Robbins and Cotran Review of Pathology, 4E (2014)

SAVE OFFLINE

G R dV te ni pe r

si

an

ss

.ir

-U 9 r9 ta

hi

vi p.

tahir99 - UnitedVRG vip.persianss.ir

Robbins and Cotran

Review of Pathology dV

R

G

FOURTH EDITION

te

Edward C. Klatt, MD

ss

.ir

-U

ni

Professor of Pathology Department of Biomedical Sciences Director, Biomedical Education Program Mercer University School of Medicine Savannah, Georgia

an

si

Donald N. Pritzker Professor Chair, Department of Pathology Biologic Sciences Division and Pritzker School of Medicine The University of Chicago Chicago, Illinois

pe r

vi p.

ta

hi

r9

9

Vinay Kumar, MBBS, MD, FRCPath

tahir99 - UnitedVRG vip.persianss.ir

1600 John F. Kennedy Blvd. Ste. 1800 Philadelphia, PA 19103-2899 ROBBINS AND COTRAN REVIEW OF PATHOLOGY, FOURTH EDITION ISBN: 978-1-4557-5155-6 Copyright © 2015, 2010, 2005, 2000 by Saunders, 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.

G

This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

R

Notices

.ir

ss

si

Library of Congress Cataloging-in-Publication Data

an

r9

9

-U

ni

te

dV

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.

pe r

vi p.

ta

hi

Klatt, Edward C., 1951- , author. Robbins and Cotran review of pathology / Edward C. Klatt, Vinay Kumar. -- Fourth edition. p. ; cm. Review of pathology Complemented by: Robbins basic pathology / [edited by] Vinay Kumar, Abul K. Abbas, Jon C. Aster. 9th ed. c2013; and Robbins and Cotran pathologic basis of disease / [edited by] Vinay Kumar, Abul K. Abbas, Jon C. Aster. Ninth edition. United VRG [2015] ISBN 978-1-4557-5155-6 I. Kumar, Vinay, 1944- , author. II. Robbins basic pathology. Complemented by (work): III. Robbins and Cotran pathologic basis of disease. Complemented by (work): IV. Title. V. Title: Review of pathology. [DNLM: 1. Pathology--Examination Questions. QZ 18.2] RB119 616.07076--dc23 2014031270

Executive Content Strategist: William R. Schmitt Content Development Specialist: Laura Schmidt Publishing Services Manager: Anne Altepeter Project Manager: Louise King Designer: Louis Forgione

Printed in Canada Last digit is the print number: 9 8 7 6 5 4 3 2 1 tahir99 - UnitedVRG vip.persianss.ir

.ir ss an

si pe r

vi p.

ta

hi

r9

9

-U

ni

te

dV

R

G

To our students, for their constant challenge and stimulation

tahir99 - UnitedVRG vip.persianss.ir

Preface

te

dV

R

G

complete reading of topics targeted for further review. Pathology is a visually oriented discipline; hence full-color images accompany many of the questions. The illustrations are taken mainly from the Robbins textbooks, so students can reinforce their study of the figures in the texts with questions that utilize the same or similar images. The revisions in this fourth edition reflect new topics and new understanding of disease processes reflected in the most recent editions of the Robbins textbooks. The questions are intentionally written to be fairly difficult, with the purpose of “pushing the envelope” of students’ understanding of pathology. We are pushing it even further with a comprehensive final examination section that includes questions drawn from challenging topics covered in the entire book. Mastery of this book will better prepare the student for further challenges. Many of the questions require the student to engage in a “multi-step” process: first, to interpret the information presented to arrive at a diagnosis, and then to solve a problem based on that diagnosis. This reinforces the clinical reasoning skills needed in delivery of health care. We must hasten to add that no review book is a substitute for textbooks and other course materials provided by individual instructors within the context of a curriculum. This book should be used in conjunction with thorough study of Robbins and Cotran Pathologic Basis of Disease and/or Robbins Basic Pathology and curricular materials. Finally, we hope that both students and their faculty will find this review book to be a useful adjunct to the learning of pathology. Edward C. Klatt, MD Vinay Kumar, MBBS, MD, FRCPath

