Sale!

Understanding Pathophysiology 4th Edition Huether Test Bank

Name: Understanding Pathophysiology 4th Edition Huether Test Bank
SKU: 22113
Price: 26.99 USD
Availability: InStock

Original price was: $50.00.Current price is: $26.99.

Understanding Pathophysiology 4th Edition Huether Test Bank.

Download sample

Categories: Health, Science, Test Bank Tags: Huether, Test Bank, Understanding Pathophysiology

Description

This is completed downloadable of Understanding Pathophysiology 4th Edition Huether Test Bank

Product Details:

ISBN-10 ‏ : ‎ 0323049907
ISBN-13 ‏ : ‎ 978-0323049900
Author: Sue E. Huether (Author), Kathryn L. McCance (Author)

This easy-to-read textbook provides you with the basic concepts of pathophysiology and the processes of specific diseases with the most accurate, up-to-date information on the treatments, manifestations, and mechanisms of disease. “Understanding Pathophysiology, 4th Edition” offers complete coverage in clear and concise detail with extensive full-color illustrations to make learning pathophysiology easy.

Table of Content:

Part One: Basic Concepts of Pathophysiology
Part Two: Body Systems and Diseases
Features To Promote Learning
Art Program
Teaching/Learning Package
For Students
For Instructors
Acknowledgments
Introduction to Pathophysiology
Part One Basic Concepts of Pathophysiology
Unit 1 The Cell
Chapter 1 Cellular Biology
Electronic Resources
Companion CD
Website
Prokaryotes and Eukaryotes
Cellular Functions
Structure and Function of Cellular Components
Nucleus
Cytoplasmic Organelles
Quick Check 1-1
Plasma Membranes
Figure 1-1 Typical Components of a Eukaryotic Cell.
Membrane composition
Lipids
Proteins
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 (here shown much larger than real 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. B from Raven PH, Johnson GB: Biology, St Louis, 1992, Mosby.
Table 1-1 Principal Cytoplasmic Organelles
Table 1-2 Plasma Membrane Functions
Figure 1-3 Amphipathic Molecule. In cellular membranes, amphipathic phospholipid molecules are organized in a bimolecular layer. The hydrophilic regions of the molecules are located at the membrane surfaces, and the hydrophobic regions are oriented toward the center of the membrane.
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. From Raven PH, Johnson GB: Understanding biology, ed 3, Dubuque, Iowa, 1995, Brown.
Carbohydrates
Fluid mosaic model
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. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Cellular Receptors
Figure 1-6 Cellular Receptors. A, 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: B, channel-linked receptors, and C, non–channel-linked receptors. Channel-linked receptors are also known as ligand-gated channels.
Cell-to-Cell Adhesions
Extracellular Matrix
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 proteogylcan 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 results in serious diseases such as arthritis, tumor growth, and others. Modified from Kumar V, Abbas A, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Specialized Cell Junctions
Figure 1-8 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. From Raven PH, Johnson GB: Biology, St Louis, 1992, Mosby.
Cellular Communication and Signal Transduction
Figure 1-9 Cellular Communication. Three primary ways in which cells communicate with one another.
Figure 1-10 Primary Modes of Chemical Signaling. Five forms of signaling mediated by secreted molecules. Hormones, paracrines, autocrines, neurotransmitters, and neurohormones are all intracellular messengers that accomplish communication between cells. Not all neurotransmitters act in the strictly synaptic mode shown; some act in a paracrine mode as local chemical mediators that influence multiple target cells in the area.
Table 1-3 Classes of Plasma Membrane Receptors
Figure 1-11 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 chemical messenger (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. Steps in the cascade can be modulated by other events in the cell.
Cellular Metabolism
Role of Adenosine Triphosphate
Food and Production of Cellular Energy
Figure 1-12 Three Phases of Catabolism: From Breakdown of Food to Elimination of Waste Products. These reactions produce adenosine triphosphate (ATP), which is used to power other processes in the cell.
Oxidative Phosphorylation
Figure 1-13 Glycolysis. Each of the numbered reactions is catalyzed by a different enzyme. At step 4, a six-carbon sugar is broken down to give two three-carbon sugars, 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.
Figure 1-14 What Happens to Pyruvate, the Product of Glycolysis? In the presence of oxygen, pyruvate is oxidized to acetyl 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 carbon dioxide (CO2) is first removed from pyruvate and the remainder is reduced, as it is in yeasts, the resulting product is ethanol.
Membrane Transport: Cellular Intake and Output
Movement of Water and Solutes
Passive transport: diffusion, filtration, and osmosis
Diffusion
Figure 1-15 Passive Diffusion of Solute Molecules Across the Plasma Membrane. Oxygen (O2), nitrogen (N2), water (H2O), urea, glycerol, and carbon dioxide (CO2) 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Filtration: hydrostatic pressure
Osmosis
Quick Check 1-2
Mediated and active transport
Mediated transport
Figure 1-16 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.
Figure 1-17 Channel Mode of Mediated Transport (Facilitated Diffusion). A channel protein forms a water-filled pore across the bilayer through which specific ions can diffuse.
Figure 1-18 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).
Figure 1-19 Active Transport and the Sodium-Potassium Pump. Three sodium (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 breaks apart, 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Active transport of Na+ and K+
Table 1-4 Major Transport Systems in Mammalian Cells
Transport by Vesicle Formation
Endocytosis and exocytosis
Figure 1-20 Endocytosis and Exocytosis. A, Endocytosis and fusion with lysosome and exocytosis. B, Electron micrograph of exocytosis. B from Raven PH, Johnson GB: Biology, ed 5, New York, 1999, McGraw-Hill.
Receptor-mediated endocytosis
Caveolae
Figure 1-21 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). B from Erlandsen SL, Magney JE: Color atlas of histology, St Louis, 1992, Mosby.
Movement of Electrical Impulses: Membrane Potentials
Figure 1-22 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 1-3
Cellular Reproduction: The Cell Cycle
Phases of Mitosis and Cytokinesis
Figure 1-23 Interphase and the Phases of Mitosis. A, The G1/S checkpoint is to “check” for cell size, nutrients, growth factors, and DNA damage. The G0 is the resting state. 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, it triggers cell cycle events.
Rates of Cellular Division
Growth Factors
Table 1-5 Examples of Growth Factors and Their Actions
Tissues
Figure 1-24 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.
Tissue Formation
Types of Tissues
Quick Check 1-4
Box 1-1 Characteristics of Epithelial Tissues
Box 1-2 Connective Tissues
Box 1-3 Muscle Tissues
Did You Understand?
Cellular Functions
Structure and Function of Cellular Components
Cell-to-Cell Adhesions
Cellular Communication and Signal Transduction
Cellular Metabolism
Membrane Transport: Cellular Intake and Output
Cellular Reproduction: The Cell Cycle
Tissues
Key Terms
References
Chapter 2 Genes and Genetic Diseases
Electronic Resources
Companion CD
Website
DNA, RNA, and Proteins: Heredity at the Molecular Level
Definitions
Composition and structure of DNA
Figure 2-1 Watson-Crick Model of the DNA Molecule. The DNA structure illustrated here is based on that published by James Watson (photograph, 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 united 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
DNA as the genetic code
Replication of DNA
Mutation
Figure 2-2 Replication of DNA. The two chains of the double helix separate, and each chain serves as the template for a new complementary chain. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, 2007, St Louis, Mosby.
Figure 2-3 Different Kinds of Mutations. C, Cytosine; A, adenine; T, thymine; G, guanine.
From Genes to Proteins
Transcription
Gene splicing
Translation
Figure 2-4 General Scheme of Ribonucleic Acid (RNA) Transcription. (See text for explanation.) From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, 2007, St Louis, Mosby.
Chromosomes
Chromosome Aberrations and Associated Diseases
Figure 2-5 Protein Synthesis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, 2007, St Louis, Mosby.
Figure 2-6 From Molecular Parts to the Whole Cell.
Polyploidy
Figure 2-7 Phases of Meiosis. From Jorde LB et al, Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Figure 2-8 Karyotype of Chromosomes. A, G-banded metaphase of a normal cell showing the bands of all normal chromosomes. B, G-banded karyotype of a normal female cell showing the banding patterns of the various chromosomes. Identical patterns characterize homologous chromosomes. The chromosomes are arranged from largest to smallest in size. From Damjanov I, Linder J: Anderson’s pathology, ed 10, vol 1, St Louis, 1996, Mosby.
Aneuploidy
Figure 2-9 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.
Figure 2-10 Nondisjunction. Causes aneuploidy when chromosomes or sister chromatids fail to divide properly. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Autosomal aneuploidy
Sex chromosome aneuploidy
Figure 2-11 Child with Down Syndrome. Courtesy Drs. A. Olney and M. MacDonald, University of Nebraska Medical Center, Omaha.
Abnormalities of chromosome structure
Figure 2-12 Down Syndrome Increases with Maternal Age. Rate is per 1000 live births related to maternal age.
Table 2-1 Characteristics of Various Chromosome Disorders
Deletions
Duplications
Inversions
Figure 2-13 Turner Syndrome. 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, 2007, St Louis, Mosby.
Figure 2-14 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). From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, 2007, St Louis, Mosby.
Figure 2-15 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.
Translocations
Fragile sites
Figure 2-16 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.
Quick Check 2-1
Elements of Formal Genetics
Phenotype and Genotype
Dominance and Recessiveness
Transmission of Genetic Diseases
Autosomal Dominant Inheritance
Characteristics of pedigrees
Figure 2-17 Symbols Commonly Used in Pedigrees. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Recurrence risks
Figure 2-18 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.
Figure 2-19 Pedigree for Achondroplasia. Pedigree showing the transmission of an autosomal dominant disease.
Delayed age of onset
Penetrance and expressivity
Figure 2-20 Pedigree for Retinoblastoma Showing Incomplete Penetrance. Female with marked arrow in line II must be heterozygous, but she does not express the trait.
Epigenetics and genomic imprinting
Figure 2-21 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. From Habif et al: Skin disease: diagnosis and treatment, ed 2, St Louis, 2005, Mosby.
Autosomal Recessive Inheritance
Characteristics of pedigrees
Recurrence risks
Figure 2-22 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.
Figure 2-23 Pedigree for Cystic Fibrosis. The double bar denotes a consanguineous mating. Because cystic fibrosis is relatively common in European populations, most cases do not involve consanguinity.
Figure 2-24 Punnett Square for the Mating of Heterozygous Carriers Typical of Most Cases of Recessive Disease.
Consanguinity
X-Linked Inheritance
X inactivation
Figure 2-25 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. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Sex determination
Figure 2-26 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 centrometric 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.
Quick Check 2-2
Characteristics of pedigrees
Recurrence risks
Sex-limited and sex-influenced traits
Figure 2-27 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).
Evaluation of Pedigrees
Linkage Analysis and Gene Mapping
Classical Pedigree Analysis
Figure 2-28 Genetic Results of Crossing Over. A, No crossing over. B, Crossing over with recombination. C, Double crossing over, resulting in no recombination.
Complete Human Gene Map: Prospects and Benefits
Figure 2-29 Example of Diseases: A Gene Map. PKU, phenylketonuria; ALD, adrenoleukodystrophy; ADA, adenosine deaminase.
Health Alert Gene Therapy
Table 2-2 Some Important Genetic Diseases That Have Been Mapped to Specific Chromosome Locations and Cloned
Multifactorial Inheritance
Figure 2-30 Multifactorial Inheritance. Analysis of mode of inheritance for grain color in wheat. The trait is controlled by three independently assorted gene loci.
Figure 2-31 Threshold of Liability for Pyloric Stenosis in Males and Females.
Box 2-1 Criteria Used to Define Multifactorial Diseases
Quick Check 2-3
Did You Understand?
DNA, RNA, and Proteins: Heredity at the Molecular Level
Chromosomes
Elements of Formal Genetics
Transmission of Genetic Diseases
Linkage Analysis and Gene Mapping
Multifactorial Inheritance
Key Terms
References
Chapter 3 Altered Cellular and Tissue Biology
Electronic Resources
Companion CD
Website
Cellular Adaptation
Atrophy
Figure 3-1 Adaptive and Dysplastic Alterations in Simple Cuboidal Epithelial Cells.
Hypertrophy
Figure 3-2 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. From Stevens A, Lowe J: Pathology: illustrated review in color, ed 2, Edinburgh, 2000, Mosby.
Hyperplasia
Dysplasia: Not a True Adaptive Change
Figure 3-3 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 occurs in response to increased intravesical pressure caused by urinary obstruction. From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Metaplasia
Figure 3-4 Reversible Changes in Cells Lining the Bronchi.
Cellular Injury
Table 3-1 Types of Progressive Cell Injury and Responses
Figure 3-5 Cellular Injury and Responses. Depiction of the relationship among normal, adapted (hypertrophied), and reversibly injured cells and cell death of myocardial cells.
General Mechanisms of Cell Injury
Hypoxic Injury
Table 3-2 Common Themes in Cell Injury and Cell Death
Figure 3-6 Hypoxic Injury Induced by Ischemia. Purple boxes involve reversible cell injury, light blue boxes involve irreversible cell death, and green boxes are clinical manifestations.
Figure 3-7 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. Redrawn from Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Health Alert Natural Antioxidants
Quick Check 3-1
Free Radicals and Reactive Oxygen Species Injury
Figure 3-8 Generation of Reactive Oxygen Species and Antioxidant Mechanisms in Biologic Systems. Mitochondria have four sites of entry for electrons coming into the electron transport system: one for reduced nicotinamide adenine dinucleotide (NADH) and three for the reduced form of flavin adenine dinucleotide (FADH2). These pathways meet at the small, lipophilic molecule, ubiquinone (coenzyme Q), at the beginning of the common electron transport pathway. Ubiquinone transfers electrons in the inner membrane, 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 one mole of adenosine triphosphate (ATP). With the transport of electrons, free radicals are generated within the mitochondria. Reactive oxygen species ( O2⋅−, H2O2, OH⋅, and nitric oxide [NO]) 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. Data from Dröge W: Physiol Rev 82:47–95, 2002; Buetler TM, Krauskopf A, Ruegg UT: News Physiol Sci 19:120–123, 2004.
Table 3-3 Biologically Relevant Free Radicals
Mechanisms of Chemical Injury
Box 3-1 Diseases and Disorders Linked to Oxygen-Derived Free Radicals
Table 3-4 Methods Contributing to Inactivation or Termination of Free Radicals
Chemical agents
Figure 3-9 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.
Lead
Table 3-5 Common Sources of Lead Exposure
Carbon monoxide
Ethanol
Figure 3-10 Major Pathway of Metabolism of Alcohol in the Liver through ADH.
Figure 3-11 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. From Fortinash KM, Holoday Worret PA: Psychiatric mental health nursing, ed 3, St Louis, 2004, Mosby.
Table 3-6 Major Sources of Mercury Exposure and Health Effects
Mercury
Figure 3-12 Alcoholic Hepatitis. Chicken-wire fibrosis extending between hepatocytes (Mallory trichrome stain.) From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Social or street drugs
Table 3-7 Social or Street Drugs and Their Effects
Quick Check 3-2
Unintentional and Intentional Injuries
Blunt-force injuries
Contusion
Abrasion
Figure 3-13 Patterned Abrasion Caused by a Piece of Rebar. Note the tissue tags at the inferior margins indicating a downward direction to the blow that caused this injury.
Laceration
Figure 3-14 Avulsed Laceration in Motor Vehicle Accident Victim. The victim was the driver, and this injury most likely was caused by the brake pedal.
Fractures
Sharp-force injuries
Incised wounds
Stab wounds
Figure 3-15 Self-inflicted Incised Wound of the Neck with Multiple Hesitation Marks.
Figure 3-16 Stab Wound with Associated Hilt Mark. Note the sharp margin away from the hilt mark with the blunt margin toward it. This wound was caused by a single-edge knife.
Puncture wounds
Chopping wounds
Gunshot wounds
Entrance wounds
Figure 3-17 Contact Range Gunshot Wound of the Chest with a Muzzle Abrasion.
Figure 3-18 Intermediate Range Gunshot Wound with Stippling and Tattooing.
Exit wounds
Figure 3-19 Indeterminate Range Entrance Wound with Eccentric Collar of Abrasion Resulting from the Bullet Striking the Skin at an Angle.
Wounding potential of firearms
Asphyxial injuries
Suffocation
Strangulation
Chemical asphyxiants
Drowning
Quick Check 3-3
Infectious Injury
Immunologic and Inflammatory Injury
Table 3-8 Mechanisms of Cellular Injury
Manifestations of Cellular Injury
Water
Figure 3-20 The Process of Oncosis (formerly referred to as “Hydropic Degeneration”). ATP, Adenosine triphosphate.
Lipids and Carbohydrates
Glycogen
Proteins
Figure 3-21 Fatty Liver. The liver appears yellow. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Pigments
Melanin
Hemoproteins
Figure 3-22 Hemosiderin Accumulation Is Noted as the Color Changes in a “Black Eye.”
Calcium
Figure 3-23 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.
Urate
Systemic Manifestations
Figure 3-24 Aortic Valve Calcification. A, This calcified aortic valve is an example of dystrophic calcification. B, This algorithm shows the dystrophic mechanism of calcification. A from Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Cellular Death
Necrosis
Table 3-9 Systemic Manifestations of Cellular Injury
Figure 3-25 Stages of Necrosis.
Figure 3-26 Coagulative Necrosis of Myocardium of Posterior Wall of Left Ventricle of Heart. A large, anemic (white) infarct is readily apparent; note also the necrosis of papillary muscle. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 3-27 Liquefactive Necrosis of the Brain. The area of infarction is softened as a result of liquefaction necrosis. From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Figure 3-28 Granuloma with Central Caseous Necrosis Typical of Pulmonary Tuberculosis. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 3-29 Fat Necrosis of Pancreas. Interlobular adipocytes are necrotic; acute inflammatory cells surround these. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 3-30 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.
Apoptosis
Figure 3-31 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 taken up by macrophages or adjacent cells. RER, Rough endoplasmic reticulum. Redrawn from Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Quick Check 3-4
Aging & Altered Cellular and Tissue Biology
Figure 3-32 Microinsults. Redrawn from Johnson HA, editor: Is aging physiological or pathological? Relations between normal aging and a disease, New York, 1985, Raven.
Normal Life Span
Life Expectancy and Gender Differences
Theories and Mechanisms of Aging
Table 3-10 Theories of Aging
Genetic and environmental lifestyle factors
Alterations of cellular control mechanisms
Degenerative extracellular changes
Cellular Aging
Tissue and Systemic Aging
Frailty
Somatic Death
Quick Check 3-5
Did You Understand?
Cellular Adaptation
Cellular Injury
Manifestations of Cellular Injury
Cellular Death
AGING & Altered Cellular and Tissue Biology
Somatic Death
Key Terms
References
Chapter 4 Fluids and Electrolytes, Acids and Bases
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Distribution of Body Fluids
Maturation and the Distribution of Body Fluids
Table 4-1 Total Body Water (%) in Relation to Body Weight
Table 4-2 Distribution of Body Water
Table 4-3 Normal Water Gains and Losses (70-kg Man)
Pediatrics & Distribution of Body Fluids
Newborn Infants
Children and Adolescents
Aging & Distribution of Body Fluids
Water Movement Between Plasma and Interstitial Fluid
Water Movement Between ICF and ECF
Alterations in Water Movement
Edema
Figure 4-1 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 in to 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 294mOsm) and water is equally distributed between the interstitial and intracellular compartments.
Pathophysiology
Figure 4-2 Examples of Changes in Osmotic Equilibrium Between ECF and ICF. A, Normal ECF and ICF volumes. Intracellular and extracellular fluid osmotic pressures are equal and water is equally distributed between the compartments. B, Extracellular fluid volume excess or sodium deficit. ECF volume excess or sodium deficit decreases the ECF osmotic pressure and water is attracted to the ICF space (see C). C, Fluid movement from the ECF to ICF to reestablish osmotic equilibrium. The intracellular osmotic pressure attracts water from the ECF causing an increase in ICF water volume with a balancing of osmotic forces between the ECF and ICF. The consequence is an increase in ICF volume and cell swelling. D, Extracellular fluid volume deficit or sodium excess. ECF volume deficit increases the ECF osmotic pressure and intracellular water is attracted to the ECF space (see E). E, Fluid movement from the ICF to the ECF to reestablish osmotic equilibrium. Water from the intracellular space has moved to the extracellular space until the osmotic forces are equal. The consequence is a decrease in ICF water volume and cell size. ICF, Intracellular fluid; ECF, extracellular fluid.
Clinical Manifestations
Quick Check 4-1
Figure 4-3 Mechanisms of Edema Formation. Na+, sodium; H2O, water.
Sodium, Chloride, and Water Balance
Water Balance
Sodium and Chloride Balance
Figure 4-4 The Antidiuretic Hormone (ADH) System.
Table 4-4 Representative Distribution of Electrolytes in Body Compartments
Figure 4-5 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; (4) Angiotensin II promotes vasoconstriction and stimulates aldosterone secretion from the adrenal cortex resulting in renal sodium and water retention and an increase in blood pressure. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 4-6 The Atrial Natriuretic Hormone (ANH) System. Na+, sodium; GFR, glomerular filtration rate. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Quick Check 4-2
Alterations in Sodium, Chloride, and Water Balance
Isotonic Alterations
Table 4-5 Water and Solute Imbalances
Hypertonic Alterations
Hypernatremia
Pathophysiology
Health Alert Breastfeeding and Hypernatremia
Clinical Manifestations
Table 4-6 Causes and Consequences of Hypertonic Imbalances
Water Deficit
Pathophysiology
Clinical Manifestations
Hyperchloremia
Hypotonic Alterations
Hyponatremia
Pathophysiology
Table 4-7 Causes and Consequences of Hypotonic Imbalances
Clinical Manifestations
Water excess
Pathophysiology
Clinical Manifestations
Hypochloremia
Quick Check 4-3
Alterations in Potassium and Other Electrolytes
Potassium
Hypokalemia
Pathophysiology
Clinical Manifestations
Figure 4-7 Electrocardiogram Changes with Potassium Imbalance.
Hyperkalemia
Pathophysiology
Table 4-8 Clinical Manifestations of Potassium Alterations
Clinical Manifestations
Quick Check 4-4
Other Electrolytes
Acid-Base Balance
Hydrogen Ion and pH
Table 4-9 Alterations in Other Body Electrolytes
Buffer Systems
Table 4-10 pH of Body Fluids
Table 4-11 Buffer Systems
Carbonic acid–bicarbonate buffering
Protein buffering
Renal buffering
Figure 4-8 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Acid-Base Imbalances
Metabolic acidosis
Figure 4-9 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 partial pressure of carbon dioxide (PaCO2 = 40mm Hg) and bicarbonate ( HCO3−=24mEq/L). Note that as the PaCO2 increases toward 60mm Hg (A), the pH decreases (respiratory acidosis), and that as it decreases toward 20mm 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).
Table 4-12 Causes of Metabolic Acidosis
Metabolic alkalosis
Figure 4-10 Metabolic Acidosis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Box 4-1 Anion Gap
Respiratory acidosis
Figure 4-11 Metabolic Alkalosis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 4-12 Respiratory Acidosis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Respiratory alkalosis
Quick Check 4-5
Figure 4-13 Respiratory Alkalosis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Did You Understand?
Distribution of Body Fluids
Alterations in Water Movement
Sodium, Chloride, and Water Balance
Alterations in Sodium, Chloride, and Water Balance
Alterations in Potassium and Other Electrolytes
Acid-Base Balance
Key Terms
References
Unit 2 Mechanisms of Self-Defense
Chapter 5 Innate Defenses: Inflammation
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Human Defense Mechanisms
Table 5-1 Overview of Human Defenses
First Line of Defense: Physical, Mechanical, and Biochemical Barriers
Physical and Mechanical Barriers
Biochemical Barriers
Second Line of Defense: Inflammation
Figure 5-1 The Sequence of Events in the Process of Inflammation. See the text for details.
Figure 5-2 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.
The Mast Cell
Figure 5-3 Degranulation (left) and Synthesis (right) of Biologic Mediators by Mast Cells during Inflammation. Mast cells are filled with darkly staining granules that contain a large number of biologically active substances. Among these are histamine, which is a major initiator of vascular changes, and a variety of chemotactic factors. These 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.
Mast Cell Degranulation
Figure 5-4 Effects of Histamine through H1 and H2 Receptors. The effects depend on (1) density and affinity of H1 or H2 receptors on the target cell and (2) the identity of the target cell. GTP, Guanosine triphosphate; cGMP, cyclic guanosine monophosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate.
Mast Cell Synthesis of Mediators
Quick Check 5-1
Plasma Protein Systems
Figure 5-5 Plasma Protein Systems in Inflammation: Complement, Clotting, and Kinin Systems. See the text for more detailed information. In this scheme some systems are activated by multiple pathways that come together (at C3 for the complement system and factor X for the clotting system). Some of the components of the pathways are activated by being split into two active components (C3 and C5 of the complement system and fibrinogen of the clotting system). The larger of the components usually activates the next component of the pathway (as do C3b and C5b of the complement system). Hageman factor participated in both the clotting and kinin pathways (i.e., activated factor XII [XIIa] helps activate factor X and prekallikrein). Many of the components of each pathway have potent biologic activities (in red colored boxes). Many other components of each pathway are not shown in this drawing but play very important roles in activation of the pathway. FP, Fibrinopeptides.
Complement System
Clotting System
Kinin System
Control and Interaction of Plasma Protein Systems
Cellular Components of Inflammation
Neutrophils
Monocytes and Macrophages
Figure 5-6 Activation of a Macrophage by Cytokines. Some cytokines produced by lymphocytes can react with surface receptors on macrophages and greatly increase their ability to kill bacteria. A, Electron micrograph of a peripheral blood monocyte. B, Electron micrograph of an activated tissue macrophage showing increases in cytoplasmic volume, plasma membrane, and numbers of lysosomal granules. Additionally, activation includes increases in glucose metabolism, phagocytic activity, and bacterial killing. (A, From Abbas AK, Lichtman AH: Cellular and molecular immunology, ed 5, Philadelphia, 2003, Saunders; B, from Bloom W, Fawcett DW: A textbook of histology, ed 11, Philadelphia, 1986, Saunders.)
Eosinophils
Natural Killer (NK) Cells
Platelets
Phagocytosis
Figure 5-7 Process of Phagocytosis. Phagocytosis is a multistep process that involves diffusion of chemotactic factors from a site of injury. Many additional factors affect the blood vessels and increase adhesion molecules on endothelial cells and neutrophils, resulting in adherence of the neutrophils to the vessel wall (pavementing), retraction of endothelial cells (vascular permeability), and movement of the neutrophils through the opened intercellular junctions (diapedesis) and into the tissue. The cells move up the gradient toward the highest concentration of chemotactic factors (chemotaxis). At the site of injury, neutrophils begin phagocytosis of contaminating bacteria. The actual process of phagocytosis involves several steps (see enlargement): (1) adherence to the bacteria, which is increased by opsonins such as antibody (Ab) and complement component C3b; (2) engulfment of the bacteria by extensions of the neutrophil’s membrane (pseudopods); (3) formation of a phagosome containing the bacterium surrounded by the neutrophil’s plasma membrane; (4) fusion of lysosomes with the vacuole to form a phagolysosome and the production of toxic oxygen molecules (H2O2, hydrogen peroxide; O2−, superoxide); and (5) killing and breakdown of the bacterium.
Figure 5-8 Steps in Phagocytosis. This scanning electron micrograph shows the progressive steps in phagocytosis of red blood cells by a macrophage. A, The macrophage (M) attaches to the red blood cells (R). B, An extension of the macrophage membrane (P; pseudopod) starts to enclose the red cell. C, The red blood cells are almost totally engulfed by the macrophage. (Modified from King DW, Fenoglio CM, Lefkowitch JH: General pathology: principles and dynamics, Philadelphia, 1983, Lea & Febiger.)
