TEST BANK for Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics 7th Edition by Burt

Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics 7th Edition Burtis Test Bank Chapter 01: Clinical Chemistry, Molecular Diagnostics, and Laboratory Medicine Test Bank MULTIPLE CHOICE 1. An individual working in a clinical chemistry laboratory is married to a sales representative

who works for a company that sells chemistry laboratory supplies. When the laboratory manager requests a list of needed supplies, cost of supplies, and vendors, this individual only recommends the spouse’s company as the vendor. This is considered to be a(n): a. accounting issue. b. possible conflict of interest. c. maintenance of confidentiality issue. d. problem with resource allocation.

ANS: B

Concern has been raised over the interrelationships between practitioners in the medical field and commercial suppliers of drugs, devices, equipment, etc., to the medical profession.

Similarly, relationships have been scrutinized between clinical laboratorians and manufacturers and providers of diagnostic equipment and supplies. These concerns led the National Institutes of Health (NIH) in 1995 to require official institutional review of financial disclosure by researchers and management of situations in which disclosure indicates potential conflicts of interest.

DIF: 1

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OBJ: 6 | 7

2. A patient visits her physiciT anEsStaTtiBnA gN thK atShEerLpLreEsR cr. ibCeO dM painkiller is not working to reduce the

pain following her recent surgery. A friend of the patient claims that the same painkiller “worked wonders” to reduce her pain after the same surgery. The physician states that the difference in the effect of the drug might be caused by , which is studied in pharmacogenetics. a. epidemiology b. an inherited disease c. a conflict of interest d. a genetic variation in drug-metabolizing enzymes ANS: D

Pharmacogenetics is the study of the genetic variation of drug metabolism between individuals.

DIF: 1

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OBJ: 1

3. John works in a molecular diagnostics laboratory and receives a blood sample that has the

name of a close friend printed on the bar-coded label. The genetic test that is ordered on the friend’s sample would provide diagnostic information about a disorder that has a poor prognosis, and the test is usually performed by John. He asks a fellow employee to analyze the sample for him and not divulge the results. This ethical issue concerns: a. confidentiality of patient genetic and medical information. b. a conflict of interest. c. resource allocation. d. diagnostic accuracy.

ANS: A

Clinical laboratorians have long been responsible for maintaining the confidentiality of all laboratory results, a situation made even more critical with the advent of increasingly powerful genetic testing.

DIF: 1

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OBJ: 6 | 7

4. Molecular diagnostic testing methods and results can be: a. qualitative only. b. quantitative only. c. either qualitative or quantitative.

ANS: C

Molecular diagnostic methods can be either qualitative or quantitative in nature, depending on the clinical need.

DIF: 1

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OBJ: 5

5. Clinical epidemiology, which is the study of the patterns, causes, and effects of health and

disease in certain populations, has provided the clinical laboratory with methods that evaluate the effects and outcomes of laboratory testing. This allows for a more effective: a. process of determining the cost of the testing methods. b. selection and interpretation of laboratory tests. c. determination of the boundaries between the components of the clinical lab. d. conduct assessment.

ANS: A

Clinical epidemiologists have introduced methods to evaluate the effects and value of laboratory testing in healthcare. These developments are expected to play an increasing role in the selection and interpretation of laboratory tests.

DIF: 1

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OBJ: 4

6. Analysis of which one of the following by molecular diagnostic methods provides a measure

of processes that are ongoing at the time of blood sampling? a. Genetic variation in an individual’s response to a drug b. Circulating plasma nucleic acids c. Malignant lymphomas d. Histocompatibility ANS: B

Molecular diagnostics, given its very high sensitivity, has been applied to the study of plasma nucleic acids (or circulating nucleic acids). Plasma nucleic acids analysis has been made possible by the discovery that dying cells in the body release their DNA and RNA into the extracellular compartment and ultimately into the bloodstream, where they can be detected and analyzed. Given their short half-life in circulation (less than 24 hours), plasma nucleic acids provide a measure of processes that are ongoing at the time of blood sampling.

DIF: 1

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OBJ: 5

7. A healthy individual with no clinical signs or symptoms of disease visits his physician for a

routine physical examination. Blood samples are collected and sent to the laboratory. The tests requested on the sample are for general laboratory analyses, including a complete blood count, a panel of general chemistry tests (including glucose, protein, cholesterol, and others), and an analysis of urine. This type of testing in laboratory medicine is directed at: a. confirming a clinical suspicion of disease. b. selecting a treatment for disease. c. ruling in a diagnosis. d. screening for disease in the absence of clinical signs or symptoms.

ANS: D

Testing in laboratory medicine may be directed at (1) confirming a clinical suspicion; (2) making, or ruling in, a diagnosis; (3) excluding, or ruling out, a diagnosis;, (4) assisting in the selection, optimization, and monitoring of treatment; (5) providing a prognosis; (6) screening for disease in the absence of clinical signs or symptoms; or (7) establishing and monitoring the severity of a physiologic disturbance. The field of laboratory medicine includes clinical chemistry and areas such as microbiology and hematology. The general tests ordered on this healthy individual are done to screen the physiologic systems despite the absence of any symptoms.

DIF: 2

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OBJ: 2

8. The discipline involved in the selection, provision, and interpretation of diagnostic testing that

uses primarily samples from patients is: a. clinical chemistry. b. hematology. c. laboratory medicine. d. molecular diagnostics.

ANS: C

The term “laboratory medicine” refers to the discipline involved in the (1) selection, (2) provision, and (3) interpretation of diagnostic testing that uses primarily samples from patients.

DIF: 1

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OBJ: 1 | 3

9. A male laboratorian works in the clinical chemistry laboratory of a large hospital. He is

approached by his friend, who is a representative of a drug company, and asked to analyze some patient samples for drug levels of a specific drug that the representative’s company sells and that these patients use. The representative wants to publish a report on the rate of drug absorption and distribution of this drug and tells his laboratorian friend that he will personally reimburse him for his time. What ethical issues come into play here? a. Resource allocation and conflict of interest b. Maintenance of confidentiality and publishing issues c. Maintenance of confidentiality, conflict of interest, and publishing issues. d. Resource allocation, maintenance of confidentiality, conflict of interest, and publishing issues.

ANS: D

Resource allocation, maintenance of confidentiality, conflict of interest, and publishing issues are being compromised by the representative and the laboratorian if the laboratorian follows through with the request. Using laboratory resources for a study that has not been approved by the institutional review board is a resource allocation issue, revealing results of laboratory tests is a confidentiality issue, receiving money to run laboratory tests from an individual with a direct interest in the laboratory results is a conflict of interest, and publishing the results of the testing would possibly be considered fraudulent and inappropriate.

DIF: 2

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OBJ: 3 | 6 | 7

TRUE/FALSE 1. Molecular diagnostics testing is only used by the clinical chemistry laboratory.

ANS: F

The discipline of molecular diagnostics, which entered the realm of laboratory medicine in multiple forms and in multiple fields, includes but is not limited to the study of hematopoietic malignancies, such as malignant lymphomas and leukemias; the existence of nonhost nucleic acids (microorganisms, graft-donor, fetal nucleic acids during pregnancy); and assessment of solid tumors.

DIF: 1

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OBJ: 1 | 5

Chapter 02: Selection and Analytical Evaluation of Methods—With Statistical Techniques Test Bank MULTIPLE CHOICE 1. A statistic is a: a. constant that describes some particular characteristic of a population. b. value calculated from the observations in a sample to describe a particular

characteristic of that sample. c. complete set of all observations that might occur as a result of performing a

particular procedure according to specified conditions. d. graphic device for displaying a large set of data.

ANS: B

A statistic is a descriptive measure of a sample; it is a value calculated from the observations in a sample to describe a particular characteristic of that sample.

DIF: 1

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OBJ: 3

2. A population mean (µ) is calculated by which one of the following formulae? a. xi/N b. (b − 1)/SE(b) c. (x2i − x1i) d. (x1 − )2/N ANS: A

The parameter most commonly used to describe the central location of a population of N values is the population mean ():

DIF: 1

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OBJ: 3 | 11

3. Which one of the following is the correct formula for calculating the percent coefficient of

variation of a set of measurements? a. CV = standard deviation  100% b. CV = standard deviation ÷ 100% c. CV = (standard deviation ÷ mean)  100% d. CV = (mean + standard deviation) ÷ 100% ANS: C

The coefficient of variation is the measure of relative imprecision. The value of CV% is determined by calculating the ratio of the SD to the mean multiplied by 100%.

DIF: 1

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OBJ: 11

4. The type of method comparison that compares the average results between two analyses with

the differences between varying concentration values of the two analyses is referred to as a(n): a. Deming analysis.

b. linear regression plot. c. ordinary least-squares plot. d. Bland-Altman difference plot.

ANS: D

When comparing values obtained with two different methodologies, the average values of the results are plotted against the differences between the values obtained from the two methods.

This examines the differences at varying analyte concentrations to determine whether a problem exists at a certain concentration.

DIF: 2

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OBJ: 1 | 6

5. How is the formula for population standard deviation () stated? a. The positive square root of the mean ÷ sum of squared differences between mean

and individual values b. Square root of the mean ÷ (N − 1) c. The positive square root of the [(sum of squared differences between mean and individual values) ÷ N] d. The sum of squared differences ÷ the positive square root of the mean ANS: C

Standard deviation describes the dispersion (or variance) of values around a central point (typically the mean). Variance is calculated by summing the squared differences between the population mean and each individual sample value and dividing this sum by the population size. This results in a large number, thus SD is the positive square root of this variance.

DIF: 1

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OBJ: 1 | 11

6. Two types of error may be encountered during analysis of a substance. The type of error that

occurs with a constant or predictable difference or trend, either positive or negative, and thus is related to bias, is a(n) error. a. systematic b. random c. analytical d. All of the above are correct.

ANS: A

Systematic error is a component of error, which in the course of a number of analyses of the same measure and/or analyte remains constant or varies in a predictable (proportional) way.

This type of error will directly influence the mean value and affects bias.

DIF: 2

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OBJ: 1 | 7

7. A research project examining cholesterol values using a new Cholestcheck assay produces the

following cholesterol values from a random sample of 14, 25-year-old women: Mean = 137 mg/dL 2 standard deviations = 6 mg/dL N = 14 The coefficient of variation percent for this assay is: a. 1.14%. b. 2.19%.

c. 4.38%. d. 9.49%.

ANS: B

CV% is calculated by dividing a standard deviation by the mean and then multiplying that value by 100%. In this case, one standard deviation is equal to 3 mg/dL (6 mg/dL ÷ 2), which is divided by 137 and equals 0.02189. This value multiplied by 100% equals 2.189 or 2.19.

DIF: 2

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OBJ: 11

8. You are performing a precision study on a new chemistry analyzer in your hospital lab by

analyzing a single sample many times. The study involves performing the analysis on different shifts using different calibrators and analysis by different laboratorians. This aspect of precision is referred to as: a. repeatability. b. reproducibility c. validity. d. reliability.

ANS: B

One aspect of precision is reproducibility, the closeness of agreement between results of measurements performed under changed conditions of measurements (e.g., time, operators, calibrators, and reagent lots).

DIF: 2

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OBJ: 1 | 4

9. Following a precision study in which repeatability and reproducibility of 20 samples are

assessed, which one of theTfoElS loT wB inA gNfoKrm ulL aeLw SE EoRu.ldCbOeMused to determine the total standard 2 deviation ( T)? a. 2within-run/2 + 2between-run b. (x2i − x1i) c. (x1 − )2/N d. 2within-run + 2 between-run ANS: D

The degree of precision is usually expressed on the basis of statistical measures of imprecision, such as the standard deviation. The total standard deviation (2T) may be split into within-run and between-run components using the principle of analysis of variance components (variance is the squared standard deviation): 2T = 2within-run + 2between-run DIF: 2

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OBJ: 4 | 11

10. The ability of an analytical method to assess small variations of the concentration of an

analyte, and that is often expressed as the slope of the calibration curve, is referred to as: a. analytical specificity. b. analytical sensitivity. c. limit of detection. d. analytical range.

ANS: B

Analytical sensitivity is the ability of an analytical method to assess small variations of the concentration of analyte. This is often expressed as the slope of the calibration curve.

DIF: 1

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OBJ: 1 | 4

11. Method selection involves consideration of several different criteria. Assessment of a

candidate method’s precision, accuracy, and analytical specificity are components of which one of the following categories? a. Analytical performance criteria b. Medical criteria c. Instrument parameters d. Descriptive measures criteria ANS: A

In evaluation of the performance characteristics of a candidate method, precision, accuracy (trueness), analytical range, detection limit, and analytical specificity are of prime importance.

These are aspects of analytical performance criteria.

DIF: 1

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OBJ: 2

12. The statistical analysis used to compare values obtained by a new method with those obtained

by an established method is: a. a Student t test. b. standard deviation. c. regression analysis. d. limit of detection.

ANS: C

Regression analysis is commonly applied when comparing the results of analytical method comparisons. Typically an experiment is carried out in which a series of paired values is collected when comparing a new method with an established method.

DIF: 1

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OBJ: 1 | 5

13. The Student t distribution: a. compares a sample mean to a population mean using the population. b. compares the means of two samples using sample statistics. c. assesses the means of samples prior to and following some intervention. d. assesses the significance of difference between more than two variables.

ANS: B

A Student t distribution analysis is commonly used in significance tests, such as the comparison of sample means. Therefore, if a random sample can be taken from a Gaussian population, then the sample SD can be calculated from the sample means.

DIF: 2

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OBJ: 1 | 3

14. A list of intervals followed by a list of frequencies is referred to as a: a. frequency histogram. b. range. c. cumulative frequency distribution. d. frequency distribution.

ANS: D

A frequency distribution is constructed by dividing the measurement scale into cells of equal width; counting the number, ni, of values that fall within each cell; and either drawing a histogram or listing the number of values in each cell.

DIF: 1

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OBJ: 1

15. The type of regression analysis that is considered to reliably estimate the relationship between

modified target values and that takes into account errors in both methods 1 and 2 is regression analysis. a. Deming b. ordinary least-squares c. nonparametric d. random error ANS: A

To reliably estimate the relationship between modified target values, a regression procedure taking into account errors in both x1 and x2 is preferable (a situation termed the Deming approach). Although the OLR procedure is commonly used in method comparison studies, it does not take errors in x1 into account but is based on the assumption that only the x2 measurements are subject to random errors.

DIF: 2

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OBJ: 8

16. Comparisons of measurement values between clinical laboratories require a hierarchical

approach that obliges routine clinical chemistry measurements to be referred back to a reference measurement proTcE edSuT reB .T s. knCoO wM n as: AhNisKcSoEncLeLptEiR a. uncertainty. b. error. c. traceability. d. reliability.

ANS: C

To ensure reasonable agreement between measurements of routine methods, the concept of traceability comes into focus. Traceability is based on an unbroken chain of comparisons of measurements leading to a known reference value. A hierarchy of methods exists with a reference measurement procedure at the top, selected measurement procedures at an intermediate level, and finally routine measurement procedures at the bottom.

DIF: 2

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OBJ: 1 | 9

17. To systematically assess errors associated with laboratory results, a parameter associated with

the result of a measurement that characterizes the dispersion of the values reasonably attributed to the substance being measured is considered. This parameter is expressed by a formula that includes preanalytical, analytical, and traceability components and is referred to as: a. uncertainty. b. error. c. traceability. d. reliability.

ANS: A

To assess in a systematic way errors associated with laboratory results, the uncertainty concept has been introduced into laboratory medicine. The formal definition of uncertainty is “a parameter associated with the result of a measurement that characterizes the dispersion of the values that could reasonably be attributed to the measurand.”

DIF: 1

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OBJ: 1 | 11

18. In a chemistry methods analysis, linearity refers to the: a. closeness of agreement between independent results of measurements obtained

under stipulated conditions. b. closeness of agreement between the average value obtained from a large series of

results of measurements and a true value. c. analyte concentration range over which measurements are within the declared tolerances for imprecision and bias of the method. d. relationship between measured and expected values over the range of analytical measurements.

ANS: D

Definition: linearity refers to the relationship between measured and expected values over the range of analytical measurements.

DIF: 1

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OBJ: 1 | 4

19. In the calibration hierarchy, a reference measurement procedure, which is a fully understood

procedure of highest analytical quality, is at the top. This procedure is associated with which one of the following types of error? a. Calibration error b. Specificity error c. Pure random error d. Systematic error ANS: C

A reference measurement procedure is associated only with pure, random error, whereas a routine method typically has some additional bias related to errors in calibration and limitations with regard to specificity.

DIF: 1

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OBJ: 9

20. In a qualitative point-of-care test, clinical sensitivity is considered as the: a. probability of classifying a result as positive. b. probability of classifying a result as negative. c. ability of an analytical method to assess small variations of the concentration of an

analyte. d. ability of an assay procedure to determine specifically the concentration of the target analyte in the presence of potentially interfering substances.

ANS: A

Qualitative point-of-care tests are primarily assessed on the basis of their ability to correctly classify results in relation to the cutoff value. The probability of classifying a result as positive is called the clinical sensitivity, while classifying a result as negative (below the cutoff) is termed the clinical specificity.

DIF: 1

REF: Page 15

OBJ: 1

Chapter 03: Clinical Evaluation of Methods Test Bank MULTIPLE CHOICE 1. True negatives ÷ (false positives + true negatives) is the formula for determining: a. sensitivity. b. specificity. c. the odds ratio. d. the likelihood ratio.

ANS: B

Clinical specificity is the absence of a particular disease in those individuals who have a negative test result for that disease expressed as a percentage.

DIF: 1

REF: Page 33

OBJ: 2

2. The proportion of a population that has the particular disease being studied is referred to as

the: a. b. c. d.

prevalence. predictive value. positive value. clinical sensitivity.

ANS: A

Prevalence is the proportion of the population (or of those being tested) with the disease.

DIF: 1

REF: Page 35

OBJ: 1

3. What is the positive predictive value of a test in which 220 tested individuals with positive

test results actually have the disease and 45 tested individuals with positive test results do not have the disease? a. 16.9% b. 66% c. 83% d. 120% ANS: C

The predictive value for a positive test examines the number of true positives (TP) and false positives (FP). The formula for calculating the predictive value is TP/(TP + FP). In this case, 220/(220 + 45)  100% = 83%.

DIF: 3

REF: Page 35

OBJ: 2

4. In regard to the number of true-positive and negative, and false-positive and negative, results

in laboratory testing, the prevalence times the sensitivity is equal to the number of: a. true positives. b. false positives. c. true negatives. d. false negatives.

ANS: A

Prevalence is the proportion of the population (or of those being tested) with the disease while sensitivity of an assay is the fraction of those subjects with a specific disease that the assay correctly predicts. The two values multiplied together is equal to the number of true-positive results (those with the disease that the assay accurately predicts).

DIF: 2

REF: Page 36

OBJ: 5

5. Calculate the sensitivity for the following data: in a group of 80 patients diagnosed with sickle

cell disease, 72 tested positively for it. The sensitivity of this test is: a. 111%. b. 100%. c. 90%. d. 75%.

ANS: C

Sensitivity is the presence of a particular disease in those individuals who have a positive test result for that disease expressed as a percentage. In this case, 72/(72+8)  100% = 90%.

DIF: 3

REF: Page 33

OBJ: 2

6. A receiver operating characteristic (ROC) curve is a plot of: a. systematic error against random error. b. tumor marker decision levels versus upper limit of reference intervals. c. true positives versus false positives. d. specificity of one method against the specificity of another method.

ANS: C

In evaluating performance of different analyses for one analyte or multiple markers for one type of cancer, a plot of the performance of each analysis is made with the x-axis as the fraction of nondiseased patients who were erroneously categorized as positive for a specific decision threshold. This “false-positive rate” is mathematically the same as 1 − specificity.

The y-axis plots the “true-positive rate” (the sensitivity).

DIF: 2

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OBJ: 1 | 6

7. ROC curves are most useful in assessing the performance of quantitative laboratory analyses

because: a. multiple tests for the same analyte can be evaluated at one time. b. they can display performance of tests over the entire range of decision values. c. they allow specific reference intervals to be determined for each analysis. d. they can evaluate combination testing in a single plot.

ANS: B

A graphical technique for displaying quantitative test performance is called a receiver operating characteristic (ROC) plot. An ROC curve is generated by plotting sensitivity (y-axis) versus 1 − specificity (x-axis) and allows for estimation of sensitivity and specificity for various decision cutoffs.

DIF: 2

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OBJ: 1 | 6

8. A laboratory analysis that produces quantitative results with an infinite number of sensitivity

and specificity pairs is referred to as a a. predictive b. qualitative c. dichotomous d. continuous

test.

ANS: D

As opposed to dichotomous tests, continuous tests are those that produce quantitative results.

Continuous tests have an infinite number of sensitivity and specificity pairs, as the cutoff varies from lowest to highest decision value.

DIF: 1

REF: Page 34

OBJ: 4

9. Nondiseased individuals that are classified as diseased by having a positive result on a

specific laboratory test are considered: a. true positives. b. false positives. c. true negatives. d. false negatives.

ANS: B

False positives (FP) are nondiseased individuals misclassified by a positive laboratory test result.

DIF: 1

REF: Page 33

OBJ: 1

sS thT eB usAeNoK fS mE ulL tiL plE eR la. boCrO atM ory tests in an attempt to decrease 10. Combination testing involvTeE costs or assist in diagnosing a specific disease. One of the problems with this type of testing is that: a. false-positive results increase. b. true-negative results increase. c. the prevalence of the disease increases. d. the predictive value of a negative test increases.

ANS: A

The use of multiple tests can increase the probability of the occurrence of false-positive or false-negative results, depending on how the tests are combined.

DIF: 1

REF: Page 37

OBJ: 9

11. A method that can be used to calculate the probability of a disease after new information is

added to previously obtained information involves: a. likelihood analysis. b. sensitivity analysis. c. Bayes theorem. d. combination testing.

ANS: C

Bayes theorem provides a method to calculate the probability of a disease after new information is added to previously obtained information.

DIF: 1

REF: Page 36

OBJ: 7

12. To calculate the sensitivity of a laboratory test to correctly classify true positives, one must

first know the number of: a. true positives and false negatives. b. true negatives and false positives. c. true positives and false positives. d. false positives and false negatives.

ANS: A

The sensitivity of a laboratory test reflects the fraction of those with a specified disease that the test correctly predicts. True positives are those diseased individuals who are correctly classified by the test. Sensitivity is calculated by dividing the true positives by the total of true positives plus false negatives.

DIF: 2

REF: Page 33

OBJ: 2

13. To calculate the predictive value of a positive test, which of the following should be known? a. Sensitivity only b. Specificity and prevalence only c. Sensitivity and specificity only d. Sensitivity, specificity, and prevalence ANS: D

Predictive values are a function of sensitivity, specificity, and prevalence. For example, to determine the predictive value of a positive test (PV+), the prevalence must be known to assess the sensitivity (true positives) of a laboratory test and the specificity (false positives) of SVE+LiL the test. The formula for caTlcEuS laT tiB ngAtN heKP nvEoR lv.esCdOivMiding the number of true positives by the number of true positives plus the number of false positives.

DIF: 2

REF: Page 35

OBJ: 5

14. The probability of occurrence of a specific test value given that the disease is present divided

by the probability of the same test value if the disease was absent is the: a. odds ratio. b. likelihood ratio. c. prevalence. d. predictive value.

ANS: B

The likelihood ratio is the probability of occurrence of a specific test value given that the disease is present divided by the probability of the same test value if the disease was absent.

DIF: 1

REF: Page 33

OBJ: 1

TRUE/FALSE 1. In regard to clinical evaluation of method, a high clinical sensitivity means few false

negatives.

ANS: T

In the calculation for sensitivity, the true positives are divided by the true positives plus the false negatives. A higher sensitivity is achieved if the false negative number is lower.

DIF: 1

REF: Page 33-34

OBJ: 3

Chapter 04: Evidence-Based Laboratory Medicine Test Bank MULTIPLE CHOICE 1. Systematic reviews are used to assess and answer very specific clinical questions in an

unbiased way. The most important of the steps in conducting a systematic review is the: a. formulation of the clinical question that will form the basis of the review. b. choosing of the reviewer who will perform the work. c. primary literature search and review. d. data extraction from the literature.

ANS: A

See Box 4-1. The most important of the steps in conducting a systematic review is the formulation of the clinical question for which the test results are expected to give an answer.

This question forms the basis of the review.

DIF: 1

REF: Page 49

OBJ: 8

2. In reading a research article, you determine that the study design was flawed because there

was no control group. This is an example of a weakness in: a. internal reliability. b. internal validity. c. external reliability. d. external validity.

ANS: B

Problems in the design of a study are considered to be poor internal validity and will produce systematic error or bias, because the estimates of diagnostic accuracy differ from those one would have obtained using an optimal design for the study.

DIF: 2

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OBJ: 1 | 4

3. When developing clinical practice guidelines, what is the critical first step? a. Requesting input from health insurance companies and government officials b. Preparing a cost analysis based on patient needs c. Determining the intended group that will be directly involved with implementation d. Selecting and refining the topic upon which the investigation will center ANS: D

Selection and refinement of the topic needing investigation must be accomplished before choosing target groups and assessing primary evidence. Scope, topic, and clinical area must all be addressed within the abilities of the group initiating guideline development.

DIF: 2

REF: Page 53

OBJ: 10

4. Another way that “bias” can be defined is as a. random b. systematic c. analytical

_ error.

d. clinical ANS: B

Bias is systematic error that occurs when there is constant overestimation or underestimation of a measured value.

DIF: 1

REF: Page 40

OBJ: 1

5. Internal validity is the: a. degree to which the variables in the study apply to all individuals in the study. b. degree to which the results of your sample can be inferred to the general

population outside of your study. c. equivalent of consistency. d. calculation of mean and variance from repeated measures.

ANS: A

Internal validity is the degree to which the results of a study can be trusted for the population of patients in the study.

DIF: 1

REF: Page 44

OBJ: 1 | 4

6. During diagnostic accuracy studies in evidence-based laboratory medicine, a laboratory test

being studied, for example, produces results that are compared with the gold standard of testing, which would be the currently used assay or assay system. The test of interest is referred to as a(n): a. index test. b. reference standard. c. outcome study. d. practice test.

ANS: A

An index test is the method being assessed, and the results of the index test are compared with the reference standard, which is the current best practice, or method, used to obtain results.

DIF: 1

REF: Page 44

OBJ: 1 | 2

7. A research study was prepared to assess the diagnostic accuracy of a therapeutic drug

monitoring assay for HMG-CoA reductase inhibitors (statins). The study was flawed with poor design. Which of the following statements are correct? a. Random error decreased. b. Systematic error decreased. c. Systematic error increased. d. Both a and b are correct.

ANS: C

Poor internal validity caused by poor study design produces systematic error.

DIF: 2

REF: Page 44

OBJ: 4

8. In a randomized control trial, the use of a new vaccine was observed to reduce the number

Chlamydia trachomatis infections in a population of college-aged women. This finding is referred to as a(n):

a. b. c. d.

clinical audit. systematic review. patient outcome. internal validator.

ANS: C

Outcomes may be defined as results of medical interventions in terms of health or cost.

“Patient outcomes” are results that are perceptible to the patient.

DIF: 2

REF: Page 45

OBJ: 6

9. If the evidence overwhelmingly points toward the introduction of a new laboratory analysis

and practice, yet physicians fail to incorporate the new test into their clinical practice, what component of evidence-based laboratory medicine will reveal this? a. Clinical audit b. Economic evaluation c. Systematic review d. Clinical practice guidelines ANS: A

In applying the principles of evidence-based laboratory medicine to everyday practice, there must be adherence to the recommendations made by those involved in formulating new clinical practice guidelines. This commitment is monitored by the clinical audit, particularly the audit of adherence to best practice.

DIF: 2

REF: Page 56

OBJ: 10

icE iaS nT asBkA sN if K thSeEreLsL ulE tsRfr.oC mOthMe therapeutic drug assay will be able 10. In a research study, a physT to predict the patient’s eventual health outcome. A study to determine this is referred to as a: a. patient outcome study. b. case-control study. c. systematic review. d. prognostic value study.

ANS: D

Studies of the prognostic value of a test ask the question, “Can the test be used to predict an outcome?”

DIF: 1

REF: Page 45

OBJ: 6

11. Following a systematic review, random control studies, clinical audit, and a cost evaluation,

an assay for assessment of growth hormone level as a predictor of bone cancer has been recommended by a group of orthopedic surgeons to be performed in your chemistry laboratory. What is the next step before implementation of the assay? a. Evaluating the costs of alternative methods to produce similar outcomes b. Developing a clinical practice guideline for implementation of the assay c. Performing a meta-analysis d. Beginning a second round of randomized control trials ANS: B

For the findings from evidence-based medicine studies to be finally applied, clinical practice guidelines must be developed to facilitate implementation of what was learned from primary studies and systematic reviews.

DIF: 3

REF: Page 53

OBJ: 10

12. Following a systematic review, random control studies, clinical audit, and a cost evaluation,

an assay for assessment of growth hormone level as a predictor of bone cancer has been recommended to be performed in your chemistry laboratory. What might be an issue if the group recommending this assay was composed of all oncologists? a. This group would likely not have the expertise needed to suggest implementation and develop a guideline. b. This specialty group of physicians might be motivated to implement this test to produce income for the group practice. c. The systematic review, research studies, and statistical analysis would be beyond the scope of this group of physicians. d. There is nothing inappropriate about this group because they are experts in the field.

ANS: B

When guidelines are developed by a professional group (such as specialist physicians), the recommendations made may be suspected of promoting the welfare of that professional group.

DIF: 3

REF: Page 53

OBJ: 10

13. STARD: a. relates to the four components of economic evaluation in an evidence-based

TBANKSELLER.COM

laboratory medicine stuTdE yS . b. is the assessment of the value of a test analysis for those individuals who are tested. c. is a set of guidelines assembled to put into practice the findings of an evidence-based laboratory medicine study. d. includes a listing of items that need to be included in reports of studies on diagnostic accuracy.

ANS: D

Standards for Reporting of Diagnostic Accuracy (STARD) is an initiative that intends to improve reporting the results of diagnostic accuracy studies. The STARD document includes a checklist of items to be included in diagnostic accuracy studies and a diagram of study design and participant action.

DIF: 2

REF: Page 41

OBJ: 1 | 5

14. QALY: a. is associated with a quality systematic review of literature. b. assesses the quality of a diagnostic accuracy study. c. is an outcome achieved in cost-utility analysis. d. relates to the implementation of the findings of a clinical audit.

ANS: C

A cost-utility analysis of an economic evaluation examines the quality of the life-years gained and includes the quality and the quantity of the health outcome. While the cost of the intervention is assessed in monetary terms, the outcomes are expressed in quantitative expressions of their relative value. An often-used metric is the “quality-adjusted life years” (QALYs).

DIF: 2

REF: Page 51

OBJ: 1 | 9

15. In a study of diagnostic accuracy, the selection of the study groups was not random and

included only a few individuals in each group. This would likely affect which one of the following? a. Internal validity b. External validity c. The clinical reference standard d. Index test ANS: B

Poor external validity limits the “extent” to which clinical research studies apply to broader populations. A research study has external validity if its results can be generalized to the larger population. In a study with only a few people who have not been randomly selected, it is much more difficult to relate the findings to the population as a whole.

DIF: 2

REF: Page 44

OBJ: 1 | 4

Chapter 05: Establishment and Use of Reference Values Test Bank MULTIPLE CHOICE 1. Even if somewhat impractical, which one of the following preanalytical factors should be

standardized when establishing a reference interval for an analyte? a. Location (building, city, etc.) in which the venipuncture is performed b. The method of specimen collection c. Reagents used in analyte analysis d. The specific method used for analysis ANS: B

In establishing a reference interval, certain preanalytical factors must be standardized. These factors include (1) preparation of individuals before sample collection, (2) sample collection itself, and (3) handling of the sample before analysis to eliminate or minimize bias or variation. These steps will reduce biological “noise.”

DIF: 1

REF: Page 62

OBJ: 5

2. To determine the confidence intervals of percentiles of ranked data (data arranged by

magnitude of value), it is most appropriately assessed using: a. nonparametric testing. b. univariate analysis. c. parametric testing. d. multivariate analysis.

ANS: A

Nonparametric statistics do not use distribution parameters such as mean, standard deviation, or coefficient of variation to assess data. Data that is first placed in a list in order of magnitude and then ranked (usually the smallest value has a rank of 1) is analyzed by nonparametric tests. These tests use the ranks of the data and the number of data points (n) to estimate the confidence intervals of percentiles.

DIF: 2

REF: Page 64

OBJ: 8

3. True negatives ÷ (false positives + true negatives)  100 is the formula for determining: a. clinical sensitivity. b. clinical specificity. c. analytical sensitivity. d. analytical specificity.

ANS: B

Clinical specificity is the absence of a particular disease in individuals who have a negative test result expressed as a percentage for that disease.

DIF: 1

REF: Page 70

OBJ: 1 | 11

4. Calculate the clinical sensitivity for the following data: in a group of 80 patients diagnosed

with sickle cell disease, 72 had positive test results. The clinical sensitivity of this test is:

a. b. c. d.

111%.

100%.

90%.

75%.

ANS: C

Clinical sensitivity is the presence of a particular disease in those individuals who have a positive test result expressed as a percentage for that disease. In this case, 72/(72+8)  100% = 90%.

DIF: 2

REF: Page 70

OBJ: 11

5. Which one of the following is an example of an exclusion criterion when establishing a

healthy population-based reference interval? a. Use of oral contraceptives b. Sex c. Age d. Ethnicity ANS: A

Certain conditions or criteria qualify individuals for exclusion from the group of reference individuals when setting health-associated reference values. The use of oral contraceptives would be an example of an exclusion criterion when assessing health-associated reference values.

DIF: 2

REF: Page 62

OBJ: 1 | 4

6. An important assumption tT haEtSisTm BaAdN eK wS heEnLuL siE ngRp.aCraOmMetric methods to estimate percentiles

and their confidence intervals in determining reference limits is that: a. the type of distribution that the reference values exhibit is a t-distribution. b. the true distribution that the reference values exhibit is Gaussian. c. the distribution parameters cannot be estimated. d. there is no set distribution pattern of reference values.

ANS: B

The majority of the parametric methods are based on the Gaussian distribution. A parametric method is used if the true distribution is believed to be Gaussian and reference limits (percentiles) are determined as the values located 2 SDs below and above the mean. These are the parameters.

DIF: 2

REF: Page 64

OBJ: 8

7. A physician asks your laboratory to begin performing thyroid-stimulating hormone (TSH)

analyses on all specimens that have a free thyroxine (FT4) analysis ordered, a practice that your laboratory currently does not perform. Your laboratory typically performs TSH only on those FT4 specimens that are outside the population-based reference interval. The physician suggests using subject-based reference intervals, claiming that population-based intervals are clinically insensitive. What is the basis of this claim? a. Subject-based reference values more closely resemble the group of reference individuals that were used to establish population-based reference intervals. b. Standardized laboratory methods produce more accurate results when examining

individual subject values. c. Subject-based reference values are more easily tracked and applied in settings in

which large numbers of specimens are analyzed. d. Changes in a subject-based reference value might indicate altered biochemical

status yet still be within the population-based healthy reference interval.

ANS: D

An individual’s particular values may form a different Gaussian distribution than that of a population’s values. As demonstrated in Figure 5-3, changes in an individual’s values might indicate a change in the biochemical status of that individual, suggesting presence or absence of disease; however, the individual’s values might still be within the population-based reference interval, thus not triggering the need for additional testing.

DIF: 3

REF: Page 67-68

OBJ: 1 | 9

8. What is the statistical range of the following distribution of data? 21 25 18 20 19 21

23 26 a. 18 to 26 b. 21.6 c. 8 d. −8 ANS: C

Statistical range is a single value that describes the minimum value in a data set subtracted from the maximum value in that set. In this case, 26 − 18 = 8.

DIF: 2

REF: Page 63

OBJ: 1

9. The proportion of a population (or of those being tested) with the disease being studied is

referred to as the: a. prevalence. b. clinical sensitivity. c. clinical specificity. d. predictive value.

ANS: A

Prevalence is the proportion of the population (or of those being tested) with the disease, while clinical sensitivity of an assay is the fraction of those subjects with a specific disease that the assay correctly predicts.

DIF: 1

REF: Page 60

OBJ: 1

10. To reduce workload in your chemistry laboratory, you are setting up a small laboratory on the

opposite side of your large city from the main laboratory. When preparing the new laboratory’s chemistry analyzer, you decide to use the reference values that have been generated by the main laboratory’s chemistry analyzer, which is a larger model (but similar in all other respects) than yours. Can this be justified? a. No, because each analyzer will produce completely different results from the other laboratory. b. No, because the populations that will be tested are completely different. c. Yes, if certain conditions have been fulfilled, such as population matching, data

comparison, analytical performance agreement, and specimen standardization. d. Yes, because you cannot afford to perform reference value determinations in your

laboratory.

ANS: C

Because establishment of reference values for all tests performed by the analyzer is a major task, reference values can be transferred to another laboratory if certain conditions are met, including those listed.

DIF: 2

REF: Page 68

OBJ: 1 | 10

11. Visually inspecting the distribution of reference values can provide a safeguard against

misinterpretation of statistical methods, and it may provide valuable information about the data. Which of the following observations might represent erroneous values? a. Skewed distributions b. Outlier values c. Partition criteria d. Bimodal distributions ANS: B

Reference values are subjected to statistical treatments, two of which are inspection of the distribution of each group and identification of outliers. An outlier is an erroneous value that deviates significantly from the proper reference values. Visual inspection of a histogram is a reliable method for identification of possible outliers.

DIF: 2

REF: Page 63

OBJ: 1 | 6

eE ofSqTuB anAtiNtyKoSbE taL inLedER fr. om 12. The results of a certain typT COa Msingle individual or group of individuals corresponding to a stated description is the definition of: a. reference intervals. b. reference limits. c. clinical decision limits. d. reference values.

ANS: D

Reference values are results of a certain type of quantity obtained from a single individual or group of individuals corresponding to a stated description, which must be spelled out and made available for use by others.

DIF: 1

REF: Page 61

OBJ: 1 | 7

Chapter 06: Specimen Collection, Processing, and Other Preanalytical Variables Test Bank MULTIPLE CHOICE 1. When a coagulated blood sample is separated by centrifugation, the liquid component is

separated from the cells. This “serum” is the: a. liquid component with all clotting factors present in it. b. liquid component with no clotting factors in it. c. unclotted cellular component. d. clot.

ANS: B

When whole blood is allowed to clot, the clotting factors are used in the formation of the clot unless an anticoagulant is used. Serum is obtained from a separated, coagulated blood sample and is the liquid fraction of blood that does not contain any clotting factors. Plasma, on the other hand, contains all clotting factors and is obtained by separating cells in an anticoagulated blood sample.

DIF: 2

REF: Page 76

OBJ: 1 | 8

2. An example of an uncontrollable preanalytical variable would be: a. improper specimen collection. b. preanalytical errors. c. prolonged bed rest. d. an individual’s age.

ANS: D

Uncontrollable variables are those associated with the physiology of the particular patient (age, sex, underlying disease, etc.).

DIF: 1

REF: Page 73

OBJ: 1 | 2

3. The best use of a saliva specimen would be for which one of the following analyses? a. Measurement of blood group substances to determine secretor status and genotype b. Determination of whether the specimen is an effusion or an exudate c. Early gestational age diagnosis of inherited genetic disorders d. Characterization of the type of arthritis present in an individual ANS: A

Clinical application of methods that use saliva has been limited. Exceptions include measurement of blood group substances to determine secretor status and genotype.

Measurement of a drug in saliva has also been suggested.

DIF: 1

REF: Page 80

OBJ: 15

4. Hemolysis will cause potassium when analyzed. a. and lactate dehydrogenase (LD) values to appear increased b. value to appear increased and LD value to appear decreased c. value to appear decreased and LD value to appear increased

d. and LD values to appear decreased ANS: A

A notable effect may be observed on those constituents that are present at a higher concentration in erythrocytes than in plasma. Thus plasma activities or concentrations of lactate dehydrogenase, potassium, magnesium, and phosphate are particularly increased by hemolysis.

DIF: 2

REF: Page 77-78

OBJ: 12

5. The type of urine specimen that is best for detection of abnormal amounts of certain analytes

such as chorionic gonadotropin for pregnancy testing is a: a. random and untimed specimen. b. 24-hour collection. c. clean, early morning, fasting specimen. d. catheter specimen.

ANS: C

A clean, early morning, fasting specimen is usually the most concentrated specimen and thus is preferred for microscopic examinations and for the detection of abnormal amounts of constituents, such as proteins, or of unusual compounds, such as chorionic gonadotropin.

DIF: 1

REF: Page 78

OBJ: 13

6. Arthrocentesis is a technique used to collect: a. pleural fluid. b. blood. c. synovial fluid. d. amniotic fluid.

ANS: C

Arthrocentesis is a procedure used to remove synovial fluid from a joint capsule for chemical and cellular assessment in the characterization of arthritis and to differentiate noninflammatory effusions from inflammatory fluids.

DIF: 1

REF: Page 79

OBJ: 15

7. An amniotic fluid specimen for bilirubin analysis is received in the laboratory in a clear

plastic collection tube. How will this affect the results of the bilirubin analysis? a. There will be no effect on the bilirubin analysis results, because this specimen is properly collected. b. Because the tube is not darkened, light will cause the bilirubin to be photo-degraded and the results will be falsely decreased. c. Because there is no additive in the tube, the amniotic fluid cells will hemolyze, leading to a false increase in bilirubin. d. Because the tube is made of plastic, the amniotic fluid will clot, and no analysis can be performed on a clotted sample.

ANS: B

Specimens for bilirubin must be protected from both daylight and fluorescent light to prevent photo-degradation.

DIF: 2

REF: Page 81

OBJ: 16

8. As an anticoagulant, heparin acts to: a. chelate calcium. b. inhibit platelet aggregation. c. antagonize vitamin K. d. activate antithrombin.

ANS: D

Heparin accelerates the action of antithrombin III, which neutralizes thrombin and thus prevents the formation of fibrin from fibrinogen.

DIF: 1

REF: Page 77

OBJ: 10

9. Which one of the following anticoagulants is considered unacceptable for a blood sample that

will be used for DNA amplification in the polymerase chain reaction? a. Heparin b. EDTA c. Iodoacetate d. Acid citrate dextrose ANS: A

Heparin is unacceptable for most tests performed using the polymerase chain reaction (PCR) because of inhibition of the polymerase enzyme by the heparin molecule.

DIF: 1

REF: Page 77

OBJ: 11

10. An individual has several lT abEoSraTtoBrA yN teK stS s oErL deLreEdRa.nC dO isMhaving blood collected. After

applying the tourniquet, the phlebotomist has to answer the phone and write down a message, leaving the tourniquet in place for approximately 3 minutes. How will this affect this individual’s serum composition of total protein and potassium? a. Both will be increased. b. Total protein will be increased and potassium will be decreased. c. Total protein will be decreased and potassium will be increased. d. Both will be decreased.

ANS: B

See Table 6-1. Marked changes have been observed for many chemistry analytes after 3 minutes of leaving a tourniquet in place. According to the table, the serum composition of protein is increased 4.9% and potassium is decreased 6.2% when venous occlusion is prolonged.

DIF: 2

REF: Page 74

OBJ: 5

11. An individual has several laboratory tests ordered and is having blood collected. After

applying the tourniquet, the phlebotomist has to answer the phone and write down a message, leaving the tourniquet in place for approximately 3 minutes. How will this affect this individual’s serum composition of bilirubin? a. It will be increased. b. It will be decreased c. It will not be affected.

ANS: A

See Table 6-1. Marked changes have been observed for many chemistry analytes after 3 minutes of leaving a tourniquet in place. According to the table, bilirubin’s serum composition will be increased by 8.4% when venous occlusion is prolonged.

DIF: 2

REF: Page 74

OBJ: 5

12. Which one of the following analytes shows no difference in composition between a serum and

a plasma specimen? a. Lactate dehydrogenase b. Potassium c. Cholesterol d. Total protein ANS: C

See Table 6-3. Sometimes considerable differences are observed between the concentrations of analytes in serum and in plasma. According to the table, lactate dehydrogenase and total protein have a plasma concentration greater than that in serum, while potassium has a greater presence in serum. Cholesterol concentration is no different between the two specimen types.

DIF: 1

REF: Page 76

OBJ: 9

13. A blood collection tube containing a specific amount of additive is only half filled with blood

instead of being completely filled. Will this collection affect laboratory test results? a. There will be no effect on the results because the additive is “calibrated” for any amount of blood in the tube. b. There will be a significant effect on the test results because the additive must be mixed with a full tube T ofEbSloToB dA toNaKchSiE evLeLitE sR ap.pC roOpM riate effect.

ANS: B

Many additives are provided in the tube based on a “full” collection; deviation or short draws can be a source of preanalytical error because they can significantly affect test results.

DIF: 1

REF: Page 75

OBJ: 5

14. When collecting a timed urine specimen for laboratory analysis: a. all of the urine must be collected at once into one large container instead of using

smaller separate containers that are emptied into the large container. b. the container used for collection must be maintained at room temperature

throughout the entire collection period. c. it is acceptable and best practice to collect the urine into one container containing

two different mixed preservatives if more than one test is ordered. d. the individual’s bladder must be emptied first at the beginning of the time of collection, and this urine is discarded.

ANS: D

When specimens are to be collected over a specified period of time, the patient’s close adherence to instructions is important. The bladder must be emptied at the time the collection is to begin and this urine discarded. Thereafter, all urine must be collected until the end of the scheduled time at which time the bladder should be emptied again as the final collection. If a collection has to be made over several hours, urine should be passed into a separate container at each voiding and then emptied into a larger container for the complete specimen. The large container should be stored at 4° C during the entire collection period. Urine should not be collected at the same time for two or more tests requiring different preservatives.

DIF: 2

REF: Page 78

OBJ: 13 | 14

15. A skin puncture of an individual’s finger is ordered for hematocrit analysis and is to be

collected into a capillary tube. It is cold in the phlebotomy area, and the phlebotomist notices that the individual appears cold and pale. What should the phlebotomist do to stimulate blood circulation to the finger so an acceptable fingerstick specimen will be obtained? a. Slap the individual’s hand to warm it up. b. Tie a tourniquet around the individual’s finger. c. Warm the finger for 3 minutes using a warming device. d. Massage the finger and hand.

ANS: C

Massage of the finger, or any other site used, to stimulate blood flow should be avoided because it causes the outflow of debris and tissue fluid, which does not have the same composition as plasma. To improve circulation of the blood, the area to be pierced may be warmed by application of a warm, wet washcloth or a specialized device for 3 minutes before the lancet is used.

DIF: 1

TESTBANKSOEBL LER.COM J: 7

REF: Page 76

16. An example of a preanalytical error would be: a. mislabeling a tube of blood with an incorrect name. b. using expired reagents in an analysis. c. sending the test results to the incorrect physician. d. failing to run controls with unknown samples.

ANS: A

Proper collection, identification, processing, storage, and transport of common sample types associated with requests for diagnostic testing are critical to the provision of quality test results. Many errors can occur during these steps; such errors are considered preanalytical errors. Mislabeling samples, a component of specimen identification, is one of the most common sources of preanalytical error.

DIF: 1

REF: Page 73

OBJ: 1 | 2

17. The best additive in a collection tube for enhancing the vitality and recovery of white blood

cells for isolation of genomic DNA is: a. sodium citrate. b. heparin. c. oxalate. d. acid citrate dextrose.

ANS: D

Samples for molecular diagnostics are often collected into acid citrate dextrose (ACD) anticoagulant to preserve both the form and the function of the cellular components. ACD additives enhance the vitality and recovery of white blood cells for several days after collection of the specimen, thus they are suitable for molecular diagnostic testing.

