Clinical Chemistry

Front 1

Which of the following is NOT an ADH-deficient cause of polyuria due to water diuresis?
a. Central diabetes insipidus
b. Dipsogenic diabetes insipidus (excessive water intake)
c. Gestational diabetes insipidus (excessive vasopressinase)
d. Pituitary or hypothalamic infection
e. ADH receptor mutation causing congenital nephrogenic diabetes insipidus

Back 1

e.
Choices A-D all describe ADH-deficient causes of polyuria due to water diuresis. Choice E is not related to this pathogenesis

Front 2

Based on a normal distribution of quality control (QC) data, which description of a QC rule best represents imprecision? For each
case, assume that the same QC material is used in one run.
a. Three sequential observations for a QC specimen that exceed 2 standard deviations from the target value in the same direction
b. 10 sequential observations that fall between 3 and 4 standard deviations above the mean
c. Eight sequential observations that exceed one standard deviation in the same direction from the target value
d. Six sequential observations that all fall exactly one and a half standard deviation below the mean
e. Two sequential observations with a range of four standard deviations between the two values

Back 2

e.
Choice A represents systematic bias. Choices B and C represent both systematic bias and a trend. Choice D represents a shift
and demonstrates excellent precision. Choice E represents a system demonstrating poor precision.

Front 3

Values for 3 consecutive days of the run are indicated by the three asterisks. The dotted
lines represent standard deviations (SD) above and below the mean and are labeled with the corresponding glucose value in mg/dL in
parentheses. What is the probability that the event below occurred by chance alone?

Back 3

1:64,000Another way of asking the same question is: “What is the probability that three consecutive values will fall greater than 2 SD
above the mean or greater than 90 mg/dL?” This question can be viewed as a normal (Gaussian) distribution with a 95%
confidence interval. The probability that one value will fall outside of this 95% confidence interval is 5%. However, the probability
of one value falling greater than 2 SD above the mean is 2.5% (1/40). Therefore, the probability that three consecutive values will
all fall greater than 2 SD above the mean is the product of each of the individual probabilities or (1/40)(1/40)(1/40) or 1 in 64,000.
This event is not likely to occur by chance alone.

Front 4

Which of the following is the best statistical test to determine if the null hypothesis is correct in stating that no significant difference
exists between the variances for two study groups?
a. Chi-square test
b. F-test
c. Analysis of variance (ANOVA)
d. T-test
e. Sign test

Back 4

b.
Chi-squared analysis evaluates observed and expected observations to determine if populations are related. ANOVA is a method
for testing the hypothesis that three or more groups with normal distributions are the same. The sign test is similar to the t-test
except that it uses the median rather than the mean. The F-test (aka: variance ratio test) is used to determine if standard
deviations of two data sets are statically different. The F-test statistic is calculated by dividing the square of the larger variance by
the square of the smaller variance. This value is evaluated using degree of freedom and an appropriate table.

Front 5

In a chronic hepatitis study, serum alkaline phosphatase (ALP) levels were reported for patients with inactive and patients with active
disease. The variances are not significantly different from one another. This data appears as follows:Which of the following is the best statistical test to determine if the means are different?

Back 5

a.
The unpaired (student) t-test is used to compare two groups of observations that are unrelated to each other, such as diseased
and non-diseased groups. The sample sizes do not have to be different. The paired t-test evaluates data derived from a single
group (samples, patients) in which two different procedures or treatments are evaluated for differences.

Front 6

Changing the limit of normal values for the test from 10 to 20 (as indicated on the figure) would result in:
a. Decreased specificity
b. Increased negative predictive value and increased sensitivity
c. Decreased false positives and decreased false negatives
d. Increased false positives and decreased false negatives
e. Decreased false positives and increased false negatives

Back 6

e.
With this change, fewer healthy individuals will be called positive. As you move to the right, the positive predictive value increases
and negative predictive value decreases.

Front 7

In which of the following common measurement variability would LEAST likely demonstrate a Gaussian statistical distribution?
a. Aspiration volume
b. Electronic noise in a measuring system
c. Control material deterioration in storage
d. Instrument temperature measurements over a 1-month period
e. Precision study results

Back 7

c.
Choice C would likely demonstrate a shift or a drift. All others should demonstrate a Gaussian distribution. This distribution type is
also known as a normal distribution wherein the population of data clusters symmetrically around a central value such that the
mean, median, and mode of the data set are all identical.