Quick Check 5-2
Cellular Products
Figure 5-9 Selected Cytokines that Mediate Inflammation and the Acquired Immune Response. See the text for a more detailed description. IL, Interleukin; IFN, interferon; TNF, tumor necrosis factor; TGF, transforming growth factor; CSFs, colony stimulating factors.
Cytokines
Interleukins
Interferons
Other cytokines
Figure 5-10 The Action of Interferon.
Chemokines
Quick Check 5-3
Health Alert Fat Is “Inflammatory”
Local Manifestations of Acute Inflammation
Systemic Manifestations of Acute Inflammation
Fever
Leukocytosis
Plasma Protein Synthesis
Table 5-2 Acute-Phase Reactants: Proteins That Are Increased or Decreased in the Blood During Inflammation
Chronic Inflammation
Figure 5-11 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 referred to in this illustration.
Figure 5-12 Tuberculous Granuloma. Granulomas frequently form around areas of infection with the organism that causes tuberculosis. The granulomas consist of a central area of amorphous caseous (cheeselike) necrosis that is surrounded by a zone of activated macrophages, in which multinucleate macrophages (Langerhans giant cells) are present. There are outer layers of lymphocytes and fibroblasts. A wall of fibrin is laid down around the granulomas, and the contents eventually breakdown and liquefy. (From Stevens A, Lowe J: Pathology, ed 2, Edinburgh, 2000, Mosby.)
Quick Check 5-4
Resolution and Repair
Figure 5-13 Wound Repair by Primary or Secondary Intention.A to D, Healing by primary intention. E to I, Healing by secondary intention. Please see the text for more details.
Reconstructive Phase
Maturation Phase
Dysfunctional Wound Healing
Dysfunction during the inflammatory response
Dysfunction during the reconstructive phase
Impaired collagen synthesis
Figure 5-14 Keloid (scar) Formation. Scar and keloid caused by excessive synthesis of collagen at a suture site. (From Damjanov I, Linder J: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.)
Impaired epithelialization
Wound disruption
Impaired contraction
Quick Check 5-5
Pediatrics & Factors Affecting Mechanisms of Self-Defense in the Newborn Child
Aging & Factors Affecting Mechanisms of Self-Defense in the Elderly
Did You Understand?
Human Defense Mechanisms
First Line of Defense: Physical, Mechanical, and Biochemical Barriers
Second Line of Defense: Inflammation
The Mast Cell
Plasma Protein Systems
Cellular Components of Inflammation
Cellular Products
Local Manifestations of Acute Inflammation
Systemic Manifestations of Acute Inflammation
Chronic Inflammation
Resolution and Repair
PEDIATRICS & Factors Affecting Mechanisms of Self-Defense in the Newborn Child
AGING & Factors Affecting Mechanisms of Self-Defense in the Elderly
Key Terms
References
Chapter 6 Adaptive Immunity
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
General Characteristics of Adaptive Immunity
Table 6-1 Clinical Use of Antigen or Antibody
Humoral and Cell-Mediated Immunity
Active and Passive Immunity
Figure 6-1 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 divisions and differentiation stages resulting in either immunocompetent T cells from the thymus or immunocompetent B cells from the bone marrow. These cells 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 take up residence in B and T cell–rich areas (more detail in Figure 6-14). The clonal selection phase is initiated by exposure to foreign antigen. The antigen is usually processed by antigen-presenting cells (APCs) for presentation to helper T cells (Th cells) (more detail in Figures 6-16 and 6-17). The intercellular cooperation among APCs, Th cells, and immunocompetent T and B cells results in a second stage of cellular proliferation and differentiation (more detail in Figures 6-19 and 6-20). 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 end 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 (cytotoxic T cells) or regulate the immune response (regulatory T cells), as well as a population of memory T 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.
Quick Check 6-1
Antigens and Immunogens
Figure 6-2 Lymphoid System. 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.
Figure 6-3 Scanning Electron Micrograph of Lymphocytes and Macrophages. The lymphocytes are small and spherical; the macrophages are larger and more irregular in shape. From Raven PH, Johnson GB: Biology, ed 5, New York, 1999, McGraw-Hill.
Figure 6-4 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 8 or 9 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.
Humoral Immune Response
Antibodies
Classes of immunoglobulins
Figure 6-5 Structure of Different Immunoglobulins. Secretory IgA, IgD, IgE, IgG, and IgM. The black circles attached to each molecule represent carbohydrate residues.
Table 6-2 Properties of Immunoglobulins
Molecular structure
Figure 6-6 Molecular Structure of an Antibody. A, The typical antibody molecule consists of four chains—two identical light (L) and two identical heavy (H)—held together by intrachain and interchain disulfide linkages. The primary interchain disulfides between heavy chains occur in the hinge region (Hi) and provide flexibility in some classes of antibody. Each heavy chain and light chain is divided into regions that have relatively constant amino acid sequences (green areas) and regions with a variable amino acid sequence (VH, VL). Within the VH and VL regions are three highly variable complementary-determining regions (CDR1, CDR2, CDR3). B, Fragmentation of IgG by limited digestion with the enzyme papain has identified three important portions of the molecule: an Fc and two identical Fab fragments. Both Fab fragments could bind antigen. C, In this molecular model of a typical antibody molecule, the light chains are represented by strands of red spheres (each represents an individual amino acid), and heavy chains are represented by strands of blue spheres. Note that the heavy chain contains sites where carbohydrates are bound. As the chains fold and interact, the six CDRs within a Fab region are placed in close proximity to form the antigen-binding site. C from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Antigen binding
Function of antibodies
Figure 6-7 Antigen-Antibody Binding. The specificity of an antibody binding with an antigen is determined by the shape and chemistry of the six complementary-determining regions (CDRs) in the combining site on the variable region of the antibody. This figure indicates two different antibodies (Fab portions of antibody 1 and antibody 2), which have different sets of CDRs and, therefore, different specificities. As indicated, the antigenic determinant that reacts well with antibody 1 is unable to react with antibody 2 because of differences in the antibody- combining site. Fab, Antigen-binding fragment.
Direct effects
Indirect effects
IgE
Figure 6-8 Direct and Indirect Functions of Antibody. Activities of antibodies can be direct (through the action of antibody alone) or indirect (requiring activation of other components of inflammation, usually through the Fc region). Direct means they include neutralization of viruses or bacterial toxins before they bind to receptors on the surface of the host’s cells. Indirect means they include activation of the classical complement pathway through C1 resulting in formation of the membrane-attack complex (MAC) or by increased phagocytosis of bacteria opsonized with antibody and complement components bound to appropriate surface receptors (FcR and C3bR) on the phagocyte.
B cell antigen receptor
Figure 6-9 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 (see Figure 6-9); (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.
Secretory immune system
Figure 6-10 IgE-Mediated Destruction of a Parasite. (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.
Monoclonal antibodies
Quick Check 6-2
Cell-Mediated Immune Response
Figure 6-11 Secretory Immune System. Lymphocytes from the mucosal-associated (secretory) 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.
T Cell Recognition of a Target Cell
T cell receptor complex
Antigen presentation molecules
Figure 6-12 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 complex also contains genes for several other molecules that participate in the innate or immune responses, including some complement proteins and cytokines, which are referred to as MHC class III molecules. 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 complex with β2 microglobulin, which is encoded by a gene on chromosome 15. The MHC class I molecules present small peptide antigens (8 or 9 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 (-S-S-). 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 β1 domain of the β chain. Both MHC class I and II molecules are anchored to the plasma membrane by hydrophobic regions on the ends of the α and β chains.
CD molecules
T Lymphocyte Function
Killing abnormal cells
Cytotoxic T lymphocytes
Figure 6-13 Cellular Killing Mechanisms. Several cells have the capacity to kill abnormal (e.g., virally infected, cancerous) target cells. (1) Cytotoxic T (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). Insert from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Other cells that kill abnormal cells
T cells that activate macrophages
Regulatory T lymphocytes
Quick Check 6-3
Generation of Clonal Diversity
Table 6-3 Generation of Clonal Diversity vs. Clonal Selection
B Lymphocytes
T Lymphocytes
Induction of the Immune Response
Figure 6-14 Secondary Lymphoid Tissues: Sites of B Cell and T Cell Differentiation. A, A lymph node is organized into an outer cortex (C) and an inner medulla (M).B, The lymph node contains areas that are rich in immunocompetent B cells (stained green) and T cells (stained red). C, In response to antigen, B cells undergo proliferation resulting in the formation of germinal centers (GC). From Kumar V, Abbas A, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Primary and Secondary Immune Responses
Figure 6-15 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.
Cellular Interactions in the Immune Response
Antigen processing and presentation
Helper T lymphocytes
Figure 6-16 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 (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).
Superantigens
Figure 6-17 Development of Th1 and Th2 Cells. Antigen presenting cells (APC) present antigen to a precursor Th cells. (1) An antigen signal is produced by the interaction of the T cell receptor (TCR) and CD4 with antigen presented by MHC class II molecules. (2) Cytokines (particularly IL-1) produced by the APC provide a second signal. (3) In response to these signals, the precursor Th cells begin producing the cytokine IL-2, which binds with the same cell to accelerate differentiation and proliferation. Commitment to a Th1 or Th2 phenotype results from the effects of other cytokines. (4) IL-12 and IFN-γ favor differentiation into the Th1 cell phenotype, whereas (5) IL-4 favors differentiation into the Th2 cell phenotype. (6) The Th1 cell produces cytokines that assist in the differentiation of cytotoxic T (Tc) cells (e.g., TNF-β, IL-2), whereas (7) the Th2 cell produces cytokines that favor B cell differentiation (e.g., IL-4, IL-5, IL-6). (8) 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.
T cell clonal selection: The cellular immune response
B cell clonal selection: The humoral immune response
Figure 6-18 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 V-β chains independently of the antigen specificity of the TCR.
Figure 6-19 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.
Figure 6-20 B 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).
Memory cells
Figure 6-21 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.
Quick Check 6-4
Pediatrics & Immune Function
Transport of IgG Across the Syncytiotrophoblast. The human placenta is covered with a specialized multinucleate cell, the syncytiotrophoblast. Transport of maternal IgG across the syncytiotrophoblast and into the fetal circulation is an active process. Maternal IgG binds to Fc receptors on the surface of the syncytiotrophoblast and is internalized by the process of endocytosis. Receptors on the syncytiotrophoblast are specific for the Fc portion of IgG and do not bind other classes of immunoglobulins. Interaction of IgG with Fc receptors protects the antibody from lysosomal digestion during transport of the vacuole across the cell (i.e., transcytosis). On the fetal side of the syncytiotrophoblast, IgG is released by exocytosis (see Chapter 1).
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
Aging & Immune Function
Did You Understand?
General Characteristics of the Immune Response
Antigens and Immunogens
Humoral Immune Response
Cell-Mediated Immune Response
Generation of Clonal Diversity
Induction of the Immune Response
PEDIATRICS & Immune Function
AGING & Immune Function
Key Terms
References
Chapter 7 Hypersensitivities, Infection, and Immune Deficiencies
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
Table 7-1 Relative Incidence and Examples of Hypersensitivity Diseases*
Mechanisms of Hypersensitivity
Type I: IgE-mediated hypersensitivity reactions
Mechanisms of IgE-mediated hypersensitivity
Table 7-2 Examples of Autoimmune Disorders
Clinical Manifestations
Table 7-3 Immunologic Mechanisms of Tissue Destruction
Evaluation and Treatment
Type II: Tissue-specific hypersensitivity reactions
Figure 7-1 Mechanism of Type I, IgE-Mediated Reactions. First exposure to an allergen stimulates B lymphocytes to mature into plasma cells that produce 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 second exposure, the allergen cross-links the surface-bound IgE and causes degranulation of the mast cell. The initial phase is characterized by vasodilation, vascular leakage, and smooth muscle spasm or glandular secretions, usually within 5 to 30 minutes after exposure to antigen. The late phase occurs 2 to 8 hours later without additional exposure to antigen and results from infiltration of tissues with inflammatory cells, including eosinophils, neutrophils, and basophils. (See Chapter 5 for more details on the role of mast cells in inflammation.)
Figure 7-2 Type I Hypersensitivity Reactions. Symptoms of type I allergic reactions are indicated.
Table 7-4 Causes of Clinical Allergic Reactions
Type III: Immune complex–mediated hypersensitivity reactions
Mechanisms of type III hypersensitivity
Figure 7-3 Type I Hypersensitivity Reactions. Photographs show diffuse allergic-like (A) eye (angioedema) and (B) skin (allergic urticaria) reactions. The skin lesions have raised edges and develop within minutes or hours, with resolution occurring after about 12 hours. From Male D et al: Immunology, ed 7, St Louis, 2006, Mosby.
Immune complex disease
Figure 7-4 Mechanisms of Type II, Tissue-Specific Reactions. Antibody binds to antigens on the cell surface and destroys or prevents the cell from functioning by A, complement-mediated lysis (an erythrocyte target is illustrated here); B, phagocytosis by macrophages in the tissue; C, neutrophil-mediated destruction; D, antibody-dependent cell-mediated cytotoxicity (ADCC); or E, modulation or blocking the normal function of receptors by antireceptor antibody. C1, Complement component C1; C3b, complement fragment produced from C3, which acts as an opsonin.
Figure 7-5 Mechanism of Type III, Immune-Complex-Mediated Reactions.(1) Immune complexes form in the blood from circulating antigen and antibody and (2) are deposited in certain target tissues. (3) The complexes activate complement through C1 and generate fragments that are chemotactic for neutrophils. (4) The neutrophils attach to the IgG and C3b in the immune complexes and (5) release a variety of degradative enzymes that destroy the healthy tissues.
Type IV: Cell-mediated hypersensitivity reactions
Figure 7-6 Mechanism of Type IV Cell-Mediated Reactions. Antigens from target cells stimulate T cells to differentiate into T cytotoxic cells, which have direct cytotoxic activity, and T helper cells, which produce cytokines (especially interferon-γ) that activate macrophages. The macrophages can attach to targets and release enzymes and reactive oxygen species that induce apoptosis of the target.
Figure 7-7 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. From Damjanov I, Linder J: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Quick Check 7-1
Antigenic Targets of Hypersensitivity Reactions
Allergy
Allergens
Allergic disease: bee sting allergy
Autoimmunity
Breakdown of tolerance
Autoimmune disease: systemic lupus erythematosus
Health Alert Autoimmune Diseases Affect Women More Than Men
Alloimmunity
Alloantigens
Alloimmune disease: transfusion reactions
ABO system
Rh system
Figure 7-8 ABO Blood Types. The relationship of antigens and antibodies associated with the ABO blood groups. The surfaces of erythrocytes of individuals with blood group A have the A antigenic carbohydrate. The blood of these individuals has IgM antibodies against the B antigen. In individuals with blood group B, the red blood cells have the B antigenic carbohydrate, and the blood contains IgM antibodies against the A antigen. In individuals of the blood group AB, the same cells have both the A and B antigens. These individuals do not have antibody to either A or B antigens. The erythrocytes of blood group O individuals have neither antigen, but their blood contains both antibodies to A and B.
Alloimmune disease: transplant rejection
Major histocompatibility complex
Figure 7-9 Human Leukocyte Antigens (HLA). 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). From Mudge-Grout C: Immunologic disorders, St Louis, 1992, Mosby.
Transplantation
Figure 7-10 Inheritance of HLA. HLA alleles are inherited in a codominant 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.
Rejection
Quick Check 7-2
Infection
Microorganisms and Humans: A Dynamic Relationship
Box 7-1 The Many Relationships Between Humans and Microorganisms
Table 7-5 Normal Indigenous Flora of the Human Body
Figure 7-11 The Spread of Infection. Redrawn from Mims CA et al: Medical microbiology, St Louis, 1993, Mosby.
Classes of Infectious Microorganisms
Pathogenic Defense Mechanisms
Table 7-6 Classes of Human Infectious Microorganisms
Infection and Injury
Bacterial disease
Table 7-7 Summary of Some Mechanisms of Tissue Damage and the Microorganisms That Cause Them
Table 7-8 Examples of Mechanisms Used by Pathogens to Resist the Immune System
Figure 7-12 Types of Gram-Positive and Gram-Negative Bacteria.
Health Alert Antibiotic-Resistant Microorganisms Have Become the Primary Cause of Skin and Soft-Tissue Infections
Viral disease
Viral replication
Figure 7-13 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). From Murray PR et al: Medical microbiology, ed 4, St Louis, 2002, Mosby.
Figure 7-14 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.
Cellular effects of viruses
Table 7-9 List of DNA and RNA Viruses of Human Importance
Fungal disease
Figure 7-15 Types of Fungi. From Mims CA et al: Medical microbiology, ed 3, London, 2004, Mosby.
Table 7-10 Common Pathologic Fungi
Clinical Manifestations of Infection
Fever
Figure 7-16 Progression of Measles. The pathogenesis of measles is representative of most viral infections in unimmunized individuals. The virus enters through the oropharynx, from where it infects the regional lymph nodes. After 5 to 7 days, virus enters the blood (viremia) and spreads to the body surfaces (respiratory, gastrointestinal, and urinary tracts, and the skin). The measles virus replicates in these tissues, leading to upper respiratory tract symptoms, with the appearance of red spots with bluish-white specks (Koplik spots) in the oral mucosa and later to an extensive rash involving most parts of the skin. At or near the onset of overt symptoms, the infected individual is shedding virus and is highly infectious to others. Antibodies against the measles virus are primarily responsible for resolving the infection. They are produced within 10 to 11 days but are immediately absorbed by viral particles in the blood so that free antibody is not measurable until about 2 weeks after the initial infection.
Countermeasures Against Pathogenic Defenses
Vaccines
Figure 7-17 The Effect of Vaccination on the Incidence of Polio Worldwide,1980–2004.The number of global cases of polio has progressively decreased as the extent of immunization (coverage) has increased. The coverage is the percent of the world’s population that has been reported to the World Health Organization (WHO) by 192 member countries as being immunized. From World Health Organization: WHO vaccine-preventable diseases: monitoring system, 2005 global summary, Geneva, Switzerland, 2006; additional information is available at www.who.int/vaccines-documents.)
Antimicrobials
Table 7-11 Immunization Schedule: Range of Ages for Routine Immunizations
Recent pathogenic adaptations
Table 7-12 Chemicals or Antimicrobials Identified That Prevent Growth of or Destroy Microorganisms
Quick Check 7-3
Deficiencies in Immunity
Initial Clinical Presentation
Primary (Congenital) Immune Deficiencies
B lymphocyte deficiencies
T lymphocyte deficiencies
Table 7-13 Examples of Primary Immune Deficiencies
Combined deficiencies
Figure 7-18 Facial Anomalies Associated With DiGeorge Syndrome. Note the wide-set eyes, low-set ears, and shortened structure of the upper lip. From Male D, et al: Immunology, ed 7, St Louis, 2006, Mosby.
Complement deficiencies
Phagocytic deficiencies
Secondary (Acquired) Immune Deficiencies
Acquired immunodeficiency syndrome (AIDS)
Epidemiology
Figure 7-19 Estimated Incidence of AIDS and Deaths Among Adults and Adolescents With AIDS in the United States (1985–2004). The incidence of AIDS and deaths related to AIDS rose almost linearly until about 1994. The introduction of effective antiviral treatments in the mid-1990s slowed the progression of the disease from HIV infection to AIDS and has maintained the number of AIDS-related deaths at about 17,000 per year. From Centers for Disease Control website, 2005; available at www.cdc.gov/hiv/topics/surveillance/resources/slides/index.htm.
Pathogenesis
Health Alert Risk of HIV Transmission Associated With Sexual Practices
High Risk (in descending order of risk)
Some Risk (in descending order of risk)
Some Risk (depending on situation, intactness of mucous membranes, etc.)
No Risk
Unresolved Issues
Clinical Manifestations
Figure 7-20 Proportion of AIDS Cases Among Adults and Adolescents, by Exposure Category and Year of Diagnosis, in the United States (1985–2004). Worldwide, AIDS is primarily spread by heterosexual transmission. In the United States, the predominant route was by male-to-male sexual contact. The trend, however, is toward increasing heterosexual transmission. Transmission by injected drug use has remained relatively stable, as has the number of cases where both male-to-male sexual activity and injected drug use risk factors occur in the same individual. Redrawn from Centers for Disease Control website, 2005; available at www.cdc.gov/hiv/topics/surveillance/resources/slides/index.htm.
Figure 7-21 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 coreceptors 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. Modified from Kumar V, Abbas A, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Figure 7-22 Summary of Human Immunodeficiency Virus (HIV) Infection on the Immune System. Redrawn from Morse SA, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 3, Edinburgh, 2003, Mosby.
Box 7-2 AIDS-Defining Opportunistic Infections and Neoplasms Found in Individuals With HIV Infection
Infections
Protozoal and Helminthic Infections
Fungal Infections
Bacterial Infections
Viral Infections
Neoplasms
Treatment and Prevention
Figure 7-23 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 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, then remain constant until the development of AIDS. A redrawn from Fauci AS, Lane HC: Human immunodeficiency virus disease: AIDS and related conditions. In Fauci AS et al, editors: Harrison’s principles of internal medicine, ed 14, New York, 1997, McGraw-Hill. B from Kumar V, Abbas A, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Evaluation and Care of Those With Immune Deficiency
Figure 7-24 Distribution of Tissues That Can Be Infected by HIV. Infection is closely linked to the presence of CD4 receptors or chemokine coreceptors on host tissue, particularly T cells and macrophages. Modified from Weber JN, Weiss RA: HIV infection: the cellular picture, in the science of AIDS: readings from Scientific American, New York, 1989, Freeman.
Replacement Therapies for Immune Deficiencies
Figure 7-25 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. A and D from Taylor PK: Diagnostic picture tests in sexually transmitted diseases, London, 1995, Mosby; B and C from Morse SA, Ballard RC, Holmes KK, et al, editors: Atlas of sexually transmitted diseases and AIDS, ed 3, Edinburgh, 2003, Mosby.
Quick Check 7-4
Table 7-14 Laboratory Evaluation of Immunodeficiencies
Did You Understand?
Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
Infection
Deficiencies in Immunity
Key Terms
References
Chapter 8 Stress and Disease
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Concepts of Stress
Table 8-1 Examples of Stress-Related Diseases and Conditions
General Adaptation Syndrome
Figure 8-1 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 8-2. ACTH, Adrenocorticotropic hormone. (From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.)
Figure 8-2 The Stress Response.
Psychologic Mediators and Specificity
Quick Check 8-1
The Stress Response
Neuroendocrine Regulation
Catecholamines
Cortisol
Table 8-2 Physiologic Effects of the Catecholamines*
Cortisol and the immune system
Table 8-3 Physiologic Effects of Cortisol
Figure 8-3 Effect of Corticotropin-Releasing Hormone (CRH)—Mast Cell—Histamine Axis, Cortisol, and Catecholamines on the Th1/Th2 Balance—Cellular and Humoral Immunity. Humoral immunity provides protection against multicellular parasites, extracellular bacteria, some viruses, soluble toxins, and allergens. Cellular 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; ↓, decreased (inhibited); ↑, increased (stimulation). (Redrawn from Elenkov IJ, Chrousos GP: Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease, Trends Endocrinol Metab 10[9]:359–368, 1999.)
Other hormones
Endorphins
Growth hormone
Prolactin
Oxytocin
Sex steroids
Psychoneuroimmunologic Regulation
Health Alert Chronic Stress, NPY, and Atherosclerosis
Role of the Immune System
Figure 8-4 Nervous System/Endocrine System/Immune System Interactions. Interconnections or pathways of communication among the immune, nervous, and endocrine systems.
Stress, Personality, Coping, and Illness
Health Alert Partner’s Survival and Spouse’s Hospitalizations and/or Death
Aging & The Stress-Age Syndrome
Figure 8-5 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.
Quick Check 8-3
Did You Understand?
Concepts of Stress
The Stress Response
Stress, Personality, Coping, and Illness
AGING & Stress-Age Syndrome
Key Terms
References
Unit 3 Cellular Proliferation: Cancer
Chapter 9 Biology of Cancer and Tumor Spread
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Cancer Characteristics and Terminology
Tumor Classification and Nomenclature
Table 9-1 Benign vs. Malignant Tumors
Figure 9-1 Progression of Dysplasia to Neoplasm. A sequence of cellular and tissue changes progressing from dysplasia to in situ neoplasia and then to invasive neoplasia is seen often in the development of cancer. In this diagram, as in real life, distinguishing between dysplasia and in situ neoplasia is difficult. Loss of normal tissue architecture signifies development of neoplasia. The in situ neoplasms are most commonly found in the squamous epithelium of the uterine cervix, the epidermis of sun-exposed skin, and colonic and gastric mucosa after long-standing inflammation. The altered cell turnover during inflammation probably allows local environmental factors to cause genetic abnormalities leading to neoplasia. Modified from Stevens A, Lowe J: Pathology: illustrated review in color, ed 2, Edinburgh, 2000, Mosby.
Figure 9-2 Loss of Cellular and Tissue Differentiation During the Development of Cancer.A, Normal colonic epithelium. B, Benign neoplasm of colon. C, Well-differentiated malignant neoplasm of colon. D, Poorly differentiated malignant neoplasm of colon. E, Anaplastic malignant neoplasm of colon. F, Benign neoplasm of smooth muscle. The cells of a benign neoplasm (B) resemble those of the normal 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 vacuolation. The cells of the benign neoplasm of smooth muscle (F) closely resemble normal muscle cells. Cells of the well-differentiated malignant neoplasm (C) have a haphazard arrangement, and although gland lumina (G) are formed, they are architecturally abnormal and irregular. Nuclei vary in shape and size. Cells in the poorly differentiated malignant neoplasm (D) have an even more haphazard arrangement, with poor formation of gland lumina (G). Nuclei show greater variation in shape and size compared with the well-differentiated malignant neoplasm (C). Cells in anaplastic malignant neoplasms (E) bear no relation to the normal epithelium, with no attempt at gland formation. Tremendous variation is found in the size of cells and nuclei, with intense staining (nuclear hyperchromatism) of the latter. Not knowing the site of origin would make it impossible to tell what sort of tumor this was by microscopic appearance alone. Well-differentiated tumors often resemble their cell of origin, as shown in the example of a benign tumor of smooth muscle (F). From Stevens A, Lowe J: Pathology: iIlustrated review in color, ed 2, Edinburgh, 2000, Mosby.
Table 9-2 Examples of Tumor Nomenclature
Box 9-1 Diagnosis and Clinical Staging of Cancer
Diagnosis
Clinical Staging
Stages of Cancer Spread
Cell Differentiation
Figure 9-3 Tumor Staging by the TNM System. Example of staging for breast cancer. (See the figure for explanation of the abbreviations.)
Tumor Markers
