Principal Essentials of Pathophysiology: Concepts of Altered Health States (Point (Lippincott Williams & Wilkins))

Essentials of Pathophysiology: Concepts of Altered Health States (Point (Lippincott Williams & Wilkins))

Designed to provide students with essential concepts of disease processes and altered health states, this text is ideal for both discrete and integrated pathophysiology courses. The Second Edition has over 200 new and revised illustrations and incorporates a new feature "Understanding", which uses large pieces of art to outline key processes using a step-by-step approach. The text continues to include such favorite features as: key concept boxes, color-coded summaries, and icons to delineate special considerations for children, the elderly, and pregnant women. The free CD-ROM now provides access to three-dimensional animations so visual learners can gain a greater understanding of common disease and cellular processes. The CD-ROM also includes student review questions.
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Probabilities of the Quantum World

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Mechanisms of Disease

Alterations in Body Defenses

1 Cell Structure and Function



Mary Pat Kunert

Edward W. Carroll

Disorders of the Stress Response

Functional Components of the Cell
Cell Metabolism and Energy Sources
Cell Membrane Transport, Signal Transduction,
and Generation of Membrane Potentials
Body Tissues

2 Tissue Adaptation and Injury


8 The Immune Response


Cynthia V. Sommer


Cellular Adaptation
Cell Injury and Death

The Immune System
Developmental Aspects of the Immune System


9 Inflammation, Tissue Repair,

3 Genetic Control of Cell Function


Edward W. Carroll

Genetic Control of Cell Function
Patterns of Inheritance
Gene Mapping and Technology

7 Stress and Adaptation


Cynthia V. Sommer, Carol M. Porth

The Inflammatory Response
Tissue Repair and Wound Healing
Temperature Regulation and Fever


10 Alterations in the


4 Genetic and Congenital Disorders
Genetic and Chromosomal Disorders
Disorders Due to Environmental Influences


and Replication: Neoplasia

Immune Response


Carol M. Porth, Kathleen Sweeney

Allergic and Hypersensitivity Disorders
Transplantation Immunopathology
Autoimmune Disorders
Immunodeficiency Disorders


5 Alterations in Cell Growth

Kathryn Ann Caudell

Concepts of Cell Growth
Characteristics of Benign
and Malignant Neoplasms
Carcinogenesis and Causes of Cancer
Clinical Features
Childhood Cancers

and Fever


Alterations in the Hematologic System

11 Alterations in White Blood Cells


Hematopoietic and Lymphoid Tissue
Non-neoplastic Disorders of White Blood Cells
Neoplastic Disorders of Hematopoietic
and Lymphoid Origin

6 Alterations in Fluids, Electrolytes,
and Acid-Base Balance
Composition and Compartmental Distribution
of Body Fluids
Sodium and Water Balance
Potassium Balance
Calcium and Magnesium Balance
Acid-Base Balance


Kathry; n Ann Caudell, Kathryn J. Gaspard



12 Alterations in Hemostasis
and Blood Coagulation


Kathryn J. Gaspard

Mechanisms of Hemostasis
Hypercoagulability States
Bleeding Disorders




13 Alterations in Red Blood Cells


21 Alterations in Respiratory Function:

Kathryn J. Gaspard

Disorders of Gas Exchange

The Red Blood Cell
Age-Related Changes in Red Blood Cells

Disorders of Lung Inflation
Obstructive Airway Disorders
Interstitial Lung Diseases
Pulmonary Vascular Disorders
Respiratory Failure




Alterations in the Cardiovascular System


Alterations in the Urinary System

14 Structure and Function of
the Cardiovascular System


Organization of the Circulatory System
Principles of Blood Flow
The Heart as a Pump
Blood Vessels and the Peripheral Circulation
Neural Control of Circulatory Function

Kidney Structure and Function
Tests of Renal Function



Congenital and Hereditary Disorders of the Kidney
Obstructive Disorders
Urinary Tract Infections
Disorders of Glomerular Function
Tubulointerstitial Disorders

24 Renal Failure

16 Alterations in Blood Pressure
Control of Blood Pressure
Orthostatic Hypotension



23 Alterations in Renal Function

15 Alterations in Blood Flow
Disorders of the Arterial Circulation
Disorders of the Venous Circulation
Disorders of Blood Flow Caused by
Extravascular Forces

22 Control of Kidney Function



Acute Renal Failure
Chronic Renal Failure
Renal Failure in Children and Elderly Persons




17 Alterations in Cardiac Function
Disorders of the Pericardium
Coronary Heart Disease
Myocardial and Endocardial Disease
Valvular Heart Disease
Heart Disease in Infants and Children


25 Alterations in Urine Elimination


Control of Urine Elimination
Alterations in Bladder Function
Cancer of the Bladder



18 Heart Failure and Circulatory Shock


Alterations in the
Gastrointestinal System

Candace Hennessy, Carol M. Porth

Heart Failure
Circulatory Failure (Shock)
Heart Failure in Children and the Elderly

26 Structure and Function of
the Gastrointestinal System



Alterations in the Respiratory System

19 Structure and Function of
the Respiratory System


Structural Organization of the Respiratory System
Exchange of Gases Between the Atmosphere
and the Lungs
Exchange and Transport of Gases
Control of Breathing


Respiratory Tract Infections
Cancer of the Lung
Respiratory Disorders in Infants and Children


27 Alterations in Gastrointestinal
Disorders of the Esophagus
Disorders of the Stomach
Disorders of the Small and Large Intestines

20 Alterations in Respiratory Function:
Infectious Disorders and Neoplasia


Structure and Organization of
the Gastrointestinal Tract
Innervation and Motility
Hormonal and Secretory Function
Digestion and Absorption
Anorexia, Nausea, and Vomiting




28 Alterations in Hepatobiliary

35 Sexually Transmitted Diseases




29 Alterations in Body Nutrition


Joan Pleuss

Regulation of Food Intake and Energy Metabolism
Overnutrition and Obesity


36 Organization and Control of
the Nervous System


Nervous Tissue Cells
Nerve Cell Communication
Development and Organization of
the Nervous System
The Spinal Cord and Brain
The Autonomic Nervous System

Alterations in the Endocrine System

30 Organization and Control of
the Endocrine System

Alterations in the Nervous System

Edward W. Carroll, Robin L. Curtis



Glenn Matfin, Safak Guven, Julie A. Kuenzi

37 Alterations in Brain Function


Diane Book


31 Alterations in Pituitary, Thyroid,
Parathyroid, and Adrenal Function


Glenn Matfin, Safak Guven, Julie A. Kuenzi

General Aspects of Altered Endocrine Function
Pituitary and Growth Hormone Disorders
Thyroid Disorders
Parathyroid Hormone Disorders
Disorders of Adrenal Cortical Function

32 Diabetes Mellitus

Brain Injury
Cerebrovascular Disease
Infections and Neoplasms
Seizure Disorders

38 Alterations in Neuromuscular


Carol M. Porth, Robin L. Curtis


Safak Guven, Julie A. Kuenzi, Glenn Matfin

Energy Metabolism
Diabetes Mellitus

The Organization and Control of Motor Function
Skeletal Muscle and Peripheral Nerve Disorders
Basal Ganglia and Cerebellum Disorders
Upper and Lower Motoneuron Disorders
Spinal Cord Injury

39 Pain


33 Alterations in the Male
Reproductive System


Elizabeth C. Devine

Alterations in the Male and Female
Reproductive Systems


Physiologic Basis of Male Reproductive Function
Disorders of the Penis, the Scrotum and Testes,
and the Prostate
Disorders in Childhood and Aging Changes

34 Alterations in the Female

Organization and Control of
Somatosensory Function
Alterations in Pain Sensitivity and Special Types
of Pain
Pain in Children and Older Adults

40 Alterations in Special Sensory


Edward W. Carroll, Susan A. Fontana

Reproductive System


Patricia McCowen Mehring

Structure and Function of the Female
Reproductive System
Disorders of the Female Reproductive Organs
Menstrual Disorders
Disorders of the Breast


Patricia McCowen Mehring

Infections of the External Genitalia
Vaginal Infections
Vaginal-Urogenital-Systemic Infections

The Liver and Hepatobiliary System
Disorders of the Liver
Disorders of the Gallbladder and Extrahepatic
Bile Ducts
Disorders of the Exocrine Pancreas

The Endocrine System



The Eye and Disorders of Vision
The Ear and Disorders of Auditory Function
The Vestibular System and Maintenance
of Equilibrium




44 Alterations in Skin Function


and Integrity

Alterations in the Skeletal
and Integumentary Systems

41 Structure and Function of
the Skeletal System
Characteristics of Skeletal Tissue
Skeletal Structures


Gladys Simandl


Structure of the Skin
Manifestations of Skin Disorders
Skin Damage Caused by Ultraviolet Radiation
Primary Disorders of the Skin
Nevi and Skin Cancers
Age-Related Skin Manifestations


42 Alterations in the Skeletal System:

Trauma, Infection, and
Developmental Disorders


Kathleen E. Gunta

Injury and Trauma of Musculoskeletal Structures
Bone Infections
Disorders of Skeletal Growth and Development
in Children


Metabolic and Rheumatoid


Debra Bancroft Rizzo, Kathleen E. Gunta

Metabolic Bone Disease
Rheumatic Disorders
Rheumatic Diseases in Children and the Elderly


Lab Values






43 Alterations in the Skeletal System:





of Disease


Cell Structure and Function
Functional Components of the Cell
The Nucleus
The Cytoplasm and Its Organelles
Endoplasmic Reticulum
Golgi Complex
Lysosomes and Peroxisomes

The Cytoskeleton

The Cell Membrane
Cell Metabolism and Energy Sources
Anaerobic Metabolism
Aerobic Metabolism
Cell Membrane Transport, Signal Transduction,
and Generation of Membrane Potentials
Movement Across the Cell Membrane
Passive Movement
Active Transport and Cotransport
Endocytosis and Exocytosis
Ion Channels

Signal Transduction and Cell Communication
Cell Membrane Receptors
Messenger-Mediated Control of Nuclear Function

Membrane Potentials
Electrical Potentials
Action Potentials

Body Tissues
Cell Differentiation
Embryonic Origin of Tissue Types
Epithelial Tissue
Simple Epithelium
Stratified and Pseudostratified Epithelium
Glandular Epithelium

Connective or Supportive Tissues
Loose Connective Tissue
Dense Connective Tissue

Muscle Tissue
Skeletal Muscle
Smooth Muscle

Cell Junctions and Cell-to-Cell Adhesion

he cell is the smallest functional unit that an organism
can be divided into and retain the characteristics necessary for life. Cells with similar embryonic origin or function are often organized into larger functional units called tissues. These tissues in turn combine to form the various body
structures and organs. Although the cells of different tissues




Unit One: Mechanisms of Disease

and organs vary in structure and function, certain characteristics are common to all cells. Cells are remarkably similar in
their ability to exchange materials with their immediate environment, obtaining energy from organic nutrients, synthesizing complex molecules, and replicating themselves. Because
most disease processes are initiated at the cellular level, an understanding of cell function is crucial to understanding the disease process. Some diseases affect the cells of a single organ,
others affect the cells of a particular tissue type, and still others
affect the cells of the entire organism.

