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All pathology residents must have a good command of clinical chemistry, toxicology, immunology, and laboratory statistics to be successful pathologists, as well as to pass the Am… Read more
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Immediately download your ebook while waiting for your print delivery. No promo code needed.
All pathology residents must have a good command of clinical chemistry, toxicology, immunology, and laboratory statistics to be successful pathologists, as well as to pass the American Board of Pathology examination. Clinical chemistry, however, is a topic in which many senior medical students and pathology residents face challenges. Clinical Chemistry, Immunology and Laboratory Quality Control meets this challenge head on with a clear and easy-to-read presentation of core topics and detailed case studies that illustrate the application of clinical chemistry knowledge to everyday patient care.
This basic primer offers practical examples of how things function in the pathology clinic as well as useful lists, sample questions, and a bullet-point format ideal for quick pre-Board review. While larger textbooks in clinical chemistry provide highly detailed information regarding instrumentation and statistics, this may be too much information for students, residents, and clinicians. This book is designed to educate senior medical students, residents, and fellows, and to "refresh" the knowledge base of practicing clinicians on how tests are performed in their laboratories (i.e., method principles, interferences, and limitations).
Residents and fellows in pathology and clinical chemistry, practicing pathologists and clinical chemists
Dedication
Preface
Chapter 1. Instrumentation and Analytical Methods
1.1 Introduction
1.2 Spectrophotometry and Related Techniques
1.3 Atomic Absorption
1.4 Enzymatic Assays
1.5 Immunoassays
1.6 Nephelometry and Turbidimetry
1.7 Chemical Sensors
1.8 Basic Principles of Chromatographic Analysis
1.9 Mass Spectrometry Coupled with Chromatography
1.10 Examples of the Application of Chromatographic Techniques in Clinical Toxicology Laboratories
1.11 Automation in the Clinical Laboratory
1.12 Electrophoresis (including Capillary Electrophoresis)
References
Chapter 2. Immunoassay Platform and Designs
2.1 Application of Immunoassays for Various Analytes
2.2 Immunoassay Design and Principle
2.3 Various Commercially Available Immunoassays
2.4 Heterogenous Immunoassays
2.5 Calibration of Immunoassays
2.6 Various Sources of Interference in Immunoassays
2.7 Interferences from Bilirubin, Hemolysis, and High Lipid Content
2.8 Interferences from Endogenous and Exogenous Components
2.9 Interferences of Heterophilic Antibodies in Immunoassays
2.10 Interferences from Autoantibodies and Macro-Analytes
2.11 Prozone (or “Hook”) Effect
References
Chapter 3. Pre-Analytical Variables
3.1 Laboratory Errors in Pre-Analytical, Analytical, and Post-Analytical Stages
3.2 Order of Draw of Blood Collection Tubes
3.3 Errors with Patient Preparation
3.4 Errors with Patient Identification and Related Errors
3.5 Error of Collecting Blood in Wrong Tubes: Effect of Anticoagulants
3.6 Issues with Urine Specimen Collection
3.7 Issues with Specimen Processing and Transportation
3.8 Special Issues: Blood Gas and Ionized Calcium Analysis
References
Chapter 4. Laboratory Statistics and Quality Control
4.1 Mean, Standard Deviation, and Coefficient of Variation
4.2 Precision and Accuracy
4.3 Gaussian Distribution and Reference Range
4.4 Sensitivity, Specificity, and Predictive Value
4.5 Random and Systematic Errors in Measurements
4.6 Laboratory Quality Control: Internal and External
4.7 Levey–Jennings Chart and Westgard Rules
4.8 Delta Checks
4.9 Method Validation/Evaluation of a New Method
4.10 How to Interpret the Regression Equation?
4.11 Bland–Altman Plot
4.12 Receiver–Operator Curve
4.13 What is Six Sigma?
4.14 Errors Associated with Reference Range
