Toxicologic pathology integrates toxicology and the disciplines within it (such as biochemistry, pharmacodynamics and risk assessment) to pathology and its related disciplines (such as physiology, microbiology, immunology, and molecular biology). Fundamentals of Toxicologic Pathology 2e updates the information presented in the first edition, including five entirely new chapters addressing basic concepts in toxicologic pathology, along with color photomicrographs that show examples of specific toxicant-induced diseases in animals. The current edition also includes comparative information that will prove a valuable resource to practicioners, including diagnostic pathologistis and toxicologists.
NOW FEATURING:
. 25% brand new information, fully revised throughout
. New chapters: Veterinary Diagnostic Toxicologic Pathology; Clinical Pathology; Nomenclature: Terminology for Morphologic Alterations; Techniques in Toxicologic Pathology
. New color photomicrographs detailing specific toxicant-induced diseases in animals
. Mechanistic information integrated from both toxicology and pathology discussing basic mechanisms of toxic injury and morphologic expression at the subcellular, cellular, and tissue levels
Author(s): Wanda M. Haschek, Colin G. Rousseaux, Matthew A. Wallig
Edition: 2
Publisher: Academic Press
Year: 2009
Language: English
Pages: 686
Cover Page......Page p0001.djvu
Dedications......Page p0002.djvu
Copyright......Page p0003.djvu
Preface......Page p0004.djvu
Acknowledgments......Page p0005.djvu
Passage through Pores......Page p0006.djvu
Blood–Brain Barrier......Page p0007.djvu
Epoxide Hydrase......Page p0008.djvu
ENZYME LOCATION IN TOXICITY......Page p0009.djvu
Biliary Excretion......Page p0010.djvu
INHIBITION......Page p0011.djvu
Electrophiles and Covalent Binding......Page p0012.djvu
Free Radicals and Lipid Peroxidation......Page p0013.djvu
Manifestations of Toxic Cell Injury: Cell Injury/Death and Chemical Carcinogenesis......Page p0014.djvu
Factors Influencing Injury......Page p0015.djvu
Adaptation......Page p0016.djvu
Hypertrophy......Page p0017.djvu
Cell Swelling......Page p0018.djvu
Fatty Change......Page p0019.djvu
Oncotic Necrosis......Page p0020.djvu
Apoptotic Necrosis......Page p0024.djvu
Sequelae to Oncotic Necrosis......Page p0026.djvu
Hyperplasia......Page p0027.djvu
Overview......Page p0028.djvu
Nomenclature of neoplasms......Page p0029.djvu
Physiological Hyperplasia......Page p0030.djvu
Anaplasia......Page p0031.djvu
Neoplastic Cell Proliferation......Page p0032.djvu
Initiation......Page p0033.djvu
Progression......Page p0034.djvu
undefined......Page p0035.djvu
Blocked Differentiation......Page p0036.djvu
Viral Hypothesis of Carcinogenesis......Page p0037.djvu
Proto-oncogene Activation......Page p0038.djvu
Oncogene Activation in Chemical Carcinogenesis......Page p0039.djvu
Retinoblastoma Checkpoint......Page p0041.djvu
In Vivo Chronic Rodent Carcinogenesis Studies......Page p0042.djvu
Rat Mammary Neoplasm Test......Page p0044.djvu
Genetically Altered Mouse Models for Carcinogenicity......Page p0045.djvu
Conclusion......Page p0046.djvu
Introduction......Page p0048.djvu
Parameters Generally Included in Study Protocols......Page p0049.djvu
Interpretative Hematology......Page p0050.djvu
Causes of Increases in Red Cells, Leukocytes, and Platelets......Page p0051.djvu
Causes of Decreases in Red Cells, Leukocytes, and Platelets......Page p0052.djvu
Bone Marrow Evaluation......Page p0054.djvu
