Name: Understanding Pathophysiology 5th Edition Huether Test Bank
SKU: 22399
Price: 26.99 USD
Availability: InStock

This is completed downloadable of Understanding Pathophysiology 5th Edition Huether Test Bank

Product Details:

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

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

Table of Content:

PART I Basic Concepts of Pathophysiology
UNIT 1 The Cell
Interactive Review – Unit 1
Chapter 1 Cellular Biology
Prokaryotes and Eukaryotes
Cellular Functions
FIGURE 1-1 Typical Components of a Eukaryotic Cell and Structure of the Cytoplasm. A, Components of a eukaryotic cell. B, The drawing is approximately to scale and emphasizes the crowding in the cytoplasm. Only the macromolecules are shown: RNAs are shown in blue, ribosomes in green, and proteins in pink. Enzymes and other macromolecules diffuse relatively slowly in the cytoplasm, in part because they interact with many other macromolecules; small molecules, by contrast, diffuse nearly as rapidly as they do in water.
Structure and Function of Cellular Components
Nucleus
Cytoplasmic Organelles
QUICK CHECK 1-1
Plasma Membranes
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 (illustrated here much larger than actual size to show the tightly packed DNA strands). Swelling at one or more points of the chromosome, shown in A, occurs at a nucleolus where genes are being copied into RNA. The nuclear envelope is studded with pores. B, The pores are visible as dimples in this freeze-etch of a nuclear envelope. C, Histone-folding DNA in chromosomes.
FIGURE 1-3 Structure of a Phospholipid Molecule. A, Each phospholipid molecule consists of a phosphate functional group and two fatty acid chains attached to a glycerol molecule. B, The fatty acid chains and glycerol form nonpolar, hydrophobic “tails,” and the phosphate functional group forms the polar, hydrophilic “head” of the phospholipid molecule. When placed in water, the hydrophobic tails of the molecule face inward, away from the water, and the hydrophilic head faces outward, toward the water.
TABLE 1-1 PRINCIPAL CYTOPLASMIC ORGANELLES
TABLE 1-2 PLASMA MEMBRANE FUNCTIONS
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.
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.
Cellular Receptors
FIGURE 1-6 Cellular Receptors. (A) 1, Plasma membrane receptor for a ligand (here, a hormone molecule) on the surface of an integral protein. A neurotransmitter can exert its effect on a postsynaptic cell by means of two fundamentally different types of receptor proteins: 2, channel-linked receptors, and 3, non–channel-linked receptors. Channel-linked receptors are also known as ligand-gated channels. (B) Example of ligand-receptor interaction. Insulin-like growth factor 1 (IGF-1) is a ligand and binds to the insulin-like growth factor 1 receptor (IGF-1R). With binding at the cell membrane the intracellular signaling pathway is activated, causing translation of new proteins to act as intracellular communicators. This pathway is important for cancer growth. Researchers are developing pharmacologic strategies to reduce signaling at and downstream of the insulin-like growth factor 1 receptor (IGF-1R), hoping this will lead to compounds useful in cancer treatment.
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 proteoglycan molecules form a gel-like ground substance in which the fibrous proteins are embedded. The gel permits rapid diffusion of nutrients, metabolites, and hormones between the blood and the tissue cells. Matrix proteins modulate cell-matrix interactions including normal tissue remodeling (which can become abnormal, for example, with chronic inflammation). Disruptions of this balance result in serious diseases such as arthritis, tumor growth, and others.
FIGURE 1-8 Fibroblasts in Connective Tissue. This micrograph shows tissue from the cornea of a rat. The extracellular matrix surrounds the fibroblasts (F).
Specialized Cell Junctions
Cellular Communication and Signal Transduction
FIGURE 1-9 Junctional Complex. A, Schematic drawing of a belt desmosome between epithelial cells. This junction, also called the zonula adherens, encircles each of the interacting cells. The spot desmosomes and hemidesmosomes, like the belt desmosomes, are adhering junctions. This tight junction is an impermeable junction that holds cells together but seals them in such a way that molecules cannot leak between them. The gap junction, as a communicating junction, mediates the passage of small molecules from one interacting cell to the other. B, Electron micrograph of desmosomes.
FIGURE 1-10 Cellular Communication. Three primary ways in which cells communicate with one another.
FIGURE 1-11 Primary Modes of Chemical Signaling. Five forms of signaling mediated by secreted molecules. Hormones, paracrines, neurotransmitters, and neurohormones are all intercellular messengers that accomplish communication between cells. Autocrines bind to receptors on the same cell. Not all neurotransmitters act in the strictly synaptic mode shown; some act in a contact-dependent mode as local chemical mediators that influence multiple target cells in the area.
FIGURE 1-12 Schematic of a Signal Transduction Pathway. Like a telephone receiver that converts an electrical signal into a sound signal, a cell converts an extracellular signal, A, into an intracellular signal, B. C, An extracellular signal molecule (ligand) bonds to a receptor protein located on the plasma membrane, where it is transduced into an intracellular signal. This process initiates a signaling cascade that relays the signal into the cell interior, amplifying and distributing it en route. Amplification is often achieved by stimulating enzymes. Steps in the cascade can be modulated by other events in the cell. D, Different cell behaviors rely on multiple extracellular signals.
TABLE 1-3 CLASSES OF PLASMA MEMBRANE RECEPTORS
Cellular Metabolism
Role of Adenosine Triphosphate
Food and Production of Cellular Energy
Oxidative Phosphorylation
FIGURE 1-13 Three Phases of Catabolism, Which Lead From Food to Waste Products. These reactions produce adenosine triphosphate (ATP), which is used to power other processes in the cell.
FIGURE 1-14 Glycolysis. Each of the numbered reactions is catalyzed by a different enzyme. At step 4, a six-carbon carbohydrate is metabolized to two three-carbon carbohydrates, so that the number of molecules at every step after this is doubled. Reactions 5 and 6 are responsible for the net synthesis of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) molecules.
Membrane Transport: Cellular Intake and Output
FIGURE 1-15 What Happens to Pyruvate, the Product of Glycolysis? In the presence of oxygen, pyruvate is oxidized to acetyl coenzyme A (CoA) and enters the citric acid cycle. In the absence of oxygen, pyruvate instead is reduced, accepting the electrons extracted during glycolysis and carried by reduced nicotinamide adenine dinucleotide (NADH). When pyruvate is reduced directly, as it is in muscles, the product is lactic acid. When CO2 is first removed from pyruvate and the remainder is reduced, as it is in yeasts, the resulting product is ethanol.
Movement of Water and Solutes
Passive Transport: Diffusion, Filtration, and Osmosis
Diffusion
Filtration: hydrostatic pressure
FIGURE 1-16 Passive Diffusion of Solute Molecules Across the Plasma Membrane. Oxygen, nitrogen, water, urea, glycerol, and carbon dioxide can diffuse readily down the concentration gradient. Macromolecules are too large to diffuse through pores in the plasma membrane. Ions may be repelled if the pores contain substances with identical charges. If the pores are lined with cations, for example, other cations will have difficulty diffusing because the positive charges will repel one another. Diffusion can still occur, but it occurs more slowly.
Osmosis
FIGURE 1-17 Hydrostatic Pressure and Oncotic Pressure in Plasma. 1, Hydrostatic pressure in plasma. 2, Oncotic pressure exerted by proteins in the plasma usually tends to pull water into the circulatory system. 3, Individuals with low protein levels (e.g., starvation) are unable to maintain a normal oncotic pressure; therefore water is not reabsorbed into the circulation and, instead, causes body edema.
FIGURE 1-18 Tonicity. Tonicity is important, especially for red blood cell function.
QUICK CHECK 1-2
Mediated and Active Transport
Mediated transport
FIGURE 1-19 Conformational Change Model of Mediated Transport (Facilitated Diffusion). The transporter protein has two states: “ping” and “pong.” In the ping state, sites for molecules of a specific solute are exposed on the outside of the bilayer. In the pong state, the sites are exposed to the inner side of the bilayer.
FIGURE 1-20 Channel Mode of Mediated Transport (Facilitated Diffusion). A channel protein forms a water-filled pore across the bilayer through which specific ions can diffuse.
FIGURE 1-21 Mediated Transport. Illustration shows simultaneous movement of a single solute molecule in one direction (uniport), of two different solute molecules in one direction (symport), and of two different solute molecules in opposite directions (antiport).
FIGURE 1-22 Active Transport and the Sodium-Potassium Pump. Three Na+ ions bind to sodium-binding sites on the carrier’s inner face. At the same time, an energy-containing adenosine triphosphate (ATP) molecule produced by the cell’s mitochondria binds to the carrier. The ATP dissociates, transferring its stored energy to the carrier. The carrier then changes shape, releases the three Na+ ions to the outside of the cell, and attracts two potassium (K+) ions to its potassium-binding sites. The carrier then returns to its original shape, releasing the two K+ ions and the remnant of the ATP molecule to the inside of the cell. The carrier is now ready for another pumping cycle.
BOX 1-1 NEW UNDERSTANDINGS ABOUT ATP
Active Transport of Na+ and K+
Transport by Vesicle Formation
Endocytosis and Exocytosis
FIGURE 1-23 Endocytosis and Exocytosis. A, Endocytosis and fusion with lysosome and exocytosis. B, Electron micrograph of exocytosis.
TABLE 1-4 MAJOR TRANSPORT SYSTEMS IN MAMMALIAN CELLS
BOX 1-2 THE NEW ENDOCYTIC MATRIX
FIGURE 1-24 Ligand Internalization by Means of Receptor-Mediated Endocytosis. A, The ligand attaches to its surface receptor (through the bristle coat or clathrin coat) and, through receptor-mediated endocytosis, enters the cell. The ingested material fuses with a lysosome and is processed by hydrolytic lysosomal enzymes. Processed molecules can then be transferred to other cellular components. B, Electron micrograph of a coated pit showing different sizes of filaments of the cytoskeleton (×82,000).
Receptor-Mediated Endocytosis
Caveolae
Movement of Electrical Impulses: Membrane Potentials
FIGURE 1-25 Sodium-Potassium Pump and Propagation of an Action Potential. A, Concentration difference of sodium (Na+) and potassium (K+) intracellularly and extracellularly. The direction of active transport by the sodium-potassium pump is also shown. B, The top diagram represents the polarized state of a neuronal membrane when at rest. The lower diagrams represent changes in sodium and potassium membrane permeabilities with depolarization and repolarization.
QUICK CHECK 1-3
Cellular Reproduction: the Cell Cycle
FIGURE 1-26 Interphase and the Phases of Mitosis. A, The G1/S checkpoint is to “check” for cell size, nutrients, growth factors, and DNA damage. See text for resting phases. The G2/M checkpoint checks for cell size and DNA replication. B, The orderly progression through the phases of the cell cycle is regulated by cyclins (so-called because levels rise and fall) and cyclin-dependent protein kinases (CDKs) and their inhibitors. When cyclins are complexed with CDKs, cell cycle events are triggered.
Phases of Mitosis and Cytokinesis
Rates of Cellular Division
Growth Factors
TABLE 1-5 EXAMPLES OF GROWTH FACTORS AND THEIR ACTIONS
Tissues
Tissue Formation
Types of Tissues
QUICK CHECK 1-4
FIGURE 1-27 How Growth Factors Stimulate Cell Proliferation. A, Resting cell. With the absence of growth factors, the retinoblastoma (Rb) protein is not phosphorylated; thus it holds the gene regulatory proteins in an inactive state. The gene regulatory proteins are required to stimulate the transcription of genes needed for cell proliferation. B, Proliferating cell. Growth factors bind to the cell surface receptors and activate intracellular signaling pathways, leading to activation of intracellular proteins. These intracellular proteins phosphorylate and thereby inactivate the Rb protein. The gene regulatory proteins are now free to activate the transcription of genes, leading to cell proliferation.
BOX 1-3 CHARACTERISTICS OF EPITHELIAL TISSUES
Simple Squamous Epithelial Cell. Photomicrograph of simple squamous epithelial cell in parietal wall of Bowman’s capsule in kidney.
Cornified Stratified Squamous Epithelium. Diagram of stratified squamous epithelium of skin.
Stratified Squamous Transitional Epithelium. Photomicrograph of stratified squamous transitional epithelium of urinary bladder.
Simple Cuboidal Epithelium. Photomicrograph of simple cuboidal epithelium of pancreatic duct.
Simple Columnar Epithelium. Photomicrograph of simple columnar epithelium.
Pseudostratified Ciliated Columnar Epithelium. Photomicrograph of pseudostratified ciliated columnar epithelium of trachea.
BOX 1-4 CONNECTIVE TISSUES
Loose Areolar Connective Tissue.
Dense, Irregular Connective Tissue.
Dense, Regular (White Fibrous) Connective Tissue.
Elastic Connective Tissue.
Adipose Tissue. A, Fat storage areas—distribution of fat in male and female bodies. B, Photomicrograph of adipose tissue.
Cartilage. A, Hyaline cartilage. B, Elastic cartilage. C, Fibrous cartilage.
Bone.
BOX 1-5 MUSCLE TISSUES
Skeletal (Striated) Muscle.
Cardiac Muscle.
Smooth (Visceral) Muscle.
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
FIGURE 2-1 Successive Enlargements from a Human to the Genetic Material.
DNA, RNA, and Proteins: Heredity at the Molecular Level
Definitions
Composition and Structure of DNA
DNA as the Genetic Code
FIGURE 2-2 Watson-Crick Model of the DNA Molecule. The DNA structure illustrated here is based on that published by James Watson (left) and Francis Crick (photograph, right) in 1953. Note that each side of the DNA molecule consists of alternating sugar and phosphate groups. Each sugar group is bonded to the sugar group opposite it by a pair of nitrogenous bases (adenine-thymine or cytosine-guanine). The sequence of these pairs constitutes a genetic code that determines the structure and function of a cell.
Replication of DNA
FIGURE 2-3 Replication of DNA. The two chains of the double helix separate, and each chain serves as the template for a new complementary chain.
FIGURE 2-4 Base Pair Substitution. Missense mutations (A) produce a single amino acid change, whereas nonsense mutations (B) produce a stop codon in the mRNA. Stop codons terminate translation of the polypeptide.
Mutation
FIGURE 2-5 Frameshift Mutations. Frameshift mutations result from the addition or deletion of a number of bases that is not a multiple of three. This mutation alters all of the codons downstream from the site of insertion or deletion.
From Genes to Proteins
Transcription
Gene Splicing
Translation
FIGURE 2-6 General Scheme of Ribonucleic Acid (RNA) Transcription. A, Transcription of messenger RNA (mRNA). A DNA molecule “unzips” in the region of the gene to be transcribed. RNA nucleotides already present in the nucleus temporarily attach themselves to exposed DNA bases along one strand of the unzipped DNA molecule according to the principle of complementary pairing. As the RNA nucleotides attach to the exposed DNA, they bind to each other and form a chainlike RNA strand called a messenger RNA (mRNA) molecule. Notice that the new mRNA strand is an exact copy of the base sequence on the opposite side of the DNA molecule. As in all metabolic processes, the formation of mRNA is controlled by an enzyme—in this case, the enzyme is called RNA polymeraseB, Editing of an mRNA transcript.
Chromosomes
FIGURE 2-7 Protein Synthesis.
FIGURE 2-8 From Molecular Parts to the Whole Somatic Cell.
FIGURE 2-9 Phases of Meiosis and Comparison to Mitosis
Chromosome Aberrations and Associated Diseases
Polyploidy
FIGURE 2-10 Karyotype of Chromosomes. A, Human karyotype. B, Homologous chromosomes and sister chromatids.
FIGURE 2-11 Structure of Chromosomes. A, Human chromosomes 2, 5, and 13. Each is replicated and consists of two chromatids. Chromosome 2 is a metacentric chromosome because the centromere is close to the middle; chromosome 5 is submetacentric because the centromere is set off from the middle; chromosome 13 is acrocentric because the centromere is at or very near the end. B, During mitosis, the centromere divides and the chromosomes move to opposite poles of the cell. At the time of centromere division, the chromatids are designated as chromosomes.
Aneuploidy
Autosomal aneuploidy
FIGURE 2-12 Nondisjunction. Nondisjunction causes aneuploidy when chromosomes or sister chromatids fail to divide properly.
Sex chromosome aneuploidy
FIGURE 2-13 Child With Down Syndrome.
FIGURE 2-14 Down Syndrome Increases With Maternal Age. Rate is per 1000 live births related to maternal age.
TABLE 2-1 CHARACTERISTICS OF VARIOUS CHROMOSOME DISORDERS
Abnormalities of Chromosome Structure
Deletions
FIGURE 2-15 Turner Syndrome. A, A sex chromosome is missing, and the person’s chromosomes are 45,X. Characteristic signs are short stature, female genitalia, webbed neck, shieldlike chest with underdeveloped breasts and widely spaced nipples, and imperfectly developed ovaries. B, As this karyotype shows, Turner syndrome results from monosomy of sex chromosomes (genotype XO).
Duplications
FIGURE 2-16 Klinefelter Syndrome. This young man exhibits many characteristics of Klinefelter syndrome: small testes, some development of the breasts, sparse body hair, and long limbs. This syndrome results from the presence of two or more X chromosomes with one Y chromosome (genotypes XXY or XXXY, for example).
FIGURE 2-17 Abnormalities of Chromosome Structure. A, Deletion occurs when a chromosome segment is lost. B, Normal crossing over. C, The generation of duplication and deletion through unequal crossing over.
Inversions
Translocations
FIGURE 2-18 Normal and Abnormal Chromosome Translocation. A, Normal chromosomes and reciprocal translocation. B, Pairing at meiosis. C, Consequences of translocation in gametes; unbalanced gametes result in zygotes that are partially trisomic and partially monosomic and consequently develop abnormally.
Fragile sites
QUICK CHECK 2-1
Elements of Formal Genetics
Phenotype and Genotype
FIGURE 2-19 Symbols Commonly Used in Pedigrees.
Dominance and Recessiveness
Transmission of Genetic Diseases
FIGURE 2-20 Punnett Square and Autosomal Dominant Traits. A, Punnett square for the mating of two individuals with an autosomal dominant gene. Here both parents are affected by the trait. B, Punnett square for the mating of a normal individual with a carrier for an autosomal dominant gene.
Autosomal Dominant Inheritance
Characteristics of Pedigrees
FIGURE 2-21 Pedigree Illustrating the Inheritance Pattern of Postaxial Polydactyly, an Autosomal Dominant Disorder. Affected individuals are represented by shading.
Recurrence Risks
Delayed Age of Onset
FIGURE 2-22 Pedigree for Retinoblastoma Showing Incomplete Penetrance. Female with marked arrow in line II must be heterozygous, but she does not express the trait.
Penetrance and Expressivity
FIGURE 2-23 Neurofibromatosis. Tumors. The most common is sessile or pedunculated. Early tumors are soft, dome-shaped papules or nodules that have a distinctive violaceous hue. Most are benign.
Epigenetics and Genomic Imprinting
FIGURE 2-24 Epigenetic Modifications. Because DNA is a long molecule, it needs packaging to fit in the tiny nucleus. Packaging involves coiling of the DNA in a “left-handed” spiral around spools, made of four pairs of proteins individually known as histones and collectively as the histone octamer. The entire spool is called a nucleosome (also see Figure 1-2). Nucleosomes are organized into chromatin, the repeating building blocks of a chromosome. Histone modifications are correlated with methylation, are reversible, and occur at multiple sites. Methylation occurs at the 5 position of cytosine and provides a “footprint” or signature as a unique epigenetic alteration (red). When genes are expressed, chromatin is open or active; however, when chromatin is condensed because of methylation and histone modification, genes are inactivated.
Autosomal Recessive Inheritance
Characteristics of Pedigrees
FIGURE 2-25 Pedigree for Cystic Fibrosis. Cystic fibrosis is an autosomal recessive disorder. The double bar denotes a consanguineous mating. Because cystic fibrosis is relatively common in European populations, most cases do not involve consanguinity.
Recurrence Risks
Consanguinity
FIGURE 2-26 Punnett Square for the Mating of Heterozygous Carriers Typical of Most Cases of Recessive Disease.
X-Linked Inheritance
X Inactivation
FIGURE 2-27 The X Inactivation Process. The maternal (m) and paternal (p) X chromosomes are both active in the zygote and in early embryonic cells. X inactivation then takes place, resulting in cells having either an active paternal X or an active maternal X. Females are thus X chromosome mosaics, as shown in the tissue sample at the bottom of the page.
Sex Determination
FIGURE 2-28 Distal Short Arms of the X and Y Chromosomes Exchange Material During Meiosis in the Male. The region of the Y chromosome in which this crossover occurs is called the pseudoautosomal region. The SRY gene, which triggers the process leading to male gonadal differentiation, is located just outside the pseudoautosomal region. Occasionally, the crossover occurs on the centromeric side of the SRY gene, causing it to lie on an X chromosome instead of a Y chromosome. An offspring receiving this X chromosome will be an XX male, and an offspring receiving the Y chromosome will be an XY female.
QUICK CHECK 2-2
Characteristics of Pedigrees
Recurrence Risks
Sex-Limited and Sex-Influenced Traits
FIGURE 2-29 Punnett Square and X-Linked Recessive Traits. A, Punnett square for the mating of a normal male (XHY) and a female carrier of an X-linked recessive gene (XHXh). B, Punnett square for the mating of a normal female (XHXH) with a male affected by an X-linked recessive disease (XhY). C, Punnett square for the mating of a female who carries an X-linked recessive gene (XHXh) with a male who is affected with the disease caused by the gene (XhY).
Evaluation of Pedigrees
Linkage Analysis and Gene Mapping
Classic Pedigree Analysis
FIGURE 2-30 Genetic Results of Crossing Over. A, No crossing over. B, Crossing over with recombination. C, Double crossing over, resulting in no recombination.
Complete Human Gene Map: Prospects and Benefits
HEALTH ALERT
FIGURE 2-31 Example of Diseases: A Gene Map. ADA, Adenosine deaminase; ALD, adrenoleukodystrophy; PKU, phenylketonuria.
Multifactorial Inheritance
FIGURE 2-32 Multifactorial Inheritance. Analysis of mode of inheritance for grain color in wheat. The trait is controlled by three independently assorted gene loci.
FIGURE 2-33 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
Cellular Adaptation
FIGURE 3-1 Adaptive and Dysplastic Alterations in Simple Cuboidal Epithelial Cells.
Atrophy
FIGURE 3-2 Atrophy. A, Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic cerebrovascular disease, resulting in reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the surface of the brain.
Hypertrophy
Hyperplasia
FIGURE 3-3 Hypertrophy of Cardiac Muscle in Response to Valve Disease. A, Transverse slices of a normal heart and a heart with hypertrophy of the left ventricle (L, normal thickness of left ventricular wall; T, thickened wall from heart in which severe narrowing of aortic valve caused resistance to systolic ventricular emptying). B, Histology of cardiac muscle from the normal heart. C, Histology of cardiac muscle from a hypertrophied heart.
Dysplasia: Not a True Adaptive Change
FIGURE 3-4 Hyperplasia of the Prostate With Secondary Thickening of the Obstructed Urinary Bladder. The enlarged prostate is seen protruding into the lumen of the bladder, which appears trabeculated. These “trabeculae” result from hypertrophy and hyperplasia of smooth muscle cells that occur in response to increased intravesical pressure caused by urinary obstruction.
Metaplasia
Cellular Injury
FIGURE 3-5 Reversible Changes in Cells Lining the Bronchi.
FIGURE 3-6 Stages of Cellular Adaptation, Injury, and Death. The normal cell responds to physiologic and pathologic stresses by adapting (atrophy, hypertrophy, hyperplasia, metaplasia). Cell injury occurs if the adaptive responses are exceeded or compromised by injurious agents, stress, and mutations. The injury is reversible if it is mild or transient, but if the stimulus persists the cell suffers irreversible injury and eventually death.
TABLE 3-1 TYPES OF PROGRESSIVE CELL INJURY AND RESPONSES
General Mechanisms of Cell Injury
Hypoxic Injury
FIGURE 3-7 Hypoxic Injury Induced by Ischemia. A, Consequences of decreased oxygen delivery or ischemia with decreased ATP. The structural and physiologic changes are reversible if oxygen is delivered quickly. Significant decreases in ATP result in cell death, mostly by necrosis. B, Mitochondrial damage can result in changes in membrane permeability, loss of membrane potential, and decreased ATP. Between the outer and inner membranes of the mitochondria are proteins that can activate the cell’s suicide pathways, called apoptosis. C, Calcium ions are critical mediators of cell injury. Calcium ions are usually maintained at low concentrations in the cell’s cytoplasm; thus ischemia and certain toxins can initially cause an increase in the release of Ca++ from intracellular stores and later an increased movement (influx) across the plasma membrane.
TABLE 3-2 COMMON THEMES IN CELL INJURY AND CELL DEATH
FIGURE 3-8 Hypoxia and Inflammation. Shown is a simplified drawing of clinical conditions characterized by tissue hypoxia that causes inflammatory changes (left) and inflammatory diseases that ultimately lead to hypoxia (right). These diseases and conditions are discussed in more detail in their respective chapters.
FIGURE 3-9 Reperfusion Injury. Without oxygen, or anoxia, the cells display hypoxic injury and become swollen. With reoxygenation, reperfusion injury increases because of the formation of reactive oxygen radicals that can cause cell necrosis.
HEALTH ALERT
QUICK CHECK 3-1
Free Radicals and Reactive Oxygen Species—Oxidative Stress
Chemical Injury
Mechanisms
FIGURE 3-10 Generation of Reactive Oxygen Species and Antioxidant Mechanisms in Biologic Systems. Free radicals are generated within cells in several ways, including from normal respiration; absorption of radiant energy; activation of leukocytes during inflammation; metabolism of chemicals or drugs; transition metals, such as iron (Fe+++) or copper (Cu+), where the metals donate or accept electrons as in the Fenton reaction; nitric oxide (NO) generated by endothelial cells (not shown); and reperfusion injury. Ubiquinone (coenzyme Q), a lipophilic molecule, transfers electrons in the inner membrane of mitochondria, ultimately enabling their interaction with oxygen (O2) and hydrogen (H2) to yield water (H2O). In so doing, the transport allows free energy change and the synthesis of 1 mole of adenosine triphosphate (ATP). With the transport of electrons, free radicals are generated within the mitochondria. Reactive oxygen species (O2·−, H2O2, OH·) act as physiologic modulators of some mitochondrial functions but may also cause cell damage. O2 is converted to superoxide (O2·−) by oxidative enzymes in the mitochondria, endoplasmic reticulum (ER), plasma membrane, peroxisomes, and cytosol. O2 is converted to H2O2 by superoxide dismutase (SOD) and further to OH· by the Cu/Fe Fenton reaction. Superoxide catalyzes the reduction of Fe++ to Fe+++, thus increasing OH· formation by the Fenton reaction. H2O2 is also derived from oxidases in peroxisomes. The three reactive oxygen species (H2O2, OH·, and O2·−) cause free radical damage to lipids (peroxidation of the membrane), proteins (ion pump damage), and DNA (impaired protein synthesis). The major antioxidant enzymes include SOD, catalase, and glutathione peroxidase.
TABLE 3-3 Biologically Relevant Free Radicals
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 Including Drugs
FIGURE 3-11 Human Exposure to Pollutants. Pollutants contained in air, water, and soil are absorbed through the lungs, gastrointestinal tract, and skin. In the body they may act at the site of absorption but are generally transported through the bloodstream to various organs where they can be stored or metabolized. Metabolism of xenobiotics may result in the formation of water-soluble compounds that are excreted, or a toxic metabolite may be created by activation of the agent.
FIGURE 3-12 Chemical Injury of Liver Cells Induced by Carbon Tetrachloride (CCl4) Poisoning. Light blue boxes are mechanisms unique to chemical injury, purple boxes involve hypoxic injury, and green boxes are clinical manifestations.
TABLE 3-5 COMMON DRUGS OF ABUSE
Lead
FIGURE 3-13 Acetaminophen Metabolism and Toxicity. CYP2E1, a cytochrome; NAPQI, toxic byproduct; GSH, glutathione.
TABLE 3-6 SOCIAL OR STREET DRUGS AND THEIR EFFECTS
TABLE 3-7 COMMON SOURCES OF LEAD EXPOSURE
Carbon Monoxide
Ethanol
FIGURE 3-14 Major Pathways of ADH Metabolism of Alcohol in the Liver.
FIGURE 3-15 Fetal Alcohol Syndrome. When alcohol enters the fetal blood, the potential result can cause tragic congenital abnormalities, such as microcephaly (“small head”), low birth weight, and cardiovascular defects, as well as developmental disabilities, such as physical and mental retardation, and even death. Note the small head, thinned upper lip, small eye openings (palpebral fissures), epicanthal folds, and receded upper jaw (retrognathia) typical of fetal alcohol syndrome.
FIGURE 3-16 Alcoholic Hepatitis. Chicken-wire fibrosis extending between hepatocytes (Mallory trichrome stain).
Mercury
QUICK CHECK 3-2
Unintentional and Intentional Injuries
TABLE 3-8 MAJOR SOURCES OF MERCURY EXPOSURE AND HEALTH EFFECTS
BOX 3-2 CLASSIFICATION OF PREVENTABLE ADVERSE EVENTS IN PRIMARY CARE
Asphyxial Injuries
Suffocation
Strangulation
HEALTH ALERT
Chemical Asphyxiants
Drowning
TABLE 3-9 UNINTENTIONAL AND INTENTIONAL INJURIES
TABLE 3-10 MECHANISMS OF CELLULAR INJURY
BOX 3-3 RECOMMENDATIONS TO AVOID MEDICAL ERRORS
What can you do? Be Involved in Your Healthcare.
Medicines
Hospital Stays
Surgery
Other Steps You Can Take
QUICK CHECK 3-3
Infectious Injury
Immunologic and Inflammatory Injury
Manifestations of Cellular Injury: Accumulations
FIGURE 3-17 Mechanisms of Intracellular Accumulations.
Water
FIGURE 3-18 The Process of Oncosis (Formerly Referred to as “Hydropic Degeneration”). ATP, Adenosine triphosphate.
Lipids and Carbohydrates
FIGURE 3-19 Fatty Liver. The liver appears yellow.
Glycogen
Proteins
Pigments
Melanin
Hemoproteins
FIGURE 3-20 Hemosiderin Accumulation Is Noted as the Color Changes in a “Black Eye.”
Calcium
FIGURE 3-21 Free Cytosolic Calcium: A Destructive Agent. Normally, calcium is removed from the cytosol by adenosine triphosphate (ATP)-dependent calcium pumps. In normal cells, calcium is bound to buffering proteins, such as calbindin or paralbumin, and is contained in the endoplasmic reticulum and the mitochondria. If there is abnormal permeability of calcium-ion channels, direct damage to membranes, or depletion of ATP (i.e., hypoxic injury), calcium increases in the cytosol. If the free calcium cannot be buffered or pumped out of cells, uncontrolled enzyme activation takes place, causing further damage. Uncontrolled entry of calcium into the cytosol is an important final common pathway in many causes of cell death.
FIGURE 3-22 Aortic Valve Calcification. A, This calcified aortic valve is an example of dystrophic calcification. B, This algorithm shows the dystrophic mechanism of calcification.
Urate
Systemic Manifestations
TABLE 3-11 SYSTEMIC MANIFESTATIONS OF CELLULAR INJURY
FIGURE 3-23 Schematic Illustration of the Morphologic Changes in Cell Injury Culminating in Necrosis or Apoptosis. Myelin figures come from degenerating cellular membranes and are noted within the cytoplasm or extracellularly.
Cellular Death
Necrosis
FIGURE 3-24 Coagulative Necrosis. A wedge-shaped kidney infarct (yellow).
TABLE 3-12 FEATURES OF NECROSIS AND APOPTOSIS
FIGURE 3-25 Liquefactive Necrosis of the Brain. The area of infarction is softened as a result of liquefaction necrosis.
FIGURE 3-26 Caseous Necrosis. Tuberculosis of the lung, with a large area of caseous necrosis containing yellow-white and cheesy debris.
FIGURE 3-27 Fat Necrosis of Pancreas. Interlobular adipocytes are necrotic; acute inflammatory cells surround these.
Apoptosis
FIGURE 3-28 Gangrene, a Complication of Necrosis. In certain circumstances, necrotic tissue will be invaded by putrefactive organisms that are both saccharolytic and proteolytic. Foul-smelling gases are produced, and the tissue becomes green or black as a result of breakdown of hemoglobin. Obstruction of the blood supply to the bowel almost inevitably is followed by gangrene.
FIGURE 3-29 Necrosis and Apoptosis in Liver Cells. Necrosis is caused by exogenous injury whereby cells are swollen and have nuclear changes in ruptured cell membrane. Apoptosis is single cell death. It is genetically programmed (suicide genes) and depends on energy. Apoptotic bodies contain part of the nucleus and cytoplasmic organelles, which are ultimately engulfed by macrophages or adjacent cells. RER, Rough endoplasmic reticulum.
Autophagy
FIGURE 3-30 Mechanisms of Apoptosis. The two pathways of apoptosis differ in their induction and regulation, and both culminate in the activation of “executioner” caspases. The induction of apoptosis by the mitochondrial pathway involves the Bcl-2 family, which causes leakage of mitochondrial proteins. The regulators of the death receptor pathway involve the proteases, called caspases.
FIGURE 3-31 Autophagy. Cellular stresses, such as nutrient deprivation, activate autophagy genes that create vacuoles in which cellular organelles are sequestered and then degraded following fusion of the vesicles with lysosomes. The digested materials are recycled to provide nutrients for the cell.
QUICK CHECK 3-4
Aging & Altered Cellular and Tissue Biology
FIGURE 3-32 Microinsults.
TABLE 3-13 THEORIES OF AGING
Normal Life Span and Life Expectancy
TABLE 3-14 BIOLOGY OF AGING
Degenerative Extracellular Changes
HEALTH ALERT
FIGURE 3-33 Some Biological Changes Associated With Aging. Insets show proportion of remaining functions in the organs of a person in late adulthood compared with a 20-year-old.
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 and Altered Cellular and Tissue Biology
Somatic Death
KEY TERMS
References
Chapter 4 Fluids and Electrolytes, Acids and Bases
Distribution of Body Fluids
TABLE 4-1 TOTAL BODY WATER (%) IN RELATION TO BODY WEIGHT*
TABLE 4-2 DISTRIBUTION OF BODY WATER (70-KG MAN)
Maturation and the Distribution of Body Fluids
Water Movement Between Plasma and Interstitial Fluid
TABLE 4-3 NORMAL WATER GAINS AND LOSSES (70-KG MAN)
PEDIATRIC CONSIDERATIONS
Newborn Infants
Children and Adolescents
GERIATRIC CONSIDERATIONS
Water Movement Between ICF and ECF
Alterations in Water Movement
Edema
Pathophysiology
FIGURE 4-1 Net Filtration—Fluid Movement Between Plasma and Interstitial Space. The movement of fluid between the vascular, interstitial spaces and the lymphatics is the result of net filtration of fluid across the semipermeable capillary membrane. Capillary hydrostatic pressure is the primary force for fluid movement out of the arteriolar end of the capillary and into the interstitial space. At the venous end, capillary oncotic pressure (from plasma proteins) attracts water back into the vascular space. Interstitial hydrostatic pressure promotes the movement of fluid and proteins into the lymphatics. Osmotic pressure accounts for the movement of fluid between the interstitial space and the intracellular space. Normally, intracellular and extracellular fluid osmotic pressures are equal (280 to 294 mOsm) and water is equally distributed between the interstitial and intracellular compartments.
FIGURE 4-2 Mechanisms of Edema Formation. H2O, Water; Na+, sodium ion.
Clinical Manifestations
Evaluation and Treatment
FIGURE 4-3 Pitting Edema.
QUICK CHECK 4-1
TABLE 4-4 REPRESENTATIVE DISTRIBUTION OF ELECTROLYTES IN BODY COMPARTMENTS
Sodium, Chloride, and Water Balance
Sodium and Chloride Balance
FIGURE 4-4 The Renin-Angiotensin-Aldosterone System. (1) Renal juxtaglomerular cells sense decrease in blood pressure and release renin; (2) renin activates angiotensinogen to angiotensin I; (3) angiotensin I is converted to angiotensin II via angiotensin-converting enzyme (ACE) in the lung capillaries; (4) angiotensin II promotes vasoconstriction and stimulates aldosterone secretion from the adrenal cortex, resulting in renal sodium and water retention, potassium excretion, and an increase in blood pressure; (5) aldosterone causes increased reabsorption of sodium and water retention.
FIGURE 4-5 The Atrial Natriuretic Hormone (ANH) System. GFR, Glomerular filtration rate; Na+, sodium ion.
Water Balance
FIGURE 4-6 The Antidiuretic Hormone (ADH) System.
TABLE 4-5 WATER AND SOLUTE IMBALANCES
QUICK CHECK 4-2
Alterations in Sodium, Water, and Chloride Balance
FIGURE 4-7 Effects of Alterations in Extracellular Sodium Concentration in RBC, Body Cell, and Neuron. A, Hypotonic Alteration: Decrease in ECF sodium (Na) concentration (hyponatremia) results in ICF osmotic attraction of water with swelling and potential bursting of cells. B, Isotonic Alteration: Normal concentration of sodium in the ECF and no change in shifts of fluid in or out of cells. C, Hypertonic Alteration: An increase in ECF sodium concentration (hypernatremia) results in osmotic attraction of water out of cells with cell shrinkage. RBC, Red blood cell.
Isotonic Alterations
Hypertonic Alterations
Hypernatremia
Pathophysiology
HEALTH ALERT
Clinical Manifestations
Evaluation and Treatment
Water Deficit
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hypotonic Alterations
Hyponatremia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Water Excess
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 4-3
Alterations in Potassium and other Electrolytes
Potassium
Hypokalemia
Pathophysiology
Clinical Manifestations
FIGURE 4-8 Electrocardiogram Changes With Potassium Imbalance.
TABLE 4-6 CLINICAL MANIFESTATIONS OF POTASSIUM LEVEL ALTERATIONS
Evaluation and Treatment
Hyperkalemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 4-4
Other Electrolytes—Calcium, Magnesium, and Phosphate
Acid-Base Balance
Hydrogen Ion and pH
TABLE 4-7 ALTERATIONS IN OTHER BODY ELECTROLYTES
Buffer Systems
Carbonic Acid–Bicarbonate Buffering
TABLE 4-8 PH OF BODY FLUIDS
Protein Buffering
Renal Buffering
Acid-Base Imbalances
Metabolic Acidosis
FIGURE 4-9 Integration of pH Control Mechanisms. Elevated carbon dioxide (CO2) levels result in increased formation of carbonic acid (H2CO3) in red blood cells. The resulting increase in hydrogen ions (H+), coupled with elevated CO2 levels, results in HHbCO2 and an increase in respiratory rate and secretion of H+ by the kidneys, thus helping to regulate the pH of body fluids.
TABLE 4-9 BUFFER SYSTEMS
Metabolic Alkalosis
FIGURE 4-10 Davenport Diagram: Classic Working Diagram for Studying Primary Uncompensated Acid-Base Imbalance. The point ⊗ represents a normal pH value (7.4) and normal values for the partial pressure of arterial carbon dioxide (PaCO2 = 40 mm Hg) and the bicarbonate concentration (HCO3− = 24 mEq/L). Note that as the Paco2 increases toward 60 mm Hg (A) the pH decreases (respiratory acidosis), and that as it decreases toward 20 mm Hg (B) the pH increases (respiratory alkalosis). Metabolic acidosis develops as the concentration of HCO3− decreases (C), and metabolic alkalosis develops as the concentration of HCO3− increases (D).
TABLE 4-10 CAUSES OF METABOLIC ACIDOSIS
FIGURE 4-11 Metabolic Acidosis.
FIGURE 4-12 Metabolic Alkalosis.
Respiratory Acidosis
FIGURE 4-13 Respiratory Acidosis.
Respiratory Alkalosis
FIGURE 4-14 Respiratory Alkalosis.
QUICK CHECK 4-5
DID YOU UNDERSTAND?
Distribution of Body Fluids
Alterations in Water Movement
Sodium, Chloride, and Water Balance
Alterations in Sodium, Water, and Chloride Balance
Alterations in Potassium and Other Electrolytes
Acid-Base Balance
KEY TERMS
References
UNIT 2 Mechanisms of Self-Defense
Interactive Review – Unit 2
Chapter 5 Innate Immunity: Inflammation and Wound Healing
Human Defense Mechanisms
TABLE 5-1 OVERVIEW OF HUMAN DEFENSES
Innate Immunity
First Line of Defense: Physical and Biochemical Barriers and Normal Flora
Physical Barriers
Epithelial Cell–Derived Chemicals
FIGURE 5-1 The Closed Barrier. The digestive, respiratory, and genitourinary tracts and skin form closed barriers between the internal organs and the environment.
Normal Flora
QUICK CHECK 5-1
Second Line of Defense: Inflammation
FIGURE 5-2 The Major Local Changes in the Process of Inflammation. Compared to the normal circulation, inflammation is characterized by (1) dilation of the blood vessels and increased blood flow, leading to erythema and warmth; (2) increased vascular permeability with leakage of plasma from the vessels, leading to edema; and (3) movement of leukocytes from the vessels into the site of injury.