Figure 9-4 Normal and Anaplastic Skeletal Muscle Cells.A, Normal skeletal muscle cells. B, Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma). Note the marked cellular and nuclear pleomorphism (cellular and nuclear variation in size and shape) hyperchromatic nuclei, and giant tumor cells. The prominent cell in the center field has an abnormal tripolar spindle. Often the tissue of origin of an anaplastic tumor can only be established by the use of molecular markers such as immunohistochemical stains and chromosome analysis. A from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby; B from Kumar V, Abbas AK, Fausto N: Pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders, courtesy Dr. Trace Worrell, Department of Pathology, University of Texas Southwestern Medical School.
Table 9-3 Examples of Tumor Markers
Figure 9-5 Example of Differentiation. There often is a block in differentiation in cancer. Differentiation occurs several times in the lifetime of a granulocyte, with each step further limiting the cell’s potential. Eventually, the cell terminally differentiates and can no longer divide, and the mature cell dies.
Quick Check 9-1
The Genetic Basis of Cancer
Cancer Is Caused by Mutations in Genes
Clonal selection
Figure 9-6 Cancer Incidence Increases Markedly With Age. The graph depicts the number of cases of colon cancer diagnosed in women in England and Wales in 1 year. The incidence of cancer increases dramatically with advancing age. This type of data suggests that accumulation of genetic mutations over time increases the risk of developing cancer. The slope of the curve suggests that five to seven mutations must occur before a full-blown cancer develops. Modified from Alberts B et al: Molecular biology of the cell, ed 4, New York, 2002, Garland.
Types of Gene Mutations in Cancer
Alteration of progrowth and antigrowth signals
Figure 9-7 Sequential Acquisition of Genetic Changes. Progression from benign to malignant colon cancer is accompanied by an accumulation of mutations. One of the earliest mutations in colon cancer is loss of the tumor suppressor gene APC. Additional mutations, often in the oncogene ras, and loss of the tumor suppressors DCC and p53 occur as the lesion progresses from a benign polyp to an invasive carcinoma. APC, adenomatosis polyposis coli; DCC, deleted in colon cancer. Modified from Kumar V, Cotran RS, Robbins SL: Basic pathology, ed 6, Philadelphia, 1997, Saunders.
Figure 9-8 Six Hallmarks of Cancer. Most cancers acquire mutations in six distinct areas of cell control during their development. All cancers must acquire the same six hallmark mutations, but their means of doing so varies mechanistically and chronologically. The order in which these capabilities are acquired is variable across different cancers. In some tumors, a particular mutation may confer several capabilities simultaneously, decreasing the number of intermediate mutational steps required for full development. Loss of the p53 tumor-suppressor gene may facilitate angiogenesis and resistance to apoptosis. In other tumors, by comparison, a collaboration of two or more distinct genetic changes may be needed to acquire a given trait. Modified from Hanahan D, Weinbert, RA: The hallmarks of cancer. Cell 100(1):57, 2000.
Figure 9-9 Model for Action of ras Genes. 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. 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. GDP, Guanosine diphosphate; GTP, guanosine triphosphate; GAP, GTPase activating protein. From Kumar V, Cotran RS, Robbins SL: Basic pathology, ed 7, Philadelphia, 2003, Saunders.
Angiogenesis
Figure 9-10 Tumor-Induced Angiogenesis. Malignant tumors, especially those in metastatic sites, induce formation of blood vessels, which serve as routes for the transport of nutrients into the tumor. The approved drug bevacizumab blocks VEGF. VEGF, Vascular endothelial growth factor. From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Telomeres and immortality
Figure 9-11 Control of Replication: Telomeres. Normal cells cannot divide indefinitely. The ends of their chromosomes are capped by telomeres. In the absence of the telomerase enzyme, telomeres get shorter with each division until the cells finally stop dividing. In cancer cells, telomerase is switched on, producing an enzyme that rebuilds the telomeres. Thus, the cancer cell can divide indefinitely.
Oncogenes and Tumor-Suppressor Genes: Accelerators and Brakes
Mutations that create oncogenes
Point mutations
Table 9-4 Types of Cancer Genes
Box 9-2 Types of Genetic Lesions in Cancers
Chromosome translocations
Figure 9-12 Chromosome Translocations Are Oncogenic in Two Ways. Chromosome translocations can lead to inappropriate activation of an oncogene by fusing the transcriptional control elements of one gene, for example, the immunoglobulin (Ig) heavy chain promoter to the coding sequence for an oncogene, in this example, the c-myc oncogene. This leads to high-level expression of c-myc in B lymphocytes as they make immunoglobulins (antibodies). This type of translocation is found in B cell lymphomas. Chromosome translocations also can fuse two genes right in the middle, leading to synthesis of novel chimeric proteins. The fusion often creates a protein that either has new cancer-promoting properties or has lost the ability to regulate a protein kinase. A novel activated protein tyrosine kinase is created in chronic myeloid leukemia.
Chromosome amplification
Tumor suppressor genes
Figure 9-13 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 is 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 N-myc is strongly associated with a poor prognosis in childhood neuroblastoma. Courtesy Arthur R. Brothman, PhD, University of Utah School of Medicine.
Table 9-5 Familial Cancer Syndromes Caused by Tumor-Suppressor Gene Function Loss
Loss of heterozygosity
Figure 9-14 Two Distinct Hits Are Required to Inactivate a Tumor Suppressor Gene. Tumor suppressor genes are often inactivated by a mutation (first hit) followed by complete loss of an entire region of chromosome encompassing the remaining normal allele (second hit, also known as loss of heterozygosity). LOH, Loss of heterozygosity.
Quick Check 9-2
Gene silencing
Guardians of the Genome
Figure 9-15 Silencing of Tumor Suppressor Genes.A, Paternal allele methylated and inactivated. In this example, the first copy of a gene is turned off by gene silencing without mutation. B, Mutation of maternal allele results in no functional protein production. In this example, the remaining normal gene can be inactivated by mutation.
Genetics and Cancer-Prone Families
Figure 9-16 Germline Mutation. Inherited mutations are carried in the DNA of reproductive cells. When reproductive cells containing mutations combine to produce offspring, the mutation will be present in all of the offspring’s body cells. Modified from Lea DN, Jenkins JF, Francomano CA: Genetics in clinical practice, Boston, 1998, Bartlett.
Figure 9-17 A Familial Colon Cancer Pedigree. Darkened symbols represent individuals diagnosed with cancer. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Quick Check 9-3
Infection, Immunity, Inflammation, and Cancer
Viral Causes of Cancer
Table 9-6 Human Viruses Associated With Cancer
Bacterial Cause of Cancer
Immunity and Cancer
An Active Immune Response Causes Cancer
Figure 9-18 The intimate association of inflammation and cancer. Cancers attract inflammatory cells by a number of methods. Cancer cell hypoxia and death releases factors that activate stromal and tumor-infiltrating macrophages. The activated Ras protein in many cancer cells also drives secretion of cytokines such as interleukin 8 (IL-8) that then stimulates inflammatory cells to secrete growth factors and pro-angiogenic factors. Redrawn from Karin M: Inflammation and cancer: the long reach of Ras. Nature Med 11(1):20–21, 2005.
Quick Check 9-4
Cancer Progression and Metastasis
Figure 9-19 Multistep Nature of Metastasis. From Fidler IT: The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Ca 3:453–458, 2003.
Patterns of Spread
Figure 9-20 Main Sites of Blood-Borne Metastasis.A, Sites of hematogenous metastasis. B, Metastasis in bone. C, Metastasis in brain. D, Metastasis in liver. E, Metastasis in adrenals. F, Metastasis in lung. Blood-borne tumor metastasis leads to growth of secondary tumors in several main sites. The macroscopic appearances of bone metastasis are shown in B, where lesions are seen in vertebrae. Numerous metastases from a neoplasm of the stomach are seen in the brain in C. The liver is the most common site for metastases from tumors in the gastrointestinal tract, as seen in D, which arose from a colonic neoplasm. In E, metastatic tumor has replaced both adrenal glands, as is commonly seen with spread from lung and breast tumors. The lung, F, is the most common site for blood-borne metastases from tumors outside the spinal tract, particularly mesenchymal tumors. From Stevens A, Lowe J: Pathology: illustrated review in color, ed 2, Edinburgh, 2000, Mosby.
Figure 9-21 Metastatic Nonsmall Cell Lung Cancer (NSCLC). This 54-year-old woman had a NSCLC resected from the left upper lobe. Five years later, these studies were obtained. The positron emission tomography (PET) scan using 18fluoro-deoxyglucose shows metastatic lesions in the brain, right shoulder, 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 spread is most likely from the primary tumor to the large mediastinal lymph nodes, followed by lymphatic spread to cervical nodes. Blood-borne spread produced the bone, brain, and liver metastases. Normally, only the heart, brain, and bladder show strong signal in PET scan. Images courtesy John Hoffman, MD, Huntsman Cancer Institute.
Table 9-7 Common Sites of Metastasis
Distant Metastasis
Quick Check 9-5
Did You Understand?
Cancer Characteristics and Terminology
The Genetic Basis of Cancer
Infection, Immunity, Inflammation, and Cancer
Cancer Progression and Metastasis
Key Terms
References
Chapter 10 Cancer Epidemiology, Manifestations, and Treatment
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Gene-Environment Interaction and Risk Factors
Figure 10-1 Estimated Numbers of New Cancer Cases (Incidence) and Deaths (Mortality) in 2002. Data shown in thousands for developing and developed countries by cancer site and sex. From Parkin DM et al: CA Cancer J Clin 55:74–108, 2005. © American Cancer Society.
Table 10-1 Estimated New Cancer Cases and Deaths by Gender, United States, 2007*
Tobacco Use
Ionizing Radiation
Radiation-induced cancer
Carcinogenesis: genomic instability
Bystander effects
Figure 10-2 Models of the Responses of Clonogenic Cells to Ionizing Radiation. Mutations 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 descendents will appear normal. B, If a cell is directly mutated by radiation, then all its descendents will express the same mutation. C, Radiation-induced genomic instability is characterized by nonclonal effects in descendant cells. From Lorimore SA, Coates PJ, Wright EG: Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation. Oncogene 22[45]:7058–7069, 2003.
Gap junction function
Ultraviolet Radiation
Electromagnetic Fields
Diet and Endogenous Hormones
Obesity
Biologic mechanisms
Table 10-2 Relationship of Dietary Factors With Risk of Major Cancers*
Figure 10-3 Energy Balance, Lipid Metabolism, and Insulin Sensitivity and Tumor Development. In obesity, increased release from adipose tissue of free fatty acids (FFA), tumor necrosis factor alpha (TNF-α) and resistin, and reduced 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 decrease 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 receptors (IRs) and IGF-1 receptor (IGF1R) to stimulate cellular proliferation and inhibit apoptosis in many tissue types. These effects could promote tumor development. Adapted from Calle EE, Kaaks R: Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591, 2004.
Endogenous hormones
Alcohol Consumption
Health Alert Possible Components of a Cancer-Prevention Diet
Increase
Decrease
Sexual and Reproductive Behavior
Physical Activity
Occupational Hazards as Carcinogens
Air Pollution
Clinical Manifestations of Cancer
Pain
Figure 10-4 Theoretical Framework for Cytokine-Induced Cancer Symptoms. Solid blue lines proinflammatory cytokines and chemokines (IL-1, TNF-α, IL-6, IFN) are released by immune cells. They exert their effect on peripheral nerves and the brain. Neurotransmitter responses by the brain are affected. The hypothalamic-pituitary-adrenal axis is activated with increased release of corticosteroids, which provide feedback (dotted red lines) to decrease cytokine production. Adapted from Cleeland CS et al: Actytokine-immunologic model of cancer symptoms, Cancer 97(11):2919–2925, 2003.
Fatigue
Cachexia
Figure 10-5 Cachexia. This severe form of malnutrition results in wasting and extensive loss of adipose tissue. From Kamal A, Brockelhurst JC: Color atlas of geriatric medicine, ed 2, St Louis, 1991, Mosby.
Anemia
Leukopenia and Thrombocytopenia
Infection
Paraneoplastic Syndromes
Table 10-3 Factors Predisposing Individuals With Cancer to Infection
Quick Check 10-1
Table 10-4 Paraneoplastic Syndromes
Cancer Treatment
Chemotherapy
Table 10-5 Examples of Treatment of Site-Specific Cancers
Figure 10-6 Chemotherapy and Resistant Cells. A cell resistant to single-agent chemotherapy can develop from the pool of fast-growing tumor cells. Combination therapy helps prevent the development of resistant cells. From Stevens A, Lowe J: Pathology: illustrated review in color, ed 2, Edinburgh, 2000, Mosby.
Table 10-6 Examples of Chemotherapeutic Drugs
Radiation
Table 10-7 Mechanisms of Action of Common Chemotherapeutic Drugs
Surgery
Hormonal Therapy
Table 10-8 Common Hormonal Agents and Types of Tumors
Immunotherapy
Health Alert l-Glutamine
Side Effects of Cancer Treatment
Gastrointestinal Tract
Bone Marrow
Hair and Skin
Reproductive Tract
Quick Check 10-2
Did You Understand?
Gene-Environment Interaction
Clinical Manifestations of Cancer
Cancer Treatment
Side Effects of Cancer Treatment
Key Terms
References
Chapter 11 Cancer in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Incidence and Types of Childhood Cancer
Table 11-1 Childhood Age-Adjusted Invasive Cancer Incidence Rates by Primary Site and Age, United States*
Table 11-2 Childhood Age-Adjusted Cancer Incidence Rates for Children 0–19 Years of Age by Primary Site and Race and Ethnicity, United States*
Etiology
Genetic Factors
Table 11-3 Congenital Factors Associated With Childhood Cancer
Environmental Factors
Table 11-4 Selected Oncogenes and Tumor-Suppressor Genes Associated With Childhood Cancer
Prenatal exposure
Childhood exposure
Prognosis
Health Alert Late Effects of Childhood Cancer
Quick Check 11-1
Did You Understand?
Incidence and Types of Childhood Cancers
Etiology
Prognosis
Key Terms
References
Part Two Body Systems and Disease
Unit 4 The Neurologic System
Chapter 12 Structure and Function of the Neurologic System
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Overview and Organization of the Nervous System
Cells of the Nervous System
The Neuron
Health Alert Neuroimaging Techniques
Figure 12-1 Neuron With Composite Parts.A, Multipolar neuron: neuron with multiple extensions from the cell body. B, Scanning electron micrograph. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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 unipolar cell; cell B represents multipolar cell.
Neuroglia and Schwann Cells
Nerve Injury and Regeneration
Figure 12-3 Types of Neuroglial Cells.A, Fibrous astrocyte; B, oligodendrocytes; C, microglia cells; D, ependymal cells. Modified from Chipps E, Clanin N, Campbell V: Neurologic disorders, St Louis, 1992, Mosby.
Table 12-1 Support Cells of the Nervous System
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.
Quick Check 12-1
The Nerve Impulse
Synapses
Neurotransmitters
Quick Check 12-2
The Central Nervous System
The Brain
Table 12-2 Substances That Are Neurotransmitters or Neuromodulators
Table 12-3 Divisions of the Central Nervous System
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.
Forebrain
Telencephalon
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.
Figure 12-7 Primary Somatic Sensory (A) and Motor (B) Areas of the Cortex. The body parts illustrated here show which parts of the body are “mapped” to specific areas of each cortical area. 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-8 Examples of Somatic Motor and Sensory Pathways.A, Motor: The pyramidal pathway illustrated by the lateral corticospinal tract and the 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. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Health Alert Surgery for Parkinson Disease
Box 12-1 Functions of the Hypothalamus
Diencephalon
Midbrain
Hindbrain
Metencephalon
Myelencephalon
Quick Check 12-3
The Spinal Cord
Figure 12-9 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. Redrawn from Rudy EB, editor: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Motor Pathways
Sensory Pathways
Figure 12-10 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. Modified from Thibodeau GA, Patton KT: Structure and function of the human body, ed 12, St Louis, 2004, Mosby.
Figure 12-11 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Protective Structures of the Central Nervous System
Cranium
Figure 12-12 Cross Section of Spinal Cord Showing Simple Reflex Arc. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-13 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Meninges
Figure 12-14 Meninges of the Brain. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Cerebrospinal fluid and the ventricular system
Table 12-4 Composition of Cerebrospinal Fluid
Vertebral column
Figure 12-15 Vertebral Column.A, Right lateral view. B, Anterior view. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-16 Vertebra and Intervertebral Disk. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Quick Check 12-4
Blood Supply of the Central Nervous System
Blood supply to the brain
Figure 12-17 Major Arteries of the Head and Neck. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-18 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Table 12-5 Arterial Systems Supplying the Brain
Figure 12-19 Areas of the Brain Affected by Occlusion of the Anterior, Middle, and Posterior Cerebral Artery Branches.A, Inferior view. B, Lateral view.
Blood-brain barrier
Blood supply to the spinal cord
Figure 12-20 Large Veins of the Head. Deep veins and dural sinuses are projected on the skull. Note connections (emissary veins) between the superficial and deep veins. From Thibodeau GA, Patton KT: Anatomy & Physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-21 Arteries of the Spinal Cord.A, Arteries of cervical cord exposed from the rear. B, Arteries of spinal cord diagrammatically shown in horizontal section. Redrawn from Rudy EB, editor: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
The Peripheral Nervous System
Quick Check 12-5
The Autonomic Nervous System
Anatomy of the Sympathetic Nervous System
Figure 12-22 Cranial and Peripheral Nerves.A, Ventral surface of the brain showing attachment of the cranial nerves. B, Peripheral nerve trunk and coverings. C, Scanning electron micrograph of a freeze-fractured preparation of peripheral nerve. A and C from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 12-6 The Cranial Nerves
Figure 12-23 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 12-24 Sympathetic Division of the Autonomic Nervous System.CiG, Ciliary ganglion; SpG, sphenopalatine ganglion; SCG, superior cervical ganglion; OG, otic ganglion; SG, submandibular ganglion; CG, celiac ganglion; SMG, superior mesenteric ganglion; IMG, inferior mesenteric ganglion; PP, pelvic plexus. Redrawn from Rudy EB, editor: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Anatomy of the Parasympathetic Nervous System
Figure 12-25 Parasympathetic Division of the Autonomic Nervous System.CiG, Ciliary ganglion; SpG, sphenopalatine ganglion; OG, otic ganglion; SG, submandibular ganglion; VN, vagus nerve; PP, pelvic plexus; PN, pelvic nerve. Redrawn from Rudy EB, editor: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Neurotransmitters and Neuroreceptors
Figure 12-26 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.
Functions of the Autonomic Nervous System
Quick Check 12-6
Table 12-7 Actions of Autonomic Nervous System Neuroreceptors
Figure 12-27 Some Important Functions of the Sympathetic Nervous System.A, Regulation of vasomotor tone. B, Regulation of strenuous muscular exercise (“fight or flight” response). (See also Chapter 8 and Figure 8-1 for more detail on the stress response.)
Aging & The Nervous System
Structural Changes With Aging
Cellular Changes With Aging
Cerebrovascular Changes With Aging
Functional Changes With Aging
Did You Understand?
Overview and Organization of the Nervous System
Cells of the Nervous System
The Nerve Impulse
The Central Nervous System
The Peripheral Nervous System
The Autonomic Nervous System
AGING & the Nervous System
Key Terms
References
Chapter 13 Pain, Temperature, Sleep, and Sensory Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Pain
The Experience of Pain
Neuroanatomy of Pain
Figure 13-1 Transmission of Pain Sensations. The Aδ and C fibers synapse in the laminae of the dorsal horn cross over to the contralateral spinothalamic tract then ascend to synapse in the midbrain through the neospinothalamic and paleospinothalamic tracts. Impulses are then conducted to the sensory cortex.
Table 13-1 Stimuli that Activate Nociceptors (Pain Receptors)
Theories of Pain
Figure 13-2 Gate Control Theory of Pain. Schematic diagram of the gate control theory of pain mechanism. Large 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).
Neuromodulation of pain
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.
Common Clinical Descriptions of Pain
Box 13-1 Categories of Pain
Figure 13-4 Sites of Referred Pain.A, Front. B, Back.
Table 13-2 Common Chronic Pain Conditions
Pain threshold and pain tolerance
Quick Check 13-1
Temperature Regulation
Table 13-3 Comparison of Acute and Chronic Pain
Table 13-4 Pain Perception in Infants, Children, and Elderly Persons
Hypothalamic Control of Temperature
Table 13-5 Mechanisms of Heat Production and Loss
Mechanisms of heat production and loss
Mechanisms of heat conservation
Temperature Regulation in Infants and Elderly Persons
Pathogenesis of Fever
Figure 13-5 Production of Fever. When monocytes/macrophages are activated, they secrete endogenous pyrogenic cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF) and interferon (IF) which reach the hypothalamic temperature-regulating center. These cytokines 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, and peripheral vasoconstriction. Adapted from Lewis SM, Heitkemper MM, Dirksen SR: Medical-surgical nursing: assessment and management of clinical problems, ed 5, St Louis, 2000, Mosby.
Benefits of Fever
Box 13-2 Effects of Fever at the Extremes of Age
Elderly Persons
Children
Disorders of Temperature Regulation
Hyperthermia
Hypothermia
Trauma and temperature
Quick Check 13-2
Box 13-3 Defining Characteristics of Hypothermia
Accidental Hypothermia*
Therapeutic Hypothermia†‡
Sleep
Sleep Disorders
Box 13-4 Sleep Characteristics of Infants and Elderly Persons
Infants
Elderly Persons
Common dyssomnias
Insomnia
Sleep disordered breathing
Disorders of the sleep-wake schedule
Common parasomnias
Box 13-5 Restless Leg Syndrome (RLS)
Quick Check 13-3
The Special Senses
Vision
The eye and its external structures
Figure 13-6 Internal Anatomy of the Eye. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Visual dysfunction
Alterations in ocular movements
Figure 13-7 Extrinsic Muscles of the Right Eye. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Alterations in visual acuity
Table 13-6 Changes in the Eye Caused by Aging
Table 13-7 Causes of Visual Acuity Changes
Alterations in accommodation
Alterations in refraction
Alterations in color vision
Neurologic disorders causing visual dysfunction
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. From Stein HA, Slatt BJ, Stein RM: The ophthalmic assistant: fundamentals and clinical practice, ed 5, St Louis, 1998, Mosby.
External eye structure disorders
Hearing
The normal ear
Figure 13-10 Visual Pathways and Defects. Modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Figure 13-11 The Ear. External, middle, and inner ears. (Anatomic structures are not drawn to scale.) From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Auditory dysfunction
Aging & Changes in Hearing
Conductive hearing loss
Sensorineural hearing loss
Mixed and functional hearing loss
Meniere disease
Ear infections
Otitis externa
Otitis media
Olfaction and Taste
Figure 13-13 Olfaction. Midsagittal section of the nasal area shows the location of major olfactory sensory structures. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Aging & Changes in Olfaction and Taste
Olfactory and taste dysfunctions
Quick Check 13-4
Somatosensory Function
Touch
Proprioception
Quick Check 13-5
Did You Understand?
Pain
Temperature Regulation
Sleep
The Special Senses
Somatosensory Function
Key Terms
References
Chapter 14 Concepts of Neurologic Dysfunction
Electronic Resources
Companion CD
Website at http://evolve.elsevier.com/Huether/
Alterations in Cognitive Networks
Alterations in Arousal
Pathophysiology
Clinical Manifestations and Evaluation
Table 14-1 Clinical Manifestations of Metabolic and Structural Causes of Comas
Level of consciousness
Pattern of breathing
Table 14-2 Differential Characteristics of States Causing Coma
Table 14-3 Levels of Altered Consciousness
Pupillary changes
Figure 14-1 Abnormal Respiratory Patterns With Corresponding Level of Central Nervous System Activity. From Urden LD, Davie JK, Lough ME: Thelan’s critical care nursing: diagnosis and management, ed 5, St Louis, 2006, Mosby.
Table 14-4 Patterns of Breathing
Oculomotor responses
Motor responses
Figure 14-2 Pupils at Different Levels of Consciousness.
Vomiting
Quick Check 14-1
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 do not turn as head position changes. From Rudy EB: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Outcomes
Figure 14-4 Test for Oculovestibular Reflex (Caloric Ice Water Test).A, Normal response—conjugate eye movements. B, Abnormal response—dysconjugate or asymmetric eye movements. C, Absent response—no eye movements.
Figure 14-5 Pathologic Reflexes.A, Grasp reflex. B, Snout reflex. C, Palmomental reflex. D, Suck reflex.
Table 14-5 Abnormal Motor Responses With Decreased Responsiveness
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. 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. From Rudy EB: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Box 14-1 Criteria for Brain Death
Seizures
Pathophysiology
Conditions associated with seizure disorders
Table 14-6 Causes of Recurrent Seizures in Different Age-Groups
Types of seizure disorders
Table 14-7 International Classification of Epileptic Seizures
Table 14-8 Terminology Applied to a Seizure Disorder
Health Alert Epilepsy Surgery Stands the Test of Time
Clinical Manifestations
Evaluation and Treatment
Quick Check 14-2
Cognitive Disorders
Pathophysiology
Table 14-9 Clinical Manifestations of Cognitive Network Deficits
Clinical Manifestations
Evaluation and Treatment
Figure 14-7 Development of Dysphasia. Portion of the left cerebral hemisphere considered most important in the development of dysphasia.
Data Processing Deficits
Agnosia
Dysphasia
Acute confusional states
Table 14-10 Major Types of Dysphagia
Quick Check 14-3
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Dementia
Pathophysiology
Table 14-11 Examples of Language Disturbances
Table 14-12 Differences Between Organic and Functional Confusion
Health Alert Exercising the Body Can Benefit the Mind
Clinical Manifestations
Evaluation and Treatment
Table 14-13 Clinical Manifestations of Dementia
Alzheimer disease
Figure 14-8 Common Pathologic Findings in Alzheimer Disease. From Beare PG, Myers JL: Principles and practice of adult health nursing, ed 3, St Louis, 1998, Mosby.
Pathophysiology
Figure 14-9 Pathologic Changes in Alzheimer Disease.A, A neuritic (mature) plaque with central amyloid core (white arrow) next to a neurofibrillary tangle (white arrow). Alzheimer disease (B) compared with age-matched and sex-matched control (C): reduced size, narrow gyri, and wide sulci, notably in frontal and temporal lobes. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Clinical Manifestations
Evaluation and Treatment
Pick disease
Alterations in Cerebral Homeostasis
Cerebral Hemodynamics
Increased Intracranial Pressure
Figure 14-10 Clinical Correlates of Compensated and Uncompensated Phases of Intracranial Hypertension. From Beare PG, Myers JL: Principles and practice of adult health nursing, ed 3, St Louis, 1998, Mosby.
Figure 14-11 Herniation.A, Normal relationship of intracranial structures. B, Shift of intracranial structures. C, Downward herniation of the cerebellar tonsils into the foramen magnum.
Cerebral Edema
Box 14-2 Herniation Syndrome
Supratentorial Herniation
Infratentorial Herniation
Figure 14-12 Brain Edema. Intercellular lakes of high protein content fluid. (Hematoxylin-eosin stain; ×90.) From Kissane JM, editor: Anderson’s pathology, ed 9, St Louis, 1993, Mosby.
Hydrocephalus
Table 14-14 Types of Hydrocephalus
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 14-4
Alterations in Motor Function
Alterations in Muscle Tone
Hypotonia
Table 14-15 Alterations in Muscle Tone
Hypertonia
Figure 14-13 A Paroxysm of Left-Sided Hemifacial Spasm. From Perkin GD: Mosby’s color atlas and text of neurology, ed 2, London, 2002, Mosby.
Figure 14-14 Dystonic Posturing of the Hand and Foot. From Perkin GD: Mosby’s color atlas and text of neurology, ed 2, London, 2002, Mosby.
Alterations in Movement
Figure 14-15 Spasmodic Torticollis. A characteristic head posture. From Perkin GD: Mosby’s color atlas and text of neurology, ed 2, London, 2002, Mosby.
Figure 14-16 Pseudohypertrophy of the Calf Muscles. From Perkin GD: Mosby’s color atlas and text of neurology, ed 2, London, 2002, Mosby.
Paresis/paralysis
Upper motor neuron syndromes
Table 14-16 Upper and Lower Motor Neuron Syndromes
Figure 14-17 Disturbances in Motor Function. 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.
