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General Principles
Third Edition
SENIOR EDITORS EDITORS

TAO LE, MD, MHS LUKE R.G. PIKE, MD, DPhil
Associate Clinical Professor Resident, Harvard Radiation Oncology Program
Chief, Section of Allergy and Immunology Massachusetts General Hospital
Department of Medicine Brigham & Women’s Hospital
University of Louisville
M. SCOTT MOORE, DO
WILLIAM L. HWANG, MD, PhD Clinical Research Fellow
Resident, Harvard Radiation Oncology Program Affiliated Laboratories, Scottsdale
Massachusetts General Hospital
Brigham & Women’s Hospital
New York / Chicago / San Francisco / Athens / London / Madrid / Mexico City
Milan / New Delhi / Singapore / Sydney / Toronto
0 GP_3e_FM_i-xiv.indd 1 10/28/16 3:14 PM

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DEDICATION
To the contributors to this and future editions, who took time to share their knowledge,
insight, and humor for the benefit of students and physicians everywhere.
and
To our families, friends, and loved ones, who supported us

in the task of assembling this guide.

This page intentionally left blank

v
Contents
Contributing Authors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi CHAPTER 4. Microbiology . . . . . . . . . . . . . . . . . . . 229
Faculty Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Bacteriology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Mycology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286
How to Use This Book . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . x Parasitology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Virology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
How to Contribute . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Microbiology: Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Antimicrobials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
CHAPTER 1. Anatomy and Histology . . . . . . . . . . . 1
Cellular Anatomy and Histology . . . . . . . . . . . . . . . . . . . . . . 2 CHAPTER 5. Pathology . . . . . . . . . . . . . . . . . . . . . . 395
Gross Anatomy and Histology . . . . . . . . . . . . . . . . . . . . . . . 15
CHAPTER 6. General Pharmacology . . . . . . . . . .417
CHAPTER 2. Biochemistry . . . . . . . . . . . . . . . . . . . . 33
Pharmacokinetics and Pharmacodynamics . . . . . . . . . 418
Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Nucleotide Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Mutations and DNA Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 CHAPTER 7. Public Health Sciences . . . . . . . . . . 435
Enzymes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
The Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445
Connective Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Public Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 449
Homeostasis and Metabolism . . . . . . . . . . . . . . . . . . . . . . . . 83 Patient Safety and Quality Improvement . . . . . . . . . . . 453
Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456
Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Life Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
Fed Versus Unfed State . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Psychology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Laboratory Tests and Techniques . . . . . . . . . . . . . . . . . . 169
Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 Image Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . 469
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
CHAPTER 3. Immunology . . . . . . . . . . . . . . . . . . . 187
About the Editors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
Principles of Immunology . . . . . . . . . . . . . . . . . . . . . . . . . 188
Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207

vi
CONTRIBUTING AUTHORS
Ezra Baraban, MD Margaret MacGibeny, MS
Yale School of Medicine Rutgers Robert Wood Johnson Medical School and
Class of 2016 Princeton University MD/PhD program
Nashid H. Chaudhury Class of 2020
Medical Scientist Training Program
Benjamin B. Massenburg
Yale School of Medicine
Icahn School of Medicine at Mount Sinai
Class of 2020
Class of 2017
Richard Giovane, MD
Resident, Department of Family Medicine Jake Prigoff, M
University of Alabama Resident, Department of Surgery
Jessica F. Johnston, MSc New York Presbyterian Hospital
Medical Scientist Training Program
Ritchell van Dams, MD, MHS
Intern, Department of Medicine
Class of 2020
Norwalk Hospital
Young H. Lim
Medical Scientist Training Program Zachary Schwam, MD
Yale School of Medicine Yale School of Medicine
Class of 2020 Class of 2016

vii
FACULTY REVIEWERS
Susan Baserga, MD, PhD Gerald Lee, MD
Professor, Molecular Biophysics & Biochemistry Genetics and Assistant Professor, Department of Pediatrics
Therapeutic Radiology University of Louisville School of Medicine
Alexandros D. Polydorides, MD, PhD
Sheldon Campbell, MD, PhD Associate Professor of Pathology and Medicine (Gastroenterology)
Associate Professor of Laboratory Medicine Icahn School of Medicine at Mount Sinai
Co-director, Attacks and Defenses Master Course
Sylvia Wassertheil-Smoller, PhD
Director, Laboratories at VA CT Healthcare System
Distinguished University Professor and
Director, Microbiology Fellowship
Molly Rosen and Maneoloff Chair in Social Medicine, Emerita
Department of Epidemiology and Population Health
Conrad Fischer, MD Albert Einstein College of Medicine
Residency Program Director, Brookdale University Hospital
Brooklyn, New York Howard M. Steinman, PhD
Associate Professor, Medicine, Physiology, and Pharmacology Professor, Department of Biochemistry
Touro College of Medicine Assistant Dean for Biomedical Science Education
Albert Einstein College of Medicine
Matthew Grant, MD
Assistant Professor of Medicine (Infectious Disease) Peter Takizawa, PhD
Director, Yale Health Travel Medicine Assistant Professor, Department of Cell Biology
Yale School of Medicine Director, Medical Studies
Marcel Green, MD
Resident Physician, Department of Psychiatry George J. Trachte, PhD
Mount Sinai Health System, St. Luke’s–Roosevelt Hospital Professor, Department of Biomedical Sciences
University of Minnesota
Peter Heeger, MD
Irene and Arthur Fishberg Professor of Medicine Prashant Vaishnava, MD
Translational Transplant Research Center Assistant Professor, Department of Medicine
Department of Medicine Mount Sinai Hospital and Icahn School of Medicine at Mount
Icahn School of Medicine at Mount Sinai Sinai
Jeffrey W. Hofmann, MD, Ph Ana A. Weil, MD
Resident, Department of Pathology Instructor in Medicine
University of California, San Francisco Massachusetts General Hospital


ix
Preface
With this third edition of First Aid for the Basic Sciences: General Principles, we con-
tinue our commitment to providing students with the most useful and up-to-date
preparation guides for the USMLE Step 1. For the past year, a team of authors and
editors have worked to update and further improve this third edition. This edition
represents a major revision in many ways.
■ Brand new Public Health and Patient Safety sections have been added.
■ Every page has been carefully reviewed and updated to reflect the most high-yield
material for the Step 1 exam.
■ New high-yield figures, tables, and mnemonics have been incorporated.
■ Margin elements, including flash cards, have been added to assist in optimizing the
studying process.
■ Hundreds of user comments and suggestions have been incorporated
■ Emphasis on integration and linkage of concepts was increased.
This book would not have been possible without the help of the hundreds of students
and faculty members who contributed their feedback and suggestions. We invite stu-
dents and faculty to please share their thoughts and ideas to help us improve First Aid
for the Basic Sciences: General Principles. (See How to Contribute, p. xiii.)
Louisville Tao Le
Boston William Hwang

x
How to Use This Book

Both this text and its companion, First Aid for the Basic Sciences: Organ Systems, are
designed to fill the need for a high-quality, in-depth, conceptually driven study guide
for the USMLE Step 1. They can be used alone or in conjunction with the original
First Aid for the USMLE Step 1. In this way, students can tailor their own studying
experience, calling on either series, according to their mastery of each subject.
Medical students who have used the previous editions of this guide have given us
feedback on how best to make use of the book.
■ It is recommended that you begin using this book as early as possible when learn-
ing the basic medical sciences. We advise that you use this book as a companion to
your preclinical medical school courses to provide a guide for the concepts that are
most important for the USMLE Step 1.
■ As you study each discipline, use the corresponding section in First Aid for the
Basic Sciences: General Principles to consolidate the material, deepen your under-
standing, or clarify concepts.
■ As you approach the test, use both First Aid for the Basic Sciences: General Principles
and First Aid for the Basic Sciences: Organ Systems to review challenging concepts.
■ Use the margin elements (ie, Flash Forward, Flash Back, Key Fact, Clinical Cor-
relation, Mnemonic, Flash Cards) to test yourself throughout your studies.
To broaden your learning strategy, you can integrate your First Aid for the Basic Sci-
ences: General Principles study with First Aid for the USMLE Step 1, First Aid Cases
for the USMLE Step 1, and First Aid Q&A for the USMLE Step 1 on a chapter-by-
chapter basis.

xi
Acknowledgments
This has been a collaborative project from the start. We gratefully acknowledge the
thoughtful comments and advice of the residents, international medical graduates,
medical students, and faculty who have supported the editors and authors in the de-
velopment of First Aid for the Basic Sciences: General Principles.
For support and encouragement throughout the process, we are grateful to Thao
Pham and Louise Petersen.
Furthermore, we wish to give credit to our amazing editors and authors, who worked
tirelessly on the manuscript. We never cease to be amazed by their dedication,
thoughtfulness, and creativity.
Thanks to our publisher, McGraw-Hill Education, for their assistance and guidance.
For outstanding editorial work, we thank Allison Battista, Christine Diedrich, Ruth
Kaufman, Isabel Nogueira, Emma Underdown, Catherine Johnson, and Hannah
Warnshuis. A special thanks to Rainbow Graphics, especially David Hommel, for
remarkable production work.
We are also very grateful to the faculty at Uniformed Services University of the
Health Sciences (USUHS) for use of their images and Dr. Richard Usatine for his
outstanding dermatologic and clinical image contributions.
For contributions and corrections, we thank Abraham Abdul-Hak, Mohamed Abdulla,
Zachary Aberman, Andranik Agazaryan, Zain Ahmed, Anas Alabkaa, Allen Avedian,
Syed Ayaz, Andrew Beck, Michael Bellew, Konstantinos Belogiannis, Candace
Benoit, Brandon Bodie, Aaron Bush, Robert Case, Jr., Anup Chalise, Rajdeep
Chana, Sheng-chieh Chang, Yu Chiu, Renee Cholyway, Alice Chuang, Diana
Dean, Douglas Dembinski, Kathryn Demitruk, Regina DePietro, Nolan Derr,
Vikram Eddy, Alejandra Ellison-Barnes, Leonel Estofan, Tim Evans, Matt Fishman,
Emerson Franke, Margaret Funk, Alejandro Garcia, William Gentry, Richard
Godby, Shawn Gogia, Marisol Gonzalez, William Graves, Jessie Hanna, Clare
Herickhoff, Joyce Ho, Jeff Hodges, David Huang, Andrew Iskandar, Anicia Ivey,
Jeffrey James, Angela Jiang, Bradford Jones, Caroline Jones, Charissa Kahue, Sophie
Kerszberg, Michael Kertzner, Mani Khorsand Askari, Peeraphol La-orkanchanakun,
Juhye Lee, Jessica Liu, Jinyu Lu, James McClurg, Gregory McWhir, Rahul Mehta,
Kristen Mengwasser, Aleksandra Miucin, Morgan Moon, Jan Neander, Michael
Nguyen, Jay Patel, Nehal Patel, Iqra Patoli, Matthew Peters, Yelyzaveta Plechysta,
Qiong Qui, Peter Francis Raguindin, Kenny Rivera, Luis Rivera, Benjamin Robbins,
Jorge Roman, Julietta Rubin, Kaivan Salehpour, Abdullah Sarkar, Hoda Shabpiray,
Neal Shah, Chris Shoff, Rachael Snow, Gregory Steinberg, Ryan Town, Michael
Turgeon, Hunter Upton, Zack Vanderlaan, Christopher Vetter, Liliana Villamil
Nunez, Sukanthi Viruthagiri, David Marcus Wang, and Andy Zureick.
Louisville Tao Le
Boston William Hwang


xiii
How to Contribute
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CHAPTER 1
Anatomy and Histology
CELLULAR ANATOMY AND HISTOLOGY 2 Splenic Anatomy 20

The Cell 2 The Lymphatic System 20
Hematopoiesis 8 Peripheral Nervous System 23
The Integumentary System 25
GROSS ANATOMY AND HISTOLOGY 15 The Respiratory System 29
Abdominal Wall Anatomy 15 The Adrenal Glands 31
The Gastrointestinal System 17
1 GP_3e_CH_01_Anat-Histol_1-32.indd 1 10/26/16 2:58 PM

2 CHAPTER 1 ANATOMY AND HISTOLOGY
Cellular Anatomy and Histology
THE CELL
The cell is the most basic structural and functional unit of life. Living organisms are com-
posed of cells, which may exist as independent units or form more complex organisms.
Each cell is a collection of integral, diverse components, required for the biochemical
processes that sustain the life of the organism. The most important eukaryotic cellular
components will be covered in the following sections.
Plasma Membrane
Every eukaryotic cell is enveloped by an asymmetric lipid bilayer membrane. This
membrane consists primarily of two sheets of phospholipids, each one-molecule thick
(Figure 1-1B). Phospholipids are amphipathic molecules, containing both a water-
soluble hydrophilic region and a fat-soluble hydrophobic region (Figure 1-1).
Aqueous phase (extracellular)
Polar or
hydrophilic groups
“Oil” or nonpolar phase
Nonpolar or
hydrophobic groups
Aqueous phase (cytoplasm)

A
A. Phospholipid B
B. Lipid bilayer/
cell membrane
Aqueous phase
Aqueous phase
Nonpolar
phase
polar phase
Non
Aqueous
phase
Lipid
bilayer
C
C. Micelle D
D. Liposome (unilamellar)
Aqueous Lipid
compartments bilayers
EE. Liposome (multilamellar)
F I G U R E 1 - 1 . Amphipathic lipids. A Phospholipid, with a phosphate head group and a lipid

tail; B lipid bilayer with both aqueous and nonpolar phases; C micelle in aqueous solution
surrounding a nonpolar core; D unilamellar; and E multilamellar liposomes.

ANATOMY AND HISTOLOGY CHAPTER 1 3
■ The hydrophilic portions (ie, phosphate groups) of each phospholipid layer face
both the aqueous extracellular environment as well as the aqueous cytoplasm.
■ The hydrophobic portions of each phospholipid layer (ie, fatty acid chains) make
up the fat-soluble center of the phospholipid membrane.
This bilayer membrane also contains steroid molecules (derived from cholesterol), KEY FACT
glycolipids (fatty acids with sugar moieties), sphingolipids, proteins, and glycoproteins
Biologically important proteins include
(proteins with sugar moieties). The cholesterol and glycolipid molecules alter the physi- transmembrane transporters, ligand-
cal properties of the membrane (eg, increase the melting point) in relative proportion receptor complexes, and ion channels.
to their quantity. The proteins serve important and specific roles in the transport and Protein dysfunction underlies many
trafficking of nutrients across the membrane, signal transduction, and interactions diseases.
between the cell and its environment.
The cell membrane performs the following functions:

■ Enhances cellular structural stability.
■ Protects internal organelles from the external environment.
■ Regulates the internal environment (chemical and electrical potential).
■ Enables interactions with the external environment (eg, signal transduction and
cellular adhesion).
FLASH
Nucleus and Nucleolus FORWARD
The nucleus is the control center of the cell. The nucleus contains genetically encoded Genetic mutations may cause
information in the form of DNA, which directs the life processes of the cell. It is sur- dysfunction of regulatory proteins,
often leading to debilitating diseases.
rounded by the nuclear membrane, which is composed of two lipid bilayers: The inner
For example, xeroderma pigmentosum
membrane defines the boundaries of the nucleus, and the outer membrane is continuous is an autosomal recessive disorder of
with the rough endoplasmic reticulum (RER) (Figure 1-2). In addition to DNA, the nucleotide excision repair that leads
nucleus houses a number of important proteins that enable the maintenance (protec- to increased sensitivity to UV light and
tion, repair, and replication), expression (transcription), and transportation of genetic increased rates of skin cancer.
material (capping, transport).
Most of the cell’s ribosomal RNA (rRNA) is produced within the nucleus by the nucleo-
lus. The rRNA then passes through the nuclear pores (transmembrane protein com-
plexes that regulate trafficking across the nuclear membrane) to the cytosol, where it
associates with the RER.
Rough Endoplasmic Reticulum and Ribosomes

As previously described, the RER is home to the majority of the cell’s ribosomes. The
rough in rough endoplasmic reticulum comes from the many ribosomes that stud the
KEY FACT
membrane of the RER. Ribosomes associate with transfer RNA (tRNA) to translate mes-
senger RNA (mRNA) into amino acid sequences and, eventually, into proteins (Figure The RER in neurons is referred to as
1-3). The RER functions primarily as the location for membrane and secretory protein Nissl body when viewed under a
production as well as protein modification (Figure 1-2). The RER is highly developed in microscope.
cell types that produce secretory proteins (eg, pancreatic acinar cells or plasma cells).
Smooth Endoplasmic Reticulum