4.15 Basic Statistical Analysis: Student t-Test and Related Tests
References
Chapter 5. Water, Homeostasis, Electrolytes, and Acid–Base Balance
5.1 Distribution of Water and Electrolytes in the Human Body
5.2 Plasma and Urine Osmolality
5.3 Hormones Involved in Water and Electrolyte Balance
5.4 Renin–Angiotensin–Aldosterone System
5.5 Diabetes Insipidus
5.6 The Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
5.7 Hyponatremia, Sick Cell Syndrome, and Hypernatremia
5.8 Hypokalemia and Hyperkalemia
5.9 Introduction to Acid–Base Balance
5.10 Diagnostic Approach to Acid–Base Disturbance
5.11 Short Cases: Acid–Base Disturbances
References
Chapter 6. Lipid Metabolism and Disorders
6.1 Lipids and Lipoproteins
6.2 Classes of Lipoproteins
6.3 Lipid Metabolism
6.4 Low Density Lipoprotein Metabolism
6.5 High Density Lipoprotein Metabolism
6.6 Lipid Profile and Risk of Cardiovascular Disease
6.7 Various Types of Hyperlipidemia
6.8 Various Types of Hypolipidemia
6.9 Newer Lipid Parameters and Other Factors Related to Risk for Cardiovascular Disease
6.10 Laboratory Measurements of Various Lipids
6.11 Drugs for Treating Lipid Disorders
References
Chapter 7. Carbohydrate Metabolism, Diabetes, and Hypoglycemia
7.1 Carbohydrates: An Introduction
7.2 Regulation of Blood Glucose Concentration
7.3 Diabetes Mellitus: Basic Concepts
7.4 Monogenic Diabetes Mellitus
7.5 Type 1 Diabetes Mellitus
7.6 Type 2 Diabetes Mellitus
7.7 Metabolic Syndrome or Syndrome X
7.8 Complications of Diabetes
7.9 Secondary Causes of Diabetes Mellitus
7.10 Diagnostic Criteria for Diabetes
7.11 Hypoglycemia
7.12 Laboratory Methods
7.13 Glucose Meters
References
Chapter 8. Cardiac Markers
8.1 Myocardial Infarction
8.2 Overview of Cardiac Markers
8.3 Myoglobin
8.4 Creatine Kinase Isoenzyme: CK-MB
8.5 Troponin I and Troponin T
8.6 High-Sensitive Cardiac Troponin Assays
8.7 Less Commonly Used Cardiac Markers
8.8 B-Type Natriuretic Peptides (BNP)
8.9 C-Reactive Protein
8.10 Myeloperoxidase
References
Chapter 9. Endocrinology
9.1 Introduction to Various Endocrine Glands
9.2 Hypothalamus
9.3 Pituitary Gland
9.4 Thyroid Gland
9.5 Thyroid Function Tests
9.6 Hypothyroidism
9.7 Hyperthyroidism
9.8 Disorders of Parathyroid Glands
9.9 Adrenal Glands
9.10 Cushing’s Syndrome
9.11 Conn’s Syndrome
9.12 Hypoadrenalism Including Addison’s Disease
9.13 Dysfunctions of Gonads
9.14 Pancreatic Endocrine Disorders
9.15 Multiple Endocrine Neoplasias
9.16 Endocrine Testings: Suppression and Stimulation Tests
References
Chapter 10. Liver Diseases and Liver Function Tests
10.1 Liver Physiology
10.2 Liver Function Tests and Interpretations
10.3 Jaundice: An Introduction
10.4 Congenital Hyperbilirubinemia
10.5 Hemolytic (Prehepatic) Jaundice
10.6 Hepatocellular Jaundice
10.7 Chronic Liver Disease
10.8 Cholestatic Jaundice
10.9 Alcohol- and Drug-Induced Liver Disease
10.10 Liver Disease in Pregnancy
10.11 Liver Disease in Neonates and Children
10.12 Macro Liver Enzymes
10.13 Laboratory Measurement of Bilirubin and Other Tests
References
Chapter 11. Renal Function Tests
11.1 Basic Functions of Kidneys
11.2 Glomerular Filtration Rate
11.3 Creatinine Clearances
11.4 Chronic Kidney Disease
11.5 Cystatin C
11.6 Urea (Blood Urea Nitrogen) and Uric Acid
11.7 Protein in Urine and Proteinuria
11.8 Other Renal Diseases
11.9 Laboratory Measurements of Creatinine and Related Tests
11.10 Urine Dipstick Analysis
References
Chapter 12. Inborn Errors of Metabolism
12.1 Overview of Inborn Errors of Metabolism
12.2 Amino Acid Disorders
12.3 Carbohydrate Metabolism Disorders
12.4 Urea Cycle Disorders
12.5 Organic Acid Disorders (Organic Aciduria)
12.6 Fatty Acid Oxidation Disorders
12.7 Mitochondrial Disorders
12.8 Peroxisomal Disorders
12.9 Lysosomal Storage Disorders
12.10 Purine or Pyrimidine Metabolic Disorders
12.11 Disorders of Porphyrin Metabolism
12.12 Newborn Screening and Evaluation
References
Chapter 13. Tumor Markers
13.1 Introduction to Tumor Markers
13.2 Clinical Uses of Tumor Markers and Common Tumor Markers
