Clinical Chemistry, Immunology and Laboratory Quality Control

A Comprehensive Review for Board Preparation, Certification and Clinical Practice

2nd Edition - May 4, 2021
Imprint: Elsevier
Authors: Amitava Dasgupta, Amer Wahed
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 5 9 6 0 - 6
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 5 9 6 1 - 3

Clinical Chemistry, Immunology and Laboratory Quality Control: A Comprehensive Review for Board Preparation, Certification and Clinical Practice, Second Edition presents core topi… Read more

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Clinical Chemistry, Immunology and Laboratory Quality Control: A Comprehensive Review for Board Preparation, Certification and Clinical Practice, Second Edition presents core topics and 70 case studies that illustrate the application of clinical chemistry knowledge to everyday patient care. This succinct reference offers practical examples of how things function in the pathology clinic with useful lists, key points, case studies 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 book is designed to educate senior medical students, residents and fellows on how tests are performed.

This second edition successfully helps pathology residents gain command of clinical chemistry, toxicology, immunology, and laboratory statistics in an effort to help them prepare for the American Board of Pathology examination. Clinical chemistry is a topic in which many senior medical students and pathology residents face challenges.

Cover image
Title page
Table of Contents
Copyright
Preface
Chapter 1: Instrumentation and analytical methods
Abstract
Instrumentation and analytical methods: An introduction
Spectrophotometry and related techniques
Atomic absorption
Enzymatic assays
Immunoassays
Turbidimetry and nephelometry: Methods based on light scattering
Ion selective electrodes
Basic principles of chromatography
Gas chromatography
High-performance liquid chromatography
Mass spectrometer as a detector
Examples of application of chromatographic techniques in clinical toxicology laboratories
Automation in clinical laboratory
Electrophoresis including capillary electrophoresis
Summary/key points
Chapter 2: Immunoassay design and issues of interferences
Abstract
Application of immunoassays for various analytes
Immunoassay design and principle
Various commercially available immunoassays
Heterogenous immunoassays
Calibration of an immunoassay
Various sources of interferences in immunoassays
Interferences from bilirubin, hemolysis, and high lipid content
Interferences from the endogenous and exogenous components
Interferences of heterophilic antibodies in immunoassays
Rheumatoid factor interferences
Interferences from autoantibodies
Macroenzyme interferences
Other macroanalytes
Prozone (or “hook”) effect
Summary/key points
Chapter 3: Preanalytical variables
Abstract
Laboratory errors
Order of draw of blood collection tubes
Errors in patient preparation
Biological rhythm and time for specimen collection
Errors with patient identification and related errors
Error of collecting blood in wrong tubes: Effect of anticoagulants
Blood collection from catheter and intravenous line
Issues with collecting urine specimens
Issues with specimen processing and transportation
Special issues: Blood gas and ionized calcium analysis
Summary/key points
Chapter 4: Laboratory statistics and quality control
Abstract
Mean, standard deviation, and coefficient of variation
Precision and accuracy
Gaussian distribution and reference range
Sensitivity, specificity, and predictive value
Random and systematic errors in measurements
Laboratory quality control: Internal and external
CAP proficiency testing
Passing CAP proficiency testing
What action to take if a laboratory failed CAP survey for certain analytes?
Levey-Jennings chart and Westgard rules
Delta checks
Method validation for a new test using existing analyzer
How to interpret regression equation?
Bland-Altman plot
How to implement a new analyzer in the laboratory?
Analytical measurement range, reference range, and critical values
Quality assurance indicators in the laboratory
Receiver operating characteristic curve
What is six sigma?
Errors associated with reference range
Basic statistical analysis: Student’s t-test and related tests
Summary/key points
Chapter 5: Water homeostasis electrolytes and acid-base balance
Abstract
Distribution of water and electrolytes in human body
Plasma and urine osmolality
Hormones involved in water and electrolyte balance