Front 8

Which of the following statements regarding proficiency testing (PT) is considered to be an UNACCEPTABLE laboratory practice?
a. PT should be used as a process of external evaluation of method performance.
b. The laboratory should use an alternative approach to verify method performance when PT is not offered.
c. PT data should be compared among laboratories using the same methods.
d. If the primary facility analyzer is undergoing maintenance, PT surveys can be resulted and reported from testing conducted at a
reference laboratory.
e. PT allows for peer group evaluation.

Back 8

d.
CLIA-88 prohibits survey material to be shared among different facilities and laboratories. The PT survey should be used only for
its intended facility and platform. Peer group evaluation allows a laboratory to verify that it is using a method according to
manufacturer's specifications. Furthermore, it demonstrates that patient results are consistent with those of other laboratories.

Front 9

A new test is developed to test for an inherited metabolic disease. The disorder is found in 1 in 10,000 newborn infants. The test was evaluated in
300 healthy newborn infants, and 6 had results that were above the normal upper reference limits. Of a series of 100 banked samples from
children with the disorder, 95 had results above the normal reference limits; sensitivity of this test for the metabolic disorder is:

Back 9

Sensitivity is defined as the percentage of individuals with a disease who have an abnormal result. Of the 100 children with the
disease, 95 (95%) had an abnormal result.

Front 10

Serum separation; for routine chemisty and immmunohematologrey

Back 10

red

Front 11

Heparin (Na or Li) Plasma separation ; for drug monitoring, electrophoresis, lipid pane l

Back 11

green

Front 12

Citrate Coagulation tests. Note: A 1 :9 ratio of anticoagulant :blood is ideal . Higher ratio s
lead to increased coag times, affecting the aPTT>PT. For polycythemic patient s
with Hct>60%, the PT and PTT can be prolonged due to decreased effectiv e
plasma .

Back 12

blue

Front 13

Buffered sodium citrate ESR

Back 13

black

Front 14

EDTA cell counts; routine hematology (eg, CBC) ; ESR, sickle cel

Back 14

purple

Front 15

Citrate & dextrose Flow cytometry studies/bone marrow donor registry

Back 15

yellow

Front 16

A new test is developed to test for an inherited metabolic disease. The disorder is found in 1 in 10,000 newborn infants. The test was evaluated in
300 healthy newborn infants, and 6 had results that were above the normal upper reference limits. Of a series of 100 banked samples from
children with the disorder, 95 had results above the normal reference limits. The specificity of this test for the metabolic disorder is:

Back 16

98%; Specificity is defined as percentage of normal results in individuals without the disease. Of the 300 children without the disease,
294 (300-6, or 98%) had a normal result.

Front 17

The positive predictive value of the test when used to screen all newborns for the disease is:
a. 0.0001%
b. 0.5%
c. 5%
d. 50%
e. 95%

Back 17

b.
When tested in a screening program, one must use the prevalence of disease to evaluate the predictive value. When calculating
predictive value problems for the boards, approximations will allow you to determine the correct answer. If the test has 95%
sensitivity, then it is likely that the one infant with disease will have a positive result. Of the 10,000 (actually 9,999) without disease,
2% would be expected to have an elevated value; this represents 200 individuals. The positive predictive value is calculated as
the true positive results (1) divided by total positive results (201), multiplied by 100 to report it as a percent, or in this case 0.5%.
It is not appropriate to use the 300 persons without disease and 100 persons with disease initially tested to calculate positive
predictive value, because this does not represent the true frequency of disease in the population tested.

Front 18

A study is done to evaluate three tests for diagnosis of a disease, as illustrated in the ROC curve in Figure 17.3. Test A is the currently
established screening test, Test B is another test that has been proposed, and Test C is a new test developed in the author's laboratory. Which of the following statements is correct about this ROC analysis?
a. False positive rate is displayed on the y axis.
b. Predictive value is displayed on the y axis.
c. Sensitivity is displayed on the x axis.
d. Specificity is displayed on the x axis.
e. True positive rate is displayed on the y axis

Back 18

e.
In an ROC curve, true positive rate or sensitivity is plotted on the y axis, and false-positive rate (100-specificity) is plotted on the
x axis. In some versions of the plot, specificity is plotted on the x axis, but in that case the numbers on the x axis go from 100 on the left to 0 on the right.

