES THAT AFFECT THEIR CIRCULATING LEVELS
  1525. FIGURE 17-3 Regulation of Target Cell Sensitivity. A, Low hormone level and up-regulation, or an increase in the number of receptors. B, High hormone level and down-regulation, or a decrease in the number of receptors.
  1526. Hormone Receptors
  1527. First and Second Messengers
  1528. FIGURE 17-4 Hormone Binding at Target Cell.
  1529. TABLE 17-3 SECOND MESSENGERS IDENTIFIED FOR SPECIFIC HORMONES
  1530. FIGURE 17-5 Example of First- and Second-Messenger Mechanisms. A non–steroid hormone (first messenger) binds to a fixed receptor in the plasma membrane of the target cell (1). The hormone-receptor complex activates the G protein (2). The activated G protein (G) reacts with guanosine triphosphate (GTP), which in turn activates the membrane-bound enzyme adenylyl cyclase (3). Adenylyl cyclase catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) (second messenger) (4). cAMP activates protein kinase A (5). Protein kinases activate specific intracellular enzymes (6). These activated enzymes then influence specific cellular reactions, thus producing the target cell’s response to the hormone (7).
  1531. Steroid (Lipid-Soluble) Hormone Receptors
  1532. QUICK CHECK 17-1
  1533. Structure and Function of the Endocrine Glands
  1534. Hypothalamic-Pituitary System
  1535. The Anterior Pituitary
  1536. FIGURE 17-6 Steroid Hormone Mechanism. Lipid-soluble steroid hormone molecules detach from the carrier protein (1) and pass through the plasma membrane (2). Hormone molecules then diffuse into the nucleus, where they bind to a receptor to form a hormone-receptor complex (3). This complex then binds to a specific site on a deoxyribonucleic acid (DNA) molecule (4), triggering transcription of the genetic information encoded there (5). The resulting messenger ribonucleic acid (mRNA) molecule moves to the cytosol, where it associates with a ribosome, initiating synthesis of a new protein (6). This new protein—usually an enzyme or channel protein—produces specific effects on the target cell (7). The classic genomic action is typically slow (red arrows). Steroids also may exact rapid effects (green arrows) by binding to receptors on the plasma membrane (A) and activating an intercellular second messenger (B).
  1537. FIGURE 17-7 Pituitary Hormones and Their Target Organs. FSH, Follicle-stimulating hormone; ICSH, male analog of LH (interstitial cell–stimulating hormone); LH, luteinizing hormone.
  1538. FIGURE 17-8 Location and Structure of the Pituitary Gland (Hypophysis). The pituitary gland is located within the sella turcica of the skull’s sphenoid bone and is connected to the hypothalamus by a stalklike infundibulum. The infundibulum passes through a gap in the portion of the dura mater that covers the pituitary (the pituitary diaphragm). The inset shows that the pituitary is divided into an anterior portion, the adenohypophysis, and a posterior portion, the neurohypophysis. The adenohypophysis is further subdivided into the pars anterior and pars intermedia. The pars intermedia is almost absent in the adult pituitary.
  1539. FIGURE 17-9 Hypophysial Portal System. Neurons in the hypothalamus secrete releasing hormones into veins that carry the releasing hormones directly to the vessels of the adenohypophysis, thus bypassing the normal circulatory route.
  1540. FIGURE 17-10 Nerve Tracts From Hypothalamus to Posterior Lobe of Pituitary Gland. Nerve tracts from hypothalamus to posterior lobe of pituitary gland.
  1541. TABLE 17-4 HYPOTHALAMIC HORMONES (HYPOPHYSIOTROPIC HORMONES)
  1542. TABLE 17-5 TROPIC HORMONES OF THE ANTERIOR PITUITARY AND THEIR FUNCTIONS
  1543. The Posterior Pituitary
  1544. Antidiuretic hormone
  1545. Oxytocin
  1546. QUICK CHECK 17-2
  1547. Pineal Gland
  1548. Thyroid and Parathyroid Glands
  1549. Thyroid Gland
  1550. Regulation of thyroid hormone secretion
  1551. FIGURE 17-11 Thyroid and Parathyroid Glands. Note the relationship of the thyroid and parathyroid glands to each other, to the larynx (voice box), and to the trachea.
  1552. Synthesis of thyroid hormone
  1553. FIGURE 17-12 Thyroid Follicle Cells.
  1554. TABLE 17-6 THYROID GLAND HORMONES AND THEIR REGULATION AND FUNCTIONS
  1555. Actions of thyroid hormone
  1556. Parathyroid Glands
  1557. QUICK CHECK 17-3
  1558. Endocrine Pancreas
  1559. HEALTH ALERT
  1560. Insulin
  1561. FIGURE 17-13 The Pancreas. A, Pancreas dissected to show main and accessory ducts. The main duct may join the common bile duct, as shown here, to enter the duodenum by a single opening at the major duodenal papilla, or the two ducts may have separate openings. The accessory pancreatic duct is usually present and has a separate opening into the duodenum. B, Exocrine glandular cells (around small pancreatic ducts) and endocrine glandular cells of the pancreatic islets (adjacent to blood capillaries). Exocrine pancreatic cells secrete pancreatic juice, alpha endocrine cells secrete glucagon, and beta cells secrete insulin.
  1562. FIGURE 17-14 Insulin Action on Cells. Binding of insulin to its receptor causes autophosphorylation of the receptor, which then itself acts as a tyrosine kinase that phosphorylates insulin receptor substrate 1 (IRS-1). Numerous target enzymes, such as protein kinase B and MAP kinase, are activated and these enzymes have a multitude of effects on cell function. The glucose transporter (GLUT4) is recruited to the plasma membrane, where it facilitates glucose entry into the cell. The transport of amino acids, potassium, magnesium, and phosphate into the cell is also facilitated. The synthesis of various enzymes is induced or suppressed, and cell growth is regulated by signal molecules that modulate gene expression. IREs, Insulin responsive elements; mRNA, messenger ribonucleic acid.
  1563. HEALTH ALERT
  1564. TABLE 17-7 INSULIN ACTIONS
  1565. Amylin
  1566. Glucagon
  1567. Pancreatic Somatostatin
  1568. Gastrin, Grehlin, and Pancreatic Polypeptide
  1569. Adrenal Glands
  1570. FIGURE 17-15 Structure of the Adrenal Gland Showing Cell Layers (Zonae) of the Cortex. A, Zona glomerulosa secretes aldosterone. Zona fasciculata secretes abundant amounts of glucocorticoids, chiefly cortisol. Zona reticularis secretes minute amounts of sex hormones and glucocorticoids. B, A portion of the medulla is visible at the lower right in the photomicrograph (×35) and at the bottom of the drawing.
  1571. Adrenal Cortex
  1572. Glucocorticoids
  1573. Functions of the glucocorticoids
  1574. BOX 17-1 MAJOR FUNCTIONS OF GLUCOCORTICOIDS
  1575. Metabolic
  1576. Inflammatory and Immune
  1577. Other
  1578. Cortisol
  1579. Mineralocorticoids: aldosterone
  1580. Adrenal estrogens and androgens
  1581. FIGURE 17-16 Feedback Control of Glucocorticoid Synthesis and Secretion.
  1582. FIGURE 17-17 The Feedback Mechanisms Regulating Aldosterone Secretion. ACTH, Adrenocorticotropic hormone; cAMP, cyclic adenosine monophosphate.
  1583. Adrenal Medulla
  1584. FIGURE 17-18 Synthesis of Catecholamines.
  1585. QUICK CHECK 17-4
  1586. Neuroendocrine Response to Stressors
  1587. BOX 17-2 METHODS OF HORMONE MEASUREMENT
  1588. Radioimmunoassay (RIA)
  1589. Enzyme-Linked Immunosorbent Assay (ELISA)
  1590. Bioassay
  1591. GERIATRIC CONSIDERATIONS
  1592. General Endocrine Changes With Aging
  1593. Pituitary
  1594. Thyroid
  1595. Growth Hormone and Insulin-like Growth Factors
  1596. Pancreas
  1597. Adrenal
  1598. Gonads
  1599. DID YOU UNDERSTAND?
  1600. Mechanisms of Hormonal Regulation
  1601. Structure and Function of the Endocrine Glands
  1602. GERIATRIC CONSIDERATIONS: Aging & Its Effects on Specific Endocrine Glands
  1603. Key Terms
  1604. References
  1605. Chapter 18 Alterations of Hormonal Regulation
  1606. Mechanisms of Hormonal Alterations
  1607. TABLE 18-1 MECHANISMS OF HORMONE ALTERATIONS
  1608. Alterations of the Hypothalamic-Pituitary System
  1609. FIGURE 18-1 Loss of Hypothalamic Hormones. GnRH, Gonadotropin-releasing hormone; TRH, thyrotropin-releasing hormone; CRH, corticotropin-releasing hormone; PIF, prolactin inhibitory factor (probably dopamine); GHRH, growth hormone–releasing hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone; ACTH, adrenocorticotropic hormone.
  1610. Diseases of the Posterior Pituitary
  1611. Syndrome of Inappropriate Antidiuretic Hormone Secretion
  1612. Pathophysiology
  1613. Clinical Manifestations
  1614. Evaluation and Treatment
  1615. Diabetes Insipidus
  1616. Pathophysiology
  1617. Clinical Manifestations
  1618. Evaluation and Treatment
  1619. TABLE 18-2 SIGNS AND SYMPTOMS OF DIABETES INSIPIDUS (DI) AND SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) SECRETION
  1620. Diseases of the Anterior Pituitary
  1621. Hypopituitarism
  1622. Pathophysiology
  1623. Clinical Manifestations
  1624. FIGURE 18-2 Hypopituitary Dwarfism. A 4-year-old boy whose height is 25 inches. Girl is also 4 years old and has a normal height of 39 inches. Boy (dwarf) has a normal face, as well as head, trunk, and limbs of approximately normal proportions.
  1625. Evaluation and Treatment
  1626. Hyperpituitarism: Primary Adenoma
  1627. Pathophysiology
  1628. Clinical Manifestations
  1629. Evaluation and Treatment
  1630. QUICK CHECK 18-1
  1631. Hypersecretion of Growth Hormone: Acromegaly
  1632. Pathophysiology
  1633. FIGURE 18-3 Giantism. A pituitary giant and dwarf contrasted with normal-size men. Excessive secretion of growth hormone by the anterior lobe of the pituitary gland during the early years of life produces giants of this type, whereas deficient secretion of this substance produces well-formed dwarfs.
  1634. Clinical Manifestations
  1635. Evaluation and Treatment
  1636. FIGURE 18-4 Acromegaly. Chronologic sequence of photographs showing slow development of acromegaly.
  1637. Prolactinoma
  1638. Pathophysiology
  1639. Clinical Manifestations
  1640. Evaluation and Treatment
  1641. Alterations of Thyroid Function
  1642. HEALTH ALERT
  1643. Hyperthyroidism
  1644. Thyrotoxicosis
  1645. FIGURE 18-5 Common Causes of Hyperthyroidism. Hyperthyroidism may have several causes, among them: 1, Graves disease; 2, toxic multinodular goiter; 3, follicular adenoma; 4, thyroid medication.
  1646. Clinical Manifestations
  1647. Evaluation and Treatment
  1648. FIGURE 18-6 Clinical Manifestations of Hyperthyroidism and Hypothyroidism.
  1649. Hyperthyroid Conditions
  1650. Graves disease
  1651. FIGURE 18-7 Evaluation of Hyperthyroidism. Radioactive iodine is used in the differential diagnosis of hyperthyroidism.
  1652. FIGURE 18-8 Thyrotoxicosis (Graves Disease). A, Exophthalmos (large and protruding eyeballs often in association with a large goiter); B, Pretibial myxedema associated with Graves disease; note lumpy and swollen appearance from accumulation of connective tissue and pinkish purple discoloration.
  1653. Hyperthyroidism resulting from nodular thyroid disease
  1654. Thyrotoxic crisis
  1655. Hypothyroidism
  1656. Pathophysiology
  1657. Clinical Manifestations
  1658. FIGURE 18-9 Mechanisms of Primary and Secondary Hypothyroidism.
  1659. Evaluation and Treatment
  1660. Hypothyroid Conditions
  1661. Primary hypothyroidism
  1662. FIGURE 18-10 Myxedema. Note edema around eyes and facial puffiness. The hair is dry.
  1663. Congenital hypothyroidism
  1664. Thyroid Carcinoma
  1665. QUICK CHECK 18-2
  1666. Alterations of Parathyroid Function
  1667. Hyperparathyroidism
  1668. Pathophysiology
  1669. Clinical Manifestations
  1670. Evaluation and Treatment
  1671. Hypoparathyroidism
  1672. Pathophysiology
  1673. Clinical Manifestations
  1674. Evaluation and Treatment
  1675. QUICK CHECK 18-3
  1676. Dysfunction of the Endocrine Pancreas: Diabetes Mellitus
  1677. TABLE 18-3 CLASSIFICATION AND CHARACTERISTICS OF DIABETES MELLITUS
  1678. Types of Diabetes Mellitus
  1679. Type 1 Diabetes Mellitus
  1680. TABLE 18-4 EPIDEMIOLOGY AND ETIOLOGY OF DIABETES MELLITUS IN THE UNITED STATES
  1681. BOX 18-1 DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS
  1682. Categories of Increased Risk for Diabetes
  1683. Pathophysiology
  1684. Insulin, amylin, and glucagon
  1685. FIGURE 18-11 Pathophysiology of Type 1 Diabetes Mellitus.
  1686. Clinical Manifestations
  1687. Evaluation and Treatment
  1688. TABLE 18-5 CLINICAL MANIFESTATIONS AND MECHANISMS FOR TYPE 1 DIABETES MELLITUS
  1689. BOX 18-2 CRITERIA FOR THE DIAGNOSIS OF METABOLIC SYNDROME
  1690. Type 2 Diabetes Mellitus
  1691. Pathophysiology
  1692. FIGURE 18-12 Pathophysiology of Type 2 Diabetes Mellitus.
  1693. Clinical Manifestations
  1694. HEALTH ALERT
  1695. Evaluation and Treatment
  1696. Other Specific Types of Diabetes Mellitus and Gestational Diabetes Mellitus
  1697. TABLE 18-6 TYPES OF ORAL HYPOGLYCEMIC DRUGS
  1698. TABLE 18-7 COMMON ACUTE COMPLICATIONS OF DIABETES MELLITUS
  1699. Acute Complications of Diabetes Mellitus
  1700. FIGURE 18-13 Pathophysiology of DKA and HHNKS in Diabetes Mellitus.
  1701. TABLE 18-8 CHRONIC COMPLICATIONS OF DIABETES MELLITUS
  1702. Chronic Complications of Diabetes Mellitus
  1703. Metabolic Mechanisms of Chronic Complications
  1704. Hyperglycemia and the polyol pathway
  1705. Hyperglycemia and protein kinase C
  1706. Hyperglycemia and nonenzymatic glycation
  1707. Hyperglycemia and the hexosamine pathway
  1708. Microvascular Disease
  1709. Diabetic retinopathy
  1710. Diabetic nephropathy
  1711. Diabetic neuropathies
  1712. Macrovascular Disease
  1713. Coronary artery disease
  1714. Stroke
  1715. Peripheral vascular disease
  1716. FIGURE 18-14 Diabetes Mellitus and Atherosclerosis. Diabetes with its associated hyperglycemia, relative hypoinsulinemia, oxidative stress, and proinflammatory state contributes to atherogenesis by causing arterial endothelial dysfunction (impaired vasodilation and adhesion of inflammatory cells), dyslipidemia, and smooth muscle proliferation. LDL, Low-density lipoprotein; NO, nitric oxide; PKC, protein kinase C; Rage, receptor advanced glycation end product.
  1717. Infection
  1718. QUICK CHECK 18-4
  1719. Alterations of Adrenal Function
  1720. Disorders of the Adrenal Cortex
  1721. FIGURE 18-15 Symptoms of Cushing Disease.
  1722. Hypercortical Function (Cushing Syndrome, Cushing Disease)
  1723. Pathophysiology
  1724. FIGURE 18-16 Cushing Syndrome. A, Patient before onset of Cushing syndrome. B, Patient 4 months later. Moon facies is clearly demonstrated.
  1725. Clinical Manifestations
  1726. Evaluation and Treatment
  1727. Congenital Adrenal Hyperplasia
  1728. Hyperaldosteronism
  1729. Pathophysiology
  1730. Clinical Manifestations
  1731. Evaluation and Treatment
  1732. Hypersecretion of Adrenal Androgens and Estrogens
  1733. Adrenocortical Hypofunction
  1734. FIGURE 18-17 Virilization. Virilization of a young girl by an androgen-secreting tumor of the adrenal cortex. Masculine features include lack of breast development, increased muscle bulk, and hirsutism (excessive hair).
  1735. Addison disease
  1736. Pathophysiology
  1737. Clinical Manifestations
  1738. Evaluation and Treatment
  1739. Secondary hypocortisolism
  1740. Disorders of the Adrenal Medulla
  1741. Tumor of the Adrenal Medulla
  1742. Pathophysiology
  1743. Clinical Manifestations
  1744. QUICK CHECK 18-5
  1745. DID YOU UNDERSTAND?
  1746. Mechanisms of Hormonal Alterations
  1747. Alterations of the Hypothalamic-Pituitary System
  1748. Alterations of Thyroid Function
  1749. Alterations of Parathyroid Function
  1750. Dysfunction of the Endocrine Pancreas: Diabetes Mellitus
  1751. Alterations of Adrenal Function
  1752. Evaluation and Treatment
  1753. Key Terms
  1754. References
  1755. UNIT 6 The Hematologic System
  1756. Interactive Review – Unit 6
  1757. Chapter 19 Structure and Function of the Hematologic System
  1758. Components of the Hematologic System
  1759. Composition of Blood
  1760. Plasma and Plasma Proteins
  1761. TABLE 19-1 ORGANIC AND INORGANIC COMPONENTS OF ARTERIAL PLASMA
  1762. FIGURE 19-1 Composition of Whole Blood. Approximate values for the components of blood in a normal adult.
  1763. TABLE 19-2 CELLULAR COMPONENTS OF THE BLOOD
  1764. Cellular Components of the Blood
  1765. Erythrocytes
  1766. Leukocytes
  1767. Granulocytes
  1768. FIGURE 19-2 Blood Cells. Leukocytes are spherical and have irregular surfaces with numerous extending pili. Leukocytes are the cotton candy–like cells in yellow. Erythrocytes are flattened spheres with a depressed center (red).
  1769. FIGURE 19-3 Leukocytes. An example of leukocytes in human blood smear. A, Neutrophil. B, Eosinophil. C, Basophil with obscured nucleus. D, Typical monocyte showing vacuolated cytoplasm and cerebriform nucleus. E, Lymphocyte.
  1770. Agranulocytes
  1771. Platelets
  1772. FIGURE 19-4 Colored Micrograph of Platelets. The platelet on the left is moderately activated, with a generally round shape and the beginning of formation of pseudopodia (foot-like extensions from the membrane). The platelet on the right is fully activated, with extensive pseudopodia.
  1773. QUICK CHECK 19-1
  1774. Lymphoid Organs
  1775. Spleen
  1776. FIGURE 19-5 Red Cells in the Spleen. Scanning electron micrograph of spleen, demonstrating erythrocytes (numbered 1 through 6) squeezing through the fenestrated wall in transit from the splenic cord to the sinus. The view shows the endothelial lining of the sinus wall, to which platelets (P) adhere, along with “hairy” white cells, probably macrophages. The arrow shows a protrusion on a red blood cell (×5000).
  1777. Lymph Nodes
  1778. FIGURE 19-6 Cross Section of Lymph Node. Several afferent valved lymphatics bring lymph to node. A single efferent lymphatic leaves the node at the hilus. Note that the artery and vein also enter and leave at the hilus. Arrows show direction of lymph flow.
  1779. The Mononuclear Phagocyte System
  1780. QUICK CHECK 19-2
  1781. TABLE 19-3 MONONUCLEAR PHAGOCYTE SYSTEM (FORMERLY CALLED THE RETICULOENDOTHELIAL SYSTEM)
  1782. Development of Blood Cells
  1783. Hematopoiesis
  1784. Bone Marrow
  1785. Cellular Differentiation
  1786. FIGURE 19-7 Differentiation of Hematopoietic Cells. Curved arrows indicate proliferation and expansion of pre-hematopoietic stem cell populations. EPO, Erythropoietin; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; M-CSF, macrophage colony-stimulating factor; NK, natural killer; SCF, stem cell factor; TPO, thrombopoietin.
  1787. QUICK CHECK 19-3
  1788. Development of Erythrocytes
  1789. FIGURE 19-8 Hematopoiesis. Hematopoiesis from the stem cell pool; activity mainly in the bone marrow and in the peripheral blood.
  1790. FIGURE 19-9 Erythrocyte Differentiation. Erythrocyte differentiation from large, nucleated stem cell to small, nonnucleated erythrocyte.
  1791. FIGURE 19-10 Role of Erythropoietin in Regulation of Erythropoiesis. (1) Decreased arterial oxygen levels result in (2) decreased tissue oxygen (hypoxia) that (3) stimulates the kidney to increase (4) production of erythropoietin. Erythropoietin is carried to the bone marrow (5) and binds to erythropoietin receptors on proerythroblasts, resulting in increased red cell production and maturation and expansion of the erythron (6). The increased release of red cells into the circulation frequently corrects the hypoxia in the tissues (7). (8) Perception of normal oxygen levels by the kidney causes (9) diminished production of erythropoietin (negative feedback) and return to normal levels of erythrocyte production. EPO, Erythropoietin; O2, oxygen in the blood and tissue; RBCs, red blood cells.
  1792. Erythropoiesis
  1793. Hemoglobin Synthesis
  1794. FIGURE 19-11 Molecular Structure of Hemoglobin. Molecule is a spherical tetramer weighing approximately 64,500 daltons. It contains a pair of α-polypeptide chains and a pair of β-polypeptide chains and several heme groups.
  1795. FIGURE 19-12 Hemoglobin (Hb) Binding to Nitric Oxide. In the lungs, hemoglobin (Hb) binds to nitric oxide (NO) as S-nitrosothiol (SNO). In tissue, this SNO is released, and free, circulating NO is bound to a different site for exhalation. Fe, Iron; N, nitrogen.
  1796. Nutritional Requirements for Erythropoiesis
  1797. Iron cycle
  1798. FIGURE 19-13 Iron Cycle. Iron (Fe) released from gastrointestinal epithelial cells circulates in the bloodstream associated with its plasma carrier, transferrin. It is delivered to erythroblasts in bone marrow, where most of it is incorporated into hemoglobin. Mature erythrocytes circulate for approximately 120 days, after which they become senescent and are removed by the mononuclear phagocyte system (MPS). Macrophages of MPS (mostly in spleen) break down ingested erythrocytes and return iron to the bloodstream directly or after storing it as ferritin or hemosiderin.
  1799. TABLE 19-4 NUTRITIONAL REQUIREMENTS FOR ERYTHROPOIESIS
  1800. Normal Destruction of Senescent Erythrocytes
  1801. QUICK CHECK 19-4
  1802. FIGURE 19-14 Metabolism of Bilirubin Released by Heme Breakdown. MPS, Mononuclear phagocyte system.
  1803. Development of Leukocytes
  1804. Development of Platelets
  1805. Mechanisms of Hemostasis
  1806. FIGURE 19-15 Three Hemostatic Compartments.
  1807. TABLE 19-5 TYPES OF BLEEDING: SOURCES, VESSEL SIZE, AND SEALING REQUIREMENTS
  1808. Function of Platelets and Blood Vessels
  1809. HEALTH ALERT
  1810. FIGURE 19-16 Platelet Activation. A, After endothelial denudation, platelets and leukocytes adhere to the subendothelium in a monolayer fashion. B, Higher-power view showing leukocytes and platelets adherent to the subendothelium. C, High magnification of a thrombus showing a mixture of red cells and platelets incorporated into the fibrin meshwork.
  1811. Function of Clotting Factors
  1812. FIGURE 19-17 Blood Vessel Damage, Blood Clot, and Clot Dissolution.
  1813. Retraction and Lysis of Blood Clots
  1814. QUICK CHECK 19-5
  1815. FIGURE 19-18 Blood Clotting Mechanism. A, The complex clotting mechanism can be distilled into three basic steps: (1) release of clotting factors from both injured tissue cells and sticky platelets at the injury site (which form temporary platelet plug), (2) series of chemical reactions that eventually result in the formation of thrombin, and (3) formation of fibrin and trapping of blood cells to form a clot. B, An electron micrograph showing entrapped RBCs in a fibrin clot.
  1816. FIGURE 19-19 The Fibrinolytic System. Fibrinolysis is initiated by the binding of plasminogen to fibrin. Although tissue plasminogen activator (t-PA) initiates intravascular fibrinolysis, urokinase plasminogen activator (u-PA) is the major activator of fibrinolysis in tissue (extravascular). Plasmin digests the fibrin into smaller soluble pieces (fibrin degradation products). u-PAR, Urokinase-like plasminogen activator receptor.
  1817. TABLE 19-6 COMMON BLOOD TESTS FOR HEMATOLOGIC DISORDERS
  1818. Pediatrics & Hematologic Value Changes
  1819. Aging & Hematologic Value Changes
  1820. TABLE 19-7 HEMATOLOGIC VALUES FROM BIRTH TO ADULTHOOD
  1821. DID YOU UNDERSTAND?
  1822. Components of the Hematologic System
  1823. Development of Blood Cells
  1824. Mechanisms of Hemostasis
  1825. Pediatrics & Hematologic Value Changes
  1826. Aging & Hematologic Value Changes
  1827. KEY TERMS
  1828. References
  1829. Chapter 20 Alterations of Hematologic Function
  1830. Alterations of Erythrocyte Function
  1831. Classification of Anemias
  1832. TABLE 20-1 MORPHOLOGIC CLASSIFICATION OF ANEMIAS
  1833. Clinical Manifestations
  1834. FIGure 20-1 Progression and Manifestations of Anemia. DPG, 2,3-Diphosphoglycerate; SV, stroke volume.
  1835. Macrocytic-Normochromic Anemias
  1836. Pernicious Anemia
  1837. Pathophysiology
  1838. FIGURE 20-2 Appearance of Red Blood Cells in Various Disorders. A, Normal blood smear. B, Hypochromic-microcytic anemia (iron deficiency). C, Macrocytic anemia (pernicious anemia). D, Macrocytic anemia in pregnancy. E, Hereditary elliptocytosis. F, Myelofibrosis (teardrop). G, Hemolytic anemia associated with prosthetic heart valve. H, Microangiopathic anemia. I, Stomatocytes. J, Spherocytes (hereditary spherocytosis). K, Sideroblastic anemia; note the double population of red blood cells. L, Sickle cell anemia. M, Target cells (after splenectomy). N, Basophil stippling in case of unexplained anemia. O, Howell-Jolly bodies (after splenectomy).
  1839. Clinical Manifestations
  1840. Evaluation and Treatment
  1841. Folate Deficiency Anemias
  1842. Microcytic-Hypochromic Anemias
  1843. Iron Deficiency Anemia
  1844. Pathophysiology
  1845. Clinical Manifestations
  1846. FIGURE 20-3 Pallor and Iron Deficiency. Pallor of the skin, mucous membranes, and palmar creases in an individual with hemoglobin level of 9 g/dl. Palmar creases become as pale as the surrounding skin when the hemoglobin level approaches 7 g/dl.
  1847. FIGURE 20-4 Koilonychia. The nails are concave, ridged, and brittle.
  1848. FIGURE 20-5 Glossitis. Tongue of individual with iron deficiency anemia has bald, fissured appearance (arrow) caused by loss of papillae and flattening.
