CLINICAL CHEMISTRY PART 2

Systematic errors: ​

Aging reagents Aging calibrators Instrument components Optical changes Fluctuations in line voltage Wear and tear of instrument Reagent lot variability Calibration differences Technologist interactions A SYSTEMATIC ERROR, on the other hand, will be seen as a trend in the data. Control values gradually rise (or fall) from the previously established limits. This type of error includes improper calibration, deterioration of reagents, sample instability, instrument drift, or changes in standard materials. All the Westgard rules that indicate trends identify systematic errors. 2(2S), 4(1S) and 10(x) rule.

Measures of spread

Coefficient of variation, Range, Standard deviation The spread represents the relationship of all the data points to the mean. There are three commonly used descriptions of spread: (1) range (2) standard deviation (SD), and (3) coecient of variation (CV).

Random errors include:

RANDOM ERROR is one with no trend or means of predicting it. Random errors include such situations as mislabeling a sample, pipetting errors, improper mixing of sample and reagent, voltage uctuations not compensated for by instrument circuitry, and temperature uctuations. Violations of the 1(2S), 1(3S) and R(4S) Westgard rules are usually associated with random error. To assess the situation, the sample is assayed using the same reagents. If a random error occurred, the same mistake may not be made again, and the result will be within appropriate control limits. RANDOM ERRORS MAY BE DUE TO: Reagent dispensing Sample evaporation Temperature of analyzer Electro-optical mechanism Calibrator reconstitution Environmental conditions Instability of instrument Variation in handling techniques: pipetting, mixing, timing Variation in operators

Ability of a method to detect small quantities of an analyte. a. Analytic sensitivity b. Analytic specificity c. Diagnostic sensitivity d. Diagnostic specificity

a. Analytic sensitivity

Symptoms of HYPOGLYCEMIA usually occur when blood glucose has fallen below ___ mg/dL a. Below 50 mg/dL b. Below 60 mg/dL c. Below 70 mg/dL d. Below 80 mg/dL

a. Below 50 mg/dL

Difference between the observed mean and the reference mean: a. Bias b. Confidence interval c. Parametric method d. Nonparametric method

a. Bias Bias: Difference between the observed mean and the reference mean. Negative bias indicates that the test values tend to be lower than the reference value, whereas positive bias indicates test values are generally higher. Bias is a type of constant systematic error.

Type of systemic error in the sample direction and magnitude; the magnitude of change is constant and not dependent on the amount of analyte. a. Constant systematic error b. Proportional systematic error

a. Constant systematic error

A trend in QC results is most likely caused by: a. Deterioration of the reagent b. Miscalibration of the instrument c. Improper dilution of standards d. Electronic noise

a. Deterioration of the reagent

LONG-TERM estimation of glucose concentration can be followed by measuring: a. Glycosylated hemoglobin (HbA1c) b. Fructosamine

a. Glycosylated hemoglobin (HbA1c) Long-term estimation of glucose concentration can be followed by measuring glycosylated hemoglobin (Hb A1c). A level of 8% or less is considered "good" glycemic control. Because the average red blood cell lives approximately 120 days, the glycosylated hemoglobin level at any one time reects the average blood glucose level over the previous 2 to 3 months. Therefore, measuring the glycosylated hemoglobin provides the clinician with a time-averaged picture of the patient's blood glucose concentration over the past 3 months.

What would an individual with CUSHING SYNDROME tend to exhibit? a. Hyperglycemia b. Hypoglycemia c. Normal blood glucose level d. Decreased 2-hr postprandial glucose

a. Hyperglycemia CORTISOL INCREASES BLOOD GLUCOSE

Which of the following plots is best for detecting all types of QC errors? a. Levy-Jennings b. Tonks-Youden c. Cusum d. Linear regression

a. Levy-Jennings The Levy-Jennings plot is a graph of all QC results with concentration plotted on the y axis and run number on the x axis.

Which of the following terms refers to deviation from the true value caused by indeterminate errors inherent in every laboratory measurement? a. Random error b. Systematic error of the mean c. Parametric analysis d. Nonparametric analysis

a. Random error Random errors are deviations from the true value caused by unavoidable errors inherent in laboratory measurements. The standard error of the mean is a statistical concept reecting sampling variation. It is the standard deviation of the entire population. Parametric statistics refer to a Gaussian (normal) distribution of data. Nonparametric statistics are more general and require no assumptions.