Cholesterol, Triglycerides, and Glucose......Page p0055.djvu
Serum Proteins......Page p0058.djvu
Indicators of Hepatic Integrity and Function......Page p0059.djvu
Electrolytes......Page p0061.djvu
Microsomal enzyme induction......Page p0062.djvu
Urinalysis......Page p0063.djvu
Interpretation of clinical pathology results......Page p0064.djvu
Species Differences......Page p0065.djvu
Comparators: Concurrent Controls, Reference Ranges......Page p0066.djvu
Direct Versus Indirect Effects......Page p0067.djvu
Biological Importance of Treatment-related Effects......Page p0068.djvu
Summary......Page p0069.djvu
Introduction......Page p0071.djvu
Terminology issues......Page p0072.djvu
Training......Page p0077.djvu
Multiple Pathologists......Page p0078.djvu
Lesion Complexity......Page p0079.djvu
Recording Pathology Data......Page p0080.djvu
Suggested practices......Page p0081.djvu
Summary......Page p0082.djvu
Introduction......Page p0084.djvu
Factors influencing evaluation of altered morphology......Page p0085.djvu
Fresh Versus Autolyzed Tissue......Page p0087.djvu
Histologic Preparation......Page p0088.djvu
Species, Strain, Sex, and Age......Page p0090.djvu
undefined......Page p0091.djvu
Physiologic Phenomena......Page p0092.djvu
Nutrition......Page p0093.djvu
Factors Related to Nomenclature......Page p0094.djvu
Introduction......Page p0096.djvu
Macroscopic and Microscopic Anatomy......Page p0097.djvu
Overview......Page p0098.djvu
Overview......Page p0099.djvu
Airway Cells......Page p0100.djvu
Cells of the Pulmonary Parenchyma......Page p0101.djvu
Blood Vessels, Lymphatics, and Nerves......Page p0102.djvu
Nonspecific Defense Mechanisms......Page p0103.djvu
Specific Defense Mechanisms......Page p0104.djvu
Deposition, Absorption, Distribution, and Excretion of Inhaled Agents......Page p0105.djvu
Uptake and Accumulation of Blood-borne Toxicants......Page p0106.djvu
Mechanisms of toxicity......Page p0107.djvu
Metabolic Activation......Page p0108.djvu
Immune-mediated Toxicity......Page p0109.djvu
Toxicity and Responses to Inhaled Particles......Page p0111.djvu
Response to injury......Page p0112.djvu
Cell-specific Versus Nonspecific Injury......Page p0113.djvu
Overview......Page p0114.djvu
undefined......Page p0115.djvu
Overview......Page p0116.djvu
Asthma......Page p0119.djvu
Overview......Page p0121.djvu
Overview......Page p0122.djvu
Specific Etiologic Agents......Page p0123.djvu
Overview......Page p0124.djvu
Interstitial Pneumonia......Page p0125.djvu
Interstial Pneumonia in Veterinary Medicine......Page p0126.djvu
Pathogenesis......Page p0127.djvu
Specific Etiologic Agents......Page p0128.djvu
Pathogenesis......Page p0129.djvu
undefined......Page p0130.djvu
Evaluation of toxicity......Page p0131.djvu
Isolated Perfused Lung......Page p0132.djvu
Bronchopulmonary Lavage......Page p0133.djvu
Tracheobronchial Tree and Pulmonary Parenchyma......Page p0134.djvu
Animal Models......Page p0135.djvu
Conclusions......Page p0136.djvu
Introduction......Page p0137.djvu
Structure and Function of Skin......Page p0138.djvu
Comparative Mechanismsof Cutaneous Toxicity......Page p0143.djvu
Response of Skin To Injury......Page p0149.djvu
Evaluation of Cutaneoustoxicity......Page p0158.djvu
Structure and Function of Theoral Mucosa......Page p0161.djvu
Response of Oral Mucosato Injury......Page p0162.djvu
Further Reading......Page p0163.djvu
Introduction......Page p0164.djvu
Esophagus......Page p0165.djvu
Stomach......Page p0166.djvu
Small Intestine......Page p0169.djvu
