Sue E. Huether, Kathryn L. McCance - Study Guide for Understanding Pathophysiology,-Mosby

Study Guide for Understanding PathophysiologyThis page intentionally left blankStudy Guide for Understanding Pathophysiology Sue E. Huether, MSN, PhD Professor Emeritus College of Nursing University of Utah Salt ...

Study Guide for Understanding PathophysiologyThis page intentionally left blankStudy Guide for Understanding Pathophysiology Sue E. Huether, MSN, PhD Professor Emeritus College of Nursing University of Utah Salt Lake City, Utah Kathryn L. McCance, MSN, PhD Professor College of Nursing University of Utah Salt Lake City, Utah Section Editors Valentina L. Brashers, MD Professor Nursing and Attending Physician in Internal Medicine University of Virginia Health System Charlottesville, Virginia Neal S. Rote, PhD Academic Vice-Chair and Director of Research Department of Obstetrics and Gynecology University Hospitals of Cleveland; Professor of Reproductive Biology and Pathology Case School of Medicine Case Western Reserve University Cleveland, Ohio Prepared by Clayton F. Parkinson, PhD Professor Emeritus College of Health Sciences Weber State University Ogden, Utah3251 Riverport Lane St. Louis, Missouri 63043 STUDY GUIDE FOR UNDERSTANDING PATHOPHYSIOLOGY, ISBN: 978-0-323-08489-5 5TH EDITION Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Vice President and Publisher: Loren S. Wilson Senior Editor: Sandra Clark Senior Developmental Editor: Charlene Ketchum Editorial Assistant: Brooke Kannady Publishing Services Managers: Jeffrey Patterson and Hemamalini Rajendrababu Senior Project Managers: Jeanne Genz and Srikumar Narayanan Designer: Paula Catalano Multimedia Producer: Lisa Godoski Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2v Reviewers Mandi Counters, RN, MSN, CNRN Assistant Professor Nursing Department Mercy College of Health Sciences Des Moines, Iowa Bradley R Harrell, DNP, ACNP-BC, CCRN Assistant Professor of Nursing School of Nursing Union University-Germantown Germantown, Tennessee Jane Cross Norman, Ph.D., R.N., CNE Professor of Nursing MSN Program Director Tennessee State University Nashville, Tennessee Marylou Virginia Robinson, PhD, FNP-C Assistant Professor College of Nursing University of Colorado Aurora, Colorado ReviewersThis page intentionally left blankvii Preface The study of pathophysiology is complex, ever expanding, and challenging. It requires correlations between normal and abnormal anatomy and physiology as well as the processes resulting in the manifestations of disease. This Study Guide is designed for students as an adjunct to Understanding Pathophysiology, fifth edition, by Sue E. Huether and Kathryn L. McCance. It is intended to facilitate an understanding of the consequences of pathologic processes on the structure and function of the human body. The Study Guide contains 40 chapters, each following the organization of the textbook. The Guide’s chapters have two different formats—one for normal anatomy and physiology and another for anatomic and physiologic alterations. For the normal anatomy and physiology chapters, it is assumed that the student possesses foundational knowledge of anatomy and physiology; therefore, no supplemental narrative is provided. n These chapters have foundational objectives that direct review of the information, principles, and concepts that are essential for understanding the specific diseases that follow in the next chapter. Chapters five and six depart from the usual normal anatomy and physiology chapter’s format. This departure is because inflammation and immunity concepts are frequently referenced throughout the following text and study guide chapters. n Each chapter has a practice examination to give students an opportunity to assess their understanding of normality. The chapters on alterations direct the learner’s study of abnormal anatomy and physiology. n These chapters include 1) foundational objectives for review and 2) learning objectives for study with narrative, charts, and tables. n Each chapter has a practice examination requiring factual and conceptual knowledge related to disease mechanisms. n Each chapter includes one or two case studies linking fact and concept to reality that require analysis and application. The objectives for all chapters are referenced to corresponding pages in the fifth edition of Understanding Pathophysiology. Huether and McCance’s philosophy that students need to grasp basic laws and principles to understand how alterations occur led them to develop an understandable and conceptually integrated textbook. I enjoyed working with Mosby, particularly with Charlene Kechum and Jeanne Genz. All of Mosby’s staff ensured that my efforts were developed into a creative, professional, and pleasing style for student learners. I wish to dedicate my efforts during the preparation of this Study Guide to students who inspired me to search for a better way to convey information to them. Clayton F. Parkinson PrefaceThis page intentionally left blankix Contents PaRt One Basic cOncePts Of PathOPhysiOlOgy Unit 1 the cell 1. Cellular Biology, 1 2. Genes and Genetic Diseases, 5 3. Altered Cellular and Tissue Biology, 11 4. Fluids and Electrolytes, Acids and Bases, 17 Unit 2 Mechanisms of self-Defense 5. Innate Immunity: Inflammation and Wound Healing, 25 6. Third Line of Defense: Adaptive Immunity, 33 7. Infection and Defects in Mechanisms of Defense, 39 8. Stress and Disease, 47 Unit 3 cellular Proliferation: cancer 9. Biology, Clinical Manifestations, and Treatment of Cancer, 53 10. Cancer Epidemiology, 63 11. Cancer in Children, 69 PaRt tWO BODy systeMs anD Diseases Unit 4 the neurologic system 12. Structure and Function of the Neurologic System, 73 13. Pain, Temperature, Sleep, and Sensory Function, 77 14. Alterations in Cognitive Systems, Cerebral Hemodynamics and Motor Function, 85 15. Disorders of the Central and Peripheral Nervous Systems and the Neuromuscular Junction, 95 16. Alterations of Neurologic Function in Children, 107 Unit 5 the endocrine system 17. Mechanisms of Hormonal Regulation, 113 18. Alterations of Hormonal Regulation, 117 Unit 6 the hematologic system 19. Structure and Function of the Hematologic System, 131 20. Alterations of Hematologic Function, 135 21. Alterations of Hematologic Function in Children, 147 Unit 7 the cardiovascular and lymphatic systems 22. Structure and Function of the Cardiovascular and Lymphatic Systems, 153 23. Alterations of Cardiovascular Function, 157 24. Alterations of