Front 19

Which of the following tubes should be filled LAST during phlebotomy?
a. Blood culture tubes
b. EDTA (lavender top)
c. Nonadditive tubes (plain red top tubes)
d. Serum separator tubes
e. Sodium citrate (light blue top)

Back 19

b.
According to the CLSI guidelines on blood collection, the suggested order of collection is blood culture tubes first, followed (in
order) by plain tubes, coagulation (sodium citrate) tubes, serum separator tubes, and tubes with additives. For plastic tubes,
however, “plain” tubes often contain additives to accelerate coagulation; when plastic tubes are used, sodium citrate tubes should be filled before the “plain” tubes.

Front 20

Prolonged use of a tourniquet would be expected to increase which of the following tests?
a. BUN
b. Calcium
c. Creatinine
d. Glucose
e. Sodium

Back 20

b.
Prolonged use of a tourniquet causes hemoconcentration, which can increase the concentration of proteins and substances bound
to proteins (calcium, iron, lipids, protein-bound hormones, and drugs).

Front 21

Which of the following substances DO NOT show significant diurnal variation?
a. Creatinine
b. Glucose tolerance
c. Growth hormone
d. N-telopeptides of collagen
e. Osteocalcin

Back 21

a.
While diurnal variation is best known for cortisol, there is significant diurnal variation for many other substances as well. Most
pituitary hormone levels are lowest at bedtime and rise significantly during sleep to peak in the morning. Substances regulated by
pituitary hormones (including many bone markers, such as osteocalcin, and collagen degradation fragments, such as Ntelopeptides)
also have marked diurnal variation. Glucose tolerance is affected by cortisol and growth hormone levels and is
significantly better in the afternoon than in the morning.

Front 22

Which of the following substances DO NOT show significant diurnal variation?
a. Creatinine
b. Glucose tolerance
c. Growth hormone
d. N-telopeptides of collagen
e. Osteocalcin

Back 22

a.
While diurnal variation is best known for cortisol, there is significant diurnal variation for many other substances as well. Most
pituitary hormone levels are lowest at bedtime and rise significantly during sleep to peak in the morning. Substances regulated by
pituitary hormones (including many bone markers, such as osteocalcin, and collagen degradation fragments, such as Ntelopeptides)
also have marked diurnal variation. Glucose tolerance is affected by cortisol and growth hormone levels and is
significantly better in the afternoon than in the morning.

Front 23

Which of the following tests should have lower reference limits during pregnancy?
a. Alkaline phosphatase
b. Creatinine
c. Estriol
d. Prolactin
e. Renin

Back 23

b.
During pregnancy, there is an increase in glomerular filtration rate of approximately 50%, resulting in a significant decrease in BUN
and creatinine. It is important to consider this decrease in interpreting renal function tests during pregnancy. Increases in
reference limits are needed for each of the other tests. Alkaline phosphatase levels increase to two-three times the nonpregnant
reference limits, both from placental alkaline phosphatase and an increase in bone isoenzyme. During the second trimester, third
spacing of fluid increases renin and aldosterone production. A number of hormones increase during pregnancy, including estriol
(a marker of the fetal-placental unit) and prolactin.

Front 24

During acute illness, increases occur in all of the following parameters EXCEPT:
a. Cholesterol
b. Cortisol
c. Glucose
d. Growth hormone
e. Triglycerides

Back 24

a.
Acute illness causes a number of changes in physiology. Cytokines lead to increased production of several pituitary hormones,
including cortisol, growth hormone, and prolactin; however, gonadotropins are typically decreased. Increased cortisol causes
increases in glucose and worsens glucose tolerance. Cytokines appear to increase uptake of cholesterol by macrophages; with
acute illness, cholesterol often falls by up to 40%, and the decrease begins within 24 hours of onset of illness. Similar decreases
occur in LDL-cholesterol, with lesser decreases in HDL-cholesterol, while triglycerides and VLDL increase by up to 35%.