FLASH
The smooth endoplasmic reticulum (SER) is the site of fatty acid and phospholipid FORWARD
production and therefore is highly developed in cells of the adrenal cortex and steroid-
The cytochrome P-450 system is a
secreting cells of the ovaries and testes. Hepatocytes also have a highly developed SER,
family of enzymes located in the SER or
as they are constantly detoxifying hydrophobic compounds through conjugation and mitochondria that metabolize millions
excretion. of endogenous and exogenous
compounds.
Golgi Apparatus
Shortly after being synthesized, proteins from the RER are packaged into transport
vesicles and secreted from the RER. These vesicles travel to and fuse with the Golgi
apparatus. Within the lumen of the Golgi apparatus, secretory and membrane-bound

Key:
brane
mem
Clathrin sma
Pla
Secretory
vesicle
COPI Late Early
endosome endosome
CLINICAL COPII
Lysosome
CORRELATION
Retrograde trans
Inclusion-cell (I-cell) disease, also
known as mucolipidosis type II, results Anterograde
from a defect in N-acetylglucosaminyl- Golgi
1-phosphotransferase, leading to apparatus
a failure of the Golgi apparatus to
phosphorylate mannose residues (ie,
mannose-6-phosphate) on N-linked cis
glycoproteins. Thus, hydrolytic
enzymes are secreted extracellularly,
rather than delivered to lysosomes, Endoplasmic
hindering the digestion of intracellular reticulum
waste. Coarse facial features and
restricted joint movements result (refer Nuclear envelope
to Biochemistry chapter for discussion
of lysosomal storage disorders).
F I G U R E 1 - 2 . Representation of the rough endoplasmic reticular branch of protein
sorting. Newly synthesized proteins are inserted into the endoplasmic reticulum membrane, or
CLINICAL enter the lumen from membrane-bound polyribosomes, depicted as light blue spheres studding
CORRELATION the endoplasmic reticulum. Those proteins are then transported out of the endoplasmic
reticulum to the Golgi apparatus. Transport to the Golgi apparatus (anterograde transport)
A number of lysosomal storage
is mediated by COPII membrane proteins. Transport from the Golgi apparatus back to the
diseases, such as Tay-Sachs disease,
endoplasmic reticulum (retrograde transport) is mediated by COPI membrane proteins.
result from lysosomal dysfunction
The proteins can be modified in the various subcompartments of the Golgi apparatus and
and the accumulation of protein are then segregated and sorted in the trans-Golgi network. Secretory proteins accumulate in
metabolites targeted for destruction or secretory storage granules, from which they may be expelled. Proteins destined for the plasma
further modification. membrane, or those that are secreted in a constitutive manner, are carried out to the cell
surface in transport vesicles. This transport is mediated by clathrin membrane proteins. Some
proteins enter prelysosomes (late endosomes) and fuse with endosomes to form lysosomes.
60S
Ribosome
proteins undergo modification. Depending on their final destination, these proteins may
be modified in one of the three major regions of Golgi networks: cis (CGN), medial
E P A (MGN), or trans (TGN). These proteins are then packaged in a second set of transport
5' 3' vesicles, which bud from the trans side and are delivered to their target locations (eg,
organelle membranes, plasma membrane, and lysosomes; Figure 1-2).
40S
Functions of the Golgi Apparatus

F I G U R E 1 - 3 . Schematic
representation of translation. Here, ■ Distributes proteins and lipids from the endoplasmic reticulum to the plasma mem-
the 40S and 60S subunits of rRNA brane, lysosomes, and secretory vesicles.
are shown, translating a portion of ■ Modifies N-oligosaccharides on asparagines.
mRNA in the 5′ to 3′ direction. Many ■ Adds O-oligosaccharides to serine and threonine residues.
of these ribosomes are located within ■ Assembles proteoglycans from core proteins.
the membrane of the RER so that
their initial protein product ends up
■ Adds sulfate to sugars in proteoglycans and tyrosine residues on proteins.
within the lumen of the RER, where ■ Adds mannose-6-phosphate to specific proteins (targets the proteins to the lysosome).
it undergoes further modification.
E site, holds Empty tRNA as it Lysosomes
Exits; P site, accommodates growing
Peptide; A site, Arriving Aminoacyl The lysosome is the trash collector of the cell. Bound by a single lipid bilayer, the lyso-
tRNA. some is responsible for hydrolytic degradation of obsolete cellular components. Extra-

cellular materials, ingested via endocytosis or phagocytosis, are enveloped in an endo- CLINICAL
some (temporary vesicle), which fuses with the lysosome, leading to enzymatic CORRELATION
degradation of endosomal contents. Lysosomal enzymes (nucleases, proteases, and
Chédiak-Higashi disease, resulting
phosphatases) are activated at a pH below 4.8. To maintain this pH, the membrane of from abnormal microtubular assembly,
the lysosome contains a hydrogen ion pump, which uses adenosine triphosphate (ATP) leads to impaired polymorphonuclear
to pump protons into the lysosome, against the concentration gradient. leukocytes (PMNs) phagocytosis and
frequent infections.
Mitochondria
The mitochondria are the primary site of ATP production in aerobic respiration. The
CLINICAL
proteins of the outer membrane enable the transport of large molecules (molecular CORRELATION
weight ~10,000 daltons) for oxidative respiration. The inner membrane is separated
Various inherited disorders can
from the outer by the intermembranous space and is more selectively permeable (Figure
be maternally transmitted via
1-4). The inner membrane has a large surface area due to its numerous folds, known as
mitochondrial chromosomes. These
cristae, and it maintains its selectivity with transmembrane proteins. These transmem- can show a variable expression in
brane proteins constitute the electron transport chain, and maintain a proton gradient a population due to heteroplasmy,
between the intermembranous space and the lumen of the inner membrane. The role or the presence of heterogenous
of the electron transport chain is to generate energy for storage in the bonds of ATP. mitochondrial DNA in an individual.
These diseases primarily affect the
Microtubules and Cilia muscles, cerebrum, or the nerves,
where energy is needed the most.
Microtubules are aggregate intracellular protein structures important for cellular sup- For example, myoclonic epilepsy with
port, rigidity, and locomotion. They consist of α- and β-tubulin dimers, each bound ragged-red fibers is a mitochondrial
to two guanosine triphosphate (GTP) molecules, giving them a positive and negative disorder characterized by progressive
polarity. They combine to form cylindrical polymers of of 24 nm in diameter and vari- myoclonic epilepsy, short stature,
able lengths (Figure 1-5A). Polymerization occurs slowly at the positive end of the hearing loss, and “ragged-red fibers” on
microtubule, but depolymerization occurs rapidly unless a GTP cap is in place. biopsy.
Microtubules are incorporated into both flagella and cilia. Within cilia, the microtu-
bules occur in pairs, known as doublets. A single cilium contains nine doublets around KEY FACT
its circumference, each linked by an ATPase, dynein (Figure 1-5B). Dynein, anchored
to one doublet, moves toward the negative end of the microtubule along the length of Drugs that act on microtubules:
a neighboring doublet in a coordinated fashion, resulting in ciliary motion. Kinesin is Drug Disease
another intracellular transport ATPase that moves toward the positive end of a micro- Mebendazole/ Parasitic
tubule, opposite of dynein. albendazole infections
Taxanes Cancers
Griseofulvin Fungal infections
Vincristine/ Cancers
Matrix:
citric acid enzymes, vinblastine
β-oxidation, pyruvate Colchicine Gout
dehydrogenase Cristae of mitochondria
CLINICAL
CORRELATION
A number of diseases arise from
ineffective or insufficient ciliary
motion.
Kartagener syndrome: A dynein arm
defect that impairs ciliary motion
and mucus clearance that results in
recurrent lung infections, hearing
loss, infertility, and dextrocardia situs
Intermembrane: Inner membrane: Outer membrane:
phosphotransferase electron carriers, ATP synthase Acyl CoA synthetase, inversus.
enzymes particles, membrane transporters glycerophosphate acyl Dextrocardia/situs inversus: Proper
transferase
directional development does
not occur during embryogenesis,
F I G U R E 1 - 4 . Structure of the mitochondrial membranes. The inner membrane contains causing all internal organs to be
many folds, or cristae, and the enzymes for the electron transport chain, used in aerobic located on the opposite side of the
cellular respiration, are located here. body.

A 24 nm α−tubulin β−tubulin
(+) end
5 nm
Cross section Longitudinal section Tubulin

dimer
B Enlarged microtubule doublet
Shared
A heterodimers
B
Microtubule B Dynein
Microtubule A
Nexin link
Radial
spokes Microtubule
doublet
Plasma
membrane
Inner
dynein arm
Outer
dynein arm
F I G U R E 1 - 5 . Microtubules. A Structure. The cylindrical structure of a microtubule is

depicted as a circumferential array of 13 dimers of α- and β-tubulin. The tubulin dimers are
being added to the positive end of the microtubule. B Ciliary structure. Nine microtubule
doublets, circumferentially arranged, create motion via coordinated dynein ATP cleavage.
Epithelial Cell Junctions

Transmembrane proteins mediate intercellular interaction by providing cellular adhe-
sion and cell signaling. Cellular adhesion and communication are vitally important to
both the integrity and the function of an organ.
Organs and tissues exposed to the external environment are the most resilient. These
tissues are referred to as epithelial, primarily due to their embryologic origin. The
epithelial cells of these external tissues contain an array of cell junctions that medi-
CLINICAL
CORRELATION ate cellular adhesion and communication processes. There are five principal types of
cell junctions: zonula occludens (tight junctions), zonula adherens (intermediate
Malignant epithelial cells contained junctions), macula adherens (desmosomes), hemidesmosomes, and gap junctions
by the basal membrane are termed (communicating junctions) (Figure 1-6).
carcinoma in situ. Loss of cell
junctions allows penetration through
the basement membrane as invasive Zonula Occludens
carcinoma. When cells enter the Tight junctions, also referred to as occluding junctions, have the following two primary
bloodstream or lymphatics and functions:
establish new tumors at distant sites,
they are considered metastatic. ■ Determine epithelial cell polarity, separating the apical pole from the basolateral
pole.
■ Regulate passage of substances across the epithelial barrier (paracellular transport).
MNEMONIC
In a typical epithelial tissue, the membranes of adjacent cells meet at regular intervals
CADHErins are Calcium-dependent to seal the paracellular space, preventing the paracellular movement of solutes. These
ADHEsion proteins. connections occur during the interaction of the junctional protein complex with neigh-
boring cells, composed of claudins and occludins.

Apical
Tight junction (zonula occludens)—prevents paracellular
E-cadherin movement of solutes; composed of claudins and occludins.
Actin Adherens junction (belt desmosome, zonula adherens)—below

filaments tight junction, forms “belt” connecting actin cytoskeletons of
adjacent cells with CADherins (Ca2+-dependent adhesion
proteins). Loss of E-cadherin may allow metastasis.
Cytokeratin
Desmosome (spot desmosome, macula adherens)—structural
Desmoplakin support via intermediate filament interactions. Autoantibodies
pemphigus vulgaris.
Connexon Gap junction—channel proteins called connexons permit

with central electrical and chemical communication between cells.
channel
Cell membrane
Basolateral Basement membrane
Integrins—membrane proteins that maintain Hemidesmosome—connects keratin in basal cells to
integrity of basolateral membrane by binding underlying basement membrane. Autoantibodies bullous
to collagen and laminin in basement membrane. pemphigoid. (Hemidesmosomes are down “bullow.”)
F I G U R E 1 - 6 . Epithelial cell junctions. Five types of epithelial cell junctions are depicted along with their supporting and component
proteins.
Zonula Adherens CLINICAL

Intermediate junctions are located just below tight junctions, near the apical surface CORRELATION
of an epithelial layer. Like the zonula occludens, the zonula adherens are located in a Pemphigus vulgaris: An
beltlike distribution. Inside the cell, these transmembrane protein complexes are associ- autoimmune disease of the skin
ated with actin microfilaments. Outside the cell, cadherins from adjacent cells use a due to anti-desmosome antibodies.
calcium-dependent mechanism to span wider intercellular spaces than can the zona This disrupts the cohesion between
occludens. Loss of E-cadherin may allow cancer cells to metastasize. keratinocytes, leading to fragile blisters.
The antibodies are distributed in a
reticular or “net-like” pattern. Nikolsky
Macula Adherens sign is positive.
As opposed to the beltlike distribution of the zonula occludens and adherens, desmo-
somes resemble spot welds—single rivets erratically spaced below the apical surface of
the epithelium. Intracellularly, they are associated with keratin intermediate filaments, CLINICAL
providing strength and rigidity to the epithelial surface. Like the zonula adherens, mac- CORRELATION
ula adherens are also mediated by calcium-dependent cadherin interactions. Bullous pemphigoid: An
autoimmune disease of the skin due
Hemidesmosomes to anti-hemidesmosome antibodies.
These disrupt the dermal-epidermal
These asymmetrical anchors provide epithelial adhesion to the underlying connective junction resulting in separation of the
tissue layer, the basement membrane. The hemidesmosomes contain integrin (instead layers in the form of tense bullae. The
of cadherins), an anchoring protein filament that binds the cell to the basement mem- antibodies are distributed linearly along
brane. Although the intracellular portion structurally resembles that of the desmosome, the basement membrane. Nikolsky sign
none of the protein components are conserved, except for the cytoplasmic association is negative.
with intermediate filaments.
Gap Junctions FLASH

FORWARD
These intercellular junctions allow for rapid transmission of electrical or chemical
Gap junctions allow for “coupling” of
information from one cell to the next. A connexon is formed from a complex of six
cardiac myocytes, enabling the rapid
connexin proteins. Each single connexon exists as a hollow cylindrical structure span- transmission of electrical depolarization
ning the plasma membrane. When a connexon of one cell is bound to a connexon of and coordinating contraction during
an adjacent cell, a gap junction is formed, creating an open channel for fluid and the cardiac cycle.
electrolyte transport across cell membranes.

HEMATOPOIESIS
Hematopoietic cells are stem cells residing in the bone marrow that can give rise to all
mature components of circulating blood cells and immune systems.
Blood
Blood is composed of cells suspended in a liquid phase. This liquid phase, which
consists of water, proteins, and electrolytes is known as plasma. O2-carrying red blood
cells, known as erythrocytes, make up about 45% of blood by volume. This percentage
is known as the hematocrit. Erythrocytes can be separated from white blood cells, or
leukocytes, and platelets by centrifugation. Erythrocytes form the lowest layer, and
leukocytes form the next layer, also known as the buffy coat. Plasma from which the
platelets and clotting factors have been extracted is called blood serum.
The Pluripotent Stem Cell

The hematopoietic stem cell is the grandfather of all major blood cells. These cells reside
within the bone marrow, where hematopoiesis (blood cell production) occurs. They are
capable of asymmetrical reproduction: simultaneous self-renewal and differentiation.
■ Self-renewal, integral to the maintenance of future hematopoietic potential, pre-
serves the pool of stem cells.
■ Differentiation leads to the production of specialized mature cells, necessary for
carrying out the major functions of blood.
CLINICAL Two differentiated cell lines derive from the pluripotent stem cell: myeloid and lym-
CORRELATION phoid (Figure 1-7). These cells are considered committed, meaning that they have
begun the process of differentiation and have lost some of their potential to become
RBC cytoskeletal abnormalities (eg,
hereditary spherocytosis, elliptocytosis)
cells in an alternate lineage. The myeloid lineage produces six different types of colony-
and hemoglobinopathies (eg, forming units (CFUs), each ending in a distinct mature cell: erythroid (producing
thalassemias, sickle cell anemia) cause erythrocytes), megakaryocyte (producing platelets), basophil, eosinophil, neutrophil,
significant morbidity and mortality. and monocyte (differentiates into macrophage). The lymphoid lineage produces two
cell lines: T cells and B cells.
Erythrocytes
Erythrocytes are nonnucleated, biconcave disks designed for gas exchange. These cells
measure approximately 8 μm in diameter, and their biconcave shape increases their
surface area for gas exchange, and allows them to squeeze through narrow capillaries.
CLINICAL These cells lack organelles, which are extruded shortly after they enter the bloodstream.
CORRELATION Instead, they contain only a plasma membrane, a cytoskeleton, hemoglobin, and gly-
The reticulocyte count increases when
colytic enzymes that help them survive via anaerobic respiration (90%) and the hexose
the bone marrow increases production monophosphate shunt (10%). This limits the red blood cell life span to approximately
to replenish red cell levels in the blood 120 days, after which they are mainly removed via macrophages in the spleen, and to
in response to anemia. a lesser extent, via the liver. Mature erythrocytes are replaced by immature reticulocytes
produced in the bone marrow. Reticulocytes are distinguished from mature erythrocytes
by their slightly larger diameter and reticular (mesh-like) network of ribosomal RNA.
Erythropoietin is the hormone that stimulates erythroid progenitor cells to mature by
binding to JAK2, a nonreceptor tyrosine kinase.
RBCs are highly dependent on glucose as their energy source, and glucose is transported
across the RBC membrane via the glucose transporter (GLUT-1). They are susceptible
to free radical damage, but can synthesize glutathione, an important antioxidant. Hemo-
globin’s ability to transport oxygen is closely associated with the production of 2,3-bisphos-
phoglycerate (2,3-BPG); 2,3-BPG decreases the affinity of hemoglobin for oxygen, thus
improving oxygen delivery to tissues. The iron in hemoglobin is maintained in the
ferrous state; ferric iron (Fe3+) is reduced to the ferrous (Fe2+) state via an NADH-
dependent methemoglobin reductase system. Finally, RBCs contain certain enzymes

Pluripotent stem cell
Myeloid stem cell Lymphoid stem cell
Erythropoiesis Thrombopoiesis Granulocytopoiesis Lymphopoiesis
Erythroid Thrombocyte Granulocyte/monocyte B– T–

progenitor cell progenitor cell progenitor cell lymphoblast lymphoblast
B– T–
Myeloblast Monoblast lymphocyte lymphocyte
Proerythroblast Megakaryoblast
Eosinophilic Basophilic Neutrophilic

promyelocyte promyelocyte promyelocyte Plasma cell
Basophilic Promegakaryocyte
erythroblast Promonocyte
T-helper T-cytotoxic
Eosinophilic Basophilic Neutrophilic
myelocyte myelocyte myelocyte
Polychromatic
erythroblast
Neutrophilic
Orthochromatic metamyelocyte Monocyte
erythroblast Megakaryocyte Eosinophilic Basophilic
metamyelocyte metamyelocyte
Band
Reticulocyte
Erythrocyte Platelets Eosinophil Basophil Neutrophil Macrophage
F I G U R E 1 - 7 . Blood cell differentiation. A chart of the pluripotent hematopoietic stem cell’s differentiation potential.