Although diverse in their organization, all eukaryotic cells
(cells with a true nucleus) have in common structures that perform unique functions. When seen under a light microscope,
three major components of the eukaryotic cell become evident:
the nucleus, the cytoplasm, and the cell membrane (Fig. 1-1).
The internal matrix of the cell is called protoplasm. Protoplasm is composed of water, proteins, lipids, carbohydrates,
and electrolytes. Water makes up 70% to 85% of the cell’s
protoplasm. The second most abundant constituents (10% to
20%) of protoplasm are the cell proteins, which form cell structures and the enzymes necessary for cellular reactions. Proteins
can also be found complexed to other compounds as nucleo-

proteins, glycoproteins, and lipoproteins. Lipids comprise
2% to 3% of most cells. The most important lipids are the
phospholipids and cholesterol, which are mainly insoluble in
water; they combine with proteins to form the cell membrane
and the membranous barriers that separate different cell compartments. Some cells also contain large quantities of triglycerides. In the fat cells, triglycerides can constitute up to 95% of
the total cell mass. The fat stored in these cells represents stored
energy, which can be mobilized and used wherever it is needed
in the body. Few carbohydrates are found in the cell, and these
are used primarily for fuel. Potassium, magnesium, phosphate,
sulfate, and bicarbonate ions are the major intracellular electrolytes. Small quantities of sodium, chloride, and calcium
ions are also present in the cell. These electrolytes facilitate the
generation and transmission of electrochemical impulses in
nerve and muscle cells. Intracellular electrolytes participate in
reactions that are necessary for cellular metabolism.

The Nucleus
The nucleus of the cell appears as a rounded or elongated structure situated near the center of the cell (see Fig. 1-1). It is enclosed in a nuclear membrane and contains chromatin and a
distinct region called the nucleolus. All eukaryotic cells have at
least one nucleus (prokaryotic cells, such as bacteria, lack a nucleus and nuclear membrane). The nucleus is the control center for the cell. It contains deoxyribonucleic acid (DNA) that is



Nuclear envelope
surrounding nucleus





■ FIGURE 1-1 ■

endoplasmic reticulum

Composite cell
designed to show in one cell all of
the various components of the
nucleus and cytoplasm.

Chapter 1: Cell Structure and Function

■ Cells are the smallest functional unit of the body.

They contain structures that are strikingly similar to
those needed to maintain total body function.
■ The nucleus is the control center for the cell. It also

contains most of the hereditary material.
■ The organelles, which are analogous to the organs

of the body, are contained in the cytoplasm. They
include the mitochondria, which supply the energy
needs of the cell; the ribosomes, which synthesize
proteins and other materials needed for cell function; and the lysosomes, which function as the cell’s
digestive system.
■ The cell membrane encloses the cell and provides for

intracellular and intercellular communication, transport of materials into and out of the cell, and maintenance of the electrical activities that power cell

essential to the cell because its genes contain the information
necessary for the synthesis of proteins that the cell must produce to stay alive. These proteins include structural proteins
and enzymes used to synthesize other substances, including
carbohydrates and lipids. The genes also represent the individual units of inheritance that transmit information from one generation to another. The nucleus is also the site of ribonucleic
acid (RNA) synthesis. There are three types of RNA: messenger
RNA (mRNA), which copies and carries the DNA instructions
for protein synthesis to the cytoplasm; ribosomal RNA (rRNA),
which moves to the cytoplasm, and becomes the site of protein
synthesis; and transfer RNA (tRNA), which also moves into the
cytoplasm, where it transports amino acids to the elongating
protein as it is being synthesized (see Chapter 3).
The complex structure of DNA and DNA-associated proteins
dispersed in the nuclear matrix is called chromatin. Each DNA
molecule is made up of two extremely long, double-stranded
helical chains containing variable sequences of four nitrogenous bases. These bases form the genetic code. In cells that are
about to divide, the DNA must be replicated before mitosis, or
cell division, occurs. During replication, complementary pairs
of DNA are generated such that each daughter cell receives an
identical set of genes.
The nucleus also contains the darkly stained round body
called the nucleolus. The rRNA is transcribed exclusively in the
nucleolus. Nucleoli are structures composed of regions from
five different chromosomes, each with a part of the genetic
code needed for the synthesis of rRNA. Cells that are actively
synthesizing proteins can be recognized because their nucleoli are large and prominent and the nucleus as a whole is
Surrounding the nucleus is a doubled-layered membrane
called the nuclear envelope or nuclear membrane. The nuclear


membrane contains many structurally complex circular pores
where the two membranes fuse to form a gap. Many classes of
molecules, including fluids, electrolytes, RNA, some proteins,
and perhaps some hormones, can move in both directions
through the nuclear pores.

The Cytoplasm and Its Organelles
The cytoplasm surrounds the nucleus, and it is in the cytoplasm that the work of the cell takes place. Cytoplasm is essentially a colloidal solution that contains water, electrolytes,
suspended proteins, neutral fats, and glycogen molecules.
Although they do not contribute to the cell’s function, pigments may also accumulate in the cytoplasm. Some pigments,
such as melanin, which gives skin its color, are normal constituents of the cell.
Embedded in the cytoplasm are various organelles, which
function as the organs of the cell. These organelles include the
ribosomes, endoplasmic reticulum, Golgi complex, lysosomes
and peroxisomes, and mitochondria.

The ribosomes serve as sites of protein synthesis in the cell.
They are small particles of nucleoproteins (rRNA and proteins) that can be found attached to the wall of the endoplasmic reticulum or as free ribosomes (Fig. 1-2). Free ribosomes
are scattered singly in the cytoplasm or joined by strands of
mRNA to form functional units called polyribosomes. Free ribosomes are involved in the synthesis of proteins, mainly as
intracellular enzymes.
Endoplasmic Reticulum
The endoplasmic reticulum (ER) is an extensive system of
paired membranes and flat vesicles that connects various parts
of the inner cell (see Fig. 1-2). The fluid-filled space, called the

Rough ER


Tubular elements
of the ER
Vesicular elements
of the ER
■ FIGURE 1-2 ■ Three-dimensional view of the rough endoplasmic reticulum (ER) with its attached ribosomal RNA and the
smooth endoplasmic reticulum.


Unit One: Mechanisms of Disease

matrix, between the paired ER membrane layers is connected
with the space between the two membranes of the doublelayered nuclear membrane, the cell membrane, and various
cytoplasmic organelles. It functions as a tubular communication system through which substances can be transported
from one part of the cell to another. A large surface area and
multiple enzyme systems attached to the ER membranes also
provide the machinery for a major share of the metabolic
functions of the cell.
Two forms of ER exist in cells: rough and smooth. Rough ER
is studded with ribosomes attached to specific binding sites on
the membrane. The ribosomes, with the accompanying strand
of mRNA, synthesize proteins. Proteins produced by the rough
ER are usually destined for incorporation into cell membranes
and lysosomal enzymes or for exportation from the cell. The
rough ER segregates these proteins from other components of
the cytoplasm and modifies their structure for a specific function. For example, the production of plasma protein by liver
cells take place in the rough ER. All cells require a rough ER for
the synthesis of lysosomal enzymes.
The smooth ER is free of ribosomes and is continuous with
the rough ER. It does not participate in protein synthesis; instead, its enzymes are involved in the synthesis of lipid molecules, regulation of intracellular calcium, and metabolism and
detoxification of certain hormones and drugs. It is the site of
lipid, lipoprotein, and steroid hormone synthesis. The sarcoplasmic reticulum of skeletal and cardiac muscle cells is a
form of smooth ER. Calcium ions needed for muscle contraction are stored and released from cisternae of the sarcoplasmic
reticulum. Smooth ER of the liver is involved in glycogen storage and metabolism of lipid-soluble drugs.

Golgi Complex
The Golgi apparatus, sometimes called the Golgi complex, consists of stacks of thin, flattened vesicles or sacs. These Golgi
bodies are found near the nucleus and function in association
with the ER. Substances produced in the ER are carried to the
Golgi complex in small, membrane-covered transfer vesicles.
Many cells synthesize proteins that are larger than the active
product. Insulin, for example, is synthesized as a large, inactive
proinsulin molecule that is cut apart to produce a smaller, active insulin molecule within the Golgi complex of the beta cells
of the pancreas. The Golgi complex modifies these substances
and packages them into secretory granules or vesicles. Enzymes
destined for export from the cell are packaged in secretory vesicles. After appropriate signals, the secretory vesicles move out
of the Golgi complex into the cytoplasm and fuse to the inner
side of the plasma membrane, where they release their contents
into the extracellular fluid. Figure 1-3 is a diagram of the synthesis and movement of a hormone through the rough ER and
Golgi complex. In addition to its function in producing secretory granules, the Golgi complex is thought to produce large
carbohydrate molecules that combine with proteins produced
by the rough ER to form glycoproteins.
Lysosomes and Peroxisomes
The lysosomes can be viewed as the digestive system of the cell.
They consist of small, membrane-enclosed sacs containing hydrolytic enzymes capable of breaking down worn-out cell parts
so they can be recycled. They also break down foreign substances such as bacteria taken into the cell. All of the lysosomal

reticulum (ER)



■ FIGURE 1-3 ■ Hormone synthesis and secretion. In hormone secretion, the hormone is synthesized by the ribosomes attached to
the rough endoplasmic reticulum. It moves from the rough ER to
the Golgi complex, where it is stored in the form of secretory granules. These leave the Golgi complex and are stored within the cytoplasm until released from the cell in response to an appropriate

enzymes are acid hydrolases, which means that they require an
acid environment. The lysosomes provide this environment by
maintaining a pH of approximately 5 in their interior. The pH
of the cytoplasm is approximately 7.2, which protects other cellular structures from this acidity.
Lysosomal enzymes are synthesized in the rough ER and
then transported to the Golgi apparatus, where they are biochemically modified and packaged as lysosomes. Unlike those
of other organelles, the sizes and functions of lysosomes vary
considerably from one cell to another. The type of enzyme
packaged in the lysosome by the Golgi complex determines
this diversity. Although enzymes in the secondary lysosomes
can break down most proteins, carbohydrates, and lipids to
their basic constituents, some materials remain undigested.
These undigested materials may remain in the cytoplasm as
residual bodies or be extruded from the cell. In some long-lived
cells, such as neurons and heart muscle cells, large quantities of
residual bodies accumulate as lipofuscin granules or age pigment. Other indigestible pigments, such as inhaled carbon particles and tattoo pigments, also accumulate and may persist in
residual bodies for decades.
Lysosomes play an important role in the normal metabolism of certain substances in the body. In some inherited diseases known as lysosomal storage diseases, a specific lysosomal
enzyme is absent or inactive, in which case the digestion of certain cellular substances does not occur. As a result, these substances accumulate in the cell. In Tay-Sachs disease, an autosomal recessive disorder, the lysosomal enzyme needed for
degrading the GM2 ganglioside found in nerve cell membranes
is deficient (see Chapter 4). Although GM2 ganglioside accumulates in many tissues, such as the heart, liver, and spleen,
its accumulation in the nervous system and retina of the eye
causes the most damage.
Smaller than lysosomes, spherical membrane-bound organelles called peroxisomes contain a special enzyme that degrades peroxides (e.g., hydrogen peroxide). Peroxisomes function in the control of free radicals (see Chapter 2). Unless
degraded, these highly unstable chemical compounds would
otherwise damage other cytoplasmic molecules. For example,
catalase degrades toxic hydrogen peroxide molecules to water.