DIF: 1

REF: Page 77

OBJ: 11

MATCHING

Using each answer only once, match the color of the evacuated blood collection tube stopper with the additive in that tube. a. Yellow b. Lavender c. Gray d. Green 1.

2.

3.

4.

Heparin EDTA Acid citrate dextrose Glycolytic inhibitor

1. ANS: C DIF: 1 REF: Page 75 MSC: See Table 6-2.

2. ANS: B DIF: 1 REF: Page 75 MSC: See Table 6-2.

3. ANS: D DIF: T1ESTBANKS L:LE RE EF PaR g. e 7C5OM MSC: See Table 6-2.

4. ANS: A DIF: 1 REF: Page 75 MSC: See Table 6-2.

OBJ: 6 OBJ: 6 OBJ: 6 OBJ: 6

Chapter 07: Quality Management Test Bank MULTIPLE CHOICE 1. If alerted to a control problem when using Westgard multirules, an analyst should first: a. assess the analytical method, equipment, reagents, and specimens. b. rerun controls several times until the values finally are acceptable. c. call the laboratory manager. d. call the manufacturer’s repair hotline.

ANS: A

When alerted to a control problem, the analyst first should conduct an inspection of the analytical method, equipment, reagents, and specimens to ensure that the test is performing correctly.

DIF: 1

REF: Page 100

OBJ: 7

2. Upon examination of the week’s analytical run of plasma glucose tests, you notice that four

consecutive normal control values are +1 s (standard deviation) from the mean. In your QC report, you note that Westgard multirule has been broken and realize that this rejection rule is sensitive to error. a. 14s; random b. 41s; systematic c. R4s; systematic d. 4Rs; random ANS: B

The multirule 41s indicates that four consecutive control observations have exceeded the mean plus 1 s or the mean minus 1 s. This multirule is sensitive to systematic error.

DIF: 2

REF: Page 99

OBJ: 8 | 10

3. Upon examination of the week’s analytical run of plasma glucose tests, you notice that four

consecutive normal control values are +1 s (standard deviation) from the mean. In your QC report, you note that a Westgard multirule has been broken and realize that this rejection rule is sensitive to a specific type of error. An example of this type of error would be: a. poor pipetting technique. b. incubator temperature change. c. improper calibrator preparation. d. unstable photometer.

ANS: C

Systematic errors often related to calibration problems are listed in Box 7-7. Random errors more likely are due to (1) lack of reproducibility in the pipetting of samples and reagents, (2) dissolving of reagent tablets and mixing of sample and reagents, and (3) lack of stability of temperature baths, timing regulation, and photometric and other sensors.

DIF: 2

REF: Page 100-101

OBJ: 6 | 8 | 10

4. Preparation of a CLSI-defined procedure document of an analytical protocol is a means of

controlling which one of the following types of variables? a. Analytical b. Preanalytical c. Postanalytical d. Reproducibility ANS: A

Certain variables specifically affect individual analytical methods, and these require the development of procedures to deal specifically with the characteristics of the methods. A procedure document provides step-by-step instructions that a single individual needs to take to successfully complete one activity in the process. Such a procedure is critical if a method is to provide the same results when used by different analysts over a long period of time.

DIF: 1

REF: Page 96-97

OBJ: 5

5. Which one of the following would be considered a postanalytical variable in regard to

laboratory services? a. Test ordering b. Specimen acquisition c. Test procedures d. Result reporting ANS: D

A variable that affects patient outcomes after laboratory analysis is considered a postanalytical variable. In this case, the only choice that occurs after analysis is reporting results.

DIF: 2

REF: TPE agSe T 95BANKS OE BL J: LE 5 R.COM

6. The Westgard multirules for quality control were designed to interpret control data and to aid

in troubleshooting. The rule stated as 22s is interpreted as meaning: a. one control value has exceeded ±2 s from the mean. b. two consecutive control values have exceeded the mean ±2 s. c. two consecutive control values have exceeded the mean ±1 s. d. four consecutive controls have exceeded the mean ±2 s.

ANS: B

Multirule 22s indicates that two consecutive control observations exceed the same mean plus 2 s or the same mean minus the 2 s limit.

DIF: 1

REF: Page 99

OBJ: 8

7. Lean Production: a. involves use of simulated patient specimens made from a common pool to

determine the “quality” of a laboratory’s performance using standard deviation calculations. b. is a quality performance goal that requires a specific number of standard deviations of process variation to fit within the tolerance limits for the process. c. is a quality process that focuses on creating more value by eliminating activities that are considered wasteful. d. is a set of international standards for quality management produced by the

International Organization for Standardization.

ANS: C

In the quality process of Lean Production, to increase efficiency any inefficient activity or process that consumes resources or adds cost or time without creating value is revised or eliminated.

DIF: 1

REF: Page 104

OBJ: 1

8. Which one of the following would be considered a cost of nonconformance? a. Performing preventive maintenance on analyzers b. Employee training c. Repeating an analytical run because the QC is out of range d. Sending an employee to a fire safety class ANS: C

Costs of nonconformance consist of internal and external failure costs. A repeat run is an internal failure cost for poor analytical performance, and repeat requests for tests—because of poor analytical quality—constitute an external failure cost.

DIF: 1

REF: Page 91

OBJ: 2

9. Six Sigma processes: a. use simulated patient specimens made from a common pool to determine the

“quality” of a laboratory’s performance using standard deviation calculations. b. are quality performance goals that require a specific number of standard deviations

of process variation to fit within the tolerance limits for the process. c. are focused on creatingTm eB vaAluNeKbS yE elL im gO acMtivities that are considered EoSrT LiEnaRti.nC

waste. d. are international standards for quality management produced by the International

Organization for Standardization.

ANS: B

The principle of Six Sigma involves the performance goal that “6 sigmas or 6 standard deviations of process variation should fit within the tolerance limits for the process.” Six Sigma provides a more quantitative framework for evaluating process performance and more objective evidence for process improvement.

DIF: 1

REF: Page 103

OBJ: 1

10. Upon examination of the control chart of the week’s analytical run of serum creatinine, you

notice that 10 consecutive level II control values lie on the same side of the mean. In your QC report, you note that Westgard multirule has been broken and realize that this rejection rule is sensitive to error. a. 10; random b. 10; systematic c. X10; random d. X10; systematic ANS: B

Westgard multirule 100 indicates that 10 consecutive control observations have fallen on one side of the mean (above or below, with no other requirement on size of the deviations). This rule is sensitive to systematic error.

DIF: 2

REF: Page 99

OBJ: 8 | 10

11. Upon examining a Levey-Jennings control chart for analyte X, you notice that on day 6 the

one control was −2.5 s from the mean and the duplicate control was +3.3 s from the mean.

Which of the following Westgard control rules was/were broken? a. 41s and 22s b. R4s and 13s c. R4s and 22s d. 22s only ANS: B

Multirule R4s indicates that one observation exceeds the mean plus 2 s and another exceeding the mean minus 2 s, while 13s indicates that one control observation has exceeded the mean ± 3 s.

DIF: 2

REF: Page 99

OBJ: 7

12. Which one of the following statements concerning the use of internal control materials is

incorrect? a. Use of control materials can aid in the identification of assay malfunctions that lead to unreliable data. b. Serum controls are prepared from human serum pools and are analyzed in analytical runs that are separate from patient samples. c. QC data are collected over a period of time and statistically analyzed using measures of central tendency. d. Controls that exceed specific limits are examined with the Westgard rules to determine what kind of error is present and what actions are to be taken.

ANS: B

Serum controls are always included in the same analytical runs with patient samples and are treated in a similar fashion to the patient samples.

DIF: 2

REF: Page 97

OBJ: 6

13. In regard to a Gaussian distribution, ±2 s from the mean encompasses a. 99.7% b. 98.0% c. 95.5% d. 68.2%

of values.

ANS: C

Error distribution of an analytical method is assumed to be Gaussian. The control limits are set to include most of the control values, usually 95% to 99.7%, which correspond to the mean ± 2 or 3 s.

DIF: 2

REF: Page 98

OBJ: 7

14. Random error would be caused by: a. contaminated reagents. b. pipetting errors. c. inappropriate preparation of calibrators. d. low volume reagent blanks.

ANS: B

Random errors more likely are due to (1) lack of reproducibility in the pipetting of samples and reagents, (2) dissolving of reagent tablets and mixing of sample and reagents, and (3) lack of stability of temperature baths, timing regulation, and photometric and other sensors.

DIF: 1

REF: Page 100-101

OBJ: 6

15. According to CLIA regulations, a score of

must be attained on three consecutive external proficiency test challenges for a laboratory to be accredited and continue patient testing. a. 50% b. 60% c. 70% d. 80% ANS: D

To succeed in a given category, a laboratory must produce correct results on four of five specimens for each of the analytes in that category and score overall at least 80% on three consecutive challenges.

DIF: 1

REF: Page 103

OBJ: 9

16. You have received your proficiency test results from the accrediting agency and note that your

creatinine result was unacceptable at greater than 2 SDI from the group mean. The value that was entered on your survey report form was 15 mg/dL. The group method mean was 1.3 mg/dL, with a method standard deviation of 0.3 mg/dL. You realize that your laboratory made an error in entering the result. If you had entered 2.0 mg/dL as the result on your survey report, what would the correct SDI be? a. 45.6 SDI b. 4.56 SDI c. 1.08 SDI d. 0.67 SDI ANS: D

The standard deviation interval (SDI) is calculated by subtracting the group method mean from the laboratory result and dividing this by the group standard deviation. In this case, (2.0 − 1.3)/0.3 = 0.67 (SDI). Differences greater than 2 indicate that a laboratory is not in agreement with the rest of the laboratories in the program.

DIF: 3

REF: Page 102

OBJ: 1 | 9

17. You have received your proficiency test results from the accrediting agency and note that your

creatinine result was unacceptable at greater than 2 SDI from the group mean. The value that was entered on your survey report form was 15 mg/dL. The group method mean was 1.3 mg/dL with a method standard deviation of 0.3 mg/dL. You realize that your laboratory made an error in entering the result. If you had entered 2.0 mg/dL as the result on your survey report, would the recalculated SDI now be in agreement with the rest of the laboratories in the testing program? a. Yes b. No c. Cannot determine from information given ANS: A

Differences greater than 2 indicate that a laboratory is not in agreement with the rest of the laboratories in the program; the value 0.67 is less than 2, so the SDI is acceptable.

DIF: 3

REF: Page 102

OBJ: 1 | 9

18. Two types of error may be encountered during chemical analysis of a substance. The type of

error that occurs as a result of contaminated calibrating solutions would be a. systematic b. random c. analytical d. calibration

error.

ANS: B

See Box 7-7. Systematic errors are often related to calibration problems.

DIF: 1

REF: TPE agSe T 10B0ANKS OE BL J: LE 6 R.COM

19. You arrive at the clinical chemistry laboratory one morning and discover that personnel from

the third shift left you the QC sheet from the thyroid-stimulating hormone (TSH) run. The technician has circled the level I TSH control values, and you realize that all six of the level I control values are +3 s from the mean. No results have been released. Now it’s your decision regarding what to do next. First, which Westgard rule(s) has (have) been violated? a. 22s b. 41s c. 13s d. All of the above rules have been broken.

ANS: D

In this case, the values are all on one side of the mean by at least +1 s (41s), at least two consecutive controls have exceeded the mean by +2 s (22s), and at least one control has exceeded the mean by +3 s (13s).

DIF: 1

REF: Page 99

OBJ: 8

20. You arrive at the clinical chemistry laboratory one morning and discover that personnel from

the third shift left you the QC sheet from the thyroid-stimulating hormone (TSH) run. The technician has circled the level I TSH control values, and you realize that all six of the level I control values are +3 s from the mean. No results have been released. Now it’s your decision regarding what to do next. What is your decision regarding the release of results in the problem stated in the preceding question? a. Hold all results, reject the run, and troubleshoot. b. Release results and do nothing else. c. Release all results and troubleshoot. d. Call the manufacturer’s representative and ask him what to do.

ANS: A

When one of the control observations exceeds a 2 s limit, the patient results are held and additional rules applied. In this case, the control data are inspected using the 13s, 22s, and 41s rules. When any of the rules indicates the run is out of control, the analytical run is rejected and the patient results are not reported.

DIF: 2

REF: Page 100

OBJ: 7 | 8 | 10

21. You arrive at the clinical chemistry laboratory one morning and discover that personnel from

the third shift left you the QC sheet from the thyroid-stimulating hormone (TSH) run. The technician has circled the level I TSH control values, and you realize that all six of the level I control values are +3 s from the mean. No results have been released. Now it’s your decision regarding what to do next. What kind of error is most likely occurring? a. Random error due to pipetting errors b. Systematic error due to calibration issues ANS: B

All three of the broken multirules are sensitive to systematic error, which many times is caused by improper calibration.

DIF: 2

REF: Page 100-101

OBJ: 7 | 8 | 10

22. According to the five-Q framework, the “QP” refers to quality: a. programming. b. planning. c. processes. d. precision.

ANS: B

Quality assessment requires that causes of problems be identified through QI and eliminated through quality planning (QP).

DIF: 1

REF: Page 93

OBJ: 1

23. What is the role of quality planning in the five-Q framework of quality? a. To monitor the laboratory as a whole for result quality b. To monitor the statistical analysis of results c. To ensure that the laboratory's performance satisfies quality requirements d. To identify the cause of a problem and find a remedy for that problem ANS: C

If a problem exists and is remedied through quality improvement, QP is necessary to (1) standardize the remedy, (2) establish measures for performance monitoring, (3) ensure that the performance achieved satisfies quality requirements, and (4) document the new QLP. DIF: 1

REF: Page 93

OBJ: 1 | 4

24. The first step in the development of an in-service training program using an instructional

system for employee competency in the laboratory is: a. direct observation of routine patient test performance. b. preparation of a written procedure. c. implementation of a schedule. d. a needs assessment or gap analysis.

ANS: D

Design of an in-service training program based on instructional systems design includes the following elements: (1) analysis, (2) design, (3) implementation, and (4) evaluation. It begins with a needs assessment or gap analysis to determine employee performance requirements, identify deficiencies, and evaluate existing education and training resources.

DIF: 1

REF: Page 94

OBJ: 3

Chapter 08: Principles of Basic Techniques and Laboratory Safety Test Bank MULTIPLE CHOICE 1. To make 20 mL of a 0.1 g/L solution from a 10 mg/mL stock solution, you should add

mL of the stock solution to a. 2; 18 b. 10; 10 c. 1; 19 d. 0.2; 19.8

mL of solvent.

ANS: D

All units in the problem must be made the same before solving the equation, so 0.1 g/L is equal to 0.1 mg/mL. Then, using the formula C1V1 = C2V2, 0.1 mg/mL  20 mL = 10 mg/mL  V2 in mL. Therefore, V2 is equal to 0.2 mL. DIF: 2

REF: Page 120

OBJ: 10

2. Which one of the following statements concerning type I water is not correct? a. Type I water is acceptable for analytical purposes. b. Testing that requires minimal interferences (such as iron or enzyme analysis)

requires the use of type I water. c. Type I water is obtained from distillation only and contains a few impurities. d. Type I water results in part from ion exchange purification and reverse osmosis.

ANS: C

Distillation involves vaporization and condensation of a liquid to purify or concentrate a substance. Water treated by distillation alone does not meet the specific conductivity requirement of type I water.

DIF: 2

REF: Page 112

OBJ: 3

3. What is the relative centrifugal force (RCF) for a centrifuge spinning at 1200 rpm with a rotor

head radius of 8 inches? a. 32.7 g b. 3200 g c. 130 g d. 1300 g ANS: A

First, calculate the number of centimeters in 8 inches: 8 inches  2.54 cm/inch = 20.32 cm.

Next, using the formula RCF = 1.118  10–2-5  r  rpm2, calculate RCF: 0.00001118  20.32 cm  12002 = 32.7.

DIF: 2

REF: Page 117

OBJ: 8

4. Reverse osmosis is: a. the process of vaporizing and condensing a liquid to purify or concentrate a

substance or to separate a volatile substance from less volatile substances.

b. a process by which water is forced through a semipermeable membrane that acts as

a molecular filter. c. a process that removes ions to produce mineral-free deionized water. d. a process used to convert a liquid or a volatile solid into vapor.

ANS: B

Reverse osmosis is a process by which water is forced through a semipermeable membrane that acts as a molecular filter. The membrane removes 95% to 99% of organic compounds, bacteria, and other particulate matter.

DIF: 1

REF: Page 112

OBJ: 4

5. The National Institute for Occupational Safety and Health of the CDC distributes a document

that specifies how U.S. clinical laboratories should handle infectious agents. This document is referred to as: a. the Chemical Hygiene Plan. b. the Exposure Control Plan. c. HAZMAT. d. Universal Precautions.

ANS: D

The National Institute for Occupational Safety and Health (NIOSH), a functional unit of the CDC, has prepared and widely distributed a document entitled Universal Precautions that specifies how U.S. clinical laboratories should handle infectious agents. In general it mandates that clinical laboratories treat all human blood and other potentially infectious materials as if they were known to contain infectious agents.

DIF: 1

REF: TPE agSe T 12B3ANKS OE BL J: LE 1R | 1.

1 COM

6. A highly purified chemical that is directly weighed or measured to produce a solution whose

concentration is exactly known is referred to as a: a. calibrator. b. primary reference material. c. secondary standard. d. working solution.

ANS: B

Primary reference materials may be weighed out directly for the preparation of solutions of selected concentration. These materials are supplied with a certificate of analysis and must adhere to strict standards of purity.

DIF: 1

REF: Page 112

7. Chemicals with the designation

laboratory analyses. a. technical grade b. analytical reagent grade c. USP (United States Pharmacopeia) d. NF (National Formulary) ANS: B

OBJ: 1 | 6

are suitable for use in most clinical chemistry

Chemicals that meet specifications of the American Chemical Society (ACS) are described as reagent or analytical reagent grade. These specifications have also become the de facto standards for chemicals used in many high-purity applications.

DIF: 1

REF: Page 112

OBJ: 5

8. What is the molarity (mol/L) of a solution containing 25 g of H2SO4 (MW= 98 g) in 150 mL

of deionized water? a. 1.7 mol/L b. 0.59 mol/L c. 0.002 mol/L d. 16.3 mol/L ANS: A

Molarity is equal to grams in a liter divided by molecular weight of a given substance. In this case, the molarity is equal to 25 g divided by 0.150 L (150 mL), the value of which is then divided by 98 g/mol (the MW of H2SO4). Therefore the molarity is 1.7 mol/L. DIF: 2

REF: Page 108-109

OBJ: 2

9. How many grams of NaCl (MW = 58.5 g) are required to prepare 250 mL of a 6 mol/L

solution of NaCl? a. 87.75 g b. 58.5 g c. 585 g d. 877.5 g ANS: A

Molarity is equal to grams in a liter divided by molecular weight. In this problem, mol/L is given and grams must be calculated. So, 6 mol/L = x g/0.250 L divided by 58.5 g/mol, which equals 87.75 g.

DIF: 2

REF: Page 108-109

OBJ: 2

10. What is the normality of a solution containing 20 g of H2SO4 (MW = 98) in 500 mL of buffer? a. 8.2 N b. 2.8 N c. 0.82 N d. 176.8 N ANS: C

Normality is calculated by dividing the grams of a substance that are in a liter of solution by the gram equivalent weight of that substance. Gram equivalent weight is the molecular weight of a compound divided by the number of gram equivalents (the valence) of that compound. In this problem, normality is equal to 20 g divided by 0.500 L (500 mL), which is 40. This is divided by 49 g equivalent weight, which equals 0.816 or 0.82.

DIF: 2

REF: Page 108-109

OBJ: 2

11. Universal Precautions: a. consist of shipping standards that divide potentially infectious specimens or

substances into risk groups.

b. state that only HIV, hepatitis, and sexually transmitted disease-positive specimens

should be considered and handled as infectious material. c. state that hand washing is only necessary before entering a clinical laboratory. d. consist of guidelines that in part necessitate the wearing of barrier protection when

handling potentially infectious material.

ANS: D

Universal Precautions are a set of guidelines developed by the National Institute for Occupational Safety and Health that specifies how U.S. clinical laboratories handle infectious agents. These guidelines state that all human blood and other potentially infectious materials should be handled as if they were known to contain infectious agents. Universal Precautions also state that barrier protection must be used by laboratory workers to prevent skin and mucous membrane contamination from specimen handling.

DIF: 1

REF: Page 123

OBJ: 1 | 11

12. You have seen another laboratorian collecting blood from a patient without using any barrier

protection. What safety mandate is this employee ignoring? a. Chemical hygiene plan b. Universal Precautions c. Clinical laboratory plan d. Tuberculosis exposure plan ANS: B

Universal Precautions specify how U.S. clinical laboratories should handle infectious agents.

In general it mandates that clinical laboratories treat all human blood and other potentially infectious materials as if they were known to contain infectious agents, such as HBV, HIV, and other blood-borne pathToE geSnT s.BUAnN ivKerSsE alLPL reEcaRu.tiC onOsMalso specify that barrier protection must be used by laboratory workers to prevent skin and mucous membrane contamination from specimens.

DIF: 2

REF: Page 123

OBJ: 11

13. The one technical aspect of a clinical laboratory that has received considerable attention in the

need for ergonomic design to decrease musculoskeletal stress would be: a. pipetting. b. chair design. c. lighting. d. flooring.

ANS: A

Although proper seating, lighting, and flooring all contribute to an ergonomically designed laboratory, the one area that has received considerable attention because of repetitiveness, force application, and use of the hand is pipetting. Pipettes are being designed with a goal of reducing an employee’s risk of having cumulative stress disorders caused by awkward posture, repetitive motion, and the repeated use of force.

DIF: 1

REF: Page 121

OBJ: 11

14. Regarding centrifugation, what is the formula for calculating relative centrifugal force (RCF)? a. RCF = 1.118  r (in cm)  rpm2

b. RCF = 1.118  10−5  r (in cm)  rpm2 c. RCF = 1.118  10−5  r2 (in cm)  rpm d. RCF = 1.118  r (in inches)  rpm2 ANS: B

The empirical factor 1.118  10−5 is multiplied times the radius in centimeters from the center of the rotor to the bottom of the tube or bucket being centrifuged times the speed in revolutions per minute squared.

DIF: 1

REF: Page 117

OBJ: 8

15. Fifty milligrams (mg) per 1000 mL is equal to: a. 0.005 g/mL. b. 0.050 g/mL. c. 0.050 g/L. d. 0.50 mg/mL. ANS: B

In the metric system, 50 mg/1000 mL equal 5 mg/100 mL and 0.05 mg/mL by reducing the fraction of 50/1000 = 0.05/1.

DIF: 2

REF: Page 108

OBJ: 3

16. What is the Clinical and Laboratory Standards Institute (CLSI) recommendation for the most

appropriate RCF and time for centrifugation of blood samples to obtain sufficient separation of cellular and liquid components? a. 2000 g for 20 min b. 1200 g for 10 min c. 500 g for 10 min d. 100 g for 15 min ANS: B

Although few standards exist, CLSI standard H18-A3 recommends and RCF of 1000 to 1200  g for 10 ± 5 minutes.

DIF: 1

REF: Page 126

OBJ: 8

17. The class of fire that involves flammable liquids and gases is class and the recommended

extinguisher agent is: a. A; water. b. B; water. c. B; dry chemical or carbon dioxide. d. C; Halon 1211 foam.

ANS: C

See Table 8-8. Various types of fire extinguishers are available. The type to use depends on the type of fire. The three classes of fire are A (wood, cloth, and paper), B (flammable liquids and gases), and C (electrical equipment). Because it is impractical to have several types of fire extinguishers present in every area, dry chemical fire extinguishers are among the best all-purpose extinguishers for laboratory areas.

DIF: 2

REF: Page 117

OBJ: 12

18. The type of pipette that is a piece of glass tubing drawn out to a tip and graduated uniformly

along its length and is used for reagent measurement is referred to as a: a. transfer pipette. b. volumetric pipette. c. micropipette. d. measuring pipette.

ANS: D

The type of pipette that is the graduated or measuring pipette consists of a piece of glass tubing that is drawn out to a tip and graduated uniformly along its length. Measuring pipettes are principally used for the measurement of reagents and are not generally considered sufficiently accurate for measuring samples and calibrators.

DIF: 1

REF: Page 127

OBJ: 7

19. The increased use of electronic health record (EHR) systems has amplified the need for

standardized communication between EHR and other systems. The newest universal code system that has standardized terms for all kinds of laboratory observations and measurements and includes a code number, a long formal name, a shorter name, and synonyms is referred to as the: a. Occupational Safety and Health Act. b. Clinical and Laboratory Standards Institute system. c. Logical Observation Identifier Names and Codes system. d. National Fire Protection Association system.

ANS: C

KS EoRd.eC The Logical Observation IT deEnS tifTieBr A NN am esEaL ndLC s sOyM stem is a universal coding system for reporting laboratory and other clinical observations to facilitate electronic transmission of laboratory data within and between institutions. For each observation, there is a code, a long formal name, a short 30-character name, and synonyms.

DIF: 1

REF: Page 114

OBJ: 1

TRUE/FALSE 1. The maximum amount of working volume of a flammable solvent allowed outside a storage

cabinet is 1 gallon per room.

ANS: F

Solvents should be stored in an OSHA-approved metal storage cabinet that is properly vented.

The maximum working volume of flammable solvents allowed outside storage cabinets is 5 gallons per room.

DIF: 1

REF: Page 110-111

OBJ: 12

Chapter 09: Optical Techniques Test Bank MULTIPLE CHOICE 1. In regard to absorption photometry, absorbance is calculated from transmittance by which one

of the following formulae? a. A = log %T − 2 b. A = log T c. A = −log T d. A = abc ANS: C

Transmittance of light through a solution containing a compound that absorbs light of a certain wavelength is defined as the intensity of the transmitted light beam (I) divided by the intensity of the transmitted light beam through a reference cell (IR). The amount of light absorbed (A) as the incident light passes through the sample is calculated by the following formula: A = -log = −log T DIF: 1

REF: Page 131-132

OBJ: 2 | 3

2. Which one of the following statements best describes Beer law? a. The concentration of a substance is inversely proportional to the logarithm of

transmitted light. b. Absorbance is inversely proportional to the logarithm of the concentration. c. Transmitted light is directly proportional to the concentration of a substance in

solution. d. Intensity of incident light divided by intensity of transmitted light equals

concentration.

ANS: A

Beer law states that the concentration of a substance is directly proportional to the amount of light absorbed or inversely proportional to the logarithm of the transmitted light.

DIF: 2

REF: Page 132

OBJ: 2

3. There are several interferences that can affect or limit fluorescence measurements. For

example, the inner filter effect: a. occurs when the solution absorbs greater than 2% of the exciting light, producing a nonlinear response between concentration and fluorescence emission. b. involves fluorophores that have overlapping excitation and emission spectra and that are susceptible to loss of detection because of background light scatter. c. involves solvents such as ethanol that cause appreciable fluorescence due to the interaction of the fluorophore with the solvent. d. is caused by light scattering of proteins and other macromolecules in the sample matrix, which might cause unwanted background fluorescence.

ANS: A

In a fluorescence measurement, the linear relationship between concentration and fluorescence emission is valid when solutions absorb less than 2% of the exciting light. As the absorbance of the solution increases above this amount, the relationship becomes nonlinear, a phenomenon known as the “inner filter effect.”

DIF: 2

REF: Page 145

OBJ: 15

4. A molecule is said to fluoresce when it absorbs light at one wavelength and emits light of: a. a lower energy. b. a shorter wavelength. c. a higher energy. d. the same wavelength.

ANS: A

Fluorescence occurs when a molecule absorbs light at one wavelength and reemits light at a longer wavelength. Longer wavelengths are associated with lower energy as indicated by the formula

, which shows that the energy of light is inversely proportional to the

wavelength. For example, UV radiation at 200 nm has more energy than infrared radiation at 750 nm.

DIF: 2

REF: Page 139

OBJ: 10 | 11

5. In regard to atomic absorption (AA) spectrophotometry, which one of the following

statements is correct? a. The technique combines laser-induced fluorometry and particle light scattering analysis to differentiate molecules, cells, or particles by size and shape. b. The technique measureT sE coSnTceBnA trN atK ioS nEthLroLuEgR h. thC eO deMtection of absorbance of electromagnetic radiation by atoms of elements instead of molecules. c. Oxidation of an organic compound such as luminol induces an excited state, and light is emitted when the electron returns to the ground state. d. The amount of light scattered at right angles to the incident light is directly proportional to the concentration of the analyte of interest.

ANS: B

AA methods measure the radiant energy given off when the chemical bonds of an element are dissociated and the element is placed in a ground or atomic state. The atom at a low energy level is capable of absorbing radiation at a very narrow bandwidth corresponding to its own line spectrum.

DIF: 2

REF: Page 138

OBJ: 7

6. Which one of the following statements concerning nephelometry is correct? a. Nephelometry is the measure of the concentration of particles by measuring the

amount of incident light blocked by the particles. b. In a nephelometric measurement, light blocked by solutes in the solution at 180°

from the incident light is measured by a photodetector. c. The decrease in the intensity of scattered light is directly proportional to the

number of particles in the solution, and the measurement of this decrease is called nephelometry. d. In a nephelometric procedure, the measurement of scattered light that is not in the

direct path of the transmitted light is made at right angles to the incident light.

ANS: D

Nephelometry is defined as the detection of light energy scattered or reflected toward a detector that is not in the direct path of the transmitted light. Common nephelometers measure scattered light at right angles to the incident light. The other responses relate to turbidimetric measurements.

DIF: 2

REF: Page 148

OBJ: 18

7. A blood specimen is obtained from an individual who is known to have elevated lipids and the

serum appears milky. This individual’s physician has ordered an estrogen immunoassay that your laboratory performs using a nephelometric technique. Which one of the following statements is correct concerning the possible outcome of this assay? a. Certain components of this individual's sample will likely produce excess fluorescence by the phenomenon called “solvent effect” in the nephelometric assay. b. The lipemic specimen will produce interfering background light intensity and excess light scatter in this type of assay. c. The sample flow rate will be affected through the analyzer’s nebulizer because of the altered density of the sample. d. Elevated serum lipids will not interfere with this assay because nephelometry is not affected by any type of sample variability.

ANS: B

Lipoproteins and chylomicrons in lipemic serum provide the highest background turbidity or nephelometric intensity in a nephelometric or turbidimetric assay.

DIF: 3

REF: Page 148

OBJ: 19

8. A monochromator’s filter must be tested to determine whether it can isolate a specific part of

the electromagnetic spectrum. Percent transmittance (%T) of light is plotted against a specific wavelength in nanometers. It is noted at which wavelengths 50%T (one half of the peak transmittance) occurred. This type of test assesses the filter’s: a. linearity. b. spectral bandwidth. c. calibration. d. absorbance spectrum.

ANS: B

The spectral purity of a filter or other monochromator is usually described in terms of its spectral bandwidth. This is defined as the width, in nanometers, of the spectral transmittance curve at a point equal to one half the peak transmittance.

DIF: 2

REF: Page 135-136

OBJ: 1

9. A manual stat protein analysis is performed on a patient sample. The patient’s unknown

sample had an absorbance reading of 0.6. The protein calibrator with an absorbance reading closest to the unknown's absorbance had a concentration of 6 g/dL and an absorbance reading of 0.5. Applying Beer law, calculate the unknown protein concentration in the patient sample. a. 6 g/dL

b. 7.2 g/dL c. 8 g/dL d. 5.5 g/dL ANS: B

Using the derived formula,

, the unknown concentration would be (0.6/0.5)  6

g/dL = 7.2 g/dL. DIF: 3

REF: Page 132

OBJ: 3

10. Which one of the following would be a limitation in a nephelometric measurement that might

produce faulty values? a. Excess antigen in the antigen/antibody reaction b. Too much fluorophore in the analyte/fluorescing compound mixture c. Incorrect filter used to isolate a specific wavelength d. Absorption by a closely related atomic species ANS: A

In a nephelometric immunoassay procedure, the turbidity increases during the addition of antigen to antibodies, and the signal intensity increases to a maximum value and then decreases. The point at which the decrease begins marks the beginning of the phase of antigen excess. If the light scatter is read after this time, there will be a falsely decreased measurement.

DIF: 2

REF: Page 149

OBJ: 10

11. In spectrophotometric deteT rm nsN, K wS hiE chLoLfEthRe.fC olO loM wing is the formula for calculating EiSnaTtiBoA

the absorbance of a solution? a. (Molar absorptivity  length of light path)/concentration in mol/L b. (Molar absorptivity  concentration in g/dL)/length of light path c. Molar absorptivity  length of light path  concentration in mol/L d. (Length of light path  concentration in g/dL)/molar absorptivity ANS: C

Beer law states that absorbance is determined by the molar absorptivity of the compound in a solution multiplied by the length of the light path in centimeters multiplied by the concentration of the compound.

DIF: 2

REF: Page 132

OBJ: 2

12. A standard calibrator solution of glucose has a concentration of 125 mg/dL and gives an

absorbance of 0.20. Assuming a linear reaction, what is the concentration of glucose in a patient’s serum that has an absorbance of 0.24? a. 104 mg/dL b. 138 mg/dL c. 150 mg/dL d. 180 mg/dL ANS: C

Using the derived formula,

, the unknown concentration would be (0.24/0.20) 

125 gm/dL = 150 mg/dL. DIF: 3

REF: Page 132

OBJ: 2

13. Which one of the following wavelengths is within the “near” ultraviolet region of the

electromagnetic spectrum? a. 320 nm b. 450 nm c. 540 nm d. 690 nm ANS: A

See Table 9-2 and footnote. Wavelengths between 220 nm and 380 nm are considered to be in the “near” ultraviolet portion of the spectrum.

DIF: 1

REF: Page 131

OBJ: 1

14. Laboratory analysis of free thyroxine (fT4) in your chemistry laboratory is performed with a

conventional fluorometric analyzer, which uses a laser light as the excitation source. You have received a sample from an individual known to have a very elevated fT4 level. For the sample’s value to be within linear range of the assay, you dilute the sample by a factor of 10 and proceed with the analysis. Upon reviewing the results, you note that the value of the diluted sample is reported as “none detected.” What is the likely reason for this result? a. Hormones cannot be assayed using fluorometry because they will produce concentration quenching.

NeKrS b. The dilution of the samTpE leShT asBlA ow edEpLroLdEuR ce.dCpO hoMtobleaching by the intense light source and photodecomposition of the analyte. c. Unwanted background fluorescence due to elevated protein hormone has produced a false-negative result. d. High intensity light emission can lead to pulse pileup in photomultiplier tubes, leading to an underestimation of the true light emission intensity.

ANS: B

In conventional fluorometry, excitation of weakly fluorescing or dilute solutions with intense light sources will cause photochemical decomposition of the analyte (photobleaching). If an intense laser light source is used, it will rapidly photodecompose some fluorescence analytes.

DIF: 3

REF: Page 145

OBJ: 15

15. A fluorometric measurement technique used to detect immunologic reactions that measures

fluorescence produced by the rotation of small versus large fluorescent-labeled molecules and their relation to analyte concentration in an unknown sample is known as: a. phosphorimetry. b. reflectance photometry. c. nephelometry. d. fluorescence polarization.

ANS: D

Fluorescence polarization is used to quantitate analytes by using the change in fluorescence depolarization following immunologic reactions. Quantitation is accomplished by adding a known quantity of fluorescent-labeled analyte molecules to a reaction solution containing an antibody specific to the analyte. The labeled analyte binds to the antibody resulting in a change in its rotational relaxation time and fluorescence polarization.

DIF: 1

REF: Page 141

OBJ: 1 | 13

16. Which component of a generic spectrophotometer isolates radiant energy of a specific

wavelength (spectral isolation) and excludes that of other wavelengths? a. Monochromator b. Entrance slit c. Cuvet d. Light source ANS: A

A system for isolating radiant energy of a desired wavelength and excluding that of other wavelengths is called a monochromator. Devices used for spectral isolation include (1) filters, (2) prisms, and (3) diffraction gratings.

DIF: 1

REF: Page 134-135

OBJ: 5

17. Atomic absorption spectrophotometry is an emission technique that is used frequently in

clinical laboratories to measure: a. complex antigen-antibody reactions. b. rotational relaxation of bound fluorophores. c. elements. d. high–molecular-weight compounds.

ANS: C

Atomic absorption spectrophotometry is used widely in clinical laboratories to measure elements such as (1) aluminum, (2) calcium, (3) copper, (4) lead, (5) lithium, (6) magnesium, and (7) zinc.

DIF: 1

REF: Page 138

OBJ: 7

18. The light source in an atomic absorption spectrophotometer is typically a: a. prism. b. tungsten light. c. laser light. d. hollow cathode tube.

ANS: D

A hollow cathode lamp serves as the light source for an atomic absorption spectrophotometer.

Such lamps are made of the metal of the substance to be analyzed; this is different for each metal analysis.

DIF: 1

REF: Page 138

OBJ: 8

19. When selecting a photometric technique that is more sensitive to a low concentration of

analyte, a laboratory director compares absorbance measuring devices against those that measure fluorescence intensity. Which technique is considered more sensitive in its measurements and why? a. Absorbance measurements are more sensitive because of the ability of the monochromator to isolate very specific parts of the spectrum. b. Fluorescence intensity measurements are more sensitive because the fluorophores used are very specific to the analytes they bind to and will bind to small analytes easily. c. Fluorescence intensity measurements are more sensitive because of the use of intense light sources, signal filtering, and sensitive light emission photometers. d. Absorbance measurements are more sensitive because the flame can break down complex compounds into elements that are specifically measured.

ANS: C

Fluorescence intensity measurements are 100 to 1000 times more sensitive than absorbance measurements. This is due to the use of (1) more intense light sources, (2) digital signal filtering techniques, and (3) sensitive emission photometers. In absorbance measurements, the magnitude of absorbance of a chromophore in solution is determined by its concentration and the path length of the cuvet, while the magnitude of fluorescence intensity of a fluorophore is determined by (1) its concentration, (2) the path length, and (3) the intensity of the light source.

DIF: 2

REF: Page 140

OBJ: 12

20. Which one of the following components is found only in a fluorometer used to make

measurements of emitted fT luE orSeT scB enAtNliK ghSt EasLoLpE pos R.edCtOoMin a spectrophotometer used to make measurements of absorbed/transmitted light? a. Monochromator b. Cuvets as sample holders c. An excitation source d. Detector ANS: C

Basic components of fluorometers and spectrofluorometers include (1) an excitation source, (2) an excitation monochromator, (3) a cuvet, (4) an emission monochromator, and (5) a detector. The basic components of a spectrophotometer include (1) a light source, (2) a means to isolate light of a desired wavelength, (3) fiber optics, (4) cuvets, (5) a photodetector, (6) a readout device, (7) a recorder, and (8) a computer.

DIF: 1

REF: Page 141

OBJ: 14

21. Which one of the following optical techniques is not considered an emission technique? a. Phosphorimetry b. Nephelometry c. Luminometry d. Fluorometry ANS: B

See Table 9-1. Nephelometry is defined as the detection of light energy scattered or reflected toward a detector that is not in the direct path of the transmitted light. The physical event of light emission in chemiluminescence, bioluminescence, and electrochemiluminescence is similar to fluorescence in that it occurs from an excited singlet state, and the light is emitted when the electron returns to the ground state.

DIF: 2

REF: Page 131

OBJ: 7 | 10 | 16 | 17

22. Which two optical techniques are combined operationally in a flow cytometer? a. Laser-induced fluorometry and light scattering techniques b. Atomic absorption spectrophotometry and light scattering techniques c. Spectrophotometry and fluorescence polarization techniques d. Fluorescence polarization and laser-induced fluorometry ANS: A

Operationally, flow cytometry combines laser-induced fluorometry and particle light-scattering analysis that allows different populations of molecules, cells, or particles to be differentiated by size and shape using low-light and right-angle light scattering. These cells, molecules, or particles are labeled with different specific fluorescent labels.

DIF: 1

REF: Page 144

OBJ: 14

23. A light-beam chopper in a double-beam-in-time spectrophotometer is used to: a. isolate light of a desired wavelength. b. compensate for light source variation. c. atomize a sample on a carbon rod in an enclosed chamber. d. provide polarized light.

ANS: B

A light-beam chopper is a rotating wheel with silvered and cutout sections used in a double-beam-in-time spectrophotometric instrument inserted after the exit slit to compensate for light source variation.

DIF: 1

REF: Page 131

OBJ: 5

24. In a fluorometric measurement, the difference between the maximum wavelength of the

excitation light and the maximum wavelength of the emitted fluorescence light is a constant referred to as: a. Beer law. b. chemiluminescence. c. polarization. d. the Stokes shift.

ANS: D

The Stokes shift is the difference between the maximum wavelength of the excitation light and the maximum wavelength of the emitted fluorescence light. This constant is a measure of energy lost during the lifetime of the excited state (radiation-less vibrational deactivation) before return to the ground singlet level (fluorescence emission).

DIF: 1

REF: Page 133

OBJ: 1

TRUE/FALSE 1. The visible spectrum is composed of those wavelengths between 380 and 750 nm.

ANS: T

See Table 9-2.

DIF: 1

REF: Page 139

OBJ: 1

Chapter 10: Electrochemistry and Chemical Sensors Test Bank MULTIPLE CHOICE 1. A physician is concerned about an emphysema patient’s PO2 level and wants to determine it

in this patient’s blood. Which one of the following would be best used to determine PO2? a. Ion-selective electrode b. Coulometric method c. Amperometric method d. Conductivity-based measurement ANS: C

The widely used Clark style amperometric oxygen sensor employs a small area planar platinum electrode as a working electrode (encased in insulating glass or other material) and an Ag/AgCl reference electrode. This two-electrode electrolytic cell is placed within a sensor housing, on which a gas-permeable membrane (e.g., polypropylene, silicone rubber, Teflon, etc.) is held at the distal end. The oxygen in the sample permeates across the membrane and is reduced in an electrochemical reaction.

DIF: 1

REF: Page 160

OBJ: 1 | 3

2. A commonly used electrode also used as an internal reference electrode in ion-selective

electrode measurements is which one of the following? a. Silver/silver chloride b. Mercury vapor c. Platinum d. Gas permeable ANS: A

The Ag/AgCl electrode is used both as an internal reference element in potentiometric ion-specific electrodes (ISEs) and as an external reference electrode half-cell of constant potential, which is required to complete a potentiometric cell.

DIF: 1

REF: Page 153

OBJ: 1

3. Measurement of pH involves which kind of electrode? a. Hydrogen ion-selective electrode b. Hydrogen redox electrode c. Gas permeable PCO2 electrode d. Voltammetric hydrogen electrode ANS: B

The hydrogen electrode is a special redox electrode for pH measurement.

DIF: 1

REF: Page 153

OBJ: 4

4. An electrochemical technique used to measure chloride in serum or plasma is: a. conductometry. b. amperometry.

c. coulometry. d. voltammetry.

ANS: C

Coulometry is used in clinical applications for the determination of chloride in serum or plasma. It is considered the gold standard for determination of chloride in serum or plasma.

DIF: 1

REF: Page 163

OBJ: 3

5. The measurement of the voltage difference between two half-cells immersed in solution is

referred to as: a. coulometry. b. turbidimetry. c. amperometry. d. potentiometry.

ANS: D

Potentiometry is the measurement of an electrical potential difference between two electrodes (half-cells) in an electrochemical cell.

DIF: 1

REF: Page 152

OBJ: 1

6. Which one of the following voltage potentials occurs as the result of chemical equilibrium

involving electron transfer reactions? a. Electrode potential b. Positive potential c. Hydrogen potential d. Redox potential ANS: D

The voltage difference due to electron transfer between a reductant and an oxidant in a balanced chemical reaction is the reduction-oxidation potential, or the redox potential.

DIF: 1

REF: Page 153

OBJ: 4

7. A commonly used glass electrode that is used as a reference electrode in pH measurements is

the a. b. c. d.

electrode. calomel mercury vapor silver/silver chloride platinum

ANS: A

Calomel electrodes are frequently used as reference electrodes for pH measurements using glass pH electrodes.

DIF: 1

REF: Page 154

OBJ: 4

8. A PCO2 electrode: a. uses coulometric titration to measure the absolute level of CO2 in blood through

the combination of CO2 with water. b. is a potentiometric cell in which carbon dioxide gas from the sample diffuses

through a membrane and forms carbonic acid. c. measures the ability of carbonate ions in solution to carry current under the

influence of a potential difference. d. utilizes a gas-permeable membrane to detect CO2 with very high selectivity over other easily reduced species that might be present in a given sample.

ANS: B

In the measurement of PCO2, a glass pH electrode is used as the internal element in a potentiometric cell for measurement of the partial pressure of carbon dioxide. Carbon dioxide gas from the sample diffuses through a thin membrane that is permeable only to gases and water vapor. Carbonic acid is formed and dissociates, shifting the hydrogen ion concentration.

DIF: 2

REF: Page 156-157

OBJ: 5

9. Incorporation of

, a neutral antibiotic, into a polyvinyl chloride membrane allows for the manufacture of an ion-selective electrode that is highly selective for potassium. a. tetracycline b. nonactin c. valinomycin d. erythromycin ANS: C

The neutral antibiotic valinomycin can be incorporated into organic liquid membranes and plasticized PVC membranes to form a sensor with high selectivity for potassium over sodium.

DIF: 1

REF: Page 155

OBJ: 4

10. The type of ion-selective eT leE ctS roTdB eA mN enKtiSoE neLdLinEtRh. eC prO ecMeding question is in a category of

electrodes referred to as a. glass b. inert metal c. polymer membrane d. participating metal

electrodes.

ANS: C

Liquid membrane ion-selective electrodes contain a number of ingredients that could be cast into a plasticized poly(vinyl chloride) (PVC) membrane that was more convenient to use than its liquid predecessor. These electrodes are called “polymer membrane” electrodes.

DIF: 1

REF: Page 155

OBJ: 4

11. Which one of the following is not measured with an enzyme-based biosensor, with a light

sensing fiber optic probe? a. Cholesterol b. PO2 c. Bilirubin d. DNA segments ANS: D

Affinity type sensors are used to bind a segment of DNA complementary to the target strand that is immobilized on a suitable electrochemical sensor. These devices operate based on electrochemical oxidation of guanine in target DNA or by indirect transduction modes.

DIF: 2

REF: Page 167

OBJ: 8

12. Which of the following conditions are among the requirements for a Nernst equilibrium

potential to exist for a given charged ion species across a semipermeable membrane as in an ion-selective electrode? a. The semipermeable membrane must be permeable to many ion species. b. A concentration gradient for a given charged ion species must exist across that membrane. c. If a membrane is permeable to two different ion species, then the ion activity of both species can be measured. d. The membrane potential across a semipermeable membrane must be constantly changing.

ANS: B

Membrane potentials are caused by the permeability of certain types of membranes to selected anions or cations. The potential produced at the membrane-sample solution interface is proportional to the logarithm of the ionic activity or concentration of the single ion in question. The chemical composition of the membrane is designed to achieve an optimal permselectivity toward the ion of interest and is immersed in a solution of constant ion activity.

DIF: 2

REF: Page 154

OBJ: 1 | 9

13. A biosensor that uses both enzyme detection and an ion-specific electrode could be

examining: a. urea using urease and the production of ammonium ions.

TxEidSaT b. glucose using glucose o seBaAnN dK thS eE prLoL duEcR tio.nCoOfMbiocarbonate ions. c. cholesterol using cholesterol oxidase with production of fluorescent cations. d. bilirubin using bilirubin oxidase and the production of hydrogen ions.