Cardiovascular Function in Children, 177 Unit 8 the Pulmonary system 25. Structure and Function of the Pulmonary System, 183 26. Alterations of Pulmonary Function, 187 27. Alterations of Pulmonary Function in Children, 199 contentsx Contents Unit 9 the Renal and Urologic systems 28. Structure and Function of the Renal and Urologic Systems, 205 29. Alterations of Renal and Urinary Tract Function, 209 30. Alterations of Renal and Urinary Tract Function in Children, 219 Unit 10 the Reproductive systems 31. Structure and Function of the Reproductive Systems, 225 32. Alterations of the Reproductive Systems, Including Sexually Transmitted Infections, 229 Unit 11 the Digestive system 33. Structure and Function of the Digestive System, 243 34. Alterations of Digestive Function, 247 35. Alterations of Digestive Function in Children, 261 Unit 12 the Musculoskeletal and integumentary systems 36. Structure and Function of the Musculoskeletal System, 267 37. Alterations of Musculoskeletal Function, 271 38. Alterations of Musculoskeletal Function in Children, 285 39. Structure, Function, and Disorders of the Integument, 291 40. Alterations of the Integument in Children, 303 Answers to Practice Examinations, 3091 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 1 Cellular Biology SECTION ONE UNITE TITLE OR SECTION TITLE Cellular Biology UNIT ONE THE CELL FOUNDATIONAL OBJECTIVES After reviewing this chapter, the learner will be able to do the following: 1. State the functions of a typical eukaryotic cell. Review pages 2-3. 2. Describe the structure and function of the nucleus and identify the cytoplasmic organelles. Review page 3; refer to Figures 1-1 and 1-2 and Table 1-1. 3. Describe the structure and function of the plasma membrane. Review pages 3 and 5-7; refer to Figures 1-3 through 1-5 and Tables 1-2 and 1-3. 4. Describe cellular receptors. Review pages 7-8; refer to Figure 1-6. 5. Identify the three mechanisms that bind cells together. Review pages 8-9; refer to Figures 1-7 and 1-8. 6. Describe the primary modes of chemical signaling. Review pages 9, 11, and 13 refer to Figures 1-9 through 1-12 and Table 1-3. 7. Describe cellular catabolism and the transfer of energy to accomplish other cellular processes. Refer to Figures 1-13 through 1-15. 8. Differentiate between passive and active transport, between endocytosis and exocytosis, and between phagocytosis and pinocytosis. Refer to Figures 1-16 through 1-24 and Table 1-4. 9. Describe the changes in the plasma membrane that result in an action potential. Review pages 21-22; refer to Figure 1-25. 10. Identify the phases of mitosis and cytokinesis. Review pages 22-23; refer to Figure 1-26. 11. Describe the stimulation of cell proliferation by growth factors. Review pages 23-24; refer to Figure 1-27 and Table 1-5. 12. Characterize pattern formation. Review page 24. 13. Identify the location and a major function for each type of tissue: epithelial, connective, muscle, and nervous. Refer to Boxes 1-3 through 1-5. PRACTICE EXAMINATION Multiple Choice Circle the correct answer for each question: 1. Which are principal parts of a eukaryotic cell? a. fat, carbohydrate, and protein b. minerals and water c. organelles d. phospholipids and protein e. protoplasm and nucleus 2. The cell membrane is described as a fluid mosaic. Some proteins have a degree of mobility within the lipid bilayer. (More than one answer may be correct.) a. The first sentence is true. b. The first sentence is false. c. The second sentence is true. d. The second sentence is false. e. The second sentence is relevant to the first. f. The second sentence is irrelevant to the first. 12 Chapter 1 Cellular Biology Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. 3. Which particle can penetrate cell membranes most easily? a. lipid soluble, transport protein present b. neutral charge, water soluble c. smaller, water soluble d. uncharged, larger 4. For a cell to engage in active transport processes, it requires: a. mitochondria. b. appropriate fuel. c. ATP. d. enzymes. e. All of the above are correct. 5. Which is inconsistent with the others? a. diffusion b. osmosis c. filtration d. phagocytosis e. facilitated diffusion 6. Which can transport substances uphill against the concentration gradient? a. active transport b. osmosis c. dialysis d. facilitated diffusion e. None of the above is correct. 7. Caveolae: a. serve as repositories for some receptors. b. provide a route for transport into a cell. c. relay signals into cells. d. All of the above are correct. 8. Which statement is true for cytoplasm? a. It is located outside the nucleus. b. It provides support for organelles. c. It is mostly water. d. a, b, and c e. a and b 9. The retinoblastoma (Rb) protein: a. is a brake on the progress of the cell cycle. b. binds to gene regulatory proteins. c. slows cell proliferation. d. a and c e. a, b, and c 10. A major function of connective tissue is: a. to form glands. b. support and binding. c. covering and lining. d. movement. e. to conduct nerve impulses. 11. Which are characteristic of epithelial tissue? (More than one answer may be correct.) a. elasticity b. protection c. fills spaces between organs d. secretion 12. Signaling molecules cause all of the following except: a. acceleration/initiative of intracellular protein kinases. b. arrest of cellular growth. c. apoptosis. d. conversion of an intracellular signal into an extracellular response. 13. Ligands that bind with membrane receptors include which of the following? (More than one answer may be correct.) a. hormones b. antigens c. neurotransmitters d. drugs e. infectious agents 14. The products from the metabolism of glucose include which of the following? (More than one answer may be correct.) a. kilocalories b. CO 2 c. H 2O d. ATP 15. Identify the correct sequence of events for initiation and conduction of a nerve impulse. 1. Sodium moves inside. 2. Potassium leaves cell. 3. Sodium permeability changes. 4. Resting potential is reestablished. 5. Potassium permeability changes. a. 1, 3, 2, 5, 4 b. 3, 1, 5, 2, 4 c. 5, 2, 3, 1, 4 d. 4, 5, 2, 3, 1 16. Increased cytoplasmic calcium: a. causes one cell to adhere to another. b. increases permeability at the junctional complex. c. decreases permeability at the junctional complex. d. None of the above is correct. 