Dr Andrew Blann, FRCPath FIBMS CSci, Consultant Clinical Scientists and Honorary Senior Lecturer in Medicine, University Department of Medicine, UK; Deputy Chief Examiner in Haematology with the Institute of Biomedical Science and an Examiner in Haematology with the Royal College of Pathologists.

Dr Nessar Ahmed, CSci FIBMS, Reader in Clinical Biochemistry, School of Healthcare Science, Manchester Metropolitan University, UK.

Preface, xiii

Acknowledgements, xv

List of Abbreviations, xvii

About the Companion Website, xxi

1 Introduction to Blood Science, 1

1.1 What is blood science?, 1

1.2 Biochemistry, 6

1.3 Blood transfusion, 8

1.4 Genetics, 10

1.5 Haematology, 14

1.6 Immunology, 17

1.7 The role of blood science in modern healthcare, 19

1.8 What this book will achieve, 22

Summary, 23

References, 23

Further reading, 23

Web sites, 23

2 Analytical Techniques in Blood Science, 25

2.1 Venepuncture, 25

2.2 Anticoagulants, 26

2.3 Sample identification and tracking, 27

2.4 Technical and analytical confidence, 27

2.5 Major techniques, 32

2.6 Molecular genetics, 43

2.7 Point of care testing, 47

2.8 Health and safety in the laboratory, 48

Summary, 49

Further reading, 50

Web sites, 50

3 The Physiology of the Red Blood Cell, 51

3.1 Introduction, 51

3.2 The development of blood cells, 52

3.3 Erythropoiesis, 56

3.4 The red cell membrane, 58

3.5 The cytoplasm of the red cell, 60

3.6 Oxygen transport, 66

3.7 Recycling the red cell, 68

3.8 Red cell indices in the full blood count, 69

3.9 Morphology of the red cell, 72

Summary, 74

Further reading, 74

4 The Pathology of the Red Blood Cell, 75

4.1 Introduction: diseases of red cells, 75

4.2 Anaemia resulting from attack on, or stress to, the bone marrow, 78

4.3 Anaemia due to deficiency, 80

4.4 Intrinsic defects in the red cell, 85

4.5 External factors acting on healthy cells, 100

4.6 Erythrocytosis and polycythaemia, 103

4.7 Molecular genetics and red cell disease, 105

4.8 Inclusion bodies, 105

4.9 Case studies, 105

Summary, 107

References, 107

Further reading, 107

5 White Blood Cells in Health and Disease, 109

5.1 Introduction, 109

5.2 Leukopoiesis, 111

5.3 Neutrophils, 115

5.4 Lymphocytes, 116

5.5 Monocytes, 117

5.6 Eosinophils, 118

5.7 Basophils, 119

5.8 Leukocytes in action, 120

5.9 White cells in clinical medicine, 127

5.10 Case studies, 132

Summary, 132

Further reading, 133

6 White Blood Cell Malignancy 135

6.1 The genetic basis of leukocyte malignancy, 135

6.2 Tissue techniques in haemato-oncology, 139

6.3 Leukaemia, 141

6.4 Lymphoma, 149

6.5 Myeloma and related conditions, 152

6.6 Myelofibrosis and myelodysplasia, 157

6.7 Case studies, 157

Summary, 158

Further reading, 159

Guidelines, 159

7 The Physiology and Pathology of Haemostasis, 161

7.1 The blood vessel wall, 162

7.2 Platelets, 163

7.3 The coagulation pathway, 165

7.4 Haemostasis as the balance between thrombus formation and removal, 168

7.5 The haemostasis laboratory, 171

7.6 The pathology of thrombosis, 173

Summary, 175

Further reading, 175

8 The Diagnosis and Management of Disorders of Haemostasis, 177

8.1 Thrombosis 1: overactive platelets and thrombocytosis, 177

8.2 Thrombosis 2: overactive coagulation, 181

8.3 Haemorrhage 1: platelet underactivity and thrombocytopenia, 193

8.4 Haemorrhage 2: coagulation underactivity, 199

8.5 Disseminated intravascular coagulation, 203

8.6 Molecular genetics in haemostasis, 204

8.7 Case studies, 205

Summary, 206

References, 206

Further reading, 207

Guidelines, 207

Web sites, 207

9 Immunopathology, 209

9.1 Introduction, 209

9.2 Basics of the immune system, 210

9.3 Humoral immunity, 212

9.4 Immunopathology 1: immunodeficiency, 215

9.5 Immunopathology 2: hypersensitivity, 221

9.6 Immunopathology 3: autoimmune disease, 226

9.7 Immunotherapy, 232

9.8 The immunology laboratory, 234

9.9 Case studies, 238

Summary, 239

References, 240

Further reading, 240

Guidelines, 240

Web sites, 240

10 Immunogenetics and Histocompatibility, 241

10.1 The genetics of antigen recognition, 241

10.2 Human leukocyte antigens, 245

10.3 Transplantation, 251

10.4 Autoimmunity and human leukocyte antigens, 257

Summary, 260

Further reading, 260

Guidelines, 260

Web sites, 260

11 Blood Transfusion, 261

11.1 Blood collection and processing, 262

11.2 Blood groups, 265

11.3 Laboratory practice of blood transfusion, 273

11.4 Clinical practice of blood transfusion, 279

11.5 Hazards of blood transfusion, 281