Which of the following describes the ability of an analytical method to maintain both accuracy and precision over an extended period of time? a. Reliability b. Validity c. Probability d. Sensitivity

a. Reliability The reliability of an analytical procedure is its ability to maintain accuracy and precision over an extended period of time during which supplies, equipment, and personnel in the laboratory may change. It is often used interchangeably with the term "consistency." It is the goal of every clinical laboratory to produce reliable results.

Which of the following statistical tests is used to compare the means of two methods? a. Student's t test b. F distribution c. Correlation coefficient (r) d. Linear regression analysis

a. Student's t test T TEST: COMPARES MEANS, ACCURACY F TEST: COMPARES S.D., PRECISION Student's t test is the ratio of mean difference to the standard error of the mean difference (bias/random error) and tests for a signicant difference in means. The F test is the ratio of variances and determines if one method is signicantly less precise.

Beta cell destruction, usually leading to absolute insulin deficiency: a. Type 1 DM b. Type 2 DM

a. Type 1 DM

VERY LOW OR UNDETECTABLE C-peptide: a. Type 1 DM b. Type 2 DM

a. Type 1 DM

Two (2) consecutive control values exceed the same 2 standard deviation limit: a. 1:2s b. 2:2s c. R:4s d. 4:1s

b. 2:2s Westgard multirule is a control procedure that utilizes control rules to assess numerical quality control data; the control rules establish the limits for data rejection in a system with two controls. Other rules apply when three controls are used. 1:2s = 1 control value exceeds the mean ±2 standard deviations; warning rule that triggers inspection of control values using the other rejection rules that follow; only rule that is not used to reject a run; results are reportable 1:3s = 1 control value exceeds the mean ±3 standard deviations; detects random error 2:2s = 2 consecutive control values exceed the same 2 standard deviation limit (same mean +2 s or same mean -2 s); detects systematic error R:4s = 1 control value in a group exceeds the mean +2 s and a second control value exceeds the mean -2 s, creating a 4 standard deviation spread; detects random error 4:ls = 4 consecutive control values are recorded on one side of the mean and exceed either the same mean +1 s or the same mean -1 s; detects systematic error 10:x =10 consecutive control values are recorded on one side of the mean (either above or below the mean); detects systematic error

Glucose measurements can be ____ mg/dL erroneously higher by reducing methods than by more accurate enzymatic methods. a. 1 to 5 mg/dL b. 5 to 15 mg/dL c. 20 to 25 mg/dL d. 30 to 35 mg/dL

b. 5 to 15 mg/dL Glucose measurements can be 5 to 15 mg/dL erroneously higher by reducing methods than by more accurate enzymatic methods.

Usual dose of LACTOSE in the oral lactose tolerance test is: a. 25 grams b. 50 grams c. 75 grams d. 100 grams

b. 50 grams ORAL LACTOSE TOLERANCE TESTS, measuring the increase in plasma glucose or galactose following ingestion of lactose, have been used to diagnose lactase deciency.

What is the recommended cutoff value for adequate control of blood glucose in diabetics as measured by glycated hemoglobin? a. 5% b. 6.5% c. 9.5% d. 11%

b. 6.5% If the result is 6.5% or more, the treatment plan should be adjusted to achieve a lower level, and the test performed every 3 months until control is improved.

Ability of a method to detect only the analyte it is designed to determine. a. Analytic sensitivity b. Analytic specificity c. Diagnostic sensitivity d. Diagnostic specificity

b. Analytic specificity

A 62-year-old patient presents to the physician with report of increased thirst and increased urination, particularly at night. The physician requests a series of tests over the next few days. The following data are received: RANDOM GLUCOSE: 186 mg/dL; FASTING GLUCOSE: 114 mg/dL; 2-HOUR OGTT: 153 mg/dL HbA1c: 5.9%. Which of the following conclusions may be made regarding these data? a. Data represents normal glucose status b. Data represents an impaired glucose status c. Data represents the presence of insulinoma d. Data represents diagnosis of diabetes

b. Data represents an impaired glucose status Resting plasma glucose NORMAL <140 IMPAIRED 140 - 199 DIAGNOSTIC ≥ 200 mg/dL Fasting plasma glucose NORMAL <100 IMPAIRED 100 - 125 DIAGNOSTIC ≥ 126 mg/dL 2-hour OGTT NORMAL <140 IMPAIRED 140 - 199 DIAGNOSTIC ≥ 200 mg/dL HbA1c NORMAL <5.7 % IMPAIRED 5.7 - 6.4% DIAGNOSTIC ≥ 6.5%

Gross hemolysis and extremely elevated bilirubin may cause ______ in HEXOKINASE RESULTS. a. False increase b. False decrease c. No effect d. Variable

b. False decrease Generally accepted as the reference method, hexokinase method is not affected by ascorbic acid or uric acid. Gross hemolysis and extremely elevated bilirubin may cause a false decrease in results.