CLINICAL of nucleotide metabolism, and a deficiency in these enzymes (eg, adenosine deaminase,
CORRELATION pyrimidine nucleotidase, and adenylate kinase) is involved in some of the hemolytic
anemias.
Activating mutations in JAK2 can
cause myeloproliferative disorders
like polycythemia vera, essential Leukocytes
thrombocythemia, and myelofibrosis. Leukopoiesis is the process of white blood cell production from hematopoietic stem
The most common mutation for
cells. Neutrophils, basophils, mast cells, and eosinophils develop through a common
polycythemia vera is V617F (Figure 1-8).
promyelocyte lineage. Monocytes develop from a monoblast. Lymphocytes, although
separate from myeloid cells, are also considered leukocytes and arise from the lymphoid
stem cell.
EPO
All leukocytes are involved in some aspect of the immune response:

brane
Cell mem ■ Neutrophils affect nonspecific innate immunity in the acute inflammatory
JAK2
P
JAK2
P
response.
P-Y343 ■ Basophils and mast cells mediate allergic responses.
SHP-1
■ Eosinophils help fight parasitic infections.
Inhibitor
recruitment ■ Lymphocytes are integral to both cellular and humoral immunity.
F I G U R E 1 - 8 . Erythropoietin Neutrophils
(EPO) receptor. These products of the myeloid lineage act as acute-phase granulocytes. They begin in
the bone marrow as myeloid stem cells (Figure 1-7) and mature over a period of 10–14
KEY FACT days, producing both primary and secondary granules (promyelocyte stage; Figures 1-9
and 1-10). Once mature, these leukocytes are vital to the success of the innate immune
Leukos = Greek for white. system and are especially prominent in the acute inflammatory response.
Cytos = Greek for cell.
Histologically, these cells are distinguished by their large spherical size, multilobed
nuclei, and azurophilic primary granules (lysosomes). These cells have earned the
CLINICAL alternative name polymorphonucleocytes (PMNs) due to their multilobed nucleus.
CORRELATION
The key to their immune function lies in the ability of PMNs to phagocytose microbes
Chronic granulomatous disease: and destroy them via reactive oxygen species (superoxide, hydrogen peroxide, peroxyl
Congenital deficiency of NADPH radicals, and hydroxyl radicals). Neutrophils contain several enzymes, most notably
oxidase impedes the oxidative burst NADPH oxidase, which produces O2− radicals, directing the oxidative burst, as well as
in neutrophils, causing a difficulty the myeloperoxidase (MPO) system, which uses hydrogen peroxide and chloride to
in forming the reactive oxygen
generate hypochlorous acid (HOCl), a potent bactericidal oxidant.
compounds used to kill pathogens.
This results in recurrent bouts of
bacterial infection, most commonly
pneumonia and skin abscesses.
KEY FACT
Important neutrophil chemotactic

agents: C5a, IL-8, leukotriene B4 (LTB4),
kallikrein, platelet-activating factor.
F I G U R E 1 - 9 . Peripheral blood smear with neutrophilia. This peripheral blood smear

displays an extreme leukemoid reaction (neutrophilia). Most cells are band and segmented
neutrophils.

A B
F I G U R E 1 - 1 0 . Electron microscopy of neutrophils. A Highly activated neutrophils (N) with apoptotic neutrophils (black arrow) and
cell debris (black arrowhead). B Neutrophil.
Eosinophils
MNEMONIC
Eosinophils follow the same pattern of maturation as neutrophils, beginning in the bone
marrow as eosinophilic CFUs. Eosinophils also contain granules with eosinophil per- Causes of eosinophilia—
oxidase. However, they differ in that they are slightly larger than neutrophils with cat- NAACP
ionic proteins, such as major basic protein (antiparasitic) and eosinophilic cationic Neoplasia
protein (antiparasitic) within acidophilic (ie, eosinophilic) granules. Once fully mature, Asthma
eosinophils possess a large, bilobed nucleus (not multi-segmented like neutrophils) and Allergic processes
sparse endoplasmic reticulum and Golgi vesicles (Figure 1-11). Chronic adrenal insufficiency
Parasites (invasive)
Basophils and Mast Cells
Distinguished by large, coarse, darkly staining granules, basophils produce peroxidase,
heparin, and histamine (Figure 1-12). Basophils also release kallikrein, which acts as
an eosinophil chemoattractant during hypersensitivity reactions, such as contact aller-
gies and skin allograft rejection. Because they share a great deal of structural similarities,
basophils can be considered the blood-borne counterpart of the mast cell, which resides
within tissues, near blood vessels. Both mast cells and basophils produce histamine and
A B
F I G U R E 1 - 1 1 . Eosinophil microscopy. A Mature eosinophil with bright red granules.

B Electron microscopy of eosinophils with bilobed nuclei and specific granules in the shape of
a football with a crystalline core made from major basic protein.

F I G U R E 1 - 1 2 . Basophil microscopy. A Electron micrograph of a normal intact mast cell

CLINICAL with homogenous electron-dense granules. B Basophil.
CORRELATION
Mast cells release histamine, which
leads to type I allergic reactions,
heparin, but mast cells also contain serotonin (5-HT), which basophils lack. Mast cells
resulting in unpleasant allergy degranulate during the acute phase of inflammation, acting, via their released granule
symptoms and anaphylaxis. contents, on the nearby vasculature. This leads to vasodilation, fluid transudation, and
swelling of interstitial tissues.
Monocyte Lineage
Monocytes
KEY FACT Monocytes are the myeloid precursor to the mononuclear phagocyte, the tissue mac-
rophage. Morphologically, they appear as spherical cells with scattered small granules,
In tissue = macrophage akin to lysosomes. The blood monocyte is a large (10–18 μm), motile cell that margin-
In blood = monocyte ates along the vessel wall in response to the expression of specific cell adhesion proteins.
During an inflammatory response, these cell adhesion proteins (namely, platelet endo-
thelial cell adhesion molecule, or PECAM-1) facilitate monocyte diapedesis (transmi-
gration) across vessel walls into surrounding tissues. Once in close proximity to the
inflammatory foci, the monocyte differentiates into a macrophage with increased phago-
cytic and lysosomal activity (Figure 1-13).
Macrophages
During differentiation, monocyte cell volume and lysosome numbers increase. These
lysosomes fuse with phagosomes to degrade ingested cellular and noncellular material.
A B
F I G U R E 1 - 1 3 . Macrophage microscopy. A Active macrophage and B multinucleated giant

cell.

Macrophages (20–80 μm) also contain a large number of cell surface receptors. These CLINICAL
differ, depending on the tissue in which the macrophage matures, contributing to the CORRELATION
diversity of macrophage functions (Table 1-1).
Lipid A from bacterial
lipopolysaccharide (LPS) binds CD14
As described in Table 1-1, monocyte-derived cells are distributed among several organs on macrophages to induce cytokine
and tissues (including connective tissue and bone) where they reside (termed tissue- release. Toxic shock syndrome is caused
resident macrophages). Alternatively, monocytes can migrate into tissues during an acute by preformed Staphylococcus aureus
inflammatory response and, there, transform into reactive macrophages to aid the innate toxic shock syndrome toxin (TSST-1),
immune system. Once out of the circulation, monocytes have a half-life of up to 70 which acts as a superantigen and
hours. Their numbers within inflamed tissues begin to overcome those of neutrophils causes massive cytokine release.
after approximately 12 hours.
Multinucleated Giant Cells KEY FACT

At sites of chronic inflammation, such as tuberculous lung tissue, macrophages some-
Macrophages are activated by IFN-γ.
times fuse to produce multinucleated phagocytes (Figure 1-13). These microbicidal cells They can function as antigen-
can be produced in vitro via interferon-γ (IFN- γ) or interleukin-3 (IL-3) stimulation. presenting cells via MHC II.
Antigen-Presenting Cells
Antigen-presenting cells (APCs) are essential to the adaptive immune system. These
monocyte-derived phagocytic cells take up antigens (primarily protein particles), process FLASH
them, display them bound to the major histocompatibility complex (MHC) II cell FORWARD
surface marker, and travel to lymph nodes, where they recruit other cells of the immune
Dendritic cells are the most important
system into action. Dendritic cells are especially important in the initial exposure to a APCs in the body and they are
new antigen. Successful differentiation from monocytes depends on an endothelial cell responsible for initiation of adaptive
signal that is secondary to foreign antigen exposure. In the absence of this second signal, immunity.
these sensitized monocytes transform into macrophages.
Lymphocytes
Lymphocytes are easily distinguished from other leukocytes by their shared morphology
(Figures 1-14 and 1-15). After differentiating from lymphoblasts within the marrow, they
migrate to the blood as spherical cells, 6–15 μm in diameter. Typically, the nucleus
contains tightly packed chromatin, which stains a deep blue or purple and occupies
approximately 90% of the cell cytoplasm.
As the primary actors in the adaptive immune response, lymphocytes undergo bio-
chemical transformation into active immune cells via coordinated stimulatory signals.
These activated lymphocytes then enter the cell cycle, producing a number of identical
daughter cells. They eventually settle into G0 as a memory cell while they await the
T A B L E 1 - 1 . Distribution of Mononuclear Phagocytes
Marrow Monoblasts, promonocytes, monocytes, macrophages
Blood Monocytes
Body cavities Pleural macrophages, peritoneal macrophages
Inflamm tory Epithelioid cells, exudate macrophages, multinucleated giant cells

tissues
Tissues Liver (Kupffer cells), lung (alveolar macrophages), connective tissue (histiocytes), F I G U R E 1 - 1 4 . Light microscopy
spleen (red pulp macrophages), lymph nodes, thymus, bone (osteoclasts), of a lymphocyte from a blood smear.
synovium (type A cells), mucosa-associated lymphoid tissue, gastrointestinal Medium-sized agranular lymphocyte
tract, genitourinary tract, endocrine organs, central nervous system (microglia), (stained purple) with a high nuclear
skin (dendritic cells) to cytoplasmic ratio and a condensed
chromatin pattern.

CD20 CD21 CD8 CD4
CD19 CD3 CD3
B cell Tc Th
A B
F I G U R E 1 - 1 5 . Lymphocytes. A B cell and B T cell.
next stimulation event. Alternatively, following replication, daughter cells can become
terminally differentiated lymphocytes, primed for effector and secretory roles in immu-
nologic defense of the host organism.
B Cells and Plasma Cells

B cells are the “long-range artillery” in the adaptive immune response. After the lympho-
blast stage, the lymphocyte lineage diverges into B cells and T cells, each performing
separate roles in the adaptive, or humoral, immune response. Once committed, B
cells develop in the Bone marrow and then migrate to other lymphoid organs. As they
develop, B cells express immunoglobulins (IgM and IgD) on their surface, in associa-
tion with costimulatory proteins. These B-cell antigen receptor complexes allow for
the recognition of foreign antigens and subsequent activation of the B cell. Downstream
cell signaling leads to the expression of necessary genes for terminal differentiation to
plasma cells that produce and secrete antibodies to aid the specific immune response.
B cells that recognize self-antigens are triggered to undergo programmed cell death, or
apoptosis, to reduce the chance of autoimmunity.
T Cells
MNEMONIC
T cells are the “infantry” of the adaptive immune response. During maturation in the
MHC × CD = 8 (eg, MHC II × CD4 = 8, Thymus, early T cells begin expressing several surface receptors simultaneously, includ-
and MHC I × CD8 = 8). ing the T-cell receptor (TCR), CD4, and CD8. If one of these CD receptors recognizes
receptors of thymic APCs, either MHC II or I, respectively, then this T cell is positively
selected, proliferates, and matures. If a T cell recognizes self-antigen, then it is nega-
KEY FACT tively selected, and undergoes apoptosis. All T cells express CD3, and either CD4
(helper T cells), or CD8 (cytotoxic T cells).
Helper T cells “help” by mediating the
specificity of the adaptive immune Helper T Cells
response. They act as a messenger
between APCs and B cells, triggering Two subtypes of T helper cells are derived from the CD4+ progenitor: Th1 and Th2.
humoral immunity. Th1 responses occur in the presence of intracellular pathogens. Helminthic or parasitic
infections, on the other hand, drive Th2-mediated immune responses.
Helper T cells spring into action when they recognize foreign antigens bound to MHC
II. Once activated, they secrete cytokines, chemical messengers that recruit and activate
other immune effector cells. These cytokines, also called interleukins, specifically attract
B cells, which, in turn, divide and differentiate into plasma cells. After the immune
response is complete, some helper T cells become memory cells—quiescent immune
cells that retain their specificity in case of a rechallenge with the same antigen in the
future. The presence of memory cells increases the speed and efficiency of future
immune responses.
Cytotoxic T Cells
CD8+ T cells also proliferate in response to cytokines; however, they only recognize
antigens in association with class I MHC. These cells are actively involved in immune
surveillance of intracellular pathogens.