Lower motor neuron syndromes
Amyotrophies
Figure 14-18 Structures Making up 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 are given off to 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).
Figure 14-19 Structures Making up 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 polar, or end, region of muscle spindle (sensory receptor of skeletal muscle). Contraction of muscle spindle fibers stretches central portion of spindle and causes afferent spindle fiber to transmit impulse centrally to cord. Muscle spindle afferent fibers in turn synapse on anterior horn cell and are transmitted by way of gamma efferent fibers to skeletal (extrafusal) muscle, causing it to contract. Muscle spindle discharge is interrupted by active contraction of extrafusal muscle fibers.
Hyperkinesia
Table 14-17 Types of Hyperkinesia
Huntington disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hypokinesia
Akinesia and bradykinesia
Loss of associated neuron syndromes
Parkinson disease
Figure 14-20 Nigrostriatal Disorders Produce the Parkinson Syndrome. Coronal section of the brain shows the basal ganglia. Pathways controlling normal and abnormal motor function are depicted in a portion of the basal ganglia (caudate nucleus), A; they are shown enlarged in B. Dopaminergic synaptic activity is mediated by dopamine. Cholinergic synaptic activity is mediated by acetylcholine. A balance between the two kinds of activity produces normal motor function. A relative excess of cholinergic activity produces akinesia and rigidity. A relative excess of dopaminergic activity produces involuntary movements. Neurons in the caudate nucleus contain gamma-aminobutyric acid (GABA) and possibly control dopaminergic neurons in the substantia nigra through a feedback pathway. A from Cutler WP: Degenerative and hereditary diseases, ed 7, Washington, DC, 1983, Scientific American Medicine.
Pathophysiology
Clinical Manifestations
Figure 14-21 Stooped Posture of Parkinson Disease. From Perkin DG: Mosby’s color atlas and text of neurology, ed 2, London, 2002, Mosby.
Evaluation and Treatment
Alterations in Complex Motor Performance
Disorders of posture (stance)
Disorders of gait
Disorders of expression
Extrapyramidal Motor Syndromes
Basal ganglia motor syndromes
Table 14-18 Dyspraxias and Apraxias
Figure 14-22 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.
Quick Check 14-5
Cerebellar motor syndromes
Table 14-19 Pyramidal vs. Extrapyramidal Motor Syndrome
Did You Understand?
Alterations in Cognitive Networks
Alterations in Cerebral Homeostasis
Alterations in Motor Function
Key Terms
References
Chapter 15 Alterations of Neurologic Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Central Nervous System Disorders
Trauma
Brain trauma
Table 15-1 Severity of Trauma Related to Trauma State Induced and Onset and Persistence of Clinical Manifestations
Table 15-2 Categories of Diffuse Brain Injury
Cause
Pathophysiology
Focal brain injury
Table 15-3 Causes of Brain Injuries
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). Modified from Rudy EB: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Figure 15-2 Acute Subdural Hematoma (Dura Removed). Leptomeninges are intact. From Damjanov I, Linder J: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 15-3 Hematomas. Recent hematomas, resulting from trauma, in frontal lobes. From Kissane JM, editor: Anderson’s pathology, ed 9, St Louis, 1993, Mosby.
Diffuse brain injury
Clinical Manifestations, Evaluation, and Treatment
Focal brain injury
Diffuse brain injury
Quick Check 15-1
Spinal cord trauma
Pathophysiology
Figure 15-4 Hyperextension Injuries of the Spine. Hyperextension injuries of the spine can result in fracture or nonfracture injuries with spinal cord damage.
Figure 15-5 Flexion Injury of the Spine. Hyperflexion produces translation (subluxation) of vertebrae that compromises the central canal and compresses spinal cord parenchyma or vascular structures.
Figure 15-6 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.
Figure 15-7 Flexion-Rotation Injuries of the Spine.
Clinical Manifestations
Table 15-4 Mechanisms of Vertebral Injury Involving Bone, Ligaments, and Joints
Table 15-5 Spinal Cord Injuries
Table 15-6 Clinical Manifestations of Spinal Cord Injury
Figure 15-8 Autonomic Hyperreflexia.A, Normal response pathway. B, Autonomic dysreflexia pathway. SA, sinoatrial. Modified from Rudy EB: Advanced neurological and neurosurgical nursing, St Louis, 1984, Mosby.
Evaluation and Treatment
Degenerative Disorders of the Spine
Degenerative joint disease (DJD)
Degenerative disk disease
Spondylolysis
Spondylolisthesis
Spinal stenosis
Low back pain
Pathogenesis
Evaluation and Treatment
Figure 15-9 Herniated Nucleus Pulposus. Modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Health Alert Percutaneous Vertebroplasty
Herniated intervertebral disk
Pathophysiology
Clinical Manifestations
Figure 15-10 Clinical Features of a Herniated Nucleus Pulposus.
Evaluation and Treatment
Cerebrovascular Disorders
Cerebrovascular accidents (stroke syndromes)
Thrombotic stroke
Health Alert Two New Warning Signs Found for Impending Stroke
Embolic stroke
Hemorrhagic stroke
Lacunar stroke
Pathophysiology
Cerebral infarction
Cerebral hemorrhage
Clinical Manifestations
Evaluation and Treatment
Intracranial aneurysm
Pathophysiology
Figure 15-11 Types of Aneurysms.
Clinical Manifestations
Evaluation and Treatment
Vascular malformation
Figure 15-12 Ophthalamic Artery Aneurysm.A, With endovascular coil; B, in situ. From Perkin GD: Mosby’s color atlas and text of neurology, London, 1998, Mosby-Wolfe.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Subarachnoid hemorrhage
Pathophysiology
Clinical Manifestations
Table 15-7 Subarachnoid Hemorrhage Classification Scale
Evaluation and Treatment
Quick Check 15-2
Infection and Inflammation of the Central Nervous System
Meningitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Health Alert Meningococcal Vaccine and Guillain-Barré Syndrome
Abscess
Pathophysiology
Figure 15-13 Brain Abscess. Early brain abscess appearing as a poorly demarcated area (arrow) of cerebritis at the gray-white junction. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Clinical Manifestations
Health Alert West Nile Virus
Evaluation and Treatment
Encephalitis
Pathophysiology
Table 15-8 Classification and Characteristics of Viruses Causing Encephalitis
Clinical Manifestations
Evaluation and Treatment
Neurologic complications of AIDS
Human immunodeficiency-associated cognitive dysfunction (HIV encephalopathy)
HIV myelopathy
HIV neuropathy
Aseptic viral meningitis
Opportunistic infections
CNS neoplasms
Other CNS complications
Degenerative Diseases
Multiple sclerosis
Pathophysiology
Figure 15-14 Chronic Multiple Sclerosis. Demyelination plaque at gray-white junction and adjacent partially remyelinated shadow plaque (arrows). From Damjanov I, Linder J: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Clinical Manifestations
Health Alert Neural Stem Cells Protect and Restore Brain Functions
Evaluation and Treatment
Amyotrophic lateral sclerosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 15-3
Peripheral Nervous System and Neuromuscular Junction Disorders
Peripheral Nervous System Disorders
Table 15-9 Peripheral Nervous System Disorders
Neuromuscular Junction Disorders
Myasthenia gravis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 15-4
Myopathies
Tumors of the Central Nervous System
Cranial Tumors
Figure 15-15 Origin of Clinical Manifestations Associated with an Intracranial Neoplasm.
Primary intracerebral tumors
Astrocytoma
Oligodendroglioma
Table 15-10 Brain and Spinal Cord Tumors
Table 15-11 Classification Systems for Astrocytomas
Ependymoma
Figure 15-16 Large Septal Ependymoma. This tumor represents the severity of tissue compression that occurs with a large brain tumor. The area in the upper-right part of the picture represents a secondary hydrocephalus that has further compressed brain tissue. Courtesy Dr. JE Olivera-Rabiela, Mexico City, Mexico. From Rosai J: Ackerman’s surgical pathology, ed 7, St Louis, 1989, Mosby.
Primary extracerebral tumors
Meningioma
Nerve sheath tumors
Metastatic carcinoma
Spinal Cord Tumors
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 15-5
Did You Understand?
Central Nervous System Disorders
Peripheral Nervous System and Neuromuscular Junction Disorders
Tumors of the Central Nervous System
Key Terms
References
Chapter 16 Alterations of Neurologic Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Normal Growth and Development of the Nervous System
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).
Table 16-1 Reflexes of Infancy
Structural Malformations
Defects of Neural Tube Closure
Clinical Manifestations
Figure 16-2 Disorders Associated With Specific Stages of Embryonic Development.
Figure 16-3 Normal Spine, Meningocele, and Myelomeningocele. Diagram showing section through normal spine (A), meningocele (B), and myelomeningocele (C).
Table 16-2 Functional Alterations in Myelodysplasia Related to Level of Lesion
Malformations of the Axial Skeleton
Spina bifida occulta
Figure 16-4 Normal Brain and Arnold-Chiari II Malformation. Diagram showing normal brain (A) and brain with Arnold-Chiari II malformation (B).
Cranial deformities
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. From Hockenberry MJ: Wong’s nursing care of infants and children, ed 7, St Louis, 2003, Mosby.
Table 16-3 Causes of Microcephaly
Quick Check 16-1
Encephalopathies
Static Encephalopathies
Inherited Metabolic Disorders of the Central Nervous System
Defects in amino acid metabolism
Phenylketonuria
Table 16-4 Inherited Metabolic Disorders of the Central Nervous System
Figure 16-6 Metabolic Error and Consequences in Phenylketonuria. From Hockenberry MJ: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Defects in lipid metabolism
Quick Check 16-2
Seizure Disorders
Epilepsy
Acute Encephalopathies
Reye syndrome
Intoxications of the central nervous system
Table 16-5 Major Types of Seizure Disorders Found in Children
Table 16-6 Commonly Ingested Poisons
Health Alert Iron and Cognitive Function
Figure 16-7 Systemic Effects of Increased Lead Absorption in Children.
Meningitis
Bacterial meningitis
Viral meningitis
Human Immunodeficiency Virus and Central Nervous System Involvement
Tumors
Brain Tumors
Table 16-7 Brain Tumors in Children
Figure 16-8 Location of Brain Tumors in Children.
Table 16-8 Treatment Strategies for Childhood Brain Tumors
Box 16-1 Clinical Manifestations of Brain Tumors
Headache
Vomiting
Neuromuscular Changes
Behavioral Changes
Cranial Nerve Neuropathy
Vital Sign Disturbances
Other Signs
Embryonal Tumors
Neuroblastoma
Retinoblastoma
Figure 16-9 Retinoblastoma. The tumor occupies a large portion of the inside of the eye bulbus. From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders. Courtesy Dr. Walter Richardson and Dr. Jamsheed Khan, Kansas City, Kansas.
Figure 16-10 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.
Quick Check 16-3
Did You Understand?
Normal Growth and Development of the Nervous System
Structural Malformations
Encephalopathies
Human Immunodeficiency Virus and Central Nervous System Involvement
Tumors
Key Terms
References
Unit 5 The Endocrine System
Chapter 17 Mechanisms of Hormonal Regulation
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Mechanisms of Hormonal Regulation
Regulation of Hormone Release
Figure 17-1 Principal Endocrine Glands. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 17-1 Structural Categories of Hormones
Hormone Transport
Figure 17-2 Feedback Loops.A, Endocrine feedback loops involving the hypothalamus-pituitary gland and end organs, in this example, the thyroid gland (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 (ultrashort feedback), anterior pituitary (short feedback), and hypothalamus (long feedback). TRH, Thyroid releasing hormone; TSH, thyroid stimulating hormone; T3, triiodothyronine; T4, tetraiodothyronine.
Table 17-2 Binding Proteins, Their Hormones, and Variables That Affect Their Circulating Levels
Mechanisms of Hormone Action
Figure 17-3 Regulation of Target Cell Sensitivity.A, Low hormone level and up-regulation, or an increase in number of receptors. B, High hormone level and down-regulation, or a decrease in number of receptors. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Hormone receptors
First and second messengers
Figure 17-4 Hormone Binding at Target Cell.
Table 17-3 Types of Hormones, Their Receptors, and Their Mechanisms of Action
Steroid (lipid-soluble) hormone receptors
Figure 17-5 Example of First- and Second-Messenger Mechanisms. A nonsteroid 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). From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 17-1
Structure and Function of the Endocrine Glands
Hypothalamic-Pituitary System
Figure 17-6 Lipid-Soluble Hormone Signaling Process. Free hormones either (1) attach to a receptor on the plasma membrane, and or readily diffuse across the cell membrane and (2) attach to a receptor in the cytosol, or (3) attach to a receptor molecule in the nucleus. DNA, Deoxyribonucleic acid.
Table 17-4 Hypothalamic Hormones
The anterior pituitary
Figure 17-7 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 pituitary stalk 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
The posterior pituitary
Antidiuretic hormone
Figure 17-8 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Oxytocin
Quick Check 17-2
Thyroid and Parathyroid Glands
Thyroid gland
Synthesis of thyroid hormone
Figure 17-9 Anterior Pituitary Hormones and Their Target Hormones.LH, Luteinizing hormone; ICSH, interstitial cell–stimulating hormone (male); FSH, follicle-stimulating hormone (female). Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Regulation of thyroid hormone secretion
Table 17-5 Hormones of the Anterior Pituitary and Their Functions
Parathyroid glands
Health Alert Recombinant PTH (rPTH)
Figure 17-10 Relationship of the Hypothalamus and Neurohypophysis. Neurosecretory cells have their cell bodies in the hypothalamus and their axon terminals in the neurohypophysis. Thus, hormones synthesized in the hypothalamus are actually released from the neurohypophysis. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 17-3
Endocrine Pancreas
Figure 17-11 Thyroid and Parathyroid Glands. Note their location in relation to each other and to the larynx and trachea. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 17-12 Thyroid Follicle Cells.
Insulin
Table 17-6 Thyroid Gland Hormones and Their Regulation and Functions
Amylin
Glucagon
Somatostatin
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Gastrin and pancreatic polypeptide
Adrenal Glands
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 signal molecules that modulate gene expression regulate cell growth. mRNA, Messenger ribonucleic acid; IREs, insulin responsive elements. From Berne RM, Levy MN: Principles of physiology, ed 3, St Louis, 2000, Mosby.
Table 17-7 Insulin Actions
Figure 17-15 Structure of the Adrenal Gland Showing Cell Layers (Zonae) of the Cortex. Zona glomerulosa secretes aldosterone. Zona fasciculata secretes abundant amounts of glucocorticoids, chiefly cortisol. Zona reticularis secretes minute amounts of sex hormones and glucocorticoids. A portion of the medulla is visible at the lower right in the photomicrograph (×35) and at the bottom of the drawing. A from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby; B from Kierszenbaum A: Histology and cell biology, St Louis, 2002, Elsevier.
Adrenal cortex
Glucocorticoids
Functions of the glucocorticoids
Box 17-1 Major Functions of Glucocorticoids
Metabolic
Inflammatory and Immune
Other
Cortisol
Figure 17-16 Feedback Control of Glucocorticoid Synthesis and Secretion.
Mineralocorticoids: aldosterone
Figure 17-17 The Feedback Mechanisms Regulating Aldosterone Secretion. cAMP, Cyclic adenosine monophosphate; ACTH, adrenocorticotropic hormone.
Adrenal estrogens and androgens
Adrenal medulla
Figure 17-18 Synthesis of Catecholamines.
Box 17-2 Methods of Hormone Measurement
Radioimmunoassay (RIA)
Enzyme-Linked Immunosorbent Assay (Elisa)
Bioassay
Quick Check 17-4
Neuroendocrine Response to Stressors
Aging & Its Effects on Specific Endocrine Glands
General Endocrine Changes With Aging
Pancreas
Thyroid
Adrenal
Gonads
Pituitary
Did You Understand?
Mechanisms of Hormonal Regulation
Structure and Function of the Endocrine Glands
AGING & Its Effects on Specific Endocrine Glands
Key Terms
References
Chapter 18 Alterations of Hormonal Regulation
Website http://evolve.elsevier.com/Huether/
Mechanisms of Hormonal Alterations
Figure 18-1 Hormone Delivery to Cells. Phases at which pathogenic mechanisms may develop in delivering appropriate amounts of hormone to the cells.
Alterations of the Hypothalamic-Pituitary System
Diseases of the Posterior Pituitary
Syndrome of inappropriate antidiuretic hormone secretion
Figure 18-2 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.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Diabetes insipidus
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Diseases of the Anterior Pituitary
Hypopituitarism
Pathophysiology
Clinical Manifestations
Figure 18-3 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. From Brashear HR, Raney RB: Handbook of orthopaedic surgery, ed 10, St Louis, 1986, Mosby.
Evaluation and Treatment
Hyperpituitarism: primary adenoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 18-1
Hypersecretion of growth hormone: acromegaly
Pathophysiology
Figure 18-4 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Clinical Manifestations
Figure 18-5 Acromegaly. Chronologic sequence of photographs showing slow development of acromegaly. From Belchetz P, Hammond P: Mosby’s color atlas and text of diabetes and endocrinology, Edinburgh, 2003, Mosby.
Evaluation and Treatment
Prolactinoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Thyroid Function
Hyperthyroidism
Thyrotoxicosis
Clinical Manifestations
Figure 18-6 Evaluation of Hyperthyroidism. Radioactive iodine is used in the differential diagnosis of hyperthyroidism.
Evaluation and Treatment
Hyperthyroid conditions
Graves disease
Table 18-1 Systemic Effects of Hyperthyroidism
Figure 18-7 Graves Disease. Note large and protruding eyeballs. From Belchetz P, Hammond P: Mosby’s color atlas and text of diabetes and endocrinology, Edinburgh, 2003, Mosby.
Hyperthyroidism resulting from nodular thyroid disease
Thyrotoxic crisis
Hypothyroidism
Health Alert Subclinical Hypothyroidism
Pathophysiology
Clinical Manifestations
Table 18-2 Systemic Manifestations of Hypothyroidism
Figure 18-8 Myxedema. Note edema around eyes and facial puffiness. From Thibodeau GA, Patton KT: Anatomy & physiology, St Louis, 1987, Mosby.
Evaluation and Treatment
Hypothyroid conditions
Primary hypothyroidism
Myxedema coma
Congenital hypothyroidism
Thyroid Carcinoma
Figure 18-9 An Adult Cretin. Note the characteristic facial features, dwarfism (44 inches), absent axillary and scant pubic hair, poorly developed breasts, potbelly, and small umbilical hernia. From Schneeberg NG: Essentials of clinical endocrinology, St Louis, 1970, Mosby.
Quick Check 18-2
Alterations of Parathyroid Function
Hyperparathyroidism
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hypoparathyroidism
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 18-3
Dysfunction of the Endocrine Pancreas: Diabetes Mellitus
Table 18-3 Classification and Characteristics of Diabetes Mellitus
Box 18-1 Diagnostic Criteria for Diabetes Mellitus
Types of Diabetes Mellitus
Type 1 diabetes mellitus
Pathophysiology
Hyperglycemia and other symptoms
Clinical Manifestations
Evaluation and Treatment
Type 2 diabetes mellitus
Table 18-4 Epidemiology and Etiology of Diabetes Mellitus
Box 18-2 Specific Environmental Factors Linked to Type 1 Diabetes
Drugs and Chemicals
Nutritional Intake
Viruses
Table 18-5 Clinical Manifestations and Mechanisms for Type 1 Diabetes Mellitus
Health Alert The Metabolic Syndrome/Insulin Resistance Syndrome/Syndrome X
Pathophysiology
Clinical Manifestations
Table 18-6 Clinical Manifestations and Mechanisms for Type 2 Diabetes Mellitus
Evaluation and Treatment
Gestational diabetes
Acute Complications of Diabetes Mellitus
Chronic Complications of Diabetes Mellitus
Hyperglycemia and nonenzymatic glycosylation
Figure 18-10 Diabetic Ketoacidosis. Contributing causes of metabolic acidosis that result from ketosis and consequences of hyperglycemia.
Hyperglycemia and the polyol pathway
Table 18-7 Common Acute Complications of Diabetes Mellitus
Protein kinase C
Diabetic neuropathies
Microvascular disease
Visual changes
Diabetic nephropathy
Macrovascular disease
Figure 18-11 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 liprotein. Data from Charo IF, Ransohoff RM: The many roles of chemokines and chemokine receptors in inflammation, N Engl J Med 354[6]:610–621, 2006; Heinecke JW: Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent bystander? J Exp Med 203[4]:813–816, 2006; Kaperonis EA et al: Inflammation and atherosclerosis, Eur J Vasc Endovasc Surg 31[4]:386–393, 2006; Tedgui A, Mallat Z: Cytokines in atherosclerosis: pathogenic and regulatory pathways, Physiol Rev 86(2):515–581, 2006.
Coronary artery disease
Stroke
Peripheral vascular disease
Infection
Quick Check 18–4
Alterations of Adrenal Function
Disorders of the Adrenal Cortex
Hypercortical function (Cushing syndrome, Cushing disease)
Pathophysiology
Clinical Manifestations
Figure 18-12 Symptoms of Cushing Disease.
Figure 18-13 Cushing Syndrome.A, Patient before onset of Cushing syndrome. B, Patient four months later. Moon facies is clearly demonstrated. From Zitelli BJ, Davis HW: Atlas of pediatric physical diagnosis, ed 3, London, 1997, Gower.
Evaluation and Treatment
Congenital adrenal hyperplasia
Hyperaldosteronism
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hypersecretion of adrenal androgens and estrogens
Hypocortical functioning
Figure 18-14 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). From Thibodeau GA, Patton KT: Anatomy & physiology, St Louis, 1987, Mosby.
Pathophysiology
Idiopathic Addison disease
Secondary hypocortisolism
Clinical Manifestations
Evaluation and Treatment
Table 18-8 Clinical Manifestations and Pathophysiologic Mechanisms of Addison Disease
Disorders of the Adrenal Medulla
Tumor of the adrenal medulla
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 18-5
Did You Understand?
Mechanisms of Hormonal Alterations
Alterations of the Hypothalamic-Pituitary System
Alterations of Thyroid Function
Alterations of Parathyroid Function
Dysfunction of the Endocrine Pancreas: Diabetes Mellitus
Alterations of Adrenal Function
Key Terms
References
Unit 6 The Hematologic System
Chapter 19 Structure and Function of the Hematologic System
Electronic Resources
Companion CD
Website
Components of the Hematologic System
Composition of Blood
Plasma and plasma proteins
Figure 19-1 Composition of Whole Blood. Approximate values for the components of blood in a normal adult. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Cellular components of the blood
Table 19-1 Organic and Inorganic Components of Arterial Plasma
Erythrocytes
Table 19-2 Cellular Components of the Blood
Leukocytes
Granulocytes
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. Copyright by Dennis Kunkel Microscopy, Inc.
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. A, C, D, and E from Rodak, BF: Hematology: clinical principles and applications, ed 2, Philadelphia, 2002, Saunders; B from Carr JC, Rodak BF: Clinical hematology atlas, Philadelphia, 1999, Saunders.
Agranulocytes
Platelets
Quick Check 19-1
Lymphoid Organs
Figure 19-4 Scanning Electron Micrograph of Moderately Active Platelet. From Bick RL: Hematology: clinical and laboratory practice, St Louis, 1993, Mosby.
Spleen
Figure 19-5 Red Cells in the Spleen. Scanning electron micrograph of spleen, demonstrating erythrocytes (numbered 1–6) 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). From Weiss L: A scanning electron microscope study of the spleen, Blood 1974;43;665; reprinted with permission.
Lymph nodes
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
The Mononuclear Phagocyte System
Table 19-3 Mononuclear Phagocyte System (Formerly Called the Reticuloendothelial System)
Quick Check 19-2
Development of Blood Cells
Hematopoiesis
Bone marrow
Cellular differentiation
Figure 19-7 Differentiation of Hematopoietic Cells.SCF, Stem cell factor; FTL-3L, fms-like tyrosine kinase 3 ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; M-CSF, macrophage colony-stimulating factor; G-CSF, granulocyte colony-stimulating factor; CFU, colony-forming unit; Eo, eosinophil; G, granulocyte; M, macrophage; BFU, burst-forming unit; IL, interleukin; E, erythrocyte; Mega, megakaryocyte; Baso, basophil. (Mast cells are discussed in Chapter 5.)
Figure 19-8 Hematopoiesis. Hematopoiesis from the stem cell pool; activity mainly in the bone marrow and in the peripheral blood.
Figure 19-9 Erythrocyte Differentiation. Erythrocyte differentiation from large, nucleated stem cell to small, nonnucleated erythrocyte.
Quick Check 19-3
Development of Erythrocytes
Erythropoiesis
Figure 19-10 Role of Erythropoietin in Regulation of Erythropoiesis. Decreased arterial oxygen levels stimulate production of erythropoietin, which in turn stimulates red cell production and expansion of the erythron. The increase in red cells frequently corrects the problem of low oxygen levels (hypoxia). This restoration to normal oxygen levels alerts the kidney to stop producing erythropoietin (negative feedback). Further erythrocyte production is not needed. RBCs, Red blood cells; PO2, partial pressure of oxygen in the blood.
Hemoglobin synthesis
Figure 19-11 Molecular Structure of Hemoglobin. Molecule is 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.
Nutritional requirements for erythropoiesis
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.
Table 19-4 Nutritional Requirements for Erythropoiesis
Iron cycle
Normal destruction of senescent erythrocytes
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 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.
Quick Check 19-4
Development of Leukocytes
Figure 19-14 Metabolism of Bilirubin Released by Heme Breakdown.MPS, Mononuclear phagocyte system.
Development of Platelets
Mechanisms of Hemostasis
Figure 19-15 Three Hemostatic Compartments.
Function of Platelets and Blood Vessels
Table 19-5 Types of Bleeding: Sources, Vessel Size, and Sealing Requirements
Figure 19-16 Platelet Degranulation.A, Plug formation and clot dissolution. B, After simple endothelial denudation, platelets adhere to the subendothelium in a monolayer fashion. C, Platelet-fibrin thrombus formation. D, Higher magnification of the thrombus shows a mixture of red cells and platelets incorporated into the fibrin meshwork. B to D from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Function of Clotting Factors
Figure 19-17 Blood Clotting Mechanism.A, The clotting mechanism involves release of platelet factors at the injury site, formation of thrombin, and trapping of red blood cells (RBCs) in fibrin to form a clot. B, An electron micrograph showing entrapped RBCs in a fibrin clot. A from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby; B copyright by Dennis Kunkel Microscopy, Inc.
Health Alert Sticky Platelets, Genetic Variations, and Cardiovascular Complications
Health Alert Changes in the Management of Abnormalities in the Hemostatic System
Retraction and Lysis of Blood Clots
Figure 19-18 The Fibrinolytic System. The central reaction is the conversion of plasminogen to the enzyme plasmin. Activity of plasminogen is achieved by the extrinsic pathway (blue) initiated by the release of tissue-type plasminogen activator t-PAI (also called T-PA) released from the endothelial cells and by the intrinsic pathway (gold) from factor XIIa and urokinase. Plasmin splits fibrin in the clot into fibrin degradation products.
Table 19-6 Common Blood Tests for Hematologic Disorders
Quick Check 19-5
Pediatrics & Hematologic Value Changes
Aging & Hematologic Value Changes
Table 19-7 Hematologic Values from Birth to Adulthood
Did You Understand?
Components of the Hematologic System
Development of Blood Cells
Mechanisms of Hemostasis
PEDIATRICS & Hematologic Value Changes
AGING & Hematologic Value Changes
Key Terms
References
Chapter 20 Alterations of Hematologic Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Alterations of Erythrocyte Function
Classification of Anemias
Clinical Manifestations
Table 20-1 Morphologic Classification of Anemias
Figure 20-1 Progression and Manifestations of Anemia.SV, Stroke volume; DPG, 2,3-diphosphoglycerate.
Macrocytic-Normochromic Anemias
Table 20-2 Laboratory Tests for Various Anemias
Pernicious anemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Folate deficiency anemias
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). From Wintrobe MM et al: Clinical hematology, ed 8, Philadelphia, 1981, Lea & Febiger.
Microcytic-Hypochromic Anemias
Iron deficiency anemia
Pathophysiology
Clinical Manifestations
Figure 20-3 Pallor and Iron Deficiency. Pallor of the skin, mucous membranes, and palmar creases in an individual with hemoglobin of 9g/dl. Palmar creases become as pale as the surrounding skin when the hemoglobin level approaches 7g/dl. From Hoffbrand AV, Pettit JE: Sandoz atlas of clinical hematology, London, 1988, Gower Medical.
Figure 20-4 Koilonychia. The nails are concave, ridged, and brittle. From Hoffbrand AV, Pettit JE: Sandoz atlas of clinical hematology, London, 1988, Gower Medical.
Figure 20-5 Glossitis. Tongue of individual with iron deficiency anemia has bald, fissured appearance caused by loss of papillae and flattening. From Hoffbrand AV, Pettit JE: Sandoz atlas of clinical hematology, London, 1988, Gower Medical.
Evaluation and Treatment
Sideroblastic anemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Normocytic-Normochromic Anemias
Quick Check 20-1
Myeloproliferative Red Cell Disorders
Polycythemia Vera
Pathophysiology
Table 20-3 Normocytic-Normochromic Anemias
Clinical Manifestations
Table 20-4 Disorders Classified as Polycythemia
Evaluation and Treatment
Alterations of Leukocyte Function
Quantitative Alterations of Leukocytes
Granulocyte and monocyte alterations