.ir

ss

an

si

pe r

vi p.

ta

hi

r9

9

-U

ni

This book is designed to provide a comprehensive review of both general and organ-specific pathology through multiple choice questions with explanations of the answers. The source materials are the ninth editions of Robbins and Cotran Pathologic Basis of Disease (PBD9) and Robbins Basic Pathology (BP9), and in several chapters, Robbins and Cotran Atlas of Pathology (AP3). The questions in this review book follow the chapters and topics in these source materials to facilitate ongoing selfassessment as students work their way through a curriculum to gain and then apply their understanding of key concepts. This book is intended to be a useful resource for students in a variety of health science training programs. In keeping with recommended question writing style for licensing examinations, we have included single best-answer questions, most with a clinical vignette, followed by a series of homogenous choices. This approach emphasizes an understanding of pathophysiologic mechanisms and manifestations of disease in a clinical context. We have incorporated relevant laboratory, radiologic, and physical diagnostic findings in the questions to emphasize clinicopathologic correlations. Although this adds to the extent of individual questions, the thoroughness reinforces learning, as a review should. Each answer includes a succinct explanation of why a particular choice is “correct” and the other choices are “incorrect.” Each answer is referenced by page numbers to both Robbins and Cotran Pathologic Basis of Disease and Robbins Basic Pathology (both the current ninth edition and the previous eighth edition of each), and in several cases, to figures in the third edition of Robbins and Cotran Atlas of Pathology, to facilitate and encourage a more

vii

tahir99 - UnitedVRG vip.persianss.ir

To Our Students

te

dV

R

G

learning to occur, there are a finite number of synaptic modifications that can be established per unit time, above which total comprehension is reduced. Increasing the rate or length of information delivery diminishes the efficiency of learning. Lack of break periods or engaging in “all nighters” presage onset of diminished performance, particularly when least desirable— during an examination. There is also decay of learning over time, with inevitable random loss of data elements. The key branch points in learning, where review with reinforcement can reduce data loss, occur at 20 to 40 minutes (transfer to intermediate memory) and at 24 to 48 hours (transfer to longterm memory) following initial learning. Develop methods for filtering information from quality sources. We live in an age of information overload. Stay on task and avoid distractions. Identify the important data and underlying concepts. Develop a specific, personalized plan for approaching, reviewing, and preparing for assessments of your knowledge. Seek quality feedback, both positive to provide motivation for your commitment to further learning, as well as negative to focus on your rate of progress toward competency. We hope, therefore, that this review will be useful not only in preparing for examinations but also for courses you take throughout your career. It is our sincere hope that this review book will make you a better health practitioner in your chosen career.

.ir

ss

an

si

pe r

vi p.

ta

hi

r9

9

-U

ni

Although medical knowledge has increased exponentially over the past 100 years, the desire to learn and apply this knowledge to the service of others has not changed. The study and practice of the healing arts requires persistence more than brilliance. By continuing as a lifelong student, it is possible to become a better health practitioner with the passage of time. Use this book to find where you are on the pathway to excellence and be inspired to continue down that path. We provide a guide to light the way toward knowledge in pathology within the welcoming environment of this book. Common mistakes made by students in answering questions result from failure to read and analyze information carefully by: (1) relying on a single finding as an exclusionary criterion, and (2) ignoring important diagnostic information. Medicine is mostly analogue, not digital, and the information you obtain is applicable across a continuum of probability. In selecting the best answer, remember these four key elements: (1) read the question thoroughly, (2) define the terms (use your vocabulary), (3) rank possible answers from common to uncommon, and (4) recognize key diagnostic information that differentiates the answers. There are no magic formulas for academic achievement. The most important thing you can do is to spend some time each day in a learning process. Learning requires modification of synaptic interfaces at the dendritic level in the brain, and for

ix

tahir99 - UnitedVRG vip.persianss.ir

Acknowledgments

We are very grateful to Laura Schmidt, content development specialist, and William Schmitt, executive content strategist, at Elsevier, for their support of this project. Special thanks is due Louise King, project manager, for her understanding of the needs of the authors, for providing good advice, and for her willingness to accommodate multiple changes. Nhu Trinh at The University of Chicago is acknowledged for crucial secretarial support to one of us. We are grateful to our families and colleagues for graciously accepting this additional demand on our time.

