Pathology for the Health Professions

Ivan Damjanov
Visit to download the full and correct content document:
https://textbookfull.com/product/pathology-for-the-health-professions-ivan-damjanov/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Pathology for the Health Professions - E-Book 5th

Edition Ivan Damjanov [Damjanov

https://textbookfull.com/product/pathology-for-the-health-
professions-e-book-5th-edition-ivan-damjanov-damjanov/

Information technology for the health professions Fifth

Edition Burke

https://textbookfull.com/product/information-technology-for-the-
health-professions-fifth-edition-burke/

Medical Terminology for Health Professions (INCOMPLETE)

8 th Edition Ann Ehrlich

https://textbookfull.com/product/medical-terminology-for-health-
professions-incomplete-8-th-edition-ann-ehrlich/

Domestic Violence in Health Contexts A Guide for

Healthcare Professions Parveen Ali

https://textbookfull.com/product/domestic-violence-in-health-
contexts-a-guide-for-healthcare-professions-parveen-ali/
Mosby’s Pocket Dictionary of Medicine, Nursing & Health
Professions Mosby

https://textbookfull.com/product/mosbys-pocket-dictionary-of-
medicine-nursing-health-professions-mosby/

Clinical Reasoning in the Health Professions, 4th ed

4th Edition Joy Higgs

https://textbookfull.com/product/clinical-reasoning-in-the-
health-professions-4th-ed-4th-edition-joy-higgs/

Sickness in Health: Bullying in Nursing and other

Health Professions 1st Edition Happell

https://textbookfull.com/product/sickness-in-health-bullying-in-
nursing-and-other-health-professions-1st-edition-happell/

Stanfield s Introduction to Health Professions 7th

Edition Nanna Cross

https://textbookfull.com/product/stanfield-s-introduction-to-
health-professions-7th-edition-nanna-cross/

Mosby's Dictionary of Medicine, Nursing & Health

Professions, 10e 10th Edition Mosby

https://textbookfull.com/product/mosbys-dictionary-of-medicine-
nursing-health-professions-10e-10th-edition-mosby/
Contents
1 Cell Pathology, 1 14 The Male Reproductive
System, 330
2 Inflammation, 21
15 The Female Reproductive
3 Immunopathology, 42 System, 347

4 Neoplasia, 70 16 The Breast, 375

5 Genetic and Developmental 17 The Endocrine System, 389

Diseases, 94
18 The Skin, 407
6 Fluid and Hemodynamic
Disorders, 117 19 Bones and Joints, 425

7 The Cardiovascular System, 133 20 Muscles and Peripheral

Nerves, 448
8 The Respiratory System, 165
21 The Nervous System, 466
9 The Hematopoietic and
Lymphoid Systems, 200 22 The Eye, 492

10 The Gastrointestinal System, 233 23 The Ear, 502

11 The Liver and Biliary System, 267 Glossary, 508

12 The Pancreas, 294 Index, 522

13 The Urinary Tract, 310

PATHOLOGY
for the HEALTH
PROFESSIONS
YOU’VE JUST PURCHASED
MORE THAN
A TEXTBOOK!
Evolve Student Resources for Damjanov: Pathology for the
Health Professions, Fifth Edition, include the following:
• Body Spectrum Electronic Anatomy Coloring Book
• Animations

Activate the complete learning experience that comes with each

textbook purchase by registering at

http://evolve.elsevier.com/Damjanov/pathologyHP/

REGISTER TODAY!

You can now purchase Elsevier products on Evolve!

Go to evolve.elsevier.com/html/shop-promo.html to search and browse for products.

2015v1.0
PATHOLOGY
for the HEALTH
PROFESSIONS
Fifth Edition

IVAN DAMJANOV, MD, PhD

Professor
Department of Pathology and Laboratory Medicine
The University of Kansas
School of Medicine
Kansas City, Kansas
3251 Riverport Lane
St. Louis, Missouri 63043

PATHOLOGY FOR THE HEALTH PROFESSIONS, FIFTH EDITION ISBN: 978-0-323-35721-0

Copyright © 2017 by Elsevier Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

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

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment
may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In using
such information or methods they should be mindful of their own safety and the safety of others,
including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the
most current information provided (i) on procedures featured or (ii) by the manufacturer of each
product to be administered, to verify the recommended dose or formula, the method and duration of
administration, and contraindications. It is the responsibility of practitioners, relying on their own
experience and knowledge of their patients, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/or damage to persons or property as a matter of products
liability, negligence or otherwise, or from any use or operation of any methods, products, instructions,
or ideas contained in the material herein.

Previous editions copyrighted 2012, 2006, 2000, 1996.

Library of Congress Cataloging-in-Publication Data

Names: Damjanov, Ivan, author.

Title: Pathology for the health professions / Ivan Damjanov.
Description: Fifth edition. | St. Louis, Missouri : Elsevier, [2017] | Includes index.
Identifiers: LCCN 2016023932 | ISBN 9780323357210 (pbk. : alk. paper)
Subjects: | MESH: Pathologic Processes
Classification: LCC RB25 | NLM QZ 140 | DDC 616.07–dc23
LC record available at https://lccn.loc.gov/2016023932

Content Strategist: Kristin Geen

Content Development Manager: Jean Sims Fornango
Senior Content Development Specialist: Danielle Frazier
Publishing Services Manager: Jeff Patterson
Senior Project Manager: Anne Konopka
Design Direction: Ashley Miner

Printed in China

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 To my agathodemons, Ivana and Milena,
with a quote from Gandhi:
“Almost anything you do will be insignificant,
but it is very important that you do it.”
Of course, because the circle is never entirely round.
TATA
Acknowledgments
It is my pleasure to acknowledge the contributions of my
St. Louis–based Elsevier technical support team who made
this edition possible. Above all, my thanks go to Senior
Content Development Specialist, Danielle Frazier, Senior
Project Manager, Anne Konopka, Content Development
Manager, Jean Sims Fornango, and Content Strategist,
Kristin Geen. They acted as my guardian angels, kept me
on track, and supported me from the beginning to the bitter
end. They also coordinated and organized anonymous
external reviews from experts who advised me on how to
revise and improve the text. I would also like to acknowledge
these external reviewers whose corrections, suggestions, and
guidance were simply invaluable. I would also like to
mention the contribution of a pre-med student, Dania
Hallak, who just so happens to be my granddaughter. Dania
spent 6 weeks with me in Split, Croatia, and learned what
it means to write/edit a medical textbook and helped me
with revising and finalizing the text of several chapters of
General Pathology.
I would also like to thank my Croatian editor Ms. Andja
Raič for allowing me to reproduce the several figures
from the book: Damjanov I, Seiwerth S, Jukić S, Nola M
vi
(editors): Patologija, fourth edition, Medicinska naklada,
Zagreb, Croatia, 2014. These figures, listed by their
numbers in the Croatian book, are as follows: Fig. 1-18,
Fig. 2-11, Fig. 2-17, Fig. 2-24, Fig. 5-14, Fig. 10-2, and
Fig. 14-16.
Finally, I must thank my wife, Andrea, for her uncon-
ditional support and for encouraging me to complete the
fifth edition of this book, which has unwittingly become an
intricate part of our marital life for the last 20-some years.
Who would have ever thought that it would live so long,
one edition after another. But as the classic Latin saying
goes, Habent sua fata libelli. In free translation it states that
the fate of most books is unpredictable, but it also implies
that the fate of each book depends on its acceptance by its
presumptive readers. Accordingly, I must finish these para-
graphs with a paean to my past and future readers and
especially to my colleagues, the professors who keep recom-
mending the book to their students.
Ivan Damjanov
March 31, 2016
Kansas City, Kansas
Reviewers and Ancillary Writers

Reviewers

Allen W. Barbaro, MS, RRT Cheri Goretti, MA, MT(ASCP), CMA(AAMA)

Department Chairman, Respiratory Care Education Professor and Coordinator
St. Luke’s College—Unity Point Health Medical Assisting & Allied Health Programs
Sioux City, Iowa Quinebaug Valley Community College
Danielson, Connecticut
Pamela Besong, CMA, CPCT, CI
Office Manager/Registrar Julie Léger-DiMaio, BPHE Honours,
Atlanta Health Careers BEd honours, CHCP
McDonough, Georgia Correactology® Health Care Practitioner
Member of the Ontario College of Teachers
Dorothy Chen-Maynard, PhD, RN, FAND Canadian Institute of Correactology
Interim Chair, Department of Health Science Sudbury, Ontario, Canada
and Human Ecology
Director, Didactic Program in Dietetics Jennifer Liao, BSc, OD
California State University San Bernardino Optometrist
San Bernardino, California Adjunct Clinical Faculty
The New England College of Optometry
Rebecca Eskew Clawson, MAT, PA-C Boston, Massachusetts;
Physician Assistant Instructor Contact Lens
LSUHSC—Shreveport The Vision Institute of Canada
School of Allied Health PA Program Toronto, Ontario, Canada
Shreveport, Louisiana
Sharon E. McCleave, PhD
Hisham S. Elbatarny, MB, BCh, MSc, MD Professor, Program Coordinator
Medical Doctor, Consultant Internist, Professor Seneca College
of Science School of Health Sciences; School of Recreation and
School of Baccalaureate Nursing Environmental Studies
St. Lawrence College King City, Ontario, Canada
School of Health Sciences—Department of
BioMedical and Molecular Sciences (DBMS) Debra Morrison, RN, BScN, MN
Queen’s University Professor
Kingston, Ontario, Canada Durham College
School of Health and Community Services
Elizabeth Elsaesser, PT, MS Oshawa, Ontario, Canada
Professor
Oakton Community College Paula D. Silver, BS, PharmD
Physical Therapist Assistant Program Medical Instructor
Division of Science and Health Careers ECPI University
Des Plaines, Illinois Medical Careers School of Health Sciences & Technology
Medical Assisting/LPN and RN Departments
Newport News, Virginia

vii
Fran Soderling, RDH, MS Amy C. VonKadich, MEd, RT(T)
Dental Hygiene Academic Administrator Department Chair
Associate Professor Diagnostic Medical Imaging
West Coast University NHTI Concord’s Community College
Department of Dental Hygiene Concord, New Hampshire
Anaheim, California

Ancillary Writers

Sharon E. McCleave, PhD Paula D. Silver, BS, PharmD

Professor, Program Coordinator Medical Instructor
Seneca College ECPI University
School of Health Sciences; School of Recreation and Medical Careers School of Health Sciences & Technology
Environmental Studies Medical Assisting/LPN and RN Departments
King City, Ontario, Canada Newport News, Virginia