ANS: A

The use of urease to break down urea to form ammonia is dissolved to ammonium ions that are measured at the surface of the ammonium selective ISE. DIF: 2

REF: Page 167

OBJ: 6

14. In an optical sensing (optode) system for the measurement of PO2 using fluorescence, what is

being measured? a. The increase in the intensity of the oxygen’s natural fluorescence b. The amount of charge passing between the optical sensing electrodes, which is directly proportional to the PO2 c. The decrease in intensity of an organic dye’s fluorescence in the presence of molecular oxygen, which is proportional to the PO2 d. The ability of oxygen in solution to carry current under the influence of a potential difference ANS: C

Optical sensors devised for PO2 measurements are typically based on the immobilization of certain organic dyes within hydrophobic polymer films in which oxygen is very soluble. The fluorescence of such species at a given wavelength is often quenched in the presence of paramagnetic species, including molecular oxygen. In the case of embedded fluorescent dyes, the intensity of the emitted fluorescence of such films will decrease in proportion to the partial pressure of O2 of the sample.

DIF: 2

REF: Page 164

OBJ: 7

15. Potentiometric measurements are based on galvanic electrochemical cells. These types of cells

consist of: a. two inert metal electrodes to which an electrical potential is applied. b. two electron or metallic conducting electrodes that are connected by an electrolyte solution that conducts ions. c. a biological recognition element and a physicochemical transducer, often an electrochemical or optical device. d. a polarizable working electrode to which an external voltage is applied with the resulting cathodic or anodic current of the cell being monitored.

ANS: B

Potentiometry is the measurement of an electrical potential difference between two electrodes (half-cells) in an electrochemical cell (Figure 10-1). Such a galvanic electrochemical cell consists of the two electrodes (electron or metallic conductors) that are connected by an electrolyte solution that conducts ions.

DIF: 1

REF: Page 152

OBJ: 10

Chapter 11: Electrophoresis Test Bank MULTIPLE CHOICE 1. In electrophoresis, the best support medium to use because it is thermostable, strong,

transparent, and eliminates endosmosis due to the lack of a charge is: a. agar. b. agarose. c. cellulose acetate. d. polyacrylamide.

ANS: D

Polyacrylamide gel is (1) thermostable, (2) transparent, (3) strong, and (4) relatively chemically inert. Furthermore, these gels are uncharged, thus eliminating endosmosis.

DIF: 1

REF: Page 174

OBJ: 1 | 4

2. The component of an electrophoresis system that carries the applied current and establishes

the pH at which electrophoresis is performed is the: a. power supply. b. buffer. c. support media. d. stain.

ANS: B

The buffer serves as a mulT tifEuS ncTtiB onAaN lK coSmEpL onLeE ntRi. nC thO eM electrophoretic process as it (1) carries the applied current, (2) establishes the pH at which electrophoresis is performed, and (3) determines the electrical charge on the solute.

DIF: 1

REF: Page 173

OBJ: 3

3. Upon receiving a serum sample for protein electrophoresis, which you perform using agarose

gel, you note that the specimen is hemolyzed. How would hemolysis affect the banding pattern of this type of electrophoresis? a. There would be an increased 1-globulin band. b. There would be an increased -globulin band. c. There would be an increase in the -globulin bands. d. There would be no effect on any of the protein bands.

ANS: B

Hemolyzed samples are frequent causes of an increased -globulin, because this is the fraction where free hemoglobin migrates.

DIF: 2

REF: Page 181

OBJ: 8

4. What is the importance of the ionic strength of the buffer used in gel electrophoresis? a. A heat-labile protein will become denatured if the ionic strength of the buffer is

too high. b. Increased ionic strength will lead to a backward electrophoretic pattern.

c. No migration will occur if a buffer’s ionic strength is too high. d. Staining of the protein fractions will not occur if the ionic strength in the buffer is

too high.

ANS: A

High ionic strength buffers yield sharper band separations but also produce more joule heat because of increased current levels, an effect that leads to denaturation of heat-labile proteins.

DIF: 2

REF: Page 173

OBJ: 4

5. On a serum protein electrophoresis, if the albumin band appears distorted and large, the likely

cause is: a. pH of electrophoretic buffer incorrect. b. instrument not connected. c. sample overload. d. inappropriate support material used.

ANS: C

Too much sample applied to the gel can produce distorted protein zones. Because albumin in serum is about 10 times more concentrated than the 1-globulins, the amount of serum applied to the gel should avoid overloading.

DIF: 2

REF: Page 181

OBJ: 8

6. If the viscosity of the support medium used in a protein electrophoresis system is too high

(thick), the rate of migration will: a. increase. b. decrease. c. not be affected.

ANS: B

Electrophoretic mobility is directly proportional to net charge and inversely proportional to molecular size and viscosity of the electrophoresis medium. Therefore the higher the viscosity, the slower the migration rate.

DIF: 1

REF: Page 172

OBJ: 4

7. You have just set up the morning protein electrophoresis. When you return 45 minutes later,

you stain the gel and notice that the bands did not migrate very far from the point of application. What is the likely explanation? a. A chemical reaction occurred between the buffer and all samples. b. The current or voltage on the power supply was set too low. c. Too much sample had been applied to the gel. d. The electrophoresis chamber was not connected to a power supply.

ANS: B

Rate of migration is dependent upon the strength of the electrical field. Electrophoretic mobility is defined as the rate of migration (cm/s) per unit field strength (volts/cm). A weak electrical field will produce little or no migration.

DIF: 2

REF: Page 172

OBJ: 1 | 4

8. In an electrophoresis system, the a. anode b. optode c. diode d. cathode

is the negative electrode.

ANS: D

Chemical species that take on electrical charge by becoming ionized move toward either the cathode (negative electrode) or the anode (positive electrode) depending on the kind of charge they carry.

DIF: 1

REF: Page 172

OBJ: 1

9. The process of transferring the electrophoresed DNA fragments out of a gel and onto a special

nylon paper is referred to as: a. Southern blotting. b. Northern blotting. c. Western blotting. d. hybridization.

ANS: A

Electrophoretic separation of DNA or DNA fragments by agarose gel electrophoresis followed by their transfer (or “blot”) onto a nylon membrane by either capillary, electro-, or vacuum blotting is referred to as “Southern” blotting.

DIF: 1

REF: Page 177

OBJ: 1 | 6

inEaSsT erB um roSteEinLeLleEcR tr. opChO orMesis gel?

10. What stains are used to staT ANpK a. Coomassie Blue and ethidium bromide b. Oil Red O and Amido Black c. Amido Black and Coomassie Brilliant Blue d. Crystal Violet and Sudan Black ANS: C

See Table 11-1. Most commercial methods for serum protein electrophoresis use Amido Black B or members of the Coomassie Brilliant Blue series of dyes for staining the support gels.

DIF: 1

REF: Page 175

OBJ: 3

11. What would the concentration of albumin be if the total protein value was 8.5 g/dL and the

densitometer measured the albumin fraction as 55% of the total? a. Albumin values cannot be calculated using densitometry. b. 15.4 g/dL c. 0.065 g/dL d. 4.68 g/dL ANS: D

Once electrophoretic separation and staining are complete, it is possible to quantify the individual zones either as a percentage of the total or as absolute concentration by direct densitometry, if the total protein concentration is known. Total protein is 8.5 g/dL, and 55% (or 0.55) of 8.5 is 4.68 g/dL.

DIF: 2

REF: Page 175

OBJ: 4

12. The main advantage of capillary electrophoresis over standard gel electrophoresis is: a. the increased amount of time required for separation. b. the small sample size required. c. more efficient heat dissipation for better separation. d. the ability to use a variety of buffers in the system.

ANS: C

Capillary tubes have an inherent ability to dissipate heat quickly, allowing higher voltages to be used in this electrophoretic system. This results in better separation of the protein fractions in less time.

DIF: 2

REF: Page 177

OBJ: 5 | 7

13. If the viscosity of the support medium used in a protein electrophoresis system is too high

(thick), the migration rate will: a. increase. b. decrease. c. not be affected.

ANS: B

Electrophoretic mobility (µ) is defined as the rate of migration (cm/s) per unit field strength (volts/cm). With the formula µ = net charge divided by viscosity, the mobility is seen as being inversely proportional to the viscosity; therefore if viscosity increases, migration rate decreases.

DIF: 2

REF: Page 172

OBJ: 3

14. A separation technique that can detect proteins in a complex mixture with the use of

antibodies directed against a protein of interest is: a. Northern blotting. b. Western blotting. c. capillary electrophoresis. d. electrokinetic chromatography.

ANS: A

Western blotting is used to separate, detect, and identify one or more proteins in a complex mixture. The protein of interest is identified through the use of an antibody raised against it.

DIF: 1

REF: Page 177

OBJ: 6

15. In capillary electrophoresis, hydrodynamic sample injection: a. involves sample injection into the capillary by applying a positive pressure to the

sample inlet. b. is best for analytes that have a higher electrophoretic mobility. c. involves sample injection into the capillary by applying a voltage. d. is sometimes considered to be a “biased” type of sample injection.

ANS: A

Hydrodynamic sample injection in capillary electrophoresis involves an aliquot of sample being introduced into the capillary by putting pressure behind it, similar to using a syringe injector.

DIF: 1

REF: Page 178

OBJ: 5

16. A type of electrophoresis that provides increased resolution in protein separation by allowing

the protein to migrate to a point where the protein’s charge becomes zero and its migration stops is electrophoresis. a. capillary b. isoelectric focusing c. disc d. zone ANS: B

Isoelectric focusing electrophoresis separates proteins with increased resolution in a medium possessing a stable pH gradient. The protein migrates to a zone in the medium where the pH of the gel matches the protein’s isoelectric point. At this point, the charge of the protein becomes zero and its migration ceases.

DIF: 1

REF: Page 176

OBJ: 5

17. The isoelectric point (pI) of a protein is the pH at which the protein: a. has a positive charge. b. has a negative charge. c. has no net charge. d. migrates best in electrophoresis.

ANS: C

The isoelectric point of a molecule is the pH at which it has no net charge and will not move in an electric field.

DIF: 1

REF: Page 172

OBJ: 1

18. Endosmosis: a. can be eliminated from an electrophoretic system if a charged gel is used. b. is the movement of solvent along with highly hydrated ions to produce the driving

force in capillary electrophoresis. c. is the movement of water toward the center of an electrophoresis gel or strip to

replace water lost by evaporation. d. is a type of electrophoresis where separation is conducted in fluid channels.

ANS: B

When an ion cloud forms on a charged gel, water moves with the highly charged ions toward a charged pole. This produces the force behind the migration of protein fractions in a capillary electrophoresis system.

DIF: 2

REF: Page 180

OBJ: 1 | 8

19. You are examining a protein electrophoresis pattern and notice an unusual band at the starting

point of the electropherogram that is not present in the normal control. If the patient were healthy, what is the most likely cause of the unusual banding pattern?

a. b. c. d.

A plasma sample was probably applied instead of serum.

The buffer used in the electrophoresis had the wrong pH. An inappropriate support medium was used for the electrophoresis.

The patient likely has a genetic abnormality.

ANS: A

A band at the starting point may be fibrinogen (present in plasma), and the sample should be verified as being serum before this band is reported as an abnormal protein.

DIF: 2

REF: Page 181

OBJ: 8

20. The theory of electrophoresis states that: a. components of a sample mixture are separated by differential distribution of

analytes between stationary and mobile phases. b. the exquisite specificity and high affinity of antibodies for specific antigens,

coupled with the unique ability of antibodies to cross-link antigens, allows for the identification and quantification of specific substances. c. the concentration of a substance is directly proportional to the amount of light absorbed or inversely proportional to the logarithm of the transmitted light. d. ionized chemical species having an electrical charge move toward either the cathode (negative electrode) or the anode (positive electrode).

ANS: D

In an electrophoresis system, ionized chemical species having an electrical charge move toward either the cathode (negative electrode) or the anode (positive electrode). Positive ions (cations) migrate toward the cathode and negative ions (anions) migrate toward the anode.

DIF: 1

REF: TPE agSe T 17B2ANKS OE BL J: LE 2 R.COM

Chapter 12: Chromatography Test Bank MULTIPLE CHOICE 1. In the isolation of nucleic acids from blood samples, a step is typically performed to separate

large molecules, such as proteins and nucleic acids, from smaller molecules such as salts.

Which type of separation mechanism would best be suited for this task? a. Ion exchange b. Affinity c. Partition d. Size-exclusion ANS: D

Size-exclusion chromatography, also known as gel-filtration, gel-permeation, steric-exclusion, molecular-exclusion, or molecular-sieve chromatography, separates solutes based on their molecular size in a solution. This technique is commonly used preparatively to separate large molecules, such as proteins and nucleic acids, from small molecules, such as salts or oligonucleotides. The latter application may be performed in small spun columns where elution is driven by spinning them in a centrifuge.

DIF: 2

REF: Page 188

OBJ: 4

2. The type of separation mechanism for chromatography that involves, as one example, use of

immunologic principles is a. ion exchange b. affinity c. partition d. adsorption

chromatography.

ANS: B

In affinity chromatography, one component of highly specific molecular interaction pairs, such as enzyme-inhibitor, hormone-receptor, antigen-antibody, or aptamer-ligand, is immobilized on a stationary phase and used to capture molecules from the mobile phase. The affinity interactions usually are quite strong. Immunoaffinity chromatography, often in a lateral-flow format, is applied in pregnancy tests, rapid microbial antigen tests, and a wide range of other clinical tests.

DIF: 1

REF: Page 188

OBJ: 4

3. In the thin layer chromatography procedure for drug screening, the retention factor (Rf) value

for a compound is given by the: a. ratio of distance moved by the unknown solute to distance moved by the solvent in the mobile phase. b. rate of movement of the mobile phase through the adsorbent compared with standards and controls. c. measurement in centimeters of the distance the solute moved in the mobile phase from the point of application. d. distance moved by the mobile phase front from the point of application compared with a control.

ANS: A

A solute’s migration is expressed by its Rf value, which is calculated from the relation:

DIF: 1

REF: Page 189

OBJ: 1 | 6

4. A toxicology screen is set up using thin layer chromatographic plates. Four positive

controls/standards are used with the following distance of migration from application point results: Std A = 8 cm; Std B = 15 cm; Std C = 22. The acetone solvent front moved 35 cm.

After processing an unknown sample, a solute had a migration distance of 16 cm. What are the retention factors (Rf) of standards A, B, and C? a. 8, 15, 22 b. 8, 12, 18 c. 4.4, 2.3, 1.5 d. 0.23, 0.43, 0.63 ANS: D

To calculate Rf, divide the distance that the standard (or unknown) solute moved from the point of application by the distance the solvent (mobile phase) front moved. So for Standard A, 8/35 = 0.23; Standard B, 15/35 = 0.43; Standard C 22/35 = 0.63.

DIF: 3

REF: Page 189

OBJ: 6

5. A toxicology screen is set up using thin layer chromatographic plates. Four positive

EiSthTtB controls/standards are usedTw heAfN olKloSwEinLgLdEisRta.nC ceOoMf migration from application point results: Std A = 8 cm; Std B = 15 cm; Std C = 22. The acetone solvent front moved 35 cm.

After processing an unknown sample, a solute had a migration distance of 16 cm. What is the Rf of the unknown solute? a. 0.23 b. 0.45 c. 1.94 d. 16 ANS: B

To calculate Rf, divide the distance that the standard (or unknown) solute moved from the point of application by the distance the solvent (mobile phase) front moved. Therefore, the Rf would be 16/35 = 0.45.

DIF: 2

REF: Page 189

OBJ: 6

6. A measure of peak separation in a chromatographic method that equals the difference in

retention time for two components divided by the average of their peak widths is the definition of: a. retention factor. b. derivatization. c. resolution. d. affinity.

ANS: C

Resolution is a measure of chromatographic separation of two peaks and it equals the difference in retention time for two components divided by the average of their peak widths.

DIF: 1

REF: Page 185

OBJ: 1

7. Examine the following HPLC chromatograms, both of which were obtained from the same

sample: A

B

Which chromatogram has the best resolution because of increased separation or chromatographic efficiency? a. Chromatogram A b. Chromatogram B ANS: A

See Figure 12-2. Improving the resolution of chromatographic peaks to obtain narrower, sharper peaks is referred to as improving chromatographic or separation efficiency.

Chromatogram A in the figure has narrow, sharp peaks indicative of good resolution.

DIF: 3

agSe T 18B6ANKS OE BL J: LE 2 R.COM REF: TPE

8. Which one of the following improvements could be made to increase the chromatographic

(separation) efficiency of a poorly resolved HPLC separation? a. Using a shorter column b. Changing the composition of the mobile phase c. Using smaller particles in the stationary phase d. Increasing the dead volume ANS: C

Efficiency can be improved by using smaller particles, changing flow rate, using a longer column, and minimizing so-called “dead volume” of the system.

DIF: 1

REF: Page 186

OBJ: 2

9. In HPLC, analyte detectors can consist of fluorometers, photometers, and electrochemical

detectors. An electrochemical detector measures an electroactive analyte by: a. monitoring the current that is generated by oxidation or reduction reaction under a constant potential voltage and that is proportional to the concentration of analyte. b. measuring an electrical potential difference between two electrodes. c. measuring the radiant energy given off when the chemical bonds of an element are dissociated and the element is placed in a ground or atomic state. d. measuring both an alteration in enzyme level and a redox reaction at a potentiometric ion-specific electrode.

ANS: A

Amperometry is used in detection systems of HPLC systems, in which an electroactive analyte enters the flow cell, where it is either oxidized or reduced at an electrode surface under a constant potential.

DIF: 3

REF: Page 197

OBJ: 14

10. You are preparing placental tissue for separation and isolation of a specific enzyme. The

enzyme has a negative charge, so you want to use chromatography to perform your task.

Which one of the following chromatographic separation mechanisms would be most useful? a. Ion-exchange b. Partition c. Affinity d. Adsorption ANS: A

Ion-exchange chromatography is based on an exchange of ions between a charged stationary surface and ions of the opposite charge in the mobile phase.

DIF: 2

REF: Page 187

OBJ: 3

11. A type of detector used in GC that is universal in its detection of compounds but has low

sensitivity compared with other detectors is a(n) _ a. flame ionization b. thermal conductance c. electron capture d. photoionization

detector.

ANS: B

See Table 12-2. Thermal conductance detectors detect all compounds with little selectivity and have lower sensitivity than most other detectors.

DIF: 1 12.

REF: Page 192

OBJ: 9

In partition chromatography, separation is based on: a. hydrogen bonding and hydrophobic interactions. b. the molecular size of solutes in a solution and the size of the pores on the beads. c. the ability of one component immobilized on a stationary phase to capture specific

molecules in the mobile phase. d. the differences in the relative solubility of compounds between the stationary and

mobile phases.

ANS: D

The differential distribution of solutes between two immiscible liquids is the basis for separation by partition chromatography. One of the liquids is immobilized as the stationary phase; a thin film of the liquid is adsorbed or chemically bonded onto particles or onto the inner wall of a capillary column. Separation is based on differences in the relative solubility of compounds between the stationary and mobile phases.

DIF: 2

REF: Page 188

OBJ: 4

13. In clinical applications using gas chromatography, which one of the following column

temperature techniques will cause the more volatile analytes to elute first and therefore produce the best separation of complex mixtures of analytes with a range of volatilities? a. Isothermal operation b. Refrigerator (4° to 8° C) temperature operation c. Temperature programmed operation d. Room temperature operation ANS: C

Depending on the application, the column temperature is constant (isothermal operation) during the chromatographic run or varied as a function of time (temperature-programmed or temperature-gradient operation), which is used for most clinical applications. With temperature programming, more volatile analytes elute first, followed by those with higher boiling points. Consequently a complex mixture of analytes with a wide range of volatility is separated into sharper chromatographic peaks and more rapidly than with the isothermal operation.

DIF: 2

REF: Page 189

OBJ: 7 | 9

14. What component of an HPLC introduces an aliquot of sample into the column and how is this

introduction accomplished with the high pressure in the flow path? a. A syringe is used with a flexible tip placed into the flow path. b. A flame ionizes the sample and sprays it into the column. c. A flexible septum is coated with sample and placed in the column. d. A fixed-loop injector with a switching valve moves the sample into the flow path.

ANS: D

LeEnRf. Because it would be difficuTlE t tS oT inBjeAcN t aKsSpE ecLim roC mOaMsyringe against the high pressure needed for HPLC, injection of specimens is by means of a switching valve. The switching valve is often called a fixed-loop injector, because it has a loop of tubing with a defined volume. The loop is switched out of the flow path and loaded with specimen by a syringe at low pressure, then the loop is switched into the high pressure flow path.

DIF: 2

REF: Page 191

OBJ: 12 | 13

15. Some analytes must be derivatized to increase their column retention or detectability.

Derivatization means: a. altering the chemical structure of the analyte to an isomeric form to increase detection and specificity. b. adding fluorescent labels or combining the analyte with chiral reagents or other chemicals to increase detectability. c. removing dissolved gases in the solvent to produce a clear chromatogram. d. using multiple detectors to assist in identification.

ANS: B

Some analytes have to be chemically derivatized before or after chromatographic separation to increase their column retention or detectability. For example, amino acids are reacted with Ninhydrin in a postcolumn reactor to provide greater specificity and sensitivity in detection.

In addition, precolumn or postcolumn derivatization can be used to chemically tag a compound with a fluorescent label. For example, amino acids or other primary amines can be labeled with either a dansyl or fluorescamine tag followed by HPLC separation and fluorometric detection.

DIF: 1

REF: Page 195

OBJ: 1 | 16

TRUE/FALSE 1. Thin layer chromatography is a type of planar chromatography with separation based on the

principles of partition chromatography.

ANS: F

The basis of separation by adsorption chromatography is differential adsorption of analytes on the surface of the stationary phase. Hydrogen-bonding and hydrophobic interactions are the forces mediating separations. Retention of solutes is favored by increasing the surface area of the stationary phase or selecting a surface that has higher affinity for the analytes.

DIF: 1

REF: Page 199

OBJ: 5

2. In column chromatography, analytes are identified by their retention times.

ANS: T

TE The retention time or volum eS orTthBeAdNisKtaSnE ceLtL raE veRle.dCoOnMa plate by a compound is often used for identification by comparison versus a reference standard. In planar chromatography, reference compounds are chromatographed simultaneously with the unknown sample, and tentative identification is made by comparison of the migration distances and detection characteristics of the reference compounds with the unknown. In column chromatography, analytes are identified by their retention times and compared with a set of standards run to identify the retention times of analytes.

DIF: 1

REF: Page 184

OBJ: 17

Chapter 13: Mass Spectrometry Test Bank MULTIPLE CHOICE 1. If tandem mass spectrometry is combined with a chromatographic separation, what is added to

the physical property characterization of the compound being analyzed? a. Molecular weight b. Ionization c. Retention time d. Ion storage characteristics ANS: C

The key to the high selectivity of tandem mass spectrometry is that it characterizes a compound by two physical properties, precursor ion mass and product ion mass, rather than a single property. If combined with a chromatographic separation, the retention time is then added to the characterization, and the analytes are characterized by three physical properties.

DIF: 2

REF: Page 211

OBJ: 7

2. In which one of the following mass spectrometers does the fragmentation of ions take place

after they have been separated by their m/z value in a first stage? a. In an inductively coupled plasma mass spectrometer b. In a mass spectrometer interfaced with a gas chromatograph c. In a quadrupole-trapping spectrometer d. In a tandem mass spectT roEmSeT teBr ANKSELLER.COM ANS: D

Fragmentation of ions can also take place in a tandem mass spectrometer. Unlike fragment ions produced before mass analysis (e.g., in an ion source), the fragmentation process takes place after ions have been separated by the m/z value in a first stage of mass spectrometry.

DIF: 2

REF: Page 211

OBJ: 5

3. What is the function of the vacuum system in a mass spectrometer? a. To produce an ion from a neutral atom or molecule in the initial step b. To keep ions from colliding during interactions with the magnetic or electric fields c. To detect, identify, and quantify ion mass in a compound d. To separate the negative ions from the positive ions with a magnetic field ANS: B

Ion separation in a mass analyzer requires that the ions do not collide with any other molecules during interaction with the magnetic or electric fields. This requires the use of a vacuum from 10−3 to 10−9 torr, depending on mass analyzer type.

DIF: 1

REF: Page 208

OBJ: 3

4. In regard to mass spectrometry, what is a molecular ion? a. It is a component of a compound in solution. b. It is the sum of all ions produced displayed as a function of time.

c. It is the unfragmented ion of the original molecule being studied. d. It is the ion with the highest abundance in the mass spectrum of a compound.

ANS: C

In mass spectrometry, a target molecule is first ionized, then the ions are separated and the mass of these fragments is measured. The molecular ion is that ion (or one of several ions) that is not yet fragmented.

DIF: 1

REF: Page 203

OBJ: 1

5. How is trapping-type spectrometry different from typical beam-type mass spectrometry? a. Trapping-type mass spectrometry uses a UV laser to ionize small amounts of

matrix and analyte that are directed to the mass analyzer, while beam-types use chemical ionization only. b. Beam-type mass spectrometry is primarily for complex compound analysis, while trapping-type mass spectrometry is used for elemental analysis only. c. Trapping-type mass spectrometry uses an ion trap designed to collect ions in three dimensions instead of two dimensions as in a typical beam-type mass spectrometer. d. Trapping-type mass spectrometers are arranged sequentially in tandem with a gas chromatograph and a “collision cell” placed between the two instruments.

ANS: C

Typical beam-type mass spectrometers use only one analyzer to produce a mass spectrum by scanning the m/z range over a period of time or in successive snapshots of the mass spectrum, while in a trapping-type analyzer, ions are held in a spatially confined region of space by a combination of magnetic, and/or electrostatic, and/or RF electrical fields.

DIF: 2

REF: Page 208

OBJ: 1 | 5

6. You would like to offer a service to the researchers in your institution for identification and

quantitative analysis of proteins produced by microorganisms in liquid media using your HPLC-mass spectrometer system. Which one of the ionization techniques is best suited for this analysis? a. Electrospray b. Chemical c. Electron d. Any of these would work with HPLC-MS. ANS: A

The most commonly used ionization methods used when a high-performance liquid chromatograph is interfaced to a mass spectrometer (HPLC-MS) include (1) electrospray ionization (ESI) and (2) atmospheric pressure chemical ionization (APCI). Electrospray ionization is largely dependent on solution-phase chemistry. Basic compounds, being easily protonated, tend to be efficiently detected in positive ion mode. One unique feature of ESI is the production of multiple charged ions from some compounds, particularly from peptides and proteins.

DIF: 2

REF: Page 206

OBJ: 2 | 4 | 7

7. You would like to offer a service to the researchers in your institution for identification and

quantification of organic acids produced by microorganisms using your gas chromatograph-mass spectrometer system. Before selecting an ionization technique, you choose to run trial samples with electron and chemical ionization. You notice that the m/z of the acidic ions produced by chemical ionization is higher than the m/z produced using electron ionization. What is the cause of this disparity? a. Your mass spectrometer has not been standardized correctly for the use of liquid media because both values should be the same. b. The organic acids are not being separated into separate peaks by the gas chromatograph, producing a faulty reading by the spectrometer’s detector. c. The fragmented ions of organic acids typically have more than one single charge. d. Organic acids are not fully fragmented by chemical ionization, yielding a higher mass number.

ANS: D

Chemical ionization is a “soft” technique that produces little fragmentation and induces proton transfer between a reactive reagent gas and the analyte. Because the protonated species is not highly excited, little fragmentation of the molecule occurs, producing a molecular ion that is not fully broken down, leaving a higher mass-to-charge ratio.

DIF: 3

REF: Page 205-206

OBJ: 1 | 2 | 4 | 7

8. In a mass spectrometer, ion detection is typically accomplished through the use of an electron

multiplier. This involves: a. a densitometer that measures ion effluent and produces a “peak” of activity visible on a computer monitor. b. a chain of dynodes thatT“E mSuT ltiBpA lieNsK ”S thE eL nuLmEbRe. r oCfOeM lectrons to provide a detectable signal. c. collection of the ion current directly. d. four parallel electrically conductive rods arranged in a square array that increases electron number.

ANS: B

Nearly all mass spectrometers use electron multipliers for ion detection. Classes of electron multipliers include (1) discrete dynode multipliers, (2) continuous dynode electron multipliers (CDEMs), and (3) microchannel plate (MCP) electron multipliers. Though different in detail, all three work using a similar multiplication process, sometimes referred to as an avalanche or cascade process that is repeated through a chain of dynodes, numbering between 12 and 24 for most designs. The multiplication process typically produces a gain of 104 to 108 electrons.

DIF: 1

REF: Page 211

OBJ: 6

9. What type of mass spectrometer uses radio frequency–generated fields to confine ions in three

dimensions? a. Quadrupole ion trapping-mass spectrometer b. Time-of-flight mass spectrometer c. Tandem mass spectrometer d. Ion cyclotron resonance mass spectrometer ANS: A

Quadrupole mass spectrometers rely on a superposition of RF and direct current (DC) potentials applied to the quadrupole rods. In a trapping mass spectrometer of this type, the RF field of an ion trap is designed to trap ions in three dimensions rather than to allow the ions to pass through.

DIF: 2

REF: Page 210

OBJ: 1 | 5

10. An example of a clinical application of an HPLC coupled to a tandem mass spectrometer

would be: a. determining the presence of trace elements in blood. b. screening and confirming the presence of inborn errors of metabolism. c. identifying specific protein. d. quantifying drugs of abuse.

ANS: B

An important area where HPLC-MS/MS is used clinically is screening and confirmation of genetic disorders and inborn errors of metabolism. The ability to analyze multiple compounds in a single analytical run makes this technique an efficient tool for screening purposes.

DIF: 1

REF: Page 213

OBJ: 7

11. In a mass spectrometer, the ion with the highest abundance in the mass spectrum that is

assigned a relative abundance of 100% is referred to as the: a. base peak. b. ion trap. c. ionic chromatogram. d. time-of-flight ion.

ANS: A

The ion with the highest abundance in the mass spectrum is assigned a relative value of 100% and is called the base peak. The base peak may be the molecular ion or a fragment ion.

DIF: 1

REF: Page 202

OBJ: 1

12. The soft ionization technique that uses a UV-absorbing compound upon which the analyte of

interest is placed and eventually vaporized into a plume of ions directed into the mass analyzer is: a. atmospheric pressure photoionization. b. electrospray ionization. c. matrix-assisted laser desorption ionization. d. inductively coupled plasma ionization.

ANS: C

In matrix-assisted laser desorption ionization, the analyte is dissolved in a solution of matrix, which is a low-molecular-weight UV-absorbing compound. This solution is placed on a target that is then introduced into the mass spectrometer. As the volatile solvents evaporate, the matrix compound crystallizes and incorporates analyte molecules. A UV laser then vaporizes small amounts of matrix and analyte into a plume of ions that is directed into a mass analyzer.

DIF: 1

REF: Page 207

OBJ: 4

13. Because of the ability to identify and quantify proteins in a complex mixture, mass

spectrometry combined with separation methods is an excellent analytical tool used specifically in the field of: a. genomic research. b. inborn errors of metabolism. c. trace metal analysis. d. proteomics.

ANS: D

Proteomic research has been devoted to analysis of complex mixtures of proteins from clinical samples. Emphasis has been placed on separation methods for proteins and/or peptides. By combining separation techniques with each other and with mass spectrometry, perhaps 10,000 “protein species” can be identified in a complex mixture. The ability of mass spectrometry to identify proteins and peptides by using MS/MS to obtain partial sequence information, followed by matching of this information to protein databases, makes mass spectrometry an important part of biomarker discovery research programs that apply proteomic methods.

DIF: 1

REF: Page 214

OBJ: 2 | 8

Chapter 14: Enzyme and Rate Analyses Test Bank MULTIPLE CHOICE 1. In regard to the expression of enzyme activity, a katal is: a. a unit that describes the amount of substrate in moles converted to product in 1

minute. b. a unit that describes the amount of enzyme that is consumed in 1 minute. c. a unit that describes the amount of enzyme that will catalyze a mole of substrate in

1 second. d. the substrate concentration at which the enzyme yields half the maximum velocity

of the reaction.

ANS: C

The International System of Units (SI)-derived unit for catalytic activity is the katal, defined as moles of substrate converted per second.

DIF: 1

REF: Page 217

OBJ: 1

2. When a coenzyme binds to an enzyme, the enzyme portion of the resulting molecule is

referred to as the: a. activator. b. holoenzyme. c. apoenzyme. d. prosthetic group.

ANS: B

A holoenzyme results from the combination of an apoenzyme with a bound coenzyme, which is then referred to as the prosthetic group.

DIF: 1

REF: Page 229

OBJ: 1

3. Which one of the following is a correct statement describing a property of an enzyme? a. Enzyme activity is not altered by heat denaturation. b. Enzymes affect the rate of a chemical reaction by being altered to fit into the active

site of a substrate. c. Enzymes are protein catalysts that decrease the activation energy of a chemical reaction. d. Enzymes contain a site to which the product binds during an enzymatic reaction.

ANS: C

A catalyst is a substance that increases the rate of a particular chemical reaction by decreasing the activation energy of that reaction. Enzymes are protein catalysts of biological origin.

DIF: 2

REF: Page 223

OBJ: 1

4. Statin drugs lower cholesterol by competitive inhibition of the cholesterol-synthesizing

enzyme HMG-CoA reductase. A competitive inhibitor binds: a. the enzyme at a site other than the active center, thereby decreasing the Vmax of the

reaction. b. to the active center of the enzyme, with no effect on the Vmax of the reaction. c. to the entire enzyme-substrate complex, thereby decreasing the Km. d. to the active center of the enzyme, thereby causing the Km to increase.

ANS: D

A competitive inhibitor is a structural analogue of the substrate and binds to the enzyme at the substrate-binding site (the active center). At low substrate concentrations, the binding of substrate is reduced because some enzyme molecules are combined with an inhibitor. Thus the overall reaction velocity is reduced, and Km is increased.

DIF: 3

REF: Page 228

OBJ: 13

5. How does pH alter an enzymatic reaction rate? a. By affecting key amino acids in the enzyme protein at the active center and other

sites b. By causing thermal inactivation through reconfiguration of the prosthetic group c. By promoting the formation of the most active state of the enzyme d. By decreasing the Km needed for maximum velocity to be reached ANS: A

The pH-dependent curve of an enzyme-catalyzed reaction is caused by a number of separate effects, including the dissociation of certain key amino acid side chains in the protein molecule, both at the active center and elsewhere in the molecule.

DIF: 2

REF: Page 226

OBJ: 8

thSeTsuBbA stN raKteScEoL ncLeE ntR ra. tiC onOaMt which the reaction velocity is equal 6. Regarding enzyme kineticsT, E to 0.5 Vmax is referred to as: a. Km. b. Vmax association constant. c. 1/. d. first order concentration.

ANS: A

Km, the Michaelis-Menten constant, is the experimentally determined substrate concentration at which v = 0.5 Vmax.

DIF: 1

REF: Page 224-225

OBJ: 1 | 10

7. Zero-order kinetics occurs during the beginning of an enzyme-catalyzed reaction when a

substrate concentration is high and the rate of the reaction is concentration. a. dependent; substrate b. dependent; coenzyme c. independent; substrate d. independent; enzyme ANS: C

on the

At the moment when the enzyme and the substrate are mixed, the rate of the reaction is zero.

The rate then typically rises rapidly to a maximum value, which remains constant for a period of time. During the period of constant reaction rate, the rate depends only on enzyme concentration and is completely independent of substrate concentration. The reaction is said to follow zero-order kinetics, because its rate is proportional to the zero power of the substrate concentration.

DIF: 2

REF: Page 230

OBJ: 9

8. True isoenzymes, which are multiple forms of an enzyme that possesses the ability to catalyze

an enzyme’s characteristic reaction, are formed by: a. alteration of a carbohydrate side chain. b. the existence of more than one gene locus coding for the structure of the enzyme protein. c. association with other proteins and cofactors. d. changes in the phosphorylation pattern of associated proteins.

ANS: B

True isoenzymes result from the existence of more than one gene locus coding for the structure of the enzyme proteins. The forms can be distinguished on the basis of different physical properties, but all forms of a particular enzyme retain the ability to catalyze its characteristic reaction.

DIF: 1

REF: Page 219-220

OBJ: 1 | 5

9. During embryonic and fetal development, changes in isoenzyme distribution patterns are

common. These changes are thought to result from: a. mutation-driven gene eT xE prS esTsiBoA nN thK atSrE eoLcL cuErsRi. nCadOuMlt malignancies. b. altered production due to a genetic defect. c. increased production and secretion from all undifferentiated proliferating cells. d. differential expression and changes in the relative activities of gene loci within developing cells.

ANS: D

Changes in isoenzyme patterns during development result from changes in the relative activities of gene loci within developing cells of a particular type. For example, during embryonic development of skeletal muscle, the proportions of LD and CD isoenzymes progressively increase in muscle tissue until 6 months gestation when the pattern of the isoenzymes more closely resembles that of mature, differentiated muscle tissue.

DIF: 2

REF: Page 222

OBJ: 5

10. Regarding enzyme kinetics, the Michaelis-Menten plot of the relationship between reaction

velocity and substrate concentration is correctly expressed as which one of the following formulae? a.  = Vmax[S]/Km + [S] b.  = Km[S]/Vmax + [S] c.  = Vmax + [S]/Km[S] d.  = Km + [S]/Vmax[S] ANS: A

Reaction rate is dependent upon enzyme concentration when excess substrate is present, and the formation of an ES complex also accounts for the hyperbolic relationship between reaction velocity and substrate concentration. A plot of this relationship is referred to as a Michaelis-Menten plot and is described by the equation above.

DIF: 1

REF: Page 224

OBJ: 10

11. Activators increase the rates of enzyme-catalyzed reactions. In some cases, these activators

interact with the nonenzymatic component of the reaction such as the substrate. However, in most cases the activator: a. acts as an uncompetitive inhibitor by binding to the product. b. binds to the enzyme similar to the enzyme/substrate combination. c. alters the enzyme’s chemical properties to produce an altered product. d. destroys enzyme activity by denaturing the protein.

ANS: B

Some phenomena of enzyme activation or inhibition are caused by interactions between the modifier and a nonenzymatic component of the reaction system, such as the substrate. In most cases, however, the modifier combines with the enzyme itself in a manner analogous to the combination of the enzyme and substrate.

DIF: 2

REF: Page 227

OBJ: 1 | 8

12. In a continuous-monitoring assessment of an enzyme reaction rate, which one of the following

is the preferable measurement? a. Measurement of the decreasing concentration of substrate b. Measurement of the increasing concentration of product c. Direct measurement ofTeE nzSyT mBeApN roK teS inELLER.COM d. Calculation of Km and Vmax ANS: B

The progress of conversion of the substrate into products in the presence of an enzyme is monitored by measuring the decreasing concentration of the substrate or the increasing concentration of the products. Measurement of product formation is preferable, as determination of the increase in concentration of a substance above an initially zero or low concentration has less analytical uncertainty than measurement of a decrease from an initially high concentration.

DIF: 1

REF: Page 230

OBJ: 14

13. When determining the activity of an enzyme in serum as in a bisubstrate reaction,

measurement of two different substances can be made. One measurement determines the decrease in substrate concentration acted upon by the enzyme and the other: a. analyzes the disappearance of enzyme used in the reaction. b. measures the increase in the concentration of a second substrate. c. measures the increase in the concentration of the second product formed. d. measures the amount of enzyme/substrate complex formed.

ANS: C

The conversion of the substrate into products in the presence of an enzyme is monitored by measuring the decreasing concentration of the substrate or the increasing concentration of the products. In a bisubstrate reaction, both of these are measured.

DIF: 2

REF: Page 230

OBJ: 18

14. In the reciprocal plot pictured below, the solid line indicates a normal enzyme reaction with

no inhibition, and the dotted line indicates a decrease in Vmax and no change in Km. This plot is an example of which type of inhibition?

a. b. c. d.

Competitive Noncompetitive Uncompetitive The type of inhibition cannot be determined with this information.

ANS: B

Noncompetitive inhibitors bind at a site on the enzyme molecule other than the active center; ST thus no competition exists T beEtw eeB nAthNeKinShE ibLitL orEaRn. dC suObM strate. This causes Vmax, or maximum reaction velocity, to be reduced, whereas Km, or the substrate concentration at 0.5 Vmax, is not, which is indicated by the common intersection of the solid line with the dashed line on the −x-axis.

DIF: 3

REF: Page 228

OBJ: 8 | 13

15. The reciprocal plot pictured below indicates a decrease in Vmax and a decrease in Km. The

solid line indicates a normal enzymatic reaction. What type of enzymatic inhibition is this?

a. Competitive b. Noncompetitive c. Uncompetitive

d. The type of inhibition cannot be determined with this information.

ANS: C

Uncompetitive inhibition is due to combination of the inhibitor with the ES complex and parallel lines that are obtained when plots of 1/v against 1/[S] with and without the inhibitor are compared; that is, both Km and Vmax are decreased.

DIF: 3

REF: Page 228

OBJ: 8 | 13

16. Regarding measurement of a property related to substrate concentration such as fluorescence

production, the assay that, although more technically demanding, theoretically provides the most accurate measurement of enzyme activity is the: a. fixed-time assay. b. equilibrium method. c. discontinuous-monitoring assay. d. two-point kinetic method.

ANS: D

Methods in which some property related to substrate concentration (such as absorbance, fluorescence, chemiluminescence, etc.) is measured at two fixed times during the course of the reaction are known as two-point kinetic methods and are considered to be the most accurate for the enzymatic determination of substrates. These methods are technically more demanding than equilibrium methods, and all factors that affect reaction rate, such as pH, temperature, and amount of enzyme, must be kept constant from one assay to the next, as must the timing of the two measurements.

DIF: 1

REF: Page 233

OBJ: 18

17. An example of a posttranslational modification of an enzyme that produces an enzyme

isoform would be: a. association of different types of subunits in various combinations in an oligomer. b. modification of genes at different loci. c. alteration of carbohydrate side chains. d. the existence of different allelic genes.

ANS: C

See Figure 14-2. Many enzymes are glycoproteins, and variations in carbohydrate side chains are a common cause of nonhomogeneity of preparations of these enzymes. Some carbohydrate moieties consequently have a profound effect on some properties of enzyme molecules. The remaining responses are examples of genetic origins of isoenzymes.

DIF: 1

REF: Page 220

OBJ: 1 | 6

18. Immobilized enzymes are used analytically in various electrochemical techniques. The use of

an ion-selective electrode that is coated with an enzyme that produces ions when placed in a substrate solution is a type of: a. potentiometric measurement. b. immunoassay. c. equilibrium method. d. consecutive enzymatic reaction.

ANS: A

Enzymes incorporated into membranes form part of enzyme electrodes. The surface of an ion-sensitive electrode is coated with a layer of porous gel in which an enzyme has been polymerized. When the electrode is immersed in a solution of the appropriate substrate, the action of the enzyme produces ions to which the electrode is sensitive. This is basic potentiometry.

DIF: 1

REF: Page 234

OBJ: 20

19. Any condition, such as extreme temperature or extremes of pH, which changes the shape of

the enzyme protein structure generally causes loss of enzymatic activity. This is referred to as: a. activation. b. inhibition. c. denaturation. d. optimization.

ANS: C

The biological activity of a protein molecule depends generally on the integrity of its structure, and any condition that changes the shape of the protein is generally accompanied by loss of activity, a process known as denaturation. Denaturing conditions include elevated temperatures, extremes of pH, changes in ionic strength, and chemical addition.

DIF: 1

REF: Page 219

OBJ: 1

20. In regard to factors that govern the rate of an enzymatic reaction, first-order reaction kinetics

occur at that part of the reaction during which the rate of the reaction is: a. directly proportional to the substrate concentration. b. proportional to the concentration of the enzyme present.

TeEeSnT c. independent of either th zyBmAeNoK rS suE bsLtrLaE teRc. onCcO enMtration. d. dependent upon the pH and temperature of the system.

ANS: A

During the period of constant enzymatic reaction rate, the rate depends only on enzyme concentration and is completely independent of substrate concentration (zero-order); however, as more substrate is consumed, the reaction rate declines and enters a phase of first-order dependence on substrate concentration. The change in substrate concentration over a fixed-time interval is directly proportional to its initial concentration. This is a general property of first-order reactions.

DIF: 2

REF: Page 230

OBJ: 1 | 9

21. The use of several enzymatic reactions linked together to provide a means of measuring the

activity of the first enzyme or the concentration of the initial substrate is referred to as a(n): a. equilibrium reaction. b. consecutive enzymatic reaction. c. self-indicating reaction. d. enzyme immunoassay.

ANS: B

Reaction sequences in which the product of one enzyme-catalyzed reaction becomes the substrate of another enzyme can be used analytically. In this case, these reactions may be linked together to provide a means of measuring the activity of the first enzyme or initial substrate in the chain.

DIF: 1

REF: Page 226

OBJ: 12

22. The interaction of the amino acid side chains with the arrangement of the -helices and

-sheets to form a three-dimensional protein structure is called the protein. a. primary b. secondary c. tertiary d. quaternary

structure of the

ANS: C

Tertiary structural characteristics of a protein enzyme include the arrangement of the secondary structural elements and amino acid side chain interactions that define the three-dimensional structure of the folded protein.

DIF: 1

REF: Page 218

OBJ: 3

23. All enzymes are classified to one of six classes based on the reaction they catalyze. Based on

this classification, creatine kinase is a member of which one of the following enzyme classes? a. Hydrolase b. Oxidoreductase c. Ligase d. Transferase ANS: D

The six classes of enzymes include the (1) oxidoreductases, (2) transferases, (3) hydrolases, (4) lyases, (5) isomerases, and (6) ligases. Creatine kinase catalyzes the reversible transfer of phosphate from ATP to creatine.

DIF: 2

REF: Page 218

OBJ: 2

24. Varying different factors and studying their effects on an enzymatic reaction rate in the

assessment of most favorable reaction conditions for an enzyme assay is referred to as: a. optimization. b. standardization. c. quality control. d. variable control.

ANS: A

To measure enzyme activity reliably, all of the factors that affect the enzyme reaction rate need to be optimized and controlled. Optimization of reaction conditions for enzyme assays is carried out by varying a single factor and studying its effect on the reaction rate, then repeating the study with a second factor and so on.

DIF: 1

REF: Page 233

OBJ: 16

TRUE/FALSE 1. In an enzyme immunoassay such as ELISA, the specificity of the labeled enzyme is the most

important aspect of the measurement.

ANS: F

In enzyme immunoassays, it is not the specificity of the enzyme labeled antibody or antigen that is most important but the sensitivity in binding to small amounts of unknown antigen or antibody.

DIF: 1

REF: Page 231

OBJ: 18

Chapter 15: Immunochemical Techniques Test Bank MULTIPLE CHOICE 1. In this heterogeneous assay, one of the reaction components is attached to the surface of a

solid phase. An aliquot of patient sample containing the analyte of interest is added, a wash step occurs, and an enzyme-labeled antibody different from the bound antibody is added followed by the substrate. This type of assay is called: a. enzyme-linked immunosorbent assay (ELISA). b. reflectance immunoassay. c. enzyme-multiplied immunoassay technique (EMIT). d. fluorescence polarization immunoassay (FPIA).

ANS: A

Typically, with ELISA, an aliquot of sample or calibrator containing the antigen to be measured is added to and allowed to bind with a solid-phase antibody. After the solid phase has been washed, an enzyme-labeled antibody different from the bound antibody is added and forms a “sandwich complex” of solid-phase-Ab: Ag: Ab-enzyme. Excess (unbound) antibody then is washed away, and enzyme substrate is added.

DIF: 2

REF: Page 248

OBJ: 9

2. The substance that is typically injected into an animal to elicit an immune response and induce

formation of an antibody is the: a. antibody. b. immunogen. c. immunochemical label. d. enzyme.