Every human cell contains MHC I, but only APCs contain MHC II. FLASH
FORWARD
■ A cell infected by an intracellular pathogen (ie, a virus) processes viral proteins and
presents them on the surface via MHC I. Cytotoxic T cells also destroy
■ A roving CD8+ T cell recognizes this signal and attaches to the infected cell via target cells via the Fas-Fas ligand
cell adhesion molecules. interaction. The interaction of Fas
■ The activated cytotoxic T cell releases perforins, which are proteins that form holes ligand of CD8+ T cells with the Fas
receptor of the infected cell leads to
in the plasma membrane of targeted cells.
apoptosis of the target cell.
Gross Anatomy and Histology KEY FACT
Th1 cells are associated with innate

ABDOMINAL WALL ANATOMY
immunity and cytolytic responses.
Th2 cells are associated with humoral
Layers of the Abdominal Wall immunity and asthma.
The order of the layers of the anterior abdominal wall differs depending on location.
They are depicted in Figure 1-16.
CLINICAL
The abdominal muscle aponeuroses comprising the rectus sheath differ above and below CORRELATION
the arcuate line. The arcuate line is a horizontal line at the level where the inferior
epigastric vessels perforate the rectus abdominis (Figure 1-16). Above the umbilicus, An indirect inguinal hernia enters the
deep inguinal ring lateral to the inferior
the rectus abdominis muscle is enveloped in the aponeurosis of the internal oblique
epigastric vessels. A direct inguinal
muscle, with the aponeurosis of the external oblique anterior to the rectus sheath. Below hernia enters the superficial inguinal
the arcuate line, the anterior rectus sheath is composed of all three abdominal muscle ring via a weakness in the abdominal
aponeuroses (external oblique, internal oblique, and transversus abdominis). Deep to muscles medial to the inferior
the muscle layer is the extraperitoneal tissue and transversalis fascia. The parietal peri- epigastric vessels.
toneum is deep to that fascia.
Inguinal Canal
The inguinal canal is an oblique, inferomedially directed channel through which the
testes and its vessels and nerves traverse the abdominal wall to reach the scrotum (Figure
1-17). As the testis descends, it carries a sheath of peritoneal sac (tunica vaginalis) into
which it invaginates acquiring a partial covering. The inguinal canal lies superior and
parallel to the inguinal ligament, allows the passage of the round ligament of the uterus
in women and the spermatic cord (ductus deferens and testicular vessels) in men. The
canal has two openings: the internal (or deep) and external (or superficial) inguinal CLINICAL
rings. The transversalis fascia evaginates through the abdominal wall and continues CORRELATION
as a covering of structures passing through the abdominal wall. The superficial ring is Internal hemorrhoids are painless
actually an opening through the external oblique aponeurosis. If the protrusion occurs because they occur above the
at the site of the deep inguinal ring, the hernia is indirect (Figure 1-18). If the weak- pectinate line where the innervation
ness occurs medial to the inferior epigastric vessels, the hernia is direct (Figure 1-18). is visceral. External hemorrhoids occur
below the pectinate line and are
Retroperitoneum painful because they receive somatic
innervation. The pectinate line is also a
The posterior abdominal cavity contains several important structures situated between site for portal systemic anastomosis—
the parietal peritoneum and the posterior abdominal wall. This region, the retroperito- rectal bleeding is therefore possible in
neum, contains portions of the gastrointestinal, genitourinary, endocrine, and vascular patients with portal hypertension.
systems (Figure 1-19).
The Pectinate Line

The pectinate (dentate) line is the mucocutaneous junction where the endoderm meets
the ectoderm in the anal canal. In the developing embryo, the endodermally derived
hindgut fuses with the ectodermally derived external anal sphincter (Figure 1-20). Tis-
sues on each side of this boundary are fed by separate neurovascular sources (Table 1-2).

Above arcuate line

Aponeurosis of external Anterior layer of External abdominal
abdominal oblique rectus sheath oblique
Aponeurosis of internal Rectus abdominis Internal abdominal
abdominal oblique oblique
Linea alba
Aponeurosis of Transversus abdominis
transversus abdominis
Posterior layer Transversalis

of rectus sheath fascia
Below arcuate line

Aponeurosis of external Anterior layer of External abdominal
abdominal oblique rectus sheath oblique
Aponeurosis of internal Rectus abdominis Internal abdominal
abdominal oblique oblique
Aponeurosis of Transversus abdominis
transversus abdominis
Urachus Medial umbilical

Transversalis (in median ligament and fold
fascia umbilical fold)
Umbilical
A prevesical fascia
Rectus abdominis Linea alba

Rectus sheath
Peritoneum
Extraperitoneal tissue
Skin
Superficial fascia
External oblique
Internal oblique
Transversus abdominis IVC Aorta

Sympathetic trunk
Transversalis fascia
Psoas
Quadratus lumborum
Latissimus dorsi
B Erector spinae
F I G U R E 1 - 1 6 . Layers of the abdomen and rectus sheath. A The major layers of the abdominal wall are shown, as well as the relation
of several retroperitoneal structures. IVC, inferior vena cava. B Superior to the arcuate line, the rectus abdominis muscle is wrapped by
the aponeurosis of the internal oblique muscle. Inferior to the arcuate line, the rectus abdominis muscle lies posterior to the aponeuroses
of both the internal oblique and transversus abdominis muscles; the posterior wall of the rectus sheath is only formed by the transversalis
fascia.

Abdominal wall
Deep (internal)
Inferior epigastric site of protrusion of
inguinal ring
vessels direct hernia
site of protrusion of
Parietal peritoneum indirect hernia Medial umbilical ligament
Extraperitoneal tissue Median umbilical ligament
Transversalis fascia Rectus abdominis muscle

Pyramidalis muscle
Transversus abdominis muscle
Conjoined tendon
Linea alba
Internal oblique muscle
Spermatic cord (ICE tie)
Aponeurosis of external
oblique muscle
Superficial (external)
Inguinal ligament inguinal ring
Internal spermatic fascia Cremasteric muscle and fascia External spermatic fascia
(transversalis fascia) (internal oblique) (external oblique)
F I G U R E 1 - 1 7 . Inguinal canal. The location and contents of the male inguinal canal, as well as the abdominal wall layers it traverses,
are shown. Other important anatomic relations are also highlighted, including umbilical ligaments and inferior epigastric vessels. The
locations of direct and indirect hernias are also labeled.
THE GASTROINTESTINAL SYSTEM

MNEMONIC
Small Intestinal Layers Retroperitoneal structures—

The small intestine, the major organ of nutrient absorption from the gut, is composed of SAD PUCKER
several layers, each contributing to the coordination of digestion and transport (Figure Suprarenal (adrenal) glands [not shown]
1-21). Aorta and IVC
Duodenum (2nd through 4th parts)
■ Mucosa: Absorption. Pancreas (except tail)
■ Submucosa: Vascular and lymphatic supply. Ureters [not shown]
■ Muscularis externa: Mechanical mixing, dissociation, and propulsion. Colon (descending and ascending)
■ Serosa: Protection. Kidneys
Esophagus (thoracic portion) [not
shown]
Mucosa
Rectum (upper segment) [not shown]
The intestinal mucosa, the absorption barrier of the alimentary canal, is composed of
polarized epithelial cells specialized in transport and uses several molecular and struc-
tural adaptations that allow it to efficiently extract nutrients from food. CLINICAL
CORRELATION
Inguinal Rectus abdominis muscle Ulcers can extend into the submucosa,
(Poupart) inner, or outer muscular layer. Erosions
Inferior
ligament
epigastric vessels
are in the mucosa only.
x Direct inguinal hernia

Indirect
inguinal hernia x Inguinal (Hesselbach) triangle FLASH BACK
x
Femoral artery Femoral hernia Molecularly, the intestinal epithelium
Femoral vein employs cell adhesion molecules to
determine polarity and maintain the
F I G U R E 1 - 1 8 . Inguinal area. Locations where indirect and direct inguinal hernias, and physical barrier between the body
femoral hernias, may occur. and the intestinal lumen (external
environment).

Right Duodenum Left

FLASH
FORWARD Peritoneum
Pancreas
Defects in lactase activity lead to
Ascending
lactose intolerance. Loss of other Descending
colon
intramembranous enzymes (eg, colon
enterocyte toxicity following Perirenal
chemotherapy) leads to osmotic space
Kidney
diarrhea.
Transversalis fascia IVC Aorta
Internal
hemorrhoids F I G U R E 1 - 1 9 . Retroperitoneal structures. The anatomic relations of important
retroperitoneal structures are shown.
Structurally, the mucosa has four adaptations that increase the absorptive surface area:
■ Plicae circulares (circular folds, or valves of Kerckring): Permanent folding of the
mucosa and submucosa into the lumen of the small intestine. They begin in the
duodenum, peak in distribution in the duodenojejunal junction, and end in the
mid ileum.
■ Intestinal villi: Finger-like projections of the mucosa into the lumen that extend
deep into the mucosa to the muscularis mucosa. At the bottom of intestinal villi are
intestinal glands.
■ Intestinal glands (or crypts of Lieberkühn): Nonsecretory glands that enhance
External
hemorrhoid
Pectinate absorption.
line
■ Microvilli (brush border): On the apical border of each enterocyte, or intestinal
F I G U R E 1 - 2 0 . Pectinate line. A epithelial cell, the surface area is approximately 30-fold. Contains a core of paral-
comparison of internal hemorrhoids lel, cross-linked actin filaments bound to cytoskeletal proteins. The brush border is
(internal rectal vessels) and external coated in a glycocalyx, a surface coat of glycoproteins excreted by columnar secretory
hemorrhoids (external rectal goblet cells.
vessels) is shown, highlighting their
separation by the pectinate line. The The luminal membrane of intestinal epithelial cells contains several intramembranous
endodermal and ectodermal origins
of these structures underlie the
enzymes (eg, maltase, lactase, enterokinase) integral to digestion and small-molecule
anatomic distinction between them. absorption. Intracytoplasmic enzymes break down absorbed di- and tripeptides.
CLINICAL Submucosa
CORRELATION
The submucosa is the site of vascular and lymphatic supply to the intestine. This layer,
Only when adenocarcinomas invade composed of loose connective tissue, contains a vascular plexus that extends capillaries
into the submucosa are they able to into the surrounding layers. The lymphatic drainage of the submucosa begins as blind-
metastasize taking advantage of the
ended channels, known as lacteals, within the core of the intestinal villi. These lacteals
rich lymphatic and vascular plexus
empty into a submucosal lymphatic plexus that shuttles antigens to nearby lymphatic
located there.
nodules and emulsified fat-soluble nutrients to the liver.
T A B L E 1 - 2 . Pectinate Line
CHARACTERISTICS ABOVE BELOW

Cell types Glandular epithelium Squamous epithelium
Cancer type Adenocarcinoma Squamous cell carcinoma
Innervation Visceral Somatic
Hemorrhoids Internal (painless) External (painful)
Arterial supply Superior rectal artery (branch of inferior mesenteric artery) Inferior rectal artery (branch of internal pudendal artery)
Venous drainage Superior rectal vein → inferior mesenteric vein → portal Inferior rectal vein → internal pudendal vein → internal iliac
system vein → common iliac vein → IVC

Tunica muscularis
externa Mucosa
Epithelium
Tunica submucosa Lamina propria
Muscularis mucosa
Mesentery
Intestinal villi
Submucosa
Vein Submucosal gland
Artery
Submucosal Lymph vessel
gland
Epithelium Lumen
Submucosal nerve
plexus (Meissner)
Muscularis mucosa
Muscularis
Myenteric nerve plexus Inner circular layer
(Auerbach) Myenteric nerve plexus
(Auerbach)
Tunica serosa Outer longitudinal layer
Enlarged view (peritoneum) Serosa
cross-section
F I G U R E 1 - 2 1 . Anatomy of the small intestines, depicting the various tissue layers and nerve plexuses.
Within the duodenum, the submucosa contains Brunner glands, tubuloacinar mucous CLINICAL
glands that produce an alkaline (pH ~ 9) secretion to neutralize acidified chyme from CORRELATION
the stomach. Within the ileum reside the lymphatic nodules that provide immunologic
MALT lymphoma: A form of lymphoma
surveillance to the intestines. These nodules, also known as Peyer patches (Figure 1-22),
involving the mucosa-associated
or mucosa-associated lymphoid tissue (MALT), contain a germinal center of B cells lymphoid tissue (MALT), frequently
surrounded by specialized APCs: M cells and dendritic cells. Antigens enter the Peyer of the stomach, and caused by
patch through antigen presentation via M cells and dendritic cells. The B cells of the Helicobacter pylori infection.
MALT germinal center are specialized; they produce a specific immunoglobulin, IgA,
which can be secreted into the intestinal lumen to neutralize pathogens before they
invade the epithelium.
The submucosa also houses one of the two neural plexuses located within the small
intestine. The other (myenteric) plexus is located between the two layers of the muscu-
laris externa. Considered part of the autonomic system, these neural networks receive
a great deal of intrinsic input from the intestinal parenchyma. This allows the gut to
operate nearly independently from the central nervous system, although its action can
be modulated via extensive extrinsic neural input. Two networks control the activity of
the small intestine: the submucosal plexus of Meissner and the myenteric plexus of
Auerbach. They are extensively interconnected and probably equally modulate mucosal F I G U R E 1 - 2 2 . Histology of Peyer
and muscular activity, coordinating action to maximize digestion. patches in small intestine.
Muscularis Externa (Propria) FLASH

FORWARD
Intestinal motility is controlled by two layers of smooth muscle. One circular layer is
Dysfunction of the enteric plexuses,
surrounded by a second longitudinal layer (Auerbach’s plexus resides between these
due to either congenital absence
two layers). Coordinated muscular contraction produces two types of mechanical results:
(Hirschsprung disease) or neurologic
propulsion and segmentation. injury (diabetic neuropathy), leads to
■ Propulsion occurs when proximal contraction is coordinated with distal relaxation. decreased intestinal motility.
This leads to increased upstream pressure, which slowly propels food through the
digestive system. Contraction of proximal sphincters ensures that the food bolus
only moves distally. CLINICAL
CORRELATION
■ Segmentation occurs when a bolus of food is mechanically compressed and split
into portions as the lumen constricts near the bolus center, not merely proximal to Pain experienced when an
it. If this contraction is not coordinated with distal relaxation, the bolus cannot be encapsulated organ enlarges is due to
propelled forward. Instead, its contents are mixed by the muscular contractions. the stimulation of the autonomic nerve
endings in the capsule, rather than
caused by the increasing size of the
organ itself.

Serosa
KEY FACT
The serosa is the visceral peritoneum covering the small intestine. It is lined by a single
Gastrosplenic ligament: Connects layer of mesothelium-derived cells.
greater curvature of the stomach to
the spleen. Contains short gastric
and left gastroepiploic vessels and SPLENIC ANATOMY
separates the greater and lesser sacs
on the left. The largest secondary lymphatic organ, the spleen, is located in the upper left quadrant
Splenorenal ligament: Connects the of the abdominal cavity. It is completely surrounded by peritoneum, except at its hilum,
spleen to the posterior abdominal where the vasculature enters and exits. It is bordered laterally and posteriorly by ribs
wall. Contains splenic artery and vein 9–11, superiorly by the diaphragm, anteriorly by the stomach, inferiorly by the left colic
as well as the tail of the pancreas. flexure (splenic flexure), and medially by the left kidney. It is attached to the greater
curvature of the stomach by the gastrosplenic ligament and to the posterior abdominal
wall by the splenorenal ligament. The parenchyma of the spleen is composed of red
pulp and white pulp.
KEY FACT
Red Pulp
Splenic dysfunction: ↓ IgM leads to ↓
complement activation, which leads to The splenic sinusoids of the red pulp make up an interconnected network of vascu-
↓ C3b opsonization and susceptibility lar channels that aid the hematopoietic system by removing senescent and damaged
to encapsulated organisms. erythrocytes from the circulation. These are lined by elongated endothelial cells and a
discontinuous basement membrane made of reticular fibers (Figure 1-23). The walls
separating the sinusoids are called splenic cords (cords of Billroth). The splenic cords
contain plasma cells, macrophages, and blood cells supported by a connective tissue
CLINICAL matrix. Macrophages adjacent to the sinusoids recognize opsonized bacteria, adherent
CORRELATION
antibodies, foreign antigens, and senescent red cells as they filter through the spleen.
Lab findings post splenectomy are as
follows: White Pulp
■ Howell-Jolly bodies (nuclear
remnants) The white pulp is a site of immunologic reinforcements and is composed of nodules
■ Target cells (Malpighian corpuscles) that contain B cells arranged in follicles and T cells arranged
■ Thrombocytosis (loss of in sheaths. Arranged around a central arteriole, the white pulp contains immune cells
sequestration and removal) in a specific orientation that facilitates hematogenous activation of the humoral immune
■ Lymphocytosis (loss of system. As an antigen enters the central arteriole, the vasculature branches into radial
sequestration) arterioles (emanating from the central arteriole like spokes of a wheel), and the antigen
passes through a surrounding sheath of T cells. This region, known as the periarterial
lymphatic sheath (PALS), allows for sampling of the arteriolar contents.
CLINICAL The radial arterioles then empty their contents into the marginal zone, between the red
CORRELATION
and white pulp. This area contains specialized B cells and APCs that capture the blood-
Disordered red cell removal borne antigens for recognition by lymphocytes (Figure 1-23).
occurs in sickle cell anemia,
leading to autosplenectomy
Activated T cells then travel to the adjacent lymphatic nodule for B-cell activation. This
and immunodeficiency (against
process produces active germinal centers within the white pulp where B cells mature.
encapsulated bacteria).
Mature B cells, or plasma cells, defend the host via soluble immunoglobulins secreted
into the circulation.
CLINICAL THE LYMPHATIC SYSTEM

CORRELATION
Asplenic patients should receive The Lymph Node
additional vaccines against
encapsulated organisms: Haemophilus Like little spleens dispersed along the lymphatic system, these small secondary lym-
influenzae type b, pneumococcus, and phatic organs aid regional adaptive immune responses by housing APCs, T cells, and
meningococcus. B cells (Table 1-3). Each node possesses multiple afferent lymphatic channels that enter
through the capsule of the lymph node near the cortex. The efferent lymphatics exit at
the hilum, along with an artery and vein (Figure 1-24). From the afferent lymphatics,
antigens and APCs in the lymph enter the medullary sinus. There, free antigens meet
macrophages for phagocytosis and presentation in association with MHC II for T-cell

