Robbins and Cotran Review of Pathology ( PDFDrive ) (1)

Robbins and Cotran
Review of Pathology



Robbins and Cotran

Review of Pathology

FOURTH EDITION

Edward C. Klatt, MD

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

Savannah, Georgia

Vinay Kumar, MBBS, MD, FRCPath

Donald N. Pritzker Professor
Chair, Department of Pathology

Biologic Sciences Division and
Pritzker School of Medicine
The University of Chicago
Chicago, Illinois

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.
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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
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on their own experience and knowledge of their patients, to make diagnoses, to determine dosages
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Library of Congress Cataloging-in-Publication Data
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. Rob-
bins 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

To our students, for their constant challenge and stimulation



Preface

This book is designed to provide a comprehensive review of complete reading of topics targeted for further review. Pathol-
both general and organ-specific pathology through multiple ogy is a visually oriented discipline; hence full-color images
choice questions with explanations of the answers. The source accompany many of the questions. The illustrations are taken
materials are the ninth editions of Robbins and Cotran Patho- mainly from the Robbins textbooks, so students can reinforce
logic Basis of Disease (PBD9) and Robbins Basic Pathology (BP9), their study of the figures in the texts with questions that utilize
and in several chapters, Robbins and Cotran Atlas of Pathology the same or similar images.
(AP3). The questions in this review book follow the chapters
and topics in these source materials to facilitate ongoing self- The revisions in this fourth edition reflect new topics and
assessment as students work their way through a curriculum new understanding of disease processes reflected in the most
to gain and then apply their understanding of key concepts. recent editions of the Robbins textbooks. The questions are
This book is intended to be a useful resource for students in a intentionally written to be fairly difficult, with the purpose
variety of health science training programs. of “pushing the envelope” of students’ understanding of pa-
thology. We are pushing it even further with a comprehensive
In keeping with recommended question writing style for final examination section that includes questions drawn from
licensing examinations, we have included single best-answer challenging topics covered in the entire book.
questions, most with a clinical vignette, followed by a series
of homogenous choices. This approach emphasizes an under- Mastery of this book will better prepare the student for fur-
standing of pathophysiologic mechanisms and manifestations ther challenges. Many of the questions require the student to en-
of disease in a clinical context. We have incorporated relevant gage in a “multi-step” process: first, to interpret the information
laboratory, radiologic, and physical diagnostic findings in presented to arrive at a diagnosis, and then to solve a problem
the questions to emphasize clinicopathologic correlations. based on that diagnosis. This reinforces the clinical reasoning
Although this adds to the extent of individual questions, the skills needed in delivery of health care. We must hasten to add
thoroughness reinforces learning, as a review should. Each an- that no review book is a substitute for textbooks and other course
swer includes a succinct explanation of why a particular choice materials provided by individual instructors within the context
is “correct” and the other choices are “incorrect.” Each answer of a curriculum. This book should be used in conjunction with
is referenced by page numbers to both Robbins and Cotran thorough study of Robbins and Cotran Pathologic Basis of Disease
Pathologic Basis of Disease and Robbins Basic Pathology (both the and/or Robbins Basic Pathology and curricular materials. Finally,
current ninth edition and the previous eighth edition of each), we hope that both students and their faculty will find this review
and in several cases, to figures in the third edition of Robbins book to be a useful adjunct to the learning of pathology.
and Cotran Atlas of Pathology, to facilitate and encourage a more
Edward C. Klatt, MD

Vinay Kumar, MBBS, MD, FRCPath

vii



To Our Students

Although medical knowledge has increased exponentially learning to occur, there are a finite number of synaptic modifi-
over the past 100 years, the desire to learn and apply this cations that can be established per unit time, above which total
knowledge to the service of others has not changed. The study comprehension is reduced. Increasing the rate or length of in-
and practice of the healing arts requires persistence more than formation delivery diminishes the efficiency of learning. Lack
brilliance. By continuing as a lifelong student, it is possible to of break periods or engaging in “all nighters” presage onset of
become a better health practitioner with the passage of time. diminished performance, particularly when least desirable—
Use this book to find where you are on the pathway to ex- during an examination. There is also decay of learning over
cellence and be inspired to continue down that path. We pro- time, with inevitable random loss of data elements. The key
vide a guide to light the way toward knowledge in pathology branch points in learning, where review with reinforcement
within the welcoming environment of this book. can reduce data loss, occur at 20 to 40 minutes (transfer to in-
termediate memory) and at 24 to 48 hours (transfer to long-
Common mistakes made by students in answering ques- term memory) following initial learning.
tions result from failure to read and analyze information care-
fully by: (1) relying on a single finding as an exclusionary Develop methods for filtering information from quality
criterion, and (2) ignoring important diagnostic information. sources. We live in an age of information overload. Stay on task
Medicine is mostly analogue, not digital, and the information and avoid distractions. Identify the important data and under-
you obtain is applicable across a continuum of probability. In lying concepts. Develop a specific, personalized plan for ap-
selecting the best answer, remember these four key elements: proaching, reviewing, and preparing for assessments of your
(1) read the question thoroughly, (2) define the terms (use knowledge. Seek quality feedback, both positive to provide
your vocabulary), (3) rank possible answers from common to motivation for your commitment to further learning, as well as
uncommon, and (4) recognize key diagnostic information that negative to focus on your rate of progress toward competency.
differentiates the answers.
We hope, therefore, that this review will be useful not only
There are no magic formulas for academic achievement. in preparing for examinations but also for courses you take
The most important thing you can do is to spend some time throughout your career. It is our sincere hope that this review
each day in a learning process. Learning requires modification book will make you a better health practitioner in your chosen
of synaptic interfaces at the dendritic level in the brain, and for career.

ix

Acknowledgments

We are very grateful to Laura Schmidt, content development The authors also are indebted to the pioneers in pathology
specialist, and William Schmitt, executive content strategist, at education for the Robbins and Cotran series, starting with the
Elsevier, for their support of this project. Special thanks is due founding author, Dr. Stanley Robbins, and continuing with
Louise King, project manager, for her understanding of the Dr. Ramzi Cotran. These lead authors have set the standard
needs of the authors, for providing good advice, and for her of excellence that characterizes the series. There continue to be
willingness to accommodate multiple changes. Nhu Trinh at numerous contributing authors who have made the Robbins
The University of Chicago is acknowledged for crucial secre- and Cotran series a valuable educational tool.
tarial support to one of us. We are grateful to our families and
colleagues for graciously accepting this additional demand on Edward C. Klatt
our time.
Vinay Kumar

x

Contents

UNIT I

General Pathology

1 The Cell as a Unit of Health and Disease 3
2 Cellular Pathology 7
3 Inflammation and Repair 18
4 Hemodynamic Disorders 31
5 Genetic Disorders 44
6 Immune System Diseases 57
7 Neoplastic Disorders 76
8 Infectious Diseases 94
9 Environmental and Nutritional Diseases 11
10 Diseases of Infancy and Childhood 130

UN I T II

Diseases of Organ Systems

11 Blood Vessels 147
12 The Heart 163
I 3 Hematopathology of W hite Blood Cells I 83
I 4 Hematopathology of Red Blood Cells and Bleeding Disorders 205

x i i Contents

IS The Lung 226
16 Head and Neck 253
17 Gastrointestinal Tract 263
IB Liver and Biliary Tract 286
19 Pancreas 306
20 Kidney 312
21 The Lower Urinary Tract and Male Genital System 332
22 Female Genital Tract 344
23 The Breast 361
24 The Endocrine System 371
25 The Skin 392
26 Bones, Joints, and Soft Tissue Tumors 405
27 Peripheral Nerve and Skeletal Muscle 424
28 Central Nervous System 432
29 The Eye 456
30 Final Review and Assessment 464

UNIT

General Pathology I



CHAPTER

1The Cell as a Unit of Health
and Disease

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

1 A study of peripheral blood smears shows that neutro- cytology specimen now shows numerous hemosiderin-laden
phil nuclei of women have a Barr body, whereas those of men macrophages. Which of the following subcellular structures in
do not. The Barr body is an inactivated X chromosome. Which these macrophages is most important for the accumulation of
of the following forms of RNA is most likely to play a role in this pigment?
Barr body formation? A Chromosome
A lncRNA B Endoplasmic reticulum
C mRNA C Golgi apparatus
B miRNA D Lysosome
D siRNA E Ribosome
E tRNA 5 An experiment is conducted in which cells in tissue
culture are subjected to high levels of ultraviolet radiant
2 In an experiment, a nuclear chromosomal gene is energy. Electron microscopy shows cellular damage in the
found to be actively transcribing messenger RNA (mRNA) form of increased cytosolic aggregates of denatured pro-
that is transported into the cell cytoplasm. However, there is teins. In situ hybridization reveals that protein components
no observed protein product from translation of this mRNA. in these aggregates also are found in proteasomes. Which
How is the silencing of this active gene’s mRNA most likely of the following substances most likely binds to the dena-
to occur? tured proteins, targeting them for catabolism by cytosolic
A Absence of tRNA proteasomes?
B Binding to miRNA A Adenosine monophosphate
C Methylation of DNA B Calcium
D Mutation of mRNA C Caspase
E Upregulation of mtDNA D Granzyme B
E Hydrogen peroxide
3 A proponent of Chilean Malbec, Syrah, and Merlot F Ubiquitin
wines (all reds) touts their contribution to longevity, but this 6 At the site of a surgical incision, endothelial cells elab-
wine aficionado also controls his dietary caloric content so that orate vascular endothelial growth factor. There is sprouting
his body mass index is <22. This lifestyle promotes increased with migration of endothelial cells into the wound to establish
insulin sensitivity and glucose utilization. He fully expects to new capillaries. Which of the following intracellular proteins
live longer because he has read that caloric restriction pro- is most important in facilitating movement of endothelial
longs life. In this man, which of the following intracellular cells?
substances will most likely mediate the effect of calorie restric- A Actin
tion upon increased longevity? B Cytokeratin
A Caspase C Desmin
B Glutathione D Lamin
C Sirtuins E Myosin
D Telomerase
E Ubiquitin 3

4 A 40-year-old woman has had chronic congestive heart
failure for the past 3 years. In the past 2 months, she devel-
oped a cough productive of rust-colored sputum. A sputum

4 U N I T I   General Pathology 12 An experiment is conducted involving cellular aspects of
wound healing. Components of the extracellular matrix are an-
7 In an experiment, release of epidermal growth factor alyzed to determine their sites of production and their binding
into an area of denuded skin causes mitogenic stimulation patterns to other tissue components. Which of the following
of the skin epithelial cells. Which of the following proteins is molecules synthesized by fibroblasts can best bind to cellular
most likely to be involved in transducing the mitogenic signal integrins and extracellular collagen and attach epidermal basal
from the epidermal cell membrane to the nucleus? cells to basement membrane?
A Cyclic AMP A Dermatan sulfate
B Cyclin D B Fibronectin
C Cyclin-dependent kinase C Heparin
D G proteins D Hyaluronic acid
E RAS proteins E Procollagen

8 Various soluble mediators are added to a cell culture 13 An experiment analyzes factors involved in the cell cycle
containing epidermal cells to determine which of the mediators during growth factor–induced cellular regeneration in a tissue
might be useful for promoting epidermal cell growth. When culture. Cyclin B synthesis is induced; the cyclin B binds and
epidermal growth factor (EGF) is added, it binds to epidermal activates cyclin-dependent kinase 1 (CDK1). The active kinase
cell surface receptors, with subsequent transcription factor produced by this process is most likely to control progression
translocation and DNA transcription. This effect in the epider- in which of the following phases of the cell cycle?
mal cells is most likely to be mediated through which of the A G0 to G1
following intracellular pathways? B G1 to S
A Calcium ion channel C S to G2
B Cyclic AMP D G2 to M
C Cyclin-dependent kinase E M to G1
D JAK/STAT system
E Mitogen-activated protein (MAP) kinase 14 In an experiment, the role of low-density lipoprotein
(LDL) receptors in uptake of lipids in the liver is studied. A
9 An experiment involves factors controlling wound heal- mouse model is created in which the LDL receptor gene is not
ing. Skin ulcerations are observed, and the factors involved in expressed in the liver. For creating such a knockout mouse,
the healing process are analyzed. Which of the following fac- which of the following cells would be most useful?
tors is most likely to be effective in promoting angiogenesis? A Adult bone marrow mesenchymal progenitor cells
A Basic fibroblast growth factor B Embryonic stem cells in culture
B Endostatin C Hematopoietic stem cells
C Epidermal growth factor D Hepatic oval cells
D Interleukin-1 E Regenerating hepatocytes
E Platelet-derived growth factor
15 Dermal fibroblasts are harvested from the skin biopsy
10 In an experiment, surgical incisions are made in a study specimen of an adult man. These fibroblasts are transduced
group of laboratory rats. Observations about the wounds are with genes encoding for transcription factors including SOX2
recorded over a 2-week period using various chemical media- and MYC. Under appropriate culture conditions these cells are
tors. Which of the following steps in the inflammatory-repair then able to generate endodermal, mesodermal, and ectoder-
response is most likely affected by neutralization of transform- mal cells. Into which of the following kinds of stem cell have
ing growth factor β (TGF-β)? these fibroblasts been transformed?
A Chemotaxis of lymphocytes A Embryonic
B Increase in vascular permeability B Lineage-committed
C Leukocyte extravasation C Mesenchymal
D Migration of epithelial cells D Pleuripotent
E Production of collagen

11 A 62-year-old man has had increasing knee pain with
movement for the past 10 years. The knee joint surfaces are
eroded and the joint space narrowed. There is loss of com-
pressibility and lubrication of articular cartilaginous surfaces.
Loss of which of the following extracellular matrix compo-
nents has most likely occurred in this man?
A Elastin
B Fibronectin
C Hyaluronan
D Integrin
E Laminin

C H A P T E R 1   The Cell as a Unit of Health and Disease 5

ANSWERS of RBCs into alveoli occurs, and pulmonary macrophages
must phagocytose the RBCs, breaking down the hemoglo-
1  A  There are forms of noncoding RNA that play a role in bin and recycling the iron by hemosiderin formation. The
gene expression. Long noncoding RNA (lncRNA) segments other listed options are components that play a role in cell
greater than 200 nucleotides in length can bind to chroma- synthetic functions.
tin to restrict access of RNA polymerase to coding segments.
The X chromosome transcribes XIST, a lncRNA that binds to PBD9 10, 13  BP9 22–23  PBD8 52–53  BP8 12
and represses X chromosome expression. However, not all
genes on the “inactive” X chromosome are switched off. The 5   F  Heat-shock proteins provide for a variety of cellular
RNA transcribed from nuclear DNA that directs protein syn- “housekeeping” activities, including recycling and restora-
thesis through translation is mRNA. MicroRNAs (miRNAs) tion of damaged proteins and removal of denatured pro-
are noncoding RNA sequences that inhibit the translation teins. Ubiquitin targets denatured proteins and facilitates
of mRNAs. Gene-silencing RNAs (small interfering RNAs their binding to proteasomes, which then break down the
[siRNAs]) have the same function as miRNAs, but they are proteins to peptides. ADP increases when ATP is depleted,
produced synthetically for experimental purposes. Transfer helping to drive anaerobic glycolysis. Cytosolic calcium lev-
RNA (tRNA) participates in the translation of mRNA to pro- els may increase with cell injury that depletes ATP; the calci-
teins by linking to specific amino acids. um activates phospholipases, endonucleases, and proteases,
which damage the cell membranes, structural proteins, and
PBD9 5–6  BP9 217–218  PBD8 150–152  BP8 235–237 mitochondria. Caspases are enzymes that facilitate apopto-
sis. Granzyme B is released from cytotoxic T lymphocytes
2  B  MicroRNAs (miRNA) are encoded by about 5% of and triggers apoptosis. Hydrogen peroxide is one of the acti-
the human genome. miRNAs do not encode for proteins, vated oxygen species generated under conditions of cellular
but bind to and inactivate or cleave to mRNA, preventing ischemia, producing nonspecific damage to cellular struc-
translation of proteins by mRNA, effectively silencing gene tures, particularly membranes.
expression without affecting the gene directly. There is
abundant tRNA present in the cytoplasm that is not a rate- PBD9 13–14  BP9 21–22  PBD8 37–38  BP8 22
limiting step to translation. DNA methylation, particularly
at CG dinucleotides, is a way of suppressing gene expres- 6  A  Actin is a microfilament involved with cell movement.
sion directly, as is seen with genomic imprinting. Mutations The other possibilities listed in B to D are intermediate fila-
that occur in genes in DNA may result in reduced mRNA ments, which are larger than actin but smaller than myosin
production or abnormal protein production, but mRNA it- (a thick filament interdigitating with actin, required for mus-
self is not mutated. Mitochondrial DNA (mtDNA) encodes cle movement). Cytokeratins form cytoskeletal elements of
for proteins mainly involved in oxidative phosphorylation epithelial cells. Desmin forms the scaffold in muscle cells on
metabolic pathways. which actin and myosin contract. Lamin is associated with
the nuclear membrane.
PBD9 4–5  BP9 217–218  BP8 137
PBD9 10–11  PBD8 50
3  C  The one sure way to increase life span is calorie re-
striction. But why do without the things we like, only to do 7  E  RAS proteins transduce signals from growth factor re-
without them longer? Dietary excesses lead to increased mor- ceptors, such as epidermal growth factor, that have intrinsic
bidity with reduced quality of life, as well as mortality, from tyrosine kinase activity. G proteins perform a similar function
chronic diseases such as diabetes mellitus. The activity of sir- for G protein–linked, seven-transmembrane receptors. Cyclic
tuins on histone acetylation and deacetylation may promote AMP is an effector in the G protein signaling pathway. Cyclins
transcription of genes encoding for proteins that increase and cyclin-dependent kinases regulate the cell cycle in the
metabolic activity and inhibit effects of free radicals. Red nucleus.
wines have been shown to increase sirtuins, but don’t drink
too much! Moderation is the key. Glutathione promotes free PBD9 17  BP9 179  PBD8 90–92  BP8 64, 66
radical breakdown, although chronic excessive alcohol con-
sumption depletes hepatocyte glutathione. Caspases trigger 8   E  The MAP kinase cascade is involved in signaling from
apoptosis and cell death. Telomerases aid in promoting con- activation via cell surface receptors for growth factors. This
tinued cell division, but cannot be altered by lifestyle, and pathway is particularly important for signaling of EGF and
turning them on is one feature of neoplasia. Ubiquitin is a fibroblast growth factor. Ligand binding, such as occurs
peptide that is part of the ubiquitin-proteasome pathway of with acetylcholine at a nerve-muscle junction, alters the
protein degradation seen with nutrient deficiencies, so when c­ onformation of ion channel receptors to allow flow of spe-
you eat less, be sure to eat a balanced diet. cific ions such as calcium into the cell, changing the electric
potential across the cell membrane. Cyclic AMP is a second
PBD9 3–4, 68  BP9 26–27  PBD8 41, 444  BP8 28 messenger that is typically activated via ligand binding to
receptors with seven transmembrane segments that associ-
4  D  Heterophagocytosis by macrophages requires that ate with GTP-hydrolyzing proteins; chemokine receptors
endocytosed vacuoles fuse with lysosomes to degrade the
engulfed material. With ­congestive heart failure, extravasation

6 U N I T I   General Pathology forms a gel that provides resilience and lubrication. Heparin
that is infused has an anticoagulant function. Hyaluronic
function in this fashion. Cyclin-dependent kinases act within acid binds water to form a gelatinous extracellular matrix.
the nucleus. JAK/STAT pathways typically are recruited by Procollagen produced by fibroblasts is formed into ropelike
cytokine receptors. strands of collagen, which provide tensile strength.

