lwbk942-fm.qxd 6/25/11 8:45 am page...

LWBK942-FM.qxd 6/25/11 8:45 AM Page x

Handbook of Pathophysiology

77251_FM 30/06/10 4:03 PM Page i

77251_FM 30/06/10 4:03 PM Page ii

F O U R T H E D I T I O N

Handbook of PathophysiologyRamona Browder Lazenby, EdD, MSN, FNP-BC, CNEProfessorAuburn University Montgomery School of NursingAuburn University MontgomeryMontgomery, Alabama

77251_FM 30/06/10 4:03 PM Page iii

Acquisitions Editor: Hilarie SurrenaProduct Manager: Eric Van OstenEditorial Assistant: Laura ScottProduction Director: Helen Ewan Senior Designer: Joan WendtIllustration Coordinator: Brett MacNaughtonManufacturing Coordinator: Karin DuffieldPrepress Vendor: MPS Limited, A Macmillan Company

4th Edition

Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Copyright © 2008, 2000, 1996 by Lippincott Williams & Wilkins, a Wolters Kluwer business.

Wolters Kluwer HealthTwo Commerce Square2001 Market StreetPhiladelphia, PA 19103

All rights reserved. This book is protected by copyright. No part of this book may be reproduced ortransmitted in any form or by any means, including as photocopies or scanned-in or other electroniccopies, or utilized by any information storage and retrieval system without written permission fromthe copyright owner, except for brief quotations embodied in critical articles and reviews. Materials ap-pearing in this book prepared by individuals as part of their official duties as U.S. government employeesare not covered by the above-mentioned copyright. To request permission, please contact LippincottWilliams & Wilkins at Two Commerce Square, 2001 Market Street, 4th Floor, Philadelphia, PA 19103,via email at [email protected], or via our website at lww.com (products and services).

Printed in China

9 8 7 6 5 4 3 2 1

Cover Art: TO COME

Library of Congress Cataloging-in-Publication Data Lazenby, Ramona Browder.Handbook of pathophysiology. —4th ed./Ramona Browder Lazenby.

p. ; cm.Rev. ed. of: Handbook of pathophysiology/Elizabeth J. Corwin. 3rd ed. c2008.Includes bibliographical references and index.Summary: “This pathophysiology handbook is ideally suited for easy reference in the classroom orclinical environment. The book presents a summary of physiology concepts for each body system,followed by an overview of important pathophysiology concepts related to ‘alterations’ in that bodysystem. These pathophysiology concepts provide the necessary foundation for understanding thedisease or injury states that are presented next in the chapter”—Provided by publisher.ISBN 978-1-60547-725-1 (pbk. : alk. paper) 1. Physiology, Pathological—Handbooks, manuals, etc.I. Corwin, Elizabeth J. Handbook of pathophysiology. II. Title. [DNLM: 1. Pathologic Processes—Handbooks. 2. Physiological Phenomena—Handbooks. QZ 39]RB113.C785 2011616.07—dc22

2010025906

Care has been taken to confirm the accuracy of the information presented and to describe generallyaccepted practices. However, the authors, editors, and publisher are not responsible for errors oromissions or for any consequences from application of the information in this book and make nowarranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contentsof the publication. Application of this information in a particular situation remains the professionalresponsibility of the practitioner; the clinical treatments described and recommended may not beconsidered absolute and universal recommendations.

The authors, editors, and publisher have exerted every effort to ensure that drug selection anddosage set forth in this text are in accordance with the current recommendations and practice at thetime of publication. However, in view of ongoing research, changes in government regulations, andthe constant flow of information relating to drug therapy and drug reactions, the reader is urged tocheck the package insert for each drug for any change in indications and dosage and for added warn-ings and precautions. This is particularly important when the recommended agent is a new or infre-quently employed drug.

Some drugs and medical devices presented in this publication have Food and Drug Administration(FDA) clearance for limited use in restricted research settings. It is the responsibility of the health careprovider to ascertain the FDA status of each drug or device planned for use in his or her clinical practice.

LWW.com

77251_FM 16/07/10 9:21 AM Page iv

To all my students who have said,

and actually meant: “I LOVE Patho.”