Peivand Pirouzi, PhD, MBA, CCPE

Full Professor, Academic Program Coordinator, and
Clinical Research Supervisor
Faculty of Applied Arts and Health Sciences
Seneca College
King City, Ontario, Canada

viii Reviewers and Ancillary Writers

Preface
More than 20 years have passed since the first edition of
this book appeared in print. The book sales and the com-
ments made by my colleagues and by students across the
country indicate that it was well received. I was most grati-
fied by this response, and I readily accepted the invitation
from the publisher to prepare a fourth edition.
The first edition that appeared in 1996 was prepared
for students in allied health professions. As the popularity
of the book grew, I discovered that the book was used not
only by students of laboratory medicine, future nurses, and
radiology technicians, but also by students preparing them-
selves to become pathology assistants, physician assistants,
pharmacists, veterinarians, and other health care profession-
als. Their comments and suggestions helped me prepare
the new edition, and I hope that it will meet with their
approval and expectations.
Like the previous four editions, this book covers both
general and systemic pathology. The material is presented
in a standard manner to enable students to study efficiently
and gain knowledge systematically. The book is divided into
23 chapters, grouped into two major sections: general
pathology and organ system pathology. More pages and
emphasis are given to systemic pathology to meet the
requirements of most curricula.
Each chapter is a self-contained teaching unit. Each
begins with an outline and a list of key terms and concepts.
Learning objectives are provided to guide students and help
them focus on the core material. Students should return to
these opening pages for review after reading each chapter.
Students who can discuss comprehensively, in their own
words, all of the learning objectives should be assured that
they know the material.
At the beginning of each chapter, students are reminded
that pathologic processes occur in organs and tissues that
were normal before the disease began. A brief review of
the normal structure and function of each organ is included
to emphasize the most important aspects of normal anatomy,
histology, and physiology that are essential to an under-
standing of pathology. Diagrams of the normal organs are
also included, and these will help students refresh their
knowledge of material that was covered in anatomy and
physiology courses.
This book contains so many new facts and concepts that
students might easily be lost in the details. To enable stu-
dents to keep their perspective, the beginning of each
chapter on systemic pathology is devoted to an overview of
major diseases and how they relate to the normal organ.
The core information in each chapter is presented in these
sections. Students are advised to keep these brief statements
in mind as they study the material in greater detail later
in the chapter. Students should spend as much time as
possible thinking about these concepts because they are
essential to an understanding of the details. These state-
ments are the actual take-home messages that should
remain with the student a long time after most of the
minutiae are forgotten. Students should avoid, at any cost,
memorizing details taken out of context. An understanding
of general principles and concepts is encouraged.
Pathology is too vast a subject to be covered in one
semester. To produce a book that could be read in a time
frame mandated by most current curricula, many diseases
had to be eliminated, and concentration was focused on a
few salient pathologic processes and entities that could serve
as prototypes or instructional paradigms. These diseases,
which are discussed in detail, were chosen either because
they are common and thus frequently encountered in prac-
tice or because they illustrate important principles and thus
provide significant insight into the reaction pattern of an
injured organ. Understanding the principles of these para-
digmatic diseases will facilitate the understanding of other
similar or related disorders.
Each major disease is presented in a standardized format
that includes, whenever feasible, a comprehensive Definition
or description of basic features of a disease; discussions of
Etiology, Pathogenesis, Pathology, and Clinical features; and
a brief comment about Therapy or prognosis. I advise stu-
dents to use this approach (which I call DEPPICT) in their
studies of pathology, as well as in their studies of clinical
medicine in general. It is a didactic approach that has
repeatedly proved its validity and usefulness in practice.
Because the students reading this text will practice clini-
cal medicine rather than pathology, all of the data presented
here have a clinical slant and were included with the ulti-
mate goal of preparing students for their work with living
patients and enabling them to understand various clinical
aspects of specific diseases. To this end, we have included
a plethora of illustrations. Colorful diagrams and photo-
graphs of pathologic lesions contain important information,
and students should spend time studying them. Illustrations
can reinforce the written message, and often a concept can
be made more vivid with figures than with words. To rein-
force the message, at the end of each chapter, students will
ix
find review questions pertaining to the main topics covered
in that chapter.
Students of pathology are asked to master a new vocabu-
lary and memorize hundreds of new words. Most of these
new pathologic terms are explained when they are first
mentioned in the text. Additional definitions and explana-
tions can be found in the glossary at the end of the book.
The contemporary layout and multicolor print were
designed to facilitate reading and comprehension and to
keep students’ attention focused on important concepts
during long hours of study. To enliven the text, material of
human interest was inserted in boxes titled “Did You
Know?” The brief stories and curious facts presented here
should serve as a reminder that, although pathology is a
clinical discipline, the knowledge acquired from this book
can be used not only in a medical setting but in everyday
life as well.
The task of revising the original work was facilitated by
the input of “users”—that is, teachers and students who
sent in suggestions and pointed out typos, misspellings, and
inaccuracies. Under ideal circumstances, they would all be
listed, but that is almost impossible; thus, I hope that they
will accept this brief acknowledgment as my heartfelt thank-
you note.
In addition to making the necessary corrections, the text
has been updated to include new concepts and discoveries.
At the suggestion of several teachers, a set of review ques-
tions has been inserted. To stimulate students to actively
use these questions, the answers have not been included in
the textbook. However, the professors may find them in the
Instructor’s Manual (IM) on the Evolve website that accom-
panies this text. The IM also contains clinicopathologic
reviews. Some professors use these clinicopathologic case
studies to enrich small group discussions or as material for
x Preface
students’ homework assignments. The IM includes match-
ing and multiple-choice questions, as well.
For the student, we have included an anatomy review
coloring book and PowerPoint® lecture notes for valuable
review.
With the generous support of the publisher, new illustra-
tions have been added and some artwork from previous
editions has been updated. To help my fellow teachers
prepare their lecture presentations, the image collection for
this text can be found in the instructor resources on the
text’s Evolve website. These lectures contain the material
in the form in which it is presented in the textbook. We
have also embedded images into the PowerPoint® slides,
along with wonderful video animations. The PowerPoint
slides reflect my own approach to pathology, and they can
be readily altered or custom adapted to reflect each profes-
sor’s personal style of lecturing. This edition features Audi-
ence Response System questions embedded within the
PowerPoints as appropriate. I hope that the professors and
students will appreciate this novelty. This student assessment
tool is in the form of questions to be used for quick feedback
or the review of the material.
All of these materials can be found on the text’s
accompanying Evolve website: http://evolve.elsevier.com/
Damjanov/pathologyHP/. I was reminded by a friend that
good textbooks share some common features with the best
Hollywood movies but differ from them in one important
aspect: textbook sequels are almost always better than the
original. I hope that I have maintained this tradition. I also
invite the users of this book to help me continue to improve
it. I can be reached by e-mail at IDAMJANO@KUMC.EDU
and eagerly await your input.
Ivan Damjanov
Contents
1 Cell Pathology, 1 14 The Male Reproductive
System, 330
2 Inflammation, 21
15 The Female Reproductive
3 Immunopathology, 42 System, 347

4 Neoplasia, 70 16 The Breast, 375

5 Genetic and Developmental 17 The Endocrine System, 389

Diseases, 94
18 The Skin, 407
6 Fluid and Hemodynamic
Disorders, 117 19 Bones and Joints, 425

7 The Cardiovascular System, 133 20 Muscles and Peripheral

Nerves, 448
8 The Respiratory System, 165
21 The Nervous System, 466
9 The Hematopoietic and
Lymphoid Systems, 200 22 The Eye, 492

10 The Gastrointestinal System, 233 23 The Ear, 502

11 The Liver and Biliary System, 267 Glossary, 508

12 The Pancreas, 294 Index, 522

13 The Urinary Tract, 310

xi
Introduction
Welcome to the Wonderful
World of Pathology!
In this book, you will read about pathology—the basic
medical science concerned with diseases. The term pathology
is derived from two Greek words: pathos, meaning disease,
and logos, meaning science. Thus pathology is the science that
studies diseases. It is also a medical specialty traditionally
divided into anatomic and clinical pathology. Anatomic
pathology—or, as the British like to call it, morbid anatomy—
deals with the dissection and microscopic examination of
human tissues removed from cadavers at postmortem
autopsies or from biopsies taken from living patients to
diagnose tumors and other diseases. Clinical pathology, on
the other hand, is a vast field that includes medical chem-
istry, microbiology, immunopathology, hematopathology,
and blood banking. It is therefore also called laboratory medi-
cine. All of you will interact with and come to know patholo-
gists, and some of you will work in pathology laboratories.
To assist you in becoming knowledgeable of and conversant
in pathology, this book is presented to you in the hope that
it will provide you with the medical knowledge essential for
the understanding of diseases.
The primary goal of this book is to teach you the basic
concepts underlying various pathologic processes. You will
study the pathogenesis of diseases, learn their mechanisms,
and understand how they develop. You will learn the etiology
of pathologic changes and understand the causes of many
diseases. However, it is important for you to know that,
although many diseases are well delineated, such as cancer
xii
and AIDS, others are still shrouded in mystery and only
poorly understood.
You will be shown gross and microscopic specimens of
human organs and tissues affected by various diseases in
order to visualize the morphology of various lesions. These
pathoanatomic facts that you learn will be correlated with
biochemical and immunologic findings, as well as with the
clinical symptoms with which a specific disease presents in
the living patient. Through clinicopathologic correlations, you
will see how important the understanding of pathology is
for your future medical practice.
Some of you will be caring for living patients and will
encounter pathology every day in different guises. Others
will be working in laboratories examining pathologic speci-
mens on a daily basis. Nonetheless, all of you will be
involved with people, and to understand and fully appreci-
ate their problems, you will have to understand pathology.
Why? Because pathology is the basis of all medical practice.
Dr. William Osler, the famous clinician who worked in the
great hospitals of Baltimore, Philadelphia, and Boston at
the turn of the twentieth century, noted that our clinical
practice is only as good as our understanding of pathology.
This adage is the motto of our textbook. Remember that
you are laying the scientific foundations of your future
medical career. Be sure that they are solid.
In the end, you will recall that the greatest pleasure from
having done a job well stems from having done it at all.
Nothing worthwhile ever comes easily. Persevere and your
efforts will be rewarded.
Good Luck and Enjoy Your Studies
Cell Pathology
LEARNING OBJECTIVES After reading this chapter, the student should e to:
1. Describe the essential components of at | II and its functions.
2. Explain homeostasis and the integr e of cell to external stimuli.
3. Define reversible cell injury.
4. Explain the cytoplasmic ch re ible cell injury and the concept of
hydropic change.
. Compare and contrast r nd irreversible cell injury.
(00040901

. List the most im ort t se of cell injury.

. Describe three t e daptations.
. Give three ex -s atrophy.
. Define and e @ , pertrophy and hyperplasia, and give appropriate

10. @ ontrast metaplasia and dysplasia, and give appropriate

11.

E Iain the significance of cellular aging.

plain the concept of brain death.
1 . Compare two forms of cell death: necrosis and apoptosis.
16. List examples of coagulative, liquefactive, caseous, and enzymatic necrosis.
17. Explain the difference between dystrophic and metastatic calcification.

The foundation of modern pathology can be traced back to the nineteenth century,
when German scientists realized that the cell represents the basic functional unit
of the body and that all diseases can be related to disturbances in cell function.
Rudolf Virchow (1821—1902) is the German scientist who first introduced the
concept of cellular pathology and is thus the father of modern pathology.
The concepts of cellular pathology have been expanded on and modified since
Virchow’s time, but most remain unchallenged. Today, we know that cells consist
of smaller functional units and cellular organelles, which can be seen under an
electron microscope. Organelles consist of molecules that can be further dissected
and studied by using the techniques of molecular biology. These research endeav-
ors have laid the groundwork for the field of molecular pathology, a science that will
encompass all living phenomena and provide explanations for pathologic processes
 at the level of the most basic units, which comprise all living things: subatomic
particles, atoms, and molecules. However, until this longtime goal of pathologists
becomes a reality, we limit our discussions to cells (cell pathology), tissues (histopathol-
ogy), and organs (organ pathology).