  1849. Evaluation and Treatment
  1850. Sideroblastic Anemia
  1851. Pathophysiology
  1852. Clinical Manifestations
  1853. Evaluation and Treatment
  1854. Normocytic-Normochromic Anemias
  1855. QUICK CHECK 20-1
  1856. Myeloproliferative Red Cell Disorders
  1857. Polycythemia Vera
  1858. TABLE 20-2 NORMOCYTIC-NORMOCHROMIC ANEMIAS
  1859. TABLE 20-3 DISORDERS CLASSIFIED AS POLYCYTHEMIA
  1860. Pathophysiology
  1861. Clinical Manifestations
  1862. Evaluation and Treatment
  1863. Iron Overload
  1864. Hereditary Hemochromatosis
  1865. Pathophysiology
  1866. Clinical Manifestations
  1867. Evaluation and Treatment
  1868. Alterations of Leukocyte Function
  1869. Quantitative Alterations of Leukocytes
  1870. Granulocyte and Monocyte Alterations
  1871. Lymphocyte Alterations
  1872. FIGURE 20-6 Origins of Leukemias and Lymphomas. Differentiation pathways of blood-forming cells and reported sites from which specific leukemias and lymphomas originate. Tumors of similar types are given the same background coloring. ALL, Acute lymphocytic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; NK, natural killer.
  1873. TABLE 20-4 OTHER CONDITIONS ASSOCIATED WITH NEUTROPHILS, EOSINOPHILS, BASOPHILS, MONOCYTES, AND LYMPHOCYTES
  1874. Infectious Mononucleosis
  1875. Clinical Manifestations
  1876. TABLE 20-5 ESTIMATED NEW CASES AND DEATHS FROM LEUKEMIA IN THE UNITED STATES—2007
  1877. Evaluation and Treatment
  1878. QUICK CHECK 20-2
  1879. Qualitative Alterations of Leukocytes
  1880. Leukemias
  1881. FIGURE 20-7 Philadelphia Chromosome. Schema of the Philadelphia (Ph) translocation (+) seen in chronic myelocytic leukemia. The Ph1 chromosome results from an exchange of materials between chromosomes 9 and 22—that is, t(9;22)(q34;q11). Because chromosome 22 loses much more of its long arm than is translocated to it from chromosome 9, chromosome 22 becomes much abbreviated and is known as Ph1.
  1882. Pathophysiology
  1883. Acute leukemias
  1884. Clinical Manifestations
  1885. Evaluation and Treatment
  1886. TABLE 20-6 CLINICAL MANIFESTATIONS AND RELATED PATHOPHYSIOLOGY IN LEUKEMIA
  1887. Chronic leukemias
  1888. Pathophysiology and Clinical Manifestations
  1889. TABLE 20-7 SOME EXAMPLES OF HUMAN COLONY-STIMULATING FACTORS
  1890. Morphologic Effects of Growth Factor. Marrow aspirate from a patient receiving granulocyte colony-stimulating factor (G-CSF) showing an early neutrophil response. There is a marked shift toward immaturity in the neutrophils with the majority at the promyelocyte and early myelocyte stages of maturation.
  1891. Evaluation and Treatment
  1892. QUICK CHECK 20-3
  1893. Alterations of Lymphoid Function
  1894. Lymphadenopathy
  1895. FIGURE 20-8 Lymphadenopathy. Individual with lymphocyte leukemia with extreme but symmetric lymphadenopathy.
  1896. Malignant Lymphomas
  1897. FIGURE 20-9 Lymph Nodes. A, Lymphocytes and histiocytes of Hodgkin lymphoma, nodular type. Large nodules with small, round lymphocytes, histiocytes, and scattered lymphocyte and histiocyte cells. B, Diagnostic Reed-Sternberg cell (arrow). A large multinucleated or multilobed cell with inclusion body–like nucleoli surrounded by a halo of clear nucleoplasm.
  1898. Hodgkin Lymphoma
  1899. Pathophysiology
  1900. TABLE 20-8 SUBTYPES OF CLASSIC HODGKIN LYMPHOMA
  1901. Clinical Manifestations
  1902. FIGURE 20-10 Hodgkin Lymphoma and Enlarged Cervical Lymph Node. Typical enlarged cervical lymph node in the neck (arrow) of a 35-year-old woman with Hodgkin lymphoma.
  1903. FIGURE 20-11 Common and Uncommon Involved Lymph Node Sites for Hodgkin Lymphoma.
  1904. Evaluation and Treatment
  1905. TABLE 20-9 DEFINITIONS OF STAGES OF HODGKIN DISEASE
  1906. Non-Hodgkin Lymphomas
  1907. Pathophysiology
  1908. TABLE 20-10 CLINICAL DIFFERENCES BETWEEN NON-HODGKIN LYMPHOMA AND HODGKIN LYMPHOMA
  1909. Clinical Manifestations
  1910. Evaluation and Treatment
  1911. FIGURE 20-12 Burkitt Lymphoma. Burkitt lymphoma involving the jaw in a young African boy.
  1912. Burkitt lymphoma
  1913. Pathophysiology
  1914. Clinical Manifestations
  1915. Evaluation and Treatment
  1916. FIGURE 20-13 Multiple Myeloma, Bone Marrow Aspirate. Normal marrow cells are largely replaced by plasma cells, including atypical forms with multiple nuclei (arrow), and cytoplasmic droplets containing immunoglobulin.
  1917. Multiple myeloma
  1918. Pathophysiology
  1919. Clinical Manifestations
  1920. FIGURE 20-14 Multiple (Plasma Cell) Myeloma. A, Roentgenogram of femur showing extensive bone destruction caused by tumor. Note absence of reactive bone formation. B, Gross specimen from same individual; myelomatous sections appear as dark granular sections.
  1921. Evaluation and Treatment
  1922. QUICK CHECK 20-4
  1923. Lymphoblastic lymphoma
  1924. Pathophysiology
  1925. Clinical Manifestations
  1926. Evaluation and Treatment
  1927. Alterations of Splenic Function
  1928. FIGURE 20-15 M Protein. Serum protein electrophoresis (PEL) is used to screen for M proteins in multiple myeloma. A, In normal serum the proteins separate into several regions between albumin (Alb) and a broad band in the gamma (γ) region, where most antibodies (gamma globulins) are found. Immunofixation (IFE) can identify the location of IgG (G), IgA (A), IgM (M), and kappa (K) and lambda (L) light chains. B, Serum from an individual with multiple myeloma contains a sharp M protein (M spike). The M protein is monoclonal and contains only one heavy chain and one light chain. In this instance the IFE identifies the M protein as an IgG containing a lambda light chain. C, Serum and urine protein electrophoretic patterns in an individual with multiple myeloma. Serum demonstrates an M protein (immunoglobulin) in the gamma region, and the urine has a large amount of the smaller-sized light chains with only a small amount of the intact immunoglobulin.
  1929. Pathophysiology
  1930. Clinical Manifestations
  1931. BOX 20-1 DISEASES RELATED TO CLASSIFICATION OF SPLENOMEGALY
  1932. Inflammation or Infection
  1933. Congestive
  1934. Infiltrative
  1935. Tumors or Cysts
  1936. Nonmalignant: Hamartoma
  1937. Evaluation and Treatment
  1938. QUICK CHECK 20-5
  1939. Alterations of Platelets and Coagulation
  1940. Disorders of Platelet Function
  1941. Thrombocytopenia
  1942. Pathophysiology
  1943. Heparin-induced thrombocytopenia
  1944. Clinical Manifestations
  1945. Evaluation and Treatment
  1946. Idiopathic (immune) thrombocytopenia purpura
  1947. Clinical Manifestations
  1948. Evaluation and Treatment
  1949. Thrombotic thrombocytopenia purpura
  1950. Clinical Manifestations
  1951. Evaluation and Treatment
  1952. Thrombocythemia
  1953. Pathophysiology
  1954. Clinical Manifestations
  1955. Evaluation and Treatment
  1956. Alterations of Platelet Function
  1957. HEALTH ALERT
  1958. Disorders of Coagulation
  1959. Impaired Hemostasis
  1960. Vitamin K deficiency
  1961. Liver disease
  1962. Consumptive Thrombohemorrhagic Disorders
  1963. Disseminated intravascular coagulation
  1964. Pathophysiology
  1965. BOX 20-2 CONDITIONS ASSOCIATED WITH DIC
  1966. FIGURE 20-16 Pathophysiology of Disseminated Intravascular Coagulation (DIC). Tissue factor initiates clot formation and this effect is increased by a decrease in natural anticoagulants (tissue factor inhibitor, antithrombin-III, and protein C). There also is a reduction in clot breakdown or fibrinolysis by plasmin. The combined effect is to cause thrombosis. The thrombotic activity consumes (uses up) coagulation factors and platelets, which can increase bleeding. Slow degradation of the fibrin clot produces fibrin degradation products (FDPs). FDPs have inhibitory effects on thrombin and platelets. The inhibition of coagulation, combined with the depletion of factors and platelets, then creates a bleeding tendency. Uncontrolled DIC will eventually lead to multiple end-organ failure. For further details of these mechanisms see Chapters 5 and 23. Inset is an example of DIC resulting from staphylococcal septicemia. Note the characteristic skin hemorrhage ranging from small purpuric lesions to larger ecchymoses.
  1967. Clinical Manifestations
  1968. BOX 20-3 CLINICAL MANIFESTATIONS ASSOCIATED WITH DIC*
  1969. Integumentary System
  1970. Central Nervous System
  1971. Gastrointestinal System
  1972. Pulmonary System
  1973. Renal System
  1974. Evaluation and Treatment
  1975. Thromboembolic Disorders
  1976. FIGURE 20-17 Thrombus. Thrombus arising in valve pocket at upper end of superficial femoral vein (arrow). Postmortem clot on the right is shown for comparison.
  1977. Hereditary hypercoagulability and thrombosis
  1978. Acquired hypercoagulability and thrombosis
  1979. QUICK CHECK 20-6
  1980. DID YOU UNDERSTAND?
  1981. Alterations of Erythrocyte Function
  1982. Myeloproliferative Red Cell Disorders
  1983. Alterations of Leukocyte Function
  1984. Alterations of Lymphoid Function
  1985. Alterations of Splenic Function
  1986. Alterations of Platelets and Coagulation
  1987. Key Terms
  1988. Thrombocytopenia (see video)
  1989. References
  1990. Chapter 21 Alterations of Hematologic Function in Children
  1991. Disorders of Erythrocytes
  1992. TABLE 21-1 ANEMIAS OF CHILDHOOD
  1993. Acquired Disorders
  1994. Iron Deficiency Anemia
  1995. Pathophysiology
  1996. Clinical Manifestations
  1997. Evaluation and Treatment
  1998. Hemolytic Disease of the Newborn
  1999. FIGURE 21-1 Hemolytic Disease of the Newborn (HDN). A, Before or during delivery, Rh-positive erythrocytes from the fetus enter the blood of an Rh-negative woman through a tear in the placenta. B, The mother is sensitized to the Rh antigen and produces Rh antibodies. Because this usually happens after delivery, there is no effect on the fetus in the first pregnancy. C, During a subsequent pregnancy with an Rh-positive fetus, Rh-positive erythrocytes cross the placenta, enter the maternal circulation, and (D) stimulate the mother to produce antibodies against the Rh antigen.
  2000. Pathophysiology
  2001. FIGURE 21-2 Sickle Cell Hemoglobin. A, Sickle cell hemoglobin is produced by a recessive allele of the gene encoding the beta-chain of the protein hemoglobin. It represents a single amino acid change—from glutamic acid to valine at the sixth position of the chain. In this model of a hemoglobin molecule, the position of the mutation can be seen near the end of the upper arm. B, Color-enhanced electron micrograph shows normal erythrocytes and sickled blood cell. C, Brief summary of sickle cell.
  2002. Clinical Manifestations
  2003. Evaluation and Treatment
  2004. FIGURE 21-3 Normal and Sickle-Shaped Blood Cells. Scanning electron micrograph of normal and sickle-shaped red blood cells. The irregularly shaped cells are the sickle cells; the circular cells are the normal blood cells.
  2005. Inherited Disorders
  2006. Sickle Cell Disease
  2007. FIGURE 21-4 Sickling of Erythrocytes.
  2008. TABLE 21-2 INHERITANCE OF SICKLE CELL DISEASE
  2009. Pathophysiology
  2010. FIGURE 21-5 Differences Between Effects of (A) Normal and (B) Sickled RBCs on Blood Circulation and Selected Consequences in a Child. C, Tissue Effects of Sickle Cell Anemia. CVA, Cerebrovascular accident.
  2011. Clinical Manifestations
  2012. FIGURE 21-6 Prepregnancy Sickle Cell Test. This technique has potential for detection of other inherited diseases. 1, Fertilization produces several embryos. 2, The embryos are tested for the presence of the gene. 3, The embryos without the gene are implanted. 4, Amniocentesis confirms whether the fetus (or fetuses) has the sickle cell gene. 5, Woman has a normal child.
  2013. Evaluation and Treatment
  2014. Thalassemias
  2015. Pathophysiology
  2016. FIGURE 21-7 Young Girl with Beta-Thalassemia Demonstrating Mild Frontal Bossing (Prominence) of the Right Forehead and Mild Maxillary Prominence.
  2017. Clinical Manifestations
  2018. FIGURE 21-8 Child with Beta-Thalassemia Major Who Has Severe Splenomegaly.
  2019. Evaluation and Treatment
  2020. QUICK CHECK 21-1
  2021. Disorders of Coagulation and Platelets
  2022. Inherited Hemorrhagic Disease
  2023. Hemophilias
  2024. Pathophysiology
  2025. TABLE 21-3 THE COAGULATION FACTORS AND ASSOCIATED DISORDERS
  2026. Clinical Manifestations
  2027. TABLE 21-4 THE HEMOPHILIAS
  2028. TABLE 21-5 LABORATORY TESTS OF COAGULATION
  2029. Evaluation and Treatment
  2030. Antibody-Mediated Hemorrhagic Disease
  2031. Idiopathic Thrombocytopenic Purpura
  2032. Pathophysiology
  2033. HEALTH ALERT
  2034. Clinical Manifestations
  2035. Evaluation and Treatment
  2036. QUICK CHECK 21-2
  2037. TABLE 21-6 MAJOR CLASSIFICATIONS OF LEUKEMIA
  2038. Neoplastic Disorders
  2039. Leukemia and Lymphoma
  2040. Leukemia
  2041. Pathogenesis
  2042. Clinical Manifestations
  2043. Evaluation and Treatment
  2044. FIGURE 21-9 Monoblasts From Acute Monoblastic Leukemia. Monoblasts in a marrow smear from an individual with acute monoblastic leukemia. The monoblasts are larger than myeloblasts and usually have abundant cytoplasm, often with delicate scattered azurophilic granules (an element that stains well with blue aniline dyes).
  2045. HEALTH ALERT
  2046. FIGURE 21-10 Lymphomas. A, Large cell lymphoma. The tumor contains prominent areas of sclerosis (arrow). B, Burkitt lymphoma. A starry sky pattern is seen at low magnification.
  2047. Lymphomas
  2048. Non-Hodgkin lymphoma
  2049. Pathogenesis
  2050. Clinical Manifestations
  2051. Evaluation and Treatment
  2052. FIGURE 21-11 Diagnostic Reed-Sternberg Cell. A large multinucleated or multilobated cell with (arrow) inclusion body–like nucleoli surrounded by a halo of clear nucleoplasm.
  2053. Hodgkin Lymphoma
  2054. FIGURE 21-12 Main Areas of Lymphadenopathy and Organ Involvement in Hodgkin Lymphoma.
  2055. QUICK CHECK 21-3
  2056. DID YOU UNDERSTAND?
  2057. Disorders of Erythrocytes
  2058. Disorders of Coagulation and Platelets
  2059. Neoplastic Disorders
  2060. KEY TERMS
  2061. Hemophilia A (see video)
  2062. References
  2063. UNIT 7 The Cardiovascular and Lymphatic Systems
  2064. Interactive Review – Unit 7
  2065. Chapter 22 Structure and Function of the Cardiovascular and Lymphatic Systems
  2066. The Circulatory System
  2067. The Heart
  2068. FIGURE 22-1 Diagram Showing Serially Connected Pulmonary and Systemic Circulatory Systems and How to Trace the Flow of Blood. Right heart chambers propel unoxygenated blood through the pulmonary circulation, and the left heart propels oxygenated blood through the systemic circulation.
  2069. Structures That Direct Circulation Through the Heart
  2070. The Heart Wall
  2071. FIGURE 22-2 Wall of the Heart. This section of the heart wall shows the fibrous pericardium, the parietal and visceral layers of the serous pericardium (with the pericardial space between them), the myocardium, and the endocardium. Note the fatty connective tissue between the visceral layer of the serous pericardium (epicardium) and the myocardium. Note also that the endocardium covers beamlike projections of myocardial muscle tissue called trabeculae.
  2072. Chambers of the Heart
  2073. FIGURE 22-3 Structures That Direct Blood Flow Through the Heart. Arrows indicate path of blood flow through chambers, valves, and major vessels.
  2074. Fibrous Skeleton of the Heart
  2075. Valves of the Heart
  2076. FIGURE 22-4 Structure of the Heart Valves. A, The heart valves in this drawing are depicted as viewed from above (looking down into the heart). Note that the semilunar (SL) valves are closed and the atrioventricular (AV) valves are open, as when the atria are contracting. View B is similar to view A except that the semilunar valves are open and the atrioventricular valves are closed, as when the ventricles are contracting.
  2077. The Great Vessels
  2078. Blood Flow During the Cardiac Cycle
  2079. FIGURE 22-5 Blood Flow Through the Heart During a Single Cardiac Cycle. A, During diastole, blood flows into atria, atrioventricular valves are pushed open, and blood begins to fill ventricles. Atrial systole squeezes any blood remaining in atria out into ventricles. B, During ventricular systole, ventricles contract, pushing blood out through semilunar valves into pulmonary artery (right ventricle) and aorta (left ventricle).
  2080. Normal Intracardiac Pressures
  2081. FIGURE 22-6 Composite Chart of Heart Function. This chart is a composite of several diagrams of heart function (cardiac pumping cycle, blood pressure, blood flow, volume, heart sounds, venous pulse, and electrocardiogram [ECG]), all adjusted to the same timescale.
  2082. TABLE 22-1 NORMAL INTRACARDIAC PRESSURES
  2083. QUICK CHECK 22-1
  2084. FIGURE 22-7 The Phases of the Cardiac Cycle. 1, Atrial systole. 2, Isovolumetric ventricular contraction. Ventricular volume remains constant as pressure increases rapidly. 3, Ejection. 4, Isovolumetric ventricular relaxation. Both sets of valves are closed, and the ventricles are relaxing. 5, Passive ventricular filling. The atrioventricular (AV) valves are forced open, and the blood rushes into the relaxing ventricles.
  2085. Structures That Support Cardiac Metabolism: The Coronary Vessels
  2086. Coronary Arteries
  2087. Collateral Arteries
  2088. FIGURE 22-8 Coronary Circulation. A, Arteries. B, Veins. Both A and B are anterior views of the heart. Vessels near the anterior surface are more darkly colored than vessels of the posterior surface seen through the heart. C, View of the anterior (sternocostal) surface.
  2089. BOX 22-1 MAIN BRANCHES OF THE CORONARY ARTERIES
  2090. Coronary Capillaries
  2091. Coronary Veins and Lymphatic Vessels
  2092. Structures That Control Heart Action
  2093. The Conduction System
  2094. FIGURE 22-9 Conduction System of Heart. Specialized cardiac muscle cells in the wall of the heart rapidly conduct an electrical impulse throughout the myocardium. The signal is initiated by the sinoatrial (SA) node (pacemaker) and spreads to the rest of the atrial myocardium and to the atrioventricular (AV) node. The AV node then initiates a signal that is conducted through the ventricular myocardium by way of the atrioventricular bundle (of His) and Purkinje fibers.
  2095. QUICK CHECK 22-2
  2096. Propagation of cardiac action potentials
  2097. TABLE 22-2 INTERCELLULAR AND EXTRACELLULAR ION CONCENTRATIONS IN THE MYOCARDIUM
  2098. The normal electrocardiogram
  2099. Automaticity
  2100. FIGURE 22-10 Electrocardiogram (ECG) and Cardiac Electrical Activity. A, Normal ECG. Depolarization and repolarization. B, ECG intervals among P, QRS, and T waves. C, Schematic representation of ECG and its relationship to cardiac electrical activity. AV, Atrioventricular; LA, left atrium; LBB, left bundle branch; LV, left ventricle; RA, right atrium; RBB, right bundle branch; RV, right ventricle.
  2101. Rhythmicity
  2102. QUICK CHECK 22-3
  2103. Cardiac Innervation
  2104. Sympathetic and parasympathetic nerves
  2105. Myocardial Cells
  2106. FIGURE 22-11 Autonomic Innervation of Cardiovascular System. Inhibition (−); activation (+).
  2107. FIGURE 22-12 Cardiac Muscle Fiber. Unlike other types of muscle fibers, cardiac muscle fiber is typically branched and forms junctions, called intercalated disks, with adjacent cardiac muscle fibers. Like skeletal muscle fibers, cardiac muscle fibers contain sarcoplasmic reticula and T tubules—although these structures are not as highly organized as in skeletal muscle fibers.
  2108. Actin, myosin, and the troponin-tropomyosin complex
  2109. Myocardial metabolism
  2110. FIGURE 22-13 Structure of Myosin. A, Each myosin molecule is a coil of two chains wrapped around one another. At the end of each chain is a globular region, much like a golf club, called the head. B, Myosin molecules usually are combined into filaments, which are stalks of myosin from which the heads protrude. C, Actin microfilament.
  2111. Myocardial Contraction and Relaxation
  2112. FIGURE 22-14 Myofilaments and Mechanisms of Muscle Contraction. A, Thin and thick myofilaments. In resting muscle, calcium ions are stored in the sarcoplasmic reticulum. When an action potential reaches the muscle cell, the T tubules carry the action potential deep into the sarcoplasm. The action potential causes the sarcoplasmic reticulum to release the store of calcium ions. B, In resting muscle the myosin binding sites are covered by troponin and tropomyosin. The calcium ions released into the sarcoplasm as a result of action potential bind to the troponin. C, This binding causes the tropomyosin and troponin to move out of the way of the myosin binding sites, leaving the myosin heads free to bind to the actin microfilament. ATP, Adenosine triphosphate.
  2113. Calcium and excitation-contraction coupling
  2114. FIGURE 22-15 Cross-Bridge Theory of Muscle Contraction. A, Each myosin cross-bridge in the thick filament moves into a resting position after an adenosine triphosphate (ATP) molecule binds and transfers its energy. B, Calcium ions released from the sarcoplasmic reticulum bind to troponin in the thin filament, allowing tropomyosin to shift from its position blocking the active sites of actin molecules. C, Each myosin cross-bridge then binds to an active site on a thin filament, displacing the remnants of ATP hydrolysis—adenosine diphosphate (ADP) and inorganic phosphate (Pi). D, The release of stored energy from step A provides the force needed for each cross-bridge to move back to its original position, pulling actin along with it. Each cross-bridge will remain bound to actin until another ATP molecule binds to it and pulls it back into its resting position, A.
  2115. Myocardial relaxation
  2116. QUICK CHECK 22-4
  2117. Factors Affecting Cardiac Output
  2118. Preload
  2119. TABLE 22-3 CARDIOVASCULAR FUNCTION IN ELDERLY PERSONS
  2120. Afterload
  2121. FIGURE 22-16 Frank-Starling Law of the Heart. Relationship between length and tension in heart. End-diastolic volume determines end-diastolic length of ventricular muscle fibers and is proportional to tension generated during systole, as well as to cardiac output, stroke volume, and stroke work. A change in myocardial contractility causes the heart to perform on a different length-tension curve. A, Increased contractility; B, normal contractility; C, heart failure or decreased contractility.
  2122. Myocardial Contractility
  2123. FIGURE 22-17 Factors Affecting Cardiac Performance. Cardiac output, which is the amount of blood (in liters) ejected by the heart per minute, depends on heart rate (beats per minute) and stroke volume (milliliters of blood ejected during ventricular systole).
  2124. Heart Rate
  2125. Cardiovascular control centers in the brain
  2126. Neural reflexes
  2127. Atrial receptors
  2128. Hormones and biochemicals
  2129. FIGURE 22-18 Heart Rate and Intravenous Infusions. Intravenous infusions of blood or electrolyte solutions tend to increase heart rate through the Bainbridge reflex and to decrease heart rate through the baroreceptor reflex. The actual change in heart rate induced by such infusions is the result of these two opposing effects.
  2130. FIGURE 22-19 Circulatory System. A, Principal arteries of body. B, Principal veins of body.
  2131. QUICK CHECK 22-5
  2132. The Systemic Circulation
  2133. Structure of Blood Vessels
  2134. FIGURE 22-20 Structure of the Blood Vessels. The tunica externa of the veins are color-coded blue and the arteries red.
  2135. FIGURE 22-21 Capillary Wall. A, Capillaries have a wall composed of only a single layer of flattened cells, whereas the walls of the larger vessels also have smooth muscle. B, Capillary with red blood cells in single file (× 500).
  2136. Arterial Vessels
  2137. Endothelium
  2138. FIGURE 22-22 Capillary Network. Blood enters network as arterial blood and exits as venous blood.
  2139. FIGURE 22-23 Endothelium. Practically imperceptible, the endothelial cells arrange themselves as a fine lining that has numerous life-support functions (see Table 22-4).
  2140. Veins
  2141. Factors Affecting Blood Flow
  2142. Pressure and Resistance
  2143. TABLE 22-4 FUNCTIONS OF THE ENDOTHELIUM
  2144. FIGURE 22-24 Endothelium Regulation of Vasomotion (Constriction and Dilation) and Platelet Aggregation by Release of a Variety of Constricting and Dilating Substances. Constricting factors include arachidonic acid and metabolites, such as thromboxane A2 (which aspirin inhibits), and a potent amino acid peptide called endothelin. The endothelium also converts angiotensin I into angiotensin II by the membrane-bound angiotensin-converting enzyme that also metabolizes the endogenous endothelium-dependent vasodilator, bradykinin.
  2145. FIGURE 22-25 Factors Causing Endothelium-Dependent Vasodilation. A variety of exogenous pharmacologic substances, platelet-derived factors, and shear stress can promote release of nitric oxide by stimulating nitric oxide synthase (NOS). Prostacyclin (PGI2) causes relaxation of vascular smooth muscle cells by a cyclic adenosine monophosphate (cAMP)-dependent mechanism, and both nitric oxide and PGI2 inhibit platelet aggregation. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; 5-HT, serotonin.
  2146. FIGURE 22-26 Valves of Vein. Pooled blood is moved toward heart as valves are forced open by pressure from volume of blood downstream.
  2147. FIGURE 22-27 Muscle Pump.
  2148. FIGURE 22-28 Lumen Diameter, Blood Flow, and Resistance. A, Effect of lumen diameter (d) on flow through vessel. B, Blood flows with great speed in the large arteries. However, branching of arterial vessels increases the total cross-sectional area of the arterioles and capillaries, reducing the flow rate. When capillaries merge into venules and venules merge into veins, the total cross-sectional area decreases, causing the flow rate to increase.
  2149. Velocity
  2150. Laminar Versus Turbulent Flow
  2151. FIGURE 22-29 Laminar and Turbulent Blood Flow. A, Laminar flow. Fluid flows in long, smooth-walled tubes as if it is composed of a large number of concentric layers. B, Turbulent flow. Turbulent flow is caused by numerous small currents flowing crosswise or oblique to the long axis of the vessel, resulting in flowing whorls and eddy currents.