77251_FM 30/06/10 4:03 PM Page v

77251_FM 30/06/10 4:03 PM Page vi

vii

REV

IEWER

S

Sophia Beydoun, MSN, RNNursing InstructorNursing DepartmentHenry Ford Community CollegeDearborn, Michigan

Barbara Coles, BS, MS, PhDAssociate Department Head, Natural

Science, Health and PE Department Wake Technical Community CollegeRaleigh, North Carolina

Deb Filer, PhD, RN, CNEAssociate ProfessorNursing DepartmentSt. Catherine UniversitySt. Paul, Minnesota

Sheila Grossman, PhD, FNP-BCProfessor & FNP Specialty Track

Coordinator Fairfield University School of NursingFairfield, Connecticut

Lorie Judson, RN, PhDAssociate Director/Undergraduate ChairCalifornia State University, Los Angeles

School of NursingLos Angeles, California

Lori Knight, CHIMInstructor, Health Information

ManagementSIAST Wascana CampusRegina, SaskatchewanCanada

DeAnn Mitchell, PhD, RNProfessor of NursingTarrant County CollegeFort Worth, Texas

Mary Ellen Morrissey, RN, MSNAssistant ProfessorNursing DepartmentSalem State CollegeSalem, Massachusetts

Cheryl Neudauer, PhD, MEdScience Division CoordinatorBiology DepartmentMinneapolis Community & Technical

CollegeMinneapolis, Minnesota

Deborah Pool, MS, RN, CCRNDepartment ChairMaricopa Nursing ProgramGlendale Community CollegeGlendale, Arizona

77251_FM 30/06/10 4:03 PM Page vii

Susan Porterfield, FNP-CNP Coordinator and Assistant ProfessorCollege of NursingFlorida State UniversityTallahassee, Florida

Elizabeth VandeWaa, PhDAdult Health Nursing DepartmentUniversity of South AlabamaMobile, Alabama

John P. Harley, PhDProfessor of Biological Sciences,Foundation ProfessorTeaching and Learning Center Fellow,Eastern Kentucky UniversityAssistant Professor,Chandler Medical CenterUniversity of KentuckyRichmond and Lexington, Kentucky

viii REVIEWERS

77251_FM 30/06/10 4:03 PM Page viii

ix

PR

EFAC

E

As a nurse educator for over 20 years, I learned rather early that a founda-tional knowledge of basic pathophysiology made other concepts make bet-

ter sense. Understanding the normal anatomy and physiology of the body laysa foundation to understanding the pathophysiology behind various diseaseprocesses. The understanding of pathophysiology then helps make sense ofwhy certain medications and other therapeutic interventions are effective intreating different health alterations. An understanding of pathophysiology isvital to safe and effective patient care.

I truly believe pathophysiology is the most important course in the cur-riculum. Every semester that I teach it to nursing students, I begin class thesame way: “I love pathophysiology and I want you to love it as much as I do.”Then, I have them repeat “We love patho!” in unison. It does not take studentslong to sense my passion for pathophysiology and I would like to believe thatmy passion is contagious. Although it may not be the most important course,historically students who have a good understanding of pathophysiology tendto have a better understanding of pharmacology and other therapeutic inter-ventions. This text is designed to present an overview of the more commonhealth alterations. While no one book can contain all the information, hope-fully this information will stimulate further research on the reader’s part. Inthe clinical setting this text will serve as a quick reference for the pathophysi-ology, clinical manifestations, diagnostic tools, possible complications, andtreatments of many disease processes.

CONTENT ORGANIZATION

The format of this edition of the Handbook of Pathophysiology continues tofollow the same outline as in the previous books, with section headings of Phys-iologic Concepts, Pathophysiologic Concepts, and Conditions of Disease or

77251_FM 30/06/10 4:03 PM Page ix

Injury. The text is organized this way because I believe not only that a solidunderstanding of physiology is essential to understanding pathophysiology,but also that understanding both physiology and pathophysiology is requiredin order for the symptoms and treatment of any disease to make sense.

NEW TO THIS EDITION

This edition of the text includes 20 chapters, with expanded discussions of cut-ting-edge research and knowledge in cell biology, cancer, and genetics. All ofthe chapters in this edition have been updated and expanded, based upon themost recent scientific studies and information available. In addition, more ta-bles have been added as a quick reference.