CHAPTER OUTLINE Structure and Function Functions and Intracellular

of Normal Cells Response to Injury Accumulations
Nucleus Integration of Function Anthracosis
Cytoplasm of Normal Cells Hemosiderosis
Mitochondria Reversible Cell Injury Lipid Accumulation
Ribosomes Irreversible Cell Injury Aging
Endoplasmic Causes of Cell Injury Death
Reticulum Cell Adaptations Cell Death
Golgi Apparatus Atrophy Necrosis
Lysosomes Hypertrophy and Apoptosis
Plasma Membrane Hyperplasia
Integration and Metaplasia
Coordination of Cell

KEY TERMS AND CONCEPTS Adaptations

Aging
Anoxia
Anthracosis
Apoptosis
Atrophy
Autophagosomes
Calcification
Chromatin
Cytoplasmic organelles
Cytoskeleton
Death
Gangrene
Golgi apparatus
Hemosiderin
Heterophagosomes
Homeostasis
Hyaloplasm
Hydropic change
Hyperplasia
Hypertrophy
Hypoxia
Intermediate filaments
Intracellular accumulations
Lipid accumulation
Lipofuscin
Lysosomes
Metaplasia
Microfilaments
Microtubules
Mitochondria
Necrosis
Nucleus
Oxygen radicals
Plasma membrane
Proteasomes
Ribosomes
Rough endoplasmic reticulum (RER)
Smooth endoplasmic reticulum (SER)
Ubiquitin

2 CHAPTER 1 ✴ Cell Pathology

 Structure and Function of
Normal Cells
Almost all normal cells of the human body have some
common features and consist of the same basic components.
These include the nucleus, the cytoplasm, and the cell
(plasma) membrane (Figure 1-1).
Nucleus
All human cells, except the erythrocytes and platelets, need
a nucleus for survival. The nucleus is the essential com-
ponent of most living cells. It consists of nucleic acids, such
as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA),
and nuclear proteins. In resting cells, these components
are arranged into aggregates known as chromatin and a
specialized organelle composed primarily of RNA known
as the nucleolus. In the dividing of cells—that is, during
mitosis—the chromatin is restructured and the strands of
DNA condense into chromosomes. The resting cells have a
nuclear membrane, which delimits the nucleus from the
cytoplasm. This membrane disintegrates in mitosis and
reappears after mitosis is completed.
The DNA of the nucleus contains essential genetic mate-
rial that is identical for all somatic cells that form various
tissues and organs of the body. This genetic material consists
of genes that are differentially expressed in various tissues
and organs. Differential expression of genes allows the cells
to assume unique features in various tissues and organs,
SER
Microvilli
Desmosome
Lysosomes
RER
Nuclear
membrane
Golgi
apparatus
Nucleus
Cell
membrane
Nucleolus Mitochondria
FIGURE 1-1 Normal cells have a nucleus and a cytoplasm.
On the outside, the cell is delimited by a plasma membrane. In
the cytoplasm, there are organelles, such as mitochondria,
smooth and rough endoplasmic reticulum (SER and RER,
respectively), the Golgi apparatus, and lysosomes.
and to perform specialized functions. Such cells are called
differentiated, in contrast to embryonic cells, which have
not undergone specialization and are therefore termed
undifferentiated.
The genetic information encoded in the DNA is tran-
scribed into the nuclear RNA. From the nuclear RNA, the
message is transmitted by transfer RNA (tRNA) and mes-
senger RNA (mRNA) into the cytoplasm (Figure 1-2). The
ribosomal RNA (rRNA) serves as a template for translating
the genetic messages into amino acids, which are assembled
into polypeptides and proteins. Protein synthesis is essential for
the maintenance of life. Proteins are needed for cellular
growth, replication, metabolism, respiration, and other
essential functions. Proteins also act as structural elements,
maintaining the cell’s shape and the internal organization
of the cytoplasm. None of these elementary functions (and
many others that are mentioned later) would be possible
without the nucleus, which acts as the main overseer of all
critical cytoplasmic events.
Cytoplasm
All cells have a cytoplasm, but the amount of cytoplasm
and its structure vary from one cell to another. In embry-
onic cells, the cytoplasm is scant and contains few distinct
components called organelles. In specialized, highly differenti-
ated cells, such as liver or kidney cells, the cytoplasm is
more abundant and is replete with organelles.
The principal cytoplasmic organelles are the mito-
chondria, ribosomes, endoplasmic reticulum, Golgi apparatus, and
lysosomes. In addition to these, some cells have organelles
for specialized functions. For example, muscle cells have
myofilaments composed of actin and myosin, which are
essential for contraction; glandular cells have secretory
granules, which contain enzymes or mucus destined for
excretion. Furthermore, it is important to note that the
cytoplasmic ground substance of all cells consists of an
amorphous matrix called hyaloplasm and a fibrillar meshwork
called cytoskeleton. Each cell is also enclosed by an outer
plasma membrane, which forms the border between the cyto-
plasm and the extracellular space.
Mitochondria
Mitochondria are cytoplasmic organelles involved pri-
marily in the generation of energy (see Figure 1-1). Hence,
mitochondria contain oxidative enzymes (e.g., cytochrome
oxidase) that participate in cellular respiration and in
the formation of energy-rich compounds like adenosine
triphosphate (ATP). Because this process uses oxygen, it is
called oxidative phosphorylation. ATP generated by the mito-
chondria is essential for all other cellular functions. Cells
with complex functions, such as liver cells and nerve cells,
require a considerable amount of energy and therefore
contain numerous mitochondria. By comparison, undiffer-
entiated cells, including many malignant tumor cells, have
few mitochondria.
CHAPTER 1 ✴ Cell Pathology 3
 NUCLEUS CYTOPLASM
C T T G
G
C U
G A
G
A A
C
G C G
C C

T A C
C

G
RNA
G C U transcript
A
G
C
G
DNA G A
C T
C G

TRANSCRIPTION

mRNA

TRANSLATION
tRNA Ribosomal
subunits

C
G
G
Ribosome

Codon

Proteins

Membranes of RER

FIGURE 1-2 Transcription and translation by RNA of the genetic code stored in the DNA
leads to protein synthesis on ribosomes. mRNA, messenger RNA; RER, rough endoplasmic
reticulum; tRNA, transfer RNA.

Ribosomes
Ribosomes are small granules composed of RNA. They
may be arranged into aggregates that float freely in the
cytoplasm, called polysomes or free ribosomes, or they may be
attached to the membranes of the rough endoplasmic
reticulum (RER). The ribosomes are involved in protein
synthesis. Structural proteins and enzymes needed for the
maintenance of basic cell functions (“proteins for internal
purposes”) are synthesized on the free ribosomes. Those
intended for excretion (“export or luxury proteins”) are
synthesized on the RER and discharged from cells through
the cisternae lined by the membranes of the RER.
Endoplasmic Reticulum
The endoplasmic reticulum is a meshwork of membranes
that is continuous with the outer plasma membranes on
one side and the nuclear membrane on the other. With the
use of electron microscopy, one can distinguish two forms
of endoplasmic reticulum: the RER and the smooth
endoplasmic reticulum (SER) (see Figure 1-1).
As stated earlier, the RER is the site of protein synthesis
for export and secretion. Cells producing large amounts
of proteins for export have a well-developed RER. For
example, liver cells, which synthesize blood proteins such
as albumin and the blood clotting factors, and plasma
cells, which synthesize immunoglobulins, contain prominent
stacks of RER.
The SER has complex metabolic functions, the most
important of which are the catabolism (i.e., metabolic deg-
radation) of drugs, hormones, and various nutrients and
the synthesis of steroid hormones. To perform these functions,
liver cells have a well-developed SER, which takes part
in the metabolic degradation, inactivation, or activation of
many chemicals, including drugs and hormones. Likewise

4 CHAPTER 1 ✴ Cell Pathology

hormone-secreting gonadal cells of the testes and ovaries,
and the adrenocortical cells that synthesize steroid hor-
mones, (e.g., estrogens, androgens, and corticosteroids) also
have a prominent SER.
Golgi Apparatus
The Golgi apparatus is a synthetic organelle composed
of tubules and flattened cisternae adjacent to the nucleus
(see Figure 1-1). Many proteins synthesized in the endo-
plasmic reticulum pass through the Golgi apparatus, where
they are biochemically modified before being packaged into
secretory granules or lysosomes budding from the cisternae
of this organelle. Proteins to be incorporated into the inter-
nal cell membranes (e.g., endoplasmic reticulum) or the
outer plasma membrane are also glycosylated in the Golgi
apparatus.
Lysosomes
Lysosomes are membrane-bound digestive cytoplasmic
organelles that are rich in lytic enzymes. They originate as
small vesicles budding from enzymes on the lateral sides of
the Golgi apparatus (Figure 1-3). These primary lysosomes
contain acid hydrolases, which are digestive enzymes that
are maximally active in an acidic milieu (i.e., at low pH
levels). Under normal circumstances, the lytic enzymes are
tightly enclosed by a lysosomal outer membrane and do
not harm the cell. Even if some lysosomal content is spilled
into the cytoplasm, the acid hydrolases would cause little
damage in normal cytoplasm, which has a neutral pH.
However, if the cell is injured and the pH of the cytoplasm
Fluid
Pinocytosis
Pinocytotic
absorptive
vacuole
Exocytosis
Heterophagosome 1 Lysosomes
Residual
body
Autophagosome
Mitochondria RER
FIGURE 1-3 Lysosomes. Primary (1°) lysosomes, which originate from the Golgi apparatus,
give rise to heterophagosomes and autophagosomes. Undigested material in phagosomes is
extruded from the cell or remains in the cytoplasm as lipofuscin-rich residual bodies. RER,
rough endoplasmic reticulum.
becomes acidic, enzymes released from lysosomes could
cause damage, as we will see in the section on cell injury.
The primary lysosomes fuse with other cytoplasmic ves-
icles to form secondary lysosomes. Typically they fuse with the
absorptive vesicles originating from the invaginated plasma
membrane to form secondary lysosomes, which are also
called heterophagosomes. Secondary lysosomes that are
involved in the digestion of a cell’s own organelles are called
autophagosomes. The digestive enzymes in secondary
lysosomes degrade the material enclosed within its mem-
brane. The metabolites obtained through this intracellular
digestion are reutilized within the cell’s cytoplasm. The
undigested residues are extruded from the cytoplasm into
the extracellular spaces by a process called exocytosis. Some
of the undigested material, mostly complex lipids derived
from cell membranes, may remain within the cytoplasm as
“residual bodies.” These residual bodies typically contain a
lipid-rich brown pigment known as lipofuscin. Lipofuscin
is also known as the brown pigment of aging, because it is
commonly found in aging cells. With aging, all cellular
processes become less efficient. Energy-dependent processes,
such as lysosomal digestion and exocytosis, are especially
affected. Therefore, cells in an old organism contain more
lipofuscin than those in a metabolically active, more vigor-
ous, young body.
The function of lysosomes and the formation of phago-
cytic vacuoles are well controlled in healthy cells. Most
importantly, the cells must control the inadvertent leakage
of lysosomal enzymes into the hyaloplasm, because these
enzymes could damage other organelles. Formation of
autophagosomes and the orderly removal of worn out
organelles are also well regulated in healthy cells. In
Particles
Phagocytosis
Phagosome
Acid hydrolases
Golgi
apparatus
cleus
Nu
Proteins
DNA
RNA
CHAPTER 1 ✴ Cell Pathology 5
damaged or abnormal cells, autophagy may escape control
and lead to cell destruction (“cell death by autophagy”).
Hyaloplasm and Cytoskeleton
The hyaloplasm, which is the ground substance of the
cytoplasm, has no distinct structure and appears as an
“empty” space on electron microscopic studies. Biochemi-
cally, the hyaloplasm consists predominantly of water, but
also contains minerals, proteins, carbohydrates, and lipids
that keep its osmolarity constant. The hyaloplasm is the
fluid portion of the cell that contains the organelles. In
between the organelles, the hyaloplasm is traversed by a
network of filaments that form the cytoskeleton. Three
types of filaments are recognized: microfilaments com-
posed of actin and myosin and measuring 5 nm in diam-
eter; microtubules, which are 22-nm thick and composed
of tubulin; and intermediate filaments, named so
because their diameter (10 nm) is intermediate between that
of microfilaments and microtubules.
In contrast to microfilaments and microtubules, which
have the same biochemical composition in all cells, the
intermediate filament proteins are cell-type-specific proteins
(Table 1-1). The intermediate filaments of epithelial cells contain
keratins, those of mesenchymal cells contain vimentin, muscle
cells contain desmin, glial cells contain glial acidic fibrillary
protein (GAFP), and neural cells contain neurofilament proteins.
Intermediate filament proteins are useful markers for those
cell types. Pathologists use antibodies to intermediate fila-
ments for typing of tumors because tumor cells retain the
same intermediate filament proteins as the normal cells
from which they arise. For example, carcinomas, which are
tumors of epithelial origin, express keratins, whereas sarco-
mas, which are tumors of mesenchymal cells, express
vimentin instead of keratins. In diagnostic pathology labo-
ratories, antibodies to these intermediate filament proteins
are widely used to establish whether a tumor is a carcinoma
or sarcoma.
The function of the cytoskeleton is to maintain cell shape
and to enable the cell to adapt to external mechanical
pressure. Cytoskeletal filaments are also important for cell
TABLE 1-1
Proteins of Cytoskeletal Filaments
Type of Diameter Protein
Filament (nm)
Microfilaments 5 Actin, myosin
Intermediate 10 Epithelial—keratins
filaments Mesenchymal—
vimentin
Muscle—desmin
Glia—GFAP
Nerve—
neurofilaments
Microtubules 22 Tubulin
GFAP, glial fibrillary acidic protein.
6 CHAPTER 1 ✴ Cell Pathology
movement and the traffic of organelles in the cytoplasm.
Microtubules also form the mitotic spindle during cell
division.
Plasma Membrane
The plasma membrane forms the outer surface of the
cell (Figure 1-4) and is composed of proteins, lipids, and
carbohydrates arranged in a polarized complex bilayer that
has an internal and external surface. On the internal side,
the plasma membrane is in continuity with the membrane
of the endoplasmic reticulum. Invaginations of the plasma
membrane give rise to endocytic vesicles, mediating the
intake of fluids (pinocytosis) or particulate matter (phagocytosis)
(see Figure 1-3). The cytoplasmic surface of the cell mem-
brane also serves as an anchorage site for cytoskeletal fila-
ments. For example, intermediate filaments composed of
keratin aggregate at the site of desmosomes, the typical inter-
cellular bridges that interconnect epithelial cells of the oral
or vaginal mucosa. Microtubules are integral parts of cilia,
which are specialized parts of the cell surface that have the
ability to move and propel the cell (e.g., sperm) or to move
the external secretions of the cell. For example, mucus is
moved by the cilia of the bronchial ciliated cells; dysfunc-
tion of these cilia may predispose an individual to bronchial
infection (bronchitis).
The external surface of the plasma membrane serves as
the site of contact between the cell and the environment.
This interaction is maintained through the action of special-
ized portions of the cell membrane that serve as receptors,
adhesion molecules, transducers of signals, or metabolic
channels. The complexity of the plasma membrane varies
from one cell type to another.
The plasma membrane is a living structure that is main-
tained by active expenditure of energy and a constant
supply of ATP. The structural integrity of the plasma mem-
brane is a prerequisite for the maintenance of all essential
cellular functions. Rupture or major damage of the cell
membrane that cannot be repaired invariably leads to cell
death.
Integration and Coordination of Cell
Functions and Response to Injury
Integration of Function of Normal Cells
Cells of the human body are arranged into tissues, and
these tissues form organs. Organs are part of organ systems,
all of which function in concert to meet the basic vital
requirements of the body and enable the body to perform
many complex functions. The integration of cells, tissues,
and organs into functional units is achieved through several
mechanisms, best illustrated by the response of cells to
growth-stimulating factors (Figure 1-5).
The simplest form of integration occurs at the level
of the single cell. For example, T lymphocytes secrete
cytokines, which stimulate the growth of other cells, such as
 Carbohydrate chains
External membrane surface Glycolipids