17. Cell junctions: a. coordinate activities of cells within tissues. b. are an impermeable part of the plasma membrane. c. hold cells together. d. Both a and c are correct. e. Both b and c are correct.3 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 1 Cellular Biology Matching Match the term with its descriptor: 18. Anaphase a. 75% to 90% H2O, lipids, and protein b. within the nucleus, stored RNA c. compartmentalizes cellular activity d. single strand of DNA, nondividing cell e. “generation plant” for ATP f. centriole migration g. chromatid pair alignment h. chromatid migration i. daughter nuclei j. protein synthesis site 19. Chromatin 20. Metaphase 21. Mitochondria 22. Prophase 23. Ribosome Match the location with the tissue type found: 24. Lining of the kidney tubules a. simple squamous b. simple cuboidal c. simple columnar, ciliated d. stratified squamous e. transitional 25. Lining of the upper respiratory tract Fill in the Blank Complete the following table identifying membrane transport of cellular intake or output: Membrane Transport Transport Mechanism Description Diffusion Filtration Osmosis Mediated transport Two molecules move simultaneously in one direction (symport) or in opposite direction (antiport) or a single molecule moves in one direction (uniport) Passive mediated transport/facilitated diffusion Does not require the expenditure of metabolic energy (ATP) Active mediated transport Requires the expenditure of metabolic energy (ATP) Endocytosis Pinocytosis PhagocytosisThis page intentionally left blank5 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 2 Genes and Genetic Diseases Genes and Genetic Diseases FounDational objectives a. Describe the interrelationships of DNA, RNA, and proteins. Review pages 35-39; refer to Figures 2-1 through 2-8. 2 MeMoRY cHecK! • The gene consists of a particular sequence of nucleotides in the deoxyribonucleic acid (DNA) of the chromosome. The sequence of nucleotides in a gene determines which proteins are found in a cell, and these proteins determine both the form and the function of the cell. • Genetic information flows from DNA to RNA to proteins. Three major processes are involved in the preservation and transmission of genetic information. The first is replication, or the copying of DNA to form identical daughter molecules. The second is transcription, in which the genetic message encoded within DNA is transcribed into RNA and is carried to the ribosomes, the sites of protein synthesis. The third is translation, in which the genetic message is decoded and converted into the 20-letter alphabet of protein structure. Because the sequence of nucleotides in the DNA bears a linear correspondence to the sequence of amino acids in the formed proteins, genetic information is preserved and transmitted to progeny. MeMoRY cHecK! Genetic Term Definition Progeny Offspring Chromosomes Structures in the nucleus that contain DNA, which transmits genetic information; each chromosome is composed of many genes arranged in linear order Gene DNA, the basic unit of heredity, located at a particular locus on the chromosome Locus The position each gene occupies along a chromosome Allele One of two or more alternative genes that contain specific inheritable characteristics (such as eye color) and occupy corresponding positions on paired, homologous chromosomes—one gene from each parent; a different version of the same paired gene Homozygous A trait of an organism produced by identical or nearly identical alleles Heterozygous Possessing different alleles at a given chromosomal location Karyotype/karyogram A display of human chromosomes based on their lengths and the locations of their centromeres Genotype The basic combination of genes of an organism Phenotype The expression of the gene or trait in an individual (e.g., physical appearance, such as eye color) Carrier An individual who has a gene for disease but is phenotypically normal Dominant traits Traits for which one of a pair of alleles is necessary for expression (e.g., brown eyes) Recessive traits Traits for which two alleles of a pair are necessary for expression (e.g., blue eyes, a recessive gene on the male’s X chromosome, will be expressed because the gene is not matched by a corresponding gene on the Y chromosome) Pedigree chart A schematic method for classifying genetic data Penetrance The percentage of individuals with a specific genotype who exhibit the expected phenotype Expressivity The extent of variation in phenotype for a particular genotype Genetic imprinting Different expression of a disease gene depending on which parent transmits the gene; it is associated with methylation b. Define general genetic terms.6 Chapter 2 Genes and Genetic Diseases Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Single-gene disorders are known to be caused by mutation in a single gene. The mutated gene may be present on one or both chromosomes of a gene pair. Multifactorial disorders result when small variations in genes combine with environmental factors to produce serious defects. Multifactorial disorders tend to cluster in families. leaRninG objectives After studying this chapter, the learner will be able to do the following: 1. Characterize the chromosome and its aberrations. Study pages 40-46; refer to Figures 2-9 through 2-18. In chromosome disorders, the defect is due to an abnormality in chromosome number or structure. The structure of the genes in chromosome disorders may be normal, but the genes may be present in multiple copies or may be situated on a different chromosome. Normal somatic cells that have two sets of 23 chromosomes are diploid (double), or 2N. Gametes with a single set of 23 chromosomes are haploid (single), or N. A cell with an exact multiple of the haploid number is euploid. Euploid numbers may be 2N, 3N (triploid), or 4N (tetraploid). Chromosome numbers that are exact multiples of N, but greater than 2N, are called triploid or polyploid. Aneuploidy refers to a chromosome complement that is abnormal in number but is not an exact multiple of N. An aneuploid cell may be trisomic (2N + 1 chromosome) or monosomic (2N − 1 chromosome). Disjunction is the normal separation and migration of chromosomes during cell division. Failure of the process, or nondisjunction, in a meiotic division results in one daughter cell receiving both homologous chromosomes and the other receiving neither. It is the primary cause of aneuploidy. If this deviation in normal processes occurs during the first meiotic division, half of the gametes will contain 22 chromosomes and half will contain 24. If joined with a normal gamete, a gamete produced in this manner will produce either a monosomic (2N − 1) or trisomic (2N + 1) zygote. Deviations in the normal structure of chromosomes result when the chromosome material breaks and reassembles in an abnormal arrangement. Structural abnormalities include deletion, duplication, inversion, and translocation. In deletion, or loss of a portion of a chromosome, usually the zygote has one normal chromosome united with a chromosome with some missing genes. Cri-duchat (“cry of the cat”) syndrome is such a deletion and is manifested by the high-pitched cat-like cry of an affected child. Duplication is the presence of a repeated gene or gene sequence. A deleted segment of one chromosome may become incorporated into its homologous chromosome. Inversion is the reversal of gene order. The linear arrangement of genes on a chromosome is broken, and the order of a portion of the gene complement is reversed in the process of reattachment. Translocation is the transfer of part of one chromosome to a nonhomologous chromosome. This occurs when two chromosomes break and the segments are rejoined in an abnormal arrangement. 2. Cite examples of chromosome disorders. Refer to Figures 2-13 through 2-16 and Table 2-1. A common example of an autosomal aneuploidy disorder that results from an abnormality of chromosome number is trisomy 21, or Down syndrome. This disorder can result when nondisjunction of chromosome 21 occurs at meiosis, producing one gamete with an extra chromosome 21 and one gamete with no chromosome 21. Union of the extra chromosome female gamete with a normal sperm produces a 47-chromosome zygote, or trisomy 21. The overall incidence of Down syndrome is 1 per 800 live births. The incidence rises with increasing maternal age. Clinical diagnosis of trisomy 21 is often based on facial appearance. A low nasal bridge, epicanthal folds, protruding tongue, and low-set ears are common. Mental retardation is consistent in children with Down syndrome, but its degree may vary. The average IQ is approximately 50. Two sex chromosome aneuploidy disorders are Turner syndrome (female) and Klinefelter syndrome (male). The most common karyotype showing female phenotype is 45,X or the absence of one X chromosome; the male karyotype is 47,XXY or an extra X chromosome. The diagnosis of Turner syndrome is suggested in the newborn by the presence of redundant neck skin and peripheral lymphedema. Later, the presence of short stature is suggestive. Klinefelter syndrome is a common cause of infertility in men. Other manifestations are long lower extremities, sparse body hair with female distribution, and female breast development in about 50% of cases. A moderate degree of mental impairment may be present. 3. Characterize single-gene disorders. Study pages 47-54; refer to Figures 2-19 through 2-31. An inherited gene may be present on one or both chromosomes of a pair. The pedigree patterns of inherited traits depend on whether the gene is located on an autosomal chromosome, any chromosome other than a sex chromosome, or the X chromosome and whether the gene is dominant or recessive. These factors allow four basic patterns of inheritance for single-gene traits, whether normal or abnormal: autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. In autosomal dominant inheritance of genetic defects, the abnormal allele is dominant and the normal allele is recessive. The phenotype is the same whether the allele is present in either a homozygous or a heterozygous state.7 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 2 Genes and Genetic Diseases Characteristics of autosomal dominant inheritance are (1) affected persons have an affected parent; (2) affected persons mating with normal persons have affected and unaffected offspring in equal proportion; and (3) males and females are equally affected. In autosomal recessive disorders, the abnormal allele is recessive. For the trait to be expressed, a person must be homozygous for the abnormal allele. Because the dominant or normal allele masks the trait, most persons who are heterozygous for an autosomal recessive allele are phenotypically normal. When two heterozygous individuals mate and an offspring receives the recessive allele from each parent, the trait is expressed. Characteristics of autosomal recessive inheritance are: (1) the trait usually appears in siblings only, not in the parents; (2) males and females are equally likely to be affected; (3) for parents of one affected child, the recurrence risk is one in four for every subsequent birth; (4) both parents of an affected child carry the recessive allele; and (5) the parents of the affected child may be blood relatives, for example, first cousins. Unlike the 44 autosomes that can be arranged in 22 homologous pairs, the two sex chromosomes in the female are XX and in the male are XY. The ovum must contain an X chromosome, so if it is fertilized by a sperm containing an X chromosome, the progeny will be a female (XX). If the sperm contributes a Y chromosome, the progeny will be male (XY). Traits determined by either dominant or recessive X-linked genes are expressed in the male. The genes on the X chromosome cannot be transmitted from father to son (fathers contribute a Y chromosome to sons) but are transmitted from father to all daughters through one X chromosome. Recessive abnormal genes on the X chromosome of a female may not be expressed because they are matched by normal genes inherited with the other X chromosome. X-linked dominant disorders are rare. The main characteristic of this inheritance pattern is that an affected male transmits the gene to all of his daughters and to none of his sons. The affected female may transmit the gene to offspring of either sex. In X-linked recessive disorders, the recessive gene located on the one X chromosome of the male is not balanced by the dominant allele on the Y chromosome and is thus expressed. Only matings between an affected male and a carrier or affected female should result in an affected female. Males affected with an X-linked recessive disorder cannot transmit the gene to sons, but transmit it to all daughters. An unaffected female who is heterozygous (a carrier) for the recessive gene transmits it to 50% of her sons and daughters. Principles of the X-linked recessive inheritance are: (1) males are predominantly affected; (2) affected males cannot transmit the gene to sons, but do transmit the gene to all daughters; (3) sons of female carriers have a 50% risk of being affected; and (4) daughters of female carriers have a 50% risk of being carriers. 