13.3 Prostate-Specific Antigen (PSA)
13.4 False Positive and Unexpected PSA Results
13.5 Cancer Antigen 125 (Carbohydrate Antigen 125: CA-125)
13.6 False Positive CA-125
13.7 Alpha-Fetal Protein
13.8 False Positive AFP
13.9 Carcinoembryonic Antigen (CEA)
13.10 False Positive CEA
13.11 Cancer Antigen-19-9
13.12 β2-Microglobulin
13.13 Human Chorionic Gonadotropin (hCG)
13.14 Causes and Evaluation of Persistent Low Levels of hCG
13.15 False Positive hCG
References
Chapter 14. Therapeutic Drug Monitoring
14.1 What is Therapeutic Drug Monitoring?
14.2 Drugs That Require Therapeutic Drug Monitoring
14.3 Free Versus Total Drug Monitoring
14.4 Therapeutic Drug Monitoring Benefits
14.5 Basic Pharmacokinetics
14.6 Effect of Gender and Pregnancy on Drug Metabolism and Disposition
14.7 Effect of Age on Drug Metabolism and Disposition
14.8 Drug Metabolism and Disposition in Uremia
14.9 Drug Metabolism and Disposition in Liver Disease
14.10 Effect of Cardiovascular Disease on Drug Metabolism and Disposition
14.11 Thyroid Dysfunction and Drug Metabolism
14.12 Effect of Food, Alcohol Consumption, and Smoking on Drug Disposition
14.13 Monitoring of Various Drug Classes: General Considerations
14.14 Monitoring of Anticonvulsants
14.15 Monitoring of Cardioactive Drugs
14.16 Monitoring of Anti-Asthmatic Drugs
14.17 Monitoring of Antidepressants
14.18 Monitoring of Immunosuppressants
14.19 Monitoring of Selected Antibiotics
14.20 Monitoring of Antineoplastic Drugs
14.21 Monitoring of Antiretrovirals
References
Chapter 15. Interferences in Therapeutic Drug Monitoring
15.1 Methodologies Used in Therapeutic Drug Monitoring and Issues of Interferences
15.2 Effect of Endogenous Factors on Therapeutic Drug Monitoring
15.3 Effect of Collecting Specimen in Gel-Separator Tube on Therapeutic Drug Monitoring Results
15.4 Digoxin Immunoassays: So Much Interference
15.5 Interferences in Analysis of Antiepileptics
15.6 Interferences in Analysis of Tricyclic Antidepressants
15.7 Interferences in Analysis of Immunosuppressants
15.8 Interferences in Analysis of Antibiotics
References
Chapter 16. Drugs of Abuse Testing
16.1 Commonly Abused Drugs in the United States
16.2 Medical vs. Workplace Drug Testing
16.3 SAMHSA vs. Non-SAMHSA Drugs
16.4 Detection Window of Various Drugs in Urine
16.5 Metabolism of Abused Drugs/Target of Immunoassay Antibodies
16.6 Immunoassays vs. GC/MS Cut-Off Concentrations
16.7 False Positive Immunoassay Test Results with Various Abused Drugs
16.8 False Negative Test Results
16.9 Derivatization in GC/MS Confirmation Testing
16.10 Analytical True Positive Due to Use of Prescription Drugs and Other Factors
16.11 Issues of Adulterated Urine Specimens in Workplace Drug Testing
16.12 Miscellaneous Issues in Drugs of Abuse Testing
References
Chapter 17. Challenges in Drugs of Abuse Testing: Magic Mushrooms, Peyote Cactus, and Designer Drugs
17.1 Negative Toxicology Report
17.2 Magic Mushroom Abuse
17.3 Peyote Cactus Abuse
17.4 Rave Party Drugs and Date Rape Drugs (Including Designer Drugs)
17.5 Abuse of Amphetamine-Like Designer Drugs (Including Bath Salts)
17.6 Abuse of Synthetic Marijuana (Spice and K2)
17.7 Designer Drugs that are Opioid Analogs
References
Chapter 18. Testing for Ethyl Alcohol (Alcohol) and Other Volatiles
18.1 Alcohol Use and Abuse
18.2 Health Benefits of Moderate Drinking
18.3 Health Hazards of Heavy Drinking
18.4 Metabolism of Ethyl Alcohol: Effect of Gender and Genetic Factors
18.5 Relation between Whole Blood Alcohol and Serum Alcohol and Legal Limit of Driving
18.6 Analysis of Alcohol in Body Fluids: Limitations and Pitfalls
18.7 Biomarkers of Alcohol Abuse
18.8 Methanol Abuse
18.9 Abuse of Ethylene Glycol and Other Alcohols
References
Chapter 19. Common Poisonings Including Heavy Metal Poisoning
19.1 Poisoning from Analgesics
19.2 Methyl Salicylate Poisoning
19.3 Carbon Monoxide Poisoning
19.4 Cyanide Poisoning
19.5 Overdose with Tricyclic Antidepressants
19.6 Benzodiazepine and Opiate Overdose