Lipid
bilayer

Internal
membrane
surface

Glycoprotein

Hydrophobic Glycoproteins
region

Hydrophilic
region

FIGURE 1-4 Plasma membrane. The bi-lipid layer also contains proteins and carbohydrates,
which perform complex functions and serve as receptors, adhesion molecules, and transduc-
ers of signals.

B Paracrine A Autocrine
Blood vessel
C Endocrine
FIGURE 1-5 Integration of cell functions occurs through inter-
action with other cells in the body. A, Autocrine stimulation:
secretions from the cell may attach to the cell’s own surface
receptors, providing autocrine stimulation. B, Paracrine stimula-
tion: closely adjacent cells act on each other. C, Endocrine
stimulation: hormones secreted by endocrine cells reach target
cells via the blood.
fibroblasts, but at the same time act on the very cells that
produced them—that is, act as their own growth factors.
This self-stimulation, known as an autocrine stimulation, is
feasible because T lymphocytes have surface receptors for
their own secretory products.
More complex integration of cells requires transmission
of hormonal signals from one cell to another. This is done
through the release of mediators from one cell and their
uptake by another, a process called paracrine stimulation.
Paracrine stimulation is typically mediated by biogenic
amines (e.g., epinephrine) and neuropeptide hormones (e.g.,
glucagon and gastrin). The best example is the release of
hydrochloric acid from gastric chief cells under the influ-
ence of gastrin. Gastrin is a hormone released by neuroen-
docrine G cells, which are located in the gastric mucosa
and are adjacent to the hydrochloric acid-secreting chief
cells. Gastrin extruded from neuroendocrine cells attaches
to receptors on the chief cells, triggering hydrochloric acid
release.
Endocrine stimulation is achieved by hormones released into
the blood circulation. This is clearly a higher form of inte-
gration of cell functions, because it may involve cells in
several anatomically distinct organs. For example, insulin
secreted by the islet cells of the pancreas, affects the liver,
muscle, fat cells, and many others. A similarly high level
of integration of cell functions can be achieved through
neural stimulation. The central and autonomic nervous systems
are the ultimate coordinators of body functions.
From the point of view of cell pathology, each cell is
best considered a distinct functional unit, in a defined inter-
nal milieu, formed by the intercellular fluids. To maintain
its life and normal functions, the cell must be in homeostasis
with its environment. Homeostasis is defined as the state
of balance between opposing pressures operating in and
around a cell or tissue. From the environment the cell
receives nutrients, oxygen, water, and essential minerals; it
generates energy by burning some of the calories derived
from the nutrients. This energy is used for the upkeep of
the nucleus, for the integrity and function of the cytoplasm,
cell organelles, and plasma membranes. By maintaining its
own integrity, the cell contributes to the stability of the

CHAPTER 1 ✴ Cell Pathology 7

internal milieu. A normal internal milieu is essential for the
normal function of the cell; likewise, the milieu remains
normal only if all the cells are functioning properly.
The supply of essential minerals, and the water in which
these minerals are dissolved, are also of paramount impor-
tance for the maintenance of homeostasis. The essential
minerals include sodium, chloride, potassium, calcium, and
iron. Magnesium, zinc, copper, and selenium—known as
oligominerals, because they are needed in minute amounts—
are essential for the function of several important enzymes.
The cell is also critically dependent on a constant supply
of oxygen and nutrients, provided to cells by the circulation
of the fluids that surround cells. At the same time, the
circulating fluids carry away the degradation products of
cellular metabolism.
When an equilibrium between the cells and their envi-
ronment is achieved and maintained, the cells are said to
be in a steady state (Figure 1-6). External stimuli may alter
this equilibrium. If the demand increases, the cell may shift
its metabolism to a higher level, achieving a new steady
state; similarly, the cell may shift to a lower steady state if
the demand decreases. In both instances the adaptation is
temporary and the cell may revert to the original steady
state after the external demands cease. However, if the
demands exceed the capacity of the cell to adapt, a per-
manent disequilibrium may ensue. Similar to a pulled
muscle that has exceeded its ability to stretch, has ruptured,
and cannot contract any more, the cell has passed its point
of no return, is irreparably damaged, and cannot return to
the original steady state. Such a cell cannot maintain
homeostasis and will die.
Hyperfunction
Removal of stimulus
(revert to normal)
Reversible Point of no return
injury Hypofunction Irreversible
injury
Necrosis
Reversal
to normal
Normal cell Reversible swelling Necrotic cell
FIGURE 1-6 Steady state. The range of the steady state is
determined by the reactivity of each cell and the ability of the
cell to respond to increased demands or stimuli. The increased
or decreased functional adaptations are reversible. However,
once response passes the point of no return, the cell injury
becomes irreversible.
8 CHAPTER 1 ✴ Cell Pathology
Reversible Cell Injury
If the adverse environmental influences evoke a cellular
response that remains within the range of homeostasis, the
changes produced are called reversible cell injury. Cessation of
injury results in the return of the cell to its original steady
state.
Reversible cell injury is typically mild or short lived.
It can be induced by exposure to toxins in low concentra-
tions. Brief hypoxia or anoxia, such as a decrease in oxygen
supply or a complete deprivation of oxygen, respectively,
can induce the same changes and are best described as
a swelling of the cytoplasm and cytoplasmic organelles
(Figure 1-7).
Cellular swelling, known as vacuolar or hydropic
change, reflects an increased influx of water into the cyto-
plasm. The water crosses the plasma membrane, enters
the hyaloplasm, and accumulates within the mitochondria
(“mitochondrial swelling”) and membrane-bound vacuoles
formed by the invagination of the plasma membrane and
endoplasmic reticulum. This vacuolization of the cytoplasm
is best appreciated by electron microscopy. Once the insult
is over, the cell recovers by pumping out the water, thereby
reverting to its original steady state.
The pathogenesis of cellular swelling is relatively easy to
explain in terms of altered permeability of the plasma mem-
brane. The plasma membrane is selectively permeable and
maintains a concentration gradient of minerals—primarily
sodium (Na+), potassium (K+), and chloride (Cl−)—inside and
outside of the cell. This is achieved through the function of
A B
Microvilli
C
Desmosome E
Desmosome
RER Mitochondrion
FIGURE 1-7 Cellular swelling. A, Normal microvilli. B, Swollen
microvilli are the consequence of an influx of water in the cyto-
plasm. C, Invagination of the cell membrane gives rise to fluid-
filled cytoplasmic vacuoles that account, in part, for the changes
known as vacuolar or hydropic. D, Swollen mitochondria and
dilated rough endoplasmic reticulum (RER) are also a part
of vacuolar degeneration. E, Swollen cells lose contact with
adjacent cells at the site of cell-to-cell junctions, such as
desmosomes.
the Na+/K+ adenosine triphosphatase (ATPase) pump, which high-energy compounds, such as ATP, anoxia or any other
constantly pumps Na+ ions from the cytoplasm into the form of energy deprivation causes dysfunction of this enzyme.
extracellular space (Figure 1-8). The pump keeps the intra- Without a functioning ATPase, the cell membrane loses its
cellular concentration of potassium high. Cl− generally capacity to maintain the gradient of intracellular and extra-
follows the Na+ ions and, accordingly, the concentration of cellular minerals. A high concentration of sodium in the
Na+ and Cl− is higher in the extracellular space than in the extracellular space results in an influx of sodium and chlo-
cytoplasm, whereas the concentration of K+ is higher inside ride into the cell. This is followed by an influx of water and
than outside of the cell. Because the ATPase is fueled by concomitant cellular swelling. Once ATPase function is
restored, the sodium and the water are pumped out of the
cell and the swelling disappears.
Reversible cell injury is associated with many functional
changes (Figure 1-9), the most important of which are as
follows:
• Reduced energy production. Swollen mitochondria gener-
ate less energy. Instead of oxidative ATP production
the cell reverts to the less efficient anaerobic glycolysis,
Na which also results in excessive production of lactic
Na K
Na acid.
ADP + P K
• Decreased protein synthesis. The pH of the cell becomes
K acidic, which further slows down the entire cell
Na
ATP Na K metabolism. The consequent dilation and fragmenta-
Na tion of the RER and the loss of membrane-attached
ribosomes (“degranulation of the RER”) results in
decreased protein synthesis.
• Increased autophagy. Damaged organelles and their frag-
ments are removed at an increased rate. Normal or
Mitochondrion
minimally damaged organelles, which are normally
FIGURE 1-8 Plasma membrane semi-permeability is a func- spared of autophagocytosis, are also sequestered into
tion of the Na+/K+-ATPase pump. ADP, adenosine diphosphate; these digestive vacuoles. Hydrolytic lysosomal enzymes
ATP, adenosine triphosphate; P, phosphorus. may leak from over-distended phagosomes into the

REVERSIBLE CELL INJURY

Cytosol pH

Mitochondria Rough Enzyme

endoplasmic activity Lysosomes
reticulum
Anaerobic ATP
glycolysis

Energy production Protein synthesis Metabolism Autophagocytosis

Cell membrane injury

Influx of water and sodium

Hydropic
change
Normal Swollen
cell cell

FIGURE 1-9 Cytoplasmic changes during reversible cell injury.