x

The authors also are indebted to the pioneers in pathology education for the Robbins and Cotran series, starting with the founding author, Dr. Stanley Robbins, and continuing with Dr. Ramzi Cotran. These lead authors have set the standard of excellence that characterizes the series. There continue to be numerous contributing authors who have made the Robbins and Cotran series a valuable educational tool. Edward C. Klatt Vinay Kumar

tahir99 - UnitedVRG vip.persianss.ir

CHAPTER

The Cell as a Unit of Health and Disease

1

PBD9 Chapter 1: The Cell as a Unit of Health and Disease   

1 A study of peripheral blood smears shows that neutrophil nuclei of women have a Barr body, whereas those of men do not. The Barr body is an inactivated X chromosome. Which of the following forms of RNA is most likely to play a role in Barr body formation? A lncRNA C mRNA B miRNA D siRNA E tRNA 2 In an experiment, a nuclear chromosomal gene is found to be actively transcribing messenger RNA (mRNA) that is transported into the cell cytoplasm. However, there is no observed protein product from translation of this mRNA. How is the silencing of this active gene’s mRNA most likely to occur? A Absence of tRNA B Binding to miRNA C Methylation of DNA D Mutation of mRNA E Upregulation of mtDNA 3 A proponent of Chilean Malbec, Syrah, and Merlot wines (all reds) touts their contribution to longevity, but this wine aficionado also controls his dietary caloric content so that his body mass index is 200 cGy) can be fatal because of injury to radiosensitive marrow and the gastrointestinal tract, but death occurs after days to weeks, not hours. Cardiac and skeletal muscle tissue is relatively radioresistant. Early findings in radiation-induced lung injury include edema; interstitial fibrosis develops over years in individuals who survive the injury. PBD9 430–431  BP9 292–293  PBD8 423–426  BP8 303–304

35  E  Body weight less than 60% of normal with muscle wasting is consistent with marasmus, a form of protein energy malnutrition that results from a marked decrease in total caloric intake. In kwashiorkor, protein intake is reduced more than total caloric intake, and body weight is usually 60% to 80% of normal. Hypoalbuminemia is a key laboratory finding. Malignancies can promote wasting, but not to this degree. This child’s problems are far more serious than a single vitamin deficiency; a lack of folate could account for the child’s anemia, but not for the wasting. Bulimia is an eating disorder of adolescents and adults that is characterized by binge eating and self-induced vomiting. Lead poisoning can lead to anemia and encephalopathy, but it does not cause severe wasting. PBD9 433–434  BP9 294  PBD8 428–429  BP8 304–306

36  A  The decreased food intake from self-imposed dieting in a woman can lead to changes such as hormonal deficiencies (e.g., follicle-stimulating hormone, luteinizing hormone, thyroxine). The result is diminished estrogen synthesis, which promotes osteoporosis, as in the postmenopausal state. Bulimia with binging and purging can be accompanied by electrolyte disturbances, and weight tends to be maintained in most cases. Kwashiorkor is a disease mainly of children who have reduced protein intake. Rickets is a specific deficiency of vitamin D that causes skeletal deformities in children. Scurvy, which results from vitamin C deficiency, does not affect hormonal function. PBD9 435  BP9 295–296  PBD8 427  BP8 304, 306

PBD9 1155  BP9 863–864  PBD8 404  BP8 309–312

3  E  Therapeutic doses of radiation can cause acute vascu3 lar injury, manifested by endothelial damage and an inflam-

37  B  The findings are consistent with kwashiorkor, a nutritional disorder predominantly of decreased protein in the diet. Hypoalbuminemia is characteristic of this condition.