A Capsule
Germinal center Trabecula
Red pulp (RBCs)
Mantle zone Sinusoid
Marginal zone
Reticular fibrous
White pulp (WBCs) framework
Follicle (B cells)
Periarteriolar
lymphoid sheath
(T cells)
Open
circulation
Closed
circulation
Pulp vein
Artery
Vein
F I G U R E 1 - 2 3 . Diagram of the functional units of the spleen and histologic section of

splenic sinusoid. A The important functional units of the spleen are delineated here, where a
central arteriole enters and supplies blood first to the periarteriolar lymphoid sheath (PALS)
T-cells, which is surrounded by the follicle of B cells. The marginal zone between the white pulp
and red pulp contains antigen-presenting cells (APCs) and macrophages to capture blood-borne
antigens for recognition by lymphocytes. B Histologic section of the splenic sinusoid showing
vascular channels through the red pulp (red arrow), and T cells in the PALS (white arrow).
FLASH
activation. Activated APCs bypass the adjacent medullary cords to reach the paracortex, FORWARD
where T cells await stimulation. Activated T cells move to the adjacent cortical follicle,
Acute lymphadenitis occurs when brisk
where B cells await costimulatory signals. Once activated, mature B cells travel back to germinal center expansion in response
the medullary cords, where they develop into plasma cells and secrete immunoglobulins to a local bacterial infection (eg, teeth
into the adjacent vascular supply. or tonsils) leads to painfully swollen
lymph nodes.
T A B L E 1 - 3 . Lymph Node Organization
REGION DIVISIONS CONTENTS AND FUNCTION

Cortex Follicle (outer ■ Site of B-cell localization and proliferation
cortex) ■ 1° follicles are dense and contain dormant B cells
■ 2° follicles have pale central active germinal centers
Paracortex ■ Helper T cells reside between follicles and the splenic medulla
QUESTION
■ High endothelial venules allow lymphocytes to enter circulation
What specific organisms classically
Medulla Sinus ■ Reticular cells and macrophages communicate with efferent cause infections in asplenic patients?
lymphatics
Cords ■ Closely packed lymphocytes and plasma cells

lymphatic
Follicles (B cells) 1º follicle

Paracortex 2º follicle
(T cells)
Germinal center
Mantle zone
Medullary cords
(lymphocytes,
Postcapillary
plasma cells)
venule
Vein
Capillary Artery
supply
lymphatic
Trabecula Medullary sinus

(reticular cells,
Capsule macrophages)
F I G U R E 1 - 2 4 . Lymph node. Schematic representation of the lymph node structure shows

the major divisions of the node. The medulla consists of cords of plasma cells and sinuses of
macrophages. The cortex consists of dormant and activated B-cell follicles, as well as a T-cell
paracortex.
Lymphatics
As part of the cardiovascular system, the lymphatic vessels drain interstitial fluid from
surrounding tissues (Tables 1-4 and 1-5, and Figure 1-25). They are also integral to
the process of transporting fats and fat-soluble nutrients and facilitating the humoral
immune response. Their role in immunity involves carrying foreign antigens and APCs
to lymph nodes for T- and B-cell activation.
The lymph vessels are analogous to veins in their structure and organization. The walls
of the lymphatic capillary are made up of a layer of loosely bound endothelial cells, lack-
ing tight junctions and bound to an incomplete basal lamina. This allows fluid to enter
the lumen via hydrostatic pressure. As distal lymphatic capillaries merge, they produce
KEY FACT larger vessels containing valves, just like veins, that maintain the direction of flow. In
addition to interstitial hydrostatic pressure, muscular contractions aid the flow of lymph.
The thoracic duct drains into the left
subclavian vein.
The right lymphatic duct drains into During its course back to the systemic circulation, lymphatic fluid is filtered through
either the right subclavian vein or lymph nodes for immune surveillance. The remaining lymph reaches the bloodstream
the right internal jugular vein. via one of two major routes: the larger thoracic duct or the smaller right lymphatic
duct.
T A B L E 1 - 4 . Primary Lymph Drainage Routes
ANSWER DRAINAGE ROUTE ANATOMIC REGIONS DRAINED

Right lymphatic duct Right arm, right half of head and right thorax
Streptococcus pneumoniae, Hae-
mophilus influenzae type b, Neisseria Thoracic duct All other regions
meningitidis, Escherichia coli, Salmo-
nella spp, Klebsiella pneumoniae, group
B Streptococci (SHiNE SKiS)

T A B L E 1 - 5 . Drainage Routes for the Major Lymph Nodes
LYMPH NODE CLUSTER AREA OF BODY DRAINED Drainage Drainage

of right of thoratic
Cervical Head and neck lymphatic duct
duct
Hilar Lungs
Mediastinal Trachea and esophagus
Axillary Upper limb, breast, skin above umbilicus
Celiac Liver, stomach, spleen, pancreas, upper duodenum
Superior mesenteric Lower duodenum, jejunum, ileum, colon to splenic fl xure
Inferior mesenteric Colon from splenic fl xure to upper rectum
Internal iliac Lower rectum to anal canal (above pectinate line), bladder, vagina
(middle third), prostate F I G U R E 1 - 2 5 . Areas of lymphatic
drainage of the thoracic and right
Para-aortic Testes, ovaries, kidneys, uterus lymphatic ducts. Note that the
thoracic duct drains the lymphatic
Superficial inguina Anal canal (below pectinate line), skin below umbilicus (except
fluid from the entire body, except for
popliteal territory), scrotum the right half of the body superior to
the diaphragm.
Popliteal Dorsolateral foot, posterior calf
PERIPHERAL NERVOUS SYSTEM
Nerve Cells
During embryonic development, neural crest cells migrate into the peripheral tissues,
where they differentiate into neurons of the following tissues:
■ Sensory neurons of the dorsal root ganglia.
■ Neurons of the cranial nerve ganglia.
■ Neurons of the autonomic system (eg, vagus nerve or sympathetic ganglia).
■ Neurons of the myenteric (Auerbach) and submucosal (Meissner) plexus.
Neuronal cells contain three major parts: the cell body (soma), dendrites, and axons.
■ The soma houses the organelles (including the prominent nucleus and the well-
developed RER, referred to as the Nissl body).
■ Dendrites are afferent cytoplasmic processes arising from the soma that provide
increased surface area for axonal synaptic connections, thus facilitating the reception
F I G U R E 1 - 2 6 . Histology of the
and integration of information. Each neuron has many dendrites (Figure 1-26). Purkinje cell of the cerebellum,
■ An axon is the efferent cytoplasmic process sprouting from the soma at the axon hillock demonstrating characteristic
and ending in many synaptic terminals, or boutons. Each neuron has one axon. extensive dendritic branching.
Because neurons are specialized cells for signal transduction, they can secrete several
different neurotransmitters (Table 1-6). These peptide molecules are produced in the QUESTION
RER, stored in secretory vesicles, transported through the axon along microtubules via
An 18-year-old man presents to his
molecular motors, and eventually released from the axon into the synaptic cleft. The
doctor complaining of fatigue and
synaptic cleft is the junction between the synaptic terminal and an adjacent cell. This
sore throat. On exam he has a fever,
vesicular secretion, which is triggered by a transmitted action potential, is the primary hepatosplenomegaly, and symmetrical
method of neural control. lymphadenopathy of the posterior
cervical chain of lymph nodes. He
Schwann Cells also has petechiae on his palate with
enlarged tonsils. What is the most
The Schwann cells (Figure 1-27) are descendents of neural crest cells and envelops
likely diagnosis?
only one peripheral nervous system (PNS) axon with myelin. This is in contrast to the

T A B L E 1 - 6 . Neurotransmitters
LOCATION OF ALZHEIMER HUNTINGTON PARKINSON

NEUROTRANSMITTER SYNTHESIS ANXIETY DEPRESSION SCHIZOPHRENIA DISEASE DISEASE DISEASE
Acetylcholine Basal nucleus of ↓ ↓ ↑
Meynert
Dopamine Ventral ↓ ↑ ↑ ↓
tegmentum,
SNpc
GABA Nucleus ↓ ↓
accumbens
Norepinephrine Locus ceruleus ↑ ↓
Serotonin Raphe nucleus ↓ ↓ ↓
SNpc, substantia nigra pars compacta

Reproduced with permission from Le T, et al. First Aid for the USMLE Step 1 2016. New York, NY: McGraw-Hill Education; 2016: 455.
CLINICAL oligodendroglia of the central nervous system (CNS), which can myelinate multiple
CORRELATION axons (Figure 1-27). Myelin increases conduction velocity due to saltatory conduction.
The endoneurium is the target of the Between myelinated segments are the nodes of Ranvier (Figure 1-28), and the myelin-
autoimmune inflammatory infiltrate in ated segments are referred to as internodes.
Guillain-Barré syndrome.
Peripheral Nerve
The peripheral nerve consists of a bundle of neuronal axons, Schwann cells, and protective
connective tissues. It carries impulses from the CNS to the entire body. Although indi-
vidual neurons are surrounded by Schwann cells, a nerve fiber is more complex (Figure
1-29). Each individual neuron, along with its associated Schwann cells, is encapsulated in
endoneurium. Bundles of these nerves are called a nerve fascicle, which is encapsulated in
perineurium. The perineurium acts as a permeability barrier that regulates nutrient trans-
port from capillaries to the nerve fibers beneath. Nerve fascicles, and their vascular supply,
are covered by epineurium (dense connective tissue), forming the peripheral nerve trunk.
ANSWER
Infectious mononucleosis caused by

Epstein-Barr virus. The diagnosis is
confirmed by the presence of atypical
lymphocytes and heterophile antibod-
ies (Monospot).
F I G U R E 1 - 2 7 . Electron micrograph of myelinated axons in the optic nerve. MVB,

multivesicular bodies.

Brachial Plexus Nucleus Schwann cell

The motor portions of spinal nerves are organized differently from the sensory neurons.
Instead of clear divisions organized by spinal level that serve successively distal regions
of the body, a great deal of mixing of neurons from each spinal level produces a single
nerve supplying a specific muscle group. The upper extremity’s brachial plexus is a Myelin sheath Node of Ranvier
prime example. As motor neurons exit the spinal column between C5 and T1, the
ventral rami begin to exchange individual fibers. These rami are considered the roots F I G U R E 1 - 2 8 . Schwann cells.
of the brachial plexus (Figure 1-30). As the five roots reach the inferior portion of the
neck, C5 and C6 unite to form the superior trunk, as C8 and T1 unite to form the
inferior trunk, leaving C7 as the middle trunk. These three trunks pass beneath the Nerve trunk
clavicle, where they each split into anterior and posterior divisions. The anterior divi- Epineurium
sions of the superior and middle trunks merge to form the lateral cord of the brachial Perineurium
plexus, and the anterior division of the inferior trunk becomes the medial cord. Both Endoneurium
of these cords eventually supply the muscles of the anterior compartments of the upper
Nerve fiber
limb. All three posterior divisions merge to form the posterior cord, which supplies the
posterior compartments of the upper limb. From cords, the plexus divides further into
its terminal infraclavicular branches. Common injuries associated with the brachial F I G U R E 1 - 2 9 . Peripheral nerve
plexus are listed in Table 1-7, and shown in Figure 1-31. layers.
Dermatomes
KEY FACT
Usually, successive spinal levels innervate successive caudal regions. The dermatomal
organization of the body is displayed in Figure 1-32A and dermatomes of the hand are Following trauma, the perineurium
displayed in Figure 1-32B, as projected onto the skin. must be repaired via microsurgery to
ensure proper nerve regeneration and
functional restoration.
THE INTEGUMENTARY SYSTEM
Skin
MNEMONIC
The skin has several functions:
Organization of the brachial
■ Mechanical protection plexus—
■ Moisture retention
Randy Travis Drinks Cold Beer:
■ Body temperature regulation
Roots
■ Nonspecific immune defense
Trunks
■ Salt excretion Divisions
■ Vitamin D synthesis Cords
■ Tactile sensation Branches
Superior
C5
Erb palsy (“waiter’s tip”) Trunk Lateral MNEMONIC
Full claw hand (Klumpke palsy) Musculocutaneous
Axillary and radial nerve palsy C6
Axillary Dermatomes—
Winged scapula
Middle Posterior T10 at the belly but-10
Deltoid paralysis C7 (Extensors) Median (flexors)
“Saturday night palsy” (wrist drop)
L1 at IL (Inguinal Ligament)
Difficulty flexing elbow, variable Inferior Radial L4, down on L-4’s “all fours” (at the
C8 Trunk Medial knees)
sensory loss
Decreased thumb function, Ulnar
“Pope’s blessing” T1
Trunks Divisions Cords Branches
Intrinsic muscles of hand,
partial claw hand
Long thoracic
Roots
F I G U R E 1 - 3 0 . Brachial plexus. Schematic representation of the brachial plexus on the

right. To the left are clinical correlations to some common brachial plexus injuries and the
location of nerve lesions that create them.

T A B L E 1 - 7 . Common Brachial Plexus Injuries
LESION LOCATION SYNDROME DEFICITS

Superior trunk C5/C6 Erb-Duchenne palsy (“waiter’s tip”) ■ Abduction (deltoid)
■ Lateral rotation (infraspinatus, teres minor)
■ Supination (biceps) and supinator muscle
Inferior trunk C8/T1 Interphalangeal joint fl xion and metacarpophalangeal Intrinsic muscles of hand, forearm fl xors of hand
joint extension paralysis (full “claw hand”)
Posterior cord C5/C6/C7/C8 Axillary and radial nerve paralyses Same as for axillary and radial nerves
Long thoracic nerve T1 Winged scapula Serratus anterior paralysis
Axillary nerve Deltoid paralysis Abduction
Radial nerve “Saturday night palsy” Wrist drop (supinator, brachioradialis, triceps,
extensors of wrist/fingers
Musculocutaneous nerve Biceps paralysis Elbow fl xion, sensation on radial/lateral side of

the forearm
Median nerve “Pope’s blessing” on making a fis Thumb abduction, thumb opposition, fourth/fi th
digit extension
Ulnar nerve Fourth/fi th digit paralysis (partial “claw hand”) Grip strength, fourth/fi th digit fl xion, intrinsic
muscles of the hand
The skin is composed of three layers: the epidermis (ectodermally derived), the deep
MNEMONIC dermis, and the hypodermis, or subcutaneous tissues (the latter two of which are mes-
enchymally derived).
Layers of the epidermis—
Californians Like Girls in String
Bikinis: Epidermis
Stratum Corneum The epidermis is predominantly made of keratinocytes, or epithelial cells named for
Stratum Lucidum the intermediate filament protein keratin. The epidermis is organized into five layers
Stratum Granulosum (Figure 1-33).
Stratum Spinosum
Stratum Basalis The stratum basale is composed of columnar keratinocytes bound to a basement mem-
brane via hemidesmosomes. Cellular proliferation occurring at this level maintains the
population of epidermal stem cells, replenishes sloughed skin cells, and contributes to
KEY FACT epidermal wound healing. These columnar keratinocytes undergo a process of differ-
entiation, as they move upwards toward the surface. At the level of the stratum spino-
The stratum lucidum is found only in sum, keratinocytes have a flattened polygonal shape and an ovoid nucleus. By the time
areas of thick skin (eg, palms and soles).
they reach the stratum corneum, they are completely flattened and lack nuclei.
CLINICAL Erb-Duchenne palsy

CORRELATION (”waiter’s tip”)
Albinism: Normal melanocyte number
with reduced melanin production
due to a decrease in tyrosinase
activity or defective tyrosine transport.
Can also be caused by failure of
neural crest cell migration during
development. Increased risk of skin
cancer.
A B C
F I G U R E 1 - 3 1 . A Erb palsy, B claw hand, and C winged scapula.