ANS: B

An immunogen is either a protein or a substance coupled to a carrier, usually a protein. When an immunogen is introduced into a foreign host, it induces the formation of an antibody.

DIF: 1

REF: Page 237

OBJ: 1

3. A homogeneous fluorescence immunoassay that involves the speed of the rotation of

molecules, which is then related to analyte concentration in a patient sample, is known as: a. ELISA. b. reflectance immunoassay. c. enzyme-multiplied immunoassay technique. d. fluorescence polarization immunoassay.

ANS: D

Fluorescence polarization immunoassay is a type of homogeneous fluoroimmunoassay that is used widely. With this technique, the polarization of the fluorescence from a fluorescein-antigen conjugate is determined by its rate of rotation during the lifetime of the excited state in a solution.

DIF: 1

REF: Page 249

OBJ: 9

4. Which immunoassay uses a label that was susceptible to making serum cause a false positive

because of background fluorescence? a. Enzyme b. Radioactive c. Chemiluminescent d. Fluorescent ANS: D

An early problem with FIA was that background fluorescence from the sample limited its utility.

DIF: 1

REF: Page 249

OBJ: 9 | 11

5. Which one of the following is considered a quantitative immunoassay? a. Immunofixation electrophoresis b. Crossed immunoelectrophoresis c. Electroimmunoassay d. Western blotting ANS: C

In electroimmunoassay, quantification is achieved by comparing calibrators on the same plate to the unknowns and calculating the concentrations of unknowns from the heights of the rockets obtained.

DIF: 1

REF: Page 242-243

OBJ: 6

6. In the majority of clinical cThE em ys. ,C thO eM analyte of interest in a patient’s serum SiTstBryAiNmKmSuEnoLaLssEaR

is typically the: a. antibody. b. antigen. c. immunochemical label. d. labeled antigen.

ANS: B

An immunoassay is an assay based on the reaction of an antigen with an antibody specific for the antigen; in a typical immunoassay an antibody is used as a reagent to detect the analyte (antigen) of interest. However, other immunoassays (e.g., ELISA) quantify antibodies in a sample in which antigen instead of an antibody is bound to a solid phase and the second reagent is an enzyme-labeled antibody specific for the analyte antibody.

DIF: 2

REF: Page 237

OBJ: 1

7. Certain immunoassays require separation of bound reactant from free-labeled reactant for

determination of analyte concentration. Which one of the following immunoassays requires this separation step? a. Fluorescence polarization immunoassay (FPIA) b. EMIT c. Cloned enzyme donor immunoassay d. ELISA ANS: D

Separation of bound and free antigen is required of heterogeneous assays, while homogeneous assays do not require this step. Of the immunoassays listed here, only the ELISA is a heterogeneous assay in which excess (unbound) antibody is washed away followed by the addition of the enzyme substrate.

DIF: 2

REF: Page 248

OBJ: 8

8. In an enzyme immunoassay with an enzyme-labeled antigen, if there is a high concentration

of patient antigen, will there be a. more b. less

enzyme available to bind substrate.

ANS: A

In the EMIT technique, the antibody against the analyte drug, hormone, or metabolite is added together with substrate to the patient’s sample. Binding of the antibody and analyte then occurs. An aliquot of the enzyme conjugate of the analyte drug, hormone, or metabolite then is added as a second reagent; the enzyme-analyte conjugate then binds with the excess analyte antibody, forming an antigen-antibody complex. This binding of the analyte antibody with the enzyme-analyte conjugate affects the enzyme and alters its activity. The relative change in enzyme activity is proportional to the analyte concentration in the patient’s sample.

DIF: 2

REF: Page 248-249

OBJ: 9

9. A substance that cannot elicit an immune response alone but that must be conjugated to a

carrier molecule to cause antibody production is referred to as a(n): a. antigen. b. immunogen. c. hapten. d. conjugate.

ANS: C

A hapten is a chemically defined determinant that, when conjugated to an immunogenic carrier, stimulates the synthesis of antibody specific for the hapten. A hapten alone will not stimulate an immune response.

DIF: 1

REF: Page 236

OBJ: 1

10. An antibody that has very strong affinity to a single antigenic epitope is referred to as a(n) a. b. c. d.

antibody. affinity-purified monoclonal polyclonal multiclonal

ANS: B

A monoclonal antibody is prepared by fusing sensitized mouse lymphocytes with a murine myeloma cell line from tissue culture. Those cell lines secreting antibody of the desired specificity are cloned, resulting in the unique ability of a monoclonal antibody to react with a single epitope on an antigen.

DIF: 1

REF: Page 237-238

OBJ: 1

11. What information does crossed immunoelectrophoresis provide that basic immunofixation

does not? a. It provides a qualitative immunologic assessment of specific myeloma protein fractions. b. It provides better resolution of closely related proteins. c. It specifically traps the immune precipitate within the gel for quantification. d. It involves initial electrophoresis with transfer of proteins to nitrocellulose and specific antibody binding to each fraction.

ANS: B

Crossed immunoelectrophoresis (CRIE) is more sensitive than immunofixation (IF) in terms of detection limit and also demonstrates improved resolution. In addition, proteins of closely related or identical electrophoretic mobilities are distinguished better by CRIE because in IF they appear as a single band.

DIF: 2

REF: Page 241

OBJ: 5

12. In an ELISA procedure, the higher the concentration of patient analyte in the test system, the

the amount of product formation. a. less b. greater ANS: B

In the final steps of an ELISA, excess (unbound) antibody is washed away and enzyme substrate is added. The enzyme label then catalyzes the conversion of substrate to product(s), the amount of which is proportional to the quantity of antigen in the sample.

DIF: 2

REF: TPE agSe T 24B8ANKS OE BL J: LE 9 R.COM

13. The component of an immunoglobulin molecule that determines the antigenic specificity of

that antibody is the: a. disulfide bond linkage between the heavy and light chains. b. light chain. c. epitope. d. sequence at the amino terminal end of the heavy and light chains.

ANS: D

The variable amino acid sequence at the amino terminal end of each heavy and light chain of an immunoglobulin molecule determines the antigenic specificity of each particular antibody.

DIF: 1

REF: Page 237

OBJ: 2

14. An immunoassay contains an antidigoxin antibody, a digoxin-enzyme conjugate, a substrate,

and the sample containing an unknown concentration of digoxin. These components are used in which one of the following immunoassays? a. ELISA b. FPIA c. EMIT d. Electroimmunoassay ANS: C

In the EMIT assay, an antibody against the analyte drug, hormone, or metabolite of interest is added together with substrate to an unknown sample. Binding of the antibody and analyte then occurs. An aliquot of the enzyme conjugate of the analyte drug, hormone, or metabolite then is added as a second reagent; the enzyme-analyte conjugate then binds with the excess analyte antibody. The change in enzyme activity is proportional to the drug, hormone, or metabolite concentration in the unknown sample.

DIF: 2

REF: Page 248-249

OBJ: 9

15. Which one of the following methods is not a quantitative immunoassay method? a. Nephelometry b. Counter immunoelectrophoresis (CIE) c. ELISA d. Electroimmunoassay ANS: B

In the CIE method, an antigen and antibody are placed in wells on an agarose plate, voltage is applied, and the two substances move toward each other. A precipitin line is formed where they meet. This qualitative information is used to identify the antigen.

DIF: 1 16.

REF: Page 241

OBJ: 5 | 6

In a precipitin reaction, an excess of antigen over an antibody will lead to: all antigen sites bound with an antibody and no precipitate formation. all antibody sites bound by antigen with no formation of precipitate. cross-linking of antigen and an antibody with maximal precipitate formation. a lack of reaction between an antibody and antigen, and no precipitate.

a. b. c. d.

ANS: B

When antigen concentration is in great excess, large soluble complexes of antigen-antibody are less probable, the ratio of antigen to antibody increases, free antigen is present, and all antibody sites are bound by antigen. This leads to lack of precipitate formation.

DIF: 2

REF: Page 239

OBJ: 4

17. You wish to determine which cells contain the protein Substance P in the skin surrounding a

flesh wound. Skin scrapings are obtained, fixed in formalin, and mounted on slides. You have an anti-Substance P antiserum. What immunochemical protocol would be most appropriate to use for this experiment? a. ELISA b. Western blotting c. Double immunodiffusion d. Immunocytochemistry ANS: D

Fixed tissues (unembedded or embedded in paraffin), which provide excellent preservation of cell morphology, are mounted on slides, and an antibody reagent specific for certain proteins is used to examine single cells for synthetic capability and for specific markers for identification of various cell lines. The visualization occurs with the use of immunoperoxidase.

DIF: 2

REF: Page 252

OBJ: 10

18. In a noncompetitive immunoassay reaction format: a. all reactants are mixed together with both the labeled and unlabeled antigens

binding to the antibody. b. an unlabeled antigen is first mixed with excess antibody and binding reaches equilibrium. Labeled antigen is then added. c. antigen from an unknown sample is allowed to react with a solid-phase antibody, and a second labeled antibody is added that reacts with bound antigen. d. bound label is inversely proportional to the unlabeled antigen concentration.

ANS: C

In a noncompetitive assay, the “capture” antibody is adsorbed or covalently bound to the surface of a solid phase. Next, the antigen from the sample is allowed to react and is captured by the solid-phase antibody. Other proteins then are washed away, and a labeled antibody (conjugate) is added that reacts with the bound antigen through a second and distinct epitope.

After additional washing to remove the excess unbound labeled antibody, the bound label is measured.

DIF: 2

REF: Page 244

OBJ: 8

19. In a noncompetitive immunoassay reaction format, a very high concentration of analyte

antigen in the unknown sample might produce a falsely: a. decreased result because the high concentration of antigen binds both the capture and labeled antibody, reducing the number of complexes formed. b. increased result because the rate of the forward reaction of antigen-antibody binding is too fast, leading to a high equilibrium constant. c. decreased result because of the free excess antigen-binding all antibody sites and not allowing any unlabeled antigen to bind. d. increased result because the second labeled antibody will be able to react with the substrate by itself since excess antigen will interfere with any binding.

ANS: A

Excess antigen in a noncompetitive assay will saturate both the capture and labeled antibodies. Under these conditions the analyte will simultaneously react with the capture and labeled antibodies, reducing the number of complexes formed and producing a falsely low result.

DIF: 3

REF: Page 245

OBJ: 8 | 11

20. The light-scattering immunochemical method that is considered to have the best sensitivity

and a lower detection limit for serum proteins is: a. nephelometry. b. electroimmunoassay. c. turbidimetry. d. Western blotting.

ANS: A

Nephelometric methods in general are more sensitive than turbidimetric assays and have a lower limit of detection of approximately 1 to 10 mg/L for a serum protein.

DIF: 1

REF: Page 243

OBJ: 6

Chapter 16: Automation Test Bank MULTIPLE CHOICE 1. The most commonly used method of reducing carryover in most automated analytical systems

is to use: a. extensive system flushing between specimens and sample probe washing. b. plastic reagent containers with closed lids. c. disposable cuvets. d. a specific measurement approach that eliminates any possibility of carryover.

ANS: A

Most manufacturers of discrete systems reduce the carryover by setting an adequate flush-to-specimen ratio and incorporating wash stations for the sample probe. As much as a 4:1 ratio of flush to specimen may be needed to limit carryover to less than 1%, although recent advances in materials and dispenser velocity control have permitted lower ratios. In some systems, carryover has been reduced by flushing of the internal and external surfaces of the sample probe. In immunoassay systems, additional washes or an additional washing device are used to reduce carryover to acceptable limits.

DIF: 1

REF: Page 259

OBJ: 3

2. Your laboratory has purchased a discrete processing analyzer that is dedicated to performing

only thyroid hormone analysis. Which type of pipetting system will likely be in place in this instrument? a. Positive liquid displacement fixed-volume b. Air displacement selectable-volume c. Positive liquid displacement selectable-volume d. Air displacement fixed-volume ANS: A

Positive liquid displacement pipettes are used for sampling in most discrete automated systems in which specimens, calibrators, and controls are delivered by a single pipette to the next stage. In analyzers that perform a single assay or a small variety of tests, fixed-volume pipettes usually are used for delivery of samples and reagents.

DIF: 2

REF: Page 258

OBJ: 4

3. An ion-selective electrode system for electrolyte analysis that uses a peristaltic pump to move

liquid reagents and samples through a system of tubing is called a a. random access b. batch c. discrete d. continuous flow

analyzer.

ANS: D

In continuous-flow systems, the sample is aspirated through the sample probe into a stream of flowing liquid, whereby it is transported to analytical stations in the instrument. The peristaltic pump still is used in some analyzers with ion-selective electrodes.

DIF: 2

REF: Page 258

OBJ: 4

4. The most significant improvement in the quality of laboratory test results can be attributed to

the ability of automation to: a. reduce costs. b. increase work capacity. c. reduce error and variability caused by manual manipulation. d. reduce sample volumes and laboratory involvement.

ANS: C

One benefit of automation is a reduction in the variability of results and errors of analysis through the elimination of tasks that are repetitive and monotonous for most individuals. The improved reproducibility gained by automation has led to a significant improvement in the quality of laboratory tests.

DIF: 2

REF: Page 255

OBJ: 2

5. In a chemiluminescent analyzer system: a. the excitation event that produces light is caused by a chemical reaction. b. reagents are impregnated on films or filter paper strips of the slide. c. the intensity of emitted light is directly proportional to the concentration of

analyte. d. diffuse reflected light is measured.

ANS: A

Chemiluminescence and bioluminescence differ from fluorometry in that the excitation event is caused by a chemical orTelEecStT roB chAeN mK icSalErL eaLcE tioRn.aCnO dM not by photoluminescence.

DIF: 1

REF: Page 262

OBJ: 8

6. What component causes carryover of the analyte in a discrete analytical system that uses

disposable reaction vessels and measuring cuvets? a. The point at which sequential samples pass through b. The pipetting system c. The peristaltic pump d. The reagent delivery system ANS: B

When reaction vessels are a disposable component, carryover is caused by the pipetting system. Disposable sample-probe tips eliminate both the contamination of one sample by another inside the probe and the carryover of one specimen into the specimen in the next cup.

DIF: 2

REF: Page 259

OBJ: 3 | 4

7. A tray of clear sample cups sits on a laboratory bench top for an extended period of time.

Which one of the following analytes might be affected? a. Protein b. Cholesterol c. Glucose d. Bilirubin

ANS: D

Bilirubin is photolabile. Photodegradation is reduced by the use of semiopaque cups and placement of smoke- or orange-colored plastic covers over the specimen cups.

DIF: 2

REF: Page 257

OBJ: 3

8. The type of automated analyzer in which the operator is able to use in-house reagents or

reagents purchased from suppliers different from the analyzer's manufacturer is referred to as a(n): a. discrete analyzer. b. random-access analyzer. c. open analyzer system. d. closed analyzer system.

ANS: C

Automated analyzers are classified as “open” or “closed.” In an open analyzer, the operator is able to change the parameters related to an analysis and to prepare “in-house” reagents or use reagents from a variety of suppliers. Such analyzers usually have considerable flexibility.

DIF: 1

REF: Page 259

OBJ: 1 | 7

9. In an automated laboratory workstation with a bidirectional laboratory information system

interface, the laboratory’s bar-coded label on an individual specimen contains information regarding identification and the laboratory tests requested. The processor reads the bar code and the analyzer performs the analyses. Where can a preanalytical error still occur in this automated system? a. When the instrument’s calibration is not successful SaTteBriAalNs KarSeEoL b. When the quality contrT olEm utLoE fR th. eC reOcoMmmended range c. When a data entry person enters incorrect laboratory test requests d. When the equipment operator ignores equipment diagnostic messages ANS: C

When a laboratory workstation is automated, there are only a few times when manual involvement is needed. One of these times that is preanalytical (meaning before the initiation of test analysis by the instrument) would be a data entry error. The other variables listed here are analytical variables (they occur during analysis).

DIF: 3

REF: Page 263

OBJ: 3 | 5

10. Using whole blood as the specimen of choice in an automated analytical system: a. essentially eliminates specimen preparation time. b. allows the operator to use a secondary tube for analysis. c. keeps the specimen from undergoing degradation. d. allows for the avoidance of carryover.

ANS: A

When whole blood is used in an assay system, specimen preparation time essentially is eliminated.

DIF: 1

REF: Page 257

OBJ: 6

11. The steps involved in the completion of an automated analytical process are collectively

referred to as: a. aliquots. b. unit operations. c. instrument clusters. d. sequential analysis.

ANS: B

The individual steps required to complete an analysis often are referred to collectively as unit operations.

DIF: 1

REF: Page 255

OBJ: 1

12. The point of interaction between the instrument operator and an automated analyzer that is

dedicated to a defined task and is monitored by integrated computers is the: a. instrument cluster. b. work cell. c. conveyor belt. d. workstation.

ANS: D

The task of integrating laboratory automation begins with the laboratory workstation. In general, a clinical laboratory workstation is usually dedicated to a defined task and contains appropriate laboratory instrumentation to carry out that task. Typically, the workstation (1) serves as the point of interaction with the instrument operator, (2) accepts test orders, (3) monitors the testing process, (4) assists with analysis of process quality, and (5) provides facilities for review and verification of test results.

DIF: 1

REF: Page 263

OBJ: 9

13. The 80% rule of thumb that is used by some laboratories in guiding decisions regarding

automating a complete laboratory to achieve cost reduction means: a. if 80% of the specimen handling situation can be standardized and automated, then the investment in automation is justified. b. that 80% of a laboratory's income will have to be dedicated to the implementation and upkeep of all automated processes. c. if 80% of the individuals involved in the laboratory process agree, then automation will be implemented. d. approximately 80% of individuals will have to give up their jobs.

ANS: A

Some laboratorians use 80% as a “rule of thumb” in guiding decisions about automation.

Clinical laboratories have many exceptional tests, specimen containers, and handling situations. Nevertheless, if 80% of the specimen containers and handling situations can be standardized and automated, the laboratory will achieve a dramatic reduction in its labor and costs, which should be sufficient to justify the investment in automation.

DIF: 2 TRUE/FALSE

REF: Page 267

OBJ: 11

1. If programmed appropriately, a multiple-channel analyzer could assess samples as a

single-channel analyzer.

ANS: T

Random-access analyzers use a type of analysis in which any specimen, by a command to the processing system, is analyzed by any available process in or out of sequence with other specimens. A single-channel analyzer uses an analysis in which each specimen is subjected to a single process so that only results for a single analyte are produced. By commanding the processing system to assess only one analyte in all samples, the random-access analyzer essentially becomes a single-channel analyzer.

DIF: 2

REF: Page 255

OBJ: 1 | 4

2. Specimen bar coding has allowed for the ability of a system operator to place specimens in

random sequence, thereby eliminating the need for specimen load lists.

ANS: T

Advantages of the use of coded labels include the following: elimination of work lists for the system and analysis of specimens in a random sequence.

DIF: 1

REF: Page 256

OBJ: 5

Chapter 17: Point-of-Care Instrumentation Test Bank MULTIPLE CHOICE 1. The component of a point-of-care testing (POCT) system that detects the reaction of the

analyte with a binding molecule or some other type of recognition element is the: a. reaction cell. b. sensor. c. sample delivery system. d. user interface.

ANS: B

Chemosensors include the addition of a transducing element such as a chemical indicator or binding molecule that recognizes the analyte to be measured and produces a signal, usually electrical or optical. A biosensor has a biological or biochemical component as the recognition element.

DIF: 1

REF: Page 275

OBJ: 1 | 4

2. One of the most important benefits of connectivity between a POCT device and information

systems is: a. the reduction of time that a laboratorian has to spend transcribing results. b. the ability of any user to interface with their physician or healthcare provider. c. the ease of comparing POCT device results with routine laboratory methods. d. facilitation of the transT feE r an apNtuKreSoEfLpL atE ieR nt.PCOOCMT and quality-related data STdBcA into permanent medical records.

ANS: D

One of the most important benefits of connectivity is that it facilitates the transfer and capture of patient POCT and quality-related data into permanent medical records.

DIF: 1

REF: Page 280

OBJ: 8

3. To document that an individual has satisfactorily completed training and been found

competent in the use of a point-of-care testing (POCT) device, it is important to: a. use a multiple choice test that is completely objective in nature and record the results. b. assess a practical demonstration of skill through performance of parallel sample analysis. c. have the individual present a demonstration seminar and quiz the participants. d. prepare a computer-assisted learning program that provides testing and recordkeeping.

ANS: B

Whatever the training strategy employed, it is important to document the satisfactory completion of training and that the individual has been tested and found competent with a combination of questions concerned with understanding and practical demonstration of the skills gained. The latter is achieved by performing tests on a series of QC materials and repeat testing of samples that have recently been analyzed (parallel testing).

DIF: 2

REF: Page 282

OBJ: 9

4. The final step in the documentation of satisfactory training of an individual in the use of a

POCT device is: a. observation of that individual’s performance of the entire procedure on three different occasions. b. submission of a certificate of completion of training to an appropriate accrediting agency. c. performance by that individual of correlation studies using the POC test and a complex piece of lab equipment. d. the formal designation of that individual as “POCT-competent.”

ANS: A

As the last step in documenting satisfactory training, the operator of the POCT device should be observed through the whole procedure involved in the POCT on a minimum of three occasions.

DIF: 2

REF: Page 282

OBJ: 9

5. One of the problems with performing conventional quality control (QC) testing on a

single-use disposable POCT device is that: a. it is a waste of time and product. b. qualitative devices will not give appropriate values when tested in this way. c. it does not assess the competency of each operator. d. only that single testing unit is monitored.

ANS: D

When conventional QC material is analyzed on a unit-use or single-test disposable POCT system, only that testing unit is monitored. Thus, it is impossible to test every unit with control material because by definition these are single-test systems and it is not possible to analyze both control material and a patient sample with the single unit.

DIF: 2

REF: Page 283

OBJ: 10

6. In the design of a POCT device, the component that coordinates all the other systems and

ensures that all the required processes for an analysis take place in the correct order is referred to as the: a. reaction cell. b. sensor. c. control subsystem. d. sample delivery system.

ANS: C

All POCT devices have a control subsystem that coordinates all the other systems and ensures that all the required processes for an analysis take place in the correct order.

DIF: 1

REF: Page 275

OBJ: 4

7. The Connectivity Industry Consortium (CIC) developed a: a. set of management standards for the whole process of delivering a high quality

POCT service.

b. standard that requires all personnel associated with the delivery of diagnostic

results demonstrate their competence. c. set of standards that ensures POCT devices meet critical user requirements such as

interfacing between POCT devices and information systems. d. standard for quality control that allows POCT devices to use a docking station to

assess the quality of that device’s results.

ANS: C

The CIC was formed to address the problem of a lack of connectivity in POCT instruments and between POCT devices and other information systems. Through the efforts of the POCT industry and CIC, a set of seamless point-of-care communication standards have been developed and subsequently incorporated in a CLSI standard called POCT01-A2. Adherence to these connectivity standards ensures that POCT devices meet critical user requirements, such as (1) bidirectionality, (2) device connection commonality, (3) commercial software intraoperability, (4) security, and (5) QC and/or regulatory compliance.

DIF: 1

REF: Page 279-280

OBJ: 8

8. An example of in vivo POCT technology would be: a. optical fluorescence. b. lateral flow immunoassay. c. light scattering such as nephelometry. d. spectrophotometry.

ANS: A

See Table 17-3. The two analytical principle types commonly used in continuous monitoring testing devices include optical fluorescence and electrochemistry.

DIF: 1

REF: Page 279

OBJ: 6

9. To assess the presence of (not the concentration of) a specific cardiac marker, such as

myoglobin in a blood sample, the best POCT analysis to use would be a(n): a. immunochromatographic technique that is part of a single-use qualitative cartridge test strip. b. reflectance spectrophotometric technique that is part of a single-use quantitative cartridge with a reader. c. electrochemical technique that is part of a panel of tests in a multiple-use quantitative bench top device. d. single use, colorimetric dipstick that is read visually.

ANS: A

See Table 17-1. Qualitative testing examines a specimen for the presence (positive or negative) of a substance and does quantify concentration. Many devices fall into this category, including (1) single-pad or multipad urine tests that are read visually; (2) more complex strips that use light reflectance for measurement; and (3) fabricated cassettes or cartridges that incorporate techniques such as immunochromatography and are used as immunosensors.

DIF: 2

REF: Page 274

OBJ: 5

10. Regarding internal quality control (QC) for a bench top analyzer: a. it is safe to assume that the manufacturer has performed all necessary QC.

b. at least one QC sample should be run a minimum of once per shift. c. one QC sample should be analyzed whenever there is a change to the testing

system. d. QC samples can be assessed once a day for frequently used devices.

ANS: B

For a bench top and/or multitest analyzer, at least one QC sample should be run a minimum of once per shift—three times a day.

DIF: 1

REF: Page 283

OBJ: 10

Chapter 18: Amino Acids, Peptides, and Proteins Test Bank MULTIPLE CHOICE 1. The isoelectric point of an amino acid or protein is defined as the: a. ability of the amino acid or protein to carry both positive and negative charges. b. pH at which the amino acid or protein has a negative charge. c. pH at which the amino acid or protein has no net charge. d. folded structure of two or more peptides.

ANS: C

The isoelectric point is the pH at which a molecule has a net charge of zero.

DIF: 1

REF: Page 288

OBJ: 1

2. C-reactive protein (CRP) is considered an acute phase protein (APP) because its concentration

in blood is increased quickly during inflammation. An example of a negative APP would be: a. haptoglobin. b. alpha1-antitrypsin. c. fibrinogen. d. albumin.

ANS: D

Proteins, such as (1) alpha1-antitrypsin, (2) 1-acid glycoprotein, (3) haptoglobin, (4) ceruloplasmin, (5) C4, (6) C3, (7) fibrinogen, (8) C-reactive protein (CRP), and (9) serum amyloid A, show increasedTcEoS ncTeB ntA raNtiK onSsEinLL reE spRo. nsCeOtoMan APR and are known as positive APPs. Other plasma proteins, including (1) transthyretin, (2) albumin, and (3) transferrin, decrease and are known as negative APPs. DIF: 1

REF: Page 300

OBJ: 1 | 10

3. The acid-base properties of amino acids are important in their function. Amino acids and

proteins are both referred to as ampholytes. This means: a. that these must be supplied by dietary intake. b. at neutral pH, they have balanced positive and negative charges. c. they have side chains. d. they are filtered by the kidney glomerulus and reabsorbed by the kidney tubules.

ANS: B

At neutral pH, there is zero net charge as the negative and positive charge balance in what sometimes is termed an ampholyte or zwitterion.

DIF: 1

REF: Page 288

OBJ: 1

4. The quaternary structure of a protein is the: a. arrangement in space of the primary structure. b. association of other peptide chains with the main protein. c. three-dimensional shape of the polypeptide chain. d. order of the amino acids linked by peptide bonds.

ANS: B

Quaternary structure refers to the association of multiple peptide chains.

DIF: 1

REF: Page 293

OBJ: 5

5. The plasma protein that demonstrates a decreased serum concentration during an intravascular

hemolytic disorder and is used to identify this occurrence is: a. haptoglobin. b. ceruloplasmin. c. albumin. d. alpha1-fetoprotein.

ANS: A

Because haptoglobin (Hp) is removed from the circulation and degraded after complexing with hemoglobin, Hp concentration drops severely when intravascular hemolysis occurs, so that Hp measurement assists in identifying hemolytic disorders.

DIF: 2

REF: Page 304

OBJ: 11

6. Which one of the following proteins is the most abundant plasma protein in early embryonic

life and is also measured to assess hepatocellular carcinoma in adults? a. Alpha-fetoprotein b. Transferrin c. 1-Antitrypsin d. Ceruloplasmin ANS: A

AFP is the most abundant T plE asSmTaBpA roNteKinSiE nLeaLrE lyRe. mC bO ryM onic life. The serum concentration of AFP serves as a tumor marker for hepatocellular and germ cell carcinoma.

DIF: 2

REF: Page 303-304

OBJ: 11

7. Hyperproteinemia is caused by: a. gastrointestinal disease. b. liver disease. c. kidney disease. d. dehydration.

ANS: D

The state of hydration of a patient may also slightly affect the concentration of all plasma proteins. Dehydration leads to an increase in protein concentration.

DIF: 1

REF: Page 300

OBJ: 10

8. An increase in Bence-Jones protein in urine typically indicates the presence of paraproteins.

What is Bence-Jones protein? a. An alpha2-globulin similar to C-reactive protein b. Immunoglobulin light chain fragments c. An acute phase reactant protein that appears during an infection d. Another name for IgM that activates complement ANS: B

Analysis of urine is helpful mainly in identifying patients with monoclonal urinary light chains, which are sometimes referred to as Bence-Jones proteins. This term originally referred to a subset of free light chains in urine that precipitated upon heating to 50° to 60° C and redissolved upon further heating to 90° to 100° C. DIF: 1

REF: Page 313

OBJ: 1

9. Which one of the following statements concerning albumin is not correct? a. Albumin is the most abundant protein in plasma. b. Albumin transports many substances in plasma. c. Albumin is a negative acute phase protein. d. Albumin is involved in plasma reduction and oxidation reactions.

ANS: D

The protein involved in redox reactions is ceruloplasmin, which functions as either an oxidant or antioxidant, depending on certain factors. The other choices are all true with regard to albumin.

DIF: 2

REF: Page 301

OBJ: 5 | 11

10. Known functions of proteins normally present in plasma include all of the following except: a. buffering. b. emulsification of fat. c. transport of iron and copper. d. oxygen transport.

ANS: B

Fat emulsification is a funcTtiE onST ofBbAilN eK acSidEsLaL ndEoRth.eC rO acMids synthesized in the liver; the remaining choices are all functions of proteins.

DIF: 1

REF: Page 299-300

OBJ: 5

11. The serum protein that is analyzed to determine the presence of emphysema is: a. alpha1-antitrypsin. b. ceruloplasmin. c. alpha fetoprotein. d. haptoglobin.

ANS: A

If there is a deficiency of alpha1-antitrypsin, unchecked action of the leukocyte elastase can cleave elastin, which is important for maintaining the architecture of lung tissue. Loss of elastin can lead to emphysema. Smoking serves as a cofactor by stimulating inflammation and neutrophil infiltration in the lungs and by lowering alpha1-antitrypsin activity.

DIF: 2

REF: Page 303

OBJ: 11

12. Which of the following proteins are important in the regulation of circulating iron? a. Haptoglobin b. Ceruloplasmin c. Transferrin d. Both b and c

ANS: C

Ceruloplasmin is vitally important in regulating the ionic state of iron, oxidizing Fe2+ to Fe3+ (from the ferrous to the ferric states), thus permitting incorporation of the iron into transferrin.

Transferrin accounts for most of the total iron-binding capacity of plasma; one molecule binds two ferric ions that physiologically are generated by oxidation of ferrous ion by ceruloplasmin. The transferrin-Fe3+ complex then transports iron to cells for incorporation into cytochromes, hemoglobin, and myoglobin.

DIF: 2

REF: Page 305

OBJ: 11

13. You operate a laboratory that receives many patient samples from the renal clinic next door.

These patients have serious kidney problems, with causes that range from diabetes and IgA nephropathy to Fanconi syndrome. Would you expect to see elevated or decreased total urine protein from the patients that go to this clinic? a. Elevated b. Decreased ANS: A

Total urine protein will be increased (proteinuria) in individuals with renal problems. This proteinuria can be glomerular or tubular in origin and is typically caused by damage to the cells of these structures that work to keep protein in the blood and out of urine.

DIF: 2

REF: Page 314-315

OBJ: 1 | 14

14. Albumin concentration in blood can be analyzed in an empty blood collection tube containing

no anticoagulant. This means that you are analyzing: a. serum that has been obtained when no anticoagulants are mixed with whole blood and then centrifuged. b. plasma that has been obtained when no anticoagulants are mixed with whole blood

and then centrifuged. c. serum that has been obtained by mixing anticoagulants with whole blood and then

centrifuged. d. plasma obtained by mixing anticoagulants with whole blood and then centrifuging the sample.

ANS: A

If blood is collected without an anticoagulant and allowed to clot, it separates into a clot containing a fibrous network of fibrin (a polymer derived from fibrinogen), red cells, white cells, and platelets and an overlying liquid layer, termed serum.

DIF: 2

REF: Page 306-307

OBJ: 8

15. Serum proteins or protein complexes that precipitate at temperatures lower than normal core

body temperature and that, if precipitated in tissues, result in vasculitis and ischemic injury to peripheral tissues are referred to as: a. essential amino acids. b. paraproteins. c. amyloids. d. cryoglobulins.

ANS: D

Cryoglobulins are serum proteins or protein complexes that precipitate at temperatures lower than normal core body temperature. Precipitation of cryoglobulins in tissues can result in vasculitis and ischemic injury to peripheral tissues at a lower temperature. Patients need to be kept in a warm environment until treatment can lower cryoglobulin concentrations.

DIF: 1

REF: Page 314

OBJ: 1

16. At a physiological pH of 7.4, most amino acids: a. are positively charged. b. have no net charge. c. are negatively charged. d. precipitate out of solution.

ANS: B

In the physiological pH range of near 7.4, the carboxyl group of an amino acid is dissociated and the amino group protonated. At neutral pH, there is zero net charge as the negative and positive charge balance.

DIF: 2

REF: Page 288

OBJ: 2 | 3

17. At a pH of 4.0, the: a. carboxyl and amino groups of an amino acid become unprotonated, causing the

amino acid to have a net negative charge. b. carboxyl and amino groups of an amino acid become protonated, causing the

amino acid to have a net positive charge. c. carboxyl group of an amino acid is dissociated and the amino group is protonated,

giving the amino acid no net charge.

d. amino group of an amiT noEaScT idBiA s dNiK ssS ocEiaLteLdEaR nd.C thO eM carboxyl group is protonated,

giving the amino acid no net charge.

ANS: B

At low pH, an amino acid has a net positive charge, with both its amino and carboxyl groups protonated (–N+H3 and –COOH).

DIF: 2

REF: Page 288

OBJ: 2 | 3

18. The element of protein structure that involves the folding of the polypeptide in three

dimensions and the formation of disulfide bonds between cysteines is the a. primary b. secondary c. tertiary d. quaternary

structure.

ANS: C

Tertiary structure refers to the folding of the chain of amino acids into a three-dimensional structure. The structure may be stabilized by disulfide bonds between cysteine residues.

DIF: 2

REF: Page 293

OBJ: 5

19. Refractometry is a rapid, semiquantitative method of total protein determination. Which of the

following will lead to a faulty interpretation of protein values obtained by refractometry?

a. b. c. d.

Serum protein less that 3.5 g/dL Lipemia Bilirubinemia All of the above

ANS: A

Refractometry can rapidly assess high concentrations of protein. Accuracy decreases at protein concentrations <3.5 g/dL, where salts, glucose, and other low-molecular-weight compounds begin to contribute more to refractive index. Lipids and bilirubin have an effect on the biuret method.

DIF: 2

REF: Page 294

OBJ: 16

20. Immunofixation electrophoresis: a. combines the techniques of zone electrophoresis, isotachophoresis, isoelectric

focusing, and gel electrophoresis in small-bore fused silica capillary tubes. b. involves exposure of electrophoresed proteins to antisera against different immunoglobulin heavy and light chains with resultant precipitation. c. involves transfer of separated proteins to a strip of nitrocellulose by electroblotting followed by an immunochemical reaction with a specific antibody. d. uses electrophoresis in two dimensions to assess global changes in protein expression.

ANS: B

Immunofixation electrophoresis relies on applying specific antibodies directed against classes of immunoglobulin (IgG, IgM, IgA) or - and -light chains on top of several lanes of an agarose gel after separation of serum proteins. The antibodies form immune precipitates by complexing in the gel withTtE heSirTsB peAcN ifiKcSaE ntL igL enEsR . .COM DIF: 2

REF: Page 296-297

OBJ: 4 | 6

21. A malignant neoplasm that is composed of plasma cells that exhibit monoclonality and are

diffusely present in the bone marrow is referred to as: a. multiple sclerosis. b. monoclonal immunoglobulinemia. c. multiple myeloma. d. plasmacytoma.

ANS: C

Multiple myeloma is a malignant neoplasm, usually of a single clone of plasma cells. The plasma cells usually proliferate diffusely throughout the bone marrow.

DIF: 1

REF: Page 313

OBJ: 13

22. The addition of sulfosalicylic acid for a qualitative turbidimetric protein determination of a

urine specimen is done to: a. dilute the protein in the specimen, because it is typically high and beyond the range of standards. b. remove interfering substances from the specimen. c. increase the volume of the specimen, because it is difficult to obtain adequate volume.

d. precipitate a protein in the specimen that might be missed by albumin urine

dipstick methods.

ANS: D

Precipitation of protein for turbidimetric or nephelometric assays is achieved with sulfosalicylic acid alone, with sulfosalicylic acid in combination with sodium sulfate or trichloroacetic acid (TCA), or with TCA alone. Precipitation methods sometimes have been used qualitatively to assess whether there is increased protein in urine that may be missed by urine dipsticks, which detect mainly albumin.

DIF: 2

REF: Page 295

OBJ: 4 | 14

23. Analyses of free light chains, particularly immunoassays that measure the ratio of free - to

free -light chains, are sensitive indicators of: a. disorders of immunoglobulin synthesis such as multiple myeloma. b. albumin increase such as that observed in dehydration. c. -globulin disorders such as decreased LDL. d. increased C-reactive protein such as that observed following myocardial infarction.

ANS: A

Free light chains are not functional, but immunoassays specific for free light chains, commonly measuring the ratio of free -:free -light chains, are very sensitive indicators of disorders of Ig synthesis such as multiple myeloma, where there are clones synthesizing an increased amount of Ig with either - or -light chains.

DIF: 2

REF: Page 311

OBJ: 13

24. The reference method for pTrE otS eiT nB deAteNrK mS inEatLioLnEthRa. tC coOnM verts nitrogen to ammonium ions by

acid digestion is the: a. biuret method. b. refractometry method. c. Kjeldahl method. d. absorption of light at 280 nm.

ANS: C

In the Kjeldahl method, the sample is digested with acid to convert nitrogen in the protein to ammonium ion and the ammonium ion is measured.

DIF: 1

REF: Page 294

OBJ: 4

25. The proteins that are deposited in tissues as aggregates and that form -sheet structures with

eventual damage to the tissues are referred to as: a. paraproteins. b. complement proteins. c. amyloid. d. Bence-Jones protein.

ANS: C

Amyloidosis is a pathological process in which proteins deposit in tissues as aggregates, termed amyloid, that form -sheet structures. The tissue infiltration can cause damage to a variety of tissues including the kidneys, heart, and peripheral nerves, depending on sites of amyloid deposition.

DIF: 1

REF: Page 314

OBJ: 1

26. A healthy 27-year-old pregnant woman in the second trimester sees her obstetrician for a

routine visit. Blood and urine samples are obtained. Total serum protein and protein electrophoresis are performed on the blood sample and total urine protein is also analyzed.

The results of the serum protein electrophoresis indicate a substantial increase in the -globulin region of the electrophoretogram. Which of the -globulins might this be and why? a. It is likely alpha1-antitrypsin because of the presence of increased surfactant. b. It is likely alpha2-macroglobulin because of decreased serum estrogen. c. It is likely alpha1-acid glycoprotein because of the presence of progesterone. d. It is likely alpha1-fetoprotein due to fetal development.

ANS: D

Alpha1-fetoprotein is the first -globulin to appear in body fluids during fetal development. It is a major protein in fetal serum, synthesized primarily by the fetal yolk sac and liver, and appears in maternal blood as well.

DIF: 3

REF: Page 303

OBJ: 11 | 16

27. A tumor of plasmacytoid cells that is diagnosed as Waldenström macroglobulinemia produces

a paraprotein that is an: a. IgA. b. IgE. c. IgG. d. IgM. ANS: D

In Waldenström macroglobulinemia, malignant proliferation of plasmacytoid cells producing IgM differs from multiple myeloma in biology, outcome, and treatment. Clonal expansion in Waldenström macroglobulinemia is of more immature B lymphocytes.

DIF: 2

REF: Page 313

OBJ: 13 | 16

28. The most abundant complement protein component that is common to all three pathways of

complement is: a. C1. b. C3. c. C5. d. C7.

ANS: B

C3 is the most abundant complement component and is a common component of the three pathways of complement activation.

DIF: 1

REF: Page 308

OBJ: 12

29. What is the globulin concentration of a specimen given the following information: total

protein, 6.5 g/dL, and albumin, 3.8 g/dL? a. 2.7 g/dL b. 10.3 g/dL c. 1.7 g/dL d. You cannot determine the globulin concentration from the information given here.

ANS: A

The concentration of globulins usually is calculated as follows: Globulins (g/dL) = Total Protein (g/dL) – Albumin (g/dL).

DIF: 1

REF: Page 299

OBJ: 9

MATCHING

Using each answer only once, match the metabolic disorder with the related plasma protein abnormality. a. Wilson disease b. Intravascular hemolysis c. Inflammation d. Chronic renal disease 1.

2.

3.

4.

Elevated serum C-reactive protein Elevated retinol-binding protein Decreased serum ceruloplasmin Decreased haptoglobin

1. ANS: 2. ANS: 3. ANS: 4. ANS:

C D A B

DIF: DIF: DIF: DIF:

2 2 2 2

REF: REF: REF: REF:

Page 305 Page 304 Page 307 Page 300

OBJ: OBJ: OBJ: OBJ:

11 | 16 11 | 16 11 | 16 11 | 16

Chapter 19: Serum Enzymes Test Bank MULTIPLE CHOICE 1. A hydrolase enzyme important during digestion that catalyzes the hydrolysis of starches while

food is still in the mouth is: a. lipase. b. lactate dehydrogenase. c. S-type amylase. d. P-type amylase.

ANS: C

-Amylase catalyzes the hydrolysis of 1,4--glucosidic linkages in polysaccharides. The greatest concentration of amylase (AMY) is present in the salivary glands, which secrete a potent AMY (S-type) to initiate hydrolysis of starches while the food is still in the mouth and esophagus. In the pancreas, the enzyme (P-type) is synthesized by acinar cells and then is secreted into the intestinal tract.

DIF: 1

REF: Page 328

OBJ: 1 | 3

2. What transferase enzyme is involved in the conversion of the stored form of energy to usable

energy (adenosine triphosphate [ATP]) within cardiac myocytes? a. Creatine kinase b. Aspartate aminotransferase c. Lactate dehydrogenase d. Troponinase ANS: A

Creatine kinase (CK; creatine N-phosphotransferase) activity is greatest in striated muscle and heart tissue. Physiologically, when muscle contracts, ATP is converted to adenosine diphosphate (ADP), and CK catalyzes the rephosphorylation of ADP to ATP using creatine phosphate (CrP) as the phosphorylation reservoir.

DIF: 1

REF: Page 319-320

OBJ: 1 | 3

3. Increased enzyme activity is typically observed in serum or plasma: a. only if a genetic abnormality is present. b. only following mitochondrial damage. c. following injury or damage to tissue. d. only if hepatic damage has occurred.

ANS: C

Injury to tissue releases cellular substances such as enzymes that are used as plasma markers of tissue damage. Knowledge of the intracellular location of enzymes assists in determining the nature and severity of a pathological process. Mild disorders increase only the permeability of the cell membrane and allow cytoplasmic enzymes to leak out into the blood, whereas a severe attack causing cell necrosis also disrupts the mitochondrial membrane, and both cytoplasmic and mitochondrial enzymes are detected in the blood.

DIF: 1

REF: Page 319

OBJ: 2

4. At present, the major diagnostic usefulness of tartrate-resistant acid phosphatase type 5b is in

its use as a marker of conditions with: a. a liver involvement. b. pancreatitis. c. involvement of the prostate gland. d. an osteolytic component.

ANS: D

Tartrate-resistant acid phosphatase (TR-ACP) type 5b is a more specific marker of osteoclastic activity. TR-ACP is a potentially useful marker of conditions with a marked osteolytic component, such as (1) Paget disease, (2) hyperparathyroidism with skeletal involvement, and (3) the presence of malignant invasion of the bones by cancers.

DIF: 1

REF: Page 334

OBJ: 3 | 4

5. Which one of the following statements concerning lipase is incorrect? a. Lipase is localized partly in cells of the pancreas. b. Following an acute attack of pancreatitis, lipase activity increases within 4 to 8

hours. c. Lipase is a small enzyme that can be detected in urine. d. Lipase is considered to be in the hydrolase class of enzymes.

ANS: C

Amylase is small enough to pass through the glomeruli of the kidneys, and AMY is the only plasma enzyme physiologically found in urine.

DIF: 2

REF: Page 330

OBJ: 3

6. The principal source of serum cholinesterase (CHE) in blood is: a. liver. b. skeletal muscle. c. pancreas. d. bone.

ANS: A

See Table 19-1. Serial measurement of CHE has been promoted as an indication of prognosis in patients with liver disease and for monitoring liver function after liver transplantation.

DIF: 1

REF: Page 333

OBJ: 3

7. Which one of the following enzymes catalyzes the transfer of an amino group to alpha-

ketoglutarate with the formation of oxaloacetate and glutamate? a. Alanine aminotransferase (ALT) b. Aspartate aminotransferase (AST) c. Alkaline phosphatase (ALP) d. 5'-Nucleotidase (NTP) ANS: B

See Figure 19-4; AST catalyzes the reaction of aspartate and oxoglutarate to oxaloacetate and glutamate.

DIF: 2

REF: Page 322

OBJ: 3

8. If you were asked by your laboratory director to set up an enzyme profile (group of tests)

specifically to assess hepatobiliary (biliary obstruction) disease, which one of the following sets of enzymes would be most appropriate? a. NTP, ALP, and -glutamyltransferase (GGT) b. ALP, GGT, and CK c. CHE, NTP, and CK d. LD, CK, ALT, and AST ANS: A

See Table 19-1. GGT is considered a sensitive indicator of the presence of hepatobiliary disease. The response of the liver to any form of biliary tree obstruction induces the synthesis of ALP by hepatocytes. Serum NTP activities appear to reflect hepatobiliary disease with considerable specificity.

DIF: 2

REF: Page 319

OBJ: 2 | 3 | 6

9. A physician orders several laboratory tests on a 55-year-old male patient who is complaining

of generalized (all-over) pain, stiffness, fatigue, and headaches. Based on the following serum test results, what is the most likely diagnosis: ALP—significantly increased, GGT— normal? a. Biliary obstruction b. Cirrhosis c. Primary metastatic liver cancer d. Bone disease ANS: D

Liver and bone are the primary sources of elevations in serum ALP. Similar to alkaline phosphatase, GGT is highest in cases of intrahepatic or posthepatic biliary obstruction, reaching activities 5 to 30 times the upper reference limit. Therefore, when tested together, a normal GGT with increased ALP indicates a bone issue.

DIF: 2

REF: Page 327

OBJ: 3 | 6

10. Which is the most sensitive enzyme for monitoring chronic alcoholic liver disease? a. ALP b. GGT c. NTP d. AST ANS: B

Elevated activities of GGT also are found in the sera of patients with alcoholic hepatitis and in the majority of sera from people who are heavy drinkers.

DIF: 1

REF: Page 325

OBJ: 3

11. Activators that are required for normal CK activity include: a. pyroxidal phosphate and magnesium. b. magnesium, manganese, and cobalt. c. magnesium only.

d. NAD and NADH. ANS: C

When muscle contracts, ATP is converted to adenosine diphosphate (ADP), and CK catalyzes the rephosphorylation of ADP to ATP using creatine phosphate (CrP) as the phosphorylation reservoir. Mg2+ is an obligate activating ion that forms complexes with ATP and ADP. DIF: 1

REF: Page 320

OBJ: 3

12. Which of the following products are formed from the forward reaction catalyzed by ALT? a. Pyruvate and glutamate b. Aspartate and alanine c. Oxaloacetate and glutamate d. Alanine and alpha ketoglutarate ANS: A

See Figure 19-5. The reaction products of the forward reaction are pyruvate and glutamate from oxaloacetate and lactate.

