Description
CBS Publishers & Distributors Textbook Of Clinical Biochemistry by Ramnik Sood
This master-piece presents complete clinical biochemistry in an easily assimilable form. It will prove as a comprehensive textbook for both pathophysiology as well as an introduction to clinical biochemistry for medical students.
Table of Contents:-
Biochemical Investigations in Clinical
Medicine 1–21
Introduction 1
Diagnosis 1
Prognosis 2
Monitoring 2
Screening 2
Specimen Collection 2
The Patient 2
The Specimen 3
Unacceptable Specimens 3
Sample Analysis and Reporting of Results 5
Point-of-care Testing Policy and Accountability 6
Bibliography 19
2. The Body Buffer Systems and Blood Gases 22–67
Introduction 22
Acid-base Homeostasis 23
Chemical Buffer Systems 24
Phosphate Buffers 26
Role of Bone Buffering 27
Respiratory Regulation 28
Acid-base Disorders 29
Respiratory Acidosis 30
Metabolic Acidosis 34
Lactic Acidosis 39
Acidosis and Renal Failure 41
Drugs and Toxins 42
Renal Causes 44
Gastrointestinal Tract Causes 46
Other Causes 46
Respiratory Alkalosis 52
Metabolic Alkalosis 54
Chloride Depletion 55
Hydrochloric Acid Infusion 57
Interpretation of Acid-base Data 59
Understanding the Oxyhemoglobin
Dissociation Curve 59
Dissociation Curve’s Clinical Uses 61
Bibliography 65
Foreword by Dr Anurag Mehta vii
Preface ix
3. Water and Electrolytes 68–113
Introduction 68
Water Distribution 68
Properties of Water 69
Water Regulation 70
Movement of Water Among Compartments 71
Water and ECF Osmolality 71
Antidiuretic Hormone 72
Water Depletion 72
Water Excess 73
Electrolytes 73
Sodium 74
Sodium and Extracellular Fluid 76
Atrial Natriuretic Peptide Hormones 76
Classification of Hyponatremia 79
Hyponatremia by Osmolality 80
Pseudohyponatremia 81
Patient History 81
Symptoms and Signs 82
Diagnosis
xii Textbook of Clinical Biochemistry
4. The Kidneys 114–148
Introduction 114
Measurement of Glomerular Filtration Rate 116
Clearance 117
Plasma Urea 120
Assessment of Glomerular Integrity 121
Tests of Renal Tubular Function 121
Acute Kidney Injury 123
Determination of Cause 125
Chronic Kidney Disease 127
Anemia and Coagulation Disorders 130
Aluminum Toxicity 132
Nephrotic Syndrome 133
Laboratory Urine Testing 134
Defects of Urinary Concentration 138
Lysinuric Protein Intolerance 140
Types of Stones 141
Bibliography 143
5. The Liver 149–188
Introduction 149
Liver Structure 149
Liver Function 151
Bilirubin Metabolism 152
Nonalcoholic Steatohepatitis 157
Alcoholic Liver Disease 158
Jaundice 161
Inborn Metabolic Disorders 164
Identification of the Cause 168
Acute Viral Hepatitis 170
Chronic Hepatitis 175
Liver Masses and Granulomas 178
Hematologic Cancers and the Liver 181
Liver Injury Caused by Drugs 182
Other Tests of Liver Function 185
Bibliography 186
6. The Gastrointestinal Tract 189–231
Introduction 189
The Structure of GI 190
Gastrointestinal Disorders 191
Peptic Ulcer Disease 195
Helicobacter Pylori Infection 196
The Small Intestine Diseases 198
Crohn’s Disease 200
Fistulas 202
Surgery 203
Investigation of Intestinal Function 205
Whipple Disease 207
Pancreatic Disorders and their Investigation 207
Laboratory Tests 209
Pancreatic Cancer 212
Cystic Fibrosis 213
Intermediate Sweat Test Results 216
Respiratory Assessment 216
Newborn Screening 217
Antibiotics 218
Pancreatic Enzyme Replacement 219
Recombinant Human Growth Hormone (RHGH) 219
Bibliography 220
7. The Hypothalamus and Pituitary Gland 232–246
Introduction 232
Anterior Pituitary Hormones 232
Gonadotrophins 233
Disorders of Anterior Pituitary Function 235
Anorexia Nervosa 236
Acromegaly 237
Pituitary Gigantism 238
Cushing’s Disease 239
Measurement of Anterior Pituitary Hormones 240
Insulin Hypoglycemia Test 241
Disorders of Posterior Pituitary Gland 242
Psychogenic Polydipsia 244
Bibliography 244
8. The Adrenal Glands 247–267
Introduction 247
Adrenal Steroid Hormone Biosynthesis 248