Chapter 1: Cell Structure and Function

Peroxisomes also contain the enzymes needed for breaking
down very–long-chain fatty acids, which are ineffectively degraded by mitochondrial enzymes. In liver cells, peroxisomal
enzymes are involved in the formation of the bile acids.

The mitochondria are literally the “power plants” of the cell because they transform organic compounds into energy that is
easily accessible to the cell. Energy is not made here but is extracted from organic compounds. Mitochondria contain the
enzymes needed for capturing most of the energy in foodstuffs
and converting it into cellular energy. This multistep process requires oxygen and is often referred to as aerobic metabolism.
Much of this energy is stored in the high-energy phosphate
bonds of compounds such as adenosine triphosphate (ATP),
which powers the various cellular activities.
Mitochondria are found close to the site of energy consumption in the cell (e.g., near the myofibrils in muscle cells).
The number of mitochondria in a given cell type is largely determined by the type of activity the cell performs and how
much energy is needed to undertake this activity. For example,
large increases in mitochondria have been observed in skeletal
muscle that has been repeatedly stimulated to contract.
The mitochondria are composed of two membranes: an
outer membrane that encloses the periphery of the mitochondrion and an inner membrane that forms shelflike projections,
called cristae (Fig. 1-4). The outer and inner membranes form
two spaces: an outer intramembranous space and an inner matrix that is filled with a gel-like material. The outer membrane
is involved in lipid synthesis and fatty acid metabolism. The
inner membrane contains the respiratory chain enzymes and
transport proteins needed for the synthesis of ATP.
Mitochondria contain their own DNA and ribosomes and
are self-replicating. The DNA is found in the mitochondrial
matrix and is distinct from the chromosomal DNA found in the
nucleus. Mitochondrial DNA, known as the “other human
genome,” is a double-stranded, circular molecule that encodes
the rRNA and tRNA required for intramitochrondial synthesis
of proteins needed for the energy-generating function of the


mitochondria. Although mitochondrial DNA directs the synthesis of 13 of the proteins required for mitochondrial function, the DNA of the nucleus encodes the structural proteins
of the mitochondria and other proteins needed to carry out cellular respiration.
Mitochondrial DNA is inherited matrilineally (i.e., from the
mother) and provides a basis for familial lineage studies.
Mutations have been found in each of the mitochondrial
genes, and an understanding of the role of mitochondrial DNA
in certain diseases is beginning to emerge. Most tissues in the
body depend to some extent on oxidative metabolism and can
therefore be affected by mitochondrial DNA mutations.

The Cytoskeleton
In addition to its organelles, the cytoplasm contains a network
of microtubules, microfilaments, intermediate filaments, and
thick filaments (Fig. 1-5). Because they control cell shape
and movement, these structures are a major component of the
structural elements called the cytoskeleton.

The microtubules are slender tubular structures composed
of globular proteins called tubulin. Microtubules function in
many ways, including the development and maintenance of

Cell membrane


Outer limiting


Inner limiting
■ FIGURE 1-4 ■

Mitochondrion. The inner membrane forms
transverse folds called cristae, where the enzymes needed for the
final step in adenosine triphosphate (ATP) production (i.e., oxidative phosphorylation) are located.


■ FIGURE 1-5 ■

Microtubes and microfilaments of the cell. The
microfilaments associate with the inner surface of the cell and aid
in cell motility. The microtubules form the cytoskeleton and maintain the position of the organelles.


Unit One: Mechanisms of Disease

cell form; participation in intracellular transport mechanisms,
including axoplasmic transport in neurons; and formation of
the basic structure for several complex cytoplasmic organelles,
including the cilia, flagella, centrioles, and basal bodies. Abnormalities of the cytoskeleton may contribute to alterations
in cell mobility and function. For example, proper functioning of the microtubules is essential for various stages of leukocyte migration.
Cilia and Flagella. Cilia and flagella are hairlike processes extending from the cell membrane that are capable of sweeping
and flailing movements, which can move surrounding fluids or
move the cell through fluid media. Cilia are found on the apical
or luminal surface of epithelial linings of various body cavities
or passages, such as the upper respiratory system. Removal of
mucus from the respiratory passages is highly dependent on
the proper functioning of the cilia. Flagella form the tail-like
structures that provide motility for sperm.
Centrioles and Basal Bodies. Centrioles and basal bodies are
structurally identical organelles composed of an array of highly
organized microtubules. The centrioles are small, barrelshaped bodies oriented at right angles to each other. In dividing cells, the two cylindrical centrioles form the mitotic
spindle that aids in the separation and movement of the chromosomes. Basal bodies are more numerous than centrioles and
are found near the cell membrane in association with cilia and

Microfilaments are thin, threadlike cytoplasmic structures.
Three classes of microfilaments exist: (1) thin microfilaments,
which are equivalent to the thin actin filaments in muscle;
(2) the thick myosin filaments, which are present in muscle
cells but may also exist temporarily in other cells; and (3) the
intermediate filaments, which are a heterogeneous group of filaments with diameter sizes between the thick and thin filaments. Muscle contraction depends on the interaction between
the thin actin filaments and thick myosin filaments.

Microfilaments are present in the superficial zone of the cytoplasm in most cells. Contractile activities involving the microfilaments and associated thick myosin filaments contribute to
associated movement of the cytoplasm and cell membrane
during endocytosis and exocytosis. Microfilaments are also present in the microvilli of the intestine. The intermediate filaments function in supporting and maintaining the asymmetric
shape of cells. Examples of intermediate filaments are the keratin filaments that are found anchored to the cell membrane of
epidermal keratinocytes of the skin and the glial filaments that
are found in astrocytes and other glial cells of the nervous system. The neurofibrillary tangle found in the brain in Alzheimer’s
disease contains microtubule-associated proteins and neurofilaments, evidence of a disrupted neuronal cytoskeleton.

The Cell Membrane
The cell is enclosed in a thin membrane that separates the intracellular contents from the extracellular environment. To differentiate it from the other cell membranes, such as the mitochondrial or nuclear membranes, the cell membrane is often
called the plasma membrane. In many respects, the plasma
membrane is one of the most important parts of the cell. It acts
as a semipermeable structure that separates the intracellular
and extracellular environments. It provides receptors for hormones and other biologically active substances, participates in
the electrical events that occur in nerve and muscle cells, and
aids in the regulation of cell growth and proliferation.
The cell membrane consists of an organized arrangement of
lipids (phospholipids, glycolipids, and cholesterol), carbohydrates, and proteins (Fig. 1-6). The lipids form a bilayer structure that is essentially impermeable to all but lipid-soluble substances. About 75% of the lipids are phospholipids, each with
a hydrophilic (water-soluble) head and hydrophobic (waterinsoluble) tails. The phospholipid molecules along with the
glycolipids are aligned such that their hydrophobic heads face
outward on each side of the membrane and their hydrophobic
tails project toward the center of the membrane. The hydrophilic heads retain water and help cells adhere to each other. At




Polar head
Fatty acid


Polar head


Channel protein
Filaments of

■ FIGURE 1-6 ■ The structure of the cell
membrane showing the hydrophilic (polar)
heads and the hydrophobic (fatty acid) tails
and the position of the integral and peripheral proteins in relation to the interior and
exterior of the cell.

Chapter 1: Cell Structure and Function

normal body temperature, the viscosity of the lipid component
of the membrane is equivalent to that of olive oil. The presence
of cholesterol stiffens the membrane.
Although the basic structure of the cell membrane is provided by the lipid bilayer, most of the specific functions are carried out by proteins. Some proteins, called transmembrane proteins, pass directly through the membrane and communicate
with the intracellular and extracellular environments. Many of
the transmembrane proteins are tightly bound to lipids in the
bilayer and are essentially part of the membrane. These transmembrane proteins are called integral proteins. The peripheral
proteins, a second type of protein, are bound to one or the other
side of the membrane and do not pass into the lipid bilayer.
Thus, the peripheral proteins are associated with functions involving the inner and outer side of the membrane where they
are located. In contrast, the transmembrane proteins can function on both sides of the membrane or transport molecules
across it. Many of the integral transmembrane proteins form
the ion channels found on the cell surface. These channel proteins have complex structures and are selective with respect to
the ions that pass through their channels.
The membrane carbohydrates are incorporated in a fuzzylooking layer, called the cell coat or glycocalyx, which surrounds
the cell surface. The glycocalyx, which is part of the cell membrane, consists of long, complex carbohydrate chains that are
attached to proteins and lipids in the form of glycoproteins and
glycolipids. The cell coat participates in cell-to-cell recognition
and adhesion. It contains tissue transplant antigens that label
cells as self or nonself. ABO blood group antigens are contained in the cell coat of red blood cells.

In summary, the cell is a remarkably autonomous structure that functions in a manner strikingly similar to that of the
total organism. The nucleus controls cell function and is the
mastermind of the cell. It contains DNA, which provides the
information necessary for the synthesis of the various proteins
that the cell must produce to stay alive and to transmit information from one generation to another.
The cytoplasm contains the cell’s organelles. Ribosomes
serve as sites for protein synthesis in the cell. The ER functions
as a tubular communication system through which substances can be transported from one part of the cell to another
and as the site of protein (rough ER), carbohydrate, and lipid
(smooth ER) synthesis. Golgi bodies modify materials synthesized in the ER and package them into secretory granules for
transport within the cell or for export from the cell. Lysosomes, which can be viewed as the digestive system of the
cell, contain hydrolytic enzymes that digest worn-out cell
parts and foreign materials. The mitochondria serve as power
plants for the cell because they transform food energy into
ATP, which is used to power cell activities. Mitochondria contain their own extrachromosomal DNA, which is used in the
synthesis of mitochondrial RNAs and proteins used in oxidative metabolism. Microtubules are slender, stiff tubular structures that influence cell shape, provide a means of moving organelles through the cytoplasm, and effect movement of the
cilia and of chromosomes during cell division. Several types of
threadlike filaments, including actin and myosin filaments,
participate in muscle contraction.