FIGURE 5-3 Acute Inflammatory Response. Inflammation is usually initiated by cellular injury and may be complicated by infection. Mast cell degranulation, the activation of three plasma systems, and the release of subcellular components from the damaged cells occur as a consequence. These systems are interdependent, so that induction of one (e.g., mast cell degranulation) can result in the induction of the other two. The result is the development of the characteristic microscopic and clinical hallmarks of inflammation. The figure numbers refer to additional figures in which more detailed information may be found on that portion of the response.
QUICK CHECK 5-2
Plasma Protein Systems and Inflammation
Complement System
FIGURE 5-4 Plasma Protein Systems in Inflammation: Complement, Clotting, and Kinin Systems. Each plasma protein system consists of a family of proteins that are activated in sequence to create potent biologic effects. The complement system can be activated by three mechanisms, each of which results in proteolytic activation of C3. The fragments of C3 activation, C3a and C3b, are major components of inflammation. C3a is a potent anaphylatoxin, which induces degranulation of mast cells. C3b can bind to the surface or cells, such as bacteria, and either serve as an opsonin for phagocytosis or proteolytically activate the next component of the complement cascade, C5. The smaller fragment of C5 activation is C5a, a powerful anaphylatoxin, and is also chemotactic for neutrophils, attracting them to the site of inflammation. The larger fragment, C5b, activates the components of the membrane attack complex (C5-C9), which damage the bacterial membrane and kill the bacteria. The clotting system can be activated by the tissue factor (extrinsic) pathway and the contact activation (intrinsic) pathway. All routes of clotting initiation lead to activation of factor X and thrombin. Thrombin is an enzyme that proteolytically activates fibrinogen to form fibrin and small fibrinopeptides (FPs). Fibrin polymerizes to form a clot, and the FPs are highly active as chemotactic factors and causing increased vascular permeability. The XIIa produced by the clotting system can also be activated by kallikrein of the kinin system (red arrow). Prekallikrein is enzymatically converted to kininogen, which activates bradykinin. Bradykinin functions similar to histamine and increases vascular permeability. Bradykinin can also stimulate nerve endings to cause pain. TF, tissue factor; FPs, Fibrinopeptides.
Clotting System
Kinin System
Control and Interaction of Plasma Protein Systems
QUICK CHECK 5-3
FIGURE 5-5 Cellular Components of the Blood. Cells in the blood can be classified as red blood cells (erythrocytes), cellular fragments (platelets), or white blood cells (leukocytes). Leukocytes consist of lymphocytes, monocytes, and granulocytes (neutrophils, eosinophils, basophils).
Cellular Components of Inflammation
Cellular Receptors
FIGURE 5-6 Principal Mediators of Inflammatory Processes. C3b, Large fragment produced from complement component C3; C5a, small fragment produced from complement component C5; ECF-A, eosinophil chemotactic factor of anaphylaxis; FGF, fibroblast growth factor; IFN, interferon; IgG, immunoglobulin G (predominant class of antibody in the blood); IL, interleukin; MCF, monocyte chemotactic factor; NCF, neutrophil chemotactic factor; PAF, platelet-activating factor; TGF, T-cell growth factor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.
FIGURE 5-7 The Action of Interferon. See text for details.
Mast Cells and Basophils
Degranulation
FIGURE 5-8 Mast Cell and Mast Cell Degranulation and Synthesis of Biologic Mediators During Inflammation. (A) Colorized photomicrograph of mast cell; dense red granules contain histamine and other biologically active substances. Among these are histamine, which is a major initiator of vascular changes, and a variety of chemotactic factors. (B) Mast cell degranulation (left) and synthesis (right). Histamine and biologically active substances are released immediately after stimulation of mast cells. Other substances are synthesized in response to mast cell stimulation. These include lipid-based molecules that originate from plasma membrane phospholipids as a result of the action of phospholipase A2. These include platelet-activating factor and a variety of prostaglandins and leukotrienes.
FIGURE 5-9 Effects of Histamine Through H1 and H2 Receptors. The effects depend on (1) the density and affinity of H1 or H2 receptors on the target cell and (2) the identity of the target cell. ATP, Adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate.
Synthesis of Mediators
Endothelium
Platelets
Phagocytes
Neutrophils
Monocytes and Macrophages
FIGURE 5-10 Process of Phagocytosis. The process that results in phagocytosis is characterized by three interrelated steps: adherence and diapedesis, tissue invasion by chemotaxis, and phagocytosis. A, Adherence, margination, diapedesis, and chemotaxis. The primary phagocyte in the blood is the neutrophil, which usually moves freely within the vessel (1). At sites of inflammation, the neutrophil progressively develops increased adherence to the endothelium, leading to accumulation along the vessel wall (margination or pavementing) (2). At sites of endothelial cell retraction the neutrophil exits the blood by means of diapedesis (3)Chemotaxis. In the tissues, the neutrophil detects chemotactic factor gradients through surface receptors (1) and migrates towards higher concentrations of the factors (2). The high concentration of chemotactic factors at the site of inflammation immobilizes the neutrophil (3)B, Specific receptors for recognition and attachment. C, Phagocytosis. Opsonized microorganisms bind to the surface of a phagocyte through specific receptors (1). The microorganism is ingested into a phagocytic vacuole, or phagosome (2). Lysosomes fuse with the phagosome, resulting in the formation of a phagolysosome (3). During this process the microorganism is exposed to products of the lysosomes, including a variety of enzymes and products of the hexose-monophosphate shunt (e.g., H2O2, O2−). The microorganism is killed and digested (4)Ab, Antibody; AbR, antibody receptor; C3b, complement component C3b; C3bR, complement C3b receptor; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor.
Eosinophils
Dendritic Cells and T Lymphocytes
Phagocytosis
FIGURE 5-11 Steps in Phagocytosis. These scanning electron micrographs show examples of the progressive steps in phagocytosis. A, A leukocyte undergoes chemotactic movement (in direction of arrow) by extending a filopodium (upper left) from the trailing body of the cell. B, Engulfment of red blood cells by a macrophage (M) that attaches to the red blood cells (R)C, An extension of the macrophage membrane (P; pseudopod) starts to enclose the red cell. D, The red blood cells are almost totally engulfed by the macrophage.
QUICK CHECK 5-4
Acute and Chronic Inflammation
Local Manifestations of Acute Inflammation
Systemic Manifestations of Acute Inflammation
Fever
Leukocytosis
TABLE 5-2 CIRCULATING LEVELS OF ACUTE-PHASE REACTANTS DURING INFLAMMATION
Plasma Protein Synthesis
Chronic Inflammation
FIGURE 5-12 The Chronic Inflammatory Response. Inflammation usually becomes chronic because of the persistence of an infection, an antigen, or a foreign body in the wound. Chronic inflammation is characterized by the persistence of many of the processes of acute inflammation. In addition, large amounts of neutrophil degranulation and death, the activation of lymphocytes, and the concurrent activation of fibroblasts result in the release of mediators that induce the infiltration of more lymphocytes and monocytes/macrophages and the beginning of wound healing and tissue repair. For more detailed information on each portion of the response, see the figures referenced in this illustration.
FIGURE 5-13 Tuberculous Granuloma. A central area of amorphous caseous necrosis (C) is surrounded by a zone of lymphocytes (L) and enlarged epithelioid cells (E). Activated macrophages frequently fuse to form multinucleated cells (Langhans giant cells). In tuberculoid granulomas the nuclei of the giant cells move to the cellular margins in a horseshoe-like formation.
QUICK CHECK 5-5
Wound Healing
FIGURE 5-14 Wound Healing by Primary and Secondary Intention and Phases of Wound Healing. Phases of wound healing (coagulation, inflammation, proliferation, remodeling, and maturation) and steps in wound healing by primary intention (left) and secondary intention (right). Note large amounts of granulation tissue and wound contraction in healing by secondary intention.
Phase I: Inflammation
Phase II: Proliferation and New Tissue Formation
FIGURE 5-15 Time Course of Cells Infiltrating a Wound. Neutrophils and macrophages are the predominant cells that infiltrate a wound during inflammation. Lymphocytes appear later and peak at day 7. Fibroblasts are the predominant cells during the proliferative and remodeling phases of the healing process.
Phase III: Remodeling and Maturation
Dysfunctional Wound Healing
Wound Disruption
FIGURE 5-16 Hypertrophic Scar and Keloid Scar Formation. Hypertrophic scar (A) and keloid scar (B) caused by excessive synthesis of collagen at suture sites.
Impaired Contraction
QUICK CHECK 5-6
PEDIATRIC CONSIDERATIONS
GERIATRIC CONSIDERATIONS
DID YOU UNDERSTAND?
Human Defense Mechanisms
Physical and Mechanical Barriers
Biochemical Barriers
The Inflammatory Process
Plasma Protein Systems
Cellular Components of Inflammation
Cellular Products
Mast Cell
Endothelium and Platelets
Phagocytes
Local Manifestations of Acute Inflammation
Systemic Manifestations of Acute Inflammation
Chronic Inflammation
Wound Healing
PEDIATRIC CONSIDERATIONS: Age-Related Factors Affecting Innate Immunity in the Newborn Child
GERIATRIC CONSIDERATIONS: Age-Related Factors Affecting Innate Immunity in the Elderly
KEY TERMS
References
Chapter 6 Adaptive Immunity
Third Line of Defense: Adaptive Immunity
FIGURE 6-1 Lymphocytes. A scanning electron micrograph showing lymphocytes (yellow, like cotton candy), red blood cells, and platelets.
TABLE 6-1 CLINICAL USE OF ANTIGEN OR ANTIBODY
Humoral and Cellular Immunity
Active and Passive Immunity
FIGURE 6-2 Lymphoid Tissues: Sites of B Cell and T Cell Differentiation. Immature lymphocytes migrate through central (primary) lymphoid tissues: the bone marrow (central lymphoid tissue for B lymphocytes) and the thymus (central lymphoid tissue for T lymphocytes). Mature lymphocytes later reside in the T and B lymphocyte–rich areas of the peripheral (secondary) lymphoid tissues.
Antigens and Immunogens
FIGURE 6-3 Overview of the Immune Response. The immune response can be separated into two phases: the generation of clonal diversity and clonal selection. During the generation of clonal diversity, lymphoid stem cells from the bone marrow migrate to the central lymphoid organs (the thymus or regions of the bone marrow), where they undergo a series of cellular division and differentiation stages resulting in either immunocompetent T cells from the thymus or immunocompetent B cells from the bone marrow. These cells are still naïve in that they have never encountered foreign antigen. The immunocompetent cells enter the circulation and migrate to the secondary lymphoid organs (e.g., spleen and lymph nodes), where they establish residence in B and T cell–rich areas. The clonal selection phase is initiated by exposure to foreign antigen. The antigen is usually processed by antigen-presenting cells (APCs) for presentation to T-helper cells (Th cells). The intercellular cooperation among APCs, Th cells, and immunocompetent T and B cells results in a second stage of cellular proliferation and differentiation. Because antigen has “selected” those T and B cells with compatible antigen receptors, only a small population of T and B cells undergo this process at one time. The result is an active cellular immunity or humoral immunity, or both. Cellular immunity is mediated by a population of effector T cells that can kill targets (T-cytotoxic cells) or regulate the immune response (T-regulatory cells), as well as a population of memory cells (T-memory cells) that can respond more quickly to a second challenge with the same antigen. Humoral immunity is mediated by a population of soluble proteins (antibodies) produced by plasma cells and by a population of memory B cells that can produce more antibody rapidly to a second challenge with the same antigen.
QUICK CHECK 6-1
Humoral Immune Response
Antibodies
Classes of Immunoglobulins
FIGURE 6-4 Structure of Different Immunoglobulins. Secretory IgA, IgD, IgE, IgG, and IgM. The black circles attached to each molecule represent carbohydrate residues.
FIGURE 6-5 Molecular Structure of an Antibody and Other Antigen-Binding Molecules. Antigen-binding molecules include antibody and cell-surface receptors. A, The typical antibody molecule consists of two identical heavy chains and two identical light chains connected by interchain disulfide bonds (— between chains in the figure). Each heavy chain is divided into three regions with relatively constant amino acid sequences (CH1, CH2, and CH3) and a region with a variable amino acid sequence (VH). Each light chain is divided into a constant region (CL) and a variable region (VL). The hinge region (Hi) provides flexibility in some classes of antibody. Within each variable region are three highly variable complementary-determining regions (CDR1, CDR2, CDR3) separated by relatively constant framework regions (FRs). B, Fragmentation of the antibody molecule by limited digestion with the enzyme papain has identified three important portions of the molecule: an Fc fragment (crystalline fragment that binds complement and Fc receptors) and two identical Fab fragments (antigen-binding fragments). C, A molecular model of a typical antibody molecule; the light chains are the strands of red spheres (each represents an individual amino acid). As the antibody folds, the CDRs are placed in proximity to form the antigen-binding site. D, The antigen receptor on the surface of B cells (BCR complex) is a monomeric antibody with a structure similar to that of circulating antibody, with an additional transmembrane region (TM) that anchors the molecule to the cell surface. The active BCR complex contains molecules (Igα and Igβ) that are responsible for intracellular signaling after the receptor has bound antigen. E, The T cell receptor (TCR) consists of an α and a β chain joined by a disulfide bond. Each chain consists of a constant region (Cα and Cβ) and a variable region (Vα and Vβ). Each variable region contains CDRs and FRs in a structure similar to that of antibody. The active TCR is associated with several molecules that are responsible for intracellular signaling. These include CD3, which is a complex of γ (gamma), ε (epsilon), and δ (delta) subunits and a complex of two ζ (zeta) molecules. The ζ molecules are attached to a cytoplasmic protein kinase (ZAP70) that is critical to intracellular signaling.
TABLE 6-2 PROPERTIES OF IMMUNOGLOBULINS
Molecular Structure
Antigen-Antibody Binding
FIGURE 6-6 Antigenic Determinants (Epitopes). Generic examples of epitopes on protein (A) and polysaccharide (B) molecules are shown. In A, an antigenic protein may have multiple different epitopes (epitopes 1 and 2) that react with different antibodies. Each sphere represents an amino acid with the red spheres representing epitope 1 and the yellow spheres representing epitope 2. Individual epitopes may consist of eight or nine amino acids. In B, a polysaccharide is constructed of a backbone with branched side chains. Each sphere represents an individual carbohydrate with the red spheres representing the carbohydrates that form the epitope. In this example, two identical epitopes are shown that would bind two identical antibodies. In C, this ribbon model of an antibody shows the heavy chains in blue and the light chains in red. Green represents antigen molecules bound to each antigen-binding site.
FIGURE 6-7 Direct and Indirect Functions of Antibody. Protective activities of antibodies can be direct (through the action of antibody alone) or indirect (requiring activation of other components of the innate immune response, usually through the Fc region). Direct means include neutralization of viruses or bacterial toxins before they bind to receptors on the surface of the host’s cells. Indirect means include activation of the classical complement pathway through C1, resulting in formation of the membrane-attack complex (MAC), or increased phagocytosis of bacteria opsonized with antibody and complement components bound to appropriate surface receptors (FcR and C3bR).
Function of Antibodies
Direct effects
BOX 6-1 MONOCLONAL ANTIBODIES
FIGURE 6-8 Immunologic Mechanisms That Activate the Inflammatory Response. Immunologic factors may activate inflammation through three mechanisms: (1) IgE can bind to the surface of a mast cell and, after binding antigen, induce the cell’s degranulation; (2) antigen and antibody can activate the complement system, releasing anaphylatoxins and chemotactic factors, especially C5a, that result in mast cell degranulation and neutrophil chemotaxis; and (3) antigen may also react with T lymphocytes, resulting in the production of lymphokines that may contribute to the development of either acute or chronic inflammation.
Indirect effects
IgE
FIGURE 6-9 IgE Function. (1) Soluble antigens from a parasitic infection cause production of IgE antibody by B cells. (2) Secreted IgE binds to IgE-specific receptors on the mast cell. (3) Additional soluble parasite antigen cross-links the IgE on the mast cell surface, (4) leading to mast cell degranulation and release of many proinflammatory products, including eosinophil chemotactic factor of anaphylaxis (ECF-A). (5) ECF-A attracts eosinophils from the circulation. (6) The eosinophil attaches to the surface of the parasite and releases potent lysosomal enzymes that damage microorganisms.
FIGURE 6-10 Secretory Immune System. A, Lymphocytes from the mucosal-associated lymphoid tissues circulate throughout the body in a pattern separate from other lymphocytes. For example, lymphocytes from the gut-associated lymphoid tissue circulate through the regional lymph nodes, the thoracic duct, and the blood and return to other mucosal-associated lymphoid tissues rather than to lymphoid tissue of the systemic immune system. B, Lymphoid tissue associated with mucous membranes is called mucosal-associated lymphoid tissue (MALT).
Secretory Immune System
Cell-Mediated Immunity
T Lymphocytes
Immune Response: Collaboration of B Cells and T Cells
Generation of Clonal Diversity
Development of B Lymphocytes
TABLE 6-3 GENERATION OF CLONAL DIVERSITY VS. CLONAL SELECTION
Development of T Lymphocytes
QUICK CHECK 6-2
Clonal Selection
FIGURE 6-11 Summary of Adaptive Immunity This simplified flowchart summarizes an example of adaptive immune responses when exposed to a microbial antigen.
FIGURE 6-12 Primary and Secondary Immune Responses. The initial administration of antigen induces a primary response during which IgM is initially produced, followed by IgG. Another administration of the antigen induces the secondary response in which IgM is transiently produced and larger amounts of IgG are produced over a longer period of time.
Primary and Secondary Immune Responses
Cellular Interactions in the Immune Response
B cell receptor for antigen
FIGURE 6-13 Activation of a B Cell by a T Cell–Independent Antigen. Molecules containing repeating identical antigenic determinants may interact simultaneously with several receptors on the surface of the B cell and induce the proliferation and production of immunoglobulins. Because Th2 cells do not participate, class switch does not occur and the resultant antibody response is IgM.
FIGURE 6-14 Antigen-Presenting Molecules. Two sets of molecules are primarily responsible for antigen presentation: MHC class I and MHC class II. The MHC molecules are encoded from the major histocompatibility complex on chromosome 6. This region contains information for the α chains of three principal class I molecules, called HLA-A, HLA-B, and HLA-C. These will be discussed in more detail in Chapter 7. Each of the MHC class I α chains forms a complex with β2-microglobulin, which is encoded by a gene on chromosome 15. The MHC class I molecules present small peptide antigens (eight or nine amino acids in length) in a pocket formed by the α1 and α2 domains of the α chain. The conformation of the molecule is stabilized by β2-microglobulin as well as by intrachain disulfide bonds. The α and β chains of class II molecules are also encoded in the MHC region. The principal class II molecules are HLA-DR, HLA-DP, and HLA-DQ. The MHC class II molecules present peptide antigens in a pocket formed by the α1 domain of the α chain and the β1 domain of the β chain. Both MHC class I and class II molecules are anchored to the plasma membrane by hydrophobic regions on the ends of the α and β chains.
Antigen processing and presentation
Antigen-presenting molecules
FIGURE 6-15 Antigen Processing. Antigen processing and presentation are required for initiation of most immune responses. Foreign antigen may be either endogenous (cytoplasmic protein) or exogenous (e.g., bacterium). Endogenous antigenic peptides are transported into the endoplasmic reticulum (ER) (1), where the MHC molecules are being assembled. In the ER, antigenic peptides bind to the α chains of the MHC class I molecule (2), and the complex is transported to the cell surface (3). The α and β chains of the MHC class II molecules are also being assembled in the endoplasmic reticulum (4), but the antigen-binding site is blocked by a small molecule (invariant chain) to prevent interactions with endogenous antigenic peptides. The MHC class II–invariant chain complex is transported to phagolysosomes (5) where exogenous antigenic fragments have been produced as a result of phagocytosis (6). In the phagolysosomes, the invariant chain is digested and replaced by exogenous antigenic peptides (7), after which the MHC class II–antigen complex is inserted into the cell membrane (8).
FIGURE 6-16 Dendritic Cells and Cell-Mediated Immunity. A, Dendritic cells are phagocytic antigen-presenting cells (APCs) found in the skin, mucosa, and lymphoid tissues. B, Dendritic cells (Langerhans cells) are marked by the blue stain in the epidermis. C, Dendritic cells capturing microbial antigens from epithelia and transporting them to regional lymph nodes. The T cells are then activated to proliferate and to differentiate into effector and memory cells, which migrate to sites of infection and promote various functions in cell-mediated immunity.
T cell receptor for antigen
CD molecules
T-helper lymphocytes
FIGURE 6-17 Development of T Cell Subsets. The most important step in clonal selection is the production of populations of T-helper (Th) cells (Th1, Th2, and Th17) and T-regulatory (Treg) cells that are necessary for the development of cellular and humoral immune responses. In this model, APCs (1) (probably multiple populations) may influence whether a precursor Th cell (Thp cell) (2) will differentiate into a Th1, Th2, Th17, or Treg cell (3). Differentiation of the Thp cell is initiated by three signaling events. The antigen signal is produced by the interaction of the T cell receptor (TCR) and CD4 with antigen presented by MHC class II molecules. A set of co-stimulatory signals is produced from interactions between adhesion molecules (not shown). A third signal is produced by the interactions of cytokines (particularly interleukin-1 [IL-1]) with appropriate cytokine receptors (IL-1R) on the Thp cell. The Thp cell up-regulates IL-2 production and expression of the IL-2 receptor (IL-2R), which acts in an autocrine fashion to accelerate Thp cell differentiation and proliferation. Commitment to a particular phenotype results from the relative concentrations of other cytokines. IL-12 and IFN-γ produced by some populations of APCs favor differentiation into the Th1 cell phenotype; IL-4, which is produced by a variety of cells, favors differentiation into the Th2 cell phenotype; IL-6 and TGF-β (T cell growth factor) facilitate differentiation into Th17 cells; IL-2 and TGF-β induce differentiation into Treg cells. The Th1 cell is characterized by the production of cytokines that assist in the differentiation of T-cytotoxic (Tc) cells, leading to cellular immunity, whereas the Th2 cell produces cytokines that favor B cell differentiation and humoral immunity. Th1 and Th2 cells affect each other through the production of inhibitory cytokines: IFN-γ will inhibit development of Th2 cells, and IL-4 will inhibit the development of Th1 cells. Th17 cells produce cytokines that affect phagocytes and increase inflammation. Treg cells produce immunosuppressive cytokines that prevent the immune response from being excessive. APC, Antigen-presenting cell; IFN, interferon; MHC, major histocompatibility complex; TGF, transforming growth factor.
T cell clonal selection: the cellular immune response
Superantigens
FIGURE 6-18 Tc Cell Clonal Selection. The immunocompetent Tc cell can react with antigen but cannot yet kill target cells. During clonal selection, this cell reacts with antigen presented by MHC class I molecules on the surface of a virally infected or cancerous abnormal cell. (1) The antigen–MHC class I complex is recognized simultaneously by the T cell receptor (TCR), which binds to antigen, and CD8, which binds to the MHC class I molecule. (2) A separate signal is provided by cytokines, particularly IL-2 from Th1 cells. (3) In response to these signals, the Tc cell develops into an effector Tc cell with the ability to kill abnormal cells.
B cell clonal selection: the humoral immune response
FIGURE 6-19 Superantigens. The T cell receptor (TCR) and major histocompatibility complex (MHC) class II molecule are normally held together by processed antigen. Superantigens, such as some bacterial exotoxins, bind directly to the variable region of the TCR β chain and the MHC class II molecule. Each superantigen activates sets of Vβ chains independently of the antigen specificity of the TCR.
Memory cells
T Lymphocyte Functions
T-Cytotoxic Lymphocytes
FIGURE 6-20 Bc Cell Clonal Selection. Immunocompetent B cells undergo proliferation and differentiation into antibody-secreting plasma cells. Multiple signals are necessary (1). The B cell itself can directly bind soluble antigen through the B cell receptor (BCR) and act as an antigen processing cell. Antigen is internalized, processed (2), and presented (3) to the TCR on a Th2 cell by MHC class II molecules (4). A cytokine signal is provided by the Th2 cell cytokines (e.g., IL-4) that react with the B cell (5). The B cell differentiates into plasma cells that secrete antibody (6).
FIGURE 6-21 Cellular Killing Mechanisms. Several cells have the capacity to kill abnormal (e.g., virally infected, cancerous) target cells. (1) T-cytotoxic (Tc) cells recognized endogenous antigen presented by MHC class I molecules. The Tc cell mobilizes multiple killing mechanisms that induce apoptosis of the target cell. (2) Natural killer (NK) cells identify and kill target cells through receptors that recognize abnormal surface changes. NK cells specifically kill targets that do not express surface MHC class I molecules. (3) Several cells, including macrophages and NK cells, can kill by antibody-dependent cellular cytotoxicity (ADCC). IgG antibodies bind to foreign antigen on the target cell, and cells involved in ADCC bind IgG through Fc receptors (FcR) and initiate killing. The insert is a scanning electron microscopic view of Tc cells (L) attacking a much larger tumor cell (Tu).
T Cells That Activate Macrophages
T-Regulatory Lymphocytes
QUICK CHECK 6-3
PEDIATRIC CONSIDERATIONS
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.
GERIATRIC CONSIDERATIONS
DID YOU UNDERSTAND?
Third Line of Defense: Adaptive Immunity
Antigens and Immunogens
Humoral Immune Response
Cell-Mediated Immunity
Immune Response: B Cells and T Cells Together
Pediatric considerations: Age-Related Factors Affecting Mechanisms of Self-Defense in the Newborn Child
Geriatric considerations: Age-Related Factors Affecting Mechanisms of Self-Defense in the Elderly
KEY TERMS
References
Chapter 7 Infection and Defects in Mechanisms of Defense
Infection
HEALTH ALERT
Microorganisms and Humans: A Dynamic Relationship
TABLE 7-1 NORMAL INDIGENOUS FLORA OF THE HUMAN BODY
BOX 7-1 THE MANY RELATIONSHIPS BETWEEN HUMANS AND MICROORGANISMS
TABLE 7-2 CLASSES OF ORGANISMS INFECTIOUS TO HUMANS
Classes of Infectious Microorganisms
TABLE 7-3 EXAMPLES OF MICROOrGANISMS THAT CAUSE TISSUE DAMAGE
TABLE 7-4 EXAMPLES OF MECHANISMS USED BY PATHOGENS TO RESIST THE IMMUNE SYSTEM
Pathogenic Defense Mechanisms
Infection and Injury
Bacterial Disease
FIGURE 7-1 General Structure of Bacteria. A, The structure of the bacterial cell wall determines its staining characteristics with gram stain. A gram-positive bacterium has a thick layer of peptidoglycan (left). A gram-negative bacterium has a thick peptidoglycan layer and an outer membrane (right)B, Example of a gram-positive (darkly stained microorganisms, arrow) group A Streptococcus. This microorganism consists of cocci that frequently form chains. C, Example of a gram-negative (pink microorganisms, arrow) Neisseria meningitides in cerebrospinal fluid. Neisseria form complexes of two cocci (diplococci).
TABLE 7-5 EXAMPLES OF COMMON BACTERIAL INFECTIONS
Viral Disease
Viral replication
FIGURE 7-2 Stages of Viral Infection of a Host Cell. The virion (1) becomes attached to the cell’s plasma membrane by absorption; (2) releases enzymes that weaken the membrane and allow it to penetrate the cell; (3) uncoats itself; (4) replicates; and (5) matures and escapes from the cell by budding from the plasma membrane. The infection then can spread to other host cells.
Cellular effects of viruses
TABLE 7-6 EXAMPLES OF HUMAN DISEASES CAUSED BY SPECIFIC VIRUSES
Fungal Disease
FIGURE 7-3 Morphology of Fungi. (A) Fungi may be either mold or yeast forms, or dimorphic. (B) Photograph showing Candida albicans with both the mycelial and the yeast forms. (C) Oral infection with C. albicans (candidiasis, i.e., thrush). (D) Gram stain of sputum showing that clinical isolates of C. albicans present as chains of elongated budding yeasts (× 1000).
TABLE 7-7 COMMON PATHOGENIC FUNGI
Parasitic Disease
TABLE 7-8 EXAMPLES OF PARASITES THAT ARE IMPORTANT IN HUMANS
Clinical Manifestations of Infection
Countermeasures Against Pathogenic Defenses
TABLE 7-9 REDUCTION IN VACCINE-PREVENTABLE DISEASES IN THE UNITED STATES
Antimicrobials
TABLE 7-10 CHEMICALS OR ANTIMICROBIALS IDENTIFIED THAT PREVENT GROWTH OF OR DESTROY MICROORGANISMS
HEALTH ALERT
Vaccines
QUICK CHECK 7-1
Deficiencies in Immunity
Initial Clinical Presentation
Primary (Congenital) Immune Deficiencies
TABLE 7-11 EXAMPLES OF PRIMARY IMMUNE DEFICIENCIES
B Lymphocyte Deficiencies
T Lymphocyte Deficiencies
Combined Deficiencies
FIGURE 7-4 Facial Anomalies Associated With DiGeorge Syndrome. Note the wide-set eyes, low-set ears, and shortened structure of the upper lip.
Complement Deficiencies
Phagocytic Deficiencies
Secondary (Acquired) Immune Deficiencies
Evaluation and Care of Those With Immune Deficiency
BOX 7-2 SOME CONDITIONS KNOWN TO BE ASSOCIATED WITH ACQUIRED IMMUNE DEFICIENCIES
Normal Physiologic Conditions
Psychologic Stress
Dietary Insufficiencies
Malignancies
Physical Trauma
Medical Treatments
Other Diseases or Genetic Syndromes
TABLE 7-12 LABORATORY EVALUATION OF IMMUNE DEFICIENCIES
Replacement Therapies for Immune Deficiencies
FIGURE 7-5 The Structure and Genetic Map of HIV-1. The HIV-1 virion consists of a core of two identical strands of viral RNA molecules of viral enzymes (reverse transcriptase [RT], protease [PR], integrase [IN]) encoated in a core capsid structure consisting primarily of the structural viral protein p24. The capsid is further encased in a matrix consisting primarily of viral protein p17. The outer surface is an envelope consisting of the plasma membrane of the cell from which the virus budded (lipid bilayer) and two viral glycoproteins: a transmembrane glycoprotein, gp41, and a noncovalently attached surface protein, gp120. The HIV-1 genome contains regions that encode the structural proteins (gag), the viral enzymes (pol), and the envelope proteins (env). The genome of complex retroviruses, like HIV-1, often contains a variety of small regions that regulate expression of the virus.
Acquired Immunodeficiency Syndrome (AIDS)
Epidemiology of AIDS
Pathogenesis of AIDS
Clinical Manifestations of AIDS
HEALTH ALERT
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
FIGURE 7-6 Life Cycle and Possible Sites of Therapeutic Intervention of Human Immunodeficiency Virus (HIV). The HIV virion consists of a core of two identical strands of viral RNA encoated in a protein structure with viral proteins gp41 and gp120 on its surface (envelope). HIV infection begins when a virion binds to CD4 and chemokine co-receptors on a susceptible cell and follows the process described here. The provirus may remain latent in the cell’s DNA until it is activated (e.g., by cytokines). The HIV life cycle is susceptible to blockage at several sites (see the text for further information), including entrance inhibitors, reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors.
FIGURE 7-7 Typical Progression from HIV Infection to AIDS in Untreated Persons. A, Clinical progression begins within weeks after infection; the person may experience symptoms of acute HIV syndrome. During this early period, the virus progressively infects T cells and other cells and spreads to the lymphoid organs, with a sharp decrease in the number of circulating CD4+ T cells. During a period of clinical latency, the virus replicates and T cell destruction continues, although the person is generally asymptomatic. The individual may develop HIV-related disease (constitutional symptoms)—a variety of symptoms of acute viral infection that do not involve opportunistic infections or malignancies. When the number of CD4+ cells is critically suppressed, the individual becomes susceptible to a variety of opportunistic infections and cancers with a diagnosis of AIDS. The length of time for progression from HIV infection to AIDS may vary considerably from person to person. B, Laboratory tests are changing throughout infection. Antibody and Tc cell (cytotoxic T lymphocytes [CTLs]) levels change during the progression to AIDS. During the initial phase antibodies against HIV-1 are not yet detectable (window period), but viral products, including proteins and RNA, and infectious virus may be detectable in the blood a few weeks after infection. Most antibodies against HIV are not detectable in the early phase. During the latent phase of infection antibody levels against p24 and other viral proteins, as well as HIV-specific CTLs, increase, and then remain constant until the development of AIDS.
BOX 7-3 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 of AIDS
FIGURE 7-8 Clinical Symptoms of AIDS. A, Severe weight loss and anorexia. B, Kaposi sarcoma lesions. C, Perianal lesions of herpes simplex infection. D, Deterioration of vision from cytomegalovirus retinitis leading to areas of infection, which can lead to blindness.
Pediatric AIDS and Central Nervous System Involvement
HEALTH ALERT
QUICK CHECK 7-2
Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
TABLE 7-13 RELATIVE INCIDENCE AND EXAMPLES OF HYPERSENSITIVITY DISEASES*
TABLE 7-14 EXAMPLES OF AUTOIMMUNE DISORDERS
Mechanisms of Hypersensitivity
Type I: IgE-Mediated Hypersensitivity Reactions
Mechanisms of IgE-mediated hypersensitivity
Clinical manifestations of IgE-mediated hypersensitivity
FIGURE 7-9 Mechanism of Type I, IgE-Mediated Reactions. First exposure to an allergen leads to antigen processing and presentation of antigen by an antigen-presenting cell (APC) to B lymphocytes, which is under the direction of T-helper 2 (Th2) cells. Th2 cells produce specific cytokines (e.g., IL-4, IL-13, and others) that favor maturation of the B lymphocytes into plasma cells that secrete IgE. The IgE is adsorbed to the surface of the mast cell by binding with IgE-specific Fc receptors. When an adequate amount of IgE is bound the mast cell is sensitized. During a reexposure, the allergen cross-links the surface-bound IgE and causes degranulation of the mast cell. Contents of the mast cell granules, primarily histamine, induce local edema, smooth muscle contraction, mucous secretion, and other characteristics of an acute inflammatory reaction.
TABLE 7-15 IMMUNOLOGIC MECHANISMS OF TISSUE DESTRUCTION
Evaluation and treatment of IgE hypersensitivity
FIGURE 7-10 Type I Hypersensitivity Reactions. Manifestations of allergic reactions as a result of type I hypersensitivity include pruritus, angioedema (swelling caused by exudation), edema of the larynx, urticaria (hives), bronchospasm (constriction of airways in the lungs), hypotension (low blood pressure), and dysrhythmias (irregular heartbeat) because of anaphylactic shock, and gastrointestinal cramping caused by inflammation of the gastrointestinal mucosa. Photographic inserts show a diffuse allergic-like eye and skin reaction on an individual. The skin lesions have raised edges and develop within minutes or hours, with resolution occurring after about 12 hours.
TABLE 7-16 CAUSES OF CLINICAL ALLERGIC REACTIONS
Type II: Tissue-Specific Hypersensitivity Reactions
Type III: Immune Complex–Mediated Hypersensitivity Reactions
Mechanisms of type III hypersensitivity
Immune complex disease
FIGURE 7-11 Mechanisms of Type II, Tissue-Specific Reactions. Antigens on the target cell bind with antibody and are destroyed or prevented from functioning by one of the following mechanisms: (A) complement-mediated lysis (an erythrocyte target is illustrated here); (B) clearance (phagocytosis) by macrophages in the tissue; (C) neutrophil-mediated immune destruction; (D) antibody-dependent cell-mediated cytotoxicity (ADCC) (apoptosis of target cells is induced by natural killer [NK] cells by two mechanisms: by the release of granzymes and perforin, which is a molecule that creates pores in the plasma membrane, and enzymes [granzymes] that enter the target through the perforin pores; by the interactions of Fas ligand [FasL; a molecule similar to TNF-α] on the surface of NK cells with Fas [the receptor for FasL] on the surface of target cells); or (E) modulation or blocking of the normal function of receptors by antireceptor antibody. This example of mechanism (E) depicts myasthenia gravis in which acetylcholine receptor antibodies block acetylcholine from attaching to its receptors on the motor end-plates of skeletal muscle, thereby impairing neuromuscular transmission and causing muscle weakness. C1, Complement component C1; C3b, complement fragment produced from C3, which acts as an opsonin; C5a, complement fragment produced from C5, which acts as a chemotactic factor for neutrophils; Fcγ receptor, cellular receptor for the Fc portion of IgG; FcR, Fc receptor.
FIGURE 7-12 Mechanism of Type III, Immune Complex–Mediated Reactions. Immune complexes form in the blood from circulating antigen and antibody. Both small and large immune complexes are removed successfully from the circulation and do not cause tissue damage. Intermediate-sized complexes are deposited in certain target tissues in which the circulation is slow or filtration of the blood occurs. The complexes activate the complement cascade through C1 and generate fragments including C5a and C3b. C5a is chemotactic for neutrophils, which migrate into the inflamed area and attach to the IgG and C3b in the immune complexes. The neutrophils attempt unsuccessfully to phagocytose the tissue and in the process release a variety of degradative enzymes that destroy the healthy tissues. Fcγ receptor is the cellular receptor for the Fc portion of IgG.
Type IV: Cell-Mediated Hypersensitivity Reactions
FIGURE 7-13 Mechanism of Type IV, Cell-Mediated Reactions. Antigens from target cells stimulate T cells to differentiate into T-cytotoxic cells (Tc cells), which have direct cytotoxic activity, and T-helper cells (Th1 cells) involved in delayed hypersensitivity. The Th1 cells produce lymphokines (especially interferon-γ [IFNγ]) that activate the macrophage through specific receptors (e.g., IFNγ receptor [IFNγR]). The macrophages can attach to targets and release enzymes and reactive oxygen species that are responsible for most of the tissue destruction.
FIGURE 7-14 Development of Allergic Contact Dermatitis. A, The development of allergy to poison ivy. The first (primary) contact with allergen sensitizes (produces reactive T cells) the individual but does not produce a rash (dermatitis). Secondary contact activates a type IV cell-mediated reaction that causes dermatitis. B, Contact dermatitis caused by a delayed hypersensitivity reaction leading to vesicles and scaling at the sites of contact.
QUICK CHECK 7-3
Antigenic Targets of Hypersensitivity Reactions
Allergy
Allergens
Allergic disease: bee sting allergy
Autoimmunity
Breakdown of tolerance
Autoimmune disease: systemic lupus erythematosus
Alloimmunity
Alloantigens
Alloimmune disease: transfusion reactions
ABO system
Rh system
Alloimmune disease: transplant rejection
Major histocompatibility complex
