Contemporary Practice in Clinical Chemistry

Contemporary Practice in Clinical Chemistry
Copyright
Contents
List of contributors
Preface
1 Preanalytical variation
	Order entry
	Patient preparation
	Specimen collection
		Tube type and order of draw
		Needle size, tourniquet use, and line collection
	Processing and transportation
	Detecting preanalytical errors
	Summary
	References
	Self-assessment questions
	Answers
2 Statistical methods in laboratory medicine
	Introduction
	Basic descriptive statistical analysis
		Central tendency and dispersion
			Mean
		Median
		Standard deviation, interquartile range, and quantiles
		Quantiles and the interquartile range
	Is my data normally distributed?
		Make a histogram
		Prepare a normal QQ plot
		Calculate the skewness and kurtosis
		Statistical tests for normality
			The Shapiro–Wilk test
			The Shapiro–Francia test
			The Lilliefors test
			The Anderson–Darling test
	Detecting outliers
		The Grubbs test
		Dixon test
		Tukey’s fences
		Chauvenet’s criterion
	Common inferential statistics
		The two-sample t-test
			Examples
		The paired t-test
		Wilcoxon rank-sum test (Mann–Whitney U-test)
		Wilcoxon signed-rank test
		The chi-square test
			Application to proportions
			General application to contingency tables
	Methods of regression
		Ordinary least squares
		Weighted ordinary least squares
		Deming regression
		Passing–Bablok regression
	Evaluation of diagnostic test performance
		Sensitivity
		Specificity
		Positive predictive value
		Negative predictive value
	Likelihood ratios
		Example calculation
	Receiver operating characteristic curves
		Interpreting a receiver operating characteristic curve
		Preparing a receiver operating characteristic curve
	Suggested additional topics for study
	References
	Self-assessment questions
	Answers
3 Reference intervals: theory and practice
	Introduction
		Concept of reference intervals and importance to laboratory medicine
		Reference intervals versus clinical decision limits
		Current gaps and recent initiatives in reference interval establishment
	Methodological approaches to establishment of reference intervals
		Population-based reference intervals
		Selection of reference individuals
			Direct versus indirect sampling
			A priori versus a posteriori sampling
		Preanalytical and analytical variables
		Outlier exclusion
		Partitioning and minimum sample size
		Statistical determination of reference intervals
			Nonparametric analysis
			Robust analysis
			Parametric analysis
		Covariates that affect reference interval determination
			Age-dependent reference curves
	Pediatric and geriatric reference intervals: challenges and recent advances
		Pediatric reference intervals
		Geriatric reference intervals
	Reference interval transference and verification
		Methodological approach to transference
		Limitations of the transference method
		Transference initiatives
		Verification of transferred reference intervals
	Toward reference interval harmonization
	Limitations of population-based reference intervals
	Concluding remarks
	References
	Self-assessment questions
	Answers
4 Method validation
	Introduction
	Regulations
	Analytical goals and method selection
	Helpful tips and tools prior to performing validation
	Method validation basics
		Precision and accuracy
		Reportable range
		Method comparison
	Validation of laboratory developed tests
		Carryover validation
		Stability validation
		Selectivity/specificity and interference validation
		Matrix effects validation
		Recovery validation
		Sensitivity validation
		Dilution validation
		Reference standards
	The role of the medical laboratory director
	References
	Self-assessment questions
	Answers
5 Quality control
	Introduction
	Implementing statistical process control
		Selection of quality control materials
		Limitations of quality control materials
		Frequency to assay quality control samples
		Establishing quality control target values and acceptance ranges that represent a stable measurement operating condition
		Establishing acceptance criteria to evaluate quality control results
		Corrective action when a quality control result indicates a measurement problem
		Verifying quality control evaluation parameters following a reagent lot change
		Verifying method performance following use of a new lot of calibrator
		Calibration issues in quality control
	Development of a quality control plan based on risk management
	Reviewing the quality control plan
	Using patient data in quality control procedures
		Delta check with a previous result for a patient
		Verify consistency between more than one instrument or method
		Using patient data for statistical process control
	Proficiency testing
		Noncommutability of proficiency testing/external quality assessment materials and peer group grading
		Reporting proficiency testing/external quality assessment results when one method is adjusted to agree with another method
		Interpretation of proficiency testing/external quality assessment results
		Accuracy-based proficiency testing/external quality assessment programs
	References
	Further reading
	Self-assessment questions
	Answers
6 Laboratory calculations
	Analytical calculations
		Dimensional analysis
		Centrifugation
		Concentration
		Dilutions
		Equilibrium calculations and pH
		Buffer calculations
		Ionic strength
		Photometry calculations
		Electrophoresis
		Electrochemistry
		Enzyme kinetics
		Chromatography
	Clinical calculations
		Electrolytes
		Osmolality and osmolal gap
		Renal function calculations
		Iron calculations
		Lipid calculations
	Statistics
		Mean
		Median
		Standard deviation
		Coefficient of variation
		Variance
		Standard error of the mean
	Method evaluation
		Accuracy: regression analysis of method comparison data
		Accuracy: recovery studies
		Precision: repeatability and within-lab precision studies
		Total error
		Detection limits
		Clinical performance of laboratory tests: predictive value theory
	Laboratory management
		Budget justification
		Full-time equivalent
		Cost per reportable result
		Capital equipment justification
	References
7 Spectrophotometry
	Principles of light absorption and emission
	Principles of spectrophotometric measurement
		Configuration of spectrophotometers
	Critical operating parameters: accuracy
		Bandpass
		Stray light
		Wavelength accuracy
		Absorbance accuracy
		Chromogen limitations
		Calibration of spectrophotometric measurements
			Molar absorptivity
			Calibration relationship
	Critical operating parameters: precision
	Interferences
		Bichromatic and polychromatic measurements
	Other applications of spectrophotometric or light emission measurements
		Cooximetry
		Reflectance spectrophotometry
		Densitometry
		Turbidimetry and nephelometry
		Atomic absorption
		Atomic emission
		Fluorescence
			Fluorescence lifetime
			Fluorescence polarization (depolarization)
		Chemiluminescence
	References
	Suggested reading
	Self-assessment questions
	Answers
8 Chromatography and electrophoresis
	Introduction to chromatography
		General terms and concepts
		Theory of chromatography
		Evaluating and optimizing chromatographic separations
	Gas chromatography
		General terms and concepts
		Gas chromatography mobile phases and elution methods
		Gas chromatography supports and stationary phases
		Gas chromatography detectors
		Methods for sample injection and pretreatment in gas chromatography
	Liquid chromatography
		General terms and concepts
		Liquid chromatography mobile phases and elution methods
		Types of liquid chromatography
			Adsorption chromatography