Most widely used to assess SHORT-TERM (3 to 6 weeks) glycemic control: a. Glycosylated hemoglobin (HbA1c) b. Fructosamine

b. Fructosamine FRUCTOSAMINE: GLYCOSYLATED ALBUMIN Fructosamine assays are the most widely used to assess short-term (3 to 6 weeks) glycemic control because the average half-life of the proteins is 2-3 weeks.

HYPERGLYCEMIC FACTOR produced by the pancreas is: a. Epinephrine b. Glucagon c. GH d. Insulin

b. Glucagon Glucagon is the primary hormone responsible for increasing glucose levels. It is synthesized by the ALPHA-cells of islets of Langerhans in the pancreas and released during stress and fasting states. ACTION OF GLUCAGON Increases glycogenolysis: glycogen → glucose Increases gluconeogenesis: fatty acids → acetyl-CoA → ketone, proteins → amino acids

Formation of glucose-6-phosphate from noncarbohydrate sources: a. Glycolysis b. Gluconeogenesis c. Glycogenolysis d. Glycogenesis

b. Gluconeogenesis Glycolysis: Metabolism of glucose molecule to pyruvate or lactate for production of energy Gluconeogenesis: Formation of glucose-6-phosphate from noncarbohydrate sources Glycogenolysis: Breakdown of glycogen to glucose for use as energy Glycogenesis: Conversion of glucose to glycogen for storage Lipogenesis: Conversion of carbohydrates to fatty acids Lipolysis: Decomposition of fat

Select the enzyme that is most specific for beta D-glucose: a. Glucose oxidase b. Glucose-6-phosphate dehydrogenase c. Hexokinase d. Phosphohexose isomerase

b. Glucose-6-phosphate dehydrogenase Glucose oxidase is the most specic enzyme reacting with only beta D-glucose. Glucose oxidase converts beta D-glucose to gluconic acid. Mutarotase may be added to the reaction to facilitate the conversion of alpha-D-glucose to beta-D-glucose.

Which of the following is a potential source of error in the HEXOKINASE METHOD? a. Galactosemia b. Hemolysis c. Sample collected in fluoride d. Ascorbic acid

b. Hemolysis Hemolyzed samples require a serum blank correction (subtraction of the reaction rate with hexokinase omitted from the reagent).

Relatively easy to measure and maintain: a. Accuracy b. Precision c. Sensitivity d. Specificity

b. Precision Accuracy is easy to dene but dicult to establish and maintain. Precision is relatively easy to measure and maintain.

Type of systemic error where the magnitude changes as a percent of the analyte present; error dependent on analyte concentration. a. Constant systematic error b. Proportional systematic error

b. Proportional systematic error

A factor, other than average plasma glucose values, that can affect the HbA1c level is: a. Serum ketone bodies b. Red blood cell life span c. Ascorbic acid intake d. Increased triglyceride levels

b. Red blood cell life span Two factors determine the glycosylated hemoglobin levels: the average glucose concentration and the red blood cell life span. If the red blood cell life span is decreased because of another disease state such as hemoglobinopathies, the hemoglobin will have less time to become glycosylated and the glycosylated hemoglobin level will be lower.

Error always in one direction: a. Random error b. Systematic error

b. Systematic error Systemic error: Error always in one direction. Random error: Error varies from sample to sample.

Which of the following plots is best for comparison of precision and accuracy among laboratories? a. Levy-Jennings b. Tonks-Youden c. Cusum d. Linear regression

b. Tonks-Youden The Tonks-Youden plot is used for interlaboratory comparison of monthly means. The method mean for level 1 is at the center of the y axis and mean for level 2 at the center of the x axis. Lines are drawn from the means of both levels across the graph, dividing it into four equal quadrants. If a laboratory's monthly means both plot in the lower left or upper right, then systematic error (SE) exists in its method.

The term R:4S means that: a. Four consecutive controls are greater than ±1 standard deviation from the mean b. Two controls in the same run are greater than 4s units apart c. Two consecutive controls in the same run are each greater than ±4s from the mean d. There is a shift above the mean for four consecutive controls

b. Two controls in the same run are greater than 4s units apart The R:4s rule is applied to two control levels within the same run. The rule is violated when the algebraic difference between them (level 1 level 2) exceeds 4s. The R:4s rule detects random error (error due to poor precision).