FIGURE 7-15 ABO Blood Types. This figure shows the relationship of antigens and antibodies associated with the ABO blood groups. The surfaces of erythrocytes of individuals with blood group O have a core carbohydrate that is present on cells of all ABO blood groups (H antigen). The sera of blood group O individuals contain IgM antibodies against both A and B carbohydrates. In individuals of the blood group A, some of the H antigens have been modified into A antigens. The sera of these individuals have IgM antibodies against the B antigen. In individuals with blood group B, some of the H antigens have been modified into B antigens. These individuals have IgM antibodies against the A antigen in their sera. In individuals of the blood group AB, some of the H antigens have been modified into both the A and B antigens. These individuals do not have antibody to either A or B antigens.
FIGURE 7-16 Human Leukocyte Antigens (HLAs). The major histocompatibility complex (MHC) is located on chromosome 6 and contains genes that code for class I antigens, class II antigens, and class III proteins (i.e., complement proteins and cytokines).
Transplantation
FIGURE 7-17 Inheritance of HLA. HLA alleles are inherited in a co-dominant fashion; both maternal and paternal antigens are expressed. Specific HLA alleles are commonly given numbers to indicate different antigens. In this example, the mother has linked genes for HLA-A3 and HLA-B12 on one chromosome 6 and genes for HLA-A10 and HLA-B5 on the second chromosome 6. The father has HLA-A28 and HLA-B7 on one chromosome and HLA-A1 and HLA-B35 on the second chromosome. The children from this pairing may have one of four possible combinations of maternal and paternal HLA.
Transplant rejection
QUICK CHECK 7-4
DID YOU UNDERSTAND?
Infection
Deficiencies in Immunity
Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity
KEY TERMS
References
Chapter 8 Stress and Disease
Historical Background and General Concepts
FIGURE 8-1 Physiologic and Behavioral Stress Responses. Stress processes arise from bidirectional communication patterns between the brain and other physiologic systems (autonomic, immune, neural, and endocrine). Importantly, these bidirectional mechanisms are protective, promoting short-term adaptation (allostasis). Chronic stress mechanisms, however, can lead to long-term dysregulation and promote behavioral responses and physiologic responses that lead to stress-induced disorders/diseases (allostatic load), compromising health.
FIGURE 8-2 The Alarm Reaction. The alarm reaction includes increased secretion of glucocorticoids (cortisol) by the adrenal cortex and increased secretion of epinephrine and small amounts of norepinephrine from the adrenal medulla. The response to the release of cortisol and sympathetic nerve activation is summarized in Figure 8-3. ACTH, Adrenocorticotropic hormone.
FIGURE 8-3 The Stress Response.
FIGURE 8-4 Hypothalamic-Pituitary-Adrenal (HPA) Axis. The response to stress begins in the brain. The hypothalamus is the control center in the brain for many hormones including corticotropin-releasing hormone (CRH).
Stress Overview: Multiple mediators and systems
TABLE 8-1 EXAMPLES OF STRESS-RELATED DISEASES AND CONDITIONS
FIGURE 8-5 Stress Interactions Are Nonlinear and Complex. Nonlinearity means that when one mediator is increased or decreased, the subsequent compensatory changes in other mediators depend on time and level of change, causing multiple interacting variables. The inevitable consequences from adapting to daily life over time include changes in behavioral responses. For example, these changes include sleeping patterns, smoking, alcohol consumption, physical activity, and social interactions. These behavioral patterns are a part of the allostatic overload with chronic elevations in cortisol level, sympathetic activity, and levels of proinflammatory cytokines, and a decrease in parasympathetic activity.
QUICK CHECK 8-1
The Stress Response
Neuroendocrine Regulation
Catecholamines
TABLE 8-2 PHYSIOLOGIC EFFECTS OF CATECHOLAMINES*
Glucocorticoids: Cortisol
HEALTH ALERT
TABLE 8-3 PHYSIOLOGIC EFFECTS OF CORTISOL
HEALTH ALERT
Stress, Inflammation, Obesity, and Type 2 Diabetes. The induction of reactive oxygen species (ROS) generation and inflammation through the proinflammatory transcription factor, NF-κβ, activates most proinflammatory genes. Macronutrient intake, obesity, free fatty acids, infection, smoking, psychologic stress, and genetic factors increase the production of ROS. Interference with insulin signaling (insulin resistance) leads to hyperglycemia and proinflammatory changes. Proinflammatory changes increase levels of TNF-α and IL-6, and also lead to the inhibition of insulin signaling and insulin resistance. Inflammation in pancreatic β cells leads to β cell dysfunction, which in combination with insulin resistance leads to type 2 diabetes. CRP, C-reactive protein.
FIGURE 8-6 Effect of Corticotropin-Releasing Hormone (CRH)–Mast Cell–Histamine Axis, Cortisol, and Catecholamines on the Th1/Th2 Balance—Innate and Adaptive Immunity. Adaptive immunity provides protection against multicellular parasites, extracellular bacteria, some viruses, soluble toxins, and allergens. Innate immunity provides protection against intracellular bacteria, fungi, protozoa, and several viruses. Type 1 cytokines or proinflammatory cytokines include IL-12, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). Type 2 cytokines or anti-inflammatory cytokines include IL-10 and IL-4. Solid lines (black) represent stimulation, whereas dashed lines (blue) represent inhibition (i.e., Th1 and Th2 are mutually inhibitory, IL-12 and IFN-γ inhibit Th2, and vice versa; IL-4 and IL-10 inhibit Th1 responses). Stress and CRH modulate inflammatory/immune and allergic responses by stimulating cortisol (glucocorticoid), catecholamines, and peripheral (immune) CRH secretion and by changing the production of regulatory cytokines and histamines. CRH (peripheral, immune), corticotropin-releasing hormone; NE, norepinephrine; Th, helper T cell; IL, interleukin; Tc, cytotoxic T cell; NK, natural killer cell; dashed lines, decreased (inhibited); solid lines, increased (stimulation).
Parasympathetic System
Other Hormones
TABLE 8-4 OTHER HORMONES THAT INFLUENCE THE STRESS RESPONSE
Role of the Immune System
FIGURE 8-7 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
Myocardial Ischemia
Left Ventricular Dysfunction
Ventricular Dysrhythmias
HEALTH ALERT
Coping
FIGURE 8-8 Health Outcome Determination in Stressful Life Situations Is Moderated by Numerous Factors. Whether a life-challenged individual experiences distress or illness depends on the subject’s appraisal of the event and the coping strategies used during the stressful period. Models (A) and (B) reflect possible outcomes in stressed healthy and symptomatic individuals. Model (C) illustrates the dynamic clinical setting in which the diagnosis of a serious illness and subsequent medical interventions may be perceived as stressful challenges and have potentially detrimental influences on physical outcome.
GERIATRIC CONSIDERATIONS
QUICK CHECK 8-2
DID YOU UNDERSTAND?
Concepts of Stress
The Stress Response
Stress, Personality, Coping, and Illness
GERIATRIC CONSIDERATIONS: Aging & The Stress-Age Syndrome
KEY TERMS
References
UNIT 3 Cellular Proliferation: Cancer
Interactive Review – Unit 3
Chapter 9 Biology, Clinical Manifestations, and Treatment of Cancer
Cancer Terminology and Characteristics
TABLE 9-1 CHARACTERISTICS OF BENIGN VERSUS MALIGNANT TUMORS
Tumor Classification and Nomenclature
Benign and Malignant
Carcinoma in Situ
Classification of Tumors—Classic Histology and Modern Genetics
FIGURE 9-1 Loss of Cellular and Tissue Differentiation During the Development of Cancer. The cells of a benign neoplasm (B) resemble those of the normal colonic epithelium (A), in that they are columnar and have an orderly arrangement. Loss of some degree of differentiation is evident in that the neoplastic cells do not show much mucin vacuolization. Cells of the well-differentiated malignant neoplasm (C) of the colon have a haphazard arrangement, and although gland lumina are formed they are architecturally abnormal and irregular. Nuclei vary in shape and size, especially when compared with (A). Cells in the poorly-differentiated malignant neoplasm (D) have an even more haphazard arrangement, with very poor formation of gland lumina. Nuclei show greater variation in shape and size compared with the well-differentiated malignant neoplasm in (C). Cells in anaplastic malignant neoplasms (E) bear no relation to the normal epithelium, with no recognizable gland formation. Tremendous variation is found in the size of cells and their nuclei, with very intense staining (hyperchromatic nuclei). Not knowing the site of origin makes it impossible to classify this tumor by microscopic appearance alone. Well-differentiated tumors often resemble their cell of origin, as shown in the example of a benign tumor of smooth muscles (F).
FIGURE 9-2 Progression from Normal to Neoplasm in the Uterine Cervix. A sequence of cellular and tissue changes progressing from low-grade to high-grade intraepithelial neoplasms (also called carcinoma in situ) and then to invasive cancer is seen often in the development of cancer. In this example of the early stages of cervical neoplastic changes, the presence of anaplastic cells and loss of normal tissue architecture signify the development of cancer. The high rate of cell division and the presence of local mutagens and inflammatory mediators all contribute to the accumulation of genetic abnormalities that lead to cancer.
BOX 9-1 TYPES OF GENETIC LESIONS IN CANCER
Tumor Markers
FIGURE 9-3 Molecular Markers Aid in Cancer Classification and Treatment Choices. A, Cancers can be classified based on gene expression patterns. In this breast cancer study, gene expression was measured in tumors from 115 patients. Each row is a different gene, and each column is a different patient sample. Red denotes high gene expression; green signifies low gene expression. Using this molecular subtyping method, breast cancer can be subdivided into at least four molecular subtypes—luminal A, luminal B, HER2, and basal. The group on the far right is normal breast tissue. B, Molecular classification predicts overall survival. In this group of women, breast cancer molecular subtypes were determined by gene expression profiles in a group of women with similar stage tumors, as in (A). The molecular subtype is a good predictor of response to chemotherapy and survival. This molecular subtyping method can help select the best therapy for women.
QUICK CHECK 9-1
TABLE 9-2 EXAMPLES OF TUMOR MARKERS
The Biology of Cancer Cells
Cancer Cells in the Laboratory
The Genetic Basis of Cancer
Cancer-Causing Mutations in Genes
FIGURE 9-4 Cancerous Cells Show Abnormal Growth in the Laboratory. Cancer cells, unlike most normal cells (A), usually continue to grow and accumulate on top of one another after they have formed a confluent monolayer in culture (loss of contact inhibition) and (B) can grow without being attached to a surface, called anchorage independence.
FIGURE 9-5 Clonal Proliferation Model of Neoplastic Progression in the Colon. During clonal proliferation, progressively altered populations of colon cells (colonocytes) arise over time. As genetic and epigenetic changes occur, different subclones (indicated by different color cells) coexist for a time. Clones that grow the fastest out-compete other clones, producing even more malignant, and abnormal-appearing, growths. The sequential accumulation of mutations has been well studied in the progression from a normal colon cell to a benign intestinal polyp to a malignant colon cancer. One of the earliest mutations in colon cancer is loss of the tumor-suppressor gene APC. Additional mutations (often in the oncogene RAS), activation of COX-2, and loss of the tumor suppressors DCC and TP53 occur as the lesion progresses from a benign polyp to an invasive carcinoma. APC, Adenomatous polyposis coli; COX-2, cyclooxygenase-2; DCC, deleted in colon cancer; TP53, p53 gene.
Clonal selection
FIGURE 9-6 Marked Increases in Cancer With Age. The incidence of cancer increases exponentially with advancing age. For example, this graph depicts the number of cases of colon cancer diagnosed per 100,000 women in England and Wales in 1 year. Similar data are seen for other cancers, and in men as well. These data suggest that stepwise accumulation of genetic and epigenetic alterations over time increases the risk of developing cancer. The slope of the curve predicts that five to seven mutations must accumulate before full-blown cancer develops.
TABLE 9-3 COMPARISON OF CANCER GENE TYPES
Oncogenes and Tumor-Suppressor Genes: Accelerators and Brakes
Passengers and drivers
What are the driver mutations?
QUICK CHECK 9-2
What Types of Changes in Genes Actually Occur in Cancer?
Mutation of normal genes into oncogenes
Point mutations
Chromosome translocations and copy number variation
FIGURE 9-7 Many Growth Factors Signal Through the RAS Protein. When a normal cell is stimulated through a growth factor receptor, inactive (GDP-bound) RAS is activated to a GTP-bound state. Activated RAS sends growth signals to the nucleus through cytoplasmic kinases, starting with the activation of kinase RAF. The mutant RAS protein is permanently activated because of its inability to hydrolyze GTP, leading to continual stimulation of the cell without any external trigger. GAP, GTPase-activating protein; GDP, guanosine diphosphate; GTP, guanosine triphosphate; MAPK, mitogen-activated protein kinase.
FIGURE 9-8 Oncogene Activation Mechanisms. Cellular genes may become cancerous oncogenes as a result of (A) point mutations that alter one or a few nucleotide base pairs, causing the production of a protein that is activated as a result of the altered sequence (e.g., RAS); (B) amplification of the cellular gene, resulting in higher levels of protein expression (e.g., MYCN in neuroblastoma); or (C) chromosomal translocations that either (1) lead to the juxtaposition of a strong promoter, causing increased protein expression (MYC in Burkitt lymphoma), or (2) produce a novel fusion protein that is derived from gene fragments normally present on different chromosomes (BCR-ABL in chronic myeloid leukemia).
FIGURE 9-9 N-myc Gene Amplification in Neuroblastoma. The N-myc gene is detected in human neuroblastoma cells using a technique called FISH (fluorescent in situ hybridization). (A) A single pair of N-myc genes are detected in normal cells and in low-grade neuroblastoma. (B) Multiple, amplified copies of the N-myc gene are detected in some cases of neuroblastoma. Amplification of the N-myc gene is strongly associated with a poor prognosis in childhood neuroblastoma.
Gene amplification
Tumor-suppressor genes
TABLE 9-4 SOME FAMILIAL CANCER SYNDROMES CAUSED BY TUMOR-SUPPRESSOR GENE FUNCTION LOSS
QUICK CHECK 9-3
Loss of heterozygosity
FIGURE 9-10 Silencing Tumor-Suppressor Genes. Tumor-suppressor genes can be deactivated by a variety of mechanisms. (A) In this example, the first hit is a point mutation in a tumor-suppressor gene (white box), followed by either epigenetic silencing or chromosome loss of the second allele (red box). (B) Genes can normally be silenced by a variety of interacting processes including DNA methylation, histone modification, nucleosomal remodeling, and microRNA changes (not shown). A number of cellular enzymes contribute to these modifications, including DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and complex nucleosomal remodeling factors (NURFs). Gene silencing is essential for normal development and differentiation. (C) Histone modification and promoter methylation regulate gene expression. Genes are transcribed when chromatin is modified by addition of acetyl (Ac) groups to specific lysine groups in histones. Gene expression can be turned off when specific acetyl groups are removed (by HDACs) or when the CpG-rich promoter regions of genes are modified by direct DNA methylation (by DNA methyltransferase). In addition, small endogenous RNA molecules (microRNAs or miRNA) can bind to mRNA and reduce gene expression. (D) Changes in promoter methylation turn cancer genes off and on. Oncogenes can be turned on by promoter hypomethylation, and tumor-suppressor genes can be turned off by promoter hypermethylation. Each of these changes can produce selective growth and survival advantages for the cancer cell. TF, Transcription factor; Me, methylation.
Turning off genes without mutation
Epigenetic silencing
MicroRNAs, oncomirs, and non–coding RNAs
Guardians of the Genome
QUICK CHECK 9-4
Genetics and Cancer-Prone Families
Types of Genes Misregulated in Cancer
Alterations in Progrowth and Antigrowth Signals
FIGURE 9-11 A Familial Colon Cancer Pedigree. Darkened symbols represent individuals diagnosed with colon cancer. One of the individuals in the first generation must have carried a mutation in the APC gene. Squares, Males; circles, females; filled circles, diagnosed with colon cancer.
FIGURE 9-12 The Hallmarks of Cancer. Cancers acquire alterations in specific pathways during their evolution. The six key pathways that must be altered are shown at the top of the circle, and supporting pathways are shown at the bottom of the circle. Mutation in key genes often alters several pathways; for example, p53 mutations alter both angiogenesis and evasion of apoptosis. = Inhibits.
Angiogenesis
QUICK CHECK 9-5
Telomeres and Unlimited Replicative Potential
FIGURE 9-13 Tumor-Induced Angiogenesis. Malignant tumors secrete angiogenic factors and tissue-remodeling matrix metalloproteinases (MMPs) that actively induce formation of new blood vessels. New blood vessels are formed from both local endothelial cells and circulating precursor cells recruited from the bone marrow. Circulating platelets can also release regulatory proteins into the tumor. bFGF and bFGFR, Basic fibroblast growth factor and its receptor, respectively; MMPs, matrix metalloproteases; PDGF and PDGFR, platelet-derived growth factor and its receptor, respectively; VEGF and VEGFR, vascular endothelial growth factor and its receptor, respectively.
Cancer Metabolism
FIGURE 9-14 Control of Immortality: Telomeres and Telomerase Normal adult somatic cells cannot divide indefinitely because the ends of their chromosomes are capped by telomeres. In the absence of the telomerase enzyme, telomeres become progressively shorter with each division until, when they are critically short, they signal to the cell to stop dividing. In germ cells, adult stem cells, and cancer cells the telomerase gene is “switched on,” producing an enzyme that rebuilds the telomeres. Thus, like germ cells, the cancer cell becomes immortal and able to divide indefinitely without losing its telomeres.
Oncogene Addiction
FIGURE 9-15 Cancers Have Altered Metabolism. Normal tissues use oxidative phosphorylation (OXPHOS) to turn glucose into CO2 and energy (in the form of ATP). Cancers take a different approach; even in the presence of oxygen, they do not use OXPHOS. Instead, they consume large quantities of glucose to make cellular building blocks, supporting rapid proliferation.
FIGURE 9-16 The Intense Glucose Requirement of Cancer Aids in Diagnosis. This 54-year-old woman had a non–small cell lung cancer (NSCLC) surgically removed. Five years later, these images were obtained. The positron emission tomography (PET) scan using 18F-deoxyglucose shows metastatic lesions in the brain, right shoulder, and mediastinal and cervical lymph nodes as well as the liver, left pelvis, and proximal femur. (Left) PET whole-body image. (Right) Representative coronal image from the whole-body FDG-PET/CT–fused image of the same patient. The fused image consists of the CT image with the metabolic information superimposed in color. The pattern of distribution is most likely from the primary tumor to the large mediastinal lymph nodes, followed by lymphatic spread to cervical lymph nodes. Blood-borne dissemination produced the bone, brain, and liver metastases. Normally, only the heart, brain, and bladder show a strong signal on PET scan. CT, Computed tomography; FDG, fluorodeoxyglucose.
Cancer Stem Cells
FIGURE 9-17 The Concept of Cancer Stem Cells. (A) Only rare cells within a cancer can initiate cancer regrowth. In laboratory experiments it takes as many as 100,000 breast cancer cells injected into a mouse mammary fat pad to form a new cancer. If the breast cancer cells are sorted, one rare subtype (shown here in red) is much more proficient at forming new cancers. (B) Conventional chemotherapy can destroy the bulk of a cancer. However, if the cancer stem cells (red cells) are not destroyed, the cancer may regrow. If therapies can be devised that kill the cancer stem cells, then durable long-term responses may be achieved.
QUICK CHECK 9-6
Stroma-Cancer Interactions
FIGURE 9-18 Cancers Live in a Complex Microenvironment. Neoplastic cells produce angiogenic factors (cytokines and chemokines) that are mitogenic or chemoattractants, or both, for numerous types of stromal cells, including fibroblasts, bone marrow–derived cells (BMDCs), macrophages, mesenchymal stem cells (MSCs), and other inflammatory and immune cells. In return, these activated stroma cells secrete additional proteolytic enzymes and growth factors that stimulate the cancer cells and promote new blood vessel growth. This stromal reaction, which in the normal situation promotes wound healing, now stimulates tumor growth and promotes metastatic dissemination.
Inflammation, Immunity, and Cancer
The Immune System Protects Us Against Viral-Associated Cancers
TABLE 9-5 CHRONIC INFLAMMATORY CONDITIONS AND INFECTIOUS AGENTS ASSOCIATED WITH NEOPLASMS
Viral Causes of Cancer
Bacterial Cause of Cancer
QUICK CHECK 9-7
Cancer Invasion and Metastasis
FIGURE 9-19 Cancer Metastasis Requires a Complex Series of Events. Cancer cells must gain access to blood and lymphatic vessels, survive the trip to distant locations, move back into the tissues, and initiate a new tumor. Because each of these steps is required, the successful metastatic cell is rare compared with the huge numbers of cancer cells at the primary site. Consequently, metastasis usually only occurs late in cancer evolution.
Very Few Cells in a Cancer Have the Ability to Metastasize
Clinical Manifestations and Treatment of Cancer
Clinical Manifestations of Cancer
Diagnosis and Staging
HEALTH ALERT
TABLE 9-6 OBTAINING TISSUE—THE BIOPSY
Paraneoplastic Syndromes
FIGURE 9-20 Tumor Staging by the TNM System. Example of staging for breast cancer.
TABLE 9-7 PARANEOPLASTIC SYNDROMES
Pain
Fatigue
Cachexia
FIGURE 9-21 Cachexia. This severe form of malnutrition results in wasting and extensive loss of adipose tissue.
Anemia
Leukopenia and Thrombocytopenia
Infection
TABLE 9-8 FACTORS PREDISPOSING INDIVIDUALS WITH CANCER TO INFECTION
Gastrointestinal Tract
Hair and Skin
Treatment of Cancer
Chemotherapy
TABLE 9-9 EXAMPLES OF MOLECULAR-ERA ANTICANCER DRUGS
Radiation Therapy
Surgery
QUICK CHECK 9-8
DID YOU UNDERSTAND?
Cancer Terminology and Characteristics
The Biology of Cancer Cells
Cancer Invasion and Metastasis
Clinical Manifestations and Treatment of Cancer
KEY TERMS
References
Chapter 10 Cancer Epidemiology
Genes, Environmental-Lifestyle Factors, and Risk Factors
TABLE 10-1 SUMMARY OF ENVIRONMENTAL AND OCCUPATIONAL LINKS WITH CANCER
BOX 10-1 ESTABLISHED ENVIRONMENTAL-LIFESTYLE FACTORS AND RISK OF CANCER
QUICK CHECK 10-1
Epigenetics and Genetics
FIGURE 10-1 Epigenetics, Genetics, Environment, and Cancer. Epigenetic mechanisms are affected by many factors and processes including development in utero and during childhood, diet, environmental chemicals, radiation, drugs/pharmaceuticals, and aging. DNA methylation occurs when methyl groups, an epigenetic factor found in some dietary sources, for example, can tag DNA and activate or repress genes. Histones are proteins around which DNA can wind for compaction and gene regulation. Histone modification occurs when the binding of epigenetic factors to histone “tails” alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated. All of these factors and processes can have an effect on and influence people’s health, possibly resulting in cancer, autoimmune disease, mental disorders, diabetes, and other diseases.
TABLE 10-2 ESTIMATED NEW U.S. CANCER CASES AND DEATHS BY GENDER, 2010*
TABLE 10-3 DIFFERENCES BETWEEN MULTIGENERATIONAL AND TRANSGENERATIONAL PHENOTYPES
FIGURE 10-2 Fetal Vulnerability to External and Internal Environments. The fetus is particularly vulnerable to changes in the external and internal environments, which can have immediate and lifelong consequences. Such environmentally induced changes can occur at multiple levels, including molecular and behavioral. Ultimately these alterations may be epigenetic, inducing mitotically heritable alterations in gene expression without changing the DNA.
TABLE 10-4 SOMATIC VERSUS GERM CELL INHERITANCE
In Utero and Early Life Conditions
QUICK CHECK 10-2
Tobacco Use
Diet
FIGURE 10-3 Dietary Factors, DNA Methylation, and Cancer. Certain dietary factors (see Table 10-5) may supply methyl groups (+CH3) that can be donated through S-adenosylmethonine (SAM) to many acceptors in the cell (DNA, proteins, lipids, and metabolites). Donation and removal (demethylation) are affected by numerous enzymes, including DNA methyltransferase (DNMT). Increased DNMT activity occurs in many tumor cells. Hypermethylation can inhibit or silence tumor-suppressor genes (see Chapter 9) and DNA methylation inhibitors as anticancer agents and can block DNMT, thus reactivating tumor-suppressor genes. DNA hypomethylation can reactivate and mutate genes, including cancer-causing oncogenes. SAH, S-Adenosylhomocysteine.
FIGURE 10-4 Methylation of a Gene Region and Its Effect on Gene Transcription. (A) (Green circles) Unmethylated cytosine guanine dinuceotide (CpG) sites (a) and (black circles) methylated CpG sites. Methylation of exons (b, c) does not block gene transcription. Mosaic methylation of promoter CpG island also does not block transcription (d). However, dense methylation of promoter CpG islands completely blocks transcription, and is often associated with hypomethylation of downstream regions (e). (B) DNA methylation in normal and cancer cells. DNA methylation in normal cells (1). A hypomethylated promoter is related to gene expression. DNA methylation in cancer cells (2). Aberrant DNA hypermethylation in the promoter leads to gene silencing (muting) and tumor development. The DNA methylation process is catalyzed by the enymes DNA methyltransferases (DNMTs) by adding a methyl group (CH3) to the 5-position of the cystosine ring of CpG dinucleotides. (Green circles) Unmethylated cytosine guanine dinucleotide (CpG) sites; (black circles) hypermethylated CpG sites.
TABLE 10-5 RELATIONSHIP OF DIETARY FACTORS TO RISK OF MAJOR CANCERS*
Obesity
NUTRITION & DISEASE
Increase
Decrease
BOX 10-2 DIET AND CANCER KEY POINTS
HEALTH ALERT
FIGURE 10-5 Weight and Risk of Dying from Cancer. A, As a man’s body mass index (BMI) rises above the normal range (18.5 to 24.9), his risk of dying of colorectal, esophageal, kidney, and other cancers also rises. For example, the risk of dying from colorectal cancer is 10% higher for men who are overweight (BMI 25 to 29.9) than for men of normal or lower BMI. For the most obese men (BMI 35 or higher) the risk is almost double (84%). B, As a woman’s BMI rises above the normal range (18.5 to 24.9), her risk of dying of breast, kidney, uterine, and other cancers rises. For example, the risk of dying of breast cancer is 34% higher for women who are overweight. For the most obese women (BMI >40), the risk of dying from breast cancer is double. The risk of kidney cancer is almost five times higher, and the risk of uterine cancer is six times higher.
TABLE 10-6 WHO CLASSIFICATION OF BODY MASS INDEX (BMI)
Alcohol Consumption
FIGURE 10-6 Energy Balance, Lipid Metabolism, and Insulin Sensitivity and Tumor Development. In obesity, increased release from adipose tissue of free fatty acids (FFAs), tumor necrosis factor-alpha (TNF-α), and resistin and decreased release of adiponectin lead to insulin resistance and compensatory chronic hyperinsulinemia. Increased insulin levels ultimately lead to decreased liver synthesis and blood levels of insulin-like growth factor binding protein-1 (IGFBP1) and, theoretically, also decreased IGFBP1 synthesis locally in other tissues. Increased fasting levels of insulin in plasma are also correlated with decreased levels of IGFBP2 in the blood, leading to increased levels of bioavailable IGF-1. Insulin and IGF-1 signal through the insulin receptor (IR) and IGF-1 receptor (IGF1R) to stimulate cellular proliferation and inhibit apoptosis in many tissue types. These effects could promote tumor development.
Ionizing Radiation
FIGURE 10-7 Pie Chart Showing Sources of Exposure to Ionizing Radiation. Percent contribution of various sources of exposure to the total collective effective dose (1,870,000 person-Sv) and the total effective dose per individual in the U.S. population (6.2 mSv) for 2006. Percent values have been rounded to the nearest 1%, except those <1%. Sv, Sievert.
Radiation-Induced Cancer
FIGURE 10-8 NCRP estimates that 67 million CT scans (compared to 3 million in 1980), 18 million nuclear medicine procedures, and 17 million interventional fluoroscopy procedures, and 18 million nuclear medicine procedures were performed in the U.S. in 2006.
FIGURE 10-9 Free Radicals. Free radicals formed by water nearby and around DNA cause indirect effects. These effects have a short life of single free radicals. Oxygen can modify the reaction, enabling longer lifetimes of oxidative free radicals.
HEALTH ALERT
HEALTH ALERT
NCRP estimates that 67 million CT scans (compared to 3 million in 1980), 18 million nuclear medicine procedures, and 17 million interventional fluoroscopy procedures, and 18 million nuclear medicine procedures were performed in the U.S. in 2006.
Median Effective Radiation Dose for Each Type of CT Study
FIGURE 10-10 Bystander Response Mechanism. Inflammatory cytokines are strongly increased after exposure to ionizing radiation or oxidants. Membrane-associated cytokines, such as tumor necrosis factor-alpha (TNFα), activate intracellular kinases (messengers), which release nuclear factor κβ (NF-κβ). NF-κβ enters the nucleus and promotes transcription of cyclooxygenase-2 (COX-2) and induces nitric oxide synthase (iNOS) genes, which stimulate production of nitric oxide (NO). Mitochondrial damage promotes the production of hydrogen peroxide that easily crosses plasma membranes and is subjected to antioxidant removal. Activation of COX-2 provides a continuous supply of reactive radicals and cytokines propagating bystander signals through gap junctions or medium. H2O2, Hydrogen peroxide; IL, interleukin; OH, hydroxyl radical; ONOO, peroxynitrite anion; PG-E2, prostaglandin E2; ROS, reactive oxygen species; TGF, transforming growth factor; TNF, tumor necrosis factor; Trail, TNF-related apoptosis-inducing ligand.
BOX 10-3 THEORETIC MODELS TO UNDERSTAND LOW-DOSE RADIATION
Theoretic Models for Estimating Risk of Low-Dose Ionizing Radiation. Collective population dose is expressed as a person-rem (roentgen equivalent, man). Estimating a collective dose then enables an application of a “constant risk factor” to obtain a statistical estimate of the number of additional cancers (above background radiation) resulting from that exposure. These computations apply to low doses—low-dose rates only (A). Many propose the best fit is the linear no-threshold (LNT) model (B). The most common alternative to the LNT model is the linear-quadratic model. The quadratic term is the square of the dose. The linear term is equal to zero (C). The threshold model is a threshold below which there is no increase in cancer risk. Proponents of this model argue that because some toxic chemicals/materials exhibit such thresholds, radiation must also have a threshold. Their arguments are related to repair of the radiation damage caused by lower doses of radiation (D). Some evidence exists that low levels of radiation produce a higher level of risk per unit dose, which is called the supralinear model.
TABLE 10-7 CANCER INCIDENCE AND FATALITY (BEIR VII) ESTIMATES OF LOW-LEVEL RADIATION PER GENDER*
Carcinogenesis: Genomic Instability
FIGURE 10-11 Models of the Responses of Clonogenic Cells to Ionizing Radiation. Mutations and/or chromosomal aberrations are shown as filled circles and apparently normal cells as open circles. A, If a cell faithfully repairs DNA damage, then its clonal descendants will appear normal. B, If a cell is directly mutated by radiation, then all of its descendants will express the same mutation. C, Radiation-induced genomic instability is characterized by nonclonal effects in descendant cells.
Gap junction intercellular communication
Ultraviolet Radiation
FIGURE 10-12 Theoretic Scheme of Multistep Skin Carcinogenesis. Ultraviolet radiation (UVR), inflammation, and xenobiotics (see p. 262) lead to oxidative stress, resulting in direct DNA damage, protein oxidation, lipid peroxidation, and apoptosis. The protective mechanisms shown in red include apoptosis, DNA repair, and antioxidants. DMBA, Dimethylbenz[a]anthracene; ROS, reactive oxygen species; UVA, ultraviolet A; UVB, ultraviolet B.
Electromagnetic Radiation
FIGURE 10-13 Electromagnetic radiation from a cell phone can penetrate the skull. EMR from a cell phone can penetrate the skull and deposit energy 4 to 6 cm into the brain.132 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.
QUICK CHECK 10-3
Sexual and Reproductive Behavior: Human Papillomaviruses
HEALTH ALERT
Other Viruses and Microorganisms
Physical Activity
Chemicals and Occupational Hazards as Carcinogens
Air Pollution
BOX 10-4 KNOWN CARCINOGENIC AGENTS CLASSIFIED BY THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER (IARC)
Agents or Group of Agents
Mixtures
Exposure Circumstances
BOX 10-5 PROBABLE CARCINOGENIC AGENTS CLASSIFIED BY THE IARC
Agents and Group of Agents
Mixtures
Exposure Circumstances
BOX 10-6 NOTABLE OUTDOOR POLLUTANTS
QUICK CHECK 10-4
DID YOU UNDERSTAND?
Genes, Environmental-Lifestyle Factors, and Risk Factors
Epigenetics and Genetics
Tobacco Use
Diet
Obesity
Alcohol Consumption
Ionizing Radiation (IR)
Ultraviolet Radiation (UVR)
Electromagnetic Radiation (EMR)
Sexual and Reproductive Behavior
Physical Activity
Chemicals and Occupational Hazards
KEY TERMS
References
Chapter 11 Cancer in Children
Incidence and Types of Childhood Cancer
TABLE 11-1 CHILDHOOD AGE-ADJUSTED INVASIVE CANCER INCIDENCE RATES BY PRIMARY SITE AND AGE, UNITED STATES*
Etiology
Genetic Factors
TABLE 11-2 CHILDHOOD AGE-ADJUSTED CANCER INCIDENCE RATES FOR CHILDREN UP TO 19 YEARS OF AGE BY PRIMARY SITE AND RACE AND ETHNICITY, UNITED STATES*
TABLE 11-3 CONGENITAL FACTORS ASSOCIATED WITH CHILDHOOD CANCER
TABLE 11-4 SELECTED ONCOGENES AND TUMOR-SUPPRESSOR GENES ASSOCIATED WITH CHILDHOOD CANCER
TABLE 11-5 DRUGS THAT MAY INCREASE RISK OF CHILDHOOD CANCER
Environmental Factors
Prenatal Exposure
Childhood Exposure
HEALTH ALERT
Prognosis
QUICK CHECK 11-1
DID YOU UNDERSTAND?
Incidence and Types of Childhood Cancers
Etiology
Prognosis
KEY TERMS
References
PART II Body Systems and Diseases
UNIT 4 The Neurologic System
Interactive Review – Unit 4
Chapter 12 Structure and Function of the Neurologic System
Overview and Organization of the Nervous System
Cells of the Nervous System
The Neuron
FIGURE 12-1 Neuron With Composite Parts. Multipolar neuron: neuron with multiple extensions from the cell body.
FIGURE 12-2 Neuronal Transmission and Synaptic Cleft. Electrical impulse travels along axon of first neuron to synapse. Chemical transmitter is secreted into synaptic space to depolarize membrane (dendrite or cell body) of next neuron in pathway. Cell A represents pseudounipolar cell; cell B represents multipolar cell.
FIGURE 12-3 Types of Neuroglial Cells. Neuroglia of the CNS: A, Astrocytes attached to the outside of a capillary blood vessel in the brain. B, A phagocytic microglial cell. C, Ciliated ependymal cells forming a sheet that usually lines fluid cavities in the brain. D, An oligodendrocyte with processes that wrap around nerve fibers in the CNS to form myelin sheaths. Neuroglia of the peripheral nervous system (PNS): E, A Schwann cell supporting a bundle of nerve fibers in the PNS. F, Another type of Schwann cell encircling a peripheral nerve fiber to form a thick myelin sheath. G, Satellite cells, another type of Schwann cell, surround and support cell bodies of neurons in the PNS.
Neuroglia and Schwann Cells
TABLE 12-1 SUPPORT CELLS OF THE NERVOUS SYSTEM
Nerve Injury and Regeneration
The Nerve Impulse
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
Synapses
TABLE 12-2 SUBSTANCES THAT ARE NEUROTRANSMITTERS OR NEUROMODULATORS
Neurotransmitters
HEALTH ALERT
QUICK CHECK 12-2
The Central Nervous System
The Brain
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.
TABLE 12-3 DIVISIONS OF THE CENTRAL NERVOUS SYSTEM
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. This illustration shows which parts of the body are “mapped” to specific cortical areas. The exaggerated face indicates that more cortical area is devoted to processing information to and from the many receptors and motor units of the face than for the leg or arm, for example.
FIGURE 12-8 Examples of Somatic Motor and Sensory Pathways. A, Motor: pyramidal pathway illustrated by the lateral corticospinal tract and extrapyramidal pathways illustrated by the rubrospinal and reticulospinal tracts. B, Sensory: pathways of the medial lemniscal system that conducts information about discriminating touch and kinesthesis and the spinothalamic pathway that conducts information about pain and temperature.
FIGURE 12-9 Basal Nuclei. A, The basal nuclei seen through the cortex of the left cerebral hemisphere. B, The basal nuclei seen in a frontal (coronal) section of the brain.
Diencephalon
BOX 12-1 FUNCTIONS OF THE HYPOTHALAMUS
Midbrain
Mesencephalon
Hindbrain
Metencephalon
Myelencephalon
QUICK CHECK 12-3
The Spinal Cord
FIGURE 12-10 Spinal Cord Within Vertebral Canal and Exiting Spinal Nerves. A, Posterior view of brain stem and spinal cord in situ with spinal nerves and plexus. B, Lateral view of brain stem and spinal cord. C, Enlargement of caudal area showing termination of spinal cord (conus medullaris) and group of nerve fibers constituting the cauda equina.
FIGURE 12-11 Coverings of the Spinal Cord. The dura mater is shown in natural color. Note how it extends to cover the spinal nerve roots and nerves. The arachnoid is highlighted in blue and the pia mater in pink.
FIGURE 12-12 Major Tracts of the Spinal Cord. The major ascending (sensory) tracts, shown only on the left here, are highlighted in blue. The major descending (motor) tracts, shown only on the right, are highlighted in red.
FIGURE 12-13 Cross Section of Spinal Cord Showing Simple Reflex Arc.
FIGURE 12-14 Neuromuscular Junction. This figure shows how the distal end of a motor neuron fiber forms a synapse, or “chemical junction,” with an adjacent muscle fiber. Neurotransmitters (specifically, acetylcholine) are released from the neuron’s synaptic vesicles and diffuse across the synaptic cleft. There they stimulate receptors in the motor end-plate region of the sarcolemma.
Motor Pathways
Sensory Pathways
Protective Structures of the Central Nervous System
Cranium
Meninges
FIGURE 12-15 Flow of Cerebrospinal Fluid and Meninges of the Brain. A, The fluid produced by filtration of blood by the choroid plexus of each ventricle flows inferiorly through the lateral ventricles, interventricular foramen, third ventricle, cerebral aqueduct, fourth ventricle, and subarachnoid space to the blood. B, Meninges of the brain in relation to CSF and venous blood flow.
TABLE 12-4 COMPOSITION OF CEREBROSPINAL FLUID
Cerebrospinal Fluid and the Ventricular System
FIGURE 12-16 Vertebral Column. A, Right lateral view. B, Anterior view.
FIGURE 12-17 A, Lumbar Vertebra, Superior View; B, Intervertebral Disk.
Vertebral Column
QUICK CHECK 12-4
FIGURE 12-18 Major Arteries of the Head and Neck.
Blood Supply of the Central Nervous System
Blood Supply to the Brain
FIGURE 12-19 Arteries at the Base of the Brain. The arteries that compose the circle of Willis are the two anterior cerebral arteries, joined to each other by the anterior communicating artery and two short segments of the internal carotids, off of which the posterior communicating arteries connect to the posterior cerebral arteries.
FIGURE 12-20 Areas of the Brain Affected by Occlusion of the Anterior, Middle, and Posterior Cerebral Artery Branches. A, Inferior view. B, Lateral view.
TABLE 12-5 ARTERIAL SYSTEMS SUPPLYING THE BRAIN
Blood-Brain Barrier
Blood Supply to the Spinal Cord
The Peripheral Nervous System
FIGURE 12-21 Large Veins of the Head. Deep veins and dural sinuses are projected on the skull. Note two superficial veins in the face are tributaries that send blood through emissary veins in the skull foramen into deep veins inside the skull terminating in the internal jugular vein.
FIGURE 12-22 Blood-Brain Barrier. Cell membranes with tight junctions create a physical barrier between capillary blood and the cytoplasm of astrocytes.
FIGURE 12-23 Arteries of the Spinal Cord. A, Arteries of cervical cord exposed from the rear. B, Arteries of spinal cord diagrammatically shown in horizontal section.
QUICK CHECK 12-5
The Autonomic Nervous System
FIGURE 12-24 Cranial and Peripheral Nerves. A, Ventral surface of the brain showing attachment of the cranial nerves. B, Peripheral nerve trunk and coverings.
FIGURE 12-25 Locations of Neurotransmitters and Receptors of the Autonomic Nervous System. In all pathways, preganglionic fibers are cholinergic, secreting acetylcholine (Ach), which stimulates nicotinic receptors in the postganglionic neuron. Most sympathetic postganglionic fibers are adrenergic, A, secreting norepinephrine (NE), thus stimulating α- or β-adrenergic receptors. A few sympathetic postganglionic fibers are cholinergic, stimulating muscarinic receptors in effector cells, B, all parasympathetic postganglionic fibers are cholinergic, C, stimulating muscarinic receptors in effector cells.