Table 20-5 Other Conditions Associated With Neutrophils, Eosinophils, Basophils, Monocytes, and Lymphocytes
Lymphocyte alterations
Infectious mononucleosis
Clinical Manifestations
Evaluation and Treatment
Quick Check 20-2
Qualitative Alterations of Leukocytes
Leukemias
Figure 20-6 Cell-Specific Leukemias. Differentiation pathways of blood-forming cells and reported sites of blockage resulting in cell-specific leukemias. Ig, Immunoglobulin.
Pathophysiology
Table 20-6 Estimated New Cases and Deaths from Leukemia in the United States—2007
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 gives up much more of its long arm than that translocated to it from chromosome 9, chromosome 22 becomes much abbreviated and is known as Ph1. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Acute leukemias
Clinical Manifestations
Table 20-7 Clinical Manifestations and Related Pathophysiology in Leukemia
Evaluation And Treatment
Table 20-8 Some Examples of Human CSFs
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. (Wright-Giemsa stain.) Courtesy Laura Schmitz, MD, Hennepin County Medical Center, Minn. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Chronic leukemias
Pathophysiology and Clinical Manifestations
Evaluation and Treatment
Quick Check 20-3
Alterations of Lymphoid Function
Lymphadenopathy
Figure 20-8 Lymphadenopathy. Individual with lymphocyte leukemia with extreme but symmetric lymphadenopathy. Courtesy Dr. AR Kagan, Los Angeles. From del Regato JA, Spjut HJ, Cox JD: Cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
Malignant Lymphomas
Hodgkin lymphoma
Pathophysiology
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. A large multinucleated or multilobed cell with inclusion body-like nucleoli surrounded by a halo of clear nucleoplasm. From Damjanov I, Linder J, editors, Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Clinical Manifestations
Table 20-9 Subtypes of Classical Hodgkin Lymphoma
Figure 20-10 Hodgkin Lymphoma and Enlarged Cervical Lymph Node. Typical enlarged cervical lymph node in the neck of a 35-year-old woman with Hodgkin lymphoma. From del Regato JA, Spjut HJ, Cox JD: Cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
Figure 20-11 Common and Uncommon Involved Lymph Node Sites for Hodgkin Lymphoma.
Table 20-10 Modified Cotswold Staging Classification System
Evaluation and Treatment
Non-Hodgkin lymphomas
Pathophysiology
Clinical Manifestations
Table 20-11 Clinical Differences Between Non-Hodgkin Lymphoma and Hodgkin Lymphoma
Evaluation and Treatment
Burkitt lymphoma
Pathophysiology
Clinical Manifestations
Figure 20-12 Burkitt Lymphoma. Burkitt lymphoma involving the jaw in young African boy. Courtesy Dr. JNP Davies, Albany, NY. From del Regato JA, Spjut HJ, Cox JD: Cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
Evaluation and Treatment
Multiple myeloma
Pathophysiology
Figure 20-13 Multiple Myeloma, Bone Marrow Aspirate. Normal marrow cells are largely replaced by plasma cells, including atypical forms with multiple nuclei, and cytoplasmic droplets containing immunoglobulin. From Kumar V, Abbas AK, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Clinical Manifestations
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. From Kissane JM, editor: Anderson’s pathology, ed 9, St Louis, 1990, Mosby.
Evaluation and Treatment
Figure 20-15 M Protein Detection. Serum protein (SP) electrophoresis is used to screen for M proteins (M) in multiple myeloma. In normal serum the proteins separate into several regions between albumin (Alb) and a broad band in the gamma (γ) region, where most antibodies (γ-globulins) are found. Serum from an individual with multiple myeloma contains a sharp M protein (M) band. Using specific antibodies the location of specific types of heavy (G, A, M) and light (κ, λ) chains can be determined. In this example, normal serum contains a broad band with polyclonal IgG molecules that contain κ and λ light chains. The M protein is monoclonal and contains only one heavy chain and one light chain. The M protein in this example is an IgG that contains κ light chain. Courtesy Dr. David Sacks, Department of Pathology, Brigham and Women’s Hospital, Boston, MA. Modified from Kumar V, Abbas A, Fausto N: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Quick Check 20-4
Lymphoblastic lymphoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Splenic Function
Pathophysiology
Clinical Manifestations
Box 20-1 Diseases Related to Classification of Splenomegaly
Inflammation or Infection
Congestive
Infiltrative
Tumors or Cysts
Evaluation and Treatment
Quick Check 20-5
Alterations of Platelets and Coagulation
Disorders of Platelet Function
Thrombocytopenia
Pathophysiology
Heparin-induced thrombocytopenia
Clinical Manifestations
Evaluation and Treatment
Idiopathic (immune) thrombocytopenia purpura
Clinical Manifestations
Evaluation and Treatment
Thrombotic thrombocytopenia purpura
Clinical Manifestations
Evaluation and Treatment
Thrombocythemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Platelet Function
Health Alert Dark Chocolate, Wine, and Platelet-Inhibitory Functions
Disorders of Coagulation
Impaired hemostasis
Vitamin K deficiency
Liver disease
Consumptive thrombohemorrhagic disorders
Disseminated intravascular coagulation
Pathophysiology
Figure 20-16 Pathophysiology of Disseminated Intravascular Coagulation (DIC). DIC is initiated by exposure of tissue factor (TF) after vessel damage, on tumor cells, or on the surface of endothelial cells or monocytes after exposure to cytokines, some of which may be produced by cytokines. TF reacts with and activates factor VII to produce a TF-VIIa complex, which can directly activate clotting factors IX and X. Activated factor IX (IXa) can interact with factors VIIIa and X to activate factor X to Xa. Factor Xa complexes with factor Va and prothrombin (PT) to form the prothrombinase complex that produces thrombin, which in turn activates fibrinogen to fibrin. Fibrin polymerizes to form clots. In DIC, natural regulators of the clotting system (tissue factor pathway inhibitor [TFPI], antithrombin-III [AT-III], and protein C [Prot C]) are decreased resulting in increased thrombin formation. Clots are normally broken down by plasmin, which is produced from plasminogen and degrades fibrin into fibrin degradation products (FDPs). In DIC, fibrinolysis is prevented by high levels of plasminogen-activator inhibitor type 1 (PAI-1), which inhibits the production of plasmin. The summation of these changes is greatly increased deposition of fibrin clots in the vessels and thrombosis.
Box 20-2 Acute Disseminated Intravascular Coagulation (DIC)
Clinical Manifestations
Box 20-3 Clinical Manifestations Associated With DIC
Integumentary System
Central Nervous System
Gastrointestinal System
Pulmonary System
Renal System
Evaluation and Treatment
Thromboembolic disorders
Figure 20-17 Thrombus arising in valve pocket at upper end of superficial femoral vein. Postmortem clot on the right is shown for comparison. From McLachlin J, Paterson JC: Some basic observations on venous thrombosis and pulmonary embolism, Surg Gynecol Obstet 93(1):1–8, 1951.
Hereditary hypercoagulability and thrombosis
Acquired hypercoagulability and thrombosis
Quick Check 20-6
Did You Understand?
Alterations of Erythrocyte Function
Myeloproliferative Red Cell Disorders
Alterations of Leukocyte Function
Alterations of Lymphoid Function
Alterations of Splenic Function
Alterations of Platelets and Coagulation
Key Terms
References
Chapter 21 Alterations of Hematologic Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Disorders of Erythrocytes
Acquired Disorders
Iron deficiency anemia
Table 21-1 Anemias of Childhood
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hemolytic disease of the newborn
Pathophysiology
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 stimulate the mother to produce antibodies against the Rh antigen. The Rh antibodies from the mother cross the placenta, using agglutination and hemolysis of fetal erythrocytes, and HDN develops. Modified from Seeley RR, Stephens TD, Tate P: Anatomy and physiology, ed 3, St Louis, 1995, Mosby.
Clinical Manifestations
Evaluation and Treatment
Inherited Disorders
Sickle cell disease
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 the folded beta-chain molecule, the sixth position contacts the alpha chain and the amino acid change causes the hemoglobins to aggregate into long chains, altering the shape of the cell. B, Characteristic shape of sickled red blood cell (or cells). A from Raven PH, Johnson GB: Biology, ed 3, Boston, 1993, Times Mirror Higher Education Group. B from Miale JB: Laboratory medicine: hematology, ed 6, St Louis, 1982, Mosby; courtesy Dr. M. Bessis.
Table 21-2 Inheritance of Sickle Cell Disease
Pathophysiology
Figure 21-3 Sickling of Erythrocytes.
Clinical Manifestations
Figure 21-4 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; RBC, red blood cell; GI, gastrointestinal. A and B adapted from Hockenberry MJ et al, editors: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Evaluation and Treatment
Health Alert Hydroxyurea Treatment for Severe Sickle Cell Disease
Thalassemias
Pathophysiology
Clinical Manifestations
Figure 21-5 A Young Girl with Beta-Thalassemia Demonstrating Mild Frontal Bossing (prominent) of the Right Forehead and Mild Maxillary Prominence. From Hockenberry MJ et al, editors: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Figure 21-6 A Child with Beta-Thalassemia Major Who Has Severe Splenomegaly. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Evaluation and Treatment
Quick Check 21-1
Disorders of Coagulation and Platelets
Inherited Hemorrhagic Disease
Hemophilias
Pathophysiology
Table 21-3 Coagulation Factors and Associated Disorders
Table 21-4 The Hemophilias
Clinical Manifestations
Evaluation and Treatment
Table 21-5 Laboratory Tests of Coagulation
Antibody-Mediated Hemorrhagic Disease
Idiopathic thrombocytopenic purpura
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 21-2
Neoplastic Disorders
Leukemia and Lymphoma
Leukemia
Table 21-6 Major Classifications of Leukemia
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Lymphomas
Figure 21-7 Monoblasts from Acute Monoblastic Leukemia. Monoblasts in a marrow smear from a patient 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). From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Health Alert Monoclonal Antibody Therapy to Treat Chronic Myeloid Leukemia
Non-Hodgkin lymphoma
Figure 21-8 Lymphomas.A, Large cell lymphoma. The tumor contains prominent areas of sclerosis. B, Burkitt lymphoma. A starry sky pattern is seen at low magnification. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Hodgkin lymphoma
Figure 21-9 Diagnostic Reed-Sternberg Cell. A large multinucleated or multilobated cell with inclusion body-like nucleoli surrounded by a halo of clear nucleoplasm. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Figure 21-10 Main Areas of Lymphadenopathy and Organ Involvement in Hodgkin Lymphoma. From Hockenberry MJ et al, editors: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Quick Check 21-3
Did You Understand?
Disorders of Erythrocytes
Disorders of Coagulation and Platelets
Neoplastic Disorders
Key Terms
References
Unit 7 The Cardiovascular and Lymphatic Systems
Chapter 22 Structure and Function of the Cardiovascular and Lymphatic Systems
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
The Circulatory System
The Heart
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. From Thibodeau GA, Patton KT: Anatomy & Physiology, ed 6, St Louis, 2007, Mosby.
Structures That Direct Circulation Through the Heart
The heart wall
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Chambers of the heart
Figure 22-3 Structures That Direct Blood Flow Through the Heart. Arrows indicate path of blood flow through chambers, valves, and major vessels.
Fibrous skeleton of the heart
Valves of the heart
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. B is similar to A except that the semilunar valves are open and the atrioventricular valves are closed, as when the ventricles are contracting. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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). Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
The great vessels
Blood flow during the cardiac cycle
Normal intracardiac pressures
Quick Check 22-1
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.
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 22-1 Normal Intracardiac Pressures
Structures That Support Cardiac Metabolism: The Coronary Vessels
Coronary arteries
Collateral arteries
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. A and B modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby; C from Seeley RR, Stephens TD, Tate P: Anatomy and physiology, ed 3, St Louis, 1995, Mosby.
Box 22-1 Main Branches of the Coronary Arteries
Coronary capillaries
Coronary veins and lymphatic vessels
Structures That Control Heart Action
The conduction system
Figure 22-9 Autonomic innervation of cardiovascular system. − = Inhibition; + = activation.
Figure 22-10 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. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 22-2
Propagation of cardiac action potentials
Table 22-2 Intercellular and Extracellular Ion Concentrations in the Myocardium
The normal electrocardiogram
Automaticity
Rhythmicity
Figure 22-11 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.RA, Right atrium; LA, left atrium; AV, atrioventricular; RV, right ventricle; LV, left ventricle; RBB, right bundle branch; LBB, left bundle branch. A and B from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 22-3
Cardiac innervation
Sympathetic and parasympathetic nerves
Myocardial cells
Figure 22-12 Sarcomere.A, Electron photomicrograph of sarcomere. B, Schematic of location and interaction of actin and myosin. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 3, St Louis, 1996, Mosby.
Actin, myosin, and the troponin-tropomyosin complex
Myocardial metabolism
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. From Raven PH, Johnson GB: Understanding biology, ed 3, Dubuque, 1995, Brown.
Myocardial contraction and relaxation
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. From Raven PH, Johnson GB: Understanding biology, ed 3, Dubuque, 1995, Brown.
Calcium and excitation-contraction coupling
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Myocardial relaxation
Quick Check 22-4
Factors Affecting Cardiac Performance
Preload
Table 22-3 Cardiovascular Function in Elderly Persons
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. (See text for further explanation.)
Afterload
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).
Myocardial contractility
Heart rate
Cardiovascular control centers in the brain
Neural reflexes
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. From Berne RM, Levy MN: Cardiovascular physiology, ed 8, St Louis, 2001, Mosby.
Atrial receptors
Hormones and biochemicals
Quick Check 22-5
The Systemic Circulation
Structure of Blood Vessels
Arterial vessels
Endothelium
Veins
Figure 22-19 Circulatory System.A, Principal arteries of body. B, Principal veins of body. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 22-20 Schematic Drawings and Micrograph of Artery and Vein.A, Shown are the comparative thickness of three layers: outer layer (tunica adventitia), muscle layer (tunica media), and lining of endothelium (tunica intima). Note that muscle and outer coats are much thinner in veins than in arteries and that veins have valves. B, Micrograph (× 250) of a cross section of tissue containing both an artery (left) and a vein (right). Note the thickness of the smooth muscle (tunica media) in the artery compared with the vein. C, Micrograph showing both an artery and vein. The tunica media is much thicker in the artery. A modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby; B from Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby; C, Copyright Ed Reschke.
Factors Affecting Blood Flow
Pressure and resistance
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). A from Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby; B, Copyright Ed Reschke.
Figure 22-22 Capillary Network. Blood enters network as arterial blood and exits as venous blood.
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).
Table 22-4 Functions of the Endothelium
Figure 22-24 Valves of Vein. Pooled blood is moved toward heart as valves are forced open by pressure from volume of blood downstream. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Figure 22-25 Muscle Pump.
Figure 22-26 Lumen Diameter, Blood Flow, and Resistance.A, Effect of lumen diameter on flow through vessel. d, Diameter. 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. B from Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Figure 22-27 Schematic Diagram of the Parallel and Series Arrangement of the Vessels Composing the Circulatory System.A, Resistance in blood vessels arranged in series or parallel. R, Resistance in an individual vessel. B, The capillary beds are represented by thin lines connecting the arterioles (right) and the veins (left). The crescent-shaped thickenings proximal to the capillary beds represent the arterioles (resistance vessels). B modified from Berne RM, Levy MN: Cardiovascular physiology, ed 8, St Louis, 2001, Mosby.
Neural control of total peripheral resistance
Velocity
Figure 22-28 Baroreceptors and Chemoreceptor Reflex Control of Blood Pressure.A, Baroreceptor reflexes. Baroreceptors located in the carotid sinuses and aortic arch detect changes in blood pressure. Action potentials are conducted to the cardioregulatory and vasomotor centers. The heart rate can be decreased by the parasympathetic system; the heart rate and stroke volume can be increased by the sympathetic system. The sympathetic system also can constrict or dilate blood vessels. B, Chemoreceptor reflexes. Chemoreceptors located in the medulla oblongata and in the carotid and aortic bodies detect changes in blood oxygen, carbon dioxide, or pH. Action potentials are conducted to the medulla oblongata. In response, the vasomotor center can cause vasoconstriction or dilation of blood vessels by the sympathetic system, and the cardioregulatory center can cause changes in the pumping activity of the heart through the parasympathetic and sympathetic systems. From Seeley RR, Stephens TD, Tate P: Anatomy and physiology, ed 3, St Louis, 1995, Mosby.
Laminar versus turbulent flow
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. From Seeley RR, Stephens TD, Tate P: Anatomy and physiology, ed 3, St Louis, 1995, Mosby.
Vascular compliance
Quick Check 22-6
Regulation of Blood Pressure
Arterial pressure
Baroreceptors
Arterial chemoreceptors
Antidiuretic hormone, renin-angiotensin system, natriuretic peptides, adrenomedullin, and insulin
Figure 22-30 Factors Regulating Blood Pressure.
Table 22-5 Factors That Affect Mean Arterial Pressure and Capillary Flow
Health Alert Aldosterone and Injury
Figure 22-31 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. NPs, Natriuretic peptides; ACE, angiotensin converting enzyme. Modified from Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Health Alert Angiotensin II
Figure 22-32 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 lung 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. Adapted from Goodfriend TL et al: N Engl J Med 334:2649–2654, 1996.
Figure 22-33 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.
Venous pressure
Regulation of the Coronary Circulation
Box 22-2 Vascular Protection and Injury Properties of Insulin
Protection
Injury
Autoregulation
Autonomic regulation
Quick Check 22-7
The Lymphatic System
Figure 22-34 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 22-35 Principle Organs of the Lymphatic System. The inset shows the areas drained by the right lymphatic duct (green) and the thoracic duct (blue). From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 22-36 Lymphatic Capillaries.A, Schematic representation of lymphatic capillaries. B, Anatomic components of microcirculation.
Quick Check 22-8
Did You Understand?
The Circulatory System
The Heart
The Systemic Circulation
The Lymphatic System
Key Terms
References
Chapter 23 Alterations of Cardiovascular Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Diseases of the Arteries and Veins
Diseases of the Veins
Varicose veins and chronic venous insufficiency
Thrombus formation in veins
Figure 23-1 Venous Stasis Ulcer. From Rosai J: Ackerman’s surgical pathology, ed 7, vol 2, St Louis, 1989, Mosby.
Figure 23-2 Multiple Venous Thrombi. From Rosai J: Ackerman’s surgical pathology, ed 7, vol 2, St Louis, 1989, Mosby.
Superior vena cava syndrome
Quick Check 23-1
Hypertension
Table 23-1 Classification of Blood Pressure for Adults Age 18 Years or Older
Factors associated with primary hypertension
Health Alert Genes and the Risk for Hypertension
Risk Factors Primary Hypertension
Pathophysiology
Primary hypertension
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. SNS, Sympathetic nervous system; RAA, renin-angiotensin-aldosterone.
Health Alert Obesity and Hypertension
Secondary hypertension
Isolated systolic hypertension
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, 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.
Complicated hypertension
Clinical Manifestations
Table 23-2 Pathologic Effects of Sustained, Complicated Primary Hypertension
Evaluation and Treatment
Orthostatic (Postural) Hypotension
Figure 23-5 Summary of Treatment Recommendations for Hypertension.BP, Blood pressure; ACE, angiotensin-converting enzyme; ARB, angiotensin-receptor blocker; CCB, calcium channel blocker. Data from Chobanian AV et al: The JNC 7 Report, JAMA 289(19):2560–2572, 2003.
Quick Check 23-2
Aneurysm
Figure 23-6 Aneurysms.A, Abdominal aortic atherosclerotic aneurysm. B, In a long-axis view of the left ventricle there is a large, thin-walled apical aneurysm that does not contain thrombus. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 23-7 Longitudinal Sections Showing Types of Aneurysms. 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.
Figure 23-8 Dissecting Aneurysm of Thoracic Aorta. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Thrombus Formation
Embolism
Table 23-3 Types of Emboli
Quick Check 23-3
Peripheral Vascular Disease
Thromboangiitis obliterans (Buerger disease)
Raynaud phenomenon and disease
Quick Check 23-4
Arteriosclerosis
Atherosclerosis
Figure 23-9 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. B from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Pathophysiology
Figure 23-10 Endothelium Regulation of Vasomotion (Constriction and Dilation) and Platelet Aggregation. With injury, the endothelium loses its normal ability to decrease clot formation (antithrombotic) and maintain vasodilation. Injury results in platelet aggregation with increases in thromboxane A2 (which aspirin inhibits) and the release of serotonin and endothelin causing vasoconstriction, a decrease in blood flow, and ischemia. Sympathetic nerve activation causes vasoconstriction with the release of epinephrine. Endothelin is a potent amino acid peptide. The endothelium also converts angiotensin I into angiotensin II by the membrane-bound angiotensin-converting enzyme (ACE). Angiotensin II plays an important role in the pathophysiology of hypertension, atherosclerosis, myocardial infarction, and left heart failure (congestive heart failure) (see text under the heading for each). Modified from Stern S, editor: Silent myocardial ischemia, St Louis, 1998, Mosby.
Figure 23-11 Factors That Cause Endothelium-Dependent Vasodilation. Several pharmacologic and physiologic factors stimulate the release of nitric oxide synthase (NOS) that results in the release of nitric oxide (NO). These factors include norepinephrine, acetylcholine, bradykinin, substance P, angiotensin II, thrombin, vasopressin, ATP, 5-HT, and ADP. In addition, the continuous normal production of NO can be increased by physiologic events including shear stress (on the vessel walls) and movement of platelets. Nitric oxide leads to relaxation of the smooth muscle cells resulting in vasodilation. Prostacyclin (PGI2) also causes relaxation of the smooth muscle cells and inhibits platelet aggregation downstream. Modified from Stern S, editor: Silent myocardial ischemia, St Louis, 1998, Mosby.
Clinical Manifestations
Figure 23-12 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 actin of free oxygen radicals formed by enzymatic or nonenzymatic reactions. This generates proinflammatory lipids that induce endothelial expression of the adhesion molecule, 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 fragments of it 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-α, 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 include NO production and inhibit growth, collagen, and actin expression. LDL, low-density lipoprotein. Modified from Crawford MH, DiMarco JP, editors: Cardiology, London, 2001, Mosby.
Evaluation and Treatment
Figure 23-13 Progression of Atherosclerosis. A, Damaged endothelium. B, Diagram of fatty streak and lipid core formation (see Figure 23-5 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.
Peripheral Artery Disease
Coronary Artery Disease, Myocardial Ischemia, and Acute Coronary Syndromes
Figure 23-14 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. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Development of coronary artery disease
Health Alert The Basics on Fats
Table 23-4 Criteria for Dyslipidemia
Dyslipidemia
Hypertension
Cigarette smoking
Diabetes mellitus
Obesity/sedentary lifestyle
Nontraditional risk factors
Markers of inflammation and thrombosis
Hyperhomocysteinemia
Infection
Health Alert Inflammatory Markers for Cardiovascular Risk
Figure 23-15 Cycle of Ischemic Events.
Myocardial ischemia
Pathophysiology
Clinical Manifestations
Figure 23-16 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. Modified from Stern S, editor: Silent myocardial ischemia, St Louis, 1998, Mosby.
Health Alert Women and Coronary Artery Disease
Figure 23-17 The Ischemic Cost of Aggravation. Linkages among daily mental and emotional stimuli, brain activity, and coronary and myocardial physiology. Modified from Papodemetrion V et al: Am Heart J 132:1299, 1996.
Evaluation and Treatment
Figure 23-18 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 patients with coronary artery disease; potentially fatal dysrhythmia; plaque rupture; or coronary thrombosis. VF, Ventricular fibrillation; VT, ventricular tachycardia; MI, myocardial infarction; LV, left ventricular. From Krantz DS et al: Mental stress as a trigger of myocardial ischemia and infarction. In Deedwania PC, Tofler GH, editors: Triggers and timing of cardiac events, ed 2, London, 1996, Saunders.
Figure 23-19 Electrocardiogram (ECG) and Ischemia.A, Normal ECG. B, Electrocardiographic alterations associated with ischemia.
Quick Check 23-5
Acute coronary syndromes
Figure 23-20 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.
Figure 23-21 Pathogenesis of Unstable Plaques and Thrombus Formation.
Figure 23-22 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 artery occlusion is probably in the right coronary artery. The infarct is on the posterior wall. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Unstable angina
Myocardial infarction
Pathophysiology
Cellular injury
Cellular death
Structural and functional changes
Figure 23-23 Myocardial Infarction.A, Local infarct confined to one region. B, Massive large infarct caused by occlusion of three coronary arteries. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Repair
Clinical Manifestations
Complications
Figure 23-24 Three Interacting Factors Related to Sudden Cardiac Death. The three factors are ischemia, left ventricular dysfunction, and electrical instability.
Evaluation and Treatment
Table 23-5 Complications With Myocardial Infarctions
Figure 23-25 Electrocardiographic Alterations Associated With the Three Zones of Myocardial Infarction.
Quick Check 23-6
Disorders of the Heart Wall
Disorders of the Pericardium
Acute pericarditis
Figure 23-26 Acute Pericarditis. Note shaggy coat of fibers covering the surface of heart. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Pericardial effusion
Figure 23-27 Exudate of Blood in the Pericardial Sac from Rupture of Aneurysm. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Constrictive pericarditis
Figure 23-28 Constrictive Pericarditis. The fibrotic pericardium encases the heart in a rigid shell. From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Disorders of the Myocardium: The Cardiomyopathies
Quick Check 23-7
Figure 23-29 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. From Kissane JM, editor: Anderson’s pathology, ed 9, St Louis, 1990, Mosby.
Disorders of the Endocardium
Valvular dysfunction
Stenosis
Aortic stenosis
Table 23-6 Pathophysiologic Effects of the Cardiomyopathies
Mitral stenosis
Regurgitation
Aortic regurgitation
Table 23-7 Clinical Manifestations of Valvular Stenosis and Regurgitation
Figure 23-30 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.
Figure 23-31 Mitral Stenosis With Classic “Fish Mouth” Orifice. From Stevens A, Lowe J: Pathology, ed 2, London, 2000, Mosby.
Mitral regurgitation
Tricuspid regurgitation
Mitral valve prolapse syndrome
Figure 23-32 Mitral Valve Prolapse.A, Normal mitral valve (lower right) and prolapsed mitral valve (left). Prolapse permits the valve leaflets to billow back 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 of the leaflets is visible. B from Stevens A, Lowe J: Pathology, ed 2, Edinburgh, 2000, Mosby.
Acute rheumatic fever and rheumatic heart disease
Pathophysiology
Figure 23-33 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. From Damjanov I: Pathology for the health professions, ed 3, St. Louis, 2006, Saunders.
Figure 23-34 Mitral Stenosis with Vegitations. Mitral stenosis and clumps of vegetation (V) containing platelets and fibrin as shown in this micrograph. Mitral leaflets are thickened and fused. From Stevens A, Lowe J: Pathology, Edinburgh, 2000, Mosby.
Clinical Manifestations
Carditis
Polyarthritis
Table 23-8 Jones Criteria (Updated) Used for Diagnosis of Initial Attack of Rheumatic Fever