  2152. Vascular Compliance
  2153. QUICK CHECK 22-6
  2154. Regulation of Blood Pressure
  2155. Arterial Pressure
  2156. Effects of Cardiac Output
  2157. Effects of Total Peripheral Resistance
  2158. FIGURE 22-30 Factors Regulating Blood Pressure.
  2159. Baroreceptors
  2160. Arterial chemoreceptors
  2161. Effect of Hormones
  2162. Antidiuretic hormone
  2163. Renin-angiotensin system
  2164. FIGURE 22-31 Baroreceptors and Chemoreceptor Reflex Control of Blood Pressure. A, Baroreceptor reflexes. B, Vasomotor chemoreflexes.
  2165. FIGURE 22-32 Three Mechanisms That Influence Total Plasma Volume. The antidiuretic hormone (ADH) mechanism and renin-angiotensin and aldosterone mechanisms tend to increase water retention and thus increase total plasma volume. The natriuretic peptides antagonize these mechanisms by promoting water loss and sodium loss, thus promoting a decrease in total plasma volume. ACE, Angiotensin-converting enzyme; ANP, atrial natriuretic peptide; NPs, natriuretic peptides.
  2166. Natriuretic peptides
  2167. Adrenomedullin
  2168. Insulin
  2169. Adipokines
  2170. FIGURE 22-33 Angiotensins and the Organs Affected. A, The shaded blue area is the classic pathway of biosynthesis that generates the renin and angiotensin I. Angiotensinogen is synthesized in the liver and is released into the blood where it is cleaved to form angiotensin I by renin secreted by cells in the kidneys. Angiotensin-converting enzyme (ACE) in the lungs catalyzes the formation of angiotensin II from angiotensin I and destroys the potent vasodilator bradykinin. Further cleavage generates the angiotensins III and IV. The reddish shading shows the organs affected by angiotensin II, including brain, heart, adrenals, kidney, and the kidney’s efferent arterioles. The dashed arrow (left) shows the inhibition of renin by angiotensin II. B, Summary of angiotensin II effects on blood vessel structure and function leading to atherosclerosis.
  2171. HEALTH ALERT
  2172. FIGURE 22-34 Angiotensins and Their Receptors, AT1 and AT2. Blocking the angiotensin-converting enzyme (ACE) with ACE inhibitors decreases the amount of angiotensin II. Blocking the receptor AT1 with drugs (AT1 antagonists) blocks the attachment of angiotensin II to the cell, preventing the cellular effects and decreasing the vascular, cardiac, and renal effects.
  2173. Venous Pressure
  2174. Regulation of the Coronary Circulation
  2175. HEALTH ALERT
  2176. Autoregulation
  2177. BOX 22-2 VASCULAR PROTECTION AND INJURY PROPERTIES OF INSULIN
  2178. Protection
  2179. Injury
  2180. Autonomic Regulation
  2181. QUICK CHECK 22-7
  2182. The Lymphatic System
  2183. FIGURE 22-35 Role of the Lymphatic System in Fluid Balance. Fluid from plasma flowing through the capillaries moves into interstitial spaces. Although much of this interstitial fluid is either absorbed by tissue cells or reabsorbed by capillaries, some of the fluid tends to accumulate in the interstitial spaces. As this fluid builds up, it tends to drain into lymphatic vessels that eventually return the fluid to the venous blood.
  2184. FIGURE 22-36 Principle Organs of the Lymphatic System. The inset shows the areas drained by the right lymphatic duct (green) and the thoracic duct (blue).
  2185. QUICK CHECK 22-8
  2186. FIGURE 22-37 Lymphatic Capillaries. A, Schematic representation of lymphatic capillaries. B, Anatomic components of microcirculation.
  2187. DID YOU UNDERSTAND?
  2188. The Circulatory System
  2189. The Heart
  2190. The Systemic Circulation
  2191. The Lymphatic System
  2192. KEY TERMS
  2193. References
  2194. Chapter 23 Alterations of Cardiovascular Function
  2195. Diseases of the Veins
  2196. Varicose Veins and Chronic Venous Insufficiency
  2197. FIGURE 23-1 Varicose Veins of the Leg (arrow).
  2198. Thrombus Formation in Veins
  2199. FIGURE 23-2 Venous Stasis Ulcer.
  2200. Superior Vena Cava Syndrome
  2201. QUICK CHECK 23-1
  2202. Diseases of the Arteries
  2203. Hypertension
  2204. TABLE 23-1 CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS AGE 18 YEARS AND OLDER
  2205. Factors Associated With Primary Hypertension
  2206. RISK FACTORS
  2207. Pathophysiology
  2208. Primary Hypertension
  2209. FIGURE 23-3 Factors That Cause a Shift in the Pressure-Natriuresis Relationship. Numerous factors have been implicated in the pathogenesis of sodium retention in individuals with hypertension. These factors cause less renal excretion of salt than would normally occur with increased blood pressure. This is called a shift in the pressure-natriuresis relationship and is believed to be a central process in the pathogenesis of primary hypertension. RAA, Renin-angiotensin-aldosterone; SNS, sympathetic nervous system.
  2210. HEALTH ALERT
  2211. HEALTH ALERT
  2212. FIGURE 23-4 Pathophysiology of Hypertension. Numerous genetic vulnerabilities have been linked to hypertension and these, in combination with environmental risks, cause neurohumoral dysfunction (sympathetic nervous system [SNS], renin-angiotensin-aldosterone [RAA] system, adducin (cytoskeleton protein involved with Na/K ATPase), and natriuretic hormones) and promote inflammation and insulin resistance. Insulin resistance and neurohumoral dysfunction contribute to sustained systemic vasoconstriction and increased peripheral resistance. Inflammation contributes to renal dysfunction, which, in combination with the neurohumoral alterations, results in renal salt and water retention and increased blood volume. Increased peripheral resistance and increased blood volume are two primary causes of sustained hypertension.
  2213. Secondary Hypertension
  2214. Complicated Hypertension
  2215. Clinical Manifestations
  2216. Evaluation and Treatment
  2217. TABLE 23-2 PATHOLOGIC EFFECTS OF SUSTAINED, COMPLICATED PRIMARY HYPERTENSION
  2218. Orthostatic (Postural) Hypotension
  2219. QUICK CHECK 23-2
  2220. Aneurysm
  2221. FIGURE 23-5 Aneurysm. A three dimensional CT scan shows the aneurysm (A) involves the ascending thoracic aorta. D, descending aorta; LV, left ventricle
  2222. FIGURE 23-6 Longitudinal Sections Showing Types of Aneurysms. A, The fusiform circumferential and fusiform saccular aneurysms are true aneurysms, caused by weakening of the vessel wall. False and saccular aneurysms involve a break in the vessel wall, usually caused by trauma. B, Dissecting aneurysm of thoracic aorta (arrow).
  2223. Thrombus Formation
  2224. QUICK CHECK 23-3
  2225. Embolism
  2226. Peripheral Vascular Disease
  2227. Thromboangiitis Obliterans (Buerger disease)
  2228. TABLE 23-3 TYPES OF EMBOLI
  2229. FIGURE 23-7 Arteriosclerosis. A, Cross section of a normal artery and an artery altered by disease. B, A small artery in the myocardium is occluded by a mass of blue-staining platelets, yellow-staining red cells, and cholesterol bodies.
  2230. Raynaud Phenomenon and Disease
  2231. QUICK CHECK 23-4
  2232. Atherosclerosis
  2233. Pathophysiology
  2234. FIGURE 23-8 Low-Density Lipoprotein Oxidation. Low-density lipoprotein (LDL) enters the arterial intima through an intact endothelium. In hypercholesterolemia, the influx of LDL exceeds the eliminating capacity and an extracellular pool of LDL is formed. This is enhanced by association of LDL with the extracellular matrix. Intimal LDL is oxidized through the action of free oxygen radicals formed by enzymatic or nonenzymatic reactions. This generates proinflammatory lipids that induce endothelial expression of the adhesion molecule (i.e., vascular cell adhesion molecule-1), activate complement, and stimulate chemokine secretion. All of these factors cause adhesion and entry of mononuclear leukocytes, particularly monocytes and T lymphocytes. Monocytes differentiate into macrophages. Macrophages up-regulate and internalize oxidized LDL and transform into foam cells. Macrophage uptake of oxidized LDL also leads to presentation of its fragments to antigen-specific T cells. This induces an autoimmune reaction that leads to production of proinflammatory cytokines. Such cytokines include interferon-γ, tumor necrosis factor-alpha, and interleukin-1, which act on endothelial cells to stimulate expression of adhesion molecules and procoagulant activity; on macrophages to activate proteases, endocytosis, nitric oxide (NO), and cytokines; and on smooth muscle cells (SMCs) to induce NO production and inhibit growth and collagen and actin expression. LDL, Low-density lipoprotein.
  2235. FIGURE 23-9 Progression of Atherosclerosis. A, Damaged endothelium. B, Diagram of fatty streak and lipid core formation (see Figure 23-8 for a diagram of oxidized low-density lipoprotein [LDL]). C, Diagram of fibrous plaque. Raised plaques are visible: some are yellow; others are white. D, Diagram of complicated lesion; thrombus is red; collagen is blue. Plaque is complicated by red thrombus deposition.
  2236. FIGURE 23-10 Atherosclerosis. A, Concentric coronary plaque. The lumen is central. There are multiple, new small blood vessels within the plaque, the late result of disruption. B, Cell types in fibrolipid plaque. The plaque cap (brownish color) contains numerous elongated, smooth muscle cells; some contain lipid. Macrophages are clustered on the edge of the core.
  2237. Clinical Manifestations
  2238. Evaluation and Treatment
  2239. Peripheral Artery Disease
  2240. Coronary Artery Disease, Myocardial Ischemia, and Acute Coronary Syndromes
  2241. Development of Coronary Artery Disease
  2242. Dyslipidemia
  2243. HEALTH ALERT
  2244. TABLE 23-4 CRITERIA FOR DYSLIPIDEMIA
  2245. Hypertension
  2246. Cigarette smoking
  2247. Diabetes mellitus
  2248. Obesity/sedentary lifestyle
  2249. Nontraditional risk factors
  2250. Markers of inflammation and thrombosis
  2251. Hyperhomocysteinemia
  2252. Adipokines
  2253. Infection
  2254. FIGURE 23-11 Cycle of Ischemic Events.
  2255. HEALTH ALERT
  2256. New Serum Markers of Cardiovascular Risk
  2257. Myocardial Ischemia
  2258. Pathophysiology
  2259. FIGURE 23-12 Angiogram of Coronary Arteries. A, Baseline. B, Transient total occlusion of left anterior descending branch of the left coronary artery after mental stress. C, After nitrates and nifedipine, artery reopened to same diameter as baseline.
  2260. Clinical Manifestations
  2261. FIGURE 23-13 Ischemic Cost of Aggravation. Linkages among daily mental and emotional stimuli, brain activity, and coronary and myocardial physiology.
  2262. Evaluation and Treatment
  2263. FIGURE 23-14 Pathophysiologic Model of the Effects of Acute Stress as a Trigger of Cardiac Clinical Events. Acting via the central and autonomic nervous systems, stress can produce a cascade of physiologic responses that may lead to myocardial ischemia, especially in persons with coronary artery disease; potentially fatal dysrhythmia; plaque rupture; or coronary thrombosis. LV, Left ventricular; MI, myocardial infarction; VF, ventricular fibrillation; VT, ventricular tachycardia.
  2264. FIGURE 23-15 Electrocardiogram (ECG) and Ischemia. A, Normal ECG. B, Electrocardiographic alterations associated with ischemia.
  2265. HEALTH ALERT
  2266. Women and Heart Disease
  2267. QUICK CHECK 23-5
  2268. Acute Coronary Syndromes
  2269. Unstable angina
  2270. FIGURE 23-16 Pathophysiology of Acute Coronary Syndromes. The atherosclerotic process can lead to stable plaque formation and stable angina or can result in unstable plaques that are prone to rupture and thrombus. Thrombus formation on a ruptured plaque that disperses in less than 20 minutes leads to transient ischemia and unstable angina. If the vessel obstruction is sustained, myocardial infarction with inflammation and necrosis of the myocardium results. In addition, myocardial infarction is associated with other structural and functional changes, including myocyte stunning and hibernation and myocardial remodeling (see Figure 23-35).
  2271. FIGURE 23-17 Pathogenesis of Unstable Plaques and Thrombus Formation.
  2272. BOX 23-1 THREE PRINCIPAL PRESENTATIONS OF UNSTABLE ANGINA
  2273. Myocardial infarction
  2274. Pathophysiology
  2275. Cellular injury
  2276. FIGURE 23-18 Plaque Disruption and Myocardial Infarction. A, Plaque disruption. The cap of the lipid-rich plaque has become torn with the formation of a thrombus, mostly inside the plaque. B, Myocardial infarction. This infarct is 6 days old. The center is yellow and necrotic with a hemorrhagic red rim. The responsible arterial occlusion is probably in the right coronary artery. The infarct is on the posterior wall.
  2277. Cellular death
  2278. Structural and functional changes
  2279. Repair
  2280. FIGURE 23-19 Myocardial Infarction. A, Local infarct confined to one region. B, Massive large infarct caused by occlusion of three coronary arteries.
  2281. Clinical Manifestations
  2282. Complications
  2283. Evaluation and Treatment
  2284. FIGURE 23-20 Three Interacting Factors Related to Sudden Cardiac Death. The three factors are ischemia, left ventricular dysfunction, and electrical instability.
  2285. FIGURE 23-21 Electrocardiographic Alterations Associated With the Three Zones of Myocardial Infarction.
  2286. TABLE 23-5 COMPLICATIONS WITH MYOCARDIAL INFARCTIONS
  2287. BOX 23-2 UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION
  2288. QUICK CHECK 23-6
  2289. Disorders of the Heart Wall
  2290. Disorders of the Pericardium
  2291. Acute Pericarditis
  2292. FIGURE 23-22 Acute Pericarditis. Note shaggy coat of fibers covering the surface of heart.
  2293. Pericardial Effusion
  2294. FIGURE 23-23 Exudate of Blood in the Pericardial Sac from Rupture of Aneurysm.
  2295. FIGURE 23-24 Constrictive Pericarditis. The fibrotic pericardium encases the heart in a rigid shell.
  2296. Constrictive Pericarditis
  2297. FIGURE 23-25 Diagram Showing Major Distinguishing Pathophysiologic Features of the Three Types of Cardiomyopathy. A, The normal heart. B, In the dilated type of cardiomyopathy, the heart has a globular shape and the largest circumference of the left ventricle is not at its base but midway between apex and base. C, In the hypertrophic type, the wall of the left ventricle is greatly thickened; the left ventricular cavity is small, but the left atrium may be dilated because of poor diastolic relaxation of the ventricle. D, In the restrictive (constrictive) type, the left ventricular cavity is of normal size, but, again, the left atrium is dilated because of the reduced diastolic compliance of the ventricle.
  2298. Disorders of the Myocardium: The Cardiomyopathies
  2299. FIGURE 23-26 Dilated cardiomyopathy. The dilated left ventricle has a thin wall (V).
  2300. FIGURE 23-27 Hypertrophic cardiomyopathy. There is marked left ventricular hypertrophy. This often affects the septum (S).
  2301. QUICK CHECK 23-7
  2302. Disorders of the Endocardium
  2303. Valvular Dysfunction
  2304. FIGURE 23-28 Valvular Stenosis and Regurgitation. A, Normal position of the valve leaflets, or cusps, when the valve is open and closed. B, Open position of a stenosed valve (left) and open position of a closed regurgitant valve (right). C, Hemodynamic effect of mitral stenosis. The stenosed valve is unable to open sufficiently during left atrial systole, inhibiting left ventricular filling. D, Hemodynamic effect of mitral regurgitation. The mitral valve does not close completely during left ventricular systole, permitting blood to reenter the left atrium.
  2305. TABLE 23-6 CLINICAL MANIFESTATIONS OF VALVULAR STENOSIS AND REGURGITATION
  2306. Stenosis
  2307. Aortic stenosis
  2308. FIGURE 23-29 Aortic Stenosis. Mild stenosis in valve leaflets of a young adult.
  2309. Mitral stenosis
  2310. FIGURE 23-30 Mitral Stenosis With Classic “Fish Mouth” Orifice.
  2311. Regurgitation
  2312. Aortic regurgitation
  2313. FIGURE 23-31 Mitral Valve Prolapse. A, Prolapsed mitral valve. Prolapse permits the valve leaflets to billow back (arrow) into the atrium during left ventricular systole. The billowing causes the leaflets to part slightly, permitting regurgitation into the atrium. B, Looking down into the mitral valve, the ballooning (arrows) of the leaflets is seen.
  2314. Mitral regurgitation
  2315. Tricuspid regurgitation
  2316. Mitral Valve Prolapse Syndrome
  2317. FIGURE 23-32 Pathogenesis and Structural Alterations of Acute Rheumatic Heart Disease. Beginning usually with a sore throat, rheumatic fever can develop only as a sequel to pharyngeal infection by group A β-hemolytic streptococcus. Suspected as a hypersensitivity reaction, it is proposed that antibodies directed against the M proteins of certain strains of streptococci cross-react with tissue glycoproteins in the heart, joints, and other tissues. The exact nature of cross-reacting antigens has been difficult to define, but it appears that the streptococcal infection causes an autoimmune response against self-antigens. Inflammatory lesions are found in various sites; the most distinctive within the heart are called Aschoff bodies. The chronic sequelae result from progressive fibrosis because of healing of the inflammatory lesions and the changes induced by valvular deformities.
  2318. Acute Rheumatic Fever and Rheumatic Heart Disease
  2319. Pathophysiology
  2320. TABLE 23-7 JONES CRITERIA (UPDATED) USED FOR DIAGNOSIS OF INITIAL ATTACK OF RHEUMATIC FEVER
  2321. Clinical Manifestations
  2322. Evaluation and Treatment
  2323. QUICK CHECK 23-8
  2324. Infective Endocarditis
  2325. RISK FACTORS
  2326. Pathophysiology
  2327. FIGURE 23-33 Pathogenesis of Infective Endocarditis.
  2328. Clinical Manifestations
  2329. Evaluation and Treatment
  2330. FIGURE 23-34 Bacterial Endocarditis of Mitral Valve. The valve is covered with large, irregular vegetations (arrow).
  2331. Cardiac Complications in Acquired Immunodeficiency Syndrome (AIDS)
  2332. QUICK CHECK 23-9
  2333. Manifestations of Heart Disease
  2334. Dysrhythmias
  2335. TABLE 23-8 DISORDERS OF IMPULSE FORMATION
  2336. TABLE 23-9 DISORDERS OF IMPULSE CONDUCTION
  2337. Heart Failure
  2338. Left Heart Failure (Congestive Heart Failure)
  2339. FIGURE 23-35 Pathophysiology of Ventricular Remodeling. Myocardial dysfunction activates the renin-angiotensin-aldosterone and sympathetic nervous systems, releasing neurohormones (angiotensin II, aldosterone, catecholamines, and cytokines). These neurohormones contribute to ventricular remodeling.
  2340. FIGURE 23-36 Effect of Elevated Preload on Myocardial Oxygen Supply and Demand. LVEDV, Left ventricular end-diastolic volume.
  2341. BOX 23-3 INFLAMMATION, IMMUNITY, AND HUMORAL FACTORS IN THE PATHOGENESIS OF HEART FAILURE
  2342. FIGURE 23-37 Role of Increased Afterload in the Pathogenesis of Heart Failure.
  2343. HEALTH ALERT
  2344. FIGURE 23-38 Vicious Cycle of Systolic Heart Failure. Although the initial insult may be one of primary decreased contractility (e.g., myocardial infarction), increased preload (e.g., renal failure), or increased afterload (e.g., hypertension), all three factors play a role in the progression of left heart failure (LHF). LVEDV, Left ventricular end-diastolic volume.
  2345. Right Heart Failure
  2346. High-Output Failure
  2347. FIGURE 23-39 Right Heart Failure. RA, Right atrial; RV, right ventricular.
  2348. FIGURE 23-40 High-Output Failure. SVR, Systemic vascular resistance.
  2349. QUICK CHECK 23-10
  2350. Shock
  2351. Impairment of Cellular Metabolism
  2352. Impairment of Oxygen Use
  2353. FIGURE 23-41 Impaired Cellular Metabolism in Shock. ATP, Adenosine triphosphate.
  2354. Impairment of Glucose Use
  2355. Clinical Manifestations of Shock
  2356. Treatment for Shock
  2357. Types of Shock
  2358. Cardiogenic Shock
  2359. FIGURE 23-42 Cardiogenic Shock. Shock becomes life-threatening when compensatory mechanisms (in blue) cause increased myocardial oxygen requirements. Renal and hypothalamic adaptive responses (i.e., renin-angiotensin-aldosterone and antidiuretic hormone [ADH]) maintain or increase blood volume. The adrenal gland releases catecholamines (e.g., mostly epinephrine, some norepinephrine), causing vasoconstriction and increases in contractility and heart rate. These adaptive mechanisms, however, increase myocardial demands for oxygen and nutrients. These demands further strain the heart, which can no longer pump an adequate volume, resulting in shock and impaired metabolism. SVR, Systemic vascular resistance.
  2360. FIGURE 23-43 Hypovolemic Shock. This type of shock becomes life-threatening when compensatory mechanisms (in purple) are overwhelmed by continued loss of intravascular volume. ADH, Antidiuretic hormone; SVR, systemic vascular resistance.
  2361. Hypovolemic Shock
  2362. Neurogenic Shock
  2363. Anaphylactic Shock
  2364. FIGURE 23-44 Neurogenic Shock. SVR, Systemic vascular resistance.
  2365. QUICK CHECK 23-11
  2366. Septic Shock
  2367. FIGURE 23-45 Anaphylactic Shock. IgE, Immunoglobulin E; SVR, systemic vascular resistance.
  2368. TABLE 23-10 CAUSES AND DEFINITIONS OF SEPTIC SHOCK
  2369. FIGURE 23-46 Septic Shock. TLR, Toll-like receptor.
  2370. HEALTH ALERT
  2371. RISK FACTORS
  2372. Interleukin-1β (IL-1β)
  2373. Tumor Necrosis Factor-alpha (TNF-α)
  2374. Platelet-Activating Factor (PAF)
  2375. High-Mobility Group Box 1 (HMGB1)
  2376. QUICK CHECK 23-12
  2377. HEALTH ALERT
  2378. Multiple Organ Dysfunction Syndrome
  2379. RISK FACTORS
  2380. Pathophysiology
  2381. FIGURE 23-47 Pathogenesis of Multiple Organ Dysfunction Syndrome.
  2382. TABLE 23-11 CELLS OF INFLAMMATION AND MULTIPLE ORGAN DYSFUNCTION
  2383. Clinical Manifestations
  2384. Evaluation and Treatment
  2385. QUICK CHECK 23-13
  2386. HEALTH ALERT
  2387. DID YOU UNDERSTAND?
  2388. Diseases of the Veins and Arteries
  2389. Disorders of the Heart Wall
  2390. Manifestations of Heart Disease
  2391. Shock
  2392. KEY TERMS
  2393. Acute Coronary Syndrome (see video)
  2394. Aortic regurgitation (see video)
  2395. Mitral regurgitation (see video)
  2396. Atrial fibrillation (see video)
  2397. Systemic inflammatory response syndrome (SIRS) (see video)
  2398. References
  2399. Chapter 24 Alterations of Cardiovascular Function in Children
  2400. Congenital Heart Disease
  2401. TABLE 24-1 MATERNAL CONDITIONS AND ENVIRONMENTAL EXPOSURES AND THE ASSOCIATED CONGENITAL HEART DEFECTS
  2402. TABLE 24-2 CONGENITAL HEART DISEASE IN SELECTED FETAL CHROMOSOMAL ABERRATIONS
  2403. Obstructive Defects
  2404. Coarctation of the Aorta
  2405. Pathophysiology
  2406. Clinical Manifestations
  2407. Evaluation And Treatment
  2408. FIGURE 24-1 Comparison of Acyanotic-Cyanotic and Hemodynamic Classification Systems of Congenital Heart Disease.
  2409. FIGURE 24-2 Shunting of Blood in Congenital Heart Disease. A, Normal. B, Acyanotic defect. C, Cyanotic defect. ASD, Atrial septal defect; AV, aortic valve; LA, left atrium; LV, left ventricle; PV, pulmonic valve; RA, right atrium; RV, right ventricle; VSD, ventricular septal defect.
  2410. FIGURE 24-3 Postductal and Preductal Coarctation of the Aorta. A, Postductal coarctation occurs distal to (“after”) the insertion of the closed ductus arteriosus into the aortic arch. Preductal coarctation occurs proximal to (“before”) the insertion of the patent ductus arteriosus. The coarctation consists of a flap of tissue that protrudes from the tunica media of the aortic wall. B, Coarctation of the aorta with typical indentation of the aortic wall (arrow) opposite the ductal arterial ligament (asterisk). Ao, Aorta.
  2411. Aortic Stenosis
  2412. Pathophysiology
  2413. FIGURE 24-4 Aortic Stenosis (AS). Narrowing of the aortic valve causing resistance to blood flow in the left ventricle, decreased cardiac output, left ventricular hypertrophy, and pulmonary congestion.
  2414. Clinical Manifestations
  2415. HEALTH ALERT
  2416. Evaluation And Treatment
  2417. Valvular aortic stenosis
  2418. FIGURE 24-5 Pulmonic Stenosis (PS). A, The pulmonary valve narrows at the entrance of the pulmonary artery. B, Balloon angioplasty is used to dilate the valve. A catheter is inserted across the stenotic pulmonic valve into the pulmonary artery, and a balloon at the end of the catheter is inflated while it is positioned across the narrowed valve opening.
  2419. Subvalvular aortic stenosis
  2420. Supravalvular aortic stenosis
  2421. Pulmonic Stenosis
  2422. Pathophysiology
  2423. Clinical Manifestations
  2424. Evaluation And Treatment
  2425. Defects With Increased Pulmonary Blood Flow
  2426. Patent Ductus Arteriosus
  2427. Pathophysiology
  2428. Clinical Manifestations
  2429. FIGURE 24-6 Patent Ductus Arteriosus (PDA). A, PDA with left-to-right shunt. B, PDA in an adult with pulmonary hypertension. Ao, Aorta; LPA, left pulmonary artery; RPA, right pulmonary artery; SCV, subclavian vein.
  2430. Evaluation And Treatment
  2431. Atrial Septal Defect
  2432. Pathophysiology
  2433. Clinical Manifestations
  2434. Evaluation and Treatment
  2435. Ventricular Septal Defect
  2436. Pathophysiology
  2437. Clinical Manifestations
  2438. Evaluation and Treatment
  2439. FIGURE 24-7 Atrioventricular Canal (AVC) Defect.
  2440. Atrioventricular Canal Defect
  2441. Pathophysiology
  2442. Clinical Manifestations
  2443. Evaluation and Treatment
  2444. Defects With Decreased Pulmonary Blood Flow
  2445. Tetralogy of Fallot
  2446. Pathophysiology
  2447. Clinical Manifestations
  2448. Evaluation and Treatment
  2449. Tricuspid Atresia
  2450. Pathophysiology
  2451. FIGURE 24-8 Tetralogy of Fallot (TOF) A, TOF hemodynamics. B, Right ventricular (RV) hypertrophy and AO.
  2452. FIGURE 24-9 Tricuspid Atresia.
  2453. Clinical Manifestations
  2454. Evaluation and Treatment
  2455. Mixing Defects
  2456. Transposition of the Great Arteries or Transposition of the Great Vessels
  2457. Pathophysiology
  2458. Clinical Manifestations
  2459. Evaluation and Treatment
  2460. FIGURE 24-10 Hemodynamics in Transposition of the Great Vessels (TGV). A, Complete transposition of the great vessels with an intact interventricular septum. The aorta arises from the right ventricle and the pulmonary artery from the left ventricle. B, Oxygen saturation in the two, parallel circuits. Ao, Aorta; ASD, atrial septal defect; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PDA, patent ductus arteriosus; RA, right atrium; RV, right ventricle; VSD, ventricular septal defect.