TABLE 12-6 THE CRANIAL NERVES
Anatomy of the Sympathetic Nervous System
FIGURE 12-26 Sympathetic Division of the Autonomic Nervous System. CG, Celiac ganglion; CiG, ciliary ganglion; IMG, inferior mesenteric ganglion; OG, otic ganglion; PP, pelvic plexus; SCG, superior cervical ganglion; SG, submandibular ganglion; SMG, superior mesenteric ganglion; SpG, sphenopalatine ganglion.
Anatomy of the Parasympathetic Nervous System
Neurotransmitters and Neuroreceptors
FIGURE 12-27 Parasympathetic Division of the Autonomic Nervous System. CiG, Ciliary ganglion; OG, otic ganglion; PN, pelvic nerve; PP, pelvic plexus; SG, submandibular ganglion; SpG, sphenopalatine ganglion; VN, vagus nerve.
FIGURE 12-28 The Autonomic Nervous System and the Type of Neurotransmitters Secreted by Preganglionic and Postganglionic Fibers. Note that all preganglionic fibers are cholinergic (Ach). A somatic nerve is used for comparison.
FIGURE 12-29 Some Important Functions of the Sympathetic Nervous System. A, Regulation of vasomotor tone. B, Regulation of strenuous muscular exercise (“fight or flight” response).
TABLE 12-7 ACTIONS OF AUTONOMIC NERVOUS SYSTEM NEURORECEPTORS
Functions of the Autonomic Nervous System
QUICK CHECK 12-6
GERIATRIC CONSIDERATIONS
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
GERIATRIC CONSIDERATIONS: Aging & the Nervous System
KEY TERMS
References
Chapter 13 Pain, Temperature, Sleep, and Sensory Function
Pain
The Experience of Pain
Evolution of Pain Theories
Neuroanatomy of Pain
FIGURE 13-1 Gate Control Theory of Pain. Schematic diagram of the gate control theory of pain mechanism. Large A-beta (Aβ) fiber non-nociceptor impulses (i.e., mechanical and thermal) activate inhibitory interneuron in spinal cord dorsal horn and decrease pain transmission (close pain gate). Small fiber impulses block the inhibitory interneuron and promote pain transmission (open pain gate).
TABLE 13-1 STIMULI THAT ACTIVATE NOCICEPTORS (PAIN RECEPTORS)
Neuromodulation of Pain
FIGURE 13-2 Transmission of Pain Sensations. The Aδ and C fibers synapse in the laminae of the dorsal horn, crossover to the contralateral spinothalamic tract, and then ascend to synapse in the midbrain through the neospinothalamic and paleospinothalamic tracts. Impulses are then conducted to the sensory cortex.
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.
Clinical Descriptions of Pain
FIGURE 13-4 Sites of Referred Pain. A, Anterior view. B, Posterior view.
BOX 13-1 CATEGORIES OF PAIN
Pain Threshold and Pain Tolerance
TABLE 13-2 COMPARISON OF ACUTE AND CHRONIC PAIN
TABLE 13-3 COMMON CHRONIC PAIN CONDITIONS
QUICK CHECK 13-1
TABLE 13-4 PAIN PERCEPTION IN INFANTS, CHILDREN, AND ELDERLY PERSONS
Temperature Regulation
Control of Body Temperature
Temperature Regulation in Infants and Elderly Persons
Pathogenesis of Fever
TABLE 13-5 MECHANISMS OF HEAT PRODUCTION AND HEAT LOSS
Benefits of Fever
Disorders of Temperature Regulation
Hyperthermia
FIGURE 13-5 Production of Fever. Pathogens release exogenous pyrogens and activate monocytes/macrophages and other inflammatory cells that secrete endogenous pyrogenic cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon (IFN), which promote the synthesis and secretion of prostaglandin E2 (PGE2) in the anterior hypothalamus. PGE2 increases the thermostatic set point, and the autonomic nervous system is stimulated, resulting in shivering, muscle contraction, peripheral vasoconstriction, and the production of fever.
BOX 13-2 EFFECTS OF FEVER AT THE EXTREMES OF AGE
Elderly Persons
Children
Hypothermia
Trauma and Temperature
QUICK CHECK 13-2
Sleep
BOX 13-3 DEFINING CHARACTERISTICS OF HYPOTHERMIA
Accidental Hypothermia
Therapeutic Hypothermia
Sleep Disorders
Common Dyssomnias
Insomnia
Sleep disordered breathing and hypersomnia
BOX 13-4 SLEEP CHARACTERISTICS OF INFANTS AND ELDERLY PERSONS
Infants
Elderly Persons
Disorders of the sleep-wake schedule
Common Parasomnias
QUICK CHECK 13-3
The Special Senses
Vision
The Eye and Its External Structures
FIGURE 13-6 Internal Anatomy of the Eye.
Visual Dysfunction
Alterations in ocular movements
FIGURE 13-7 Extrinsic Muscles of the Right Eye.
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.
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
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.
Alterations in color vision
Neurologic disorders causing visual dysfunction
External Eye Structure Disorders
FIGURE 13-10 Visual Pathways and Defects.
Hearing
The Normal Ear
FIGURE 13-11 The Ear. External, middle, and inner ears. (Anatomic structures are not drawn to scale.)
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.
Auditory Dysfunction
GERIATRIC CONSIDERATIONS
Conductive hearing loss
Sensorineural hearing loss
Mixed and functional hearing loss
Ménière disease
Ear Infections
Otitis externa
Otitis media
FIGURE 13-13 Olfaction. Midsagittal section of the nasal area shows the location of major olfactory sensory structures.
Olfaction and Taste
GERIATRIC CONSIDERATIONS
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
Retinal Detachment (see video)
References
Chapter 14 Alterations in Cognitive Systems, Cerebral Hemodynamics, and Motor Function
Alterations In Cognitive Systems
Alterations in Arousal
Pathophysiology
TABLE 14-1 CLINICAL MANIFESTATIONS OF METABOLIC AND STRUCTURAL CAUSES OF ALTERED AROUSAL
Clinical Manifestations and Evaluation
TABLE 14-2 DIFFERENTIAL CHARACTERISTICS OF STATES CAUSING ALTERED AROUSAL
FIGURE 14-1 Abnormal Respiratory Patterns With Corresponding Level of Central Nervous System Activity.
FIGURE 14-2 Pupils at Different Levels of Consciousness.
TABLE 14-3 LEVELS OF ALTERED CONSCIOUSNESS
TABLE 14-4 PATTERNS OF BREATHING
FIGURE 14-3 Test for Oculocephalic Reflex Response (Doll’s Eyes Phenomenon). A, Normal response—eyes turn together to side opposite from turn of head. B, Abnormal response—eyes do not turn in conjugate manner. C, Absent response—eyes move in direction of head movement (brain stem injury).
QUICK CHECK 14-1
Outcomes of Alterations in Arousal
FIGURE 14-4 Test for Oculovestibular Reflex (Caloric Ice Water Test). A, Ice water is injected into the ear canal. Normal response—conjugate eye movements. B, Abnormal response—dysconjugate or asymmetric eye movements. C, Absent response—no eye movements.
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. Both sides. B, Decerebrate response. All four extremities in rigid extension, with hyperpronation of forearms and plantar extension of feet. C, Decorticate response on right side of body and decerebrate response on left side of body.
BOX 14-1 Criteria for Brain Death
Alterations in Awareness
HEALTH ALERT
Pathophysiology
Clinical Manifestations
Evaluation and treatment
TABLE 14-6 CLINICAL MANIFESTATIONS OF ALTERATIONS IN ATTENTION AND MEMORY
Seizure Disorders
Conditions Associated With Seizure Disorders
Types of seizure disorders
TABLE 14-7 CAUSES OF RECURRENT SEIZURES IN DIFFERENT AGE GROUPS
Clinical Manifestations
TABLE 14-8 INTERNATIONAL CLASSIFICATION OF EPILEPTIC SEIZURES
Evaluation and treatment
QUICK CHECK 14-2
FIGURE 14-7 Right Cortical, Subcortical, and Brain Stem Areas of the Brain Mediating Cognitive Function.
TABLE 14-9 TERMINOLOGY APPLIED TO A SEIZURE DISORDER
Data Processing Deficits
Agnosia
Dysphasia
Acute Confusional States
Pathophysiology
Clinical Manifestations
Evaluation and treatment
QUICK CHECK 14-3
Dementia
Pathophysiology
TABLE 14-10 MAJOR TYPES OF DYSPHASIA
Clinical Manifestations
Evaluation and treatment
TABLE 14-11 EXAMPLES OF LANGUAGE DISTURBANCES
TABLE 14-12 DIFFERENCES BETWEEN ORGANIC AND FUNCTIONAL CONFUSION
Alzheimer Disease
TABLE 14-13 COMPARISON OF DELIRIUM AND DEMENTIA
Pathophysiology
Clinical Manifestations
FIGURE 14-8 Common Pathologic Findings in Alzheimer Disease. The middle panel represents coronal slices through the left brain.
TABLE 14-14 CLINICAL MANIFESTATIONS OF THE MAJOR DEGENERATIVE DEMENTIAS
Evaluation and treatment
HEALTH ALERT
TABLE 14-15 PROGRESSION OF ALZHEIMER DISEASE
Frontotemporal Dementia
Alterations in Cerebral Hemodynamics
Increased Intracranial Pressure
FIGURE 14-9 Clinical Correlates of Compensated and Uncompensated Phases of Intracranial Hypertension.
FIGURE 14-10 Herniation. Herniations can occur both above and below the tentorial membrane. Suprateneorial: 1, uncal (transtentorial); 2, central 3, cinculate 4, transcalvarial; infratentorial:5, upward, 6, cerebellar tonsillar.
Cerebral Edema
BOX 14-2 Herniation Syndrome
Supratentorial Herniation
Infratentorial Herniation
Hydrocephalus
FIGURE 14-11 Brain Edema. Intercellular lakes of high protein content fluid. (Hematoxylin-eosin stain; ×90.)
TABLE 14-16 TYPES OF HYDROCEPHALUS
Pathophysiology
Clinical Manifestations
Evaluation and treatment
QUICK CHECK 14-4
Alterations in Neuromotor Function
Alterations in Muscle Tone
Hypotonia
TABLE 14-17 ALTERATIONS IN MUSCLE TONE
Hypertonia
Alterations in Movement
FIGURE 14-12 Paroxysm of Left-Sided Hemifacial Spasm.
Paresis/Paralysis
FIGURE 14-13 Dystonic Posturing of the Hand and Foot.
FIGURE 14-14 Spasmodic Torticollis. A characteristic head posture.
TABLE 14-18 UPPER AND LOWER MOTOR NEURON SIGNS AND SYMPTOMS
Upper Motor Neuron Syndromes
FIGURE 14-15 Motor Function Syndromes. Disturbances in motor function are classified pathologically along upper and lower motor neuron structures. It should be noted that the same pathologic condition occurs at more than one site in an upper motor neuron (above right). A few pathologic conditions involve both upper and lower motor neuron structures, as in amyotrophic lateral sclerosis, for example. Other lesion sites include myoneural junction and primary muscle, making it possible to classify conditions as neuromuscular and muscular, respectively.
FIGURE 14-16 Structures of the Upper Motor Neuron, or Pyramidal, System. Pyramidal system fibers are shown to originate primarily in cells in precentral gyrus of motor cortex; to converge at internal capsule; to descend to form central third of cerebral peduncle; to descend further through pons, where small fibers supply cranial nerve motor nuclei along the way; to form pyramids at medulla, where most of the fibers decussate; and then to continue to descend in lateral column of white matter of spinal cord. A few fibers descend without crossing at medulla level (see Figure 12-8).
Lower Motor Neuron Syndromes
FIGURE 14-17 Structures Composing Lower Motor Neuron, Including Motor (Efferent) and Sensory (Afferent) Elements. (Top) Anterior horn cell (in anterior gray column of spinal cord and its axon), terminating in motor end-plate as it innervates extrafusal muscle fibers in quadriceps muscle. (Detailed enlargement) Sensory and motor elements of gamma loop system. Gamma efferent fibers shown innervating the muscle spindle (sensory receptor of skeletal muscle). Contraction of muscle spindle fibers stretches central portion of the spindle and causes the gamma afferent spindle fiber to transmit impulse centrally to cord. Muscle spindle gamma afferent fibers in turn synapse on the anterior horn cell and impulses are transmitted by way of alpha efferent fibers to skeletal (extrafusal) muscle, causing it to contract. Muscle spindle discharge is interrupted by active contraction of skeletal muscle fibers.
Amyotrophies
Hyperkinesia
Huntington Disease
HEALTH ALERT
Pathophysiology
TABLE 14-19 TYPES OF HYPERKINESIA AND TREMOR
Clinical Manifestations
Evaluation and treatment
Hypokinesia
Akinesia and bradykinesia
Loss of associated movement
Parkinson Disease
Pathophysiology
Clinical Manifestations
FIGURE 14-18 Pathophysiology of Parkinson Disease.
FIGURE 14-19 Stooped Posture of Parkinson Disease.
Evaluation and treatment
Alterations in Complex Motor Performance
Disorders of Posture (Stance)
Disorders of Gait
Disorders of Expression
FIGURE 14-20 Pathways Disrupted in Dyspraxias. Formulation of the idea of the motor act is thought to originate in the region of the supramarginal gyrus in the inferior left parietal lobe. This area is connected via associational pathways to the left premotor cortex. The left premotor cortex is connected through the corpus callosum to the right premotor and motor areas. An injury that interrupts the pathways between the left supramarginal gyrus and the premotor region produces a dyspraxia that involves the entire body. An injury that disrupts the callosal pathways produces a dyspraxia of the left side of the body only.
Extrapyramidal Motor Syndromes
QUICK CHECK 14-5
TABLE 14-20 PYRAMIDAL VS. EXTRAPYRAMIDAL MOTOR SYNDROME
DID YOU UNDERSTAND?
Alterations in Cognitive Systems
Alterations in Cerebral Hemodynamics
Alterations in Neuromotor Function
Alterations in Tone
Alterations in Movement
Alterations in Complex Motor Performance
Extrapyramidal Motor Syndromes
KEY TERMS
Generalized seizure (see video)
Alzheimer disease (see video)
Parkinson disease (see video)
References
Chapter 15 Disorders of the Central and Peripheral Nervous Systems and Neuromuscular Junction
Central Nervous System Disorders
Traumatic Brain and Spinal Cord Injury
Brain Trauma
TABLE 15-1 CAUSES OF BRAIN INJURIES
TABLE 15-2 SEVERITY OF TRAUMA RELATED TO TRAUMA STATE INDUCED AND ONSET AND PERSISTENCE OF CLINICAL MANIFESTATIONS
TABLE 15-3 CATEGORIES OF DIFFUSE BRAIN INJURY
Primary brain injury
Focal brain injury
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).
FIGURE 15-2 Brain Hematomas.
Diffuse brain injury
Secondary brain trauma
QUICK CHECK 14-1
Spinal Cord Trauma
Pathophysiology
FIGURE 15-3 Hyperextension Injuries of the Spine. Hyperextension injuries of the spine can result in fracture or nonfracture injuries with spinal cord damage.
FIGURE 15-4 Flexion Injury of the Spine. Hyperflexion produces translation (subluxation) of vertebrae that compromises the central canal and compresses spinal cord parenchyma or vascular structures.
FIGURE 15-5 Axial Compression Injuries of the Spine. In axial compression injuries of the spine, the spinal cord is contused directly by retropulsion of bone or disk material into the spinal canal.
FIGURE 15-6 Flexion-Rotation Injuries of the Spine.
TABLE 15-4 MECHANISMS OF VERTEBRAL INJURY INVOLVING BONE, LIGAMENTS, AND JOINTS
TABLE 15-5 SPINAL CORD INJURIES
Clinical Manifestations
TABLE 15-6 CLINICAL MANIFESTATIONS OF SPINAL CORD INJURY
FIGURE 15-7 Autonomic Hyperreflexia. A, Normal response pathway. B, Autonomic dysreflexia pathway. SA, Sinoatrial.
Evaluation and Treatment
Degenerative Disorders of the Spine
Degenerative Joint Disease (DJD)
Degenerative disk disease
Spondylolysis
Spondylolisthesis
Spinal stenosis
Low Back Pain
FIGURE 15-8 Herniated Nucleus Pulposus.
Pathogenesis
Evaluation and Treatment
Herniated Intervertebral Disk
Pathophysiology
Clinical Manifestations
FIGURE 15-9 Clinical Features of a Herniated Nucleus Pulposus.
Evaluation and Treatment
Cerebrovascular Disorders
Cerebrovascular Accidents (Stroke Syndromes)
Thrombotic stroke
Embolic stroke
Hemorrhagic stroke
Lacunar stroke
Pathophysiology
Cerebral infarction
Cerebral hemorrhage
Clinical Manifestations
Evaluation and Treatment
Intracranial Aneurysm
Pathophysiology
FIGURE 15-10 Types of Aneurysms.
FIGURE 15-11 Berry Aneurysm, Angiogram. In this lateral view with contrast filling a portion of the cerebral arterial circulation can be seen a berry aneurysm (arrow) involving the middle cerebral artery of the circle of Willis at the base of the brain.
Clinical Manifestations
Evaluation and Treatment
Vascular Malformation
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Subarachnoid Hemorrhage
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 14-2
TABLE 15-7 SUBARACHNOID HEMORRHAGE CLASSIFICATION SCALE
Headache
Migraine
TABLE 15-8 CHARACTERISTICS OF COMMON HEADACHES
Cluster Headache
Tension-type headache
Infection and Inflammation of the Central Nervous System
FIGURE 15-12 Viral Infection in the Central Nervous System (CNS). Viruses infect specific cell types within the CNS depending on the particular properties of the virus together with individual cell membrane proteins expressed on permissive cell types. Normally the brain is protected from circulating pathogens and toxins by the blood-brain barrier. CMV, Cytomegalovirus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV-1, human T cell lymphotropic virus (causes T cell leukemia); JCV, John Cunningham virus (a polyomavirus causing progressive multifocal leukoencephalopathy); SSPE, subacute sclerosing panencephalitis; VZV, varicella-zoster virus.
Meningitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Brain or Spinal Cord Abscess
Pathophysiology
Clinical Manifestations
FIGURE 15-13 Brain Abscess. Early brain abscess appearing as a poorly demarcated area (arrow) of cerebritis at the gray-white junction.
Evaluation and Treatment
Encephalitis
Pathophysiology
Clinical Manifestations
TABLE 15-9 CLASSIFICATION AND CHARACTERISTICS OF ARBOVIRUSES CAUSING ENCEPHALITIS
HEALTH ALERT
Evaluation and Treatment
Neurologic Complications of AIDS
Human immunodeficiency virus–associated dementia (HIV encephalopathy)
HIV myelopathy
HIV peripheral neuropathy
Aseptic viral meningitis
Opportunistic infections
CNS neoplasms
Other CNS complications
Demyelinating Degenerative Disorders
Multiple Sclerosis
Pathophysiology
FIGURE 15-14 Pathogenesis of Multiple Sclerosis.
Clinical Manifestations
Evaluation and Treatment
HEALTH ALERT
Amyotrophic Lateral Sclerosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
TABLE 15-10 PERIPHERAL NERVOUS SYSTEM DISORDERS
QUICK CHECK 14-3
Peripheral Nervous System and Neuromuscular Junction Disorders
Peripheral Nervous System Disorders
Neuromuscular Junction Disorders
Myasthenia Gravis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 14-4
Tumors of the Central Nervous System
Cranial Tumors
Primary Brain (Intracerebral) Tumors
FIGURE 15-15 Common Sites of Intracranial Tumors.
FIGURE 15-16 Origin of Clinical Manifestations Associated With an Intracranial Neoplasm.
TABLE 15-11 BRAIN AND SPINAL CORD TUMORS
TABLE 15-12 CLASSIFICATION SYSTEMS FOR ASTROCYTOMAS
Astrocytoma
HEALTH ALERT
Oligodendroglioma
Ependymoma
Primary Extracerebral Tumors
Meningioma
Nerve sheath tumors
Metastatic carcinoma
Spinal Cord Tumors
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 14-5
DID YOU UNDERSTAND?
Central Nervous System Disorders
Demyelinating Degenerative Disorders
Peripheral Nervous System and Neuromuscular Junction Disorders
Tumors of the Central Nervous System
KEY TERMS
Epidural hematoma (see video)
Embolic stroke (see video)
Cerebral Infarction (see video)
Arteriovenous malformation (AVM) (see video)
Subarachnoid hemorrhage (see video)
Meningitis (see video)
Brain abscess (see video)
Guillain-Barré syndrome (see video)
References
Chapter 16 Alterations of Neurologic Function in Children
Normal Growth and Development of the Nervous System
HEALTH ALERT
Structural Malformations
Defects of Neural Tube Closure
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).
FIGURE 16-2 Disorders Associated With Specific Stages of Embryonic Development.
TABLE 16-1 REFLEXES OF INFANCY
FIGURE 16-3 Normal Spine, Meningocele, and Myelomeningocele. Diagram showing section through normal spine (A), meningocele (B), and myelomeningocele (C).
Clinical Manifestations
TABLE 16-2 FUNCTIONAL ALTERATIONS IN MYELODYSPLASIA RELATED TO LEVEL OF LESION
FIGURE 16-4 Normal Brain and Arnold-Chiari II Malformation. A, Diagram of normal brain. B, Diagram of Arnold-Chiari II malformation with downward displacement of cerebellar tonsils and medulla through foramen magnum causing compression and obstruction to flow of CSF.
Malformations of the Axial Skeleton
Spina Bifida
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.
TABLE 16-3 CAUSES OF MICROCEPHALY
QUICK CHECK 16-1
Encephalopathies
Static Encephalopathies
Inherited Metabolic Disorders of the Central Nervous System
FIGURE 16-6 Metabolic Error and Consequences in Phenylketonuria.
TABLE 16-4 INHERITED METABOLIC DISORDERS OF THE CENTRAL NERVOUS SYSTEM
Defects in Amino Acid Metabolism
Phenylketonuria
Defects in Lipid Metabolism
TABLE 16-5 MAJOR TYPES OF SEIZURE DISORDERS FOUND IN CHILDREN
QUICK CHECK 16-2
Seizure Disorders
Epilepsy
Acute Encephalopathies
Reye Syndrome
Intoxications of the Central Nervous System
Meningitis
Bacterial meningitis
TABLE 16-6 COMMONLY INGESTED POISONS
Viral meningitis
Cerebrovascular Disease in Children
Tumors
Brain Tumors
FIGURE 16-7 Location of Brain Tumors in Children.
TABLE 16-7 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
FIGURE 16-8 Retinoblastoma. The tumor occupies a large portion of the inside of the eye bulbus.
Retinoblastoma
FIGURE 16-9 The Two-Mutation Model of Retinoblastoma Development. In inherited retinoblastoma, the first mutation is transmitted through the germline of an affected parent. The second mutation occurs somatically in a retinal cell, leading to development of the tumor. In sporadic retinoblastoma, development of a tumor requires two somatic mutations.
QUICK CHECK 16-3
DID YOU UNDERSTAND?
Normal Growth and Development of the Nervous System
Structural Malformations
Encephalopathies
Cerebrovascular Disease in Children
Tumors
Key Terms
References
UNIT 5 The Endocrine System
Interactive Review – Unit 5
Chapter 17 Mechanisms of Hormonal Regulation
Mechanisms of Hormonal Regulation
Regulation of Hormone Release
FIGURE 17-1 Principal Endocrine Glands.
TABLE 17-1 STRUCTURAL CATEGORIES OF HORMONES
Hormone Transport
Mechanisms of Hormone Action
FIGURE 17-2 Feedback Loops. A, Endocrine feedback loops involving the hypothalamus-pituitary gland and end organs; in this example, the thyroid gland is illustrated (endocrine regulation). B, General model for control and negative feedback to hypothalamic-pituitary target organ systems. Negative feedback regulation is possible at three levels: target organ (ultra-short feedback), anterior pituitary (short feedback), and hypothalamus (long feedback). TRH, Thyroid-releasing hormone; TSH, thyroid-stimulating hormone; T3, triiodothyronine; T4, tetraiodothyronine (thyroxine).
TABLE 17-2 BINDING PROTEINS, THEIR HORMONES, AND VARIABLES THAT AFFECT THEIR CIRCULATING LEVELS
FIGURE 17-3 Regulation of Target Cell Sensitivity. A, Low hormone level and up-regulation, or an increase in the number of receptors. B, High hormone level and down-regulation, or a decrease in the number of receptors.
Hormone Receptors
First and Second Messengers
FIGURE 17-4 Hormone Binding at Target Cell.
TABLE 17-3 SECOND MESSENGERS IDENTIFIED FOR SPECIFIC HORMONES
FIGURE 17-5 Example of First- and Second-Messenger Mechanisms. A non–steroid hormone (first messenger) binds to a fixed receptor in the plasma membrane of the target cell (1). The hormone-receptor complex activates the G protein (2). The activated G protein (G) reacts with guanosine triphosphate (GTP), which in turn activates the membrane-bound enzyme adenylyl cyclase (3). Adenylyl cyclase catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP) (second messenger) (4). cAMP activates protein kinase A (5). Protein kinases activate specific intracellular enzymes (6). These activated enzymes then influence specific cellular reactions, thus producing the target cell’s response to the hormone (7).
Steroid (Lipid-Soluble) Hormone Receptors
QUICK CHECK 17-1
Structure and Function of the Endocrine Glands
Hypothalamic-Pituitary System
The Anterior Pituitary
FIGURE 17-6 Steroid Hormone Mechanism. Lipid-soluble steroid hormone molecules detach from the carrier protein (1) and pass through the plasma membrane (2). Hormone molecules then diffuse into the nucleus, where they bind to a receptor to form a hormone-receptor complex (3). This complex then binds to a specific site on a deoxyribonucleic acid (DNA) molecule (4), triggering transcription of the genetic information encoded there (5). The resulting messenger ribonucleic acid (mRNA) molecule moves to the cytosol, where it associates with a ribosome, initiating synthesis of a new protein (6). This new protein—usually an enzyme or channel protein—produces specific effects on the target cell (7). The classic genomic action is typically slow (red arrows). Steroids also may exact rapid effects (green arrows) by binding to receptors on the plasma membrane (A) and activating an intercellular second messenger (B).
FIGURE 17-7 Pituitary Hormones and Their Target Organs. FSH, Follicle-stimulating hormone; ICSH, male analog of LH (interstitial cell–stimulating hormone); LH, luteinizing hormone.
FIGURE 17-8 Location and Structure of the Pituitary Gland (Hypophysis). The pituitary gland is located within the sella turcica of the skull’s sphenoid bone and is connected to the hypothalamus by a stalklike infundibulum. The infundibulum passes through a gap in the portion of the dura mater that covers the pituitary (the pituitary diaphragm). The inset shows that the pituitary is divided into an anterior portion, the adenohypophysis, and a posterior portion, the neurohypophysis. The adenohypophysis is further subdivided into the pars anterior and pars intermedia. The pars intermedia is almost absent in the adult pituitary.
FIGURE 17-9 Hypophysial Portal System. Neurons in the hypothalamus secrete releasing hormones into veins that carry the releasing hormones directly to the vessels of the adenohypophysis, thus bypassing the normal circulatory route.
FIGURE 17-10 Nerve Tracts From Hypothalamus to Posterior Lobe of Pituitary Gland. Nerve tracts from hypothalamus to posterior lobe of pituitary gland.
TABLE 17-4 HYPOTHALAMIC HORMONES (HYPOPHYSIOTROPIC HORMONES)
TABLE 17-5 TROPIC HORMONES OF THE ANTERIOR PITUITARY AND THEIR FUNCTIONS
The Posterior Pituitary
Antidiuretic hormone
Oxytocin
QUICK CHECK 17-2
Pineal Gland
Thyroid and Parathyroid Glands
Thyroid Gland
Regulation of thyroid hormone secretion
FIGURE 17-11 Thyroid and Parathyroid Glands. Note the relationship of the thyroid and parathyroid glands to each other, to the larynx (voice box), and to the trachea.
Synthesis of thyroid hormone
FIGURE 17-12 Thyroid Follicle Cells.
TABLE 17-6 THYROID GLAND HORMONES AND THEIR REGULATION AND FUNCTIONS
Actions of thyroid hormone
Parathyroid Glands
QUICK CHECK 17-3
Endocrine Pancreas
HEALTH ALERT
Insulin
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.
FIGURE 17-14 Insulin Action on Cells. Binding of insulin to its receptor causes autophosphorylation of the receptor, which then itself acts as a tyrosine kinase that phosphorylates insulin receptor substrate 1 (IRS-1). Numerous target enzymes, such as protein kinase B and MAP kinase, are activated and these enzymes have a multitude of effects on cell function. The glucose transporter (GLUT4) is recruited to the plasma membrane, where it facilitates glucose entry into the cell. The transport of amino acids, potassium, magnesium, and phosphate into the cell is also facilitated. The synthesis of various enzymes is induced or suppressed, and cell growth is regulated by signal molecules that modulate gene expression. IREs, Insulin responsive elements; mRNA, messenger ribonucleic acid.
HEALTH ALERT
TABLE 17-7 INSULIN ACTIONS
Amylin
Glucagon
Pancreatic Somatostatin
Gastrin, Grehlin, and Pancreatic Polypeptide
Adrenal Glands
FIGURE 17-15 Structure of the Adrenal Gland Showing Cell Layers (Zonae) of the Cortex. A, Zona glomerulosa secretes aldosterone. Zona fasciculata secretes abundant amounts of glucocorticoids, chiefly cortisol. Zona reticularis secretes minute amounts of sex hormones and glucocorticoids. B, A portion of the medulla is visible at the lower right in the photomicrograph (×35) and at the bottom of the drawing.
Adrenal Cortex
Glucocorticoids
Functions of the glucocorticoids
BOX 17-1 MAJOR FUNCTIONS OF GLUCOCORTICOIDS
Metabolic
Inflammatory and Immune
Other
Cortisol
Mineralocorticoids: aldosterone
Adrenal estrogens and androgens
FIGURE 17-16 Feedback Control of Glucocorticoid Synthesis and Secretion.
FIGURE 17-17 The Feedback Mechanisms Regulating Aldosterone Secretion. ACTH, Adrenocorticotropic hormone; cAMP, cyclic adenosine monophosphate.
Adrenal Medulla
FIGURE 17-18 Synthesis of Catecholamines.
QUICK CHECK 17-4
Neuroendocrine Response to Stressors
BOX 17-2 METHODS OF HORMONE MEASUREMENT
Radioimmunoassay (RIA)
Enzyme-Linked Immunosorbent Assay (ELISA)
Bioassay
GERIATRIC CONSIDERATIONS
General Endocrine Changes With Aging
Pituitary
Thyroid
Growth Hormone and Insulin-like Growth Factors
Pancreas
Adrenal
Gonads
DID YOU UNDERSTAND?
Mechanisms of Hormonal Regulation
Structure and Function of the Endocrine Glands
GERIATRIC CONSIDERATIONS: Aging & Its Effects on Specific Endocrine Glands
Key Terms
References
Chapter 18 Alterations of Hormonal Regulation
Mechanisms of Hormonal Alterations
TABLE 18-1 MECHANISMS OF HORMONE ALTERATIONS
Alterations of the Hypothalamic-Pituitary System
FIGURE 18-1 Loss of Hypothalamic Hormones. GnRH, Gonadotropin-releasing hormone; TRH, thyrotropin-releasing hormone; CRH, corticotropin-releasing hormone; PIF, prolactin inhibitory factor (probably dopamine); GHRH, growth hormone–releasing hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone; ACTH, adrenocorticotropic hormone.
Diseases of the Posterior Pituitary
Syndrome of Inappropriate Antidiuretic Hormone Secretion
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Diabetes Insipidus
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
TABLE 18-2 SIGNS AND SYMPTOMS OF DIABETES INSIPIDUS (DI) AND SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE (SIADH) SECRETION
Diseases of the Anterior Pituitary
Hypopituitarism
Pathophysiology
Clinical Manifestations
FIGURE 18-2 Hypopituitary Dwarfism. A 4-year-old boy whose height is 25 inches. Girl is also 4 years old and has a normal height of 39 inches. Boy (dwarf) has a normal face, as well as head, trunk, and limbs of approximately normal proportions.
Evaluation and Treatment
Hyperpituitarism: Primary Adenoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 18-1
Hypersecretion of Growth Hormone: Acromegaly
Pathophysiology
FIGURE 18-3 Giantism. A pituitary giant and dwarf contrasted with normal-size men. Excessive secretion of growth hormone by the anterior lobe of the pituitary gland during the early years of life produces giants of this type, whereas deficient secretion of this substance produces well-formed dwarfs.
Clinical Manifestations
Evaluation and Treatment
FIGURE 18-4 Acromegaly. Chronologic sequence of photographs showing slow development of acromegaly.
Prolactinoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Thyroid Function
HEALTH ALERT
Hyperthyroidism
Thyrotoxicosis
FIGURE 18-5 Common Causes of Hyperthyroidism. Hyperthyroidism may have several causes, among them: 1, Graves disease; 2, toxic multinodular goiter; 3, follicular adenoma; 4, thyroid medication.
Clinical Manifestations
Evaluation and Treatment
FIGURE 18-6 Clinical Manifestations of Hyperthyroidism and Hypothyroidism.
Hyperthyroid Conditions
Graves disease
FIGURE 18-7 Evaluation of Hyperthyroidism. Radioactive iodine is used in the differential diagnosis of hyperthyroidism.
FIGURE 18-8 Thyrotoxicosis (Graves Disease). A, Exophthalmos (large and protruding eyeballs often in association with a large goiter); B, Pretibial myxedema associated with Graves disease; note lumpy and swollen appearance from accumulation of connective tissue and pinkish purple discoloration.
Hyperthyroidism resulting from nodular thyroid disease
Thyrotoxic crisis
Hypothyroidism
Pathophysiology
Clinical Manifestations
FIGURE 18-9 Mechanisms of Primary and Secondary Hypothyroidism.
Evaluation and Treatment
Hypothyroid Conditions
Primary hypothyroidism
FIGURE 18-10 Myxedema. Note edema around eyes and facial puffiness. The hair is dry.
Congenital hypothyroidism
Thyroid Carcinoma
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
Types of Diabetes Mellitus
Type 1 Diabetes Mellitus
TABLE 18-4 EPIDEMIOLOGY AND ETIOLOGY OF DIABETES MELLITUS IN THE UNITED STATES
BOX 18-1 DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS
Categories of Increased Risk for Diabetes
Pathophysiology
Insulin, amylin, and glucagon
FIGURE 18-11 Pathophysiology of Type 1 Diabetes Mellitus.
Clinical Manifestations
Evaluation and Treatment
TABLE 18-5 CLINICAL MANIFESTATIONS AND MECHANISMS FOR TYPE 1 DIABETES MELLITUS
BOX 18-2 CRITERIA FOR THE DIAGNOSIS OF METABOLIC SYNDROME
Type 2 Diabetes Mellitus
Pathophysiology
FIGURE 18-12 Pathophysiology of Type 2 Diabetes Mellitus.
Clinical Manifestations
HEALTH ALERT
Evaluation and Treatment
Other Specific Types of Diabetes Mellitus and Gestational Diabetes Mellitus
TABLE 18-6 TYPES OF ORAL HYPOGLYCEMIC DRUGS
TABLE 18-7 COMMON ACUTE COMPLICATIONS OF DIABETES MELLITUS
Acute Complications of Diabetes Mellitus
FIGURE 18-13 Pathophysiology of DKA and HHNKS in Diabetes Mellitus.
TABLE 18-8 CHRONIC COMPLICATIONS OF DIABETES MELLITUS
Chronic Complications of Diabetes Mellitus
Metabolic Mechanisms of Chronic Complications
Hyperglycemia and the polyol pathway
Hyperglycemia and protein kinase C
Hyperglycemia and nonenzymatic glycation
Hyperglycemia and the hexosamine pathway
Microvascular Disease
Diabetic retinopathy
Diabetic nephropathy
Diabetic neuropathies
Macrovascular Disease
Coronary artery disease
Stroke
Peripheral vascular disease
FIGURE 18-14 Diabetes Mellitus and Atherosclerosis. Diabetes with its associated hyperglycemia, relative hypoinsulinemia, oxidative stress, and proinflammatory state contributes to atherogenesis by causing arterial endothelial dysfunction (impaired vasodilation and adhesion of inflammatory cells), dyslipidemia, and smooth muscle proliferation. LDL, Low-density lipoprotein; NO, nitric oxide; PKC, protein kinase C; Rage, receptor advanced glycation end product.
Infection
QUICK CHECK 18-4
Alterations of Adrenal Function
Disorders of the Adrenal Cortex
FIGURE 18-15 Symptoms of Cushing Disease.
Hypercortical Function (Cushing Syndrome, Cushing Disease)
Pathophysiology
FIGURE 18-16 Cushing Syndrome. A, Patient before onset of Cushing syndrome. B, Patient 4 months later. Moon facies is clearly demonstrated.
Clinical Manifestations
Evaluation and Treatment
Congenital Adrenal Hyperplasia
Hyperaldosteronism
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hypersecretion of Adrenal Androgens and Estrogens
Adrenocortical Hypofunction
FIGURE 18-17 Virilization. Virilization of a young girl by an androgen-secreting tumor of the adrenal cortex. Masculine features include lack of breast development, increased muscle bulk, and hirsutism (excessive hair).
Addison disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Secondary hypocortisolism
Disorders of the Adrenal Medulla
Tumor of the Adrenal Medulla
Pathophysiology
Clinical Manifestations
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
Evaluation and Treatment
Key Terms
References
UNIT 6 The Hematologic System
Interactive Review – Unit 6
Chapter 19 Structure and Function of the Hematologic System
Components of the Hematologic System
Composition of Blood
Plasma and Plasma Proteins
TABLE 19-1 ORGANIC AND INORGANIC COMPONENTS OF ARTERIAL PLASMA
FIGURE 19-1 Composition of Whole Blood. Approximate values for the components of blood in a normal adult.
TABLE 19-2 CELLULAR COMPONENTS OF THE BLOOD
Cellular Components of the Blood
Erythrocytes
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 (red).
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.
Agranulocytes
Platelets
FIGURE 19-4 Colored Micrograph of Platelets. The platelet on the left is moderately activated, with a generally round shape and the beginning of formation of pseudopodia (foot-like extensions from the membrane). The platelet on the right is fully activated, with extensive pseudopodia.
QUICK CHECK 19-1
Lymphoid Organs
Spleen
FIGURE 19-5 Red Cells in the Spleen. Scanning electron micrograph of spleen, demonstrating erythrocytes (numbered 1 through 6) squeezing through the fenestrated wall in transit from the splenic cord to the sinus. The view shows the endothelial lining of the sinus wall, to which platelets (P) adhere, along with “hairy” white cells, probably macrophages. The arrow shows a protrusion on a red blood cell (×5000).
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.
The Mononuclear Phagocyte System
QUICK CHECK 19-2
TABLE 19-3 MONONUCLEAR PHAGOCYTE SYSTEM (FORMERLY CALLED THE RETICULOENDOTHELIAL SYSTEM)
Development of Blood Cells
Hematopoiesis
Bone Marrow
Cellular Differentiation
FIGURE 19-7 Differentiation of Hematopoietic Cells. Curved arrows indicate proliferation and expansion of pre-hematopoietic stem cell populations. EPO, Erythropoietin; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; M-CSF, macrophage colony-stimulating factor; NK, natural killer; SCF, stem cell factor; TPO, thrombopoietin.
QUICK CHECK 19-3
Development of Erythrocytes
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.
FIGURE 19-10 Role of Erythropoietin in Regulation of Erythropoiesis. (1) Decreased arterial oxygen levels result in (2) decreased tissue oxygen (hypoxia) that (3) stimulates the kidney to increase (4) production of erythropoietin. Erythropoietin is carried to the bone marrow (5) and binds to erythropoietin receptors on proerythroblasts, resulting in increased red cell production and maturation and expansion of the erythron (6). The increased release of red cells into the circulation frequently corrects the hypoxia in the tissues (7). (8) Perception of normal oxygen levels by the kidney causes (9) diminished production of erythropoietin (negative feedback) and return to normal levels of erythrocyte production. EPO, Erythropoietin; O2, oxygen in the blood and tissue; RBCs, red blood cells.
Erythropoiesis
Hemoglobin Synthesis
FIGURE 19-11 Molecular Structure of Hemoglobin. Molecule is a spherical tetramer weighing approximately 64,500 daltons. It contains a pair of α-polypeptide chains and a pair of β-polypeptide chains and several heme groups.
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.
Nutritional Requirements for Erythropoiesis
Iron cycle
FIGURE 19-13 Iron Cycle. Iron (Fe) released from gastrointestinal epithelial cells circulates in the bloodstream associated with its plasma carrier, transferrin. It is delivered to erythroblasts in bone marrow, where most of it is incorporated into hemoglobin. Mature erythrocytes circulate for approximately 120 days, after which they become senescent and are removed by the mononuclear phagocyte system (MPS). Macrophages of MPS (mostly in spleen) break down ingested erythrocytes and return iron to the bloodstream directly or after storing it as ferritin or hemosiderin.
TABLE 19-4 NUTRITIONAL REQUIREMENTS FOR ERYTHROPOIESIS
Normal Destruction of Senescent Erythrocytes
QUICK CHECK 19-4
FIGURE 19-14 Metabolism of Bilirubin Released by Heme Breakdown. MPS, Mononuclear phagocyte system.
Development of Leukocytes
Development of Platelets
Mechanisms of Hemostasis
FIGURE 19-15 Three Hemostatic Compartments.
TABLE 19-5 TYPES OF BLEEDING: SOURCES, VESSEL SIZE, AND SEALING REQUIREMENTS
Function of Platelets and Blood Vessels
HEALTH ALERT
FIGURE 19-16 Platelet Activation. A, After endothelial denudation, platelets and leukocytes adhere to the subendothelium in a monolayer fashion. B, Higher-power view showing leukocytes and platelets adherent to the subendothelium. C, High magnification of a thrombus showing a mixture of red cells and platelets incorporated into the fibrin meshwork.
Function of Clotting Factors
FIGURE 19-17 Blood Vessel Damage, Blood Clot, and Clot Dissolution.
Retraction and Lysis of Blood Clots
QUICK CHECK 19-5
FIGURE 19-18 Blood Clotting Mechanism. A, The complex clotting mechanism can be distilled into three basic steps: (1) release of clotting factors from both injured tissue cells and sticky platelets at the injury site (which form temporary platelet plug), (2) series of chemical reactions that eventually result in the formation of thrombin, and (3) formation of fibrin and trapping of blood cells to form a clot. B, An electron micrograph showing entrapped RBCs in a fibrin clot.
FIGURE 19-19 The Fibrinolytic System. Fibrinolysis is initiated by the binding of plasminogen to fibrin. Although tissue plasminogen activator (t-PA) initiates intravascular fibrinolysis, urokinase plasminogen activator (u-PA) is the major activator of fibrinolysis in tissue (extravascular). Plasmin digests the fibrin into smaller soluble pieces (fibrin degradation products). u-PAR, Urokinase-like plasminogen activator receptor.
TABLE 19-6 COMMON BLOOD TESTS FOR HEMATOLOGIC DISORDERS
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
Alterations of Erythrocyte Function
Classification of Anemias
TABLE 20-1 MORPHOLOGIC CLASSIFICATION OF ANEMIAS
Clinical Manifestations
FIGure 20-1 Progression and Manifestations of Anemia. DPG, 2,3-Diphosphoglycerate; SV, stroke volume.
Macrocytic-Normochromic Anemias
Pernicious Anemia
Pathophysiology
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).
Clinical Manifestations
Evaluation and Treatment
Folate Deficiency Anemias
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 level of 9 g/dl. Palmar creases become as pale as the surrounding skin when the hemoglobin level approaches 7 g/dl.
FIGURE 20-4 Koilonychia. The nails are concave, ridged, and brittle.
FIGURE 20-5 Glossitis. Tongue of individual with iron deficiency anemia has bald, fissured appearance (arrow) caused by loss of papillae and flattening.
Evaluation and Treatment
Sideroblastic Anemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Normocytic-Normochromic Anemias
QUICK CHECK 20-1
Myeloproliferative Red Cell Disorders
Polycythemia Vera
TABLE 20-2 NORMOCYTIC-NORMOCHROMIC ANEMIAS
TABLE 20-3 DISORDERS CLASSIFIED AS POLYCYTHEMIA