C H A P T E R 9   Environmental and Nutritional Diseases Abetalipoproteinemia is a rare disorder that causes vitamin E deficiency. Hypocalcemia can occur as a consequence of vitamin D deficiency. Hyperglycemia occurs in diabetes mellitus; the wasting associated with this disease affects adipose tissue and muscle, and edema is not a feature. Megaloblastic anemia is a feature of specific deficiencies of vitamin B12 or folate. PBD9 434–435  BP9 294–295  PBD8 428–429  BP8 304–306

8  A  Vitamin A is important in maintaining epithelial sur3 faces. Deficiency of this vitamin can lead to squamous metaplasia of respiratory epithelium, predisposing to infection. ­Increased keratin buildup leads to follicular plugging and papular dermatosis. Desquamated keratinaceous debris in the urinary tract forms the nidus for stones. Ocular complications of vitamin A deficiency include xerophthalmia and corneal scarring, which can lead to blindness. Vitamin B1 (thiamine) deficiency causes problems such as Wernicke disease, neuropathy, and cardiomyopathy. Vitamin D deficiency in children causes rickets, characterized by bone deformities. Vitamin E deficiency occurs rarely; it causes neurologic symptoms related to degeneration of the axons in the posterior columns of the spinal cord. Vitamin K deficiency can result in a bleeding diathesis. PBD9 436–438  BP9 296–298   PBD8 431–433  BP8 306–309

39  C  Rickets, which is caused by vitamin D deficiency, is characterized by skeletal deformity such as the bowing of the legs seen in this boy. Lack of bone mineralization (osteopenia) leads to this deformation. Beriberi, from thiamine deficiency, can result in heart failure and peripheral edema. A diet containing insufficient protein can result in kwashiorkor, characterized by areas of flaking, depigmented skin. Pellagra, resulting from niacin deficiency, is characterized by dermatitis in sun-exposed areas of skin. Scurvy, resulting from vitamin C deficiency, can produce bone deformities, particularly at the epiphyses, because of abnormal bone matrix, not abnormal calcification. The absence of hemorrhages in this child makes this unlikely, however. PBD9 438–442  BP9 298–299  PBD8 433–436  BP8 309–312

40  D  Vitamin A is essential to maintain epithelia. The lack of vitamin A affects the function of lacrimal glands and conjunctival epithelium, promoting keratomalacia. Dr. Alfred Sommer’s research convinced UNICEF that it would cost just pennies per child to eliminate vitamin A deficiency in 250 million children on earth. Iron is essential for production of heme, which is needed to manufacture hemoglobin in RBCs. Niacin is involved with nicotinamide in many metabolic pathways, and deficiency leads to diarrhea, dermatitis, and dementia. Dietary protein is essential for building tissues, particularly muscle, but it has no specific effect in maintaining ocular structures. Vitamin K is beneficial for synthesis of coagulation factors by the liver to prevent bleeding problems. PBD9 437–438  BP9 296–298  PBD8 431–433  BP8 306–309

41  A  Vitamin D can be synthesized endogenously in skin with exposure to ultraviolet (UV) light. Together, vitamin D

127

and calcium help build and maintain growing bone. Exercise helps build bone mass, which protects against osteoporosis later in life, particularly in women. Renal function is not greatly affected by environment. There are some deleterious effects on the eye (cataracts) and the skin (cancer, elastosis) from increased exposure to UV radiation in sunlight. Increased air pollution in many cities has led to an increased incidence of pulmonary diseases, and children are particularly at risk. PBD9 439–441  BP9 298–300  PBD8 433–435  BP8 309–312

42  D  The osteopenia in this patient can result from osteomalacia, the adult form of vitamin D deficiency. Vitamin D is a fat-soluble vitamin, and it requires fat absorption, which can be impaired by chronic cholestatic liver disease, biliary tract disease, and pancreatic disease. Atrophic gastritis affects vitamin B12 absorption. Leukemias do not tend to erode bone. Heart disease caused by atherosclerosis does not affect bone density. Emphysema can result in a hypertrophic osteoarthropathy, but not osteopenia. PBD9 439–441  BP9 298–300  PBD8 435–436  BP8 310–312