  2461. Total Anomalous Pulmonary Venous Connection
  2462. Pathophysiology
  2463. FIGURE 24-11 Total Anomalous Pulmonary Venous Connection (TAPVC).
  2464. Clinical Manifestations
  2465. Evaluation and Treatment
  2466. Truncus Arteriosus
  2467. Pathophysiology
  2468. Clinical Manifestations
  2469. FIGURE 24-12 Truncus Arteriosus (TA).
  2470. Evaluation and Treatment
  2471. Hypoplastic Left Heart Syndrome
  2472. Pathophysiology
  2473. Clinical Manifestations
  2474. Evaluation and Treatment
  2475. FIGURE 24-13 Hypoplastic Left Heart Syndrome (HLHS).
  2476. QUICK CHECK 24-1
  2477. Congestive Heart Failure
  2478. TABLE 24-3 CAUSES OF CONGESTIVE HEART FAILURE RESULTING FROM CONGENITAL HEART DISEASE
  2479. BOX 24-1 CLINICAL MANIFESTATIONS OF CONGESTIVE HEART FAILURE
  2480. Impaired Myocardial Function
  2481. Pulmonary Congestion
  2482. Acquired Cardiovascular Disorders
  2483. Kawasaki Disease
  2484. Pathophysiology
  2485. Clinical Manifestations
  2486. Evaluation and Treatment
  2487. Systemic Hypertension
  2488. TABLE 24-4 NORMATIVE BLOOD PRESSURE LEVELS (SYSTOLIC/DIASTOLIC [MEAN]) BY DINAMAP MONITOR IN CHILDREN 5 YEARS OLD AND YOUNGER
  2489. BOX 24-2 DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE
  2490. HEALTH ALERT
  2491. TABLE 24-5 SUGGESTED NORMAL BP VALUES (mm Hg) BY AUSCULTATORY METHOD (SYSTOLIC/DIASTOLIC K5)
  2492. BOX 24-3 CONDITIONS ASSOCIATED WITH SECONDARY HYPERTENSION IN CHILDREN
  2493. Renal Disorders
  2494. Cardiovascular Disease
  2495. Metabolic and Endocrine Diseases
  2496. Neurologic Disorders
  2497. Miscellaneous Causes
  2498. Pathophysiology
  2499. Clinical Manifestations
  2500. Evaluation and Treatment
  2501. TABLE 24-6 MOST COMMON CAUSES OF CHRONIC SUSTAINED HYPERTENSION
  2502. TABLE 24-7 ROUTINE AND SPECIAL LABORATORY TESTS FOR HYPERTENSION
  2503. QUICK CHECK 24-2
  2504. DID YOU UNDERSTAND?
  2505. Congenital Heart Disease
  2506. Acquired Cardiovascular Disorders in Children
  2507. KEY TERMS
  2508. Subaortic stenosis (see video)
  2509. Congestive heart failure (see video)
  2510. References
  2511. UNIT 8 The Pulmonary System
  2512. Interactive Review – Unit 8
  2513. Chapter 25 Structure and Function of the Pulmonary System
  2514. Structures of the Pulmonary System
  2515. Conducting Airways
  2516. FIGURE 25-1 Structure of the Pulmonary System. The enlargement in the circle depicts the acinus, where oxygen and carbon dioxide are exchanged.
  2517. TABLE 25-1 PULMONARY DEFENSE MECHANISMS
  2518. FIGURE 25-2 Structures of the Upper Airway.
  2519. FIGURE 25-3 Structures of the Lower Airway.
  2520. FIGURE 25-4 Changes in the Bronchial Wall With Progressive Branching.
  2521. Gas-Exchange Airways
  2522. QUICK CHECK 25-1
  2523. Pulmonary and Bronchial Circulation
  2524. FIGURE 25-5 Alveoli. Bronchioles subdivide to form tiny tubes called alveolar ducts, which end in clusters of alveoli called alveolar sacs.
  2525. Chest Wall and Pleura
  2526. Function of the Pulmonary System
  2527. FIGURE 25-6 Section Through the Alveolar Septum (Gas-Exchange Membrane). Inset shows a magnified view of the respiratory membrane composed of the alveolar wall (fluid coating, epithelial cells, basement membrane), interstitial fluid, and wall of a pulmonary capillary (basement membrane, endothelial cells). The gases CO2 (carbon dioxide) and O2 (oxygen) diffuse across the respiratory membrane.
  2528. FIGURE 25-7 Thoracic (Chest) Cavity and Related Structures. The thoracic (chest) cavity is divided into three subdivisions (left and right pleural divisions and mediastinum) by a partition formed by a serous membrane called the pleura.
  2529. Ventilation
  2530. FIGURE 25-8 Functional Components of the Respiratory System. The central nervous system responds to neurochemical stimulation of ventilation and sends signals to the chest wall musculature. The response of the respiratory system to these impulses is influenced by several factors that impact the mechanisms of breathing and, therefore, affect the adequacy of ventilation. Gas transport between the alveoli and pulmonary capillary blood depends on a variety of physical and chemical activities. Finally, the control of the pulmonary circulation plays a role in the appropriate distribution of blood flow.
  2531. FIGURE 25-9 Neurochemical Respiratory Control System.
  2532. QUICK CHECK 25-2
  2533. Neurochemical Control of Ventilation
  2534. Lung Receptors
  2535. Chemoreceptors
  2536. HEALTH ALERT
  2537. QUICK CHECK 25-3
  2538. Mechanics of Breathing
  2539. Major and Accessory Muscles
  2540. FIGURE 25-10 Muscles of Ventilation. A, Anterior view. B, Posterior view.
  2541. Alveolar Surface Tension
  2542. Elastic Properties of the Lung and Chest Wall
  2543. Airway Resistance
  2544. FIGURE 25-11 Interaction of Forces During Inspiration and Expiration. A, Outward recoil of the chest wall equals inward recoil of the lungs at the end of expiration. B, During inspiration, contraction of respiratory muscles, assisted by chest wall recoil, overcomes the tendency of lungs to recoil. C, At the end of inspiration, respiratory muscle contraction maintains lung expansion. D, During expiration, respiratory muscles relax, allowing elastic recoil of the lungs to deflate the lungs.
  2545. Work of Breathing
  2546. QUICK CHECK 25-4
  2547. Gas Transport
  2548. FIGURE 25-12 Spirogram. During normal, quiet respirations, the atmosphere and lungs exchange about 500 ml of air (VT). With a forcible inspiration, about 3300 ml more air can be inhaled (IRV). After a normal inspiration and normal expiration, approximately 1000 ml more air can be forcibly expired (ERV). Vital capacity (VC) is the amount of air that can be forcibly expired after a maximal inspiration and indicates, therefore, the largest amount of air that can enter and leave the lungs during respiration. Residual volume (RV) is the air that remains trapped in the alveoli.
  2549. FIGURE 25-13 Relationship Between Number of Gas Molecules and Pressure Exerted by the Gas in an Enclosed Space. A, Theoretically, 10 molecules of the same gas exert a total pressure of 10 within the space. B, If the number of molecules is increased to 20, total pressure is 20. C, If there are different gases in the space, each gas exerts a partial pressure: here the partial pressure of nitrogen (N2) is 20, that of oxygen (O2) is 6, and the total pressure is 26.
  2550. Measurement of Gas Pressure
  2551. TABLE 25-2 COMMON PULMONARY ABBREVIATIONS
  2552. FIGURE 25-14 Pulmonary Blood Flow and Gravity. The greatest volume of pulmonary blood flow normally will occur in the gravity-dependent areas of the lung. Body position has a significant effect on the distribution of pulmonary blood flow.
  2553. Distribution of Ventilation and Perfusion
  2554. FIGURE 25-15 Gravity and Alveolar Pressure. Effects of gravity and alveolar pressure on pulmonary blood flow in the three lung zones. In zone I, alveolar pressure (PA) is greater than arterial and venous pressures, and no blood flow occurs. In zone II, arterial pressure (Pa) exceeds alveolar pressure, but alveolar pressure exceeds venous pressure (PV). Blood flow occurs in this zone, but alveolar pressure compresses the venules (venous ends of the capillaries). In zone III, both arterial and venous pressures are greater than alveolar pressure and blood flow fluctuates depending on the difference between arterial pressure and venous pressure.
  2555. Oxygen Transport
  2556. Diffusion across the alveolocapillary membrane
  2557. Determinants of arterial oxygenation
  2558. FIGURE 25-16 Partial Pressure of Respiratory Gases in Normal Respiration. The numbers shown are average values near sea level. The values of PO2, PCO2, and PN2 fluctuate from breath to breath.
  2559. Oxyhemoglobin association and dissociation
  2560. Carbon Dioxide Transport
  2561. FIGURE 25-17 Oxyhemoglobin Dissociation Curve. The horizontal or flat segment of the curve at the top of the graph is the arterial or association portion, or that part of the curve where oxygen is bound to hemoglobin and occurs in the lungs. This portion of the curve is flat because partial pressure changes of oxygen between 60 and 100 mm Hg do not significantly alter the percentage saturation of hemoglobin with oxygen and allow adequate hemoglobin saturation at a variety of altitudes. If the relationship between SaO2 and PaO2 was linear (in a downward sloping straight line) instead of flat between 60 and 100 mm Hg, there would be inadequate saturation of hemoglobin with oxygen. The steep part of the oxyhemoglobin dissociation curve represents the rapid dissociation of oxygen from hemoglobin that occurs in the tissues. During this phase there is rapid diffusion of oxygen from the blood into tissue cells. The P50 is the PaO2 at which hemoglobin is 50% saturated, normally 26.6 mm Hg. A lower than normal P50 represents increased affinity of hemoglobin for O2; a high P50 is seen with decreased affinity. Note that variation from the normal is associated with decreased (low P50) or increased (high P50) availability of O2 to tissues (dashed lines). The shaded area shows the entire oxyhemoglobin dissociation curve under the same circumstances. 2,3-DPG, 2,3-Diphosphoglycerate.
  2562. QUICK CHECK 25-5
  2563. Control of the Pulmonary Circulation
  2564. QUICK CHECK 25-6
  2565. GERIATRIC CONSIDERATIONS
  2566. Elasticity/Chest Wall
  2567. Gas Exchange
  2568. Exercise
  2569. Changes in Lung Volumes With Aging. With aging, note particularly the dense vital capacity and the increase in residual volume.
  2570. DID YOU UNDERSTAND?
  2571. Structures of the Pulmonary System
  2572. Function of the Pulmonary System
  2573. GERIATRIC CONSIDERATIONS: Aging & the Pulmonary System
  2574. KEY TERMS
  2575. References
  2576. Chapter 26 Alterations of Pulmonary Function
  2577. Clinical Manifestations of Pulmonary Alterations
  2578. Signs and Symptoms of Pulmonary Disease
  2579. Dyspnea
  2580. Cough
  2581. Abnormal Sputum
  2582. Hemoptysis
  2583. Abnormal Breathing Patterns
  2584. Hypoventilation/Hyperventilation
  2585. Cyanosis
  2586. Clubbing
  2587. Pain
  2588. FIGURE 26-1 Clubbing of Fingers Caused by Chronic Hypoxemia.
  2589. Conditions Caused by Pulmonary Disease or Injury
  2590. Hypercapnia
  2591. Hypoxemia
  2592. FIGURE 26-2 Ventilation-Perfusion (V·Q·) Abnormalities.
  2593. QUICK CHECK 26-1
  2594. Acute Respiratory Failure
  2595. Disorders of the Chest Wall and Pleura
  2596. Chest Wall Restriction
  2597. FIGURE 26-3 Flail Chest. Normal respiration: A, inspiration; B, expiration. Paradoxical motion: C, inspiration, area of lung underlying unstable chest wall flattens on inspiration; D, expiration, unstable area inflates. Note movement of mediastinum toward opposite lung during inspiration.
  2598. Pleural Abnormalities
  2599. Pneumothorax
  2600. FIGURE 26-4 Pneumothorax. Air in the pleural space causes the lung to collapse around the hilus and may push mediastinal contents (heart and great vessels) toward the other lung.
  2601. TABLE 26-1 MECHANISM OF PLEURAL EFFUSION*
  2602. Pleural effusion
  2603. Empyema
  2604. QUICK CHECK 26-2
  2605. Pulmonary Disorders
  2606. Restrictive Lung Diseases
  2607. Aspiration
  2608. FIGURE 26-5 Pores of Kohn. A, Absorption atelectasis caused by lack of collateral ventilation through pores of Kohn. B, Restoration of collateral ventilation during deep breathing.
  2609. Atelectasis
  2610. Bronchiectasis
  2611. Bronchiolitis
  2612. Pulmonary Fibrosis
  2613. Idiopathic pulmonary fibrosis
  2614. Inhalation Disorders
  2615. Exposure to toxic gases
  2616. Pneumoconiosis
  2617. Allergic alveolitis
  2618. Pulmonary Edema
  2619. FIGURE 26-6 Pathogenesis of Pulmonary Edema.
  2620. Acute Respiratory Distress Syndrome
  2621. Pathophysiology
  2622. FIGURE 26-7 Pathogenesis of Acute Respiratory Distress Syndrome (ARDS). IL-1, Interleukin-1; ROS, reactive oxygen species; TGF-β, transforming growth factor-beta; TNF, tumor necrosis factor.
  2623. Clinical Manifestations
  2624. Evaluation and Treatment
  2625. QUICK CHECK 26-3
  2626. Obstructive Lung Diseases
  2627. Asthma
  2628. Pathophysiology
  2629. FIGURE 26-8 Airway Obstruction Caused by Emphysema, Chronic Bronchitis, and Asthma. A, The normal lung. B, Emphysema: enlargement and destruction of alveolar walls with loss of elasticity and trapping of air; (left) panlobular emphysema showing abnormal weakening and enlargement of all air spaces distal to the terminal bronchioles (normal alveoli shown for comparison only); (right) centrilobular emphysema showing abnormal weakening and enlargement of the respiratory bronchioles in the proximal portion of the acinus. C, Chronic bronchitis: inflammation and thickening of mucous membrane with accumulation of mucus and pus leading to obstruction; characterized by cough. D, Bronchial asthma: thick mucus, mucosal edema, and smooth muscle spasm causing obstruction of small airways; breathing becomes labored, and expiration is difficult.
  2630. Clinical Manifestations
  2631. FIGURE 26-9 Pathophysiology of Asthma. Allergen or irritant exposure results in a cascade of inflammatory events leading to acute and chronic airway dysfunction (also see Figure 27-7).
  2632. Evaluation and Treatment
  2633. Chronic Obstructive Pulmonary Disease
  2634. FIGURE 26-10 Pathogenesis of Chronic Bronchitis and Emphysema (Chronic Obstructive Pulmonary Disease [COPD]).
  2635. FIGURE 26-11 Mechanisms of Air Trapping in COPD. Mucous plugs and narrowed airways cause air trapping and hyperinflation of alveoli on expiration. During inspiration, the airways are pulled open, allowing gas to flow past the obstruction. During expiration, decreased elastic recoil of the bronchial walls results in collapse of the airways and prevents normal expiratory airflow.
  2636. HEALTH ALERT
  2637. Chronic Bronchitis
  2638. Pathophysiology
  2639. TABLE 26-2 CLINICAL MANIFESTATIONS OF CHRONIC OBSTRUCTIVE LUNG DISEASE
  2640. Clinical Manifestations
  2641. Evaluation and Treatment
  2642. Emphysema
  2643. FIGURE 26-12 Bullous Emphysema with Large Apical and Subpleural Bullae (see arrows).
  2644. Pathophysiology
  2645. Clinical Manifestations
  2646. Evaluation and Treatment
  2647. QUICK CHECK 26-4
  2648. Respiratory Tract Infections
  2649. Pneumonia
  2650. Pathophysiology
  2651. HEALTH ALERT
  2652. Pneumococcal pneumonia
  2653. FIGURE 26-13 Pathophysiologic Course of Pneumococcal Pneumonia.
  2654. Viral pneumonia
  2655. Clinical Manifestations
  2656. Evaluation and Treatment
  2657. HEALTH ALERT
  2658. Tuberculosis
  2659. Pathophysiology
  2660. Clinical Manifestations
  2661. Evaluation and Treatment
  2662. Acute Bronchitis
  2663. Abscess Formation and Cavitation
  2664. QUICK CHECK 26-5
  2665. Pulmonary Vascular Disease
  2666. Pulmonary Embolism
  2667. Pathophysiology
  2668. FIGURE 26-14 Pathogenesis of Massive Pulmonary Embolism Caused by a Thrombus (Pulmonary Thromboembolism).
  2669. Clinical Manifestations
  2670. Evaluation and Treatment
  2671. Pulmonary Hypertension
  2672. Pathophysiology
  2673. FIGURE 26-15 Pathogenesis of Pulmonary Hypertension and Cor Pulmonale.
  2674. Clinical Manifestations
  2675. Evaluation and Treatment
  2676. Cor Pulmonale
  2677. Pathophysiology
  2678. Clinical Manifestations
  2679. Evaluation and Treatment
  2680. QUICK CHECK 26-6
  2681. Malignancies of the Respiratory Tract
  2682. Lip Cancer
  2683. FIGURE 26-16 Lip Cancer. Carcinoma of lower lip with central ulceration and raised, rolled borders.
  2684. BOX 26-1 STAGING OF LIP CANCER
  2685. Stage I
  2686. Stage II
  2687. Stage III
  2688. Stage IV
  2689. Pathophysiology
  2690. Clinical Manifestations
  2691. Evaluation and Treatment
  2692. Laryngeal Cancer
  2693. FIGURE 26-17 Laryngeal Cancer. A, Mirror view of carcinoma of the right false cord partially hiding the true cord. B, Lateral view.
  2694. Pathophysiology
  2695. Clinical Manifestations
  2696. Evaluation and Treatment
  2697. Lung Cancer
  2698. Types of lung cancer
  2699. Non–small cell lung cancer
  2700. FIGURE 26-18 Lung Cancer. A, Squamous cell carcinoma. This hilar tumor originates from the main bronchus. B, Peripheral adenocarcinoma. The tumor shows prominent black pigmentation, suggestive of having evolved in an anthracotic scar. C, Small cell carcinoma. The tumor forms confluent nodules. On cross section, the nodules have an encephaloid appearance.
  2701. TABLE 26-3 CHARACTERISTICS OF LUNG CANCERS
  2702. Small cell lung cancer
  2703. Pathophysiology
  2704. Clinical Manifestations
  2705. Evaluation and Treatment
  2706. HEALTH ALERT
  2707. QUICK CHECK 26-7
  2708. DID YOU UNDERSTAND?
  2709. Clinical Manifestations of Pulmonary Alterations
  2710. Disorders of the Chest Wall and Pleura
  2711. Pulmonary Disorders
  2712. KEY TERMS
  2713. Open pneumothorax (see video)
  2714. Tension pneumothorax (see video)
  2715. Asthma (see video)
  2716. Tuberculosis (see video)
  2717. Pulmonary embolism (see video)
  2718. Pulmonary hypertension (see video)
  2719. References
  2720. Chapter 27 Alterations of Pulmonary Function in Children
  2721. Disorders of the Upper Airways
  2722. Infections of the Upper Airways
  2723. Croup
  2724. FIGURE 27-1 The Larynx and Subglottic Trachea. A, Normal trachea. B, Narrowing and obstruction from edema caused by croup.
  2725. FIGURE 27-2 Upper Airway Obstruction With Croup.
  2726. TABLE 27-1 COMPARISON OF UPPER AIRWAY INFECTIONS
  2727. Pathophysiology
  2728. FIGURE 27-3 Listening Can Help Locate the Site of Airway Obstruction. A loud, gasping snore suggests enlarged tonsils or adenoids. In inspiratory stridor, the airway is compromised at the level of the supraglottic larynx, vocal cords, subglottic region, or upper trachea. Expiratory stridor results from a narrowing or collapse in the trachea or bronchi. Airway noise during both inspiration and expiration often represents a fixed obstruction of the vocal cords or subglottic space. Hoarseness or a weak cry is a by-product of obstruction at the vocal cords. If a cough is croupy, suspect constriction below the vocal cords.
  2729. Clinical Manifestations
  2730. Evaluation and Treatment
  2731. FIGURE 27-4 Areas of Chest Muscle Retraction.
  2732. Acute Epiglottitis
  2733. Pathophysiology
  2734. Clinical Manifestations
  2735. Evaluation and Treatment
  2736. Tonsillar Infections
  2737. Aspiration of Foreign Bodies
  2738. Obstructive Sleep Apnea
  2739. Pathophysiology
  2740. Clinical Manifestations
  2741. Evaluation and Treatment
  2742. QUICK CHECK 27-1
  2743. Disorders of the Lower Airways
  2744. Respiratory Distress Syndrome of the Newborn
  2745. RISK FACTORS
  2746. Pathophysiology
  2747. FIGURE 27-5 Pathogenesis of Respiratory Distress Syndrome (RDS) of the Newborn.
  2748. Clinical Manifestations
  2749. Evaluation and Treatment
  2750. Bronchopulmonary Dysplasia
  2751. RISK FACTORS
  2752. Pathophysiology
  2753. Clinical Manifestations
  2754. FIGURE 27-6 Pathophysiology of Bronchopulmonary Dysplasia (BPD).
  2755. Evaluation and Treatment
  2756. QUICK CHECK 27-2
  2757. Respiratory Tract Infections
  2758. Bronchiolitis
  2759. Pathophysiology
  2760. Clinical Manifestations
  2761. Evaluation and Treatment
  2762. Pneumonia
  2763. TABLE 27-2 COMMON TYPES OF PNEUMONIA IN CHILDREN
  2764. Evaluation and Treatment
  2765. QUICK CHECK 27-3
  2766. Aspiration Pneumonitis
  2767. Bronchiolitis Obliterans
  2768. Asthma
  2769. Pathophysiology
  2770. Clinical Manifestations
  2771. Evaluation and Treatment
  2772. FIGURE 27-7 Asthmatic Responses. A, In the early asthmatic response, inhaled antigen (1) binds to preformed IgE on mast cells. Mast cells degranulate (2) and release mediators such as histamine, leukotrienes, prostaglandin D2, platelet activating factor, and others. Acute inflammation opens intercellular tight junctions, allowing allergen to penetrate and activate submucosal mast cells. Secreted mediators (3) induce active bronchospasm, edema, and mucus secretion causing airway obstruction. Inflammatory responses are triggered by chemotactic factors and up-regulation of adhesion molecules (not shown). At the same time, as shown on the left, antigen may be received by dendritic cells and later presented, either to regional lymph nodes of naïve (Tho) T lymphocytes or locally to memory Th2 cells in the airway mucosa (see B). B, In the late asthmatic response, there are areas of epithelial damage and shedding caused at least in part by toxicity of eosinophil products (major basic protein, eosinophilic cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase). Many inflammatory cells are recruited by chemokines and up-regulation of vascular cell adhesion molecules. Local T lymphocytes display a predominant Th2 cytokine profile. They produce IL-4 and IL-13, which promote switching of B cells to favor IgE production; and IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor, which encourage eosinophil differentiation and survival. Inflammatory mediators also activate sensory nerves, further stimulating bronchoconstriction (also see Figure 26-9).
  2773. HEALTH ALERT
  2774. QUICK CHECK 27-4
  2775. Acute Respiratory Distress Syndrome
  2776. Pathophysiology
  2777. Clinical Manifestations
  2778. Evaluation and Treatment
  2779. Cystic Fibrosis
  2780. Pathophysiology
  2781. FIGURE 27-8 Pathology of the Lung in End-Stage Cystic Fibrosis. Key features are widespread mucus impaction of airways and bronchiectasis (especially from the upper lobe [U]), with hemorrhagic pneumonia in the lower lobe (L). Small cysts (C) are present at the apex of the lung.
  2782. Clinical Manifestations
  2783. Evaluation and Treatment
  2784. HEALTH ALERT
  2785. FIGURE 27-9 Pathogenesis of Cystic Fibrosis Lung Disease. CFTR, Cystic fibrosis transmembrane conductance regulator.
  2786. Sudden Infant Death Syndrome
  2787. HEALTH ALERT
  2788. RISK FACTORS
  2789. QUICK CHECK 27-5
  2790. DID YOU UNDERSTAND?
  2791. Disorders of the Upper Airways
  2792. Disorders of the Lower Airways
  2793. Sudden Infant Death Syndrome (SIDS)
  2794. KEY TERMS
  2795. References
  2796. UNIT 9 The Renal and Urologic Systems
  2797. Interactive Review – Unit 9
  2798. Chapter 28 Structure and Function of the Renal and Urologic Systems
  2799. Structures of the Renal System
  2800. Structures of the Kidney
  2801. FIGURE 28-1 Organs of the Urinary System.
  2802. FIGURE 28-2 Kidney Structure.
  2803. FIGURE 28-3 Components of Nephron.
  2804. FIGURE 28-4 Epithelial Cells of the Various Segments of Nephron Tubules. The brush border and high number of mitochondria in cells of the proximal tubule promote reabsorption of 50% of the glomerular filtrate. Intercalated cells secrete H+ (through K+ exchange) or reabsorb HCO3−. Principal cells are influenced by aldosterone and reabsorb Na+ and water and secrete K+.
  2805. Nephron
  2806. FIGURE 28-5 Nephron Unit with Its Blood Vessels. Blood flows through nephron vessels as follows: interlobular artery, afferent arteriole, glomerulus, efferent arteriole, peritubular capillaries (around the tubules), venules, interlobular vein. The vasa recta capillaries distribute along the long loops of Henle of the juxtamedullary nephrons.
  2807. FIGURE 28-6 Anatomy of the Glomerulus and Juxtaglomerular Apparatus. A, Longitudinal cross section of glomerulus and juxtaglomerular apparatus. B, Horizontal cross section of glomerulus. C, Enlargement of glomerular capillary filtration membrane.
  2808. Blood Vessels of the Kidney
  2809. QUICK CHECK 28-1
  2810. Urinary Structures
  2811. Ureters
  2812. Bladder and Urethra
  2813. FIGURE 28-7 Structure of the Urinary Bladder. Frontal view of a dissected urinary bladder (male) in a fully distended position.
  2814. Renal Blood Flow
  2815. Autoregulation of Intrarenal Blood Flow
  2816. FIGURE 28-8 Renal Autoregulation. Blood flow and glomerular filtration rate are stabilized in the face of changes in perfusion pressure.
  2817. Neural Regulation of Renal Blood Flow
  2818. FIGURE 28-9 Renin-Angiotensin-Aldosterone System. Activation of tubuloglomerular feedback mechanisms stimulates the release of renin with activation of the renin-angiotensin-aldosterone cascade. Plasma volume and blood pressure are increased with the reabsorption of sodium chloride and water from the renal tubules. The restoration of plasma volume and blood pressure then decreases the release of renin, forming a negative feedback loop.