CHAPTER 1 ✴ Cell Pathology 9

 acidified cytoplasm, contributing to the damage of enzymes are widely used as clinical laboratory evidence of
other cellular components. cell injury and cell death.

Irreversible Cell Injury Causes of Cell Injury

Cells exposed to heavy doses of toxins, anoxia, severe or Cell injury may be induced by numerous pathogenetic
prolonged hypoxia, or other overwhelming insults cannot mechanisms, the most important of which are hypoxia,
recover, hence the term irreversible cell injury. Morphologically, toxins, microbial pathogens, endogenous mediators of
irreversible cell injury may be recognized by typical changes inflammation and immune reactions, and genetic and meta-
in the nucleus or by a loss of cell integrity and rupture of bolic disturbances. Depending on the severity of the insult,
the cell membrane. Functional tests will show that the the cell injury may be reversible or irreversible. The most
nuclear function has been disrupted, the energy production important causes of cell injury, together with clinical exam-
within mitochondria has fallen below the essential minimum ples, are listed in Table 1-2.
and cannot be restored, and that plasma membrane func-
tion is irrevocably lost. Hypoxia and Anoxia
Irreversible cell injury is characterized by typical ultra- Hypoxia, a reduced availability of oxygen, and anoxia,
structural changes, many of which can be recognized by the complete lack of oxygen, are among the most important
light microscopy. The most characteristic are nuclear changes; and most common causes of cell injury. Oxygen is essential
clearly, without a viable nucleus, the cell cannot survive. for cellular respiration and a lack of oxygen results in ces-
Microscopically, damage to the nucleus can appear in three sation of energy production. Without energy, the cell cannot
forms: survive. Short-term anoxia induces reversible cell injury.
• Pyknosis, marked by condensation of the chromatin However, if the oxygen supply is interrupted for long
• Karyorrhexis, characterized by fragmentation into periods, the injury becomes irreversible.
smaller particles, colloquially called nuclear dust Some cells are more sensitive to hypoxia and anoxia
• Karyolysis, involves dissolution of nuclear structure and than others. For example, brain cells cannot survive without
lysis of chromatin by enzymes such as DNAase and
RNAase (Figure 1-10)
Dead cells release their contents into the extracellular fluid, TABLE 1-2
whereby they reach the circulation. Cytoplasmic enzymes, Major Causes of Cell Injury
such as aspartate aminotransferase (AST), alanine amino-
Cause Pathogenesis Clinical
transferase (ALT), or lactate dehydrogenase (LDH), which Examples
are released from damaged cells, can be measured in blood
and are clinically useful signs of cell injury. Levels of AST, Hypoxia and Circulatory Myocardial
ALT, and LDH are typically elevated in the serum of anoxia disturbances infarct
patients with myocardial infarct or viral hepatitis. These Inadequate oxygen Strangulation
intake
Toxin Direct toxicity Mercury
Indirect toxicity poisoning
Carbon
tetrachloride
poisoning
Microbes Bacterial exotoxins Food poisoning
Direct (viral) Viral infection
Normal cell A Pyknosis cytopathic effect
Indirect (immune-
mediated
cytotoxicity)
Inflammation Action of cytokines Autoimmune
B Karyorrhexis and immune and complement diseases
reactions
Genetic and Disruption of Lysosomal
metabolic metabolic storage
disorders pathways disease (e.g.,
C Karyolysis Tay-Sachs
disease)
FIGURE 1-10 Nuclear changes during irreversible cell injury. Abnormal Diabetes
A, Pyknosis (condensation of chromatin). B, Karyorrhexis (frag- metabolism
mentation of nucleus). C, Karyolysis (lysis of chromatin).

10 CHAPTER 1 ✴ Cell Pathology

 Thrombus Swollen cell
Anoxia

Blood vessel
O2
Nose serves O2
to inhale air

1 Reperfusion Necrotic cell

Lungs O2–, H2O2, OH•

oxygenate O2 Radicals
blood

FIGURE 1-12 Post-perfusion injury by oxygen radicals.

2

Heart
pumps the
blood Arteries transport
oxygenated blood
Veins
3
Red blood cells
4 carry oxygen
Tissue cells have
respiratory enzymes
FIGURE 1-11 The major causes of hypoxia-anoxia include
(1) interruption of the oxygen supply, (2) inhibition of blood
oxygenation in the lungs, (3) inadequate transport of oxygen in
circulation, and (4) inhibition of cellular respiration.
oxygen for more than a few minutes, heart cells can survive
1 to 2 hours, and kidney cells can survive for several hours.
Connective tissue cells are most resistant to anoxia; indeed,
viable fibroblasts can be obtained from a cadaver even 1
day after death.
In clinical practice, hypoxia or anoxia may occur under
many circumstances, including the following examples
(Figure 1-11):
• Obstruction of the airways (e.g., suffocation by a
foreign body in the larynx)
• Impeded passage of oxygen across the respiratory
surfaces of the lung (e.g., pneumonia)
• Inadequate transport of oxygen in the blood (e.g., low
red blood cell count, “anemia”)
• Blockade of cellular respiration and oxidative phos-
phorylation (e.g., cyanide poisoning)
Did You Know?
Official U.S life insurance statistics show that every
month approximately 30 Americans choke to death
trying to swallow a big bite of an incompletely chewed
beef steak. Think of this statistic and chew your steak
carefully to avoid this form of anoxic death!
Short-lived reversible cell injury, secondary to hypoxia, may
be repaired completely by reoxygenation. For example, a
patient who suffers a heart block and loses consciousness
as a result of brain anoxia can resume a normal life if
resuscitation is timely and adequate. Ischemic myocardial
injury caused by coronary artery thrombosis can be mini-
mized by rapid coronary catheterization aimed at removing
the occluding thrombus. However, reoxygenation of the
heart carries an additional risk, because the oversupply of
oxygen may have a deleterious effect on the reversibly
damaged cardiac cells (Figure 1-12). Oxygen toxicity results
in such cases from activated oxygen radicals. These toxic
compounds are formed in tissues as a result of oxygen
activated by ionized iron, or by chemical reactions that
produce hydrogen peroxide (H2O2), superoxide (O2−), and hydroxyl
radical (OH.). Under normal circumstances, these activated
oxygen radicals are formed in small amounts and are inac-
tivated by the cellular enzymatic scavenger mechanisms.
However, if oxygen consumption by the tissues decreases
and scavenger enzyme systems (e.g., catalase or superoxide
dismutase) are inoperative, excessive formation of oxygen
radicals may result in additional tissue loss. In patients with
myocardial infarction, this is called postperfusion myocardial
injury.
Toxic Injury
Toxic injury may be induced by substances known for their
direct toxic effects on cells and by those that are not directly
toxic but must be metabolically activated to become toxins
(indirect toxicity). Heavy metals, such as mercury, are directly
toxic because they inactivate cytoplasmic enzymes by dis-
rupting the sulfhydryl (S-S) groups that hold the polypeptide
chains of an enzyme together in an active state. Carbon
tetrachloride (CCl4), a component of commercial metal-
cleaning solutions (e.g., metal polish), is the best studied
indirect toxin. On ingestion, CCl4 is metabolized to carbon
trichloride (CCl3), which acts as a toxic free radical, damag-
ing cell membranes.

CHAPTER 1 ✴ Cell Pathology 11

 Many drugs and their metabolites cause cell injury, A Directly cytopathic virus B Indirectly cytopathic
virus
especially if given in large amounts. The mechanism of cell RNA
virus
injury varies from one drug to another. Because various DNA
drugs affect various organs, the clinical presentations vary virus

considerably. The effect of drugs is also dose dependent; in

large amounts, most drugs may be toxic and many are even Reverse
lethal. transcriptase

Did You Know?
Potassium cyanide is a potent toxin that can be used as
a poison. In Germany, during World War II, many high-
ranking Nazi officials carried a capsule of cyanide placed
into a hole in their teeth that could be used for suicide
in case they were captured by Allied soldiers.
Note that small amounts of cyanide are also found
naturally in some fruit pits. Apricot seeds were used by
quack doctors for production of an alleged anticancer
drug called laetrile. Laetrile did not cure any cancers,
and it is not known how many patients developed
cyanide toxicity from this so-called cancer treatment.
Microbial Pathogens
Microbial pathogens cause cell injury in several ways. Bac-
teria most often produce toxins, which may inhibit various
cell functions, such as respiration or protein synthesis. For
example, food poisoning from spoiled, unrefrigerated left-
over food is caused by exotoxins, which are released by
bacteria growing on contaminated food. Ingestion of these
exotoxins produces nausea, vomiting, and diarrhea. All
these symptoms are a consequence of “cell poisoning”—that
is, the adverse effects of bacterial exotoxins on the gastro-
intestinal cells.
Viruses that are directly cytopathic invade cells and “kill
from within” by disturbing various cellular processes, or by
disrupting the integrity of the nucleus or plasma membrane
(Figure 1-13). Other viruses that are not directly cytopathic
integrate themselves into the cellular genome. The genetic
material of these viruses encodes the production of foreign
proteins, which are mixed with the cell’s own proteins and
incorporated into the cell’s membrane. The body’s immune
system will recognize the foreign viral proteins in the cell
membrane and attack them. By attacking the foreign
protein, the immune system will also damage and ultimately
kill the virus-infected cell.
Mediators of Inflammatory and
Immune Reactions
Mediators of inflammation and immune reactions, such as
cytokines, interferons, or complement proteins, may injure
cells in several ways. These biologically active substances
are produced by the body in response to infection or in
other various immune reactions. Although such substances
are valuable for eliminating the infectious agents, often they
kill not only the microbes but also the body’s own cells.
These substances are discussed in greater detail in Chapters
2 and 3.
RER
DNA
DNA
Cell Chromosomes
membrane RNA
injury
Nucleus
Lytic viral
protein
RER
Foreign viral
Binding site
protein in
cell membrane
Lymphocyte
FIGURE 1-13 Viral cell injury. A, Direct cytopathic effect.
B, Indirect cytopathic effect mediated by immune mechanisms.
RER, rough endoplasmic reticulum.
Genetic and Metabolic Disturbances
Genetic and metabolic disturbances are important causes
of cell injury. Many genetic diseases adversely affect the
normal intermediate metabolism with subsequent accumu-
lation of toxic metabolites in the cells. These diseases will
be discussed in greater detail in Chapter 5.
Metabolic disturbances of adulthood also may cause
various forms of cell injury. In some instances, the injury
affects the cells directly, whereas in others the injury is
indirect. For example, diabetes mellitus, a disease caused by
insulin deficiency, is characterized by hyperglycemia (excess
of glucose in blood), which alters the metabolism of major
organs, such as the liver or kidney. At the same time, dia-
betes produces pathologic changes in small blood vessels,
which impede microcirculation and cause pathologic tissue
changes related to chronic hypoxia.
Cell Adaptations
Prolonged exposure of cells to adverse or exaggerated
normal stimuli evokes various adaptations at the level of
individual cells, tissues, or organs. Once the cause is
removed, most cells that have adapted to chronic stimula-
tion revert to normalcy again. However, some forms of
adaptation, especially those associated with cell loss (e.g.,
bone loss in osteoporosis), are irreversible.