V1 C2
V2 C3
V3 C4
Important Dermatomes
C5 Median nerve
C6 T1 Forehead V1
Thumb C6 Ulnar nerve
T4 C6
T6 Nipples T4 Radial nerve
T8 C7 Umbilicus T10 Palm of hand
T10
C8 Knee L3/4
T12
S2 L1 C8 Great toe L5 Median nerve
S3 Anus S5
Ulnar nerve
Radial nerve
L4
A L5 B Dorsum of hand
F I G U R E 1 - 3 2 . Landmark dermatomes A , and dermatomes of the hand B .
The epidermis also contains other cell types: melanocytes, Langerhans cells, and
Merkel cells. C
L
■ Melanocytes, derived from the neural crest, produce melanin, a tyrosine derivative
G
responsible for skin pigmentation (Figure 1-34). S
■ Langerhans cells are bone marrow–derived dendritic cells residing in the skin. Once B
activated, they migrate to secondary lymph organs to present antigens to T cells.
■ Merkel cells, found in the stratum basale, contribute to the function of the numer- Dermis
ous mechanoreceptors present in the epidermis. A myelinated sensory axon actually
ends in an unmyelinated portion, called the nerve plate, which synapses on the F I G U R E 1 - 3 3 . Epidermis layers.
Merkel cell. This synapse allows the Merkel cell to signal tactile sensation. C = stratum corneum; L = stratum
lucidum; G = stratum granulosum;
S = stratum spinosum; B = stratum
In addition to Merkel cells, two other specialized sensory structures exist within the basale.
body: Meissner corpuscles in the dermis and Pacinian corpuscles in the deep tissues
(Figure 1-36).
CLINICAL
CORRELATION
Dermis
Vitiligo: Irregular areas of
The epidermis is anchored to its basement membrane by hemidesmosomes. Two indis- complete depigmentation. Caused
tinct layers of the dermis, the papillary layer and the reticular layer, reside just below. by autoimmune destruction of
The uppermost papillary layer (primarily loose connective tissue) consists of fibroblasts, melanocytes (Figure 1-35).
collagen, and fine elastic fibers; the lower reticular layer contains mostly irregularly and
densely packed collagen and elastic fibers.
Phenylalanine
Tyrosine Tyroxine
Tyrosinase
Dopa Tyroxine Norepinephrine Epinephrine
Tyrosinase
Melanin F I G U R E 1 - 3 5 . Clinical findings
on a patient with vitiligo.
F I G U R E 1 - 3 4 . Albinism results from a complete deficien y of the tyrosinase. Thus, the
pigments eumelanin and phaeomelanin are not produced in the albinism tyrosine metabolic
pathway.

Meissner - Small, encapsulated nerve endings found in the

dermis of palms, soles, and digits of skin. Involved
in light discriminatory touch of glabrous (hairless)
skin.
Pacinian - Large, encapsulated nerve endings found in deeper

layers of skin at ligaments, joint capsules, serous
membranes, and mesenteries. Involved in pressure,
coarse touch, vibration, and tension.
Merkel - Cup-shaped nerve endings (tactile disks) in the stratum

basale of the epidermis of fingertips, hair follicles, hard
palate. Involved in light, and crude touch.
F I G U R E 1 - 3 6 . Sensory corpuscles.
MNEMONIC
Skin Appendages
Relation of the pulmonary Skin appendages (hair follicles, sweat glands, and sebaceous glands) are present in
artery to the bronchus at each the dermis, as is the blood supply to the skin (Figure 1-37). Hair shafts are made of
lung hilum— hardened keratin, and the follicular bulb where the hair originates contains stem cells
RALS capable of repopulating the follicular shaft, or even the epidermis following injury.
Right Anterior Sebaceous glands are oil-producing glands that actually empty their contents into the
Left Superior hair follicle, the tubular invagination that the hair shaft follows as it grows to the surface.
Sweat glands occur in two forms: (1) The eccrine sweat gland is a ubiquitous coiled
gland innervated by sympathetic cholinergic nerves and used in temperature regulation.
MNEMONIC (2) The apocrine glands, regulated by adrenergic stimuli, only become active following
puberty. These coiled glands are found in the axilla, mons pubis, and perianal regions.
Eccrine glands: Everywhere
Dermal
Erector pili muscle Sebaceous vascular
gland plexus
Epidermis
Papillary
dermis
Reticular
dermis
Subcutaneous
tissues
Hair Eccrine
follicle gland
Adnexal structures
F I G U R E 1 - 3 7 . Skin appendages. The histologic schematic representation of skin demonstrates

a complex organization of cells, connective tissue, blood vessels, and adnexal structures.

THE RESPIRATORY SYSTEM

Pulmonary artery Alveolar duct
Alveolar sacs
Respiratory Histology
Pulmonary vein
Once air has traveled through the conducting zone (nasal cavities, nasopharynx, oro-
pharynx, larynx, trachea, bronchi, and bronchioles), it enters the respiratory zone (respi-
ratory bronchioles, alveolar ducts, alveolar sacs, and alveoli [Figure 1-38]). Air exchange
occurs in the respiratory zone.
Alveolar capillary beds
Bronchi and Bronchioles Alveoli
Except for their smallest divisions, these airways are involved in conducting inhaled air
F I G U R E 1 - 3 8 . Lung alveolus.
to the lung, rather than gas exchange. Primarily, the walls of the conducting airways The respiratory unit of the lung is the
contain a pseudostratified ciliated columnar epithelium, composed of three cell types: alveolus.
■ Ciliated epithelial cells: Coordinated ciliary motion clears mucus (with trapped
pathogens and debris) from the lungs. These cells extend distally to the begin- KEY FACT
ning of the terminal bronchioles before transitioning to the cuboidal cells.
■ Goblet cells: Produce mucus and protect the airway and lung tissue from inspired Type I pneumocytes are squamous
particles. Goblet cells extend to the end of the bronchi. and thin for optimal gas diffusion. They
■ Basal cells: Provide structural support to the airway and can differentiate into other make up 97% of alveolar surfaces.
epithelial cell types after injury.
Alveolus KEY FACT

The alveolus is the basic functional unit of the lung. The lungs contain about 300 mil- Type II pneumocytes are cuboidal
lion alveoli, which increase the surface area for gas exchange to approximately 75 m2. and clustered cells that secrete
Each alveolar wall consists of two cell types, type I and type II alveolar cells (pneumo- pulmonary surfactant to decrease
cytes), serving separate physiologic functions (Figure 1-39). alveolar surface tension and prevent
alveolar collapse (atelectasis). Also
The primary function of the type I pneumocytes is to form the first layer of the air-blood serve as precursors to type I cells
barrier. They are continuous with the low cuboidal epithelium of the adjacent respira- and other type II cells. Type II cells
tory bronchiole, and cover 97% of the alveolar surface, allowing deoxygenated blood to proliferate during lung damage.
come into close proximity with inhaled environmental O2. Below the type I cells is a
fused (double) layer of basement membranes (from type I cells and endothelial cells)
completing a semipermeable barrier that allows O2 and CO2 diffusion. FLASH
FORWARD
Pulmonary surfactant reduces the
Surfactant surface tension at the air-fluid interface,
(constitutive secretion)
thus decreasing the tendency for
Macrophage
alveolar collapse.
Type II Alveolar
epithelial cell space
Lamellar bodies CO2
Type I
epithelial cell
O2
Blood-air Tight junction
barrier (continuous endothelium) Capillary
lumen
F I G U R E 1 - 3 9 . Gas exchange barrier. The thickness of the gas exchange barrier is

highlighted, as well as the anatomic relations of important cell types: type I and type II
epithelial cells, endothelial cells, macrophages, and red blood cells.

FLASH The type II alveolar cell’s primary function is the production of pulmonary surfactant.
FORWARD Type II alveolar cells also retain the ability to differentiate into type I alveolar cells if
there is an injury to the lung. Clara cells, also known as C cells, also help produce
Amniotic fluid surfactant levels can
be used as a surrogate measure of surfactant in the lungs. C cells act as stem cells, which means they can differentiate
fetal lung maturity. Steroids are given and replace other damaged lung cells. Finally, C cells contain enzymes that can detoxify
to premature infants to increase noxious substances in the lungs.
pneumocyte surfactant production.
Lung Anatomy
The lungs are enveloped in a serosal membrane, known as pleura, which has two layers.
Apposed directly to the lung is the visceral pleura. The parietal pleura is adherent to
KEY FACT the chest wall. Small amounts of fluid within the potential space between the visceral
and parietal pleura, the pleural space or cavity, allows respiratory tissues to slide effort-
Aspirated foreign bodies end up in the
lessly as the lung expands.
right main bronchus more often than
in the left, because the right is wider
and its course is more vertical than that Each lung is divided into lobes, which are further divided into bronchopulmonary
of the left. segments. Each bronchopulmonary segment corresponds to a branch of the bronchial
tree that delivers O2 to the lung. The right lung is composed of three lobes, and the left
lung, two (Figure 1-40). However, the superior lobe of the left lung contains a region,
the lingula, which is analogous to the right lung’s middle lobe. The cardiac notch, into
which the apex of the heart protrudes, replaces the middle lobe on the left side. The
KEY FACT
bronchial tree begins at the trachea, which branches into right and left main-stem
Divisions of the bronchial tree: bronchi. The left bronchus is slightly longer, and the right bronchus makes a shallower
Trachea angle (runs more vertically), with the trachea at its bifurcation. The intersection of the
Right and left main bronchi two mainstem bronchi with the trachea is called the carina.
Lobar bronchi
Segmental bronchi The major vascular supply to each lung begins as a single branch of the pulmonary
Bronchioles artery (carrying deoxygenated blood) and ends as two pulmonary veins (carrying oxy-
Terminal bronchioles genated blood to the left atrium). Between these large vessels, the vasculature branches
Respiratory bronchioles into intrasegmental pulmonary arteries, which travel with branching airways. The pul-
Alveolar ducts
monary veins are along the boundaries of the bronchopulmonary segment. Both end
Alveoli
in a capillary network, within the alveolar septae, which facilitates gas exchange. The
bronchial circulation delivers oxygenated blood from the thoracic aorta to supply the
lung tissue.
MNEMONIC
Anatomic Relations
RALS The lungs reside within the rib cage, under the protection of the bony skeleton. The
Right Anterior apices are at the level of the first rib, and the bases rest in the left and right costodia-
Left Superior phragmatic recesses. Posteriorly, the lungs extend more distally, deep into the costodia-
phragmatic recess, at the 11th or 12th rib. Within the chest, each of the three lung
Trachea Upper lobe
Horizontal
fissure Oblique fissure
Middle lobe Lingula

Lower Lower
lobe lobe
Inferior lobe
Right Left R L L R
A bronchus bronchus B Anterior view Posterior view
F I G U R E 1 - 4 0 . Lungs and bronchi. A Right bronchus is more vertical and wider in diameter than the left bronchus. B Right lung has
three lobes: superior lobe, middle lobe, and inferior lobe. In the left lung, there are two lobes and the lingula. The lingula is a small
projection of the left lung homologous to the middle lobe.

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MR. JAMES G. BLAINE, OF MAINE.
Among those who have in the public press been charged with
improper participation in Credit Mobilier stock is the present
Speaker, Mr. Blaine, who moved the resolution for this investigation.
The committee have, therefore, taken evidence in regard to him.
They find from it that Mr. Ames had conversation with Mr. Blaine in
regard to taking ten shares of the stock, and recommended it as a
good investment. Upon consideration Mr. Blaine concluded not to
take the stock, and never did take it, and never paid or received
anything on account of it; and Mr. Blaine never had any interest,
direct or indirect, in Credit Mobilier stock or stock of the Union
Pacific Railroad Company.
MR. HENRY L. DAWES, OF MASSACHUSETTS.
Mr. Dawes had, prior to December, 1867, made some small

investments in railroad bonds through Mr. Ames. In December,
1867, Mr. Dawes applied to Mr. Ames to purchase a thousand-dollar
bond of the Cedar Rapids road, in Iowa. Mr. Ames informed him that
he had sold them all, but that he would let him have for his thousand
dollars ten shares of Credit Mobilier stock, which he thought was
better than the railroad bond. In answer to inquiries by Mr. Dawes
Mr. Ames said the Credit Mobilier Company had the contract to
build the Union Pacific road, and thought they would make money
out of it, and that it would be a good thing; that he would guarantee
that he should get 10 per cent. on his money, and that if at any time
Mr. Dawes did not want the stock he would pay back his money with
10 per cent. interest. Mr. Dawes made some further inquiry in
relation to the stock of Mr. John B. Alley, who said he thought it was
good stock, but not as good as Mr. Ames thought, but that Mr.
Ames’s guarantee would make it a perfectly safe investment.
Mr. Dawes thereupon concluded to purchase the ten shares, and
on the 11th of January he paid Mr. Ames $800, and in a few days
thereafter the balance of the price of this stock, at par and interest
from July previous. In June, 1868, Mr. Ames received a dividend of
60 per cent. in money on this stock, and of it paid to Mr. Dawes
$400, and applied the balance of $200 upon accounts between them.
This $400 was all that was paid over to Mr. Dawes as a dividend
upon this stock. At some time prior to December, 1868, Mr. Dawes
was informed that a suit had been commenced in the courts of
Pennsylvania by former owners of the charter of the Credit Mobilier,
claiming that those then claiming and using it had no right to do so.
Mr. Dawes thereupon informed Mr. Ames that as there was a
litigation about the matter he did not desire to keep the stock. On the
9th of December, 1868, Mr. Ames and Mr. Dawes had a settlement of
their matters in which Mr. Dawes was allowed for the money he paid
for the stock with 10 per cent. interest upon it, and accounted to Mr.
Ames for the $400 he had received as a dividend. Mr. Dawes
received no other benefit under the contract than to get 10 per cent.
upon his money, and after the settlement had no further interest in
the stock.
MR. GLENNI W. SCOFIELD, OF PENNSYLVANIA.
In 1866 Mr. Scofield purchased some Cedar Rapids bonds of Mr.

Ames, and in that year they had conversations about Mr. Scofield
taking stock in the Credit Mobilier Company, but no contract was
consummated. In December, 1867, Mr. Scofield applied to Mr. Ames
to purchase more Cedar Rapids bonds, when Mr. Ames suggested he
should purchase some Credit Mobilier stock, and explained generally
that it was a contracting company to build the Union Pacific road;
that it was a Pennsylvania corporation, and he would like to have
some Pennsylvanians in it; that he would sell it to him at par and
interest, and that he would guarantee he should get 8 per cent. if Mr.
Scofield would give him half the dividends above that. Mr. Scofield
said he thought he would take $1,000 of the stock; but before
anything further was done Mr. Scofield was called home by sickness
in his family. On his return, the latter part of January, 1868, he spoke
to Mr. Ames about the stock, when Mr. Ames said he thought it was
all sold, but he would take his money and give him a receipt, and get
the stock for him if he could. Mr. Scofield thereupon paid Mr. Ames
$1,041, and took his receipt therefor.
Not long after Mr. Ames informed Mr. Scofield he could have the
stock, but could not give him a certificate for it until he could get a
larger certificate dividend. Mr. Scofield received the bond dividend of
80 per cent., which was payable January 3, 1868, taking a bond for
$1,000 and paying Mr. Ames the difference. Mr. Ames received the
60 per cent. cash dividend on the stock in June, 1868, and paid over
to Mr. Scofield $600, the amount of it.
Before the close of that session of Congress, which was toward the
end of July, Mr. Scofield became, for some reason, disinclined to take
the stock, and a settlement was made between them, by which Mr.
Ames was to retain the Credit Mobilier stock and Mr. Scofield took a
thousand dollars Union Pacific bond and ten shares of Union Pacific
stock.
The precise basis of the settlement does not appear, neither Mr.
Ames nor Mr. Scofield having any full date in reference to it; Mr.
Scofield thinks that he only received back his money and interest
upon it, while Mr. Ames states that he thinks Mr. Scofield had ten
shares of Union Pacific stock in addition. The committee do not
deem it specially important to settle this difference of recollection.
Since that settlement Mr. Scofield has had no interest in the Credit
Mobilier stock and derived no benefit therefrom.
MR. JOHN A. BINGHAM, OF OHIO.
In December, 1867, Mr. Ames advised Mr. Bingham to invest in