43  A  Signs and symptoms of scurvy can be subtle. The diet must contain a constant supply of vitamin C (ascorbic acid) because none is produced endogenously. Older individuals with an inadequate diet are as much at risk as younger individuals. Folate deficiency can lead to anemia, but it does not cause capillary fragility with hematoma formation or skin rash. Niacin deficiency can lead to an erythematous skin rash in sun-exposed areas, but not to anemia. Riboflavin deficiency can lead to findings such as glossitis, cheilosis, and neuropathy. Vitamin A deficiency can produce a skin rash, but it does not cause anemia. Vitamin K is important in maintaining proper coagulation, but a deficiency state is not associated with anemia or skin rash. PBD9 442–443  BP9 301–302  PBD8 437  BP8 312

44  E  Pellagra is caused by a deficiency of niacin. The classic presentation includes the “3 D's”: diarrhea, dermatitis, and dementia. Beriberi, resulting from thiamine (vitamin B1) deficiency, can lead to heart failure, neuropathy, and Wernicke disease. Cheilosis describes the fissuring at the corners of the mouth that accompanies riboflavin (vitamin B2) deficiency. In hypothyroidism, which could be due to iodine deficiency, the skin tends to be coarse and dry. Marasmus describes the severe wasting that occurs in individuals with a diet that is markedly deficient in all nutrients. PBD9 442  BP9 302  PBD8 438  BP8 306, 314

45  F  Vitamin E deficiency is uncommon, but it may be seen in low-birth-weight infants with poor hepatic function and fat malabsorption. The neurologic manifestations are similar to those seen in vitamin B12 deficiency; affected infants may have anemia, but it is not of the megaloblastic type. Vitamin A deficiency in infants and children can lead to blindness from keratomalacia. It is the most common cause of preventable blindness in this population group. Vitamin B1 (thiamine) deficiency can lead to beriberi. Vitamin B3 (niacin)

128

U N I T I   General Pathology

deficiency can lead to pellagra. Vitamin C deficiency leads to scurvy, which can be accompanied by anemia from bleeding and from decreased iron absorption. Vitamin K deficiency leads to bleeding problems. PBD9 442–443  BP9 302  PBD8 438  BP8 314

46  E  Individuals with a history of chronic alcoholism are often deficient in thiamine and other nutrients (ethanol provides empty calories). Thiamine deficiency can lead to neuropathy, cardiomyopathy, and Wernicke disease. Alcoholic individuals often have folate deficiency, with resultant macrocytic anemia, but this finding is not present here. Niacin deficiency leads to pellagra. Pyridoxine and riboflavin deficiencies can lead to neuropathy, but do not produce cerebral findings.

50  C  Iron deficiency, which gives rise to microcytic anemia, is common in women of reproductive age because of menstrual blood loss and in children with a poor diet. During pregnancy, women have greatly increased iron needs. Low serum ferritin is indicative of iron deficiency. Dermatitis can be seen in pellagra (niacin deficiency). Goiter results from iodine deficiency, but this is a rare occurrence today because of newborn testing and widely available foods with iodine. Peripheral neuropathy is more characteristic of beriberi (thiamine deficiency) and deficiencies in riboflavin (vitamin B2) and pyridoxine (vitamin B6). Bowing of the long bones and epiphyseal widening can be seen in rickets (vitamin D deficiency). Soft tissue hemorrhages can be seen in scurvy (vitamin C deficiency). PBD9 443  BP9 303  PBD8 439, 659  BP8 304, 435–436

PBD9 419, 433, 442  BP9 302  PBD8 414, 438  BP8 290–292

7  F  Isoniazid is a pyridoxine (vitamin B6) antagonist. In4 dividuals receiving isoniazid therapy for tuberculosis may need supplementation to prevent vitamin B6 deficiency. Ascorbic acid (vitamin C) is antiscorbutic (prevents scurvy). Calciferol (vitamin D) helps maintain calcium levels. Calcium intake helps maintain bone mass and serum calcium level; hypocalcemia can lead to neural excitability with muscular contractions. Cobalamin (vitamin B12) deficiency may produce a macrocytic anemia and a peripheral neuropathy, but it does not result from isoniazid therapy. Niacin deficiency causes pellagra (diarrhea, dermatitis, dementia). Riboflavin deficiency may produce neuropathy, glossitis, and cheilosis.