PBD9 17  BP9 61–62  PBD8 90–92  BP8 64–66 PBD9 21, 24  BP9 64  PBD8 96–97  BP8 68

9   A  Basic fibroblast growth factor is a potent inducer of 13  D  CDK1 controls an extremely important transition
angiogenesis. It can participate in all steps of angiogenesis. point, the G2 to M transition, during the cell cycle, which can
Endostatin is an inhibitor of angiogenesis. Epidermal growth be regulated by CDK inhibitors. The other checkpoints listed
factor and interleukin-1 have no significant angiogenic ac- are regulated by a distinct set of proteins.
tivity. Platelet-derived growth factor plays a role in vascular
remodeling. PBD9 26  BP9 59, 180–181  PBD8 86–87  BP8 63

PBD9 19–20  BP9 62  PBD8 88  BP8 64, 72

1 0  E  TGF-β stimulates many steps in fibrogenesis, includ- 14  B  Embryonic stem (ES) cells are multipotent and can
ing fibroblast chemotaxis and production of collagen by fi- give rise to all cells, including hepatocytes. Gene targeting to
broblasts, while inhibiting degradation of collagen. All of the produce knockout mice is done in cultures of ES cells, which
other steps listed are unaffected by TGF-β. are then injected into mouse blastocysts and implanted into
the uterus of a surrogate mother. Mesenchymal stem cells
PBD9 20  BP9 62  PBD8 87–89  BP8 64, 73 also are multipotential, but they are not useful for gene tar-
geting. Hematopoietic stem cells can give rise to all hema-
11  C  He has osteoarthritis, or degenerative joint disease, topoietic cells, but not other types of cells. Hepatocytes and
with loss of articular hyaline cartilage. Hyaluronan (hyaluron- oval cells within the liver can give rise only to liver cells.
ic acid) is a large mucopolysaccharide, one form of proteogly-
can, which forms a hydrated, compressible gel contributing PBD9 27–28  BP9 60–61  PBD8 83  BP8 61–63
to the shock-absorbing function of joint surfaces. Elastin is a
fibrillar protein that provides recoil in tissues such as skin, 15  D  These transformed cells are designated iPS cells be-
arterial walls, and ligaments that need to stretch and return cause they have been induced to become pleuripotent. This
to their original shape. Fibronectin is a form of glycoprotein transformation process gets around the problem of using em-
that serves an adhesive function. Integrins are glycoproteins bryonic stem (ES) cells derived from manipulation of human
that serve as cellular receptors for extracellular matrix com- embryos, which raises ethical and religious concerns. Embry-
ponents; they can link to intracellular actin so that cells can onic stem cells are totipotent, but they become pleuripotent
alter their shape and mobility. Laminins are a form of glyco- cells that can further divide into many different cell lines, yet
protein that help to anchor epithelial surfaces in basement maintain themselves in a replicating pool. Thus pleuripotent
membranes. cells are the next best thing compared to embryonic cells for
deriving human cells that could replace damaged or diseased
PBD9 21–24  BP9 63–64  PBD8 94–95  BP8 66–67 tissues. Further differentiation of pleuripotent cells gives rise to
cells with more restricted developmental capacity, such as mes-
12  B  Fibronectin is a key component of the extracellu- enchymal stem cells that can give rise to tissues such as muscle
lar matrix and has a structure that looks like a paper clip. and cartilage but not to endodermal or ectodermal cells.
­Fibronectin can be synthesized by monocytes, fibroblasts,
and endothelium. Dermatan sulfate, a glycosaminoglycan, PBD9 28–29  BP9 60–61  PBD8 82–84  BP8 62

2C H A P T E R

Cellular Pathology

PBD9 Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury, and Death

PBD8 Chapter 1: Cellular Responses to Stress and Toxic Insults

BP9 and BP8 Chapter 1: Cell Injury, Cell Death, and Adaptations
  

1 A 77-year-old woman has chronic renal failure. Her serum expressed from both nipples. Which of the following process-
urea nitrogen is 40 mg/dL. She is given a diuretic medication es that occurred in her breasts during pregnancy enables her
and loses 2 kg (4.4 lb). She reduces the protein in her diet and to breastfeed the infant?
her serum urea nitrogen decreases to 30 mg/dL. Which of the A Ductal metaplasia
following terms best describes cellular responses to disease and B Epithelial dysplasia
treatment in this woman? C Intracellular lipid deposition
A Adaptation D Lobular hyperplasia
B Apoptosis E Stromal hypertrophy
C Necroptosis
D Irreversible injury 5 A 16-year-old boy sustained blunt trauma to his abdo-
E Metabolic derangement men when he struck a bridge abutment at high speed while
driving a motor vehicle. Peritoneal lavage shows a hemoperi-
2 A 53-year-old woman with no prior illnesses has a toneum, and at laparotomy, a small portion of the left lobe of
routine checkup by her physician. On examination she has a the injured liver is removed. Two months later, a CT scan of
blood pressure of 150/95 mm Hg. If her hypertension remains the abdomen shows that the liver has nearly regained its size
untreated for years, which of the following cellular alterations before the injury. Which of the following processes best ex-
would most likely be seen in her myocardium? plains this CT scan finding?
A Apoptosis A Apoptosis
B Dysplasia B Dysplasia
C Fatty change C Hyperplasia
D Hemosiderosis D Hydropic change
E Hyperplasia E Steatosis
F Hypertrophy
G Metaplasia 6 A 71-year-old man has had difficulty with urination, in-
cluding hesitancy and increased frequency, for the past 5 years.
3 A 22-year-old woman becomes pregnant. A fetal ultra- A digital rectal examination reveals that his prostate gland is
sound examination at 13 weeks’ gestation shows her uterus palpably enlarged to twice normal size. A transurethral resection
measures 7 × 4 × 3 cm. At delivery of a term infant, her uterus of the prostate is performed, and the microscopic appearance of
measures 34 × 18 × 12 cm. Which of the following cellular pro- the prostate “chips” obtained is that of nodules of glands with
cesses has contributed most to the increase in her uterine size? intervening stroma. Which of the following pathologic processes
A Endometrial glandular hyperplasia has most likely occurred in his prostate?
B Myometrial fibroblast proliferation A Apoptosis
C Endometrial stromal hypertrophy B Dysplasia
D Myometrial smooth muscle hypertrophy C Fatty change
E Vascular endothelial hyperplasia D Hyperplasia
E Hypertrophy
4 A 20-year-old woman breastfeeds her infant. On exami- F Metaplasia
nation, her breasts are slightly increased in size. Milk can be
7

8 U N I T I   General Pathology C Nuclear fragmentation
D Plasma membrane blebs
7 A 29-year-old man sustains a left femoral fracture in a mo- E Ribosomal disaggregation
torcycle accident. His leg is placed in a plaster cast. After his left   
leg has been immobilized for 6 weeks, the diameter of the left calf
has decreased in size. This change in size is most likely to result
from which of the following alterations in his calf muscles?
A Aplasia
B Atrophy
C Dystrophy
D Hyalinosis
E Hypoplasia
  

8 A 34-year-old obese woman has experienced heartburn 11 A 50-year-old man has experienced an episode of chest
from gastric reflux for the past 5 years after eating large meals. pain for 6 hours. A representative histologic section of his
She undergoes upper gastrointestinal endoscopy, and a biopsy left ventricular myocardium is shown in the figure. There
specimen of the distal esophagus is obtained. Which of the is no hemorrhage or inflammation. Which of the following
following microscopic changes, seen in the figure, has most conditions most likely produced these myocardial changes?
likely occurred? A Arterial thrombosis
A Columnar metaplasia B Autoimmunity
B Goblet cell hyperplasia C Blunt chest trauma
C Lamina propria atrophy D Protein-deficient diet
D Squamous dysplasia E Viral infection
E Mucosal hypertrophy   

9 An 11-year-old girl becomes infected with hepatitis A 12 A 38-year-old woman has experienced severe abdomi-
and experiences mild nausea for 1 week. On physical exami- nal pain over the past day. On examination she is hypotensive
nation, she has minimal right upper quadrant tenderness and and in shock. Laboratory studies show elevated serum lipase.
scleral icterus. Laboratory findings include a serum AST of 68 From the representative gross appearance of the mesentery
U/L, ALT of 75 U/L, and total bilirubin of 5.1 mg/dL. Her shown in the figure, which of the following events has most
laboratory findings most likely result from which of the fol- likely occurred?
lowing changes in her hepatocytes? A Acute pancreatitis
A Cell membrane defects B Gangrenous cholecystitis
B Lysosomal autophagy C Hepatitis B virus infection
C Mitochondrial swelling D Small intestinal infarction
D Nuclear chromatin clumping E Tuberculous lymphadenitis
E Ribosomal dispersion

10 A 33-year-old woman has had increasing lethargy and
decreased urine output for the past week. Laboratory studies
show her serum creatinine is 4.3 mg/dL and urea nitrogen
40 mg/dL. A renal biopsy is performed, and the specimen is
examined using electron microscopy. Which of the following
morphologic cellular changes most likely suggests a diagnosis
of acute tubular necrosis?
A Chromatin clumping
B Mitochondrial swelling

C H A P T E R 2   Cellular Pathology 9

13 A 68-year-old woman suddenly lost consciousness and injury from decreased systemic arterial perfusion of multiple
on awakening 1 hour later, she could not speak or move her organs and tissues?
right arm. Two months later, a head CT scan showed a large A Carbon dioxide
cystic area in the left parietal lobe. Which of the following B Creatinine
pathologic processes has most likely occurred in her brain? C Glucose
A Apoptosis D Lactic acid
B Coagulative necrosis E Troponin I
C Fat necrosis
D Karyolysis 17 A tissue preparation is experimentally subjected to a
E Liquefactive necrosis hypoxic environment. The cells in this tissue begin to swell,
   and chromatin begins to clump in cell nuclei. ATPases are acti-
vated, and ATP production decreases. Which of the following
14 A screening chest radiograph of an asymptomatic ions accumulating in mitochondria and the cytosol contributes
37-year-old man shows a 3-cm nodule in the middle lobe most to these findings and to eventual cell death?
of his right lung. The nodule is excised with a pulmonary A Ca2+
wedge resection, and sectioning shows a sharply circum- B Cl−
scribed mass with a soft, white center. The microscopic ap- C HCO3−
pearance is shown in the figure. The serum interferon gamma D K+
release assay is positive. Which of the following pathologic E Na+
processes has most likely occurred in this nodule? F PO43−
A Apoptosis
B Caseous necrosis 18 In an experiment, a large amount of a drug is admin-
C Coagulative necrosis istered to experimental organisms and is converted by cy-
D Fat necrosis tochrome P-450 to a toxic metabolite. Accumulation of this
E Fatty change metabolite leads to increased intracellular lipid peroxidation.
F Gangrenous necrosis Depletion of which of the following intracellular substances
G Liquefactive necrosis within the cytosol exacerbates this form of cellular injury by
15 An experimental drug administered to a tissue prepa- this mechanism?
ration is found to inhibit cellular oxidative phosphorylation A ADP
when given in high doses, and ATP production drops to 5% of B Glutathione
normal. Cell membrane function is diminished. Which of the C NADPH oxidase
following substances is most likely to be present at increased D Nitric oxide synthase
concentration in culture fluid bathing the tissue? E mRNA
A Calcium F Sodium
B Glucose
C Ketones 19 In an experiment, metabolically active cells are subject-
D Potassium ed to radiant energy in the form of x-rays. This results in cell
E Sodium injury caused by hydrolysis of water. Which of the following
16 A 47-year-old woman has poorly controlled diabetes intracellular enzymes helps to protect the cells from this type
mellitus and develops coronary artery disease. She now has de- of injury?
creasing cardiac output with blood pressure of 80/40 mm Hg A Endonuclease
and ejection fraction of 18%. An increase in which of the follow- B Glutathione peroxidase
ing substances in her blood is most indicative of reversible cell C Lactate dehydrogenase
D Phospholipase
E Protease

20 A 5-year-old child ingests 50 iron tablets, each with 27
mg of iron. Within 6 hours the child develops abdominal pain
and lethargy. On physical examination he is hypotensive. Lab-
oratory studies show metabolic acidosis. Through formation
of which of the following compounds is the cell injury in this
child most likely mediated?
A Ascorbic acid
B Hemosiderin
C Hydroxyl radical
D Nitric oxide
E Superoxide dismutase
  

1 0 U N I T I   General Pathology

24 An experiment introduces a knockout gene mutation
into a cell line. The frequency of shrunken cells with chromatin
clumping, karyorrhexis, and cytoplasmic blebbing is increased
compared with a cell line without the mutation. Overall sur-
vival of the mutant cell line is reduced. Which of the following
genes is most likely to be affected by this mutation?
A BAX
B BCL2
C C-MYC
D FAS
E p53
  

21 A 63-year-old man has a 2-year history of worsening 25 A 22-year-old woman with leukemia undergoes bone
congestive heart failure. An echocardiogram shows mitral marrow transplantation and receives a partially mismatched
valve stenosis with left atrial dilation. A mural thrombus is donor marrow. One month later, she has a scaling skin rash. A
present in the left atrium. One month later, he experiences skin biopsy is obtained, and on microscopic examination, it has
left flank pain and notes hematuria. Laboratory testing shows the cellular change shown in the figure. This change most likely
an elevated serum AST. The representative microscopic ap- results from which of the following biochemical reactions?
pearance of the lesion is shown in the figure. Which of the fol- A Activation of caspases
lowing patterns of tissue necrosis is most likely to be present B Elaboration of lipases
in this man? C Increase in glycolysis
A Caseous D Peroxidation of lipids
B Coagulative E Reduction of ATP synthesis
C Fat
D Gangrenous 26 A 47-year-old man has a lung carcinoma with metas-
E Liquefactive tases. He receives chemotherapy. A month later, histologic
examination of a metastatic lesion shows many foci in which
22 A 54-year-old man experienced severe substernal chest individual tumor cells appear shrunken and deeply eosino-
pain for 3 hours. An ECG showed changes consistent with an philic. Their nuclei exhibit condensed aggregates of chromatin
acute myocardial infarction. After thrombolytic therapy with under the nuclear membrane. The pathologic process affecting
tissue plasminogen activator (t-PA), his serum creatine kinase these shrunken tumor cells is most likely triggered by release
(CK) level increased. Which of the following tissue events of which of the following substances into the cytosol?
most likely occurred in the myocardium after t-PA therapy? A BCL2
A Cellular regeneration B Catalase
B Drug toxicity C Cytochrome c
C Increased synthesis of CK D Lipofuscin
D Myofiber atrophy E Phospholipase
E Reperfusion injury

23 On day 28 of her menstrual cycle, a 23-year-old woman
experiences onset of menstrual bleeding that lasts for 6 days. She
has had regular cycles since menarche. Which of the following
processes most likely occurs in her endometrial cells to initiate
the onset of menstrual bleeding?
A Apoptosis
B Atrophy
C Caseous necrosis
D Heterophagocytosis
E Liquefactive necrosis