19.7 Alcohol Poisoning
19.8 Poisoning from Organophosphorus and Carbamate Insecticides
19.9 Lead Poisoning
19.10 Mercury Poisoning
19.11 Arsenic Poisoning
19.12 Poisoning from Other Metals/SOURCES
References
Chapter 20. Pharmacogenomics
20.1 Introduction to Pharmacogenomics
20.2 Polymorphism of Enzymes Responsible for Drug Metabolism
20.3 Polymorphism of Transporter Proteins and Receptors
20.4 Pharmacogenomics and Warfarin Therapy
20.5 Pharmacogenomics of Selected Anticancer Drugs
20.6 Pharmacogenomics of Selected Opioid Drugs
20.7 Pharmacogenomics of Selected Psychoactive Drugs
20.8 Pharmacogenomics of Miscellaneous Other Drugs
20.9 Methods for Pharmacogenomics Testing
References
Chapter 21. Hemoglobinopathy
21.1 Hemoglobin Structure and Synthesis
21.2 Introduction to Hemoglobinopathies
21.3 Alpha-Thalassemia
21.4 Beta-Thalassemia
21.5 Delta-Thalassemia
21.6 Sickle Cell Disease
21.7 Hereditary Persistence of Fetal Hemoglobin
21.8 Other Hemoglobin Variants
21.9 Laboratory Investigation of Hemoglobin Disorders
21.10 Diagnostic Tips for Thalassemia, Sickle Cell Disease, and Other Hemoglobinopathies
21.11 Apparent Hemoglobinopathy After Blood Transfusion
References
Chapter 22. Protein Electrophoresis and Immunofixation
22.1 Monoclonal Gammopathy
22.2 Serum Protein Electrophoresis
22.3 Urine Electrophoresis
22.4 Immunofixation Studies
22.5 Capillary Zone Electrophoresis
22.6 Free Light Chain Assay
22.7 Paraprotein Interferences in Clinical Laboratory Tests
22.8 Cerebrospinal Fluid Electrophoresis
References
Chapter 23. Human Immunodeficiency Virus (HIV) and Hepatitis Testing
23.1 Human Immunodeficiency Virus (HIV) Testing
23.2 Window Period in HIV Infection
23.3 Standard HIV Testing
23.4 Rapid HIV Antibody Testing
23.5 Confirmatory HIV Test
23.6 HIV Viral Load Test and Related Assays
23.7 Introduction to Hepatitis Testing
23.8 Testing for Hepatitis B
23.9 Testing for Hepatitis C
23.10 Immunization and False Positive HIV and Hepatitis Testing
23.11 Testing for Epstein–Barr Virus (EBV)
References
Chapter 24. Autoimmunity, Complement, and Immunodeficiency
24.1 Introduction to the Immune System and Complement
24.2 Pathways of Complement Activation
24.3 Immunodeficiency
24.4 Major Histocompatibility Complex (MHC)
24.5 Human Leukocyte Antigen Testing
24.6 Transplant Rejection
24.7 Autoimmune Serology
24.8 Hypersensitivity Reaction-Mediated Diseases
References
Chapter 25. Effect of Herbal Supplements on Clinical Laboratory Test Results
25.1 Use of Herbal Remedies in the United States
25.2 How Herbal Remedies Affect Clinical Laboratory Test Results
25.3 Liver Damage as Reflected by Abnormal Liver Function Test After Using Certain Herbals
25.4 Kidney Damage and Herbal Supplements
25.5 Kelp and Thyroid Function
25.6 Miscellaneous Abnormal Test Results Due to Use of Certain Herbals
25.7 Drug–Herb Interactions Involving St. John’s Wort and Warfarin–Herb Interactions
25.8 Herbs Adulterated with Western Drugs and Contaminated with Heavy Metals
References
Index
Color Plates
AD
Amitava Dasgupta received his Ph. D in chemistry from Stanford University and completed his fellowship training in Clinical Chemistry from the Department of Laboratory Medicine at the University of Washington School of Medicine at Seattle. He is board certified in both Toxicology and Clinical Chemistry by the American Board of Clinical Chemistry. Currently, he is a tenured Full Professor of Pathology and Laboratory Medicine at the University of Kansas Medical Center and Director of Clinical Laboratories at the University of Kansas Hospital. Prior to this appointment he was a tenured Professor of Pathology and Laboratory Medicine at the University of Texas McGovern medical School from February 1998 to April 2022. He has 252 papers to his credit. He is in the editorial board of four journals including Therapeutic Drug Monitoring, Clinica Chimica Acta, Archives of Pathology and Laboratory Medicine, and Journal of Clinical Laboratory Analysis.
AW