			Partition chromatography
			Ion-exchange chromatography
			Size-exclusion chromatography
			Affinity chromatography
		Liquid chromatography detectors
	Introduction to electrophoresis
		General terms and concepts
		Theory of electrophoresis
	Gel electrophoresis
		General terms and concepts
		Supports and sample application in gel electrophoresis
		Detection in gel electrophoresis
		Special types of gel electrophoresis
	Capillary electrophoresis
		General terms and concepts
		Supports and sample application in capillary electrophoresis
		Detection in capillary electrophoresis
		Special types of capillary electrophoresis
	References
	Self-assessment questions
	Answers
9 Electrochemistry
	Introduction
	Potentiometric methods in clinical chemistry
		Redox electrodes
		Ion-selective electrodes
			Glass membrane electrodes
			Polymer membrane electrodes
			Gas-sensing electrodes
			Ion-selective electrodes—units of measure and reporting for clinical application
	Amperometric methods in clinical chemistry
	Conductometric methods in clinical chemistry
	Coulometric methods in clinical chemistry
	Interferences for potentiometric and amperometric sensors
	Biosensors based on electrochemical methods
		Enzyme-based biosensors with amperometric and potentiometric detection
		Affinity biosensors with electrochemical detection
	References
	Self-assessment questions
	Answers
10 Mass spectrometry
	Basic mass spectrometry concepts
	Sample introduction
	Ion sources
		Electron ionization
		Chemical ionization
		Electrospray ionization
		Atmospheric pressure chemical ionization and atmospheric pressure photoionization
		Inductively coupled plasma ionization
		Matrix-assisted laser desorption ionization
		Desorption electrospray ionization and direct analysis in real time
		Emerging ionization methods of interest
	Mass analyzers
		Beam-type design
			Magnetic sector
			Quadrupole
			Time of flight
		Trapping mass spectrometers
			Quadrupole ion trap
			Linear ion trap
			Ion cyclotron resonance
			Orbitrap
		Ion mobility
		Tandem mass spectrometers
	Detectors and processors
	Clinical mass spectrometry applications
	Challenges and opportunities in the implementation of clinical mass spectrometry methods
	Acknowledgments
	References
	Further reading
	Self-assessment questions
	Answers
11 Nuclear magnetic resonance technology and clinical applications
	Introduction
	Theory of nuclear magnetic resonance
	Proton nuclear magnetic resonance spectroscopy
	Nuclear magnetic resonance analyzers in clinical analysis
		Benchtop nuclear magnetic resonance spectrometers
			Nuclear magnetic resonance expansion into the clinical laboratory
			Clinical utility of lipoprotein particle numbers
			Standard lipid panel and apolipoprotein B are measured by nuclear magnetic resonance
			LP-IR, a measure of insulin resistance that predicts future type 2 diabetes
			GlycA, a nuclear magnetic resonance-specific marker of systemic inflammation
			Clinical utility for nuclear magnetic resonance quantified metabolites
			Branched-chain amino acids (BCAA) for prediction of T2D risk
			Ketone bodies for diagnosis of diabetic or alcoholic ketoacidosis
			Trimethylamine-N-oxide for assessment of gut dysfunction and cardiovascular disease risk
			Nuclear magnetic resonance instrument and diagnostic test manufacturers entering the US diagnostic market
	Conclusions
	Disclosure
	References
	Self-assessment questions
	Answers
12 Immunoassays
	Introduction
	Immunoassays
		Homogenous versus heterogeneous immunoassays
		Competitive immunoassays
		Noncompetitive (immunometric) immunoassays
		Immunoassay detection methods
			Fluorescence
			Enzymes
			Chemiluminescence
			Particle-based immunoassays
			Alternative labels and technologies
		Immunoassay interferences
		Advances in immunoassay testing
	HIV Ag/Ab combination assay
	Mass spectrometry measurement of thyroglobulin
	Multiplexed immunoassay testing
		Point-of-care immunoassays
	References
	Self-assessment questions
	Answers
13 Nucleic acid analysis in the clinical laboratory
	Introduction
	The biochemistry of deoxyribonucleic acid
	The human genome
	Complementarity
	Southern blot
	Fluorescence in situ hybridization
	FISH probes
	The polymerase chain reaction
	The process of polymerase chain reaction amplification
	Reverse transcriptase polymerase chain reaction
	Analysis of polymerase chain reaction amplicons
	Multiplex polymerase chain reaction
	Real-time polymerase chain reaction
	Probes for real-time polymerase chain reaction
	Post real-time polymerase chain reaction analysis
	Multiplexing with real-time polymerase chain reaction
	Digital polymerase chain reaction
	Digital polymerase chain reaction and multiplexing
	Microarrays
	Sequencing
		Sanger sequencing
		Next-generation sequencing
		Library preparation
		Amplification-based enrichment methods
		Hybrid capture enrichment methods
		Template amplification
		Emulsion polymerase chain reaction
		Isothermal bridge amplification (bridge polymerase chain reaction)
		Sequencing by reversible termination or sequencing by synthesis
		pH-mediated sequencing
		Data analysis
		Third-generation sequencing
	Implementation of molecular assays in the clinical laboratory
	Conclusion
	References
	Self-assessment questions
	Answers
14 Laboratory automation
	Goals of automation
	Components of laboratory automation
	Expectations of automation
	Automation beyond the chemistry analyzer
	Measurements of success
	Oversight
	Limitations of automation
	Ongoing monitoring
	Future perspective
	Conclusion
	References
	Self-assessment questions
	Answers
15 Laboratory regulations and compliance
	Introduction
	Regulatory responsibility in the laboratory
	Federal regulations
		Clinical Laboratory Improvement Amendments of 1988
			Administrative provisions
			Certification process
				Waived tests
				Provider-performed microscopy
				Moderate- and high-complexity testing
				Inspecting organizations
			Proficiency testing
			Patient test management
			Quality control
			Personnel standards
			Enforcement
	Patient privacy
		Privacy standard
		The security standard
		Health Information Technology for Economic and Clinical Health Act
		Genetic privacy
	Biobanking and providing specimens for research
	Occupational Safety and Health Administration regulations
		Bloodborne pathogens
		Chemical hygiene rule
	Reimbursement regulations: fraud and abuse
		Early examples of fraud and abuse
		The False Claims Act
		Inducements and kickbacks
		Office of the Inspector General’s Compliance Guidelines
		Direct billing
		Stark amendments
		Key financial compliance considerations
		Food and Drug Administration oversight of laboratory developed tests
	State regulations
	Negligence
	Acknowledgments
	References
	Self-assessment questions
	Answers
16 Evidence-based laboratory medicine
	Introduction
	Elements of evidence-based laboratory medicine
		The clinical question
		Finding the evidence
			Resources for searches on diagnostic tests
			Approaches to evidence-based laboratory medicine—types of analyses
			Critical appraisal of evidence
		Using the evidence to develop clinical practice guidelines
			Clinical practice guidelines
		Best practices in guideline development
		Steps in guideline development
		Additional resources for developing clinical practice guidelines
			Implementation of clinical practice guidelines
	Metrics for evaluating diagnostic laboratory tests
		Measures of diagnostic accuracy
		Receiver operating characteristic curves
		Likelihood ratios
		Test as a probability modifier: example
		Is the test cost-effective?