C H A P T E R 2   Cellular Pathology 11

27 In a study of viral hepatitis infection, it is observed that 31 A 46-year-old man has noted increasing abdominal
cytotoxic T lymphocytes (CTLs) induce death in virally infected size for the past 6 years. On physical examination his liver
hepatocytes. The CTLs release perforin to allow entry of their span is increased to 18 cm. An abdominal CT scan shows an
granules. Which of the following substances is found in those enlarged liver with diffusely decreased attenuation. Labora-
granules that directly activates programmed cell death? tory findings include increased total serum cholesterol and
A BCL2 triglyceride levels, increased prothrombin time, and a de-
B Endonuclease creased serum albumin concentration. The representative
C Granzyme B microscopic appearance of his liver is shown in the figure.
D Nitric oxide Which of the following activities most likely led to these
E p53 findings?
A Drinking beer
28 An experimental study of steatohepatitis in metabolic B Ingesting aspirin
syndrome reveals that hepatocyte cell membrane injury with C Injecting heroin
necrosis occurs in response to increased amounts of tumor D Playing basketball
necrosis factor (TNF). When a pharmacologic agent inhibit- E Smoking cigarettes
ing caspases is administered, cell necrosis still occurs. Which
of the following substances forms a supramolecular complex 32 A 69-year-old woman has had transient ischemic attacks
that increases the generation of reactive oxygen species? for the past 3 months. On physical examination, she has an
A Catalase audible bruit on auscultation of the neck. A right carotid end-
B Cytochrome c arterectomy is performed. The curetted atheromatous plaque
C Interleukin 1-beta converting enzyme has a grossly yellow-tan, firm appearance. Microscopically,
D Receptor-interacting protein which of the following materials can be found in abundance in
E Ubiquitin ligase the form of crystals within cleftlike spaces?
A Cholesterol
29 A 71-year-old man diagnosed with pancreatic cancer is B Glycogen
noted to have decreasing body mass index. His normal con- C Hemosiderin
nective tissues undergo atrophy by sequestering organelles D Immunoglobulin
and cytosol in a vacuole, which then fuses with a lysosome. E Lipofuscin
However, the cancer continues to increase in size. Which of
the following processes is most likely occurring in the normal 33 A 45-year-old woman has had worsening dyspnea for the
cells but is inhibited in the cancer cells of this man? past 5 years. A chest CT scan shows panlobular emphysema.
A Aging Laboratory studies show a deficiency of α1-antitrypsin (AAT).
B Apoptosis Her AAT genotype is PiZZ. A liver biopsy specimen examined
C Autophagy microscopically shows abundant PAS-positive globules with-
D Hyaline change in periportal hepatocytes. Which of the following molecular
E Karyorrhexis mechanisms is most likely responsible for this finding in her
hepatocytes?
30 A new drug is developed that binds to cellular microtu- A Decreased catabolism of AAT in lysosomes
bules. The function of the microtubules is diminished, so that B Excessive hepatic synthesis of AAT
mitotic spindle formation is inhibited. Which of the following C Impaired dissociation of AAT from chaperones
is the most likely use for this drug? D Inability to metabolize AAT in Kupffer cells
A Antimicrobial therapy E Retained misfolded AAT in endoplasmic reticulum
B Chemotherapy   
C Pain management
D Prevention of atherosclerosis
E Weight reduction
  

1 2 U N I T I   General Pathology

34 At autopsy, the heart of a 63-year-old man weighs only 37 A 72-year-old man died suddenly from congestive heart
250 g (normal 330 g) and has small right and left ventricles. failure. At autopsy, his heart weighed 580 g (normal 330 g)
The myocardium is firm, with a dark chocolate-brown color and showed marked left ventricular hypertrophy and minimal
throughout. The coronary arteries show minimal atheroscle- coronary arterial atherosclerosis. A serum chemistry panel or-
rotic changes. An excessive amount of which of the following dered before death showed no abnormalities. Which of the fol-
substances, shown in the figure, would most likely be found in lowing pathologic processes best accounts for the appearance
the myocardial fibers of this heart? of the aortic valve seen in the figure?
A Bilirubin A Amyloidosis
B Glycogen B Dystrophic calcification
C Hemosiderin C Hemosiderosis
D Lipofuscin D Hyaline change
E Melanin E Lipofuscin deposition

35 A 69-year-old woman has had a chronic cough for the 38 A 70-year-old man with hypercalcemia died suddenly.
past year. A chest radiograph shows a 6-cm mass in the left At autopsy, microscopic examination showed noncrystalline
lung. A needle biopsy specimen of the mass shows carcinoma. amorphous deposits of calcium salts in gastric mucosa, renal in-
A pneumonectomy is performed, and examination of the hilar terstitium, and alveolar walls of lungs. Which of the following
lymph nodes reveals a uniform, dark black cut surface. Which underlying conditions would most likely explain these findings?
of the following factors most likely accounts for the appear- A Chronic active hepatitis
ance of these lymph nodes? B Diffuse parathyroid hyperplasia
A Aging effects C Disseminated tuberculosis
B Bleeding disorder D Generalized atherosclerosis
C Cigarette smoking E Normal aging process
D Liver failure F Pulmonary emphysema
E Multiple metastases
39 An experiment analyzes cells for enzyme activity associ-
36 A 22-year-old woman from Albania has a congenital ated with sustained cellular proliferation. Which of the follow-
anemia requiring multiple transfusions of RBCs for many ing cells is most likely to have the highest telomerase activity?
years. On physical examination, her skin has a bronze color. A Endothelial cells
Liver function tests show reduced serum albumin. Which of B Erythrocytes
the following findings would most likely appear in a liver C Germ cells
biopsy specimen? D Neurons
A Amyloid in portal triads E Neutrophils
B Bilirubin in canaliculi
C Glycogen in hepatocytes 40 A study of aging shows that senescent cells have accu-
D Hemosiderin in hepatocytes mulated damage from toxic byproducts of metabolism. There
E Steatosis in hepatocytes is increased intracellular lipofuscin deposition. Prolonged in-
   gestion of which of the following substances is most likely to
counteract this aging mechanism?
A Antioxidants
B Analgesics
C Antimicrobials
D Antineoplastic agents
E Glucocorticoids

C H A P T E R 2   Cellular Pathology 13

ANSWERS when the liver has attained its normal size. Hepatocytes can
reenter the cell cycle and proliferate to regenerate the liver;
1  A  Normal cells handle physiologic demands and main- they do not just hypertrophy (increase in size). Apoptosis is
tain metabolic functions within narrow ranges, termed homeo- single cell death and frequently occurs with viral hepatitis.
stasis. Under disease conditions with stress on cells, there is Dysplasia is disordered epithelial cell growth that can be
adaptation to a new steady state. In this case, the loss of renal premalignant. Hydropic change, or cell swelling, does not
function leads to a higher urea nitrogen level as well as reten- produce regeneration. Steatosis (fatty change) can lead to
tion of fluid. The diuretic induces loss of the excess fluid to hepatomegaly, but not as a regenerative process. It is the
yield a new steady state. The protein restriction reduces urea result of toxic/metabolic hepatocyte injury.
nitrogen excretion, which also leads to a new steady state.
Both are adaptations. Apoptosis refers to single cell necro- PBD9 35–36  BP9 4  PBD8 8–9  BP8 4
sis in response to injury. An irreversible injury leads to cell
death, but the changes described here are not evidence for 6  D  Nodular prostatic hyperplasia (also known as benign
cellular necrosis. The metabolism of cells is maintained for prostatic hyperplasia [BPH]) is a common condition in older
adaptation, with response to the diuretic and to protein re- men that results from proliferation of both prostatic glands
striction. and stroma. The prostate becomes more sensitive to andro-
genic stimulation with age. This is an example of pathologic
PBD9 32–33  BP9 2  PBD8 4–5  BP8 2 hyperplasia. Apoptosis results in a loss of, not an increase
in, cells. Dysplasia refers to disordered epithelial cell growth
2  F  The pressure load on the left ventricle results in an and maturation. Fatty change in hepatocytes may produce
increase in myofilaments in the existing myofibers, so they hepatomegaly. Although BPH is often called “benign pros-
enlarge. The result of continued stress from hypertension is tatic hypertrophy,” this term is technically incorrect; it is the
eventual heart failure with decreased contractility. Apoptosis number of glands and stromal cells that is increased, rather
would lead to loss of cells and diminished size. Dysplasia is than the size of existing cells. A change in the glandular epi-
not a diagnosis made for the heart. Hemosiderin deposition thelium to squamous epithelium around a prostatic infarct
in the heart is a pathologic process resulting from increased would be an example of metaplasia.
iron stores in the body. Though hyperplasia from prolifera-
tion of myofibroblasts is possible, this does not contribute PBD9 35–36  BP9 4  PBD8 8–9  BP8 4
significantly to cardiac size. Metaplasia of muscle does not
occur, although loss of muscle occurs with aging and ischemia 7   B  Reduced workload causes cell to shrink through loss of
as myofibers are replaced by fibrous tissue. cell substance, a process called atrophy. The cells are still pres-
ent, just smaller. Aplasia refers to lack of embryonic develop-
PBD9 34–35  BP9 3–4  PBD8 6–8  BP8 3–4 ment; hypoplasia describes poor or subnormal development
of tissues. Dystrophy of muscles refers to inherited disorders
3  D  The increase in uterine size is primarily the result of an of skeletal muscles that lead to muscle fiber destruction,
increase in the size of myometrial smooth muscle cells. The en- weakness, and wasting. Hyaline change (hyalinosis) refers to
dometrium also increases in size, mainly via hyperplasia, but a nonspecific, pink, glassy eosinophilic appearance of cells.
it remains as a thin lining to the muscular wall and does not
contribute as much to the change in size. There is little stroma PBD9 36–37  BP9 4–5  PBD8 9–10  BP8 4–5
in myometrium and a greater proportion in endometrium,
so stroma contributes a smaller percentage to the gain in size 8  A  Inflammation from reflux of gastric acid has resulted
than muscle. The vessels are a minor but essential component in replacement of normal esophageal squamous epithelium
in this increase in size, but not the largest component. by intestinal-type columnar epithelium with goblet cells.
Such conversion of one adult cell type to another cell type
PBD9 34–35  BP9 3–4  PBD8 6–8  BP8 2–3 is called metaplasia, and it occurs when stimuli reprogram
stem cells. Goblet cells are not normal constituents of the
4  D  Breast lobules have an increased number of cells un- esophageal mucosa, and they are a minor part of this meta-
der hormonal influence (mainly progesterone) to provide plastic process. The lamina propria has some inflammatory
for normal lactation. Ductal metaplasia in the breast is a cells, but it does not atrophy. The squamous epithelium does
pathologic process. Epithelial dysplasia denotes disordered not become dysplastic from acid reflux, but the columnar
growth and maturation of epithelial cells that may progress metaplasia may progress to dysplasia, not seen here, if the
to cancer. Accumulation of fat within cells is a common man- abnormal stimuli continue. These cells are not significantly
ifestation of sublethal cell injury or, uncommonly, of inborn increased in size (hypertrophic).
errors in fat metabolism. The breast stroma plays no role in
lactation and may increase with pathologic processes. PBD9 37–38  BP9 5  PBD8 10–11  BP8 5

PBD9 35–36  BP9 3  PBD8 8–9  BP8 4

5  C  The liver is one of the few organs in the human body 9  A  Irreversible cell injury is associated with loss of mem-
that can partially regenerate. This is a form of compensatory brane integrity. This allows intracellular enzymes such as
hyperplasia. The stimuli to hepatocyte mitotic activity cease AST and ALT to leak into the serum. All other morphologic

1 4 U N I T I   General Pathology

changes listed are associated with reversible cell injury, in Coagulative necrosis is more typical of ischemic tissue injury.
which the cell membrane remains intact and the cells do Fat necrosis most often occurs in the breast and pancreas.
not die. Fatty change is most often a feature of hepatocyte injury,
and the cell integrity is maintained. Gangrene characterizes
PBD9 38–39  BP9 7–8  PBD8 11–12  BP8 8–12 extensive necrosis of multiple cell types in a body region or
organ. Liquefactive necrosis is seen in neutrophilic abscesses
1 0  C  Cell death occurs with loss of the cell nucleus, and or ischemic cerebral injury.
tubular cells become necrotic. All other cellular morphologic
changes listed represent forms of reversible cellular injury. PBD9 43–44  BP9 10–11  PBD8 16  BP8 10
The plasma membrane and intracellular organelles retain
some function unless severe damage causes loss of mem- 1 5  D  Reduction in oxidative phosphorylation leads to re-
brane integrity. duction in synthesis of ATP and diminished activity of the
plasma membrane sodium pump, which maintains high
PBD9 39, 42  BP9 8–9  PBD8 12  BP8 6, 9 intracellular potassium concentration. Loss of ATP leads to
efflux of intracellular potassium, while net influx of sodium
11  A  The figure shows deep eosinophilic staining, loss of and water promote cell swelling. A marked rise in plasma
myocardial fiber nuclei, and loss of cell structure consis- potassium can indicate significant cell damage or death
tent with an early ischemic injury, resulting in coagulative (such as skeletal muscle crush injury or hemolysis). When
necrosis. Myocardial ischemia and infarction are typically cells are not consuming glucose via oxidative metabolism,
caused by loss of coronary arterial blood flow. An immu- the glucose is metabolized via other pathways, and glucose
nological process may produce focal myocardial injury. is maintained within normal ranges. Though cell membranes
Blunt trauma produces hemorrhage. Lack of protein leads are composed of lipid, dysfunction or disruption of those
to a catabolic state with gradual decrease in cell size, but membranes does not significantly alter plasma lipid concen-
it does not cause ischemic changes. Viral infection could trations.
cause focal necrosis of the myocardium, but this is usually
accompanied by an inflammatory infiltrate consisting of PBD9 45–46  BP9 12–13  PBD8 14–15  BP8 14–15
lymphocytes and macrophages.
16  D  Decreased tissue perfusion from hypotensive shock
PBD9 42–43  BP9 9–10  PBD8 15–16  BP8 2, 7, 10 leads to hypoxemia and depletion of ATP when cell metabo-
lism shifts from aerobic to anaerobic glycolysis. This shift
1 2  A  The many focal, chalky white deposits in the mesen- causes depletion of glycogen stores and increased produc-
tery, composed mainly of adipocytes, are areas of fat necrosis. tion and accumulation of lactic acid, reducing intracellular
The deposits result from the release of pancreatic enzymes pH. Creatinine would increase with reduced renal func-
such as lipases in a patient with acute pancreatitis. Gangre- tion from decreased renal perfusion, but this would not
nous necrosis is mainly coagulative necrosis, but occurs over explain the changes in other tissues. An increased glucose
an extensive area of tissues. Viral hepatitis does not cause cell level would be indicative of poorly controlled diabetes mel-
necrosis in organs other than liver, and hepatocyte necrosis litus, not decreased perfusion. Carbon dioxide is likely to be
from viral infections occurs mainly by means of apoptosis. In- cleared via normal lungs, which are still sufficiently perfused
testinal infarction is a form of coagulative necrosis. Infection by a failing heart. An increase in troponin I suggests irrevers-
with tuberculosis leads to caseous necrosis. ible myocardial injury.

PBD9 43–44  BP9 10–11  PBD8 16–17  BP8 11 PBD9 45–46  BP9 12–13  PBD8 14–15  BP8 14, 18

13  E  The high lipid content of central nervous system 17  A  Irreversible cellular injury is likely to occur when
tissues results in liquefactive necrosis as a consequence of cytoplasmic calcium increases. Calcium can enter cells and
ischemic injury, as in this case of stroke. Apoptosis affects also accumulate in mitochondria and endoplasmic reticu-
single cells and typically is not grossly visible. Coagulative lum. The excess calcium activates ATPases, phospholipases,
necrosis is the typical result of ischemia in most solid or- proteases, and endonucleases, which injure cell components.
gans. Fat necrosis is seen in breast and pancreatic tissues. Mitochondrial permeability is increased to release cyto-
Karyolysis refers to fading away of cell nuclei in dead cells. chrome c, which activates caspases leading to apoptosis. Of
the other ions listed, sodium enters the cell, while potassium
PBD9 43  BP9 10–11  PBD8 16–17  BP8 10–11 diffuses out when the sodium pump fails as ATP levels fall;
but this is potentially reversible.
1 4  B  The grossly cheeselike appearance gives this form of
necrosis its name—caseous necrosis. The figure shows amor- PBD9 46–47  BP9 13–14  PBD8 18–20  BP8 15
phous pink acellular material at the upper right surrounded
by epithelioid macrophages, and a Langhans giant cell is vis- 18  B  The drug acetaminophen can be converted to toxic
ible at the upper left. In the lung, tuberculosis and fungal metabolites in this manner. Glutathione in the cytosol helps
infections are most likely to produce this pattern of tissue to reduce cellular injury from many toxic metabolites and
injury. Apoptosis involves individual cells, without gross- free radicals. ADP is converted to ATP by oxidative and
ly apparent extensive or localized areas of tissue necrosis. glycolytic cellular pathways to provide energy that drives

C H A P T E R 2   Cellular Pathology 15

cellular functions, and a reduction in ATP leaves the cell cells results in generation of oxygen-derived free radicals,
vulnerable to injury. NADPH oxidase generates superoxide, causing a reperfusion injury. The elevation in the CK level is
which is used by neutrophils in killing bacteria. Nitric oxide indicative of myocardial cell necrosis, because this intracel-
synthase in macrophages produces nitric oxide, which aids lular enzyme does not leak in large quantities from intact
in destroying organisms undergoing phagocytosis. Protein myocardial cells. Myocardial fibers do not regenerate to a
synthesis in cells depends on mRNA for longer survival and significant degree, and atrophic fibers would have less CK
recovery from damage caused by free radicals. Failure of the to release. t-PA does not produce a toxic chemical injury;
sodium pump leads to increased cytosolic sodium and cell it induces thrombolysis to restore blood flow in occluded
swelling with injury. coronary arteries.