Pediatric and Geriatric Considerations are highlighted at the end of eachchapter. As in the previous editions, they are included to alert the reader tovariations in both normal and pathophysiologic processes in children and olderadults. Many of these features have been expanded to include pearls gleanedfrom practice.

SPECIAL FEATURES

Each chapter includes features designed to assist the reader’s understanding ofpathophysiology.

• Key Words are indicated in boldface type and are defined in the text in orderto help readers quickly master what can sometimes be a difficult vocabulary.

• Figures, especially chosen or created for the Handbook, are used throughoutthe text to visually explain concepts that are not easily grasped by wordsalone.

• Geriatric Considerations at the end of each chapter alert readers to the im-portant differences in the physiologic and pathophysiologic systems and con-ditions of disease or injury in the older adults.

• Pediatric Considerations highlight developmental, physiologic, and patho-physiologic differences in both wellness and illness in children.

Ramona Browder Lazenby, EdD, MSN, FNP-BC, CNE

x PREFACE

77251_FM 30/06/10 4:03 PM Page x

xi

AC

KN

OW

LEDG

MEN

TS

It would be impossible to acknowledge everyone who has contributed to mygrowth as a person and a professional. First and foremost is my husband,

John, who has always supported anything and everything I have pursued.Thank you to my dean who has allowed me to continue teaching pathophysi-ology despite my administrative role. Also, to my colleagues at Auburn Mont-gomery School of Nursing who constantly encourage each other as we all strivefor excellence. Finally, a great big thank you to all the students who I have hadthe privilege of teaching. Your enthusiasm and desire for knowledge has keptme motivated to continue my lifelong learning—and of course hearing yousay “We love patho” stirs more passion for the content.

77251_FM 30/06/10 4:03 PM Page xi

77251_FM 30/06/10 4:03 PM Page xii

xiii

CO

NTEN

TS

UNIT ONEFundamental Mechanisms of Health and Disease 1

CHAPTER 1 Cell Structure and Function 3

CHAPTER 2 Genetics 37

CHAPTER 3 Cancer 72

UNIT TWOEffective and Ineffective Health Protection 109

CHAPTER 4 The Immune System 111

CHAPTER 5 The Integument 153

CHAPTER 6 Homeostasis and the Stress Response 203

CHAPTER 7 Neuroendocrine—Immune Interaction 220

UNIT THREEIntegrated Control and Dysfunction 231

CHAPTER 8 The Nervous System 233

CHAPTER 9 The Endocrine System 306

CHAPTER 10 The Musculoskeletal System 350

CHAPTER 11 The Senses 401

77251_FM 30/06/10 4:03 PM Page xiii

UNIT FOUROxygen Balance and Deficiencies 441

CHAPTER 12 The Hematologic System 443

CHAPTER 13 The Cardiovascular System 488

CHAPTER 14 The Respiratory System 571

UNIT FIVENutrition, Elimination, and Reproductive Function and Dysfunction 631

CHAPTER 15 The Gastrointestinal System 633

CHAPTER 16 The Pancreas and Diabetes Mellitus 672

CHAPTER 17 The Liver 702

CHAPTER 18 The Genitourinary System 737

CHAPTER 19 Fluid and Electrolyte and Acid-Base Balance 791

CHAPTER 20 The Reproductive System 818

Index 865

Pathophysiology in Color Following page

xiv CONTENTS

77251_FM 30/06/10 4:03 PM Page xiv

UN

IT O

NE

Fundamental Mechanisms of Health and Disease

77251_ch01 30/06/10 11:52 AM Page 1

77251_ch01 30/06/10 11:52 AM Page 2

Cell Structure and Function

3

CH

AP

TER

The cell is the building block of each living organism. Each cell is a self-contained system that undergoes the functions of energy production and

usage, respiration, reproduction, and excretion. Cells join together to form tis-sues, tissues join to form organs, and organs form body systems. To understandhow the organs and systems of the body work, one must first understand thecell. This understanding requires an investigation of the individual structuresthat make up the cell and of the separate function each structure carries outto serve the whole.

l Physiologic Concepts

CELL STRUCTURES

A cell is made up of internal structures separated from each other by semi-permeable membranes. These internal structures are bound together insideone cell membrane to form a single unit. Although cells differ as to theirfunction in the body, all cells contain the same internal structures. The insideof each cell can be divided into two main compartments: the cytoplasm andthe nucleus. All internal structures reside in the cytoplasm or the nucleus(Table1-1).

