Clinical Chemistry: Week1

Includes the following topics; Quality Assurance, Analytical Methods and Instrumentation

Quality Control

A system of ensuring accuracy and precision in the lab by including quality control reagents in every series of measurements.

Sensitivity

The ability of an analytical method to measure the smallest concentration of the analyte of interest.

Specificity

The ability of an analytical method to measure only the analyte of interest.

Accuracy

The nearness or closeness of the assayed value to the true or target value.

Precision/Reproducibility

The ability of an analytical method to give repeated results on the same sample that agree with one another.

Practicability

The degree by which a method is easily repeated.

Reliability

The ability of an analytical method to maintain accuracy and precision over an extended period of time.

Diagnostic Sensitivity

The ability of the analytical method to detect the proportion of individuals with the disease.

Diagnostic Specificity

The ability of the analytical method to detect the proportion of individuals without the disease.

Intralab Quality Control (Internal QC)

Involves the analyses of control samples together with the patient specimens.

Interlab Quality Control (External QC)

Involves proficiency testing programs that periodically provide samples of unknown concentrations to participating clinical laboratories.

College of American Pathologists (CAP) proficiency program

The gold standard for clinical laboratory external QC testing.

Control Limits/Control Values

Expected values represented by intervals of acceptable values with upper and lower limits.

Variations in Laboratory Results

Errors encountered in the collection, preparation, and measurement of samples.

Random Error

Error that is present in all measurements and is due to chance.

Systematic Error

Error that influences observations consistently in one direction.

Constant Error

Difference between the target value and the assayed value that is independent of sample concentration.

Proportional Error

Error that results in greater deviation from the target value due to higher sample concentration.

Clerical Error

Error that occurs with the use of handwritten labels and request forms.

Pre-analytical Errors

Activities that take place before testing, such as test ordering and sample collection.

Analytical Errors

Laboratory activities that actually produce a result, such as running a sample on an automated analyzer.

Post-analytical Errors

Comprises patient reporting and result interpretation.

Allowable Error (Ea)

Determined for each test method and is based on the quantity of error that will negatively affect clinical decisions.

Statistics

Science of gathering, analyzing, interpreting, and presenting data.

Mean

Measure of central tendency associated with symmetrical or normal distribution.

Standard Deviation (SD)

Measure of the dispersion of values from the mean.

Coefficient of Variation (CV)

Percentile expression of the mean; an index of precision.

Variance

Standard deviation squared; a measure of variability.

Inferential Statistics

Used to compare the means or standard deviations of two groups of data.

F-test

Used to determine whether there is a statistically significant difference between the standard deviations of two groups of data.

Median

Value of the observation that divides the observations into two groups, each containing equal numbers of observations.

Mode

The most frequent observation.

Range

Simplest expression of spread or distribution.

Standard Deviation Index (SDI)

Difference between the value of a data point and the mean value divided by the group's SD.

T-test

Used to determine whether there is a statistically significant difference between the means of two groups of data.

Quality Control Chart

Used to observe values of control materials over time to determine reliability of the analytical method.

Gaussian Curve (Bell-Shaped Curve)

Occurs when the data set can be accurately described by the SD and the mean.

Cumulative Sum Graph (CUSUM)

Calculates the difference between QC results and the target means.

Youden/Twin Plot

Used to compare results obtained on a high and low control serum from different laboratories.

Shewhart Levey-Jennings Chart

Most widely used QC chart in the clinical laboratory.

Westgard Control Chart

Used to indicate if the analytical process is out of control

Six Sigma (6σ)

Performance improvement program with the goal to improve the process by eliminating variations or errors.

Lean System

System for reducing waste ("nonvalued activities").

Analytical Run

Set of control and patient specimens assayed, evaluated, and reported together.

Delta check

Most commonly used patient-based QC technique where current results are compared with past results.

Interference experiments

Used to measure systematic errors or inaccuracy caused by substances other than the analyte.

Linear Range/Dynamic Range

Concentration range over which the measured concentration is equal to the actual concentration without modification of the method.

Physiologic Limit

Helps detect sample contamination or dilution, inadequate sample volume, sudden major problems with the method, or incorrect recording/transmission of results.

Point Of Care Testing (POCT)/Decentralized Testing

Analytical testing performed outside the confines of the central laboratory, usually by nonlaboratorian personnel.

Quality Assurance (QA)

Systematic action necessary to provide adequate confidence that laboratory services will satisfy given medical needs for patient care.

Quality Patient Care

Includes effective test request forms, clear instructions for patient preparation, appropriate turnaround time, and intelligent result reports.

Recovery experiment

Shows whether a method measures all the analytes or only part of it. It estimates inaccuracy or systematic error.

Predictive Value

Depends on sensitivity, specificity, and prevalence of the disease being tested.