The plasma membrane is a lipid bilayer that surrounds the
cell and separates it from its surrounding external environment. It contains receptors for hormones and other biologically active substances, participates in the electrical events
that occur in nerve and muscle cells, and aids in the regulation of cell growth and proliferation. The cell surface is surrounded by a fuzzy-looking layer called the cell coat or glycocalyx. The cell coat participates in cell-to-cell recognition and
adhesion, and it contains tissue transplant antigens.

Energy metabolism refers to the processes by which fats, proteins,
and carbohydrates from the foods we eat are converted into energy or complex energy sources in the cell. Catabolism and anabolism are the two phases of metabolism. Catabolism consists
of breaking down stored nutrients and body tissues to produce
energy. Anabolism is a constructive process in which more complex molecules are formed from simpler ones.
The special carrier for cellular energy is ATP. ATP molecules consist of adenosine, a nitrogenous base; ribose, a fivecarbon sugar; and three phosphate groups (see Fig. 1-7). The
last two phosphate groups are attached to the remainder of
the molecule by two high-energy bonds, which are indicated
by the symbol ∼. Each bond releases a large amount of energy
when hydrolyzed. ATP is hydrolyzed to form adenosine
diphosphate (ADP) with the loss of one high-energy bond
and to adenosine monophosphate (AMP) with the loss of two
such bonds. The energy liberated from the hydrolysis of ATP
is used to drive reactions that require free energy, such as muscle contraction and active transport mechanisms. Energy from
foodstuffs is used to convert ADP back to ATP. ATP is often
called the energy currency of the cell; energy can be “saved” or
“spent” using ATP as an exchange currency.
Two types of energy production are present in the cell: the
anaerobic (i.e., without oxygen) glycolytic pathway, occurring
in the cytoplasm, and the aerobic (i.e., with oxygen) pathways
occurring in the mitochondria. The glycolytic pathway serves
as the prelude to the aerobic pathways.

High-energy bonds


















■ FIGURE 1-7 ■


Structure of the adenosine triphosphate (ATP)


Unit One: Mechanisms of Disease

Anaerobic Metabolism
Glycolysis is anaerobic process by which energy is liberated
from glucose (Fig. 1-8). It is an important source of energy for
cells that lack mitochondria. This process provides energy in
situations when delivery of oxygen to the cell is delayed or
impaired. Glycolysis involves a sequence of reactions that
converts glucose to pyruvate, with the concomitant production of ATP from ADP. The net gain of energy from the glycolysis of one molecule of glucose is two ATP molecules.
Although relatively inefficient as to energy yield, the glycolytic
pathway is important during periods of decreased oxygen delivery, such as occurs in skeletal muscle during the first few
minutes of exercise.
Glycolysis requires the presence of nicotinamide-adenine
dinucleotide (NAD+), a hydrogen carrier. The end-products of
glycolysis are pyruvate and NADH. When oxygen is present,
pyruvate moves into the aerobic mitochondrial pathway, and

glucose-6- P



fructose-6- P

fructose-1, 6-di P

2(3 carbon compounds P )
2 NAD + 2 P
2(3 carbon compounds di P ) + 2 NADH 2
2(3 carbon compounds P ) + 2 ATP
Intermediate compounds
2 pyruvate + 2 ATP
2 NADH 2
Pyruvic acid
CO 2
Acetyl CoA

Citric acid

Oxaloacetic acid
Malic acid
Fumaric acid
Succinic acid
ATP + CO 2

■ FIGURE 1-8 ■



• Aconitic acid

NADH subsequently enters into oxidative chemical reactions
that remove the hydrogen atoms. The transfer of hydrogen
from NADH during the oxidative reactions allows the glycolytic process to continue by facilitating the regeneration of
NAD+. Under anaerobic conditions, such as cardiac arrest or
circulatory shock, pyruvate is converted to lactic acid, which
diffuses out of the cells into the extracellular fluid. Conversion
of pyruvate to lactic acid is reversible, and after the oxygen supply has been restored, lactic acid is reconverted back to pyruvate and used directly for energy or to synthesize glucose.

Aerobic Metabolism
Aerobic metabolism, which supplies 90% of the body’s energy
needs, occurs in the cell’s mitochondria and requires oxygen. It
is here that hydrogen and carbon molecules from dietary fats,
proteins, and carbohydrates are broken down and combined
with molecular oxygen to form carbon dioxide, and water as
energy is released. Unlike lactic acid, which is an end-product
of anaerobic metabolism, carbon dioxide and water are relatively harmless and easily eliminated from the body. In a
24-hour period, oxidative metabolism produces 300 to 500 mL
of water.
Aerobic metabolism uses the citric acid cycle, sometimes
called the tricarboxylic acid or Krebs cycle, as the final common
pathway for the metabolism of nutrients (see Fig. 1-8). In the
citric acid cycle, each of the two pyruvate molecules formed in
the cytoplasm from the glycolysis of one molecule of glucose
yields another molecule of ATP along with two molecules of
carbon dioxide and eight hydrogen ions. In addition to pyruvate from the glycolysis of glucose, products from amino acid
and fatty acid breakdown enter the citric acid cycle.
In the initial stage of the citric acid cycle, acetyl coenzyme A
(acetyl-CoA) combines with oxaloacetic acid to form citric acid.
The coenzyme A portion of acetyl-CoA can be used again and
again to generate more acetyl-CoA from pyruvate, while the
acetyl portion becomes part of the citric acid cycle and moves
through a series of enzyme-mediated steps that produce carbon
dioxide and hydrogen atoms. The carbon dioxide is carried to
the lungs and exhaled. The hydrogen atoms are transferred to
the electron transport system on the inner mitochondrial membrane for oxidation. Oxidation of hydrogen is accomplished
through a series of enzyme-mediated steps that change the hydrogen atoms to hydrogen ions and electrons. The electrons are
used to reduce elemental oxygen, which combines with the hydrogen ions to form water. During this sequence of oxidative
reactions, large amounts of energy are released and used to convert ADP to ATP. Because the formation of ATP involves the addition of a high-energy phosphate bond to ADP, the process is
called oxidative phosphorylation. Cyanide poisoning kills by
binding to the enzymes needed for a final step in the oxidative
phosphorylation sequence.

Isocitric acid
Oxalosuccinic acid



Glycolytic pathway and citric acid cycle.

In summary, metabolism is the process whereby the carbohydrates, fats, and proteins we eat are broken down and
subsequently converted into the energy needed for cell function. Energy is stored in the high-energy phosphate bonds of
ATP, which serves as the energy currency for the cell. Two
sites of energy conversion are present in cells: the glycolytic or
anaerobic pathway in the cell’s cytoplasmic matrix and the

Chapter 1: Cell Structure and Function
aerobic or citric acid cycle in the mitochondria. The most efficient of these pathways is the citric acid pathway. This pathway, which requires oxygen, produces carbon dioxide and
water as end-products and results in the release of large
amounts of energy that is used to convert ADP to ATP. The
glycolytic pathway, which is located in the cytoplasm, involves the breakdown of glucose to form ATP. This pathway
can function without oxygen by producing lactic acid.


A. Diffusion

B. Osmosis



Movement Across the Cell Membrane
The unique properties of the cell’s membrane are responsible
for differences in the composition of the intracellular and extracellular fluids. However, a constant movement of molecules and ions across the cell membrane is required to maintain the functions of the cell. Movement through the cell
membrane occurs in essentially two ways: passively, without
an expenditure of energy, or actively, using energy-consuming
processes. The cell membrane can also engulf substances,
forming a membrane-coated vesicle; this membrane-coated
vesicle is moved into the cell by endocytosis or out of the cell
by exocytosis.

Passive Movement
The passive movement of particles or ions across the cell membrane is directly influenced by chemical or electrical gradients
and does not require an expenditure of energy. A difference in
the number of particles on either side of the membrane creates
a chemical gradient, and a difference in charged particle or ions
creates an electrical gradient. Chemical and electrical gradients
are often linked and are called electrochemical gradients.
Diffusion. Diffusion refers to the process by which molecules
and other particles in a solution become widely dispersed and
reach a uniform concentration because of energy created by
their spontaneous kinetic movements (Fig. 1-9). In the process
of reaching a uniform concentration, these molecules and particles move from an area of higher to an area of lower concentration. With ions, diffusion is affected by energy supplied by
their electrical charge. Lipid-soluble molecules, such as oxygen,
carbon dioxide, alcohol, and fatty acids, become dissolved in
the lipid matrix of the cell membrane and diffuse through the
membrane in the same manner that diffusion occurs in water.
Other substances diffuse through minute pores of the cell
membrane. The rate of movement depends on how many particles are available for diffusion and the velocity of the kinetic
movement of the particles. Temperature changes the motion of
the particles; the greater the temperature, the greater is the thermal motion of the molecules.
Osmosis. Most cell membranes are semipermeable in that they
are permeable to water but not all solute particles. Water moves
through a semipermeable membrane along a concentration
gradient, moving from an area of higher to one of lower con-

C. Facilitated Diffusion

D. Active Transport


= Na

E. Pinocytosis

■ FIGURE 1-9 ■ Mechanisms of membrane transport. (A) Diffusion, in which particles move to become equally distributed
across the membrane. (B) The osmotically active particles regulate
the flow of water. (C) Facilitated diffusion uses a carrier system.
(D) In active transport, selected molecules are transported across
the membrane using the energy-driven (ATP) pump. (E) The
membrane forms a vesicle that engulfs the particle and transports it across the membrane, where it is released. This is called

centration (see Fig. 1-9). This process is called osmosis, and the
pressure that water generates as it moves through the membrane is called osmotic pressure.
Osmosis is regulated by the concentration of nondiffusible
particles on either side of a semipermeable membrane. When
there is a difference in the concentration of particles, water


Unit One: Mechanisms of Disease

moves from the side with the lower concentration of particles
and higher concentration of water to the side with the higher
concentration of particles and lower concentration of water.
The movement of water continues until the concentration of
particles on both sides of the membrane is equally diluted or
until the hydrostatic (osmotic) pressure created by the movement of water opposes its flow.
Facilitated Diffusion. Facilitated diffusion occurs through a
transport protein that is not linked to metabolic energy (see
Fig. 1-9). Some substances, such as glucose, cannot pass unassisted through the cell membrane because they are not lipid
soluble or are too large to pass through the membrane’s pores.
These substances combine with special transport proteins at
the membrane’s outer surface, are carried across the membrane
attached to the transporter, and then released. In facilitated diffusion, a substance can move only from an area of higher concentration to one of lower concentration. The rate at which a
substance moves across the membrane because of facilitated
diffusion depends on the difference in concentration between
the two sides of the membrane. Also important are the availability of transport proteins and the rapidity with which they
can bind and release the substance being transported. It is
thought that insulin, which facilitates the movement of glucose
into cells, acts by increasing the availability of glucose transporters in the cell membrane.