DIF: 2

REF: Page 322

OBJ: 3

13. All of the statements below about the clinically significant phosphatases are true except they: a. catalyze the transfer of amine groups to ketoacids. b. are divided into two classes based upon pH required for their respective reactions. c. are isoenzyme forms of the phosphatases. d. are classified as hydrolases.

ANS: A

The phosphatases do not transfer amine groups but catalyze various hydrolytic reactions. ACP and ALP both catalyze the cleavage of orthophosphate from orthophosphoric monoesters but under differing pH conditions.

DIF: 2

REF: Page 333

OBJ: 1 | 3

14. A 10-year-old girl visits her pediatrician with the complaint of bone pain. Following enzyme

studies, these results were obtained: ALP 3.5 higher than upper reference limit; NTP normal.

These results are consistent with a diagnosis of: a. hepatobiliary disease. b. normal bone growth. c. viral hepatitis. d. bone cancer.

ANS: B

Physiological bone growth increases bone ALP in serum, and this accounts for the fact that in the sera of growing children, enzyme concentration is 1.5 to 7 times that in healthy adult serum.

DIF: 3

REF: Page 326

OBJ: 3 | 6

15. A 37-year-old woman who thinks she might be pregnant visits her physician with a complaint

of upper right quadrant pain. Blood samples are obtained. Increased enzyme activity was seen for ALP, AST, lactate dehydrogenase (LD), and GGT. The ALP was 10 times higher than the upper reference limit. A hepatitis panel and a pregnancy test had negative results. Gel electrophoresis was done to separate ALP isoenzymes, with a dense liver band and what appeared to be a diffuse placental band. If this woman’s physician has ruled out pregnancy, activity of what other serum enzyme could be measured to differentiate between hepatobiliary disease and liver disease? a. NTP b. ALT c. Aldolase d. CHE ANS: A

Assay of NTP activity has been considered of value as an addition to measurement of nonspecific total ALP. Abnormal NTP activity is routinely interpreted as evidence of a hepatic origin of increased ALP activity in serum.

DIF: 3

REF: Page 328

OBJ: 3 | 6

16. A 37-year-old woman who thinks she might be pregnant visits her physician with a complaint

of upper right quadrant pain. Blood samples are obtained. Increased enzyme activity was seen for ALP, AST, LD, and GGT. The ALP was 10 times higher than the upper reference limit. A hepatitis panel and a pregnancy test had negative results. Gel electrophoresis was done to separate ALP isoenzymes, with a dense liver band and what appeared to be a diffuse placental band. If there is not a pregnancy, what is the name given to the observed isoenzyme band that migrates in the same regioT nE asStT heBpAlaNcK enStaEl L isL oeEnR zy.mCeO?M a. Stable placental isoenzyme b. Regan isoenzyme c. S-AMY isoenzyme d. LD-X isoenzyme ANS: B

ALP forms, essentially identical to the normal placental or germ cell isoenzymes, appear in the sera of some patients with malignant disease. These carcinoplacental isoenzymes (e.g., Regan isoenzyme) result from de-repression of the placental or placental-like 2 ALP genes.

DIF: 2

REF: Page 326

OBJ: 4 | 6

17. Tartrate-resistant acid phosphatase (TR-ACP) that is present in unhemolyzed serum is

synthesized mainly in: a. erythrocytes. b. cells of the prostate gland. c. osteoclasts. d. hepatocytes.

ANS: C

The majority of the physiologically low ACP activity of unhemolyzed serum is of a tartrate-resistant type (TR-ACP) and probably originates mainly in osteoclasts.

DIF: 1

REF: Page 333

OBJ: 2 | 3

18. Heart tissue contains which of the following CK isoenzymes? a. MM only b. MB only c. BB only d. MM and MB ANS: D

See Table 19-2 Both CK-MM (78%) and MB (22%) are localized to skeletal muscle and heart tissue.

DIF: 2

REF: Page 320

OBJ: 4

19. Why is heparin the only acceptable anticoagulant to use when obtaining blood samples for

ALP analysis? a. Heparin contains necessary cofactors for ALP to reach full enzyme activity. b. Other anticoagulants contain inhibitors of magnesium, which is a required cofactor for ALP activation. c. Heparin maintains the integrity of the ALP molecule through freeze-thaw cycles. d. Other anticoagulants bind ALP and reduce its ability to react with substrate in enzyme reactions.

ANS: B

Obtaining specimens for ALP analysis in EDTA, oxalate, and citrate must be avoided because these anticoagulants bind cations, such as Mg2+ and Zn2+, which are necessary cofactors for ALP activity measurement.

DIF: 2

REF: TPE agSe T 32B7ANKS OE BL J: LE 3 R.COM

20. A specimen is received in a green top tube (heparin) with a request for alkaline phosphatase

analysis. The plasma is separated and the test is performed. How will this specimen type affect the ALP results? a. There will be no effect, because this is an acceptable specimen for this test. b. Results will be falsely decreased. c. Results will be falsely increased.

ANS: A

Heparin is an appropriate anticoagulant for assessing ALP activity, because it does not bind the cofactors magnesium and zinc that are required of ALP activity.

DIF: 1

REF: Page 327

OBJ: 3

21. Which one of the following statements concerning lipase (LPS) is incorrect? a. When comparing LPS with amylase in diagnosis of acute pancreatitis, amylase is a

more specific diagnostic finding. b. Following an acute attack of pancreatitis, lipase levels elevate within 4 to 8 hours. c. Lipase is a hydrolase that breaks down glycerol esters of long chain free fatty

acids. d. Most serum lipase activity is derived from pancreas, but gastrointestinal mucosa contributes a small amount.

ANS: A

In differential diagnosis of acute pancreatitis, elevation of serum LPS activity greater than 5 times the upper reference limit is a more specific diagnostic finding than increases in serum amylase activity.

DIF: 1

REF: Page 330

OBJ: 3

22. Which of the following statements is incorrect concerning creatine kinase (CK)? a. CK catalyzes the conversion of creatine and ADP to creatine phosphate and ATP. b. Total CK activity can be elevated in skeletal muscle disease. c. The subunits of CK can combine to form three different CK isoenzymes. d. CK is classified as a transferase enzyme.

ANS: A

The forward reaction that is catalyzed by CK is Cr + ATP → ADP + CrP, and the reverse reaction is CrP + ADP  ATP + Cr. Therefore, it is creatine and ATP that are acted upon.

DIF: 2

REF: Page 320

OBJ: 1 | 3

23. The recommended assay, because of its specificity and sensitivity for the measurement of the

activity of the CK-MB isoenzyme, is the: a. immunoinhibition assay. b. polyclonal competitive binding immunoassay. c. monoclonal sandwich immunoassay. d. isoenzyme electrophoresis.

ANS: C

The recommended approach is to measure concentrations of the CK-MB protein (“mass”) by .C using immunoassays with T mE onSoTclBoA naNl K anStiEbL odLieEsR .M eaO suMrements use the “sandwich” technique, in which one antibody specifically recognizes only the MB dimer. Mass assays are very sensitive, with a limit of detection for CK-MB usually less than 1 µg/L. DIF: 1

REF: Page 322

OBJ: 4

24. The usefulness of analyzing lipoprotein-associated phospholipase A2 for the identification of

individuals at risk for future cardiovascular events is because of its: a. release of granules that destabilize complex plaque. b. ability to transform stable coronary artery plaques to unstable ones. c. release during inflammatory events such as coronary artery blockage. d. upregulation in atherosclerotic lesions, particularly complex plaque.

ANS: D

Several cells typical for atherosclerotic plaque secrete enzyme molecules that mirror plaque destabilization and rupture. Their concentrations in the circulation have been shown to be associated with future cardiovascular (CV) events. Lipoprotein-associated phospholipase A2 has been found to be upregulated in atherosclerotic lesions, especially in complex plaque prone to rupture. It also has proatherogenic properties by promoting modification of oxidized LDLs. DIF: 1

REF: Page 334

OBJ: 5

25. Because your immunoassay analyzer is down for maintenance, you have performed an

immunoinhibition assay to determine the relative presence of CK isoenzymes in an individual who has presented with acute upper body pain. The assay reveals a strong activity after inhibition of CK-M subunits using a monoclonal antibody. This result indicates: a. definitive evidence for an acute cardiac event having occurred. b. that the individual takes part in strenuous exercise. c. a nonspecific result due to possible presence of CK-B subunits. d. definitive evidence for possible gastrointestinal problems.

ANS: C

In the immunoinhibition technique, an anti-CK-M subunit antiserum is used to inhibit both M subunits of CK-MM and the single M subunit of CK-MB and thus allow determination of the enzyme activity of the B subunit of CK-MB. However, when immunoinhibition techniques are used to determine CK-MB, the absence of CK-BB is assumed, a circumstance that does not always occur. Due to their lack of specificity, immunoinhibition assays are not widely used.

DIF: 3

REF: Page 321-322

OBJ: 4

26. Certain muscle relaxants are hydrolyzed by CHE during surgical procedures. If an individual

with the atypical (Ea) gene variant is exposed to this relaxant, what would occur? a. Decreased drug metabolism at the neuromuscular junction with resulting muscle weakness b. Increased drug metabolism over time with a shortened period of relaxant effect and the patient awakening during surgery c. Decreased drug metabolism over time with resultant paralysis of respiratory muscles d. Formation of autoantibodies against choline receptors, with resulting general weakness ANS: C

Succinyldicholine (suxamethonium) and mivacurium, drugs used in surgery as muscle relaxants, are hydrolyzed by CHE, and their pharmacologic effect normally persists only long enough to meet the needs of the surgical procedure. In patients with low enzyme activities or in those with a weak active variant, destruction of the drug will not occur rapidly enough, and the patient may enter a period of prolonged paralysis of the respiratory muscles (apnea), requiring mechanical ventilation until the drug effects gradually wear off.

DIF: 2

REF: Page 333

OBJ: 3 | 6

27. A severely hemolyzed serum specimen from an individual with hemolytic anemia is received

in the laboratory with a request for total CK and LD enzymes. How will the results of these analyses be falsely affected by the condition of the specimen? a. LD decreased, CK increased b. LD increased, CK increased c. LD decreased, CK decreased d. LD increased, CK decreased ANS: B

Severely hemolyzed specimens are unsatisfactory for both CK and LD analysis because enzymes and intermediates (adenylate kinase, ATP, and G6P) liberated from the erythrocytes will mimic CK activity. Hemolytic anemias significantly increase LD concentrations in serum.

DIF: 2

REF: Page 321

OBJ: 3 | 6

28. A phosphotransferase enzyme that has increased activity when injury, inflammation, or

necrosis of skeletal muscle occurs is: a. ALP. b. ACP. c. CK. d. LD. ANS: C

Creatine kinase (CK) (EC 2.7.3.2; adenosine triphosphate: creatine N-phosphotransferase) is a dimeric enzyme (82 kDa) that catalyzes the reversible phosphorylation of creatine (Cr) by adenosine triphosphate (ATP). Serum CK is increased in nearly all patients when (1) injury, (2) inflammation, or (3) necrosis of skeletal or heart muscle occurs.

DIF: 1

REF: Page 319-320

OBJ: 1 | 3

MATCHING

Match the enzyme with its correct enzyme classification. a. Creatine kinase b. Lactate dehydrogenase c. Alkaline phosphatase 1. Oxidoreductase 2. Transferase 3. Hydrolase 1. ANS: B DIF: 1 REF: Page 318 OBJ: 1 | 3 MSC: CK, along with GGT, ALT, and AST, are transferases in that they transfer amino acids or phosphates from one molecule to another. LD is an oxidoreductase because it moves hydrogen molecules. ALP and amylase are both hydrolases because they catalyze hydrolysis reactions.

2. ANS: A DIF: 1 REF: Page 331 OBJ: 1 | 3 MSC: CK, along with GGT, ALT, and AST, are transferases in that they transfer amino acids or phosphates from one molecule to another. LD is an oxidoreductase because it moves hydrogen molecules. ALP and amylase are both hydrolases because they catalyze hydrolysis reactions.

3. ANS: C DIF: 1 REF: Page 325 OBJ: 1 | 3 MSC: CK, along with GGT, ALT, and AST, are transferases in that they transfer amino acids or phosphates from one molecule to another. LD is an oxidoreductase because it moves hydrogen molecules. ALP and amylase are both hydrolases because they catalyze hydrolysis reactions.

Match the enzyme with its correct substance required for enzyme reaction. Answers may be used more than once, once, or not at all. a. Creatine kinase b. Aspartate aminotransferase c. Amylase

4. Pyridoxal phosphate 5. Magnesium 6. Calcium 4. ANS: B DIF: 2 REF: Page 320 OBJ: 3 MSC: CK requires magnesium, which is an obligatory activating ion that forms complexes with ATP and ADP; ALP requires magnesium as its activator also. AST requires pyridoxal-5'-phosphate (P-5'-P) and its amino analogue, pyridoxamine-5'-phosphate, as coenzymes in the amino-transfer reaction.

Calcium is absolutely required for functional integrity of amylase.

5. ANS: A DIF: 2 REF: Page 322 OBJ: 3 MSC: CK requires magnesium, which is an obligatory activating ion that forms complexes with ATP and ADP; ALP requires magnesium as its activator also. AST requires pyridoxal-5'-phosphate (P-5'-P) and its amino analogue, pyridoxamine-5'-phosphate, as coenzymes in the amino-transfer reaction.

Calcium is absolutely required for functional integrity of amylase.

6. ANS: C DIF: 2 REF: Page 328 OBJ: 3 MSC: CK requires magnesium, which is an obligatory activating ion that forms complexes with ATP and ADP; ALP requires magnesium as its activator also. AST requires pyridoxal-5'-phosphate (P-5'-P) and its amino analogue, pyridoxamine-5'-phosphate, as coenzymes in the amino-transfer reaction.

Calcium is absolutely required for functional integrity of amylase.

Chapter 20: Tumor Markers and Cancer Genes Test Bank MULTIPLE CHOICE 1. Which of the following is considered to be a nonspecific tumor-associated marker? a. Prostate-specific antigen (PSA) b. Alkaline phosphatase (ALP) c. CA 125 d. Tumor suppressor genes ANS: B

Most tumor markers are found with different tumors of the same tissue type (tumor-associated markers) and most enzymes are not unique for a specific organ. Therefore, enzymes are most suitable as nonspecific tumor markers. Elevated ALP is seen in primary or secondary liver cancer. Greatest elevations are seen in patients with osteoblastic lesions, such as in those with prostatic cancer with bone metastases. Minimal elevations are seen in patients with osteolytic lesions, such as those with breast cancer with bone metastases. The ALP in the sera of normal adults comes primarily from the liver or biliary tract.

DIF: 1

REF: Page 342

OBJ: 4

2. An example of a blood group antigen that would be elevated in pancreatic cancer and is US

Food and Drug Administration (FDA) approved as an aid in monitoring pancreatic cancer patients is: a. CA 125. b. CA 15-3. c. CA 19-9. d. PSA. ANS: C

CA 19-9 is a marker for gastrointestinal cancers and is used primarily in patients with pancreatic carcinoma. CA 19-9 has been approved by the FDA for quantitative measurement in serum and as an aid in monitoring pancreatic cancer patients.

DIF: 1

REF: Page 354

OBJ: 4

3. Upon receipt of a test request for assay of human chorionic gonadotropin (hCG) on a

60-year-old male, you would: a. refuse the request because hCG is a pregnancy test and not performed on men. b. assume the physician wanted a prostate-specific antigen (PSA) test. c. perform the test because hCG can be elevated in testicular germ cell tumors. d. contact the physician.

ANS: C

Human CG is a useful marker for some tumors of the testes. It is also elevated in 70% of those with nonseminomatous testicular germ cell tumors and less frequently in those with seminoma. It is a useful tumor marker for tumors of the placenta (trophoblastic tumors) and for some tumors of the testes.

DIF: 2

REF: Page 348

OBJ: 4 | 6

4. The primary clinical usefulness of assessing alpha-fetoprotein (AFP) as a tumor marker is for: a. monitoring patients with pancreatic cancer. b. assessing patients with colon cancer. c. monitoring therapy in patients with liver cancer. d. assessing chemotherapy response in patients with breast cancer.

ANS: C

AFP is a marker for hepatocellular and germ cell (nonseminoma) carcinoma. AFP is also useful for determining prognosis and for monitoring therapy for hepatocellular carcinoma.

The concentration of AFP is a prognostic indicator of survival.

DIF: 1

REF: Page 349

OBJ: 4

5. Proteins found in normal fetal tissue and also in certain tumors are referred to as: a. embryonic proteins. b. tumor-associated antigens. c. oncogenes. d. oncofetal antigens.

ANS: D

Proteins produced during fetal life decrease to low or undetectable levels after birth but can reappear in some forms of cancer due to reactivation of a gene in the transformed malignant cells.

DIF: 1

REF: Page 349

OBJ: 1

6. The properties of an ideal tumor marker include all of the following, except it should: a. be able to distinguish between benign and malignant tumors. b. be produced by tumor cells and detectable in body fluids. c. not be present in healthy people. d. be specific for a given type of cancer.

ANS: A

An ideal tumor marker should be both specific for a given type of cancer and sensitive enough to detect small tumors for early diagnosis or during screening. Ideally, a tumor marker should be produced by tumor cells and should be detectable in body fluids. It should not be present in healthy people or in benign conditions. Therefore, it could be used for screening for the presence of cancer in asymptomatic individuals in the general population. Most tumor markers, however, are present in (1) normal, (2) benign, and (3) cancerous tissues and lack specificity.

DIF: 1

REF: Page 339

OBJ: 2

7. Follicular lymphoma occurs when the: a. c-abl proto-oncogene and the BCR gene on a chromosome reciprocally translocate. b. HER-2/neu gene is overamplified, causing excess p105 to be released. c. c-myc gene becomes juxtaposed to the heavy-chain locus on chromosome 14. d. bcl-2 gene on chromosome 18 is translocated to the immunoglobulin heavy chain

locus on chromosome 14.

ANS: D

The bcl-2 proto-oncogene was identified in follicular lymphomas when a 14:18 translocation resulted in formation of a bcl-2-immunoglobulin heavy-chain fusion gene. Activation of the bcl-2 gene through the immunoglobulin promoter results in production of high levels of bcl-2 protein.

DIF: 2

REF: Page 359

OBJ: 4 | 5

8. A physical agent, such as exposure to ultraviolet light for an extended period of time, or a

biological agent, such as a virus, may cause cancer. These agents are referred to as: a. tumor markers. b. carcinogens. c. tumor suppressors. d. oncogenes.

ANS: B

A carcinogen is an agent that causes cancer. A carcinogen may be physical (e.g., radiation), chemical (e.g., a polycyclic hydrocarbon), or biological (e.g., a virus).

DIF: 1

REF: Page 339

OBJ: 1

9. Proto-oncogenes are present in the human genome to serve the function of: a. virus suppressors. b. repairmen of DNA. c. regulators of cell growth and proliferation. d. directors of apoptosis.

ANS: C

Proto-oncogenes code for protein products that are involved in normal cellular processes, such as growth factor signaling pathways.

DIF: 1

REF: Page 359

OBJ: 1 | 5

10. Which one of the following tumor markers is not a carbohydrate-related tumor marker with its

most important clinical use in the assessment of breast cancer recurrence? a. CA 15-3 b. CA 549 c. CA 125 d. CA 27.29 ANS: C

CA 15-3, CA 549, and CA 27.29 assays detect a high molecular weight glycoprotein mucin expressed by the mammary epithelium, known as episialin. Although CA 125 elevation is seen in endometrial, pancreatic, lung, breast, colorectal, and other gastrointestinal tumors, its primary clinical use is in assessment of ovarian cancer and not breast cancer.

DIF: 2

REF: Page 352

OBJ: 4

11. Tumor markers that are antigens located on the surface of tumor cells are called: a. carbohydrate-related tumor markers. b. cell surface tumor markers. c. oncogenes.

d. paraprotein.

ANS: A

Carbohydrate-related tumor markers may be (1) antigens on the tumor cell surface or (2) secreted by the tumor cells. These markers have been found to be clinically useful as tumor markers.

DIF: 1

REF: Page 337

OBJ: 1 | 4

12. Which of the following tumor markers is useful for monitoring germ cell tumors or placental

tumors? a. CEA b. PSA c. CA-19 d. hCG ANS: D

Elevated hCG concentrations are seen in (1) pregnancy, (2) trophoblastic disease, and (3) germ cell tumors. It is a useful tumor marker for tumors of the placenta (trophoblastic tumors) and for some tumors of the testes.

DIF: 1

REF: Page 349

OBJ: 4

13. A 35-year-old man has blood work done to assess his hypertension and weight gain. He has

also felt fatigued and moody with some respiratory difficulties. His physical appearance indicates possible Cushing’s syndrome and his physician obtains blood for lab analysis. The man’s adrenocorticotropic hormone (ACTH) level is extremely elevated (>300 ng/L), but upon ultrasound analysis thTeEaS drTeB naAl N glK anSdEaLpL peEaR rs.nC orOmMal. What might be the cause of the elevated ACTH? a. Ectopic synthesis of ACTH by small cell lung carcinoma b. Ectopic synthesis of ACTH by tumor of thyroid gland c. Cross-reaction of ACTH with other analytes to produce a false increase d. Normotopic production of ACTH by overactive adrenal gland ANS: A

Elevated serum levels of ACTH could be the result of pituitary or ectopic production. A high level of ACTH (greater than 200 ng/L) is suggestive of an ectopic origin.

DIF: 2

REF: Page 348

OBJ: 1 | 4 | 6

14. An individual with a history of miscarriage visits her physician to discuss her positive hCG

test done with a qualitative point-of-care device. The patient says she "feels pregnant" but wants to be certain. Following an ultrasound analysis, she is diagnosed with a germ cell tumor of unknown type. What two tumor markers are useful in classifying germ cell tumors? a. CEA and AFP b. AFP and hCG c. hCG and CEA d. CEA and CA 125 ANS: B

The combination of AFP and hCG is useful in classifying and staging germ cell tumors. Germ cell tumors may be predominantly one type of cell or may be a mixture of (1) seminoma, (2) yolk sac, (3) choriocarcinomatous elements (embryonal carcinoma), and (4) teratoma. Serum concentrations of AFP are elevated in yolk sac tumors, whereas hCG is elevated in choriocarcinoma. Both are elevated in embryonal carcinoma.

DIF: 2

REF: Page 350

OBJ: 4 | 6

15. An oncofetal antigen commonly used to assess recurrence of tumor growth following removal

of a colon tumor would be: a. CEA. b. AFP. c. CA 125. d. cathepsin D. ANS: A

In the monitoring of metastatic colon cancer, CEA is useful in following patients throughout therapy and the clinical course of the disease. Rising CEA values may indicate recurrence of the disease.

DIF: 2

REF: Page 351

OBJ: 4

16. Activated forms of normal cellular genes are termed: a. oncogenes. b. proto-oncogenes. c. pre-oncogenes. d. oncofetal antigens.

ANS: A

Oncogenes are mutated normal cellular genes (proto-oncogenes) that cause the malignant transformation of normal cells when activated.

DIF: 1

REF: Page 338

OBJ: 1

17. The loss of a gene that codes for a tumor suppressor protein would predispose certain cells to

cancerous transformation and unchecked proliferation. This class of genetic alteration is referred to as: a. point mutation. b. aneuploidy. c. translocation. d. deletion.

ANS: D

The ability of suppressor genes to develop cancers is derived from the loss of the gene rather than their activation as with oncogenes. Deletion or monosomy may lead to the loss of tumor suppressor genes.

DIF: 2

REF: Page 359

OBJ: 5

18. A 49-year-old man visits his physician with complaints of back pain; urinary frequency,

especially at night; and difficulty passing urine. Results of prostate-specific antigen analysis reveal a value of 2.0 µg/L. The physician diagnoses the problem as benign prostatic hyperplasia (BPH); however, because the man’s father had prostate cancer, the physician wants to track this patient for possible prostate cancer development. Each year, the man’s PSA value increases 0.5 µg/L. This increase indicates: a. a normal increase in PSA over time with age and likely BPH. b. an increase in PSA common to risk of prostate cancer. c. an increase in PSA concomitant with development of male breast cancer. d. the need for further studies including digital rectal examination and transrectal ultrasonography.

ANS: A

Elevations of PSA over 0.75 µg/L/year are observed in prostate cancer. At the age of 49, the PSA value of 2.0 µg/L is appropriate, and an elevation of 0.5 µg/L/year to a level of 3.5 µg/L at the end of 3 years is a level that indicates benign hyperplasia.

DIF: 3

REF: Page 345

OBJ: 4 | 6

19. A translocation between chromosomes 9 and 22 produces the BCR-ABL fusion gene. This is

the transforming event in 90% of individuals with chronic myelogenous leukemia (CML).

Which one of the following statements regarding the protein product of this fusion gene is correct? a. It is a nuclear phosphoprotein that deregulates DNA syntheses and increases cellular proliferation. b. It is a cytoplasmic tyrosine kinase that activates a number of signaling pathways leading to growth and iTnE hiS biT tiB onAoNfKaS poEpL toL siE s.R.COM c. It is a mitotic control gene that allows cells to move through the cell cycle and contribute to the autonomous growth of cancer. d. It interacts with other proteins, such as - and -catenin, involved in cell-cell interactions in epithelial cells to form polyps.

ANS: B

The Philadelphia chromosome is produced when a balanced translocation between chromosomes 9 and 22 occurs. The fused gene produces a protein that is a constitutively active cytoplasmic tyrosine kinase that activates a number of signaling pathways leading to growth and inhibition of apoptosis.

DIF: 2

REF: Page 360

OBJ: 5

20. A 25-year-old married woman has developed unusual abdominal pain. Her mother died of

ovarian cancer and she is concerned that she is developing the same disease. Her physician orders CA 125 and hCG analyses, both of which return with a moderately elevated value.

How should the physician interpret these results? a. The physician should inform the woman that she is pregnant and not to be concerned about the likelihood of ovarian cancer. b. The physician should perform more laboratory testing and transvaginal ultrasonography to determine whether the patient has ovarian cancer or is just pregnant. c. The physician should prepare for surgical removal of the ovaries based on the

tumor marker values. d. The physician should examine these tumor marker values to determine whether

they fall within specific cutoff intervals for healthy, benign, or cancerous groups.

ANS: D

The distribution of tumor marker values is usually shown as the percentage of patients with elevated values as determined using various cutoff values in the healthy, benign, and cancerous groups. In this case, the elevated values of CA 125 and hCG should be considered based on the cutoff values available for these three decision levels.

DIF: 3

REF: Page 353

OBJ: 3 | 4 | 6

21. One of the mutations that is found most frequently in cancers and can ultimately lead to colon

cancer involves a: a. translocation of the K-ras proto-oncogene to chromosome 14. b. point mutation in the K-ras proto-oncogene. c. frameshift mutation in the N-ras proto-oncogene. d. large deletion in the N-ras proto-oncogene.

ANS: B

The proto-oncogene K-ras is activated in association with protein–tyrosine kinase receptors and is required for growth factor–induced proliferation. A single point mutation at the twelfth K-ras codon changes the coded amino acid from glycine to valine in the p21 protein. This mutation is by far the most frequently found in cancers.

DIF: 2

REF: Page 360

OBJ: 5

orLmEaRrk.eC r aOnMalysis assay, receiver operating 22. Regarding predictive valueTm EoSdTelBs AofNaKtSum EL characteristic curves are most useful in assessing tumor marker analyses because: a. single tests for the same analyte can be evaluated over different times. b. they allow specific reference intervals to be determined for each tumor marker. c. they can display performance of tests or markers over the entire range of decision levels. d. they can serve as delta checks by assessing changes in an individual’s tumor marker concentration over time.

ANS: C

A useful approach to evaluating multiple tests for the same analyte or multiple markers for the same type of cancer is the receiver operating characteristic (ROC) curve. The advantage of the ROC curve is the display of performance over the entire range of decision points. One can pinpoint the decision cut point at which optimal sensitivity and specificity can be achieved.

DIF: 2

REF: Page 341

23. Most oncogenes are activated through: a. dominant mutations. b. loss of gene expression. c. monosomy. d. loss of function recessive mutations.

ANS: A

OBJ: 3

Oncogenes are derived from proto-oncogenes that may be activated by dominant mutations, such as (1) point mutations, (2) insertions, (3) deletions, (4) translocations, or (5) inversions.

DIF: 1

REF: Page 359

OBJ: 5

24. A 65-year-old man has been diagnosed with prostate cancer and is being prepared for

radiation therapy. His physician is concerned that the cancer may have metastasized to the patient’s skeletal system. Which one of the following laboratory analytes would give this information to the physician? a. ALP b. Calcitonin c. AFP d. Growth hormone ANS: A

Alkaline phosphatase in the sera of normal adults originates primarily from the liver or biliary tract, although it may also arise from bone. Based on this presence, ALP levels can be helpful in evaluating metastatic cancer with bone or liver involvement. Greatest elevations are seen in patients with osteoblastic lesions, such as in prostatic cancer with bone metastases.

DIF: 2

REF: Page 342

OBJ: 4 | 6

Chapter 21: Kidney Function Tests—Creatinine, Urea, and Uric Acid Test Bank MULTIPLE CHOICE 1. Which one of the following statements regarding creatinine is correct? a. Most intraindividual variation in serum creatinine is due to muscle mass. b. Serum creatinine levels are not affected by renal disease. c. Creatinine production increases when serum creatinine is elevated. d. Creatinine is completely reabsorbed (not excreted) by the renal tubules.

ANS: A

The amount of creatinine produced each day is fairly constant and is related to the muscle mass. In health, the concentration of creatinine in the bloodstream is also fairly constant.

DIF: 2

REF: Page 365

OBJ: 2

2. Urea: a. biosynthesis is carried out exclusively in the renal system. b. is 100% reabsorbed (thus not excreted) by the kidney. c. is decreased in plasma by a variety of renal diseases. d. concentration in plasma is increased by a high-protein diet.

ANS: D

Because urea is formed by the catabolism of protein, plasma urea concentration is increased by a high-protein diet.

DIF: 2

REF: Page 369

OBJ: 7 | 8

3. Creatinine clearance is used to assess the a. glomerular filtration rate b. creatine concentration c. renal threshold d. renal hormonal function

of a patient.

ANS: A

Because creatinine is produced endogenously and released into body fluids at a constant rate, both plasma creatinine concentration and its renal clearance (creatinine clearance) have been used as markers of the glomerular filtration rate (GFR).

DIF: 1

REF: Page 365

OBJ: 2

4. Which of the following is the primary reagent used in the Jaffe reaction for creatinine? a. Alkaline copper sulfate b. Phosphotungstic acid c. Alkaline picric acid d. Diacetyl monoxime ANS: C

Most chemical methods for measuring creatinine are based on its reaction with alkaline picrate. Jaffe noted that creatinine reacts with picrate ion in an alkaline medium to yield an orange-red complex.

DIF: 1

REF: Page 365

OBJ: 4

5. A practicing physician at a university student healthcare facility often recommends to student

patients that they take large doses of vitamin C (ascorbic acid) to fend off colds during the semester. As director of the chemistry laboratory that serves this facility, you notice a trend in that many of this physician’s students’ serum creatinine levels are unusually high. You are currently using a type of analysis based on the Jaffe reaction. What might be the cause of the elevated values? a. High doses of ascorbic acid cause increased hepatic synthesis of bilirubin, which interferes with the enzymes used in the assay. b. Elevated ascorbic acid in serum produces a Jaffe-like chromogen in this analysis that can be interpreted as increased serum creatinine. c. It may be that this physician’s patients all are exhibiting increased muscle breakdown. d. The ketones and ketoacids produced from the breakdown of creatinine in the students’ serum are interfering with the development of the color reaction.

ANS: B

Large doses of vitamin C will lead to transient increases in serum ascorbic acid. Ascorbic acid is a significant interferant in the Jaffe reaction for creatinine because of its ability to produce a chromogen with an absorbance reading in the same range as that of the Jaffe reaction.

DIF: 3

REF: Page 365

J: 4 TESTBANKSOEBL LER.COM

6. Plasma urea concentration: a. is a more reliable indicator of renal function than creatinine. b. can increase because of decreased renal perfusion. c. is decreased in intrinsic renal failure. d. is not affected by diet.

ANS: B

Serum urea concentration is increased by many factors including decreased renal blood flow as observed in heart failure. If renal blood flow is decreased, then urea cannot be excreted in urine and will diffuse back into the bloodstream.

DIF: 2

REF: Page 369

OBJ: 8

7. In the measurement of urea, urea is initially hydrolyzed by urease to form ammonium ions.

This assay combined with the spectrophotometric measurement of the resulting ammonia is referred to as the: a. ammonia-selective electrode method. b. Berthelot reaction. c. Jaffe reaction. d. urea method.

ANS: B

Enzymatic methods for the measurement of urea are based on hydrolysis of urea with urease to generate ammonia. Spectrophotometric approaches to ammonia quantitation include the Berthelot reaction.

DIF: 2

REF: Page 370

OBJ: 9

8. Urea is produced from: a. catabolism of purine nucleosides. b. phosphorylation of creatine in muscle. c. reduction of bilirubin. d. catabolism of proteins and amino acids.

ANS: D

Urea is the major nitrogen-containing metabolic product of protein catabolism in humans.

Protein goes through enzymatic proteolysis to form amino acids, which are deaminated and transaminated to produce ammonia, which enters the urea cycle to produce urea.

DIF: 1

REF: Page 368-369

OBJ: 7

9. The major nonprotein nitrogen degradation product of endogenous purines is: a. urea. b. creatinine. c. uric acid. d. ammonia.

ANS: C

Breakdown of guanine occurs when guanine monophosphate is split into the base guanine and ribose. Guanine is deaminaTteEdStoTB xaAnN thK inSe,Ew tuO rnMis oxidized to uric acid. This last LhLicEhRin.C reaction is irreversible. Similarly, adenine monophosphate is deaminated to inosine monophosphate, from which the ribose unit is removed to form hypoxanthine. Hypoxanthine is oxidized to xanthine and finally to uric acid.

DIF: 1

REF: Page 370

OBJ: 11

10. Why do values obtained with the Jaffe reactions for creatinine measurement overestimate

creatinine concentration by ~20%? a. The components of the reaction mixture often continue to react at endpoint and synthesize excess creatinine. b. The rate of Jaffe complex formation is temperature dependent, and excess heat formed by the reaction leads to increased absorptivity and falsely increased creatinine value. c. Noncreatinine chromogens in the reaction that react with the picrate in the end-point Jaffe methods overestimate true plasma creatinine concentration. d. Hydroxide concentrations above 0.5 mmol/L produce a decreased degradation of the Jaffe complex.

ANS: C

Because of the nonspecificity of the Jaffe reaction, chromogens in serum will react with the picric acid and produce a slight falsely elevated creatinine measurement.

DIF: 2

REF: Page 366

OBJ: 6

11. Why does persistently acidic urine lead to formation of uric acid renal stones? a. Uric acid has a pKa of 5.57, which makes it insoluble in acidic solutions. b. At a pH of 10, uric acid is insoluble and aggregates to form stones. c. Elevated urine purines cause uric acid crystals to aggregate and form stones. d. Supersaturation of acidic urine causes calcium to form complexes with uric acid,

which is the initial step in stone formation.

ANS: A

Because uric acid has a pKa of 5.57, it becomes insoluble at pH less than 6.0. Urine becomes supersaturated with uric acid if there is excess present and forms crystals that aggregate to form stones. At urine pH above 6.0, uric acid is present as the urate ion.

DIF: 2

REF: Page 373

OBJ: 12 | 13

12. All of the following conditions are associated with hyperuricemia except: a. excessive cell turnover as in malignancy treated with chemotherapy. b. deficiency of hypoxanthine-guanine phosphoribosyl transferase. c. preeclampsia toxemia. d. severe hepatocellular disease.

ANS: D

Hepatocellular disease produces hypouricemia. Because liver is the major organ of synthesis of new (as opposed to recycled) nucleotides, liver damage leads to decreased synthesis of these and therefore of uric acid.

DIF: 2

REF: Page 372

OBJ: 1 | 12 | 13

eaStiT niB neAaNsK seSssEmLeL ntE : R.COM 13. Creatininase reactions for cTrE a. yield sarcosine and urea. b. require the addition of potassium ferricyanide to reduce interference. c. catalyze the conversion of creatinine to creatine. d. catalyze the conversion of creatinine to N-methylhydantoin and ammonia.

ANS: C

Creatininase catalyzes the forward reaction of creatinine and water in the presence of ATP to form creatine.

DIF: 2

REF: Page 366

OBJ: 5

14. Uricase is used in the assay of uric acid to: a. decarboxylate uric acid to form tungsten blue. b. oxidize uric acid to form allantoin. c. reduce uric acid to form allantoin. d. reduce uric acid to form tungsten blue.

ANS: B

Uricase, also known as urate oxidase, catalyzes the reaction uric acid + O2 + H2O + hydrogen peroxide + CO2.

DIF: 1

REF: Page 373

OBJ: 16

15. Primary gout is distinguished from secondary gout by:

allantoin

a. b. c. d.

decreased renal excretion (increased renal retention) of uric acid. its polygenic basis. having increased dietary intake of purines. the increased catabolism of purines due to chemotherapy.

ANS: B

Primary gout, or “essential” hyperuricemia, has a polygenic, or “many gene” basis. This disorder is caused by rare inherited metabolic defects; however, in most cases the cause is idiopathic. Purine overproduction, decreased renal uric acid excretion, and excess dietary intake are hallmarks of both primary and secondary gout.

DIF: 1

REF: Page 372

OBJ: 14

16. A hemolyzed serum sample from an individual is assayed for creatinine and a result is

obtained that is decreased compared to the normal reference interval. If this individual has a normal glomerular filtration rate, which one of the following statements is true? a. The individual’s diet contains high levels of protein. b. The individual must be receiving chemotherapy. c. The assay must be subject to interference from bilirubin. d. The assay must be subject to interference from ketones.

ANS: C

Bilirubin is a negative interferant in the Jaffe reaction for creatinine because of its oxidation, which interferes with the absorbance measurement.

DIF: 2

REF: Page 366

OBJ: 4 | 13

ulT tsBinAdNicKaS teEinLcL reE asRe. dC seOruMm creatinine and urea values, and his 17. An individual’s laboratoryTreEsS physician’s diagnosis indicates a postrenal obstruction. What would the glomerular filtration rate in this individual likely be? a. Decreased b. Increased c. No change ANS: A

Serum creatinine concentration is maintained within narrow limits predominantly by glomerular filtration. Increased serum creatinine and urea are typically caused by a decreased glomerular filtration rate. Kidney disease is associated with accumulation of urea in blood and in obstructive postrenal conditions (e.g., malignancy, nephrolithiasis, and prostatism), and both serum creatinine and urea concentrations will be increased.

DIF: 3

REF: Page 369

OBJ: 3 | 8

Chapter 22: Carbohydrates Test Bank MULTIPLE CHOICE 1. Conversion of glucose into lactate or pyruvate is referred to as: a. glycogenesis. b. glycogenolysis. c. glyconeogenesis. d. glycolysis.

ANS: D

The conversion or oxidation of glucose or other hexoses into lactate or pyruvate is called glycolysis. Glycolysis is the initial process of carbohydrate metabolism.

DIF: 1

REF: Page 379

OBJ: 1 | 4

2. An example of a monosaccharide would be: a. glucose. b. maltose. c. sucrose. d. starch.

ANS: A

Glucose is one of the most common examples of a monosaccharide.

DIF: 1

REF: TPE agSe T 37B6ANKS OE BL J: LE 1R | 2.COM

3. The breakdown of glycogen stores in the liver to increase serum glucose is referred to as: a. glycogenolysis. b. glycolysis. c. gluconeogenesis. d. glycogenesis.

ANS: A

The breakdown of glycogen to glucose and other intermediate products is termed glycogenolysis.

DIF: 1

REF: Page 379

OBJ: 1

4. Blood is collected in a tube containing no anticoagulant and is transported uncentrifuged to

the laboratory from an outpatient clinic. Transport time at room temperature, accessioning, and sample preparation time equal approximately hours. If a serum glucose level is requested for this tube of blood, how might the results be affected by the timing? a. The glucose value would be decreased by 50%. b. The glucose value would be increased by approximately 15%. c. The glucose value would be decreased by approximately 5%. d. There would be no effect on the glucose value.

ANS: B

Glycolysis decreases serum glucose by approximately 5% to 7% in 1 hour (5 to 10 mg/dL) in normal uncentrifuged coagulated blood at room temperature.

DIF: 3

REF: Page 383

OBJ: 10

5. By what mechanism does glucagon promote hyperglycemia? a. Glucagon promotes glycogenesis. b. Glucagon stimulates insulin release. c. Glucagon stimulates glucose synthesis by gluconeogenesis. d. Glucagon promotes hypoglycemia, not hyperglycemia.

ANS: C

Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.

DIF: 2

REF: Page 380

OBJ: 3

6. What is the classic test to determine a diagnosis of hypoglycemia? a. Assessment of fasting blood glucose during a hypoglycemic episode b. A 72-hour fast c. Postprandial glucose analysis d. Oral glucose tolerance test ANS: B

In the classic test a 72-hour fast involves samples being drawn for analysis of plasma glucose, insulin, C-peptide, and proinsulin every 6 hours. When plasma glucose concentration is 60 mg/dL or less, analysis should be performed every 1 to 2 hours. The fast should be concluded when plasma glucose concT enEtrSaT tioBnAfN alK lsStoEaLpLrE edRe. teC rmOiM ned concentration (such as 45 mg/dL or less) or the patient exhibits signs or symptoms of hypoglycemia, or after 72 hours. Most patients with true hypoglycemia show an abnormally low value within 12 hours of beginning a fast.

DIF: 1

REF: Page 380

OBJ: 7

7. A 75-year-old man was brought by his daughter to a hospital emergency department. He was

in a confused state, trembling, sweating, with a rapid pulse, lightheadedness, and complaining of hunger and epigastric discomfort. His daughter claims that he does not drink alcohol and that he takes oral hypoglycemic drugs to control his diabetes. What is the likely cause of his symptoms? a. The oral hypoglycemic drugs are affecting his thyroid gland. b. He is likely suffering from pheochromocytoma and the effects of increased epinephrine. c. He has possibly taken too much of his medication and is suffering from hypoglycemia. d. His diabetes is not being adequately controlled and is leading to lactic alkalosis.

ANS: C

Oral hypoglycemic agents are the most frequent cause of drug-induced hypoglycemia. The symptoms indicate hypoglycemia, which is not consistent with the symptoms in Options a and b. Lactic acidosis might cause these symptoms, but not alkalosis.

DIF: 3

REF: Page 380

OBJ: 7 | 15

8. In an individual with a normal hematocrit, whole-blood glucose values are approximately

what percent different from plasma glucose values? a. 20% higher b. 10% lower c. 50% higher d. There is no difference between whole blood glucose and plasma glucose values.

ANS: B

In individuals with a normal hematocrit, fasting whole-blood glucose concentration is approximately 10% to 12% lower than plasma glucose. While glucose concentrations in the water phase of red blood cells and plasma are similar (the erythrocyte plasma membrane is freely permeable to glucose), the water content of plasma (93%) has a glucose concentration that is approximately 11% higher than that of whole blood.

DIF: 2

REF: Page 382

OBJ: 9

9. The glucose assay on an analyzer uses hexokinase as the enzyme that phosphorylates glucose.

What are the initial products formed from the first step of this reaction? a. Nicotinamide adenine dinucleotide and NADH b. 6-Phosphogluconate and hydrogen ions c. Glycosylated hemoglobin d. Glucose-6-phosphate and adenosine diphosphate (ADP) ANS: D

In the hexokinase (HK) method of glucose determination, glucose is first phosphorylated by TPE)SinTtBhA RK .CanOdMMg2+. Glucose-6-phosphate and adenosine triphosphate (AT eN prK esSeE ncLeLoE fH ADP are the products of this initial step.

DIF: 2

REF: Page 383

OBJ: 11

10. Which one of the following coupled-enzyme glucose methods requires extended incubation

time to allow for the spontaneous conversion of the -form of glucose to the -form so that both forms can react with the initial enzyme in the reaction? a. Hexokinase method b. Glucose oxidase method c. Self-monitoring method d. Polarographic method ANS: B

Glucose oxidase is highly specific for -D-glucose. Because 36% and 64% of glucose in solution are in the - and -forms, respectively, complete reaction requires mutarotation of the - to -form. Extended incubation time allows spontaneous conversion of the -form to the -form.

DIF: 2

REF: Page 384

OBJ: 12

11. The major storage carbohydrate in animals is

. a. cellulose; vegetable fibers

, which is located most abundantly in

b. glycoprotein; cell membranes c. glycogen; the liver d. starch; skeletal muscle ANS: C

The major storage carbohydrates are starch in plants and glycogen in animals, and glycogen is most abundant in the liver and also is found in skeletal muscle.

DIF: 1

REF: Page 379

OBJ: 1

12. Which one of the following has as one of its biological functions the regulation of the lifespan

of proteins? a. Glycoproteins b. Glucose c. Lactate d. Ketones ANS: A

Integral membrane proteins have oligosaccharides covalently attached to the extracellular region, forming glycoproteins. One of the biological functions of the carbohydrate chains is to regulate the lifespan of proteins. For example, loss of sialic acid residues from the end of oligosaccharide chains on erythrocytes results in the removal of red blood cells from the circulation.

DIF: 1

REF: Page 379

OBJ: 1

13. A type 1 diabetic who is in the early stages of the disease is taken to the emergency room with

symptoms of hypoglycemiT a.EW eS ofEtL heLfE olRlo.wCinOgMendogenous hormones might be the ShTicBhAoNnK cause of this? a. Epinephrine b. Glucagon c. Cortisol d. Lactate ANS: B

Hypoglycemia occurs frequently in individuals with type 1 or type 2 diabetes.

Counterregulatory responses become impaired in type 1 diabetes patients, increasing the risk of hypoglycemia. The secretion of glucagon in response to hypoglycemia is impaired by an unknown mechanism early in the course of type 1 diabetes.

DIF: 1

REF: Page 381

OBJ: 8 | 15

14. A heparinized blood sample is received in the chemistry laboratory. After centrifugation, the

plasma appears markedly hemolyzed. If the hexokinase method is used in this lab to measure glucose, why should this specimen be re-collected? a. Heparin interferes with the second enzyme in the hexokinase assay. b. Hemoglobin competes with the chromogen for hydrogen peroxide and inhibits the hexokinase reaction. c. Red blood cells contain phosphate esters and enzymes that interfere with the hexokinase assay. d. There is no need for re-collection as neither hemolysis nor heparin interfere with

the hexokinase assay.

ANS: C

Hemolyzed specimens containing more than 0.5 g of hemoglobin/dL are unsatisfactory because phosphate esters and enzymes released from red blood cells interfere with the assay.

DIF: 2

REF: Page 384

OBJ: 11

15. What effect does ethanol have on blood glucose value? a. Increases b. Decreases ANS: B

Ethanol produces hypoglycemia by inhibiting gluconeogenesis.

DIF: 2

REF: Page 380

OBJ: 3 | 6

16. What effect does salicylate have on blood glucose value? a. Increases b. Decreases ANS: B

Certain drugs, including salicylates, produce hypoglycemia.

DIF: 2

REF: Page 380

OBJ: 3 | 6

17. What effect does septicemia have on blood glucose value? a. Increases b. Decreases ANS: B

Septicemia depletes glycogen stores, impairs gluconeogenesis, and increases peripheral use of glucose.