1

77251_ch01 30/06/10 11:52 AM Page 3

4 UNIT I Fundamental Mechanisms of Health and Disease

TABLE 1-1 Cell Structures (Fig. 1-1)

Structure Description/Function

Cytoplasm Mitochondria Energy source

Endoplasmic reticulum Protein synthesis

Ribosomes Protein synthesis

Golgi apparatus Secretes synthesized protein

Lysosomes Digestive enzymes

Cytoskeleton Support; movement of substances(microtubules, microfilaments)

Microtubules Chromosome separation during cell division; maintain structural integrity

Nucleus Control center

Deoxyribonucleic acid (DNA) Genetic material

Cell Membrane Semipermeable barrier surrounding each cell

Composed of phospholipids bilayer

Phospholipid Bilayer Consist of polar head with phosphateand nonpolar head

Diffusion of lipid-soluble substances

Integral Proteins Extend through the membrane

Glucose or lipid bound on extracellu-lar side

Receptor molecules for hormones

Facilitate cell communication

Channels for movement of ions

Some are enzymes to catalyze reactions

Necessary for nonlipid substances toenter the cell

MOVEMENT THROUGH THE MEMBRANE

Lipid-soluble substances, such as oxygen, carbon dioxide, alcohol, and urea,move across the lipid bilayer by simple diffusion. Other substances that are notlipid soluble, such as most small ions, glucose, amino acids, and proteins, movebetween the extracellular fluid and the intracellular compartments throughpores provided by the integral proteins or through carrier-mediated transportsystems. Carrier-mediated transport also originates in the integral proteins. Theextracellular fluid consists of the fluid between the cells, called the interstitialfluid, and the blood. The fluid inside the cell is called the intracellular fluid.

77251_ch01 30/06/10 11:52 AM Page 4

Simple Diffusion through the Cell Membrane

Simple diffusion occurs through random movement of molecules from an areaof higher concentration to an area of lower concentration until equilibrium isreached (Fig. 1-2). This process does not require energy, but can result in themovement of a substance across a membrane. However, the substance cannotaccumulate in higher concentration on one side of the membrane comparedto the other.

Osmosis

The movement of water across a semipermeable membrane from an area oflower particle concentration to an area of higher concentration is called os-mosis. The drive for water to move in one direction or the other is describedas the osmotic pressure. The osmotic pressure of a solution depends on thenumber of particles or ions present in the water solution and the hydrostaticpressure (mechanical water force against cell membranes). The more ions are


Cilia

MicrovilliSecretoryvesicles

Peroxisome

Golgiapparatus

Mitochondrion

Roughendoplasmicreticulum

Nuclearenvelopesurroundingnucleus

Nuclearpores

Lysosome

Cellmembrane

Smoothendoplasmic reticulum

Freeribosomes

Nucleolus

Chromatin

Microtubule

F I G U R E 1 - 1 Cell structure with major components. (From Porth, C. &Matfin, G [2009]. Pathophysiology, concepts of altered health states [8th edition]. Philadelphia: Lippincott Williams & Wilkins.)

77251_ch01 30/06/10 11:52 AM Page 5

present in the solution, the lesser is the water concentration and the greaterthe osmotic pressure (i.e., the pressure for water to diffuse into the solution).Osmosis continues until equilibrium is reached or hydrostatic pressure opposesthe flow.

Simple Diffusion through Protein Pores

Small ions, such as hydrogen, sodium, potassium, and calcium, are too elec-trically charged to diffuse through the lipid membrane of the cell. Instead, theydiffuse through the pores provided by the integral proteins. Selectivity of theprotein channels is based on the shape and size of the channel and the electricalnature of the ion.

Many protein channels are gated; they can be open or closed to an ion.Whether the gate is open or closed usually depends on the electrical potentialacross the gate (i.e., the voltage-gated sodium channel), or on binding to the


F I G U R E 1 - 2 Simple diffusion across a membrane. Molecules randomlydiffuse from an area of high concentration to an area of low concentration (A)until equilibrium is reached (B).