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Iron Overload
Hereditary Hemochromatosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Leukocyte Function
Quantitative Alterations of Leukocytes
Granulocyte and Monocyte Alterations
Lymphocyte Alterations
FIGURE 20-6 Origins of Leukemias and Lymphomas. Differentiation pathways of blood-forming cells and reported sites from which specific leukemias and lymphomas originate. Tumors of similar types are given the same background coloring. ALL, Acute lymphocytic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; NK, natural killer.
TABLE 20-4 OTHER CONDITIONS ASSOCIATED WITH NEUTROPHILS, EOSINOPHILS, BASOPHILS, MONOCYTES, AND LYMPHOCYTES
Infectious Mononucleosis
Clinical Manifestations
TABLE 20-5 ESTIMATED NEW CASES AND DEATHS FROM LEUKEMIA IN THE UNITED STATES—2007
Evaluation and Treatment
QUICK CHECK 20-2
Qualitative Alterations of Leukocytes
Leukemias
FIGURE 20-7 Philadelphia Chromosome. Schema of the Philadelphia (Ph) translocation (+) seen in chronic myelocytic leukemia. The Ph1 chromosome results from an exchange of materials between chromosomes 9 and 22—that is, t(9;22)(q34;q11). Because chromosome 22 loses much more of its long arm than is translocated to it from chromosome 9, chromosome 22 becomes much abbreviated and is known as Ph1.
Pathophysiology
Acute leukemias
Clinical Manifestations
Evaluation and Treatment
TABLE 20-6 CLINICAL MANIFESTATIONS AND RELATED PATHOPHYSIOLOGY IN LEUKEMIA
Chronic leukemias
Pathophysiology and Clinical Manifestations
TABLE 20-7 SOME EXAMPLES OF HUMAN COLONY-STIMULATING FACTORS
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.
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.
Malignant Lymphomas
FIGURE 20-9 Lymph Nodes. A, Lymphocytes and histiocytes of Hodgkin lymphoma, nodular type. Large nodules with small, round lymphocytes, histiocytes, and scattered lymphocyte and histiocyte cells. B, Diagnostic Reed-Sternberg cell (arrow). A large multinucleated or multilobed cell with inclusion body–like nucleoli surrounded by a halo of clear nucleoplasm.
Hodgkin Lymphoma
Pathophysiology
TABLE 20-8 SUBTYPES OF CLASSIC HODGKIN LYMPHOMA
Clinical Manifestations
FIGURE 20-10 Hodgkin Lymphoma and Enlarged Cervical Lymph Node. Typical enlarged cervical lymph node in the neck (arrow) of a 35-year-old woman with Hodgkin lymphoma.
FIGURE 20-11 Common and Uncommon Involved Lymph Node Sites for Hodgkin Lymphoma.
Evaluation and Treatment
TABLE 20-9 DEFINITIONS OF STAGES OF HODGKIN DISEASE
Non-Hodgkin Lymphomas
Pathophysiology
TABLE 20-10 CLINICAL DIFFERENCES BETWEEN NON-HODGKIN LYMPHOMA AND HODGKIN LYMPHOMA
Clinical Manifestations
Evaluation and Treatment
FIGURE 20-12 Burkitt Lymphoma. Burkitt lymphoma involving the jaw in a young African boy.
Burkitt lymphoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 20-13 Multiple Myeloma, Bone Marrow Aspirate. Normal marrow cells are largely replaced by plasma cells, including atypical forms with multiple nuclei (arrow), and cytoplasmic droplets containing immunoglobulin.
Multiple myeloma
Pathophysiology
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.
Evaluation and Treatment
QUICK CHECK 20-4
Lymphoblastic lymphoma
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Alterations of Splenic Function
FIGURE 20-15 M Protein. Serum protein electrophoresis (PEL) is used to screen for M proteins in multiple myeloma. A, In normal serum the proteins separate into several regions between albumin (Alb) and a broad band in the gamma (γ) region, where most antibodies (gamma globulins) are found. Immunofixation (IFE) can identify the location of IgG (G), IgA (A), IgM (M), and kappa (K) and lambda (L) light chains. B, Serum from an individual with multiple myeloma contains a sharp M protein (M spike). The M protein is monoclonal and contains only one heavy chain and one light chain. In this instance the IFE identifies the M protein as an IgG containing a lambda light chain. C, Serum and urine protein electrophoretic patterns in an individual with multiple myeloma. Serum demonstrates an M protein (immunoglobulin) in the gamma region, and the urine has a large amount of the smaller-sized light chains with only a small amount of the intact immunoglobulin.
Pathophysiology
Clinical Manifestations
BOX 20-1 DISEASES RELATED TO CLASSIFICATION OF SPLENOMEGALY
Inflammation or Infection
Congestive
Infiltrative
Tumors or Cysts
Nonmalignant: Hamartoma
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
Disorders of Coagulation
Impaired Hemostasis
Vitamin K deficiency
Liver disease
Consumptive Thrombohemorrhagic Disorders
Disseminated intravascular coagulation
Pathophysiology
BOX 20-2 CONDITIONS ASSOCIATED WITH DIC
FIGURE 20-16 Pathophysiology of Disseminated Intravascular Coagulation (DIC). Tissue factor initiates clot formation and this effect is increased by a decrease in natural anticoagulants (tissue factor inhibitor, antithrombin-III, and protein C). There also is a reduction in clot breakdown or fibrinolysis by plasmin. The combined effect is to cause thrombosis. The thrombotic activity consumes (uses up) coagulation factors and platelets, which can increase bleeding. Slow degradation of the fibrin clot produces fibrin degradation products (FDPs). FDPs have inhibitory effects on thrombin and platelets. The inhibition of coagulation, combined with the depletion of factors and platelets, then creates a bleeding tendency. Uncontrolled DIC will eventually lead to multiple end-organ failure. For further details of these mechanisms see Chapters 5 and 23. Inset is an example of DIC resulting from staphylococcal septicemia. Note the characteristic skin hemorrhage ranging from small purpuric lesions to larger ecchymoses.
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. Thrombus arising in valve pocket at upper end of superficial femoral vein (arrow). Postmortem clot on the right is shown for comparison.
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
Thrombocytopenia (see video)
References
Chapter 21 Alterations of Hematologic Function in Children
Disorders of Erythrocytes
TABLE 21-1 ANEMIAS OF CHILDHOOD
Acquired Disorders
Iron Deficiency Anemia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Hemolytic Disease of the Newborn
FIGURE 21-1 Hemolytic Disease of the Newborn (HDN). A, Before or during delivery, Rh-positive erythrocytes from the fetus enter the blood of an Rh-negative woman through a tear in the placenta. B, The mother is sensitized to the Rh antigen and produces Rh antibodies. Because this usually happens after delivery, there is no effect on the fetus in the first pregnancy. C, During a subsequent pregnancy with an Rh-positive fetus, Rh-positive erythrocytes cross the placenta, enter the maternal circulation, and (D) stimulate the mother to produce antibodies against the Rh antigen.
Pathophysiology
FIGURE 21-2 Sickle Cell Hemoglobin. A, Sickle cell hemoglobin is produced by a recessive allele of the gene encoding the beta-chain of the protein hemoglobin. It represents a single amino acid change—from glutamic acid to valine at the sixth position of the chain. In this model of a hemoglobin molecule, the position of the mutation can be seen near the end of the upper arm. B, Color-enhanced electron micrograph shows normal erythrocytes and sickled blood cell. C, Brief summary of sickle cell.
Clinical Manifestations
Evaluation and Treatment
FIGURE 21-3 Normal and Sickle-Shaped Blood Cells. Scanning electron micrograph of normal and sickle-shaped red blood cells. The irregularly shaped cells are the sickle cells; the circular cells are the normal blood cells.
Inherited Disorders
Sickle Cell Disease
FIGURE 21-4 Sickling of Erythrocytes.
TABLE 21-2 INHERITANCE OF SICKLE CELL DISEASE
Pathophysiology
FIGURE 21-5 Differences Between Effects of (A) Normal and (B) Sickled RBCs on Blood Circulation and Selected Consequences in a Child. C, Tissue Effects of Sickle Cell Anemia. CVA, Cerebrovascular accident.
Clinical Manifestations
FIGURE 21-6 Prepregnancy Sickle Cell Test. This technique has potential for detection of other inherited diseases. 1, Fertilization produces several embryos. 2, The embryos are tested for the presence of the gene. 3, The embryos without the gene are implanted. 4, Amniocentesis confirms whether the fetus (or fetuses) has the sickle cell gene. 5, Woman has a normal child.
Evaluation and Treatment
Thalassemias
Pathophysiology
FIGURE 21-7 Young Girl with Beta-Thalassemia Demonstrating Mild Frontal Bossing (Prominence) of the Right Forehead and Mild Maxillary Prominence.
Clinical Manifestations
FIGURE 21-8 Child with Beta-Thalassemia Major Who Has Severe Splenomegaly.
Evaluation and Treatment
QUICK CHECK 21-1
Disorders of Coagulation and Platelets
Inherited Hemorrhagic Disease
Hemophilias
Pathophysiology
TABLE 21-3 THE COAGULATION FACTORS AND ASSOCIATED DISORDERS
Clinical Manifestations
TABLE 21-4 THE HEMOPHILIAS
TABLE 21-5 LABORATORY TESTS OF COAGULATION
Evaluation and Treatment
Antibody-Mediated Hemorrhagic Disease
Idiopathic Thrombocytopenic Purpura
Pathophysiology
HEALTH ALERT
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 21-2
TABLE 21-6 MAJOR CLASSIFICATIONS OF LEUKEMIA
Neoplastic Disorders
Leukemia and Lymphoma
Leukemia
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
FIGURE 21-9 Monoblasts From Acute Monoblastic Leukemia. Monoblasts in a marrow smear from an individual with acute monoblastic leukemia. The monoblasts are larger than myeloblasts and usually have abundant cytoplasm, often with delicate scattered azurophilic granules (an element that stains well with blue aniline dyes).
HEALTH ALERT
FIGURE 21-10 Lymphomas. A, Large cell lymphoma. The tumor contains prominent areas of sclerosis (arrow). B, Burkitt lymphoma. A starry sky pattern is seen at low magnification.
Lymphomas
Non-Hodgkin lymphoma
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
FIGURE 21-11 Diagnostic Reed-Sternberg Cell. A large multinucleated or multilobated cell with (arrow) inclusion body–like nucleoli surrounded by a halo of clear nucleoplasm.
Hodgkin Lymphoma
FIGURE 21-12 Main Areas of Lymphadenopathy and Organ Involvement in Hodgkin Lymphoma.
QUICK CHECK 21-3
DID YOU UNDERSTAND?
Disorders of Erythrocytes
Disorders of Coagulation and Platelets
Neoplastic Disorders
KEY TERMS
Hemophilia A (see video)
References
UNIT 7 The Cardiovascular and Lymphatic Systems
Interactive Review – Unit 7
Chapter 22 Structure and Function of the Cardiovascular and Lymphatic Systems
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.
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.
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. View B is similar to view A except that the semilunar valves are open and the atrioventricular valves are closed, as when the ventricles are contracting.
The Great Vessels
Blood Flow During the Cardiac Cycle
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).
Normal Intracardiac Pressures
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.
TABLE 22-1 NORMAL INTRACARDIAC PRESSURES
QUICK CHECK 22-1
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.
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.
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 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.
QUICK CHECK 22-2
Propagation of cardiac action potentials
TABLE 22-2 INTERCELLULAR AND EXTRACELLULAR ION CONCENTRATIONS IN THE MYOCARDIUM
The normal electrocardiogram
Automaticity
FIGURE 22-10 Electrocardiogram (ECG) and Cardiac Electrical Activity. A, Normal ECG. Depolarization and repolarization. B, ECG intervals among P, QRS, and T waves. C, Schematic representation of ECG and its relationship to cardiac electrical activity. AV, Atrioventricular; LA, left atrium; LBB, left bundle branch; LV, left ventricle; RA, right atrium; RBB, right bundle branch; RV, right ventricle.
Rhythmicity
QUICK CHECK 22-3
Cardiac Innervation
Sympathetic and parasympathetic nerves
Myocardial Cells
FIGURE 22-11 Autonomic Innervation of Cardiovascular System. Inhibition (−); activation (+).
FIGURE 22-12 Cardiac Muscle Fiber. Unlike other types of muscle fibers, cardiac muscle fiber is typically branched and forms junctions, called intercalated disks, with adjacent cardiac muscle fibers. Like skeletal muscle fibers, cardiac muscle fibers contain sarcoplasmic reticula and T tubules—although these structures are not as highly organized as in skeletal muscle fibers.
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.
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.
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.
Myocardial relaxation
QUICK CHECK 22-4
Factors Affecting Cardiac Output
Preload
TABLE 22-3 CARDIOVASCULAR FUNCTION IN ELDERLY PERSONS
Afterload
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.
Myocardial Contractility
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).
Heart Rate
Cardiovascular control centers in the brain
Neural reflexes
Atrial receptors
Hormones and biochemicals
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.
FIGURE 22-19 Circulatory System. A, Principal arteries of body. B, Principal veins of body.
QUICK CHECK 22-5
The Systemic Circulation
Structure of Blood Vessels
FIGURE 22-20 Structure of the Blood Vessels. The tunica externa of the veins are color-coded blue and the arteries red.
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).
Arterial Vessels
Endothelium
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).
Veins
Factors Affecting Blood Flow
Pressure and Resistance
TABLE 22-4 FUNCTIONS OF THE ENDOTHELIUM
FIGURE 22-24 Endothelium Regulation of Vasomotion (Constriction and Dilation) and Platelet Aggregation by Release of a Variety of Constricting and Dilating Substances. Constricting factors include arachidonic acid and metabolites, such as thromboxane A2 (which aspirin inhibits), and a potent amino acid peptide called endothelin. The endothelium also converts angiotensin I into angiotensin II by the membrane-bound angiotensin-converting enzyme that also metabolizes the endogenous endothelium-dependent vasodilator, bradykinin.
FIGURE 22-25 Factors Causing Endothelium-Dependent Vasodilation. A variety of exogenous pharmacologic substances, platelet-derived factors, and shear stress can promote release of nitric oxide by stimulating nitric oxide synthase (NOS). Prostacyclin (PGI2) causes relaxation of vascular smooth muscle cells by a cyclic adenosine monophosphate (cAMP)-dependent mechanism, and both nitric oxide and PGI2 inhibit platelet aggregation. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; 5-HT, serotonin.
FIGURE 22-26 Valves of Vein. Pooled blood is moved toward heart as valves are forced open by pressure from volume of blood downstream.
FIGURE 22-27 Muscle Pump.
FIGURE 22-28 Lumen Diameter, Blood Flow, and Resistance. A, Effect of lumen diameter (d) on flow through vessel. B, Blood flows with great speed in the large arteries. However, branching of arterial vessels increases the total cross-sectional area of the arterioles and capillaries, reducing the flow rate. When capillaries merge into venules and venules merge into veins, the total cross-sectional area decreases, causing the flow rate to increase.
Velocity
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.
Vascular Compliance
QUICK CHECK 22-6
Regulation of Blood Pressure
Arterial Pressure
Effects of Cardiac Output
Effects of Total Peripheral Resistance
FIGURE 22-30 Factors Regulating Blood Pressure.
Baroreceptors
Arterial chemoreceptors
Effect of Hormones
Antidiuretic hormone
Renin-angiotensin system
FIGURE 22-31 Baroreceptors and Chemoreceptor Reflex Control of Blood Pressure. A, Baroreceptor reflexes. B, Vasomotor chemoreflexes.
FIGURE 22-32 Three Mechanisms That Influence Total Plasma Volume. The antidiuretic hormone (ADH) mechanism and renin-angiotensin and aldosterone mechanisms tend to increase water retention and thus increase total plasma volume. The natriuretic peptides antagonize these mechanisms by promoting water loss and sodium loss, thus promoting a decrease in total plasma volume. ACE, Angiotensin-converting enzyme; ANP, atrial natriuretic peptide; NPs, natriuretic peptides.
Natriuretic peptides
Adrenomedullin
Insulin
Adipokines
FIGURE 22-33 Angiotensins and the Organs Affected. A, The shaded blue area is the classic pathway of biosynthesis that generates the renin and angiotensin I. Angiotensinogen is synthesized in the liver and is released into the blood where it is cleaved to form angiotensin I by renin secreted by cells in the kidneys. Angiotensin-converting enzyme (ACE) in the lungs catalyzes the formation of angiotensin II from angiotensin I and destroys the potent vasodilator bradykinin. Further cleavage generates the angiotensins III and IV. The reddish shading shows the organs affected by angiotensin II, including brain, heart, adrenals, kidney, and the kidney’s efferent arterioles. The dashed arrow (left) shows the inhibition of renin by angiotensin II. B, Summary of angiotensin II effects on blood vessel structure and function leading to atherosclerosis.
HEALTH ALERT
FIGURE 22-34 Angiotensins and Their Receptors, AT1 and AT2. Blocking the angiotensin-converting enzyme (ACE) with ACE inhibitors decreases the amount of angiotensin II. Blocking the receptor AT1 with drugs (AT1 antagonists) blocks the attachment of angiotensin II to the cell, preventing the cellular effects and decreasing the vascular, cardiac, and renal effects.
Venous Pressure
Regulation of the Coronary Circulation
HEALTH ALERT
Autoregulation
BOX 22-2 VASCULAR PROTECTION AND INJURY PROPERTIES OF INSULIN
Protection
Injury
Autonomic Regulation
QUICK CHECK 22-7
The Lymphatic System
FIGURE 22-35 Role of the Lymphatic System in Fluid Balance. Fluid from plasma flowing through the capillaries moves into interstitial spaces. Although much of this interstitial fluid is either absorbed by tissue cells or reabsorbed by capillaries, some of the fluid tends to accumulate in the interstitial spaces. As this fluid builds up, it tends to drain into lymphatic vessels that eventually return the fluid to the venous blood.
FIGURE 22-36 Principle Organs of the Lymphatic System. The inset shows the areas drained by the right lymphatic duct (green) and the thoracic duct (blue).
QUICK CHECK 22-8
FIGURE 22-37 Lymphatic Capillaries. A, Schematic representation of lymphatic capillaries. B, Anatomic components of microcirculation.
DID YOU UNDERSTAND?
The Circulatory System
The Heart
The Systemic Circulation
The Lymphatic System
KEY TERMS
References
Chapter 23 Alterations of Cardiovascular Function
Diseases of the Veins
Varicose Veins and Chronic Venous Insufficiency
FIGURE 23-1 Varicose Veins of the Leg (arrow).
Thrombus Formation in Veins
FIGURE 23-2 Venous Stasis Ulcer.
Superior Vena Cava Syndrome
QUICK CHECK 23-1
Diseases of the Arteries
Hypertension
TABLE 23-1 CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS AGE 18 YEARS AND OLDER
Factors Associated With Primary Hypertension
RISK FACTORS
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. RAA, Renin-angiotensin-aldosterone; SNS, sympathetic nervous system.
HEALTH ALERT
HEALTH ALERT
FIGURE 23-4 Pathophysiology of Hypertension. Numerous genetic vulnerabilities have been linked to hypertension and these, in combination with environmental risks, cause neurohumoral dysfunction (sympathetic nervous system [SNS], renin-angiotensin-aldosterone [RAA] system, adducin (cytoskeleton protein involved with Na/K ATPase), and natriuretic hormones) and promote inflammation and insulin resistance. Insulin resistance and neurohumoral dysfunction contribute to sustained systemic vasoconstriction and increased peripheral resistance. Inflammation contributes to renal dysfunction, which, in combination with the neurohumoral alterations, results in renal salt and water retention and increased blood volume. Increased peripheral resistance and increased blood volume are two primary causes of sustained hypertension.
Secondary Hypertension
Complicated Hypertension
Clinical Manifestations
Evaluation and Treatment
TABLE 23-2 PATHOLOGIC EFFECTS OF SUSTAINED, COMPLICATED PRIMARY HYPERTENSION
Orthostatic (Postural) Hypotension
QUICK CHECK 23-2
Aneurysm
FIGURE 23-5 Aneurysm. A three dimensional CT scan shows the aneurysm (A) involves the ascending thoracic aorta. D, descending aorta; LV, left ventricle
FIGURE 23-6 Longitudinal Sections Showing Types of Aneurysms. A, The fusiform circumferential and fusiform saccular aneurysms are true aneurysms, caused by weakening of the vessel wall. False and saccular aneurysms involve a break in the vessel wall, usually caused by trauma. B, Dissecting aneurysm of thoracic aorta (arrow).
Thrombus Formation
QUICK CHECK 23-3
Embolism
Peripheral Vascular Disease
Thromboangiitis Obliterans (Buerger disease)
TABLE 23-3 TYPES OF EMBOLI
FIGURE 23-7 Arteriosclerosis. A, Cross section of a normal artery and an artery altered by disease. B, A small artery in the myocardium is occluded by a mass of blue-staining platelets, yellow-staining red cells, and cholesterol bodies.
Raynaud Phenomenon and Disease
QUICK CHECK 23-4
Atherosclerosis
Pathophysiology
FIGURE 23-8 Low-Density Lipoprotein Oxidation. Low-density lipoprotein (LDL) enters the arterial intima through an intact endothelium. In hypercholesterolemia, the influx of LDL exceeds the eliminating capacity and an extracellular pool of LDL is formed. This is enhanced by association of LDL with the extracellular matrix. Intimal LDL is oxidized through the action of free oxygen radicals formed by enzymatic or nonenzymatic reactions. This generates proinflammatory lipids that induce endothelial expression of the adhesion molecule (i.e., vascular cell adhesion molecule-1), activate complement, and stimulate chemokine secretion. All of these factors cause adhesion and entry of mononuclear leukocytes, particularly monocytes and T lymphocytes. Monocytes differentiate into macrophages. Macrophages up-regulate and internalize oxidized LDL and transform into foam cells. Macrophage uptake of oxidized LDL also leads to presentation of its fragments to antigen-specific T cells. This induces an autoimmune reaction that leads to production of proinflammatory cytokines. Such cytokines include interferon-γ, tumor necrosis factor-alpha, and interleukin-1, which act on endothelial cells to stimulate expression of adhesion molecules and procoagulant activity; on macrophages to activate proteases, endocytosis, nitric oxide (NO), and cytokines; and on smooth muscle cells (SMCs) to induce NO production and inhibit growth and collagen and actin expression. LDL, Low-density lipoprotein.
FIGURE 23-9 Progression of Atherosclerosis. A, Damaged endothelium. B, Diagram of fatty streak and lipid core formation (see Figure 23-8 for a diagram of oxidized low-density lipoprotein [LDL]). C, Diagram of fibrous plaque. Raised plaques are visible: some are yellow; others are white. D, Diagram of complicated lesion; thrombus is red; collagen is blue. Plaque is complicated by red thrombus deposition.
FIGURE 23-10 Atherosclerosis. A, Concentric coronary plaque. The lumen is central. There are multiple, new small blood vessels within the plaque, the late result of disruption. B, Cell types in fibrolipid plaque. The plaque cap (brownish color) contains numerous elongated, smooth muscle cells; some contain lipid. Macrophages are clustered on the edge of the core.
Clinical Manifestations
Evaluation and Treatment
Peripheral Artery Disease
Coronary Artery Disease, Myocardial Ischemia, and Acute Coronary Syndromes
Development of Coronary Artery Disease
Dyslipidemia
HEALTH ALERT
TABLE 23-4 CRITERIA FOR DYSLIPIDEMIA
Hypertension
Cigarette smoking
Diabetes mellitus
Obesity/sedentary lifestyle
Nontraditional risk factors
Markers of inflammation and thrombosis
Hyperhomocysteinemia
Adipokines
Infection
FIGURE 23-11 Cycle of Ischemic Events.
HEALTH ALERT
New Serum Markers of Cardiovascular Risk
Myocardial Ischemia
Pathophysiology
FIGURE 23-12 Angiogram of Coronary Arteries. A, Baseline. B, Transient total occlusion of left anterior descending branch of the left coronary artery after mental stress. C, After nitrates and nifedipine, artery reopened to same diameter as baseline.
Clinical Manifestations
FIGURE 23-13 Ischemic Cost of Aggravation. Linkages among daily mental and emotional stimuli, brain activity, and coronary and myocardial physiology.
Evaluation and Treatment
FIGURE 23-14 Pathophysiologic Model of the Effects of Acute Stress as a Trigger of Cardiac Clinical Events. Acting via the central and autonomic nervous systems, stress can produce a cascade of physiologic responses that may lead to myocardial ischemia, especially in persons with coronary artery disease; potentially fatal dysrhythmia; plaque rupture; or coronary thrombosis. LV, Left ventricular; MI, myocardial infarction; VF, ventricular fibrillation; VT, ventricular tachycardia.
FIGURE 23-15 Electrocardiogram (ECG) and Ischemia. A, Normal ECG. B, Electrocardiographic alterations associated with ischemia.
HEALTH ALERT
Women and Heart Disease
QUICK CHECK 23-5
Acute Coronary Syndromes
Unstable angina
FIGURE 23-16 Pathophysiology of Acute Coronary Syndromes. The atherosclerotic process can lead to stable plaque formation and stable angina or can result in unstable plaques that are prone to rupture and thrombus. Thrombus formation on a ruptured plaque that disperses in less than 20 minutes leads to transient ischemia and unstable angina. If the vessel obstruction is sustained, myocardial infarction with inflammation and necrosis of the myocardium results. In addition, myocardial infarction is associated with other structural and functional changes, including myocyte stunning and hibernation and myocardial remodeling (see Figure 23-35).
FIGURE 23-17 Pathogenesis of Unstable Plaques and Thrombus Formation.
BOX 23-1 THREE PRINCIPAL PRESENTATIONS OF UNSTABLE ANGINA
Myocardial infarction
Pathophysiology
Cellular injury
FIGURE 23-18 Plaque Disruption and Myocardial Infarction. A, Plaque disruption. The cap of the lipid-rich plaque has become torn with the formation of a thrombus, mostly inside the plaque. B, Myocardial infarction. This infarct is 6 days old. The center is yellow and necrotic with a hemorrhagic red rim. The responsible arterial occlusion is probably in the right coronary artery. The infarct is on the posterior wall.
Cellular death
Structural and functional changes
Repair
FIGURE 23-19 Myocardial Infarction. A, Local infarct confined to one region. B, Massive large infarct caused by occlusion of three coronary arteries.
Clinical Manifestations
Complications
Evaluation and Treatment
FIGURE 23-20 Three Interacting Factors Related to Sudden Cardiac Death. The three factors are ischemia, left ventricular dysfunction, and electrical instability.
FIGURE 23-21 Electrocardiographic Alterations Associated With the Three Zones of Myocardial Infarction.
TABLE 23-5 COMPLICATIONS WITH MYOCARDIAL INFARCTIONS
BOX 23-2 UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION
QUICK CHECK 23-6
Disorders of the Heart Wall
Disorders of the Pericardium
Acute Pericarditis
FIGURE 23-22 Acute Pericarditis. Note shaggy coat of fibers covering the surface of heart.
Pericardial Effusion
FIGURE 23-23 Exudate of Blood in the Pericardial Sac from Rupture of Aneurysm.
FIGURE 23-24 Constrictive Pericarditis. The fibrotic pericardium encases the heart in a rigid shell.
Constrictive Pericarditis
FIGURE 23-25 Diagram Showing Major Distinguishing Pathophysiologic Features of the Three Types of Cardiomyopathy. A, The normal heart. B, In the dilated type of cardiomyopathy, the heart has a globular shape and the largest circumference of the left ventricle is not at its base but midway between apex and base. C, In the hypertrophic type, the wall of the left ventricle is greatly thickened; the left ventricular cavity is small, but the left atrium may be dilated because of poor diastolic relaxation of the ventricle. D, In the restrictive (constrictive) type, the left ventricular cavity is of normal size, but, again, the left atrium is dilated because of the reduced diastolic compliance of the ventricle.
Disorders of the Myocardium: The Cardiomyopathies
FIGURE 23-26 Dilated cardiomyopathy. The dilated left ventricle has a thin wall (V).
FIGURE 23-27 Hypertrophic cardiomyopathy. There is marked left ventricular hypertrophy. This often affects the septum (S).
QUICK CHECK 23-7
Disorders of the Endocardium
Valvular Dysfunction
FIGURE 23-28 Valvular Stenosis and Regurgitation. A, Normal position of the valve leaflets, or cusps, when the valve is open and closed. B, Open position of a stenosed valve (left) and open position of a closed regurgitant valve (right). C, Hemodynamic effect of mitral stenosis. The stenosed valve is unable to open sufficiently during left atrial systole, inhibiting left ventricular filling. D, Hemodynamic effect of mitral regurgitation. The mitral valve does not close completely during left ventricular systole, permitting blood to reenter the left atrium.
TABLE 23-6 CLINICAL MANIFESTATIONS OF VALVULAR STENOSIS AND REGURGITATION
Stenosis
Aortic stenosis
FIGURE 23-29 Aortic Stenosis. Mild stenosis in valve leaflets of a young adult.
Mitral stenosis
FIGURE 23-30 Mitral Stenosis With Classic “Fish Mouth” Orifice.
Regurgitation
Aortic regurgitation
FIGURE 23-31 Mitral Valve Prolapse. A, Prolapsed mitral valve. Prolapse permits the valve leaflets to billow back (arrow) into the atrium during left ventricular systole. The billowing causes the leaflets to part slightly, permitting regurgitation into the atrium. B, Looking down into the mitral valve, the ballooning (arrows) of the leaflets is seen.
Mitral regurgitation
Tricuspid regurgitation
Mitral Valve Prolapse Syndrome
FIGURE 23-32 Pathogenesis and Structural Alterations of Acute Rheumatic Heart Disease. Beginning usually with a sore throat, rheumatic fever can develop only as a sequel to pharyngeal infection by group A β-hemolytic streptococcus. Suspected as a hypersensitivity reaction, it is proposed that antibodies directed against the M proteins of certain strains of streptococci cross-react with tissue glycoproteins in the heart, joints, and other tissues. The exact nature of cross-reacting antigens has been difficult to define, but it appears that the streptococcal infection causes an autoimmune response against self-antigens. Inflammatory lesions are found in various sites; the most distinctive within the heart are called Aschoff bodies. The chronic sequelae result from progressive fibrosis because of healing of the inflammatory lesions and the changes induced by valvular deformities.
Acute Rheumatic Fever and Rheumatic Heart Disease
Pathophysiology
TABLE 23-7 JONES CRITERIA (UPDATED) USED FOR DIAGNOSIS OF INITIAL ATTACK OF RHEUMATIC FEVER
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 23-8
Infective Endocarditis
RISK FACTORS
Pathophysiology
FIGURE 23-33 Pathogenesis of Infective Endocarditis.
Clinical Manifestations
Evaluation and Treatment
FIGURE 23-34 Bacterial Endocarditis of Mitral Valve. The valve is covered with large, irregular vegetations (arrow).
Cardiac Complications in Acquired Immunodeficiency Syndrome (AIDS)
QUICK CHECK 23-9
Manifestations of Heart Disease
Dysrhythmias
TABLE 23-8 DISORDERS OF IMPULSE FORMATION
TABLE 23-9 DISORDERS OF IMPULSE CONDUCTION
Heart Failure
Left Heart Failure (Congestive Heart Failure)
FIGURE 23-35 Pathophysiology of Ventricular Remodeling. Myocardial dysfunction activates the renin-angiotensin-aldosterone and sympathetic nervous systems, releasing neurohormones (angiotensin II, aldosterone, catecholamines, and cytokines). These neurohormones contribute to ventricular remodeling.
FIGURE 23-36 Effect of Elevated Preload on Myocardial Oxygen Supply and Demand. LVEDV, Left ventricular end-diastolic volume.
BOX 23-3 INFLAMMATION, IMMUNITY, AND HUMORAL FACTORS IN THE PATHOGENESIS OF HEART FAILURE
FIGURE 23-37 Role of Increased Afterload in the Pathogenesis of Heart Failure.
HEALTH ALERT
FIGURE 23-38 Vicious Cycle of Systolic Heart Failure. Although the initial insult may be one of primary decreased contractility (e.g., myocardial infarction), increased preload (e.g., renal failure), or increased afterload (e.g., hypertension), all three factors play a role in the progression of left heart failure (LHF). LVEDV, Left ventricular end-diastolic volume.
Right Heart Failure
High-Output Failure
FIGURE 23-39 Right Heart Failure. RA, Right atrial; RV, right ventricular.
FIGURE 23-40 High-Output Failure. SVR, Systemic vascular resistance.
QUICK CHECK 23-10
Shock
Impairment of Cellular Metabolism
Impairment of Oxygen Use
FIGURE 23-41 Impaired Cellular Metabolism in Shock. ATP, Adenosine triphosphate.
Impairment of Glucose Use
Clinical Manifestations of Shock
Treatment for Shock
Types of Shock
Cardiogenic Shock
FIGURE 23-42 Cardiogenic Shock. Shock becomes life-threatening when compensatory mechanisms (in blue) cause increased myocardial oxygen requirements. Renal and hypothalamic adaptive responses (i.e., renin-angiotensin-aldosterone and antidiuretic hormone [ADH]) maintain or increase blood volume. The adrenal gland releases catecholamines (e.g., mostly epinephrine, some norepinephrine), causing vasoconstriction and increases in contractility and heart rate. These adaptive mechanisms, however, increase myocardial demands for oxygen and nutrients. These demands further strain the heart, which can no longer pump an adequate volume, resulting in shock and impaired metabolism. SVR, Systemic vascular resistance.
FIGURE 23-43 Hypovolemic Shock. This type of shock becomes life-threatening when compensatory mechanisms (in purple) are overwhelmed by continued loss of intravascular volume. ADH, Antidiuretic hormone; SVR, systemic vascular resistance.
Hypovolemic Shock
Neurogenic Shock
Anaphylactic Shock
FIGURE 23-44 Neurogenic Shock. SVR, Systemic vascular resistance.
QUICK CHECK 23-11
Septic Shock
FIGURE 23-45 Anaphylactic Shock. IgE, Immunoglobulin E; SVR, systemic vascular resistance.
TABLE 23-10 CAUSES AND DEFINITIONS OF SEPTIC SHOCK
FIGURE 23-46 Septic Shock. TLR, Toll-like receptor.
HEALTH ALERT
RISK FACTORS
Interleukin-1β (IL-1β)
Tumor Necrosis Factor-alpha (TNF-α)
Platelet-Activating Factor (PAF)
High-Mobility Group Box 1 (HMGB1)
QUICK CHECK 23-12
HEALTH ALERT
Multiple Organ Dysfunction Syndrome
RISK FACTORS
Pathophysiology
FIGURE 23-47 Pathogenesis of Multiple Organ Dysfunction Syndrome.
TABLE 23-11 CELLS OF INFLAMMATION AND MULTIPLE ORGAN DYSFUNCTION
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 23-13
HEALTH ALERT
DID YOU UNDERSTAND?
Diseases of the Veins and Arteries
Disorders of the Heart Wall
Manifestations of Heart Disease
Shock
KEY TERMS
Acute Coronary Syndrome (see video)
Aortic regurgitation (see video)
Mitral regurgitation (see video)
Atrial fibrillation (see video)
Systemic inflammatory response syndrome (SIRS) (see video)
References
Chapter 24 Alterations of Cardiovascular Function in Children
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 Comparison of Acyanotic-Cyanotic and Hemodynamic Classification Systems of Congenital Heart Disease.
FIGURE 24-2 Shunting of Blood in Congenital Heart Disease. A, Normal. B, Acyanotic defect. C, Cyanotic defect. ASD, Atrial septal defect; AV, aortic valve; LA, left atrium; LV, left ventricle; PV, pulmonic valve; RA, right atrium; RV, right ventricle; VSD, ventricular septal defect.
FIGURE 24-3 Postductal and Preductal Coarctation of the Aorta. A, Postductal coarctation occurs distal to (“after”) the insertion of the closed ductus arteriosus into the aortic arch. Preductal coarctation occurs proximal to (“before”) the insertion of the patent ductus arteriosus. The coarctation consists of a flap of tissue that protrudes from the tunica media of the aortic wall. B, Coarctation of the aorta with typical indentation of the aortic wall (arrow) opposite the ductal arterial ligament (asterisk). Ao, Aorta.
Aortic Stenosis
Pathophysiology
FIGURE 24-4 Aortic Stenosis (AS). Narrowing of the aortic valve causing resistance to blood flow in the left ventricle, decreased cardiac output, left ventricular hypertrophy, and pulmonary congestion.
Clinical Manifestations
HEALTH ALERT
Evaluation And Treatment
Valvular aortic stenosis
FIGURE 24-5 Pulmonic Stenosis (PS). A, The pulmonary valve narrows at the entrance of the pulmonary artery. B, Balloon angioplasty is used to dilate the valve. A catheter is inserted across the stenotic pulmonic valve into the pulmonary artery, and a balloon at the end of the catheter is inflated while it is positioned across the narrowed valve opening.
Subvalvular aortic stenosis
Supravalvular aortic stenosis
Pulmonic Stenosis
Pathophysiology
Clinical Manifestations
Evaluation And Treatment
Defects With Increased Pulmonary Blood Flow
Patent Ductus Arteriosus
Pathophysiology
Clinical Manifestations
FIGURE 24-6 Patent Ductus Arteriosus (PDA). A, PDA with left-to-right shunt. B, PDA in an adult with pulmonary hypertension. Ao, Aorta; LPA, left pulmonary artery; RPA, right pulmonary artery; SCV, subclavian vein.
Evaluation And Treatment
Atrial Septal Defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Ventricular Septal Defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 24-7 Atrioventricular Canal (AVC) Defect.
Atrioventricular Canal Defect
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Defects With Decreased Pulmonary Blood Flow
Tetralogy of Fallot
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Tricuspid Atresia
Pathophysiology
FIGURE 24-8 Tetralogy of Fallot (TOF) A, TOF hemodynamics. B, Right ventricular (RV) hypertrophy and AO.
FIGURE 24-9 Tricuspid Atresia.
Clinical Manifestations
Evaluation and Treatment
Mixing Defects
Transposition of the Great Arteries or Transposition of the Great Vessels
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 24-10 Hemodynamics in Transposition of the Great Vessels (TGV). A, Complete transposition of the great vessels with an intact interventricular septum. The aorta arises from the right ventricle and the pulmonary artery from the left ventricle. B, Oxygen saturation in the two, parallel circuits. Ao, Aorta; ASD, atrial septal defect; LA, left atrium; LV, left ventricle; PA, pulmonary artery; PDA, patent ductus arteriosus; RA, right atrium; RV, right ventricle; VSD, ventricular septal defect.
Total Anomalous Pulmonary Venous Connection
Pathophysiology
FIGURE 24-11 Total Anomalous Pulmonary Venous Connection (TAPVC).
Clinical Manifestations
Evaluation and Treatment
Truncus Arteriosus
Pathophysiology
Clinical Manifestations
FIGURE 24-12 Truncus Arteriosus (TA).
Evaluation and Treatment
Hypoplastic Left Heart Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 24-13 Hypoplastic Left Heart Syndrome (HLHS).
QUICK CHECK 24-1
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
Systemic Hypertension
TABLE 24-4 NORMATIVE BLOOD PRESSURE LEVELS (SYSTOLIC/DIASTOLIC [MEAN]) BY DINAMAP MONITOR IN CHILDREN 5 YEARS OLD AND YOUNGER
BOX 24-2 DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE
HEALTH ALERT
TABLE 24-5 SUGGESTED NORMAL BP VALUES (mm Hg) BY AUSCULTATORY METHOD (SYSTOLIC/DIASTOLIC K5)
BOX 24-3 CONDITIONS ASSOCIATED WITH SECONDARY HYPERTENSION IN CHILDREN
Renal Disorders
Cardiovascular Disease
Metabolic and Endocrine Diseases
Neurologic Disorders
Miscellaneous Causes
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
TABLE 24-6 MOST COMMON CAUSES OF CHRONIC SUSTAINED HYPERTENSION
TABLE 24-7 ROUTINE AND SPECIAL LABORATORY TESTS FOR HYPERTENSION
QUICK CHECK 24-2
DID YOU UNDERSTAND?
Congenital Heart Disease
Acquired Cardiovascular Disorders in Children
KEY TERMS
Subaortic stenosis (see video)
Congestive heart failure (see video)
References
UNIT 8 The Pulmonary System
Interactive Review – Unit 8
Chapter 25 Structure and Function of the Pulmonary System
Structures of the Pulmonary System
Conducting Airways
FIGURE 25-1 Structure of the Pulmonary System. The enlargement in the circle depicts the acinus, where oxygen and carbon dioxide are exchanged.
TABLE 25-1 PULMONARY DEFENSE MECHANISMS
FIGURE 25-2 Structures of the Upper Airway.
FIGURE 25-3 Structures of the Lower Airway.
FIGURE 25-4 Changes in the Bronchial Wall With Progressive Branching.
Gas-Exchange Airways
QUICK CHECK 25-1
Pulmonary and Bronchial Circulation
FIGURE 25-5 Alveoli. Bronchioles subdivide to form tiny tubes called alveolar ducts, which end in clusters of alveoli called alveolar sacs.
Chest Wall and Pleura
Function of the Pulmonary System
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.
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.
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.
FIGURE 25-9 Neurochemical Respiratory Control System.
QUICK CHECK 25-2
Neurochemical Control of Ventilation
Lung Receptors
Chemoreceptors
HEALTH ALERT
QUICK CHECK 25-3
Mechanics of Breathing
Major and Accessory Muscles
FIGURE 25-10 Muscles of Ventilation. A, Anterior view. B, Posterior view.
Alveolar Surface Tension
Elastic Properties of the Lung and Chest Wall
Airway Resistance
FIGURE 25-11 Interaction of Forces During Inspiration and Expiration. A, Outward recoil of the chest wall equals inward recoil of the lungs at the end of expiration. B, During inspiration, contraction of respiratory muscles, assisted by chest wall recoil, overcomes the tendency of lungs to recoil. C, At the end of inspiration, respiratory muscle contraction maintains lung expansion. D, During expiration, respiratory muscles relax, allowing elastic recoil of the lungs to deflate the lungs.
Work of Breathing
QUICK CHECK 25-4
Gas Transport