Positive Predictive Value

Probability that a positive test indicates disease.

Negative Predictive Value

Probability that a negative test indicates absence of disease.

Reference Limit/Reference Interval/Reference Value

Values obtained by observation or measurement of a particular type of quantity on a reference individual.

Critical/Panic Value

Laboratory result that may represent a life-threatening situation that should be communicated immediately to the clinicians.

Wavelength

Distance between two successive peaks measured in nanometers.

Frequency

Number of vibrations of wave motion per second.

Didymium/Holmium Oxide Filter

Used to check wavelength accuracy (wavelength calibration).

Photometry

Measurement of light intensity.

Spectrophotometry

Measurement of the light transmitted by a solution to determine the concentration of the light-absorbing substances.

Double-Beam Spectrophotometer

Splits the monochromatic light into two components - one through the sample, one through reference.

Light/Radiant Source

Provides polychromatic light and must generate sufficient radiant energy or power to measure the analyte of interest.

Entrance Slit

Minimizes unwanted or stray light and prevents scattered light from entering the monochromator system.

Monochromator

Isolates specific or individual wavelengths of light.

Exit Slit

Controls the width of the light beam (bandpass) and allows only a narrow fraction of the spectrum to reach the sample cuvette.

Cuvet

Holds the solution whose concentration is to be measured.

Photodetector

Detects and converts transmitted light into photoelectric energy.

Meter/Read-Out Device

Displays the output of the detection system.

Beer's Law

Concentration of the unknown substance is directly proportional to the absorbed light and inversely proportional to the amount of transmitted light.

Absorbance (A)

Amount of light absorbed.

Percent Transmittance

Ratio of the radiant energy transmitted divided by the radiant energy incident on the sample.

Reagent Blank

Corrects absorbance caused by the color of the reagents by subtracting the absorbance of the reagents from each unknown reading.

Sample Blank

Measures absorbance of the sample and reagent in the absence of the endproduct, and corrects the measurement for optical interference.

Flame Emission Photometry (FEP)

Measures the light emitted by a single atom burned in a flame.

Atomic Absorption Spectrophotometry (AAS)

Measures the light absorbed by atoms dissociated by heat.

Turbidimetry

Determines the amount of light blocked by a particulate matter in a turbid solution thereby depending on specimen concentration and particle size.

Nephelometry

Determines the amount of scattered light by a particulate matter suspended in a turbid solution.

Electrophoresis

Migration of charged particles in an electric field.

Amphoteric

Having a net charge that can be either positive or negative depending on pH conditions.

Isoelectric Focusing

Separates molecules by migration through a pH gradient.

Capillary Electrophoresis

Sample molecules are separated by electro-osmotic flow (EOF).

Chromatography

Involves separation of soluble components in a solution by specific differences in physical-chemical characteristics of the different constituents.

Paper Chromatography

For fractionation of sugar and amino acid utilizing Whatman paper

Thin Layer Chromatography (TLC)

Semi-quantitative drug screening test utilizing thin plastic plates impregnated with a layer of silica gel or alumina.

Gas Chromatography (GC)

Used for separation of steroids, barbiturates, blood alcohol and lipids.

Mass Spectroscopy (MS)

Based on the fragmentation and ionization of molecules using a suitable source of energy.

Gas Chromatography-Mass Spectroscopy (GC-MS)

Gold standard for drug testing that utilizes an electron beam to split the drug emerging from the column into its component ions.

Liquid Chromatography

Based on the distribution of solutes between a liquid mobile phase and a stationary phase.

High Performance Liquid Chromatography (HPLC)

Uses pressure for fast separations, controlled temperature, in-line detectors and gradient elution technique.

Gel/Gel Permeation/Gel Filtration/Size Exclusion/Molecular Sieve Chromatography

Separates molecules based on differences in their size and shape.

Ion Exchange Chromatography

Describes the exchange of sample ions and mobile-phase ions with the charged group of the stationary phase

Partition Chromatography (Liquid-Liquid Chromatography)

Separation of compounds based on their partition between a liquid mobile phase and a liquid stationary phase coated on a solid support.

Affinity Chromatography

Uses immobilized biochemical ligands as the stationary phase to separate a few solutes from other unretained solutes.

Adsorption Chromatography (Liquid-Solid Chromatography)

Compounds are adsorbed to a solid support in this type of chromatography such as silica or alumina.

Fluorometry/Molecular Luminescence Spectrophotometry

Measures the amount of light emitted by a molecule after excitation by electromagnetic radiation.

Chemiluminescence

Emission of light is created from a chemical or electrochemical reaction.

Osmometry

Measurement of the osmolality of an aqueous solution.

Colligative Properties of the Solution

Based on measuring changes in the colligative properties of solutions that occur owing to variations in particle concentration.