Ultrastructural Pathology

Norman F. Cheville, DVM, PhD, is Professor Emeritus of Veterinary Pathology at Iowa State University. Previously, he was Chair of the Department of Veterinary Pathology and Dean of the College of Veterinary Medicine at Iowa State University, and was Chief of Pathology at the National Animal Disease Center in Ames, Iowa.

Preface xi

Contributors xiii

Prologue xv

Part I: Structural Basis of Cell Injury 3

1 Response to Cellular Injury  5

Acute Cell Swelling 5

Adaptive Responses to Persistent Injury 21

2 Cell Death 33

Necrosis 35

Programmed Cell Death 40

Interplay of Necrosis and PCD 49

Getting Rid of the Dead Cell 52

Endothelial Cell Death 54

3 Cellular Defense and Recovery 61

Plasma Membrane in Recovery 61

Detoxification: Smooth Endoplasmic Reticulum and Peroxisomes 62

Mitochondria in Recovery 63

Nucleoli, DNA, and the Genome in Recovery 64

Proteostasis 67

Autophagy: Removal of Debris 69

Part II: Organelle Pathology 75

4 The Cell Surface 77

The Plasma Membrane 77

Cytoskeleton 86

Intercellular Junctions 97

Surface Structures 101

5 Intracellular Trafficking 109

Endocytosis 109

Phagocytosis 115

Lysosomes and Cytoplasmic Trafficking 116

Exocytosis 118

6 Nucleus, Ribosomes, the Golgi Complex, and Secretion 125

Nucleus 125

Ribosomes 136

Rough Endoplasmic Reticulum 138

Golgi Complex 139

Secretion 142

7 Peroxisomes, Smooth Endoplasmic Reticulum, and Lipids 153

Peroxisomes 153

Smooth Endoplasmic Reticulum 156

Glycogen 161

Lipids 164

Lipoproteins 169

Lipid Metabolism Disorders 173

8 Mitochondria 181

The Normal Mitochondrion 181

Mitochondrial Swelling: Response to Acute Injury 184

Mitochondriopathy of Metabolic and Chronic Diseases 188

Mitochondrial DNA-Based Disorders 193

Part III: Inflammation and Hemostasis 199

9 Endothelium 201

Endothelial Interface with Blood and Perivascular Space 201

Endothelial Thromboresistance vs. Procoagulation 206

Endothelial Response to Hypoxia and Circulatory Dysfunction 208

Inflammation 209

Mast Cell and Basophil Interface with Endothelium 217

Angiogenesis 223

10 Leukocytes and Platelets 231

The Neutrophil 231

Eosinophils 243

Platelets 246

Thrombosis 257

11 The Mononuclear Phagocyte System and Lymphocytes 269

The Monocyte-Macrophage System 269

Dendritic Cells 274

Lymphocytes 283

12 The Extracellular Matrix 295

Collagen Fibers 297

Microfibrils 303

Extracellular Ground Substance 304

Basement Membranes 307

Mucins and Other Barriers 310

Part IV: Infectious Diseases 317

13 Cytopathology of Viral Diseases 319

Family Poxviridae 319

Family Herpesviridae 327

Family Adenoviridae 338

Family Papillomaviridae 343

Family Polyomaviridae 347

Family Parvoviridae 349

Family Iridoviridae 353

Family Asfarviridae 353

Family Hepadnaviridae 354

Family Circoviridae 355

Family Orthomyxoviridae 356

Family Paramyxoviridae 358

Family Rhabdoviridae 366

Family Filoviridae 369

Family Coronaviridae 370

Family Reoviridae 373

Family Arenaviridae 379

Family Togaviridae 381

Family Arteriviridae 384

Family Bornaviridae 386

Family Flaviviridae 386

Family Bunyaviridae 391

Family Birnaviridae 392

Family Nadoviridae 394

Family Picornaviridae 394

Family Caliciviridae 399

Family Astroviridae 401

Family Retroviridae 401

14 Cytopathology of Pathogenic Prokaryotes 425

Structure of the Bacterial Cell 425

Phylum Tenericutes, Order Mycoplasmatales 442

Order Entomoplasmatales 447

Order Incertae Sedis 447

Phylum Proteobacteriae, Order Rickettsiales 448

Order Rhizobiales 453

Order Burkholderiales 457

Order Neisseriales 459

Order Campylobacterales 461

Order Aeromonadales 466