Renin-angiotensin-aldosterone system
Diabetes insipidus
The syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Hyponatremia, sick cell syndrome, and hypernatremia
Hypokalemia and hyperkalemia
Introduction to acid-base balance
Diagnostic approach to acid-base disturbance
Short cases: Acid-base disturbances
Key points
Chapter 6: Lipid metabolism and disorders
Abstract
Lipids and lipoproteins
Various classes of lipoproteins
Lipid metabolism
LDL metabolism
HDL metabolism
Lipid profile and risk of cardiovascular disease
Various types of hyperlipidemia
Various types of hypolipidemia
Newer lipid parameters and other factors related to risk for cardiovascular disease
Laboratory measurements of various lipids
Drugs for treating lipid disorders
Summary/key points
Chapter 7: Carbohydrate metabolism, diabetes, and hypoglycemia
Abstract
Carbohydrates: An introduction
Regulation of blood glucose concentration
Diabetes mellitus: Basic concepts
Monogenic diabetes mellitus
Type 1 diabetes mellitus
Metabolic syndrome or syndrome X
Complications of diabetes
Secondary causes of diabetes mellitus
Diagnostic criteria for diabetes
Hypoglycemia
Laboratory methods
Glucose meters
Summary/key points
Chapter 8: Cardiac markers
Abstract
Myocardial infarction
Overview of cardiac markers
Myoglobin
CK isoenzyme: CK-MB
Troponin I and troponin T
High-sensitivity troponin assays
Elevated troponin levels in conditions other than myocardial infarction
Issues of interferences
LDH: An old cardiac marker
Biomarkers of myocardial ischemia
Biomarkers of hemodynamic stress of the heart
Inflammatory and prognostic biomarkers
Pregnancy-associated plasma protein A
Summary/key points
Chapter 9: Endocrinology
Abstract
Introduction to various endocrine glands
Hypothalamus
Pituitary gland
Thyroid gland
Thyroid function tests
Hypothyroidism
Hyperthyroidism
Disorders of parathyroid glands
Adrenal glands
Cushing’s syndrome
Conn’s syndrome
Hypoadrenalism including Addison’s disease
Dysfunctions of gonads
Pancreatic endocrine disorders
Multiple endocrine neoplasia
Endocrine testing: Suppression and stimulation tests
Summary/key points
Chapter 10: Liver diseases and liver function tests
Abstract
Liver physiology
Liver function tests and interpretations
Jaundice: An introduction
Congenital hyperbilirubinemia
Hemolytic (prehepatic) jaundice
Hepatocellular jaundice
Chronic liver disease
Cholestatic jaundice
Alcohol and drug-induced liver disease
Liver disease in pregnancy
Liver disease in neonates and children
Nonalcoholic fatty liver disease
Macro liver enzymes
Delta bilirubin
Laboratory measurement of bilirubin and other tests
Summary/key points
Chapter 11: Renal function tests
Abstract
Basic functions of kidneys
Glomerular filtration rate
Creatinine clearances and estimated GFR
Biochemical assessment of renal function
Assessment of glomerular integrity
Tests for renal tubular function
Acute renal failure
BUN/creatinine ratio
Fractional excretion of sodium
Chronic kidney disease
Proteinuria
Nephrotic syndrome
Nephritic syndrome
Hematuria
Glomerular versus nonglomerular bleeding
Fanconi syndrome
Renal tubular acidosis
Renal calculi
Laboratory measurements of creatinine and related tests
Urine dipstick analysis
Summary/key points
Chapter 12: Inborn errors of metabolism
Abstract
Overview of inborn errors of metabolism
Amino acid disorders
Carbohydrate metabolism disorders
Urea cycle disorders
Organic acid disorders (organic aciduria)
Fatty acid oxidation disorders
Mitochondrial disorders
Peroxisomal disorders
Lysosomal storage disorders
Purine or pyrimidine metabolic disorders
Disorders of porphyrin metabolism
Newborn screening and evaluation
Summary/key points
Chapter 13: Tumor markers
Abstract
Introduction to tumor markers
Clinical uses of tumor markers and common tumor markers
Prostate-specific antigen (PSA)
False-positive and unexpected PSA results
Cancer antigen 125 (carbohydrate antigen 125: CA-125)
False-positive CA-125
Cancer antigen-19-9 (carbohydrate antigen: 19-9: CA 19-9)
Alpha-fetal protein (AFP, α-fetoprotein)
False-positive AFP
Carcinoembryonic antigen (CEA)
False-positive CEA
β2-Microglobulin
Human chorionic gonadotropin (hCG)
Causes and evaluation of persistent low level of hCG
False-positive hCG
CA-15-3 and HER2
CA 72-4
Markers for thyroid cancer
Less commonly monitored cancer biomarkers
Summary/key points
Chapter 14: Therapeutic drug monitoring
Abstract
What is therapeutic drug monitoring?
Drugs that require therapeutic drug monitoring
Free versus total drug monitoring
Therapeutic drug monitoring benefits