Colon......Page p0171.djvu
Enteric Lymphoid System......Page p0172.djvu
Biotransformation......Page p0173.djvu
Enterohepatic Circulation......Page p0175.djvu
Intestinal Barrier Function......Page p0176.djvu
Stomach......Page p0178.djvu
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)......Page p0179.djvu
Steroidal Compounds......Page p0180.djvu
Heavy Metals......Page p0181.djvu
Hypersensitivity......Page p0182.djvu
Stomach......Page p0184.djvu
Diarrhea......Page p0185.djvu
Inflammatory Response......Page p0187.djvu
General......Page p0188.djvu
Small and Large Intestines......Page p0189.djvu
Esophagus......Page p0190.djvu
Small Intestine......Page p0191.djvu
In Vitro Strategies......Page p0192.djvu
Molecular Pathology......Page p0193.djvu
Morphologic Methods......Page p0194.djvu
Specific Models......Page p0195.djvu
Metabolism......Page p0196.djvu
Structure and function......Page p0198.djvu
The Hepatocyte......Page p0199.djvu
Mechanisms of toxicity......Page p0201.djvu
Cellular Mechanisms of Toxicity......Page p0202.djvu
Non-neoplastic responses to injury......Page p0203.djvu
Central Lobular (Centrilobular) Necrosis......Page p0209.djvu
Periportal Necrosis......Page p0211.djvu
Massive (Diffuse) Necrosis......Page p0212.djvu
Focal (Non-zonal) Necrosis......Page p0213.djvu
Apoptosis......Page p0214.djvu
Hepatic Lipidosis......Page p0215.djvu
Glycogen Accumulation......Page p0216.djvu
Iron Accumulation and Toxicity......Page p0217.djvu
Copper Accumulation and Toxicity......Page p0218.djvu
Polysome Breakdown......Page p0219.djvu
Peroxisomes......Page p0220.djvu
Hepatocellular Proliferation......Page p0221.djvu
Acute Necrosis of Bile Ducts......Page p0222.djvu
Bile Duct Hyperplasia......Page p0223.djvu
Oval Cell Hyperplasia......Page p0224.djvu
Stellate Cell Lesions......Page p0225.djvu
Hepatitis......Page p0226.djvu
Specific Etiologic Examples......Page p0227.djvu
Hepatocellular Neoplasia......Page p0229.djvu
Bile Duct Neoplasms......Page p0231.djvu
Evaluation of toxicity......Page p0232.djvu
Specialized Evaluation......Page p0233.djvu
Clinical Chemistry Evaluation......Page p0234.djvu
Use of Animals as Models......Page p0235.djvu
Summary and conclusions......Page p0236.djvu
Introduction......Page p0237.djvu
Microscopic Anatomy and Ultrastructure......Page p0238.djvu
Physiology of Exocrine Pancreas......Page p0240.djvu
Comparative Mechanisms of Exocrine Pancreatic Toxicity......Page p0241.djvu
undefined......Page p0243.djvu
undefined......Page p0244.djvu
Mutation......Page p0246.djvu
Carcinogenesis......Page p0247.djvu
Evaluation of Exocrine Pancreatic Toxicity......Page p0248.djvu
Methods of Testing......Page p0249.djvu
Summary and Conclusions......Page p0250.djvu
Microscopic Anatomy and Ultrastructure......Page p0251.djvu
Physiology of Endocrine Pancreas......Page p0252.djvu
Insulin-dependent Diabetes Mellitus......Page p0253.djvu
Non-insulin-dependent Diabetes Mellitus......Page p0254.djvu
Cyproheptadine......Page p0255.djvu
Necrosis......Page p0256.djvu
Insulitis......Page p0257.djvu
Summary and Conclusions......Page p0258.djvu
Introduction......Page p0261.djvu
Renal Structure and Function......Page p0262.djvu
Mechanisms of Toxicity......Page p0273.djvu
Response To Injury......Page p0303.djvu
Evaluation of Toxicity......Page p0314.djvu
Further Reading......Page p0317.djvu
Cardiovascular and Skeletal Muscle Systems\rsection I Heart......Page p0319.djvu
Gross and Microscopic Anatomy......Page p0320.djvu
Ventricular Myocytes......Page p0321.djvu