PBD9 48, 52  BP9 14–15  PBD8 20–21  BP8 15–17 PBD9 51  BP9 17  PBD8 24  BP8 18

19  B  The body has intracellular mechanisms that prevent 23  A  The onset of menstruation is orderly, programmed
damage from free radicals generated by exposure to x-rays. cell death (apoptosis) through hormonal stimuli, an ex-
Glutathione peroxidase reduces such injury by catalyzing ample of the intrinsic (mitochondrial) apoptotic pathway.
the breakdown of hydrogen peroxide. Endonucleases dam- As hormone levels drop, the endometrium breaks down,
age DNA in nuclear chromatin. Lactate dehydrogenase is sloughs off, and then regenerates. With cellular atrophy,
present in a variety of cells, and its elevation in the serum there is often no visible necrosis, but the tissues shrink,
is an indicator of cell injury and death. Phospholipases de- something that occurs in the endometrium after meno-
crease cellular phospholipids and promote cell membrane pause. Caseous necrosis is typical of granulomatous in-
injury. Proteases can damage cell membranes and cytoskel- flammation, resulting most commonly from mycobacterial
etal proteins. infection. Heterophagocytosis is typified by the clearing of
an area of necrosis through macrophage ingestion of the
PBD9 47–48  BP9 14–15  PBD8 20–21  BP8 15–17 necrotic cells. Liquefactive necrosis can occur in any tissue
after acute bacterial infection or in the brain after ischemia.
2 0  C  Excessive iron ingestion, particularly by a child, can
overwhelm the body’s ability to bind the absorbed free iron PBD9 52–56  BP9 18  PBD8 25–29  BP8 19–22
with the transport protein transferrin. The free iron contrib-
utes to generation of cellular free radicals via the Fenton 2 4  B  These histologic findings are typical of apoptosis.
reaction. Ascorbic acid (vitamin C) and vitamin E both act The BCL2 gene product inhibits cellular apoptosis by bind-
as antioxidants to protect against free radical injury, albeit ing to Apaf-1. Hence, the knockout removes this inhibition
over a long time frame. Hemosiderin is a storage form of iron The BAX gene product promotes apoptosis, and a knockout
from excess local or systemic accumulation of ferritin, and by would protect against apoptosis. The C-MYC gene is in-
itself does not cause cell injury until large amounts are pres- volved with oncogenesis. The FAS gene encodes for a cellular
ent, as with hemochromatosis. Nitric oxide generated within receptor for Fas ligand that signals apoptosis. Activity of the
macrophages can be to kill microbes. It can be converted to p53 (TP53) gene normally stimulates apoptosis, but mutation
a highly reactive peroxynitrite anion. Superoxide dismutase favors cell survival.
helps break down superoxide anion to hydrogen peroxide,
thus scavenging free radicals. PBD9 54–55  BP9 18, 20–28  PBD8 28–30  BP8 19–22

PBD9 47–48  BP9 14–15  PBD8 20–22  BP8 16 2 5  A  There is an apoptotic cell (arrow) that is shrunken and
has been converted into a dense eosinophilic mass. There is a
2 1  B  Embolization of the thrombus led to blockage of surrounding inflammatory reaction with cytotoxic lympho-
a renal arterial branch, causing an acute renal infarction cytes. This pattern is typical of apoptosis. Caspase activation
in this patient. An ischemic injury to most internal organs is a universal feature of apoptosis, regardless of the initiat-
produces a pattern of cell death called coagulative necrosis. ing cause. Apoptosis induced in recipient cells from donor
Note the faint outlines of renal tubules and glomerulus lymphocytes occurs with graft-versus-host disease. Lipases
in the figure, but no cellular nuclei. Caseous necrosis can are activated in enzymatic fat necrosis. Reduced ATP synthe-
be seen in various forms of granulomatous inflamma- sis and increased glycolysis occur when a cell is subjected to
tion, typified by tuberculosis. Fat necrosis is usually seen anoxia, but these changes are reversible. Lipid peroxidation
in pancreatic and breast tissue. Gangrenous necrosis is occurs when the cell is injured by free radicals.
a form of coagulative necrosis that usually results from
ischemia and affects limbs. Liquefactive necrosis occurs PBD9 53–54  BP9 18–19  PBD8 26–27  BP8 13–14
after ischemic injury to the brain and is the pattern seen
with abscess formation. 26  C  This histologic picture is typical of apoptosis pro-
duced by chemotherapeutic agents. The release of cytochrome
PBD9 50–51  BP9 17  PBD8 23–24  BP8 2, 3, 10 c from the mitochondria is a key step in many forms of apop-
tosis, and it leads to the activation of caspases. BCL2 is an
22  E  If existing cell damage is not great after myocardial antiapoptotic protein that prevents cytochrome c release and
infarction, the restoration of blood flow can help prevent fur- prevents caspase activation. Catalase is a scavenger of hydro-
ther cellular damage. However, the reperfusion of damaged gen peroxide. Lipofuscin is a pigmented residue representing

1 6 U N I T I   General Pathology

undigested cellular organelles in autophagic vacuoles, much 31  A  The appearance of lipid vacuoles in many of the he-
like old clothes in a closet. Phospholipases are activated during patocytes is characteristic of fatty change (steatosis) of the
necrosis and cause cell membrane damage. liver. Abnormalities in lipoprotein metabolism can lead to
steatosis. Alcohol is a hepatotoxin acting via increased ac-
PBD9 57  BP9 19–21  PBD8 30  BP8 19–22 etaldehyde accumulation that promotes hepatic steatosis.
Decreased serum albumin levels and increased prothrombin
2 7  C  Granzyme B is a serine protease found in CTLs that time suggest alcohol-induced hepatocyte damage. Aspirin
can directly trigger apoptosis. CTLs express Fas ligand on has a significant effect on platelet function, but not on hepa-
their surfaces, and when contacting Fas receptors on the tocytes. Substance abuse with heroin produces few organ-
target cell, the ligand can induce apoptosis by the extrinsic specific pathologic findings. Exercise has little direct effect
(death receptor–initiated) pathway. BCL2 favors cell survival. on hepatic function. Smoking directly damages lung tissue,
Nitric oxide helps destroy phagocytized microbes. Endonu- but has no direct effect on the liver.
cleases are generated following caspase activation and lead
to nuclear fragmentation. When p53 is activated by intrinsic PBD9 61–62  BP9 23  PBD8 33–34  BP8 23–24
DNA damage during cell proliferation, apoptosis is triggered.
Mutations in p53 may allow accumulation of genetic damage, 32  A  Cholesterol is a form of lipid commonly depos-
a process that promotes unregulated cell growth (neoplasia). ited within atheromas in arterial walls, imparting a yel-
low color to these plaques and a glistening appearance
PBD9 58  BP9 19–20  PBD8 31  BP8 21–22 if abundant. Direct damage to the atheroma can yield
cholesterol emboli. Glycogen is a storage form of carbo-
2 8  D  Necroptosis occurs when the mechanism of apop- hydrate seen mainly in liver and muscle. Hemosiderin is
tosis yields morphologic necrosis following cell membrane a storage form of iron that appears in tissues of the mono-
rupture, independent of caspase release. The RIP1-RIP3 nuclear phagocyte system (e.g., marrow, liver, spleen),
complex is called a necrosome. Catalases help destroy hydro- but can be widely deposited with hereditary hemochro-
gen peroxide to prevent free radical damage. Cytochrome c matosis. Immunoglobulin occasionally may be seen as
participates in apoptosis and an inflammasome in necropto- rounded globules in plasma cells (i.e., Russell bodies).
sis. Ubiquitin ligase is part of misfolded protein processing Lipofuscin is a golden brown pigment that increases with
in proteasomes. aging in cell cytoplasm, mainly in cardiac myocytes and
in hepatocytes.
PBD9 58–59
PBD9 62  BP9 23  PBD8 34–35  BP8 24
29  C  Autophagy is a form of cellular downsizing in re-
sponse to stress, as the cell consumes itself, by upregulat- 33  E  Mutations in the AAT gene give rise to AAT mol-
ing Atgs genes. Lipofuscin granules are residual bodies ecules that cannot fold properly. In the PiZZ genotype, both
left over from this process. Cell death may eventually be alleles have the mutation. The partially folded molecules
triggered by autophagy, but by a different mechanism than accumulate in hepatocyte endoplasmic reticulum and can-
apoptosis, a form of single cell necrosis in which cell frag- not be secreted. Impaired dissociation of the CFTR protein
mentation occurs. Cancer cells acquire the ability to prevent from chaperones causes many cases of cystic fibrosis. There
autophagy, perhaps by downregulating PTEN gene expres- is no abnormality in the synthesis, catabolism, or metabolism
sion, and maintain a survival advantage even as the patient of AAT in patients with AAT deficiency. AAT is the major
is dying. There is slow autophagy with aging, but autoph- circulating alpha globulin that protects tissues such as lung
agy is accelerated with stressors such as malnutrition and from damaging proteases.
chronic disease. Hyaline is a generic term for intracellular
or extracellular protein accumulations appearing pink and PBD9 63  PBD8 35
homogeneous with H&E staining. Karyorrhexis is nuclear
fragmentation in a necrotic cell. 34  D  Lipofuscin is a “wear-and-tear” pigment that in-
creases with aging, particularly in liver and myocardium.
PBD9 59–60  BP9 22–23  PBD8 32, 304  BP8 12 This granular golden brown pigment seen adjacent to the
myocyte nucleus in the figure has minimal effect on cellu-
30  B  Microtubules are cytoskeletal components required lar function in most cases. Rarely, there is marked lipofus-
for cell movement. Mitotic spindles are required for cell di- cin deposition in a small heart, a so-called brown atrophy.
vision, and if cancer cells cannot divide, then the neoplasm Bilirubin, another breakdown product of hemoglobin, im-
cannot grow. Antibiotics are directed at microorganisms that parts a yellow appearance (icterus) to tissues. Hemosiderin
do not have microtubules. Pain is produced largely through is the breakdown product of hemoglobin that contains the
release of mediators of inflammation. Atheroma formation is iron. Hearts with excessive iron deposition tend to be large.
affected by endothelial damage and lipid accumulation, and Glycogen is increased in some inherited enzyme disorders,
though there is cellular proliferation, it occurs over many and when the heart is involved, heart size increases. Melanin
years. Weight reduction is accomplished primarily via atro- pigment is responsible for skin tone: the more melanin, the
phy of adipocytes, not inhibition of cell proliferation. darker the skin.

PBD9 60  PBD8 34 PBD9 64  BP9 24  PBD8 39–40  BP8 25

C H A P T E R 2   Cellular Pathology 17

35  C  Lung and hilar lymph nodes accumulate anthracotic to metastases, paraneoplastic syndromes, and, less commonly,
pigmentation when carbon pigment is inhaled from polluted vitamin D toxicity or sarcoidosis. Chronic renal disease re-
air. The tar in cigarette smoke is a major source of such car- duces phosphate excretion by the kidney, resulting in an in-
bonaceous pigment. Older individuals generally have more crease in serum phosphate. Because the solubility product of
anthracotic pigment, but this is not inevitable with aging— calcium and phosphorus must be maintained, the serum cal-
individuals living in rural areas with good environmental cium is depressed, triggering increased parathyroid hormone
air quality have less pigment. Resolution of hemorrhage can output to increase the calcium level, which promotes calcium
produce hemosiderin pigmentation, which imparts a brown deposition. Chronic hepatitis leads to hyperbilirubinemia and
color to tissues. Hepatic failure may result in jaundice, char- jaundice. The granulomas of tuberculosis have caseous necro-
acterized by a yellow color in tissues. Metastases are mass sis with dystrophic calcification. Another form of dystrophic
lesions that impart a tan-to-white appearance to tissues. calcification occurs when atherosclerotic lesions calcify. Dys-
trophic calcification is seen more often in the elderly, but it is
PBD9 64  BP9 24  PBD8 36  BP8 25 the result of a lifetime of pathologic changes, not aging itself.
Pulmonary emphysema can lead to respiratory acidosis that
3 6  D  Each unit of blood contains about 250 mg of iron. The is compensated by metabolic alkalosis, with the result that the
body has no mechanism for getting rid of excess iron. About serum calcium level remains relatively unchanged.
10 to 20 mg of iron per day is lost with normal desquama-
tion of epithelia; menstruating women lose slightly more. PBD9 65  BP9 25–26  PBD8 38–39  BP8 26–27
Any excess iron becomes storage iron, or hemosiderin. Over
time, hemosiderosis involves more and more tissues of the 3 9  C  Germ cells have the highest telomerase activity, and
body, particularly the liver, but also skin. Initially, hemo- the telomere length can be stabilized in these cells. This al-
siderin deposits are found in Kupffer cells and other mono- lows testicular germ cells to retain the ability to divide
nuclear phagocytes in the bone marrow, spleen, and lymph throughout life. Normal somatic cells have no telomerase
nodes. With great excess of iron, liver cells also accumulate activity, and telomeres progressively shorten with each cell
iron. Amyloid is an abnormal protein derived from a variety division until growth arrest occurs. Erythrocytes do not even
of precursors, such as immunoglobulin light chains. Bilirubin, have a nucleus.
a breakdown product of blood, can be excreted in the bile so
that a person does not become jaundiced. Glycogen storage PBD9 67  BP9 26–27  PBD8 39–40  BP8 28–29
diseases are inherited and present in childhood. Steatosis usu-
ally occurs with ingestion of hepatotoxins, such as alcohol. 40  A  Antioxidants may counteract the effects of reactive
oxygen species (ROS) that may accumulate acutely and
PBD9 64–65  BP9 24  PBD8 36  BP8 26 chronically within cells as a consequence of environmental
insults and pathologic processes. Certainly, health food
37  B  The valve is stenotic because of nodular deposits of stores promote this concept with sales of products such as
calcium. The process is “dystrophic” because calcium deposi- vitamin E. However, cellular damage is multifactorial, and
tion occurs in damaged tissues. The damage in this patient is a proving that one compound has a significant effect is dif-
result of excessive wear and tear with aging. Amyloid deposi- ficult. Analgesics ameliorate the perception of pain from
tion in the heart typically occurs within the myocardium and cellular damage, but they do not prevent or diminish cell
the vessels. Hereditary hemochromatosis is a genetic defect damage; they only mask it. Antimicrobials may help the
in iron absorption that results in extensive myocardial iron body’s own immune defenses against infectious agents and
deposition (hemosiderosis). Hyaline change is a descriptive shorten and/or diminish tissue damage. However, long-
term used by histologists to describe protein deposits that term use of antimicrobials is discouraged because it may
are glassy and pale pink. The amount of lipofuscin increases alter the body’s own useful microbial flora, and it can pro-
within myocardial fibers (not valves) with aging. mote development of drug-resistant strains that pose a seri-
ous health risk for the general population. (As Mr. Spock
PBD9 65  BP9 25–26  PBD8 38  BP8 26–27 noted, “The needs of the many outweigh the needs of the
few.”) Antineoplastic agents are given for malignancies and
38  B  The microscopic findings suggest metastatic calci- rarely have benefit for cancer prevention. Glucocorticoids
fication, with deposition of calcium salts in tissues that have provide short-term improvement in well-being, but when
physiologic mechanisms for losing acid, creating an internal used for longer periods, they have deleterious effects.
alkaline environment that favors calcium precipitation. Hyper-
calcemia can have a variety of causes, including primary and PBD9 66–67  BP9 26–27  PBD8 40–41  BP8 28–29
secondary hyperparathyroidism, bone destruction secondary

3C H A P T E R
Inflammation and Repair

PBD9 Chapter 3: Inflammation and Repair

PBD8 Chapter 2: Acute and Chronic Inflammation

PBD8 Chapter 3: Tissue Renewal, Repair, and Regeneration

BP9 Chapter 2: Inflammation and Repair

BP8 Chapter 2: Acute and Chronic Inflammation
  

1 An 11-year-old child falls and cuts his hand. The wound signs include temperature of 37.8° C, pulse 103/min, res-
becomes infected. Bacteria extend into the extracellular matrix pirations 25/min, and blood pressure 100/60 mm Hg. On
around capillaries. In the inflammatory response to this infec- auscultation of the chest, crackles are audible in both lung
tion, which of the following cells removes the bacteria? bases. A chest radiograph shows bilateral patchy pulmonary
A B lymphocyte infiltrates. The microscopic appearance of her lung is shown
B Fibroblast in the figure. Which of the following inflammatory cell types
C Macrophage is most likely to be seen in greatly increased numbers in her
D Mast cell sputum specimen?
E T lymphocyte A Langhans giant cells
   B Macrophages
C Mast cells
2 A 53-year-old woman has had a high fever and cough D Neutrophils
productive of yellowish sputum for the past 2 days. Her vital E T lymphocytes

3 A 4-year-old child has had a high-volume diarrhea for
the past 2 days. On examination she is dehydrated. A stool
sample examined by serologic assay is positive for rotavirus.
She is treated with intravenous fluids and recovers. Which of
the following components is found on intestinal cells and rec-
ognizes double-stranded RNA of this virus to signal transcrip-
tion factors that upregulate interferon production for viral
elimination?
A Caspase-1
B Complement receptor
C Lectin
D T cell receptor
E Toll-like receptor

