Haschek and Rousseaux's Handbook of toxicologic pathology. Volume 5, Toxicologic pathology of organ systems /

Haschek and Rousseaux's Handbook of Toxicologic Pathology, Fourth Edition, Volume Five: Toxicologic Pathology of Organ Systems is a key reference on the integration of structure and functional changes in tissues associated with the response to pharmaceuticals, chemicals, and biologics. This boo...

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Bibliographic Details
Corporate Author:	ScienceDirect (Online service)
Other Authors:	Haschek, Wanda M. (Editor), Rousseaux, Colin G. (Editor), Wallig, Matthew A. (Editor), Bolon, Brad (Editor)
Format:	eBook
Language:	English
Published:	London, United Kingdom : Academic Press, 2025.
Edition:	Fourth edition.
Subjects:	Toxicology > Handbooks, manuals, etc. Physiology, Pathological > Handbooks, manuals, etc. Electronic books.
Online Access:	Connect to the full text of this electronic book

Table of Contents:

Front Cover
HASCHEK AND ROUSSEAUX'S HANDBOOK OF TOXICOLOGIC PATHOLOGY
HASCHEK AND ROUSSEAUX'S HANDBOOK OF TOXICOLOGIC PATHOLOGY
Copyright
Dedication
Contents
Contributors
About the Editors
EDITORS
ASSOCIATE EDITORS
ILLUSTRATIONS EDITOR
Preface
1
Cardiovascular System
1 INTRODUCTION
PART I: HEART
2 STRUCTURE AND FUNCTION
2.1 Gross and Microscopic Anatomy
2.1.1 Cellular and Extracellular Elements of the Heart
2.1.1.1 VENTRICULAR MYOCYTES
2.1.1.2 ATRIAL MYOCYTES
2.1.1.3 ELECTRICAL CONDUCTION SYSTEM
2.1.1.4 CELLULAR COMPONENTS OF MYOCARDIAL INTERSTITIUM
2.1.1.5 EXTRACELLULAR COMPONENTS OF MYOCARDIAL INTERSTITIUM
2.1.1.6 CELLULAR COMPONENTS OF THE MYOCARDIAL VASCULATURE
2.1.1.7 MYOCARDIAL INNERVATION
2.1.1.8 PERICARDIUM
2.1.1.9 ENDOCARDIUM
2.1.1.10 CARDIAC VALVES
2.2 Physiology and Functional Considerations
2.2.1 Phases of the Cardiac Cycle
2.2.2 Resting and Action Potentials of Cardiac Myocytes
2.2.3 Initiation and Conduction of Cardiac Impulses
2.2.4 Excitation-Contraction Coupling
2.2.5 Myocardial Metabolism
2.2.6 Innervation of the Heart
2.3 Xenobiotic Exposure
3 EVALUATION OF TOXICITY
3.1 Bioactivity Screening for Cardiac Toxicity
3.2 Functional Evaluation of Toxicity
3.2.1 Monitoring Myocardial Contractile Function
3.2.1.1 EX VIVO ISOLATED MUSCLE PREPARATIONS
3.2.1.2 EX VIVO ISOLATED PERFUSED HEART PREPARATIONS
3.2.1.3 IN VIVO INVASIVE PREPARATIONS
3.2.1.4 IN VIVO NONINVASIVE METHODS
3.2.2 Monitoring Myocardial Electrical Activity
3.2.2.1 EX VIVO HEART MUSCLE PREPARATION
3.2.2.2 IN VITRO CULTURED HEART CELLS
3.2.3 Complex In Vitro Modeling Systems
3.2.3.1 INTACT ANIMALS
3.2.4 Monitoring Arterial Blood Pressure
3.2.4.1 DIRECT METHODS TO MONITOR ARTERIAL BLOOD PRESSURE.
3.2.4.2 INDIRECT METHODS TO MONITOR ARTERIAL BLOOD PRESSURE
3.3 Morphologic Evaluation of Toxicity
3.3.1 Gross Examination
3.3.2 Microscopic Examination
3.3.3 Ultrastructural Examination
3.3.4 Quantification of Morphologic Alterations
3.3.5 Artificial Intelligence and Machine Learning
3.4 Background Alterations, Artifacts, and Spontaneous and Age-Related Lesions
3.5 Biomarkers
3.6 Biochemical Evaluation of Toxicity
4 RESPONSES TO INJURY
4.1 Developmental Cardiotoxicity
4.2 Cardiac Dysfunction as a Manifestation of Toxicity
4.2.1 Arrhythmias
4.2.2 Changes in Contractility
4.3 Changes in Cardiac Mass as a Response to Toxicity
4.4 Drug-Induced Cardiomyopathies
4.4.1 Alcoholic Cardiomyopathy
4.4.2 Antimicrobial Cardiomyopathy
4.4.3 Antineoplastic Cardiomyopathy
4.5 Cardiomyocellular Injury
4.5.1 Vacuolar Degeneration
4.5.2 Myofibrillar Degeneration
4.5.3 Lipofuscinosis
4.5.4 Phospholipidosis
4.5.5 Cardiomyocyte Necrosis
4.5.5.1 PROGRESSION OF MORPHOLOGIC ALTERATIONS FOLLOWING LETHAL CARDIOMYOCYTE INJURY
4.5.5.2 AGENTS THAT PRODUCE MYOCARDIAL NECROSIS
4.5.6 Myocardial Infarction Associated with Toxic Reactions
4.5.7 Hypersensitivity Myocarditis
4.6 Endocardium
4.6.1 Fibrosis
4.7 Neoplasia
4.8 Valves
4.8.1 Proliferative Valvulopathies