Active Transport and Cotransport
The process of diffusion describes particle movement from an
area of higher concentration to one of lower concentration,
resulting in an equal distribution across the cell membrane.
However, sometimes different concentrations of a substance
are needed in the intracellular and extracellular fluids. For example, the intracellular functioning of the cell requires a much
higher concentration of potassium than is present in the extracellular fluid while maintaining a much lower concentration of
sodium than in the extracellular fluid. In these situations, energy is required to pump the ions “uphill” or against their concentration gradient. When cells use energy to move ions against
an electrical or chemical gradient, the process is called active
The active transport system studied in the greatest detail is
the sodium–potassium pump, or Na+/K+ ATPase pump (see
Fig. 1-9). The Na+/K+ ATPase pump moves sodium from inside
the cell to the extracellular region, where its concentration is
approximately 14 times greater than inside; the pump also returns potassium to the inside, where its concentration is approximately 35 times greater than it is outside the cell. If it were
not for the activity of the sodium–potassium pump, the osmotically active sodium particles would accumulate in the cell,
causing cellular swelling because of an accompanying influx of
water (see Chapter 2).
There are two types of active transport: primary active transport and secondary active transport. In primary active transport,
the source of energy (e.g., ATP) is used directly in the transport
of a substance. Secondary active transport mechanisms harness
the energy derived from the primary active transport of one
substance, usually sodium ions, for the cotransport of a second
substance. For example, when sodium ions are actively transported out of a cell by primary active transport, a large concentration gradient develops (i.e., high concentration on the out-

side and low on the inside). This concentration gradient represents a large storehouse of energy because sodium ions are always attempting to diffuse into the cell. Similar to facilitated
diffusion, secondary transport mechanisms use membrane
transport proteins. These proteins have two binding sites: one
for sodium ions and the other for the substance undergoing
secondary transport. Secondary transport systems are classified
into two groups: cotransport, in which the sodium ion and solute are transported in the same direction, and countertransport,
in which sodium ions and the solute are transported in the opposite direction (Fig. 1-10). An example of cotransport occurs
in the intestine, where the absorption of glucose and amino
acids is coupled with sodium transport.

Endocytosis and Exocytosis
Endocytosis is the process by which cells engulf materials from
their surroundings. It includes pinocytosis and phagocytosis.
Pinocytosis involves the ingestion of small solid or fluid particles. The particles are engulfed into small, membranesurrounded vesicles for movement into the cytoplasm. The
process of pinocytosis is important in the transport of proteins and strong solutions of electrolytes (see Fig. 1-9).
Phagocytosis literally means cell eating and can be compared
with pinocytosis, which means cell drinking. Phagocytosis involves the engulfment and subsequent killing or degradation
of microorganisms and other particulate matter. During phagocytosis, a particle contacts the cell surface and is surrounded
on all sides by the cell membrane, forming a phagocytic vesicle or phagosome. Once formed, the phagosome breaks away
from the cell membrane and moves into the cytoplasm, where
it eventually fuses with a lysosome, allowing the ingested material to be degraded by lysosomal enzymes. Certain cells, such

■ FIGURE 1-10 ■ Secondary

active transport systems. (A) carries
the transported solute (S) in the same direction as the Na+ ion.
(B) Counter-transport carries the solute and Na+ in the opposite

Chapter 1: Cell Structure and Function


as macrophages and polymorphonuclear leukocytes (neutrophils), are adept at engulfing and disposing of invading organisms, damaged cells, and unneeded extracellular constituents
(see Chapter 9).
Exocytosis is the mechanism for the secretion of intracellular
substances into the extracellular spaces. It is the reverse of endocytosis in that a secretory granule fuses to the inner side of
the cell membrane, and an opening occurs in the cell membrane. This opening allows the contents of the granule to be
released into the extracellular fluid. Exocytosis is important in
removing cellular debris and releasing substances, such as hormones, synthesized in the cell.
During endocytosis, portions of the cell membrane become
an endocytotic vesicle. During exocytosis, the vesicular membrane is incorporated into the plasma membrane. In this way,
cell membranes can be conserved and reused.

Ion Channels
The electrical charge on small ions such as Na+ and K+ makes it
difficult for these ions to move across the lipid layer of the cell
membrane. However, rapid movement of these ions is required
for many types of cell functions, such as nerve activity. This
is accomplished by facilitated diffusion through selective ion
channels. Ion channels are made up of integral proteins that
span the width of the cell membrane and are normally composed of several polypeptides or protein subunits that form a
gating system. Specific stimuli cause the protein subunits to
undergo conformational changes to form an open channel or
gate through which the ions can move. In this way, ions do not
need to cross the lipid-soluble portion of the membrane but
can remain in the aqueous solution that fills the ion channel.
Ion channels are highly selective; some channels allow only for
passage of sodium ions, and others are selective for potassium,
calcium, or chloride ions.
The plasma membrane contains two basic groups of ion
channels: nongated and gated channels (Fig. 1-11). Nongated
or leakage channels are open even in the unstimulated state,
whereas gated channels open and close in response to specific
stimuli. There are two types of gated channels: voltage-gated
and ligand-gated channels. Voltage-gated channels have electrically operated gates that open when the membrane potential
changes beyond a certain point. Ligand-gated channels have
chemically operated gates that respond to specific receptorbound ligands, such as the neurotransmitter acetylcholine.

Signal Transduction and Cell Communication
Cells in multicellular organisms need to communicate with
one another to coordinate their function and control their
growth. Cells communicate with each other by means of chemical messenger systems. In some tissues, messengers move from
cell to cell through gap junctions without entering the extracellular fluid. In other tissues, cells communicate by chemical
messengers secreted into the extracellular fluid. Many types of
chemical messengers that cannot cross the cell membrane bind
to receptors on or near the cell surface. These chemical messengers are sometimes called first messengers because, by one
means or another, their external signal is converted into internal signals carried by a second chemical called a second messenger. It is the second messenger that triggers the intracellular
changes that produce the desired physiologic effect. Some

■ FIGURE 1-11 ■

Ion channels. (A) Nongated ion channel remains open, permitting free movement of ions across the membrane. (B) Ligand-gated channel is controlled by ligand binding to
the receptor. (C) Voltage-gated channel is controlled by a change
in membrane potential. (Rhoades R.A., Tanner G.A. [1996].
Medical physiology. Boston: Little, Brown)

lipid-soluble chemical messengers move through the membrane and bind to cytoplasmic or nuclear receptors to exert
their physiologic effects.

Cell Membrane Receptors
Neurotransmitters, protein and peptide hormones, and other
chemical messengers do not exert their effects by entering
cells. Instead, they attach to receptors on the cell surface, and
their messages are conveyed across the membrane and converted by cell membrane proteins into signals within the cell,
a process often called signal transduction. Many molecules involved in signal transduction are proteins. A unique property
of proteins that allows them to function in this way is their
ability to change their shape or conformation, thereby changing their function and consequently the functions of the cell.
These conformational changes are often accomplished through


Unit One: Mechanisms of Disease



(First messenger)
Extracellular fluid

■ Cells communicate with each other and with the in-

ternal and external environments by a number of
mechanisms, including electrical and chemical signaling systems that control electrical potentials, the
overall function of a cell, and gene activity needed
for cell division and cell replication.
■ Chemical messengers exert their effects by binding

Cell membrane


G Protein

Amplifier Enzyme


Adenylate cyclase
Guanylate cyclase
Phospholipase C

Intracellular fluid

to cell membrane proteins or receptors that convert
the chemical signal into signals within the cell, in a
process called signal transduction.
■ Cells regulate their responses to chemical messen-

gers by increasing or decreasing the number of
active receptors on their surface.

enzymes called protein kinases that catalyze the phosphorylation of amino acids in the protein structure.
Each cell type in the body contains a distinctive set of receptor proteins that enable it to respond to a complementary
set of signaling molecules in a specific, preprogrammed way.
These receptors, which span the cell membrane, relay information to a series of intracellular intermediates that eventually
pass the signal to its final destination. Many receptors for chemical messengers have been isolated and characterized. These
proteins are not static components of the cell membrane; they
increase or decrease in number, according to the needs of the
cell. When excess chemical messengers are present, the number
of active receptors decreases in a process called down-regulation;
when there is a deficiency of the messenger, the number of active receptors increases through up-regulation. There are three
known classes of cell surface receptor proteins: ion channel
linked, G protein linked, and enzyme linked.
Ion-Channel–Linked Receptors. Ion-channel–linked receptors
are involved in the rapid synaptic signaling between electrically
excitable cells. This type of signaling is mediated by a small
number of neurotransmitters that transiently open or close ion
channels formed by integral proteins in the cell membrane.
This type of signaling is involved in the transmission of impulses in nerve and muscle cells.
G-Protein–Linked Receptors and Signal Transduction. G proteins constitute the on–off switch for signal transduction.
Although there are numerous intercellular messengers, many
of them rely on a class of molecules called G proteins to convert external signals (first messengers) into internal signals
(second messengers). These internal signals induce biochemical changes in the cell that lead to the desired physiologic effects. G proteins are so named because they bind to guanine
nucleotides, such as guanine diphosphate (GDP) and guanine triphosphate (GTP).
G-protein–mediated signal transduction relies on a series of
orchestrated biochemical events (Fig. 1-12). All signal trans-

Phosphorylated Precursor

Second Messenger
Inositol 1,4,5-trisphosphate
and diacylglycerol
Intracellular Effector

Cell Response
■ FIGURE 1-12 ■

Signal transduction pattern common to several
second messenger systems. A protein or peptide hormone is the
first messenger to a membrane receptor, stimulating or inhibiting
a membrane-bound enzyme by means of a G protein. The amplifier enzyme catalyzes the production of a second messenger from
a phosphorylated precursor. The second messenger then activates an internal effector, which leads to the cell response.
(Redrawn from Rhoades R.A., Tanner G.A. [1996]. Medical physiology. Boston: Little, Brown)

duction systems have a receptor component that functions as a
signal discriminator by recognizing a specific first messenger.
After a first messenger binds to a receptor, conformational
changes occur in the receptor, which activates the G protein.
The activated G protein, in turn, acts on other membranebound intermediates called effectors. Often, the effector is an
enzyme that converts an inactive precursor molecule into a second messenger, which diffuses into the cytoplasm and carries
the signal beyond the cell membrane.
Although there are differences between the G proteins, all
share a number of features. All are found on the cytoplasmic
side of the cell membrane, and all incorporate the GTPase
cycle, which functions as the on–off switch for G-protein activity. Certain bacterial toxins can bind to the G proteins, causing inhibition or stimulation of its signal function. One such
toxin, the toxin of Vibrio cholerae, binds and activates the stimulatory G protein linked to the cAMP system that controls the
secretion of fluid into the intestine. In response to the cholera
toxin, these cells overproduce fluid, leading to severe diarrhea
and life-threatening depletion of extracellular fluid volume.
There is also interest in the role that G-protein signaling may
play in the pathogenesis of cancer.