  2819. Hormonal Regulation of Renal Blood Flow
  2820. FIGURE 28-10 Major Functions of Nephron Segments. ADH, Antidiuretic hormone.
  2821. QUICK CHECK 28-2
  2822. Kidney Function
  2823. Nephron Function
  2824. Glomerular Filtration
  2825. FIGURE 28-11 Glomerular Filtration Pressures.
  2826. TABLE 28-1 GLOMERULAR FILTRATION PRESSURES
  2827. Filtration rate
  2828. Tubular Transport
  2829. Proximal tubule
  2830. Glomerulotubular balance
  2831. Loop of Henle and distal tubule
  2832. FIGURE 28-12 Countercurrent Mechanism for Concentrating and Diluting Urine. ADH, Antidiuretic hormone.
  2833. BOX 28-1 Substances Transported by Renal Tubules
  2834. Acidification of urine
  2835. FIGURE 28-13 Acidification of Urine by Tubule Excretion of Phosphate and Ammonia (NH3). A, Acidification of urine and conservation of base by distal renal tubule excretion of H+ via phosphate buffers. B, An amino acid (glutamine) moves into the tubule cell and forms ammonia (NH3), which is secreted into the urine and combines with H+ to form ammonium ion (NH4+) and an ammonium salt (NH4Cl). In exchange, the tubule cell absorbs a basic salt (mainly NaHCO3) into blood from urine.
  2836. Urine
  2837. HEALTH ALERT
  2838. Hormones and Nephron Function
  2839. Antidiuretic Hormone
  2840. Aldosterone
  2841. Atrial Natriuretic Peptide
  2842. Diuretics as a Factor in Urine Flow
  2843. Renal Hormones
  2844. Urodilatin
  2845. Vitamin D
  2846. TABLE 28-2 ACTION OF DIURETICS
  2847. Erythropoietin
  2848. QUICK CHECK 28-3
  2849. Test of Renal Function
  2850. The Concept of Clearance
  2851. Clearance and Glomerular Filtration Rate
  2852. Plasma Creatinine Concentration
  2853. Blood Urea Nitrogen
  2854. Urinalysis
  2855. TABLE 28-3 NORMAL RENAL FUNCTION TESTS
  2856. TABLE 28-4 BLADDER FUNCTION TESTS
  2857. PEDIATRIC CONSIDERATIONS
  2858. QUICK CHECK 28-4
  2859. GERIATRIC CONSIDERATIONS
  2860. DID YOU UNDERSTAND?
  2861. Structures of the Renal System
  2862. Renal Blood Flow
  2863. Kidney Function
  2864. Tests of Renal Function
  2865. PEDIATRIC CONSIDERATIONS: Pediatrics & Renal Function
  2866. GERIATRIC CONSIDERATIONS: Aging & Renal Function
  2867. KEY TERMS
  2868. References
  2869. Chapter 29 Alterations of Renal and Urinary Tract Function
  2870. Urinary Tract Obstruction
  2871. Upper Urinary Tract Obstruction
  2872. FIGURE 29-1 Major Sites of Urinary Tract Obstruction.
  2873. FIGURE 29-2 Hydronephrosis. Hydronephrosis with renal stones in renal pelvis and calyces.
  2874. Kidney Stones
  2875. Pathophysiology
  2876. Clinical Manifestations
  2877. Evaluation And Treatment
  2878. Lower Urinary Tract Obstruction
  2879. Neurogenic Bladder
  2880. Overactive Bladder Syndrome
  2881. TABLE 29-1 TYPES OF INCONTINENCE
  2882. TABLE 29-2 NEUROGENIC BLADDER
  2883. Obstructions to Urine Flow
  2884. Evaluation and Treatment
  2885. FIGURE 29-3 Neurogenic Detrusor Overactivity with Vesico-Sphincter. The arrow indicates narrowing of the striated sphincter consistent with electromyographic activity (line 6) noted on the urodynamic tracing. Note the characteristic poor flow pattern (line 1) with elevated voiding pressures (lines 4 and 5) indicating obstruction. Line 1, Urine flow rate; line 2, urine volume; line 3, abdominal pressure (Pabd); line 4, intravesicular (inside bladder) pressure (Pves); line 5, detrusor muscle pressure (Pdet); line 6, bladder electromyelogram (EMG).
  2886. Tumors
  2887. Renal Tumors
  2888. FIGURE 29-4 Renal Cell Carcinoma. Renal cell carcinomas usually are spheroidal masses composed of yellow tissue mottled with hemorrhage, necrosis, and fibrosis.
  2889. Pathogenesis
  2890. Clinical Manifestations
  2891. Evaluation and Treatment
  2892. Bladder Tumors
  2893. Pathogenesis
  2894. TABLE 29-3 STAGING OF RENAL CELL CARCINOMA
  2895. TABLE 29-4 STAGING OF BLADDER CARCINOMA (TNM SYSTEM)
  2896. Clinical Manifestations
  2897. Evaluation and Treatment
  2898. QUICK CHECK 29-1
  2899. Urinary Tract Infection
  2900. Causes of Urinary Tract Infection
  2901. Types of Urinary Tract Infection
  2902. Acute Cystitis
  2903. Pathophysiology
  2904. Clinical Manifestations
  2905. Evaluation and Treatment
  2906. Painful Bladder Syndrome/Interstitial Cystitis
  2907. HEALTH ALERT
  2908. TABLE 29-5 COMMON CAUSES OF PYELONEPHRITIS
  2909. Acute Pyelonephritis
  2910. Pathophysiology
  2911. Clinical Manifestations
  2912. FIGURE 29-5 Pyelonephritis. (Right) Small, shrunken, irregularly scarred kidney of an individual with chronic pyelonephritis. (Left) Kidney is of normal size but also shows scarring on the upper pole.
  2913. Evaluation and Treatment
  2914. Chronic Pyelonephritis
  2915. Pathophysiology
  2916. Clinical Manifestations
  2917. Evaluation and Treatment
  2918. QUICK CHECK 29-2
  2919. Glomerular Disorders
  2920. Glomerulonephritis
  2921. FIGURE 29-6 Mechanisms of Glomerular Injury. Ab, Antibody; GBM, glomerular basement membrane; GFR, glomerular filtration rate; NO, nitric oxide.
  2922. Pathophysiology
  2923. TABLE 29-6 TYPES OF GLOMERULAR LESIONS
  2924. Clinical Manifestations
  2925. Evaluation and Treatment
  2926. TABLE 29-7 IMMUNOLOGIC PATHOGENESIS OF GLOMERULONEPHRITIS
  2927. Types of Glomerulonephritis
  2928. Membranous Nephropathy
  2929. Chronic Glomerulonephritis
  2930. FIGURE 29-7 Chronic Glomerulonephritis. The kidneys appear small, are uniformly shrunken, and have a finely granular external surface.
  2931. TABLE 29-8 FEATURES OF THE COMMON TYPES OF GLOMERULONEPHRITIS
  2932. Nephrotic and Nephritic Syndromes
  2933. Pathophysiology
  2934. Clinical Manifestations
  2935. Evaluation and Treatment
  2936. QUICK CHECK 29-3
  2937. Acute Kidney Injury
  2938. Classification of Kidney Dysfunction
  2939. Pathophysiology
  2940. TABLE 29-9 CLINICAL MANIFESTATIONS OF NEPHROTIC SYNDROME
  2941. TABLE 29-10 RIFLE CRITERIA FOR ACUTE KIDNEY DYSFUNCTION/FAILURE
  2942. Clinical Manifestations
  2943. TABLE 29-11 CLASSIFICATION OF ACUTE KIDNEY INJURY
  2944. FIGURE 29-8 Mechanisms of Oliguria in Acute Kidney Failure. GFR, Glomerular filtration rate.
  2945. Evaluation and Treatment
  2946. Chronic Kidney Disease
  2947. Pathophysiology
  2948. TABLE 29-12 DIFFERENTIATION OF ACUTE OLIGURIC KIDNEY FAILURE
  2949. TABLE 29-13 STAGES OF CHRONIC KIDNEY DISEASE
  2950. FIGURE 29-9 Common Signs and Symptoms of Kidney Failure (see text for reference site).
  2951. Clinical Manifestations
  2952. TABLE 29-14 SYSTEMIC EFFECTS OF CHRONIC KIDNEY FAILURE
  2953. Creatinine and urea clearance
  2954. Fluid and electrolyte balance
  2955. FIGURE 29-10 Mechanisms Related to the Progression of Chronic Kidney Disease.
  2956. TABLE 29-15 FACTORS REPRESENTING PROGRESSION OF CHRONIC KIDNEY FAILURE
  2957. Calcium, phosphate, and bone
  2958. Protein, carbohydrate, and fat metabolism
  2959. Cardiovascular system
  2960. Pulmonary system
  2961. Hematologic system
  2962. Immune system
  2963. Neurologic system
  2964. Gastrointestinal system
  2965. Endocrine and reproductive systems
  2966. Integumentary system
  2967. Evaluation and Treatment
  2968. QUICK CHECK 29-4
  2969. DID YOU UNDERSTAND?
  2970. Urinary Tract Obstruction
  2971. Urinary Tract Infection
  2972. Glomerular Disorders
  2973. Acute Kidney Injury
  2974. Chronic Kidney Disease
  2975. KEY TERMS
  2976. References
  2977. Chapter 30 Alterations of Renal and Urinary Tract Function in Children
  2978. Structural Abnormalities
  2979. Hypospadias
  2980. FIGURE 30-1 Hypospadias.
  2981. FIGURE 30-2 Hypospadias with Significant Chordee.
  2982. Epispadias and Exstrophy of the Bladder
  2983. FIGURE 30-3 Exstrophy of Bladder.
  2984. Bladder Outlet Obstruction
  2985. Ureteropelvic Junction Obstruction
  2986. Hypoplastic/Dysplastic Kidneys
  2987. Polycystic Kidney Disease
  2988. Renal Agenesis
  2989. QUICK CHECK 30-1
  2990. Glomerular Disorders
  2991. Glomerulonephritis
  2992. Acute Poststreptococcal Glomerulonephritis
  2993. Immunoglobulin A Nephropathy
  2994. Nephrotic Syndrome
  2995. Pathophysiology
  2996. Clinical Manifestations
  2997. Evaluation And Treatment
  2998. Hemolytic Uremic Syndrome
  2999. Pathophysiology
  3000. Clinical Manifestations
  3001. Evaluation And Treatment
  3002. Other Renal Disorders
  3003. Bladder Disorders
  3004. Urinary Tract Infections
  3005. HEALTH ALERT
  3006. Vesicoureteral Reflux
  3007. Pathophysiology
  3008. FIGURE 30-4 Normal and Abnormal Configurations of the Ureterovesical ureter. A refluxing ureterovesical ureter has the same anatomic features as a nonrefluxing ureter, except for the shorter length of the intravesical ureter which allows reflux of urine during filling of the bladder.
  3009. Clinical Manifestations
  3010. Evaluation and Treatment
  3011. QUICK CHECK 30-2
  3012. Nephroblastoma
  3013. FIGURE 30-5 Grades of Vesicoureteral Reflux.
  3014. Pathogenesis
  3015. Clinical Manifestations
  3016. Evaluation and Treatment
  3017. Urinary Incontinence
  3018. Types of Incontinence
  3019. TABLE 30-1 STAGING OF NEPHROBLASTOMA TUMOR*
  3020. TABLE 30-2 CLASSIFICATION OF INCONTINENCE
  3021. Pathogenesis
  3022. Evaluation and Treatment
  3023. QUICK CHECK 30-3
  3024. DID YOU UNDERSTAND?
  3025. Structural Abnormalities
  3026. Glomerular Disorders
  3027. Bladder Disorders
  3028. Nephroblastoma
  3029. Urinary Incontinence
  3030. KEY TERMS
  3031. References
  3032. UNIT 10 The Reproductive Systems
  3033. Interactive Review – Unit 10
  3034. Chapter 31 Structure and Function of the Reproductive Systems
  3035. Development of the Reproductive Systems
  3036. Sexual Differentiation in Utero
  3037. TABLE 31-1 SUMMARY OF FEMALE AND MALE SEX AND REPRODUCTIVE HORMONES
  3038. FIGURE 31-1 Internal Genitalia Development. Embryonic and fetal development of the internal genitalia.
  3039. Puberty and Reproductive Maturation
  3040. FIGURE 31-2 External Genitalia Development. Embryonic and fetal development of the external genitalia.
  3041. QUICK CHECK 31-1
  3042. The Female Reproductive System
  3043. FIGURE 31-3 Hormonal Stimulation of the Gonads. The hypothalamic-pituitary-gonadal axis.
  3044. External Genitalia
  3045. FIGURE 31-4 External Female Genitalia.
  3046. Internal Genitalia
  3047. Vagina
  3048. FIGURE 31-5 Internal Female Genitalia and Other Pelvic Organs.
  3049. Uterus
  3050. FIGURE 31-6 Uterine Positions.
  3051. FIGURE 31-7 Cross Section of Uterus, Fallopian Tube, and Ovary.
  3052. QUICK CHECK 31-2
  3053. Fallopian Tubes
  3054. Ovaries
  3055. FIGURE 31-8 Cross Section of Ovary and Development of an Ovarian Follicle. Schematic representation (not to scale) of the structure of the ovary, showing the various stages in the development of the follicle and its successor structure, the corpus luteum.
  3056. Female Sex Hormones
  3057. Estrogens and Androgens
  3058. BOX 31-1 Summary of Nonreproductive Effects of Estrogen
  3059. Progesterone
  3060. TABLE 31-2 COMPLEMENTARY AND OPPOSING EFFECTS OF ESTROGEN AND PROGESTERONE
  3061. QUICK CHECK 31-3
  3062. Menstrual Cycle
  3063. Phases of the Menstrual Cycle
  3064. FIGURE 31-9 Female Reproductive Cycles. This figure illustrates the interrelationships among the cerebral, hypothalamic, pituitary, ovarian, and uterine functions throughout a standard 28-day menstrual cycle. The variations in basal body temperature are also illustrated.
  3065. TABLE 31-3 HORMONAL FEEDBACK MECHANISM IN THE MENSTRUAL CYCLE
  3066. Hormonal Controls
  3067. Ovarian Cycle
  3068. Uterine Phases
  3069. Vaginal Response
  3070. Body Temperature
  3071. QUICK CHECK 31-4
  3072. Structure and Function of the Breast
  3073. FIGURE 31-10 Schematic Diagram of Breast.
  3074. Female Breast
  3075. FIGURE 31-11 Lymphatic Drainage of the Female Breast.
  3076. Male Breast
  3077. FIGURE 31-12 Structure of the Male Reproductive Organs.
  3078. QUICK CHECK 31-5
  3079. The Male Reproductive System
  3080. FIGURE 31-13 Descent of a Testis. The testes descend from the abdominal cavity to the scrotum during the last 3 months of fetal development.
  3081. External Genitalia
  3082. Testes
  3083. Epididymis
  3084. FIGURE 31-14 The Testes. External and sagittal views showing interior anatomy.
  3085. Scrotum
  3086. Penis
  3087. FIGURE 31-15 Cross Section of the Penis.
  3088. Internal Genitalia
  3089. FIGURE 31-16 Anatomy of the Prostate Gland and Seminal Vesicles.
  3090. Spermatogenesis
  3091. Male Sex and Reproductive Hormones
  3092. FIGURE 31-17 Seminiferous Tubule. Section shows process of meiosis and sperm cell formation (spermatogenesis).
  3093. FIGURE 31-18 Mature Sperm Cell (Spermatozoon). Anatomy of mature sperm cell.
  3094. QUICK CHECK 31-6
  3095. HEALTH ALERT
  3096. Aging & Reproductive Function
  3097. Aging and the Female Reproductive System
  3098. FIGURE 31-19 Perimenopausal Hormone Transition. Mean circulating hormone levels. FSH, Follicle-stimulating hormone; LH, luteinizing hormone.
  3099. HEALTH ALERT
  3100. Aging and the Male Reproductive System
  3101. QUICK CHECK 31-7
  3102. DID YOU UNDERSTAND?
  3103. Development of the Reproductive Systems
  3104. The Female Reproductive System
  3105. Structure and Function of the Breast
  3106. The Male Reproductive System
  3107. Aging & Reproductive Function
  3108. KEY TERMS
  3109. References
  3110. Chapter 32 Alterations of the Reproductive Systems, Including Sexually Transmitted Infections
  3111. Alterations of Sexual Maturation
  3112. Delayed or Absent Puberty
  3113. BOX 32-1 CAUSES OF DELAYED PUBERTY
  3114. Hypergonadotropic Hypogonadism (Increased Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH])
  3115. Hypogonadotropic Hypogonadism (Decreased LH, Depressed FSH)
  3116. Eugonadism
  3117. BOX 32-2 PRIMARY FORMS OF PRECOCIOUS PUBERTY
  3118. Complete Precocious Puberty
  3119. Partial Precocious Puberty
  3120. Mixed Precocious Puberty
  3121. Precocious Puberty
  3122. QUICK CHECK 32-1
  3123. Disorders of the Female Reproductive System
  3124. Hormonal and Menstrual Alterations
  3125. Dysmenorrhea
  3126. PATHOPHYSIOLOGY
  3127. CLINICAL MANIFESTATIONS
  3128. EVALUATION AND TREATMENT
  3129. Primary Amenorrhea
  3130. PATHOPHYSIOLOGY
  3131. CLINICAL MANIFESTATIONS
  3132. EVALUATION AND TREATMENT
  3133. Secondary Amenorrhea
  3134. PATHOPHYSIOLOGY
  3135. CLINICAL MANIFESTATIONS
  3136. EVALUATION AND TREATMENT
  3137. FIGURE 32-1 Causes of Secondary Amenorrhea. Of note, hypothyroidism is a relatively common condition and should be ruled out as the cause of hyperprolactinemia before more extensive evaluation (i.e., computed tomography or magnetic resonance imaging) occurs.
  3138. Abnormal Uterine Bleeding
  3139. TABLE 32-1 ABNORMAL MENSTRUAL BLEEDING
  3140. PATHOPHYSIOLOGY
  3141. CLINICAL MANIFESTATIONS
  3142. EVALUATION AND TREATMENT
  3143. TABLE 32-2 COMMON CAUSES OF ABNORMAL (VAGINAL/GENITAL) BLEEDING IN DESCENDING ORDER OF FREQUENCY
  3144. Polycystic Ovary Syndrome
  3145. FIGURE 32-2 Polycystic Ovary. A, Surgical view of polycystic ovaries. B, Ultrasound of polycystic ovary.
  3146. PATHOPHYSIOLOGY
  3147. FIGURE 32-3 Insulin Resistance and Hyperinsulinemia in Polycystic Ovary Syndrome (PCOS). See text for explanation. FSH, Follicle-stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone–binding globulin.
  3148. CLINICAL MANIFESTATIONS
  3149. EVALUATION AND TREATMENT
  3150. BOX 32-3 CLINICAL MANIFESTATIONS OF POLYCYSTIC OVARY SYNDROME
  3151. Presenting Signs and Symptoms (% of Women Affected)
  3152. Hormonal Disturbances
  3153. Possible Late Sequelae
  3154. Other
  3155. Premenstrual Syndrome
  3156. PATHOPHYSIOLOGY
  3157. CLINICAL MANIFESTATIONS
  3158. EVALUATION AND TREATMENT
  3159. BOX 32-4 AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) CRITERIA
  3160. QUICK CHECK 32-2
  3161. Infection and Inflammation
  3162. Pelvic Inflammatory Disease
  3163. FIGURE 32-4 Pelvic Inflammatory Disease. A, Drawing depicting involvement of both ovaries and fallopian tubes. B, Total abdominal hysterectomy and bilateral salpingo-oophorectomy specimen showing unilateral pyosalpinx.
  3164. PATHOPHYSIOLOGY
  3165. CLINICAL MANIFESTATIONS
  3166. FIGURE 32-5 Salpingitis. A, Note the swollen fallopian tubes. B, Bilateral, retort-shaped, swollen sealed tubes and adhesions of ovaries are typical of salpingitis.
  3167. EVALUATION AND TREATMENT
  3168. Vaginitis
  3169. Cervicitis
  3170. Vulvovestibulitis
  3171. Bartholinitis
  3172. FIGURE 32-6 Inflammation of Bartholin Glands.
  3173. Pelvic Organ Prolapse
  3174. TABLE 32-3 PELVIC ORGAN PROLAPSE: SYMPTOMS AND TREATMENTS
  3175. FIGURE 32-7 Degrees of Uterine Prolapse. A, Normal uterus (grade 0). B, Grade 1 prolapse: descent within the vagina. C, Grade 2 prolapse: descent into the hymen. D, Grade 4 prolapse: minimal possible descent of the uterus. Grade 3 (not shown) protrudes just beyond the introitus.
  3176. FIGURE 32-8 Cystocele and Rectocele. A, Grade 2: anterior vaginal wall prolapse (i.e., cystocele). B, Grade 4: prolapse. C, Grade 2: posterior wall prolapse (i.e., rectocele). D, Grade 4: associated with ulceration of vaginal wall. Grades 1 and 3 not shown.
  3177. Benign Growths and Proliferative Conditions
  3178. Benign Ovarian Cysts
  3179. FIGURE 32-9 Depiction of Ovarian Cyst.
  3180. HEALTH ALERT
  3181. QUICK CHECK 32-3
  3182. Endometrial Polyps
  3183. FIGURE 32-10 Endometrial Polyp. Polyp is protruding through the cervical os.
  3184. Leiomyomas
  3185. PATHOPHYSIOLOGY
  3186. FIGURE 32-11 Leiomyomas. A, Uterine section showing whorl-like appearance and locations of leiomyomas, which are also called uterine fibroids. B, Multiple leiomyomas in sagittal section. Typical, well-circumscribed, solid, light gray nodules distort uterus.
  3187. CLINICAL MANIFESTATIONS
  3188. EVALUATION AND TREATMENT
  3189. Adenomyosis
  3190. Endometriosis
  3191. PATHOPHYSIOLOGY
  3192. CLINICAL MANIFESTATIONS
  3193. FIGURE 32-12 Pelvic Sites of Endometrial Implantation in Endometriosis. Endometrial cells may enter the pelvic cavity during retrograde menstruation.
  3194. BOX 32-5 THEORIES OF ENDOMETRIOSIS
  3195. EVALUATION AND TREATMENT
  3196. Cancer
  3197. Cervical Cancer
  3198. PATHOGENESIS
  3199. FIGURE 32-13 Cervical Intraepithelial Neoplasia (CIN). A, Normal multiparous cervix including the transformation zone (TZ) where precancerous and cancerous changes occur (see next photos). CIN stage 1, note the white appearance of part of the anterior lip of the cervix associated with neoplastic changes; CIN stage 2, lesions also are reflected in distant capillaries; CIN stage 3, lesions predominantly around the external os. B, Normal epithelium, HPV infection progressing to CIN stage 1, and then with more time persistent HPV infections progressing to precancerous lesions CIN 2 and CIN 3 and eventually cervical cancer. Most cervical lesions do not progress to cervical cancer.
  3200. TABLE 32-4 CLINICAL STAGING FOR CANCER OF THE CERVIX
  3201. HEALTH ALERT
  3202. CLINICAL MANIFESTATIONS
  3203. EVALUATION AND TREATMENT
  3204. TABLE 32-5 RECOMMENDED TREATMENT BASED ON CLINICAL STAGING FOR CANCER OF THE CERVIX
  3205. Vaginal Cancer
  3206. FIGURE 32-14 Endometrial Cancer. Tumor fills the endometrial cavity. Obvious myometrial invasion is shown.
  3207. Vulvar Cancer
  3208. Endometrial Cancer
  3209. RISK FACTORS
  3210. Other Risk Factors
  3211. Ovarian Cancer
  3212. RISK FACTORS
  3213. FIGURE 32-15 Ovarian Tumors. A serous borderline tumor displays a cyst cavity lined by papillary tumor growths (A). The cyst is opened (B) to reveal a large bulky tumor mass called cystadenocarcinoma (C), a tumor on the ovarian surface. Bilaterality of tumors is common, occurring in 20% of benign tumors, 30% of serous borderline tumors, and approximately 66% of serous carcinomas. A significant proportion of both borderline malignant and malignant tumors involve the surface of the ovary (C).
  3214. PATHOGENESIS
  3215. CLINICAL MANIFESTATIONS
  3216. FIGURE 32-16 Metastasis of Ovarian Cancer. Pattern of spread for epithelial cancer of the ovary.
  3217. TABLE 32-6 FIGO STAGING OF CARCINOMA OF THE OVARY
  3218. EVALUATION AND TREATMENT
  3219. TABLE 32-7 POSSIBLE EFFECTS OF CHRONIC DISEASE ON SEXUAL FUNCTIONING IN WOMEN
  3220. HEALTH ALERT
  3221. Sexual Dysfunction
  3222. Impaired Fertility
  3223. QUICK CHECK 32-4
  3224. Disorders of the Male Reproductive System
  3225. Disorders of the Urethra
  3226. Urethritis
  3227. Urethral Strictures
  3228. Disorders of the Penis
  3229. Phimosis and Paraphimosis
  3230. FIGURE 32-17 Phimosis and Paraphimosis. A, Phimosis: the foreskin has a narrow opening that is not large enough to permit retraction over the glans. B, Lesions on the prepuce secondary to infection cause swelling, and retraction of foreskin may be impossible. Circumcision is usually required. C, Paraphimosis: the foreskin is retracted over the glans but cannot be reduced to its normal position. Here it has formed a constricting band around the penis. D, Ulcer on the retracted prepuce with edema.
  3231. Peyronie Disease
  3232. FIGURE 32-18 Peyronie Disease. This person complained of pain and deviation of his penis to one side on erection.
  3233. FIGURE 32-19 Priapism.
  3234. Priapism
  3235. FIGURE 32-20 Balanitis.
  3236. Balanitis
  3237. Tumors of the Penis
  3238. Penile Cancer
  3239. BOX 32-6 STAGING FOR PENILE CANCER
  3240. QUICK CHECK 32-5
  3241. FIGURE 32-21 Depiction of a Varicocele. Dilation of veins within the spermatic cord.
  3242. Disorders of the Scrotum, Testis, and Epididymis
  3243. Disorders of the Scrotum
  3244. FIGURE 32-22 Depiction of a Hydrocele. Accumulation of clear fluid between the visceral (inner) and parietal (outer) layers of the tunica vaginalis.
  3245. FIGURE 32-23 Spermatocele. Retention cyst of the head of the epididymis or of an aberrant tubule or tubules of the rete testis. The spermatocele lies outside the tunica vaginalis; therefore, on palpation it can be readily distinguished and separated from the testis.
  3246. Cryptorchidism and Ectopy
  3247. Torsion of the Testis and Testicular Appendages
  3248. Orchitis
  3249. FIGURE 32-24 Torsion of the Testis. The testes appear dark red and partially necrotic as a result of hemorrhagic infarction.
  3250. FIGURE 32-25 Depiction of Orchitis.
  3251. Cancer of the Testis
  3252. PATHOPHYSIOLOGY
  3253. FIGURE 32-26 Testicular Tumor.
  3254. RISK FACTORS
  3255. CLINICAL MANIFESTATIONS
  3256. EVALUATION AND TREATMENT
  3257. Epididymitis
  3258. PATHOPHYSIOLOGY
  3259. CLINICAL MANIFESTATIONS
  3260. FIGURE 32-27 Epididymitis Secondary to Gonorrhea or Nongonococcal Urethritis. This infection spread to the testes, and rupture through the scrotal wall is threatened.