			Cost–benefit analysis
			Cost-effectiveness analysis
			Cost–utility analysis
	Using clinical laboratory medicine data for decision-making
		From evidence to action: changing clinical practice and improving outcomes
		Quality indicators and metrics
	Summary
	References
	Self-assessment questions
	Answers
17 Harmonization of results among laboratories
	Why harmonized results are important?
		Definition
		Impact of harmonization
	Infrastructure to support harmonization
		International Organization for Standardization
		Joint Committee for Traceability in Laboratory Medicine
	How to achieve harmonized results
		Metrological traceability of calibration to a reference system
		Calibration traceability when reference system components are missing
			Traceability to a secondary reference material
			Traceability to a measurement procedure producer’s working calibrator
			Traceability to a harmonization protocol
	Commutability
		Validating commutability of a reference material
	How to verify traceability of a clinical laboratory measurement procedure
		Calibration of laboratory developed tests
	References
	Self-assessment questions
	Answers
18 Laboratory information management
	Introduction
	Management of digital laboratory information
		Laboratory information systems
			Key concepts
				Dictionaries and worksheets
	Laboratory information systems: preanalytic phase
		Patient identification
		Order generation
		Specimen collection
		Specimen accessioning
		Specimen identification
	Laboratory information systems: analytic phase
		Manual results entry
		Instrument interfaces
		Quality control and quality assurance
		Results review
		Autoverification
		Middleware
	Laboratory information systems: postanalytic phase
		Reporting
		Result interpretation
		Billing
		Point-of-care results
	Data exchange and standards
		Health Level 7 standards
	Logical observation identifier names and codes
		Management of nonlaboratory information systems data
		Standalone software systems
			Document control
			Quality control
			Inventory control
	Servers, directories, and security
		Security and access control
	File types
	Secondary data use
	Data warehousing
	Data analysis
		Machine learning and artificial intelligence
	Data privacy
	Opportunities
		Research
	Summary
	Acknowledgments
	Suggested reading
	Self-assessment questions
	Answers
19 Point-of-care testing
	Introduction
	Quality point-of-care testing
	Point-of-care testing regulations
	Point-of-care testing connectivity and interfacing
	Point-of-care testing quality assurance programs
	Interdisciplinary communication
	Self-management
	Analytical performance
	Method limitations
	Risk management
	Summary
	References
	Self-assessment questions
	Answers
20 Applications of molecular techniques in the clinical laboratory
	Molecular diagnostics
		Somatic gene variants
		Loss of heterozygosity
		Circulating tumor cells and cell-free DNA
	Genetic variants in hemostasis
		Prothrombin polymorphisms
		Factor V Leiden polymorphism
		Methylenetetrahydrofolate reductase polymorphism
	Nucleic acid testing in pathogen detection and monitoring
		Hepatitis B virus
		Hepatitis C virus
		Human immunodeficiency virus type 1
		Viral drug resistance and genotyping
	Assay approaches
		Next-generation sequencing
		Digital polymerase chain reaction
		Universal biosensors for pathogen detection
	Regulatory considerations for molecular approaches
		Limitations to molecular detection of allelic variants
	Conclusions
	References
	Self-assessment questions
	Answers
21 Applications of mass spectrometry in the clinical laboratory
	Mass spectrometric applications for measuring small molecules
		Sample preparation for small molecule methods
		Qualitative and quantitative testing
		Toxicology
		Therapeutic drug monitoring
		Endocrinology
		Newborn screening
		Trace elements
	Mass spectrometry applications for measuring proteins
	Techniques used in clinical proteomics
		Bottom-up approach
		Top-down approach
		Sample preparation
		Quantitation
		Instrumentation
	Examples of clinical protein mass spectrometric assays
		Thyroglobulin
		Insulin-like-growth-factor 1
		Monoclonal immunoglobulins (M-proteins)
		Classification of amyloidosis
		Identification of microorganisms
	Use of mass spectrometry in method standardization and harmonization
	Regulatory considerations for clinical mass spectrometry
	Challenges of implementing mass spectrometry in the clinical laboratory
	Future of clinical mass spectrometry
	Conclusion
	References
	Self-assessment questions
	Answers
22 Proteins: analysis and interpretation in serum, urine, and cerebrospinal fluid
	Introduction
	Prealbumin region
	Albumin region
	αl Region
	α2 Region
	β Region
	β1 Region
	β2 Region
	γ Region
	Standard analytical techniques
	Turbidimetry and nephelometry
	Radial immunodiffusion
	Calculated results
	Quantitative assessment of proteins
		Serum protein electrophoresis
		Case example
		Immunofixation electrophoresis
		Capillary zone electrophoresis
		Mass spectrometry
		Serum free κ and λ light chains in serum and urine
		β2 Microglobulin
	Interferences
		Endogenous interferences
		Exogenous interferences
	Protein analysis and interpretation
		Protein electrophoresis examples
		Acute-phase response
		Monoclonal gammopathies
		Multiple myeloma
		Waldenström macroglobulinemia and immunoglobulin M multiple myeloma
		Cryoglobulinemia
		Amyloidosis
		Light-chain deposition disease
		Multiple sclerosis and cerebrospinal fluid electrophoresis
		Summary
	References
	Suggested readings
	Self-assessment questions
	Answers
23 The complement system
	Introduction
	Overview of the complement system
		The classical pathway
		The lectin pathway
		The alternative pathway
		The terminal pathway
		Complement regulation
	Assays in the clinical laboratory
		Serologic complement assays
			Preanalytical considerations
			Postanalytical challenges
		Methods for analysis of complement function or activity
		Complement component concentrations
		Complement activation products
		Autoantibodies to complement components
		Complement genetic testing
	Disorders associated with complement deficiency or dysregulation
		Complement deficiencies
		Complement in autoimmune diseases
			Disease presentations
		Hereditary and acquired angioedema
		Atypical hemolytic uremic syndrome
		Paroxysmal nocturnal hemoglobinuria
		Complement in C3 glomerulopathies
		Complement and other conditions
			Monoclonal gammopathies
			Cryoglobulinemia
			Hepatitis C virus infections
			Complement in age-related macular degeneration
	Complement therapeutics
		Therapeutics for hereditary angioedema
		The C5 inhibitor
	Future directions