Basic pharmacokinetics
Effect of gender and pregnancy on drug metabolism and disposition
Effect of age on drug metabolism and disposition
Drug metabolism and disposition in uremia
Drug metabolism and disposition in liver disease
Effect of cardiovascular disease on drug metabolism and disposition
Thyroid dysfunction and drug metabolism
Effect of food, alcohol consumption, and smoking on drug disposition
Therapeutic drug monitoring of various drug classes: General considerations
Preanalytical issues in therapeutic drug monitoring
Therapeutic drug monitoring of anticonvulsants
Therapeutic drug monitoring of cardioactive drugs
Therapeutic drug monitoring of antiasthmatic drugs
Therapeutic drug monitoring of antidepressants
Therapeutic drug monitoring of immunosuppressants
Therapeutic drug monitoring of selected antibiotics
Therapeutic drug monitoring of antineoplastic drugs
Therapeutic drug monitoring of antiretrovirals
Therapeutic drug monitoring using oral fluids
Therapeutic drug monitoring using dried blood spot
Summary/key points
Chapter 15: Interferences in therapeutic drug monitoring
Abstract
Methodologies used in therapeutic drug monitoring and issues of interferences
Effect of endogenous factors on therapeutic drug monitoring
Digoxin immunoassays: So much interference
Interferences in analysis of antiepileptics
Interferences in analysis of tricyclic antidepressants
Interferences in analysis of immunosuppressants
Interferences in analysis of antibiotics
Interferences of paraprotein in therapeutic drug monitoring
Summary/key points
Chapter 16: Drugs of abuse testing
Abstract
Commonly abused drugs in the United States
Medical versus workplace drug testing
SAMHSA versus non-SAMHSA drugs
Detection window of various drugs in urine
Metabolism of abused drugs/target of immunoassay antibody
Immunoassays versus confirmation
False-positive immunoassay test results with various abused drugs
False-negative test results
Derivatization in GC/MS vs direct analysis using LC-MS/MS
Analytical true positive due to use of prescription drugs and other factors
Issues of adulterated urine specimens in workplace drug testing
Miscellaneous other issues in drugs of abuse testing
Summary/key points
Chapter 17: Designer drugs, date rape drugs, LSD, volatiles, magic mushroom, and peyote cactus abuse
Abstract
Negative toxicology report
Abuse of amphetamine-like designer drugs including bath salts
Abuse of synthetic marijuana (Spice, K2)
Designer drugs that are opioid analogs
Meperidine and phencyclidine-like designer drugs
Rave party drugs and date rape drugs
LSD abuse
Abuse of volatiles (solvents)
Magic mushroom abuse
Peyote cactus abuse
Summary/key points
Chapter 18: Testing for ethyl alcohol (alcohol) and other volatiles
Abstract
Alcohol use and abuse
Health benefits of moderate drinking
Health hazards of heavy drinking
Metabolism of alcohol: Effect of gender
Metabolism of ethyl alcohol: Effect of genetic factors
Relation between whole blood alcohol and serum alcohol and legal limit of driving
Analysis of alcohol in body fluids: Limitations and pitfalls
Headspace gas chromatography for alcohol determination
Breath alcohol measurement
Biomarkers of alcohol abuse
Methanol abuse
Abuse of ethylene glycol and other alcohols
Summary/key points
Chapter 19: Common poisonings including heavy metal poisoning
Abstract
Poisoning from analgesics
Methyl salicylate poisoning
Carbon monoxide poisoning
Cyanide poisoning
Overdose with tricyclic antidepressants
Benzodiazepine and opiate overdose
Alcohol poisoning
Poisoning from organophosphorus and carbamate insecticides
Lead poisoning
Mercury poisoning
Arsenic poisoning
Poisoning from other metals
Summary/key points
Chapter 20: Pharmacogenomics
Abstract
Introduction to pharmacogenomics
Basic pharmacogenomics
Nomenclature
Various metabolizer types
Other polymorphic enzymes that metabolize drugs
Polymorphism of transporter proteins and receptors
Pharmacogenomics and warfarin therapy
Pharmacogenomics of selected anticancer drugs
Pharmacogenomics of selected opioid drugs
Pharmacogenomics of selected psychoactive drugs
Pharmacogenomics of miscellaneous other drugs
Methods for pharmacogenomics testing
Summary/key points
Chapter 21: Point-of-care testing
Abstract
Introduction to point-of-care testing
POCT devices: Methodologies
Glucose measurement using POCT
Measuring multiple analytes using POCT
Cardiac markers
Pregnancy test
Coagulation POCT
Infectious disease
POCT for drugs of abuse
Important issues with POCT devices
Key points
