Essentials of pathology for toxicologists

Contents List of tables vii List of figures viii Acknowledgements ix Preface x On the threshold xii Introduction xiii The pathologist’s tools xv The pathologist’s report xvi 1 Cellular pathology 1 1.1 The cell and cell damage 1 1.2 Necrosis and apoptosis 8 1.3 Reactive responses 9 2 Tissue pathology 12 2.1 Obstructive lesions 12 2.2 Inflammation—acute 13 2.3 Inflammation—chronic 15 2.4 Tissue injury, restitution, repair 18 3 Cancer 22 3.1 Neoplasia 22 3.2 Causation of tumours 26 4 Immunology—an introduction 28 4.1 Innate (non-specific) immunity 28 4.2 Acquired (specific) immunity 29 5 Causation of disease 32 5.1 Genetically determined 32 5.2 Acquired—infective agents 32 5.3 Congenital disease 33 6 Some recent advances in pathology 35 6.1 Recurrent themes in pathology 36 6.2 Apoptosis 36 6.3 Adaptation 37 6.4 Target organ toxicity 37 6.5 Oncogenes 38 7 Clinical chemistry 39 7.1 Enzymes 40 7.2 Proteins in plasma 49 7.3 Hormones and steroids in plasma 52 7.4 Biochemical changes related to chemical toxicity 53 7.5 Methodologies—general 57 7.6 Summary and conclusion 59 8 Haematology 62 8.1 Cytology 62 8.2 Haematology and toxicology studies 64 8.3 Historical data 66 Glossary 71 Further reading on pathology 116 Further reading on clinical chemistry 118 Further reading on haematology 119 Index 120 vi Tables 1.1 Comparative composition of oedema fluid 11 2.1 Inflammatory lesion 17 3.1 Character of a tumour 23 4.1 Summary of innate and acquired immunity defenses 30 7.1 International classification of enzymes and major sub-classes 41 7.2 Intracellular location of some major enzyme systems in mammalian metabolism pathways (also included are some enzymes in the G.I.Microflora) 43 7.3 Serum enzymes of diagnostic value indicative of tissue injury 44 7.4 Enzymic processes mediating the metabolic bioactivation and detoxification of foreign compounds 45 7.5 Isoforms of the Cytochrome P–450 superfamily mediating mixed function oxidase reaction 49 7.6 Examples of proteins in plasma of potential diagnostic value for monitoring disease 50 7.7 Examples of plasma proteins as markers of tumours 51 7.8 Examples of some hypothalamic releasing hormones and their effects on anterior pituitary hormone production 53 7.9 Examples of some endocrine derived substances of diagnostic value 54 7.10 Changes in biochemical markers in body fluid indicative of target organ toxicity 57 8.1 The life cycle of red and white cells 63 8.2 Measurements commonly included in haematological examinations 67 8.3 Examples of measurements that may be included for the investigation of haematological effects 68 Figures 1.1 Cellular organelles—they carry out most of the important functions of the cell. 2 1.2 Cell nutrition. 3 1.3 Mitosis. 4 1.4 Intracellular oedema—an early marker of cell damage. 5 1.5 Fatty change—a marker of cell damage. 7 1.6 Programmed and random cell death. 10 2.1 A developing abscess. 14 2.2 An abscess in a portion of lung. 16 2.3 Chronic inflammation. 16 2.4 Repair by restitution. 19 2.5 Repair by fibrosis. 20 3.1 Spread of cancer in tissues (macroscopic). 23 3.2 Papilloma—a benign tumour. 24 3.3 Advanced growth by permeation of the tissue spaces. 24 3.4 Tumour breaching basement member prior to infiltration. 26 4.1 Antigen surrounded by complement and antibodies prior to lysis. 29 4.2 B-lymphocyte. 30 4.3 T-lymphocyte. 31 7.1 Bioactivation and detoxification scheme for foreign chemicals. 47