Chapter 1: Cell Structure and Function

Messenger-Mediated Control of Nuclear Function
Some messengers, such as thyroid hormone and steroid hormones, do not bind to membrane receptors but move directly
across the lipid layer of the cell membrane and are carried to the
cell nucleus, where they influence DNA activity. Many of these
hormones bind to a cytoplasmic receptor, and together they
are carried to the nucleus. In the nucleus, the receptor–hormone
complex binds to DNA, thereby increasing transcription of
mRNA. The mRNAs are translated in the ribosomes, with the
production of increased amounts of proteins that alter cell

Membrane Potentials
The human body runs on a system of self-generated electricity.
Electrical potentials exist across the membranes of most cells in
the body. Because these potentials occur at the level of the cell
membrane, they are called membrane potentials. In excitable tissues, such as nerve or muscle cells, changes in the membrane
potential are necessary for generation and conduction of nerve
impulses and muscle contraction. In other types of cells, such
as glandular cells, changes in the membrane potential contribute to hormone secretion and other functions.

Electrical Potential
Electrical potential, measured in volts (V), describes the ability
of separated electrical charges of opposite polarity (+ and −) to
do work. The potential difference is the difference between
the separated charges. The terms potential difference and voltage
are synonymous. Voltage is always measured with respect to
two points in a system. For example, the voltage in a car battery
(6 or 12 V) is the potential difference between the two battery
terminals. Because the total amount of charge that can be separated by a biologic membrane is small, the potential differences are small and are measured in millivolts (1/1000 of a
volt). Potential differences across the cell membrane can be
measured by inserting a very fine electrode into the cell and another into the extracellular fluid surrounding the cell and connecting the two electrodes to a voltmeter. The movement of
charge between two points is called current. It occurs when a

potential difference has been established and a connection is
made such that the charged particles can move between the
two points.
Extracellular and intracellular fluids are electrolyte solutions
containing approximately 150 to 160 mmol/L of positively
charged ions and an equal concentration of negatively charged
ions. These are the current-carrying ions responsible for generating and conducting membrane potentials. Usually, a small
excess of positively charged ions exists at the outer surface of
the cell membrane. This is represented as positive charges on
the outside of the membrane and is balanced by an equal number of negative charges on the inside of the membrane. Because
of the extreme thinness of the cell membrane, the accumulation of these ions at the surfaces of the membrane contributes
to the establishment of a membrane potential.

Action Potentials
Action potentials are abrupt, pulselike changes in the membrane potential that last a few ten thousandths to a few thousandths of a second (Fig 1-13). In a nerve fiber, an action potential can be elicited by any factor that suddenly increases the
membrane potential, usually by opening a voltage-gated sodium channel. The threshold potential represents the membrane
potential at which the ion channels open and neurons and
other excitable tissues are stimulated to “fire.” In large nerve

Membrane potential (mv)

Enzyme-Linked Receptors. The receptors for certain protein
hormones, such as insulin, and peptide growth factors activate
an intracellular domain with enzyme (protein-tyrosine kinase)
activity. The enzyme catalyzes the phosphorylation of tyrosine
residues of intracellular proteins, thereby transferring an external message to the cell interior. Enzyme-linked receptors
mediate cellular responses such as calcium influx, increased
sodium/potassium exchange, and stimulation of the uptake of
sugars and amino acids.
Growth factors are signal molecules that are similar to hormones in function but act closer to their sites of synthesis. As
their name implies, many of the growth factors are important
messengers in signaling cell replacement and cell growth. Most
of the growth factors belong to one of three groups: factors
that foster the multiplication and development of various cell
types (e.g., growth factor and epidermal growth factor); lymphokines and cytokines, which are important in the regulation
of the immune system; and colony-stimulating factors, which
regulate the proliferation and maturation of white and red
blood cells.


– 20
Threshold potential
– 40
Resting potential
– 60
– 80




A = Absolute refractory period (active potential
and partial recovery)
B = Relative refractory period
C = Positive relative refractory period
■ FIGURE 1-13 ■

Time course of the action potential recorded at
one point of an axon with one electrode inside and one on the outside of the plasma membrane. The rising part of the action potential is called the spike. The rising phase plus approximately the
first half of the repolarization phase is equal to the absolute refractory period (A). The portion of the repolarization phase that
extends from the threshold to the resting membrane potential represents the relative refractory period (B). The remaining portion of
the repolarization phase to the resting membrane potential is equal
to the negative after potential (C). Hyperpolarization is equal to the
positive relative refractory period.


Unit One: Mechanisms of Disease

fibers the sodium channels open at approximately −60 mV.
Under normal circumstances, the threshold potential is sufficient to open large numbers of ion channels, triggering massive
depolarization of the membrane.
Action potentials can be divided into three phases: (1) resting, (2) depolarization, and (3) repolarization phases. The
resting phase is the undisturbed period of the action potential,
during which neurons and other excitable tissues are not transmitting impulses. During this phase, the membrane is highly
permeable to potassium and there is approximately 70 to
90 mV less charge (−70 mV to −90 mV) on the inside than on
the outside of the membrane. This difference in charge is necessary for establishment of current flow once the membrane
becomes permeable to the flow of charged ions. During this
period, the membrane is said to be polarized because charges
of opposite polarity (+ and −) are aligned across the membrane. Depolarization is characterized by the flow of positively
charged sodium ions to the interior of the membrane. During
the depolarization phase of the action potential, the interior
side of the membrane becomes positive (approximately +30 mV
to +45 mV). Repolarization is the phase in which the polarity
of the resting membrane is re-established. This is accomplished by closure of the sodium channels and opening of the
potassium channels. The outflow of positively charged potassium ions returns the membrane potential to negativity. The
activity of the Na+/K+ ATPase pump helps to reestablish the
resting membrane potential. During repolarization, the membrane remains refractory (i.e., does not fire) until the repolarization is approximately one-third complete. This period,
which lasts approximately one half of a millisecond, is called
the absolute refractory period (Fig. 1-13). During the relative refractory period, which follows the absolute refractory period,
the membrane can be excited, although only by a strongerthan-normal stimuli.
Two main factors alter membrane excitability: (1) the difference in the concentration of ions on the inside and outside
of the membrane and (2) changes in membrane permeability.
The resting membrane potential is strongly influenced by
serum potassium levels and the resulting difference in concentration on the inside and outside of the membrane. When
serum levels of potassium are decreased, the resting membrane
potential becomes more negative, and nerve and muscle cells
become less excitable, sometimes to the extent that they cannot
be re-excited (see Chapter 6). An increase in serum potassium
has the opposite effect, causing the resting membrane to become more positive, moving closer to threshold. When this
happens, the amplitude of the action potential is decreased because the membrane has not been fully repolarized. Should the
resting membrane potential reach the level of the threshold potential during the absolute refractory period, the nerve or muscle cell will remain depolarized and unexcitable.
Neural excitability is markedly altered by changes in membrane permeability to current-carrying ions such as sodium.
Calcium ions decrease membrane permeability to sodium ions
and increase the threshold for initiation of action potentials. If
insufficient calcium ions are available, the permeability of the
membrane to sodium increases, and as a result, membrane excitability increases, sometimes causing spontaneous muscle
movements (tetany) to occur. Local anesthetic agents (e.g., procaine, cocaine) act directly on neural membranes to decrease
their permeability to sodium.

In summary, the movement of materials across the cell’s
membrane is essential for survival of the cell. Diffusion is a
process by which substances such as ions move from areas of
greater concentration to areas of lesser concentration in an attempt to reach a uniform distribution. Osmosis refers to the
diffusion of water molecules through a semipermeable membrane along a concentration gradient. Facilitated diffusion is a
passive process, in which molecules that cannot normally pass
through the cell’s membranes, do so with the assistance of a
carrier molecule. Another type of transport, called active
transport, requires the cell to expend energy in moving ions
against a concentration gradient. The Na+/K+ ATPase pump is
the best-known type of active transport. Endocytosis is a
process by which cells engulf materials from the surrounding
medium. Small particles are ingested by a process called
pinocytosis; larger particles are engulfed by a process called
phagocytosis. Exocytosis involves the removal of large particles from the cell and is essentially the reverse of endocytosis.
Ion channels are integral transmembrane proteins that span
the width of the cell membrane to form a gating system that
controls the movement of ions across the cell membrane.
Cells communicate with each other by means of chemical
messenger systems. In some tissues, chemical messengers
move from cell to cell through gap junctions without entering
the extracellular fluid. Other types of chemical messengers
bind to receptors on or near the cell surface. There are three
known classes of cell surface receptor proteins: ion channel
linked, G protein linked, and enzyme linked. Ion-channel–
linked signaling is mediated by neurotransmitters that transiently open or close ion channels formed by integral proteins
in the cell membrane. G-protein–linked receptors rely on a
class of molecules called G proteins that function as an on–off
switch to convert external signals (first messengers) into internal signals (second messengers). Enzyme-linked receptors
interact with certain peptide hormones (e.g., insulin and
growth factors) to directly initiate the activity of an intracellular enzyme, which in turn, triggers multiple cellular responses,
such as stimulation of glucose and amino acid uptake or transcription of certain genes that control cell proliferation.
Electrical potentials (negative on the inside and positive on
the outside) exist across the membranes of most cells in the
body. Membrane excitability depends on a separation of
charge across the membrane and the permeability of the
membrane to the current-carrying ion. Action potentials are
abrupt pulselike changes in the membrane potential that last
a few ten thousandths to a few thousandths of a second.
Action potentials can be divided into three phases: the resting
phase, during which neurons and excitable tissues are not
generating or transmitting impulses; the depolarization
phase, which is characterized by flow of current across the
membrane; and the repolarization phase, during which the
resting membrane potential is restored.

In the preceding sections, we discussed the individual cell, its
metabolic processes, and mechanisms of communication.
Although cells are similar, their structure and function vary ac-

Chapter 1: Cell Structure and Function

cording to the special needs of the body. For example, muscle
cells perform functions different from those of skin cells or
nerve cells. Groups of cells that are closely associated in structure and have common or similar functions are called tissues.
Four categories of tissue exist: epithelium, connective (supportive) tissue, muscle, and nerve. These tissues do not exist in
isolated units, but in association with each other and in variable proportions, forming different structures and organs. This
section provides a brief overview of the cells in epithelial, connective, and muscle tissue. Nervous tissue is described in
Chapter 36.