  3261. EVALUATION AND TREATMENT
  3262. QUICK CHECK 32-6
  3263. Disorders of the Prostate Gland
  3264. Benign Prostatic Hyperplasia
  3265. FIGURE 32-28 Prostate Zones, Benign Prostatic Hyperplasia (BPH), and Prostate Cancer Locations. Benign prostatic hyperplasia (BPH) occurs in the peripheral zone of the prostate gland that can enlarge (not shown). BPH nodules and atrophy are associated with inflammation in the transition zone. Most cancer lesions occur in the peripheral zone. Carcinoma can involve the central zone but rarely occurs in isolation, suggesting that prostatic intraepithelial neoplasia (PIN) lesions do not easily progress to carcinoma in this region.
  3266. PATHOGENESIS
  3267. CLINICAL MANIFESTATIONS
  3268. EVALUATION AND TREATMENT
  3269. Prostatitis
  3270. Bacterial prostatitis
  3271. BOX 32-7 NIH CLASSIFICATION OF THE PROSTATITIS SYNDROME
  3272. Chronic prostatitis/chronic pelvic pain syndrome
  3273. Cancer of the Prostate
  3274. FIGURE 32-29 Selected World Population Age-Standardized (to the World Population) Incidence Rates of Prostate Cancer. ASR, Age-standardized rate.
  3275. Dietary factors
  3276. BOX 32-8 SUMMARY OF DIET FOR PROSTATE CANCER
  3277. General References
  3278. Hormones
  3279. FIGURE 32-30 Sources of Androgens and Aromatase and Estrogen Signaling in the Prostate. A, Body sources of androgens in the prostate gland. Hypothalamic GnRH causes the release of LH from the anterior pituitary gland. LH stimulates the testes to produce testosterone, which then accumulates in the blood. Pituitary ACTH release stimulates the adrenal glands, which secrete the androgen precursor DHEA into the blood. DHEA is converted into testosterone and then into DHT in the prostate. B, Aromatase and estrogen signaling in the prostate. In normal and benign tissue, aromatase is expressed within the stroma and regulated by promoter PII. Estrogen then exerts its effects in an autocrine fashion through the stromal ER-α receptor and also in a paracrine fashion through both ER-α and ER-β receptors. With prostate cancer, aromatase is now expressed within the tumor cells and in stromal cells, and regulated by aromatase promoters 1.3, 1.4, and PII. Thus estrogen exerts its effects in an autocrine way through stromal and epithelial ER-α and ER-β. Consequently, the increased levels of estrogen and abnormal ER-α signaling promote inflammation, which increases aromatase expression and the development of a positive feedback cycle. Inflammation drives aromatase expression, thus increasing estrogen, which in turn promotes further inflammation. ACTH, Adrenocorticotropic hormone; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.
  3280. Vasectomy
  3281. Chronic inflammation
  3282. Genetic and epigenetic factors
  3283. PATHOGENESIS
  3284. Hormonal factors
  3285. FIGURE 32-31 Possible Causes of Prostate Inflammation. A, Infection, including viruses, bacteria, fungi, and parasites. B, Hormones, for example, estrogen at key times during development. C, Physical trauma, any type of blunt physical injury. D, Urine reflex. E, Certain dietary factors (see text).
  3286. FIGURE 32-32 Photomicrograph of Prostate Cancer Cells. Pink ruffled cells are prostate cancer cells.
  3287. BOX 32-9 DETERMINING THE GRADE OF PROSTATE CANCER WITH THE GLEASON SCORE
  3288. FIGURE 32-33 Testosterone and Conversion to Dihydrotestosterone (DHT).
  3289. Androgen receptor signaling
  3290. Prostate epithelial neoplasia
  3291. FIGURE 32-34 Cellular and Molecular Model of Early Prostate Neoplasia Progression. A, This stage includes infiltration of lymphocytes, macrophages, and neutrophils caused by repeated infections, dietary factors, urine reflux, injury, onset of autoimmunity (which triggers inflammation), and wound healing. B, Epigenetic alterations mediate telomere shortening. C, Genetic instability and accumulation of genetic alterations. D, Continued proliferation of genetically unstable cells leading to cancer progression. PIN, Prostatic intraepithelial neoplasia.
  3292. Stromal environment
  3293. FIGURE 32-35 Carcinoma of Prostate. A, Schematic of carcinoma of the prostate. B, Carcinoma of the prostate extending into the rectum and urinary bladder.
  3294. CLINICAL MANIFESTATIONS
  3295. FIGURE 32-36 Distribution of Hematogenous Metastases in Prostate Cancer. Study of 556 individuals with metastatic prostate cancer.
  3296. EVALUATION AND TREATMENT
  3297. Sexual Dysfunction
  3298. PATHOPHYSIOLOGY
  3299. CLINICAL MANIFESTATIONS AND TREATMENT
  3300. Impairment of Sperm Production and Quality
  3301. QUICK CHECK 32-7
  3302. Disorders of the Breast
  3303. Disorders of the Female Breast
  3304. Galactorrhea
  3305. PATHOPHYSIOLOGY
  3306. CLINICAL MANIFESTATIONS
  3307. EVALUATION AND TREATMENT
  3308. Benign Breast Disease/Conditions
  3309. Nonproliferative breast lesions
  3310. BOX 32-10 CLASSIFICATION OF BREAST BIOPSY TISSUE ACCORDING TO RISK FOR BREAST CANCER
  3311. No Increased Risk
  3312. Slightly Increased Risk (1½ to 2 Times)
  3313. Moderately Increased Risk (3 to 5 Times)
  3314. Proliferative breast lesions without atypia
  3315. TABLE 32-8 EXAMPLES OF BENIGN BREAST DISORDERS
  3316. Proliferative breast lesions with atypia
  3317. EVALUATION AND TREATMENT
  3318. Breast Cancer
  3319. FIGURE 32-37 Age-Specific Incidence Rates of Breast Cancer Among Women.
  3320. HEALTH ALERT
  3321. TABLE 32-9 CHANCE OF BEING DIAGNOSED WITH BREAST CANCER
  3322. TABLE 32-10 ESTABLISHED RISK FACTORS FOR BREAST CANCER
  3323. Reproductive factors: pregnancy
  3324. Lobular involution and age
  3325. Hormonal factors
  3326. FIGURE 32-38 Female Endocrine System. The different mammary growth (mammotropic) hormone sites are shown in ovals, hormones are noted in blue boxes, and mammotropic hormones are noted in red boxes.
  3327. FIGURE 32-39 Factors Involved in Mammary Gland Development. Work of many laboratories led to the identification of many genes important in mammary gland development that are summarized in the scheme.
  3328. FIGURE 32-40 Local Biosynthesis of Estrogens. Three main enzyme complexes (yellow) involved in estrogen formation in breast tissue, including aromatase, sulfatase, and 17β-estradiol hydroxysteroid dehydrogenase (17β-HSD). Thus, despite low levels of circulating estrogens in postmenopausal women with breast cancer, the tissue levels are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. Data suggest that most abundant is sulfatase in both premenopausal and postmenopausal women with breast cancer. Numerous agents can block the aromatase action, exploration of progesterone, and various progestins to inhibit sulfatase and 17β-HSD or stimulate sulfotransferase (i.e., breast cancer cells cannot inactivate estrogens because they lack sulfotransferase) may provide new possibilities for treatment. LOH, Loss of heterozygosity (see Chapter 8).
  3329. Hormone replacement therapy and breast cancer risk: estrogen plus progesterone therapy (HRT) and estrogen only therapy (ERT)
  3330. TABLE 32-11 HORMONAL TREATMENTS ASSESSED BY THE IARC MONOGRAPH WORKING GROUP
  3331. Insulin and insulin-like growth factors
  3332. Prolactin and growth hormone
  3333. Human chorionic gonadotropin
  3334. Oral contraceptives
  3335. Mammographic breast density
  3336. FIGURE 32-41 Breast Density Varies Among Women. The sensitivity of mammography for detecting malignancy is significantly reduced if the breast consists of a high proportion of fibroglandular (dense) breast tissue (A) compared to a breast that is fatty (B).
  3337. BOX 32-11 SUMMARY OF THE USPSTF RECOMMENDATIONS ON SCREENING FOR BREAST CANCER
  3338. Environmental factors
  3339. Radiation
  3340. Diet
  3341. Obesity
  3342. Environmental chemicals
  3343. Physical activity
  3344. Familial factors and tumor-related genes
  3345. TABLE 32-12 TYPES OF BREAST CARCINOMAS AND MAJOR DISTINGUISHING FEATURES
  3346. PATHOGENESIS
  3347. Ductal and lobular carcinoma in situ
  3348. FIGURE 32-42 Cells of the Tumor Microenvironment. A, Distinct cell types constitute most solid tumors including breast tumors. Both the main cellular tissue, called parenchyma, and the surrounding tissue, or stroma, of tumors contain cell types that enable tumor growth and progression. For example, the immune-inflammatory cells present in tumors can include both tumor-promoting and tumor-killing subclasses of cells. B, The microenvironment of tumors. Multiple stromal cell types create a succession of tumor microenvironments that change as tumors invade normal tissue, eventually seeding and colonizing distant tissues. The organization, numbers, and phenotypic characteristics of the stromal cell types and the extracellular matrix (hatched background) evolve during progression and enable primary, invasive, and metastatic growth. (Not shown are the premalignant stages.)
  3349. CLINICAL MANIFESTATIONS
  3350. EVALUATION AND TREATMENT
  3351. FIGURE 32-43 Signaling Interactions in the Tumor Microenvironment During Malignant Progression. Upper panel: Numerous cell types constitute the tumor microenvironment and are orchestrated and maintained by reciprocal interactions. Lower panel: The reciprocal interactions between the breast main tissue or parenchyma and the surrounding stroma are important for cancer progression and growth. Certain organ sites of “fertile soil” or “metastasis niches” facilitate metastatic seeding and colonization. Cancer stem cells are involved in some or all stages of tumor development and progression.
  3352. FIGURE 32-44 Ductal Carcinoma in Situ (DCIS). A, Malignant microcalcifications. Extensive area of pleomorphic microcalcifications; granular, rod-shaped, and branching microcalcifications can be identified. The appearances are typical of high-grade DCIS. B, Craniocaudal mammography reveals fine and coarse granular calcifications. Histopathologic analysis revealed low-grade DCIS.
  3353. FIGURE 32-45 Retraction of Nipple Caused by Carcinoma.
  3354. TABLE 32-13 CLINICAL MANIFESTATIONS OF BREAST CANCER
  3355. BOX 32-12 STAGING OF BREAST CANCER
  3356. Stage 0: Tis, N0, M0
  3357. Stage IA: T1, N1mi, M0
  3358. Stage 1B: T0 or T1, N1mi, M0
  3359. Stage IIA
  3360. T0 or T1, N1 (but not N1mi), M0
  3361. Or
  3362. T2, N0, M0
  3363. Stage IIB
  3364. T2, N1, M0
  3365. Or
  3366. T3, N0, M0
  3367. Stage IIIA
  3368. T0 to T2, N2, M0
  3369. Or
  3370. T3, N1 or N2, M0
  3371. Stage IIIB: T4, N0 to N2, M0
  3372. Stage IIIC: Any T, N3, M0
  3373. Stage IV: Any T, Any N, M1
  3374. QUICK CHECK 32-8
  3375. Disorders of the Male Breast
  3376. Gynecomastia
  3377. PATHOPHYSIOLOGY
  3378. EVALUATION AND TREATMENT
  3379. Carcinoma
  3380. Sexually Transmitted Infections
  3381. TABLE 32-14 ESTIMATED NEW CASES OF REPORTABLE AND NONREPORTABLE STIs EACH YEAR
  3382. TABLE 32-15 CURRENTLY RECOGNIZED SEXUALLY TRANSMITTED INFECTIONS
  3383. HEALTH ALERT
  3384. HEALTH ALERT
  3385. QUICK CHECK 32-9
  3386. TABLE 32-16 MAJOR SEXUALLY TRANSMITTED INFECTIONS
  3387. Bacterial Sources
  3388. Gonococcal infections
  3389. Symptomatic gonococcal urethritis.
  3390. Endocervical gonorrhea.
  3391. Skin lesions of disseminated gonococcal infection.
  3392. Bacterial vaginosis
  3393. Vaginal examination showing mild bacterial vaginosis.
  3394. Syphilis
  3395. Erythematous penile plaques of secondary syphilis.
  3396. Multiple primary syphilitic chancres of labia and perineum.
  3397. Papular secondary syphilis.
  3398. Lymphogranuloma
  3399. “Groove sign” in man with lymphogranuloma venereum (LV).
  3400. Chlamydial infections
  3401. Beefy red mucosa in chlamydial infection.
  3402. Chlamydial epididymitis.
  3403. Chlamydial ophthalmia: erythematous conjunctiva in infant.
  3404. Viral Sources
  3405. Genital herpes
  3406. Early lesions of primary genital herpes.
  3407. Primary vulvar herpes.
  3408. Generalized herpes simplex in patient with atopic dermatitis.
  3409. Parasite Sources
  3410. Trichomonisasis
  3411. “Strawberry cervix” seen with trichomoniasis.
  3412. Human papillomavirus (HPV)
  3413. Human papillomavirus (HPV) infection of the cervix.
  3414. Exophytic (outward-growing) condyloma, subclinical human papillomavirus (HPV) infection, and high-grade cervical intraepithelial neoplasia (CIN).
  3415. Condylomata acuminata
  3416. Condylomata acuminata: vulva and perineum.
  3417. Condylomata acuminata: perianal.
  3418. Condylomata acuminata: penile.
  3419. Scabies
  3420. Nodular lesions of scabies on male genitalia.
  3421. Urticaria associated with scabies.
  3422. Scabies of palm with secondary pyoderma in infant.
  3423. Pediculosis pubis (Phthirus pubis [crablouse])
  3424. Phthirus pubis feeding on its host.
  3425. Pubic hair with multiple nits.
  3426. DID YOU UNDERSTAND?
  3427. Alterations of Sexual Maturation
  3428. Disorders of the Female Reproductive System
  3429. Disorders of the Male Reproductive System
  3430. Disorders of the Breast
  3431. Sexually Transmitted Infections
  3432. KEY TERMS
  3433. Pelvic inflammatory disease (see video)
  3434. Ovarian cyst (see video)
  3435. Ovarian torsion (see video)
  3436. Torsion of the testis (see video)
  3437. Breast cancer metastasis (see video)
  3438. References
  3439. UNIT 11 The Digestive System
  3440. Interactive Review – Unit 11
  3441. Chapter 33 Structure and Function of the Digestive System
  3442. The Gastrointestinal Tract
  3443. FIGURE 33-1 Structures of the Digestive System.
  3444. FIGURE 33-2 Wall of the Gastrointestinal Tract The wall of the gastrointestinal tract is made up of four layers with a network of nerves between the layers. This generalized diagram shows a segment of the gastrointestinal tract. Note that the serosa is continuous with a fold of serous membrane called the mesentery. Note also that digestive glands may empty their products into the lumen of the gastrointestinal tract by way of ducts.
  3445. Mouth and Esophagus
  3446. Salivation
  3447. FIGURE 33-3 Salivary Glands.
  3448. Swallowing
  3449. FIGURE 33-4 Salivary Electrolyte Concentrations and Flow Rate. Changes in concentrations of sodium (Na+), potassium (K+), chloride (Cl−), and bicarbonate (HCO3−) increase flow rate of saliva. Green line, sodium; orange line, bicarbonate; red line, chloride; blue line, potassium. At low rates of salivary flow (i.e., between meals), sodium, chloride, and bicarbonate are reabsorbed in the collecting ducts of the salivary glands, and the saliva contains fewer of these electrolytes (i.e., is more hypotonic). At higher flow rates (i.e., stimulated by food), reabsorption decreases and saliva is hypertonic. By this mechanism, sodium, chloride, and bicarbonate are recycled until they are released to help with digestion and absorption.
  3450. QUICK CHECK 33-1
  3451. Stomach
  3452. Gastric Motility
  3453. FIGURE 33-5 Stomach A portion of the anterior wall has been excised to reveal the muscle layers of the stomach wall. Note that the mucosa lining the stomach forms folds called rugae. The dashed lines distinguish the fundus, body, and antrum of the stomach.
  3454. FIGURE 33-6 Major Blood Vessels and Organs Supplied with Blood in the Splanchnic Circulation. Numbers in parentheses reflect approximate blood flow values (ml/min) for each major vessel in an 80-kg normal, resting, adult human subject. Arrows indicate the direction of blood flow.
  3455. TABLE 33-1 Selected hormones* and neurotransmitters of the digestive system
  3456. Phases of Gastric Secretion
  3457. FIGURE 33-7 Gastric Pits and Gastric Glands. Gastric pits are depressions in the epithelial lining of the stomach. At the bottom of each pit are one or more tubular gastric glands. Chief cells produce pepsinogen, which is converted to pepsin (a proteolytic enzyme); parietal cells secrete hydrochloric acid and intrinsic factor; G cells produce gastrin; endocrine cells (enterochromaffin-like cells and D cells) secrete histamine and somatostatin.
  3458. Gastric Secretion
  3459. Acid
  3460. FIGURE 33-8 Relationship Between Secretory Rate and Electrolyte Composition of the Gastric Juice. Sodium (Na+) concentration is lower in the gastric juice than in the plasma, whereas hydrogen (H+), potassium (K+), and chloride (Cl−) concentrations are higher. Red line, chloride; orange line, hydrogen; green line, sodium; blue line, potassium.
  3461. Pepsin
  3462. FIGURE 33-9 Hydrochloric Acid Secretion by Parietal Cell.
  3463. Mucus
  3464. QUICK CHECK 33-2
  3465. Small Intestine
  3466. FIGURE 33-10 The Small Intestine.
  3467. BOX 33-1 DIETARY FAT
  3468. Saturated Fatty Acids (e.g., Palmitic Acid [C16H32O2])
  3469. Unsaturated Fatty Acids
  3470. Monounsaturated Fatty Acids (e.g., Oleic Acid [C18H34O2])
  3471. Polyunsaturated Fatty Acids (e.g., Linoleic Acid [C18H32O2])
  3472. The Gastrointestinal Tract and Immunity
  3473. Intestinal Digestion and Absorption
  3474. FIGURE 33-11 Digestion and Absorption of Foodstuffs.
  3475. FIGURE 33-12 Sites of Absorption of Major Nutrients.
  3476. Intestinal Motility
  3477. BOX 33-2 MAJOR NUTRIENTS ABSORBED IN THE SMALL INTESTINE
  3478. Water and Electrolytes
  3479. Carbohydrates
  3480. Proteins
  3481. Fats
  3482. Minerals
  3483. Vitamins
  3484. QUICK CHECK 33-3
  3485. Large Intestine
  3486. FIGURE 33-13 Division of the Large Intestine.
  3487. QUICK CHECK 33-4
  3488. Intestinal Bacteria
  3489. HEALTH ALERT
  3490. Splanchnic Blood Flow
  3491. FIGURE 33-14 Location of the Liver, Gallbladder, and Exocrine Pancreas, Which Are the Accessory Organs of Digestion.
  3492. Accessory Organs of Digestion
  3493. Liver
  3494. FIGURE 33-15 Gross Structure of the Liver. A, Anterior view. B, Inferior view.
  3495. FIGURE 33-16 Hepatic Portal Circulation. In this unusual circulatory route, a vein is located between two capillary beds. The hepatic portal vein collects blood from capillaries in visceral structures located in the abdomen and empties into the liver. Hepatic veins return blood to the inferior vena cava. (Organs are not drawn to scale.)
  3496. FIGURE 33-17 Diagrammatic Representation of a Liver Lobule. A central vein is located in the center of the lobule with plates of hepatic cells disposed radially. Branches of the portal vein and hepatic artery are located on the periphery of the lobule and blood from both perfuses the sinusoids. Peripherally located bile ducts drain the bile canaliculi that run between the hepatocytes.
  3497. QUICK CHECK 33-5
  3498. Secretion of Bile
  3499. FIGURE 33-18 Enterohepatic Circulation of Bile Salts.
  3500. Metabolism of Bilirubin
  3501. FIGURE 33-19 Bilirubin Metabolism.
  3502. Vascular and Hematologic Functions
  3503. Metabolism of Nutrients
  3504. Fats
  3505. TABLE 33-2 Importance of proteins in the body
  3506. Proteins
  3507. Carbohydrates
  3508. Metabolic Detoxification
  3509. HEALTH ALERT
  3510. Storage of Minerals and Vitamins
  3511. Gallbladder
  3512. TABLE 33-3 Selected tests of liver function
  3513. Exocrine Pancreas
  3514. FIGURE 33-20 Associated Structures of the Gallbladder, Pancreas, and Pancreatic Acinar Cells and Duct.
  3515. QUICK CHECK 33-6
  3516. TABLE 33-4 Selected laboratory tests of exocrine pancreatic function
  3517. GERIATRIC CONSIDERATIONS
  3518. Oral Cavity and Esophagus
  3519. Stomach and Intestines
  3520. Liver
  3521. Pancreas and Gallbladder
  3522. DID YOU UNDERSTAND?
  3523. The Gastrointestinal Tract
  3524. Accessory Organs of Digestion
  3525. KEY TERMS
  3526. References
  3527. Chapter 34 Alterations of Digestive Function
  3528. Disorders of the Gastrointestinal Tract
  3529. Clinical Manifestations of Gastrointestinal Dysfunction
  3530. Anorexia
  3531. Vomiting
  3532. Constipation
  3533. Pathophysiology
  3534. Clinical Manifestations
  3535. Evaluation and Treatment
  3536. Diarrhea
  3537. Pathophysiology
  3538. Clinical Manifestations
  3539. Evaluation and Treatment
  3540. Abdominal Pain
  3541. Gastrointestinal Bleeding
  3542. TABLE 34-1 PRESENTATIONS OF GASTROINTESTINAL BLEEDING
  3543. FIGURE 34-1 Pathophysiology of Gastrointestinal (GI) Bleeding.
  3544. QUICK CHECK 34-1
  3545. Disorders of Motility
  3546. Dysphagia
  3547. Pathophysiology
  3548. Clinical Manifestations
  3549. Evaluation and Treatment
  3550. Gastroesophageal Reflux Disease (GERD)
  3551. FIGURE 34-2 Achalasia. Increased LES muscle tone and loss of peristaltic function prevent food from entering the stomach, causing esophageal distention. LES, Lower esophageal sphincter.
  3552. Pathophysiology
  3553. Clinical Manifestations
  3554. Evaluation and Treatment
  3555. Hiatal Hernia
  3556. Pathophysiology
  3557. Clinical Manifestations
  3558. Evaluation and Treatment
  3559. FIGURE 34-3 Types of Hiatal Hernia. A, Sliding hiatal hernia. B, Paraesophageal hiatal hernia.
  3560. Pyloric Obstruction
  3561. Pathophysiology
  3562. Clinical Manifestations
  3563. Evaluation and Treatment
  3564. Intestinal Obstruction and Paralytic Ileus
  3565. TABLE 34-2 COMMON CAUSES OF INTESTINAL OBSTRUCTION
  3566. TABLE 34-3 LARGE AND SMALL BOWEL OBSTRUCTION
  3567. TABLE 34-4 CLASSIFICATIONS OF INTESTINAL OBSTRUCTION
  3568. FIGURE 34-4 Intestinal Obstructions. A, Hernia. B, Intussusception. C, Volvulus. D, Constriction adhesions.
  3569. Pathophysiology
  3570. FIGURE 34-5 Pathophysiology of Intestinal Obstruction.
  3571. Clinical Manifestations
  3572. Evaluation and Treatment
  3573. QUICK CHECK 34-2
  3574. Gastritis
  3575. Peptic Ulcer Disease
  3576. FIGURE 34-6 Lesions Caused by Peptic Ulcer Disease.
  3577. RISK FACTORS
  3578. Duodenal Ulcers
  3579. Pathophysiology
  3580. Clinical Manifestations
  3581. Evaluation and Treatment
  3582. Gastric Ulcers
  3583. Pathophysiology
  3584. FIGURE 34-7 Duodenal Ulcer. A, A deep ulceration in the duodenal wall extending as a crater through the entire mucosa and into the muscle layers. B, Sequence of ulcerations from normal mucosa to duodenal ulcer. C, Bilateral (kissing) duodenal ulcers in a person using nonsteroidal anti-inflammatory drugs (NSAIDs).
  3585. FIGURE 34-8 Pathophysiology of Gastric Ulcer Formation. NSAIDs, Nonsteroidal anti-inflammatory drugs.
  3586. TABLE 34-5 CHARACTERISTICS OF GASTRIC AND DUODENAL ULCERS
  3587. Clinical Manifestations
  3588. Stress-Related Mucosal Disease
  3589. Surgical Treatment of Ulcer
  3590. QUICK CHECK 34-3
  3591. Postgastrectomy Syndromes
  3592. Malabsorption Syndromes
  3593. Pancreatic Exocrine Insufficiency
  3594. Lactase Deficiency (Lactose Intolerance)
  3595. Bile Salt Deficiency
  3596. Inflammatory Bowel Disease
  3597. Ulcerative Colitis
  3598. Pathophysiology
  3599. Clinical Manifestations
  3600. TABLE 34-6 FEATURES OF ULCERATIVE COLITIS AND CROHN DISEASE
  3601. Evaluation and Treatment
  3602. Crohn Disease
  3603. Pathophysiology
  3604. Clinical Manifestations
  3605. Evaluation and Treatment
  3606. Diverticular Disease of the Colon
  3607. Pathophysiology
  3608. Clinical Manifestations
  3609. Evaluation and Treatment
  3610. FIGURE 34-9 Diverticular Disease. In diverticular disease, the outpouches (arrows) of mucosa seen in the sigmoid colon appear as slitlike openings from the mucosal surface of the opened bowel.
  3611. Appendicitis
  3612. Pathophysiology
  3613. Clinical Manifestations
  3614. Evaluation and Treatment
  3615. Irritable Bowel Syndrome
  3616. Pathophysiology
  3617. Clinical Manifestations
  3618. Evaluation and Treatment
  3619. BOX 34-1 ROME III—DIAGNOSTIC CRITERIA FOR IRRITABLE BOWEL SYNDROME (IBS)
  3620. Vascular Insufficiency
  3621. Disorders of Nutrition
  3622. Obesity
  3623. Pathophysiology
  3624. BOX 34-2 EXAMPLES OF ADIPOCYTOKINES AND OTHER HORMONES RELATED TO COMPLICATIONS OF OBESITY
  3625. Cytokines from Adipose Cells
  3626. Adipocytokines
  3627. Proinflammatory Cytokines
  3628. Other Hormones
  3629. Clinical Manifestations
  3630. FIGURE 34-10 Pathophysiology and Common Complications of Obesity. CRP, C-reactive protein; FFA, free fatty acids; GERD, gastroesophageal reflux disease; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; PAI-1, plasminogen activator inhibitor-1.
  3631. Evaluation and Treatment
  3632. Anorexia Nervosa and Bulimia Nervosa
  3633. HEALTH ALERT
  3634. Malnutrition and Starvation
  3635. QUICK CHECK 34-4
  3636. Disorders of the Accessory Organs of Digestion
  3637. Common Complications of Liver Disorders
  3638. Portal Hypertension
  3639. Pathophysiology
  3640. FIGURE 34-11 Varices Related to Portal Hypertension. Portal vein, its major tributaries, and the most important shunts (collateral veins) between the portal and caval systems. The shunted blood returns to the systemic venous system, bypassing the liver.
  3641. Clinical Manifestations
  3642. Evaluation and Treatment
  3643. Ascites
  3644. Pathophysiology
  3645. Clinical Manifestations
  3646. FIGURE 34-12 Mechanisms of Ascites Caused by Cirrhosis.
  3647. Evaluation and Treatment
  3648. FIGURE 34-13 Massive Ascites in an Individual With Cirrhosis. Distended abdomen, dilated upper abdominal veins, and inverted umbilicus are classic manifestations.