DIF: 2

REF: Page 381

OBJ: 3 | 6

18. What effect does epinephrine have on blood glucose value? a. Increases b. Decreases ANS: A

Epinephrine stimulates glycogen breakdown and decreases glucose use, thereby increasing glucose.

DIF: 2

REF: Page 380

OBJ: 3 | 6

19. What effect does glucagon have on blood glucose value? a. Increases b. Decreases ANS: A

Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis and enhances ketogenesis in the liver.

DIF: 2

REF: Page 380

OBJ: 3 | 6

Chapter 23: Lipids, Lipoproteins, Apolipoproteins, and Other Cardiac Risk Factors Test Bank MULTIPLE CHOICE 1. A 46-year-old man visits his physician complaining of fatigue and chest pains. His family

history reveals that his father and grandfather both died of heart attacks at the age of 50.

Laboratory results indicated elevated total cholesterol, elevated low-density lipoprotein (LDL), and normal triglyceride. He is eventually diagnosed with familial hypercholesterolemia and atherosclerosis. What is the likely cause? a. Genetic lack of LDL receptors on cell surfaces b. Insulin deficiency c. Lipoprotein lipase deficiency d. Tangier disease ANS: A

Familial hypercholesterolemia is caused by defects in the LDL receptor pathway, which binds and removes LDL from the circulation. LDL thus accumulates in the plasma, resulting in its increased deposition in the skin, tendons, and in arteries where it causes atherosclerosis. LDL particles tend to be larger, carrying increased amounts of cholesterol. The majority of these patients have gene defects in the LDL receptor itself.

DIF: 3

REF: Page 404

OBJ: 6 | 12

2. The lipoprotein with the smallest diameter and that has a 50:50 lipid:lipoprotein ratio is the: a. LDL. b. chylomicron. c. HDL. d. VLDL. ANS: C

See Table 23-4. HDL has a diameter of 4 to 10 nm and a 50:50 ratio of lipid to lipoprotein.

DIF: 1

REF: Page 398

3. In the small intestine, a. lipase b. cholesterol c. starch d. monosaccharides

OBJ: 4

is (are) solubilized by emulsification to form micelles.

ANS: B

Cholesterol is first solubilized through a process called emulsification, which occurs by the formation of micelles that contain unesterified cholesterol, fatty acids, monoglycerides, phospholipids, and conjugated bile acids.

DIF: 1

REF: Page 390

OBJ: 3

4. Cholesterol is esterified to form a cholesteryl ester by acylcholesterol acyltransferase in the

cell. In the circulation, cholesteryl esters are formed by the action of which one of the following enzymes? a. HMG CoA reductase b. Cholesterol oxidase c. Lecithin cholesterol acyltransferase d. Fatty acid hydrolase ANS: C

Cholesteryl esters also are formed in the circulation by the action of a plasma enzyme called lecithin cholesterol acyltransferase (LCAT) bound to lipoproteins, particularly high-density lipoproteins (HDL).

DIF: 1

REF: Page 391

OBJ: 3

5. Recognized abnormalities of fatty acid catabolism associated with uncontrolled diabetes

mellitus include the development of ketone formation. This ketosis is caused by: a. loss of apolipoprotein receptors on the surfaces of cells. b. dysbetalipoproteinemia. c. destruction of mitochondria within cells. d. excess acetyl-CoA being diverted to form ketone bodies.

ANS: D

During prolonged starvation or when the carbohydrate metabolism is impaired, such as in uncontrolled diabetes mellitus, the formation of acetyl-CoA exceeds the supply of oxaloacetate. The resulting acetyl-CoA excess is diverted to an alternative pathway in the mitochondria for the formation of (1) acetoacetic acid, (2) -hydroxybutyric acid, and (3) acetone, the three compounTdEs S knToBwAnNcK olS leEctLivLeE lyRa. sC keOtoMne bodies.

DIF: 2

REF: Page 393

OBJ: 1 | 6

6. Why would high sensitivity C-reactive protein (CRP) be an indicator of potential coronary

heart disease (CHD)? a. It is an acute phase reactant plasma protein that rises in response to inflammation, which has been demonstrated to be associated with risk of future CHD. b. CRP levels rise because of its presence in cardiac muscle and release upon muscle cell death. c. It is a myocardial protein that regulates muscle contraction through interaction with myosin and actin. d. It is an enzyme found in skeletal muscle and cardiac muscle and is released upon tissue injury.

ANS: A

CRP is known to be an acute phase reactant. It is routinely monitored as an indication of infection and autoimmune diseases. Numerous epidemiologic studies have demonstrated that increased serum CRP concentrations are also positively associated with a risk of future CHD events. Prospective epidemiologic studies have shown that a single hsCRP measurement is a strong predictor of myocardial infarction.

DIF: 2

REF: Page 410

OBJ: 11

7. A 6-year-old girl has complained about painful urination and is taken to her pediatrician.

There is no family history of CHD or any lipid abnormalities. After a fasting blood specimen and urine specimen are obtained, laboratory findings are as follows (healthy reference intervals are in parentheses): serum albumin 1.8 g/dL (3.5 to 5.5 g/dL), total serum cholesterol 200 mg/dL (<170 mg/dL), LDL cholesterol 130 mg/dL (<110 mg/dL), serum triglyceride 250 mg/dL (<200 mg/dL), serum urea nitrogen 20 mg/dL (7 to 18 mg/dL), heavy urine protein (normal is negative), and 1+ urine blood (normal is negative). All other laboratory values were normal. These findings are most compatible with: a. acute poststreptococcal glomerulonephritis with dysbetalipoproteinemia. b. a renal disorder with secondary hyperlipidemia. c. acute pyelonephritis and familial hypercholesterolemia. d. mild glomerular disease with lipoprotein lipase deficiency.

ANS: B

The decreased serum albumin and increased urea nitrogen are common in renal disorders, as are the urine findings, but the lipid values and symptoms indicate a hyperlipidemia that is present as well. Since there is no family history of lipid abnormalities, the issue here is not familial, and children that present with a marked increase in triglycerides over 500 mg/dL may have a primary genetic defect, such as lipoprotein lipase (LPL) deficiency. In the pediatric population, the most common pattern of dyslipidemia in children is a (1) moderate to severe increase in triglycerides, (2) mild increase in LDL cholesterol, and (3) decreased HDL cholesterol. According to Table 23-7, a secondary cause of hyperlipidemia is renal disease.

DIF: 3

REF: Page 403

OBJ: 8 | 12

8. What distinguishes lipoprotein(a), or Lp(a), from LDL? a. Lp(a) contains more coTreElS ipTidBsA , tN rigl ycEeL ridLeE, R an.dCcO hoMlesteryl ester and a smaller KS

percent of protein.

b. Lp(a) interacts with ABCA1 in peripheral cells, such as the macrophages, to

remove additional cholesterol. c. Lp(a) contains a carbohydrate-rich protein called apo(a) that is covalently bound to

apo B-100 through a disulfide linkage. d. Lp(a) does not contain any apo B-100.

ANS: C

Lp(a) is structurally related to LDL because both lipoproteins possess one molecule of apo B-100 per particle and have similar lipid compositions. However, unlike LDL, Lp(a) also contains a carbohydrate-rich protein [apo(a)] that is covalently bound to the apo B-100 through a disulfide linkage.

DIF: 1

REF: Page 398

OBJ: 1 | 4

9. An individual visits a physician, who notes that the patient has splenomegaly, enlarged and

orange-colored tonsils, and tingling feelings in the extremities, indicating peripheral neuropathy. Upon examination of the blood smear for a white blood cell differential, many foamy-appearing cells were noted. Normal triglyceride and total cholesterol values were noted; however, a marked decrease of HDL was also noted. What is the name of this disorder? a. Familial hypercholesterolemia b. Tangier disease c. Dysbetalipoproteinemia d. Coronary heart disease

ANS: B

Tangier disease is a rare autosomal recessive disorder that is also associated with a notable reduction of HDL. The major clinical signs of Tangier disease are (1) hyperplastic orange tonsils, (2) splenomegaly, and (3) peripheral neuropathy. There is an increased deposition of cholesteryl esters in various tissues of the body, particularly macrophages, which form foam cells.

DIF: 3

REF: Page 404

OBJ: 6 | 12

10. An individual visits his physician with splenomegaly, enlarged and orange-colored tonsils,

and tingling feelings in the extremities, indicating peripheral neuropathy. Upon examination of the blood smear for a white blood cell differential, many foamy-appearing cells were noted.

Normal triglyceride and total cholesterol values were noted; however, a marked decrease of HDL was also noted. What is the cause of this disorder? a. Mutations in the apo B-100 gene b. Defects in the expression or function of the LDL receptor c. Genetic mutations in the apo E gene d. Mutations in the ABCA1 transporter gene ANS: D

Tangier disease is due to mutations in the ABCA1 transporter, which mediates the first step of the reverse-cholesterol transport pathway, the efflux of cholesterol from cells.

DIF: 2

REF: Page 404

OBJ: 6 | 12

11. The lipoprotein that, because it is considered proatherogenic, is often measured by the

laboratory to assess the likT elE ihS ooTdBoAf N CK HSDEiL nL anEiR nd.iC viO duMal with normal lipid values but a strong family history of cardiovascular disease is: a. LDL. b. HDL. c. lipoprotein(a). d. chylomicrons.

ANS: C

Although Lp(a) particles typically carry only a relatively small fraction of total cholesterol, these lipoprotein particles are particularly proatherogenic. Lp(a) is, therefore, often measured in individuals with a normal lipid panel but with a history of premature cardiovascular disease and/or a strong family history of cardiovascular disease.

DIF: 1

REF: Page 409

OBJ: 4

12. The apolipoprotein that functions to facilitate uptake of chylomicron remnants by the liver, is

involved in dysbetalipoproteinemia, and that has an isoform associated with the risk of Alzheimer disease development is apo: a. E. b. B-100. c. B-48. d. A-I. ANS: A

Dysbetalipoproteinemia is caused by a defect in the removal of lipoprotein remnants from both chylomicrons and very low-density-lipoprotein (VLDL). Apo E present on the surface of lipoprotein remnant particles interacts with specific hepatic receptors and facilitates the removal of lipoprotein remnants. Genotyping of apo E is done to identify the apo E4 isoform, which is associated with increased cholesterol and a risk for Alzheimer disease.

DIF: 1

REF: Page 404

OBJ: 4

13. There is an inverse relationship between which of the following cholesterol-containing

lipoproteins and increased risk of CHD? a. VLDL b. LDL c. Chylomicrons d. HDL ANS: D

In contrast to LDL cholesterol, increased HDL cholesterol concentrations have been shown to be protective for CHD. DIF: 1

REF: Page 401

OBJ: 4

14. In the 3-step assay for determination of cholesterol concentration, cholesteryl esters must be

cleaved by an enzyme. This hydrolytic cleavage forms: a. free triglyceride and fatty acids. b. triglyceride and glycerol-1-phosphate. c. cholesterol and fatty acids. d. choles-4-en-3-one and hydrogen peroxide.

ANS: C

Enzymatic methods have become the assays of choice for the routine measurement of cholesterol. A commonly used 3-step procedure typically uses a bacterial cholesteryl ester hydrolase to cleave cholesteryl esters in the following way: cholesteryl ester + H2O with cholesteryl ester hydrolase to form cholesterol and fatty acid.

DIF: 2

REF: Page 408

OBJ: 9

15. In the 3-step assay for determination of cholesterol concentration, cholesteryl esters must be

cleaved by which of the following enzymes for the initial step to occur? a. Cholesterol oxidase b. Lipase c. Peroxidase d. Cholesteryl ester hydrolase ANS: D

Enzymatic methods have become the assays of choice for the routine measurement of cholesterol. A commonly used 3-step procedure typically uses a bacterial cholesteryl ester hydrolase to cleave cholesteryl esters in the following way: cholesteryl ester + H2O with cholesteryl ester hydrolase to form cholesterol and fatty acid.

DIF: 2

REF: Page 408

OBJ: 9

16. The difference between traditional HDL cholesterol assays and the direct homogeneous assay

is that: a. there is no physical separation of HDL from the non-HDL fractions and HDL is selectively measured. b. precipitation of non-HDL lipoproteins must occur using polyanions. c. enzymatic measurement of HDL occurs after non-HDL lipoproteins are removed by ultracentrifugation. d. measurement of the rate of oxygen consumption occurs before removal of non-HDL lipoproteins.

ANS: A

In traditional HDL cholesterol assays, non-HDL lipoproteins are first physically removed by precipitation or are effectively masked, and then total cholesterol is measured to give a concentration of HDL cholesterol. Direct HDL cholesterol assays, also known as homogeneous assays, are now the most common method to measure HDL cholesterol. Unlike precipitation-based assays, there is no physical separation of HDL from the non-HDL fractions. Instead, HDL cholesterol is selectively measured.

DIF: 2

REF: Page 408

OBJ: 9

17. Cholesterol plays a role in all of the following except: a. myelinization of the central nervous system. b. steroid hormone precursor. c. cell membrane component. d. bile acid precursor.

ANS: A

The sphingolipids, particulTarElySsTpB hiA ngNoKmSyE elL inLaEnR d. linCoOleMic acid converted to arachidonic acid, are important in the myelinization of the central nervous system. Cholesterol has a role in each of the other functions.

DIF: 1

REF: Page 391-392

OBJ: 2

18. The polar amphipathic lipid that forms a surface coating around a core of cholesterol esters

and triglyceride in a lipoprotein is: a. chylomicron. b. sphingolipid. c. phospholipid. d. HDL. ANS: C

Lipoproteins are typically spherical particles with nonpolar neutral lipids (triglycerides and cholesterol esters) in their core and more polar amphipathic lipids (phospholipids and free cholesterol) at their surface.

DIF: 1

REF: Page 397

OBJ: 1

19. The class of lipid that is derived from fatty acids and that alters blood pressure by its action on

arterial smooth muscle cells is: a. sphingolipids. b. acylglycerols.

c. terpenes. d. prostaglandins.

ANS: D

Prostaglandins and related compounds, such as thromboxanes and leukotrienes, are derivatives of fatty acids, primarily arachidonate. These bioactive lipids exert diverse physiological actions, one of which is to alter blood pressure (see Table 23-2).

DIF: 1

REF: Page 396

OBJ: 1 | 2

20. Essential fatty acids are: a. straight-chain monocarboxylic acids that can be classified as unsaturated,

monounsaturated, or polyunsaturated. b. fatty acids that cannot be synthesized by the human body. c. lipids that contain phosphorous. d. a group of compounds derived from unsaturated 20-carbon fatty acids.

ANS: B

Humans are unable to synthesize some fatty acids, such as linoleic acid (C18:29,12), which is found only in plants. Because it is vital for health, growth, and development, it is termed an essential fatty acid.

DIF: 1

REF: Page 393

OBJ: 1

21. What is (are) the principal apo B-100 containing lipoprotein(s) secreted by the liver? a. LDL and VLDL b. VLDL c. LDL d. HDL ANS: B

VLDL, which contains approximately 55% triglyceride by mass, one molecule of apo B-100, and some apo E and C, is the principal apo B-100–containing lipoprotein that is secreted by the liver.

DIF: 1

REF: Page 400

OBJ: 4

22. A 9-year-old boy was referred by his dermatologist for a lipid evaluation after the boy

developed what appeared to be a raised yellowish rash over his palms and elbows. The boy had no previous history of heart problems and no family history of any coronary disorders.

However, when he was 8, he did have two acute attacks of pancreatitis and abdominal pain.

His lipid workup is as follows (specimen was a fasting blood draw): triglyceride 3200 mg/dL (normal <200 mg/dL), total cholesterol 190 mg/dL (normal <200 mg/dL), glucose 160 mg/dL (normal 60 to 110 mg/dL). His HDL concentration was in normal range, but LDL was elevated. Specimen was grossly lipemic. What is the likely cause of these symptoms? a. Lipoprotein lipase deficiency b. Familial hypercholesterolemia c. Tangier disease d. Genetic deficiency of LDL ANS: A

Deficient lipoprotein lipase activity due to mutations in the LPL gene is a rare autosomal recessive disorder characterized by hyperchylomicronemia, with triglyceride concentrations reaching as high as 10,000 mg/dL. LPL is critical for the hydrolysis of triglycerides on chylomicrons and their subsequent conversion to chylomicron remnants. This disorder is often first diagnosed in childhood, usually after recurrent episodes of severe abdominal pain and repeated attacks of pancreatitis. Eruptive xanthomas are usually present when plasma triglyceride concentrations exceed 2000 and 4000 mg/dL. DIF: 3

REF: Page 402

OBJ: 6

23. Which one of the following lipid metabolic pathways involves the removal of excess cellular

cholesterol from cells and returning it to the liver for excretion? a. Exogenous b. Endogenous c. Intracellular-cholesterol transport d. Reverse-cholesterol transport ANS: D

The function of the reverse cholesterol transport pathway is to remove excess cellular cholesterol from peripheral cells and return it to the liver for excretion. This process is largely mediated by HDL. DIF: 2

REF: Page 400-401

OBJ: 5

24. You have received two blood samples, one in a sodium citrate tube for coagulation studies

and the other in an oxalate tube for glucose analysis from a patient diagnosed with diabetes mellitus. This patient’s physician contacts you to request that lipid and lipoprotein analyses be NoKuS added to the previous studiTesE. S WThBatAw ldEbLeLthEeRb. esCt O blM ood specimen for lipoprotein analyses and why? a. The submitted specimens (citrate and oxalate) would be the most appropriate to use for lipoprotein analysis. b. Ethylenediaminetetraacetic acid (EDTA) anticoagulant would be best because it inhibits the oxidation of lipids. c. A special yellow-top tube must be used for lipoprotein analysis because it contains a special anticoagulant that maintains the integrity of the lipoproteins. d. Serum would be best because it has no osmotic effects on cells and current cut points are based on serum values.

ANS: D

The preferred anticoagulant for lipoprotein measurements is EDTA, because it inhibits the oxidation of lipids and the proteolysis of apolipoproteins. It causes, however, a slight dilution of about 3% when compared with lipoprotein measurements on serum, upon which current cut points are based. Therefore serum would be the best sample for lipoprotein analysis.

DIF: 3

REF: Page 408

OBJ: 9

25. In addition to unesterified cholesterol, what is the second constituent of the outer coating of a

lipoprotein, labeled with a question mark and represented by a white circle in this diagram?

a. b. c. d.

Protein Phospholipid Lipoprotein A Chylomicrons

ANS: B

See Figure 23-16. Lipoproteins are typically spherical particles with nonpolar neutral lipids (triglycerides and cholesterol esters) in their core and more polar amphipathic lipids (phospholipids and free cholesterol) at their surface.

DIF: 1

REF: Page 398

OBJ: 1

26. The Friedewald formula is used to indirectly determine the concentration of which one of the

following? a. Triglyceride b. Phospholipid c. HDL cholesterol d. LDL cholesterol ANS: D

In the most widely used indirect method, (1) total cholesterol, (2) triglyceride, and (3) HDL cholesterol are measured in a fasting sample and LDL cholesterol is calculated from the primary measurements by use of the empirical Friedewald equation.

DIF: 1

REF: Page 409

OBJ: 10

27. Approximately one-third of the daily production of circulating cholesterol is converted in the

liver to form: a. bilirubin. b. estrogen. c. bile acids. d. hydrochloric acid.

ANS: C

See Figure 23-6. Approximately one-third of the daily production of cholesterol, or about 400 mg/day, is converted in the liver into bile acids.

DIF: 1

REF: Page 391-392

OBJ: 3

28. The high-sensitivity detection method for CRP (hs-CRP) used to detect low concentrations of

this protein is typically a(n): a. colorimetric assay. b. immunoassay. c. light-scattering technique. d. HPLC assay.

ANS: C

Of various techniques used to lower the limits of detection of CRP assays, the most successful approach has been to amplify the light-scattering properties of the antigen-antibody complex by covalently coupling latex particles to a specific antibody.

DIF: 1

REF: Page 410

OBJ: 11

29. The major component of a lipoprotein that functions to maintain the structural integrity of the

lipoprotein complex and that modulates the activity of the enzymes that act on lipoproteins is the: a. apolipoprotein. b. phospholipid. c. lipid core. d. lipoprotein lipase.

ANS: A

Apolipoproteins are the major protein components of lipoproteins. They have the following major functions: (1) modulating the activity of enzymes that act on lipoproteins, (2) maintaining the structural integrity of the lipoprotein complex, and (3) facilitating the uptake of lipoprotein by acting as ligands for specific cell surface receptors.

DIF: 1

REF: Page 399

OBJ: 4

30. In the intracellular-cholesterol transport pathway of lipoprotein metabolism, cholesterol

homeostasis is maintained through control of cellular uptake. The LDL cell surface receptor delivers lipoprotein particles containing cholesteryl esters to lysosomes. The apolipoprotein that is recognized by this receptor is apo: a. E. b. C-II. c. B-100. d. A2.

ANS: C

Cells receive cholesterol via uptake of extracellular lipoproteins by cell surface receptors, such as the LDL receptor (Figure 23-20). Most lipoprotein receptors deliver the intact lipoprotein particles to lysosomes, where they are degraded. The LDL receptor recognizes apo B-100.

DIF: 2

REF: Page 400

OBJ: 5

Chapter 24: Electrolytes and Blood Gases Test Bank MULTIPLE CHOICE 1. When arterial blood is exposed to air (as in air bubbles in a collection syringe), which one of

the following sets of changes occur? a. PO2 increased, PCO2 decreased, pH decreased b. PO2 decreased, PCO2 increased, pH decreased c. PO2 increased, PCO2 decreased, pH increased d. PO2 decreased, PCO2 decreased, pH decreased ANS: C

The CO2 content and PCO2 of blood exposed to air will decrease, and blood pH, which is a function of PCO2, will rise. In addition, blood from patients breathing room air that is exposed to atmospheric air gains O2. Blood can also be exposed to air simply from the air in the needle and the syringe hub dead space.

DIF: 2

REF: Page 426

OBJ: 12 | 13

2. Uptake of O2 by the blood in the lungs is controlled primarily by: a. the hemoglobin binding capacity of blood. b. how much hemoglobin A is available to bind O2. c. the amount of total CO2 bound to hemoglobin. d. the PO2 of alveolar air.

ANS: D

Uptake of O2 by the blood in the lungs is governed primarily by the PO2 of alveolar air and by the ability of O2 to diffuse freely across the alveolar membrane into the blood.

DIF: 1

REF: Page 424

OBJ: 9

3. Quantitative sweat chloride testing remains the standard for diagnostic testing of cystic

fibrosis (CF) because: a. a total gene deletion of the cystic fibrosis (CF) gene cannot be detected by direct mutational analysis. b. there are many mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein and direct mutational analysis is not always informative. c. a gene deletion on the X chromosome results in loss of an intracellular receptor protein, which can only be detected by protein analysis. d. an amino acid deletion in the CFTR gene resulting in the loss of electrolyte transport across cell membranes can only be detected by sweat testing.

ANS: D

CF is caused by a defect in the CFTR protein, and more than 1500 mutations of CFTR have been identified. Although direct mutational analysis is available, it is not informative in all cases, and a quantitative sweat chloride test remains the standard for diagnostic testing.

DIF: 1

REF: Page 417

OBJ: 4

4. The anticoagulant that is considered best for anaerobic collection of an arterial or venous

whole blood specimen for blood gas analysis is: a. lyophilized heparin. b. liquid heparin. c. sodium citrate. d. EDTA. ANS: A

Arterial or venous specimens are best collected anaerobically with lyophilized heparin anticoagulant in 1 to 3 mL sterile syringes. Lyophilized heparin is preferable to liquid heparin because liquid heparin, which has atmospheric PO2 and PCO2 values, dilutes the sample, with the effect being greatest when the syringe is not completely filled.

DIF: 1

REF: Page 426

OBJ: 12

5. Which one of the following is a cause of decreased fractional oxyhemoglobin (FO2Hb)? a. Elevated red blood cell (RBC) count b. Conversion of part of hemoglobin to dyshemoglobin c. Hyperventilation d. Change in PCO2 of arterial blood ANS: B

Decreases in arterial FO2Hb indicate either a low arterial PO2 or an impaired ability of hemoglobin to bind O2. Forms of hemoglobin that are not capable of reversibly binding of O2 include (1) methemoglobin (MetHb), (2) carboxyhemoglobin (COHb), (3) sulfhemoglobin (SulfHb), and (4) cyanmethemoglobin.

DIF: 2

REF: Page 423

OBJ: 1 | 11

6. An increase in blood pH with a concomitant decrease in PCO2 and a decreased body

temperature and 2,3-diphosphoglycerate will cause the oxygen dissociation curve to: a. shift to the right. b. shift to the left. c. remain unchanged.

ANS: B

See Figure 24-2. The location of the curve relative to the PO2 required to achieve a particular concentration of SO2 in the blood is a function of the affinity of the hemoglobin for O2.

The main causes for the curve to be displaced to the left are (1) hypothermia, (2) acute alkalemia, (3) hypocapnia, (4) low concentration of 2,3-DPG, (5) increased COHb and MetHb, or (6) a hemoglobin variant.

DIF: 3

REF: Page 426

OBJ: 1 | 10

7. In the Henderson-Hasselbalch equation, the term “pK'” is the: a. coefficient for oxygen in blood. b. solubility coefficient for potassium. c. negative log of hydrogen ion activity. d. negative log of the combined dissociation constant for carbonic acid.

ANS: D

Hasselbalch showed that a logarithmic transformation of the Henderson-Hasselbalch equation was a more useful form and used the symbols pH (= –log cH+) and pK' (= –log K'). K' is the apparent overall (combined) dissociation constant for carbonic acid.

DIF: 1

REF: Page 423

OBJ: 8

8. The PO2 at which the hemoglobin of the blood is half saturated with O2 is referred to as: a. oxygen saturation. b. oxygen dissociation. c. P50. d. the half-life of oxygen.

ANS: C

P50 is defined as the PO2 at which the hemoglobin of the blood is half saturated with O2.

DIF: 1

REF: Page 413

OBJ: 1

9. In regard to the colligative properties of a solution, the addition of solutes to pure solvent will

the vapor pressure of that solution compared with pure solvent. a. increase b. decrease c. not affect ANS: B

When solute is added to solvent, osmotic pressure increases and the vapor pressure of the solution is lowered below that of the pure solvent.

DIF: 2

REF: TPE agSe T 42B0ANKS OE BL J: LE 6 R.COM

10. Historically, chloride was measured in blood by spectrophotometry. Now the methods of

choice for chloride measurement include ion-selective electrodes and: a. enzymatic measurement of acidified chloride. b. atomic absorption spectrophotometry. c. immunoassay. d. coulometric-amperometric titration.

ANS: D

Historically, chloride was measured in body fluids and solids by mercurimetric titration and spectrophotometric methods. As these methods are no longer used, coulometric-amperometric titration and ISEs are the methods of choice today.

DIF: 1

REF: Page 416

OBJ: 2

11. A 24-hour-old infant is tested for quantitative sweat chloride because her older brother was

diagnosed with cystic fibrosis. After iontophoresis of pilocarpine nitrate and collection of sweat, the sample is analyzed by coulometric titration. The value of the infant’s sweat chloride was 23 mmol/L (reference interval: 29 mmol/L). The next day, the infant’s physician calls the laboratory to report that the infant has difficulty breathing and that the parents report the infant’s skin tasted salty. The physician is considering a diagnosis of cystic fibrosis. What type of error has likely occurred? a. The specimen likely evaporated before being analyzed in the laboratory. b. The infant was tested at too young of an age for accurate results to be obtained.

c. The specimen was collected over a site of a rash and contaminated with serous

fluid. d. The infant’s average sweat rate was too high to obtain accurate results.

ANS: B

Because of transient increases in sweat electrolytes shortly after birth, individuals should be at least 48 hours old before a sweat chloride test is performed.

DIF: 3

REF: Page 418

OBJ: 4 | 15

12. To stimulate sweating for a quantitative sweat chloride test,

is iontophoresed into the

skin. a. pilocarpine b. chloride c. epinephrine d. alcohol ANS: A

To stimulate sweat, localized sweating is produced by pilocarpine iontophoresis into an area of the skin. Iontophoresis uses a small electric current to deliver pilocarpine into the sweat glands from the positive electrode, while an electrolyte solution at the negative electrode completes the circuit.

DIF: 1

REF: Page 418

OBJ: 4

13. The high extracellular concentration of which cation contributes to the osmotic strength of

extracellular fluid? a. Chloride b. Potassium c. Sodium d. Bicarbonate ANS: C

Sodium is the major cation of extracellular fluid. Because it represents approximately 90% of the approximately 154 mmol of inorganic cations per liter of plasma, Na+ is responsible for almost one half the osmotic strength of plasma.

DIF: 1

REF: Page 414

OBJ: 2

14. Which of the following electrolytes is regulated in part by dietary intake? a. Chloride b. Potassium c. Sodium d. All of the above ANS: D

All of the electrolyte states are absorbed from ingested food, and excess is excreted by the renal system.

DIF: 1

REF: Page 416

OBJ: 2

15. The most common laboratory method of sodium/potassium measurement in a high-throughput

automated chemistry analyzer is: a. atomic absorption spectrophotometry. b. spectrophotometry. c. indirect ion-selective electrode measurement. d. direct ion-selective electrode measurement.

ANS: C

Indirect ion-selective electrode (ISE) methods are the methods used most commonly on today’s automated, high-throughput clinical chemistry systems. With direct ISE methods, the sample is presented to the electrodes without dilution. Direct ISEs are most common in blood gas analyzers and point-of-care devices where whole blood is directly presented to the electrodes.

DIF: 1

REF: Page 415

OBJ: 2 | 3

16. Osmolality is defined as the number of of solution. a. moles per liter b. equivalents per liter c. moles of osmotic substances per kilogram d. moles of osmotic substances per liter ANS: C

The term osmolality expresses concentrations relative to mass of solvent (1 osm solution is defined to contain 1 osm/kg H2O) as opposed to volume of solution.

DIF: 1

REF: Page 420

OBJ: 1

17. The “electrolyte exclusion effect” is: a. an underestimation of electrolyte concentration by indirect ISE methods when

hyperproteinemia is present. b. an overestimation of electrolyte concentration by direct ISE measurements only

when serum is used. c. the exclusion of certain solids by increased activity of electrolytes when

determining concentration of those solids. d. the exclusion of electrolytes in certain measurements when pH, PCO2, and PO2 are

elevated in arterial blood.

ANS: A

The electrolyte exclusion effect is the exclusion of electrolytes from the fraction of the total plasma volume that is occupied by solids. The volume of total solids (primarily protein and lipid) in an aliquot of plasma is approximately 7%. This electrolyte exclusion effect becomes problematic when pathophysiological conditions are present that alter the plasma water volume, such as hyperlipidemia or hyperproteinemia. In these settings, falsely low electrolyte values are obtained whenever samples are diluted before analysis, as in flame photometry or with indirect ISE methods.

DIF: 2 18.

REF: Page 415

OBJ: 1 | 3

The correct formula for calculating plasma osmolality is: a. 1.86  Na (mEq/L) + glucose (mg/dL) + urea (g/dL).

b. 1.86  Na (mmol/L) + glucose (mmol/L) + urea (mmol/L) + 9. c. 1.86  Na (mmol/L) + glucose (mmol/L)/18 + urea (mmol/L)/18 + 9. d. Na (mEq/L) + glucose (mg/dL) + urea (mg/dL).

ANS: B

The major osmotic substances in normal plasma are Na+, Cl–, glucose, and urea; thus expected plasma osmolality is calculated from an empirical equation.

DIF: 1

REF: Page 415

OBJ: 6

19. Which one of the following statements concerning electrolytes and electrolyte measurement is

incorrect? a. Routine laboratory analysis of electrolytes includes measurement of sodium, potassium, chloride, and bicarbonate as total carbon dioxide. b. Ion-selective electrode measurements are based on the measurement of the potential difference between the ISE and the reference electrode. c. Whole blood specimens should be stored at 4° C before separation. d. Specimen requirements for electrolyte analysis include use of unhemolyzed serum or plasma.

ANS: C

If a whole blood specimen is maintained at 4° C versus 25° C before separation, glycolysis is inhibited and the energy-dependent Na+, K+-ATPase, will not maintain the Na+/ K+ gradient.

An increase in plasma K+ will occur as a result of K+ leakage from erythrocytes and other cells.

DIF: 2

REF: Page 414

OBJ: 2 | 15

20. Which blood gas parameter is most affected by the choice of arterial versus venous blood? a. pH b. PCO2 c. ctCO2 d. PO2 ANS: D

Differences in measured blood gas values between arterial and venous are most pronounced for PO2. PO2 is generally 50 to 60 mm Hg lower in venous blood after O2 is released in the capillaries.

DIF: 2

REF: Page 426

OBJ: 9

21. A blood gas parameter is affected by the choice of arterial versus venous blood. What is the

reason for the difference in the value of this correctly identified parameter? a. The pH of arterial blood is significantly higher because oxygen affects it, as noted in the Henderson-Hasselbalch equation. b. The hemoglobin in arterial blood is much richer in CO2 because it has just returned from the lungs. c. PO2 is generally lower in venous blood after O2 is released in the capillaries and higher in arterial blood because this blood has passed through the lungs. d. Arterial blood contains much more because it has passed through the glomerulus.

ANS: C

Differences in measured blood gas values between arterial and venous blood are most pronounced for PO2. In fact, PO2 is the only clinical reason for arterial collections. PO2 is generally 60 mm Hg lower in venous blood after O2 is released in the capillaries.

DIF: 2

REF: Page 426

OBJ: 9

22. Although aqueous fluid control materials are the most commonly used commercial controls

for blood gas and pH measurements, what is their main disadvantage? a. They are dissimilar to blood by having lower viscosity and surface tension. b. They must be shaken vigorously before being opened. c. The buffer that is used contains high levels of lead. d. They overestimate pH because the buffer is a weak base.

ANS: A

The disadvantages of aqueous controls stem from their dissimilarity to blood. Lower viscosity and surface tension confer different washout characteristics and impair their ability to reflect clogging. Greater electrical conductivity reduces their effectiveness in detecting inadequate grounding, and lower thermal coefficients make them slower to detect failures of temperature control.

DIF: 1

REF: Page 428

OBJ: 14

23. An instrument that hemolyzes whole blood by sonication then determines total hemoglobin

fractions by spectrophotometry and calculation is called a(n): a. pulse oximeter. b. potentiometer. c. co-oximeter. d. ion-selective electrode.

ANS: C

A co-oximeter is present in many modern blood gas analyzers. These instruments prepare a hemolysate from whole blood by sonication, and by spectrophotometry they determine the total amount of hemoglobin and the percent of each of the hemoglobin species present in the sample.

DIF: 1

REF: Page 424

OBJ: 1

24. The basic methodology used to measure pH, PCO2, and PO2 is: a. tonometry. b. potentiometry. c. osmometry. d. spectrophotometry.

ANS: B

The tip of the pH measuring electrode typically used in blood gas analyzers is made of H+-sensitive glass, and most pH measuring and reference electrodes differ little from those of free-standing pH meters. The membrane of the PCO2 electrode usually consists of Teflon or silicone rubber approximately 25 µm thick. The electrolyte solution is a thin film containing sodium bicarbonate at 0.005 mol/L and sodium chloride (NaCl) at 0.1 mol/L saturated with AgCl. The membrane of a PO2 electrode in a standard blood gas analyzer is usually 20 µm thick polypropylene. The electrolyte solution is a thin film of phosphate buffer saturated with AgCl but also containing KCl. As O2 diffuses into the electrolyte, it reacts with the cathode to cause current to flow.

DIF: 1

REF: Page 427

OBJ: 14

25. In an individual older than 6 months of age, which one of the following laboratory results is

usually associated with cystic fibrosis? a. Sweat chloride concentration greater than 60 mmol/L b. Sweat chloride less than or equal to 10 mmol/L c. Sweat chloride concentration greater than 160 mmol/L d. Sweat chloride concentration between 40 and 60 mmol/L ANS: A

Sweat chloride values greater than 60 mmol/L are considered to be diagnostic for cystic fibrosis. Few other disorders will produce this concentration of chloride in sweat.

DIF: 1

REF: Page 419

OBJ: 4 | 5

26. A blood sample from an individual with leukemia is submitted for blood gas analysis. The

transport of the sample is delayed for approximately an hour before analysis. What affect, if any, will these two variablT esEhSavTeBoAnNthKeSbE loLoL dE gaRs.aC naOlyMsis results? a. There will be no effect on any of the blood gas parameters. b. All blood gas parameters will increase in value with an elevated white blood cell count due to the presence of azurophilic granules. c. Because of leukocyte glycolysis, pH decreases, PCO2 increases, and PO2 decreases. d. All blood gas parameters will decrease in value because of the leukocytosis-induced hemolysis.

ANS: C

Glycolysis by leukocytes, platelets, and reticulocytes changes blood gas values. In freshly drawn blood with a normal PO2 that is maintained anaerobically, cell respiration causes PO2 to decrease at a rate of 2 mm Hg/h at room temperature and 5 to 10 mm Hg/h at 37° C. Adverse effects of glycolysis and cellular respiration on pH, ctCO2, PO2, and PCO2 of blood are best prevented by analysis within 30 minutes after collection. The small changes in values that are to be expected with delays in analysis are true only when the white blood cell count (WBC) is normal or is only slightly elevated. Glycolysis and the resulting effects on pH, PO2, and PCO2 increase dramatically with markedly elevated WBC, such as occurs in leukemia.

DIF: 3

REF: Page 426

OBJ: 12 | 13 | 15

27. The most commonly measured colligative property of urine or plasma that is tested in the

clinical laboratory to determine osmolality is: a. vapor pressure.

b. the boiling point. c. osmotic pressure. d. the freezing point.

ANS: D

Freezing point depression is most commonly used in clinical laboratories as a basis for the measurement of osmolality because of its simplicity. Furthermore, freezing point depression, unlike vapor pressure, is independent of changes in ambient temperature.

DIF: 1

REF: Page 414

OBJ: 6

28. The specimen of choice for measurement of potassium (K+) is plasma because: a. anticoagulants preserve the potassium ionic activity better than serum. b. platelets release potassium during the coagulation process in a serum sample. c. hemolysis is easily avoided when obtaining a plasma sample. d. the electrolyte exclusion effect is avoided in a plasma sample.

ANS: B

Potassium concentrations in plasma and whole blood are 0.1 to 0.7 mmol/L lower than those in serum, and most reference intervals for serum K+ are 0.2 to 0.5 mmol/L higher than those for plasma K+. The extent of this difference depends on the platelet count, because the additional K+ in serum is primarily a result of platelet rupture during coagulation.

DIF: 1

REF: Page 421

OBJ: 2

TRUE/FALSE

TrEedSaTt B37A°NCKw SiEllLdLem EoRn.stCraOteMa falsely increased potassium value 1. Whole blood specimens sto because of red blood cell hemolysis.

ANS: F

A falsely decreased K+ value has been observed if an unseparated sample is stored at 37° C, because glycolysis occurs and K+ shifts intracellularly.

DIF: 1

REF: Page 414

OBJ: 2

Chapter 25: Hormones Test Bank MULTIPLE CHOICE 1. The half-life of a protein hormone in plasma is: a. long, usually greater than 90 minutes. b. long, at least 24 hours. c. short, more than 1 hour but less than 3 hours. d. short, approximately 10 to 30 minutes.

ANS: D

The half-life of polypeptide or protein hormones in plasma is short ( 10 to 30 minutes), and wide fluctuations in their concentration may be seen in several physiological and pathological circumstances.

DIF: 1

REF: Page 431

OBJ: 2

2. Which one of the following statements concerning steroid hormones is correct? a. Steroid hormones attach to a receptor on the surface of a cell, which eventually

induces enzyme phosphorylation within the cell. b. Steroid hormones are hydrophobic when free and bind to intracellular receptors in

the nucleus. c. Steroid hormones, because of their structure, are not bound to carrier proteins as

they circulate in the blood. d. Steroid hormones haveTaEvS erTyBsA hoNrtKhSaE lf-LliL feE(R us.uC alO lyM<30 minutes) in the

circulation.

ANS: B

Free steroid hormones, being hydrophobic, enter the cell by passive diffusion and bind with intracellular receptors in the cytoplasm or the nucleus.

DIF: 2

REF: Page 431

OBJ: 1 | 2 | 4

3. The analytical method that provides better analytical sensitivity in hormone detection than

other methods such as immunoassay or receptor-based assays is: a. tandem mass spectrometry. b. bioassay. c. immunometric assay. d. spectrophotometry.

ANS: A

Compared with older methods, tandem mass spectrometry offers greater analytical sensitivity, accuracy, and speed.

DIF: 1

REF: Page 440

OBJ: 6

4. Which of the following protein hormones produces a decrease in blood glucose by causing

glucose to enter cells for energy production? a. Insulin

b. Aldosterone c. Thyroid hormone d. Cortisol ANS: A

In the regulation of blood glucose and in response to a glucose load, insulin is promptly released from the pancreas, which regulates the dispersal of glucose into cells (fat, muscle, liver, and brain) for the metabolism necessary to produce energy from glucose.

DIF: 2

REF: Page 436

OBJ: 2 | 3

5. Considering the classification of hormones by structure, an example of a steroid hormone

would be: a. testosterone. b. parathyroid hormone (PTH). c. cortisol. d. all of the above.

ANS: C

Steroid hormones (e.g., cortisol, estrogen) are hydrophobic and insoluble in water. These hormones circulate in plasma, reversibly bound to transport proteins with only a small fraction free, or unbound and available to exert physiological action.

DIF: 1

REF: Page 431

OBJ: 2

6. An example of a protein hormone synthesized in the hypothalamus, with the principal action

to control the release of thyroid-stimulating hormone, is: a. prolactin. b. thyroid stimulating hormone. c. ACTH. d. thyrotropin releasing hormone.

ANS: D

See Table 25-1. Hypothalamic hormones are typically releasing hormones that affect protein hormones in the pituitary gland.

DIF: 1

REF: Page 432

OBJ: 2

7. Which one of the following hormones requires a transport protein to move it through the

circulation? a. Prolactin b. Aldosterone c. Estrogen d. Parathyroid hormone ANS: C

Steroid hormones (e.g., cortisol, estrogen) are hydrophobic and insoluble in water. These hormones circulate in plasma, reversibly bound to transport proteins.

DIF: 2

REF: Page 431

OBJ: 1 | 2

8. Which one of the following statements concerning protein hormones is correct?

a. A protein hormone binds to a receptor within the cell or on the nucleus of the cell,

thereby directly affecting protein synthesis. b. A protein hormone, once bound to its receptor, activates adenylyl cyclase, which

leads to eventual phosphorylation of other cellular enzymes. c. The complex of protein hormone/receptor diffuses into the cell nucleus and has a

suppressing effect on RNA synthesis. d. All protein hormones are bound to a transport protein to move through the circulation.

ANS: B

Protein hormones bind cell surface receptors, which are G-protein coupled. Binding to these G-protein-coupled receptors begins a cascade of activation of specific enzymes that generate molecules that serve as second messengers to affect the hormone response. One of these second messengers is adenylyl cyclase.

DIF: 2

REF: Page 437

OBJ: 2 | 4

9. A group of hormones produced by the gastrointestinal tract that stimulates insulin secretion

from the pancreas and slows the rate of gastric emptying is referred to as: a. incretins. b. insulinomas. c. calcitriols. d. steroids.

ANS: A

A group of gastrointestinal hormones termed incretins is released during eating and stimulates insulin secretion from the pancreas in advance of any measurable increase in blood glucose.

Incretins also affect the ratT eE ofSaTbB soArpNtiK oS nE ofLnLuE triRen.tC sO froMm the gut by slowing down the rate of gastric emptying.

DIF: 1

REF: Page 436

OBJ: 1

10. Which of the following is an effect of increased parathyroid hormone (PTH) secretion from

the parathyroid gland in the homeostatic control of serum calcium? a. Decreased blood calcium levels b. Increased renal absorption of phosphate c. Decreased bone calcium efflux from the skeleton d. Increased intestinal absorption of calcium ANS: D

When ionized calcium concentrations fall, PTH synthesis and secretion are stimulated. This additional PTH will attempt to restore serum-ionized calcium by enhancing renal tubular reabsorption of calcium and calcium efflux from the skeleton. PTH also catalyzes the synthesis of the renal hormone calcitriol (1,25-dihyroxycholecalciferol), which acts on the gut to increase intestinal absorption of calcium.

DIF: 2

REF: Page 436

OBJ: 3 | 5

11. As part of homeostatic control by hormones, the metabolism of electrolytes and water balance

is controlled in part by the renal system. What hormone synthesized by the kidneys affects water and electrolyte balance?

a. b. c. d.

Aldosterone Renin Vasopressin; antidiuretic hormone (ADH) Insulin

ANS: B

Water and electrolyte metabolism is regulated by aldosterone from the adrenal gland, renin from the kidney, and vasopressin [antidiuretic hormone (ADH)] from the posterior pituitary gland.

DIF: 2

REF: Page 436

OBJ: 3

12. Calcium concentration in the blood is regulated by which of the following hormones? a. Calcitriol b. Parathyroid hormone c. Cortisol d. Both a and b ANS: D

When serum calcium is low, PTH will attempt to restore serum (free) calcium by enhancing renal tubular reabsorption of calcium and also calcium efflux from the skeleton. PTH in turn catalyzes the synthesis of the renal hormone calcitriol (1,25-dihydroxyvitamin D), which acts on the intestine to increase absorption of calcium.

DIF: 2

REF: Page 436

OBJ: 1 | 3

13. Binding to a receptor at the outer cell membrane to induce phosphorylation via adenylyl

cyclase and cAMP of certaTinEiS ntTraBcA elN luK laS rE enLzL ym EeRs.isCaOpMroperty of which class of hormone? a. Protein b. Steroid c. Amino acid-derived d. Both a and c ANS: D

Both protein and amino acid-derived hormones utilize the G-protein coupled receptor system.

These hormones interact with membrane-associated receptors and use a second messenger system to exert a physiological effect.

DIF: 2

REF: Page 437

OBJ: 4

14. The release of thyroid-stimulating hormone (from the pituitary gland) stimulates the release of

thyroid hormones from the thyroid gland. When the level of thyroid hormones increases in the circulation, they shut off the release of TSH from the pituitary. This is an example of which type of feedback? a. Open loop feedback b. Positive feedback c. Negative feedback d. None of the above ANS: C

Several pituitary hormones are responsible specifically for the growth and development of endocrine glands themselves, and thus are responsible for control of synthesis and secretion of other hormones. Those other hormones provide negative feedback on secretion of the pituitary hormones. Thyroid-stimulating hormone (TSH) regulates growth of the thyroid gland and iodination of amino acids to produce the thyroid hormones triiodothyronine and thyroxine.

DIF: 2

REF: Page 435

OBJ: 5

15. An example of a polypeptide hormone that is part of the complex integrative function of many

hormones involved in development of the human organism is: a. growth hormone. b. estrogen. c. cortisol. d. thyroxine.

ANS: A

Normal growth and development of the whole human organism is dependent on the complex integrative function of many hormones, including (1) gonadal steroids (estrogen and androgen), (2) growth hormone, (3) cortisol, and (4) thyroxine. Of these, only growth hormone is a protein or polypeptide hormone.

DIF: 2

REF: Page 435

OBJ: 2 | 3

Chapter 26: Catecholamines and Serotonin Test Bank MULTIPLE CHOICE 1. In the gastrointestinal (GI) tract, dopamine functions as a modulator of the enteric nervous

system or as a paracrine substance. What essential enzyme is required for synthesis of dopamine in the dopaminergic system in the GI tract? a. Tryptophan hydroxylase b. Tyrosine hydroxylase c. Catechol-O-methyltransferase (COMT) d. Monoamine oxidase (MAO) ANS: B

In the kidneys, dopamine is produced mainly from circulating L-dopa, while in the gastrointestinal tract, production of dopamine requires the presence of tyrosine hydroxylase or other sources of L-dopa.