	Acknowledgments
	References
	Self-Assessment Questions
	Answers
24 Hemoglobin variant detection
	Introduction
	Blood smears and cell counts
		Case Example 1
		Case 1 Resolution
	Biochemical techniques
		Quantitative measurement of hemoglobin variants
			High-performance liquid chromatography
			Capillary zone electrophoresis
			Case Example 2
			Case 2 Resolution
			Case Example 3
			Case 3 Resolution
		Qualitative measurement of hemoglobin variants
			Slab gel electrophoresis
			Sickle solubility test
			Unstable hemoglobins
			Case Example 4
			Case 4 Resolution
		Mass spectrometry
	Molecular techniques
		Targeted assays for known variants
			Gap-PCR
			Case Example 5
			Case 5 Resolution
		Assays to detect unknown variants
			Nonsequencing methods
			Multiplex ligation-dependent probe amplification
			Chain-terminating dideoxynucleotide sequencing (Sanger sequencing)
			Case Example 6
			Case 6 Resolution
		Next-generation sequencing
	References
	Further reading
	Self-assessment questions
	Answers
25 The complete blood count and white blood cell differential
	The cellular components of the peripheral blood
		Red blood cells
		Platelets
		White blood cells
	The complete blood count and white blood cell differential
		Laboratory techniques used in the complete blood count
		The red blood cell and platelet counts and indices
			Red blood cell and platelet counts
			Fluorescent platelet count
			Reticulocyte count
			Hemoglobin
			Mean corpuscular volume and mean platelet volume
			Hematocrit
			Mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration
			Red blood cell and platelet distribution widths
		The white blood cell count and differential
	Interpretation of abnormal results for the complete blood count or white blood cell differential
		Abnormal red blood cell count or indices
			Anemia
			Polycythemia
			Increased red cell distribution width
		Abnormal platelet count or indices
			Thrombocytosis
			Thrombocytopenia
		Abnormal white blood cell count or differential
			Leukocytosis
			Leukopenia
		Common errors seen with automated cell counters
			Errors in red blood cell count
			Errors in the hemoglobin measurement
			Errors in the mean corpuscular volume measurement
			Errors in the platelet count
			Errors in the white blood cell count
	Interpretation of the peripheral blood smear
		Red blood cell morphology
		Platelet morphology
		White blood cell morphology
	References
	Self-assessment questions
	Answers
26 Hemostasis
	The physiology of hemostasis
		Primary hemostasis
			Von Willebrand factor
			Platelet function
			Platelet receptors
		Secondary hemostasis
		Tertiary hemostasis
			Anticoagulation
			Fibrinolysis
	Laboratory testing
		Activated partial thromboplastin time
		Prothrombin time
		International normalized ratio
		Mixing studies
		Activated clotting time
		Fibrinogen
		Factor assays
		Anti-Xa
		Thrombin time
		D-dimer
		Thromboelastography
	Pathophysiology and advanced coagulation testing
		Bleeding disorders
			Von Willebrand disease
			Hemophilia A and B
			Factor deficiencies
			Platelet disorders
			Acquired platelet disorders
			Congenital platelet disorders
			Testing for bleeding disorders
		Thrombophilias
			Activated protein C resistance
			Prothrombin G20210A
			Protein C and S deficiency
				Protein C
				Protein S
			Antithrombin deficiency
			Plasminogen deficiency
			Heparin-induced thrombocytopenia
			Antiphospholipid syndrome
			ADAMTS13 deficiency
			Thrombophilia testing
	References
	Self-assessment questions
	Answers
27 Diagnostic body fluid testing
	Introduction
	Regulations
	Specific body fluids
		Cerebrospinal fluid
		Pleural fluid
		Peritoneal fluid/ascites
			Ascitic fluid methods
		Dialysate
		Pericardial fluid
		Synovial fluid
		Amniotic fluid
		Feces
	References
	Self-assessment questions
	Answers
28 Lipids and lipoproteins
	Background
	Clinically relevant lipids
	Lipoprotein metabolism
		Apolipoprotein B lipoproteins and triglyceride redistribution
		Apolipoprotein A-I lipoproteins and reverse cholesterol transport
	Clinical laboratory lipid measurements
		The basic lipid panel
			Total cholesterol
			Triglycerides
			High-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol
		Low-density lipoprotein cholesterol
			Beta-quantification of low-density lipoprotein cholesterol
			Estimation of low-density lipoprotein cholesterol
			Direct homogeneous low-density lipoprotein cholesterol
	Lipoprotein electrophoresis
		Apolipoproteins
			Apolipoprotein B
				Apolipoprotein A-I
					Apolipoprotein (a)
	Nonfasting lipid assessment
	Lipoprotein subfraction methods
	Lipoprotein disorders
	Hyperlipoproteinemias
		Exogenous hyperlipemia
		Familial hypercholesterolemia
		Combined hyperlipidemia
		Remnant hyperlipidemia
		Endogenous hyperlipemia
		Mixed hyperlipemia
		Lipoprotein (a) disorder
		Lipoprotein X
	Hypolipoproteinemias
		Hypobetalipoproteinemia
		Abetalipoproteinemia
		Hypoalphalipoproteinemia
	Lipids and cardiovascular disease
	Lipid lowering for treatment of cardiovascular disease
	Clinical practice lipid measurement guidelines
	References
	Self-assessment questions
	Answers
29 Pediatric laboratory medicine
	Blood volume and sample volume requirements
	Challenges associated with small blood volumes
	Specimen types and collection
	Reference intervals in pediatrics
	Newborn screening
		Inborn errors of metabolism
		Cystic fibrosis
		Other conditions
		Follow-up
	Lead
		Treatment
	Transient hyperphosphatasemia
	Potassium and hemolysis
	Hemolysis and plasma hemoglobin
	Lipids
	Bilirubin
	Implications for testing in the pediatric population
	Transitioning to adult care
	References
	Self-assessment questions
	Answers
30 Biomarkers for coronary artery disease and heart failure
	Introduction
	Pathophysiology of acute coronary syndrome and myocardial infarction classification
	Evolving definitions of myocardial infarction with an increasing focus on biomarkers
	Cardiac troponins T and I
		Biochemistry
		Clinical utility of cardiac troponins in acute coronary syndrome
			Diagnosis and risk stratification
			Optimum cutoff concentrations
	Other biomarkers of acute myocardial infarction
	High-sensitivity cardiac troponin assays
	Pathophysiology of heart failure
	B-type natriuretic peptide and N-terminal-proBNP
		Biochemistry
		Clinical utility of B-type natriuretic peptide and N-terminal-proBNP in heart failure
			Diagnosis
			Staging
			Monitoring and management
	Clinical utility of B-type natriuretic peptide and N-terminal-proBNP in acute coronary syndrome
	Clinical need for future biomarkers of acute cardiovascular diseases
		Early acute coronary syndrome diagnosis