4. Cite examples of single-gene disorders. Refer to Figures 2-23 and 2-31. One of the best-known autosomal dominant diseases is Huntington disease, a neurologic disorder that exhibits progressive dementia and increasingly uncontrollable movements of the limbs. A key feature of this disease is that symptoms are not usually evident until after age 40 years. Thus, those in whom the disease develops often have had children before they are aware that they have the gene. The severity of an autosomal dominant disease can vary greatly. An example of variable expressivity in an autosomal dominant disease is type 1 neurofibromatosis, or von Recklinghausen disease, which has been mapped to the long arm of chromosome 17. The expression of this gene can vary from a few harmless café au lait–colored spots on the skin to numerous malignant neurofibromas, scoliosis, seizures, gliomas, neuromas, hypertension, and mental retardation. The cystic fibrosis gene, the cause of an autosomal recessive disease, has been mapped to the long arm of chromosome 7. In this disease, defective transport of chloride ion leads to a salt imbalance that results in secretions of abnormally thick, dehydrated mucus. Some of the digestive organs, particularly the pancreas, become obstructed with mucus, resulting in malnutrition. The lung airways tend to become clogged with mucus, making them highly susceptible to bacterial infections. The most common and severe of all X-linked recessive disorders is Duchenne muscular dystrophy, which affects males. This disorder is characterized by progressive muscle degeneration; individuals are usually unable to walk by age 10 or 12. The disease also affects the heart and respiratory muscles, and death due to respiratory or cardiac failure may occur before age 20 years. These cases result from an absence of dystrophin, without which the muscle cell cannot survive, and muscle deterioration follows. 5. Characterize multifactorial inheritance, and cite examples. Study pages 55 and 56; refer to Figures 2-30 and 2-31. Not all traits are produced by single genes; some traits are the result of several genes acting together. When several genes act together, the trait is referred to as polygenic traits. When environmental factors also influence the expression of the trait, the term multifactorial inheritance is used. Both genes and environment contribute to variation in traits. Multifactorial disorders tend to cluster in families. Although genes determine both height and IQ, the environment also influences these traits. Also, IQ scores can be improved by exposing children to enriched learning environments. A number of diseases do not follow the bell-shaped distribution of polygenic and multifactorial traits. Instead, a certain threshold of liability must be crossed before the8 Chapter 2 Genes and Genetic Diseases Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. disease is expressed. A well-known example of a threshold trait is pyloric stenosis, a disorder characterized by narrowing or obstruction of the pylorus. Chronic vomiting, constipation, weight loss, and electrolyte imbalance can result from this condition. Pyloric stenosis is much more common in males than in females. The reason for this difference is that the threshold of liability is much lower in males than in females. Thus, fewer defective alleles are required to generate the disorder in males. This situation also means that the offspring of affected females are more likely to have pyloric stenosis because affected females carry more disease-causing alleles than do most affected males. Other multifactorial diseases include cleft lip and cleft palate, neural tube defects, clubfoot, and some forms of congenital heart disease. Hypertensive heart disease and diabetes mellitus likely can be grouped in the category of multifactorial disorders. PRactice exaMination Multiple Choice Circle the correct answer for each question: 1. Which genetic disease is caused by an abnormal karyotype? a. Down syndrome b. Huntington disease c. phenylketonuria (PKU) d. neurofibromatosis e. cystic fibrosis 2. Which is not characteristic of Down syndrome? a. It is an autosomal aneuploidy. b. It is a genetic error of metabolism. c. Mental retardation is consistently expressed. d. Clinical diagnosis can be suggested by facial appearance. e. The karyotype is 47,XY + 21. 3. Cri-du-chat syndrome is an abnormality of chromosomal structure involving: a. translocation. b. inversion. c. duplication. d. deletion. 4. An individual’s karyotype lacks a homologous X chromosome and has only a single X chromosome present. Which statement is not true? a. The karyotype is 45,X. b. Features include ribbed neck and short stature. c. The karyotype is 46,XY. d. The disorder is a sex chromosome aneuploidy. 5. If homologous chromosomes fail to separate during meiosis, the disorder is: a. polyploidy. b. aneuploidy. c. disjunction. d. nondisjunction. e. translocation. 6. Cystic fibrosis has been mapped to chromosome: a. 17. b. 7. c. X. d. 16. 7. In autosomal dominant inherited disorders: a. affected individuals do not have an affected parent. b. affected persons mating with normal persons have a 50% risk of having an affected offspring. c. male offspring are most often affected. d. unaffected children born to affected parents will have affected children. 8. Indentify the characteristic(s) of X-linked recessive inherited disorders: a. affected males have normal sons. b. affected males have affected daughters. c. sons of female carriers have a 50% risk of being affected. d. the affected female may transmit the gene to both sons and daughters. 9. Which is/are not autosomal dominant disease(s)? a. Huntington disease b. neurofibromatosis c. Duchenne muscular dystrophy d. von Recklinghausen disease e. pyloric stenosis 10. When environmental influences cause varied phenotypic expressions of genotypes, the result is: a. a multifactorial trait. b. a threshold liability. c. an autosomal dominant trait. d. an X-linked recessive trait. 