Components of Myocardial Interstitium......Page p0322.djvu
Myocardial Metabolism......Page p0323.djvu
Physiological Mechanisms of Functional Alterations......Page p0324.djvu
Biochemical Mechanisms of Cardiotoxicosis......Page p0328.djvu
Hypersensitivity Reactions......Page p0329.djvu
Organellar Localization of Injury......Page p0330.djvu
Response to Injury......Page p0331.djvu
Developmental Cardiotoxicities......Page p0334.djvu
Agents which Alter Cardiac Functions without Causing Morphologic Alterations......Page p0335.djvu
Dilated Cardiomyopathies......Page p0336.djvu
Degeneration Due to Sublethal Cardiac Muscle Cell Injury (See Figure 12.3)......Page p0338.djvu
Necrosis, Myocarditis, and Postnecrotic Resolution (see Figure 12.4)......Page p0340.djvu
Necrosis with Contraction Bands......Page p0344.djvu
Evaluation of Cardiotoxicity......Page p0346.djvu
Monitoring Myocardial Contractile Function......Page p0347.djvu
Monitoring Myocardial Electrical Activity......Page p0348.djvu
Microscopic Examination......Page p0349.djvu
Introduction......Page p0351.djvu
Blood Circulation and Tissue Perfusion......Page p0352.djvu
Vascular Function......Page p0353.djvu
Vasculotoxic Effects of Xenobiotics......Page p0355.djvu
Brain......Page p0356.djvu
Response to Injury......Page p0357.djvu
Atherosclerosis......Page p0358.djvu
Calcification......Page p0360.djvu
Medial Hemorrhagic Necrosis......Page p0361.djvu
Vasculitis......Page p0362.djvu
Direct Observations of Blood Vessels......Page p0363.djvu
Use of Animals as Models......Page p0364.djvu
Skeletal Muscle Fibers......Page p0365.djvu
Satellite Cells......Page p0366.djvu
Altered Neurogenic Function......Page p0367.djvu
Cell Membrane Alterations......Page p0368.djvu
Altered Protein Synthesis......Page p0369.djvu
Injury, Regeneration, and Repair......Page p0370.djvu
Degeneration and Necrosis (Myopathy)......Page p0371.djvu
Evaluation of Skeletal Muscle toxicity......Page p0373.djvu
Gross Examination......Page p0374.djvu
Microscopic Evaluation......Page p0375.djvu
Use of Animals as Models......Page p0376.djvu
Introduction......Page p0377.djvu
Structure and Function......Page p0378.djvu
Mechanisms of Disease and Classification......Page p0387.djvu
Evaluation of Neurotoxicity......Page p0405.djvu
Conclusions......Page p0409.djvu
Further Reading......Page p0410.djvu
Introduction......Page p0411.djvu
Skeletal Structure and Composition......Page p0412.djvu
Bone Physiology and Function......Page p0417.djvu
Mechanisms of Toxicity......Page p0420.djvu
Response of The Skeleton Totoxic Injury......Page p0428.djvu
Evaluation of Skeletal Toxicity......Page p0442.djvu
Summary......Page p0448.djvu
Further Reading......Page p0449.djvu
Function of the Immune System......Page p0451.djvu
Choice of the Effector Reaction......Page p0453.djvu
Neuroendocrine System–Immune System Interactions......Page p0455.djvu
Overview......Page p0456.djvu
Thymus......Page p0457.djvu
Lymph Nodes......Page p0460.djvu
Spleen......Page p0463.djvu
Lymphoid Tissue......Page p0465.djvu
Antigen-specific Interactions......Page p0467.djvu
Steroid Hormones......Page p0468.djvu
2 3,7,8-Tetrachlorodibenzo-p-dioxin and Related Compounds......Page p0471.djvu
Organotin Compounds......Page p0472.djvu
Irradiation......Page p0473.djvu
Heavy Metals......Page p0474.djvu
Cyclosporin......Page p0476.djvu
Response of the immune system to toxic injury......Page p0477.djvu
Morphology......Page p0478.djvu
Effects on Non-thymic Organs: Irradiation......Page p0479.djvu