		Improved risk stratification for adverse cardiac events
		Other heart failure biomarkers
	Laboratory analysis for cardiac biomarkers
	Conclusions
	References
	Self-assessment questions
	Answers
31 Laboratory diagnosis of liver disease
	Review of normal liver structure and function
		Anatomical features
		Liver functions
			Synthesis
			Excretion
			Metabolism
	Tests of liver injury
		Liver-injury markers
			Aspartate aminotransferase
			Alanine aminotransferase
			Lactate dehydrogenase
			Alkaline phosphatase
			Gamma-glutamyl transferase
		Other liver biomarkers
			Alpha-fetoprotein
			Des-gamma-carboxy prothrombin
			Autoantibodies
	Assessment of liver disease
		Clinical manifestations of liver disease
	Acute liver disease
		Clinical presentation and patterns of injury associated with immunologically mediated acute hepatitis
		Causes of viral acute hepatitis
			Hepatitis A
			Hepatitis B
			Hepatitis C
			Hepatitis D
			Hepatitis E
		Toxic and ischemic hepatitis
		Biliary tract obstruction
	Chronic liver disease
		Chronic hepatitis
			Chronic viral hepatitis
			Other causes of chronic hepatitis
		Cirrhosis
		Chronic cholestatic disorders
	Hepatic tumors
	Suggested reading
	Self-assessment questions
	Answers
32 Clinical chemistry of the gastrointestinal disorders
	Anatomy/physiology
		Duodenum
		Jejunum
		Ileum
	Pathology
		Oral cavity
		Esophagus
		Stomach—gastritis
		Stomach—Helicobacter pylori infection
			Biopsy
			Serologic testing
			Breath/urea breath testing
			Stool testing
		Stomach—pernicious anemia
		Stomach—pepsinogen
		Stomach—gastrin
	Small intestine
		Small intestine—duodenum–gastrinoma
		Small intestine—carcinoid
		Small intestine—carcinoid syndrome
		Small intestine—malabsorption
		Small intestine—fat malabsorption
		Small intestine—carbohydrate malabsorption
			D-Xylose test
			Lactose tolerance test
			Breath testing
		Small intestine—celiac disease
			Small intestine—bacterial overgrowth
	Colon
		Colon—diarrhea
			Stool electrolytes
		Colon—Clostridium difficile-related diarrhea
		Colon—gastrointestinal bleeding
		Fecal occult blood testing
		Colon—tumor markers
		Colon—inflammatory bowel disease
	References
	Further reading
	GI CHEMISTRY—Self-assessment questions
	Answers
33 Evaluation of exocrine pancreatic function
	Anatomy and physiology of the pancreas
	Laboratory measurement of pancreatic enzymes
		Amylase
		Determination of total amylase activity
		Commutable reference material for α-amylase
		Determination of pancreatic-specific amylase activity
		Lipase
		Determination of lipase activity
		Trypsin
		Chymotrypsin
		Elastase-1
		Quantitative fecal fat
		CA 19-9
	Disorders of the pancreas
		Exocrine pancreatic insufficiency
		Direct assessment of pancreatic insufficiency
		Acute pancreatitis
		Diagnosis of acute pancreatitis
		Assessment of disease severity
		Chronic pancreatitis
		Diagnosis of chronic pancreatitis
		Pancreatic cancer
		Pancreatic cyst fluid analysis
	Conclusion
	References
	Self-assessment questions
	Answers
34 Carbohydrate disorders
	Introduction
	Glucose measurements
	Common specimen sources for glucose measurement
	Hypoglycemia
		Clinical presentation of hypoglycemia
		Mechanisms and causes of hypoglycemia
		Laboratory evaluation of hypoglycemia
	Hypoglycemic conditions in children
	Hyperglycemia
		Type 1 diabetes
		Type 2 diabetes
		Other specific types of diabetes
		Gestational diabetes mellitus
		Diagnosis of diabetes mellitus
		Oral glucose tolerance test
		Prediabetes
		Diagnosis of gestational diabetes mellitus
		Screening for type 2 diabetes in adults and children
		Special aspects of blood glucose testing
		Transient hyperglycemia
		Long-term glycemic monitoring in diabetes
			Glycated hemoglobin measurements
		Glycated serum protein measurements
		Future therapies for type 1 diabetes
		Metabolic syndrome
	Galactose disorders
	References
	Self-assessment questions
	Answers
35 Laboratory evaluation of kidney function
	Physiology of kidney function
	Chronic kidney disease
		Definition
		Categories of chronic kidney disease
		Public health efforts
	Measurement of glomerular filtration rate
		Clearance methods
		Exogenous substances to measure glomerular filtration rate
		Endogenous substances to measure glomerular filtration rate
		Creatinine
			Physiology of creatinine
			Measurement of creatinine
			Standardized calibration of creatinine measurements
			Limitations of serum creatinine interpretation
		Cystatin C
			Physiology of cystatin C
			Measurement of cystatin C
	Estimating equations
		Estimated glomerular filtration rate
		Creatinine-based estimating equations
			Cockcroft–Gault equation
			Modification of diet in renal disease study equation
			Chronic kidney disease epidemiology collaboration equation
			Limitations of creatinine-based estimates of glomerular filtration rate
		Cystatin-C-based estimating equations
		Estimating glomerular filtration rate in children
	Kidney function assessment and drug dose adjustment
	Urine protein
		Definitions
		Urine total protein measurement
		Urine albumin measurement
		Urine creatinine measurement
			Recommendations for measuring and reporting urine albumin and creatinine
	Other biomarkers of kidney damage
		Markers of tubular function
		Urinalysis
		Acute kidney injury and emerging biomarkers
		Kidney stones
	References
	Self-assessment questions
	Answers
36 Contemporary practice in clinical chemistry: blood gas and critical care testing
	Introduction
	Explanations of blood gas, acid–base, and cooximetry terms
		pH
		pCO2
		pO2
		Bicarbonate
		Base excess
		Anion gap
		Strong ion difference
		Hb and its derivatives
		Percent O2 saturation and %O2Hb
		COHb and Met-Hb
		DO2 and VO2
	Physiology of acids and bases
		How are acids and bases produced?
			Metabolic acid
			Lactate acidosis
			Ketoacidosis
			Production of base
		Buffer systems
			Bicarbonate–carbon dioxide
			Hb
			Phosphate
			Albumin and other proteins
		Acid-base regulation
			Respiratory (ventilatory) system
			Metabolic (renal) system
			Compensation
	Clinical abnormalities of acid–base balance
		Metabolic (nonrespiratory) acidosis
			Use of the anion gap in metabolic acidosis
			Expected compensation in metabolic acidosis
			Treatment of metabolic acidosis
		Metabolic (nonrespiratory) alkalosis
			Expected compensation in metabolic alkalosis
			Treatment of metabolic alkalosis
		Respiratory acidosis
			Expected compensation in respiratory acidosis
			Treatment of respiratory acidosis
		Respiratory alkalosis
			Expected compensation in respiratory alkalosis
			Treatment of respiratory alkalosis
		Detecting mixed acid–base disorders
		Does the expected compensation occur?