Chorea
Erythema marginatum
Evaluation and Treatment
Quick Check 23-8
Infective endocarditis
Risk Factors Infective Endocarditis
Pathophysiology
Figure 23-35 Pathogenesis of Infective Endocarditis.
Clinical Manifestations
Figure 23-36 Bacterial Endocarditis of Mitral Valve. The valve is covered with large, irregular vegetations (arrow). From Damjanov I, Linder J: Pathology: a color atlas, St Louis, 2000, Mosby.
Evaluation and Treatment
Cardiac Complications in Acquired Immunodeficiency Syndrome (AIDS)
Quick Check 23-9
Manifestations of Heart Disease
Dysrhythmias
Table 23-9 Disorders of Impulse Formation
Table 23-10 Disorders of Impulse Conduction
Heart Failure
Left heart failure (congestive heart failure)
Box 23-1 Inflammation, Immunity, and Humoral Factors in the Pathogenesis of Congestive Heart Failure
Figure 23-37 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. Redrawn from Carelock J, Clark AP: Heart failure: pathophysiologic mechanisms, Am J Nurs 101[12]:27, 2001.
Figure 23-38 The Effect of Elevated Preload on Myocardial Oxygen Supply and Demand.LVEDV, Left ventricular end-diastolic volume.
Figure 23-39 The Role of Increased Afterload in the Pathogenesis of Heart Failure.
Figure 23-40 The 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.
Health Alert Brain Natriuretic Peptide (BNP) and Heart Failure
Right heart failure
Figure 23-41 Right Heart FailureRV, Right ventricular; RA, right atrial; JVD, jugular venous distension.
High-output failure
Quick Check 23-10
Shock
Figure 23-42 High-Output Failure.SVR, Systemic vascular resistance.
Impairment of Cellular Metabolism
Impairment of oxygen use
Figure 23-43 Impaired Cellular Metabolism in Shock.ATP, Adenosine triphosphate.
Impairment of glucose use
Types of Shock
Cardiogenic shock
Hypovolemic shock
Figure 23-44 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.
Neurogenic shock
Figure 23-45 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.
Anaphylactic shock
Figure 23-46 Neurogenic Shock.SVR, Systemic vascular resistance.
Figure 23-47 Anaphylactic Shock.IgE, Immunoglobulin E; SVR, systemic vascular resistance.
Quick Check 23-11
Septic shock
Table 23-11 Causes and Definitions of Septic Shock
Figure 23-48 Septic Shock Cascade.
Health Alert The Role of Nitric Oxide in Severe Sepsis
Risk Factors Inflammatory and Anti-inflammatory Mediators Contributing to Septic Shock
The Interleukins
Tumor Necrosis Factor
Platelet-Activating Factor
Myocardial Depressant Factor
Clinical Manifestations of Shock
Treatment for Shock
Quick Check 23-12
Multiple Organ Dysfunction Syndrome
Risk Factors Development of Multiple Organ Dysfunction Syndrome
Pathophysiology
Figure 23-49 Pathogenesis of Multiple Organ Dysfunction Syndrome.
Clinical Manifestations
Table 23-12 Cells of Inflammation and Multiple Organ Dysfunction
Evaluation and Treatment
Health Alert Nutritional Support to Prevent and Treat MODS
Quick Check 23-13
Did You Understand?
Diseases of the Arteries and Veins
Disorders of the Heart Wall
Manifestations of Heart Disease
Shock
Key Terms
References
Chapter 24 Alterations of Cardiovascular Function in Children
Electronic Resources
Companion CD
Website
Congenital Heart Disease
Table 24-1 Maternal Conditions and Environmental Exposures and the Associated Congenital Heart Defects
Table 24-2 Congenital Heart Disease in Selected Fetal Chromosomal Aberrations
Obstructive Defects
Coarctation of the aorta
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 24-1 Shunting of Blood in Congenital Heart Disease.A, Normal. B, Acyanotic defect. C, Cyanotic defect. ASD, Atrial septal defect; VSD, ventricular septal defect; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle. From Wong DL: Whaley & Wong’s essentials of pediatric nursing, ed 4, St Louis, 1993, Mosby.
Figure 24-2 Comparison of Acyanotic-Cyanotic and Hemodynamic Classification Systems of Congenital Heart Disease. From Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Figure 24-3 Coarctation of the Aorta (COA) (Postductal). From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Aortic stenosis
Pathophysiology
Figure 24-4 Aortic Stenosis (AS). From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Clinical Manifestations
Evaluation and Treatment
Valvular aortic stenosis
Subvalvular aortic stenosis
Pulmonic stenosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
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 across the narrowed valve opening. A from James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders. B redrawn from Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Defects With Increased Pulmonary Blood Flow
Patent ductus arteriosus
Pathophysiology
Clinical Manifestations
Figure 24-6 Patent Ductus Arteriosus (PDA). From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Evaluation and Treatment
Atrial septal defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Ventricular septal defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Atrioventricular canal defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 24-7 Atrioventricular Canal (AVC) Defect. From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Defects With Decreased Pulmonary Blood Flow
Tetralogy of fallot
Pathophysiology
Clinical Manifestations
Figure 24-8 Tetralogy of Fallot (TOF). From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Evaluation and Treatment
Tricuspid atresia
Pathophysiology
Figure 24-9 Tricuspid Atresia. From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Clinical Manifestations
Evaluation and Treatment
Mixing Defects
Transposition of the great arteries or transposition of the great vessels
Pathophysiology
Clinical Manifestations
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. B, Oxygen saturation in the two parallel circuits. RA, Right atrium; RV, right ventricle; Ao, aorta; ASD, atrial septal defect; VSD, ventricular septal defect; PDA, patent ductus arteriosus; LA, left atrium; LV, left ventricle; PA, pulmonary artery. A redrawn from Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Evaluation and Treatment
Total anomalous pulmonary venous connection
Pathophysiology
Figure 24-11 Total Anomalous Pulmonary Venous Connection (TAPVC). Redrawn from Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Clinical Manifestations
Evaluation and Treatment
Truncus arteriosus
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 24-12 Truncus Arteriosus (TA). From James SR, Ashwill JW: Nursing care of children: principles and practice, ed 3, St Louis, 2007, Saunders.
Hypoplastic left heart syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 24-13 Hypoplastic Left Heart Syndrome (HLHS). Redrawn from Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Quick Check 24-1
Health Alert Endocarditis Risk
Congestive Heart Failure
Table 24-3 Causes of Congestive Heart Failure Resulting From Congenital Heart Disease
Box 24-1 Clinical Manifestations of Congestive Heart Failure
Impaired Myocardial Function
Pulmonary Congestion
Acquired Cardiovascular Disorders
Kawasaki Disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Box 24-2 Diagnostic Criteria for Kawasaki Disease
Systemic Hypertension
Table 24-4 Diagnosing Hypertension in Children (Selected Ages)
Pathophysiology
Box 24-3 Conditions Associated With Secondary Hypertension in Children
Renal Disorders
Cardiovascular Disease
Metabolic and Endocrine Diseases
Neurologic Disorders
Miscellaneous Causes
Clinical Manifestations
Health Alert U.S. Childhood Obesity and Its Association With Cardiovascular Disease
Evaluation and Treatment
Table 24-5 Most Common Causes of Chronic Sustained Hypertension
Table 24-6 Routine and Special Laboratory Tests for Hypertension
Quick Check 24-2
Did You Understand?
Congenital Heart Disease
Acquired Cardiovascular Disorders in Children
Key Terms
References
Unit 8 The Pulmonary System
Chapter 25 Structure and Function of the Pulmonary System
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Structures of the Pulmonary System
Conducting Airways
Figure 25-1 Structures of the Pulmonary System. The enlargement in the circle depicts the acinus, where oxygen and carbon dioxide are exchanged. From Thibodeau GA, Patton, KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 25-1 Pulmonary Defense Mechanisms
Figure 25-2 Structures of the Upper Airway. Redrawn from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Gas-Exchange Airways
Figure 25-3 Structures of the Lower Airway. Redrawn from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Quick Check 25-1
Pulmonary and Bronchial Circulation
Figure 25-4 Changes in the Bronchial Wall With Progressive Branching. From Wilson SF, Thompson JM: Respiratory disorders, St Louis, 1990, Mosby.
Figure 25-5 Alveoli. Bronchioles subdivide to form tiny tubes called alveolar ducts, which end in clusters of alveoli called alveolar sacs. From Thibodeau GA, Patton, KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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.
Chest Wall and Pleura
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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 3, St Louis, 1996, Mosby.
Function of the Pulmonary System
Ventilation
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.
Quick Check 25-2
Neurochemical Control of Ventilation
Lung receptors
Figure 25-9 Spirogram. During normal, quiet respirations, the atmosphere and lungs exchange about 500ml of air (VT). With a forcible inspiration, about 3300ml more air can be inhaled (IRV). After a normal inspiration and normal expiration, approximately 1000ml 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Chemoreceptors
Figure 25-10 Neurochemical Respiratory Control System.
Health Alert Changes in the Chemical Control of Breathing During Sleep
Quick Check 25-3
Mechanics of Breathing
Major and accessory muscles
Alveolar surface tension
Figure 25-11 Muscles of Ventilation.A, Anterior view. B, Posterior view. Modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Elastic properties of the lung and chest wall
Figure 25-12 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.
Airway resistance
Work of breathing
Quick Check 25-4
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 total pressure is 26.
Gas Transport
Measurement of gas pressure
Table 25-2 Common Pulmonary Abbreviations
Distribution of ventilation and perfusion
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.
Oxygen transport
Diffusion across the alveolocapillary membrane
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 pressure, 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 and venous pressure.
Determinants of arterial oxygenation
Oxyhemoglobin association and dissociation
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. Modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Carbon dioxide transport
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 100mm 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 were linear (in a downward sloping straight line) instead of flat between 60 and 100mm 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 26.6mm 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 (dotted lines). The shaded area shows the entire oxyhemoglobin dissociation curve under the same circumstances. 2,3-DPG, 2,3-Diphosphoglycerate. From Lane EE, Walker JF: Clinical arterial blood gas analysis, St Louis, 1987, Mosby.
Quick Check 25-5
Control of the Pulmonary Circulation
Quick Check 25-6
Aging & The Pulmonary System
Elasticity/Chest Wall
Gas Exchange
Exercise
Changes in Lung Volumes With Aging. With aging, note particularly the dense vital capacity and the increase in residual volume. See also McClaran SR et al: Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults, J Appl Physiol 78(5):1957–1968, 1995; Hardie JA et al: Reference values for arterial blood gases in the elderly, Chest 125(6):2053–2060, 2004; Zeleznik J: Normative aging of the respiratory system, Clin Geriatr Med 19(1):1–18, 2003; Meyer KC: The role of immunity in susceptibility to respiratory infection in the aging lung, Respir Physiol 128(1):23–31, 2001.
Did You Understand?
Structures of the Pulmonary System
Function of the Pulmonary System
AGING & the Pulmonary System
Key Terms
References
Chapter 26 Alterations of Pulmonary Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Clinical Manifestations of Pulmonary Alterations
Signs and Symptoms of Pulmonary Disease
Dyspnea
Abnormal breathing patterns
Hypoventilation/hyperventilation
Cyanosis
Clubbing
Cough
Figure 26-1 Clubbing of Fingers Caused by Chronic Hypoxemia. Modified from Seidel HM et al: Mosby’s guide to physical examination, ed 5, St Louis, 2003, Mosby.
Hemoptysis
Abnormal sputum
Pain
Conditions Caused by Pulmonary Disease or Injury
Hypercapnia
Hypoxemia
Figure 26-2 Ventilation-Perfusion ( V./Q.) Abnormalities.
Quick Check 26-1
Acute respiratory failure
Pulmonary edema
Figure 26-3 Pathogenesis of Pulmonary Edema.
Aspiration
Atelectasis
Figure 26-4 Pores of Kohn.A, Absorption atelectasis caused by lack of collateral ventilation through pores of Kohn. B, Restoration of collateral ventilation during deep breathing.
Bronchiectasis
Bronchiolitis
Pleural abnormalities
Pneumothorax
Figure 26-5 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.
Pleural effusion
Table 26-1 Mechanism of Pleural Effusion
Empyema
Chest wall restriction
Flail chest
Figure 26-6 Flail Chest. Normal respiration: A, inspiration; B, expiration. Paradoxical motion: C, inspiration, area of lung underlying unstable chest wall sucks in on inspiration; D, expiration, unstable area balloons out. Note movement of mediastinum toward opposite lung during inspiration.
Quick Check 26-2
Pulmonary Disorders
Restrictive Lung Diseases
Pulmonary fibrosis
Inhalation disorders
Exposure to toxic gases
Pneumoconiosis
Allergic alveolitis
Acute respiratory distress syndrome
Pathophysiology
Figure 26-7 Proposed Mechanisms for the Pathogenesis of Acute Respiratory Distress Syndrome (ARDS). IL-1-β, Interleukin-1-β; TNF, tumor necrosis factor; ROS, reactive oxygen species; TGF-β, transforming growth factor-β; PDGF, platelet derived growth factor. From Soubani AO, Pieroni R: Acute respiratory distress syndrome: a clinical update, South Med J 92[5]:452, 1999.
Clinical Manifestations
Evaluation and Treatment
Quick Check 26-3
Obstructive Lung Diseases
Asthma
Pathophysiology
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. Modified from Des Jardins T, Burton GG: Clinical manifestations and assessment of respiratory disease, ed 5, St Louis, 2006, Mosby.
Clinical Manifestations
Figure 26-9 Pathophysiology of Asthma. Allergen or irritant exposure results in a cascade of inflammatory events leading to acute and chronic airway dysfunction.
Evaluation and Treatment
Chronic obstructive pulmonary disease
Health Alert Monoclonal Antibodies to IgE for Treatment of Asthma
Chronic bronchitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Table 26-2 Clinical Manifestations of Chronic Obstructive Lung Disease
Figure 26-10 Pathogenesis of Chronic Bronchitis and Emphysema (Chronic Obstructive Pulmonary Disease [COPD]).
Health Alert Nutrition and Chronic Obstructive Pulmonary Disease
Figure 26-11 Mechanisms of Air Trapping in COPD. Mucus plugs and narrowed airways cause air trapping and hyperinflation 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.
Emphysema
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 26-12 Types of Emphysema.A, Centriacinar emphysema. B, Panacinar emphysema. Micrographs from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Quick Check 26-4
Respiratory Tract Infections
Pneumonia
Pathophysiology
Pneumococcal pneumonia
Viral pneumonia
Health Alert Avian Influenza
Clinical Manifestations
Figure 26-13 Pathophysiologic Course of Pneumococcal Pneumonia.
Evaluation and Treatment
Tuberculosis
Health Alert Multidrug Resistant Tuberculosis in HIV Infection
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Acute bronchitis
Abscess formation and cavitation
Quick Check 26-5
Pulmonary Vascular Disease
Pulmonary embolism
Pathophysiology
Clinical Manifestations
Figure 26-14 Pathogenesis of Massive Pulmonary Embolism Caused by a Thrombus (Pulmonary Thromboembolism).
Evaluation and Treatment
Pulmonary hypertension
Pathophysiology
Clinical Manifestations
Figure 26-15 Pathogenesis of Pulmonary Hypertension and Cor Pulmonale.
Evaluation and Treatment
Cor pulmonale
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 26-6
Respiratory Tract Malignancies
Lip cancer
Pathophysiology
Clinical Manifestations
Figure 26-16 Lip Cancer. Carcinoma of lower lip with central ulceration and raised, rolled borders. From del Regato JA, Spjut HJ, Cox JD: Ackerman and del Regato’s cancer, ed 2, St Louis, 1985, Mosby.
Evaluation and Treatment
Laryngeal cancer
Pathophysiology
Clinical Manifestations
Box 26-1 Staging of Lip Cancer
Stage I
Stage II
Stage III
Stage IV
Figure 26-17 Laryngeal Cancer.A, Mirror view of carcinoma of the right false cord partially hiding the true cord. B, Lateral view. Redrawn from del Regato JA, Spjut HJ, Cox JD: Ackerman and del Regato’s cancer, ed 2, St Louis, 1985, Mosby.
Evaluation and Treatment
Lung cancer
Types of lung cancer
Non–small cell lung cancer
Table 26-3 Characteristics of Lung Cancers
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. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Small cell lung cancer
Pathophysiology
Clinical Manifestations
Evaluation AND Treatment
Health Alert Genetic and Immunologic Breakthroughs in Lung Cancer Treatment
Quick Check 26-7
Did You Understand?
Clinical Manifestations of Pulmonary Alterations
Pulmonary Disorders
Key Terms
References
Chapter 27 Alterations of Pulmonary Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Pulmonary Disorders
Disorders of the Upper Airways
Croup
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Table 27-1 Comparison of Upper Airway Infections
Figure 27-1 Upper Airway Obstruction With Croup.
Acute epiglottitis
Figure 27-2 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 Redrawn from Eavey RD: Contemp Ped 3(6):79, 1986; original illustration by Paul Singh-Roy.
Figure 27-3 The Larynx and Subglottic Trachea.A, Normal. B, Narrowing and obstruction from edema caused by croup. From Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Figure 27-4 Areas of Chest Muscle Retraction.
Clinical Manifestations
Evaluation and Treatment
Aspiration of foreign bodies
Obstructive sleep apnea
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 27-1
Disorders of the Lower Airways
Respiratory distress syndrome of the newborn
Risk Factors Respiratory Distress Syndrome of the Newborn
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 27-5 Pathogenesis of Respiratory Distress Syndrome (RDS) of the Newborn.
Bronchopulmonary dysplasia
Risk Factors Bronchopulmonary Dysplasia (BPD)
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 27-2
Respiratory infections
Bronchiolitis
Pathophysiology
Figure 27-6 Pathophysiology of Bronchopulmonary Dysplasia (BPD).
Clinical Manifestations
Evaluation and Treatment
Pneumonia
Table 27-2 Common Types of Pneumonia in Children
Evaluation and Treatment
Quick Check 27-3
Aspiration pneumonitis
Bronchiolitis obliterans
Asthma
Health Alert Asthma Genes and Tailored Therapies
Pathophysiology
Clinical Manifestations
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. Inflammatory responses are set in motion 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 present it, either in regional lymph nodes to 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 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.
Evaluation and Treatment
Quick Check 27-4
Acute respiratory distress syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Cystic fibrosis
Pathophysiology
Figure 27-8 Pathology of the Lung in End-Stage Cystic Fibrosis. Key features are widespread mucus impaction of airways and bronchiectasis (especially from upper lobe [U]), with hemorrhagic pneumonia in the lower lobe (L). Small cysts (C) are present at the apex of the lung. From Kleinerman J, Vauthy P: Pathology of the lung in cystic fibrosis, Atlanta, 1976, Cystic Fibrosis Foundation.
Figure 27-9 Pathogenesis of Cystic Fibrosis Lung Disease.CFTR, Cystic fibrosis transmembrane conductance regulator.
Clinical Manifestations
Health Alert Newborn Screening for Cystic Fibrosis
Evaluation and Treatment
Health Alert A Cure for Cystic Fibrosis?
Sudden Infant Death Syndrome
Risk Factors Sudden Infant Death Syndrome (SIDS)
Quick Check 27-5
Did You Understand?
Pulmonary Disorders in Children
Sudden Infant Death Syndrome (SIDS)
Key Terms
References
Further Reading
Unit 9 The Renal and Urologic Systems
Chapter 28 Structure and Function of the Renal and Urologic Systems
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Structures of the Renal System
Structures of the Kidney
Nephron
Figure 28-1 Organs of the Urinary System. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 28-2 Kidney Structure. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 28-3 Components of Nephron. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Blood vessels of the kidney
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 (blue type) secrete either H+ (resorb) HCO3− or HCO3− and reabsorb K+. Principal cells (magenta type) reabsorb Na+ and water and secrete K+.
Quick Check 28-1
Urinary Structures
Ureters
Bladder and urethra
Figure 28-5 The 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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.
Figure 28-7 Structure of the Urinary Bladder. Frontal view of a dissected urinary bladder (male) in a fully distended position. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Renal Blood Flow
Autoregulation of Intrarenal Blood Flow
Figure 28-8 Renal Autoregulation. Blood flow and glomerular filtration rate are stabilized in the face of changes in perfusion pressure. From Levy MN, editors: Berne & Levy Principles of physiology, ed 4, Philadelphia, 2006, Mosby.
Neural Regulation of Renal Blood Flow
Hormonal Regulation of Renal Blood Flow
Figure 28-9 Cooperative Roles of Antidiuretic Hormone (ADH) and Aldosterone in Regulating Urine and Plasma Volume. The drop in blood pressure that accompanies loss of fluid from the internal environment triggers the hypothalamus to rapidly release ADH from the posterior pituitary gland. ADH increases water reabsorption by the kidney by increasing water permeability of the distal tubules and collecting ducts. The drop in blood pressure is also detected by each nephron’s juxtaglomerular apparatus, which responds by secreting renin. Renin triggers the formation of angiotensin II, which stimulates release of aldosterone from the adrenal cortex. Aldosterone then slowly boosts water reabsorption by the kidneys by increasing reabsorption of Na+. Because angiotensin II also stimulates secretion of ADH, it serves as an additional link between the ADH and aldosterone mechanisms. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 28-2
Kidney Function
Nephron Function
Glomerular filtration
Figure 28-10 Major Functions of Nephron Segments.ADH, Antidiuretic hormone. Modified from Hockenberry MJ et al: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Figure 28-11 Glomerular Filtration Pressures.
Table 28-1 Glomerular Filtration Pressures
Filtration rate
Tubular transport
Proximal tubule
Glomerulotubular balance
Loop of Henle and distal tubule
Box 28-1 Substances Transported by Renal Tubules
Figure 28-12 Countercurrent Mechanism for Concentrating and Diluting Urine. (note: Numbers on illustration represent milliosmoles [mOsm].)
Acidification of urine
Figure 28-13 Acidification of Urine by Tubule Excretion of Ammonia (NH3).A, Acidification of urine and conservation of base by distal renal tubule excretion of H+. B, An amino acid (glutamine) moves into tubule cell and forms ammonia (NH3) which is secreted into the urine. To combine with H+ to form ammonia (NH4+) and an ammonium salt (NH4Cl). From Thibodeau, GA, Patton KT: Anatomy & physiology, ed 4, St Louis, 1999, Mosby.
Urine
Health Alert Cranberry Juice and Urinary Tract Infection
Hormones and Nephron Function
Antidiuretic hormone
Aldosterone
Atrial natriuretic peptide
Table 28-2 Action of Diuretics
Diuretics as a factor in urine flow
Renal Hormones
Urodilatin
Vitamin D
Erythropoietin
Quick Check 28-3
The Concept of Clearance
Clearance and glomerular filtration rate
Plasma creatinine concentration
Blood urea nitrogen
Table 28-3 Normal Renal Function Tests
Table 28-4 Bladder Function Tests
Pediatrics & Renal Function
Quick Check 28-4
Aging & Renal Function
Did You Understand?
Structures of the Renal System
Renal Blood Flow
Kidney Function
PEDIATRICS & Renal Function
AGING & Renal Function
Key Terms
References
Chapter 29 Alterations of Renal and Urinary Tract Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Urinary Tract Obstruction
Upper Urinary Tract Obstruction
Figure 29-1 Major Sites of Urinary Tract Obstruction.
Figure 29-2 Hydronephrosis. Hydronephrosis with renal stones in renal pelvis and calyces. From Kissane JM, editor: Anderson’s pathology, ed 9, St Louis, 1990, Mosby.
Kidney stones
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Lower Urinary Tract Obstruction
Table 29-1 Types of Incontinence
Table 29-2 Neurogenic Bladder
Neurogenic bladder
Overactive bladder syndrome
Obstructions to urine flow
Evaluation and Treatment
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 (Pues); line 5, detrusor muscle pressure (Pdet); line 6, bladder electromyelogram (EMG).
Tumors
Renal tumors
Pathogenesis
Clinical Manifestations
Figure 29-4 Renal Cell Carcinoma. Renal cell carcinomas usually are spheroidal masses composed of yellow tissue mottled with hemorrhage, necrosis, and fibrosis. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Evaluation and Treatment
Bladder tumors
Table 29-3 Staging of Renal Cell Carcinoma
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Table 29-4 Staging of Bladder Carcinoma (TNM* System)
Quick Check 29-1
Urinary Tract Infection
Causes of Urinary Tract Infection
Types of Urinary Tract Infection
Acute cystitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Health Alert Urinary Tract Infection and Antibiotic Resistance
Painful bladder syndrome/interstitial cystitis
Acute pyelonephritis
Pathophysiology
Table 29-5 Common Causes of Pyelonephritis
Clinical Manifestations
Evaluation and Treatment
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. From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Chronic pyelonephritis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 29-2
Glomerular Disorders
Glomerulonephritis
Types of glomerulonephritis
Table 29-6 Types of Glomerular Lesions
Table 29-7 Features of the Common Types of Glomerulonephritis
Acute glomerulonephritis
Rapidly progressive glomerulonephritis
Chronic glomerulonephritis
Pathophysiology
Figure 29-6 Chronic Glomerulonephritis. The kidneys appear small, are uniformly shrunken, and have a finely granular external surface From Damjanov I: Pathology for the health professions, ed 3, St Louis, 2006, Saunders.
Clinical Manifestations
Evaluation and Treatment
Table 29-8 Immunologic Pathogenesis of Glomerulonephritis
Nephrotic Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Table 29-9 Clinical Manifestations of Nephrotic Syndrome
Quick Check 29-3
Renal Failure
Types of Renal Failure
Acute renal failure
Table 29-10 Classification of Acute Renal Failure
Pathophysiology
Clinical Manifestations
Figure 29-7 Mechanisms of Oliguria in Acute Renal Failure.GFR, Glomerular filtration rate.
Evaluation and Treatment
Table 29-11 Differentiation of Acute Oliguric Renal Failure
Chronic renal failure
Stages of chronic renal failure
Pathophysiology
Clinical Manifestations
Creatinine and urea clearance
Table 29-12 Systemic Effects of Uremia
Table 29-13 Stages of Chronic Kidney Disease
Table 29-14 Factors Representing Progression of Chronic Renal Failure
Fluid and electrolyte balance
Figure 29-8 Mechanisms Related to the Progression of Chronic Renal Failure.
Musculoskeletal system
Protein, carbohydrate, and fat metabolism
Cardiovascular system
Pulmonary system
Hematologic system
Immune system
Neurologic system
Gastrointestinal system
Endocrine and reproductive systems
Integumentary system
Evaluation and Treatment
Quick Check 29-4
Did You Understand?
Urinary Tract Obstruction
Urinary Tract Infection
Glomerular Disorders
Renal Failure
Key Terms
References
Chapter 30 Alterations of Renal and Urinary Tract Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Structural Abnormalities
Hypospadias
Figure 30-1 Hypospadias. Courtesy H. Gil Rushton, MD, Children’s National Medical Center, Washington, DC; from Hockenberry MJ, Wilson D: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Figure 30-2 Hypospadias with Significant Chordee. From Shirkey HC, editor: Pediatric therapy, ed 6, St Louis, 1980, Mosby.
Epispadias and Exstrophy of the Bladder
Figure 30-3 Exstrophy of Bladder. Courtesy H. Gil Rushton, MD, Children’s National Medical Center, Washington, DC; from Hockenberry MJ, Wilson D: Wong’s nursing care of infants and children, ed 8, St Louis, 2007, Mosby.
Bladder Outlet Obstruction
Ureteropelvic Junction Obstruction
Hypoplastic/Dysplastic Kidneys
Polycystic Kidneys
Renal Agenesis
Quick Check 30-1
Glomerular Disorders
Glomerulonephritis
Poststreptococcal glomerulonephritis
Box 30-1 Primary Glomerulonephritis in Children
Cause
Immunologic Mechanism
Glomerular Histopathology
Manifestations of Glomerulonephritis
Immunoglobulin A Nephropathy
Nephrotic Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hemolytic Uremic Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Other Renal Disorders
Bladder Disorders
Urinary Tract Infections
Figure 30-4 Normal and Abnormal Configuration of the Ureterovesical Junction. Shown from left to right, progressive lateral displacement of the ureteral orifices and shortening of the intramural tunnels. (Top) Endoscopic appearance. (Bottom) Sagittal view through the intramural ureter. From Behrman R et al, editors: Nelson textbook of pediatrics, ed 16, Philadelphia, 2000, Saunders.
Health Alert Childhood Urinary Tract Infections
Vesicoureteral Reflux
Pathophysiology
Clinical Manifestations
Figure 30-5 Grades of Visicoureteral Reflux.
Evaluation and Treatment
Quick Check 30-2
Nephroblastoma
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Enuresis