Disorders of the Adrenal Cortex 250
Adrenal Crisis 251
Adrenal Hyperfunction 253
Conn’s Syndrome 257
Congenital Adrenal Hyperplasia 258
Disorders of the Adrenal Medulla 261
Pheochromocytoma 261
Imaging Tests to Localize Tumors 262
Bibliography 263
9. The Thyroid Gland 268–288
Introduction 268
Synthesis of Thyroid Hormones 269
Hyperthyroidism 271
Thyroid Storm 273
Hypothyroidism 275
Subclinical Hy+pothyroidism 277
Hashimoto Thyroiditis 277
Euthyroid Sick Syndrome 278
Silent Lymphocytic Thyroiditis 278
Subacute Thyroiditis 279
Simple Nontoxic Goiter (Euthyroid Goiter) 279
Thyroid Cancers 280
Radiation-induced Thyroid Cancer 281
Screening for Thyroid Disease 284
Bibliography 284
xiii Contents
10. The Gonads 289–325
Androgens and Testicular Function 289
Estrogens and Ovarian Function 291
Progesterone 292
Biosynthesis of Estrogens and Progesterone 292
Transport of Hormones in the Blood 294
Disorders of Male Gonadal Function 294
Gynecomastia 296
Disorders of Female Gonadal Function 298
Anovulatory Amenorrhea 299
Dysfunctional Uterine Bleeding 303
Polycystic Ovary Syndrome 305
Primary Ovarian Insufficiency 306
Hirsutism and Virilism 308
Gonadotropin and Inhibin Measurements 311
Measurement of Unbound Testosterone Levels 312
Ovulatory Dysfunction 314
Tubal Dysfunction and Pelvic Lesions 315
Assisted Pregnancy 316
Specific Hormonal Changes 316
Maternal Monitoring 319
Metabolic Effects of Oral Contraceptives 320
Bibliography 320
11. Disorders of Carbohydrate Metabolism 326–355
Introduction 326
Insulin 326
Proinsulin 328
Insulin-like Growth Factors 331
Disorders of Carbohydrate Metabolism 333
Complications 335
Gestational Diabetes 337
Metabolic Complications of Diabetes 339
Nonketotic Hyperglycemia 340
Hypoglycemia in Diabetic Patients 342
Postprandial Hypoglycemia 343
Hepatic and Renal Disease 345
Hypoglycemia in Childhood 345
Measurement of Glucose Concentration 346
Specimen Collection and Storage 346
Glycosuria 347
Specimen Collection and Storage 347
Glycogen Storage Disorders 348
Mucopolysaccharidoses 351
Bibliography 352
12. Disorders of Bone and Mineral Metabolism 356–388
Introduction 356
Cell Signaling in Bone 357
Measurement of Calcium 360
Specimen Requirements 360
Measurement of Parathyroid Hormone 362
Measurement of Vitamin D Metabolites 364
Calcium and Phosphate Homeostasis 365
Magnesium 368
Paget Disease of Bone 371
Osteomalacia and Rickets 372
Renal Osteodystrophy 373
Bibliography 382
13. Plasma Proteins 389–429
Introduction 389
Physical Properties of Proteins 390
Plasma Protein Concentrations 390
Major Plasma Proteins 391
Specific Plasma Proteins 393
Increased Plasma Concentrations 393
Clinical Significance of Albumin 395
Laboratory Testing 396
1 Acid Glycoprotein 397
1 Antitrypsin 398
2 Macroglobulin 400
Ceruloplasmin 400
Haptoglobin 402
Transferrin 404
2 Microglobulin 405
C-Reactive Protein 405
Complement Proteins 406
Cytokines 410
Immunoglobulins 410
Free Immunoglobulin Light Chains 413
Polyclonal Hyperimmunoglobulinemia 415
Macroglobulinemia 419
Heavy Chain Diseases 420
Specimen Collection and Storage for
Immunoassay 423
Immunofixation Electrophoresis 424
Mass Spectrometry 424
Bibliography 425
14. Serum Enzymes 430–454
Introduction 430
Diagnostic Enzymology 430
Muscle Enzymes 432
Creatine Kinase 432
Methods for Determination of Creatine
Kinase Activity 434
Aldolase 435
Methods for Measurement of Aldolase Activity 435
Liver Enzymes 435
Alkaline Phosphatase 435
Methods for Determination of Alkaline
Phosphatase Activity 436
Aminotransferases 438
Methods for Measurement of Transaminase
Activity 440
Glutamate Dehydrogenase 441
Methods for Determination of Glutamate 441
xiv Textbook of Clinical Biochemistry
-Glutamyl Transferase 442
5’-Nucleotidase 443
Pancreatic Enzymes 444
Amylase 444
Lipase 446
Methods for Measuring Lipase Activity 447
Trypsin 448
Methods for Determination of Trypsin 449