11. Which likely is not a multifactorial inherited disorder? a. cleft palate b. hypertension c. diabetes mellitus d. cystic fibrosis e. heart disease9 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 2 Genes and Genetic Diseases Case study Mrs. S.J., a 42-year-old woman who is pregnant for the first time, was admitted to the labor and delivery unit. She appeared to be in excellent health, and this anticipated delivery would be the culmination of an uneventful pregnancy. Eight hours later, she delivered a 7-pound, 3-ounce baby boy. The infant had low-set ears, a flat facial profile with a small nose, wide epicanthal folds, and simian creases. The parents were told that the baby’s features were the result of a genetic aberration and that he had Down syndrome. The father asked, “Why did this happen, and what does the future hold?” How would you answer the father’s questions? Matching Match the term with the circumstance: 12. Recessive disorder a. results from numerical or structural aberrations b. many genes are common c. two or more cell lines with different karyotypes d. individual is homozygous for a gene e. failure of homologous chromosomes to separate during meiosis or mitosis f. outward appearance of an individual g. a probability of .25 h. summarizes family relationships 13. Multifactorial inheritance 14. Aneuploidy 15. Chromosomal aberration 16. Phenotype 17. Pedigree 18. Autosomal recessive inheritance Match the term with the circumstance: 19. Expressivity a. a probability of 0.5 b. females are unlikely to be affected c. species chromosomal morphology d. expressed by one allele e. Turner syndrome f. different version of the same paired gene g. Klinefelter syndrome h. no loss or gain of genetic material, reversed order i. extent of phenotypic variation of a particular genotype 20. X-linked 21. Inversion 22. Dominant trait 23. Allele 24. 47,XXY 25. Karyotype Complete the following table comparing the transmission patterns of single-gene and multifactorial diseases: Transmission Patterns for Genetic Diseases Single-Gene Diseases Multifactorial Diseases Inheritance patternThis page intentionally left blank11 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 3 Altered Cellular and Tissue Biology Altered Cellular and Tissue Biology FoundATionAl oBjeCTives a. Describe processes of cellular intake and output. Review pages 13-18 and 20. 3 MeMoRY CHeCK! • The intact, normally functioning plasma membrane is selectively or differentially permeable to substances; that is, it allows some substances to pass while excluding others. Water and small, uncharged substances move through pores of the lipid bilayer by passive transport, which requires no expenditure of energy. This process is driven by the forces of osmosis, hydrostatic pressure, and diffusion. Larger molecules and molecular complexes are moved into the cell by active transport, which requires the expenditure of energy or ATP by the cell. In active transport, materials move from low concentrations to high concentrations. The largest molecules and fluids are ingested by endocytosis (from the extracellular medium) and expelled by exocytosis (into the extracellular medium) after cellular synthesis of smaller building blocks. When the plasma membrane is injured, it becomes permeable to virtually everything, and substances move into and out of the cells in an unrestricted manner. Notably, such substances may affect: (1) the nucleus and its genetic information or (2) the cytoplasmic organelles and their varied functions. Then, there is altered cellular physiology and pathology. leARning oBjeCTives After studying this chapter, the learner will be able to do the following: 1. Describe the cellular adaptations occurring in atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. Identify the conditions under which each can occur. Study pages 59-62; refer to Figures 3-1 through 3-5. When confronted with environmental stresses that disrupt normal structure and function, the cell undergoes adaptive changes that permit survival and maintain function. The adaptation is a reversible, structural, or functional response to normal or adverse conditions; it enables the cell to maintain a steady state called homeostasis. These changes may lead to atrophy, hypertrophy, hyperplasia, dysplasia, or metaplasia. Cellular atrophy decreases the cell substance and results in cell shrinkage. Causes of atrophy may be physiologic (associated with normal development), pathologic (accompanying disease), or disuse (because of lack of stimulation). All three causes may result in decreased protein synthesis, increased protein catabolism, or both. A ubiquitin-proteosome pathway degrades proteins to ubiquitin, a smaller protein, and then proteosomes in the cytoplasm complete the proteolysis. Hypertrophy increases cell size. Hypertrophy is commonly seen in cardiac and skeletal muscle tissue. The increase in cell components is related to an increased rate of protein synthesis. Mechanical signals, such as stretch, and trophic signals, such as growth factors, hormones, and vasoactive agents, are triggers for hypertrophy. Physiologic hypertrophy is observed in uterine tissue and mammary glands during pregnancy. Hyperplasia is an increase in the number of cells of a tissue or organ. It occurs in tissues where cells are capable of mitotic division. Breast and uterine enlargement during pregnancy are examples of physiologic hyperplasia and hypertrophy that are hormonally regulated. A pathologic hyperplasia occurs when the endometrium enlarges because of excessive estrogen production. Then, the abnormally thickened uterine layer may bleed excessively and frequently. Compensatory hyperplasia enables certain organs, such as the liver, to regenerate after loss of substance. Hyperplasia and hypertrophy often occur together if cells can synthesize DNA; however, in nondividing cells, only hypertrophy occurs. Dysplasia is deranged cell growth that results in cells that vary in size, shape, and appearance in comparison with mature cells and is related to hyperplasia. Dysplasia occurs in association with chronic irritation or inflammation in the uterine cervix, oral cavity, gallbladder, and respiratory passages. Dysplasia is potentially reversible once the irritating cause has been removed. Dysplastic changes do not indicate cancer and may not progress to neoplastic disease. Metaplasia is a reversible conversion from one adult cell type to another adult cell type. It allows for replacement with cells that are better able to tolerate environmental stresses. In metaplasia, one type of cell may be converted to another type of cell within its tissue class.12 Chapter 3 Altered Cellular and Tissue Biology Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. An example of metaplasia is the substitution of stratified squamous epithelial cells for ciliated columnar epithelial cells in the airways of an individual who is a habitual cigarette smoker. 