Effect on Immature Thymocytes......Page p0480.djvu
Relation to Autoimmune Disease......Page p0483.djvu
Neoplasia......Page p0484.djvu
Inflammation in Nonlymphoid Tissues......Page p0485.djvu
Testing for Direct Immunotoxicity......Page p0486.djvu
Morphologic Techniques......Page p0487.djvu
Animal Models......Page p0488.djvu
Summary......Page p0489.djvu
Phylogeny......Page p0490.djvu
Gross and Microscopic Anatomy......Page p0491.djvu
Hematopoiesis......Page p0493.djvu
Cellular Kinetics......Page p0494.djvu
Idiosyncratic Reactions......Page p0495.djvu
Direct Damage......Page p0498.djvu
Damage to Erythrocytes......Page p0499.djvu
Myelotoxicity......Page p0500.djvu
General Considerations......Page p0502.djvu
Specific Responses......Page p0503.djvu
General Considerations......Page p0504.djvu
Specific Responses Resulting from Marrow Suppression......Page p0506.djvu
Specific Responses Associated with Increased Proliferation (Clonal Hemopathies)......Page p0508.djvu
Hematopoietic assessment......Page p0509.djvu
Summary......Page p0511.djvu
Gross and Microscopic Anatomy......Page p0512.djvu
Physiological and Functional Considerations......Page p0513.djvu
Disorders of Hyperfunction and Hypofunction......Page p0515.djvu
Morphologic Alterations......Page p0517.djvu
Characteristics of Proliferative Lesions......Page p0522.djvu
Anatomy......Page p0524.djvu
Functional Cytology......Page p0525.djvu
Neoplastic Lesions......Page p0526.djvu
Functional Characteristics of Pituitary Adenomas......Page p0528.djvu
Structure and Function......Page p0529.djvu
Proliferative Lesions of C-cells......Page p0530.djvu
Organogenesis......Page p0531.djvu
Species Differences in Thyroid Hormone Economy......Page p0532.djvu
Thyroid Hormone Secretion......Page p0533.djvu
Biological Action......Page p0534.djvu
Inhibition of thyroid peroxidase.......Page p0535.djvu
Blockage of thyroid hormone release by excess iodide and lithium.......Page p0536.djvu
Histopathological Criteria of Proliferative Lesions......Page p0537.djvu
Disorders of Thyroid Function......Page p0538.djvu
Diffuse hyperplastic (iodine-deficient) goiter.......Page p0540.djvu
Congenital (dyshormonogenetic) goiter.......Page p0541.djvu
Introduction......Page p0542.djvu
Parathyroid Hormone......Page p0543.djvu
Modification of Parathyroid Function Associated with Metabolic Disorders......Page p0545.djvu
Response of Parathyroid Chief Cells to Injury......Page p0546.djvu
Proliferative Lesions of Parathyroid Chief Cells......Page p0547.djvu
Assay of Circulating Parathyroid Hormone......Page p0549.djvu
Introduction......Page p0551.djvu
Gross Structure......Page p0552.djvu
Histology and Cell Biology......Page p0553.djvu
Spermatogenesis......Page p0556.djvu
Formation of the Blood-Tubule Barrier and Compartmetalization of the Seminiferous Epithelium......Page p0558.djvu
Testosterone Synthesis......Page p0560.djvu
Endocrine Regulation......Page p0561.djvu
Rete Testis......Page p0564.djvu
Vas Deferens......Page p0565.djvu
Seminal Vesicles......Page p0566.djvu
Mechanisms of Toxicity......Page p0567.djvu
Role of metabolism......Page p0568.djvu
Leydig cell......Page p0569.djvu
Germ Cells......Page p0570.djvu
Vascular effects and indirect toxicity to the testis......Page p0571.djvu
Epididymal and sperm toxicity......Page p0573.djvu
Leydig Cell Neoplasia......Page p0574.djvu
Effects via Estrogen Receptors, the Example of Methoxychlor......Page p0575.djvu
5-Reductase Inhibition, the Example of Finasteride......Page p0576.djvu