DIF: 1

REF: Page 444

OBJ: 2

2. In the diagnosis of pheochromocytoma, what hormone is being assessed by measuring urine

metanephrine? a. Epinephrine b. Dopamine c. Serotonin d. Norepinephrine ANS: A

Metanephrine is a physiologically inactive catecholamine metabolite resulting from O-methylation of epinephrine. Increases in plasma or urinary fractionated metanephrines are usually high enough to establish conclusively the presence of most cases of pheochromocytomas.

DIF: 1

REF: Page 443

OBJ: 2 | 3 | 5

3. A neoplasm considered to be a pediatric cancer that is derived from the neural crest cells of

the sympathetic nervous system is referred to as a: a. pheochromocytoma. b. gastroenteropancreatic neuroendocrine tumor. c. neuroblastoma. d. carcinoid tumor.

ANS: C

Neuroblastomas are neoplasms that derive from primordial neural crest cells of the sympathetic nervous system. Neuroblastomas are almost exclusively a pediatric cancer, accounting for approximately 7% of all childhood neoplasms.

DIF: 1

REF: Page 451

OBJ: 1

4. Measurement of urinary metanephrine and vanillylmandelic acid (VMA) assesses the amount

of hormone secreted by the and is done to detect the presence of a. gastrointestinal (GI) tract; carcinoid tumor b. adrenal medulla; pheochromocytoma c. adrenal cortex; Cushing syndrome d. medulla of the brain; neuroblastoma

.

ANS: B

Excess production of metabolites of norepinephrine and epinephrine by a pheochromocytoma are measured in urine as VMA and metanephrine.

DIF: 1

REF: Page 449

OBJ: 1 | 3 | 5

5. Which one of the following substances is measured in urine to determine the presence of a

gastroenteropancreatic neuroendocrine tumor in an individual with carcinoid syndrome? a. VMA b. Metanephrine c. Homovanillic acid (HVA) d. 5-Hydroxyindole acetic acid (5-HIAA) ANS: D

The clinical laboratory evaluation of the carcinoid syndrome relies on measurements of serotonin and its metabolites in body fluids and tissue. Most physicians rely on the measurement of 5-HIAA to diagnose carcinoid syndrome.

DIF: 2

REF: Page 453

OBJ: 1 | 6

ocEalSrT esBuA ltsNiK nS pE heLoL chEroRm ytM oma testing, the clonidine 6. In the assessment of equivT .oCcO suppression test is used to differentiate between: a. elevated blood pressure caused by pheochromocytoma versus that caused by carcinoid tumor. b. increased serotonin production by the GI tract versus serotonin from the brain. c. adrenal gland and GI tract increased synthesis of dopamine. d. adrenal gland and sympathetic nervous system increases in catecholamine synthesis.

ANS: D

The clonidine suppression test may be useful for distinguishing patients with increases in plasma catecholamines caused by pheochromocytomas from those with increases caused by sympathetic activation. Clonidine suppresses norepinephrine release by sympathetic nerves, so decreases in elevated plasma norepinephrine after clonidine suggest sympathetic activation, whereas lack of a decrease suggests a pheochromocytoma.

DIF: 2

REF: Page 450

OBJ: 1 | 5

7. Pheochromocytomas: a. produce hypotension (decreased blood pressure). b. tend to secrete serotonin in increased amounts. c. are benign in the majority of cases. d. are tumors derived from enterochromaffin cells.

ANS: C

Catecholamine-producing tumors that derive from chromaffin cells are referred to as pheochromocytomas, with hypertension as the most common sign. Increases in plasma or urinary fractionated metanephrines (not serotonin) are usually high enough to conclusively establish the presence of most cases of pheochromocytomas. Although mostly benign, about 10% of pheochromocytomas metastasize.

DIF: 1

REF: Page 449

OBJ: 1 | 5

8. The amino acid precursor for the neurotransmitter serotonin (5HT) is: a. tyrosine. b. tryptophan. c. threonine. d. cytosine.

ANS: B

The conversion of tryptophan to 5-hydroxytryptophan is the first step of serotonin synthesis.

DIF: 1

REF: Page 444

OBJ: 2

9. Metabolism of norepinephrine and epinephrine in adrenal chromaffin cells requires the

presence of which one of the following enzymes for conversion into normetanephrine and metanephrine? a. Catechol-O-methyltransferase b. Dopamine--hydroxylase c. Tyrosine hydroxylase d. Monoamine oxidase ANS: A

See Figure 26-4. In adrenal chromaffin cells, the presence of COMT leads to metabolism of norepinephrine to normetanephrine and of epinephrine to metanephrine.

DIF: 1

REF: Page 445

OBJ: 2 | 3

10. In the sympathetic component of the autonomic nervous system, norepinephrine acts to: a. increase heart rate and blood pressure. b. induce hypotension. c. dilate the peripheral blood vessels. d. increase the release of serotonin from the brain.

ANS: A

Most sympathetic postganglionic nerves liberate norepinephrine as their neurotransmitter.

With sympathetic activation, the heart rate is increased, peripheral arterioles are constricted, skeletal arterioles are dilated, and the blood pressure is elevated.

DIF: 1

REF: Page 448

OBJ: 2 | 4

11. Regarding catecholamines, the amino acid from which dopamine is synthesized? a. Threonine b. Tryptophan c. Tyrosine d. Cytosine

ANS: C

Conversion of tyrosine to 3,4-dihydroxyphenylalanine and then to dopamine is the initiation of catecholamine synthesis. Dopamine is further converted to norepinephrine by dopamine -hydroxylase, and the additional presence of phenylethanolamine N-methyltransferase in adrenal medullary chromaffin cells leads to further conversion of norepinephrine to epinephrine.

DIF: 1

REF: Page 444

OBJ: 2

12. An overnight fast is recommended for individuals being tested for carcinoid syndrome

because: a. dietary interference, particularly with foods that contain 5-hydroxyindoles, will produce a false increase in plasma 5-HIAA measurement. b. no food should be present in the GI tract for 12 hours before analysis of catecholamine metabolites. c. monoamine systems are targets of certain components of foods that contain tyrosine, and a false-negative result will occur in HVA testing. d. certain foods interfere with the methods of analysis used for serotonin analysis, particularly the high performance liquid chromatography (HPLC) assays.

ANS: A

Dietary interference can be particularly troublesome for measurements of serotonin metabolites, requiring detailed dietary instruction for these patients. Dietary sources of 5-hydroxyindoles (e.g., walnuts, bananas, avocados, eggplants, pineapples, plums, and tomatoes) should be restricted. Measurements in plasma after an overnight fast have been advocated as more reliable since this avoids the confounding influence of dietary serotonin.

DIF: 2

TESTBANKSOEBL LER.COM J: 8

REF: Page 455

13. The urinary metabolite measured as an indicator of dopamine synthesis is: a. metanephrine. b. homovanillic acid. c. vanillylmandelic acid. d. catechol-O-methyltransferase.

ANS: B

Excreted dopamine metabolites include homovanillic acid (HVA) and dopamine sulfate.

DIF: 1

REF: Page 448

OBJ: 3

14. The rate-limiting step in the biosynthesis of catecholamines is the: a. conversion of 3-methoxy-4-hydroxyphenylglycol (MHPG) to VMA by alcohol

dehydrogenase. b. conversion of tryptophan to 5-hydroxytryptophan by tryptophan hydroxylase. c. metabolism by catechol-O-methyltransferase (COMT) to MHPG. d. conversion of tyrosine to 3,4-dihydroxyphenylalanine by tyrosine hydroxylase.

ANS: D

The rate-limiting step in catecholamine biosynthesis involves conversion of tyrosine to 3,4-dihydroxyphenylalanine (L-dopa) by the enzyme, tyrosine hydroxylase. Tissue sources of catecholamines are principally dependent on the presence of tyrosine hydroxylase.

DIF: 1

REF: Page 444

OBJ: 2

15. The use of tricycle antidepressants by an individual may produce incorrect results in the

measurement of norepinephrine and normetanephrine during testing for pheochromocytoma.

How will results be affected and why? a. The results will be falsely elevated because of inhibition of monoamine reuptake. b. The results will be falsely decreased because of increased synthesis of monoamine oxidase. c. The results will be falsely elevated because these drugs increase synthesis of dopamine. d. The results will be falsely decreased because these drugs inhibit tyrosine hydroxylase.

ANS: A

Tricyclic antidepressants are a major source of false-positive results for measurements of norepinephrine and normetanephrine, a result of the primary actions of these agents to inhibit monoamine reuptake.

DIF: 3

REF: Page 455

OBJ: 8

16. A man visits his physician complaining of hypertension (elevated heart rate and blood

pressure), periodic bouts of profuse sweating, and occasional severe headaches. These symptoms are indicative of: a. Cushing syndrome. b. carcinoid syndrome. c. pheochromocytoma. d. neuroblastoma.

ANS: C

Hypertension is the most common sign of pheochromocytoma, and other symptoms include headache, palpitations, diaphoresis (excessive sweating), pallor, nausea, attacks of anxiety, and generalized weakness. These symptoms are all caused by the effect of elevated epinephrine and norepinephrine.

DIF: 2

REF: Page 449

OBJ: 5 | 10

17. Currently, the most common method of analysis for plasma catecholamines is: a. liquid chromatography (LC) with electrochemical (EC) detection. b. HPLC. c. mass spectrometry. d. spectrophotometry.

ANS: A

LC-EC methods remain commonly used for measurements of plasma catecholamines, whereas mass spectrometric methods are being increasingly used for measurements of urinary catecholamines.

DIF: 1

REF: Page 455

OBJ: 9

18. All of the following represent metabolic effects caused by the action of epinephrine secreted

from the adrenal gland except:

a. b. c. d.

increased lipolysis. bronchodilation. increased protein synthesis. glycogenolysis.

ANS: C

Epinephrine stimulates lipolysis, ketogenesis, thermogenesis, and glycolysis and raises plasma glucose by stimulating glycogenolysis and gluconeogenesis. Epinephrine also has potent effects on pulmonary function, causing dilation of the airway.

DIF: 2

REF: Page 446

OBJ: 2

TRUE/FALSE 1. Dopamine in the central nervous system functions as a neurotransmitter important for

regulating an overall state of attention and vigilance.

ANS: F

Dopamine in the brain influences reward-seeking behavior and is important for the initiation and maintenance of movement, while norepinephrine-producing neurons of the brainstem participate in regulating the activity of the sympathetic nervous system and the overall state of attention and vigilance.

DIF: 1

REF: Page 448-449

OBJ: 2 | 4

MATCHING

Match the disorder with the diagnostic analyte measured in the laboratory. a. Gastroenteropancreatic endocrine tumor b. Tumor of adrenal medullary chromaffin cells c. Pineal gland tumor d. Neuroblastoma 1.

2.

3.

4.

Plasma/urine metanephrines Urinary VMA Melatonin Urinary 5-HIAA

1. ANS: D DIF: 3 REF: Page 452 OBJ: 2 | 5 | 6 MSC: A tumor of the adrenal medullary chromaffin cells is a pheochromocytoma, which produces elevated catecholamine metabolites such as metanephrine.

2. ANS: A DIF: 3 REF: Page 444 OBJ: 2 | 5 | 6 MSC: HVA and VMA, produced respectively from dopamine and norepinephrine, are most widely used for diagnosis of a neuroblastoma.

3. ANS: C DIF: 3 REF: Page 444 OBJ: 2 | 5 | 6 MSC: Melatonin is synthesized in the pineal gland.

4. ANS: B DIF: 3 REF: Page 451 OBJ: 2 | 5 | 6 MSC: Carcinoid tumors of the GI tract result in elevated 5-HIAA because of elevated serotonin produced by the tumor.

Chapter 27: Vitamins, Trace Elements, and Nutritional Assessment Test Bank MULTIPLE CHOICE 1. Which one of the following statements concerning folic acid is correct? a. Folic acid is a component of coenzyme A and is required for fat metabolism. b. Folic acid acts as a hormone in calcium regulation. c. Folic acid deficiency results in megaloblastic anemia. d. One form of folic acid is referred to as pyridoxal phosphate.

ANS: C Megaloblastic anemia (characterized by large, abnormally nucleated erythrocytes in the bone marrow) is the major clinical manifestation of folate deficiency, although sensory loss and neuropsychiatric changes may also occur.

DIF:

2

REF: Page 479

OBJ: 5

2. Deficiency of which of the following vitamins will result in decreased heme synthesis? a. Niacin b. Thiamine c. Pyridoxal phosphate (PLP) d. Riboflavin ANS: C The biosynthesis of hemT eE deSpT enBdA sN onKtS heEeLaL rlE yR fo.rm CaOtiMon of 5-aminolevulinate from PLP-dependent condensation of glycine and succinyl-CoA followed by decarboxylation.

DIF:

2

REF: Page 472

OBJ: 4 | 5

3. Which one of the following vitamins will aid in the absorption of iron by the intestine? a. C b. B12 c. A d. D ANS: A Ascorbic acid acts as a cofactor for a number of mixed function oxidases in processes in which it promotes enzyme activity by maintaining metal ions in their reduced form, particularly iron and copper.

DIF:

1

REF: Page 475

OBJ: 4

4. Absorption of vitamin B12 requires the presence of: a. intrinsic factor. b. vitamin C. c. insulin. d. folic acid.

ANS: A Vitamin B12 binds to intrinsic factor (IF), a glycoprotein with a molecular weight of approximately 50 kDa, which is produced by the gastric mucosa. When the vitamin B12-IF complex reaches the distal ileum, it is bound by receptors on the surface of mucosal epithelial cells and then enters the cells.

DIF:

1

REF: Page 473

OBJ: 4

5. Which vitamin is given to a newborn within minutes of birth? a. D b. B12 c. A d. K ANS: D Hemorrhagic disease of the newborn condition is prevented by the prophylactic administration of 0.5 to 1.0 mg of phylloquinone intramuscularly, or 2.0 mg given orally immediately after birth.

DIF:

1

REF: Page 467

OBJ: 3

6. Scurvy is associated with deficiency of which one of the following vitamins? a. A b. C c. B12 d. D ANS: B Protracted deficiency of vitamin C leads to the classic disease of scurvy. The lack of vitamin C causes an inability to form adequate intercellular substance in connective tissue; it is reflected in swollen, tender, and often bleeding or bruised loci at joints and in other areas.

DIF:

1

REF: Page 476

OBJ: 5

7. Which one of the following vitamins would be least affected by long periods of fat malabsorption? a. A b. E c. D d. C ANS: D Vitamin C, being a water-soluble vitamin, would not be affected by fat malabsorption syndromes.

DIF:

2

REF: Page 461

OBJ: 2

8. The trace element that is important in the stabilization of the surface of a regenerating tooth is: a. copper.

b. boron. c. fluoride. d. manganese.

ANS: C The fluoride ion can be exchanged for hydroxyl in the crystal structure of apatite, a main component of skeletal bone and teeth. This stabilizes the regenerating tooth surface.

DIF:

1

REF: Page 488

OBJ: 10

9. A 65-year-old woman was admitted to the hospital in mild congestive heart failure. She complained of a burning sensation in her calves and feet and of weight loss. Upon admission she appeared confused, depressed, and pale. She had some edema around her ankles. Her lab results were as follows: low hemoglobin and hematocrit, increased RBC size, decreased RBC and WBC count, and hypersegmented neutrophils. All basic chemistry values were normal. Which vitamin should be tested for deficiency? a. Vitamin A b. Vitamin B12 c. Vitamin C d. Vitamin D ANS: B Deficiency of vitamin B12 in humans is associated with megaloblastic anemia and neuropathy, and required maintenance of vitamin B12 levels is based on the amount necessary for the maintenance of hematological status. Classic morphological changes in the blood, in approximate order of appearance, are (1) hypersegmentation of neutrophils, (2) macrocytosis, (3) anemiaT, E (4S) T leB ukAoNpK enSiaE, L anLdE(R 5).thCrO om Mbocytopenia.

DIF:

3

REF: Page 474

OBJ: 4 | 5 | 7

leads to the symptoms observed in vitamin B12 deficiency.

10. A lack of a. retinol binding protein b. calcium ingestion c. adequate vitamin intake d. intrinsic factor ANS: D Vitamin B12 binds to intrinsic factor (IF), which is produced by the gastric mucosa. When the vitamin B12–IF complex reaches the distal ileum, it is bound by receptors on the surface of mucosal epithelial cells and then enters the cells. Intrinsic factor is required for B12 to enter cells. An autoimmune disease, pernicious anemia, leads to chronic atrophic gastritis, which results in formation of autoantibodies to gastric parietal cells and intrinsic factor.

DIF:

2

REF: Page 473

OBJ: 4

11. What is the common cause of vitamin B12 deficiency? a. Hyperkeratosis b. Scurvy c. Pernicious anemia d. Rickets

ANS: C The most common cause of vitamin B12 deficiency is pernicious anemia, an autoimmune disease.

DIF:

2

REF: Page 474

OBJ: 1 | 4

12. Trace elements are: a. organic molecules derived from a vitamin that functions catalytically in an enzyme system. b. inorganic molecules found in human and animal tissues in milligram per kilogram amounts or less. c. organic micronutrients that must be supplied exogenously and are often the precursors to a metabolically derived coenzyme. d. natural reactants, usually either a metal ion or coenzyme, required in an enzyme-catalyzed reaction.

ANS: B Inorganic micronutrients present at very low concentrations in body fluids and tissue.

DIF:

1

REF: Page 482

OBJ: 1

13. What specific specimen collection procedures should be observed when assessing zinc deficiency? a. Plasma is the specimen of choice to avoid contamination by RBCs, WBCs, and platelets. b. Steel collection needles and EDTA-containing blood-collection tubes should be used. c. A 24-hour urine collection with no preservative added should be used for analysis. d. Plastic cannulae and special collection tubes should be used for collection of this element.

ANS: A Plasma samples are preferred to serum for zinc analysis because of possible zinc contamination from erythrocytes, platelets, and leukocytes during clotting and centrifugation.

DIF:

2

REF: Page 495

OBJ: 12

14. Which one of the following trace elements, when combined with an enzyme, is essential for stabilization of extracellular matrixes such as collagen and elastin? a. Cobalt b. Chromium c. Copper d. Zinc ANS: C Protein-lysine 6-oxidase (lysyl oxidase) is a cuproenzyme that is essential for stabilization of extracellular matrixes, specifically the enzymatic cross-linking of collagen and elastin.

DIF:

2

REF: Page 486

OBJ: 10

15. The most commonly used method of analysis for assessing vitamins A, K, and B6 is: a. spectrophotometry. b. high performance liquid chromatography (HPLC). c. immunoassay. d. competitive protein binding.

ANS: B See Table 27-2. Although any of these methods is appropriate for vitamin analysis, HPLC is most often used in the assessment of the vitamins listed.

DIF:

1

REF: Page 463, Table 27-2

OBJ: 6

16. A 10-year-old girl visits her pediatrician. The physician notes that the girl has immature secondary sex characteristics and small stature. Her mother who has accompanied her complains that the adolescent also exhibits very slow healing of cuts and scrapes and has had some hair loss. Your laboratory has ruled out any inborn error of metabolism and possible cancer. Deficiency of what trace element might be responsible for the stated symptoms? a. Copper b. Chromium c. Selenium d. Zinc ANS: D In children, reduced growth and other developmental abnormalities can develop with zinc deficiency. Other symptoTmEsSinTcB luAdN eK (1S )E diL arLrhEeR a,.(2C)OmMental depression, (3) dermatitis, (4) delayed wound healing, and (5) alopecia.

DIF:

3

REF: Page 495

OBJ: 10 | 12 | 14

17. Which one of the following trace elements would be most affected when a hemolyzed sample is used for analysis? a. Copper b. Chromium c. Manganese d. Cobalt ANS: C Hemolysis should be prevented during sample collection and separation when assessing manganese. Whole blood has about 10 times as much manganese as plasma or serum, and if serum or plasma is used for testing, hemolysis will produce a falsely increased result.

DIF:

2

REF: Page 490

OBJ: 12

18. Activity of which one of the following enzymes might be markedly affected by a deficiency of zinc? a. Creatinine kinase b. Cholinesterase c. Alkaline phosphatase

d. Gamma glutamyl-transferase ANS: C Examples of zinc metalloenzymes in human tissue include (1) carbonic anhydrase, (2) alkaline phosphatase, (3) RNA and DNA polymerases, (4) thymidine kinase carboxypeptidases, and (5) alcohol dehydrogenase. Deficiency of zinc incorporation into the apoenzyme will lead to decreased enzyme availability.

DIF:

3

REF: Page 494

OBJ: 13

19. In trace element analysis, the coupling of an analytical procedure with a technique that separates the chemical complexes of individual elements present in any medium is referred to as a(n): a. speciation analysis. b. hyphenated technique. c. atomic absorption spectrometry procedure. d. complexed analysis.

ANS: B Speciation methods involve techniques to separate the chemical complexes of individual elements present in any particular medium. These separative techniques coupled with analytical procedures, in particular ICP-OES or ICP-MS, are known collectively as hyphenated techniques.

DIF:

1

REF: Page 484

OBJ: 11

20. Poor dark adaptation or nTigEhSt T blB inAdN neKssSiE sL asLsoEcR ia. teCdOwMith: a. pernicious anemia. b. hypervitaminosis B12. c. scurvy. d. deficiency of vitamin A. ANS: D The clinical features of vitamin A deficiency are degenerative changes in eyes and skin and poor dark adaptation or night blindness (nyctalopia).

DIF:

1

REF: Page 464

OBJ: 5

21. The ease with which iron can move from a reduced form to an oxidized form in its metalloprotein transferrin is important because: a. only the reduced form of iron can be stored as transferrin. b. transport of iron in transferrin occurs only in the oxidized state. c. it can block the excessive uptake of copper in hepatocytes. d. the oxidized form of iron reacts best when binding oxygen.

ANS: B All elements (with the possible exception of selenium) behave in the charged ionized form, and the relative ease with which they are able to pass from one state to another is key in the role they exert in their respective metalloproteins. Transport of Fe occurs as the Fe3+ (oxidation) state in transferrin but in the reduced state (Fe2+) when functioning to bind oxygen in hemoglobin.

DIF:

2

REF: Page 487

OBJ: 9

22. The vitamin that is an antioxidant that acts as a scavenger for lipid Peroxyl-free radicals and that has a role in RBC protection from hemolysis is: a. A. b. B6. c. E. d. K. ANS: C Vitamin E is considered necessary for (1) neurological and reproductive functions, (2) protecting the red cell from hemolysis, (3) prevention of retinopathy in premature infants, and (4) inhibition of free-radical chain reactions of lipid peroxidation. The latter occurs mainly within the polyunsaturated fatty acids of membrane phospholipids. Tocopherols and tocotrienols inhibit lipid peroxidation largely because they scavenge lipid Peroxyl radicals faster than the radical reacts with adjacent fatty acid side chains.

DIF:

1

REF: Page 465

OBJ: 4

23. The trace element that is thought to mimic insulin because of its activation of the cellular insulin response is: a. boron. b. silicon. c. fluoride d. vanadium.

ANS: D Clinical interest in the vanadate compounds involves their potential role in the treatment of diabetes. Various studies have suggested that these compounds reduce the requirement for insulin by activating the cellular response without the presence of insulin, in effect mimicking its action.

DIF:

1

REF: Page 497

OBJ: 14

MATCHING Match the correct vitamin to the disorder that the vitamin deficiency would cause. a. Impaired blood coagulation b. Megaloblastic anemia c. Night blindness d. Beriberi 1.

2.

3.

4.

Thiamine Retinol Quinone Cobalamin

1. ANS: D OBJ: 2 | 4

DIF:

2

REF: Page 463, Table 27-2

MSC: Because of its importance in decarboxylation reactions, thiamine deficiency will primarily involve the nervous and cardiovascular systems; this deficiency is called beriberi.

2. ANS: C DIF: 2 REF: Page 463, Table 27-2 OBJ: 2 | 4 MSC: Retinol, a vitamer of vitamin A, has a major role in the generation of photopigments in the eye.

3. ANS: A DIF: 2 REF: Page 465 OBJ: 2 | 4 MSC: Quinone, or vitamin K, is involved in the process of forming thrombin, which catalyzes the conversion of fibrinogen to a fibrin clot.

4. ANS: B DIF: 2 REF: Page 474 OBJ: 2 | 4 MSC: Cobalamin, or vitamin B12, is required in coenzyme form for more than 12 different enzyme systems and is important in nucleic acid synthesis.

Match the trace or ultratrace elements with the clinical disorders associated with either deficiency or toxicity. a. Menkes disease b. Lung cancer c. Loss of immunocompetence d. Parkinson disease-like symptoms 5.

6.

7.

8.

Chromium Manganese Copper Selenium

DIT FE : 2 5. ANS: B REF: Page 485 OBJ: 10 | 13 STBANKSELLER.COM MSC: For chromium, chron ic exposure to and inhalation of high amounts of this element lead to lung cancer.

6. ANS: D DIF: 2 REF: Page 490 OBJ: 10 | 13 MSC: Prolonged exposure to manganese-containing dust can lead to neurological symptoms resembling Parkinson disease.

7. ANS: A DIF: 2 REF: Page 487 OBJ: 10 | 13 MSC: Menkes syndrome is caused by a defective gene that regulates the metabolism of copper in the body.

8. ANS: C DIF: 2 REF: Page 492 OBJ: 10 | 13 MSC: Deficiency of selenium is accompanied by loss of immunocompetence related to the reduction of selenoproteins in the liver, spleen, and lymph nodes.

Chapter 28: Hemoglobin, Iron, and Bilirubin Test Bank MULTIPLE CHOICE 1. Bilirubin is considered to be the breakdown product of: a. cholesterol. b. protoporphyrin IX. c. glucose and maltose. d. urobilinogen.

ANS: B

Bilirubin IX is produced from the catabolism of protoporphyrin IX. Approximately 85% of the total bilirubin produced is derived from this heme moiety of hemoglobin released from senescent erythrocytes that are destroyed in the reticuloendothelial cells of the liver, spleen, and bone marrow.

DIF: 1

REF: Page 514

OBJ: 1 | 22

2. In blood, bilirubin is unconjugated but is bound to a. hemoglobin b. albumin c. bilirubin-transporting protein d. urobilinogen

as it is transported to the liver.

ANS: B

AN In blood, bilirubin is boundTtEoSaT lbB um inKaS ndEtL raLnE spRo. rteCdOtM o the liver. Bilirubin then dissociates from albumin at the membrane of the hepatocyte.

DIF: 1

REF: Page 514

OBJ: 22

3. An 80-year-old patient visits his physician with an elevated serum iron value and a decreased

TIBC. The most likely diagnosis in this case is: a. iron deficiency anemia. b. chronic inflammation. c. hemochromatosis. d. acute bleeding ulcer.

ANS: C

See Table 28-3. Hemochromatosis, an iron overload disorder, presents with an elevated iron in serum, and since all sites are saturated on transferrin because of the increased iron, a decreased TIBC is observed.

DIF: 2

REF: Page 510,Table 28-3

OBJ: 1 | 14 | 16

4. The most popular assay used to determine iron deficiency anemia is ferritin. What are the

ferritin levels in the correctly identified diagnosis in the preceding question compared to normal? a. Increased b. Decreased

c. Unaffected ANS: A

More than 50% of individuals that are homozygous for a mutation of the HFE gene have elevated transferrin saturations and/or ferritin concentrations. Excess iron in circulation is due in part to the increased absorption of iron, and ferritin incorporates the excess.

DIF: 2

REF: Page 511

OBJ: 21

5. Regarding serum iron analysis, the maximum concentration of iron that transferrin can bind is

reflected in what laboratory measurement? a. Transferrin saturation b. Hemoglobin c. Serum iron d. Total iron binding capacity (TIBC) ANS: D

TIBC is a measurement of the maximum concentration of iron that transferrin binds. It is a measure of the reserve capacity that transferrin has to bind iron.

DIF: 1

REF: Page 512

OBJ: 18

6. Iron is transported as ferric iron through the plasma by means of: a. transferrin. b. alpha1-fetoprotein. c. ferritin. d. albumin.

ANS: A

Transferrin is a beta globulin that carries iron in the blood.

DIF: 1

REF: Page 500

OBJ: 1 | 13

7. In an individual using progesterone-based oral contraceptives, serum iron a. b. c. d.

and TIBC

. increases; decreases is normal; increases decreases; decreases increases; increases

ANS: D

See Table 28-3. Oral contraceptives containing progesterone typically reduce loss of blood during the reproductive cycle, leading to increased iron and iron stores.

DIF: 2

REF: Page 510, Table 28-3

OBJ: 21

8. Regarding the individual using progesterone-based oral contraceptives, would the transferrin

saturation be increased, decreased, or not affected? a. Increased b. Decreased c. Not affected ANS: A

See Table 28-3. Since TSAT is calculated using serum iron and TIBC, which are both increased in an individual using progesterone-like oral contraceptives, the TSAT will be increased as well. TSAT values can increase to as high as 75%.

DIF: 2

REF: Page 510, Table 28-3

OBJ: 21

9. Which one of the following statements concerning TIBC is not correct? a. TIBC is decreased in chronic inflammatory disorders. b. TIBC is proportional to the amount of transferrin present. c. TIBC is decreased in an iron deficiency anemia. d. Transferrin saturation = (serum iron/TIBC)  100.

ANS: C

In iron deficiency, decreased serum iron occurs. Since TIBC is a measurement of the maximum concentration of iron that transferrin binds, it is a measure of the reserve capacity that transferrin has to bind iron. With little or no iron to bind, transferrin saturation is decreased.

DIF: 2

REF: Page 512

OBJ: 18

10. In the initial step of the diazo reaction for direct bilirubin determination: a. the absorption of light by bilirubin near 460 nm is measured. b. bilirubin fractions are oxidized to biliverdin, which is further oxidized to purple. c. serum is added to an aqueous solution of caffeine, sodium acetate, and sodium

benzoate. d. large quantities of ascorbic acid worsen the detection limit.

ANS: C

In this reaction, diazotized sulfanilic acid—the diazo reagent—reacts with bilirubin to produce two azodipyrroles, which are reddish purple at neutral pH and blue at low or high pH values. The fraction of bilirubin that reacts with the diazo reagent in the absence of alcohol is termed direct bilirubin.

DIF: 2

REF: Page 517

OBJ: 25

11. What soluble iron-protein complex is the form in which iron is stored in tissues? a. Ferritin b. Transferrin c. Hemosiderin d. Hemoglobin ANS: A

While hemosiderin is aggregated deproteinized ferritin, in contrast to ferritin, hemosiderin is insoluble in aqueous solutions. Ferritin is soluble and easily dissolved for iron release.

DIF: 1

REF: Page 509

OBJ: 1 | 10

12. Which one of the following is formed by the reduction of unconjugated bilirubin in the

intestines, is found in urine, and is further oxidized to form urobilin? a. Hemoglobin b. Conjugated bilirubin

c. Iron d. Urobilinogen ANS: D

Unconjugated bilirubin is reduced by intestinal microbial flora to three colorless tetrapyrroles collectively called urobilinogens.

DIF: 1

REF: Page 515

OBJ: 1

13. The major substance formed from the breakdown of hemoglobin when senescent red blood

cells are phagocytized by the reticuloendothelial system is: a. myoglobin. b. bilirubin. c. urobilinogen. d. urobilin.

ANS: B

Bilirubin is the orange-yellow pigment derived from senescent red blood cells. Following formation in the reticuloendothelial cells, bilirubin is transported to and biotransformed in the liver.

DIF: 1

REF: Page 513

OBJ: 1

14. The most common cause of iron deficiency anemia in children is: a. bleeding ulcers. b. hemolytic anemias. c. dietary deficiency. d. megaloblastic anemia.

ANS: C

In children, iron deficiency anemia is frequently due to dietary deficiency because milk has low iron content. In older children, lack of iron ingestion that is in red meat and other iron containing foods is common.

DIF: 1

REF: Page 509

OBJ: 15

15. What is the percent transferrin saturation given the following data: serum iron 150 g/dL,

TIBC 350 g/dL, transferrin 300 mg/dL, and ferritin 65 ng/mL? a. 43% b. 55% c. 233% d. 500% ANS: A

Transferrin saturation is calculated by dividing serum iron by TIBC and multiplying this value by 100 to obtain a percentage. In this case, 150/350 = 0.428, and this value multiplied by 100 equals 42.8% or 43%.

DIF: 3

REF: Page 512

OBJ: 19

16. The inherited disorders caused by an underproduction of certain globin chains are referred to

as the:

a. b. c. d.

hemoglobinopathies. iron deficiency disorders. hemoglobin variant disorders. thalassemias.

ANS: D

Thalassemias are a group of hereditary hemoglobin disorders having in common a decreased globin chain production that produces a quantitative change in these chains.

DIF: 2

REF: Page 502

OBJ: 7

17. Which one of the following sets of laboratory values correctly reflects an iron deficiency

state? a. Transferrin saturation high, serum iron decreased, TIBC high b. Transferrin saturation high, serum iron increased, TIBC high to normal c. Transferrin saturation low, serum iron decreased, TIBC low to normal d. Transferrin saturation low, serum iron increased, TIBC normal ANS: C

See Table 28-3. With decreased serum iron, the binding sites on transferrin are mostly decreased while TIBC can remain normal.

DIF: 2

REF: Page 510, Table 28-4

OBJ: 21

18. What is the mutational basis of an “elongation hemoglobin?” a. A gene deletion of the entire alpha2 globin gene b. A reciprocal chromosomal translocation between chromosomes 16 and 14 of the

alpha and beta globin cThE aiS nT geBnA esNKSELLER.COM c. Many fixed mutations occurring along the genes encoding for alpha2 globin d. A single base pair mutation or frameshift at either the 3' end of exon 3 or the 5' end of exon 1 of the alpha2 or beta globin chain ANS: D

Hemoglobin variants are classified according to the type of mutation. Single point mutations in a globin chain give rise to a substitution of one amino acid residue. Elongation hemoglobins result from a single base pair mutation or frameshift mutation.

DIF: 2

REF: Page 506

OBJ: 5

19. A patient presents with yellowish skin and eyes, fatigue, and mild motor system dysfunction.

Upon assessment in the laboratory, the total bilirubin concentration was shown to be 3.0 mg/dL (normal 0.2-1.0 mg/dL) with negative urinary bilirubin. Liver function tests are normal. The most likely diagnosis in this case would be: a. Crigler-Najjar syndrome type II. b. Lucey-Driscoll syndrome. c. hemolytic anemia. d. Gilbert syndrome.

ANS: D

Gilbert syndrome is a benign condition manifested by mild unconjugated hyperbilirubinemia.

The serum concentration of bilirubin fluctuates between 1.5 and 3 mg/dL (26 and 51 µmol/L).

Gilbert syndrome is easily distinguished from chronic hepatitis by the absence of anemia and bilirubin in urine.

DIF: 3

REF: Page 515-116

OBJ: 23

20. High levels of unconjugated bilirubin that accumulate in the brain are called: a. hyperbilirubinemia. b. Crigler-Najjar syndrome. c. hemolysis. d. kernicterus.

ANS: D

Unconjugated hyperbilirubinemia poses a risk for development of kernicterus, especially in premature, low-birth-weight infants. Kernicterus refers to a neurological syndrome that results in brain damage owing to deposition of bilirubin in the basal ganglia and brainstem nuclei.

DIF: 1

REF: Page 516

OBJ: 1 | 24

21. The oxidation of the Fe+2 of hemoglobin to the Fe+3 of methemoglobin by ferricyanide is the

initial step in the: a. Mentzer index reaction for screening of -thalassemia. b. cyanmethemoglobin method of hemoglobin determination. c. Ehrlich reaction for the determination of bilirubin. d. HPLC methods for separating hemoglobin fractions.

ANS: B

The cyanmethemoglobin method of hemoglobin determination is based upon the oxidation of the Fe+2 of hemoglobin to the Fe+3 of methemoglobin by ferricyanide, with the methemoglobin then converted into stable cyanmethemoglobin by addition of potassium cyanide.

DIF: 2

REF: Page 506

OBJ: 9

22. In a certain hemoglobin structural variant, a deletion in the coding gene results in a reduction

of the production of the beta globin chain. This will result in: a. decreased quantity of HbA. b. hemolysis of red blood cells due to unstable hemoglobin. c. a sickling disorder due to insoluble hemoglobin. d. an -thalassemia due to overproduction of alpha-globin chains.

ANS: A

-Thalassemias result from a decrease in synthesis of beta-globin chain. The HPLC of blood from children with -thalassemia major shows a large HbF peak with no HbA peak, while in +-thalassemia there is a significant reduction in the production of the beta-globin chain with subsequent reduction in the quantity of HbA present.

DIF: 2

REF: Page 503

OBJ: 6

23. Increased total iron in serum is common in all of the following except:

a. b. c. d.

iron intoxication. hemosiderosis. chronic inflammation. sideroblastic anemia.

ANS: C

See Table 28-3. In chronic inflammation, which can produce an anemia that is normocytic and normochronic, total serum iron level is typically normal or slightly decreased.

DIF: 2

REF: Page 510, Table 29-3

OBJ: 15

24. The two pairs of globin chains in normal HbA hemoglobin are: a. alpha and gamma. b. beta and gamma. c. alpha and beta. d. beta and delta.

ANS: C

The two pairs of globin chains in normal hemoglobin (HbA) are called  and .

DIF: 2

REF: Page 501

OBJ: 4

25. In hemoglobin F, which globin chains are different from adult hemoglobin chains and what

replaces them in the adult? a. Gamma chains are replaced by betas. b. Delta chains are replaced by alphas. c. Gamma chains are replaced by alphas. d. Delta chains are replacT edEbSyTbBetAasN. KSELLER.COM ANS: A

In fetal hemoglobin, HbF, the -chain is the same as that found in HbA, but the non -chain is the -chain that has the same number of amino acid residues and substantial structural homology to the -chain.

DIF: 2

REF: Page 501

OBJ: 4

Chapter 29: Porphyrins and Porphyrias Test Bank MULTIPLE CHOICE 1. A group of compounds containing four monopyrrole rings connected by methane bridges is

the: a. b. c. d.

porphyrins. porphyrias. porphobilinogens. heme precursors.

ANS: A

The basic porphyrin structure consists of four monopyrrole rings connected by methene bridges to form a tetrapyrrole ring; see Figure 29-1.

DIF: 1

REF: Page 523, Figure 29-1

OBJ: 1

2. A deficiency of the enzyme hydroxymethylbilane synthase (HMBS) results in which one of

the following acute porphyrias? a. Variegate porphyria (VP) b. Hereditary coproporphyria (HCP) c. Acute intermittent porphyria (AIP) d. Porphyria cutanea tarda (PCT) ANS: C

ChOiM In AIP the primary defect iTs Ea S deTfB icA ieN ncKySoEf L HL MEBRS. ,w ch results in accumulation of its substrate PBG (and to a lesser extent ALA).

DIF: 2

REF: Page 527

OBJ: 4 | 5

3. An individual visits his physician with porphyria-like symptoms. The results of porphyrin

analysis are as follows: urine 5-aminolevulinic acid (ALA), positive; urine coproporphyrin III, increased; RBC zinc protoporphyrin (ZPP), increased. What laboratory test should the physician order to determine the exact diagnosis? a. Blood lead b. Urinary PBG c. Hemoglobin and hematocrit d. Blood alcohol ANS: A

Lead exposure increases urinary ALA and coproporphyrin-III excretion and causes accumulation of ZPP in erythrocytes. The definitive test for lead toxicity is measurement of blood lead, but occasionally lead exposure is responsible for porphyria-like symptoms.

DIF: 3

REF: Page 530

OBJ: 6 | 10

4. An individual is suspected of having some type of porphyria although he has no skin lesions.

The qualitative screen demonstrates an elevated PBG and ALA in urine. Upon quantitation, the PBG was noted as being more increased than the ALA. Further quantitative tests indicated increased uroporphyrin and fecal porphyrin. The plasma fluorescence emission peak was at 624 to 628 nm. What is the likely diagnosis? a. Congenital erythropoietic porphyria (CEP) b. Acute intermittent porphyria (AIP) c. Variegate porphyria (VP) d. Porphyria cutanea tarda (PCT) ANS: C

See Table 29-3. In VP, protoporphyrin-IX (and other dicarboxylate porphyrins) is elevated and there is a smaller increase in coproporphyrin. If total fecal porphyrin is normal, then VP and HCP are excluded and the patient must have AIP. If the fecal porphyrin pattern resembles VP, plasma should be examined by fluorescence emission spectroscopy for the characteristic fluorescence maximum at 624 to 628 nm.

DIF: 3

REF: Page 528, Table 29-3

OBJ: 4 | 5 | 10

5. Moderate elevations of which of the following occur secondary to lead toxicity or

iron-deficiency anemia? a. Porphobilinogen b. Protoporphyrin IX c. ALA d. Heme ANS: C

STexBcAreNtiKonSE In lead toxicity, increased T AE LA is LseLcE onRd.arCyOtoMinhibition of ALAD (PBG synthase) caused by lead displacing zinc at its catalytic center. PBG is not increased because inhibition of ALAD will not catalyze PBG formation from ALA. In iron-deficiency anemia, zinc acts as an alternative substrate for ferrochelatase, leading to decreased iron incorporation into heme.

DIF: 2

REF: Page 530

OBJ: 6 | 9

6. The skin lesions observed in individuals with nonacute porphyria are caused by: a. brain dysfunction and peripheral neuropathy. b. excessive production of retinoic acid in the eye. c. the excess of porphyrin intermediates in the liver. d. the excess presence of porphyrins in the skin that generate oxygen radicals.

ANS: D

Lesions on sun-exposed skin, particularly the backs of the hands, forearms, and face, are present in all patients with nonacute porphyria. Skin lesions are caused by porphyrin-catalyzed photo damage, of which singlet oxygen is the main mediator. The skin lesions of the cutaneous porphyrias are always accompanied by overproduction of porphyrins.

DIF: 2

REF: Page 527

OBJ: 4

7. An important amino acid in the synthesis of ALA is: a. glutamine. b. glycine.

c. cysteine. d. methionine.

ANS: B

The tetrapyrrole ring structure of heme is built up in a stepwise fashion from the very simple succinyl-CoA and glycine precursors. The initial step in the formation of heme involves ALA synthase catalyzing the reaction between succinyl CoA and glycine to form ALA. DIF: 1

REF: Page 524

OBJ: 2

8. Porphyrin synthesis is regulated by modulation of which one of the following enzymes? a. Ferrochelatase b. ALA-dehydrase (ALAD) c. ALA-synthase (ALAS) d. Phorphyrinas ANS: C

ALAS is the initial enzyme of the pathway and catalyzes the formation of ALA from succinyl-CoA and glycine. The activity of ALAS is rate limiting as long as the catalytic capacities of other enzymes in the pathway are normal.

DIF: 2

REF: Page 524

OBJ: 2

9. Which one of the following cofactors is required for heme synthesis? a. Ascorbic acid b. Pyridoxal phosphate c. Cobalamin d. Niacin ANS: B

ALAS is the initial enzyme of the heme synthetic pathway with a housekeeping (ALAS1) and an erythroid (ALAS2) isozyme and catalyzes the formation of ALA from succinyl-CoA and glycine. The enzyme is mitochondrial and requires pyridoxal phosphate as a cofactor.

DIF: 1

REF: Page 524

OBJ: 2

10. The enzyme that is an iron-sulfur protein located in the inner mitochondrial membrane that

inserts ferrous iron into protoporphyrin to form heme is: a. ferrochelatase. b. protoporphyrin oxidase. c. ALAS. d. hematin.

ANS: A

Ferrochelatase (also known as heme synthase) is an iron-sulfur protein located in the inner mitochondrial membrane. This enzyme inserts ferrous iron into protoporphyrin to form heme.

DIF: 1

REF: Page 526

OBJ: 1

11. The immediate precursor of the porphyrins is: a. ALA. b. succinyl CoA.

c. porphobilinogen. d. hydroxymethylbilane.

ANS: C

PBG is considered to be the immediate precursor of the porphyrins. It is composed of a pyrrole ring with acetyl, propionyl, and aminomethyl side chains. Four molecules of porphobilinogen condense to form one molecule of 1-hydroxymethylbilane, which is then converted successively to uroporphyrinogen III, coproporphyrinogen III, protoporphyrinogen IX, protoporphyrin IX, and heme.

DIF: 1

REF: Page 533

OBJ: 1

12. A physician calls the laboratory stating that one of her patients is exhibiting what she suspects

to be an acute porphyric attack. The patient is having acute abdominal pains and seems apathetic and distant. Initial laboratory analysis should include: a. quantitative porphyrin analyses of all porphyrins. b. urine ALA screen. c. serum iron. d. urinary PBG. ANS: D

The one essential investigation in patients with suspected acute porphyria is an adequately sensitive test for excess urinary PBG. During an attack, PBG excretion is grossly elevated, and the increase is usually in excess of 10 times the upper reference limit. Normal PBG, at a time when symptoms are present, excludes all acute porphyrias.

DIF: 2

REF: Page 531

OBJ: 4

13. A physician calls the laboratory stating that one of her patients is exhibiting what she suspects

to be an acute porphyric attack. The patient is having acute abdominal pains and seems apathetic and distant. If the urine test for PBG in the preceding question is strongly positive and remains elevated for 2 weeks or longer, which one of the following is the most likely disease process? a. Lead poisoning b. EPP c. AIP d. PCT ANS: C

In AIP, PBG usually remains elevated for weeks or even months after an attack. The primary defect in AIP is a deficiency of HMBS, which results in accumulation of its substrate PBG. DIF: 2

REF: Page 527-528

14. Erythrocyte protoporphyria (EPP): a. consists only of coproporphyrins. b. leads to progressive hepatic failure. c. has as its principal component coproporphyrin IX. d. is decreased in cases of lead toxicity.

ANS: B

OBJ: 4

The most severe complication of EPP is progressive hepatic failure, which is caused by accumulation of protoporphyrin in the liver. The primary biochemical abnormality in EPP is decreased ferrochelatase activity.

DIF: 2

REF: Page 529

OBJ: 4

15. What is the name of the oxygen storage protein found in muscle that uses heme as its

prosthetic group? a. Myoglobin b. Hemoglobin c. Cytochrome b1 d. Catalase ANS: A

Heme functions as a prosthetic group in various proteins in which it participates in a variety of redox reactions, including oxygen transport (by hemoglobin in the blood) and storage (by myoglobin in muscle).

DIF: 1

REF: Page 526

OBJ: 3

16. An individual with jaundice reports to the emergency department with symptoms of an acute

porphyric attack, including severe abdominal pain, pain in her thighs, vomiting, and muscle weakness. A hepatitis screen is negative and unconjugated bilirubin and urobilinogen are increased. Your laboratory receives a dark orange-colored urine sample for qualitative PBG analysis, results of which are difficult to interpret. When you contact the physician with this information, the physician informs you that this patient is an alcohol abuser and asks you to run a quantitative urine porphyrin analysis. Results of this analysis show an increased KhSyEwLaLsEthRe.PCBOGMdifficult to interpret? uroporphyrin and coproporTpE hySrT inBIIAI.NW a. In individuals with congenital erythrocytic porphyria, PBG is negative. b. There was interference from elevated urobilinogen in the urine sample. c. PBG only demonstrates an increase in fecal samples, not in urine. d. Alcohol in the urine sample produced a false-negative value for PBG. ANS: B

Most methods for PBG are based on the reaction of Ehrlich reagent with the -methene carbon of the pyrrole ring to form a colored product described as “rose-red” or “magenta.”

Some other substances in urine react with the reagent to give red products, notably urobilinogen.