18

C H A P T E R 3   Inflammation and Repair 19

4 A 72-year-old man with severe emphysema has had not in his own serum. The neutrophils migrate normally in a
worsening right ventricular failure for the past 5 years. For chemotaxis assay. Which of the following is the most likely
the past 4 days, he has had fever and increasing dyspnea. A cause of this boy’s increased susceptibility to infection?
chest radiograph shows an accumulation of fluid in the pleu- A Abnormality of selectin expression
ral spaces. Fluid obtained by thoracentesis has a specific grav- B Diminished opsonization
ity of 1.030 and contains degenerating neutrophils. The most C Defective neutrophil generation of hydrogen
likely cause of this fluid accumulation is due to changes in
which of the following? peroxide
A Colloid osmotic pressure D Deficiency of integrins
B Leukocytic diapedesis E Phagocytic cell microtubular protein defect
C Lymphatic pressure
D Renal sodium retention 9 A 5-year-old child has a history of recurrent bacterial
E Vascular permeability infections, including pneumonia and otitis media. Analysis
of leukocytes collected from the peripheral blood shows a
5 A 35-year-old man has had increasing dyspnea for the deficiency in myeloperoxidase. A reduction in which of the
past 24 hours. A chest radiograph shows large, bilateral pleu- following processes is the most likely cause of this child’s in-
ral effusions. Thoracentesis yields 500 mL of slightly cloudy creased susceptibility to infections?
yellow fluid from the right pleural cavity. Cytologic examina- A Hydrogen peroxide (H2O2) elaboration
tion of the fluid shows many neutrophils, but no lymphocytes B Hydroxy-halide radical (HOCl–) formation
or RBCs. Which of the following mechanisms contributes most C Failure of migration resulting from complement
to the pleural fluid accumulation?
A Arteriolar vasoconstriction deficiency
B Endothelial contraction D Phagocytic cell oxygen consumption
C Inhibition of platelet adherence E Prostaglandin production
D Lymphatic obstruction
E Neutrophil release of lysosomes 10 In an experiment, neutrophils collected from peripheral
blood are analyzed for a “burst” of oxygen consumption. This
6 A 6-year-old child has a history of recurrent infections respiratory burst is an essential step for which of the following
with pyogenic bacteria, including Staphylococcus aureus and events in an acute inflammatory response?
Streptococcus pneumoniae. The infections are accompanied by A Attachment to endothelial cells
a neutrophilic leukocytosis. Microscopic examination of a B Generation of microbicidal activity
biopsy specimen obtained from an area of soft tissue necro- C Increased production in bone marrow
sis shows microbial organisms, but very few neutrophils. D Opsonization of bacteria
An analysis of neutrophil function shows a defect in rolling. E Phagocytosis of bacteria
This child’s increased susceptibility to infection is most
likely caused by a defect involving which of the following 11 A 4-year-old girl has had numerous infections with
molecules? Staphylococcus aureus since infancy. Genetic testing shows a
A Complement C3b defect leading to a lack of β2 integrin production. Which of the
B Integrins following abnormalities of neutrophil function is most likely
C Leukotriene B4 responsible for these clinical symptoms?
D NADPH oxidase A Decreased generation of hydroxy-halide radicals
E Selectins
(HOCl–)
7 In an experiment, bacteria are introduced into a per- B Diminished phagocytosis of bacteria opsonized
fused tissue preparation. Leukocytes leave the vasculature
and migrate to the site of bacterial inoculation. The movement with IgG
of these leukocytes is most likely to be mediated by which of C Failure of migration to the site of infection
the following substances? D Inadequate adhesion on cytokine-activated
A Bradykinin
B Chemokines endothelium
C Complement C3a E Reduced respiratory burst after phagocytosis
D Histamine
E Prostaglandins 12 In an experiment, peripheral blood cells are isolated and
placed into a culture medium that preserves their metabolic
8 A 12-month-old boy with a 6-month history of repeat- activity. Interferon-γ is added to this culture, along with viable
ed infections has had a fever and cough for the past 3 days. Escherichia coli organisms. Which of the following blood cell
A Gram stain of sputum shows many gram-positive cocci in types in this medium is the most likely to have bactericidal
chains. CBC shows neutrophilia. Laboratory studies show activity against E. coli?
that the patient’s neutrophils phagocytose and kill organ- A Basophil
isms promptly in the presence of normal human serum, but B B lymphocyte
C CD4+ lymphocyte
D CD8+ lymphocyte
E Monocyte
F Natural killer cell
G Neutrophil

2 0 U N I T I   General Pathology

13 In an experiment, T lymphocytes from peripheral blood 18 A 77-year-old woman experiences a sudden loss of con-
are placed in a medium that preserves their function. The lym- sciousness, with loss of movement on the right side of the
phocytes are activated by contact with antigen and incubated body. Cerebral angiography shows an occlusion of the left
for 4 hours. The supernatant fluid is collected and is found to middle cerebral artery. Elaboration of which of the following
contain a substance that is a major stimulator of monocytes and mediators will be most beneficial in preventing further ischemic
macrophages. Which of the following substances released into injury to her cerebral cortex?
this fluid medium is most likely to stimulate macrophages? A Bradykinin
A Histamine B Leukotriene E4
B Interferon-γ C Nitric oxide
C Leukotriene B4 D Platelet-activating factor
D Nitric oxide E Thromboxane A2
E Phospholipase C
F Tumor necrosis factor (TNF) 19 In an experiment, bacteria are inoculated into aliquots of
normal human blood that have been treated with an anticoag-
14 A woman who is allergic to cats visits a neighbor who ulant. It is observed that the bacteria are either phagocytized
has several cats. During the visit, she inhales cat dander, and by neutrophils or undergo lysis. Which of the following blood
within minutes, she develops nasal congestion with abundant plasma components is most likely to facilitate these effects?
nasal secretions. Which of the following substances is most A Complement
likely to produce these findings? B Fibrin
A Bradykinin C Kallikrein
B Complement C5a D Plasmin
C Histamine E Thrombin
D Interleukin-1 (IL-1)
E Phospholipase C 20 Patients with extensive endothelial injury from Esch-
F Tumor necrosis factor (TNF) erichia coli sepsis have consumption of coagulation factors as
well as an extensive inflammatory response. Administration
15 In a 6-month randomized trial of a pharmacologic agent, of activated protein C is most likely to decrease this inflam-
one group of patients receives a cyclooxygenase-2 (COX-2) inhib- matory response by reducing the amount of which of the
itor, and a control group does not. Both groups of adult males had following substances?
mild congestive heart failure and bilateral symmetric arthritis of A Complement
small joints. Laboratory measurements during the trial show no B Fibrin
significant differences between the groups in WBC count, platelet C Kallikrein
count, hemoglobin, and creatinine. The group receiving the drug D Plasmin
reports subjective findings different from those of the control E Thrombin
group. Which of the following findings was most likely reported
by the group receiving the drug? 21 A 95-year-old woman touches a pot of boiling water.
A Increased ankle swelling Within 2 hours, she has marked erythema of the skin of the
B Increased susceptibility to bruising fingers of her hand, and small blisters appear on the finger
C Increased bouts of asthma pads. This has led to which one of the following inflammatory
D Reduced severity of urticaria responses?
E Numerous febrile episodes A Fibrinous inflammation
F Reduced arthritis pain B Granulomatous inflammation
C Purulent inflammation
16 A 19-year-old woman develops a sore throat and fever D Serous inflammation
during the past day. Physical examination shows pharyngeal E Ulceration
erythema and swelling. Laboratory findings include leukocyto-
sis. She is given naproxen. Which of the following features of 22 A 24-year-old, sexually active woman has experienced
the acute inflammatory response is most affected by this drug? lower abdominal pain for the past day. Her temperature is
A Chemotaxis 37.9° C, and on palpation, the left lower abdomen is mark-
B Emigration edly tender. Laboratory findings include a total WBC count of
C Leukocytosis 29,000/mm3 with 75% segmented neutrophils, 6% bands, 14%
D Phagocytosis lymphocytes, and 5% monocytes. Laparotomy reveals a dis-
E Vasodilation tended, fluid-filled, reddened left fallopian tube that is about
to rupture. A left salpingectomy is performed. Which of the
17 A 35-year-old woman takes acetylsalicylic acid (aspirin) following is most likely to be seen on microscopic examination
for arthritis. Although her joint pain is reduced with this ther- of the excised fallopian tube?
apy, the inflammatory process continues. The aspirin therapy A Fibroblastic proliferation
alleviates her pain mainly through reduction in the synthesis B Langhans giant cells
of which of the following mediators? C Liquefactive necrosis
A Complement C1q D Mononuclear infiltrates
B Histamine E Squamous metaplasia
C Leukotriene E4
D Nitric oxide
E Prostaglandins

C H A P T E R 3   Inflammation and Repair 21

23 A 68-year-old man has had worsening shortness of 26 A 92-year-old woman is diagnosed with Staphylococcus
breath for the past week. On physical examination, his tem- aureus pneumonia and receives a course of antibiotic thera-
perature is 38.3° C. On percussion, there is dullness over the py. Two weeks later, she no longer has a productive cough,
left lung fields. Thoracentesis performed on the left pleural but she still has a temperature of 38.1° C. A chest radiograph
cavity yields 800 mL of cloudy yellow fluid that has a WBC shows the findings in the figure. Which of the following terms
count of 2500/mm3 with 98% neutrophils and 2% lympho- best describes the outcome of the patient’s pneumonia?
cytes. A Gram stain of the fluid shows gram-positive cocci in A Abscess formation
clusters. Which of the following terms best describes the pro- B Complete resolution
cess occurring in his left pleural cavity? C Fibrous scarring
A Abscess D Chronic inflammation
B Chronic inflammation E Tissue regeneration
C Edema
D Fibrinous inflammation 27 A 29-year-old woman with a congenital ventricular
E Purulent exudate septal defect has had a persistent temperature of 38.6° C and
F Serous effusion headache for the past 3 weeks. A head CT scan shows an en-
24 An 87-year-old woman has had a cough productive of hancing 3-cm, ring like lesion in the right parietal lobe of her
yellowish sputum for the past 2 days. On examination her brain. Which of the following actions by inflammatory cells
temperature is 37° C. A chest radiograph shows bilateral has most likely produced this CT finding?
patchy infiltrates. Her peripheral blood shows leukocytosis. A A Elaboration of nitric oxide by macrophages
week later she is afebrile. Which of the following is the most B Formation of immunoglobulin by B lymphocytes
likely outcome of her pulmonary disease? C Generation of prostaglandin by endothelium
A Chronic inflammation D Production of interferon-γ by T lymphocytes
B Fibrous scarring E Release of lysosomal enzymes from neutrophils
C Neoplasia
D Resolution 28 A 37-year-old man has had midepigastric pain for the
E Ulceration past 3 months. An upper gastrointestinal endoscopy shows a
   2-cm, sharply demarcated, shallow ulceration of the gastric
antrum. Microscopic examination of a biopsy from the ulcer
25 A 53-year-old woman has experienced abdominal pain base shows angiogenesis, fibrosis, and mononuclear cell in-
for 2 weeks. She is afebrile. There is mild upper abdominal filtrates with lymphocytes, macrophages, and plasma cells.
tenderness on palpation, and bowel sounds are present. An Which of the following terms best describes this pathologic
upper gastrointestinal endoscopy is performed. The figure process?
shows microscopic examination of a biopsy specimen of a du- A Acute inflammation
odenal lesion. Which of the following pathologic processes is B Chronic inflammation
most likely present? C Fibrinous inflammation
A Abscess D Granulomatous inflammation
B Caseating granuloma E Serous inflammation
C Chronic inflammation
D Purulent exudate
E Serous effusion
F Ulceration
  

2 2 U N I T I   General Pathology

29 A 65-year-old man develops worsening congestive heart A
failure 2 weeks after an acute myocardial infarction. An echo-
cardiogram shows a markedly decreased ejection fraction. B
Now, capillaries, fibroblasts, collagen, and inflammatory cells 33 A 43-year-old man has had a cough and fever for the
have largely replaced the infarcted myocardium. Which of the past 2 months. A chest CT scan shows the findings in the fig-
following inflammatory cell types in this lesion plays the most ure (A). A transbronchial lung biopsy is performed, yielding
important role in the healing process? a specimen with the microscopic appearance shown in the
A Eosinophils figure (B). Which of the following chemical mediators is most
B Epithelioid cells important in the pathogenesis of this lesion?
C Macrophages A Bradykinin
D Neutrophils B Complement C5a
E Plasma cells C Interferon-γ
D Nitric oxide
30 A 9-year-old boy has had a chronic cough and fever E Prostaglandins
for the past month. A chest radiograph shows enlargement 34 An 8-year-old girl has had difficulty swallowing for
of hilar lymph nodes and bilateral pulmonary nodular inter- the past day. On examination, her pharynx is swollen and
stitial infiltrates. A sputum sample contains acid-fast bacilli. erythematous with an overlying yellow exudate. Laboratory
A transbronchial biopsy specimen shows granulomatous studies show neutrophilia. Streptococcus pyogenes (group A
inflammation with epithelioid macrophages and Langhans streptococcus) is cultured from her pharynx. Which of the
giant cells. Which of the following mediators is most likely following substances is most likely to increase in response to
to contribute to giant cell formation? pyrogens released by this organism?
A Complement C3b A Hageman factor
B Interferon-γ B Immunoglobulin E
C Interleukin-1 (IL-1) C Interleukin-12 (IL-12)
D Leukotriene B4 D Nitric oxide
E Tumor necrosis factor (TNF) E Prostaglandins

31 A 32-year-old woman has had a chronic cough with fever
for the past month. On physical examination, her temperature
is 37.5° C. A chest radiograph shows many small, ill-defined
nodular opacities in all lung fields. A transbronchial biopsy
specimen shows interstitial infiltrates with lymphocytes, plas-
ma cells, and epithelioid macrophages. Which of the following
infectious agents is the most likely cause of this appearance?
A Candida albicans
B Cytomegalovirus
C Enterobacter aerogenes
D Mycobacterium tuberculosis
E Plasmodium falciparum
F Staphylococcus aureus

32 One month after an appendectomy, a 25-year-old woman
palpates a small nodule beneath the skin at the site of the healed
right lower quadrant sutured incision. The nodule is excised,
and microscopic examination shows macrophages, collagen
deposition, small lymphocytes, and multinucleated giant cells.
Polarizable, refractile material is seen in the nodule. Which of
the following complications of the surgery best accounts for
these findings?
A Abscess formation
B Chronic inflammation
C Exuberant granulation tissue
D Granuloma formation
E Healing by second intention
  

C H A P T E R 3   Inflammation and Repair 23

35 A 41-year-old man has had a severe headache for the of which of the following extracellular matrix components is
past 2 days. On examination, his temperature is 39.2° C. A most affected by this deficiency?
lumbar puncture is performed, and the cerebrospinal fluid A Collagen
obtained has a WBC count of 910/mm3 with 94% neutrophils B Elastin
and 6% lymphocytes. Which of the following substances is the C Fibronectin
most likely mediator for the fever observed in this man? D Integrin
A Bradykinin E Laminin
B Histamine   
C Leukotriene B4
D Nitric oxide 40 In an experiment, glass beads are embolized into the
E Tumor necrosis factor (TNF) coronary arteries of rats, resulting in myocardial injury. After
7 days, sections of the myocardium are studied using light mi-
36 A 43-year-old man with a ventricular septal defect has croscopy. The microscopic appearance of one of these sections
had a cough and fever for the past 2 days. On examination, he is shown in the figure. Which of the following mediators is
has a temperature of 37.6° C and a cardiac murmur. A blood most likely being expressed to produce this appearance?
culture grows Streptococcus, viridans group. His erythrocyte A Epidermal growth factor
sedimentation rate (ESR) is increased. Microbial cells are opso- B Interleukin-2 (IL-2)
nized and cleared. Which of the following chemical mediators C Leukotriene B4
is most important in producing these findings? D Thromboxane A2
A Bradykinin E Tumor necrosis factor (TNF)
B C-reactive protein F Vascular endothelial growth factor
C Interferon-γ 41 A 20-year-old woman undergoes cesarean section to
D Nitric oxide deliver a term infant, and the lower abdominal incision is su-
E Prostaglandin tured. The sutures are removed 1 week later. Which of the
F Tumor necrosis factor (TNF) following statements best describes the wound site at the time
of suture removal?
37 In an experiment, a group of test animals is infected with A Collagen degradation exceeds synthesis
viral hepatitis. Two months later, complete recovery of the B Granulation tissue is still present
normal liver architecture is observed microscopically. A con- C No more wound strength will be gained
trol test group is infected with bacterial organisms, and after D Type IV collagen predominates
the same period of time, fibrous scars from resolving hepatic E Wound strength is 80% of normal tissue
abscesses are seen microscopically. Which of the following   
factors best explains the different outcomes for the two test
groups?
A Extent of damage to the biliary ducts
B Extent of the hepatocyte injury
C Injury to the connective tissue framework
D Location of the lesion within the liver
E Nature of the injurious etiologic agent

38 A 51-year-old woman tests positive for hepatitis A anti-
body. Her serum AST level is 275 U/L, and ALT is 310 U/L.
One month later, these enzyme levels have returned to normal.
Which phase of the cell cycle best describes the hepatocytes 1
month after her infection?
A G0
B G1
C S
D G2
E M

39 A 54-year-old man undergoes laparoscopic hernia re-
pair. In spite of the small size of the incisions, he has poor
wound healing. Further history reveals that his usual diet has
poor nutritional value and is deficient in vitamin C. Synthesis

2 4 U N I T I   General Pathology

A Collagen deposition
B Elaboration of VEGF
C Neutrophil infiltration
D Reepithelialization
E Serine proteinase production
  

42 A 24-year-old man with acute appendicitis undergoes 46 An 18-year-old man lacerated his left ear and required
surgical removal of the inflamed appendix. The incision site is sutures. The sutures were removed 1 week later. Wound
sutured. A trichrome-stained section representative of the site healing continued, but the site became disfigured over the
with blue appearing collagen is shown in the figure. How long next 2 months by the process shown in the figure. Which of
after the surgery would this appearance most likely be seen? the following terms best describes the process that occurred
A 1 day in this man?
B 2 to 3 days A Dehiscence
C 4 to 5 days B Keloid formation
D 2 weeks C Organization
E 1 month D Resolution
E Secondary union
43 A 40-year-old man underwent laparotomy for a per-
forated sigmoid colon diverticulum. A wound infection 47 A 58-year-old man had chest pain persisting for 4 hours.
complicated the postoperative course, and surgical wound A radiographic imaging procedure showed an infarction in-
dehiscence occurred. Primary closure was no longer pos- volving a 4-cm area of the posterior left ventricular free wall.
sible, and the wound “granulated in.” Six weeks later, the Laboratory findings showed serum creatine kinase of 600
wound is only 10% of its original size. Which of the fol- U/L. Which of the following pathologic findings would most
lowing processes best accounts for the observed decrease in likely be seen in the left ventricular lesion 1 month later?
wound size over the past 6 weeks? A Chronic inflammation
A Elaboration of adhesive glycoproteins B Coagulative necrosis
B Increase in synthesis of collagen C Complete resolution
C Inhibition of metalloproteinases D Fibrous scar
D Myofibroblast contraction E Nodular regeneration
E Resolution of subcutaneous edema

44 In an experiment involving observations on wound
healing, researchers noted that intracytoplasmic cytoskel-
etal elements, including actin, interact with the extracellular
matrix to promote cell attachment and migration in wound
healing. Which of the following substances is most likely re-
sponsible for such interaction between the cytoskeleton and
the extracellular matrix?
A Epidermal growth factor
B Fibronectin
C Integrin
D Platelet-derived growth factor
E Type IV collagen
F Vascular endothelial growth factor

45 A 23-year-old woman receiving corticosteroid therapy
for an autoimmune disease has an abscess on her upper outer
right arm. She undergoes minor surgery to incise and drain
the abscess, but the wound heals poorly over the next month.
Which of the following aspects of wound healing is most likely
to be deficient in this patient?