Cell Differentiation
After conception, the fertilized ovum undergoes a series of divisions, ultimately forming approximately 200 different cell
types. The formation of different types of cells and the disposition of these cells into tissue types is called cell differentiation, a
process controlled by a system that switches genes on and off.
Embryonic cells must become different to develop into all of
the various organ systems, and they must remain different after
the signal that initiated cell diversification has disappeared. The
process of cell differentiation is controlled by cell memory,
which is maintained through regulatory proteins contained in
the individual members of a particular cell type. Cell differentiation also involves the sequential activation of multiple genes
and their protein products. This means that after differentiation
has occurred, the tissue type does not revert to an earlier stage
of differentiation. The process of cell differentiation normally
moves forward, producing cells that are more specialized than
their predecessors. Usually, highly differentiated cell types,


■ Cells with a similar embryonic origin or function are

often organized into larger functional units called
tissues, and these tissues in turn associate with other,
dissimilar tissues to form the various organs of
the body.
■ Epithelial tissue forms sheets that cover the body’s

outer surface, lines internal surfaces, and forms glandular tissue. It is supported by a basement membrane, is avascular, and must receive nourishment
from capillaries in supporting connective tissues.
■ Connective tissue is the most abundant tissue of the

body. It is found in a variety of forms, ranging from
solid bone to blood cells that circulate in the vascular system.
■ Muscle tissue contains actin and myosin filaments

that allow it to contract and provide locomotion and
movement of skeletal structures (skeletal muscle),
pumping of blood through the heart (cardiac muscle), and contraction of blood vessels and visceral
organs (smooth muscle).


such as skeletal muscle and nervous tissue, lose their ability to
undergo cell division. Cancer is a disorder of cell differentiation in which cells of a single cell line fail to differentiate properly (see Chapter 5).

Embryonic Origin of Tissue Types
All of the approximately 200 different types of body cells can
be classified into four basic or primary tissue types: epithelial,
connective, muscle, and nervous (Table 1-1). These basic tissue
types are often described by their embryonic origin. The embryo is essentially a three-layered tubular structure. The outer
layer of the tube is called the ectoderm; the middle layer, the
mesoderm; and the inner layer, the endoderm. All of the adult
body tissues originate from these three cellular layers.
Epithelium has its origin in all three embryonic layers; connective tissue and muscle develop mainly from the mesoderm;
and nervous tissue develops from the ectoderm.

Epithelial Tissue
Epithelial tissue forms sheets that cover the body’s outer surface, line the internal surfaces, and form the glandular tissue.
Underneath all types of epithelial tissue is an extracellular matrix, called the basement membrane, which serves to attach the
epithelial cells to adjacent connective tissue and provides them
with flexible support.
Epithelial cells have strong intracellular protein filaments
(i.e., cytoskeleton) that are important in transmitting mechanical stresses from one cell to another. The cells of epithelial tissue are tightly bound together by specialized junctions. These
specialized junctions enable these cells to form barriers to the
movement of water, solutes, and cells from one body compartment to the next. Epithelial tissue is avascular (i.e., without
blood vessels) and must therefore receive oxygen and nutrients
from the capillaries of the connective tissue on which the epithelial tissue rests (Fig. 1-14). To survive, the epithelial cells
must be kept moist. Even the seemingly dry skin epithelium is
kept moist by a nonvitalized, waterproof layer of superficial
skin cells called keratin, which prevents evaporation of moisture from the deeper living cells. Epithelium is able to regenerate quickly when injured
Epithelial tissues are classified according to the shape of the
cells and the number of layers that are present: simple, stratified, and pseudostratified. Glandular epithelial tissue is formed
by cells specialized to produce a fluid secretion. The terms squamous (thin and flat), cuboidal (cube shaped), and columnar (resembling a column) refer to the cells’ shape (Fig. 1-15).

Simple Epithelium
Simple epithelium contains a single layer of cells, all of which
rest on the basement membrane. Simple squamous epithelium
is adapted for filtration; it is found lining the blood vessels,
lymph nodes, and alveoli of the lungs. The single layer of
squamous epithelium lining the heart and blood vessels is
known as the endothelium. A similar type of layer, called the
mesothelium, forms the serous membranes that line the pleural,
pericardial, and peritoneal cavities and cover the organs of
these cavities. A simple cuboidal epithelium is found on the surface of the ovary and in the thyroid. Simple columnar epithelium
lines the intestine. One form of a simple columnar epithelium


Unit One: Mechanisms of Disease


Classification of Tissue Types

Tissue Type


Epithelial Tissue
Covering and lining of body surfaces
Simple epithelium
Stratified epithelium
Squamous keratinized
Squamous nonkeratinized
Reproductive epithelium

Lining of blood vessels, body cavities, alveoli of lungs
Collecting tubules of kidney; covering of ovaries
Lining of intestine and gallbladder
Mucous membranes of mouth, esophagus, and vagina
Ducts of sweat glands
Large ducts of salivary and mammary glands; also found in conjunctiva
Bladder, ureters, renal pelvis
Tracheal and respiratory passages
Pituitary gland, thyroid gland, adrenal, and other glands
Sweat glands and glands in gastrointestinal tract
Olfactory mucosa, retina, tongue
Seminiferous tubules of testis; cortical portion of ovary

Connective Tissue
Embryonic connective tissue
Adult connective tissue
Loose or areolar
Dense regular
Dense irregular
Specialized connective tissue

Embryonic mesoderm
Umbilical cord (Wharton’s jelly)
Subcutaneous areas
Tendons and ligaments
Dermis of skin
Fat pads, subcutaneous layers
Framework of lymphoid organs, bone marrow, liver
Long bones, flat bones
Tracheal rings, external ear, articular surfaces
Blood cells, myeloid tissue (bone marrow)

Muscle Tissue

Skeletal muscles
Heart muscles
Gastrointestinal tract, blood vessels, bronchi, bladder, and others

Nervous Tissue
Supporting cells

Central and peripheral neurons and nerve fibers
Glial and ependymal cells in central nervous system; Schwann and satellite
cells in peripheral nervous system

has hairlike projections called cilia, often with specialized
mucus-secreting cells called goblet cells. This form of simple
columnar epithelium lines the airways of the respiratory tract.

Stratified and Pseudostratified Epithelium
Stratified epithelium contains more than one layer of cells,
with only the deepest layer resting on the basement membrane.
It is designed to protect the body surface. Stratified squamous keratinized epithelium makes up the epidermis of the skin. Keratin
is a tough, fibrous protein existing as filaments in the outer cells
of skin. A stratified squamous keratinized epithelium is made
up of many layers. The layers closest to the underlying tissues
are cuboidal or columnar. The cells become more irregular and
thinner as they move closer to the surface. Surface cells become
totally filled with keratin and die, are sloughed off, and then re-

placed by the deeper cells. A stratified squamous nonkeratinized epithelium is found on moist surfaces, such as the mouth
and tongue. Stratified cuboidal and columnar epithelia are
found in the ducts of salivary glands and the larger ducts of the
mammary glands. In smokers, the normal columnar ciliated
epithelial cells of the trachea and bronchi are often replaced
with stratified squamous epithelium cells that are better able to
withstand the irritating effects of cigarette smoke.
Pseudostratified epithelium is a type of epithelium in which all
of the cells are in contact with the underlying intercellular matrix, but some do not extend to the surface. A pseudostratified
ciliated columnar epithelium with goblet cells forms the lining
of most of the upper respiratory tract. All of the tall cells reaching the surface of this type of epithelium are either ciliated cells
or mucus-producing goblet cells. The basal cells that do not

Chapter 1: Cell Structure and Function


Simple squamous


Simple cuboidal


Nerve fiber

Simple columnar

■ FIGURE 1-14 ■ Typical arrangement of epithelial cells in relation

to underlying tissues and blood supply. Epithelial tissue has no
blood supply of its own but relies on the blood vessels in the
underlying connective tissue for nutrition (N) and elimination of
wastes (W).

reach the surface serve as stem cells for ciliated and goblet cells.
Transitional epithelium is a stratified epithelium characterized by
cells that can change shape and become thinner when the tissue is stretched. Such tissue can be stretched without pulling
the superficial cells apart. Transitional epithelium is well
adapted for the lining of organs that are constantly changing
their volume, such as the urinary bladder.

Glandular Epithelium
Glandular epithelial tissue is formed by cells specialized to produce a fluid secretion. This process is usually accompanied by
the intracellular synthesis of macromolecules. The chemical
nature of these macromolecules is variable. The macromolecules typically are stored in the cells in small, membranebound vesicles called secretory granules. For example, glandular
epithelia can synthesize, store, and secrete proteins (e.g., insulin), lipids (e.g., adrenocortical hormones, secretions of the
sebaceous glands), and complexes of carbohydrates and proteins (e.g., saliva). Less common are secretions such as those
produced by the sweat glands, which require minimal synthetic
All glandular cells arise from surface epithelia by means of
cell proliferation and invasion of the underlying connective
tissue. Epithelial glands can be divided into two groups: exocrine and endocrine glands. Exocrine glands, such as the sweat
glands and lactating mammary glands, retain their connection
with the surface epithelium from which they originated. This
connection takes the form of epithelium-lined tubular ducts
through which the secretions pass to reach the surface. Exocrine
glands are often classified according to the way secretory products are released by their cells. In holocrine type cells (e.g., sebaceous glands), the glandular cell ruptures, releasing its entire
contents into the duct system. New generations of cells are replaced by mitosis of basal cells. Merocrine or eccrine type glands
(e.g., salivary glands, exocrine glands of the pancreas) release
their glandular products by exocytosis. In apocrine secretions
(e.g., mammary glands, certain sweat glands), the apical por-

Pseudostratified columnar


Stratified squamous

■ FIGURE 1-15 ■


Representation of the various epithelial tissue


Unit One: Mechanisms of Disease

tion of the cell, along with small portions of the cytoplasm, is
pinched off the glandular cells. Endocrine glands are epithelial
structures that have had their connection with the surface obliterated during development. These glands are ductless and produce secretions (i.e., hormones) that move directly into the

Connective or Supportive Tissue
Connective tissue (or supportive tissue) is the most abundant
tissue in the body. As its name suggests, it connects and binds
or supports the various tissues. The capsules that surround organs of the body are composed of connective tissue. Bone, adipose tissue, and cartilage are specialized types of connective tissue that function to support the soft tissues of the body and
store fat. Connective tissue is unique in that its cells produce
the extracellular matrix that supports and holds tissues together. Connective tissue has a role in tissue nutrition. The close
proximity of the extracellular matrix to blood vessels allows it
to function as an exchange medium through which nutrients
and metabolic wastes pass.
Adult connective tissue proper can be divided into two main
types: loose or areolar and dense connective tissue.