12 CHAPTER 1 ✴ Cell Pathology

Atrophy
Atrophy denotes a decrease in the size of a cell, tissue,
organ, or the entire body. Atrophy can refer to the reduced
size of individual cells, reduced number of cells in a tissue
or organ (also known as involution), or a combination of these
two processes. Like all adaptations, atrophy can be classified
as physiologic or pathologic.
Physiologic atrophy occurs with age and involves essentially
the entire body. For example, in the brain, a certain
number of cells is lost every day from birth on; over the
years, this results in a decrease in overall brain size. An
atrophic brain has narrow gyri, widened sulci, and dilated
lateral ventricles (Figure 1-14). The atrophic bones of
elderly people are thin and are thus more prone to fracture;
the atrophic muscles of this population are also thin and
weak.
Physiologic atrophy is not limited to very old age. The
thymus undergoes physiologic atrophy during childhood,
and only traces of thymic tissue are found after puberty.
The ovaries, uterus, and breasts atrophy after menopause.
Pathologic atrophy typically occurs as a result of inadequate
nutrition, oxygen supply, or hormonal stimulation. Ischemic
organs are typically small, such as the kidneys affected by
atherosclerosis. Denervated muscles (e.g., leg muscles after
spinal cord injury) are atrophic and flaccid. General body
wasting (cachexia), caused by cancer or malnutrition, is
marked by weakness as a result of a loss of the muscle,
which appears microscopically as atrophy of numerous
muscle fibers.
Atrophy of individual cells is associated with an obvious
reduction in cell size and reduced metabolism. The cyto-
plasm of atrophic cells contains fewer mitochondria and
endoplasmic reticulum. Effete, aging, and damaged organ-
elles are taken up by autophagosomes and degraded. Undi-
gested residues remain in the cytoplasm in the form of
lipid-rich brown pigment residues (lipofuscin), which impart
a brown color on the atrophic organs of elderly persons
(e.g., old age brown atrophy of the heart or brown atrophy of
the testis).
S
G trophy of skeletal muscles is commonly induced by exercise and
FIGURE 1-14 Atrophic brain. The gyri (G) are narrow and the
sulci (S) are wide.
Proteins released from damaged organelles, as well as
those that are no longer needed in the cytoplasm of atrophic
cells, are bound to a scavenger protein called ubiquitin.
Ubiquitin marks them for destruction in proteasomes,
large protease complexes specializing in degradation of
effete proteins.
Did You Know?
We are all born with a finite number of nerve cells in our
brains. It has been estimated that we lose thousands of
nerve cells every day, and millions and millions over our
lifespan. Because nerve cells cannot regenerate, this
loss results in gradual atrophy of the brain. However, do
not be concerned. Although many old people are not as
astute as when they were young, many others continue
to function normally into their eighties and nineties.
Loss of brain substance does not leave any air—
holes in the head. Instead, the spaces formed by atrophy
of the brain gyri are filled with cerebrospinal fluid (CSF)
that normally bathes the brain. Brain atrophy can be
demonstrated with modern x-ray techniques using com-
puted tomography, also known as CT scanning.
Hypertrophy and Hyperplasia
Hypertrophy is an increase in the size of tissues or organs
caused by an enlargement of individual cells. Etymologically
the term is related to the Greek word trophe, meaning
“food,” and thus actually means enlargement of “overfed”
cells. By contrast, hyperplasia is an increase in the size
of tissues and organs caused by an increased number of
cells (Figure 1-15). Hypertrophy and hyperplasia are often
combined. Pure hypertrophy occurs only in the heart and
striated muscles, because these organs consist of cells that
cannot divide.
Hypertrophy of the heart is a common pathologic finding
that occurs as an adaptation of the heart muscle to an
increased workload (Figure 1-16). Hypertrophy of the left
ventricle of the heart is a typical complication of hyperten-
sion. The increased pressure in the outflow side of the left
ventricle requires more force to be overcome, and this is
achieved by hypertrophy of muscle fibers. Hypertrophic
heart cells increase in size. Such cells contain more myofila-
ments, which allow them to contract more efficiently. Hyper-
is typically found in bodybuilders.
Hypertrophy with hyperplasia occurs under a variety of con-
ditions. For example, smooth muscle cells in the wall of the
urinary bladder, when obstructed by a hyperplastic prostate,
increase in size and number. This contributes to thickening
of the wall of the urinary bladder (Figure 1-17). Physiologic
hypertrophy of uterine smooth muscle cells during preg-
nancy is also accompanied by hyperplasia.
Pure hyperplasia typically occurs as a result of hor-
monal stimulation. For example, when continuously stimu-
lated by estrogen, the endometrium may become very thick
(endometrial hyperplasia). Microscopic examination reveals an
CHAPTER 1 ✴ Cell Pathology 13
 Atrophy
A Hypertrophy
Normal
B
C
Hyperplasia

D
E
Hypertrophy and
F hyperplasia

Metaplasia

Dysplasia
G

FIGURE 1-15 Hypertrophy and hyperplasia.

FIGURE 1-16 Hypertrophy of the left ventricle of the heart

caused by hypertension.

FIGURE 1-17 Hyperplasia of the prostate with secondary

increased number of glandular and stromal cells. In benign
prostatic hyperplasia (a common cause of prostatic enlarge-
ment in elderly individuals, which is also hormonally
induced), hyperplasia of epithelial and stromal cells leads
to the formation of grossly visible nodules (Figure 1-17).
Hyperplasia may also occur in response to chronic
injury, and in some cases the cause is obvious. For example,
tight shoes may cause chronic irritation of the skin. In
such cases, the epidermal cells undergo hyperplasia and
form a callus or corn. However some hyperplastic lesions,
such as hyperplastic polyps of the large intestine, have no
obvious cause and probably represent early neoplasia. Some
forms of endometrial hyperplasia may undergo additional
genetic changes and if left untreated may progress to
neoplasia.
thickening of the obstructed urinary bladder. The enlarged
prostate (P) is seen protruding into the lumen of the bladder,
which appears trabeculated (T). These “trabeculae” result from
hypertrophy and hyperplasia of smooth muscle cells that occurs
in response to increased intravesical pressure caused by urinary
obstruction.
Metaplasia
Metaplasia is a form of adaptation characterized by the
change of one cell type into another. For example, columnar
cells of the bronchial mucosa, when irritated by cigarette
smoke, transform into stratified squamous epithelium.
Metaplasia represents a reversible change. If the smoker
stops smoking, the squamous epithelium will revert back to