2. Identify the mechanism of cellular injury from hypoxia, free radicals, chemicals, unintentional and intentional injuries, infectious agents, immunologic and inflammatory responses, and genetic factors. Study pages 62-66, 68-75, and 78-80; refer to Figures 3-6 through 3-16 and Tables 3-1 through 3-10. Hypoxia deprives the cell of oxygen and interrupts oxidative metabolism and the generation of ATP. As oxygen tension within the cell falls, oxidative metabolism ceases and the cell reverts to anaerobic metabolism. One of the earliest effects of reduced ATP is acute cellular swelling caused by failure of the sodium-potassium membrane pump. With impaired function of this pump, intracellular potassium levels decrease and sodium and water accumulate within the cell. As fluid and ions move into the cell, there is dilation of the endoplasmic reticulum, increased membrane permeability, and decreased mitochondrial function as extracellular calcium accumulates in the mitochondria. If the oxygen supply is not restored, loss of essential enzymes, proteins, and ribonucleic acid continues through the permeable membrane of the cell. Hypoxia can result from inadequate oxygen in the air, respiratory disease, decreased blood flow due to circulatory disease, anemia, or inability of the cells to utilize oxygen. Restoration of oxygen, however, can cause reperfusion injury. Reperfusion injury results from the generation of highly reactive oxygen intermediates, including hydroxyl radical, superoxide, and hydrogen peroxide (free radicals; see next paragraph). An important mechanism of membrane damage is caused by reactive oxygen species (ROS), especially by activated oxygen species. A free radical is an atom or group of atoms with an unpaired electron. The unpaired electron makes the atom or group unstable. To gain stability, the radical gives up an electron to another molecule or steals an electron. These highly reactive radicals have low chemical specificity and can bond with key molecules in membranes and nucleic acids. These reactive species cause injury by: (1) lipid peroxidation, which destroys unsaturated fatty acids; (2) fragmentation of polypeptide chains within proteins; and (3) alteration of DNA by breakage of single strands. Free radicals may be initiated within cells by the absorption of ultraviolet light or x-rays, oxidative reactions that occur during normal metabolism, and enzymatic metabolism of exogenous chemicals or drugs. Toxic chemical agents can injure the cell membrane and cell structures, block enzymatic pathways, coagulate cell proteins, and disrupt the osmotic and ionic balance of cells. Chemicals may injure cells during the process of metabolism or elimination. Carbon tetrachloride, for example, causes little damage until it is metabolized by liver enzymes to highly reactive free radicals, and then it is extremely toxic to liver cells. Carbon monoxide has a special affinity for the hemoglobin molecule and reduces hemoglobin’s ability to carry oxygen. Liver disease, nutritional disorders, and CNS impairment are serious consequences of alcohol abuse. The hepatic changes, initiated by ethanol conversion to acetaldehyde, include deposition of fat, enlargement of the liver, interruption of transport of proteins and their secretion, increase in intracellular water, depression of fatty acid oxidation, greater membrane rigidity, and acute liver cell necrosis. In the CNS, alcohol is a depressant, initially affecting subcortical structures. Consequently, motor and intellectual activity becomes disoriented. At high blood alcohol levels, respiratory medullary centers become depressed. Unintentional and intentional injuries affect more men than women and more blacks than whites or other racial groups. Injuries by blunt force result from mechanical energy applied to the body. Contusion (bleeding in skin or underlying tissue) and abrasion (removal of skin) are consequences of blunt blows. Contusions and abrasions exhibit a patterned appearance that mirrors the shape and features of an injuring object. Asphyxial injuries are caused by a failure of cells to receive or use oxygen; these injuries can be categorized as suffocation, strangulation, chemical, and drowning. Infectious agents that survive and proliferate in the body may produce toxic substances and hypersensitivity reactions that injure cells and tissues. Immunologic and inflammatory injuries are important causes of cellular injury. Cellular membranes are injured by direct contact with cellular and chemical components of the innate and adaptive immune responses. Such mediators are lymphocytes and macrophages and chemicals such as histamine, antibodies, lymphokines, complement, and proteases. Complement, a serum protein, is responsible for many of the membrane alterations that occur during immunologic injury. Membrane alterations are associated with rapid leakage of potassium out of the cell and rapid influx of water. Antibodies can interfere with membrane function by binding to and occupying receptor molecules on the plasma membrane. (Later chapters deal with these injurious consequences, as well as with hypersensitivity and autoimmune disease.) Genetic disorders may alter the cell’s nucleus and the plasma membrane’s structure, shape, receptors, or transport mechanisms. (Mechanisms causing genetic abnormalities are discussed in Chapter 2.) Errors in health care are unintended events that harm individuals. Such errors involve medications, surgery, diagnosis, equipment, and laboratory reports. They can occur in hospitals, clinics, outpatient surgery centers, health provider offices, pharmacies, and individuals’ homes.13 Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. Chapter 3 Altered Cellular and Tissue Biology 3. Identify various cellular accumulations occurring in response to injury and the subsequent manifestations of cellular damage. Study pages 80-84; refer to Figures 3-17 through 3-22 and Table 3-11. Cellular accumulations or infiltrations occur whenever normal substances are produced in excess, normal and abnormal substances are ineffectively catabolized, or harmful exogenous materials accumulate intracellularly. 