			Metabolic acidosis
			Metabolic alkalosis
			Respiratory acidosis or respiratory alkalosis
		Delta ratio or delta gap: does the change in anion gap match the change in bicarbonate?
		Tips for diagnosing mixed acid–base disorders
	Evaluating blood gas results
		Reference and critical ranges
	Evaluating the acid–base status
	Step 1: evaluate the patient’s status and history to anticipate possible acid–base abnormalities
	Step 2: evaluate the pH
	Step 3: evaluate the ventilatory and metabolic statuses
		Examples
	Steps 4a–4c: evaluate for a possible mixed disorder
		4a. Is the compensation adequate for the primary disorder?
		4b. Do other laboratory results suggest an additional acid–base disorder is present?
			Potassium
			pH
			Chloride
			Anion gap
			Delta ratio
			Lactate
			Creatinine
		4c. Does the patient have other conditions associated with an acid–base disorder?
	Evaluating oxygen status
		Hemoglobin binding
			Hb binding to O2
	Disorders of oxygenation: hypoxemia and tissue hypoxia
	O2 delivery to tissues
		Gas exchange in the lungs
		Blood flow to tissues
	Evaluation of oxygenation status and arterial oxygenation
	Arterial O2 tension and sO2 of Hb
	paO2/FIO2 ratio
	Hb concentration
	Blood O2 content
	Alveolar–arterial oxygen difference or gradient (A–a)
	V/Q mismatch and intrapulmonary shunting
	Evaluating tissue oxygenation
	Collection and handling of samples for blood gas analysis
		Use of arterial versus venous blood for blood gas and acid–base measurements
	Collection and handling of blood
		Storage of blood specimen
	Cord blood gases
	Temperature correction of blood gas results
	Usefulness of other tests on modern blood gas analyzer menus
		Lactate
		Glucose
	Met-Hb
	References
	Self-assessment questions
	Answers
37 Water and electrolyte balance
	Normal physiology of water and electrolytes
		Distribution of water and electrolytes between body fluid compartments
		Regulation of water
			Osmoregulators
			Volume regulators
			Natriuretic peptides
		Regulation of electrolytes
			Sodium regulation in blood
			Potassium regulation in blood
			Chloride regulation in blood
	Laboratory tests used to evaluate fluid and electrolyte abnormalities
		Electrolytes
			Sodium
			Potassium
			Chloride
		Osmolality
	Disorders of water and sodium
		Disorders causing hyponatremia
			Decreased sodium
			Increased water
		Disorders causing hypernatremia
			Case example
			Case resolution
	Disorders of potassium
		Disorders causing hypokalemia
			Renal potassium loss
			Shift of potassium into cells
		Disorders causing hyperkalemia
			Decreased renal excretion
			Shift of potassium out of cells
			Case example
			Case resolution
	Disorders of chloride
		Disorders causing hypochloremia
		Disorders causing hyperchloremia
	Acknowledgments
	Suggested reading
	Self-assessment questions
	Answers
38 Urinalysis
	Introduction
	Specimen collection and handling
	Routine urinalysis
	Physical examination
		Appearance
			Color
			Turbidity
			Odor
		Concentration
			Specific gravity
			Osmolality
	Chemical examination
		Reagent-strip testing
		Confirmatory testing: tablet and chemical tests
		Tests results often indicating urinary tract disease
			Protein
			Blood
			Leukocyte esterase
			Nitrite
		Test results occasionally indicating urinary tract disease
			pH
			Sugars
		Test results rarely indicating urinary tract disease
			Ketones
			Bilirubin
			Urobilinogen
	Microscopic examination
		Crystals
		Blood cells
			Red blood cells
			White blood cells
		Epithelial cells
			Renal tubular epithelial cells
			Collecting duct epithelial cells
			Urothelial cells
			Squamous cells
		Casts
		Microorganisms
	Automated urinalysis platforms
	Suggested reading
	Self-assessment questions
	Answers
39 Disorders of the anterior and posterior pituitary
	Introduction
	Anatomy
	Physiology and regulation
	Anterior pituitary hormone pathophysiology and lab findings
		Hyperfunction
		Hypofunction
	Adrenocorticotropic hormone
		Dexamethasone suppression test
		Adrenocorticotropic hormone stimulation test
		Insulin tolerance test
		Metyrapone test
		Corticotropin-releasing hormone stimulation test
	Thyroid-stimulating hormone
	Growth hormone
	Follicle-stimulating hormone and luteinizing hormone
	Prolactin
		Evaluation for potential high-dose hook interference
		Evaluation for potential macroprolactinemia
	Posterior pituitary hormone pathophysiology and lab findings
		Antidiuretic hormone
			Water deprivation test
			Desmopressin challenge test
	Oxytocin
	References
40 Laboratory evaluation of thyroid function
	Thyroid: anatomy, physiology, and biochemistry
	Thyroid hormone regulation
		Hypothalamus–pituitary–thyroid axis
	Thyroid hormone synthesis
		1) Thyroglobulin synthesis
		2) Iodine transportation and processing
		3) Monoiodo tyrosine and diiodotyrosine formation
		4) Triiodothyronine and thyroxine formation
		5) Thyroid hormone release and monoiodo tyrosine/diiodotyrosine recycling
	Thyroxine versus triiodothyronine
	Thyroid hormone transport, conversion, and mechanism of action
		Thyroxine and triiodothyronine transport to tissues
		Conversion of thyroxine into triiodothyronine
		Reverse triiodothyronine
		Mechanism of action
	Clinical assessment of thyroid function
		Overview
		Autoantibodies
	Hyperthyroidism (thyrotoxicosis)
		Laboratory findings
		Graves’ disease
		Laboratory findings
		Nodule/multinodular goiter
		Laboratory findings
	Hypothyroidism
		Laboratory findings
		Hashimoto’s thyroiditis
		Laboratory findings
		Other causes
		Laboratory findings
	Nonthyroidal illness
		Laboratory findings
	Thyroid function and pregnancy
		Laboratory findings
	Thyroid cancer
		Laboratory findings
	Laboratory measurements of thyroid function
		Overview
	Thyroid-stimulating hormone (thyrotropin)
		Overview and indications
		Methods
		Considerations
	Total thyroxine
		Overview and indications
		Methods
		Considerations
	Free thyroxine
		Overview and indications
		Methods
			Direct measurement of FT4
		Considerations
			Indirect measurement of free thyroxine: index methods
			Indirect measurement of free thyroxine: immunoassay
		Considerations
	Total triiodothyronine and free triiodothyronine
		Overview and indications
		Methods
		Considerations
	Reverse triiodothyronine
	Thyroxine-binding globulin
	Thyroglobulin
	Thyroid autoantibodies
	References
41 Disorders of the adrenal cortex and medulla
	Introduction