14 CHAPTER 1 ✴ Cell Pathology

ciliated columnar cells. If the stimulus that has induced
squamous metaplasia persists (i.e., if the smoker does not
stop smoking), the squamous metaplasia may progress to
dysplasia. In contrast to the regular layering of normal squa-
mous cells that is typical of metaplasia, dysplasia is charac-
terized by a disorderly arrangement of cells and nuclear
atypia. Dysplasia may still be reversible if the stimulus is
discontinued, but more often than not it progresses to neo-
plasia (discussed in Chapter 4; also see Chapter 8 for content
on lung carcinoma in smokers).
Intracellular Accumulations
Intracellular accumulations may occur as a result of
an overload of various metabolites or exogenous materials,
or they may be attributable to metabolic disturbances that
prevent excretion of metabolic byproducts or normal secre-
tions from cells. In most instances, the underlying mecha-
nisms are complex and involve both, an overload and
underutilization, or reduced excretion.
Anthracosis
Anthracosis (accumulation of coal particles) is the best
example of exogenous material accumulation. The term is
derived from the Greek word anthrax, meaning “carbon.”
Severe anthracosis is seen in the lungs and bronchial lymph
nodes of people who work in coal mines. Coal particles are
released into the air from chimneys; in essence, any air
pollution could cause anthracosis. Pulmonary anthracosis is
also caused by cigarette smoke.
Hemosiderosis
Hemosiderosis is an accumulation of blood-derived brown
pigment called hemosiderin. Hemosiderin is usually
A B
FIGURE 1-18 Hereditary hemochromatosis. A, The disease is characterized by an accumu-
lation of hemosiderin, an iron-rich brown pigment, in liver and Kupffer cells. B, The so-called
Prussian blue reaction gives hemosiderin a blue hue.
derived from hemolyzed blood. Remember that red blood
cells contain iron-rich hemoglobin, which disintegrates into
globin and heme. Heme gives rise to micelles of ferritin,
which aggregates into hemosiderin. Iron in hemosiderin can
be demonstrated in tissues with the so-called Prussian blue
reaction. Hemosiderosis of the liver develops in people who
have received many blood transfusions and in those suffer-
ing from hemolytic anemia. It is also a constant feature of
a genetic disorder of iron absorption from food called
hereditary hemochromatosis (Figure 1-18). Accumulation of iron
pigment in hereditary hemochromatosis causes liver damage
and may also lead to cirrhosis (i.e., end-stage liver disease).
Lipid Accumulation
Lipid accumulation in the liver is an example of intra-
cellular accumulation of intermediate metabolites. Fat is
normally stored in liver cells in the form of triglycerides.
Obese people have fatty livers because of an overload of
fat. Fat accumulation in the liver, also known as steatosis, is
a typical finding in persons suffering from chronic alcohol
abuse or from diabetes mellitus.
As shown in Figure 1-19, alcohol stimulates accumula-
tion of fat in the liver through several mechanisms. The fat
is derived, in part, from free fatty acids mobilized from
peripheral stores at an accelerated rate. Alcohol has a high
caloric content and serves as a substrate for new fat forma-
tion in liver cells (neo-lipogenesis). It also inhibits several
hepatic lipolytic enzymes and thus impedes utilization of
intrahepatic fat. Finally, alcohol inhibits apoprotein synthe-
sis and the export of fat from the liver in the form of
lipoproteins.
The clinical consequences of cytoplasmic lipid accumula-
tion in the liver are variable. For example, fatty change in
liver cells of most obese persons may be fully reversible if
the affected person loses weight and subsequently reduces
CHAPTER 1 ✴ Cell Pathology 15
Another random document with
no related content on Scribd:
 CO-OPERATION AS WE KNOW IT.
When or where Co-operation, in the sense in which the word is
used to-day, first came into being there is no means of knowing. Mr
Maxwell, in his “History of Co-operation in Scotland,” tells the story
of the old society originated by the weavers of Fenwick one hundred
and fifty years ago, before Robert Owen was born; but, although this
is the oldest Co-operative society of which any record remains, it by
no means follows that others did not exist even earlier. Indeed, Mr
Maxwell himself mentions that traditions of other old societies exist
in various parts of the country. Of these, no records remain. It is only
ten years since there vanished from the ken of the people of Govan a
society which kept proudly painted over its door a record of the fact
that it was established in 1777—eight years later than Fenwick. There
still exists in Glasgow a society which dates back to the first year of
the nineteenth century, and the Lennoxtown Society celebrated its
centenary seven years ago. All over Scotland there exist societies
which are nearing a century of life, and Mr Maxwell has rescued from
oblivion the names, and sometimes part of the records, of others
which long ago disappeared.
In their practice these old-time societies differed in material points
from the practice which takes its name from the Lancashire weaving
town where it originated—Rochdale—but the spirit which inspired
those pioneers and the broad principles of self-help in Co-operation
under which they worked, are the spirit and principles of the Co-
operators of to-day. They were, in fact, the spirit and principles
which combine to make progress possible, and in the absence of
which come stagnation and decay.
 CO-OPERATIVE BAKERIES.
Like the inception of Co-operation itself, the beginnings of baking
Co-operatively are lost in the misty past. Where the first Co-
operative bakery was started, or when, there is no means of knowing.
Research has shown that, in the early years of last century, bread
was being produced and distributed by Co-operative bakeries in
Glasgow, but how many in number these bakeries were, where
exactly they were situated, or what turnover they had it is not
possible to discover; indeed, it is probable that we should never have
known of their existence, except as a tradition, had it not been for the
fact that a Glasgow writer, who published in 1816 a book in two
volumes dealing with the affairs of Glasgow, thought it necessary to
defend the private bakers of the city at that time against any possible
accusation of overcharging for bread, by describing the methods
which were adopted by the Co-operative societies, and emphasising
the fact that they sold bread at the cost of production, and only to
their own members.
This Glasgow author, Mr Cleland by name, had been describing
the means which had been taken by the Governments of George II.
and George III. to regulate the price of bread in accordance with
price of wheat. His description is very interesting, if only for the fact
that it shows that steps had to be taken to regulate the exactions of
the profiteer, even in those early days. It shows, also, that the
methods of our various “Controllers,” “Food Committees,” etc., are
not new, but are very much along the same lines as those devised to
keep down the price of bread a century and a half ago. The price of
bread was regulated in accordance with the price of wheat, and the
baker was allowed a fixed sum per sack of flour for his expenses of
baking and distributing.
In the various cities and towns the application of this Act was in
the hands of the magistrates; and, in Glasgow, bread prices were
fixed at various intervals until 1800, when it was decided at the last
Bread Court held to cease the practice, as, in the opinion of the
magistrates, such a course was unnecessary; but the weight of loaves
continued to be standardised at 4 lbs. 5 oz. 8 drams for the quartern
loaf, and 2 lbs. 2 oz. 12 drams for the half-quartern loaf. In view of
the price of bread to-day, it is interesting to note that the price of the
half-quartern loaf was fixed by the last Glasgow Assize, held in 1800,
at 10d. for fine wheaten bread and 7½d. for household bread, which
was evidently of a much coarser and poorer quality.
Some of the Bread Assize regulations were peculiar. For instance,
the baker had to produce eighty loaves from the sack of flour, and
sell these eighty loaves at the exact price which they cost him, in
accordance with the cost of flour. “As, however,” says Mr Cleland,
“they usually were able to get two loaves more from the sack, and
these two loaves were clear profit, the price at which they were sold
was a consideration.” At the beginning of the nineteenth century the
expenses per sack allowed to the bakers were 14/, but by 1816 this
sum had been increased to 16/9.
It was within the right of any two bakers to call the attention of the
magistrates to the fact that the price of bread or flour had risen or
fallen, and to offer proof. When this was done the magistrates or
Justices of the Peace were obliged to take evidence as to the current
prices, and, if they found any variation from the last price fixed,
“they shall immediately set a new price, which shall remain
unaltered until a new Assize has been held.” One wonders whether
the magistrates of those days were as difficult to convince that any
alteration was necessary as have been the Food Control officials
during the last year of the war.
“In 1801 no Assize was held, and it was left to the bakers to sell
bread at such price as they could afford.” It is probable that in the
results of this decision the reason for the starting of Co-operative
societies is to be found, for human nature and the practices of the
times being what they were, we may be sure that the bakers saw to it
that, however much their profits might increase, they did not go
down at all.
Mr Cleland goes on to say:—
“During the last fifteen years, when no Assize has been fixed in Glasgow, the
bakers have uniformly proportioned the price of bread to the price of wheat,
similarly to what it would have been had the Assize been sitting. There are
instances, however, of individual bakers selling their bread somewhat lower
than the general run of the trade; and baking societies have been established
 in the suburbs who uniformly sell their bread one penny, twopence, and
sometimes even threepence on the quartern loaf lower than the bakers’ price.
These societies do not sell their bread to anyone but their own members; they
give no credit and receive neither profit from the concern nor interest on their
capital; besides, the members are subjected to the risk of loss incident to the
breach of trust in their servants. The greater part of these societies make no
household or coarse bread, and no loaf less than quartern; by which
arrangement it is evident the lower classes are excluded, as they neither can
advance their share of capital nor at all times purchase a quartern loaf.
Moreover, the bakeries belonging to these societies being all situated outside
the royalty, the flour is exempt from ‘multures,’ a tax to which the flour baked
within the royalty is subject, amounting to one eighty-fourth of the whole. As
the Assize laws wisely determined (for the sake of the lower classes of the
people) that bread shall be baked from a peck loaf down to a quarter-quartern
loaf, in exact proportion, and that the twopenny and penny loaves shall be of a
weight exactly corresponding to the price of the quartern loaf, it is evident that
the person who manufactured the small and the coarse bread, from which the
labouring classes of the community are generally supplied, all bearing the
same proportion to the wheaten quartern loaf, cannot sell so cheap as the
societies; among other reasons because the additional labour is very
considerable, and in weighing out the aliquot parts, unless some allowance is
made in the dough, the small bread will be deficient in weight when it comes
out of the oven; besides, the regular baker must support his family, pay his
business, and pay local taxes; he has also to run the risk attending credit, and
frequently to give one penny to the shilling discount to chandlers who retail
his bread.”
The above is the sum of our knowledge of these early Glasgow
baking societies, but the fact that they were able to sell their bread a
penny to threepence per quartern loaf below the prices charged by
the private bakers, at a time when the quartern loaf cost 1/8 and 1/3,
is significant. It meant that the baker was getting from 6/8 to 20/ per
sack of flour over the cost of production of the societies, and that,
therefore, the cost to the consumer was extortionate. Doubtless, also,
the conditions which led to the formation of Co-operative societies in
Glasgow prevailed elsewhere, and it is quite likely that baking
societies existed at that early date in other parts of Scotland, had
their day, and passed out of existence without a trace remaining.
Even of those of the existence of which we do know particulars are
absent; in most cases the name alone remains, and often not even
that but only a tradition.
 STIRLINGSHIRE AND HILLFOOTS
SOCIETIES.
Early in the nineteenth century Co-operation found a home in
Stirlingshire. In the thirtieth year of the century the Bannockburn
Co-operative Society came into being as the result of a lecture on
“Co-operation,” which was given by Mr William Buchanan, a resident
medical man. So impressed were members of his audience with what
they had heard that a committee was formed immediately to draft
rules and take the steps necessary for the formation of a society. The
rules were agreed to at a meeting which was held on 27th November
1830. Bannockburn Society still exists and flourishes to-day, after an
unbroken career of eighty-nine years.
About the same time—it may have been earlier or a little later, for
no information about its beginning can be found—a baking society
was formed in Bannockburn, and continued to flourish for a number
of years. Of the fact that the members of the other Bannockburn
Society were interested in the doings of the baking society evidence is
given in a minute of that society in the early ’thirties, in which it is
noted that the baking society had agreed to supply Alva Society with
bread. Incidentally, this entry would seem to fix a period at which the
Alva Baking Society was not in existence. The Bannockburn Baking
Society was amalgamated with the Bannockburn Society in 1846.
In the year 1847 one of the most flourishing baking societies in the
country came into existence, for on the 23rd June in that year the
Bainsford and Grahamston Baking Society was formed.
Notwithstanding that general societies have grown up all round the
town of Falkirk, this society continues to maintain a separate and
flourishing existence, its latest balance-sheet showing a membership
of 4,733 and an average output of 371 sacks per week.
Other baking societies were formed in the same district. Quite
recently one of these, Stenhousemuir Baking Society, was
amalgamated with the Stenhousemuir Equitable Society, after a
separate existence of many years. Another baking society was
situated in the little village of Carronshore. In the Hillfoots district
some time in the late ’forties baking societies came into existence at
Alva and Tillicoultry. The baking society at Tillicoultry amalgamated
with the Tillicoultry Society in 1905, and the Alva Society with the
Alva Bazaar Society a few years later.
 BAKING SOCIETIES IN FIFE AND THE
NORTH.
In Fifeshire, also, baking societies were coming into being; indeed,
the earliest baking society whose name is known was formed at
Leven in 1828. In 1840 Kingskettle Baking Society was formed, and
it remains strong and vigorous to-day. It is one of the few of these
early baking societies about which it is possible to give a little
information. The society was only a small affair at the beginning;
indeed it is not very large even to-day; but what it lacked in size it
made up for in vigour, and since its formation it has never looked
back. It is recorded that in its early days the bread was delivered by
the aid of a donkey cart; to-day the society has several vans on the
road and supplies a population of several thousands with bread.
Somewhat earlier than the formation of the society in Kingskettle a
baking society was formed in the village of Leslie, situated a few
miles from Kirkcaldy. The reason for its formation was the same as
that responsible for the formation of others in these early days—
small wages and the extortionate charges for their bread made by the
local bakers. The success which attended the baking venture led in
1840 to the formation of a general society. In later years this society
split over the question of adopting the Rochdale system of disposing
of the surpluses, and a new society was formed which continues
strong and vigorous; and with this new society the baking society
finally amalgamated. Later still a society was formed in Dunfermline,
which in 1866 showed a surplus on working of £493.
Meantime Co-operation was going ahead in the North. Societies
had been formed in Kirriemuir, Brechin, Arbroath, and Forfar, and
very early in its history Kirriemuir took up the baking of bread.
Arbroath West Port Association began the baking of bread in 1846,
while in the year immediately preceding—1845—Arbroath Guthrie
Port Association, in altering their rules, placed first in the list of the
objects of the society “to make bread and to deal in bread,” so that it
is evident that the society was then baking or had baking in
contemplation. This is the society which is now known by the name
of Arbroath Equitable Society.
 BAKING IN THE BORDERLAND.
Co-operation does not seem to have found a footing in the South
quite as early as it did in the North and West, but the Borderers were
not far behind, and they have proved that having once started they
believed in perseverance. It was in 1839 that Galashiels Store
Company was formed, and the question of bread supply was soon
under consideration. In its earliest years the society seems to have
had considerable difficulty in getting a satisfactory supply of bread,
with the result that by 1844 they had established a bakery of their
own. An interesting fact which is related by Mr Maxwell in his
“History of Scotland” is that they applied for information about
baking to two societies, long disappeared, Coupar Angus and Alyth.
Probably some one connected with the society was a native of
Forfarshire, and, knowing that these societies had bakeries,
suggested that information be got from them. The number of these
efforts to cheapen the staff of life must have been very great, for
references to them keep cropping up in old newspapers and
pamphlets, showing that Co-operative activity, much of it inspired
doubtless by the teachings of Owen, was widespread in Scotland.
Hawick Store Company began a few months later than the
Galashiels venture, but it was not until 1851 that the members added
baking to the list of their enterprises.
 GLASGOW SOCIETY.
Turning again to Glasgow, where the first Co-operative bakeries of
which there is any record were established, we find that many
attempts had been made in the interval to establish Co-operative
trading on a firm foundation, but in vain. How many of these early
Co-operative failures were due to the fact that the surpluses accruing
from the trading transactions were divided in proportion to the
capital held, without any regard being paid to the trade done with the
society by the holders of the capital, it is not possible to say, but the
system was bound to have a disturbing effect on the minds of those
members who, although too poor to invest much capital, were loyal
purchasers from the store.
However that may be, after a lecture by Holyoake, a fresh attempt
to establish Co-operation in the city was made, and for a time the
new venture seemed to flourish, only to perish eventually like its
predecessors. What makes this society interesting at this point is that
of it is recorded the fact that it possessed “a modern baking
department,” and is said to have supplied the neighbouring societies
with bread. The society came to an end in 1865, and with it ended
Co-operative baking in the city for the time being. When next we
hear of it it is in a new, and as it turned out, a stabler and more
permanent form.
At this point it may be interesting to note some particulars of the
Co-operative baking societies in existence in Scotland in 1866, as
taken from the returns sent in to the Registrar of Friendly Societies
in Scotland. It is probable that the list is far from complete, and it
takes no account of the societies having bakeries of their own who
dealt in other goods as well. These societies were:—
 Value of Property. Profits.
Airdrie Bread No property. £252
Alva Baking £l,184 331
Bainsford and Grahamston 1,484 788
Coatbridge Bread 857 466
Dalry Baking 20 50
Dunfermline Baking 116 493
Edinburgh Bread 422 271
Leven Baking 200 120
Roslin Baking 82
Stenhousemuir Baking 782 350