Table 30-1 Staging of Nephroblastoma Tumor*
Types of Enuresis
Pathogenesis
Table 30-2 Classification of Incontinence
Quick Check 30-3
Did You Understand?
Structural Abnormalities
Glomerular Disorders
Obstructive Disorders
Nephroblastoma
Enuresis
Key Terms
References
Unit 10 The Reproductive Systems
Chapter 31 Structure and Function of the Reproductive Systems
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Development of the Reproductive Systems
Sexual Differentiation in Utero
Figure 31-1 Internal Genitalia Development. Embryonic and fetal development of the internal genitalia.
Puberty
Figure 31-2 External Genitalia Development. Embryonic and fetal development of the external genitalia.
Figure 31-3 Hormonal Stimulation of the Gonads. The hypothalamic-pituitary-gonadal axis.
Quick Check 31-1
The Female Reproductive System
External Genitalia
Figure 31-4 External Female Genitalia.
Internal Genitalia
Vagina
Figure 31-5 Internal Female Genitalia and Other Pelvic Organs. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Uterus
Figure 31-6 Uterine Positions.
Figure 31-7 Cross Section of Uterus, Fallopian Tube, and Ovary. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Quick Check 31-2
Fallopian tubes
Ovaries
Figure 31-8 Cross Section of Ovary During Reproductive Years. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Female Sex Hormones
Estrogens
Figure 31-9 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. Adapted from Berne RM, Levy MN, editors: Physiology, ed 5, St Louis, 2003, Mosby.
Progesterone
Androgens
Table 31-1 Complementary and Opposing Effects of Estrogen and Progesterone
Quick Check 31-3
Menstrual Cycle
Phases of the menstrual cycle
Figure 31-10 The Menstrual Cycle. From Lowdermilk DL, Perry SE, Bobak IM: Maternity and women’s health care, ed 8, St Louis, 2004, Mosby.
Hormonal controls
Table 31-2 Hormonal Feedback Mechanism in the Menstrual Cycle
Figure 31-11 Estrogen, Progesterone, Gonadotropin, and Inhibin Fluctuations Over the Menstrual Cycle. Inhibin rises slowly but steadily throughout the follicular phase, peaking at midcycle and again during the midluteal phase. The midcycle peak coincides with surges of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Ovarian cycle
Uterine phases
Vaginal response
Body temperature
Quick Check 31-4
The Male Reproductive System
External Genitalia
Testes
Figure 31-12 Structure of the Male Reproductive Organs. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Epididymis
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.
Scrotum
Penis
Figure 31-14 The Testes. External and sagittal views showing interior anatomy. Redrawn from Seidel HM et al: Mosby’s guide to physical examination, ed 5, St Louis, 2003, Mosby.
Figure 31-15 Cross Section of the Penis. From Thompson JM et al, editors: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Internal Genitalia
Figure 31-16 Anatomy of the Prostate Gland and Seminal Vesicles. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Health Alert Lycopene and Prostate Cancer
Spermatogenesis
Figure 31-17 Seminiferous Tubule. Section shows process of meiosis and sperm cell formation. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 31-18 Mature Sperm Cell (Spermatozoon). Anatomy of mature sperm cell.
Male Sex Hormones
Quick Check 31-5
Structure and Function of the Breast
Female Breast
Figure 31-19 The Female Breast. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Figure 31-20 Lymphatic Drainage of the Female Breast. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Male Breast
AGING & Reproductive Function
Aging and the Female Reproductive System
Figure 31-21 The Perimenopausal Transition. Mean circulating hormone levels. From Speroff L et al: Clinical gynecologic endocrinology and infertility, ed 7, Baltimore, 2005, Lippincott.
Aging and the Male Reproductive System
Quick Check 31-6
Did You Understand?
Development of the Reproductive Systems
The Female Reproductive System
The Male Reproductive System
Structure and Function of the Breast
Key Terms
References
Chapter 32 Alterations of the Reproductive Systems, Including Sexually Transmitted Infections
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Alterations of Sexual Maturation
Delayed Puberty
Box 32-1 Causes of Delayed Puberty
Hypergonadotropic Hypogonadism (Increased Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH])
Hypogonadotropic Hypogonadism (Decreased LH, Depressed FSH)
Eugonadism
Precocious Puberty
Box 32-2 The Three Forms of Precocious Puberty
Isosexual Precocious Puberty
Heterosexual Precocious Puberty
Incomplete Precocious Puberty
Quick Check 32-1
Disorders of the Female Reproductive System
Hormonal and Menstrual Alterations
Dysmenorrhea
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Primary amenorrhea
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Secondary amenorrhea
Figure 32-1 Causes of Secondary Amenorrhea.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Abnormal uterine bleeding
Pathophysiology
Table 32-1 Definitions of Abnormal Menstrual Bleeding
Table 32-2 Common Causes of Abnormal (Vaginal/Genital) Bleeding in Descending Order of Frequency
Clinical Manifestations
Evaluation and Treatment
Polycystic ovary syndrome
Pathophysiology
Figure 32-2 Polycystic Ovary. Both ovaries shown are enlarged with multiple cysts. From Symonds EM, Macpherson, MBA: Diagnosis in color: obstetrics and gynecology, London, 1997, Mosby.
Clinical Manifestations
Figure 32-3 Insulin Resistance and Hyperinsulinemia in PCOS. See text for explanation. SHBG, Sex hormone-binding globulin; LH, luteinizing hormone; FSH, follicle-stimulating hormone.
Evaluation and Treatment
Premenstrual syndrome
Pathophysiology
Clinical Manifestations
Box 32-3 Clinical Manifestations of Polycystic Ovary Syndrome (PCOS)
Presenting Signs and Symptoms (Percentage of Women Affected)
Hormonal Disturbances
Possible Late Sequelae
Other
Box 32-4 General Criteria for Premenstrual Dysphoric Disorder
Evaluation and Treatment
Quick Check 32-2
Infection and Inflammation
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. A from Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby; B from Morse SA, Ballard RC, Holmes KK, Moreland AA: Atlas of sexually transmitted diseases and AIDS, ed 3, Edinburgh, 2003, Mosby.
Pelvic inflammatory disease
Pathophysiology
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. A from Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby; B from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Clinical Manifestations
Evaluation and Treatment
Vaginitis
Cervicitis
Vulvitis
Bartholinitis
Figure 32-6 Inflammation of Bartholin Glands. From Gardner HL, Kaufman RH: Benign diseases of the vulva and vagina, St Louis, 1969, Mosby.
Pelvic Relaxation Disorders
Figure 32-7 Vaginal Prolapse.A, Anatomic positioning involving cystocele. B, Large cystocele. C, Anatomic positioning involving rectocele. D, Rectocele associated with ulceration of vaginal wall. A and C from Seidel HM et al: Mosby’s guide to physical examination, ed 4, St Louis, 1999, Mosby; B and D from Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, London, 1994, Mosby.
Table 32-3 Cystocele, Urethrocele, and Rectocele
Figure 32-8 Degrees of Uterine Prolapse.A, Normal positioning of uterus. B, First-degree prolapse: descent within the vagina. C, Second-degree prolapse: the cervix protrudes through the introitus. D, Third-degree prolapse: the vagina is completely everted.
Health Alert Dietary Interventions and Lifestyle Changes for Pelvic Prolapse
Benign Growths and Proliferative Conditions
Benign ovarian cysts
Figure 32-9 Depiction of Ovarian Cyst.
Quick Check 32-3
Endometrial polyps
Leiomyomas
Figure 32-10 Endometrial Polyp. Polyp is protruding through the cervical os. From Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, London, 1994, Mosby.
Pathophysiology
Clinical Manifestations
Figure 32-11 Leiomyomas. Depiction of uterine section showing whorl-like appearance and locations of leiomyomas, also called uterine fibroids.
Evaluation and Treatment
Adenomyosis
Endometriosis
Pathophysiology
Clinical Manifestations
Box 32-5 Theories of Endometriosis
Figure 32-12 Pelvic Sites of Endometrial Implantation. Endometrial cells may enter the pelvic cavity during retrograde menstruation.
Evaluation and Treatment
Cancer
Cervical cancer
Health Alert Vaccine Offers Promise of Cervical Cancer Prevention
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Table 32-4 Clinical Staging for Cancer of the Cervix
Vaginal cancer
Figure 32-13 Cervical Intraepithelial Neoplasia (CIN).A, Diagram of cervical endothelium showing progressive degrees of CIN. B, Normal multiparous cervix. C, CIN stage 1. Note the white appearance of part of the anterior lip of the cervix associated with neoplastic changes. A from Herbst AL et al: Comprehensive gynecology, ed 2, St Louis, 1992, Mosby; B and C from Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, London, 1994, Mosby.
Table 32-5 Recommended Treatment Based on Clinical Staging for Cancer of the Cervix
Vulvar cancer
Endometrial cancer
Figure 32-14 Endometrial Cancer. Tumor fills the endometrial cavity. Obvious myometrial invasion is shown. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis. 1996, Mosby.
Risk Factors Endometrial Cancer
Ovarian cancer
Figure 32-15 Ovarian Tumors. Bilateral multicystic ovarian tumors. From Symonds EM, Macpherson MBA: Color atlas of obstetrics and gynecology, London, 1994, Mosby.
Risk Factors Ovarian Cancer
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Figure 32-16 Metastasis of Ovarian Cancer. Pattern of spread for epithelial cancer of the ovary.
Table 32-6 FIGO* Staging of Carcinoma of the Ovary
Health Alert Recovery After Cancer Treatment
Table 32-7 Possible Effects of Chronic Disease on Sexual Functioning in Women
Sexual Dysfunction
Impaired Fertility
Quick Check 32-4
Disorders of the Male Reproductive System
Disorders of the Urethra
Urethritis
Urethral strictures
Disorders of the Penis
Phimosis and paraphimosis
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. A and C from Monahan FD et al: Phipps’ Medical-surgical nursing: health and illness perspectives, ed 8, St Louis, 2007, Mosby; B from Taylor PK: Diagnostic picture tests in sexually transmitted diseases, St Louis, 1995, Mosby; D from Morse SA, Ballard RC, Holmes KK, Moreland AA: Atlas of sexually transmitted diseases and AIDS, ed 3, Edinburgh, 2003, Mosby.
Peyronie disease
Figure 32-18 Peyronie Disease. This person complained of pain and deviation of his penis to one side on erection. From Taylor PK: Diagnostic picture tests in sexually transmitted diseases, London, 1995, Mosby.
Priapism
Balanitis
Figure 32-19 Priapism. From Lloyd-Davies RW et al: Color atlas of urology, ed 2, London, 1994, Wolfe Medical.
Figure 32-20 Balanitis. From Taylor PK: Diagnostic picture tests in sexually transmitted diseases, London, 1995, Mosby.
Penile cancer
Box 32-6 Tumor, Node, Metastasis (TNM)* Staging for Penile Cancer
Quick Check 32-5
Disorders of the Scrotum, Testis, and Epididymis
Disorders of the scrotum
Figure 32-21 Depiction of a Varicocele. Dilation of veins within the spermatic cord. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Cryptorchidism
Figure 32-22 Depiction of a Hydrocele. Accumulation of clear fluid between the visceral (inner) and parietal (outer) layers of the tunica vaginalis.
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. From Lloyd-Davies RW et al: Color atlas of urology, ed 2, London, 1994, Wolfe Medical.
Torsion of the testis
Figure 32-24 Torsion of the Testis. The testes appear dark red and partially necrotic owing to hemorrhagic infarction. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Orchitis
Figure 32-25 Depiction of Orchitis. From Seidel HM et al: Mosby’s guide to physical examination, ed 6, St Louis, 2006, Mosby.
Cancer of the testis
Pathophysiology
Figure 32-26 Testicular Tumor. From 400 Self-assessment picture tests in clinical medicine, London, 1984, Wolfe Medical.
Risk Factors Cancer of the Testis
Clinical Manifestations
Evaluation and Treatment
Impairment of sperm production and quality
Epididymitis
Figure 32-27 Epididymitis Secondary to Gonorrhea or Nongonococcal Urethritis. This infection spread to the testes, and rupture through the scrotal wall is threatened. From Taylor PK: Diagnostic picture tests in sexually transmitted disease, London, 1995, Mosby.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 32-6
Disorders of the Prostate Gland
Benign prostatic hyperplasia
Figure 32-28 Benign Prostatic Hyperplasia (BPH).A, Condition becomes a problem as prostatic tissue compresses the urethra. B, Gross appearance of BPH showing transition zone resulting from bulging nodules of varying size. B from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Prostatitis
Bacterial prostatitis
Nonbacterial prostatitis
Cancer of the prostate
Figure 32-29 Selected World Population Age-Standardized (to the World Population) Incidence Rates of Prostate Cancer. ASR, Age-standardized rate. Data from Ferlay J et al: GLOBOCAN 2000: cancer incidence, mortality, and prevalence worldwide, Lyon, 2001, International Agency for Research on Cancer.
Dietary factors
Health Alert Nutritional and Chemopreventive Agents for Risk Reduction of Prostate Cancer
Hormones
Vasectomy
Chronic inflammation
Familial factors
Pathogenesis
Box 32-7 Determining the Grade of Prostate Cancer With the Gleason Score
Figure 32-30 Testosterone and Conversion to Dihydrotestosterone (DHT).
Clinical Manifestations
Figure 32-31 Carcinoma of Prostate.A, Schematic of carcinoma of the prostate. B, Carcinoma of the prostate extending into the rectum and urinary bladder. B from Damjanov I, Linder J, editors: Pathology: a color atlas, St Louis, 2000, Mosby.
Figure 32-32 Distribution of Hematogenous Metastases in Prostate Cancer. Study of 556 individuals with metastatic prostate cancer. Adapted from Budendorf L et al: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients, Hum Pathol 31:578, 2000.
Evaluation and Treatment
Sexual Dysfunction
Pathophysiology
Clinical manifestations and treatment
Quick Check 32-7
Disorders of the Breast
Disorders of the Female Breast
Galactorrhea
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Benign breast conditions
Nonproliferative breast lesions
Box 32-8 Classification of Breast Biopsy Tissue According to Risk for Breast Cancer
No Increased Risk
Slightly Increased Risk (One and One-Half to Two Times)
Moderately Increased Risk (Three to Five Times)
Proliferative breast lesions without atypia
Table 32-8 Examples of Benign Breast Disorders
Proliferative breast lesions with atypia
Breast cancer
Figure 32-33 Age-Specific Incidence Rates of Breast Cancer Among Women. Data from Ferlay J et al: GLOBOCAN 2000: cancer incidence, mortality, and prevalence worldwide, Lyon, 2001, International Agency for Research on Cancer.
Reproductive factors
Table 32-9 Factors Associated With Increased Risk of Breast Cancer*
Hormonal factors
Figure 32-34 Local Biosynthesis of Estrogens. Three main enzyme complexes (yellow) involved in estrogen formation in breast tissue, including aromatase, sulfatase, and 17β-estradiol hydroxysteroid dehydrogenase (HSD). Thus, despite low levels of circulating estrogens in postmenopausal women with breast cancer, the tissue levels are several-fold higher than these 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 9). Adapted from Russo J, Russo I: Molecular basis of breast cancer: prevention and treatment, Germany, 2004, Springer.
Figure 32-35 Formation, Metabolism, and DNA Adducts of Estrogen. Catechol estrogens are the major metabolites of E1 and E2. If these metabolites are oxidized to the electrophilic (CE-Q), they may react with DNA. The carcinogenic 4-OHE1 (E2) are oxidized to E1 (E2-3,4-Q), which reacts with DNA to form depurinating adducts. These adducts are complexes that form when a chemical (e.g., estrogen metabolites) binds to DNA and damages DNA. These adducts generate the damaged sites—known as apurinic sites—that may lead to misrepair and cancer-initiating pathways. Activating enzymes and depurinating adducts are in purple.
Box 32-9 Estrogen Carcinogenesis
Standard Theory
Updated Theory
Environmental factors
Radiation
Diet
Environmental Chemicals
Physical Activity
Familial factors
Pathogenesis
Table 32-10 Types of Breast Carcinomas and Major Distinguishing Features
Figure 32-36 Control of Breast Cell Growth. Two levels of control of breast cell growth: (1) paracrine signaling by estrogen (E-receptor) and progesterone (P-receptor) steroids and (2) autocrine signaling by locally secreted growth factors, such as transforming growth factor (TGF-α and -β) and others, including insulin-like growth factor (IGF), epidermal growth factor (EGF), and platelet-derived growth factor (PGF). mRNA, Messenger ribonucleic acid.
Clinical Manifestations
Evaluation and Treatment
Figure 32-37 Retraction of Nipple Caused by Carcinoma. From del Regato JA, Spjut HJ, Cox JD: Ackerman and del Regato’s cancer: diagnosis, treatment, and prognosis, ed 6, St Louis, 1985, Mosby.
Quick Check 32-8
Table 32-11 Clinical Manifestations of Breast Cancer
Disorders of the Male Breast
Gynecomastia
Pathophysiology
Evaluation and Treatment
Table 32-12 Staging of Breast Cancer
Carcinoma
Sexually Transmitted Infections
Table 32-13 Estimated New Cases of STIs Each Year
Table 32-14 Currently Recognized Sexually Transmitted Infections
Health Alert Anti-Infective Treatment for Victims of Sexual Assault
Table 32-15 Major Sexually Transmitted Infections
Did You Understand?
Alterations of Sexual Maturation
Disorders of the Female Reproductive System
Disorders of the Male Reproductive System
Disorders of the Breast
Sexually Transmitted Infections
Key Terms
References
Unit 11 The Digestive System
Chapter 33 Structure and Function of the Digestive System
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
The Gastrointestinal Tract
Mouth and Esophagus
Figure 33-1 Structure and Function of the Digestive System. Digestion begins in the mouth with chewing, which breaks down food mechanically and mixes it with saliva. Swallowing propels chewed food through the esophagus to the stomach, where acids and stomach motility liquefy it further. Next the liquefied food enters the small intestine, where secretions of the intestinal walls, liver, gallbladder, and pancreas digest it into absorbable nutrients. Nutrients are absorbed through intestinal walls, and unabsorbed wastes enter the large intestine (colon), where fluids are removed. Solid wastes then enter the rectum and leave the body through the anus. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Salivation
Swallowing
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 amesentery. Note also that digestive glands may empty their products into the lumen of the gastrointestinal tract by way of ducts. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 33-3 Salivary Glands. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 33-4 Salivary Electrolyte Concentrations and Flow Rate. Changes in concentration of sodium (Na+), potassium (K+), chloride (Cl−), and bicarbonate () HCO3−increases in 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.
Figure 33-5 Stomach. A portion of the anterior wall has been cut away to reveal the muscle layers of the stomach wall. Note that the mucosa lining the stomach forms folds calledrugae. The dotted lines distinguish the fundus, body, and antrum of the stomach. Modified from Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 33-1
Stomach
Table 33-1 Selected Hormones and Neurotransmitters of the Digestive System
Gastric motility
Gastric secretion
Acid
Figure 33-6 Gastric Pits and Gastric Glands. Gastric pits are depressions in the epithelial lining of the stomach. At the bottom of each pit is one or more tubulargastric glands. Chief cells produce the enzymes of gastric juice (such as pepsinogen), parietal cells produce stomach acid, and G cells produce the hormone gastrin. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 33-7 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.
Figure 33-8 Hydrochloric Acid Secretion by Parietal Cell.
Pepsin
Mucus
Phases of gastric secretion
Quick Check 33-2
Small Intestine
Figure 33-9 The Small Intestine.
Intestinal digestion and absorption
Box 33-1 Dietary Fat
Saturated Fatty Acids (Palmitic Acid [C16H32O2])
Unsaturated Fatty Acids
Monounsaturated Fatty Acids (Oleic Acid [C18H34O2])
Polyunsaturated Fatty Acids (Linoleic Acid [C18H32O2])
Intestinal motility
Figure 33-10 Digestion and Absorption of Foodstuffs.
Figure 33-11 Sites of Absorption of Major Nutrients.
Box 33-2 Major Nutrients Absorbed in the Small Intestine
Water and Electrolytes
Carbohydrates
Proteins
Fats
Minerals
Vitamins
Quick Check 33-3
Large Intestine
Figure 33-12 Division of the Large Intestine. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 33-13 The Major Blood Vessels and Organs Supplied with Blood in the Splanchnic Circulation. Numbers in parentheses reflect approximate blood flow values (ml/minute) for each major vessel in an 80-kg normal, resting, adult human subject. Arrows indicate the direction of blood flow. Modified from Johnson LR:Gastrointestinal pathophysiology, St Louis, 2001, Mosby.
Health Alert Diet and Colon Cancer Prevention
Quick Check 33-4
Intestinal Bacteria
Splanchnic Blood Flow
Accessory Organs of Digestion
Liver
Figure 33-14 Location of the Liver, Gallbladder, and Exocrine Pancreas, Which Are the Accessory Organs of Digestion.
Figure 33-15 Gross Structure of the Liver.A, Anterior view. B, Inferior view. From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Quick Check 33-5
Secretion of bile
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.) From Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
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 perfuse the sinusoids. Peripherally located bile ducts drain the bile canaliculi that run between the hepatocytes. Modified from Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Metabolism of bilirubin
Figure 33-18 The Enterohepatic Circulation of Bile Salts.
Vascular and hematologic functions
Metabolism of nutrients
Fats
Proteins
Figure 33-19 Bilirubin Metabolism.
Carbohydrates
Metabolic detoxification
Table 33-2 Importance of Proteins in the Body
Storage of minerals and vitamins
Gallbladder
Exocrine Pancreas
Table 33-3 Selected Tests of Liver Function
Figure 33-20 Associated Structures of the Gallbladder, Pancreas, and Pancreatic Acinar Cells and Duct. Main illustration from Thibodeau GA, Patton KT:Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 33-4 Selected Laboratory Tests of Pancreatic Function
Aging & The Gastrointestinal System
Oral Cavity and Esophagus
Stomach and Intestines
Liver
Pancreas and Gallbladder
Quick Check 33-6
Did You Understand?
The Gastrointestinal Tract
Accessory Organs of Digestion
Key Terms
References
Chapter 34 Alterations of Digestive Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Disorders of the Gastrointestinal Tract
Clinical Manifestations of Gastrointestinal Dysfunction
Anorexia
Vomiting
Constipation
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Diarrhea
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Abdominal pain
Gastrointestinal bleeding
Table 34-1 Presentations of Gastrointestinal Bleeding
Quick Check 34-1
Disorders of Motility
Dysphagia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 34-1 Pathophysiology of Gastrointestinal (GI) Bleeding.
Gastroesophageal reflux
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.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hiatal hernia
Pathophysiology
Figure 34-3 Types of Hiatal Hernia.A, Sliding hiatal hernia. B, Paraesophageal hiatal hernia.
Clinical Manifestations
Evaluation and Treatment
Pyloric obstruction
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Intestinal obstruction
Pathophysiology
Table 34-2 Common Causes of Intestinal Obstruction
Table 34-3 Large and Small Bowel Obstruction
Table 34-4 Classifications of Intestinal Obstruction
Clinical Manifestations
Evaluation and Treatment
Figure 34-4 Intestinal Obstructions.A, Hernia. B, Intussusception. C, Volvulus. D, Constriction adhesions. A, B, and C from Damjanov I:Pathology for the health professions, ed 3, Philadelphia, 2006, Saunders. D from Monahan FD et al:Phipps’ medical-surgical nursing: concepts and clinical practice, ed 8, St Louis, 2007, Mosby.
Figure 34-5 Pathophysiology of Intestinal Obstruction.
Quick Check 34-2
Gastritis
Figure 34-6 Lesions Caused by Peptic Ulcer Disease.
Peptic Ulcer Disease
Risk Factors Peptic Ulcer
Duodenal ulcers
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Gastric ulcers
Pathophysiology
Clinical Manifestations
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). C courtesy David Bjorkman, MD, University of Utah School of Medicine, Department of Gastroenterology.
Table 34-5 Characteristics of Gastric and Duodenal Ulcers
Stress ulcers
Surgical treatment of ulcer
Quick Check 34-3
Postgastrectomy syndromes
Figure 34-8 Pathophysiology of Gastric Ulcer Formation.NSAIDs, nonsteroidal antiinflammatory drugs.
Malabsorption Syndromes
Pancreatic insufficiency
Lactase deficiency
Bile salt deficiency
Inflammatory Bowel Disease
Ulcerative colitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Crohn disease
Pathophysiology
Clinical Manifestations
Table 34-6 Features of Ulcerative Colitis and Crohn Disease
Evaluation and Treatment
Diverticular disease of the colon
Pathophysiology
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. Modified from Stevens A, Lowe, J:Pathology, ed 2, Edinburgh, 2000, Mosby.
Clinical Manifestations
Evaluation and Treatment
Appendicitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Irritable Bowel Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Vascular Insufficiency
Box 34-1 Rome III—Diagnostic Criteria for Irritable Bowel Syndrome
Disorders of Nutrition
Obesity
Pathophysiology
Box 34-2 Examples of Adipocytokines and Hormones From Adipose Tissue
Adipocytokines
Other Hormones
Clinical Manifestations
Figure 34-10 Leptin Theory of Obesity. The hypothalamus controls appetite, fat cell mass, and energy expenditure by responding to circulating levels of leptin and other hormones. Regulation of normal body weight is presented in the green boxes. Changes occurring with obesity are presented in the orange boxes, and changes occurring with starvation or weight loss are presented in the yellow boxes.
Evaluation And Treatment
Anorexia nervosa and bulimia nervosa
Health Alert Refeeding Syndrome
Malnutrition and starvation
Quick Check 34-4
Disorders of the Accessory Organs of Digestion
Clinical Manifestations of Liver Disorders
Portal hypertension
Pathophysiology
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. From Mohahan FD et al:Phipps’ medical-surgical nursing: concepts and clinical practice, ed 8, St Louis, 2007, Mosby.
Clinical Manifestations
Evaluation and Treatment
Ascites
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hepatic encephalopathy
Figure 34-12 Mechanisms of Ascites Caused by Cirrhosis.
Figure 34-13 Massive Ascites in an Individual With Cirrhosis. Distended abdomen, dilated upper abdominal veins, and inverted umbilicus are classic manifestations. From Prior JA, Silberstein JS, Stang JM:Physical diagnosis: the history and examination of the patient, ed 6, St Louis, 1981, Mosby.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Jaundice
Pathophysiology
Figure 34-14 Mechanisms of Jaundice.
Clinical Manifestations
Table 34-7 Three Common Types of Jaundice
Evaluation and Treatment
Hepatorenal syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 34-5
Disorders of the Liver
Viral hepatitis
Table 34-8 Characteristics of Viral Hepatitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Health Alert Hepatitis
Fulminant hepatitis
Cirrhosis
Table 34-9 Cirrhosis of the Liver
Alcoholic liver disease
Pathophysiology
Figure 34-15 Clinical Manifestations of Cirrhosis.ADH, Antidiuretic hormone;AST, aspartate transaminase;ALT, alanine transaminase.
Clinical Manifestations
Evaluation and Treatment
Biliary cirrhosis
Quick Check 34-6
Disorders of the Gallbladder
Cholelithiasis
Pathophysiology
Figure 34-16 Resected Gallbladder Containing Mixed Gallstones. From Kissane JM, editor:Anderson’s pathology, ed 9, St Louis, 1990, Mosby.
Clinical Manifestations
Evaluation and Treatment
Cholecystitis
Disorders of the Pancreas
Acute pancreatitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Chronic pancreatitis
Cancer of the Digestive System
Cancer of the Gastrointestinal Tract
Cancer of the esophagus
Pathogenesis
Risk Factors Esophageal Cancer
Clinical Manifestations
Evaluation and Treatment
Table 34-10 Cancer of the Gut, Liver, and Pancreas
Cancer of the stomach
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Figure 34-17 Typical Sites of Stomach Cancer. From del Regato JA, Spjut HJ, Cox JD:Cancer: diagnosis, treatment, and prognosis, ed 2, St Louis, 1985, Mosby.
Quick Check 34-7
Cancer of the colon and rectum
Pathogenesis
Risk Factors Cancer of the Colon and Rectum
Figure 34-18 Neoplastic Polyps.A, Tubular adenomata(A) are rounded lesions 0.5 to 2cm 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 0.6cm thick that occupy a broad area of mucosa generally 1 to 5cm in diameter. From Stevens A, Lowe J:Pathology, ed 2, Edinburgh, 2000, Mosby.
Figure 34-19 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).
Clinical Manifestations
Table 34-11 Conditions Commonly Confused With Colorectal Cancer
Evaluation and Treatment
Figure 34-20 Development of Cancer of the Colon From Adenomatous Polyps. The tumor becomes invasive if it penetrates the muscularis mucosae and enters the submucosal layer. From del Regato JA, Spjut HJ, Cox JD:Cancer: diagnosis, treatment, and prognosis, ed 2, St Louis, 1985, Mosby.
Box 34-3 Screening for Colorectal Cancer
Cancer of the Accessory Organs of Digestion
Cancer of the liver
Risk Factors Primary Liver Cancer
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Cancer of the gallbladder
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Cancer of the pancreas
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Quick Check 34-8
Did You Understand?
Disorders of the Gastrointestinal Tract
Disorders of the Accessory Organs of Digestion
Cancer of the Digestive System
Key Terms
References