C H A P T E R 3   Inflammation and Repair 25

ANSWERS proposed, including formation of interendothelial gaps by
contraction of endothelium. This contraction can be caused
1   C  Macrophages in tissues derived from circulating by mediators such as histamine and leukotrienes. The vessels
blood monocytes are phagocytic cells that respond to a va- then become more “leaky,” and the fluid leaves the intravas-
riety of stimuli, and they represent the janitorial crew of the cular space to accumulate extravascularly, forming effusions
body. The other cells listed are not phagocytes. B cells can in body cavities or edema within tissues. Arteriolar vasocon-
differentiate into plasma cells secreting antibodies to neutral- striction is a transient response to injury that helps d­ iminish
ize infectious agents. Fibroblasts form collagen as part of a blood loss. Platelets adhere to damaged endothelium and
healing response. Mast cells can release a variety of inflam- promote hemostasis. Lymphatic obstruction results in the ac-
matory mediators. T cells are a key part of chronic inflamma- cumulation of protein-rich lymph and lymphocytes, produc-
tory processes in cell-mediated immune responses. ing a chylous effusion within a body cavity. After neutrophils
reach the site of tissue injury outside of the vascular space,
PBD9 70–71  BP9 30  PBD8 51–52  BP8 38 they release lysosomal enzymes that promote liquefaction.

2   D  These signs and symptoms suggest acute bacterial PBD9 73–74  BP9 33–34  PBD8 47  BP8 32
pneumonia. Such infections induce an acute inflammation
dominated by neutrophils that fill alveoli, as shown in the 6  E  Leukocyte rolling is the first step in transmigration
figure, and are coughed up, which gives the sputum its yel- of neutrophils from the vasculature to the tissues. Rolling
lowish, purulent appearance. Langhans giant cells are seen depends on interaction between selectins (P-selectin and
with granulomatous inflammatory responses. Macrophages E-selectin on endothelial cells, and L-selectin on neutro-
become more numerous after initiation of acute events, phils) and their sialylated ligands (e.g., sialylated Lewis
cleaning up tissue and bacterial debris through phagocyto- X). Integrins are involved in the next step of transmigra-
sis. Mast cells are better known as participants in allergic tion, during which there is firm adhesion between neutro-
and anaphylactic responses. Lymphocytes are a feature of phils and endothelial cells. Complement C3b acts as an
chronic inflammation. opsonin to facilitate phagocytosis. Leukotriene B4 is a che-
motactic agent. NADPH oxidase is involved in phagocytic
PBD9 71, 73  BP9 30–32  PBD8 45, 75  BP8 32–33, 38 cell microbicidal activity.

3   E  Nonhuman microbial substances such as double- PBD9 75–76  BP9 35–36  PBD8 49–50  BP8 36–37
stranded RNA of viruses, bacterial DNA, and bacterial en-
dotoxin, can be recognized by Toll-like receptors (TLRs) on 7  B  Chemokines include many molecules that are chemo-
human cells as part of an innate defense mechanism against tactic for neutrophils, eosinophils, lymphocytes, monocytes,
infection. Caspase-1 is activated by an inflammasome com- and basophils. Bradykinin causes pain and increased vascu-
plex of proteins responding to bacterial organisms, and pro- lar permeability. Complement C3a causes increased vascular
duces biologically active interleukin-1 (IL-1). Complement permeability by releasing histamine from mast cells. Hista-
receptors on inflammatory cells recognize complement com- mine causes vascular leakage. Prostaglandins have multiple
ponents that aid in triggering immune responses through co- actions, but they do not cause chemotaxis.
stimulatory signals. Lectins found on cell surfaces can bind
a variety of substances, such as fungal polysaccharides, that PBD9 75–76  BP9 37–39  PBD8 50–51  BP8 49
trigger cellular defenses. T cell receptors respond to peptide
antigens to trigger a cell-mediated immune response. 8  B  This immunoglobulin deficiency prevents opsoniza-
tion and phagocytosis of microbes. Deficiency of integrins
PBD9 72, 79  BP9 32–33  PBD8 51–52  BP8 39 and selectins, or a defect in microtubules, would prevent
adhesion and locomotion of neutrophils. H2O2 production
4  E  The formation of an exudate containing a significant is part of the oxygen-dependent killing mechanism. This
amount of protein and cells depends on the “leakiness” of mechanism is intact in this patient because the neutrophils
blood vessels, principally venules. When exudation has oc- are able to kill bacteria when immunoglobulins in normal
curred, the protein content of the extravascular space in- serum allow phagocytosis.
creases, and extravascular colloid osmotic pressure increases,
causing extracellular fluid accumulation. Leukocytosis alone PBD9 78  BP9 37–39  PBD8 51–52  BP8 38
is insufficient for exudation because the leukocytes must be
driven to emigrate from the vessels by chemotactic factors. 9  B  Myeloperoxidase is present in the azurophilic gran-
The lymphatics scavenge exuded proteinaceous fluid and ules of neutrophils. It converts H2O2 into HOCl–, a power-
reduce the amount of extravascular and extracellular fluid. ful oxidant and antimicrobial agent. Degranulation occurs
Sodium and water retention helps drive transudation of fluid. as phagolysosomes are formed with engulfed bacteria in
phagocytic vacuoles within the neutrophil cytoplasm. Oxy-
PBD9 73  BP9 33–34  PBD8 46–47  BP8 34 gen consumption with an oxidative or respiratory burst after
phagocytosis is aided by glucose oxidation and activation
5   B  Exudation of fluid from venules and capillaries is a of neutrophil NADPH oxidase, resulting in generation of
key component of the acute inflammatory process. Several
mechanisms of increased vascular permeability have been

2 6 U N I T I   General Pathology

superoxide that is converted by spontaneous dismutation 13  B  Interferon-γ secreted from lymphocytes stimulates
to H2O2. In contrast, prostaglandin production depends on monocytes and macrophages, which secrete their own cyto-
a functioning cyclooxygenase pathway of arachidonic acid kines that further activate lymphocytes. Interferon-γ also is im-
metabolism. portant in transforming macrophages into epithelioid cells in
a granulomatous inflammatory response. Histamine released
PBD9 79–80  BP9 38–39  PBD8 53  BP8 39 from mast cells is a potent vasodilator, increasing vascular
permeability. Leukotriene B4, generated in the lipoxygenase
10  B  The respiratory, or oxidative, burst of neutrophils pathway of arachidonic acid metabolism, is a potent neutrophil
generates reactive oxygen species (e.g., superoxide anion) chemotactic factor. Nitric oxide generated by macrophages
that are important in destruction of engulfed bacteria. This aids in destruction of microorganisms; nitric oxide released
burst can be quantitated by flow cytometric analysis. Neu- from endothelium mediates vasodilation and inhibits platelet
trophil attachment to endothelium is aided by adhesion mol- activation. Binding of agonists such as epinephrine, collagen,
ecules on both the endothelium and the neutrophil surface. or thrombin to platelet surface receptors activates phospholi-
These molecules include selectins and integrins. Myelopoi- pase C, which catalyzes the release of arachidonic acid from
esis does not depend on generation of superoxide. Bacteria two of the major membrane phospholipids, phosphatidylino-
are opsonized by complement C3b and IgG, allowing the sitol and phosphatidylcholine. Tumor necrosis factor (TNF),
bacteria to be more readily phagocytosed. produced by activated macrophages, mediates many systemic
effects, including fever, metabolic wasting, and hypotension.
PBD9 79  BP9 38–39  PBD8 53  BP8 39
PBD9 94–95  BP9 56  PBD8 52  BP8 55–56
1 1  D  During acute inflammation, in the first stage of ex-
travasation, the neutrophils “roll over” the endothelium. At 14  C  Histamine is found in abundance in mast cells, which
this stage, the adhesion between the neutrophils and endo- are normally present in connective tissues next to blood
thelial cells is weak. Rolling is mediated by binding of selectins vessels beneath mucosal surfaces in airways. Binding of an
to sialylated oligosaccharides. The next step, firm adhesion, antigen (allergen) to IgE antibodies that have previously
is mediated by binding of integrins on the leukocytes to their attached to the mast cells by the Fc receptor triggers mast
receptors, intercellular adhesion molecule-1 or vascular cell cell degranulation, with release of histamine. This response
adhesion molecule-1 (VCAM-1), on endothelial cells. Inte- causes increased vascular permeability and mucous secre-
grins have two chains, α and β. A genetic lack of β chains tions. Bradykinin, generated from the kinin system on surface
prevents firm adhesion of leukocytes to endothelial cells. contact of Hageman factor with collagen and basement mem-
This process depends on adhesion molecules expressed on brane from vascular injury, promotes vascular permeability,
the neutrophils and endothelial cells. Formation of HOCl– re- smooth muscle contraction, and pain. Complement C5a is a
quires myeloperoxidase released from neutrophil granules. potent chemotactic factor for neutrophils. Interleukin-1 (IL-1)
Phagocytosis of opsonized organisms depends on engulf- and tumor necrosis factor (TNF), both produced by activated
ment, which requires contractile proteins in the neutrophil macrophages, mediate many systemic effects, including fe-
cytoplasm. Neutrophil migration to a site of infection depends ver, metabolic wasting, and hypotension. Phospholipase C,
on the presence of chemotactic factors such as complement which catalyzes the release of arachidonic acid, is generated
C5a that bind to the neutrophil and activate phospholipase from platelet activation.
C to begin a series of events that culminate in the influx of
calcium, which triggers contractile proteins. The respiratory PBD9 83  BP9 55–56  PBD8 57–58  BP8 32, 34
burst to kill phagocytized organisms depends on NADPH
oxidase, and a deficiency of this enzyme leads to chronic 15  F  The COX-2 enzyme is inducible with acute inflamma-
granulomatous disease. tory reactions, particularly in neutrophils, in synovium, and
in the central nervous system. The cyclooxygenase pathway
PBD9 75–76  BP9 35–36  PBD8 49–50  BP8 36–37 of arachidonic acid metabolism generates prostaglandins,
which mediate pain, fever, and vasodilation. Ankle swelling
1 2  E  Monocytes transforming to macrophages contain is most likely to result from peripheral edema secondary to
cytokine-inducible nitric oxide synthase (iNOS), which gener- congestive heart failure. Increased susceptibility to bruising
ates nitric oxide. Nitric oxide, by itself and on interaction with results from prolonged glucocorticoid administration, which
other reactive oxygen species, has antimicrobial activity. CD4 also causes leukopenia. Asthma results from bronchocon-
or CD8 lymphocytes can be the source for interferon-γ (IFN-γ), striction mediated by leukotrienes that are generated by the
which stimulates macrophage production of NOS. Endothe- lipoxygenase pathway of arachidonic acid metabolism. In-
lial cells contain a form of NOS (eNOS) that acts to promote hibition of histamine released from mast cells helps reduce
vasodilation. B lymphocytes produce immunoglobulins that urticaria. Fever can be mediated by prostaglandin release,
can opsonize bacteria. Basophils release histamine and arachi- not inhibition.
donic acid metabolites, which participate in the acute inflam-
matory process. Natural killer cells have Fc receptors and can PBD9 84–85  BP9 46–47  PBD8 58–60  BP8 47–48
lyse IgG-coated target cells; they also generate IFN-γ. Neutro-
phils can phagocytize microbes, but they use NAPDH oxidase 16  E  Naproxen, a nonsteroidal anti-inflammatory drug,
and enzymes other than NOS to kill the microbes. targets the cyclooxygenase pathway of arachidonic acid
metabolism and leads to reduced prostaglandin generation.
PBD9 79–80  BP9 54  PBD8 54  BP8 40

C H A P T E R 3   Inflammation and Repair 27

Prostaglandins promote vasodilation at sites of inflamma- 2 1  D  Serous inflammation is the mildest form of acute in-
tion. Chemotaxis is a function of various chemokines, and flammation. A blister is a good example of serous inflamma-
complement C3b may promote phagocytosis, but neither is tion. It is associated primarily with exudation of fluid into the
affected by aspirin. Leukocyte emigration is aided by vari- subcorneal or subepidermal space. Because the injury is mild,
ous adhesion molecules. Leukocyte release from bone marrow the fluid is relatively protein-poor. A protein-rich exudate
can be driven by the cytokines interleukin-1 (IL-1) and tumor results in fibrin accumulation. Granulomatous inflammation
necrosis factor (TNF). is characterized by collections of transformed macrophages
called epithelioid cells. Acute inflammatory cells, mainly neu-
PBD9 83–84  BP9 46–47  PBD8 58–59  BP8 47–48 trophils, exuded into a body cavity or space form a purulent
(suppurative) exudate, typically associated with liquefactive
17  E  Prostaglandins are produced through the cyclooxy- necrosis. Loss of the epithelium leads to ulceration.
genase pathway of arachidonic acid metabolism. Aspirin
and other nonsteroidal anti-inflammatory drugs block the PBD9 90  BP9 43  PBD8 67–68  BP8 43
synthesis of prostaglandins, which can produce pain. Com-
plement C1q is generated in the initial stage of complement 2 2  C  This patient is experiencing an acute inflammatory
a­ctivation, which can eventually result in cell lysis. Hista- response, with edema, erythema, and pain of short duration.
mine is mainly a vasodilator. Leukotrienes are generated by Neutrophils form an exudate and release various proteases,
the lipoxygenase pathway, which is not blocked by aspirin. which can produce liquefactive necrosis, starting at the mucosa
Nitric oxide released from endothelium is a vasodilator. and extending through the wall of the tube. This mechanism
results in perforation. Fibroblasts are more likely participants
PBD9 83–84  BP9 46–47  PBD8 58–59  BP8 47–48 in chronic inflammatory responses and in healing responses,
generally appearing more than 1 week after the initial event.
18  C  Endothelial cells can release nitric oxide to promote Langhans giant cells are a feature of granulomatous inflam-
vasodilation in areas of ischemic injury. Bradykinin mainly mation. Mononuclear infiltrates are more typical of chronic in-
increases vascular permeability and produces pain. Leuko­ flammation of the fallopian tube, in which rupture is less likely.
triene E4, platelet-activating factor, and thromboxane A2 have Epithelial metaplasia is most likely to occur in the setting of
vasoconstrictive properties. chronic irritation with inflammation.