Alkaline Phosphatase (Bone Isoform) 449
Methods for Determination of Lactate 451
Enzyme Activity 451
Disadvantages of Enzyme Assays 451
Bibliography 452
15. Lipids, Lipoproteins and Apolipoproteins 455–486
Introduction 455
Cholesterol 455
Cholesterol Synthesis 456
Cholesterol Catabolism 458
Fatty Acids 459
Glycerol Esters (Acyl Glycerols) 461
Lipoproteins 462
Apolipoproteins 464
Exogenous Pathway 466
Endogenous Pathway 468
Reverse Cholesterol Transfer Pathway 469
Lipid Disorders 469
Dyslipidemia (Hyperlipidemia) 469
Primary Causes 470
Secondary Causes 472
Elevated LDL Cholesterol in Children 476
Hypolipidemia 478
Hypobetalipoproteinemia 479
Elevated High-density Lipoprotein Low-density
Lipoprotein Level 479
Bibliography 482
16. Therapeutic Drug Monitoring 487–528
Introduction 487
Routes of Drug Administration 487
Drug Metabolism 488
Drug Excretion 489
Anti-epileptic Drugs 489
Carbamazepine 491
Ethosuximide 491
Phenobarbital 492
Primidone 492
Phenytoin 493
Valproic Acid 493
Contemporary Anti-epileptics 494
Epilepsy 497
Generalized Seizures 498
Physical Examination 501
Antimicrobial Agents 502
Aminoglycosides 503
Glycopeptides 503
Tuberculosis Therapy 503
Other Antibiotics 504
Protease Inhibitors 506
Enzyme-multiplied Immunoassay 510
Everolimus 514
Ethanol and Alcohol Testing 519
Metabolism and Excretion of Ethanol 519
Automated Immunoassay Methods 521
Chromatography Methods 522
Heavy Metal Toxicity 522
Mercury Exposure 523
Bibliography 524
17. Tumor Markers 529–550
Introduction 529
Enzymes 529
Alkaline Phosphatase 530
Neuron-specific Enolase 531
Kallikreins 531
Prostate-specific Antigen 532
The Urokinase-plasminogen Activator System 534
Hormones 534
Oncofetal Antigens 537
Carcinoembryonic Antigen 538
Carbohydrate Markers 539
Proteins 543
Bladder Cancer Markers 543
Receptors and Other Markers 544
Bibliography 545
18. Vitamins 551–580
Introduction 551
Fat-soluble Vitamins 553
Vitamin A Deficiency 554
Vitamin E 555
Vitamin D 557
Vitamin K 560
Water Soluble Vitamins 562
Riboflavin 563
Riboflavin Deficiency 564
Vitamin B6 564
Niacin 565
Folic Acid 567
Vitamin B12 568
Biotin 572
Pantothenic Acid 572
Ascorbic Acid 572
Bibliography 574
19. Trace and Toxic Elements 581–600
Introduction 581
Trace Elements Homeostasis 581
Copper 582
xv Contents
Absorption, Transport, and Excretion 582
Inherited Copper Deficiency 582
Wilson Disease 583
Selenium 586
Chromium 587
Manganese 587
Iodine 588
Molybdenum 589
Fluoride 589
Aluminum 590
Arsenic 591
Cadmium 592
Lead 592
Mercury 593
Inductively Coupled Plasma Mass Spectrometry 596
Interferences 597
Elemental Speciation 598
Bibliography 599
20. Toxicology of Specific Agents 601–625
Introduction 601
Agents that Cause Cellular Hypoxia 602
Carbon Monoxide 602
Analytical Methods 602
Cyanide 603
Methemoglobin-forming Agents 604
Alcohols of Toxicologic Interest 605
Ethanol 605
Methanol 606
Isopropanol and Acetone 607
Ethylene Glycol 607
Estimation of Blood Alcohol 608
Ethyl Glucuronide 609
Analysis of Volatile Alcohols (Methanol,
Isopropanol, and Acetone) 609
Pharmacologic Response 611
Morphine 614
Codeine 615
Semisynthetic Opiates 615
Heroin 615
Hydrocodone 615
Hydromorphone 615
Oxycodone 615
Oxymorphone 616
Fully Synthetic Opioids 616
Fentanyl 616
Meperidine 616
Methadone 616
Propoxyphene 616
Tramadol 616
Opioid Antagonists and Mixed Agonist/
Antagonists 617
Buprenorphine 617
Naloxone 617
Sample Preparation and Extraction 618
Drugs of Abuse Related to the Sympathomimetic
Syndrome 619
Cocaine 619
Pharmacologic Response 620
Bibliography 622
21. The Porphyrias and Other Disorders of
Porphyrin Metabolism 626–649
Introduction 626
Chemistry of Porphyrins 626
Porphyrin Synthesis 627
Porphyria Disorders 627
Acute Porphyrias 630
Cutaneous Porphyrias 636
Pseudoporphyria 637
Erythropoietic Protoporphyria and X-linked
Protoporphyria 639
Laboratory Diagnosis of Porphyria 640
Methods for Porphyrin Precursors 641