51  B  Water in some areas naturally contains fluoride, and dental problems in children are fewer in these areas because tooth enamel is strengthened. Fluoride can be added to drinking water, but opposition to this practice, from ignorance or fear, is common. Copper deficiency can produce neurologic defects. Iodine deficiency can predispose to thyroid goiter. Selenium is a trace mineral that forms a component of glutathione peroxidase; deficiency may be associated with myopathy and heart disease. Serious illnesses from trace element deficiencies are rare. Zinc is a trace mineral that aids in wound healing; a deficiency state can lead to stunted growth in children and a vesicular, erythematous rash. PBD9 443  BP9 303  PBD8 439  BP8 315

PBD9 433, 442  BP9 302  PBD8 438  BP8 314

8  E  Coagulation factors II, VII, IX, and X synthesized 4 by the liver require vitamin K for their production. Hemorrhagic disease of the newborn can occur in infants who lack sufficient intestinal bacterial flora to produce this nutrient. Breastfeeding transiently potentiates this effect, because Lactobacillus found in breast milk does not synthesize vitamin K. Routine intramuscular injection of vitamin K soon after birth prevents this complication. Iron deficiency leads to anemia, not to bleeding. Vitamin E is an antioxidant and is rarely deficient to a degree that would cause serious illness. Folic acid helps to prevent macrocytic anemia. Iodine is needed in small quantities for thyroid hormone synthesis. PBD9 420, 442  BP9 302  PBD8 438, 670  BP8 306, 314

49  F  Humans do not generate vitamin C endogenously, so they must have a continuous dietary supply. The lack of fresh fruits and vegetables containing vitamin C led to scurvy in many sailors and explorers in centuries past. Beriberi leads to heart failure and results from thiamine deficiency. Kwashiorkor results from protein deficiency. Pellagra, characterized by the “3 D's” of diarrhea, dermatitis, and dementia, is seen in niacin deficiency. Pernicious anemia from vitamin B12 deficiency can be complicated by neurologic deterioration in severe cases. Rickets is seen in children who are deficient in vitamin D. PBD9 442–443  BP9 301–302  PBD8 437  BP8 312–313

52  B  This vignette is just as imaginative as those appearing in many public media sources, so beware the claims and apply principles of evidence-based medicine. Some would agree that there is never quite enough chocolate, and much of the world’s population must get by without it. However, countries with the highest chocolate consumption have produced the most Nobel laureates! Serious dietitians would probably choose option A (iron deficiency), which is a deficiency most likely to be seen in menstruating women, in pregnant women, and in children. Calcium is most important in growing children for building bones. Folate deficiency leads to macrocytic anemia and is most likely to occur in adults with an inadequate diet, such as individuals with chronic alcoholism. Vitamin C deficiency occurs in individuals who do not eat adequate amounts of fresh fruits and vegetables. PBD9 443  BP9 303  PBD8 439, 659  BP8 304

53  B  This patient is morbidly obese. The extra weight puts a strain on joints, particularly the knees, increasing the risk for osteoarthritis. Although the overall risk of cancer increases with obesity, the relationship between endometrial carcinoma and obesity is well established. About 80% of individuals with type 2 diabetes mellitus are obese. The relationship of diet and obesity to colon cancer is not as well established. Worldwide, most hepatocellular carcinomas arise in individuals infected with hepatitis B; chronic alcoholism also is a risk factor. Pulmonary adenocarcinoma is the least likely