Order Enterobacteriales 466

Order Legionellales 476

Order Pasteurellales 477

Order Pseudomonadales 482

Order Thiotricales 484

Order Vibrionales 484

Phylum Chlamydiae, Order Chlamydiales 485

Order Actinomycetales 487

Phylum Firmicutes, Order Bacillales 496

Order Lactobacillales 500

Order Clostridiales 502

Order Spriochaetales 505

Order Bacteroidales 509

Order Fusobacteriales 510

Other Bacteria 510

15 Pathogenic Protozoa 525

Amoebas 526

Ciliates 528

Flagellates 529

Hemosporidians 538

The Malarial Organisms 543

The Coccidia 549

The Microsporans 560

Protozoa of Uncertain Taxonomy 563

16 Algae, Fungi, and Other Eukaryotes 573

Algae 573

Fungi 576

The Myxozoans 595

Intracelllar Metazoan Parasites 597

Part V: Toxicologic Diseases 605

17 Toxicologic Pathology 607

Lysosomotropic Hepatotoxins 609

Rough Endoplasmic Reticulum Hepatotoxins 613

Hepatotoxins and the Golgi Complex 619

Smooth Endoplasmic Reticulum and Hepatotoxicity 619

Mitochondrial Hepatotoxins 623

Steatosis and Hepatotoxicity 626

Hepatic Toxins That Act on the Nucleus 626

Hepatocyte Toxins That Act on the Cytoskeleton 627

Particulate Hepatotoxins 627

18 Myotoxins 635

Cardiotoxicity 635

Myocardial Toxins 643

Skeletal Muscle 651

Smooth Muscle Toxicity 658

19 Neurotoxins and Neurodegeneration 667

Introduction 667

Neuronopathies 668

Myelin Toxins: Myelinopathies 678

Neuropathies: The Peripheral Nerves 681

Neurotoxins That Act at Nerve Termini and Synapses 683

Glial Toxins 687

Vascular Neurotoxins and the Blood-Brain Barrier 688

20 Nephrotoxins 695

Glomerular Toxins 695

Proximal Convoluted Tubule Toxins 697

Distal Tubule Toxins 705

Toxins in the Medulla 705

The Juxtaglomerular Apparatus 708

Crystal Nephropathy 710

Confounding Lesions in Nephrotoxicity 711

21 Toxicity of Respiratory Systems 717

The Normal Mammalian Lung 717

Reaction to Pulmonary Toxins 719

Substances Damaging to Lung 723

Acute Toxic Pulmonary Injury 726

Chronic Inhalant Injury 728

Chronic Exhalant Toxicity 734

Comparative Respiratory Systems 736

Part VI: Pathologic Growth 741

22 The Cell Cycle: Dysfunction in Aging, Senescence, and Hibernation 743

The Cell Cycle 743

Regeneration 747

Aging and Senescence 750

Hibernation 751

Cell Senescence 752

23 The Neoplastic Cell 757

The Genomic Landscape 758

Benign or Malignant 761

Neoplastic Cell Structure 761

Neoplastic Cell Surfaces 763

The Nucleus of the Neoplastic Cell 766

Cytoplasm 769

The Tumor Microenvironment 775

Metastasis 780

Neoplastic Cell Death 785

Part VII: Diagnostic Pathology 795

24 Calcification 797

Intracellular Calcification 797

Extracellular Calcification 798

Microliths 802

25 Pigments 811

Melanin 811

Chromatophores 815

Hemoglobin-Derived Pigments 815

Erythrophagocytosis 817

Copper-Containing Pigments 822

Exogenous Pigments 824

26 Amyloid, Protein Misfolding Defects, and Inclusions 829

Amyloid 829

Tauopathies 839

Synucleinopathies 840

Misfolded Proteins and Inspissated Inclusions 842

27 Metabolic and Storage Diseases 857

Lipid Storage Diseases 857

Neuronal Ceroid Lipofuscinoses 862

Glycoproteinoses 863

Mucopolysaccharidoses 864

Mucolipidoses 866

Glycogen Storage Diseases 866

Amino Acid Transport Storage Diseases 869

Other Storage Diseases 870

28 Arteriopathy 875

Responses of the Artery to Injury 875

Atherosclerosis 881

29 The Renal Glomerulopathies 891

Membranous Glomerulonephritis 891

Proliferative Glomerulonephritis 898

Minimal Change Disease 900

Glomerulonephritis Associated with Systemic Disease 900

Diabetes 903

30 Prions 911

Prions Defi ned 911

The Transmissible Spongiform Encephalopathies 912

Index 917