the stock of the Credit Mobilier, assuring him that it would return
him his money with profitable dividends. Mr. Bingham agreed to
take twenty shares, and about the 1st of February, 1868, paid to Mr.
Ames the par value of the stock, for which Mr. Ames executed to him
some receipt or agreement. Mr. Ames received all the dividends on
the stock, whether in Union Pacific bonds, or stock, or money; some
were delivered to Mr. Bingham and some retained by Mr. Ames. The
matter was not finally adjusted between them until February, 1872,
when it was settled, Mr. Ames retaining the twenty shares of Credit
Mobilier stock, and accounting to Mr. Bingham for such dividends
upon it as Mr. Bingham had not already received. Mr. Bingham was
treated as the real owner of the stock from the time of the agreement
to take it, in December, 1867, to the settlement in February, 1872,
and had the benefit of all the dividends upon it. Neither Mr. Ames
nor Mr. Bingham had such records of their dealing as to be able to
give the precise amount of those dividends.
MR. WILLIAM D. KELLEY, OF PENNSYLVANIA.
The committee find from the evidence that in the early part of the
second session of the Fortieth Congress, and probably in December,
1867, Mr. Ames agreed with Mr. Kelley to sell him ten shares of
Credit Mobilier stock at par and interest from July 1, 1867. Mr.
Kelley was not then prepared to pay for the stock, and Mr. Ames
agreed to carry the stock for him until he could pay for it. On the
third day of January, 1868, there was a dividend of 80 per cent. on
Credit Mobilier stock in Union Pacific bonds. Mr. Ames received the
bonds, as the stock stood in his name, and sold them for 97 per cent.
of their face. In June, 1868, there was a cash dividend of 60 per cent.,
which Mr. Ames also received. The proceeds of the bonds sold, and
the cash dividends received by Mr. Ames, amounted to $1,376. The
par value of the stock and interest thereon from the previous July
amounted to $1,047; so that, after paying for the stock, there was a
balance of dividends due Mr. Kelley of $329. On the 23d day of June,
1868, Mr. Ames gave Mr. Kelley a check for that sum on the
Sergeant-at-Arms of the House of Representatives, and Mr. Kelley
received the money thereon.
The committee find that Mr. Kelley then understood that the
money he thus received was a balance of dividends due him after
paying for the stock.
All the subsequent dividends upon the stock were either in Union
Pacific stock or bonds, and they were all received by Mr. Ames. In
September, 1868, Mr. Kelley received from Mr. Ames $750 in
money, which was understood between them to be an advance to be
paid out of dividends. There has never been any adjustment of the
matter between them, and there is now an entire variance in the
testimony of the two men as to what the transaction between them
was, but the committee are unanimous in finding the facts above
stated. The evidence reported to the House gives some subsequent
conversations and negotiations between Mr. Kelley and Mr. Ames on
this subject. The committee do not deem it material to refer to it in
their report.
MR. JAMES A. GARFIELD, OF OHIO.
The facts in regard to Mr. Garfield, as found by the committee, are

identical with the case of Mr. Kelley to the point of reception of the
check for $329. He agreed with Mr. Ames to take ten shares of Credit
Mobilier stock, but did not pay for the same. Mr. Ames received the
80 per cent. dividend in bonds and sold them for 97 per cent., and
also received the 60 per cent. cash dividend, which together paid the
price of the stock and interest, and left a balance of $329. This sum
was paid over to Mr. Garfield by a check on the Sergeant-at-Arms,
and Mr. Garfield then understood this sum was the balance of
dividends after paying for the stock. Mr. Ames received all the
subsequent dividends, and the committee do not find that, since the
payment of the $329, there has been any communication between
Mr. Ames and Mr. Garfield on the subject until this investigation
began. Some correspondence between Mr. Garfield and Mr. Ames,
and some conversations between them during this investigation, will
be found in the reported testimony.
The committee do not find that Mr. Ames, in his negotiations with
the persons above named, entered into any detail of the relations
between the Credit Mobilier Company and the Union Pacific
Company, or gave them any specific information as to the amount of
dividends they would be likely to receive further than has been
already stated. They all knew from him, or otherwise, that the Credit
Mobilier was a contracting company to build the Union Pacific road,
but it does not appear that any of them knew that the profits and
dividends were to be in stock and bonds of that company.
The Credit Mobilier Company was a State corporation, not subject
to congressional legislation, and the fact that its profits were
expected to be derived from building the Union Pacific road did not,
apparently, create such an interest in that company as to disqualify
the holder of Credit Mobilier stock from participating in any
legislation affecting the railroad company. In his negotiations with
these members of Congress, Mr. Ames made no suggestion that he
desired to secure their favorable influence in Congress in favor of the
railroad company, and whenever the question was raised as to
whether the ownership of this stock would in any way interfere with
or embarrass them in their action as members of Congress, he
assured them it would not.
The committee, therefore, do not find, as to the members of the
present House above named, that they were aware of the object of
Mr. Ames, or that they had any other purpose in taking this stock
than to make a profitable investment. It is apparent that those who
advanced their money to pay for their stock present more the
appearance of ordinary investors than those who did not, but the
committee do not feel at liberty to find any corrupt purpose or
knowledge founded upon the fact of non-payment alone.
It ought also to be observed that those gentlemen who surrendered
their stock to Mr. Ames before there was any public excitement upon
the subject, do not profess to have done so upon any idea of
impropriety in holding it, but for reasons affecting the value and
security of the investment. But the committee believe that they must
have felt that there was something so out of the ordinary course of
business in the extraordinary dividends they were receiving as to
render the investment itself suspicious, and that this was one of the
motives of their action.
The committee have not been able to find that any of these
members of Congress have been affected in their official action in
consequence of their interest in Credit Mobilier stock.
It has been suggested that the fact that none of this stock was
transferred to those with whom Mr. Ames contracted was a
circumstance from which a sense of impropriety, if not corruption,
was to be inferred. The committee believe this is capable of
explanation without such inference. The profits of building the road,
under the Ames contract, were only to be divided among such
holders of Credit Mobilier stock as should come in and become
parties to certain conditions set out in the contract of transfer to the
trustees, so that a transfer from Mr. Ames to new holders would cut
off the right to dividends from the trustees, unless they also became
parties to the agreement; and this the committee believe to be the
true reason why no transfers were made.
The committee are also of opinion that there was a satisfactory
reason for delay on Mr. Ames’s part to close settlements with some of
these gentlemen for stock and bonds he had received as dividends
upon the stock contracted to them. In the fall of 1868 Mr. McComb
commenced a suit against the Credit Mobilier Company, and Mr.
Ames and others, claiming to be entitled to two hundred and fifty
shares of the Credit Mobilier stock upon a subscription for stock to
that amount. That suit is still pending. If McComb prevailed in that
suit, Mr. Ames might be compelled to surrender so much of the stock
assigned to him as trustee, and he was not therefore anxious to have
the stock go out of his hands until that suit was terminated. It ought
also to be stated that no one of the present members of the House
above named appears to have had any knowledge of the dealings of
Mr. Ames with other members.
The committee do not find that either of the above named
gentlemen, in contracting with Mr. Ames, had any corrupt motive or
purpose himself, or was aware that Mr. Ames had any, nor did either
of them suppose he was guilty of any impropriety or even indelicacy
in becoming a purchaser of this stock. Had it appeared that these
gentlemen were aware of the enormous dividends upon this stock,
and how they were to be earned, we could not thus acquit them. And
here as well as anywhere, the committee may allude to that subject.
Congress had chartered the Union Pacific road, given to it a liberal
grant of lands, and promised a liberal loan of Government bonds, to
be delivered as fast as sections of the road were completed. As these
alone might not be sufficient to complete the road, Congress
authorized the company to issue their own bonds for the deficit, and
secured them by a mortgage upon the road, which should be a lien
prior to that of the Government. Congress never intended that the
owners of the road should execute a mortgage on the road prior to
that of the Government, to raise money to put into their own pockets,
but only to build the road.
The men who controlled the Union Pacific seem to have adopted as
the basis of their action the right to encumber the road by a mortgage
prior to that of the Government to the full extent, whether the money
was needed for the construction of the road or not.
It was clear enough they could not do this directly and in terms,
and therefore they resorted to the device of contracting with
themselves to build the road, and fix a price high enough to require
the issue of bonds to the full extent, and then divide the bonds or the
proceeds of them under the name of profits on the contract. All those
acting in the matter seem to have been fully aware of this, and that
this was to be the effect of the transaction. The sudden rise of value
of Credit Mobilier stock was the result of the adoption of this
scheme. Any undue and unreasonable profits thus made by
themselves were as much a fraud upon the Government as if they
had sold their bonds and divided the money without going through
the form of denominating them profits on building the road.
Now had these facts been known to these gentlemen, and had they
understood they were to share in the proceeds of the scheme, they
would have deserved the severest censure.
Had they known only that the profits were to be paid in stock and
bonds of the Union Pacific Company, and so make them interested in
it, we cannot agree to the doctrine, which has been urged before us
and elsewhere, that it was perfectly legitimate for members of
Congress to invest in a corporation deriving all its rights from and
subject at all times to the action of Congress.
In such case the rules of the House, as well as the rules of decency,
would require such member to abstain from voting on any question
affecting his interest. But, after accepting the position of a member of
Congress, we do not think he has the right to disqualify himself from
acting upon subjects likely to come before Congress without some
higher and more urgent motive than merely to make a profitable
investment. But it is not so much to be feared that in such case an
interested member would vote as that he would exercise his
influence by personal appeal to his fellow-members, and by other
modes, which often is far more potent than a single silent vote.
We do not think any member ought to feel so confident of his own
strength as to allow himself to be brought into this temptation. We
think Mr. Ames judged shrewdly in saying that a man is much more
likely to be watchful of his own interests than those of other people.
But there is a broader view still which we think ought to be taken.
This country is fast becoming filled with gigantic corporations,
wielding and controlling immense aggregations of money, and
thereby commanding great influence and power. It is notorious in
many State legislatures that these influences are often controlling, so
that in effect they become the ruling power of the State. Within a few
years Congress has, to some extent, been brought within similar
influences, and the knowledge of the public on that subject has
brought great discredit upon the body, far more, we believe, than
there were facts to justify.
But such is the tendency of the time, and the belief is far too
general that all men can be ruled with money, and that the use of
such means to carry public measures is legitimate and proper. No
member of Congress ought to place himself in circumstances of
suspicion, so that any discredit of the body shall arise on his account.
It is of the highest importance that the national legislature should be
free of all taint of corruption, and it is of almost equal necessity that
the people should feel confident that it is so.
In a free government like ours, we cannot expect the people will
long respect the laws, if they lose respect for the law-makers.
For these reasons we think it behooves every man in Congress or
in any public position to hold himself aloof, as far as possible, from
all such influences, that he may not only be enabled to look at every
public question with an eye only to the public good, but that his
conduct and motives be not suspected or questioned. The only
criticism the committee feel compelled to make on the action of these
members in taking this stock is that they were not sufficiently careful
in ascertaining what they were getting, and that in their judgment
the assurance of a good investment was all the assurance they
needed. We commend to them, and to all men, the letter of the
venerable Senator Bayard, in response to an offer of some of this
stock, found on page 74 of the testimony.
The committee find nothing in the conduct or motives of either of
these members in taking this stock, that calls for any
recommendation by the committee of the House.
MR. JAMES BROOKS, OF NEW YORK.
The case of Mr. Brooks stands upon a different state of facts from
any of those already given. The committee find from the evidence as
follows: Mr. Brooks had been a warm advocate of a Pacific Railroad,
both in Congress and in the public press. After persons interested in
the Union Pacific road had obtained control of the Credit Mobilier
charter and organized under it for the purpose of making it a
construction company to build the road, Dr. Durant, who was then
the leading man in the enterprise, made great efforts to get the stock
of the Credit Mobilier taken. Mr. Brooks was a friend of Dr. Durant,
and he made some efforts to aid Dr. Durant in getting subscriptions
for the stock, introduced the matter to some capitalists of New York,
but his efforts were not crowned with success.
During this period Mr. Brooks had talked with Dr. Durant about
taking some of the stock for himself, and had spoken of taking fifteen
or twenty thousand dollars of it, but no definite contract was made
between them, and Mr. Brooks was under no legal obligation to take
the stock, or Durant to give it to him. In October, 1867, Mr. Brooks
was appointed by the President one of the Government directors of
the Union Pacific road. In December, 1867, after the stock of the
Credit Mobilier was understood, by those familiar with the affairs
between the Union Pacific and the Credit Mobilier, to be worth very
much more than par, Mr. Brooks applied to Dr. Durant, and claimed
that he should have two hundred shares of Credit Mobilier stock. It
does not appear that Mr. Brooks claimed he had any legal contract
for stock that he could enforce, or that Durant considered himself in
any way legally bound to let him have any, but still, on account of
what had been said, and the efforts of Mr. Brooks to aid him, he
considered himself under obligations to satisfy Mr. Brooks in the
matter.
The stock had been so far taken up, and was then in such demand,
that Durant could not well comply with Brooks’s demand for two
hundred shares. After considerable negotiation, it was finally
adjusted between them by Durant’s agreeing to let Brooks have one
hundred shares of Credit Mobilier stock, and giving him with it
$5,000 of Union Pacific bonds, and $20,000 of Union Pacific stock.
Dr. Durant testifies that he then considered Credit Mobilier stock
worth double the par value, and that the bonds and stock he was to
give Mr. Brooks worth about $9,000, so that he saved about $1,000
by not giving Brooks the additional hundred shares he claimed. After
the negotiation had been concluded between Mr. Brooks and Dr.
Durant, Mr. Brooks said that as he was a Government director of the
Union Pacific road, and as the law provided such directors should
not be stockholders in that company, he would not hold this stock,
and directed Dr. Durant to transfer it to Charles H. Neilson, his son-
in-law. The whole negotiation with Durant was conducted by Mr.
Brooks himself, and Neilson had nothing to do with the transaction,
except to receive the transfer. The $10,000 to pay for the one
hundred shares was paid by Mr. Brooks, and he received the $5,000
of Pacific bonds which came with the stock.
The certificate of transfer of the hundred shares from Durant to
Neilson is dated December 26, 1867. On the 3d of January, 1868,
there was a dividend of 80 per cent. in Union Pacific bonds paid on
the Credit Mobilier stock. The bonds were received by Neilson, but
passed over at once to Mr. Brooks. It is claimed, both by Mr. Brooks
and Neilson, that the $10,000 paid by Mr. Brooks for the stock was a
loan of that sum by him to Neilson, and, that the bonds he received
from Durant, and those received for the dividend, were delivered and
held by him as collateral security for the loan.
No note or obligation was given for the money by Neilson, nor, so
far as we can learn from either Brooks or Neilson, was any account or
memorandum of the transaction kept by either of them. At the time
of the arrangement or settlement above spoken of between Brooks
and Durant, there was nothing said about Mr. Brooks being entitled
to have 50 per cent. more stock by virtue of his ownership of the
hundred shares. Neither Brooks nor Durant thought of any such
thing.
Some time after the transfer of the shares to Neilson, Mr. Brooks
called on Sidney Dillon, then the president of the Credit Mobilier,
and claimed he or Neilson was entitled to fifty additional shares of
the stock, by virtue of the purchase of the one hundred shares of
Durant.
This was claimed by Mr. Brooks as his right by virtue of the 50 per
cent. increase of the stock hereinbefore described. Mr. Dillon said he
did not know how that was, but he would consult the leading
stockholders, and be governed by them. Mr. Dillon, in order to justify
himself in the transaction, got up a paper authorizing the issue of
fifty shares of the stock to Mr. Brooks, and procured it to be signed
by most of the principal shareholders. After this had been done, an
entry of fifty shares was made on the stock-ledger to some person
other than Neilson. The name in two places on the book has been
erased, and the name of Neilson inserted. The committee are
satisfied that the stock was first entered on the books in Mr. Brooks’s
name.
Mr. Neilson soon after called for the certificate for the fifty shares,
and on the 29th of February, 1868, the certificate was issued to him,
and the entry on the stock-book was changed to Neilson.
Neilson procured Mr. Dillon to advance the money to pay for the
stock, and at the same time delivered to Dillon $4,000 Union Pacific
bonds, and fifty shares of Union Pacific stock as collateral security.
These bonds and stock were a portion of dividends received at the
time, as he was allowed to receive the same per centage of dividends
on these fifty shares that had previously been paid on the hundred.
This matter has never been adjusted between Neilson and Dillon.
Brooks and Neilson both testify they never paid Dillon. Dillon thinks
he has received his pay, as he has not now the collaterals in his
possession. If he has been paid it is probable that it was from the
collaterals in some form. The subject has never been named between
Dillon and Neilson since Dillon advanced the money, and no one
connected with the transaction seems able to give any further light
upon it. The whole business by which these fifty shares were
procured was done by Mr. Brooks. Neilson knew nothing of any right
to have them, and only went for the certificate when told to do so by
Mr. Brooks.
The committee find that no such right to fifty shares additional
stock passed by the transfer of the hundred. And from Mr. Brooks’s
familiarity with the affairs of the company, the committee believe he
must have known his claim to them was unfounded. The question
naturally arises, How was he able to procure them? The stock at this
time by the stockholders was considered worth three or four times its
par value. Neilson sustained no relations to any of these people that
commanded any favor, and if he could have used any influence he
did not attempt it; if he had this right he was unaware of it till told by
Mr. Brooks, and left the whole matter in his hands. It is clear that the
shares were procured by the sole efforts of Mr. Brooks, and, as the
stockholders who consented to it supposed, for the benefit of Mr.
Brooks. What power had Mr. Brooks to enforce an unfounded claim,
to have for $5,000, stock worth $15,000 or $20,000? Mr. McComb
swears that he heard conversation between Mr. Brooks and Mr. John
B. Alley, a large stockholder, and one of the executive committee, in
which Mr. Brooks urged that he should have the additional fifty
shares, because he was or would procure himself to be made a
Government director, and also that, being a member of Congress, he
“would take care of the democratic side of the House.”
Mr. Brooks and Mr. Alley both deny having had any such
conversation, or that Mr. Brooks ever made such a statement to Mr.
Alley. If, therefore, this matter rested wholly upon the testimony of
Mr. McComb, the committee would not feel justified in finding that
Mr. Brooks procured the stock by such use of his official position; but
all the circumstances seem to point exactly in that direction, and we
can find no other satisfactory solution of the question above
propounded. Whatever claim Mr. Brooks had to stock, either legal or
moral, had been adjusted and satisfied by Dr. Durant. Whether he
was getting this stock for himself or to give to his son-in-law, we
believe, from the circumstances attending the whole transaction, that
he obtained it knowing that it was yielded to its official position and
influence, and with the intent to secure his favor and influence in
such positions. Mr. Brooks claims that he has had no interest in this
stock whatever; that the benefit and advantage of his right to have it
he gave to Mr. Neilson, his son-in-law, and that he has had all the
dividends upon it. The committee are unable to find this to be the
case, for in their judgment all the facts and circumstances show Mr.
Brooks to be the real and substantial owner, and that Neilson’s
ownership is merely nominal and colorable.
In June, 1868, there was a cash dividend of $9,000 upon this one
hundred and fifty shares of stock. Neilson received it, of course, as
the stock was in his name; but on the same day it was paid over to
Mr. Brooks, as Neilson says, to pay so much of the $10,000 advanced
by Mr. Brooks to pay for the stock. This, then, repaid all but $1,000
of the loan; but Mr. Brooks continued to hold $16,000 of Union
Pacific bonds, which Neilson says he gave him as collateral security,
and to draw the interest upon all but $5,000. The interest upon the
others, Neilson says, he was permitted to draw and retain, but at one
time in his testimony he spoke of the amount he was allowed as
being Christmas and New Year’s presents. Neilson says that during
the last summer he borrowed $14,000 of Mr. Brooks, and he now
owes Mr. Brooks nearly as much as the collaterals; but, according to
his testimony, Mr. Brooks for four years held $16,000 in bonds as
security for $1,000, and received the interest on $11,000 of the
collaterals. No accounts appear to have been kept between Mr.
Brooks and Neilson, and doubtless what sums he has received from
Mr. Brooks, out of the dividends, were intended as presents rather
than as deliveries of money belonging to him.
Mr. Brooks’s efforts procured the stock; his money paid for it; all
the cash dividends he has received; and he holds all the bonds,
except those Dillon received, which seem to have been applied
toward paying for the fifty shares. Without further comment on the
evidence, the committee find that the one hundred and fifty shares of
stock appearing on the books of the Credit Mobilier in the name of
Neilson were really the stock of Mr. Brooks, and subject to his
control, and that it was so understood by both the parties. Mr.
Brooks had taken such an interest in the Credit Mobilier Company,
and was so connected with Dr. Durant, that he must be regarded as
having full knowledge of the relations between that company and the
railroad company, and of the contracts between them. He must have
known the cause of the sudden increase in value of the Credit
Mobilier stock, and how the large expected profits were to be made.
We have already expressed our views of the propriety of a member of
Congress becoming the owner of stock, possessing this knowledge.
But Mr. Brooks was not only a member of Congress, but he was a
Government director of the Union Pacific Company. As such it was
his duty to guard and watch over the interests of the Government in
the road and to see that they were protected and preserved. To insure
such faithfulness on the part of Government directors, Congress
wisely provided that they should not be stockholders in the road. Mr.
Brooks readily saw that, though becoming a stockholder in the Credit
Mobilier was not forbidden by the letter of the law, yet it was a
violation of its spirit and essence, and therefore had the stock placed
in the name of his son-in-law. The transfer of the Oakes Ames
contract to the trustees and the building of the road under that
contract, from which the enormous dividends were derived, were all
during Mr. Brooks’s official life as a Government director, must have
been within his knowledge, and yet passed without the slightest
opposition from him. The committee believed this could not have
been done without an entire disregard of his official obligation and
duty, and that while appointed to guard the public interests in the
road he joined himself with the promoters of a scheme whereby the
Government was to be defrauded, and shared in the spoil.
In the conclusions of fact upon the evidence, the committee are
entirely agreed.
In considering what action we ought to recommend to the House
upon these facts, the committee encounter a question which has
been much debated: Has this House power and jurisdiction to
inquire concerning offenses committed by its members prior to their
election, and to punish them by censure or expulsion? The
committee are unanimous upon the right of jurisdiction of this
House over the cases of Mr. Ames and Mr. Brooks, upon the facts
found in regard to them. Upon the question of jurisdiction the
committee present the following views:
The Constitution, in the fifth section of the first article, defines the
power of either House as follows:
“Each House may determine the rules of its proceedings, punish
its members for disorderly behavior, and with the concurrence of
two-thirds expel a member.”
It will be observed that there is no qualification of the power, but
there is an important qualification of the manner of its exercise—it
must be done “with the concurrence of two-thirds.”
The close analogy between this power and the power of
impeachment is deserving of consideration.
The great purpose of the power of impeachment is to remove an
unfit and unworthy incumbent from office, and though a judgment of
impeachment may to some extent operate as punishment, that is not
its principal object. Members of Congress are not subject to be
impeached, but may be expelled, and the principal purpose of
expulsion is not as punishment, but to remove a member whose
character and conduct show that he is an unfit man to participate in
the deliberations and decisions of the body, and whose presence in it
tends to bring the body into contempt and disgrace.
In both cases it is a power of purgation and purification to be
exercised for the public safety, and, in the case of expulsion, for the
protection and character of the House. The Constitution defines the
causes of impeachment, to wit, “treason, bribery, or other high
crimes and misdemeanors.” The office of the power of expulsion is so
much the same as that of the power to impeach that we think it may
be safely assumed that whatever would be a good cause of
impeachment would also be a good cause of expulsion.
It has never been contended that the power to impeach for any of
the causes enumerated was intended to be restricted to those which
might occur after appointment to a civil office, so that a civil officer
who had secretly committed such offense before his appointment
should not be subject upon detection and exposure to be convicted
and removed from office. Every consideration of justice and sound
policy would seem to require that the public interests be secured, and
those chosen to be their guardians be free from the pollution of high
crimes, no matter at what time that pollution had attached.
If this be so in regard to other civil officers, under institutions
which rest upon the intelligence and virtue of the people, can it well
be claimed that the law-making Representative may be vile and
criminal with impunity, provided the evidences of his corruption are
found to antedate his election?
In the report made to the Senate by John Quincy Adams in
December, 1807, upon the case of John Smith, of Ohio, the following
language is used: “The power of expelling a member for misconduct
results, on the principles of common sense, from the interests of the
nation that the high trust of legislation shall be invested in pure
hands. When the trust is elective, it is not to be presumed that the
constituent body will commit the deposit to the keeping of worthless
characters. But when a man whom his fellow-citizens have honored
with their confidence on a pledge of a spotless reputation, has
degraded himself by the commission of infamous crimes, which
become suddenly and unexpectedly revealed to the world, defective
indeed would be that institution which should be impotent to discard
from its bosom the contagion of such a member; which should have
no remedy of amputation to apply until the poison had reached the
heart.”
The case of Smith was that of a Senator, who, after his election, but
not during a session of the Senate, had been involved in the
treasonable conspiracy of Aaron Burr. Yet the reasoning is general,
and was to antagonize some positions which had been taken in the
case of Marshall, a Senator from Kentucky; the Senate in that case
having, among other reasons, declined to take jurisdiction of the
charge for the reason that the alleged offence had been committed
prior to the Senator’s election, and was matter cognizable by the
criminal courts of Kentucky. None of the commentators upon the
Constitution or upon parliamentary law assign any such limitation as
to the time of the commission of the offense, or the nature of it,
which shall control and limit the power of expulsion. On the contrary
they all assert that the power in its very nature is a discretionary one,
to be exercised of course with grave circumspection at all times, and
only for good cause. Story, Kent, and Sergeant, all seem to accept and
rely upon the exposition of Mr. Adams in the Smith case as sound.
May, in his Parliamentary Practice, page 59, enumerates the causes
for expulsion from Parliament, but he nowhere intimates that the
offense must have been committed subsequent to the election.
When it is remembered that the framers of our Constitution were
familiar with the parliamentary law of England, and must have had
in mind the then recent contest over Wilkes’s case, it is impossible to
conclude that they meant to limit the discretion of the Houses as to
the causes of expulsion. It is a received principle of construction that
the Constitution is to be interpreted according to the known rules of
law at the time of its adoption, and therefore, when we find them
dealing with a recognized subject of legislative authority, and while
studiously qualifying and restricting the manner of its exercise,
assigning no limitations to the subject-matter itself, they must be
assumed to have intended to leave that to be determined according
to established principles, as a high prerogative power to be exercised
according to the sound discretion of the body. It was not to be
apprehended that two-thirds of the Representatives of the people
would ever exercise this power in any capricious or arbitrary manner,
or trifle with or trample upon constitutional rights. At the same time
it could not be foreseen what necessities for self-preservation or self-
purification might arise in the legislative body. Therefore it was that
they did not, and would not, undertake to limit or define the
boundaries of those necessities.
The doctrine that the jurisdiction of this House over its members is
exclusively confined to matters arising subsequent to their election,
and that the body is bound to retain the vilest criminal as a member
if his criminal secret was kept until his election was secured, has
been supposed by many to have been established and declared in the
famous case of John Wilkes before alluded to. A short statement of
that case will show how fallacious is that supposition. Wilkes had
been elected a member of Parliament for Middlesex, and in 1764 was
expelled for having published a libel on the ministry. He was again
elected and again expelled for a similar offense on the 3d of
February, 1769. Being again elected on the 17th of February, 1769,
the commons passed the following resolution: “That John Wilkes,
Esq., having been in this session of Parliament expelled this house
was and is incapable of being elected a member to serve in this
present Parliament.” Wilkes was again elected, but the House of
Commons declared the seat vacant and ordered a new election. At
this election Wilkes was again elected by 1,143 votes, against 296 for
his competitor, Luttrell.
On the 15th of April, 1769, the house decided that by the previous
action Wilkes had become ineligible, and that the votes given for him
were void and could not be counted, and gave the seat to Luttrell.
Subsequently, in 1783, the House of Commons declared the
resolution of February 17, 1769, which had asserted the incapacity of
an expelled member to be re-elected to the same Parliament, to be
subversive of the rights of the electors, and expunged it from the
journal. It will be seen from this concise statement of Wilkes’s case
that the question was not raised as to the power of the house to expel
a member for offenses committed prior to his election; the point
decided, and afterward most properly expunged, was that expulsion
per se rendered the expelled member legally ineligible, and that
votes cast for him could not be counted. Wilkes’s offense was of
purely a political character, not involving moral turpitude; he had
attacked the ministry in the press, and the proceedings against him
in Parliament were then claimed to be a partisan political
persecution, subversive of the rights of the people and of the liberty
of the press. These proceedings in Wilkes’s case took place during the
appearance of the famous Junius letters, and several of them are
devoted to the discussion of them. The doctrine that expulsion
creates ineligibility was attacked and exposed by him with great
force. But he concedes that if the cause of expulsion be one that
renders a man unfit and unworthy to be a member, he may be
expelled for that cause as often as he shall be elected.
The case of Matteson, in the House of Representatives, has also
often been quoted as a precedent for this limitation of jurisdiction. In
the proceedings and debates of the House upon that case it will be
seen that this was one among many grounds taken in the debate; but
as the whole subject was ended by being laid on the table, it is quite
impossible to say what was decided by the House. It appeared,
however, in that case that the charge against Matteson had become
public, and his letter upon which the whole charge rested had been
published and circulated through his district during the canvass
preceding his election. This fact, we judge, had a most important
influence in determining the action of the House in his case.
The committee have no occasion in this report to discuss the
question as to the power or duty of the House in a case where a
constituency, with a full knowledge of the objectionable character of
a man, have selected him to be their Representative. It is hardly a
case to be supposed that any constituency, with a full knowledge that
a man had been guilty of an offense involving moral turpitude, would
elect him. The majority of the committee are not prepared to concede
such a man could be forced upon the House, and would not consider
the expulsion of such a man any violation of the rights of the electors,
for while the electors have rights that should be respected, the House
as a body has rights also that should be protected and preserved. But
that in such case the judgment of the constituency would be entitled
to the greatest consideration, and that this should form an important
element in its determination, is readily admitted.
It is universally conceded, as we believe, that the House has ample
jurisdiction to punish or expel a member for an offense committed
during his term as a member, though committed during a vacation of
Congress and in no way connected with his duties as a member.
Upon what principle is it that such a jurisdiction can be maintained?
It must be upon one or both of the following: that the offense shows
him to be an unworthy and improper man to be a member, or that
his conduct brings odium and reproach upon the body. But suppose
the offense has been committed prior to his election, but comes to
light afterward, is the effect upon his own character, or the reproach
and disgrace upon the body, if they allow him to remain a member,
any the less? We can see no difference in principle in the two cases,
and to attempt any would be to create a purely technical and
arbitrary distinction, having no just foundation. In our judgment, the
time is not at all material, except it be coupled with the further fact
that he was re-elected with a knowledge on the part of his
constituents of what he had been guilty, and in such event we have
given our views of the effect.
It seems to us absurd to say that an election has given a man
political absolution for an offense which was unknown to his
constituents. If it be urged again, as it has sometimes been, that this
view of the power of the House, and the true ground of its proper
exercise, may be laid hold of and used improperly, it may be
answered that no rule, however narrow and limited, that may be
adopted can prevent it. If two-thirds of the House shall see fit to
expel a man because they do not like his political or religious
principles, or without any reason at all, they have the power, and
there is no remedy except by appeal to the people. Such exercise of
the power would be wrongful, and violative of the principles of the
Constitution, but we see no encouragement of such wrong in the
views we hold.
It is the duty of each House to exercise its rightful functions upon
appropriate occasions, and to trust that those who come after them
will be no less faithful to duty, and no less jealous for the rights of
free popular representation than themselves. It will be quite time
enough to square other cases with right reason and principle when
they arise. Perhaps the best way to prevent them will be to maintain
strictly public integrity and public honor in all cases as they present
themselves. Nor do we imagine that the people of the United States
will charge their servants with invading their privileges when they
confine themselves to the preservation of a standard of official
integrity which the common instincts of humanity recognize as
essential to all social order and good government.
The foregoing are the views which we deem proper to submit upon
the general question of the jurisdiction of the House over its
members. But apart from these general views, the committee are of
opinion that the facts found in the present case amply justify the
taking jurisdiction over them, for the following reasons:
The subject-matter upon which the action of members was
intended to be influenced was of a continuous character, and was as
likely to be a subject of congressional action in future Congresses as