PBD9 80  BP9 49  PBD8 60–61  BP8 49–50 PBD9 91–92  BP9 30–31  PBD8 45–46  BP8 32–33

19  A  Activation of complement may occur via microbial 2 3  E  Bacterial infections often evoke an acute inflammatory
cell wall components such as polysaccharides (alternative response dominated by neutrophils. The extravasated neutro-
pathway) or mannose (lectin pathway), or antibody attached phils attempt to phagocytose and kill the bacteria. In the pro-
to surface antigens (classic pathway). A variety of comple- cess, some neutrophils die, and the release of their ­lysosomal
ment components are generated, including complement C5a, enzymes can cause liquefactive necrosis of the tissue. This
a neutrophil chemoattractant; complement C3b, an opsonin; liquefied tissue debris and both live and dead neutrophils
and complement C5-9, the membrane attack complex. The comprise pus, or purulent exudate. Such an exudate is typi-
remaining options are more closely associated with coagula- cal of bacterial infections that involve body cavities. Another
tion. Fibrin is generated by the coagulation system, but not term for purulent exudate in the pleural space is empyema. An
with anticoagulation. Kallikrein may aid in generation of abscess is a localized collection of neutrophils within tissues.
bradykinin and plasmin, but participates just in complement Chronic inflammation occurs when there is a preponderance
C5a generation. Plasmin is generated from plasminogen and of mononuclear cells, such as lymphocytes, macrophages, and
helps lyse clots. Thrombin is generated by the coagulation plasma cells, in a process that has gone on for more than a few
cascade. days—more likely weeks or months—or that accompanies re-
peated bouts of acute inflammation. Edema refers to increased
PBD9 88  BP9 50–51  PBD8 63  BP8 51 cellular and interstitial fluid collection within tissues, leading
to tissue swelling. In fibrinous inflammation, exudation of
20  E  Ongoing activation of coagulation generates an blood proteins (including fibrinogen, which polymerizes to
i­nflammatory response that further amplifies coagulation, cre- fibrin) gives a grossly shaggy appearance to surfaces overly-
ating a vicious cycle. Protein C antagonizes coagulation factor ing the inflammation. A serous effusion is a watery-appearing
V, which catalyzes activation of prothrombin to thrombin, transudate that resembles an ultrafiltrate of blood plasma,
thereby breaking the cycle of thrombin generation. Comple- with a low cell and protein content.
ment components can become activated by plasmin (C3) and
kallikrein (C5), forming anaphylatoxins (C3a and C5a) that PBD9 91  BP9 31–32  PBD8 46, 68  BP8 33, 38
promote inflammation. Fibrin, the end product of coagulation
pathways, forms a meshwork entrapping platelets and creat- 24  D  If inflammation is limited and brief, and the in-
ing a plug. Kallikrein is generated by activation of Hageman volved tissue can regenerate, then resolution is the likely
factor (XII) and leads to formation of bradykinin. Plasmin is outcome, without significant loss of function. In older per-
generated from plasminogen activated by thrombosis to pro- sons this may take longer, but can still occur. Multiple bouts
mote clot lysis. of acute inflammation, or ongoing inflammation, can become
chronic, and there tends to be loss of some tissue function. If
PBD9 89  BP9 51–52  PBD8 64–65  BP8 51–52

2 8 U N I T I   General Pathology

significant tissue destruction occurs, there is likely to be for- 2 8  B  One outcome of acute inflammation with ulceration
mation of a fibrous scar in the region of the tissue loss. Acute is chronic inflammation. This is particularly true when
inflammation is not a preneoplastic event. Ulceration refers the inflammatory process continues for weeks to months.
to loss of an epithelial surface with acute inflammation; if the Chronic inflammation is characterized by tissue destruc-
epithelium regenerates, then there is resolution. tion, mononuclear cell infiltration, and repair. In acute
inflammation, the healing process of fibrosis and angio-
PBD9 92–93  BP9 42  PBD8 66–67  BP8 42–43 genesis has not begun. In fibrinous inflammation, typically
involving a mesothelial surface, there is an outpouring
2 5  F  Inflammation involving an epithelial surface may of protein-rich fluid that results in precipitation of fibrin.
cause such extensive necrosis that the surface becomes Granulomatous inflammation is a form of chronic inflam-
eroded, forming an ulcer. If the inflammation continues, mation in which epithelioid macrophages form aggregates.
the ulcer can continue to penetrate downward into submu- Serous inflammation is an inflammatory process involving
cosa and muscularis. Alternatively, the ulcer may heal, or it a mesothelial surface (e.g., lining of the pericardial cavity),
may remain chronically inflamed. An abscess is a localized with an outpouring of fluid having little protein or cellular
collection of neutrophils in tissues. A caseating granuloma content.
is granulomatous inflammation with central necrosis; the
necrosis has elements of both liquefaction and coagula- PBD9 92–93  BP9 53–55  PBD8 68–69  BP8 44, 53–55
tive necrosis. Chronic inflammation occurs when there is
a preponderance of mononuclear cells, such as lympho- 2 9  C  Macrophages, present in such lesions, play a promi-
cytes, macrophages, and plasma cells, in a process that has nent role in the healing process. Activated macrophages can
gone on for more than a few days—more likely weeks or secrete various cytokines that promote angiogenesis and fi-
months—or that accompanies repeated bouts of acute in- brosis, including platelet-derived growth factor, fibroblast
flammation. Pus, or a purulent exudate, appears semiliquid growth factor, interleukin-1 (IL-1), and tumor necrosis factor
and yellowish because of the large numbers of granulocytes (TNF). Eosinophils are most prominent in allergic inflamma-
present. A serous effusion is a watery-appearing transudate tions and in parasitic infections. Epithelioid cells, which are
that resembles an ultrafiltrate of blood plasma, with a low aggregations of activated macrophages, are typically seen
cell and protein content. with granulomatous inflammation, and the healing of acute
inflammatory processes does not involve granulomatous in-
PBD9 91–92  BP9 44  PBD8 68–69  BP8 44–45 flammation. Neutrophils are most numerous within the initial
48 hours after infarction, but are not numerous after the first
26  A  The rounded density in the right lower lobe of the week. Plasma cells can secrete immunoglobulins and are not
lung has liquefied contents that form a central air-fluid level. instrumental to healing of an area of tissue injury.
There are surrounding infiltrates. The formation of a fluid-
filled cavity after infection with Staphylococcus aureus suggests PBD9 92–94  BP9 54  PBD8 54, 71  BP8 54–55
that liquefactive necrosis has occurred. The cavity is filled
with tissue debris and viable and dead neutrophils (pus). Lo- 3 0  B  Interferon-γ is secreted by activated T cells and is an
calized, pus-filled cavities are called abscesses. Some bacterial important mediator of granulomatous inflammation. It causes
organisms, such as S. aureus, are more likely to be pyogenic, activation of macrophages and their transformation into epi-
or pus-forming. With complete resolution, the structure of thelioid cells and then giant cells. Complement C3b acts as an
the lung remains almost unaltered. Scarring or fibrosis may opsonin in acute inflammatory reactions. Interleukin-1 (IL-1)
follow acute inflammation as the damaged tissue is replaced can be secreted by macrophages to produce various effects,
by fibrous connective tissue. Most bacterial pneumonias re- including fever, leukocyte adherence, fibroblast proliferation,
solve, and progression to continued chronic inflammation is and cytokine secretion. Leukotriene B4 induces chemotaxis in
uncommon. Lung tissue, in contrast to liver, is incapable of acute inflammatory processes. Tumor necrosis factor (TNF)
regeneration, except for epithelium and endothelium. can be secreted by activated macrophages and induces activa-
tion of lymphocytes and proliferation of fibroblasts, which are
PBD9 91  BP9 43–44  PBD8 68–69  BP8 42, 44–45 other elements of a granuloma.

27  E  This patient has an infective endocarditis with septic PBD9 97–98  BP9 56  PBD8 52  BP8 55–56
embolization, producing a cerebral abscess. The tissue de-
struction that accompanies abscess formation as part of acute 31  D  These findings suggest a granulomatous inflamma-
inflammatory processes occurs from lysosomal enzymatic de- tion, and tuberculosis is a common cause. Candida is often a
struction, aided by release of reactive oxygen species. Nitric commensal organism in the oropharyngeal region and rarely
oxide generated by macrophages aids in destruction of infec- causes pneumonia in healthy (non-immunosuppressed) indi-
tious agents. Immunoglobulin formed by B cells neutralizes viduals. Viral infections tend to produce a mononuclear inter-
and opsonizes infectious agents. Prostaglandins produced stitial inflammatory cell response. Bacteria such as Enterobacter
by endothelium promote vasodilation. Interferon-γ released and Staphylococcus are more likely to produce acute inflamma-
from lymphocytes plays a major role in chronic and granulo- tion. Plasmodium produces malaria, a parasitic infection without
matous inflammatory responses. a significant degree of lung involvement.

PBD9 91  BP9 43–44  PBD8 68–69  BP8 42–43 PBD9 97–98  BP9 56–57  PBD8 73–74  BP8 56–57

C H A P T E R 3   Inflammation and Repair 29

32  D  The polarizable material is the suture, and a mul- of Hageman factor with collagen and basement membrane
tinucleated giant cell reaction, typically with foreign body from vascular injury, promotes vascular permeability,
giant cells, is characteristic of a granulomatous reaction to smooth muscle contraction, and pain. Histamine released
foreign material. Granulation tissue may form a nodular ap- from mast cells is a potent vasodilator, increasing vascular
pearance, and begins to appear 3 to 5 days following injury, permeability. Leukotriene B4, generated in the lipoxygenase
but is unlikely to persist for a month. Chronic inflammation pathway of arachidonic acid metabolism, is a potent neu-
alone is unlikely to produce a localized nodule with giant trophil chemotactic factor. Nitric oxide generated by macro-
cells. Edema refers to accumulation of fluid in the intersti- phages aids in destruction of microorganisms; nitric oxide
tial space. It does not produce a cellular nodule. If a large, released from endothelium mediates vasodilation and in-
gaping wound is not closed by sutures, it can granulate it hibits platelet activation.
and myofibroblastic contraction eventually helps close the
wound by second intention. PBD9 99  BP9 48–49  PBD8 61, 74  BP8 49

PBD9 97–98  BP9 56–57  PBD8 74  BP8 56 3 6  B  This acute inflammatory process leads to production
of acute-phase reactants, such as C-reactive protein (CRP), fi-
33  C  Figure A shows diffuse reticulonodular pulmonary brinogen, and serum amyloid A (SAA) protein. These proteins,
densities, and Figure B shows noncaseating granulomas with particularly fibrinogen, and immunoglobulins increase RBC
many epithelioid cells and two prominent large Langhans gi- rouleaux formation to increase the erythrocyte sedimenta-
ant cells. If special stains and/or cultures for organisms (usu- tion rate (ESR), which is a nonspecific indicator of inflamma-
ally mycobacteria or fungi) are negative, then this is likely tion. CRP production is upregulated by interleukin-6 (IL-6),
sarcoidosis. Macrophage stimulation and transformation to whereas fibrinogen and SAA are upregulated mainly by tumor
epithelioid cells and giant cells are characteristic of granu- necrosis factor (TNF) and interleukin-1 (IL-1). Interferon-γ is
loma formation. Interferon-γ promotes the formation of epi- a potent stimulator of macrophages. Nitric oxide can induce
thelioid cells and giant cells. Bradykinin is released in acute vasodilation or can assist in microbial killing within macro-
inflammatory responses and results in pain. Complement C5a phages. Prostaglandins are vasodilators.
is chemotactic for neutrophils. Although occasional neutro-
phils are seen in granulomas, neutrophils do not form a major PBD9 99–100  BP9 57–58  PBD8 74–75  BP8 57
component of granulomatous inflammation. Macrophages
can release nitric oxide to destroy other cells, but nitric oxide 3 7  C  Hepatocytes are stable cells with an extensive abil-
does not stimulate macrophages to form a granulomatous re- ity to regenerate. The ability to restore normal architecture
sponse. Prostaglandins are mainly involved in the causation of an organ such as the liver depends on the viability of
of vasodilation and pain in acute inflammatory responses. the supporting connective tissue framework. If the connec-
tive tissue cells are not injured, hepatocyte regeneration can
PBD9 97–98  BP9 56–57  PBD8 73–74  BP8 56–57 restore normal liver architecture. This regeneration occurs in
many cases of viral hepatitis. A liver abscess associated with
34  E  The findings here are those of strep throat with acute liquefactive necrosis of hepatocytes and the supporting con-
inflammation. Bacterial organisms often lead to fever accom- nective tissue heals by scarring. The other options listed may
panying infection through release of exogenous pyrogens explain the amount of liver injury, but not the nature of the
that induce inflammatory cells to release endogenous pyro- response.
gens such as tumor necrosis factor (TNF) and interleukin-1
(IL-1). The pyrogens stimulate prostaglandin synthesis in the PBD9 101–102  PBD8 81  BP8 70
hypothalamus to “reset the thermostat,” so that fever occurs
as a sign of the acute inflammatory response. Hageman fac- 3 8  A  Hepatocytes are quiescent (stable) cells that can reen-
tor initiates the coagulation cascade. Immunoglobulin E is ter the cell cycle and proliferate in response to hepatic injury,
often increased in response to inflammatory responses with enabling the liver to regenerate partially. Acute hepatitis
allergens and with invasive parasites. Interleukin-12 (IL-12) results in hepatocyte necrosis, marked by elevations in AST
released by macrophages stimulates T-cell responses. Nitric and ALT. After the acute process has ended, cells return to
oxide generated in endothelium leads to vasodilation, where- the G0 phase, and the liver becomes quiescent again.
as nitric oxide produced in macrophages aids in microbial
killing. PBD9 101–102  PBD8 93  BP8 70  BP7 64

PBD9 99  BP9 57  PBD8 74–75  BP8 57 3 9  A  Vitamin C deficiency leads to scurvy, with reduced
lysyl oxidase enzyme activity that helps cross-link fibrillar
35  E  Fever is produced by various inflammatory media- collagens to provide tensile strength. Though elastin is a fi-
tors, but the major cytokines that produce fever are inter- brillar protein, it tends to regenerate poorly in scar tissue,
leukin-1 (IL-1) and tumor necrosis factor (TNF), which are even with the best of nutrition, explaining why a scar does
produced by macrophages and other cell types. IL-1 and not stretch like the skin around it. The other listed choices
TNF can have autocrine, paracrine, and endocrine effects. are glycoproteins that have an adhesive quality and are not
They mediate the acute phase responses, such as fever, vitamin C dependent.
nausea, and neutrophil release from bone marrow. Brady-
kinin, generated from the kinin system on surface contact PBD9 106  BP9 69

3 0 U N I T I   General Pathology

4 0  F  The figure shows a subacute infarction with granu- that modulate cell growth, differentiation, and migration
lation tissue formation containing numerous capillaries during wound healing. Epidermal growth factor stimulates
stimulated by vascular endothelial growth factor, repre- epithelial cell and fibroblast proliferation. Platelet-derived
senting a healing response. Epidermal growth factor aids in growth factor (PDGF) can be produced by endothelium,
reepithelialization of a surface wound. Interleukin-2 (IL-2) macrophages, smooth muscle cells, and platelets; PDGF me-
mediates lymphocyte activation. Leukotriene B4 mediates diates migration and proliferation of fibroblasts and smooth
vasoconstriction and bronchoconstriction. Thromboxane A2 muscle cells and migration of monocytes. Type IV collagen is
aids vasoconstriction and platelet aggregation. Tumor ne- found in basement membranes on which cells are anchored.
crosis factor (TNF) induces endothelial activation and many Vascular endothelial growth factor promotes angiogenesis
responses that occur secondary to inflammation, including (capillary proliferation) through endothelial cell proliferation
fever, loss of appetite, sleep disturbances, hypotension, and and migration in a healing response.
increased corticosteroid production.
PBD9 104–105  BP9 63–64  PBD8 96–97  BP8 67–68
PBD9 106–107  BP9 66  PBD8 102–103  BP8 70–71
4 5  A  Glucocorticoids inhibit wound healing by impairing
41  A  At 1 week, wound healing is incomplete, and gran- collagen synthesis. This is a desirable side effect if the amount of
ulation tissue is still present. More collagen is synthesized scarring is to be reduced, but it results in the delayed healing of
in the following weeks. Wound strength peaks at about surgical wounds. Angiogenesis driven by vascular endothelial
80% by 3 months. Type IV collagen is found in basement growth factor (VEGF) is not significantly affected by corticoste-
membranes. roids. Neutrophil infiltration is not prevented by glucocorticoids.
Reepithelialization, in part driven by epidermal growth factor, is
PBD9 106–108  BP9 70–71  PBD8 103, 106  BP8 74–77 not affected by corticosteroid therapy. Serine proteinases are
important in wound remodeling.
42  E  The figure shows dense collagen with some remain-
ing dilated blood vessels, typical of the final phase of wound PBD9 106  BP9 69  PBD8 106  BP8 77
healing, which is extensive by the end of the first month. On
day 1, the wound is filled only with fibrin and inflamma- 46  B  The healing process sometimes results in an exuber-
tory cells. Macrophages and granulation tissue are seen 2 to ant production of collagen, giving rise to a keloid, which is a
3 days postoperatively. Neovascularization is most promi- prominent raised, nodular scar, as shown in the figure. This
nent by days 4 and 5. By week 2, collagen is prominent, and tendency may run in families. Dehiscence occurs when a
fewer vessels and inflammatory cells are seen. wound pulls apart. Organization occurs as granulation tissue
is replaced by fibrous tissue. If normal tissue architecture is
PBD9 107  BP9 71  PBD8 104–105  BP8 75–76 restored, resolution of inflammation has occurred. Second-
ary union describes the process by which large wounds fill
4 3  D  Wound contraction is a characteristic feature of in and contract.
healing by second intention that occurs in larger wounds.
Collagen synthesis helps fill the defect, but does not contract PBD9 109–110  BP9 69  PBD8 106  BP8 77
it. Adhesive glycoproteins such as fibronectin help to main-
tain a cellular scaffolding for growth and repair, but they do 47  D  The elevated creatine kinase level indicates that myo-
not contract. The inhibition of metalloproteinases leads to cardial necrosis has occurred. A fibrous scar gradually replaces
decreased degradation of collagen and impaired connective the area of myocardial necrosis. Chronic inflammation is typi-
tissue remodeling in wound repair. Edema diminishes over cally driven by ongoing stimuli such as persistent infection,
time, but this does not result in much contraction. autoimmunity, or irritation from endogenous or exogenous
chemical agents, and it is not a feature of ischemic myocardial
PBD9 107–108  BP9 70–72  PBD8 104–105  BP8 74–75 injury. Coagulative necrosis is typical of myocardial infarction,
but after 1 month, a scar would be present. The destruction of
44  C  Integrins interact with the extracellular matrix pro- myocardial fibers precludes complete resolution. Nodular
teins (e.g., fibronectin). Engagement of integrins by extracel- regeneration is typical of hepatocyte injury because hepatocytes
lular matrix proteins leads to the formation of focal adhesions are stable cells.
where integrins link to intracellular cytoskeletal elements
such as actin. These interactions lead to intracellular signals PBD9 103  BP9 66  PBD8 107–108  BP8 70–74

CHAPTER

4Hemodynamic Disorders

PBD9 Chapter 4: Hemodynamic Disorders

PBD8 Chapter 4: Hemodynamic Disorders, Thromboembolic Disease, and Shock

BP9 Chapter 3: Hemodynamic Disorders, Thromboembolism, and Shock

BP8 Chapter 4: Hemodynamic Disorders, Thrombosis, and Shock
  

1 A 45-year-old woman who works while standing for 3 A 37-year-old woman has noticed a lump in her left
long periods notices at the end of her 8-hour shift that her breast over the past 2 months. On physical examination, the
lower legs and feet are swollen, although there was no swell- skin overlying the left breast is thickened, reddish orange,
ing at the beginning of the day. There is no pain or erythema and pitted. Mammography shows a 3-cm underlying density.
associated with this swelling. She is otherwise healthy and A fine-needle aspirate of the density is performed and on mi-
takes no medications; laboratory testing reveals normal liver croscopic examination shows carcinoma. Which of the follow-
and renal function. Which of the following mechanisms best ing mechanisms best explains the gross appearance of the skin
explains this phenomenon? of her left breast?
A Excessive free water intake A Chronic inflammation
B Hypoalbuminemia B Chronic passive congestion
C Increased hydrostatic pressure C Ischemic necrosis
D Lymphatic obstruction D Lymphatic obstruction
E Secondary aldosteronism E Venous thrombosis