4.8.2 Degenerative/Inflammatory Valvulopathies
4.9 Epicardium
4.9.1 Epicardial Hemorrhage
4.10 Pericardium
5 MECHANISMS OF TOXICITY
5.1 Mechanisms of Altered Cardiac Function
5.1.1 Changes in Rate and Rhythm
5.1.2 Contractility
5.2 Mechanisms of Direct Cellular Injury
5.3 Mechanisms of Indirect Injury
5.4 Cardiotoxicity of Cardiac Drugs
5.5 Hypersensitivity Reactions
5.6 Xenobiotic Interactions
5.7 Modifying Factors in Cardiac Toxicity
6 CARDIOTOXICITY ISSUES IN DRUG DEVELOPMENT.
6.1 Cardiovascular-Related Drug Development Attrition
6.2 Rodent Progressive Cardiomyopathy
6.3 Animal Models of Human Cardiac Disease
6.4 Clinical Translation of Nonclinical Cardiotoxicity
PART II: BLOOD VESSELS
7 STRUCTURE AND FUNCTION
7.1 Microscopic Anatomy
7.2 Cellular and Extracellular Components of the Vasculature: Biology
7.2.1 Endothelial Cells
7.2.2 Smooth Muscle Cells
7.2.3 Pericytes and Veil Cells
7.2.4 Connective Tissue
7.3 Physiology and Functional Considerations
7.3.1 Blood Circulation and Tissue Perfusion
7.3.2 Endothelial Permeability
7.3.3 Metabolic Activities in Vascular Cells
7.3.4 Vascular Function
7.3.4.1 NEURAL INFLUENCES
7.3.4.2 LOCAL HUMORAL AND ENVIRONMENTAL INFLUENCES
7.3.4.3 RESPONSES OF BLOOD VESSELS TO VASOACTIVE SUBSTANCES
7.3.4.4 ELECTRICAL ACTIVITY AND INTRACELLULAR CALCIUM RESPONSES TO VASOACTIVE SUBSTANCES
7.3.4.5 EFFECTS OF ENDOTHELIAL CELL FUNCTION AND DAMAGE ON BLOOD-VESSEL ACTIVITY
8 EVALUATION OF TOXICITY: VASOTOXIC EFFECTS
8.1 Physiological Methods for Testing
8.1.1 Noninvasive Measurements of Blood Flow
8.1.2 Invasive Measurements of Blood Flow, Vascular Tone, and Microvasculature
8.2 In Vitro Methods for Detecting Vascular Toxicity
8.2.1 Isolated Vascular Preparations
8.2.2 Cellular Electrophysiological Methods
8.2.3 Cultured Vascular Smooth Muscle Cells
8.2.4 Human-Derived Induced Pluripotent Stem Cells
8.2.5 Emerging Technologies
8.3 Morphologic Evaluation
8.3.1 Gross Examination
8.3.1.1 PREPARATION OF TISSUES
8.3.2 Microscopic and Biochemical Evaluation
8.4 Background Alterations, Artifacts, Spontaneous and Age-Related Lesions
8.5 Use of Animals as Models for Vascular Toxicity
8.6 Biomarkers of Vascular Injury
9 RESPONSES TO INJURY
9.1 Atherosclerosis Acceleration by Toxic Agents.
9.2 Medial Proliferation
9.3 Intimal Proliferation
9.4 Calcification
9.5 Aneurysms
9.6 Medial Hemorrhagic Necrosis
9.7 Fibrinoid Necrosis
9.8 Microangiopathy
9.9 Immune-Mediated Vascular Inflammation
9.9.1 Hypersensitivity Vasculitis
9.9.2 Immune Complex-Mediated Vascular Injury
9.9.3 Lupus-Like Syndromes
9.10 Regeneration and Repair
10 VASCULAR TOXICITY IN SPECIFIC ORGANS
10.1 Brain
10.2 Lungs
10.3 Heart
10.4 Liver
10.5 Kidney
10.6 Stomach
11 CONCLUSION
REFERENCES
2
Kidney
1 INTRODUCTION
2 STRUCTURE, FUNCTION, AND CELL BIOLOGY
2.1 Renal Ontogeny
2.2 Renal Structure
2.2.1 Gross and Subgross Anatomy
2.2.2 Vasculature and Innervations
2.2.3 Microscopic and Ultrastructural Functional Anatomy
2.2.4 Glomerulus
2.2.5 Proximal Convoluted Tubule
2.2.6 Pars Recta
2.2.7 Thin Limbs of the Loop of Henle
2.2.8 Thick Ascending Limb and Distal Tubule
2.2.9 Juxtaglomerular Apparatus
2.2.10 Distal Convoluted Tubule
2.2.11 Collecting Ducts
2.2.12 Interstitium
2.2.13 Comparative Considerations-Age, Sex, and Species
2.3 Renal Function
2.3.1 Control of Body Water and Electrolytes
2.3.2 Potassium
2.3.3 Calcium and Phosphate
2.3.4 Magnesium
2.3.5 Elaboration of Hormones and Regulatory Peptides
2.3.6 Erythropoietin
2.3.7 Renin
2.3.8 Prostaglandins
2.3.8.1 RENAL TRANSPORTERS
2.3.8.1.1 COTRANSPORTERS (SECONDARY ACTIVE TRANSPORT)
2.3.9 Glucose Transporters
2.3.10 Xenobiotic Renal Transporters
2.3.11 Uptake Transporters
2.3.12 Efflux Transporters
2.3.13 Protein and Amino Acid Transport
2.3.14 Control of Acid-Base Balance
2.3.15 Insulin Metabolism
2.3.16 Fatty Acid Utilization
2.3.17 Cholesterol Control
2.3.18 Renal Xenobiotic Metabolism
2.3.19 Renal Clearance and Toxicity
2.4 Renal Cell Biology.