Summary, 284

References, 284

Further reading, 284

Guidelines, 284

Web sites, 285

12 Waste Products, Electrolytes and Renal Disease, 287

12.1 Renal anatomy and physiology, 287

12.2 Homeostasis, 288

12.3 Excretion, 295

12.4 Renal endocrinology, 297

12.5 Renal disease, 298

12.6 Case studies, 301

Summary, 303

Further reading, 303

Guidelines, 303

Web sites, 303

13 Hydrogen Ions, pH, and Acid–Base Disorders, 305

13.1 Ions and molecules, 305

13.2 Blood gases, 308

13.3 Acidosis (pH <7.3), 312

13.4 Alkalosis (pH >7.5), 313

13.5 Mixed acid–base conditions, 314

13.6 Clinical interpretation, 314

13.7 Case studies, 315

Summary, 316

Further reading, 317

Web site, 317

14 Glucose, Lipids and Atherosclerosis, 319

14.1 Glucose, 319

14.2 Dyslipidaemia, 333

14.3 Atherosclerosis, 343

14.4 Case studies, 347

Summary, 348

Further reading, 348

Guidelines, 349

Web sites, 349

15 Calcium, Phosphate, Magnesium and Bone Disease, 351

15.1 Calcium, 352

15.2 Phosphates, 355

15.3 Magnesium, 355

15.4 The laboratory, 355

15.5 Disorders of calcium homeostasis, 357

15.6 Disorders of phosphate homeostasis, 360

15.7 Disorders of magnesium homeostasis, 362

15.8 Bone physiology, 363

15.9 Bone disease, 364

15.10 Case studies, 368

Summary, 369

Further reading, 370

Guidelines, 370

Web sites, 370

16 Nutrients and Gastrointestinal Disorders, 371

16.1 Nutrients, 371

16.2 The intestines, 375

16.3 Case studies, 381

Summary, 382

Further reading, 382

Guidelines, 382

17 Liver Function Tests and Plasma Proteins, 383

17.1 Anatomy and physiology of the liver, 384

17.2 Liver function tests, 389

17.3 Diseases of the liver, 390

17.4 Plasma proteins, 396

17.5 Case studies, 405

Summary, 406

Further reading, 406

Web sites, 406

18 Hormones and Endocrine Disorders, 407

18.1 Endocrine physiology, 407

18.2 The pathology of the endocrine system, 417

18.3 Case studies, 434

Summary, 435

Further reading, 435

Web sites, 436

19 Cancer and Tumour Markers, 437

19.1 General concepts in cancer biology, 437

19.2 Blood science and cancer, 440

19.3 Molecular genetics, 444

19.4 Case studies, 445

Summary, 446

Further reading, 446

Guidelines, 447

Web sites, 447

20 Inherited Metabolic Disorders, 449

20.1 The genetics of inheritance, 449

20.2 Molecular inherited metabolic disorders, 451

20.3 Organelle inherited metabolic disorders, 455

20.4 Antenatal diagnosis and neonatal screening, 455

20.5 Case studies, 456

Summary, 457

Further reading, 457

21 Drugs and Poisons, 459

21.1 Toxicology, 459

21.2 Toxicology of specific compounds, 461

21.3 Therapeutic drug monitoring, 465

21.4 Case studies, 468

Summary, 469

References, 469

Further reading, 469

22 Case Reports in Blood Science, 471

Abbreviations, 471

Case report 1, 472

Anaemia, hypercalcaemia, proteinuria, myeloma
Case report 2, 473

Diabetes, glycated haemoglobin, chronic renal failure
Case report 3, 474

Acute kidney injury, leucocytosis, neutrophilia, viruses
Case report 4, 475

Part 1: Obesity, colorectal cancer, CEA, hypothyroidism. Part 2: Alcoholism, raised GGT and triacylglycerols
Case report 5, 477

Part 1: No abnormalities. Part 2: Asthma, raised IgE. Part 3: Falling haemoglobin, rising ESR, lung cancer
Case report 6, 479

Hypothyroidism, marginally reduced haemoglobin
Case report 7, 480

Raised CRP, ESR, rheumatoid factor and anti-nuclear antibodies; borderline anti-dsDNA antibodies, low C3, low eGFR and so mild renal failure, systemic lupus erythematosus
Case report 8, 481

Normal blood results in renal transplantation
Case report 9, 482

Falling albumin, eGFR, haemoglobin, red cell count and platelets, rising ESR, white cell count and neutrophila, CRP, urea and creatinine, septicaemia
Case report 10, 484

Microcytic anaemia, thrombocytopenia, lymphocytosis, abnormal LFTs, falling albumin, raised CRP, myositis with raised CK, viruses
Case report 11, 486

Acidosis, hyperglycaemia, diabetic ketoacidosis, acute renal injury, raised urea and creatinine
Case report 12, 487

Low haemoglobin, thrombocytopenia, raised CRP and d-dimers, abnormal LFTs, malaria, pregnancy
Case report 13, 488

Raised aldosterone, hypernatraemia, hypokalaemia, Conn’s syndrome Case report 14, 489

Paediatric diabetic ketoacidosis, hyperglycaemia, low bicarbonate, raised phosphates, ALP and proteins

References, 490

Appendix: Reference Ranges, 491

Further Reading, 493

Glossary, 495

Index, 519

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