C H A P T E R 9   Environmental and Nutritional Diseases bronchogenic cancer to be associated with smoking. Some renal cell carcinomas are associated with smoking. PBD9 444–448  BP9 302–305  PBD8 442  BP8 313–317

54  E  Leptin signaling from adipocytes that have taken up an adequate supply of fatty acids ordinarily feeds back to the hypothalamus, which decreases synthesis of neuropeptide Y. This neurotransmitter acts as an appetite stimulant, and a decrease in its synthesis causes satiety. Adenosine is a nucleoside used to treat cardiac dysrhythmias. Glucagon opposes insulin by increasing hepatic glycogen storage. An increasing blood glucose level results in an increased release of insulin to promote glucose uptake into connective tissues, muscle, and adipose tissue. PBD9 444–447  BP9 303–304  PBD8 439–441  BP8 314–317

129

57  C  IGF-1 increases in response to the hyperinsulinemia of obese persons, who are also more likely to have metabolic syndrome and type 2 diabetes mellitus. IGF-1 promotes cell growth as well as increased synthesis of estrogens and androgens that favor neoplastic transformation in cells. Adiponectin that is elaborated by adipocytes acts as an insulin-sensitizing agent that prevents hyperinsulinemia. Aflatoxin from growth of Aspergillus on foods such as cereals acts as a carcinogen via mutation of the TP53 gene. Leptin normally decreases when fat stores are high, and derangements in its receptor may underlie some forms of obesity. Selenium is a trace metal thought to have antioxidant properties protective against cancer. Trans fats are derived from artificial hydrogenation of dietary fats and are atherogenic by increasing LDL cholesterol while decreasing HDL cholesterol. PBD9 447–449  BP9 303–305  PBD8 442–444  BP8 313–316

55  C  Appetite and satiety are controlled by a complex system of short-acting and long-acting signals. The levels of ghrelin produced in the stomach increase rapidly before every meal and decrease promptly after the stomach is filled. Leptin released from adipocytes exerts long-term control by activating catabolic circuits and by inhibiting anabolic circuits. α-MSH is an intermediate in leptin signaling. TRH and CRF are among the efferent mediators of leptin signaling, and they increase energy consumption. PBD9 444–446  BP9 303–304  PBD8 441–442  BP8 314–315

56  B  There are “obesity” genes that may play a role in metabolic pathways. About 5% to 8% of obese adults have a mutation in the MC4R gene, and even though there are abundant fat stores and plenty of leptin, the lack of MC4R to drive energy consumption leads to weight gain. Leptin is the product of the ob gene, and mutations reduce leptin levels that signal satiety, but such mutations are rare. Mutations in OB-R encoding the leptin receptor are seen in about 3% of cases of early-onset obesity with hyperphagia in children. POMC is in a catabolic pathway stimulated by leptin, but mutations are rare, and affected individuals typically have childhood onset with hyperphagia. Peroxisome proliferator–activated receptor gamma (PPARγ) is stimulated by the thiazolidinedione drugs and leads to a reduction in free fatty acids, reduction in resistin, and decreased insulin resistance. PBD9 444–447  BP9 303–305  PBD8 439–442  BP8 314–315

58  D  These findings suggest a diagnosis of diabetes mellitus. The patient is obese and most likely has type 2 diabetes mellitus. Type 1 and type 2 diabetes mellitus greatly increase the risk of early and accelerated atherosclerosis. Decreasing total caloric intake, particularly saturated fat, helps reduce the risk of coronary artery disease. Vegetable and fish oils are preferable to animal fat as sources of dietary lipid for prevention of atherosclerosis. Reducing dietary sodium helps to decrease blood pressure. Increased fluid intake aids renal function. Dietary fiber helps to reduce the incidence of diverticulosis. Vitamin A has no significant effect on atherogenesis. PBD9 447  BP9 305  PBD8 442  BP8 316–317