4. Identify the major types of cellular necrosis and cite examples of the tissues involved in each type. Compare necrosis with apoptosis and describe autophagy. Study pages 84-88 and 90; refer to Figures 3-23 through 3-31 and Table 3-12. Cellular death leads to cellular dissolution, or necrosis. It is likely that under certain conditions, such as activation of proteases, necrosis is regulated or programmed in a well-orchestrated way. Hence, it is termed programmed necrosis or necroptosis. Necrosis is local cell death and involves the process of cellular self-digestion known as autodigestion or autolysis. As necrosis progresses, most organelles are disrupted and karyolysis, nuclear dissolution from the action of hydrolytic enzymes, becomes evident. In some cells, the nucleus shrinks and is termed pyknosis. The process of the fragmentation of nucleus into nuclear dust is known as karyorrhexis. There are four major types of necrosis: coagulative, liquefactive, caseous, and fatty. Gangrenous necrosis is not a distinctive type of cell death, but instead refers to large areas of tissue death. Coagulative necrosis occurs primarily in the kidneys, heart, and adrenal glands and usually results from hypoxia caused by severe ischemia. Protein denaturation causes coagulation. Liquefactive necrosis is common following ischemic injury to neurons and glial cells in the brain. Because brain cells are rich in digestive hydrolytic enzymes and lipids, the brain cells are digested by their own hydrolases. The brain tissue becomes soft, liquefies, and is walled off from healthy tissue to form cysts. Bacterial infections are causes of liquefactive necrosis. Caseous necrosis, which is commonly seen in tuberculous pulmonary infection, is a combination of liquefactive necrosis and coagulative necrosis. The necrotic debris is not digested completely by hydrolases, so tissues appear soft and granular and resemble clumped cheese. A granulomatous inflammatory wall may enclose the central areas of caseous necrosis. The fatty necrosis found in the breast, pancreas, and other abdominal structures is a specific cellular dissolution caused by lipases. Lipases break down triglycerides and release free fatty acids, which then combine with calcium, magnesium, and sodium ions to create soaps, in a process known as saponification. The necrotic tissue appears opaque and chalk white. Gangrenous necrosis refers to death of tissue, usually in considerable mass and with putrefaction. It results from severe hypoxic injury subsequent to arteriosclerosis or blockage of major arteries followed by bacterial invasion. Dry gangrene is usually caused by a coagulative necrosis, whereas wet gangrene develops when neutrophils Cellular Accumulations Accumulation Causes Consequence of Cellular Damage H 2O Shift of extracellular H2O into cell, reduced ATP and ATPase, sodium accumulates in cell Cellular swelling, vacuolation, oncosis cell, reduced ATP and ATPase, accumulation of sodium in cell Lipids, carbohydrates Imbalance in production, utilization, or mobilization of lipids or carbohydrates Vacuolation, displacement of nucleus and organelles leading to fibrosis and scarring Glycogen Genetic disorders, diabetes mellitus Cytoplasmic vacuolation Proteins Enzyme digestion of cellular organelles, renal disorders, plasma cell tumors Disrupted function and intracellular communication, displaced cellular organelles Pigments Exogenous particle ingestion, UV light stimulates melanin production malignancy, loss of hormonal feedback, genetic defects, hemosiderin increase due to bruising and hemorrhage, liver dysfunction Membrane injury, disruption of cellular metabolism Calcium Altered membrane permeability, influx of extracellular calcium excretion of H+ leading to more OH−, which precipitates Ca++, endocrine disturbances Hardening of cellular structure, interference with function Urate Absence of enzymes Crystal deposition, inflammation14 Chapter 3 Altered Cellular and Tissue Biology Copyright © 2012, 2008, 2004, 2000, 1996 by Mosby, an imprint of Elsevier Inc. All rights reserved. invade the site and cause liquefactive necrosis. Gas gangrene, a special type of gangrene, results from bacterial infection of injured tissue by species of Clostridium. These anaerobic bacteria produce hydrolytic enzymes and toxins that destroy connective tissue and cellular membrane; bubbles of gas likely form in muscle cells. Apoptosis is an important, distinct type of cell death that differs from necrosis. It is a regulated or programmed cell program characterized by “dropping off” cellular fragments known as apoptotic bodies. It is an active process of cellular self-destruction in both normal and pathologic tissue changes. Apoptosis likely plays a role in deletion of cells during embryonic development and in endocrine-dependent tissues that are undergoing atrophic change. It may occur spontaneously in malignant tumors and in normal, rapidly proliferating cells treated with cancer chemotherapeutic agents and ionizing radiation. Defective apoptosis may not eliminate lymphocytes that react to self-antigens, leading to autoimmune disorders. Increased apoptosis occurs in neurodegenerative diseases, myocardial infarction and stroke, and death in virus-infected host cells. Apoptosis affects scattered, single cells and results in shrinkage of a cell, whereas in necrosis, cells swell and lyse. Autophagy, which literally means “eating of self,” is a self-destructive and a survival mechanism. When cells are nutrient deprived, autophagy cannibalizes and recycles the digested contents. Autophagy may be an immune defense against infectious microbes that penetrate intracellularly. 5. Describe the biology of aging; characterize frailty. Study pages 90-93; refer to Figures 3-32 and 3-33, and Tables 3-13 and 3-14. Three mechanisms of aging have emerged, as follows: (1) cellular changes produced by genetic, environmental, and behavioral factors; (2) changes in regulatory mechanisms, especially in the cells of the endocrine, immune, and central nervous systems, that are responsible for aging; and (3) degenerative extracellular and vascular alterations. Alterations of cellular control mechanisms include increased hormonal degradations, decreased hormonal synthesis and secretion, and a reduction in receptors for hormones and neuromodulators. Immune function declines with age, and the number of autoantibodies that attack body tissues increases with age. These observations implicate the immune system in the aging process. A degenerative extracellular change that affects the aging process is collagen cross-linking, which makes collagen more rigid and results in decreased cell permeability to nutrients. It is believed that free radicals of oxygen damage tissues as they age. These reactive species not only permanently damage cells, but also may lead to cell death. Damage accumulates over time