Responses to Injury......Page p0577.djvu
Germ Cell Apoptosis......Page p0578.djvu
Tubular and testicular necrosis......Page p0581.djvu
Disruption of sperm maturation......Page p0583.djvu
Gonadotroph Hypertrophy and Hyperplasia in the Pituitary......Page p0584.djvu
Reversibility......Page p0587.djvu
Phytoestrogens......Page p0588.djvu
Chlorinated Naphthalenes......Page p0590.djvu
Morphological Characterization......Page p0591.djvu
Quantitative Techniques......Page p0592.djvu
In Vitro Models......Page p0593.djvu
Conclusions......Page p0594.djvu
Introduction......Page p0596.djvu
Ovary......Page p0597.djvu
Uterus......Page p0600.djvu
Vagina......Page p0601.djvu
Hormonal Events during a Given Reproductive Cycle......Page p0603.djvu
Regulation of Hormonal Secretion......Page p0604.djvu
Type I Toxicity: Factors Which Induce Inactivity in Ovary, Uterus, and Vagina......Page p0606.djvu
Type III Toxicity: Factors Which Induce Hyperactivity in Ovary, Uterus, and Vagina......Page p0609.djvu
Uterus......Page p0610.djvu
Vagina......Page p0611.djvu
Type I Response: Atrophic Ovary, Uterus, and Vagina......Page p0612.djvu
Type II Response: Atrophic Ovary with Hyperactive Uterus and Vagina......Page p0613.djvu
Type III Response: Hyperplastic or Hypertrophic Ovary, Uterus, and Vagina......Page p0616.djvu
Irritation......Page p0617.djvu
Delayed Hypersensitivity......Page p0618.djvu
Phytoestrogens......Page p0619.djvu
Zearalenone......Page p0620.djvu
Chlorinated Naphthalenes......Page p0621.djvu
Ovary......Page p0622.djvu
Uterus......Page p0624.djvu
Design of Animal Study......Page p0625.djvu
Histological Examination......Page p0626.djvu
Summary......Page p0627.djvu
Overview of Fetal Toxicologic Pathology......Page p0629.djvu
Normal morphologic development......Page p0630.djvu
Morphogenic Movements......Page p0631.djvu
Restriction......Page p0633.djvu
Critical Phases of Intrauterine Development......Page p0634.djvu
Embryo and Fetus......Page p0635.djvu
Embryonic and Fetal Pharmacokinetics......Page p0636.djvu
Placenta......Page p0637.djvu
Death......Page p0638.djvu
Impeded Morphogenetic Movements......Page p0639.djvu
Mechanical Disruption......Page p0641.djvu
Perinatal Toxicology......Page p0642.djvu
Congenital Neoplasia......Page p0643.djvu
Hydrocephalus (Hydrocephaly)......Page p0644.djvu
Exencephaly......Page p0648.djvu
Anophthalmia and Microphthalmia......Page p0649.djvu
Agnathia and Micrognathia......Page p0650.djvu
Tricuspid Valve Anomalies......Page p0651.djvu
Renal Agenesis......Page p0652.djvu
Cryptorchidism......Page p0653.djvu
Digit Anomalies......Page p0654.djvu
Reduction Deformities......Page p0655.djvu
Default Assumptions......Page p0656.djvu
Laboratory Animal Studies......Page p0657.djvu
Human Studies......Page p0658.djvu
Short-term Tests......Page p0659.djvu
Dose–Response Evaluation......Page p0660.djvu
Clinical Examination and Pathology......Page p0661.djvu
Defining the Maternal Environment......Page p0662.djvu
“Natural” Experiments......Page p0663.djvu
Experimental Methodology......Page p0664.djvu
A......Page p0668.djvu
B......Page p0669.djvu
C......Page p0670.djvu
D......Page p0671.djvu
E......Page p0672.djvu
G......Page p0673.djvu
H......Page p0674.djvu
I......Page p0675.djvu
K......Page p0676.djvu
L......Page p0677.djvu
M......Page p0678.djvu
N......Page p0680.djvu
P......Page p0681.djvu
R......Page p0682.djvu
S......Page p0683.djvu
T......Page p0684.djvu
U......Page p0685.djvu
Z......Page p0686.djvu