	Adrenal cortex
		Mineralocorticoids
		Disorders of mineralocorticoid excess
		Disorders of mineralocorticoid excess: laboratory testing
		Disorders of mineralocorticoid deficiency
		Disorders of mineralocorticoid deficiency: laboratory testing
		Glucocorticoids
		Disorders of glucocorticoid excess
		Disorders of glucocorticoid excess: laboratory testing
		Disorders of glucocorticoid deficiency (adrenal insufficiency)
		Congenital adrenal hyperplasia
		Disorders of glucocorticoid deficiency (adrenal insufficiency): laboratory testing
		Adrenal androgens
		Disorders of adrenal androgen excess (hyperandrogenism)
		Disorders of adrenal androgen excess (hyperandrogenism) laboratory testing
		Disorders of adrenal androgen deficiency
		Disorders of adrenal androgen deficiency laboratory testing
	The adrenal medulla
		Disorders of catecholamine excess
		Disorders of catecholamine excess laboratory testing
		Catecholamine deficiency
	References
	Further readings
	Self-assessment questions
	Answers
42 Laboratory testing in pregnancy
	Normal pregnancy
		Physiological changes during pregnancy
		Prenatal laboratory assessment
	Human chorionic gonadotropin
		Biochemistry of human chorionic gonadotropin
		Function and expression of human chorionic gonadotropin in normal pregnancy
		Expression of human chorionic gonadotropin in abnormal pregnancy
		Human chorionic gonadotropin immunoassays
			Qualitative human chorionic gonadotropin assays
			Quantitative human chorionic gonadotropin assays
	Progesterone expression in pregnancy
	Abnormal pregnancy
		Ectopic pregnancy
		Molar pregnancy and gestational trophoblastic disease
			Hyperemesis gravidarum
			Preeclampsia
		Thyroid dysfunction during pregnancy
		Hemolytic disease of the fetus/newborn
			Pathophysiology
			Prevention
			Diagnosis and management of alloimmunization in pregnancy
			Treatment of the symptomatic fetus
	Laboratory testing for fetal anomalies
		Open neural tube defects
		Fetal aneuploidy
			Down syndrome
			Trisomy 18
			Trisomy 13
			Multifetal gestations
			Cell-free DNA or noninvasive prenatal testing
	Preterm birth
		Prediction of preterm birth
			Fetal fibronectin testing
			Other biochemical markers for the prediction of preterm birth
		Prevention of preterm birth
		Fetal lung maturity testing
		Laboratory assessment of fetal lung maturity
			The surfactant–albumin ratio
			Lamellar body count
			Lecithin–sphingomyelin ratio
			Phosphatidyl glycerol
	References
	Further reading
	Self-assessment questions
	Answers
43 Laboratory testing in reproductive disorders
	Introduction
	Hypothalamic–pituitary–gonadal axis
	Male reproductive endocrinology
		Control of testicular function
		Androgens
			Testosterone
			Measurement of testosterone
			Free and bioavailable testosterone
			Dehydroepiandrosterone and dehydroepiandrosterone sulfate
		Male reproductive development
		Male reproductive disorders
			Hypogonadism
			Defects in androgen action
			Erectile dysfunction
			Gynecomastia
	Female reproductive endocrinology
		Control of ovarian function
			Ovarian steroids
			Estrogens
			Measurement of estrogen
			Progesterone
		Female reproductive development
		Menstrual cycle
			Follicular phase
			Luteal phase
		Female reproductive disorders
			Hypothalamic–pituitary dysfunction
			Congenital disorders
			Androgen excess
			Amenorrhea
			Laboratory evaluation of amenorrhea
		Assessment of infertility in males and females
			Assessment of infertility in males
			Assessment of infertility in females
	Suggested reading
	Self-assessment questions
	Answers
44 Tumor markers
	Introduction to cancer
	Introduction to tumor markers
		Definition
		Characteristics
		Classes
		Measurement and evaluation
			Reference values
			Analytical considerations
			Clinical considerations
	Specific tumor markers
		Breast cancer
		Gastrointestinal cancers
		Genitourinary cancers
			Prostate cancer
				Prostate specific antigen
				Prostate cancer gene of antigen 3
			Bladder cancer markers
		Hepatocellular cancer
			α-Fetoprotein
			Des-γ-carboxy prothrombin
		Thoracic cancer
			Lung
				CYFRA 21-1
			Mesothelioma
				Soluble mesothelin-related peptides
		Ovarian cancer
			Cancer antigen 125
			Human epididymis 4 protein
		Thyroid cancer
			Thyroglobulin
	Guidelines for the use of tumor markers
	References
	Self-assessment questions
	Answers
45 Calcium biology and disorders
	Introduction
	Calcium
		Calcium function and distribution
		Calcium sensing by the parathyroid glands
		Parathyroid hormone synthesis, release, and metabolism
		Parathyroid hormone actions
		Vitamin D metabolism and biology
		Phosphate biology
		Bone biology
	Hypocalcemia
		Decreased parathyroid hormone action
		Hypoparathyroidism
		Pseudohypoparathyroidism
		Deficient vitamin D action
		Other causes of hypocalcemia
		Clinical approach to hypocalcemia
	Hypercalcemia
		Primary hyperparathyroidism
		Familial forms of hyperparathyroidism
		Secondary hyperparathyroidism
		Tertiary hyperparathyroidism
		Malignancy
		Endocrine disorders
		Granulomatous diseases
		Drugs
		Immobilization and other miscellaneous causes of hypercalcemia
		Approach to hypercalcemia
		Mutations in the parathyroid hormone/parathyroid hormone-related peptide receptor
	Calcitonin
	Phosphate
	Magnesium
	Markers of bone turnover
	Summary
	References
	Self-assessment questions
	Answers
46 Vitamins: functions and assessment of status through laboratory testing
	Introduction
	Vitamins
	Fat-soluble vitamins
		Intestinal uptake and transport
	Vitamin A
		Biochemical assessment of vitamin A status
	Vitamin D
		Biochemical assessment of vitamin D status
	Vitamin E
		Biochemical assessment of vitamin E status
	Vitamin K
		Biochemical assessment of vitamin K status
	Water-soluble vitamins
		Transport and absorption
	The B vitamin complex
	Thiamine
		Biochemical assessment of thiamine status
	Riboflavin
		Biochemical assessment of riboflavin status
	Niacin
		Biochemical assessment of niacin status
	Pantothenic acid
		Biochemical assessment of pantothenic acid status
	Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal)
		Biochemical assessment of vitamin B6 status
	Biotin
		Biochemical assessment of vitamin biotin status
	Folic acid
		Biochemical assessment of vitamin folate status
	Vitamin B12
		Biochemical assessment of vitamin B12 status
	Choline
		Biochemical assessment of choline status
	Vitamin C