77251_ch01 30/06/10 11:52 AM Page 6

gate by a ligand that causes it to open or close. An example of ligand gating iswhen acetylcholine binds to proteins on the neuromuscular junction, therebyopening gates to many small molecules, especially sodium and, to a lesser ex-tent, calcium ions. Diffusion through a gate continues until the concentrationson either side of the membrane are equal or the gate is closed. Several humandiseases are related to dysfunction of transmembrane protein channels. Cysticfibrosis is the best-known human disease caused by a defective transmembraneprotein that results in abnormal ion movement through a pore.

Mediated Transport

For many substances like glucose and amino acids, simple diffusion is impos-sible. These molecules are too charged to pass through the lipid portion of themembrane or too large to pass through a pore. Instead, these substances, calledsubstrates, are transported across the membrane with the assistance of a carrier. This type of movement is called mediated transport and may requireenergy derived from the splitting of adenosine triphosphate (ATP) (see EnergyProduction section).

Active transport is mediated transport that requires energy (Fig. 1-3A).With active transport, energy is used by the cell to maintain a substance athigher concentration on one side of the membrane than the other. Examplesof substances moved by active transport include sodium, potassium, calcium,and the amino acids. Each of these substances is actively transported, with theassistance of a carrier, in one direction against a concentration gradient. It thenmoves down its concentration gradient by simple diffusion in the opposite direction.

Facilitated diffusion is mediated transport that does not require energy,but cannot concentrate a substance (Fig. 1-3B). Simple diffusion continuesat some level in all carrier-mediated systems. Facilitated diffusion is similarto simple diffusion in that no energy is used by the cell to transport a sub-stance; therefore, the substance cannot be transported against its concentra-tion gradient. With facilitated diffusion, a molecule that is limited in its abilityto cross the cell membrane on its own is assisted (facilitated) by a carrier tocross the membrane. For example, insulin increases the transport of glucoseinto most cells.

The Sodium–Potassium Pump

An important example of active transport is the pumping of sodium andpotassium across cell membranes. This transport depends on an integral car-rier protein known as the sodium–potassium pump. Associated with the pumpis an enzyme that splits ATP and provides the energy needed for the pump tofunction. This enzyme is known as the sodium–potassium ATPase. Thesodium–potassium pump transports sodium ions out of the cells to the extra-cellular region where the concentration is approximately 14 times that inside


77251_ch01 30/06/10 11:52 AM Page 7

the cell. Potassium ions are moved into the cell where the concentration is ap-proximately 35 times greater than outside the cell. This transport causes greatersodium concentration in the extracellular fluid (142 mEq/L) compared to theintracellular fluid (14 mEq/L), and greater potassium concentration in the in-tracellular fluid (140 mEq/L) compared to the extracellular fluid (4 mEq/L).The sodium–potassium pump carries three sodium molecules out of the cellfor every two potassium molecules it carries in.

The Effects of Pumping Sodium and Potassium

Because sodium and potassium are cations (carrying a positive charge), thetransport of three sodium ions out of the cell and only two potassium ionsinto the cell creates an electrical gradient across the cell membrane. It is thiselectrical membrane potential that allows nerve and muscle function and ac-tion potentials to occur (see Chapter 8).

The sodium–potassium pump is essential in controlling cell volume. Thepresence of intracellular proteins and other organic substances that cannotcross the cell membrane increases intracellular osmotic pressure and creates


F I G U R E 1 - 3 Carrier transport. Active transport (A) requires energy to pro-vide a final difference in concentration; facilitated diffusion (B) does not re-quire energy, but cannot concentrate a substance. Simple diffusion continuesat some level in all carrier-mediated systems.

77251_ch01 30/06/10 11:52 AM Page 8

a tendency for water to diffuse into the cell. This diffusion of water, if unlim-ited, would cause the cell to swell and eventually burst. However, with the activetransport of three sodium ions out of the cell, the osmotic pressure inside thecell is reduced and the diffusion of water into the cell is contained.

Coupled Transport

Many substances are transported coupled to the active transport of sodium.These substances include glucose, amino acids, hydrogen ions, and calcium.The energy required for the transport of these other substances is indirectlysupplied through the splitting of ATP by the sodium–potassium ATPase. Thistype of transport is called secondary active transport.