FIGURE 25-12 Spirogram. During normal, quiet respirations, the atmosphere and lungs exchange about 500 ml of air (VT). With a forcible inspiration, about 3300 ml more air can be inhaled (IRV). After a normal inspiration and normal expiration, approximately 1000 ml more air can be forcibly expired (ERV). Vital capacity (VC) is the amount of air that can be forcibly expired after a maximal inspiration and indicates, therefore, the largest amount of air that can enter and leave the lungs during respiration. Residual volume (RV) is the air that remains trapped in the alveoli.
FIGURE 25-13 Relationship Between Number of Gas Molecules and Pressure Exerted by the Gas in an Enclosed Space. A, Theoretically, 10 molecules of the same gas exert a total pressure of 10 within the space. B, If the number of molecules is increased to 20, total pressure is 20. C, If there are different gases in the space, each gas exerts a partial pressure: here the partial pressure of nitrogen (N2) is 20, that of oxygen (O2) is 6, and the total pressure is 26.
Measurement of Gas Pressure
TABLE 25-2 COMMON PULMONARY ABBREVIATIONS
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.
Distribution of Ventilation and Perfusion
FIGURE 25-15 Gravity and Alveolar Pressure. Effects of gravity and alveolar pressure on pulmonary blood flow in the three lung zones. In zone I, alveolar pressure (PA) is greater than arterial and venous pressures, and no blood flow occurs. In zone II, arterial pressure (Pa) exceeds alveolar pressure, but alveolar pressure exceeds venous pressure (PV). Blood flow occurs in this zone, but alveolar pressure compresses the venules (venous ends of the capillaries). In zone III, both arterial and venous pressures are greater than alveolar pressure and blood flow fluctuates depending on the difference between arterial pressure and venous pressure.
Oxygen Transport
Diffusion across the alveolocapillary membrane
Determinants of arterial oxygenation
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.
Oxyhemoglobin association and dissociation
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 100 mm Hg do not significantly alter the percentage saturation of hemoglobin with oxygen and allow adequate hemoglobin saturation at a variety of altitudes. If the relationship between SaO2 and PaO2 was linear (in a downward sloping straight line) instead of flat between 60 and 100 mm Hg, there would be inadequate saturation of hemoglobin with oxygen. The steep part of the oxyhemoglobin dissociation curve represents the rapid dissociation of oxygen from hemoglobin that occurs in the tissues. During this phase there is rapid diffusion of oxygen from the blood into tissue cells. The P50 is the PaO2 at which hemoglobin is 50% saturated, normally 26.6 mm Hg. A lower than normal P50 represents increased affinity of hemoglobin for O2; a high P50 is seen with decreased affinity. Note that variation from the normal is associated with decreased (low P50) or increased (high P50) availability of O2 to tissues (dashed lines). The shaded area shows the entire oxyhemoglobin dissociation curve under the same circumstances. 2,3-DPG, 2,3-Diphosphoglycerate.
QUICK CHECK 25-5
Control of the Pulmonary Circulation
QUICK CHECK 25-6
GERIATRIC CONSIDERATIONS
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.
DID YOU UNDERSTAND?
Structures of the Pulmonary System
Function of the Pulmonary System
GERIATRIC CONSIDERATIONS: Aging & the Pulmonary System
KEY TERMS
References
Chapter 26 Alterations of Pulmonary Function
Clinical Manifestations of Pulmonary Alterations
Signs and Symptoms of Pulmonary Disease
Dyspnea
Cough
Abnormal Sputum
Hemoptysis
Abnormal Breathing Patterns
Hypoventilation/Hyperventilation
Cyanosis
Clubbing
Pain
FIGURE 26-1 Clubbing of Fingers Caused by Chronic Hypoxemia.
Conditions Caused by Pulmonary Disease or Injury
Hypercapnia
Hypoxemia
FIGURE 26-2 Ventilation-Perfusion (V·Q·) Abnormalities.
QUICK CHECK 26-1
Acute Respiratory Failure
Disorders of the Chest Wall and Pleura
Chest Wall Restriction
FIGURE 26-3 Flail Chest. Normal respiration: A, inspiration; B, expiration. Paradoxical motion: C, inspiration, area of lung underlying unstable chest wall flattens on inspiration; D, expiration, unstable area inflates. Note movement of mediastinum toward opposite lung during inspiration.
Pleural Abnormalities
Pneumothorax
FIGURE 26-4 Pneumothorax. Air in the pleural space causes the lung to collapse around the hilus and may push mediastinal contents (heart and great vessels) toward the other lung.
TABLE 26-1 MECHANISM OF PLEURAL EFFUSION*
Pleural effusion
Empyema
QUICK CHECK 26-2
Pulmonary Disorders
Restrictive Lung Diseases
Aspiration
FIGURE 26-5 Pores of Kohn. A, Absorption atelectasis caused by lack of collateral ventilation through pores of Kohn. B, Restoration of collateral ventilation during deep breathing.
Atelectasis
Bronchiectasis
Bronchiolitis
Pulmonary Fibrosis
Idiopathic pulmonary fibrosis
Inhalation Disorders
Exposure to toxic gases
Pneumoconiosis
Allergic alveolitis
Pulmonary Edema
FIGURE 26-6 Pathogenesis of Pulmonary Edema.
Acute Respiratory Distress Syndrome
Pathophysiology
FIGURE 26-7 Pathogenesis of Acute Respiratory Distress Syndrome (ARDS). IL-1, Interleukin-1; ROS, reactive oxygen species; TGF-β, transforming growth factor-beta; TNF, tumor necrosis factor.
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.
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 (also see Figure 27-7).
Evaluation and Treatment
Chronic Obstructive Pulmonary Disease
FIGURE 26-10 Pathogenesis of Chronic Bronchitis and Emphysema (Chronic Obstructive Pulmonary Disease [COPD]).
FIGURE 26-11 Mechanisms of Air Trapping in COPD. Mucous plugs and narrowed airways cause air trapping and hyperinflation of alveoli on expiration. During inspiration, the airways are pulled open, allowing gas to flow past the obstruction. During expiration, decreased elastic recoil of the bronchial walls results in collapse of the airways and prevents normal expiratory airflow.
HEALTH ALERT
Chronic Bronchitis
Pathophysiology
TABLE 26-2 CLINICAL MANIFESTATIONS OF CHRONIC OBSTRUCTIVE LUNG DISEASE
Clinical Manifestations
Evaluation and Treatment
Emphysema
FIGURE 26-12 Bullous Emphysema with Large Apical and Subpleural Bullae (see arrows).
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 26-4
Respiratory Tract Infections
Pneumonia
Pathophysiology
HEALTH ALERT
Pneumococcal pneumonia
FIGURE 26-13 Pathophysiologic Course of Pneumococcal Pneumonia.
Viral pneumonia
Clinical Manifestations
Evaluation and Treatment
HEALTH ALERT
Tuberculosis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Acute Bronchitis
Abscess Formation and Cavitation
QUICK CHECK 26-5
Pulmonary Vascular Disease
Pulmonary Embolism
Pathophysiology
FIGURE 26-14 Pathogenesis of Massive Pulmonary Embolism Caused by a Thrombus (Pulmonary Thromboembolism).
Clinical Manifestations
Evaluation and Treatment
Pulmonary Hypertension
Pathophysiology
FIGURE 26-15 Pathogenesis of Pulmonary Hypertension and Cor Pulmonale.
Clinical Manifestations
Evaluation and Treatment
Cor Pulmonale
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 26-6
Malignancies of the Respiratory Tract
Lip Cancer
FIGURE 26-16 Lip Cancer. Carcinoma of lower lip with central ulceration and raised, rolled borders.
BOX 26-1 STAGING OF LIP CANCER
Stage I
Stage II
Stage III
Stage IV
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Laryngeal Cancer
FIGURE 26-17 Laryngeal Cancer. A, Mirror view of carcinoma of the right false cord partially hiding the true cord. B, Lateral view.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Lung Cancer
Types of lung cancer
Non–small cell lung cancer
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.
TABLE 26-3 CHARACTERISTICS OF LUNG CANCERS
Small cell lung cancer
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
HEALTH ALERT
QUICK CHECK 26-7
DID YOU UNDERSTAND?
Clinical Manifestations of Pulmonary Alterations
Disorders of the Chest Wall and Pleura
Pulmonary Disorders
KEY TERMS
Open pneumothorax (see video)
Tension pneumothorax (see video)
Asthma (see video)
Tuberculosis (see video)
Pulmonary embolism (see video)
Pulmonary hypertension (see video)
References
Chapter 27 Alterations of Pulmonary Function in Children
Disorders of the Upper Airways
Infections of the Upper Airways
Croup
FIGURE 27-1 The Larynx and Subglottic Trachea. A, Normal trachea. B, Narrowing and obstruction from edema caused by croup.
FIGURE 27-2 Upper Airway Obstruction With Croup.
TABLE 27-1 COMPARISON OF UPPER AIRWAY INFECTIONS
Pathophysiology
FIGURE 27-3 Listening Can Help Locate the Site of Airway Obstruction. A loud, gasping snore suggests enlarged tonsils or adenoids. In inspiratory stridor, the airway is compromised at the level of the supraglottic larynx, vocal cords, subglottic region, or upper trachea. Expiratory stridor results from a narrowing or collapse in the trachea or bronchi. Airway noise during both inspiration and expiration often represents a fixed obstruction of the vocal cords or subglottic space. Hoarseness or a weak cry is a by-product of obstruction at the vocal cords. If a cough is croupy, suspect constriction below the vocal cords.
Clinical Manifestations
Evaluation and Treatment
FIGURE 27-4 Areas of Chest Muscle Retraction.
Acute Epiglottitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Tonsillar Infections
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
Pathophysiology
FIGURE 27-5 Pathogenesis of Respiratory Distress Syndrome (RDS) of the Newborn.
Clinical Manifestations
Evaluation and Treatment
Bronchopulmonary Dysplasia
RISK FACTORS
Pathophysiology
Clinical Manifestations
FIGURE 27-6 Pathophysiology of Bronchopulmonary Dysplasia (BPD).
Evaluation and Treatment
QUICK CHECK 27-2
Respiratory Tract Infections
Bronchiolitis
Pathophysiology
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
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 27-7 Asthmatic Responses. A, In the early asthmatic response, inhaled antigen (1) binds to preformed IgE on mast cells. Mast cells degranulate (2) and release mediators such as histamine, leukotrienes, prostaglandin D2, platelet activating factor, and others. Acute inflammation opens intercellular tight junctions, allowing allergen to penetrate and activate submucosal mast cells. Secreted mediators (3) induce active bronchospasm, edema, and mucus secretion causing airway obstruction. Inflammatory responses are triggered by chemotactic factors and up-regulation of adhesion molecules (not shown). At the same time, as shown on the left, antigen may be received by dendritic cells and later presented, either to regional lymph nodes of naïve (Tho) T lymphocytes or locally to memory Th2 cells in the airway mucosa (see B). B, In the late asthmatic response, there are areas of epithelial damage and shedding caused at least in part by toxicity of eosinophil products (major basic protein, eosinophilic cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase). Many inflammatory cells are recruited by chemokines and up-regulation of vascular cell adhesion molecules. Local T lymphocytes display a predominant Th2 cytokine profile. They produce IL-4 and IL-13, which promote switching of B cells to favor IgE production; and IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor, which encourage eosinophil differentiation and survival. Inflammatory mediators also activate sensory nerves, further stimulating bronchoconstriction (also see Figure 26-9).
HEALTH ALERT
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 the upper lobe [U]), with hemorrhagic pneumonia in the lower lobe (L). Small cysts (C) are present at the apex of the lung.
Clinical Manifestations
Evaluation and Treatment
HEALTH ALERT
FIGURE 27-9 Pathogenesis of Cystic Fibrosis Lung Disease. CFTR, Cystic fibrosis transmembrane conductance regulator.
Sudden Infant Death Syndrome
HEALTH ALERT
RISK FACTORS
QUICK CHECK 27-5
DID YOU UNDERSTAND?
Disorders of the Upper Airways
Disorders of the Lower Airways
Sudden Infant Death Syndrome (SIDS)
KEY TERMS
References
UNIT 9 The Renal and Urologic Systems
Interactive Review – Unit 9
Chapter 28 Structure and Function of the Renal and Urologic Systems
Structures of the Renal System
Structures of the Kidney
FIGURE 28-1 Organs of the Urinary System.
FIGURE 28-2 Kidney Structure.
FIGURE 28-3 Components of Nephron.
FIGURE 28-4 Epithelial Cells of the Various Segments of Nephron Tubules. The brush border and high number of mitochondria in cells of the proximal tubule promote reabsorption of 50% of the glomerular filtrate. Intercalated cells secrete H+ (through K+ exchange) or reabsorb HCO3−. Principal cells are influenced by aldosterone and reabsorb Na+ and water and secrete K+.
Nephron
FIGURE 28-5 Nephron Unit with Its Blood Vessels. Blood flows through nephron vessels as follows: interlobular artery, afferent arteriole, glomerulus, efferent arteriole, peritubular capillaries (around the tubules), venules, interlobular vein. The vasa recta capillaries distribute along the long loops of Henle of the juxtamedullary nephrons.
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.
Blood Vessels of the Kidney
QUICK CHECK 28-1
Urinary Structures
Ureters
Bladder and Urethra
FIGURE 28-7 Structure of the Urinary Bladder. Frontal view of a dissected urinary bladder (male) in a fully distended position.
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.
Neural Regulation of Renal Blood Flow
FIGURE 28-9 Renin-Angiotensin-Aldosterone System. Activation of tubuloglomerular feedback mechanisms stimulates the release of renin with activation of the renin-angiotensin-aldosterone cascade. Plasma volume and blood pressure are increased with the reabsorption of sodium chloride and water from the renal tubules. The restoration of plasma volume and blood pressure then decreases the release of renin, forming a negative feedback loop.
Hormonal Regulation of Renal Blood Flow
FIGURE 28-10 Major Functions of Nephron Segments. ADH, Antidiuretic hormone.
QUICK CHECK 28-2
Kidney Function
Nephron Function
Glomerular Filtration
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
FIGURE 28-12 Countercurrent Mechanism for Concentrating and Diluting Urine. ADH, Antidiuretic hormone.
BOX 28-1 Substances Transported by Renal Tubules
Acidification of urine
FIGURE 28-13 Acidification of Urine by Tubule Excretion of Phosphate and Ammonia (NH3). A, Acidification of urine and conservation of base by distal renal tubule excretion of H+ via phosphate buffers. B, An amino acid (glutamine) moves into the tubule cell and forms ammonia (NH3), which is secreted into the urine and combines with H+ to form ammonium ion (NH4+) and an ammonium salt (NH4Cl). In exchange, the tubule cell absorbs a basic salt (mainly NaHCO3) into blood from urine.
Urine
HEALTH ALERT
Hormones and Nephron Function
Antidiuretic Hormone
Aldosterone
Atrial Natriuretic Peptide
Diuretics as a Factor in Urine Flow
Renal Hormones
Urodilatin
Vitamin D
TABLE 28-2 ACTION OF DIURETICS
Erythropoietin
QUICK CHECK 28-3
Test of Renal Function
The Concept of Clearance
Clearance and Glomerular Filtration Rate
Plasma Creatinine Concentration
Blood Urea Nitrogen
Urinalysis
TABLE 28-3 NORMAL RENAL FUNCTION TESTS
TABLE 28-4 BLADDER FUNCTION TESTS
PEDIATRIC CONSIDERATIONS
QUICK CHECK 28-4
GERIATRIC CONSIDERATIONS
DID YOU UNDERSTAND?
Structures of the Renal System
Renal Blood Flow
Kidney Function
Tests of Renal Function
PEDIATRIC CONSIDERATIONS: Pediatrics & Renal Function
GERIATRIC CONSIDERATIONS: Aging & Renal Function
KEY TERMS
References
Chapter 29 Alterations of Renal and Urinary Tract Function
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.
Kidney Stones
Pathophysiology
Clinical Manifestations
Evaluation And Treatment
Lower Urinary Tract Obstruction
Neurogenic Bladder
Overactive Bladder Syndrome
TABLE 29-1 TYPES OF INCONTINENCE
TABLE 29-2 NEUROGENIC BLADDER
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 (Pves); line 5, detrusor muscle pressure (Pdet); line 6, bladder electromyelogram (EMG).
Tumors
Renal Tumors
FIGURE 29-4 Renal Cell Carcinoma. Renal cell carcinomas usually are spheroidal masses composed of yellow tissue mottled with hemorrhage, necrosis, and fibrosis.
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Bladder Tumors
Pathogenesis
TABLE 29-3 STAGING OF RENAL CELL CARCINOMA
TABLE 29-4 STAGING OF BLADDER CARCINOMA (TNM SYSTEM)
Clinical Manifestations
Evaluation and Treatment
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
Painful Bladder Syndrome/Interstitial Cystitis
HEALTH ALERT
TABLE 29-5 COMMON CAUSES OF PYELONEPHRITIS
Acute Pyelonephritis
Pathophysiology
Clinical Manifestations
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.
Evaluation and Treatment
Chronic Pyelonephritis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 29-2
Glomerular Disorders
Glomerulonephritis
FIGURE 29-6 Mechanisms of Glomerular Injury. Ab, Antibody; GBM, glomerular basement membrane; GFR, glomerular filtration rate; NO, nitric oxide.
Pathophysiology
TABLE 29-6 TYPES OF GLOMERULAR LESIONS
Clinical Manifestations
Evaluation and Treatment
TABLE 29-7 IMMUNOLOGIC PATHOGENESIS OF GLOMERULONEPHRITIS
Types of Glomerulonephritis
Membranous Nephropathy
Chronic Glomerulonephritis
FIGURE 29-7 Chronic Glomerulonephritis. The kidneys appear small, are uniformly shrunken, and have a finely granular external surface.
TABLE 29-8 FEATURES OF THE COMMON TYPES OF GLOMERULONEPHRITIS
Nephrotic and Nephritic Syndromes
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 29-3
Acute Kidney Injury
Classification of Kidney Dysfunction
Pathophysiology
TABLE 29-9 CLINICAL MANIFESTATIONS OF NEPHROTIC SYNDROME
TABLE 29-10 RIFLE CRITERIA FOR ACUTE KIDNEY DYSFUNCTION/FAILURE
Clinical Manifestations
TABLE 29-11 CLASSIFICATION OF ACUTE KIDNEY INJURY
FIGURE 29-8 Mechanisms of Oliguria in Acute Kidney Failure. GFR, Glomerular filtration rate.
Evaluation and Treatment
Chronic Kidney Disease
Pathophysiology
TABLE 29-12 DIFFERENTIATION OF ACUTE OLIGURIC KIDNEY FAILURE
TABLE 29-13 STAGES OF CHRONIC KIDNEY DISEASE
FIGURE 29-9 Common Signs and Symptoms of Kidney Failure (see text for reference site).
Clinical Manifestations
TABLE 29-14 SYSTEMIC EFFECTS OF CHRONIC KIDNEY FAILURE
Creatinine and urea clearance
Fluid and electrolyte balance
FIGURE 29-10 Mechanisms Related to the Progression of Chronic Kidney Disease.
TABLE 29-15 FACTORS REPRESENTING PROGRESSION OF CHRONIC KIDNEY FAILURE
Calcium, phosphate, and bone
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
Acute Kidney Injury
Chronic Kidney Disease
KEY TERMS
References
Chapter 30 Alterations of Renal and Urinary Tract Function in Children
Structural Abnormalities
Hypospadias
FIGURE 30-1 Hypospadias.
FIGURE 30-2 Hypospadias with Significant Chordee.
Epispadias and Exstrophy of the Bladder
FIGURE 30-3 Exstrophy of Bladder.
Bladder Outlet Obstruction
Ureteropelvic Junction Obstruction
Hypoplastic/Dysplastic Kidneys
Polycystic Kidney Disease
Renal Agenesis
QUICK CHECK 30-1
Glomerular Disorders
Glomerulonephritis
Acute Poststreptococcal 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
HEALTH ALERT
Vesicoureteral Reflux
Pathophysiology
FIGURE 30-4 Normal and Abnormal Configurations of the Ureterovesical ureter. A refluxing ureterovesical ureter has the same anatomic features as a nonrefluxing ureter, except for the shorter length of the intravesical ureter which allows reflux of urine during filling of the bladder.
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 30-2
Nephroblastoma
FIGURE 30-5 Grades of Vesicoureteral Reflux.
Pathogenesis
Clinical Manifestations
Evaluation and Treatment
Urinary Incontinence
Types of Incontinence
TABLE 30-1 STAGING OF NEPHROBLASTOMA TUMOR*
TABLE 30-2 CLASSIFICATION OF INCONTINENCE
Pathogenesis
Evaluation and Treatment
QUICK CHECK 30-3
DID YOU UNDERSTAND?
Structural Abnormalities
Glomerular Disorders
Bladder Disorders
Nephroblastoma
Urinary Incontinence
KEY TERMS
References
UNIT 10 The Reproductive Systems
Interactive Review – Unit 10
Chapter 31 Structure and Function of the Reproductive Systems
Development of the Reproductive Systems
Sexual Differentiation in Utero
TABLE 31-1 SUMMARY OF FEMALE AND MALE SEX AND REPRODUCTIVE HORMONES
FIGURE 31-1 Internal Genitalia Development. Embryonic and fetal development of the internal genitalia.
Puberty and Reproductive Maturation
FIGURE 31-2 External Genitalia Development. Embryonic and fetal development of the external genitalia.
QUICK CHECK 31-1
The Female Reproductive System
FIGURE 31-3 Hormonal Stimulation of the Gonads. The hypothalamic-pituitary-gonadal axis.
External Genitalia
FIGURE 31-4 External Female Genitalia.
Internal Genitalia
Vagina
FIGURE 31-5 Internal Female Genitalia and Other Pelvic Organs.
Uterus
FIGURE 31-6 Uterine Positions.
FIGURE 31-7 Cross Section of Uterus, Fallopian Tube, and Ovary.
QUICK CHECK 31-2
Fallopian Tubes
Ovaries
FIGURE 31-8 Cross Section of Ovary and Development of an Ovarian Follicle. Schematic representation (not to scale) of the structure of the ovary, showing the various stages in the development of the follicle and its successor structure, the corpus luteum.
Female Sex Hormones
Estrogens and Androgens
BOX 31-1 Summary of Nonreproductive Effects of Estrogen
Progesterone
TABLE 31-2 COMPLEMENTARY AND OPPOSING EFFECTS OF ESTROGEN AND PROGESTERONE
QUICK CHECK 31-3
Menstrual Cycle
Phases of the Menstrual Cycle
FIGURE 31-9 Female Reproductive Cycles. This figure illustrates the interrelationships among the cerebral, hypothalamic, pituitary, ovarian, and uterine functions throughout a standard 28-day menstrual cycle. The variations in basal body temperature are also illustrated.
TABLE 31-3 HORMONAL FEEDBACK MECHANISM IN THE MENSTRUAL CYCLE
Hormonal Controls
Ovarian Cycle
Uterine Phases
Vaginal Response
Body Temperature
QUICK CHECK 31-4
Structure and Function of the Breast
FIGURE 31-10 Schematic Diagram of Breast.
Female Breast
FIGURE 31-11 Lymphatic Drainage of the Female Breast.
Male Breast
FIGURE 31-12 Structure of the Male Reproductive Organs.
QUICK CHECK 31-5
The Male Reproductive System
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.
External Genitalia
Testes
Epididymis
FIGURE 31-14 The Testes. External and sagittal views showing interior anatomy.
Scrotum
Penis
FIGURE 31-15 Cross Section of the Penis.
Internal Genitalia
FIGURE 31-16 Anatomy of the Prostate Gland and Seminal Vesicles.
Spermatogenesis
Male Sex and Reproductive Hormones
FIGURE 31-17 Seminiferous Tubule. Section shows process of meiosis and sperm cell formation (spermatogenesis).
FIGURE 31-18 Mature Sperm Cell (Spermatozoon). Anatomy of mature sperm cell.
QUICK CHECK 31-6
HEALTH ALERT
Aging & Reproductive Function
Aging and the Female Reproductive System
FIGURE 31-19 Perimenopausal Hormone Transition. Mean circulating hormone levels. FSH, Follicle-stimulating hormone; LH, luteinizing hormone.
HEALTH ALERT
Aging and the Male Reproductive System
QUICK CHECK 31-7
DID YOU UNDERSTAND?
Development of the Reproductive Systems
The Female Reproductive System
Structure and Function of the Breast
The Male Reproductive System
Aging & Reproductive Function
KEY TERMS
References
Chapter 32 Alterations of the Reproductive Systems, Including Sexually Transmitted Infections
Alterations of Sexual Maturation
Delayed or Absent 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
BOX 32-2 PRIMARY FORMS OF PRECOCIOUS PUBERTY
Complete Precocious Puberty
Partial Precocious Puberty
Mixed Precocious Puberty
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
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
FIGURE 32-1 Causes of Secondary Amenorrhea. Of note, hypothyroidism is a relatively common condition and should be ruled out as the cause of hyperprolactinemia before more extensive evaluation (i.e., computed tomography or magnetic resonance imaging) occurs.
Abnormal Uterine Bleeding
TABLE 32-1 ABNORMAL MENSTRUAL BLEEDING
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
TABLE 32-2 COMMON CAUSES OF ABNORMAL (VAGINAL/GENITAL) BLEEDING IN DESCENDING ORDER OF FREQUENCY
Polycystic Ovary Syndrome
FIGURE 32-2 Polycystic Ovary. A, Surgical view of polycystic ovaries. B, Ultrasound of polycystic ovary.
PATHOPHYSIOLOGY
FIGURE 32-3 Insulin Resistance and Hyperinsulinemia in Polycystic Ovary Syndrome (PCOS). See text for explanation. FSH, Follicle-stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone–binding globulin.
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
BOX 32-3 CLINICAL MANIFESTATIONS OF POLYCYSTIC OVARY SYNDROME
Presenting Signs and Symptoms (% of Women Affected)
Hormonal Disturbances
Possible Late Sequelae
Other
Premenstrual Syndrome
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
BOX 32-4 AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) CRITERIA
QUICK CHECK 32-2
Infection and Inflammation
Pelvic Inflammatory Disease
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.
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
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.
EVALUATION AND TREATMENT
Vaginitis
Cervicitis
Vulvovestibulitis
Bartholinitis
FIGURE 32-6 Inflammation of Bartholin Glands.
Pelvic Organ Prolapse
TABLE 32-3 PELVIC ORGAN PROLAPSE: SYMPTOMS AND TREATMENTS
FIGURE 32-7 Degrees of Uterine Prolapse. A, Normal uterus (grade 0). B, Grade 1 prolapse: descent within the vagina. C, Grade 2 prolapse: descent into the hymen. D, Grade 4 prolapse: minimal possible descent of the uterus. Grade 3 (not shown) protrudes just beyond the introitus.
FIGURE 32-8 Cystocele and Rectocele. A, Grade 2: anterior vaginal wall prolapse (i.e., cystocele). B, Grade 4: prolapse. C, Grade 2: posterior wall prolapse (i.e., rectocele). D, Grade 4: associated with ulceration of vaginal wall. Grades 1 and 3 not shown.
Benign Growths and Proliferative Conditions
Benign Ovarian Cysts
FIGURE 32-9 Depiction of Ovarian Cyst.
HEALTH ALERT
QUICK CHECK 32-3
Endometrial Polyps
FIGURE 32-10 Endometrial Polyp. Polyp is protruding through the cervical os.
Leiomyomas
PATHOPHYSIOLOGY
FIGURE 32-11 Leiomyomas. A, Uterine section showing whorl-like appearance and locations of leiomyomas, which are also called uterine fibroids. B, Multiple leiomyomas in sagittal section. Typical, well-circumscribed, solid, light gray nodules distort uterus.
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
Adenomyosis
Endometriosis
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
FIGURE 32-12 Pelvic Sites of Endometrial Implantation in Endometriosis. Endometrial cells may enter the pelvic cavity during retrograde menstruation.
BOX 32-5 THEORIES OF ENDOMETRIOSIS
EVALUATION AND TREATMENT
Cancer
Cervical Cancer
PATHOGENESIS
FIGURE 32-13 Cervical Intraepithelial Neoplasia (CIN). A, Normal multiparous cervix including the transformation zone (TZ) where precancerous and cancerous changes occur (see next photos). CIN stage 1, note the white appearance of part of the anterior lip of the cervix associated with neoplastic changes; CIN stage 2, lesions also are reflected in distant capillaries; CIN stage 3, lesions predominantly around the external os. B, Normal epithelium, HPV infection progressing to CIN stage 1, and then with more time persistent HPV infections progressing to precancerous lesions CIN 2 and CIN 3 and eventually cervical cancer. Most cervical lesions do not progress to cervical cancer.
TABLE 32-4 CLINICAL STAGING FOR CANCER OF THE CERVIX
HEALTH ALERT
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
TABLE 32-5 RECOMMENDED TREATMENT BASED ON CLINICAL STAGING FOR CANCER OF THE CERVIX
Vaginal Cancer
FIGURE 32-14 Endometrial Cancer. Tumor fills the endometrial cavity. Obvious myometrial invasion is shown.
Vulvar Cancer
Endometrial Cancer
RISK FACTORS
Other Risk Factors
Ovarian Cancer
RISK FACTORS
FIGURE 32-15 Ovarian Tumors. A serous borderline tumor displays a cyst cavity lined by papillary tumor growths (A). The cyst is opened (B) to reveal a large bulky tumor mass called cystadenocarcinoma (C), a tumor on the ovarian surface. Bilaterality of tumors is common, occurring in 20% of benign tumors, 30% of serous borderline tumors, and approximately 66% of serous carcinomas. A significant proportion of both borderline malignant and malignant tumors involve the surface of the ovary (C).
PATHOGENESIS
CLINICAL MANIFESTATIONS
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
EVALUATION AND TREATMENT
TABLE 32-7 POSSIBLE EFFECTS OF CHRONIC DISEASE ON SEXUAL FUNCTIONING IN WOMEN
HEALTH ALERT
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.
Peyronie Disease
FIGURE 32-18 Peyronie Disease. This person complained of pain and deviation of his penis to one side on erection.
FIGURE 32-19 Priapism.
Priapism
FIGURE 32-20 Balanitis.
Balanitis
Tumors of the Penis
Penile Cancer
BOX 32-6 STAGING FOR PENILE CANCER
QUICK CHECK 32-5
FIGURE 32-21 Depiction of a Varicocele. Dilation of veins within the spermatic cord.
Disorders of the Scrotum, Testis, and Epididymis
Disorders of the Scrotum
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.
Cryptorchidism and Ectopy
Torsion of the Testis and Testicular Appendages
Orchitis
FIGURE 32-24 Torsion of the Testis. The testes appear dark red and partially necrotic as a result of hemorrhagic infarction.
FIGURE 32-25 Depiction of Orchitis.
Cancer of the Testis
PATHOPHYSIOLOGY
FIGURE 32-26 Testicular Tumor.
RISK FACTORS
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
Epididymitis
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
FIGURE 32-27 Epididymitis Secondary to Gonorrhea or Nongonococcal Urethritis. This infection spread to the testes, and rupture through the scrotal wall is threatened.
EVALUATION AND TREATMENT
QUICK CHECK 32-6
Disorders of the Prostate Gland
Benign Prostatic Hyperplasia
FIGURE 32-28 Prostate Zones, Benign Prostatic Hyperplasia (BPH), and Prostate Cancer Locations. Benign prostatic hyperplasia (BPH) occurs in the peripheral zone of the prostate gland that can enlarge (not shown). BPH nodules and atrophy are associated with inflammation in the transition zone. Most cancer lesions occur in the peripheral zone. Carcinoma can involve the central zone but rarely occurs in isolation, suggesting that prostatic intraepithelial neoplasia (PIN) lesions do not easily progress to carcinoma in this region.
PATHOGENESIS
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
Prostatitis
Bacterial prostatitis
BOX 32-7 NIH CLASSIFICATION OF THE PROSTATITIS SYNDROME
Chronic prostatitis/chronic pelvic pain syndrome
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.
Dietary factors
BOX 32-8 SUMMARY OF DIET FOR PROSTATE CANCER
General References
Hormones
FIGURE 32-30 Sources of Androgens and Aromatase and Estrogen Signaling in the Prostate. A, Body sources of androgens in the prostate gland. Hypothalamic GnRH causes the release of LH from the anterior pituitary gland. LH stimulates the testes to produce testosterone, which then accumulates in the blood. Pituitary ACTH release stimulates the adrenal glands, which secrete the androgen precursor DHEA into the blood. DHEA is converted into testosterone and then into DHT in the prostate. B, Aromatase and estrogen signaling in the prostate. In normal and benign tissue, aromatase is expressed within the stroma and regulated by promoter PII. Estrogen then exerts its effects in an autocrine fashion through the stromal ER-α receptor and also in a paracrine fashion through both ER-α and ER-β receptors. With prostate cancer, aromatase is now expressed within the tumor cells and in stromal cells, and regulated by aromatase promoters 1.3, 1.4, and PII. Thus estrogen exerts its effects in an autocrine way through stromal and epithelial ER-α and ER-β. Consequently, the increased levels of estrogen and abnormal ER-α signaling promote inflammation, which increases aromatase expression and the development of a positive feedback cycle. Inflammation drives aromatase expression, thus increasing estrogen, which in turn promotes further inflammation. ACTH, Adrenocorticotropic hormone; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.
Vasectomy
Chronic inflammation
Genetic and epigenetic factors
PATHOGENESIS
Hormonal factors
FIGURE 32-31 Possible Causes of Prostate Inflammation. A, Infection, including viruses, bacteria, fungi, and parasites. B, Hormones, for example, estrogen at key times during development. C, Physical trauma, any type of blunt physical injury. D, Urine reflex. E, Certain dietary factors (see text).
FIGURE 32-32 Photomicrograph of Prostate Cancer Cells. Pink ruffled cells are prostate cancer cells.
BOX 32-9 DETERMINING THE GRADE OF PROSTATE CANCER WITH THE GLEASON SCORE
FIGURE 32-33 Testosterone and Conversion to Dihydrotestosterone (DHT).
Androgen receptor signaling
Prostate epithelial neoplasia
FIGURE 32-34 Cellular and Molecular Model of Early Prostate Neoplasia Progression. A, This stage includes infiltration of lymphocytes, macrophages, and neutrophils caused by repeated infections, dietary factors, urine reflux, injury, onset of autoimmunity (which triggers inflammation), and wound healing. B, Epigenetic alterations mediate telomere shortening. C, Genetic instability and accumulation of genetic alterations. D, Continued proliferation of genetically unstable cells leading to cancer progression. PIN, Prostatic intraepithelial neoplasia.
Stromal environment
FIGURE 32-35 Carcinoma of Prostate. A, Schematic of carcinoma of the prostate. B, Carcinoma of the prostate extending into the rectum and urinary bladder.
CLINICAL MANIFESTATIONS
FIGURE 32-36 Distribution of Hematogenous Metastases in Prostate Cancer. Study of 556 individuals with metastatic prostate cancer.
EVALUATION AND TREATMENT
Sexual Dysfunction
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS AND TREATMENT
Impairment of Sperm Production and Quality
QUICK CHECK 32-7
Disorders of the Breast
Disorders of the Female Breast
Galactorrhea
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
Benign Breast Disease/Conditions
Nonproliferative breast lesions
BOX 32-10 CLASSIFICATION OF BREAST BIOPSY TISSUE ACCORDING TO RISK FOR BREAST CANCER
No Increased Risk
Slightly Increased Risk (1½ to 2 Times)
Moderately Increased Risk (3 to 5 Times)
Proliferative breast lesions without atypia
TABLE 32-8 EXAMPLES OF BENIGN BREAST DISORDERS
Proliferative breast lesions with atypia
EVALUATION AND TREATMENT
Breast Cancer
FIGURE 32-37 Age-Specific Incidence Rates of Breast Cancer Among Women.
HEALTH ALERT
TABLE 32-9 CHANCE OF BEING DIAGNOSED WITH BREAST CANCER
TABLE 32-10 ESTABLISHED RISK FACTORS FOR BREAST CANCER
Reproductive factors: pregnancy
Lobular involution and age
Hormonal factors
FIGURE 32-38 Female Endocrine System. The different mammary growth (mammotropic) hormone sites are shown in ovals, hormones are noted in blue boxes, and mammotropic hormones are noted in red boxes.
FIGURE 32-39 Factors Involved in Mammary Gland Development. Work of many laboratories led to the identification of many genes important in mammary gland development that are summarized in the scheme.
FIGURE 32-40 Local Biosynthesis of Estrogens. Three main enzyme complexes (yellow) involved in estrogen formation in breast tissue, including aromatase, sulfatase, and 17β-estradiol hydroxysteroid dehydrogenase (17β-HSD). Thus, despite low levels of circulating estrogens in postmenopausal women with breast cancer, the tissue levels are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. Data suggest that most abundant is sulfatase in both premenopausal and postmenopausal women with breast cancer. Numerous agents can block the aromatase action, exploration of progesterone, and various progestins to inhibit sulfatase and 17β-HSD or stimulate sulfotransferase (i.e., breast cancer cells cannot inactivate estrogens because they lack sulfotransferase) may provide new possibilities for treatment. LOH, Loss of heterozygosity (see Chapter 8).
Hormone replacement therapy and breast cancer risk: estrogen plus progesterone therapy (HRT) and estrogen only therapy (ERT)
TABLE 32-11 HORMONAL TREATMENTS ASSESSED BY THE IARC MONOGRAPH WORKING GROUP
Insulin and insulin-like growth factors
Prolactin and growth hormone
Human chorionic gonadotropin
Oral contraceptives
Mammographic breast density
FIGURE 32-41 Breast Density Varies Among Women. The sensitivity of mammography for detecting malignancy is significantly reduced if the breast consists of a high proportion of fibroglandular (dense) breast tissue (A) compared to a breast that is fatty (B).
BOX 32-11 SUMMARY OF THE USPSTF RECOMMENDATIONS ON SCREENING FOR BREAST CANCER
Environmental factors
Radiation
Diet
Obesity
Environmental chemicals
Physical activity
Familial factors and tumor-related genes
TABLE 32-12 TYPES OF BREAST CARCINOMAS AND MAJOR DISTINGUISHING FEATURES
PATHOGENESIS
Ductal and lobular carcinoma in situ
FIGURE 32-42 Cells of the Tumor Microenvironment. A, Distinct cell types constitute most solid tumors including breast tumors. Both the main cellular tissue, called parenchyma, and the surrounding tissue, or stroma, of tumors contain cell types that enable tumor growth and progression. For example, the immune-inflammatory cells present in tumors can include both tumor-promoting and tumor-killing subclasses of cells. B, The microenvironment of tumors. Multiple stromal cell types create a succession of tumor microenvironments that change as tumors invade normal tissue, eventually seeding and colonizing distant tissues. The organization, numbers, and phenotypic characteristics of the stromal cell types and the extracellular matrix (hatched background) evolve during progression and enable primary, invasive, and metastatic growth. (Not shown are the premalignant stages.)
CLINICAL MANIFESTATIONS
EVALUATION AND TREATMENT
FIGURE 32-43 Signaling Interactions in the Tumor Microenvironment During Malignant Progression. Upper panel: Numerous cell types constitute the tumor microenvironment and are orchestrated and maintained by reciprocal interactions. Lower panel: The reciprocal interactions between the breast main tissue or parenchyma and the surrounding stroma are important for cancer progression and growth. Certain organ sites of “fertile soil” or “metastasis niches” facilitate metastatic seeding and colonization. Cancer stem cells are involved in some or all stages of tumor development and progression.
FIGURE 32-44 Ductal Carcinoma in Situ (DCIS). A, Malignant microcalcifications. Extensive area of pleomorphic microcalcifications; granular, rod-shaped, and branching microcalcifications can be identified. The appearances are typical of high-grade DCIS. B, Craniocaudal mammography reveals fine and coarse granular calcifications. Histopathologic analysis revealed low-grade DCIS.
FIGURE 32-45 Retraction of Nipple Caused by Carcinoma.
TABLE 32-13 CLINICAL MANIFESTATIONS OF BREAST CANCER
BOX 32-12 STAGING OF BREAST CANCER
Stage 0: Tis, N0, M0
Stage IA: T1, N1mi, M0
Stage 1B: T0 or T1, N1mi, M0
Stage IIA
T0 or T1, N1 (but not N1mi), M0
Or
T2, N0, M0
Stage IIB
T2, N1, M0
Or
T3, N0, M0
Stage IIIA
T0 to T2, N2, M0
Or
T3, N1 or N2, M0
Stage IIIB: T4, N0 to N2, M0
Stage IIIC: Any T, N3, M0
Stage IV: Any T, Any N, M1
QUICK CHECK 32-8
Disorders of the Male Breast
Gynecomastia
PATHOPHYSIOLOGY
EVALUATION AND TREATMENT
Carcinoma
Sexually Transmitted Infections
TABLE 32-14 ESTIMATED NEW CASES OF REPORTABLE AND NONREPORTABLE STIs EACH YEAR
TABLE 32-15 CURRENTLY RECOGNIZED SEXUALLY TRANSMITTED INFECTIONS
HEALTH ALERT
HEALTH ALERT
QUICK CHECK 32-9
TABLE 32-16 MAJOR SEXUALLY TRANSMITTED INFECTIONS
Bacterial Sources
Gonococcal infections
Symptomatic gonococcal urethritis.
Endocervical gonorrhea.
Skin lesions of disseminated gonococcal infection.
Bacterial vaginosis
Vaginal examination showing mild bacterial vaginosis.
Syphilis
Erythematous penile plaques of secondary syphilis.
Multiple primary syphilitic chancres of labia and perineum.
Papular secondary syphilis.
Lymphogranuloma
“Groove sign” in man with lymphogranuloma venereum (LV).
Chlamydial infections
Beefy red mucosa in chlamydial infection.
Chlamydial epididymitis.
Chlamydial ophthalmia: erythematous conjunctiva in infant.
Viral Sources
Genital herpes
Early lesions of primary genital herpes.
Primary vulvar herpes.
Generalized herpes simplex in patient with atopic dermatitis.
Parasite Sources
Trichomonisasis
“Strawberry cervix” seen with trichomoniasis.
Human papillomavirus (HPV)
Human papillomavirus (HPV) infection of the cervix.
Exophytic (outward-growing) condyloma, subclinical human papillomavirus (HPV) infection, and high-grade cervical intraepithelial neoplasia (CIN).
Condylomata acuminata
Condylomata acuminata: vulva and perineum.
Condylomata acuminata: perianal.
Condylomata acuminata: penile.
Scabies
Nodular lesions of scabies on male genitalia.
Urticaria associated with scabies.
Scabies of palm with secondary pyoderma in infant.
Pediculosis pubis (Phthirus pubis [crablouse])
Phthirus pubis feeding on its host.
Pubic hair with multiple nits.
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
Pelvic inflammatory disease (see video)
Ovarian cyst (see video)
Ovarian torsion (see video)
Torsion of the testis (see video)
Breast cancer metastasis (see video)
References
UNIT 11 The Digestive System
Interactive Review – Unit 11
Chapter 33 Structure and Function of the Digestive System
The Gastrointestinal Tract
FIGURE 33-1 Structures of the Digestive System.
FIGURE 33-2 Wall of the Gastrointestinal Tract The wall of the gastrointestinal tract is made up of four layers with a network of nerves between the layers. This generalized diagram shows a segment of the gastrointestinal tract. Note that the serosa is continuous with a fold of serous membrane called the mesentery. Note also that digestive glands may empty their products into the lumen of the gastrointestinal tract by way of ducts.
Mouth and Esophagus
Salivation
FIGURE 33-3 Salivary Glands.
Swallowing