Analysis of Porphyrins in Urine and Feces 642
HPLC Fractionation of Porphyrins in
Urine and Feces 643
Methods for Blood Porphyrins 643
Analysis of Plasma Porphyrins 644
Bibliography 645
22. Inherited Disorders of Metabolism and
Newborn Screening 650–695
Introduction 650
Clinical Presentation 650
History and Physical Examination 650
Amino Acid and Organic Acid Metabolism
Disorders 653
Maple Syrup Urine Disease 658
Propionic Acidemia 659
Methylmalonic Acidemia 659
Methionine Metabolism Disorders 659
Classic Homocystinuria 660
Other Forms of Homocystinuria 661
Cystathioninuria 661
Sulfite Oxidase Deficiency 661
Phenylketonuria 661
Transient Tyrosinemia of the Newborn 662
Alkaptonuria 664
Oculocutaneous Albinism 665
Urea Cycle Disorders 665
Carbohydrate Metabolism Disorders 672
Galactosemia 672
Glycogen Storage Diseases 673
Pyruvate Metabolism Disorders 675
Fatty Acid and Glycerol Metabolism Disorders 676
Beta-oxidation Cycle Disorders 677
Glutaric Acidemia Type II 680
Glycerol Metabolism Disorders 680
xvi Textbook of Clinical Biochemistry
Lysosomal Storage Disorders 681
Mucopolysaccharidosis 681
Sphingolipidoses 683
Cholesteryl Ester Storage Disease 686
Fabry Disease 686
Gaucher Disease 686
Krabbe Disease 687
Metachromatic Leukodystrophy 687
Purine and Pyrimidine Metabolism Disorders 687
Adenosine Deaminase Deficiency 689
Purine Nucleoside Phosphorylase Deficiency 690
Uridine Monophosphate Synthase Deficiency
(Hereditary Orotic Aciduria) 691
Plasma Acylcarnitine Profile 693
Bibliography 693
23. Analytic Techniques and Instrumentation 696–727
Introduction 696
Spectrophotometry 696
Beer’s Law 697
Spectrophotometric Instruments 698
Components of a Spectrophotometer 699
Photodetectors 700
Atomic Absorption Spectrophotometer 701
Flame Photometry 703
Basic Instrumentation 703
Advantages and Disadvantages of Fluorometry 704
Chemiluminescence 705
Turbidity and Nephelometry 705
Galvanic and Electrolytic Cells 706
Indicator Electrode 707
Liquid Junctions 707
Gas-sensing Electrodes 709
Enzyme Electrodes 709
Osmometry 713
Automation of Specimen Preparation 713
Mobile Robots 714
Sample Introduction and Internal Transport 715
Reagent Handling and Storage 716
Barcoding 717
Modes of Separation 718
Steric Exclusion 718
Chromatographic Procedures 719
High-performance Liquid Chromatography 720
Sample Injectors 721
Gas Chromatography 722
Electron Ionization 723
Atmospheric Pressure Chemical Ionization 724
Tandem Mass Spectrometry 725
High-resolution Mass Spectroscopy 726
Bibliography 727
24. Point-of-Care Testing 728–742
Introduction 728
Laboratory Regulations 729
Implementation 730
Quality Management 732
Informatics and POCT 734
Equipment Procurement and Evaluation 736
Training and Certification of Operators 736
Maintenance and Inventory Control 737
Documentation 738
Bibliography 739
25. Clinical Chemistry and the Geriatric Patient 743–772
Introduction 743
Aging 743
General Physiologic Changes with Aging 744
Evaluation of the Elderly Patient 745
Polypharmacy 746
Physical Examination 750
Head and Neck 751
Cranial Nerves 754
Reflexes 755
Comprehensive Geriatric Assessment 756
Increased Hormone Level 757
Decreased Hormone Level 758
Establishing Reference Intervals for the Elderly 758
Hepatic Metabolism 759
Pharmacodynamics in the Elderly 761
Drug-related Problems in the Elderly 762
Reasons for Drug-related Problems 762
Drug-disease Interactions 762
Drug Categories of Concern in the Elderly 764
Anticoagulants 767
Anxiolytics and Hypnotics 769
Bibliography 770
26. Lean Six Sigma Methodology for Quality
Improvement in the Clinical Chemistry
Laboratory 773–782
Introduction 773
Lean Six Sigma 773
Adoption and Implementation of Lean
Six Sigma 773
Senior Roles 774
Process Improvement 775
Measurements of Success Using Lean and
Six Sigma 776
Practical Application of Six Sigma Metrics 779
Bibliography 780
Appendix A to C 783–817
Index 818–824