Coupled transport can be in the same direction as sodium transport (co-transport) or it may occur in the direction opposite to that of sodium transport(countertransport). Both types of transport depend on the diffusion of sodiumdown its concentration gradient, which in turn depends on the active transportof sodium by the sodium–potassium pump. In cotransport, sodium attachesto a carrier that assists it in moving down its concentration gradient, from out-side the cell to inside; the other substance attaches to the same carrier, also onthe outside of the cell, and as sodium is moved into the cell, the coupled sub-stance moves with it. In countertransport, the coupled substance binds to thesodium carrier on the inside of the cell membrane with sodium on the outside.Therefore, when sodium is delivered to the inside of the cell, the other sub-stance is delivered to the outside.

Calcium Transport

Calcium can move by simple diffusion through the cell membrane, be trans-ported by coupled transport with sodium, or be moved by primary activetransport through a calcium pump. There are two known calcium pumps. Oneis part of an integral protein present in the cell membrane, which moves cal-cium out of the cell. The other is an intracellular pump, which pumps calciumout of the cytoplasm into intracellular compartments such as the sarcoplasmicreticulum. This results in sequestering calcium inside the cell. Both pumpskeep free intracellular calcium concentration low. The calcium pumps serveas ATPases, which derive energy needed to pump the calcium against its con-centration gradient by the splitting of ATP.

Characteristics of Carriers

Active transport and facilitated diffusion require carriers. All carriers are af-fected by the properties of specificity, saturation, and competition.

Specificity of carriers means that only certain substrates will be transportedby any one carrier. The carrier and its specific substrate appear to fit togetherlike a lock and a key.


77251_ch01 30/06/10 11:52 AM Page 9

Saturation of carriers means that at a certain concentration of substrate,all carriers will be filled and transport will level off. Additional substrate willnot increase transport across the membrane.

Competition of carriers occurs when there is more than one substratetransported by the same carrier. The multiple substrates compete with eachother for the limited number of carrier sites available. Many drugs, naturallyoccurring and synthetic, compete with endogenous hormones and neurotrans-mitters for various carrier molecules.

Endocytosis and Exocytosis

When large substances cannot enter the cell by diffusion or mediated transport,endocytosis (engulfment) of the substance by the cell membrane occurs.Pinocytosis is the engulfment of, fluids and small particles by vesicles and isimportant in the transport of proteins to the cytoplasm. Phagocytosis involvesthe engulfment and degradation of microorganisms such as bacteria. Bothprocesses require energy. Only cells of the immune system (i.e., macrophagesand neutrophils) perform phagocytosis.

Exocytosis involves the transport of intracellular substances such as debrisinto the extracellular spaces. It also plays a role in the release of substances syn-thesized in the cell such as hormones.

ENERGY PRODUCTION

Cells must produce energy for their own use. Cells extract energy from chem-ical bonds of food molecules by combining the food molecules with oxygeninside the mitochondria of the cell. The food molecules include glucose fromcarbohydrate metabolism, amino acids from protein metabolism, and fattyacids and glycerol from fat metabolism.

The process whereby the food molecules are combined with oxygen, leadingto the production of energy, is called oxidative phosphorylation. This processrequires several enzymes, working in sequential fashion in the mitochondria.The net result is the synthesis of the energy-rich molecule ATP. ATP is com-posed of the nitrogen base adenosine, the sugar ribose, and three phosphatemolecules bound together. As the major source of cellular energy, ATP containstwo high-energy bonds both of which contain approximately 12 kcal of po-tential energy.

Oxidative Phosphorylation of Glucose

Glycolysis, an anaerobic (without oxygen) process occurring in the cytoplasmis the initial step in the oxidative phosphorylation of glucose that occurs inthe mitochondria. During glycolysis, cytoplasmic enzymes convert glucose intopyruvic acid. This process requires two molecules of ATP and produces fourmolecules of ATP: a result of two net molecules. In times of oxygen deprivation,


77251_ch01 30/06/10 11:52 AM Page 10

glycolysis plays a limited but important role in supplying the cell with ATP (seeAnaerobic Glycolysis section).