		Biochemical assessment of vitamin C status
	References
	Self-assessment questions
	Answers
47 Trace elements: functions and assessment of status through laboratory testing
	Introduction
	Iron
		Assessment of iron status
	Iodine
		Assessment of iodine status
	Zinc
		Assessment of zinc status
	Selenium
		Assessment of selenium status
	Copper
		Assessment of copper status
	Manganese
		Assessment of manganese status
	Cobalt
		Assessment of cobalt status
	Molybdenum
		Assessment of molybdenum status
	Boron
		Assessment of boron status
	Chromium
		Assessment of chromium status
	Fluorine
		Assessment of fluorine status
	References
	Self-assessment questions
	Answers
48 Newborn screening and inborn errors of metabolism
	Introduction to inborn errors of metabolism
	Newborn screening
	Metabolic testing
		Amino acid analysis
		Acylcarnitine analysis
		Urine organic acid analysis
		Other metabolic testing
	The disorders
		Amino acid disorders
			Phenylketonuria
			Hereditary tyrosinemias
			Maple syrup urine disease
			Homocystinuria
			Other amino acid disorders
		Organic acid disorders
			3-Methylcrotonylglycinuria
			Isovaleric aciduria
			Propionic acidemia and methylmalonic aciduria
			Glutaric academia type I
		Urea cycle disorders
		Fatty acid oxidation disorders
		Mitochondrial disorders
		Glycogen storage diseases
		Peroxisomal disorders
		Lysosomal storage diseases
		Congenital disorders of glycosylation
	Conclusion
	Acknowledgment
	References
	Further readings
	Self-assessment questions
	Answers
49 The porphyrias: fundamentals and laboratory assessment
	Introduction
	Biochemistry: heme formation
	Genetic disorders: porphyrias
		Acute porphyrias
		Cutaneous porphyrias
	Diagnosis: laboratory evaluation
		Initial testing for suspected porphyria
		Additional biochemical testing
		Enzyme and molecular testing
	Secondary causes of increased porphyrin excretion
		Specimen requirements
	Treatment and management of the porphyrias
	Summary
	References
	Self-assessment questions
	Answers
50 Basic pharmacokinetics
	Introduction
	Pharmacokinetics and influencing factors
		Drug dosing and administration
		Absorption
		Distribution
		Metabolism
		Excretion
	Pharmacokinetic calculations
		Elimination constant
		Elimination half-life
		Volume of distribution
		Clearance
		Steady-state dose adjustment
	Population pharmacokinetics and modeling
	Special populations
		Neonate/pediatric
		Geriatric
		Obese
	References
	Self-assessment questions
	Answers
51 Therapeutic drug monitoring
	Management of therapeutic drugs
	Principles of therapeutic drug monitoring
	Analytical and clinical laboratory considerations for therapeutic drug monitoring
	Clinical areas where therapeutic drug monitoring is routine practice
		Epilepsy
		Transplantation
		Cardioactive drugs
		Psychoactive drugs
		Infectious disease
		Oncology
	References
	Self-assessment questions
	Answers
52 Toxicology and the clinical laboratory
	Background
	Laboratory methods
	Toxidromes
		Cholinergic toxidrome
		Anticholinergic toxidrome
		Opioid toxidrome
		Sedative hypnotic toxidrome
		Sympathomimetic toxidrome
	Key laboratory formulas
		Anion gap
		Osmolal gap
	Pharmacology and analysis of specific drugs and toxic agents
		Agents that cause cellular hypoxia
			Carbon monoxide
			Methemoglobin
			Cyanide
	Alcohols
		Ethanol
		Methanol
		Isopropanol and acetone
		Ethylene glycol
		Analysis of ethanol
			Serum/plasma and blood ethanol
		Analysis of volatile alcohols (methanol, isopropanol, and acetone)
		Ethanol biomarkers
	Analgesics (nonprescription)
		Acetaminophen
		Salicylate
	Drugs of abuse
		Amphetamine-type stimulants
			Amphetamine and methamphetamine
			Designer stimulants
			3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine
			Cathinone and derivatives
			Methylphenidate (Ritalin)
		Analytical methods for amphetamine-type stimulants
		Barbiturates
		Benzodiazepines
		Cannabinoids
		Synthetic cannabinoids
		Cocaine
		Lysergic acid diethylamide
		Opioids
		Natural opium alkaloids
			Morphine
			Codeine
		Semisynthetic opiates
			Heroin
			Hydrocodone and hydromorphone
			Oxycodone and oxymorphone
		Fully synthetic opioids
			Fentanyl
			Meperidine
			Methadone
			Tramadol
		Opioid antagonists and mixed agonist/antagonists
			Buprenorphine
			Naloxone
		Opioid analysis
		Phencyclidine and ketamine
		Specimen validity testing
		Pain management
		Drugs of abuse testing using other types of specimens
			Meconium
			Umbilical cord tissue
			Oral fluid
			Hair
	Metals
		Diagnosing metal toxicity
		Lead
		Arsenic
		Cadmium
		Chromium
		Gadolinium
		Mercury
	Tricyclic antidepressants
	Agents related to cholinergic syndrome
		Pesticides (organophosphate and carbamate compounds)
	References
	Self-assessment questions
	Answers
53 Pharmacogenomics
	Introduction
	Drug response
	Pharmacogenetic testing
	Pharmacogenetics implementation
	Limitations
	References
	Self-assessment questions (True/False)
	Answers
54 Infectious diseases
	Herpesviruses
		Herpes simplex viruses
			Laboratory testing
		Human cytomegalovirus
			Laboratory testing
		Epstein–Barr virus
			Laboratory testing
				Heterophile antibodies.
				Anti-EBV antibodies.
	Hepatitis viruses
		Hepatitis A
			Laboratory testing
		Hepatitis B
			Laboratory testing
			Hepatitis B surface antigen and antibodies
			Hepatitis B e antigen and antibodies
			Hepatitis B core antigen and antibodies
			Hepatitis B DNA
		Hepatitis C
			Laboratory testing
		Hepatitis D
		Hepatitis E
			Laboratory testing
	Human immunodeficiency virus
		Laboratory testing
	Conclusion
	References
	Self-assessment questions
	Answers
55 Clinical microbiology
	Specimen collection
	Laboratory automation in clinical microbiology
	Components of automation
		Inoculation unit
		Automated track
		Automated “smart” incubators
		Imaging
		Workstations
	Commercially available systems
	Benefits of lab automation and future directions
		Improved turnaround times
		Automated culture reading
	Methods for identification of microorganisms
	DNA sequencing
	Biochemical/phenotypical methods
	Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
		Beyond colony identification
	Point-of-care microbiology
	Syndromic-based multiplex molecular testing
		Introduction
		Respiratory panels
		Gastroenteritis panels
	Blood culture identification panels
	Meningitis and encephalitis panel
	Conclusion
	References
	Self-assessment questions
	Answers
Index