59  C  More fruits and vegetables are recommended in the diet to help prevent colon cancer. Vitamins C and E have an antioxidant and antimutagenic effect. Red wine in moderation may have a beneficial antiatherogenic effect. Ice cream can include animal fat that may promote cancer, as would the animal fat of beef. Chocolate includes vegetable fat, which is not as harmful as animal fat, and persons consuming chocolate perform at a higher level. PBD9 448–449  BP9 306  PBD8 444  BP8 317–318

CHAPTER

10

Diseases of Infancy and Childhood

PBD9 Chapter 10 and PBD8 Chapter 10: Diseases of Infancy and Childhood BP9 Chapter 6: Genetic and Pediatric Diseases BP8 Chapter 7: Genetic and Pediatric Diseases   

A Congenital cytomegalovirus infection B Early amnion disruption C Oligohydramnios D Maternal fetal Rh incompatibility E Trisomy 18

1 A 31-year-old woman, G3, P2, has had an uneventful pregnancy except for lack of any fetal movement. She has a spontaneous abortion at 20 weeks’ gestation and delivers a stillborn boy. On examination at birth, the fetus has an abdominal wall defect lateral to the umbilical cord insertion; a short umbilical cord; marked vertebral scoliosis; and a thin, fibrous band constricting the right upper extremity. A radiograph is shown in the figure. None of the woman’s other pregnancies, which ended in term births, were similarly affected. Which of the following is the most likely cause of these findings?

130

2 A 16-year-old primigravida in her 18th week of pregnancy has not felt any fetal movement, and an ultrasound is performed. The amniotic fluid index is markedly decreased. Both fetal kidneys are cystic, and one is larger than the other. There is no fetal cardiac activity. The pregnancy is terminated, and a fetal autopsy is performed. Findings include multicystic renal dysplasia, hemivertebra, anal atresia, tracheoesophageal fistula, and lungs that are equivalent in size to 14 weeks’ gestation. Which of the following errors in morphogenesis most likely led to the appearance of the fetal lungs? A Agenesis B Aplasia C Deformation D Disruption E Malformation F Teratogenesis   

C H A P T E R 1 0   Diseases of Infancy and Childhood

131

5 A healthy, 44-year-old woman, G2, P1, has a screening ultrasound at 18 weeks’ gestation that shows no fetal anomalies. There is decreased fetal movement at 32 weeks’ gestation, and ultrasound shows fetal growth restriction with relative sparing of the fetal head. The placenta appears normally positioned in the lateral fundus, but appears small, and the amniotic fluid index is reduced. Maternal blood pressure is normal. Which of the following conditions is most likely to be present? A Uteroplacental insufficiency B Congenital Treponema pallidum infection C Galactosemia D Preeclampsia E Rh incompatibility F Trisomy 21 6 A 22-year-old primigravida gives birth to a boy at 38 weeks’ gestation. On physical examination, the infant appears normal except for an abnormal right hip click with the Ortolani maneuver. Ligamentous laxity of the hip is noted. The mother asks if there is any risk that future children will be born with a similar malformation. What is the most likely recurrence risk for future pregnancies?

3 A 31-year-old woman, G1, P0, has noticed very little fetal movement during her pregnancy. At 36 weeks’ gestation, she gives birth to an infant with the facial features and positioning of extremities shown in the figure. Soon after birth, the infant develops severe respiratory distress. Which of the following conditions affecting the infant best explains these findings? A Congenital rubella infection B Bilateral renal agenesis C Maternal diabetes mellitus D Hyaline membrane disease E Trisomy 13 4 A 28-year-old high school teacher, who is pregnant, presents with severe acne on the face and is concerned that these will disfigure her face. Before she visited the doctor, she does an Internet search and finds that a compound related to Vitamin A has proven effective in the treatment of acne. However, her obstetrician is reluctant to prescribe it because he thinks that it may cause fetal malformations. The teratogenic effect of this medication is most likely related to which of the following processes? A  Disruption of the pattern of expression of homeobox genes B Increase in the risk of maternal infections C  Increase in the likelihood of aneuploidy during cell division D  Promotion of abnormal development of blood vessels in the placenta E  Reduction in the resistance of the fetus to transplacental infections

A