Chapter 35 Alterations of Digestive Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Disorders of the Gastrointestinal Tract
Congenital Impairment of Motility
Cleft lip and cleft palate
Pathophysiology
Cleft lip
Figure 35-1 Variations in Clefts of the Lip and Palate.A, Notch in vermilion border. B, Unilateral cleft lip and palate. C, Bilateral cleft lip and cleft palate. D, Cleft palate.
Cleft palate
Clinical Manifestations
Evaluation and Treatment
Esophageal malformations
Pathophysiology
Clinical Manifestations
Figure 35-2 Five Types of Esophageal Atresia and Tracheoesophageal Fistulas.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.
Evaluation and Treatment
Pyloric stenosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Intestinal malrotation
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 35-1
Meconium ileus
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Distal intestinal obstruction syndrome
Obstructions of the duodenum, jejunum, and ileum
Meckel diverticulum
Congenital aganglionic megacolon
Pathophysiology
Clinical Manifestations
Figure 35-3 Congenital Aganglionic Megacolon (Hirschsprung Disease).
Evaluation and Treatment
Anorectal malformations
Acquired Impairment of Motility
Intussusception
Pathophysiology
Clinical Manifestations
Figure 35-4 Anorectal Stenosis and Imperforate Anus.
Figure 35-5 Ileocolic Intussusception.
Evaluation and Treatment
Gastroesophageal reflux
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 35-2
Impairment of Digestion, Absorption, and Nutrition
Cystic fibrosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Gluten-sensitive enteropathy
Table 35-1 Pathophysiology, Clinical Manifestations, and Complications of Cystic Fibrosis
Pathophysiology
Figure 35-6 Pathophysiology of Gluten-Sensitive Enteropathy.
Clinical Manifestations
Evaluation and Treatment
Protein energy malnutrition
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Failure to thrive
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Necrotizing enterocolitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Quick Check 35-3
Diarrhea
Acute diarrhea
Health Alert Rotavirus Vaccine
Chronic diarrhea
Chronic nonspecific diarrhea
Primary lactose intolerance
Disorders of the Liver
Disorders of Biliary Metabolism and Transport
Neonatal jaundice
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Biliary atresia
Inflammatory Disorders
Hepatitis
Hepatitis A (HAV)
Health Alert Hepatitis Vaccines for Children
Hepatitis B Vaccine Guidelines
Hepatitis B (HBV)
Hepatitis C (HCV)
Chronic hepatitis
Cirrhosis
Portal Hypertension
Types of portal hypertension
Extrahepatic portal hypertension
Intrahepatic portal hypertension
Course of the disease
Clinical Manifestations
Evaluation and Treatment
Metabolic Disorders
Quick Check 35-4
Table 35-2 Galactosemia, Fructosemia, and Wilson Disease
Did You Understand?
Disorders of the Gastrointestinal Tract
Disorders of the Liver
Key Terms
References
Unit 12 The Musculoskeletal and Integumentary Systems
Chapter 36 Structure and Function of the Musculoskeletal System
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Structure and Function of Bones
Elements of Bone Tissue
Table 36-1 Structural Elements of Bone
Bone cells
Osteoblast
Osteoclast
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, Scanning electron micrograph showing an osteocyte within a lacuna. The cell is surrounded by collagen fibers and mineralized bone. C, Osteoclasts actively resorb mineralized tissue. The scalloped surface in which the multinucleated osteoclasts rest is termed Howship lacuna. A and C from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby; B from Erlandsen S, Magney J: Color atlas of histology, St Louis, 1992, Mosby.
Table 36-2 Effects of Selected Cytokines (Growth Factors) on Skeletal Tissues
Osteocyte
Bone matrix
Collagen fibers
Proteoglycans
Glycoproteins
Bone minerals
Types of Bone Tissue
Table 36-3 Sequence of Calcium and Phosphate Compound Formation and Crystallization
Figure 36-2 Cross Section of Bone. Longitudinal section of long bone (tibia) showing spongy (cancellous) and compact bone. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Characteristics of Bone
Maintenance of Bone Integrity
Remodeling
Figure 36-3 Structure of Compact and Cancellous Bone.A, Longitudinal section of a long bone showing both cancellous and compact bone. B, A 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 36-4 Anterior View of Skeleton. Axial skeleton in blue; appendicular skeleton in tan. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Repair
Quick Check 36-1
Structure and Function of Joints
Figure 36-5 Bone Remodeling. In the remodeling sequence, bone sections are removed by bone-resorbing cells (osteoclasts) and replaced with a new section laid down by bone-forming cells (osteoblasts). The cells work in response to signals generated in that environment. Only the multinucleated 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 5 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. D from Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Fibrous Joints
Cartilaginous Joints
Joint (articular) capsule
Figure 36-6 Main Tissues of a Joint. Micrographs from Gartner LP, Hiatt JL: Color textbook of histology, ed 3, Philadelphia, 2007, Saunders.
Synovial membrane
Joint (synovial) cavity
Synovial fluid
Articular cartilage
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.
Synovial Joints
Structure of synovial joints
Movement of synovial joints
Quick Check 36-2
Structure and Function of Skeletal Muscles
Whole Muscle
Figure 36-8 Knee Joint (Synovial Joint).A, Frontal view. B, Lateral view.
Figure 36-9 Movements of Synovial (Diarthrodial) Joints.
Motor unit
Figure 36-10 Body Movements Made Possible by Synovial (Diarthrodial) Joints.
Sensory receptors
Muscle fibers
Figure 36-11 Skeletal Muscles of Body.A, Anterior view. B, Posterior view.
Figure 36-12 Cross Section of Skeletal Muscle Showing Muscle Fibers and Their Coverings. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Figure 36-13 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.
Figure 36-14 Myofibrils. Myofibrils of a skeletal muscle fiber (cells) and overall organization of skeletal muscle. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Table 36-4 Characteristics of Muscle Fibers
Myofibrils
Muscle proteins
Nonprotein constituents of muscle
Components of Muscle Function
Figure 36-15 Muscle Fibers.A, Lines and bands in striated muscle. B, Relationships of bands, actin, myosin, and lines in relaxed and contracted muscle fibers. A modified from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Muscle contraction at the molecular level
Table 36-5 Contractile Proteins of Skeletal Muscle Fibrils
Muscle metabolism
Table 36-6 Energy Sources for Muscular Activity
Health Alert Soft Tissue Repair
Muscle mechanics
Types of muscle contraction
Movement of muscle groups
AGING & The Musculoskeletal System
Aging of Bones
Aging of Joints
Figure 36-16 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. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 6, St Louis, 2007, Mosby.
Aging of Muscles
Quick Check 36-3
Did You Understand?
Structure and Function of Bones
Structure and Function of Joints
Structure and Function of Skeletal Muscles
AGING & the Musculoskeletal System
Key Terms
References
Chapter 37 Alterations of Musculoskeletal Function
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Musculoskeletal Injuries
Skeletal Trauma
Fractures
Classification of fractures
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 tolerances. 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. Redrawn from Mourad L: Musculoskeletal system. In Thompson JM et al, editors: Mosby’s clinical nursing, ed 7, St Louis, 2002, Mosby.
Table 37-1 Types of Fractures
Pathophysiology
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 up as osteoclasts destroy dead bone. E, Remodeling is accomplished as excess callus is reabsorbed and trabecular bone is laid down. From Monahan FD et al: Phipps’ Medical-surgical nursing: health and illness perspectives, ed 8, St Louis, 2007, Mosby.
Clinical Manifestations
Figure 37-3 Exuberant Callus Formation Following Fracture. From Rosai J: Ackerman’s surgical pathology, ed 8, St Louis, 1996, Mosby.
Evaluation and Treatment
Dislocation and subluxation
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Support Structures
Sprains and strains of tendons and ligaments
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Tendonitis, epicondylitis, and bursitis
Figure 37-4 Tendionitis and Epicondylitis.A, Medial or lateral epicondyles of humerus, site of epicondylitis. B, Achilles tendon, site of commonly occurring tendonitis.
Pathophysiology
Clinical Manifestations
Figure 37-5 Olecranon Bursitis. A case of olecranon bursitis in a patient with rheumatoid arthritis. A rheumatoid nodule is also shown. From Klippel JH, Deippe PA, editors: Rheumatology, ed 2, London, 1998, Mosby.
Evaluation and Treatment
Muscle strains
Table 37-2 Muscle Strain
Myoglobinuria
Figure 37-6 Pathogenesis of Compartment Syndrome and Crush Syndrome Caused by Prolonged Muscle Compression.ECF, Extracellular fluid.
Pathophysiology
Clinical Manifestations
Figure 37-7 The Muscle Compartments of the Lower Leg. From Mohahan FD et al: Phipps’ Medical-surgical nursing: health and illness perspectives, ed 8, St Louis, 2007, Mosby.
Evaluation and Treatment
Quick Check 37-1
Disorders of Bones
Metabolic Bone Diseases
Osteoporosis
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. From, Kumar V et al: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Figure 37-9 Osteoporosis in Cortical and Trabecular Bone.
Health Alert Osteoporosis in Men
Health Alert Osteoporosis Facts and Figures at a Glance
Table 37-3 T-score and World Health Organization Diagnosis of Bone Density
Risk Factors Osteoporosis
Genetic
Anthropometric
Hormonal and Metabolic
Dietary
Lifestyle
Concurrent
Illness and Trauma
Liver Disease
Drugs
Figure 37-10 OPG/RANKL/RANK System. RANKL, receptor activator of nuclear factor κβ ligand, a cytokine and part of the tumor necrosis factor (TNF) family, expression and OPG, a glycoprotein receptor antagonist, are 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) that increases resorption and bone loss. OPG, secreted by stromal cells and osteoblasts, acts as a “decoy” receptor and blocks RANKL binding to and activating RANK. BMP, Bone morphogenic protein; IL, interleukin; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor alpha; PTH, parathyroid hormone. Adapted from Hofbauer LC, Schoppet M: JAMA 292(4):490–495, 2004.
Pathophysiology
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.
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.
Health Alert Vitamin D and Fracture Risk
Clinical Manifestations
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. From Kamal A, Brocklehurst JC: Color atlas of geriatric medicine, ed 2, St Louis, 1992, Mosby.
Evaluation and Treatment
Box 37-1 Biochemical Markers of Bone Turnover
Health Alert Newer Treatments for Osteoporosis: Strontium and Teriparatide
Osteomalacia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Paget disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Infectious Bone Disease: Osteomyelitis
Figure 37-14 Osteomyelitis Showing Sequestration and Involucrum.
Pathophysiology
Clinical Manifestations
Figure 37-15 Resected Femur in a Patient With Draining Osteomyelitis. The drainage tract in the subperiosteal shell of viable new bone (involucrum) reveals the inner native necrotic cortex (sequestrum). From Kumar V et al: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Evaluation and Treatment
Quick Check 37-2
Disorders of Joints
Osteoarthritis
Types of osteoarthritis
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. C from Kumar V, et al: Robbins and Cotran pathologic basis of disease, ed 7, Philadelphia, 2005, Saunders.
Pathophysiology
Clinical Manifestations
Risk Factors Osteoarthritis
Evaluation and Treatment
Figure 37-17 Typical Varus Deformity of Knee Osteoarthritis. From Doherty M: Color atlas and text of osteoarthritis, London, 1994, Wolfe.
Health Alert Body Weight and Osteoarthritis
Classic Inflammatory Joint Disease
Rheumatoid arthritis
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. Redrawn from Mourad LA: Orthopedic disorders, St Louis, 1991, Mosby.
Pathophysiology
Figure 37-19 Synovitis. Inflamed synovium showing typical arrangements of macrophages (red) and fibroblastic cells.
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 that eventually destroys 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 prostaglandins (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.
Clinical Manifestations
Evaluation and Treatment
Health Alert New Rheumatoid Arthritis Treatments
Ankylosing spondylitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 37-21 Ankylosing Spondylitis. Characteristic posture and primary pathologic sites of inflammation and resulting damage. Redrawn from Mourad LA: Orthopedic disorders, St Louis, 1991, Mosby.
Gout
Table 37-4 Mean Urate Concentrations by Age and Gender
Pathophysiology
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. Redrawn from Klippel JH, Dieppe PA, editors: Rheumatology, ed 2, St Louis, 1998, Mosby.
Clinical Manifestations
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. IgG, Immunoglobulin G; Apo E, apolipoprotein E; PGE2, prostaglandin E2; LTB4, leukotriene B4; IL, interleukin. B, Sequence of events in the production of inflammatory response to urate crystals. C, Gouty tophus on right foot. C from Dieppe PA et al: Arthritis and rheumatism in practice, London, 1991, Gower.
Figure 37-24 Theoretic Pathophysiologic Model of Fibromyalgia.
Treatment
Quick Check 37-3
Disorders of Skeletal Muscle
Secondary Muscular Dysfunction
Contractures
Stress-induced muscle tension
Disuse atrophy
Fibromyalgia
Table 37-5 Comparison of Fibromyalgia and Myofascial Pain Syndromes
Pathophysiology
Clinical Manifestations
Figure 37-25 Location of Specific Tender Points for Diagnostic Classification of Fibromyalgia. Redrawn from Freundlich B, Leventhal L: The fibromyalgia syndrome. In Schumacher HR Jr, Klippel JH, Koopman WJ, editors: Primer on the rheumatic diseases, ed 11, Atlanta, 1997, Arthritis Foundation.
Evaluation and Treatment
Muscle Membrane Abnormalities
Myotonia
Box 37-2 Educating and Providing Reassurance for Individuals With Fibromyalgia
Periodic paralysis
Metabolic Muscle Diseases
Endocrine disorders
Diseases of energy metabolism
McArdle disease
Acid maltase deficiency
Myoadenylate deaminase deficiency
Lipid deficiencies
Inflammatory Muscle Diseases: Myositis
Viral, bacterial, and parasitic myositis
Polymyositis, dermatomyositis, and inclusion-body myositis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 37-26 Dermatomyositis. Heliotrope (violaceous) discoloration around the eyes and periorbital edema. From Habif TP: Clinical dermatology, ed 3, St Louis, 1996, Mosby.
Toxic Myopathies
Quick Check 37-4
Musculoskeletal Tumors
Bone Tumors
Figure 37-27 Derivation of Bone Tumors.
Epidemiology
Patterns of bone destruction
Evaluation
Table 37-6 Patterns of Bone Destruction Caused by Bone Tumors
Types
Osteogenic tumors: osteosarcoma
Table 37-7 Surgical Staging System for Bone Tumors
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. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Chondrogenic tumors: chondrosarcoma
Collagenic tumors: fibrosarcoma
Myelogenic tumors
Giant cell tumor
Muscle Tumors
Rhabdomyoma
Rhabdomyosarcoma
Other tumors
Quick Check 37-5
Did You Understand?
Musculoskeletal Injuries
Disorders of Bones
Disorders of Joints
Disorders of Skeletal Muscle
Musculoskeletal Tumors
Key Terms
References
Chapter 38 Alterations of Musculoskeletal Function in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Congenital Defects
Clubfoot
Developmental Dysplasia of the Hip
Table 38-1 Terms Used to Describe Foot Abnormalities
Figure 38-1 Infant with Bilateral Congenital Talipes Equinovarus. From Brashear HR, Raney RB: Shand’s handbook of orthopedic surgery, ed 9, St Louis, 1978, Mosby.
Figure 38-2 Idiopathic Clubfoot. Idiopathic clubfoot displaying forefoot adduction (toward midline of body), supination (upturning), and hindfoot equinus (pointed downward). Note skin creases along arch and back of heel.
Osteogenesis Imperfecta
Figure 38-3 Surgically Treated Bilateral Hip Dislocation. Postoperative x-ray of 5-year-old child after femoral, acetabular, and joint surgery bilaterally. The plates will be removed once the child heals. The extent of surgery necessitated staged (i.e., one side at a time) intervention.
Bone Infection
Osteomyelitis
Figure 38-4 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.) From Crenshaw AH, editor: Campbell’s operative orthopaedics, ed 8, vol 3, St Louis, 1992, Mosby.
Septic Arthritis
Box 38-1 Causative Microorganisms of Osteomyelitis According to Age
Newborns
Infants
Older Children
Adolescents and Adults
Juvenile Rheumatoid Arthritis
Figure 38-5 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.
Figure 38-6 The Routes of Infection to the Joint.1, The 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.
Table 38-2 Characteristics of Juvenile Arthritis Related to Mode of Onset
Quick Check 38-1
Osteochondroses
Legg-Calvé-Perthes Disease
Pathophysiology
Figure 38-7 Stages of Legg-Calvé-Perthes Disease, a Form of Osteochondrosis.
Clinical Manifestations
Evaluation and Treatment
Osgood-Schlatter Disease
Figure 38-8 Pelvis of a 7-Year-Old Boy With Legg-Calvé-Perthes Disease. The femoral head is flat and extruded from the edge of the joint. This hip is at risk for early arthritis if left to revascularize and heal in this position.
Figure 38-9 Surgical Replacement of Femoral Head of a 7-Year-Old Boy With Legg-Calvé-Perthes Disease. As the Perthes heals, the ball has taken on a round shape that matches the socket well.
Scoliosis
Figure 38-10 Rotation and Curvature of Scoliosis. Scoliosis screening involves viewing the individual from behind, which discloses scapular asymmetry caused by not only curvature but also true rotation of the spine.
Muscular Dystrophy
Figure 38-11 Duchenne Muscular Dystrophy.A, Patient with late-stage Duchenne muscular dystrophy showing severe muscle loss. B, Transverse section of gastrocnemius muscle from a normal boy. C, Transverse section of gastrocnemius muscle from a boy with Duchenne muscular dystrophy. Normal muscle fiber is replaced with fat and connective tissue. From Jorde LB et al: Medical genetics, ed 3, updated, St Louis, 2006, Mosby.
Duchenne Muscular Dystrophy
Pathophysiology
Clinical Manifestations
Table 38-3 Major Muscular Dystrophy Syndromes
Evaluation and Treatment
Quick Check 38-2
Musculoskeletal Tumors
Benign Bone Tumors
Osteochondroma
Nonossifying fibroma
Malignant Bone Tumors
Osteosarcoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Ewing sarcoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Figure 38-12 Ewing Sarcoma.A, Most common anatomic sites. B, Closeup view of Ewing sarcoma of the distal end of the tibia. Tumor extends into the soft tissue. From Damjanov I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.
Figure 38-13 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.
Quick Check 38-3
Nonaccidental Trauma
Fractures in Nonaccidental Trauma
Evaluation
Treatment
Did You Understand?
Congenital Defects
Bone Infection
Juvenile Rheumatoid Arthritis
Osteochondroses
Scoliosis
Muscular Dystrophy
Musculoskeletal Tumors
Nonaccidental Trauma
Key Terms
References
Chapter 39 Structure, Function, and Disorders of the Integument
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Structure and Function of the Skin
Layers of the Skin
Health Alert Tissue Adhesives for Closure of Skin Lacerations
Figure 39-1 Structure of the Skin. From Thibodeau GA, Patton KT: Anatomy & physiology, ed 5, St Louis, 2003, Mosby.
Dermal appendages
Table 39-1 Layers of the Skin
Figure 39-2 Structures of the Nail. Redrawn from Thompson JM et al: Mosby’s clinical nursing, ed 5, St Louis, 2002, Mosby.
Blood supply and innervation
Quick Check 39-1
Clinical Manifestations of Skin Dysfunction
Lesions
Pressure ulcers
Risk Factors Pressure Ulcer
Figure 39-3 Progression of Decubitus Ulcer. Sustained pressure over a bony prominence compresses the tissue and reduces blood flow resulting in progressive ischemia and necrosis of tissue.
Table 39-2 Primary and Secondary Skin Lesions
Table 39-3 Clinical Manifestations of Select Skin Lesions
Keloids
Pruritus
Figure 39-4 Keloid Formation. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Quick Check 39-2
Aging & Changes in Skin Integrity
Disorders of the Skin
Inflammatory Disorders
Allergic contact dermatitis
Irritant contact dermatitis
Figure 39-5 Poison Ivy.A, Poison ivy on knee. B, Poison ivy dermatitis. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Atopic dermatitis
Stasis dermatitis
Seborrheic dermatitis
Figure 39-6 Stasis Ulcer. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Papulosquamous Disorders
Psoriasis
Figure 39-7 Seborrheic Dermatitis. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 39-8 Psoriasis. Typical oval plaque with well-defined borders and silvery scale. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 39-9 Guttate Psoriasis Following Streptococcal Infection. Numerous uniformly small lesions may abruptly occur following streptococcal pharyngitis. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Health Alert Biologic Treatment for Psoriasis
Pityriasis rosea
Figure 39-10 Pityriasis Rosea Herald Patch. A collarette pattern has formed around the margins. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Lichen planus
Figure 39-11 Hypertrophic Lichen Planus on Arms. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Quick Check 39-3
Acne vulgaris
Acne rosacea
Figure 39-12 Granulomatous Rosacea. Pustules and erythema occur on the forehead, cheeks, and nose. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Lupus erythematosus
Discoid lupus erythematosus
Figure 39-13 Subacute Cutaneous Lupus (Discoid Lupus Erythematosus). Courtesy Department of Dermatology, School of Medicine, University of Utah.
Vesiculobullous Disorders
Pemphigus
Figure 39-14 Bullous Pemphigoid. Generalized eruption with blisters arising from an edematous, erythematous annular base. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Erythema multiforme
Quick Check 39-4
Infections
Bacterial infections
Folliculitis
Furuncles and carbuncles
Figure 39-15 Furuncle of the Forearm. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Cellulitis
Erysipelas
Impetigo
Viral infections
Herpes simplex virus
Figure 39-16 Herpes Simplex Labialis. Typical presentation with tense vesicles appearing on the lips and extending onto the skin. From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 4, St Louis, 2004, Mosby.
Herpes zoster and varicella
Warts
Figure 39-17 Herpes Zoster. Diffuse involvement of a dermatome. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 39-18 Verruca Vulgaris. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Fungal infections
Tinea infections
Figure 39-19 Tinea Pedis. Inflammation has extended from the web area onto the dorsum of the foot. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Candidiasis
Table 39-4 Common Sites of Tinea Infections
Vascular Disorders
Cutaneous vasculitis
Table 39-5 Sites of Candidiasis Infection
Urticaria
Scleroderma
Figure 39-20 Scleroderma (Acrosclerosis). Note inflammation and shiny skin. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Quick Check 39-5
Insect Bites
Mosquitoes, flies, and bees
Benign Tumors
Seborrheic keratosis
Keratoacanthoma
Figure 39-21 Seborrheic Keratosis. Typical lesion that is broad, flat, and comparatively smooth surfaced. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Actinic keratosis
Nevi (moles)
Quick Check 39-6
Cancer
Box 39-1 Important Trends for Skin Cancer
Incidence
Mortality
Risk Factors
Warning Signals
Prevention and Early Detection
Treatment
Survival
Basal cell carcinoma
Squamous cell carcinoma
Figure 39-22 Basal Cell Carcinoma. Center has ulcerated. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Malignant melanoma
Figure 39-23 Squamous Cell Carcinoma. The sun-exposed ear is a common site for squamous cell carcinoma. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Table 39-6 Classification of Nevi
Figure 39-24 Lentigo Malignant Melanoma. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Kaposi sarcoma
Figure 39-25 Kaposi Sarcoma. The purple lesion commonly seen on the skin. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Quick Check 39-7
Burns
Table 39-7 Depth of Burn Injury
Burn wound depth
Figure 39-26 Superficial Partial-Thickness Injury. Scald injury following débridement of overlying blister and nonadherent epithelium. Courtesy Intermountain Burn Center, University of Utah.
Figure 39-27 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. Courtesy Intermountain Burn Center, University of Utah.
Figure 39-28 Deep Partial-Thickness Wound. Note pale appearance and minimal exudate. Courtesy Intermountain Burn Center, University of Utah.
Figure 39-29 Full-Thickness Thermal Injury. The wound is dry and insensate. Courtesy Intermountain Burn Center, University of Utah.
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).
Box 39-2 Burn Unit Referral Criteria
Pathophysiology and Clinical Manifestations
Figure 39-31 Immediate Cellular and Immunologic Alterations of Burn Shock.
Evaporative water loss
Box 39-3 Maintenance Fluid Replacements After Major Burn Injury*
Cardiovascular response to burn
Cellular response to burn injury
Metabolic response to burn injury
Immunologic response to burn injury
Evaluation and Treatment
Figure 39-32 Hypertrophic Scarring. Deep partial-thickness thermal injury can result in extensive hypertrophic scarring. Courtesy Intermountain Burn Center, University of Utah.
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. Courtesy Intermountain Burn Center, University of Utah.
Frostbite
Disorders of the Hair
Alopecia
Male-pattern alopecia (androgenic alopecia)
Female-pattern alopecia
Alopecia areata
Hirsutism
Disorders of the Nail
Paronychia
Onychomycosis
Quick Check 39-8
Did You Understand?
Structure and Function of the Skin
Disorders of the Skin
Disorders of the Hair
Disorders of the Nail
Key Terms
References
Chapter 40 Alterations of the Integument in Children
Electronic Resources
Companion CD
Website http://evolve.elsevier.com/Huether/
Dermatitis
Atopic Dermatitis
Figure 40-1 Atopic Dermatitis. Characteristic lesions with crusting from irritation and scratching over knees and around ankles. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Diaper Dermatitis
Acne Vulgaris
Figure 40-2 Diaper Dermatitis.A, Diaper dermatitis with erosions. B, Diaper dermatitis with Candida albicans secondary infection. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 40-3 Cystic Acne. Multiple pustules (erythematous papules and pustules) are present, and several have become confluent. Note areas of scarring. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Quick Check 40-1
Infections of the Skin
Bacterial Infections
Impetigo contagiosum
Box 40-1 Impetigo
Vesicular Impetigo
Bullous Impetigo
Figure 40-4 Impetigo and Herpes Simplex Virus (HSV) of Upper Lip. Note weeping and crusting lesions. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Staphylococcal scalded-skin syndrome
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. From Levine G, Norden C: N Engl J Med 287:1339, 1972.
Fungal Infections
Tinea capitis
Tinea corporis
Figure 40-6 Tinea Capitis. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Thrush
Viral Infections
Molluscum contagiosum
Figure 40-7 Molluscum Contagiosum. Waxy pink globules with umbilicated centers. From Habif TP: Clinical dermatology: a color guide to diagnosis and therapy, ed 4, St Louis, 2004, Mosby.
Rubella (German or 3-day measles)
Health Alert MMR and Varicella Vaccines
Figure 40-8 Rubella (3-Day Measles). Typical distribution of full-blown maculopapular rash with tendency to coalesce.
Table 40-1 Differential Presentation of Viral Diseases Producing Rashes
Rubeola (red measles)
Roseola (exanthema subitum)
Chickenpox, herpes zoster, and smallpox
Chickenpox
Figure 40-9 Chickenpox. Pattern of generalized, polymorphous eruption.
Herpes zoster
Smallpox
Quick Check 40-2
Insect Bites and Parasites
Scabies
Figure 40-10 Scabies.A, Scabies mite, as seen clinically when removed from its burrow. B, Characteristic scabies bites. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Pediculosis (Lice Infestation)
Fleas
Ticks
Figure 40-11 Flea Bites. Fleabite producing an urticarial wheal with central puncture.
Bedbugs
Hemangiomas and Vascular Malformations
Hemangiomas
Vascular Malformations
Figure 40-12 Capillary Hemangioma. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 40-13 Cavernous Hemangioma. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Figure 40-14 Port-Wine Hemangioma. Port-wine hemangioma in a child. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Other Skin Disorders
Miliaria
Figure 40-15 Miliaria Rubra. Note discrete erythematous papules or papulovesicles. Courtesy Department of Dermatology, School of Medicine, University of Utah.
Erythema Toxicum Neonatorum
Quick Check 40-3
Did You Understand?
Dermatitis
Acne Vulgaris
Infections of the Skin
Insect Bites and Parasites
Vascular Disorders
Other Skin Disorders
Key Terms
References
Back Matter
Appendix: Most Common Laboratory Values
Glossary

People Also Search:

understanding pathophysiology huether

understanding pathophysiology 4th edition huether

understanding pathophysiology

understanding pathophysiology 4th edition

understanding pathophysiology 4th edition testbank download pdf

understanding pathophysiology 4th edition download scribd

Sign up for Newsletter

Understanding Pathophysiology 4th Edition Huether Test Bank

This is completed downloadable of Understanding Pathophysiology 4th Edition Huether Test Bank

Product Details:

Table of Content:

People Also Search:

Instant download after Payment is complete

Sign up for Newsletter

Understanding Pathophysiology 4th Edition Huether Test Bank

This is completed downloadable of Understanding Pathophysiology 4th Edition Huether Test Bank

Product Details:

Table of Content:

People Also Search:

Instant download after Payment is complete

Related products

Login