Front 25

Which of the following preanalytical variables is most likely related to specimen handling?
a. Drug regimen
b. Physical activity
c. Site preparation
d. Clotting
e. Body posture

Back 25

d.
Drug regimen and physical activity are more related to subject preparation. Site preparation and body posture are more related to
specimen collection. Clotting is the only choice most likely related to specimen handling.

Front 26

Which of the following would have the highest interand intraindividual CV?
a. C-peptide
b. Calcium
c. Blood glycohemoglobin
d. Total protein
e. Plasma glucose

Back 26

.
C-peptide has about a 65% inter- and a 30% intraindividual CV. Calcium, glycohemoglobin, total protein, and glucose demonstrateat most ~ 10% CV for either inter- or intraindividual CV.

Front 27

Which of the following additives causes an increase in the corresponding analyte?
a. EDTA Iron
b. Oxalate Calcium
c. Citrate Amylase
d. Fluorides Alkaline phosphatase
e. Heparin Free thyroxine

Back 27

e.
Heparin causes increases in laboratory testing such as thyroid hormone, PT, PTT, Li (Li-Heparin tubes), and sodium (Na-Heparin
tubes). EDTA decreases iron; oxalate decreases calcium levels; citrate decreases amylase, and fluorides inhibit alkaline
phosphatase activity.

Front 28

The correlation coefficient for the experiment, r, was 0.998. Which of the following statements is correct?
a. The probability of a given X value accurately predicting the corresponding Y value (within the range measured) is >99%.
b. Since the r value was >0.9, it is not necessary to evaluate the method for constant or proportional bias.
c. There is no significant difference between the results using the two methods.
d. The square of the r value, R, is a measure of average difference between the two methods.
e. The low value for r (<1) indicates that there is poor agreement between the two methods.

Back 28

a.
Correlation coefficient is only a measure of fit of points to the line and an indicator of the range of the values measured. A perfect
positive correlation would occur with an r value of 1, while a perfect negative correlation would be indicated by an r of - 1. A value
of 0 indicates that there is no correlation between the two methods. The square of r (also called R), when expressed as a
percentage, indicates the likelihood of predicting the value percentage, indicates the likelihood of predicting the value of
y
for a given
x
value.

Front 29

The correlation coefficient for the experiment, r, was 0.998. Which of the following statements is correct?
a. The probability of a given X value accurately predicting the corresponding Y value (within the range measured) is >99%.
b. Since the r value was >0.9, it is not necessary to evaluate the method for constant or proportional bias.
c. There is no significant difference between the results using the two methods.
d. The square of the r value, R, is a measure of average difference between the two methods.
e. The low value for r (<1) indicates that there is poor agreement between the two methods.

Back 29

For method comparison studies, values of r should ideally be >0.97, and for most methods will be >0.99 unless there are
significant problems with the comparison study. The square of the r value indicates how much of the individual value for y can be
explained by the
x
variable; for method comparison studies, this should therefore be a very high number. The correlation coefficient does not
indicate that values are equal; for example, a new method for an enzyme could give results three times those of the old method,
but as long as that relationship always held, the r value would be high; as a consequence of this fact, correlation coefficient
cannot be used to evaluate methods for bias.

Front 30

Which scenario is LEAST helpful in determining that a sample being tested for prostate specific antigen (PSA) is falsely elevated due
to the presence of human anti-mouse antibodies (HAMA)?
a. A 1:2 sample dilution gives linear and proportional PSA results.
b. The PSA results from the sample are 10 times above the upper reference limit when using one method and not detectable when using
another method.
c. The use of an antibody blocking agent gives an undetectable PSA result on a sample that was previously elevated without the blocking
agent.
d. The sample is positive for interference using a PSA HAMA specific immunoassay.
e. Medical records consistently indicate the patient's PSA is elevated due to HAMA.

Back 30

a.
Some reports indicate that as many as 50% of HAMAs are likely to dilute linearly. Therefore, the lack of proportional results with
dilution provides useful information. However, proportional results alone are uninformative. Single dilutions should not be used to
make decisions regarding the presence or absence of a heterophilic antibody. A more robust determination would consider a
multipronged approach using blocking agents, measuring specifically for HAMA, and assaying the sample on more than one
analytical platforms that use different antibodies.