  3649. Hepatic Encephalopathy
  3650. Pathophysiology
  3651. Clinical Manifestations
  3652. Evaluation and Treatment
  3653. FIGURE 34-14 Mechanisms of Jaundice.
  3654. Jaundice
  3655. Pathophysiology
  3656. Clinical Manifestations
  3657. Evaluation and Treatment
  3658. TABLE 34-7 COMMON TYPES OF JAUNDICE
  3659. Hepatorenal Syndrome
  3660. Pathophysiology
  3661. Clinical Manifestations
  3662. Evaluation and Treatment
  3663. QUICK CHECK 34-5
  3664. Disorders of the Liver
  3665. Viral Hepatitis
  3666. Pathophysiology
  3667. TABLE 34-8 CHARACTERISTICS OF VIRAL HEPATITIS
  3668. Clinical Manifestations
  3669. Evaluation and Treatment
  3670. Fulminant Viral Hepatitis
  3671. Cirrhosis
  3672. BOX 34-3 CAUSES OF CIRRHOSIS
  3673. Alcoholic liver disease
  3674. Pathophysiology
  3675. FIGURE 34-15 Clinical Manifestations of Cirrhosis. ADH, Antidiuretic hormone; ALT, alanine transaminase; AST, aspartate transaminase.
  3676. Clinical Manifestations
  3677. Evaluation and Treatment
  3678. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
  3679. Biliary cirrhosis
  3680. QUICK CHECK 34-6
  3681. Disorders of the Gallbladder
  3682. Cholelithiasis (Gallstones)
  3683. Pathophysiology
  3684. Clinical Manifestations
  3685. Evaluation and Treatment
  3686. FIGURE 34-16 Resected Gallbladder Containing Mixed Gallstones.
  3687. Cholecystitis
  3688. Disorders of the Pancreas
  3689. Acute Pancreatitis
  3690. Pathophysiology
  3691. Clinical Manifestations
  3692. Evaluation and Treatment
  3693. Chronic Pancreatitis
  3694. Cancer of the Digestive System
  3695. Cancer of the Gastrointestinal Tract
  3696. Cancer of the Esophagus
  3697. Pathogenesis
  3698. RISK FACTORS
  3699. Clinical Manifestations
  3700. Evaluation and Treatment
  3701. Cancer of the Stomach
  3702. TABLE 34-9 CANCER OF THE GUT, LIVER, AND PANCREAS
  3703. Pathogenesis
  3704. FIGURE 34-17 Typical Sites of Stomach Cancer.
  3705. Clinical Manifestations
  3706. Evaluation and Treatment
  3707. QUICK CHECK 34-7
  3708. Cancer of the Colon and Rectum
  3709. RISK FACTORS
  3710. Pathogenesis
  3711. Clinical Manifestations
  3712. FIGURE 34-18 The Molecular Basis of Colorectal Cancer. Colorectal carcinoma develops from the sequential progression of genetic alterations. 1, Mutations in the APC gene are the earliest known event and inactivation of APC accelerates cell cycle progression. K-ras over expression leads to loss of p53. Loss of p53 transforms an adenoma into a metastatic carcinoma. 2, Mutation of mismatch repair genes (MMR) that encode key molecules that repair DNA result in replication errors and deactivation of proteins from other downstream mutations (TGFβ, IIR, BAX). Deletions or mutations in MMR genes exists in 95% of tumors in individuals with hereditary non-polyposis colorectal cancer (HNPCC), but only 10~15% of sporadic tumors. 3, p53 loss occur in ~75% of colorectal carcinomas, but infrequently in benign lesions. APC, APC gene (a tumor suppressor gene); LOH, loss of heterozygosity; K-ras, a proto oncogene (promotes cell growth); p53, protein 53 or tumor protein 53 (a tumor suppressor protein); FAP, familial adenomatous polyposis; MMR, mutation mismatch repair; MSI, microsatellite instability; TGFβ, transforming growth factor-β; IIR, type II receptor; BAX, apoptosis-related protein; HNPCC, hereditary nonpolyposis colorectal cancer; CRC, colorectal cancer.
  3713. Evaluation and Treatment
  3714. FIGURE 34-19 Neoplastic Polyps. A, Tubular adenomata (A) are rounded lesions 0.5 to 2 cm in size that are generally red and sit on a stalk (S) of normal mucosa that has been dragged up by traction of the polyp in the bowel lumen. B, Villous adenomata are velvety lesions about 0.6 cm thick that occupy a broad area of mucosa generally 1 to 5 cm in diameter.
  3715. FIGURE 34-20 Signs and Symptoms of Colorectal Cancer by Location of Primary Lesion. Clinical manifestations are listed in order of frequency for each region (lymphatics of colon also shown).
  3716. BOX 34-4 SCREENING FOR COLORECTAL CANCER
  3717. Tests That Find Polyps and Cancer
  3718. Tests That Primarily Find Cancer
  3719. Cancer of the Accessory Organs of Digestion
  3720. Cancer of the Liver
  3721. RISK FACTORS
  3722. Pathogenesis
  3723. Clinical Manifestations
  3724. Evaluation and Treatment
  3725. Cancer of the Gallbladder
  3726. Pathogenesis
  3727. Clinical Manifestations
  3728. Evaluation and Treatment
  3729. Cancer of the Pancreas
  3730. Pathogenesis
  3731. Clinical Manifestations
  3732. Evaluation and Treatment
  3733. QUICK CHECK 34-8
  3734. DID YOU UNDERSTAND?
  3735. Disorders of the Gastrointestinal Tract
  3736. Disorders of the Accessory Organs of Digestion
  3737. Cancer of the Digestive System
  3738. KEY TERMS
  3739. Hematemesis (see video)
  3740. Melena (see video)
  3741. Early bowel obstruction (see video)
  3742. Late bowel obstruction (see video)
  3743. Duodenal ulcer (see video)
  3744. Diverticulitis (see video)
  3745. Peritonitis (see video)
  3746. Appendicitis (see video)
  3747. Portal hypertension (see video)
  3748. Cholecystitis (see video)
  3749. References
  3750. Chapter 35 Alterations of Digestive Function in Children
  3751. Disorders of the Gastrointestinal Tract
  3752. Congenital Impairment of Motility
  3753. Cleft Lip and Cleft Palate
  3754. Pathophysiology
  3755. Cleft lip
  3756. Cleft palate
  3757. Clinical Manifestations
  3758. Evaluation and Treatment
  3759. Esophageal Malformations
  3760. Pathophysiology
  3761. Clinical Manifestations
  3762. FIGURE 35-1 Variations in Clefts of the Lip and Palate. A, Unilateral cleft lip. B, Unilateral cleft lip and palate. C, Bilateral cleft lip and cleft palate. D, Cleft palate.
  3763. FIGURE 35-2 Five Types of Esophageal Atresia and Tracheoesophageal Fistulae. A, Simple esophageal atresia. Proximal esophagus and distal esophagus end in blind pouches, and there is no tracheal communication. Nothing enters the stomach; regurgitated food and fluid may enter the lungs. B, Proximal and distal esophageal segments end in blind pouches, and a fistula connects the proximal esophagus to the trachea. Nothing enters the stomach; food and fluid enter the lungs. C, Proximal esophagus ends in a blind pouch, and a fistula connects the trachea to the distal esophagus. Air enters the stomach; regurgitated gastric secretions enter the lungs through the fistula. D, Fistula connects both proximal and distal esophageal segments to the trachea. Air, food, and fluid enter the stomach and the lungs. E, Simple tracheoesophageal fistula between otherwise normal esophagus and trachea. Air, food, and fluid enter the stomach and the lungs. Between 85% and 90% of esophageal anomalies are type C; 6% to 8% are type A; 3% to 5% are type E; and fewer than 1% are type B or D.
  3764. Evaluation and Treatment
  3765. Infantile Pyloric Stenosis
  3766. Pathophysiology
  3767. Clinical Manifestations
  3768. Evaluation and Treatment
  3769. Intestinal Malrotation
  3770. Pathophysiology
  3771. Clinical Manifestations
  3772. Evaluation and Treatment
  3773. QUICK CHECK 35-1
  3774. Meconium Ileus
  3775. Pathophysiology
  3776. Clinical Manifestations
  3777. Evaluation and Treatment
  3778. Distal Intestinal Obstruction Syndrome
  3779. Obstructions of the Duodenum, Jejunum, and Ileum
  3780. Meckel Diverticulum
  3781. Congenital Aganglionic Megacolon
  3782. Pathophysiology
  3783. Clinical Manifestations
  3784. FIGURE 35-3 Congenital Aganglionic Megacolon (Hirschsprung Disease).
  3785. Evaluation and Treatment
  3786. Anorectal Malformations
  3787. FIGURE 35-4 Anorectal Stenosis and Imperforate Anus. NOTE: With the exception of the rectovaginal fistula, all of the malformations shown occur in both males and females.
  3788. Acquired Impairment of Motility
  3789. Intussusception
  3790. Pathophysiology
  3791. FIGURE 35-5 Ileocolic Intussusception.
  3792. Clinical Manifestations
  3793. Evaluation and Treatment
  3794. Gastroesophageal Reflux
  3795. Pathophysiology
  3796. Clinical Manifestations
  3797. Evaluation and Treatment
  3798. QUICK CHECK 35-2
  3799. Impairment of Digestion, Absorption, and Nutrition
  3800. Cystic Fibrosis
  3801. Pathophysiology
  3802. Clinical Manifestations
  3803. Evaluation and Treatment
  3804. Gluten-Sensitive Enteropathy
  3805. TABLE 35-1 PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS, AND COMPLICATIONS OF CYSTIC FIBROSIS
  3806. Pathophysiology
  3807. Clinical Manifestations
  3808. FIGURE 35-6 Pathophysiology of Gluten-Sensitive Enteropathy.
  3809. Evaluation and Treatment
  3810. Protein Energy Malnutrition
  3811. Pathophysiology
  3812. Clinical Manifestations
  3813. Evaluation and Treatment
  3814. Failure to Thrive
  3815. Pathophysiology
  3816. Clinical Manifestations
  3817. Evaluation and Treatment
  3818. Necrotizing Enterocolitis
  3819. Pathophysiology
  3820. Clinical Manifestations
  3821. Evaluation and Treatment
  3822. QUICK CHECK 35-3
  3823. Diarrhea
  3824. Acute or Chronic Diarrhea in Infants and Children
  3825. Primary lactose intolerance
  3826. Disorders of the Liver
  3827. Disorders of Biliary Metabolism and Transport
  3828. Neonatal Jaundice
  3829. Pathophysiology
  3830. Clinical Manifestations
  3831. Evaluation and Treatment
  3832. Biliary Atresia
  3833. Inflammatory Disorders
  3834. Hepatitis
  3835. Hepatitis A virus (HAV)
  3836. Hepatitis B virus (HBV)
  3837. Hepatitis C virus (HCV)
  3838. Chronic hepatitis
  3839. Cirrhosis
  3840. Portal Hypertension
  3841. HEALTH ALERT
  3842. Types of Portal Hypertension
  3843. Extrahepatic portal hypertension
  3844. Intrahepatic portal hypertension
  3845. Course of the Disease
  3846. Clinical Manifestations
  3847. Evaluation and Treatment
  3848. TABLE 35-2 GALACTOSEMIA, FRUCTOSEMIA, AND WILSON DISEASE
  3849. Metabolic Disorders
  3850. QUICK CHECK 35-4
  3851. DID YOU UNDERSTAND?
  3852. Disorders of the Gastrointestinal Tract
  3853. Disorders of the Liver
  3854. KEY TERMS
  3855. References
  3856. UNIT 12 The Musculoskeletal and Integumentary Systems
  3857. Interactive Review – Unit 12
  3858. Chapter 36 Structure and Function of the Musculoskeletal System
  3859. Structure and Function of Bones
  3860. Elements of Bone Tissue
  3861. TABLE 36-1 STRUCTURAL ELEMENTS OF BONE
  3862. Bone Cells
  3863. Osteoblasts
  3864. FIGURE 36-1 Bone Cells. A, Osteoblasts are responsible for the production of collagenous and noncollagenous proteins that compose osteoid. Active osteoblasts are lined up on the osteoid. Note the eccentrically located nuclei. B, Electron photomicrograph of an osteocyte. Osteocytes reside within the lacunae of compact bone. C, Osteoclasts actively resorb mineralized tissue. The scalloped surface in which the multinucleated osteoclasts rest is termed Howship lacuna.
  3865. TABLE 36-2 SELECTED FACTORS AFFECTING BONE FORMATION, MAINTENANCE, AND REMODELING
  3866. Osteoclasts
  3867. OPG/RANKL/RANK System
  3868. Osteocytes
  3869. Bone Matrix
  3870. Collagen fibers
  3871. Proteoglycans
  3872. Glycoproteins
  3873. Bone Minerals
  3874. FIGURE 36-2 Cross Section of Bone. Longitudinal section of long bone (tibia) showing spongy (cancellous) and compact bone.
  3875. TABLE 36-3 SEQUENCE OF CALCIUM AND PHOSPHATE COMPOUND FORMATION AND CRYSTALLIZATION*
  3876. Types of Bone Tissue
  3877. FIGURE 36-3 Structure of Compact and Cancellous Bone. A, Longitudinal section of a long bone showing both cancellous and compact bone. B, Magnified view of compact bone. C, Section of a flat bone. Outer layers of compact bone surround cancellous bone. Fine structure of compact and cancellous bone is shown to the right.
  3878. Characteristics of Bone
  3879. FIGURE 36-4 A, Anterior View of Skeleton. B, Posterior View of Skeleton. Axial skeleton in blue; appendicular skeleton in tan.
  3880. FIGURE 36-5 Bone Remodeling. All bone cells participate in bone remodeling. In the remodeling sequence bone sections are removed by bone-resorbing cells (osteoclasts) and replaced a with new section laid down by bone-forming cells (osteoblasts). Bone remodeling is necessary because it allows the skeleton to respond to mechanical loading, maintains quality control (repair and prevent microdamage), and allows the skeleton to release growth factors and minerals (calcium and phosphate) stored in bone matrix to the circulation. The cells work in response to signals generated in the environment (see F). Only the osteoclastic cells mediate the first phase of remodeling. They are activated, scoop out bone (A), and resorb it, then the work of the osteoblasts begins (B). They form new bone that replaces bone removed by the resorption process (C). The sequence takes 4 to 6 months. D, Micrograph of active bone remodeling seen in the settings of primary or secondary hyperparathyroidism. Note the active osteoblasts surmounted on red-stained osteoid. Marrow fibrosis is present. E, Bone remodeling cycle in normal bone with (F). Numerous signaling factors are necessary for remodeling. Factors most important for resorption include granulocyte macrophage-colony stimulating factor (GM-CSF), Interleukins (IL) 1 and 6, receptor activator for nuclear factor κβ ligand (RANKL), prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-α). Important factors for bone formation include osteoprotegerin (OPG), transforming growth factor beta (TGF-β) and estrogen.
  3881. Maintenance of Bone Integrity
  3882. Remodeling
  3883. Repair
  3884. QUICK CHECK 36-1
  3885. Structure and Function of Joints
  3886. FIGURE 36-6 Main Tissues of a Joint.
  3887. FIGURE 36-7 Types of Joints. Cartilaginous (amphiarthrodial) joints, which are slightly movable, include (A) a synchondrosis that attaches ribs to costal cartilage, (B) a symphysis that connects vertebrae, and (C) the symphysis that connects the two pubic bones. Fibrous (synarthrodial) joints, which are immovable, include (D) the syndesmosis between the tibia and fibula and (E) sutures that connect the skull bones and the gomphosis (not shown), which holds teeth in their sockets. The synovial joints include (F) the spheroid type at the shoulder, (G) the hinge type at the elbow, and (H) the gliding joints of the hand.
  3888. Fibrous Joints
  3889. Cartilaginous Joints
  3890. Joint (Articular) Capsule
  3891. Synovial Membrane
  3892. Joint (Synovial) Cavity
  3893. FIGURE 36-8 Collagen Zones. The three collagen zones (reserve, proliferative, and hypertrophic) are distinctly shown in a growth plate.
  3894. Synovial Fluid
  3895. Articular Cartilage
  3896. FIGURE 36-9 Knee Joint (Synovial Joint). A, Frontal view. B, Lateral view.
  3897. Synovial Joints
  3898. Structure of Synovial Joints
  3899. Movement of Synovial Joints
  3900. QUICK CHECK 36-2
  3901. Structure and Function of Skeletal Muscles
  3902. Whole Muscle
  3903. FIGURE 36-10 Movements of Synovial (Diarthrodial) Joints.
  3904. FIGURE 36-11 Body Movements Made Possible by Synovial (Diarthrodial) Joints.
  3905. FIGURE 36-12 Skeletal Muscles of Body. A, Anterior view. B, Posterior view.
  3906. Motor Unit
  3907. FIGURE 36-13 Cross Section of Skeletal Muscle Showing Muscle Fibers and Their Coverings.
  3908. FIGURE 36-14 Motor Units of a Muscle. Each motor unit consists of a motor neuron and all the muscle fibers (cells) supplied by the neuron and its axon branches.
  3909. FIGURE 36-15 Myofibrils. Myofibrils of a skeletal muscle fiber (cells) and overall organization of skeletal muscle.
  3910. Sensory receptors
  3911. Muscle fibers
  3912. TABLE 36-4 CHARACTERISTICS OF HUMAN SKELETAL MUSCLE FIBERS
  3913. TABLE 36-5 CONTRACTILE PROTEINS OF SKELETAL MUSCLE SARCOMERE
  3914. Myofibrils
  3915. Muscle proteins
  3916. Nonprotein constituents of muscle
  3917. Components of Muscle Function
  3918. Muscle Contraction at the Molecular Level
  3919. FIGURE 36-16 Muscle Fibers. A, The Z disks define the end of an individual sarcomere. The M line (which lies within the H band) is made of cross-connecting elements of the cytoskeleton. B, Actin is the primary protein of the I band (thin filament). Nebulin also extends along the I band and contains binding sites for actin and myosin. Myosin (thick filament) extends through the A band. Titin extends from the Z disk to the M band, binding with myosin; strong titin anchoring within the I band is necessary for proper muscle function. During contraction, the I bands and H bands shorten, moving the Z disks closer together. C, Electron photomicrograph of human muscle tissue corresponding to schematics in A and B.
  3920. Muscle Metabolism
  3921. TABLE 36-6 ENERGY SOURCES FOR MUSCULAR ACTIVITY
  3922. Muscle Mechanics
  3923. FIGURE 36-17 Isotonic and Isometric Contraction. A, In isotonic contraction, the muscle shortens, producing movement. B, In isometric contraction, the muscle pulls forcefully against a load but does not shorten.
  3924. Types of Muscle Contraction
  3925. Movement of Muscle Groups
  3926. Tendons and Ligaments
  3927. Aging & The Musculoskeletal System
  3928. Aging of Bones
  3929. HEALTH ALERT
  3930. Aging of Joints
  3931. Aging of Muscles
  3932. FIGURE 36-18 Cartilage-Bone, Tendon/Ligament-Bone, Meniscus-Bone, and Muscle-Tendon Interfaces. This diagram depicts the cartilage-bone, tendon/ligament-bone, meniscus-bone, and muscle-tendon interfaces and their compositions. Orange indicates levels of aggrecan concentration, light blue indicates collagen fibers, dark blue indicates mineralized tissue, and red indicates muscle fibers. Gradients of matrix composition, interdigitation of tissue zones, and interconnecting collagen fibers all enable load transfer between disparate tissues.
  3933. QUICK CHECK 36-3
  3934. DID YOU UNDERSTAND?
  3935. Structure and Function of Bones
  3936. Structure and Function of Joints
  3937. Structure and Function of Skeletal Muscles
  3938. Aging & the Musculoskeletal System
  3939. KEY TERMS
  3940. References
  3941. Chapter 37 Alterations of Musculoskeletal Function
  3942. Musculoskeletal Injuries
  3943. Skeletal Trauma
  3944. Fractures
  3945. FIGURE 37-1 Examples of Types of Bone Fractures. A, Oblique: fracture at oblique angle across both cortices. Cause: Direct or indirect energy, with angulation and some compression. B, Occult: fracture that is hidden or not readily discernible. Cause: Minor force or energy. C, Open: skin broken over fracture; possible soft tissue trauma. Cause: Moderate to severe energy that is continuous and exceeds tissue tolerance. D, Pathologic: transverse, oblique, or spiral fracture of bone weakened by tumor pressure or presence. Cause: Minor energy or force, which may be direct or indirect. E, Comminuted: fracture with two or more pieces or segments. Cause: Direct or indirect moderate to severe force. F, Spiral: fracture that curves around cortices and may become displaced by twist. Cause: Direct or indirect twisting energy or force with distal part held or unable to move. G, Transverse: horizontal break through bone. Cause: Direct or indirect energy toward bone. H, Greenstick: break in only one cortex of bone. Cause: Minor direct or indirect energy. I, Impacted: fracture with one end wedged into opposite end of inside fractured fragment. Cause: Compressive axial energy or force directly to distal fragment.
  3946. Classification of fractures
  3947. TABLE 37-1 TYPES OF FRACTURES
  3948. Pathophysiology
  3949. FIGURE 37-2 Bone Healing (Schematic Representation). A, Bleeding at broken ends of the bone with subsequent hematoma formation. B, Organization of hematoma into fibrous network. C, Invasion of osteoblasts, lengthening of collagen strands, and deposition of calcium. D, Callus formation; new bone is built while osteoclasts destroy dead bone. E, Remodeling is accomplished while excess callus is reabsorbed and trabecular bone is deposited.
  3950. Clinical Manifestations
  3951. FIGURE 37-3 Exuberant Callus Formation Following Fracture.
  3952. Evaluation And Treatment
  3953. Dislocation and Subluxation
  3954. Pathophysiology
  3955. Clinical Manifestations
  3956. Evaluation and Treatment
  3957. Support Structures
  3958. Sprains and Strains of Tendons and Ligaments
  3959. Pathophysiology
  3960. Clinical Manifestations
  3961. Evaluation and Treatment
  3962. Tendinopathy, Epicondylopathy, and Bursitis
  3963. FIGURE 37-4 Epicondylopathy and Tendinopathy. A, Lateral and medial epicondyles of the distal humerus, sites of tennis elbow (lateral) and golfer’s elbow (medial). B, Achilles tendon, common site of tendinopathy.
  3964. Pathophysiology
  3965. FIGURE 37-5 Olecranon Bursitis. Note swelling at the point of the elbow (olecranon). A smaller, rheumatoid nodule also is present.
  3966. Clinical Manifestations
  3967. Evaluation and Treatment
  3968. Muscle Strains
  3969. HEALTH ALERT
  3970. Rhabdomyolysis
  3971. Pathophysiology
  3972. Clinical Manifestations
  3973. TABLE 37-2 MUSCLE STRAIN
  3974. Evaluation and Treatment
  3975. BOX 37-1 SELECTED CAUSES OF RHABDOMYOLYSIS
  3976. Direct Trauma
  3977. Drugs
  3978. Excessive Muscular Contraction
  3979. Infectious Agents
  3980. Toxins
  3981. Hereditary Enzyme Disorders (Rare)
  3982. Miscellaneous Causes
  3983. BOX 37-2 FACTORS AFFECTING DEVELOPMENT OF COMPARTMENT SYNDROME
  3984. Increased Intracompartmental Pressure
  3985. Reduced Compartment Volume
  3986. Conditions That Disturb Microcirculation
  3987. Compartment Syndrome
  3988. Pathophysiology
  3989. Clinical Manifestations
  3990. Evaluation and Treatment
  3991. Malignant Hyperthermia
  3992. Evaluation and Treatment
  3993. FIGURE 37-6 Pathogenesis of Compartment Syndrome and Crush Syndrome Caused by Prolonged Muscle Compression. ECF, Extracellular fluid.
  3994. QUICK CHECK 37-1
  3995. FIGURE 37-7 Muscle Compartments of the Lower Leg.
  3996. Disorders of Bones
  3997. Metabolic Bone Diseases
  3998. Osteoporosis
  3999. FIGURE 37-8 Vertebral Body. Osteoporotic vertebral body (right) shortened by compression fractures compared with a normal vertebral body. Note that the osteoporotic vertebra has a characteristic loss of horizontal trabeculae and thickened vertical trabeculae.
  4000. FIGURE 37-9 Osteoporosis in Cortical and Trabecular Bone.
  4001. TABLE 37-3 T-SCORE AND WORLD HEALTH ORGANIZATION DIAGNOSIS OF BONE DENSITY
  4002. TABLE 37-4 COMPARISON OF STUDY OF FRACTURES (SOF), GARVAN, AND FRAX FRACTURE PREDICTION TOOLS
  4003. HEALTH ALERT
  4004. RISK FACTORS
  4005. Genetic
  4006. Anthropometric
  4007. Hormonal and Metabolic
  4008. Dietary
  4009. Lifestyle
  4010. Concurrent
  4011. Illness and Trauma
  4012. Liver Disease
  4013. Drugs
  4014. Pathophysiology
  4015. FIGURE 37-10 OPG/RANKL/RANK System. Expression of RANKL, a cytokine and part of the TNF family, and OPG, a glycoprotein receptor antagonist, is modulated by various cytokines, hormones, drugs, and mechanical strains (see inserts). In bone RANKL is expressed by both stromal cells and osteoblasts. RANKL stimulates the receptor RANK on osteoclast precursor cells and mature osteoclasts and activates intracellular signaling pathways to promote osteoclast differentiation and activation as well as cytoskeletal reorganization and survival (PKB/Akt pathway), which increase resorption and bone loss. OPG, secreted by stromal cells and osteoblasts, acts as a “decoy” receptor and blocks RANKL binding to and activation of RANK. BMP, Bone morphogenic protein; IL, interleukin; OPG, osteoprotegerin; PTH, parathyroid hormone; RANK, receptor activator nuclear factor κβ; RANKL, receptor activator nuclear factor κβ ligand; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha.
  4016. FIGURE 37-11 Mechanism of Loss of Trabecular Bone in Women and Trabecular Thinning in Men. Bone thinning predominates in men because of reduced bone formation. Loss of connectivity and complete trabeculae predominates in women.
  4017. FIGURE 37-12 Bone Loss in Men and Women. Absolute amount of bone resorbed on the inner bone surface and formed on the outer bone surface is more in men than women during aging.
  4018. Clinical Manifestations
  4019. FIGURE 37-13 Kyphosis. This elderly woman’s condition was caused by a combination of spinal osteoporotic vertebral collapse and chronic degenerative changes in the vertebral column.
  4020. Evaluation and Treatment
  4021. HEALTH ALERT
  4022. BOX 37-3 BIOCHEMICAL MARKERS OF BONE TURNOVER
  4023. Osteomalacia
  4024. HEALTH ALERT
  4025. Pathophysiology
  4026. Clinical Manifestations
  4027. Evaluation and Treatment
  4028. Paget Disease
  4029. Pathophysiology
  4030. Clinical Manifestations
  4031. Evaluation and Treatment
  4032. FIGURE 37-14 Osteomyelitis Showing Sequestration and Involucrum.
  4033. Infectious Bone Disease: Osteomyelitis
  4034. Pathophysiology
  4035. Clinical Manifestations
  4036. FIGURE 37-15 Resected Femur in a Person With Draining Osteomyelitis. The drainage tract in the subperiosteal shell of viable new bone (involucrum) reveals the inner native necrotic cortex (sequestrum).