2 A 56-year-old woman diagnosed with cancer in her left 4 A 7-year-old boy has had increasing lethargy for a week.
breast underwent a mastectomy with axillary lymph node On physical examination, he has periorbital edema and pit-
dissection. Postoperatively, she develops marked swelling of ting edema at the ankles, but is normotensive and afebrile.
the left arm that has persisted for 6 months. Now on physical Laboratory studies show marked albuminuria. He is given a
examination, her temperature is 36.9° C. Her left arm is not thiazide diuretic and his urine output increases and his edema
tender or erythematous, and it is not painful with movement resolves. Which of the following changes most likely potenti-
or to touch, but it is enlarged with a doughy consistency. ated his edema?
Which of the following is the most likely mechanism for these A Decreased aldosterone
findings? B Decreased renin
A Cellulitis C Increased albumin
B Congestive heart failure D Increased cortisol
C Decreased plasma oncotic pressure E Decreased antidiuretic hormone
D Lymphedema F Increased salt retention
E Sodium and water retention   
F Phlebothrombosis

31

3 2 U N I T I   General Pathology

5 A 94-year-old woman has dyspnea and an increasing 7 A 58-year-old man with pulmonary emphysema has a
cough with frothy sputum production for the past month. She 10-year history of congestive heart failure. On physical exami-
is afebrile. A chest radiograph shows the findings in the figure. nation, he has lower leg swelling with grade 2 pitting edema
Which of the following is the most likely mechanism for to the knees and prominent jugular venous distention to the
development of her pulmonary infiltrates? level of the mandible. His serum levels of AST and ALT are
A Decreased sodium intake increased. The representative gross appearance of his liver is
B Hypoalbuminemia shown in the figure. Which of the following underlying condi-
C Increased hydrostatic pressure tions is most likely to be present in this man?
D Inflammation A Chronic renal failure
E Pulmonary venous obstruction B Common bile duct obstruction
C Congestive heart failure
6 A 50-year-old man suffers an infarction of the anterior D Portal vein thrombosis
left ventricular wall. He receives therapy with anti-arrhythmic E Thrombocytopenia
and pressor agents. He is in stable condition until he develops
severe breathlessness 3 days later. An echocardiogram shows 8 An 85-year-old man falls in the bathtub and strikes the
a markedly decreased ejection fraction. Representative chest back of his head. Over the next 24 hours, he becomes increas-
radiographic findings are shown in the figure above. Which of ingly somnolent. A head CT scan shows an accumulation of
the following microscopic changes is most likely to be present fluid beneath the dura, compressing the left cerebral hemi-
in his lungs? sphere. Which of the following terms best describes this col-
A Alveolar neutrophilic exudate lection of fluid?
B Alveolar transudate A Congestion
C Alveolar wall fibrosis B Ecchymosis
D Pleural fibrosis C Hematoma
E Pleural space neutrophilic exudate D Petechiae
F Pleural space transudate E Purpura
     

C H A P T E R 4   Hemodynamic Disorders 33

9 An autopsy study is performed to correlate patterns of 12 In an experiment, thrombus formation is studied in ar-
hemorrhage with underlying causes. Patients with the gross eas of vascular damage. The propagation of a thrombus in an
appearance of hemorrhage shown in the figure had minimal area of vascular injury to adjacent normal arteries is prevent-
blood volume loss, but an appearance similar to this in many ed. Which of the following substances diminishes thrombus
other organs. Which of the following terms best describes this propagation by activating protein C?
pattern? A Calcium
A Congestion B Fibrin
B Ecchymosis C Platelet factor 4
C Hematoma D Prothrombin
D Petechiae E Thrombomodulin
E Purpura F Tumor necrosis factor (TNF)

10 A superficial puncture wound from a needlestick injury 13 A 26-year-old woman has a history of frequent nose-
leads to a small amount of bleeding in a healthy person. Sec- bleeds and increased menstrual blood flow. On physical exam-
onds after this injury occurs, the bleeding stops. Which of the ination, petechiae and purpura are present on the skin of her
following mechanisms is most likely to stop small arteriolar extremities. Laboratory studies show normal partial thrombo-
blood loss from this injury? plastin time (PTT), prothrombin time (PT), and platelet count,
A Fibrin polymerization but decreased von Willebrand factor activity. This patient
B Neutrophil chemotaxis most likely has a derangement in which of the following steps
C Platelet aggregation in hemostasis?
D Protein C activation A Fibrin polymerization
E Vasoconstriction B Platelet adhesion
C Platelet aggregation
11 A 15-year-old girl incurs a cut to the sole of her foot D Prothrombin generation
after stepping on a piece of broken glass. On examination, a E Prothrombin inhibition
superficial 0.5-cm laceration ceases to bleed within 5 minutes F Vasoconstriction
after application of local pressure. Which of the following
substances is released by endothelium and is most likely to 14 A 59-year-old woman with a history of diabetes mellitus
counteract platelet aggregation near this site of injury? had a myocardial infarction 3 months ago. Her BMI is 35. She
A Glycoprotein IIb/IIIa is now taking a low dose of aspirin to reduce the risk for recur-
B Platelet-activating factor rent arterial thrombosis. On which of the following steps in
C Prostacyclin hemostasis does aspirin have its greatest effect?
D Tissue-type plasminogen activator A Adhesion of platelets to collagen
E Thrombomodulin B Aggregation of platelets
F Thromboxane C Production of tissue factor
D Synthesis of von Willebrand factor
E Synthesis of antithrombin III

15 In an experiment, platelet function is analyzed. A sub-
stance is obtained from the dense body granules of normal
pooled platelets from healthy blood donors. When this sub-
stance is added to platelets obtained from patients with a
bleeding disorder, no platelet aggregation occurs. Adding the
substance to platelets from a normal control group induces
platelet aggregation. Which of the following substances is
most likely to produce these effects?
A Adenosine diphosphate
B Antithrombin III
C Fibronectin
D Fibrinogen
E Plasminogen
F Thromboxane A2

3 4 U N I T I   General Pathology 20 A 21-year-old woman has had multiple episodes of deep
venous thrombosis during the past 10 years and one episode
16 A 12-year-old boy has a 10-year history of multiple soft of pulmonary thromboembolism during the past year. Labora-
tissue hemorrhages and acute upper airway obstruction from tory tests show that her prothrombin time (PT), partial throm-
hematoma formation in the neck. On physical examination, he boplastin time (PTT), platelet count, and platelet function
has decreased range of motion of the large joints, particularly studies all are normal. Which of the following risk factors is
the knees and ankles. He has no petechiae or purpura of the the most common cause for such a coagulopathy?
skin. Laboratory studies show normal prothrombin time, el- A Antithrombin III deficiency
evated partial thromboplastin time (PTT), and normal platelet B Factor V mutation
count, but markedly decreased factor VIII activity. Which of C Hyperhomocysteinemia
the following mechanisms best describes the development of D Mutation in protein C
his disease? E Occult malignancy
A Decrease in production of thrombin F Oral contraceptive use
B Decrease in membrane phospholipid G Smoking cigarettes
C Failure of platelet aggregation 21 A 23-year-old woman has had altered consciousness and
D Failure of fibrin polymerization slurred speech for the past 24 hours. A head CT scan shows a
E Inability to neutralize antithrombin III right temporal hemorrhagic infarction. Cerebral angiography
F Inability of platelets to release thromboxane A2 shows a distal right middle cerebral arterial occlusion. Within
17 A 58-year-old man has had episodes of prolonged epi- the past 3 years, she has had an episode of pulmonary embo-
staxis in the past 6 months. On examination he has occult lism. A pregnancy 18 months ago ended in miscarriage. Labo-
blood detected in his stool. Coagulation studies show that his ratory studies show a false-positive serologic test for syphilis,
prothrombin time is elevated, but his partial thromboplastin normal prothrombin time (PT), elevated partial thromboplas-
time (PTT), platelet count, and platelet function are all normal. tin time (PTT), and normal platelet count. Which of the follow-
When his plasma is mixed with an equal amount of normal ing is the most likely cause of these findings?
plasma, the prothrombin time corrects to normal. Which of the A Antiphospholipid antibody
following underlying diseases is most likely to be associated B Disseminated intravascular coagulation
with these findings? C Factor V mutation
A Antiphospholipid syndrome D Hypercholesterolemia
B Factor V Leiden mutation E Von Willebrand disease
C Hemophilia A   
D Scurvy
E Sepsis with Escherichia coli 22 A 71-year-old man with a history of diabetes mellitus
F Vitamin K deficiency died of an acute myocardial infarction. At autopsy, the a­ orta,
opened longitudinally and with the superior aspect of the
18 A 66-year-old woman has the sudden onset of chest pain kidneys below the forceps, appeared as shown in the figure.
that radiates to her neck and left arm. On examination 30 min- Which of the following complications associated with this aor-
utes later, she is diaphoretic and hypotensive. Her serum tro- tic disease would most likely have been present during his life?
ponin I level is elevated. Which of the following drugs is most A Edema of the left leg
likely to be administered emergently as thrombolytic therapy B Gangrene of the foot
for this woman? C Pulmonary thromboembolism
A Acetylsalicylic acid (aspirin) D Renal infarction
B Low-molecular-weight heparin E Thrombocytopenia
C Nitric oxide
D Tissue plasminogen activator
E Vitamin K

19 A 60-year-old woman with a history of diabetes mellitus
has had left-sided chest pain radiating to the arm for the past 5
hours. Serial measurements of serum creatine kinase–MB lev-
els show an elevated level 24 hours after the onset of pain. Par-
tial thromboplastin time (PTT) and prothrombin time (PT) are
normal. Coronary angiography shows occlusion of the left an-
terior descending artery. Which of the following mechanisms
is the most likely cause of thrombosis in this patient?
A Antibody inhibitor to coagulation
B Damage to endothelium
C Decreased antithrombin III level
D Decreased tissue plasminogen activator
E Mutation in factor V gene
F Stasis of blood flow

C H A P T E R 4   Hemodynamic Disorders 35

23 A 55-year-old woman following major abdominal sur- 26 A 59-year-old woman with hyperlipidemia has had
gery has had discomfort and swelling of her left leg for the anginal pain for the past 24 hours. Laboratory findings show
past week. On physical examination, the leg is slightly diffi- no increase in serum troponin I or creatine kinase–MB. She is
cult to move, and on palpation there is tenderness. A Doppler in stable condition 2 weeks later and has no chest pain, but
sonogram shows thrombosis of deep left leg veins. Which of a small artery in the epicardium has undergone the changes
the following mechanisms is most likely to contribute to her seen in the figure. Which of the following terms best describes
condition? this finding in this epicardial artery?
A Hypercalcemia A Air embolus
B Immobilization B Cholesterol embolization
C Ingestion of aspirin C Chronic passive congestion
D Nitric oxide release D Fat embolism syndrome
E Turbulent blood flow E Mural thrombosis
24 A 75-year-old man is hospitalized after falling and frac- F Organization with occlusion
turing his left femoral trochanter. Two weeks later, the left leg G Phlebothrombosis
is swollen, particularly below the knee. He experiences pain
on movement of the leg; on palpation, there is swelling and 27 A 77-year-old woman has a brief fainting episode. She
tenderness. Which of the following complications is most like- was diagnosed 1 year ago with pancreatic adenocarcinoma.
ly to occur in this man? On auscultation of her chest, a heart murmur is heard. Echo-
A Disseminated intravascular coagulation cardiography shows a 1-cm nodular lesion on the superior as-
B Fat embolism syndrome pect of an intact anterior mitral valve leaflet. A blood culture
C Gangrenous necrosis of the foot is negative. Which of the following terms best describes this
D Hematoma of the thigh mitral valve lesion?
E Pulmonary thromboembolism A Atheroma
   B Chronic passive congestion
C Mural thrombus
25 A 65-year-old woman sustained fractures of the right fe- D Myxoma
mur, pelvis, and left humerus in a motor vehicle collision. The E Phlebothrombosis
fractures were stabilized, and the patient’s recovery was un- F Vegetation
eventful. During a physical examination 3 weeks later, while   
still in the hospital, she has swelling and warmth in the left
leg, and there is local pain and tenderness in the left thigh.
Which of the following processes, as shown in the figure, is
most likely occurring in her left femoral vein?
A Atherosclerosis
B Chronic passive congestion
C Inflammation
D Mural thrombosis
E Phlebothrombosis
F Vegetation
  

3 6 U N I T I   General Pathology 31 A 31-year-old man is on a scuba diving trip and de-
scends to a depth of 50 m in the Blue Hole off the coast of Be-
28 A 70-year-old man was hospitalized 3 weeks ago for a lize. After 30 minutes, he has a malfunction in his equipment
cerebral infarction. He is now is ambulating for the first time. and quickly returns to the boat on the surface. He develops
Within minutes of returning to his hospital room, he has sud- difficulty breathing within 5 minutes, with dyspnea and sub-
den onset of dyspnea with diaphoresis. He cannot be resus- sternal chest pain, followed by a severe headache and vertigo.
citated. The gross appearance of the hilum of the left lung at An hour later, he develops severe, painful myalgias and ar-
autopsy is shown in the figure. Which of the following risk thralgias. These symptoms abate within 24 hours. Which of
factors most likely contributed to this finding? the following occluding his arterioles is the most likely cause
A Antiphospholipid antibody of his findings?
B Bronchopneumonia A Fat globules
C Factor V mutation B Fibrin clots
D Leg vein thrombosis C Nitrogen gas bubbles
E Pulmonary arterial atherosclerosis D Platelet thrombi
29 A 32-year-old man is involved in a vehicular accident E Ruptured atheromatous plaque
and sustains fractures of the right femur and tibia and the left   
humerus. The fractures are stabilized surgically. He is in stable
condition for 2 days, but then suddenly becomes severely dys- 32 A 53-year-old man with congestive heart failure devel-
pneic. Which of the following complications from his injuries ops pulmonary Streptococcus pneumoniae infection after a bout
is the most likely cause of his sudden respiratory difficulty? of influenza. After recuperating for 2 weeks, he notes pleuritic
A Cardiac tamponade chest pain. The pain is caused by the development of the lesion
B Fat embolism shown in the figure. Which of the following events has most
C Pulmonary edema likely occurred in this man?
D Pulmonary infarction A Acute pulmonary congestion
E Right hemothorax B Chronic pulmonary congestion
30 A 22-year-old woman with an uncomplicated pregnan- C Pulmonary edema
cy develops sudden dyspnea with cyanosis and hypotension D Pulmonary infarction
intrapartum during routine vaginal delivery of a term infant. E Pulmonary venous thrombosis
She has a generalized seizure and becomes comatose. Her con-   
dition does not improve over the next 2 days. Which of the fol-
lowing findings is most likely to be present in her peripheral
pulmonary arteries?
A Aggregates of platelets
B Amniotic fluid
C Fat globules
D Gas bubbles
E Thromboemboli

C H A P T E R 4   Hemodynamic Disorders 37

33 A 44-year-old man with dilated cardiomyopathy and 35 An 80-year-old woman with dysuria for 1 week now
heart failure develops left atrial mural thrombosis. He develops has a fever. On examination, her temperature is 37.9° C, pulse
the complication shown in the figure, manifested by hematuria. 103/min, and blood pressure 80/40 mm Hg. She has right
Which of the following is the best term for this complication? flank pain. A urinalysis shows numerous WBCs. Her plasma
A Abscess lactate is increased. Urine culture and blood culture grow
B Ischemic infarct Escherichia coli. Which of the following is most likely to con-
C Liquefactive necrosis tribute to her cardiovascular collapse by triggering Toll-like
D Multiorgan failure cell receptors?
E Venous thrombosis A Complement C3b
B Lipopolysaccharide
34 A 28-year-old woman with a 15-year history of recur- C Nitric oxide
rent thrombosis from a prothrombin gene mutation develops D Platelet-activating factor
septicemia after a urinary tract infection with Pseudomonas E Toxic shock syndrome toxin-1
aeruginosa. She develops multiple infarcts and organ failure
over the next 2 weeks. Which of the following organs is most 36 A 63-year-old woman has had a fever and felt faint for
likely to be spared from the effects of ischemic injury in this the past 2 days. On physical examination, her temperature is
woman? 38.4° C, pulse is 101/min, respirations are 17/min, and blood
A Brain pressure is 85/40 mm Hg. She has marked peripheral vaso-
B Heart dilation. The serum lactic acid level is 6.8 mg/dL. Which of
C Kidney the following laboratory findings is most likely related to the
D Liver cause of her clinical condition?
E Spleen A Blood culture positive for Citrobacter
B Decreased hematocrit
C Elevated serum creatine kinase
D Increased blood urea nitrogen
E Reduced Po2 on blood gas measurement

37 A 20-year-old man develops palpitations within 1 hour
after a gunshot wound to the abdomen. On examination his
heart rate is 112/minute and blood pressure 80/30 mm Hg.
His skin is cool and clammy to the touch. Which of the fol-
lowing organ-specific changes is most likely to occur within
2 days after this injury?
A Acute hepatic infarction
B Cerebral basal ganglia hemorrhage
C Gangrenous necrosis of the lower legs
D Pulmonary diffuse alveolar damage
E Renal passive congestion

38 A 30-year-old man is cutting wood alone in the forest
and incurs a deep cut to his leg from his chain saw. He loses a
large amount of blood. He is not found until the next day. A
marked increase in which of the following blood analytes is
most likely to indicate that he has reached an irreversible stage
of shock?
A Antidiuretic hormone
B Bicarbonate
C Catecholamines
D Lactate dehydrogenase
E Prothrombin