Chapter 22: Biotin interferences with immunoassays
Abstract
Biotin
Serum biotin levels
Biotin interference
FDA safety communication on biotin
Biotin interferences in thyroid function tests
Biotin falsely lower parathyroid hormone level
Biotin interferes with cardiac function tests
Biotin interferences in multiple immunoassays
Diagnostic companies using biotin-based assays: A review
Approaches to overcome biotin interference
Key points
Chapter 23: Hemoglobinopathies and thalassemia
Abstract
Introduction
Hemoglobin structure and synthesis
Introduction to hemoglobinopathies
Alpha-thalassemia
Beta-thalassemia
Delta-thalassemia
Sickle cell disease
Hereditary persistence of fetal hemoglobin (HPFH)
Other hemoglobin variants
Laboratory investigation of hemoglobinopathies
Gel electrophoresis
Interpretation of alkaline and acid gels
High-performance liquid chromatography (HPLC)
Capillary electrophoresis
Reporting normal hemoglobin pattern
Diagnostics tips for thalassemia, sickle cell disease, and other hemoglobinopathies
Apparent hemoglobinopathy after blood transfusion
Universal newborn screening
Key points
Chapter 24: Protein electrophoresis and immunofixation
Abstract
Introduction
Serum protein electrophoresis
Urine electrophoresis
Immunofixation studies
Capillary zone electrophoresis
Free light chain assay
Mass spectrometry in diagnosis of multiple myeloma
Paraprotein interferences in clinical laboratory tests
Other plasma cell disorders
Morphology of plasma cells in myeloma
Cerebrospinal fluid electrophoresis
Summary/key points
Chapter 25: Human immunodeficiency virus (HIV) and hepatitis testing
Abstract
Human immunodeficiency virus testing
Window period in HIV infection
Standard HIV testing
Testing algorithm
Rapid HIV antibody testing
Confirmatory HIV test
HIV viral load test and related assays
Introduction to hepatitis testing
Testing for hepatitis B
Testing for hepatitis C
Immunization and false-positive HIV and hepatitis testing
Testing for Epstein-Bar virus
Summary/key points
Chapter 26: Autoimmunity, complement, and immunodeficiency
Abstract
Introduction to immune system and complement
T lymphocytes and cell-mediated immunity
B cells and humoral immunity
Pathways of complement activation
Immunodeficiency
Major histocompatibility complex
HLA testing
Transplant rejection
Autoimmune serology
Hypersensitivity reactions and hypersensitivity-mediated disorders
Summary/key points
Chapter 27: Effect of herbal supplements on clinical laboratory test results
Abstract
Use of herbal remedies in the United States
How herbal remedies affect clinical laboratory test results
Liver damage as reflected by abnormal liver function test after using certain herbals
Kidney damage and herbal supplements
Kelp and thyroid function
Miscellaneous abnormal test results due to use of certain herbals
Drug-herb interactions
Herbs adulterated with western drugs and herbs contaminated with heavy metals
Grapefruit juice-drug interaction
Summary/key points
Index

Amitava Dasgupta

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.

Affiliations and expertise

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States

Amer Wahed

Amer Wahed is a graduate of Medicine, training initially in Internal Medicine at Royal Postgraduate Medical School, London, England. He subsequently trained in Anatomic and Clinical Pathology from the University of Texas-Houston Medical School. After working for several years in a private setting, he joined the Department of Pathology and Laboratory Medicine at the University of Texas-Houston Health Sciences Center. Currently he is an Assistant Professor of Pathology and Laboratory Medicine and Associate Director of Clinical Chemistry and Immunology at Memorial-Hermann Hospital at the Texas Medical Center. He is also the Associate Director of the Pathology Residency Program at the University of Texas-Houston Medical School. Dr. Wahed has a strong interest in teaching and is actively involved in the education of medical students, graduate students, residents, and fellows. He has been recognized for his teaching contributions through awards from his department, as well as the Office of the Dean. He is also active in mentoring pathology residents in research and has published multiple papers in peer-reviewed journals.

Affiliations and expertise

Associate Professor of Pathology and Laboratory Medicine, University of Texas, McGovern School of Medicine, Houston, TX, USA

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

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