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Anatomy and Histology

CELLULAR ANATOMY AND HISTOLOGY 2 Splenic Anatomy 20

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Cellular Anatomy and Histology

Aqueous phase (extracellular)

“Oil” or nonpolar phase

Aqueous phase (cytoplasm)

F I G U R E 1 - 1 . Amphipathic lipids. A Phospholipid, with a phosphate head group and a lipid

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The cell membrane performs the following functions:

Rough Endoplasmic Reticulum and Ribosomes

Smooth Endoplasmic Reticulum

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Functions of the Golgi Apparatus

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Cross section Longitudinal section Tubulin

B Enlarged microtubule doublet

F I G U R E 1 - 5 . Microtubules. A Structure. The cylindrical structure of a microtubule is

Epithelial Cell Junctions

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Actin Adherens junction (belt desmosome, zonula adherens)—below

Connexon Gap junction—channel proteins called connexons permit

Zonula Adherens CLINICAL

Gap Junctions FLASH

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The Pluripotent Stem Cell

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Pluripotent stem cell

Myeloid stem cell Lymphoid stem cell

Erythropoiesis Thrombopoiesis Granulocytopoiesis Lymphopoiesis

Erythroid Thrombocyte Granulocyte/monocyte B– T–

Eosinophilic Basophilic Neutrophilic

Erythrocyte Platelets Eosinophil Basophil Neutrophil Macrophage

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All leukocytes are involved in some aspect of the immune response:

Important neutrophil chemotactic

F I G U R E 1 - 9 . Peripheral blood smear with neutrophilia. This peripheral blood smear

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F I G U R E 1 - 1 1 . Eosinophil microscopy. A Mature eosinophil with bright red granules.

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F I G U R E 1 - 1 2 . Basophil microscopy. A Electron micrograph of a normal intact mast cell

F I G U R E 1 - 1 3 . Macrophage microscopy. A Active macrophage and B multinucleated giant

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