If oxygen is present (aerobic), the molecules of pyruvic acid move into themitochondria where they enter the citric acid cycle, also called the Krebs cycle(Fig. 1-4) and are converted by enzymes present there into a compound calledacetyl coenzyme A (acetyl CoA). This process produces two more ATP molecules.Acetyl CoA is then enzymatically converted to carbon dioxide and hydrogen.The carbon dioxide diffuses out of the mitochondria and out of the cell, whereit is picked up by the blood supplying that cell. It is then carried to the lungs andexhaled from the body. The hydrogen atoms remaining in the mitochondriabegin the process of oxidative phosphorylation, during which they are combinedwith molecules of oxygen through an elaborate electron transport chain presentin the mitochondrial membrane. The result of this process is to produce atremendous amount of energy in the form of 36 ATP molecules. From the me-tabolism of one molecule of glucose, therefore, a total of 38 net ATP moleculesare formed (36 from oxidative phosphorylation and 2 from glycolysis).


NADH + H+

NADH + H+

NADH + H+

FADH2

ATP

Pyruvic acid

Acetyl-coenzyme ATo electrontransport

chain

To electrontransport

chain

Citric acidcycle

CoA

CO2

CO2

F I G U R E 1 - 4 Kreb’s or citric acid cycle. (From Porth, C. & Matfin, G [2009].Pathophysiology, concepts of altered health states [8th edition]. Philadelphia:Lippincott Williams & Wilkins.)

77251_ch01 30/06/10 11:52 AM Page 11

Oxidative Phosphorylation of Fatty Acids and Glycerol

The cell also uses free fatty acids and glycerol in oxidative phosphorylation toproduce ATP. Glycerol is a three-carbon carbohydrate, which undergoes gly-colysis in the cytoplasm and enters the Krebs cycle as acetyl CoA. Free fattyacids diffuse directly into the mitochondria where they are acted on by enzymesand transformed into acetyl CoA. This acetyl CoA also enters the Krebs cycle.The breakdown of one molecule of fat results in 463 molecules of ATP. Fat hasa five times greater weight per mole than glucose. Thus, gram for gram, themetabolism of fat provides about three times as much ATP as glucose metab-olism. Therefore, fat is a more efficient form of energy storage than carbohy-drate.

Oxidative Phosphorylation of Amino Acids

Amino acids enter the mitochondria after removal of the nitrogen molecule(deamination). After deamination, amino acids enter the Krebs cycle at variouspoints. Some, such as alanine, enter as pyruvic acid; others enter as later inter-mediates. Where the amino acids enter the Krebs cycle determines how manyhydrogen atoms they add to the electron transfer chain and thus how manyATP molecules are synthesized.

Anaerobic Glycolysis

If oxygen is unavailable, the pyruvic acid produced by glycolysis does notenter the Krebs cycle, but combines with hydrogen in the cytoplasm to formlactic acid. Although the two molecules of ATP produced in the breakdownof one molecule of glucose to pyruvic acid are available to keep the cell alive,this is a wasteful use of glucose because it results in the loss of the other 36molecules of ATP that would have been produced had pyruvic acid enteredthe Krebs cycle. This process can only continue for a short while before glu-cose is depleted.

The lactic acid produced by anaerobic glycolysis diffuses out of the cell andinto the bloodstream. This can create a decrease in plasma pH (an increase inplasma acidity). With the return of oxygen, lactic acid will be reconverted topyruvic acid, primarily in the liver, and the Krebs cycle will resume.

ENERGY USAGE

ATP formed in the mitochondria moves into the cytoplasm by a combinationof simple and facilitated diffusion. When needed by the cell, ATP can be brokendown rapidly into adenosine diphosphate (ADP) by enzymatic splitting of thebond between the last two phosphates. This results in the release of energy,which is used by the cell to perform its duties of solute transport, protein syn-thesis, reproduction, and movement.


77251_ch01 30/06/10 11:52 AM Page 12

Although it is through ATP synthesis and breakdown that energy is trans-ferred in the cell, very little ATP is stored in the cell. Instead, energy is storedin the form of substrates for ATP—as carbohydrates, fats, proteins, and theirmetabolic products. The other essential component for ATP production, oxy-gen, is continually delivered to all cells by the combined efforts of the cardio-vascular and respiratory systems.