FIGURE 33-4 Salivary Electrolyte Concentrations and Flow Rate. Changes in concentrations of sodium (Na+), potassium (K+), chloride (Cl−), and bicarbonate (HCO3−) increase flow rate of saliva. Green line, sodium; orange line, bicarbonate; red line, chloride; blue line, potassium. At low rates of salivary flow (i.e., between meals), sodium, chloride, and bicarbonate are reabsorbed in the collecting ducts of the salivary glands, and the saliva contains fewer of these electrolytes (i.e., is more hypotonic). At higher flow rates (i.e., stimulated by food), reabsorption decreases and saliva is hypertonic. By this mechanism, sodium, chloride, and bicarbonate are recycled until they are released to help with digestion and absorption.
QUICK CHECK 33-1
Stomach
Gastric Motility
FIGURE 33-5 Stomach A portion of the anterior wall has been excised to reveal the muscle layers of the stomach wall. Note that the mucosa lining the stomach forms folds called rugae. The dashed lines distinguish the fundus, body, and antrum of the stomach.
FIGURE 33-6 Major Blood Vessels and Organs Supplied with Blood in the Splanchnic Circulation. Numbers in parentheses reflect approximate blood flow values (ml/min) for each major vessel in an 80-kg normal, resting, adult human subject. Arrows indicate the direction of blood flow.
TABLE 33-1 Selected hormones* and neurotransmitters of the digestive system
Phases of Gastric Secretion
FIGURE 33-7 Gastric Pits and Gastric Glands. Gastric pits are depressions in the epithelial lining of the stomach. At the bottom of each pit are one or more tubular gastric glands. Chief cells produce pepsinogen, which is converted to pepsin (a proteolytic enzyme); parietal cells secrete hydrochloric acid and intrinsic factor; G cells produce gastrin; endocrine cells (enterochromaffin-like cells and D cells) secrete histamine and somatostatin.
Gastric Secretion
Acid
FIGURE 33-8 Relationship Between Secretory Rate and Electrolyte Composition of the Gastric Juice. Sodium (Na+) concentration is lower in the gastric juice than in the plasma, whereas hydrogen (H+), potassium (K+), and chloride (Cl−) concentrations are higher. Red line, chloride; orange line, hydrogen; green line, sodium; blue line, potassium.
Pepsin
FIGURE 33-9 Hydrochloric Acid Secretion by Parietal Cell.
Mucus
QUICK CHECK 33-2
Small Intestine
FIGURE 33-10 The Small Intestine.
BOX 33-1 DIETARY FAT
Saturated Fatty Acids (e.g., Palmitic Acid [C16H32O2])
Unsaturated Fatty Acids
Monounsaturated Fatty Acids (e.g., Oleic Acid [C18H34O2])
Polyunsaturated Fatty Acids (e.g., Linoleic Acid [C18H32O2])
The Gastrointestinal Tract and Immunity
Intestinal Digestion and Absorption
FIGURE 33-11 Digestion and Absorption of Foodstuffs.
FIGURE 33-12 Sites of Absorption of Major Nutrients.
Intestinal Motility
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 33-13 Division of the Large Intestine.
QUICK CHECK 33-4
Intestinal Bacteria
HEALTH ALERT
Splanchnic Blood Flow
FIGURE 33-14 Location of the Liver, Gallbladder, and Exocrine Pancreas, Which Are the Accessory Organs of Digestion.
Accessory Organs of Digestion
Liver
FIGURE 33-15 Gross Structure of the Liver. A, Anterior view. B, Inferior view.
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.)
FIGURE 33-17 Diagrammatic Representation of a Liver Lobule. A central vein is located in the center of the lobule with plates of hepatic cells disposed radially. Branches of the portal vein and hepatic artery are located on the periphery of the lobule and blood from both perfuses the sinusoids. Peripherally located bile ducts drain the bile canaliculi that run between the hepatocytes.
QUICK CHECK 33-5
Secretion of Bile
FIGURE 33-18 Enterohepatic Circulation of Bile Salts.
Metabolism of Bilirubin
FIGURE 33-19 Bilirubin Metabolism.
Vascular and Hematologic Functions
Metabolism of Nutrients
Fats
TABLE 33-2 Importance of proteins in the body
Proteins
Carbohydrates
Metabolic Detoxification
HEALTH ALERT
Storage of Minerals and Vitamins
Gallbladder
TABLE 33-3 Selected tests of liver function
Exocrine Pancreas
FIGURE 33-20 Associated Structures of the Gallbladder, Pancreas, and Pancreatic Acinar Cells and Duct.
QUICK CHECK 33-6
TABLE 33-4 Selected laboratory tests of exocrine pancreatic function
GERIATRIC CONSIDERATIONS
Oral Cavity and Esophagus
Stomach and Intestines
Liver
Pancreas and Gallbladder
DID YOU UNDERSTAND?
The Gastrointestinal Tract
Accessory Organs of Digestion
KEY TERMS
References
Chapter 34 Alterations of Digestive Function
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
FIGURE 34-1 Pathophysiology of Gastrointestinal (GI) Bleeding.
QUICK CHECK 34-1
Disorders of Motility
Dysphagia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Gastroesophageal Reflux Disease (GERD)
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
Clinical Manifestations
Evaluation and Treatment
FIGURE 34-3 Types of Hiatal Hernia. A, Sliding hiatal hernia. B, Paraesophageal hiatal hernia.
Pyloric Obstruction
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Intestinal Obstruction and Paralytic Ileus
TABLE 34-2 COMMON CAUSES OF INTESTINAL OBSTRUCTION
TABLE 34-3 LARGE AND SMALL BOWEL OBSTRUCTION
TABLE 34-4 CLASSIFICATIONS OF INTESTINAL OBSTRUCTION
FIGURE 34-4 Intestinal Obstructions. A, Hernia. B, Intussusception. C, Volvulus. D, Constriction adhesions.
Pathophysiology
FIGURE 34-5 Pathophysiology of Intestinal Obstruction.
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 34-2
Gastritis
Peptic Ulcer Disease
FIGURE 34-6 Lesions Caused by Peptic Ulcer Disease.
RISK FACTORS
Duodenal Ulcers
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Gastric Ulcers
Pathophysiology
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).
FIGURE 34-8 Pathophysiology of Gastric Ulcer Formation. NSAIDs, Nonsteroidal anti-inflammatory drugs.
TABLE 34-5 CHARACTERISTICS OF GASTRIC AND DUODENAL ULCERS
Clinical Manifestations
Stress-Related Mucosal Disease
Surgical Treatment of Ulcer
QUICK CHECK 34-3
Postgastrectomy Syndromes
Malabsorption Syndromes
Pancreatic Exocrine Insufficiency
Lactase Deficiency (Lactose Intolerance)
Bile Salt Deficiency
Inflammatory Bowel Disease
Ulcerative Colitis
Pathophysiology
Clinical Manifestations
TABLE 34-6 FEATURES OF ULCERATIVE COLITIS AND CROHN DISEASE
Evaluation and Treatment
Crohn Disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Diverticular Disease of the Colon
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
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.
Appendicitis
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Irritable Bowel Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
BOX 34-1 ROME III—DIAGNOSTIC CRITERIA FOR IRRITABLE BOWEL SYNDROME (IBS)
Vascular Insufficiency
Disorders of Nutrition
Obesity
Pathophysiology
BOX 34-2 EXAMPLES OF ADIPOCYTOKINES AND OTHER HORMONES RELATED TO COMPLICATIONS OF OBESITY
Cytokines from Adipose Cells
Adipocytokines
Proinflammatory Cytokines
Other Hormones
Clinical Manifestations
FIGURE 34-10 Pathophysiology and Common Complications of Obesity. CRP, C-reactive protein; FFA, free fatty acids; GERD, gastroesophageal reflux disease; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; PAI-1, plasminogen activator inhibitor-1.
Evaluation and Treatment
Anorexia Nervosa and Bulimia Nervosa
HEALTH ALERT
Malnutrition and Starvation
QUICK CHECK 34-4
Disorders of the Accessory Organs of Digestion
Common Complications 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. The shunted blood returns to the systemic venous system, bypassing the liver.
Clinical Manifestations
Evaluation and Treatment
Ascites
Pathophysiology
Clinical Manifestations
FIGURE 34-12 Mechanisms of Ascites Caused by Cirrhosis.
Evaluation and Treatment
FIGURE 34-13 Massive Ascites in an Individual With Cirrhosis. Distended abdomen, dilated upper abdominal veins, and inverted umbilicus are classic manifestations.
Hepatic Encephalopathy
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 34-14 Mechanisms of Jaundice.
Jaundice
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
TABLE 34-7 COMMON TYPES OF JAUNDICE
Hepatorenal Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 34-5
Disorders of the Liver
Viral Hepatitis
Pathophysiology
TABLE 34-8 CHARACTERISTICS OF VIRAL HEPATITIS
Clinical Manifestations
Evaluation and Treatment
Fulminant Viral Hepatitis
Cirrhosis
BOX 34-3 CAUSES OF CIRRHOSIS
Alcoholic liver disease
Pathophysiology
FIGURE 34-15 Clinical Manifestations of Cirrhosis. ADH, Antidiuretic hormone; ALT, alanine transaminase; AST, aspartate transaminase.
Clinical Manifestations
Evaluation and Treatment
Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Biliary cirrhosis
QUICK CHECK 34-6
Disorders of the Gallbladder
Cholelithiasis (Gallstones)
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 34-16 Resected Gallbladder Containing Mixed Gallstones.
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
Clinical Manifestations
Evaluation and Treatment
Cancer of the Stomach
TABLE 34-9 CANCER OF THE GUT, LIVER, AND PANCREAS
Pathogenesis
FIGURE 34-17 Typical Sites of Stomach Cancer.
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 34-7
Cancer of the Colon and Rectum
RISK FACTORS
Pathogenesis
Clinical Manifestations
FIGURE 34-18 The Molecular Basis of Colorectal Cancer. Colorectal carcinoma develops from the sequential progression of genetic alterations. 1, Mutations in the APC gene are the earliest known event and inactivation of APC accelerates cell cycle progression. K-ras over expression leads to loss of p53. Loss of p53 transforms an adenoma into a metastatic carcinoma. 2, Mutation of mismatch repair genes (MMR) that encode key molecules that repair DNA result in replication errors and deactivation of proteins from other downstream mutations (TGFβ, IIR, BAX). Deletions or mutations in MMR genes exists in 95% of tumors in individuals with hereditary non-polyposis colorectal cancer (HNPCC), but only 10~15% of sporadic tumors. 3, p53 loss occur in ~75% of colorectal carcinomas, but infrequently in benign lesions. APC, APC gene (a tumor suppressor gene); LOH, loss of heterozygosity; K-ras, a proto oncogene (promotes cell growth); p53, protein 53 or tumor protein 53 (a tumor suppressor protein); FAP, familial adenomatous polyposis; MMR, mutation mismatch repair; MSI, microsatellite instability; TGFβ, transforming growth factor-β; IIR, type II receptor; BAX, apoptosis-related protein; HNPCC, hereditary nonpolyposis colorectal cancer; CRC, colorectal cancer.
Evaluation and Treatment
FIGURE 34-19 Neoplastic Polyps. A, Tubular adenomata (A) are rounded lesions 0.5 to 2 cm in size that are generally red and sit on a stalk (S) of normal mucosa that has been dragged up by traction of the polyp in the bowel lumen. B, Villous adenomata are velvety lesions about 0.6 cm thick that occupy a broad area of mucosa generally 1 to 5 cm in diameter.
FIGURE 34-20 Signs and Symptoms of Colorectal Cancer by Location of Primary Lesion. Clinical manifestations are listed in order of frequency for each region (lymphatics of colon also shown).
BOX 34-4 SCREENING FOR COLORECTAL CANCER
Tests That Find Polyps and Cancer
Tests That Primarily Find Cancer
Cancer of the Accessory Organs of Digestion
Cancer of the Liver
RISK FACTORS
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
Hematemesis (see video)
Melena (see video)
Early bowel obstruction (see video)
Late bowel obstruction (see video)
Duodenal ulcer (see video)
Diverticulitis (see video)
Peritonitis (see video)
Appendicitis (see video)
Portal hypertension (see video)
Cholecystitis (see video)
References
Chapter 35 Alterations of Digestive Function in Children
Disorders of the Gastrointestinal Tract
Congenital Impairment of Motility
Cleft Lip and Cleft Palate
Pathophysiology
Cleft lip
Cleft palate
Clinical Manifestations
Evaluation and Treatment
Esophageal Malformations
Pathophysiology
Clinical Manifestations
FIGURE 35-1 Variations in Clefts of the Lip and Palate. A, Unilateral cleft lip. B, Unilateral cleft lip and palate. C, Bilateral cleft lip and cleft palate. D, Cleft palate.
FIGURE 35-2 Five Types of Esophageal Atresia and Tracheoesophageal Fistulae. A, Simple esophageal atresia. Proximal esophagus and distal esophagus end in blind pouches, and there is no tracheal communication. Nothing enters the stomach; regurgitated food and fluid may enter the lungs. B, Proximal and distal esophageal segments end in blind pouches, and a fistula connects the proximal esophagus to the trachea. Nothing enters the stomach; food and fluid enter the lungs. C, Proximal esophagus ends in a blind pouch, and a fistula connects the trachea to the distal esophagus. Air enters the stomach; regurgitated gastric secretions enter the lungs through the fistula. D, Fistula connects both proximal and distal esophageal segments to the trachea. Air, food, and fluid enter the stomach and the lungs. E, Simple tracheoesophageal fistula between otherwise normal esophagus and trachea. Air, food, and fluid enter the stomach and the lungs. Between 85% and 90% of esophageal anomalies are type C; 6% to 8% are type A; 3% to 5% are type E; and fewer than 1% are type B or D.
Evaluation and Treatment
Infantile 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
FIGURE 35-4 Anorectal Stenosis and Imperforate Anus. NOTE: With the exception of the rectovaginal fistula, all of the malformations shown occur in both males and females.
Acquired Impairment of Motility
Intussusception
Pathophysiology
FIGURE 35-5 Ileocolic Intussusception.
Clinical Manifestations
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
Clinical Manifestations
FIGURE 35-6 Pathophysiology of Gluten-Sensitive Enteropathy.
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 or Chronic Diarrhea in Infants and Children
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 virus (HAV)
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Chronic hepatitis
Cirrhosis
Portal Hypertension
HEALTH ALERT
Types of Portal Hypertension
Extrahepatic portal hypertension
Intrahepatic portal hypertension
Course of the Disease
Clinical Manifestations
Evaluation and Treatment
TABLE 35-2 GALACTOSEMIA, FRUCTOSEMIA, AND WILSON DISEASE
Metabolic Disorders
QUICK CHECK 35-4
DID YOU UNDERSTAND?
Disorders of the Gastrointestinal Tract
Disorders of the Liver
KEY TERMS
References
UNIT 12 The Musculoskeletal and Integumentary Systems
Interactive Review – Unit 12
Chapter 36 Structure and Function of the Musculoskeletal System
Structure and Function of Bones
Elements of Bone Tissue
TABLE 36-1 STRUCTURAL ELEMENTS OF BONE
Bone Cells
Osteoblasts
FIGURE 36-1 Bone Cells. A, Osteoblasts are responsible for the production of collagenous and noncollagenous proteins that compose osteoid. Active osteoblasts are lined up on the osteoid. Note the eccentrically located nuclei. B, Electron photomicrograph of an osteocyte. Osteocytes reside within the lacunae of compact bone. C, Osteoclasts actively resorb mineralized tissue. The scalloped surface in which the multinucleated osteoclasts rest is termed Howship lacuna.
TABLE 36-2 SELECTED FACTORS AFFECTING BONE FORMATION, MAINTENANCE, AND REMODELING
Osteoclasts
OPG/RANKL/RANK System
Osteocytes
Bone Matrix
Collagen fibers
Proteoglycans
Glycoproteins
Bone Minerals
FIGURE 36-2 Cross Section of Bone. Longitudinal section of long bone (tibia) showing spongy (cancellous) and compact bone.
TABLE 36-3 SEQUENCE OF CALCIUM AND PHOSPHATE COMPOUND FORMATION AND CRYSTALLIZATION*
Types of Bone Tissue
FIGURE 36-3 Structure of Compact and Cancellous Bone. A, Longitudinal section of a long bone showing both cancellous and compact bone. B, Magnified view of compact bone. C, Section of a flat bone. Outer layers of compact bone surround cancellous bone. Fine structure of compact and cancellous bone is shown to the right.
Characteristics of Bone
FIGURE 36-4 A, Anterior View of Skeleton. B, Posterior View of Skeleton. Axial skeleton in blue; appendicular skeleton in tan.
FIGURE 36-5 Bone Remodeling. All bone cells participate in bone remodeling. In the remodeling sequence bone sections are removed by bone-resorbing cells (osteoclasts) and replaced a with new section laid down by bone-forming cells (osteoblasts). Bone remodeling is necessary because it allows the skeleton to respond to mechanical loading, maintains quality control (repair and prevent microdamage), and allows the skeleton to release growth factors and minerals (calcium and phosphate) stored in bone matrix to the circulation. The cells work in response to signals generated in the environment (see F). Only the osteoclastic cells mediate the first phase of remodeling. They are activated, scoop out bone (A), and resorb it, then the work of the osteoblasts begins (B). They form new bone that replaces bone removed by the resorption process (C). The sequence takes 4 to 6 months. D, Micrograph of active bone remodeling seen in the settings of primary or secondary hyperparathyroidism. Note the active osteoblasts surmounted on red-stained osteoid. Marrow fibrosis is present. E, Bone remodeling cycle in normal bone with (F). Numerous signaling factors are necessary for remodeling. Factors most important for resorption include granulocyte macrophage-colony stimulating factor (GM-CSF), Interleukins (IL) 1 and 6, receptor activator for nuclear factor κβ ligand (RANKL), prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-α). Important factors for bone formation include osteoprotegerin (OPG), transforming growth factor beta (TGF-β) and estrogen.
Maintenance of Bone Integrity
Remodeling
Repair
QUICK CHECK 36-1
Structure and Function of Joints
FIGURE 36-6 Main Tissues of a Joint.
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.
Fibrous Joints
Cartilaginous Joints
Joint (Articular) Capsule
Synovial Membrane
Joint (Synovial) Cavity
FIGURE 36-8 Collagen Zones. The three collagen zones (reserve, proliferative, and hypertrophic) are distinctly shown in a growth plate.
Synovial Fluid
Articular Cartilage
FIGURE 36-9 Knee Joint (Synovial Joint). A, Frontal view. B, Lateral view.
Synovial Joints
Structure of Synovial Joints
Movement of Synovial Joints
QUICK CHECK 36-2
Structure and Function of Skeletal Muscles
Whole Muscle
FIGURE 36-10 Movements of Synovial (Diarthrodial) Joints.
FIGURE 36-11 Body Movements Made Possible by Synovial (Diarthrodial) Joints.
FIGURE 36-12 Skeletal Muscles of Body. A, Anterior view. B, Posterior view.
Motor Unit
FIGURE 36-13 Cross Section of Skeletal Muscle Showing Muscle Fibers and Their Coverings.
FIGURE 36-14 Motor Units of a Muscle. Each motor unit consists of a motor neuron and all the muscle fibers (cells) supplied by the neuron and its axon branches.
FIGURE 36-15 Myofibrils. Myofibrils of a skeletal muscle fiber (cells) and overall organization of skeletal muscle.
Sensory receptors
Muscle fibers
TABLE 36-4 CHARACTERISTICS OF HUMAN SKELETAL MUSCLE FIBERS
TABLE 36-5 CONTRACTILE PROTEINS OF SKELETAL MUSCLE SARCOMERE
Myofibrils
Muscle proteins
Nonprotein constituents of muscle
Components of Muscle Function
Muscle Contraction at the Molecular Level
FIGURE 36-16 Muscle Fibers. A, The Z disks define the end of an individual sarcomere. The M line (which lies within the H band) is made of cross-connecting elements of the cytoskeleton. B, Actin is the primary protein of the I band (thin filament). Nebulin also extends along the I band and contains binding sites for actin and myosin. Myosin (thick filament) extends through the A band. Titin extends from the Z disk to the M band, binding with myosin; strong titin anchoring within the I band is necessary for proper muscle function. During contraction, the I bands and H bands shorten, moving the Z disks closer together. C, Electron photomicrograph of human muscle tissue corresponding to schematics in A and B.
Muscle Metabolism
TABLE 36-6 ENERGY SOURCES FOR MUSCULAR ACTIVITY
Muscle Mechanics
FIGURE 36-17 Isotonic and Isometric Contraction. A, In isotonic contraction, the muscle shortens, producing movement. B, In isometric contraction, the muscle pulls forcefully against a load but does not shorten.
Types of Muscle Contraction
Movement of Muscle Groups
Tendons and Ligaments
Aging & The Musculoskeletal System
Aging of Bones
HEALTH ALERT
Aging of Joints
Aging of Muscles
FIGURE 36-18 Cartilage-Bone, Tendon/Ligament-Bone, Meniscus-Bone, and Muscle-Tendon Interfaces. This diagram depicts the cartilage-bone, tendon/ligament-bone, meniscus-bone, and muscle-tendon interfaces and their compositions. Orange indicates levels of aggrecan concentration, light blue indicates collagen fibers, dark blue indicates mineralized tissue, and red indicates muscle fibers. Gradients of matrix composition, interdigitation of tissue zones, and interconnecting collagen fibers all enable load transfer between disparate tissues.
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
Musculoskeletal Injuries
Skeletal Trauma
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 tolerance. D, Pathologic: transverse, oblique, or spiral fracture of bone weakened by tumor pressure or presence. Cause: Minor energy or force, which may be direct or indirect. E, Comminuted: fracture with two or more pieces or segments. Cause: Direct or indirect moderate to severe force. F, Spiral: fracture that curves around cortices and may become displaced by twist. Cause: Direct or indirect twisting energy or force with distal part held or unable to move. G, Transverse: horizontal break through bone. Cause: Direct or indirect energy toward bone. H, Greenstick: break in only one cortex of bone. Cause: Minor direct or indirect energy. I, Impacted: fracture with one end wedged into opposite end of inside fractured fragment. Cause: Compressive axial energy or force directly to distal fragment.
Classification of fractures
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 while osteoclasts destroy dead bone. E, Remodeling is accomplished while excess callus is reabsorbed and trabecular bone is deposited.
Clinical Manifestations
FIGURE 37-3 Exuberant Callus Formation Following Fracture.
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
Tendinopathy, Epicondylopathy, and Bursitis
FIGURE 37-4 Epicondylopathy and Tendinopathy. A, Lateral and medial epicondyles of the distal humerus, sites of tennis elbow (lateral) and golfer’s elbow (medial). B, Achilles tendon, common site of tendinopathy.
Pathophysiology
FIGURE 37-5 Olecranon Bursitis. Note swelling at the point of the elbow (olecranon). A smaller, rheumatoid nodule also is present.
Clinical Manifestations
Evaluation and Treatment
Muscle Strains
HEALTH ALERT
Rhabdomyolysis
Pathophysiology
Clinical Manifestations
TABLE 37-2 MUSCLE STRAIN
Evaluation and Treatment
BOX 37-1 SELECTED CAUSES OF RHABDOMYOLYSIS
Direct Trauma
Drugs
Excessive Muscular Contraction
Infectious Agents
Toxins
Hereditary Enzyme Disorders (Rare)
Miscellaneous Causes
BOX 37-2 FACTORS AFFECTING DEVELOPMENT OF COMPARTMENT SYNDROME
Increased Intracompartmental Pressure
Reduced Compartment Volume
Conditions That Disturb Microcirculation
Compartment Syndrome
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Malignant Hyperthermia
Evaluation and Treatment
FIGURE 37-6 Pathogenesis of Compartment Syndrome and Crush Syndrome Caused by Prolonged Muscle Compression. ECF, Extracellular fluid.
QUICK CHECK 37-1
FIGURE 37-7 Muscle Compartments of the Lower Leg.
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.
FIGURE 37-9 Osteoporosis in Cortical and Trabecular Bone.
TABLE 37-3 T-SCORE AND WORLD HEALTH ORGANIZATION DIAGNOSIS OF BONE DENSITY
TABLE 37-4 COMPARISON OF STUDY OF FRACTURES (SOF), GARVAN, AND FRAX FRACTURE PREDICTION TOOLS
HEALTH ALERT
RISK FACTORS
Genetic
Anthropometric
Hormonal and Metabolic
Dietary
Lifestyle
Concurrent
Illness and Trauma
Liver Disease
Drugs
Pathophysiology
FIGURE 37-10 OPG/RANKL/RANK System. Expression of RANKL, a cytokine and part of the TNF family, and OPG, a glycoprotein receptor antagonist, is modulated by various cytokines, hormones, drugs, and mechanical strains (see inserts). In bone RANKL is expressed by both stromal cells and osteoblasts. RANKL stimulates the receptor RANK on osteoclast precursor cells and mature osteoclasts and activates intracellular signaling pathways to promote osteoclast differentiation and activation as well as cytoskeletal reorganization and survival (PKB/Akt pathway), which increase resorption and bone loss. OPG, secreted by stromal cells and osteoblasts, acts as a “decoy” receptor and blocks RANKL binding to and activation of RANK. BMP, Bone morphogenic protein; IL, interleukin; OPG, osteoprotegerin; PTH, parathyroid hormone; RANK, receptor activator nuclear factor κβ; RANKL, receptor activator nuclear factor κβ ligand; TGF-β, transforming growth factor-beta; TNF-α, tumor necrosis factor-alpha.
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.
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.
Evaluation and Treatment
HEALTH ALERT
BOX 37-3 BIOCHEMICAL MARKERS OF BONE TURNOVER
Osteomalacia
HEALTH ALERT
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
Paget Disease
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 37-14 Osteomyelitis Showing Sequestration and Involucrum.
Infectious Bone Disease: Osteomyelitis
Pathophysiology
Clinical Manifestations
FIGURE 37-15 Resected Femur in a Person With Draining Osteomyelitis. The drainage tract in the subperiosteal shell of viable new bone (involucrum) reveals the inner native necrotic cortex (sequestrum).
Evaluation and Treatment
QUICK CHECK 37-2
Disorders of Joints
Osteoarthritis
Pathophysiology
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.
Clinical Manifestations
RISK FACTORS
FIGURE 37-17 Typical Varus Deformity of Knee Osteoarthritis.
Evaluation and Treatment
HEALTH ALERT
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.
Pathophysiology
Clinical Manifestations
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 eventually destroy the joint. T cells stimulate cells in the joint to produce cytokines that are key mediators of synovial damage. Apparently, immune complex deposition also plays a role. Tumor necrosis factor (TNF) and interleukin-1 (IL-1), as well as some other cytokines, stimulate synovial cells to proliferate and produce other mediators of inflammation, such as prostaglandin E2 (PGE2), matrix metalloproteinases, and enzymes that all contribute to destruction of cartilage. Activated T cells and synovial fibroblasts also produce receptor activator of nuclear factor κβ ligand (RANKL), which activates the osteoclasts and promotes bone destruction. Pannus is a mass of synovium and synovial stroma with inflammatory cells, granulation tissue, and fibroblasts that grows over the articular surface and causes its destruction.
Evaluation and Treatment
HEALTH ALERT
Ankylosing Spondylitis
TABLE 37-5 THE 2010 AMERICAN COLLEGE OF RHEUMATOLOGY/EUROPEAN LEAGUE AGAINST RHEUMATISM CLASSIFICATION CRITERIA FOR RHEUMATOID ARTHRITIS
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
FIGURE 37-21 Ankylosing Spondylitis. Characteristic posture and primary pathologic sites of inflammation and resulting damage.
TABLE 37-6 MEAN URATE CONCENTRATIONS BY AGE AND GENDER
Gout
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.
Pathophysiology
FIGURE 37-23 Pathogenesis of Acute Gouty Arthritis. A, Depending on the urate crystal coating, a variety of cells may be stimulated to produce a wide range of inflammatory mediators. Apo-E, Apolipoprotein E; IgG, immunoglobulin G; IL, interleukin; LTB4, leukotriene B4; PGE2, prostaglandin E2B, Sequence of events in the production of the inflammatory response to urate crystals. C, Gouty tophus on right foot.
Clinical Manifestations
Treatment
QUICK CHECK 37-3
Disorders of Skeletal Muscle
Secondary Muscular Dysfunction
Contractures
Stress-Induced Muscle Tension
Disuse Atrophy
Fibromyalgia
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
BOX 37-4 EDUCATING AND PROVIDING REASSURANCE FOR INDIVIDUALS WITH FIBROMYALGIA
FIGURE 37-24 Theoretic Pathophysiologic Model of Fibromyalgia.
FIGURE 37-25 Location of Specific Tender Points for Diagnostic Classification of Fibromyalgia.
Muscle Membrane Abnormalities
Myotonia
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
Clinical Manifestations
FIGURE 37-26 Dermatomyositis. Heliotrope (violaceous) discoloration around the eyes and periorbital edema.
Evaluation and Treatment
Toxic Myopathies
BOX 37-5 AGENTS THAT CAN CAUSE TOXIC MYOPATHY
Drug-Induced
Endocrine Disorders
Infectious
Miscellaneous
QUICK CHECK 37-4
Musculoskeletal Tumors
Bone Tumors
FIGURE 37-27 Derivation of Bone Tumors.
BOX 37-6 WORLD HEALTH ORGANIZATION (WHO) CLASSIFICATION OF BONE TUMORS
Cartilage Tumors
Osteogenic Tumors
Fibrogenic Tumors (Often Produce Collagen; Do Not Have a Mineralizing Matrix)
Fibrohistiocytic Tumors (Comprised of Fibroblasts)
Ewing Sarcoma
Hematopoietic Tumors
Giant Cell Tumor
Smooth Muscle Tumors
Miscellaneous Tumors
Miscellaneous Lesions
Joint Lesions
Epidemiology
Patterns of Bone Destruction
TABLE 37-7 PATTERNS OF BONE DESTRUCTION CAUSED BY BONE TUMORS
TABLE 37-8 SURGICAL STAGING SYSTEM FOR BONE TUMORS
Evaluation
Types
Osteogenic tumors: osteosarcoma
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.
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
Congenital Defects
Clubfoot
TABLE 38-1 TERMS USED TO DESCRIBE FOOT ABNORMALITIES
Developmental Dysplasia of the Hip
FIGURE 38-1 A, Infant with Bilateral Congenital Talipes Equinovarus. B, Ponseti Casting.
FIGURE 38-2 Idiopathic Clubfoot. Idiopathic clubfoot displaying forefoot adduction (toward midline of body) and supination (upturning) and hindfoot equinus (pointed downward). Note skin creases along arch and back of heel.
FIGURE 38-3 Hip Dysplasia in Children. Development dysplasia of the hip (DDH) with residual acetabular dysplasia. Radiographs at birth, 3, 10, and 19 years (top to bottom) show persisting dysplasia.
FIGURE 38-4 Congenital Dislocation of the Hip. A, Barlow maneuver (left side). With one hand pressing the symphysis in front and the sacral spine in back, lateral pressure is applied to the thigh with the thumb of the other hand while pressure is applied with the palm to the knee on the side being examined. The hip that has been flexed to 90 degrees is then adducted. A positive sign is a sensation of abnormal movement, indicating dislocation of the femoral head from the acetabulum. The hands are reversed for examining the other hip. This sign and Ortolani sign may be found only in the first weeks of life. B, Ortolani maneuver (right side). Sign of jerking into correct position. After Barlow maneuver (A), the hip should be abducted to about 80 degrees while the femur is lifted anteriorly with the fingers along the thigh. A positive sign is a sensation of a jerk or snap with reduction into the joint socket.
FIGURE 38-5 Pavlik Harness for Bilateral Hip Dislocation.
FIGURE 38-6 Osteogenesis Imperfecta Treated with Osteotomies and Telescoping Medullary Rods. A, Severe deformity of both femurs. B, Same individual after multiple osteotomies with telescoping medullary rod fixation. C, Same individual 4 years later demonstrating growth of femurs, no recurrence of deformity, and elongation of rods. (Plaster casts are in place for immobilization of tibial osteotomies.)
Osteogenesis Imperfecta
Bone Infection
Osteomyelitis
BOX 38-1 CAUSATIVE MICROORGANISMS OF OSTEOMYELITIS ACCORDING TO AGE
Newborns
Infants
Older Children
Adolescents and Adults
FIGURE 38-7 Pathogenesis of Acute Osteomyelitis Differs With Age. A, In infants younger than 1 year the epiphysis is nourished by arteries penetrating through the physis, allowing development of the condition within the epiphysis. B, In children up to 15 years of age, the infection is restricted to below the physis because of interruption of the vessels.
Septic Arthritis
Juvenile Idiopathic Arthritis
FIGURE 38-8 Routes of Infection to the Joint. 1, Hematogenous route. 2, Dissemination from osteomyelitis. 3, Spread from an adjacent soft tissue infection. 4, Diagnostic or therapeutic measures. 5, Penetrating damage by puncture or cutting.
QUICK CHECK 38-1
Osteochondroses
Legg-Calvé-Perthes Disease
Pathophysiology
FIGURE 38-9 Stages of Legg-Calvé-Perthes Disease, a Form of Osteochondrosis.
TABLE 38-2 CHARACTERISTICS OF JUVENILE IDIOPATHIC ARTHRITIS RELATED TO MODE OF ONSET
Clinical Manifestations
FIGURE 38-10 Pelvis of a 7-Year-Old Boy with Legg-Calvé-Perthes Disease.
Evaluation and Treatment
Osgood-Schlatter Disease
FIGURE 38-11 Surgical Replacement of Femoral Head of a 7-Year-Old Boy with Legg-Calvé-Perthes Disease. As the Perthes heals, the ball has assumed a round shape that matches the socket well.
Scoliosis
FIGURE 38-12 Scoliosis in Children. Normal spine alignment and abnormal spinal curvatures associated with scoliosis. A, Normal. B, Mild. C, Severe. D, Rotation and curvature of scoliosis.
Muscular Dystrophy
Duchenne Muscular Dystrophy
Pathophysiology
TABLE 38-3 MAJOR MUSCULAR DYSTROPHY SYNDROMES
Clinical Manifestations
FIGURE 38-13 Duchenne Muscular Dystrophy. A, Young boy with DMD but on horseback. B, Transverse section of gastrocnemius muscle from a healthy boy. C, Transverse section of gastrocnemius muscle from a boy with Duchenne muscular dystrophy. Normal muscle fiber is replaced with fat and connective tissue.
Evaluation and Treatment
Becker Muscular Dystrophy
FIGURE 38-14 Multisystem Approach for Evaluation and Treatment of Duchenne Muscular Dystrophy.
Facioscapulohumeral Muscular Dystrophy
Myotonic Muscular Dystrophy
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 38-2
Musculoskeletal Tumors
Benign Bone Tumors
Osteochondroma
Nonossifying Fibroma
Malignant Bone Tumors
Osteosarcoma
Pathophysiology
Clinical Manifestations
FIGURE 38-15 Ewing Sarcoma. A, Most common anatomic sites. B, Close-up view of Ewing sarcoma of the distal end of the tibia. Tumor extends into the soft tissue.
Evaluation and Treatment
Ewing Sarcoma
FIGURE 38-16 Ewing Sarcoma of the Distal Radius. Radiograph of an 8-year-old boy showing a permeative lesion of the distal radius. Note the loss of bone cortex on the ulnar border suggesting an aggressive process. Bone biopsy revealed Ewing sarcoma.
Pathophysiology
Clinical Manifestations
Evaluation and Treatment
QUICK CHECK 38-3
Nonaccidental Trauma
Fractures in Nonaccidental Trauma
Evaluation
FIGURE 38-17 Corner Fracture. Bilateral knee radiograph showing healing corner fractures of bilateral proximal tibias and distal femurs. Note the varying amount of callus formation signifying fractures at different stages of healing.
Treatment
QUICK CHECK 38-4
DID YOU UNDERSTAND?
Congenital Defects
Bone Infection
Juvenile Idiopathic Arthritis
Osteochondroses
Scoliosis
Muscular Dystrophy
Musculoskeletal Tumors
Nonaccidental Trauma
KEY TERMS
References
Chapter 39 Structure, Function, and Disorders of the Integument
Structure and Function of the Skin
Layers of the Skin
Dermal Appendages
FIGURE 39-1 Structure of the Skin. A, Cross section showing major skin structures. B, Layers of the epidermis.
FIGURE 39-2 Structures of the Nail.
TABLE 39-1 LAYERS OF THE SKIN
Blood Supply and Innervation
QUICK CHECK 39-1
GERIATRIC CONSIDERATIONS
Other Skin Changes with Aging
Clinical Manifestations of Skin Dysfunction
Lesions
Pressure ulcers
TABLE 39-2 PRIMARY AND SECONDARY SKIN LESIONS
TABLE 39-3 CLINICAL MANIFESTATIONS OF SELECT SKIN LESIONS
FIGURE 39-3 Progression of Pressure Ulcer. Sustained pressure over a bony prominence compresses the tissue and reduces blood flow, resulting in progressive ischemia and necrosis of tissue.
RISK FACTORS
External Factors
Disease/Tissue Factors
Keloids and Hypertrophic Scars
FIGURE 39-4 Keloid Formation.
Pruritus
QUICK CHECK 39-2
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.
Atopic Dermatitis
Stasis Dermatitis
Seborrheic Dermatitis
FIGURE 39-6 Stasis Ulcer.
Papulosquamous Disorders
Psoriasis
FIGURE 39-7 Seborrheic Dermatitis.
FIGURE 39-8 Psoriasis. Typical oval plaque with well-defined borders and silvery scale.
FIGURE 39-9 Guttate Psoriasis Following Streptococcal Infection. Numerous uniformly small lesions may abruptly occur following streptococcal pharyngitis.
HEALTH ALERT
Pityriasis Rosea
FIGURE 39-10 Pityriasis Rosea Herald Patch. A collarette pattern has formed around the margins (arrows).
Lichen Planus
FIGURE 39-11 Hypertrophic Lichen Planus on Arms.
QUICK CHECK 39-3
Acne Vulgaris
Acne Rosacea
Lupus Erythematosus
FIGURE 39-12 Granulomatous Rosacea. Pustules and erythema occur on the forehead, cheeks, and nose.
Discoid (cutaneous) lupus erythematosus
Vesiculobullous Disorders
Pemphigus
FIGURE 39-13 Subacute Cutaneous Lupus (Discoid Lupus Erythematosus).
Erythema Multiforme
FIGURE 39-14 Bullous Pemphigoid. Generalized eruption with blisters arising from an edematous, erythematous annular base.
QUICK CHECK 39-4
Infections
Bacterial Infections
Folliculitis
Furuncles and carbuncles
Cellulitis
FIGURE 39-15 Furuncle of the Forearm.
Erysipelas
Impetigo
Viral Infections
Herpes simplex virus
FIGURE 39-16 Herpes Simplex of the Lips (Labialis). Typical presentation with tense vesicles appearing on the lips and extending onto the skin.
Herpes zoster and varicella
Warts
FIGURE 39-17 Herpes Zoster. Diffuse involvement of a dermatome.
FIGURE 39-18 Verruca Vulgaris (Near Toes).
Fungal Infections
Tinea infections
TABLE 39-4 COMMON SITES OF TINEA INFECTIONS
Candidiasis
FIGURE 39-19 Tinea Pedis. Inflammation has extended from the web area onto the dorsum of the foot.
Vascular Disorders
Cutaneous Vasculitis
TABLE 39-5 SITES OF CANDIDIASIS INFECTION
Urticaria
Scleroderma (Systemic Sclerosis)
FIGURE 39-20 Scleroderma. Note inflammation and shiny skin resulting from a combination of Raynaud phenomena and scleroderma affecting the fingers (acrosclerosis).
QUICK CHECK 39-5
Insect Bites
Mosquitoes, Flies, Bees, and Ants
Benign Tumors
Seborrheic Keratosis
FIGURE 39-21 Seborrheic Keratosis. Typical lesion that is broad, flat, and comparatively smooth surfaced.
Keratoacanthoma
Actinic Keratosis
Nevi (Moles)
QUICK CHECK 39-6
Cancer
HEALTH ALERT
BOX 39-1 IMPORTANT TRENDS FOR SKIN CANCER
Incidence
Mortality
Risk Factors
Warning Signs
Prevention and Early Detection
Treatment
Survival
Basal Cell Carcinoma
FIGURE 39-22 Basal Cell Carcinoma. Center has ulcerated.
Squamous Cell Carcinoma
Cutaneous Melanoma
FIGURE 39-23 Squamous Cell Carcinoma. The sun-exposed ear is a common site for squamous cell carcinoma.
FIGURE 39-24 Lentigo Malignant Melanoma. Lentigo malignant melanoma is most common on the head and neck.
TABLE 39-6 CLASSIFICATION OF NEVI
Kaposi Sarcoma
QUICK CHECK 39-7
FIGURE 39-25 Kaposi Sarcoma. The purple lesion commonly seen on the skin.
Burns
Burn Wound Depth
FIGURE 39-26 Superficial Partial-Thickness Burn. Scald injury following débridement of overlying blister and nonadherent epithelium.
FIGURE 39-27 Deep Partial-Thickness Burn. Note pale appearance and minimal exudates.
FIGURE 39-28 Axillary Burn Scar Contracture. Note the blanching of the anterior axillary fold and small ulceration from a deep partial-thickness burn, both indicating the diminished range of motion.
FIGURE 39-29 Full-Thickness Burn. The wound is dry and insensate.
TABLE 39-7 DEPTH OF BURN INJURY
Pathophysiology and Clinical Manifestations
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
FIGURE 39-31 Immediate Cellular and Immunologic Alterations of Burn Shock.
Cardiovascular and Systemic Response to Burn
Cellular Response to Burn Injury
Metabolic Response to Burn Injury
Immunologic Response to Burn Injury
Evaporative Water Loss
Evaluation and Treatment
Frostbite
FIGURE 39-32 Hypertrophic Scarring. Deep partial-thickness thermal injury can result in extensive hypertrophic scarring.
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.
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
Acne Vulgaris
FIGURE 40-1 Inflammatory (Cystic) Acne. Multiple pustules (erythematous papules and pustules) are present, and several have become confluent. Note areas of scarring.
HEALTH ALERT
Dermatitis
Atopic Dermatitis
FIGURE 40-2 Atopic Dermatitis. Characteristic lesions with crusting from irritation and scratching over knees and around ankles.
Diaper Dermatitis
FIGURE 40-3 Diaper Dermatitis. A, Diaper dermatitis with erosions. B, Diaper dermatitis with Candida albicans secondary infection.
QUICK CHECK 40-1
Infections of the Skin
Bacterial Infections
Impetigo Contagiosum
FIGURE 40-4 Impetigo and Herpes Simplex Virus (HSV) of Upper Lip. Note weeping and crusting lesions.
BOX 40-1 IMPETIGO
Vesicular Impetigo
Bullous Impetigo
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.
Fungal Infections
Tinea Capitis
FIGURE 40-6 Tinea Capitis.
Tinea Corporis
Thrush
FIGURE 40-7 Molluscum Contagiosum. Waxy pink globules with umbilicated centers.
Viral Infections
Molluscum Contagiosum
FIGURE 40-8 Rubella (3-Day Measles). A, Typical distribution of full-blown maculopapular rash with tendency to coalesce; B, Rash of rubella.
Rubella (German or 3-Day Measles)
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. A, Pattern of generalized, polymorphous eruption; B, Chickenpox lesions on 5th day of illness.
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.
Pediculosis (Lice Infestation)
Fleas
Ticks
FIGURE 40-11 Fleabites. Fleabite producing an urticarial wheal with central puncture.
Bedbugs
FIGURE 40-12 Capillary Hemangioma.
Hemangiomas and Vascular Malformations
Hemangiomas
FIGURE 40-13 Cavernous Hemangioma.
Vascular Malformations
FIGURE 40-14 Port-Wine Hemangioma. Port-wine hemangioma in a child.
Other Skin Disorders
Miliaria
FIGURE 40-15 Miliaria Rubra. Note discrete erythematous papules or papulovesicles.
Erythema Toxicum Neonatorum
QUICK CHECK 40-3
DID YOU UNDERSTAND?
Acne Vulgaris
Dermatitis
Infections of the Skin
Insect Bites and Parasites
Vascular Disorders
Other Skin Disorders
KEY TERMS
Smallpox infection (see video)
References
Appendixes
APPENDIX A Most Common Laboratory Values
Glossary
Glossary*
Index
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
IBC
IBC
PREFIXES AND SUFFIXES USED IN MEDICAL TERMINOLOGY
WORD ROOTS COMMONLY USED IN MEDICAL TERMINOLOGY