A notable absentee from the above list is the name of Kingskettle

Baking Society.
 THE FIRST FEDERATED BAKERY.
As it was in Ayrshire, in the little village of Fenwick, that, so far as
is known, the first Co-operative society was established, so also to
Ayrshire belongs the honour of having established the first federated
bakery. Co-operation in Fenwick had died in 1801 with the demise of
the old Meal Society, and it was not until 1840, when Darvel
Industrial Society was founded, that it again secured a footing in the
land of Burns. The society founded 79 years ago continues to
flourish, but for the first twenty years it had to flourish alone. Then,
in 1860, Kilmarnock Society was founded, and following it there
came in quick succession Crosshouse, Auchinleck, Mauchline,
Galston, Newmilns, and Catrine. In 1867 five of these societies—
Kilmarnock, Crosshouse, Galston, Mauchline, and Newmilns—
combined to form a baking society, while three other societies—
Troon, Catrine, and Darvel—although not members, took bread from
the federation. In 1870 premises were built for the federation, and
the trade increased steadily. Gradually, however, the more distant
societies began to erect bakeries of their own, and in the early
’nineties of last century the bakery was taken over by Kilmarnock
Society, who erected a new and up-to-date bakery for themselves on
the site of the old one.
COBURG STREET PREMISES

ST JAMES STREET PREMISES

M‘NEIL STREET PREMISES (1886–1890)

M‘NEIL STREET PREMISES (1890–1894)

 CHAPTER III.
THE FIRST YEAR.

GLASGOW IN THE ’SIXTIES—THE SOCIETY FORMED—MEN

WHO WROUGHT—THE FIRST BAKERY—STARTING
BUSINESS—A DISASTER AVOIDED—BETTER PROSPECTS
—A MANAGER APPOINTED—LARGER PREMISES WANTED
—SOMETHING ATTEMPTED, SOMETHING DONE.

In the ’sixties of last century Glasgow was not a pleasant place for
working men to live in. The city was contained in the four parishes of
Barony, City, Govan, and Gorbals; only a small proportion of its
population being resident in the last-named parish, however. The
conditions of life for the workers were not good. Houses were small
and inconvenient, disease was rampant, and poverty the common
lot. There were 87,604 inhabited houses in the city in the year 1864,
and of these 35,788 were rented at £5 per annum, or under; the
average rental being £3, 7s. 3d. Other 35,393 houses had rentals of
between £5 and £10, the average rental being £6, 17s. 3d., and the
average rental of these 71,181 houses, forming 81·75 per cent. of the
total housing accommodation of the city, was £5, 5s. per annum.
Further light is thrown on the housing conditions by the fact that,
while the aggregate rental for these 71,181 houses was £373,441, the
aggregate rental for the remaining 16,423 houses was £502,687; an
average rental per house of £30, 10s. The proportions of these lowly-
rented houses were fairly equal in all four parishes, and even when
allowance is made for the fact that rents were much lower in those
days than they have been in recent years for similar accommodation
it is evident that the housing conditions left much to be desired, and
that the “homes of the people” must have been veritable hotbeds of
disease. In the statistics consulted the proportion of one-apartment
houses is not given, but in view of the whole-hearted condemnation
of such houses voiced by Dr Russell, Medical Officer of Health for
Glasgow, twenty years later, and the large proportion of Glasgow’s
citizens who were then living in houses which were kitchen, parlour,
bedroom, and washhouse all in one, it is easy to believe that the
houses of the earlier period were no better than the low rentals
would warrant.
Further evidence of the correctness of this assumption is found in
the vital statistics of the period. In 1864 the deaths of children under
five years of age were 46·93 per cent. of the total deaths; in 1862 they
had been 48·85 per cent. of the total. In those years the children were
dying at the rate of one in every nine of the population, a deathrate
nearly equal to that of the British Army during the four years of war.
The effects of poverty and bad housing on the health of the
population were further evidenced by the number of deaths of
children under five from tubercular diseases. In 1863 these were 381;
in 1864, 378; while the total deaths from tuberculosis were 1562 and
1763 respectively for the same years. In his report to the Corporation
for the year 1864, Mr Watson, Town Chamberlain, points out that
there was ample scope in the statistics he had compiled for showing
the need for benevolence “in alleviating the character of the
dwellings of the very poor,” and he urged the need which existed to
provide other and better houses. At the same time he notes that
employment generally was good in this year. In 1868, 786 children
under five died from consumption, and in 1869 the total infantile
deathrate (children under one year) was 48·20 per 1,000. In the
Clyde area it was 56·81 per 1,000.
It was in a city in which the conditions of the people were such as
the figures quoted above reveal that, on the last Monday in January
1869, what was destined in the course of fifty years to become the
largest business of its kind in the world opened its doors for trade.
For six years the idea of the federation of Co-operative societies for
trading purposes had been occupying the minds of the Co-operators
of Scotland, keenly interested as they were in the progress of the
North of England Co-operative Wholesale Society. Only a little over
two years before, also, those of them in the West who took an
interest in the affairs of their Co-operative neighbours had seen the
Co-operative societies of Ayrshire join together to form a baking
association for the purpose of supplying themselves with bread; and
in September 1868 the Scottish Co-operative Wholesale Society had
been safely launched, after several years of anxious consultation and
consideration. No sooner had the S.C.W.S. been sent on its way than
the stalwarts of the West turned their attention to yet another
venture. Since the collapse of the second Glasgow Society there had
been no Co-operatively-produced bread in the city. The price which
was being charged for bread by the private bakers was considered too
high, and yet not one of the societies thought itself strong enough to
finance a bakery of its own.
They had faith in the Co-operative principle, however, and what
they could not do as individuals they fancied they would be able to do
in combination. They reasoned that, if a number of people by
combining together could procure the goods they needed more
cheaply than any one of them alone could do, there was no good
reason why a number of societies by combining together could not do
what no one of them acting alone was strong enough to do.
It is to Mr Gabriel Thomson of St Rollox Society, then treasurer of
the newly formed S.C.W.S., that the honour of first bringing the idea
of a federated bakery publicly before the co-operators of the West
belongs. The first idea was that the work should be undertaken by
the recently-formed Wholesale Society, but a little consideration
showed that this plan was hardly feasible. It was thought that it
would scarcely be right to adventure the capital of societies scattered
all over Scotland in an undertaking from which many of them could
not possibly derive any direct benefit, and so this idea was dropped,
and finally it was decided to start a federated baking society.
In the new venture St Rollox Society was the prime mover. In
those days the men who controlled St Rollox Society believed in the
infinite possibilities of the application of Co-operative principles.
They were joined with other Glasgow societies in a drapery
federation. They took up shares in the St Rollox Cooperage Society,
in the Ironworks, and in the Oakmill Society, each as it arose, and to
Co-operation they looked for escape from the exactions of the master
bakers of Glasgow. A meeting was convened by them in the month of
October 1868, and to that meeting Mr Gabriel Thomson read a paper
on “Federation,” in which he dealt at length with the principle as it
could be applied to the baking of bread. This paper so strongly
influenced the delegates that there and then they approved of the
principle, and went back to their societies to report. In a few weeks
another meeting was called, which was attended by representatives
from Barrhead, St Rollox, Paisley Provident, Paisley Equitable,
Glasgow Eastern, Anderston, Parkhead, Johnstone, Howwood,
Glasgow Southern, Motherwell, Lennoxtown, and others. At this
meeting the proposal was discussed further, and at the close the
delegates pledged themselves to go back to their societies and do all
in their power to get these to take part in the formation of the
federation.
 THE SOCIETY FORMED.
A third meeting was held a fortnight later, and at this meeting
eight societies intimated their willingness to join in forming the
Federation. These were Anderston, Barrhead, Cathcart, Johnstone,
Lennoxtown, Motherwell, St Rollox, and Thornliebank. An interim
committee was formed, consisting of Messrs Gabriel Thomson and
John West (St Rollox), James Borrowman and Alexander Douglas
(Anderston), James Ferguson and Alexander Johnstone (Barrhead),
and Joseph Gibb and Donald Cameron (Thornliebank). Three of
their number—Messrs Thomson, Borrowman, and Cameron—were
appointed a sub-committee to look out for suitable premises,
consider the working of the bakery and the delivery of the bread, and
report to a future meeting.
No better men could have been selected for the task. Mr Thomson
was the originator of the scheme, and was also the treasurer of the
S.C.W.S. Mr Borrowman had already made a name for himself as the
most powerful advocate of Co-operation that Scotland had produced.
He had taken a leading part in establishing the S.C.W.S., and was
now its manager; while Mr Cameron was not only a shrewd and
earnest Co-operator, but appears also to have had some knowledge
of the baking trade. We can well imagine the zeal and earnestness
with which they set about their task. They knew that they were
setting out on a journey along an untrodden path, but they had a
faith which lighted up the dark places before them, and a
determination to see the mission on which they had entered, the first
step to the fulfilment of their hopes, accomplished as soon as
possible. Inside two weeks they were back to the parent committee,
their task accomplished, bringing with them particulars of a
bakehouse which they thought would suit the requirements of the
new society, a scheme for carrying on the business, and particulars
about methods of delivery. Their report was approved, the bakery at
52 South Coburg Street was leased, and instructions were given for
its immediate repair.
 The minute of committee, the first minute of the new Society, is as
follows:—
“16th January 1869.

“A meeting was convened to-day to hear the report of the committee in the
office of the Scottish Co-operative Wholesale Society. At this meeting the
following societies were represented—Barrhead, St Rollox, Anderston,
Eastern, Motherwell, Dalziel, Cadder, and Thornliebank. A report was
submitted by the committee stating that premises had been secured and that
they were convinced that the business would pay well, and recommended an
immediate start. The report was accepted and the following sub-committee
was appointed to carry out the resolution—viz., Gabriel Thomson, president;
John West, treasurer; James Borrowman, secretary; and Alexander Douglas.
Same committee to get the rules printed in accordance with the alterations
made on the Ayrshire United Co-operative Societies Baking Association, and
submit the same to the general meeting of the delegates before registration.”
All that now remained to be done was to get the bakery into
working order, and ten days sufficed to have this work completed.
Meantime, however, the committee were not idle. Vans had to be
procured and other details of the work inside and outside seen to,
and bakers had to be employed. The committee met on 23rd
January, and appointed a Mr Currie as foreman baker, while on 6th
February they decided to purchase a second van at a cost of £18 and
a horse for a similar sum. A vanman was also engaged at a wage of
20/ a week.
These little details are all in the minutes, but no mention of the
situation of the bakery appears therein, nor is there any mention
made of the date of beginning business. These old-time Co-operators
were so engrossed in the work they were doing that they had no
thought for the people who would come after them, eager for
information about what they had done and how they had done it. It
would appear from the minute book itself that it was written up at a
date later than the beginning of the Society, probably from notes
made by Mr Borrowman at the time, and this may account for the
omission of any mention of the date of beginning business or of the
location of the bakery.
We know, however, that the bakery was situated in South Coburg
Street, a street which connected Bedford Street with Norfolk Street,
parallel with and immediately behind Eglinton Street. The buildings