CELL TYPES

Epithelial Cells

The tissue that lines most internal and external structures of the body is madeup of epithelial cells. These cells are packed together, providing support foroverlying structures. Epithelial tissue also acts as a protective barrier and amedium for absorption, secretion, and excretion. Examples of epithelial tis-sue include the skin (epidermis), the covering on all internal organs andtubules, the microvilli of the intestine, and the cilia lining the respiratorypassageways. Glandular cells that secrete substances into ducts (exocrineglands) or into the bloodstream (endocrine glands) are made of epithelialtissue. Sensory organs also contain epithelial cells. Epithelial layers are usuallyone (simple epithelium) to two (stratified and pseudostratified epithelia)cells thick.

Connective Tissue Cells

Connective tissue is represented by many different cell types, including fibrob-lasts, adipose (fat) cells, mast cells, blood cells, and cells of the blood-formingorgans. Connective tissue holds different tissues together by the accumulationof protein and gel-like substances secreted from the fibroblasts into the spacessurrounding the cells. Protein substances secreted include collagen, a thick,white fiber that acts to provide structural support; elastin, a stretchy proteinthat allows tissues to give when stretched; and reticular fibers, thin flexiblestrands that allow organs to accommodate increases in volume. Tissue gel consists primarily of hyaluronic acid, which intersperses throughout the in-terstitial spaces to retain water and provide support and protection.

Adipose tissue and endothelial cells provide nourishment and support forthe fibroblasts. Mast cells contain granules filled with histamine and other va-soactive substances. Mast cell degranulation is an important step in initiatingan inflammatory reaction.

Hematopoietic tissue is considered connective tissue. Hematopoietic tissueincludes bone marrow, blood cells, and lymphatic tissue. The basement mem-brane found along the interface between connective tissue and an adjacent tis-sue is also considered a connective tissue layer. This membrane bonds,supports, and allows for tissue repair.


77251_ch01 30/06/10 11:52 AM Page 13

Muscle Cells

Muscle cells are highly differentiated (specialized) cells that have the ability tocontract and cause movement or increased tension. Groups of muscle cellsform one of the three types of muscle tissue: skeletal, smooth, or cardiac.

Muscle cells are composed of the proteins actin and myosin. Cross-bridgeslocated between the actin and myosin connect and swing when stimulated inthe proper sequence (see Chapter 10). This causes the muscle as a whole tocontract and do work or produce tension. All types of muscles require an in-crease in intracellular calcium to contract. Different muscles may use differentsources of calcium and thus have slightly different methods of contractionstimulation.

Skeletal muscle is attached to bones by tendons. When stimulated by motorneuron impulses, skeletal muscle voluntarily contracts. Skeletal muscle usescalcium released from intracellular compartments to initiate contraction. Ma-ture skeletal muscle does not undergo further cell division. Skeletal muscle mayeven be considered a paracrine endocrine organ because it secretes cytokinessuch as interleukin-8 (IL-8), a peptide that induces angiogenesis (new capillaryformation).

Cardiac muscle, found in the heart, contracts spontaneously because of anintrinsic ability to depolarize and fire action potentials. Cardiac muscle is in-nervated by the nerves of the autonomic nervous system: the sympathetic andparasympathetic nerves. These inputs can increase or decrease the inherentrate or strength of cardiac contraction. Cardiac contraction involves entry ofcalcium into the muscle cell from the extracellular fluid and from an intracel-lular compartment, the sarcoplasmic reticulum. During embryogenesis, cardiacmuscle cells become highly differentiated and do not undergo further cell di-vision. Cardiac muscle is also an endocrine organ in that it secretes the hor-mone atrial natriuretic peptide (ANP) that acts on the kidney to participatein the control of blood volume.

Smooth muscle is found throughout the body, including the vascular sys-tem, the genitourinary tract, and all parts of the gut. Its function is often con-sidered involuntary. Smooth muscle is innervated by the autonomic nervoussystem, which can increase or decrease the rate of contraction. When stretched,smooth muscle responds with an increase in contraction. Smooth muscle reliesprimarily on calcium entry from the extracellular fluid to initiate contraction.Mature smooth muscle cells can undergo cell division.

STEM CELLS

In general, as body cells become differentiated (specialized), they become lessable to reproduce and thus eventually die. Stem cells are undifferentiated (non-specialized) cells that have the ability to reproduce indefinitely and act as pro-genitors of other, specialized body cells. As specialized cells die, they can be


77251_ch01 30/06/10 11:52 AM Page 14

lwbk942-fm.qxd 6/25/11 8:45 am page...

Documents