People Also Search:

understanding pathophysiology huether

understanding pathophysiology 5th edition huether

understanding pathophysiology

understanding pathophysiology 5th edition

understanding pathophysiology 5th edition testbank download pdf

understanding pathophysiology ebook

understanding pathophysiology 5th edition download scribd

huether understanding pathophysiology

huether s. mccance k. understanding pathophysiology

Test bank and solution manual

Understanding Pathophysiology 5th Edition Huether Test Bank

Goulds Pathophysiology for the Health Professions 5th Edition VanMeter Test Bank

Pathophysiology The Biologic Basis for Disease in Adults And Children 5th Edition McCance Test Bank

Pathophysiology 4th Edition Ellen Test Bank

Understanding Pathophysiology 6th Edition Huether Test Bank

Understanding Pathophysiology 4th Edition Huether Test Bank

Pathophysiology 6th Edition Banasik Test Bank

This is completed downloadable of Understanding Pathophysiology 5th Edition Huether Test Bank

Product Details:

Table of Content:

People Also Search:

Instant download after Payment is complete

Main Menu

Understanding Pathophysiology 5th Edition Huether Test Bank

You may also like

This is completed downloadable of Understanding Pathophysiology 5th Edition Huether Test Bank

Product Details:

Table of Content:

People Also Search:

Instant download after Payment is complete

Related products

Main Menu