DETECTABLE C-peptide: a. Type 1 DM b. Type 2 DM

b. Type 2 DM

May range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance: a. Type 1 DM b. Type 2 DM

b. Type 2 DM

What percentage of values will fall between ±2 s in a Gaussian (normal) distribution? a. 34.13% b. 68.26% c. 95.45% d. 99.74%

c. 95.45% 68.26% will lie within ±1 s 95.45% will lie within ±2 s 99.74% will lie within ±3 s

Which of the following terms refers to the closeness with which the measured value agrees with the true value? a. Random Error b. Precision c. Accuracy d. Variance

c. Accuracy The accuracy of an analytical result is the closeness with which the measured value agrees with the true value. Precision is reproducibility. Accuracy and precision are independent, but it is the goal of the clinical laboratory to design methods that are both precise and accurate.

Positive predictive value: a. Ability of a test to detect a given disease or condition b. Ability of a test to correctly identify the absence of a given disease or condition. c. Chance of an individual having a given disease or condition if the test is abnormal. d. Chance an individual does not have a given disease or condition if the test is within the reference interval.

c. Chance of an individual having a given disease or condition if the test is abnormal.

Which plot will give the earliest indication of a shift or trend? a. Levy-Jennings b. Tonks-Youden c. Cusum d. Linear regression

c. Cusum Cusum points are the algebraic sum of the difference between each QC result and the mean. The y axis is the sum of differences and the x axis is the run number. The center of the y axis is 0. Because QC results follow a random distribution, the points should distribute about the zero line. Results are out of control when the slope exceeds 45° or a decision limit (e.g., ±2.7s) is exceeded.

Ability of a test to detect a given disease or condition. a. Analytic sensitivity b. Analytic specificity c. Diagnostic sensitivity d. Diagnostic specificity

c. Diagnostic sensitivity

Select the coupling enzyme used in the hexokinase method for glucose: Select the coupling enzyme used in the hexokinase method for glucose: a. Glucose dehydrogenase b. Glucose-6-phosphatase c. Glucose-6-phosphate dehydrogenase d. Peroxidase

c. Glucose-6-phosphate dehydrogenase The hexokinase method is considered more accurate than the glucose oxidase methods because the coupling reaction using glucose-6-phosphate dehydrogenase is highly specic; therefore, it has less interference than the coupled glucose oxidase procedure.

Most frequently occurring value in a dataset: a. Mean b. Median c. Mode d. Range

c. Mode The mode is the most frequently occurring value in a dataset. Although it is seldom used to describe data, it is referred to when in reference to the shape of data, a bimodal distribution, for example.

In a person with normal glucose metabolism, the blood glucose level usually increases rapidly after carbohydrates are ingested but returns to a normal level after: a. 30 mins b. 45 mins c. 60 mins d. 120 mins

d. 120 mins / 2 hours

Negative predictive value: a. Ability of a test to detect a given disease or condition b. Ability of a test to correctly identify the absence of a given disease or condition. c. Chance of an individual having a given disease or condition if the test is abnormal. d. Chance an individual does not have a given disease or condition if the test is within the reference interval.

d. Chance an individual does not have a given disease or condition if the test is within the reference interval.

Ability of a test to correctly identify the absence of a given disease or condition. a. Analytic sensitivity b. Analytic specificity c. Diagnostic sensitivity d. Diagnostic specificity

d. Diagnostic specificity

HYPOGLYCEMIC FACTOR produced by the pancreas is: a. Epinephrine b. Glucagon c. GH d. Insulin

d. Insulin Insulin is the only hormone that decreases glucose levels and can be referred to as a hypoglycemic agent. Insulin is the primary hormone responsible for the entry of glucose into the cell. It is synthesized by the beta cells of islets of Langerhans in the pancreas. It decreases plasma glucose levels by increasing the transport entry of glucose in muscle and adipose tissue by way of nonspecic receptors. It also regulates glucose by increasing glycogenesis, lipogenesis, and glycolysis and inhibiting glycogenolysis. ACTION OF INSULIN Increases glycogenesis and glycolysis: glucose → glycogen → pyruvate → acetyl-CoA Increases lipogenesis Decreases glycogenolysis

Measures of center

mean, median, mode The three most commonly used descriptions of the center of a dataset are the mean, the median, and the mode.