Loose Connective Tissue
Loose connective tissue, also known as areolar tissue, is soft and
pliable. Although it is more cellular than dense connective tissue, it contains large amounts of intercellular substance. It fills


spaces between muscle sheaths and forms a layer that encases
blood and lymphatic vessels. Areolar connective tissue supports the epithelial tissues and provides the means by which
these tissues are nourished. In an organ containing functioning
epithelial tissue and supporting connective tissue, the term
parenchymal tissue is used to describe the functioning epithelium as opposed to the connective tissue framework or stroma.
Cells of loose connective tissue include fibroblasts, mast
cells, adipose or fat cells, macrophages, plasma cells, and leukocytes (Fig. 1-16). Loose connective tissue cells secrete substances that form the extracellular matrix that supports and
connects body cells. Fibroblasts are the most abundant of these
cells. They are responsible for the synthesis of the fibrous and
gel-like substance that fills the intercellular spaces of the body
and for the production of collagen, elastic, and reticular fibers.
Adipose tissue is a special form of connective tissue in which
adipocytes predominate. Adipocytes do not generate an extracellular matrix but maintain a large intracellular space. These
cells store large quantities of triglycerides and are the largest
repository of energy in the body. Adipose tissue helps fill spaces
between tissues and helps to keep organs in place. Subcutaneous layers of fat help to shape the body. Because fat is a poor
conductor of heat, adipose tissue serves as thermal insulation
for the body. Adipose tissue exists in two forms. Unilocular
(white) adipose tissue is composed of cells in which the fat is
contained in a single, large droplet in the cytoplasm. Multilocular (brown) adipose tissue is composed of cells that contain multiple droplets of fat and numerous mitochondria.

Amorphous intercellular substance
Plasma cell
Fat cell

Mast cell


■ FIGURE 1-16 ■


Endothelial cell and Pericyte
of capillary

Smooth muscle cell

Diagrammatic representation of cells that may be seen in
loose connective tissue. The cells lie in
an intercellular matrix that is bathed
in tissue fluid that originates in capillaries. (From Cormack D.H. [1987]. Ham’s
histology [9th ed.]. Philadelphia: J.B.

Chapter 1: Cell Structure and Function

Reticular tissue is characterized by a network of reticular
fibers associated with reticular cells. Reticular fibers provide the
framework for capillaries, nerves, and muscle cells. They also
constitute the main supporting elements for the blood forming
tissues and the liver.


Three types of muscle tissues exist: skeletal, cardiac, and smooth.
Skeletal and cardiac muscles are striated muscles. The actin and
myosin filaments are arranged in large parallel arrays in bundles, giving the muscle fibers a striped or striated appearance
when they are viewed through a microscope.
Skeletal muscle is the most abundant tissue in the body,
accounting for 40% to 45% of the total body weight. Most
skeletal muscles are attached to bones, and their contractions
are responsible for movements of the skeleton. Cardiac muscle, which is found in the heart, is designed to pump blood
continuously. Smooth muscle is found in the iris of the eye, the
walls of blood vessels, hollow organs such as the stomach and
urinary bladder, and hollow tubes, such as the ureters, that connect internal organs.
Neither skeletal nor cardiac muscle can undergo the mitotic
activity needed to replace injured cells. However, smooth muscle may proliferate and undergo mitotic activity. Some increases in smooth muscle are physiologic, as occurs in the
uterus during pregnancy. Other increases, such as the increase
in smooth muscle that occurs in the arteries of persons with
chronic hypertension, are pathologic.
Although the three types of muscle tissue differ significantly
in structure, contractile properties, and control mechanisms,
they have many similarities. In the following section, the structural properties of skeletal muscle are presented as the prototype of striated muscle tissue. Smooth muscle and the ways in
which it differs from skeletal muscle are also discussed. Cardiac
muscle is described in Chapter 14.

nective tissue hold the individual muscle fibers together. A
dense connective tissue covering called the epimysium forms the
outermost layer surrounding the whole muscle (Fig. 1-17).
Each muscle is subdivided into smaller bundles called fascicles,
which are surrounded by a connective tissue covering called the
perimysium. The number of fascicles and their size vary among
muscles. Fascicles consist of many elongated structures called
muscle fibers, each of which is surrounded by connective tissue
called the endomysium.
Skeletal muscles are syncytial or multinucleated structures,
meaning there are no true cell boundaries within a skeletal
muscle fiber. The cytoplasm or sarcoplasm of the muscle fiber
is contained within the sarcolemma, which represents the cell
membrane. Embedded throughout the sarcoplasm are the contractile elements actin and myosin, which are arranged in parallel bundles (i.e., myofibrils). The thin, lighter-staining myofilaments are composed of actin, and the thicker, darker-staining
myofilaments are composed of myosin. Each myofibril consists
of regularly repeating units along the length of the myofibril;
each of these units is called a sarcomere (see Fig. 1-17). Sarcomeres are the structural and functional units of cardiac and
skeletal muscle. A sarcomere extends from one Z line to another Z line. Within the sarcomere are alternating light and
dark bands. The central dark band (A band) contains mainly
myosin filaments, with some overlap with actin filaments.
The lighter I band contains only actin filaments and straddles
the Z band; therefore, it takes two sarcomeres to complete an
I band. An H zone is found in the middle of the A band and
represents the region where only myosin filaments are found.
In the center of the H zone is a thin, dark band, the M band or
line, that is produced by linkages between the myosin filaments. Z bands consist of short elements that interconnect and
provide the thin actin filaments from two adjoining sarcomeres
with an anchoring point.
The sarcoplasmic reticulum, which is comparable to the
smooth ER, is composed of longitudinal tubules that run parallel to the muscle fiber and surround each myofibril. This network ends in enlarged, saclike regions called the lateral sacs or
terminal cisternae. These sacs store calcium to be released during muscle contraction. A second system of tubules consists of
the transverse or T tubules, which are extensions of the plasma
membrane and run perpendicular to the muscle fiber. The hollow portion or lumen of the transverse tubule is continuous
with the extracellular fluid compartment. Action potentials,
which are rapidly conducted over the surface of the muscle
fiber, are in turn propagated by the T tubules and into the sarcoplasmic reticulum. As the action potential moves through the
lateral sacs, the sacs release calcium, initiating muscle contraction. The membrane of the sarcoplasmic reticulum also has an
active transport mechanism for pumping calcium ions back
into the reticulum. This prevents interactions between calcium
ions and the actin and myosin myofilaments after cessation of
a muscle contraction.

Skeletal Muscle
Skeletal muscle tissue is packaged into skeletal muscles that attach to and cover the body skeleton. Each skeletal muscle is a
discrete organ made up of hundreds and thousands of muscle
fibers. Even though muscle fibers predominate, substantial
amounts of connective tissue, blood vessels, and nerve fibers
are present. In an intact muscle, several different layers of con-

Skeletal Muscle Contraction. Muscle contraction involves the
sliding of the thick myosin and thin actin filaments over each
other to produce shortening of the muscle fiber, while the actual length of the individual thick and thin filaments remains
unchanged. The thick myosin filaments consist of a thin tail,
which provides the structural backbone for the filament, and
a globular head that forms cross-bridges with the thin actin

Dense Connective Tissue
Dense connective tissue exists in two forms: dense irregular and
dense regular. Dense irregular connective tissue consists of the
same components found in loose connective tissue, but there
is a predominance of collagen fibers and fewer cells. This type
of tissue can be found in the dermis of the skin (i.e., reticular
layer), the fibrous capsules of many organs, and the fibrous
sheaths of cartilage (i.e., perichondrium) and bone (i.e., periosteum). It also forms the fascia that covers muscles and organs. Dense regular connective tissues are rich in collagen fibers
and form the tendons and aponeuroses that join muscles to
bone or other muscles and the ligaments that join bone to
bone. Tendons and ligaments are white fibers because of an
abundance of collagen. Ligaments such as the ligamenta flava
of the vertebral column and the true vocal folds are called yellow fibers because of the abundance of elastic fibers.

Muscle Tissue


Unit One: Mechanisms of Disease

■ FIGURE 1-17 ■ (A) Connective tissue components of a skeletal muscle. (B) Structure of the myofibril
and the relationship between actin and myosin myofilaments. (C) Sarcoplasmic reticulum and system of
transverse tubules.

filaments (Fig. 1-18). Myosin molecules are bundled together
side by side in the thick filaments such that one half have their
heads toward one end of the filament and their tails toward the
other end; the other half are arranged in the opposite manner.
Each globular myosin head contains a binding site able to bind
to a complementary site on the actin molecule. In addition to
the binding site for actin, each myosin head has a separate active site that catalyzes the breakdown of ATP to provide the energy needed to activate the myosin head so it can form a crossbridge with actin. After contraction, myosin also binds ATP,
thus breaking the linkage between actin and myosin.
The thin filaments are composed mainly of actin, a globular protein lined up in two rows that coil around each other to
form a long helical strand. Associated with each actin filament
are two regulatory proteins, tropomyosin and troponin. Tropomyosin, which lies in grooves of the actin strand, provides the
site for attachment of the globular heads of the myosin filament.
In the noncontracted state, troponin covers the tropomyosin
binding sites and prevents formation of cross-bridges between
the actin and myosin. During an action potential, calcium ions


Troponin Thin filament

Myosin head

Thick filament


Z line

■ FIGURE 1-18 ■ Molecular structure of the thin actin filament
and the thicker myosin filament of striated muscle. The thin filament is a double-stranded helix of actin molecules with
tropomyosin and troponin molecules lying along the grooves of
the actin strands. During muscle contraction, the ATP-activated
heads of the thick myosin filament swivel into position, much like
the oars on a boat, form a cross-bridge with a reactive site on
tropomyosin, and then pull the actin filament forward. During
muscle relaxation, the troponin molecules cover the reactive sites
on tropomyosin.

Chapter 1: Cell Structure and Function

released from the sarcoplasmic reticulum diffuse to the adjacent myofibrils, where they bind to troponin. The binding of
calcium to troponin uncovers the tropomyosin binding sites
such that the myosin heads can attach and form cross-bridges.
Muscle contraction begins with activation of the crossbridges from the myosin filaments and uncovering of the tropomyosin binding sites on the actin filament. When activated
by ATP, the heads of the myosin heads swivel in a fixed arc,
much like the oars of a boat, as they become attached to the
actin filament. During contraction, each myosin head undergoes its own cycle of movement, forming a bridge attachment
and releasing it, and moving to another site where the same sequence of movement occurs. This pulls the thin and thick filaments past each other. Energy from ATP is used to break the
actin and myosin cross-bridges, stopping the muscle contraction. With the breaking of the linkage between actin and
myosin, the concentration of calcium around the myofibrils
decreases as calcium is actively transported into the sarcoplasmic reticulum