  4037. Evaluation and Treatment
  4038. QUICK CHECK 37-2
  4039. Disorders of Joints
  4040. Osteoarthritis
  4041. Pathophysiology
  4042. FIGURE 37-16 Osteoarthritis (OA). A, Cartilage and degeneration of the hip joint from osteoarthritis. B, Heberden nodes and Bouchard nodes. C, Severe osteoarthritis with small islands of residual articular cartilage next to exposed subchondral bone. 1, Eburnated articular surface. 2, Subchondral cyst. 3, Residual articular cartilage.
  4043. Clinical Manifestations
  4044. RISK FACTORS
  4045. FIGURE 37-17 Typical Varus Deformity of Knee Osteoarthritis.
  4046. Evaluation and Treatment
  4047. HEALTH ALERT
  4048. Classic Inflammatory Joint Disease
  4049. Rheumatoid Arthritis
  4050. FIGURE 37-18 Rheumatoid Arthritis of the Hand. Note swelling from chronic synovitis of metacarpophalangeal joints, marked ulnar drift, subcutaneous nodules, and subluxation of metacarpophalangeal joints with extension of proximal interphalangeal joints and flexion of distal joints. Note also deformed position of thumb. Hand has wasted appearance.
  4051. Pathophysiology
  4052. Clinical Manifestations
  4053. FIGURE 37-19 Synovitis. Inflamed synovium showing typical arrangements of macrophages (red) and fibroblastic cells.
  4054. FIGURE 37-20 Emerging Model of Pathogenesis of Rheumatoid Arthritis. Rheumatoid arthritis is an autoimmune disease of a genetically susceptible host triggered by an unknown antigenic agent. Chronic autoimmune reaction with activation of CD4+ helper T cells and possibly other lymphocytes and the local release of inflammatory cytokines and mediators eventually destroy the joint. T cells stimulate cells in the joint to produce cytokines that are key mediators of synovial damage. Apparently, immune complex deposition also plays a role. Tumor necrosis factor (TNF) and interleukin-1 (IL-1), as well as some other cytokines, stimulate synovial cells to proliferate and produce other mediators of inflammation, such as prostaglandin E2 (PGE2), matrix metalloproteinases, and enzymes that all contribute to destruction of cartilage. Activated T cells and synovial fibroblasts also produce receptor activator of nuclear factor κβ ligand (RANKL), which activates the osteoclasts and promotes bone destruction. Pannus is a mass of synovium and synovial stroma with inflammatory cells, granulation tissue, and fibroblasts that grows over the articular surface and causes its destruction.
  4055. Evaluation and Treatment
  4056. HEALTH ALERT
  4057. Ankylosing Spondylitis
  4058. TABLE 37-5 THE 2010 AMERICAN COLLEGE OF RHEUMATOLOGY/EUROPEAN LEAGUE AGAINST RHEUMATISM CLASSIFICATION CRITERIA FOR RHEUMATOID ARTHRITIS
  4059. Pathophysiology
  4060. Clinical Manifestations
  4061. Evaluation and Treatment
  4062. FIGURE 37-21 Ankylosing Spondylitis. Characteristic posture and primary pathologic sites of inflammation and resulting damage.
  4063. TABLE 37-6 MEAN URATE CONCENTRATIONS BY AGE AND GENDER
  4064. Gout
  4065. FIGURE 37-22 Uric Acid Synthesis and Elimination. Uric acid is derived from purines ingested or synthesized from ingested foods, as well as being recycled after cell breakdown. Uric acid is then eliminated through the kidneys and gastrointestinal tract.
  4066. Pathophysiology
  4067. FIGURE 37-23 Pathogenesis of Acute Gouty Arthritis. A, Depending on the urate crystal coating, a variety of cells may be stimulated to produce a wide range of inflammatory mediators. Apo-E, Apolipoprotein E; IgG, immunoglobulin G; IL, interleukin; LTB4, leukotriene B4; PGE2, prostaglandin E2B, Sequence of events in the production of the inflammatory response to urate crystals. C, Gouty tophus on right foot.
  4068. Clinical Manifestations
  4069. Treatment
  4070. QUICK CHECK 37-3
  4071. Disorders of Skeletal Muscle
  4072. Secondary Muscular Dysfunction
  4073. Contractures
  4074. Stress-Induced Muscle Tension
  4075. Disuse Atrophy
  4076. Fibromyalgia
  4077. Pathophysiology
  4078. Clinical Manifestations
  4079. Evaluation and Treatment
  4080. BOX 37-4 EDUCATING AND PROVIDING REASSURANCE FOR INDIVIDUALS WITH FIBROMYALGIA
  4081. FIGURE 37-24 Theoretic Pathophysiologic Model of Fibromyalgia.
  4082. FIGURE 37-25 Location of Specific Tender Points for Diagnostic Classification of Fibromyalgia.
  4083. Muscle Membrane Abnormalities
  4084. Myotonia
  4085. Periodic Paralysis
  4086. Metabolic Muscle Diseases
  4087. Endocrine Disorders
  4088. Diseases of Energy Metabolism
  4089. McArdle disease
  4090. Acid maltase deficiency
  4091. Myoadenylate deaminase deficiency
  4092. Lipid deficiencies
  4093. Inflammatory Muscle Diseases: Myositis
  4094. Viral, Bacterial, and Parasitic Myositis
  4095. Polymyositis, Dermatomyositis, and Inclusion-Body Myositis
  4096. Clinical Manifestations
  4097. FIGURE 37-26 Dermatomyositis. Heliotrope (violaceous) discoloration around the eyes and periorbital edema.
  4098. Evaluation and Treatment
  4099. Toxic Myopathies
  4100. BOX 37-5 AGENTS THAT CAN CAUSE TOXIC MYOPATHY
  4101. Drug-Induced
  4102. Endocrine Disorders
  4103. Infectious
  4104. Miscellaneous
  4105. QUICK CHECK 37-4
  4106. Musculoskeletal Tumors
  4107. Bone Tumors
  4108. FIGURE 37-27 Derivation of Bone Tumors.
  4109. BOX 37-6 WORLD HEALTH ORGANIZATION (WHO) CLASSIFICATION OF BONE TUMORS
  4110. Cartilage Tumors
  4111. Osteogenic Tumors
  4112. Fibrogenic Tumors (Often Produce Collagen; Do Not Have a Mineralizing Matrix)
  4113. Fibrohistiocytic Tumors (Comprised of Fibroblasts)
  4114. Ewing Sarcoma
  4115. Hematopoietic Tumors
  4116. Giant Cell Tumor
  4117. Smooth Muscle Tumors
  4118. Miscellaneous Tumors
  4119. Miscellaneous Lesions
  4120. Joint Lesions
  4121. Epidemiology
  4122. Patterns of Bone Destruction
  4123. TABLE 37-7 PATTERNS OF BONE DESTRUCTION CAUSED BY BONE TUMORS
  4124. TABLE 37-8 SURGICAL STAGING SYSTEM FOR BONE TUMORS
  4125. Evaluation
  4126. Types
  4127. Osteogenic tumors: osteosarcoma
  4128. FIGURE 37-28 Osteosarcoma. A, Common locations of osteosarcoma. B, Femur has a large mass involving the metaphysis of the bone; the tumor has destroyed the cortex, forming a soft tissue component.
  4129. Chondrogenic tumors: chondrosarcoma
  4130. Collagenic tumors: fibrosarcoma
  4131. Myelogenic tumors
  4132. Giant cell tumor
  4133. Muscle Tumors
  4134. Rhabdomyoma
  4135. Rhabdomyosarcoma
  4136. Other Tumors
  4137. QUICK CHECK 37-5
  4138. DID YOU UNDERSTAND?
  4139. Musculoskeletal Injuries
  4140. Disorders of Bones
  4141. Disorders of Joints
  4142. Disorders of Skeletal Muscle
  4143. Musculoskeletal Tumors
  4144. KEY TERMS
  4145. References
  4146. Chapter 38 Alterations of Musculoskeletal Function in Children
  4147. Congenital Defects
  4148. Clubfoot
  4149. TABLE 38-1 TERMS USED TO DESCRIBE FOOT ABNORMALITIES
  4150. Developmental Dysplasia of the Hip
  4151. FIGURE 38-1 A, Infant with Bilateral Congenital Talipes Equinovarus. B, Ponseti Casting.
  4152. FIGURE 38-2 Idiopathic Clubfoot. Idiopathic clubfoot displaying forefoot adduction (toward midline of body) and supination (upturning) and hindfoot equinus (pointed downward). Note skin creases along arch and back of heel.
  4153. FIGURE 38-3 Hip Dysplasia in Children. Development dysplasia of the hip (DDH) with residual acetabular dysplasia. Radiographs at birth, 3, 10, and 19 years (top to bottom) show persisting dysplasia.
  4154. FIGURE 38-4 Congenital Dislocation of the Hip. A, Barlow maneuver (left side). With one hand pressing the symphysis in front and the sacral spine in back, lateral pressure is applied to the thigh with the thumb of the other hand while pressure is applied with the palm to the knee on the side being examined. The hip that has been flexed to 90 degrees is then adducted. A positive sign is a sensation of abnormal movement, indicating dislocation of the femoral head from the acetabulum. The hands are reversed for examining the other hip. This sign and Ortolani sign may be found only in the first weeks of life. B, Ortolani maneuver (right side). Sign of jerking into correct position. After Barlow maneuver (A), the hip should be abducted to about 80 degrees while the femur is lifted anteriorly with the fingers along the thigh. A positive sign is a sensation of a jerk or snap with reduction into the joint socket.
  4155. FIGURE 38-5 Pavlik Harness for Bilateral Hip Dislocation.
  4156. FIGURE 38-6 Osteogenesis Imperfecta Treated with Osteotomies and Telescoping Medullary Rods. A, Severe deformity of both femurs. B, Same individual after multiple osteotomies with telescoping medullary rod fixation. C, Same individual 4 years later demonstrating growth of femurs, no recurrence of deformity, and elongation of rods. (Plaster casts are in place for immobilization of tibial osteotomies.)
  4157. Osteogenesis Imperfecta
  4158. Bone Infection
  4159. Osteomyelitis
  4160. BOX 38-1 CAUSATIVE MICROORGANISMS OF OSTEOMYELITIS ACCORDING TO AGE
  4161. Newborns
  4162. Infants
  4163. Older Children
  4164. Adolescents and Adults
  4165. FIGURE 38-7 Pathogenesis of Acute Osteomyelitis Differs With Age. A, In infants younger than 1 year the epiphysis is nourished by arteries penetrating through the physis, allowing development of the condition within the epiphysis. B, In children up to 15 years of age, the infection is restricted to below the physis because of interruption of the vessels.
  4166. Septic Arthritis
  4167. Juvenile Idiopathic Arthritis
  4168. FIGURE 38-8 Routes of Infection to the Joint. 1, Hematogenous route. 2, Dissemination from osteomyelitis. 3, Spread from an adjacent soft tissue infection. 4, Diagnostic or therapeutic measures. 5, Penetrating damage by puncture or cutting.
  4169. QUICK CHECK 38-1
  4170. Osteochondroses
  4171. Legg-Calvé-Perthes Disease
  4172. Pathophysiology
  4173. FIGURE 38-9 Stages of Legg-Calvé-Perthes Disease, a Form of Osteochondrosis.
  4174. TABLE 38-2 CHARACTERISTICS OF JUVENILE IDIOPATHIC ARTHRITIS RELATED TO MODE OF ONSET
  4175. Clinical Manifestations
  4176. FIGURE 38-10 Pelvis of a 7-Year-Old Boy with Legg-Calvé-Perthes Disease.
  4177. Evaluation and Treatment
  4178. Osgood-Schlatter Disease
  4179. FIGURE 38-11 Surgical Replacement of Femoral Head of a 7-Year-Old Boy with Legg-Calvé-Perthes Disease. As the Perthes heals, the ball has assumed a round shape that matches the socket well.
  4180. Scoliosis
  4181. FIGURE 38-12 Scoliosis in Children. Normal spine alignment and abnormal spinal curvatures associated with scoliosis. A, Normal. B, Mild. C, Severe. D, Rotation and curvature of scoliosis.
  4182. Muscular Dystrophy
  4183. Duchenne Muscular Dystrophy
  4184. Pathophysiology
  4185. TABLE 38-3 MAJOR MUSCULAR DYSTROPHY SYNDROMES
  4186. Clinical Manifestations
  4187. FIGURE 38-13 Duchenne Muscular Dystrophy. A, Young boy with DMD but on horseback. B, Transverse section of gastrocnemius muscle from a healthy boy. C, Transverse section of gastrocnemius muscle from a boy with Duchenne muscular dystrophy. Normal muscle fiber is replaced with fat and connective tissue.
  4188. Evaluation and Treatment
  4189. Becker Muscular Dystrophy
  4190. FIGURE 38-14 Multisystem Approach for Evaluation and Treatment of Duchenne Muscular Dystrophy.
  4191. Facioscapulohumeral Muscular Dystrophy
  4192. Myotonic Muscular Dystrophy
  4193. Pathophysiology
  4194. Clinical Manifestations
  4195. Evaluation and Treatment
  4196. QUICK CHECK 38-2
  4197. Musculoskeletal Tumors
  4198. Benign Bone Tumors
  4199. Osteochondroma
  4200. Nonossifying Fibroma
  4201. Malignant Bone Tumors
  4202. Osteosarcoma
  4203. Pathophysiology
  4204. Clinical Manifestations
  4205. FIGURE 38-15 Ewing Sarcoma. A, Most common anatomic sites. B, Close-up view of Ewing sarcoma of the distal end of the tibia. Tumor extends into the soft tissue.
  4206. Evaluation and Treatment
  4207. Ewing Sarcoma
  4208. FIGURE 38-16 Ewing Sarcoma of the Distal Radius. Radiograph of an 8-year-old boy showing a permeative lesion of the distal radius. Note the loss of bone cortex on the ulnar border suggesting an aggressive process. Bone biopsy revealed Ewing sarcoma.
  4209. Pathophysiology
  4210. Clinical Manifestations
  4211. Evaluation and Treatment
  4212. QUICK CHECK 38-3
  4213. Nonaccidental Trauma
  4214. Fractures in Nonaccidental Trauma
  4215. Evaluation
  4216. FIGURE 38-17 Corner Fracture. Bilateral knee radiograph showing healing corner fractures of bilateral proximal tibias and distal femurs. Note the varying amount of callus formation signifying fractures at different stages of healing.
  4217. Treatment
  4218. QUICK CHECK 38-4
  4219. DID YOU UNDERSTAND?
  4220. Congenital Defects
  4221. Bone Infection
  4222. Juvenile Idiopathic Arthritis
  4223. Osteochondroses
  4224. Scoliosis
  4225. Muscular Dystrophy
  4226. Musculoskeletal Tumors
  4227. Nonaccidental Trauma
  4228. KEY TERMS
  4229. References
  4230. Chapter 39 Structure, Function, and Disorders of the Integument
  4231. Structure and Function of the Skin
  4232. Layers of the Skin
  4233. Dermal Appendages
  4234. FIGURE 39-1 Structure of the Skin. A, Cross section showing major skin structures. B, Layers of the epidermis.
  4235. FIGURE 39-2 Structures of the Nail.
  4236. TABLE 39-1 LAYERS OF THE SKIN
  4237. Blood Supply and Innervation
  4238. QUICK CHECK 39-1
  4239. GERIATRIC CONSIDERATIONS
  4240. Other Skin Changes with Aging
  4241. Clinical Manifestations of Skin Dysfunction
  4242. Lesions
  4243. Pressure ulcers
  4244. TABLE 39-2 PRIMARY AND SECONDARY SKIN LESIONS
  4245. TABLE 39-3 CLINICAL MANIFESTATIONS OF SELECT SKIN LESIONS
  4246. FIGURE 39-3 Progression of Pressure Ulcer. Sustained pressure over a bony prominence compresses the tissue and reduces blood flow, resulting in progressive ischemia and necrosis of tissue.
  4247. RISK FACTORS
  4248. External Factors
  4249. Disease/Tissue Factors
  4250. Keloids and Hypertrophic Scars
  4251. FIGURE 39-4 Keloid Formation.
  4252. Pruritus
  4253. QUICK CHECK 39-2
  4254. Disorders of the Skin
  4255. Inflammatory Disorders
  4256. Allergic Contact Dermatitis
  4257. Irritant Contact Dermatitis
  4258. FIGURE 39-5 Poison Ivy. A, Poison ivy on knee. B, Poison ivy dermatitis.
  4259. Atopic Dermatitis
  4260. Stasis Dermatitis
  4261. Seborrheic Dermatitis
  4262. FIGURE 39-6 Stasis Ulcer.
  4263. Papulosquamous Disorders
  4264. Psoriasis
  4265. FIGURE 39-7 Seborrheic Dermatitis.
  4266. FIGURE 39-8 Psoriasis. Typical oval plaque with well-defined borders and silvery scale.
  4267. FIGURE 39-9 Guttate Psoriasis Following Streptococcal Infection. Numerous uniformly small lesions may abruptly occur following streptococcal pharyngitis.
  4268. HEALTH ALERT
  4269. Pityriasis Rosea
  4270. FIGURE 39-10 Pityriasis Rosea Herald Patch. A collarette pattern has formed around the margins (arrows).
  4271. Lichen Planus
  4272. FIGURE 39-11 Hypertrophic Lichen Planus on Arms.
  4273. QUICK CHECK 39-3
  4274. Acne Vulgaris
  4275. Acne Rosacea
  4276. Lupus Erythematosus
  4277. FIGURE 39-12 Granulomatous Rosacea. Pustules and erythema occur on the forehead, cheeks, and nose.
  4278. Discoid (cutaneous) lupus erythematosus
  4279. Vesiculobullous Disorders
  4280. Pemphigus
  4281. FIGURE 39-13 Subacute Cutaneous Lupus (Discoid Lupus Erythematosus).
  4282. Erythema Multiforme
  4283. FIGURE 39-14 Bullous Pemphigoid. Generalized eruption with blisters arising from an edematous, erythematous annular base.
  4284. QUICK CHECK 39-4
  4285. Infections
  4286. Bacterial Infections
  4287. Folliculitis
  4288. Furuncles and carbuncles
  4289. Cellulitis
  4290. FIGURE 39-15 Furuncle of the Forearm.
  4291. Erysipelas
  4292. Impetigo
  4293. Viral Infections
  4294. Herpes simplex virus
  4295. FIGURE 39-16 Herpes Simplex of the Lips (Labialis). Typical presentation with tense vesicles appearing on the lips and extending onto the skin.
  4296. Herpes zoster and varicella
  4297. Warts
  4298. FIGURE 39-17 Herpes Zoster. Diffuse involvement of a dermatome.
  4299. FIGURE 39-18 Verruca Vulgaris (Near Toes).
  4300. Fungal Infections
  4301. Tinea infections
  4302. TABLE 39-4 COMMON SITES OF TINEA INFECTIONS
  4303. Candidiasis
  4304. FIGURE 39-19 Tinea Pedis. Inflammation has extended from the web area onto the dorsum of the foot.
  4305. Vascular Disorders
  4306. Cutaneous Vasculitis
  4307. TABLE 39-5 SITES OF CANDIDIASIS INFECTION
  4308. Urticaria
  4309. Scleroderma (Systemic Sclerosis)
  4310. FIGURE 39-20 Scleroderma. Note inflammation and shiny skin resulting from a combination of Raynaud phenomena and scleroderma affecting the fingers (acrosclerosis).
  4311. QUICK CHECK 39-5
  4312. Insect Bites
  4313. Mosquitoes, Flies, Bees, and Ants
  4314. Benign Tumors
  4315. Seborrheic Keratosis
  4316. FIGURE 39-21 Seborrheic Keratosis. Typical lesion that is broad, flat, and comparatively smooth surfaced.
  4317. Keratoacanthoma
  4318. Actinic Keratosis
  4319. Nevi (Moles)
  4320. QUICK CHECK 39-6
  4321. Cancer
  4322. HEALTH ALERT
  4323. BOX 39-1 IMPORTANT TRENDS FOR SKIN CANCER
  4324. Incidence
  4325. Mortality
  4326. Risk Factors
  4327. Warning Signs
  4328. Prevention and Early Detection
  4329. Treatment
  4330. Survival
  4331. Basal Cell Carcinoma
  4332. FIGURE 39-22 Basal Cell Carcinoma. Center has ulcerated.
  4333. Squamous Cell Carcinoma
  4334. Cutaneous Melanoma
  4335. FIGURE 39-23 Squamous Cell Carcinoma. The sun-exposed ear is a common site for squamous cell carcinoma.
  4336. FIGURE 39-24 Lentigo Malignant Melanoma. Lentigo malignant melanoma is most common on the head and neck.
  4337. TABLE 39-6 CLASSIFICATION OF NEVI
  4338. Kaposi Sarcoma
  4339. QUICK CHECK 39-7
  4340. FIGURE 39-25 Kaposi Sarcoma. The purple lesion commonly seen on the skin.
  4341. Burns
  4342. Burn Wound Depth
  4343. FIGURE 39-26 Superficial Partial-Thickness Burn. Scald injury following débridement of overlying blister and nonadherent epithelium.
  4344. FIGURE 39-27 Deep Partial-Thickness Burn. Note pale appearance and minimal exudates.
  4345. FIGURE 39-28 Axillary Burn Scar Contracture. Note the blanching of the anterior axillary fold and small ulceration from a deep partial-thickness burn, both indicating the diminished range of motion.
  4346. FIGURE 39-29 Full-Thickness Burn. The wound is dry and insensate.
  4347. TABLE 39-7 DEPTH OF BURN INJURY
  4348. Pathophysiology and Clinical Manifestations
  4349. FIGURE 39-30 Estimation of Burn Injury: Rule of Nines. A commonly used assessment tool with estimates of the percentages (in multiples of 9) of the total body surface area burned. A, Adults (anterior view). B, Adults (posterior view).
  4350. BOX 39-2 BURN UNIT REFERRAL CRITERIA
  4351. FIGURE 39-31 Immediate Cellular and Immunologic Alterations of Burn Shock.
  4352. Cardiovascular and Systemic Response to Burn
  4353. Cellular Response to Burn Injury
  4354. Metabolic Response to Burn Injury
  4355. Immunologic Response to Burn Injury
  4356. Evaporative Water Loss
  4357. Evaluation and Treatment
  4358. Frostbite
  4359. FIGURE 39-32 Hypertrophic Scarring. Deep partial-thickness thermal injury can result in extensive hypertrophic scarring.
  4360. FIGURE 39-33 Application of Cultured Epithelial Autografts. The thin sheets of keratinocytes are attached to gauze backing to allow application onto the clean, excised thigh.
  4361. Disorders of The Hair
  4362. Alopecia
  4363. Male-Pattern Alopecia (Androgenic Alopecia)
  4364. Female-Pattern Alopecia
  4365. Alopecia Areata
  4366. Hirsutism
  4367. Disorders of the Nail
  4368. Paronychia
  4369. Onychomycosis
  4370. QUICK CHECK 39-8
  4371. DID YOU UNDERSTAND?
  4372. Structure and Function of the Skin
  4373. Disorders of the Skin
  4374. Disorders of the Hair
  4375. Disorders of the Nail
  4376. KEY TERMS
  4377. References
  4378. Chapter 40 Alterations of the Integument in Children
  4379. Acne Vulgaris
  4380. FIGURE 40-1 Inflammatory (Cystic) Acne. Multiple pustules (erythematous papules and pustules) are present, and several have become confluent. Note areas of scarring.
  4381. HEALTH ALERT
  4382. Dermatitis
  4383. Atopic Dermatitis
  4384. FIGURE 40-2 Atopic Dermatitis. Characteristic lesions with crusting from irritation and scratching over knees and around ankles.
  4385. Diaper Dermatitis
  4386. FIGURE 40-3 Diaper Dermatitis. A, Diaper dermatitis with erosions. B, Diaper dermatitis with Candida albicans secondary infection.
  4387. QUICK CHECK 40-1
  4388. Infections of the Skin
  4389. Bacterial Infections
  4390. Impetigo Contagiosum
  4391. FIGURE 40-4 Impetigo and Herpes Simplex Virus (HSV) of Upper Lip. Note weeping and crusting lesions.
  4392. BOX 40-1 IMPETIGO
  4393. Vesicular Impetigo
  4394. Bullous Impetigo
  4395. Staphylococcal Scalded-Skin Syndrome
  4396. FIGURE 40-5 Staphylococcal Scalded-Skin Syndrome (SSSS). The skin lesions, showing desquamation and wrinkling of the skin margins, appeared 1 day after drainage of a staphylococcal abscess.
  4397. Fungal Infections
  4398. Tinea Capitis
  4399. FIGURE 40-6 Tinea Capitis.
  4400. Tinea Corporis
  4401. Thrush
  4402. FIGURE 40-7 Molluscum Contagiosum. Waxy pink globules with umbilicated centers.
  4403. Viral Infections
  4404. Molluscum Contagiosum
  4405. FIGURE 40-8 Rubella (3-Day Measles). A, Typical distribution of full-blown maculopapular rash with tendency to coalesce; B, Rash of rubella.
  4406. Rubella (German or 3-Day Measles)
  4407. TABLE 40-1 DIFFERENTIAL PRESENTATION OF VIRAL DISEASES PRODUCING RASHES
  4408. Rubeola (Red Measles)
  4409. Roseola (Exanthema Subitum)
  4410. Chickenpox, Herpes Zoster, and Smallpox
  4411. Chickenpox
  4412. FIGURE 40-9 Chickenpox. A, Pattern of generalized, polymorphous eruption; B, Chickenpox lesions on 5th day of illness.
  4413. Herpes zoster
  4414. Smallpox
  4415. QUICK CHECK 40-2
  4416. Insect bites and Parasites
  4417. Scabies
  4418. FIGURE 40-10 Scabies. A, Scabies mite, as seen clinically when removed from its burrow. B, Characteristic scabies bites.
  4419. Pediculosis (Lice Infestation)
  4420. Fleas
  4421. Ticks
  4422. FIGURE 40-11 Fleabites. Fleabite producing an urticarial wheal with central puncture.
  4423. Bedbugs
  4424. FIGURE 40-12 Capillary Hemangioma.
  4425. Hemangiomas and Vascular Malformations
  4426. Hemangiomas
  4427. FIGURE 40-13 Cavernous Hemangioma.
  4428. Vascular Malformations
  4429. FIGURE 40-14 Port-Wine Hemangioma. Port-wine hemangioma in a child.
  4430. Other Skin Disorders
  4431. Miliaria
  4432. FIGURE 40-15 Miliaria Rubra. Note discrete erythematous papules or papulovesicles.
  4433. Erythema Toxicum Neonatorum
  4434. QUICK CHECK 40-3
  4435. DID YOU UNDERSTAND?
  4436. Acne Vulgaris
  4437. Dermatitis
  4438. Infections of the Skin
  4439. Insect Bites and Parasites
  4440. Vascular Disorders
  4441. Other Skin Disorders
  4442. KEY TERMS
  4443. Smallpox infection (see video)
  4444. References
  4445. Appendixes
  4446. APPENDIX A Most Common Laboratory Values
  4447. Glossary
  4448. Glossary*
  4449. Index
  4450. Index
  4451. A
  4452. B
  4453. C
  4454. D
  4455. E
  4456. F
  4457. G
  4458. H
  4459. I
  4460. J
  4461. K
  4462. L
  4463. M
  4464. N
  4465. O
  4466. P
  4467. Q
  4468. R
  4469. S
  4470. T
  4471. U
  4472. V
  4473. W
  4474. X
  4475. Y
  4476. Z
  4477. IBC
  4478. IBC
  4479. PREFIXES AND SUFFIXES USED IN MEDICAL TERMINOLOGY
  4480. WORD ROOTS COMMONLY USED IN MEDICAL TERMINOLOGY

 

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