DIF: 3

REF: Page 533

OBJ: 9

17. When using DNA analysis to screen a new family to identify a genetic mutation that has

caused porphyria, what must be examined? a. A single mutation is all that needs to be assessed. b. The entire genome of each family member must be examined. c. A Bayesian analysis must be calculated first. d. All exons with promoters and flanking intron sequences around the mutation must be analyzed.

ANS: D

Screening families for porphyria by DNA analysis is a two-stage process. First, the mutation that causes porphyria in the family under investigation needs to be identified by analysis of DNA from a family member in whom the diagnosis of a specific type of porphyria has been established unequivocally. Second, that patient’s relatives are then screened for the mutation.

The first part of this process is the more complex. Because most mutations are restricted to one or a few families, identification of a mutation in a new family almost always requires at least analysis of all exons with their flanking intronic sequences and the promoter region.

DIF: 2

REF: Page 534

OBJ: 9

18. Protoporphyrin that contains iron is known as: a. ferrochelatase. b. heme. c. porphyrin. d. porphyria.

ANS: B

Protoporphyrin that contains iron is known as heme; ferroheme refers specifically to the Fe2+ complex and ferriheme to Fe3+.

DIF: 1

REF: Page 534

OBJ: 1

19. The heme precursor that is elevated in PCT is: a. PBG. b. coproporphyrin. c. uroporphyrin. d. protoporphyrin.

ANS: C

PCT results from a decrease in activity of UROD in the liver, which leads to overproduction of uroporphyrinogen and other carboxymethyl-substituted porphyrinogens.

DIF: 2

REF: Page 523

OBJ: 5

TRUE/FALSE 1. In the analysis of plasma porphyrins, porphyrins at neutral pH fluoresce between 610 to 640

nm.

ANS: T

Plasma porphyrins may be determined by fluorescence emission spectroscopy of saline-diluted plasma. Porphyrins at neutral pH fluoresce in the 610 to 640 nm region; the wavelength of maximum emission depends primarily on the porphyrin structure but is also influenced by the nature of the porphyrin-protein complex.

DIF: 1

REF: Page 529

OBJ: 9

Chapter 30: Therapeutic Drugs and Their Management Test Bank MULTIPLE CHOICE 1. When a drug concentration exceeds the available metabolic capacity of the body, what does the drug’s metabolism become dependent on? a. The health of the renal system b. The number of doses given per hour c. The drug concentration itself d. The amount of metabolizing enzyme ANS: D Nonlinear kinetics occur when drug concentrations exceed the available metabolic capacity.

In this situation, the amount of metabolizing enzyme is the rate-limiting factor and the rate of metabolism is independent of drug concentration.

DIF:

2

REF: Page 540

OBJ: 1 | 6

2. A hospital patient is receiving amikacin for her Enterobacter infection, which seems to be resistant to all other antibiotics. Her physician is somewhat unfamiliar with the antibiotic and wants to know what laboratory analyses can be performed to assess this antibiotic’s efficacy and risk of toxicity. You suggest: a. immunoassay for amikacin at the peak blood concentration. b. assessment of hearing by a speech pathologist. c. both peak and troughTaE mSikTaB ciA nN coKnS ceEnL trL atE ioR n.asCsO esM sment. d. that amikacin should not be used in this case because it is not suitable for Enterobacter infections.

ANS: C Aminoglycoside samples for therapeutic drug management can be drawn at peak (1 hour post dose) and at trough (immediately predose, or at minimum 10 to 12 hours post infusion) to monitor efficacy and risk of toxicity, respectively.

DIF:

2

REF: Page 549-550

OBJ: 1 | 8 | 11

3. Which of the following could account for drug toxicity following a prescribed dose? a. Decreased renal elimination leading to increased free drug concentration b. Using a single drug as opposed to multiple drugs for treatment c. Using a different route of administration than is typically used for that drug d. Increased drug metabolism caused by central nervous system disease ANS: A The most common routes of drug elimination are excretion into urine or stool. Physiological (e.g., pregnancy, aging) or pathological conditions can affect the concentration of drug-binding molecules or the rate of elimination of free drug. Patients may experience adverse effects, even severe toxicity, as a direct consequence of increased free drug concentrations.

DIF:

2

REF: Page 541

OBJ: 2 | 4

4. The fraction of drug absorbed into a physiological system that is based on the amount of drug given is referred to as: a. bioavailability. b. dosing. c. volume of distribution. d. steady state.

ANS: A The amount of drug absorbed relative to the quantity given is referred to as its bioavailability.

DIF:

1

REF: Page 539

OBJ: 1

5. If a drug is acidic in nature, which of the following proteins will it associate with primarily for transport and distribution? a. Lipoprotein b. 1-Glycoprotein c. Albumin d. All of the above ANS: C Many drugs bind to one or more plasma proteins, most notably albumin, globulins such as 1-acid glycoprotein, and lipoproteins. In general, acidic drugs associate primarily with albumin, whereas basic drugs preferentially bind globulins and lipoproteins.

DIF:

1

REF: Page 540

OBJ: 2 | 4

6. The therapeutic range of a drug is: a. dependent on renal function. b. the range of concentrations within which the drug is effective yet not toxic. c. the range of concentrations at which there are no drug interactions. d. dependent on the route of drug administration.

ANS: B The therapeutic range represents the range of drug concentrations within which the probability of the desired clinical response is relatively high and the probability of unacceptable toxicity or failure to achieve further clinical benefit is relatively low.

DIF:

1

REF: Page 538

OBJ: 1

7. The period of time during which the concentration of a therapeutic drug decays by 50% is referred to as the drug’s: a. subtherapeutic range. b. dosing curve. c. volume of distribution. d. half-life.

ANS: D A drug half-life is the time required to metabolize 50% of the drug present.

DIF:

1

REF: Page 540

OBJ: 1

8. A hospitalized patient is being given gentamicin to treat a gram-negative bacterial infection.

The patient’s physician contacts you regarding monitoring of this antibiotic because this patient is beginning to exhibit signs of hearing loss and renal failure. When you assess the patient’s 10-hour postinfusion trough antibiotic concentration, it is increased. You learn from the physician that he has been dosing the patient to keep the antibiotic concentration high, “at a steady state” he tells you. You state that: a. it would be better to change antibiotics because the patient is obviously allergic to gentamicin. b. you have made an error in the method of assessment of this antibiotic and need to repeat the analysis. c. with aminoglycoside antibiotics, trough concentrations must be allowed to decrease because of the postantibiotic effect. d. aminoglycosides display peak level concentration–dependent killing of microorganisms and the dosage should be increased even more.

ANS: C Aminoglycosides are associated with the risk of serious toxicity, particularly nephrotoxicity (renal tubular necrosis) and potentially irreversible ototoxicity (auditory nerve degeneration) leading to hearing loss. To avoid toxicity, trough concentrations must be allowed to decline substantially before the next dose, thus these drugs do not reach steady state. Allowing the drug to clear does not adversely affect therapy because aminoglycosides show a considerable postantibiotic effect; that is, they enhance bactericidal activity that lasts after the drug has been cleared from the body.

DIF:

3

REF: Page 549-550

OBJ: 3 | 8 | 11

9. The steady state of a drug is defined as the: a. point at which the body concentration of the drug is in equilibrium with the rate of dose administered and the rate of elimination. b. time required for one-half of an administered drug to be lost through metabolism and elimination. c. metabolism of a drug with a high hepatic extraction rate by the liver before it reaches the systemic circulation. d. action of one drug on another.

ANS: A Steady state is the point at which the body concentration of the drug is in equilibrium with the rate of dose administered and the rate of elimination.

DIF:

1

REF: Page 540

OBJ: 1

10. A woman is treated for a seizure disorder with levetiracetam. She began experiencing dizziness and fatigue. Blood cell values indicated decreased RBC count and low hematocrit.

Trough blood concentration of levetiracetam was assessed to be 15 µg/mL, although her dosing should have resulted in a trough therapeutic concentration of 3 µg/mL. She claimed that she was not taking antacids or any other medication. What is the likely cause of the elevated levetiracetam?

a. Levetiracetam is metabolized to gabapentin in systemic circulation, leading to an increase in antiepileptic activity. b. The patient might have an issue with her renal function, leading to decreased elimination of the drug. c. The patient was probably also taking phenytoin, which reacts with levetiracetam resulting in increased concentration. d. The physician made an error in calculating the correct dosage of gabapentin.

ANS: B Levetiracetam is not extensively metabolized. Renal function and age are the major determinants of elimination kinetics, and toxicity known to be associated with levetiracetam includes decreased RBC count and hematocrit, decreased neutrophil count, somnolence, asthenia, and dizziness.

DIF:

3

REF: Page 548

OBJ: 2 | 7 | 11

11. Which of the following is a major active metabolite of procainamide that must be monitored along with the parent drug? a. Disopyramide b. Glycinexylidide c. N-acetylprocainamide d. Procainamide does not have an active metabolite.

ANS: C Procainamide is monitored along with its active metabolite, N-acetylprocainamide.

DIF:

1

RETFE: ST PaBgA eN 55K1SELLOEBRJ. : C7OM

12. What do both cyclosporine and tacrolimus inhibit? a. Erythrocyte precursor proliferation b. Plasma cell proliferation c. Gram-negative bacterial growth d. Calcineurin ANS: D Tacrolimus, like cyclosporine, is considered to be a calcineurin inhibitor and acts by blocking T lymphocyte function.

DIF:

2

REF: Page 553

OBJ: 7

13. Which one of the following immunosuppressant prodrugs inhibits inosine monophosphate dehydrogenase (IMPDH) to reduce the pool of intracellular guanine nucleotides and arrest T-cell proliferation? a. Tacrolimus b. Mycophenolate mofetil c. Disopyramide d. Imipramine ANS: B

Mycophenolate mofetil (MMF) is the ester prodrug form of the active immunosuppressant mycophenolic acid (MPA). MPA is a reversible and uncompetitive inhibitor of IMPDH. T-cell proliferation is arrested by the suppression of guanine nucleotide production when IMPDH is inhibited by MPA. The proliferative response of activated T cells is dependent on a continuous and increased supply of intracellular guanine nucleotides. The sustained and greatly increased rate of guanine nucleotide production catalyzed by IMPDH is the rate-limiting step in de novo purine biosynthesis. When IMPDH is inhibited, the pool of guanine nucleotides decreases.

DIF:

2

REF: Page 554

OBJ: 5 | 7

14. The therapeutic drug used to treat all but absence seizures by prolonging inactivation of the synaptic sodium channel and reducing synaptic transmission is: a. phenytoin. b. ethosuximide. c. carbamazepine. d. gabapentin.

ANS: A Phenytoin (diphenylhydantoin), most commonly available as Dilantin, is used in the treatment of all but absence seizures. Phenytoin interferes with sodium channel activity by prolonging inactivation, which reduces synaptic transmission, and aids in control of abnormal neuronal excitability.

DIF:

2

REF: Page 547

OBJ: 7

15. What is occurring in phaT seEISmTeB taA boNlK isS mEoL fL aE thR er.apCeO utMic drug? a. Conjugation to a different moiety b. Elimination c. Chemical modification such as hydrolysis d. First-pass metabolism ANS: C Metabolic processes are typically classified as phase I or phase II. Phase I metabolism is chemical modification (e.g., reduction/oxidation or hydrolysis); phase II involves conjugation to another moiety such as glucuronic acid.

DIF:

2

REF: Page 541

OBJ: 6

16. Which of the following therapeutic drugs is considered to be a selective serotonin reuptake inhibitor? a. Fluoxetine b. Imipramine c. Lithium d. Both a and b ANS: A Selective serotonin reuptake inhibitors (SSRIs) are second-generation antidepressants whose primary activity is modulation of synaptic serotonin concentrations. SSRIs include, for example, citalopram, escitalopram, and fluoxetine.

DIF:

1

REF: Page 556

OBJ: 7

17. A class III antiarrhythmic drug that acts by blocking potassium channels and that is used to manage atrial fibrillation is: a. procainamide. b. digoxin. c. amiodarone. d. quinidine.

ANS: C Class III antiarrhythmics, such as amiodarone, act primarily via K+ channel blockade.

Amiodarone is used to manage atrial fibrillation.

DIF:

2

REF: Page 552

OBJ: 7

18. Which one of the following therapeutic drugs is used in the management of acute lymphoblastic leukemia and inhibits DNA synthesis by decreasing methylation of pyrimidine nucleotides and their synthesis? a. Mycophenolic acid b. Cyclosporine c. Tacrolimus d. Methotrexate ANS: D Methotrexate has proved useful in the management of acute lymphoblastic leukemia.

Methotrexate inhibits DNTA syTnB thA esNisKaSnE dL coLmEpR et. itC ivO elM y inhibits the enzyme dihydrofolate ES reductase, thus decreasing the concentrations of the tetrahydrofolate essential to the methylation of the pyrimidine nucleotides and consequently the rate of pyrimidine nucleotide synthesis.

DIF:

2

REF: Page 551

OBJ: 7

19. Which one of the following is not a good rationale for monitoring the blood concentration of a therapeutic drug? a. To check patient compliance b. To determine drug concentrations in a pathophysiological state c. To monitor drugs with a broad therapeutic range d. To monitor significant drug-drug interactions ANS: C A drug with a wide therapeutic range has a large therapeutic index, indicating a broad interval of concentrations between the minimum toxic concentration and the minimum effective concentration. The smaller the difference between MEC and MTC, the narrower the therapeutic index and the more likely TDM will be necessary.

DIF:

1

REF: Page 538

OBJ: 3

20. Mycophenolate mofetil (MMF) is rapidly hydrolyzed by widely distributed esterases in blood and tissue to produce MPA. In regard to drug metabolism, this chemical reaction is referred to as: a. enzyme induction. b. a phase I reaction. c. a first pass effect. d. a phase II reaction.

ANS: B Phase I reactions modify chemical structure by oxidation, reduction, or hydrolysis.

DIF:

2

REF: Page 541

OBJ: 2

21. The method of monitoring therapeutic drug concentrations that is replacing HPLC-based methods and is now considered to be the best technology for analysis of biological specimens with high specificity and fewer interferences is: a. gas-liquid chromatography. b. spectrophotometry. c. high performance liquid chromatography. d. liquid chromatography–mass spectrometry/mass spectrometry.

ANS: D LC-MS/MS is progressively replacing other HPLC-based methods; it displays greater selectivity and fewer analytical interferences, allowing development of multianalyte assays with higher throughput and less influence from metabolites.

DIF:

1

RETFE: ST PaBgA eN 54K4SELLOEBRJ. : C1O0M

22. For a therapeutic drug that has a short half-life, for example levetiracetam, when is the appropriate time to collect a blood sample for therapeutic drug assessment? a. Immediately after a dose of the drug is given b. Immediately before a dose of the drug is given c. At 8 AM, when liver metabolism is highest d. There is no specific time that is the best for blood collection.

ANS: B Most TDM protocols require sampling at trough (i.e., immediately before the next scheduled dose), particularly for compounds with short half-lives or variable pharmacokinetics.

DIF:

1

REF: Page 544

OBJ: 8

23. The name given to the group of enzymes that are particularly involved in phase I metabolism of drugs and that involve reduction/oxidation or hydrolysis is: a. methyltransferases. b. glucuronyltransferases. c. urokinases. d. cytochromes P-450.

ANS: D

Phase I metabolism is chemical modification (e.g., reduction/oxidation or hydrolysis); the most important phase I enzymes are the cytochromes P-450 (CYPs).

DIF:

1

REF: Page 541

OBJ: 2

MATCHING Match each therapeutic drug with its major therapeutic use. a. Antiepileptic b. Antiarrhythmic c. Antidepressant d. Antimetabolic 1.

2.

3.

4.

Imipramine Methotrexate Quinidine Lamotrigine

1. ANS: C DIF: 1 REF: Page 556 OBJ: 7 MSC: Imipramine acts on norepinephrine in the central nervous system as an antidepressant.

2. ANS: D DIF: 1 REF: Page 551 OBJ: 7 MSC: Methotrexate acts on purines to reduce their availability in DNA replication.

3. ANS: B DIF: 1 REF: Page 551 OBJ: 7 MSC: Quinidine blocks the influx of sodium into cardiac myocytes to act as an antiarrhythmic.

4. ANS: A DIF: 1 REF: Page 548 OBJ: 7 MSC: Lamotrigine binds to the GABA receptor and is considered a GABA agonist to decrease excitation in the central nervous system.

Match each drug with its major mode of action. a. Antiarrhythmic b. Tricyclic antidepressant c. Immunosuppressant d. Antiepileptic 5.

6.

7.

8.

Amitriptyline Procainamide Phenobarbital Sirolimus

5. ANS: B DIF: 1 REF: Page 555 OBJ: 7 MSC: A common tricyclic antidepressant is amitriptyline, used to treat depression.

6. ANS: A DIF: 1 REF: Page 551 OBJ: 7 MSC: Class IA antiarrhythmic agents are moderate Na+ channel blockers and include procainamide.

7. ANS: D DIF: 1 REF: Page 547 OBJ: 7 MSC: Phenobarbital is a broad-spectrum antiepileptic drug that was introduced clinically in

1912.

8. ANS: C DIF: 1 REF: Page 554 OBJ: 7 MSC: Sirolimus inhibits T-lymphocyte activation and proliferation.

Chapter 31: Clinical Toxicology Test Bank MULTIPLE CHOICE 1. An individual who appears to be very inebriated is brought to a hospital emergency department by the police. Laboratory blood gas results indicate metabolic acidosis with an increased serum osmol gap, the presence of serum acetone, and many urine oxalate crystals.

Which alcohol did this individual ingest? a. Isopropanol b. Ethanol c. Methanol d. Ethylene glycol ANS: A See Table 31-3. Compounds that, when present at significant concentrations to increase serum osmolality, include volatile alcohols, such as (1) ethanol, (2) methanol, (3) isopropanol, and (4) acetone and ethylene glycol. Isopropanol is rapidly metabolized by alcohol dehydrogenase to acetone, which is eliminated much more slowly than isopropanol.

DIF:

3

REF: Page 564, Table 31-3

OBJ: 4 | 10

2. What is the major metabolite of acetaminophen that is formed in the liver? a. Ascorbic acid b. Formic acid c. Sulfanilic acid d. Glucuronide ANS: D Acetaminophen is normally metabolized in the liver to glucuronide (50% to 60%) and sulfate (approximately 30%) conjugates.

DIF:

1

REF: Page 569

OBJ: 5

3. In a clinical laboratory without gas chromatography instrumentation, the common method of choice used to measure ethanol in serum or plasma is a(n): a. enzymatic analysis using alcohol dehydrogenase and measurement of nicotinamide adenine dinucleotide (NADH) formation. b. immunoassay using antibodies directed against acetaldehyde. c. planar chromatography method combined with mass spectrometry. d. potentiometric measurement of changes in voltage potential across electrodes.

ANS: A To measure ethanol in serum/plasma, enzymatic analysis is the method of choice for many clinical laboratories. In this method, ethanol is measured by oxidation to acetaldehyde with NAD, a reaction catalyzed by ADH. With this reaction, the formation of NADH, measured at 340 nm, is proportional to the amount of ethanol in the specimen.

DIF:

1

REF: Page 568

OBJ: 4

4. In the liver, methanol is metabolized by a. aldehyde dehydrogenase; acetic acid b. alcohol dehydrogenase; formaldehyde c. methanol hydroxylase; acetaldehyde d. -glutamyltransferase; water

to form

.

ANS: B Methanol is oxidized by liver alcohol dehydrogenase to formaldehyde, which is then rapidly oxidized by aldehyde dehydrogenase to formic acid.

DIF:

1

REF: Page 566

OBJ: 4

5. Your toxicology testing facility tests urine samples. New screening tests for methamphetamine and amphetamine have been added to the drug profiles. Occasionally a positive methamphetamine immunoassay screening test is followed by a negative amphetamine confirmatory test result. What might cause this discrepancy? a. Recent use of hydrocodone would give a negative amphetamine result, as it blocks the reaction on the screening test. b. If the specimen contained ephedrine or pseudoephedrine, it might test positively for methamphetamine but not amphetamine. c. False-negative results are common, especially when the immunoassay is performed without prior glucuronide hydrolysis. d. Other chemically related compounds such as pseudoephedrine have been shown to produce positive results in amphetamine immunoassays.

ANS: D All positive immunoassay results should be confirmed by a second independent method.

Most “amphetamine” immunoassays have been designed to detect amphetamine/methamphetamine, and other chemically related compounds such as pseudoephedrine have been shown to produce positive results. Additionally, many psychotropic medications have been reported to interfere with immunoassays.

DIF:

2

REF: Page 584

OBJ: 7 | 10

6. In which one of the following specimen types is there a strong relationship between it and plasma free drug concentration, but the window of detection is short compared with that in a urine specimen? a. Serum b. Meconium c. Oral fluid d. Hair ANS: C Oral fluid drug concentration is related to plasma-free drug concentration, therefore oral fluid has the potential to show a relationship between behavior/impairment and drug concentration. One significant disadvantage of oral fluid is that the window of detection is about equivalent to that of blood or serum and is short compared with that of urine.

DIF:

1

REF: Page 590

OBJ: 9

7. Which one of the following enzymes is inhibited by organophosphate or carbamate compounds, such as those found in pesticides? a. Amylase b. Alcohol dehydrogenase c. Acetylcholinesterase d. Alkaline phosphatase ANS: C Organophosphate insecticides are toxic because they inactivate acetylcholinesterases that are required for hydrolyzing acetylcholine at nerve junctions.

DIF:

1

REF: Page 572

OBJ: 6

8. A drug of abuse that stimulates the central nervous system by blocking dopamine reuptake and rapidly metabolizes to inactive benzoylecgonine and ecgonine methyl ester is: a. cocaine. b. heroin. c. methamphetamine. d. ethanol.

ANS: A Cocaine has cardiovascular effects and is a potent CNS stimulant that blocks dopamine reuptake at nerve synapses; it is rapidly metabolized to benzoylecgonine (BE) and ecgonine methyl ester, both of which are inactive.

DIF:

1

RETFE: ST PaBgA eN 58K5SELLOEBRJ. : C7OM

9. Respiratory alkalosis is a clinical feature of overdose ingestion of salicylate because: a. salicylates induce hyperventilation. b. the central nervous system is stimulated to depress breathing. c. uncoupling of oxidative phosphorylation occurs in all cells. d. salicylates enhance anaerobic glycolysis.

ANS: A Salicylates directly stimulate the central respiratory center in the brain, causing hyperventilation and respiratory alkalosis. Hyperventilation resulting in excessive elimination of CO2 leads to an increase in blood pH and alkalosis.

DIF:

2

REF: Page 570

OBJ: 5

10. An individual is found unconscious with two empty pill bottles nearby, one of aspirin and the other of phenobarbital. The best antidote for this type of double drug overdose would be: a. N-acetylcysteine. b. forced alkaline diuresis. c. hemodialysis. d. atropine.

ANS: B

See Table 31-1. Elimination of salicylate may be enhanced by alkaline diuresis and in severe cases by hemodialysis. Urine alkalinization may enhance the elimination of long-acting barbiturates, such as phenobarbital.

DIF:

2

REF: Page 570

OBJ: 5 | 7 | 10

11. The most common laboratory method for detection, discrimination, and quantitation of alcohols in biological specimens is: a. immunoassay. b. HPLC. c. spectrophotometry. d. flame ionization gas chromatography (GC).

ANS: D Flame ionization GC remains the most common method for the detection and quantitation of volatile alcohols in biological samples. Not only does it distinguish between (1) ethanol, (2) methanol, (3) isopropanol, and (4) acetone, it has the capability to measure concentrations as low as 10 mg/dL. DIF:

1

REF: Page 569

OBJ: 4

12. In a chronic user of marijuana, the metabolite will remain in urine for what period of time? a. 2 to 7 days b. 3 to 4 weeks c. Up to 73 days d. 3 to 4 months ANS: C The window of detection for the urine concentration of THC-COOH varies among casual (2 to 7 days) and chronic abusers (up to 73 days) of marijuana and is dose dependent.

DIF:

1

REF: Page 578

OBJ: 7

13. A type of drug test that is used to rule out the presence of drugs or to suggest the presence of a particular drug group and that has been replaced by rapid immunoassay tests is the test. a. gas chromatography b. confirmatory c. forensic drug d. spot ANS: D Spot tests are qualitative procedures that are (1) rapid, (2) easily performed, and (3) non-instrument based. They are potentially valuable to rule out the presence of drugs or to suggest (but not prove) the presence of a drug of a particular group. Spot tests are less frequently employed now because some have been largely replaced by rapid immunoassays.

DIF:

1

REF: Page 562

OBJ: 1

14. The correct formula for determining anion gap is:

a. [HCO –] – [Na+ + Cl–]. b. [Na+] – [Cl- + HCO –]. c. [Na+] + [Cl- + HCO –]. d. [Cl–] + [Na+ + HCO –].

ANS: B The formula most commonly used for the anion gap (AG) calculation is as follows: AG = [Na+] – [Cl− + HCO –].

DIF:

1

REF: Page 563

OBJ: 2

15. An 18-year-old man who had been found unresponsive and face down in his bed after spending the day working in his garage is brought to the hospital emergency department. He had not responded to naloxone administration given by the paramedics. His history reveals that he was despondent over the recent death of his father, with whom he enjoyed restoring antique automobiles. Laboratory results indicate negative serum acetone, elevated serum urea and creatinine, normal PO2, decreased bicarbonate, increased PCO2, and increased osmol gap (corrected for ethanol) and anion gap. Urinalysis indicated many oxalate crystals.

Based on these laboratory results, what is the likely compound that has affected this individual? a. Carbon monoxide b. Methanol c. Ethylene glycol d. Codeine ANS: C Ethylene glycol, present in products such as antifreeze, may be ingested accidentally or for the purpose of inebriation or suicide. Metabolism of ethylene glycol by alcohol dehydrogenase (ADH) results in the formation of numerous acid metabolites, including oxalic acid and glycolic acid, which are responsible for much of the toxicity of ethylene glycol.

DIF:

3

REF: Page 568

OBJ: 2 | 4 | 10

16. An 18-year-old man who had been found unresponsive and face down in his bed after spending the day working in his garage is brought to the hospital emergency department. He had not responded to naloxone administration given by the paramedics. His history reveals that he was despondent over the recent death of his father, with whom he enjoyed restoring antique automobiles. Laboratory results indicate negative serum acetone, elevated serum urea and creatinine, normal PO2, decreased bicarbonate, increased PCO2, and increased osmol gap and anion gap. Urinalysis indicated many oxalate crystals. Based on these laboratory results and the likely compound that has affected this individual, what are the metabolizing enzyme and the metabolite(s) formed from the toxic compound? a. CYP2D6; morphine b. Alcohol dehydrogenase; glycolic and oxalic acids c. Alcohol hydroxylase; acetone d. Aldehyde dehydrogenase; formaldehyde ANS: B

Metabolism of ethylene glycol by alcohol dehydrogenase results in the formation of a number of acid metabolites, including oxalic acid and glycolic acid.

DIF:

3

REF: Page 568

OBJ: 2 | 4 | 10

17. An 18-year-old man who had been found unresponsive and face down in his bed after spending the day working in his garage is brought to the hospital emergency department. He had not responded to naloxone administration given by the paramedics. His history reveals that he was despondent over the recent death of his father, with whom he enjoyed restoring antique automobiles. Laboratory results indicate negative serum acetone, elevated serum urea and creatinine, normal PO2, decreased bicarbonate, increased PCO2, and increased osmol gap and anion gap. Urinalysis indicated many oxalate crystals. Based on these laboratory results and the likely compound that has affected this individual, what is the best therapy? a. Fomepizole b. Increased naloxone dose c. Folate administration d. Activated charcoal ANS: A The mainstay of therapy for ethylene glycol toxicity includes administration of ethanol or fomepizole as a competitive alcohol dehydrogenase inhibitor.

DIF:

3

REF: Page 568

OBJ: 2 | 4 | 10

18. An 18-year-old man who had been found unresponsive and face down in his bed after spending the day workinT gE inShTisBgAaN raK geSiE sL brLoE ugRh. t tCoOthMe hospital emergency department. He had not responded to naloxone administration given by the paramedics. His history reveals that he was despondent over the recent death of his father, with whom he enjoyed restoring antique automobiles. Laboratory results indicate negative serum acetone, elevated serum urea and creatinine, normal PO2, decreased bicarbonate, increased PCO2, and increased osmol gap and anion gap. Urinalysis indicated many oxalate crystals. A second anion gap is calculated and the value has increased from the initial value. Based on these laboratory results and the likely compound that has affected this individual, what type of acid-base imbalance is present? a. Respiratory acidosis b. Respiratory alkalosis c. Metabolic alkalosis d. Metabolic acidosis ANS: D The glycolic acid metabolite is responsible for the toxicity of ethylene glycol, the clinical manifestations of which include (1) neurological abnormalities, (2) severe metabolic acidosis, (3) acute renal failure, and (4) cardiopulmonary failure. If, despite adequate supportive care, an anion gap metabolic acidosis worsens in a poisoned patient, the clinician should consider as potential causes continued absorption of exogenous acids (e.g., salicylate ethylene glycol, methanol).

DIF:

3

REF: Page 568

OBJ: 2 | 4 | 10

19. Which one of the following best explains the toxic effect of acetaminophen overdose? a. The coma produced is caused by an immediate decrease in sensitivity to CO2 concentration through depression of respiratory centers in the brain. b. The myocardial infarction is caused by the effect on respiratory centers in the brain and eventual lack of stimulation of the heart. c. The hepatic necrosis is caused by depletion of a substance in the liver and eventual accumulation of the oxidized metabolite. d. The metabolic acidosis produced is caused by increased formation of formic acid by the liver during metabolism.

ANS: C With acetaminophen overdose, the sulfation pathway formed by glutathione conjugation of metabolites becomes saturated, and consequently a greater portion is metabolized by the P-450 mixed-function oxidase pathway. When the tissue stores of glutathione become depleted, arylation of cellular molecules by the benzoquinone imine intermediate leads to hepatic necrosis.

DIF:

2

REF: Page 569

OBJ: 5

20. Following a school field trip to the country, four teenage boys are admitted to the hospital emergency department with visual system impairment and severe abdominal pain.

Laboratory evaluation reveals metabolic acidosis, increased anion gap and osmol gap, negative serum acetone, and no unusual urine sediments. Intoxication by which of the following is most likely responsible? a. Methanol b. Carbon monoxide c. Isopropanol d. Ethanol ANS: A Methanol is oxidized by liver alcohol dehydrogenase to formaldehyde. Formaldehyde in turn is rapidly oxidized by aldehyde dehydrogenase to formic acid, which may cause serious acidosis and optic neuropathy, resulting in blindness or death.

DIF:

2

REF: Page 566-567

OBJ: 3 | 10

21. You receive a filled purple-top (EDTA-containing) tube with a request for a cyanide assay that requires a whole blood sample. You: a. realize that the tube you received will not yield any red blood cells, so you call to request a new sample collection. b. realize that the tube you received will give you serum when separated, so you call to request a new sample collection. c. know that the tube you received is perfectly fine if well mixed and proceed to run the sample to check for evidence of cyanide. d. know that urine is the only specimen you can use for this type of assay, so you call to have a new sample collected.

ANS: C

Following microdiffusion, whole blood cyanide is measured by spectrophotometry or by headspace gas chromatography. A purple-top EDTA anticoagulant-containing tube produces a whole blood sample.

DIF:

2

REF: Page 565

OBJ: 3 | 10

22. The enzyme responsible for the metabolism of delta-9-tetrahydrocannabinol (THC) to its various metabolites is: a. alcohol dehydrogenase. b. CYP2D6. c. CYP3A. d. aldehyde dehydrogenase.

ANS: B THC is metabolized by CYP2D6 liver enzymes to greater than 100 metabolites.

DIF:

1

REF: Page 557

OBJ: 7

23. To recognize a poisoning pattern, groups of drugs with similar actions, symptoms, and clinical signs are examined. These common signs and symptoms are referred to as the: a. metabolic pattern. b. pattern constellation. c. toxin effect. d. toxidrome.

ANS: D Toxic syndromes (“toxidT roEmSeT s”B) A arNeKclSinEicLaL l sEyR nd.rC om OeMs that are essential for the successful recognition of poisoning patterns. A toxidrome is the constellation of clinical signs and symptoms that suggests a specific class of poisoning.

DIF:

1

REF: Page 561

OBJ: 1

24. An example of a nonbenzodiazepine sedative-hypnotic that is used in drug-facilitated sexual assault that interacts with a subtype of the GABAA receptor complex is: a. diazepam. b. zolpidem. c. chloral hydrate. d. -hydroxybutyrate.

ANS: B A new generation of sedative-hypnotics are available that are structurally different from benzodiazepines and also used as DFSAs. They include (1) zopiclone, (2) eszopiclone (Lunesta), (3) zolpidem (Ambien), and (4) zaleplon (Sonata). The pharmacologic effects of these agents result from their interaction with a specific subtype of GABAA receptor complex.

DIF:

1

REF: Page 587

OBJ: 8

25. Agents related to the anticholinergic toxidrome include all of the following except: a. tricyclic antidepressants.

b. antihistamines. c. phenothiazines. d. organophosphates.

ANS: D Agents related to the anticholinergic toxidrome include the (1) tricyclic antidepressants, (2) phenothiazines, and (3) antihistamines. Organophosphates are related to the cholinergic syndrome because they inactivate acetylcholinesterases to increase acetylcholine.

DIF:

1

REF: Page 570-571

OBJ: 6

26. A sympathomimetic drug that can be a drug of abuse but has legitimate pharmacologic use as a treatment for narcolepsy is: a. fentanyl. b. marijuana. c. amphetamine. d. diazepam.

ANS: C Amphetamine and methamphetamine are sympathomimetic CNS stimulant drugs (they mimic endogenous neurotransmitters in the sympathetic nervous system) that have limited legitimate pharmacologic uses, such as treatment for (1) narcolepsy, (2) obesity, and (3) attention-deficit hyperactivity disorders.

DIF:

1

REF: Page 582

OBJ: 1 | 7

27. Because of its rapid turnaTrE ouSnT d BtiA mN e,KthSeElL abLoE raR to.ryCm OeMthod of choice used to screen urine samples for their opiate content is: a. immunoassay. b. gas chromatography. c. liquid chromatography. d. ferric chloride test.

ANS: A Given their relatively rapid turnaround time and ability to detect several opiates, immunoassays are the methods of choice to screen urine samples for their opiate content.

DIF:

1

REF: Page 582

OBJ: 7

28. Cocaine is subject to recreational abuse because it: a. has CNS depressant effects resulting in sedation and hypnosis, and increases growth hormone release. b. increases the effect of peripheral and central cholinergic nervous systems to induce feelings of happiness. c. depresses the CNS but not the peripheral nervous system, depending on the blood ethanol concentration, to produce euphoria and decreased inhibition. d. blocks dopamine reuptake at nerve synapses and prolongs the action of dopamine in the CNS, leading to feelings of euphoria.

ANS: D

The CNS effects produced by cocaine use are thought to be largely associated with the ability of cocaine to block dopamine reuptake at nerve synapses, thereby prolonging the action of dopamine in the CNS. It is this response that leads to recreational abuse of cocaine.

DIF:

2

REF: Page 585

OBJ: 7

29. Meconium is a difficult substance to analyze in a clinical laboratory for drug assessment because: a. there is a shorter window of detection for drugs compared to urine. b. it is a difficult material to work with, and drug testing is far less standardized than for a urine specimen. c. external environmental exposure to drugs causes them to be falsely detected in this substance. d. contains analytes that cross-react with most drug tests.

ANS: B In the clinical laboratory, meconium is an unfamiliar matrix; it is a sticky material that is more difficult to work with than urine. Confirmation assays for meconium are more difficult than those for urine and meconium drug testing is far less standardized than urine drug testing.

DIF:

2

REF: Page 589

OBJ: 9

30. A positive urine immunoassay screening test for a drug of abuse must be confirmed by: a. GC-MS. b. a more sensitive and specific immunoassay procedure. c. electrophoresis. d. a spot test.

ANS: A All positive immunoassay results should be confirmed by a second independent method.

The most widely accepted method for drug confirmation is GC-MS. DIF:

1

REF: Page 584

OBJ: 1

31. The best antidote for overdose with heroin is: a. activated charcoal. b. naloxone. c. forced alkaline diuresis. d. forced acid diuresis.

ANS: B See Table 31-1. Naloxone binds to all three opioid receptor types, particularly the µ-opioid receptor, making it a competitive antagonist of heroin binding.

DIF:

1

REF: Page 561, Table 31-1

OBJ: 7

32. Laboratory analysis of which one of the following enzyme activities is performed to assess acute neurotoxicity from organophosphate or carbamate poisoning? a. Aldehyde dehydrogenase

b. CYP2D6 c. Acetylcholinesterase d. Transaminase enzymes ANS: C Acetylcholinesterase activity present at nerve junctions is similar to that present in red blood cells and is an appropriate index of neurotoxicity. This assay is more sensitive than serum cholinesterase activity and often is used to confirm exposure and to predict enzyme reactivation during treatment.

DIF:

2

REF: Page 574

OBJ: 6

33. An individual is brought to the hospital emergency department with nausea, vomiting, and an altered mental status. An empty bottle of nonprescription enteric-coated acetylsalicylic acid (aspirin) was found at her bedside by her husband 30 minutes earlier. Although all signs and symptoms point to salicylate overdose, laboratory analysis indicated no acid-base disorder and low salicylate concentration using a photometric procedure. What is the explanation of this discrepancy? a. Aspirin overdose does not produce toxic effects, so the emergency department physicians should request different laboratory tests. b. The laboratory analyses were likely not specific or sensitive enough to discern the salicylate level or the acid-base disorder. c. There has been too lengthy a period of time between pill ingestion and laboratory analysis, and all laboratory values have returned to normal levels. d. The enteric-coated pills delayed aspirin absorption and blood work was collected before the salicylate could reach maximum concentration.

ANS: D The absorptive phase of salicylates is often unpredictable (delayed or erratic) as a result of (1) bezoar formation, (2) enteric-coated product, (3) gastric outlet obstruction, or (4) pylorospasm. Therefore, a specimen collected soon after the original ingestion may not be reflective of the potential peak concentration. Initial serial concentrations should be performed every 2 hours while the patient is monitored clinically. In addition, lack of metabolic acidosis does not rule out the potential for salicylate toxicity.

DIF:

2

REF: Page 570

OBJ: 5 | 10

34. The laboratory method of analysis that is accurate and precise for very low concentrations of carbon monoxide is: a. spectrophotometry. b. immunoassay. c. gas chromatography. d. potentiometry.

ANS: C Gas chromatographic methods are accurate and precise even for very low concentrations of carbon monoxide. Spectrophotometric methods are (1) rapid, (2) convenient, (3) accurate, and (4) precise, except at very low concentrations of carboxyhemoglobin (<3%).

DIF:

1

REF: Page 565

OBJ: 3

MATCHING Match the compound with the appropriate antidote for overdose. a. Salicylic acid b. Acetaminophen c. Cyanide d. Organophosphates 1.

2.

3.

4.

N-acetylcysteine Activated charcoal Atropine Hydroxycobalamin

1. ANS: B DIF: 1 REF: Page 561 OBJ: 3 | 5 | 6 MSC: See Table 31-1. Antidotal therapy for acetaminophen overdose with N-acetylcysteine (NAC) is most effective when administered before hepatic injury occurs.

2. ANS: A DIF: 1 REF: Page 561 OBJ: 3 | 5 | 6 MSC: See Table 31-1. Activated charcoal binds aspirin and prevents its absorption while elimination of salicylate may be enhanced by alkaline diuresis.

3. ANS: D DIF: 1 REF: Page 561 OBJ: 3 | 5 | 6 MSC: See Table 31-1. Specific therapy for organophosphate and carbamate insecticide poisoning includes administration of atropine to block the muscarinic (but not nicotinic) actions of acetylcholine.

4. ANS: C DIF: 1 REF: Page 561 OBJ: 3 | 5 | 6 TyEdS MSC: See Table 31-1. H roTxB ycAoN baKlaSmEiL nL orEtR he.cCyO anMide antidote kit should be administered as soon as cyanide poisoning is suspected.

Match the compound with its metabolite. a. Ethanol b. Barbiturate c. Heroin d. Ethylene glycol 5.

6.

7.

8.

Glycolic acid Morphine Carboxylic acid Acetaldehyde

5. ANS: D DIF: 1 REF: Page 566-567 OBJ: 4 | 7 MSC: Metabolism of ethylene glycol by alcohol dehydrogenase results in the formation of numerous acid metabolites, including oxalic acid and glycolic acid.

6. ANS: C DIF: 1 REF: Page 577 OBJ: 4 | 7 MSC: Heroin is rapidly converted to 6-monoacetylmorphine, which in turn is hydrolyzed to morphine.

7. ANS: B DIF: 1 REF: Page 580 OBJ: 4 | 7 MSC: Barbiturates are transformed to alcohols, phenols, ketones, or carboxylic acids in the

liver.

8. ANS: A DIF: 1 REF: Page 563 OBJ: 4 | 7 MSC: Ethanol is metabolized by ADH to form acetaldehyde in the liver Match the drug with its correct elimination half-life. a. 2 to 6 minutes b. 30 minutes to 1.5 hours c. 5 to 6 hours d. 21 to 37 hours 9.

10.

11.

12.

Diazepam Heroin Cocaine Carboxyhemoglobin

9. ANS: D DIF: 1 REF: Page 575-576 OBJ: 3 | 7 MSC: See Tables 31-7 and 31-8. Diazepam, a benzodiazepine, is considered a long-acting agent, with a long half-life greater than 24 hours.

10. ANS: A DIF: 1 REF: Page 575-576 OBJ: 3 | 7 MSC: See Tables 31-7 and 31-8. Heroin itself is rarely found in body fluids because of its extremely short half-life (2 to 6 minutes).

11. ANS: B DIF: 1 REF: Page 575-576 OBJ: 3 | 7 MSC: See Tables 31-7 and 31-8. The half-life of cocaine is 0.5 to 1.5 hours and its metabolite's half-life is 4 to 7 hours.

12. ANS: C DIF: 1 REF: Page 575-576 OBJ: 3 | 7 MSC: See Tables 31-7 and 31-8. The half-life of carboxyhemoglobin is 5 to 6 hours when the patient breathes room air; it is reduced to about 1.5 hours when the patient breathes 100% oxygen.

Match the substance with the suggested antidote for its overdose. a. Flumazenil b. Physostigmine c. Ethanol d. Methylene blue 13.

14.

15.

16.

Anticholinergic agents Ethylene glycol Methemoglobinemia Benzodiazepine

13. ANS: B DIF: 1 REF: Page 561 OBJ: 4 | 6 | 7 MSC: See Table 31-1. Anticholinergic agent overdose such as that with tricyclic antidepressants is treated with physostigmine.

14. ANS: C DIF: 1 REF: Page 561 OBJ: 4 | 6 | 7 MSC: See Table 31-1. Ethylene glycol is treated with ethanol or fomepizole.

15. ANS: D DIF: 1 REF: Page 561 OBJ: 4 | 6 | 7 MSC: See Table 31-1. Methylene blue hastens the conversion of methemoglobin to hemoglobin.

16. ANS: A DIF: 1 REF: Page 561 OBJ: 4 | 6 | 7 MSC: See Table 31-1. Flumazenil, used with care, treats overdose with benzodiazepine.

Match the toxicant with its specific effect. a. Central nervous system depressant b. Central nervous system stimulant c. Blocks oxygen binding to hemoglobin d. Interferes with enzyme action 17.

18.

19.

20.

Pesticides (carbamates) Carbon monoxide Methamphetamine Ethanol

17. ANS: D DIF: 2 REF: Page 574 OBJ: 3 | 4 | 7 MSC: Carbamates bind to acetylcholinesterase in the central nervous system (CNS) and in the periphery.

18. ANS: C DIF: 2 REF: Page 565 OBJ: 3 | 4 | 7 MSC: Carbon monoxide binds with high affinity to hemoglobin to block binding of oxygen.

19. ANS: B DIF: 2 REF: Page 582 OBJ: 3 | 4 | 7 MSC: Methamphetamine is a stimulant as is cocaine, which acts on dopamine receptors to block reuptake.

20. ANS: A DIF: 2 REF: Page 566 OBJ: 3 | 4 | 7 MSC: The principal pharmacologic action of ethanol is depression of the CNS. TRUE/FALSE 1. The long elimination half-life of marijuana that affects the duration of detection is due to the reentry of THC from tissue fat stores into the circulation.

ANS: T Variables affecting the duration of detection include (1) dose, (2) frequency of exposure, (3) route of exposure, (4) body composition, (5) fluid excretion, and (6) method of detection.

Because of the slow release of THC from tissue storage sites, it can be identified in urine for long periods depending on the usage by an individual. After cessation of marijuana smoking, THC and its metabolites are slowly released from fat stores.

DIF:

1

REF: Page 578

OBJ: 7

Chapter 32: Toxic Metals Test Bank MULTIPLE CHOICE 1. The occurrence of cell membrane damage causing normal cells to be replaced with fibroblasts occurs in the heart because of a deficiency of which one of the following metals? a. Selenium b. Chromium c. Silica d. Copper ANS: A In humans, cardiac muscle is the tissue most susceptible to Se deficiency; with cell membrane damage, normal cells are replaced with fibroblasts. This condition, known as cardiomyopathy, is characterized by an enlarged heart consisting of predominantly nonfunctioning fibrotic tissue.

DIF:

2

REF: Page 604

OBJ: 1 | 4

2. In blood collection for chromium or other trace metal analysis, what aspect of specimen collection is critical? a. Timing of the blood draw, whether morning or afternoon b. Use of serum and not plasma c. Using specially manufactured collection tubes with unique stoppers OM d. Using a special tournT iqEuS etTthBaA t dNoKeS s nEoLt L caEuR se.hCem olysis ANS: C Preanalytical handling of the specimen for chromium (Cr) analysis is critically important.

Many specimen collection products contain Cr in the rubber stopper or O-rings to add plasticity to the rubber. Special rubber was created to manufacture evacuated blood collection tubes suitable for use in trace metal testing.

DIF:

1

REF: Page 599

OBJ: 5

3. What blood analyte does a toxic overdose of aluminum affect? a. Acid phosphatase b. Vitamin C (ascorbic acid) c. Lactate dehydrogenase d. Parathyroid hormone ANS: D Deposition of aluminum at the bone mineralization front and binding to parathyroid calcium receptors interrupts physiological calcium exchange; the calcium in bone becomes unavailable for resorption into blood, a process under the physiological control of parathyroid hormone (PTH). The usual parathyroid response to these conditions decreases secretion of PTH. DIF:

2

REF: Page 596

OBJ: 4

4. An individual is admitted to the hospital with markedly increased liver enzymes (transferases) and unusual behavioral changes noted by her family. A protein electrophoresis reveals decreased ceruloplasmin. Which one of the following toxic metals might be implicated in this individual’s symptoms? a. Beryllium b. Copper c. Aluminum d. Lead ANS: B The classical presentation of copper (Cu) toxicosis is represented by the genetic disease of Cu accumulation known as Wilson disease. This disease is typified by hepatocellular damage (increased transferases) and/or changes in mood and behavior caused by accumulation of Cu in central neurons. Because most Cu circulating in blood is bound to ceruloplasmin, and ceruloplasmin formation is decreased in Wilson disease, blood copper is less than normal.

DIF:

2

REF: Page 600

OBJ: 4

5. A byproduct of zinc and lead smelting, this metal is also used in the production of rechargeable batteries. Chronic exposure to this metal results in renal damage and breathing its fumes causes pulmonary congestion resembling chronic emphysema. a. Beryllium b. Copper c. Cadmium d. Aluminum ANS: C Cd is a byproduct of zinc and lead smelting. It is used (1) in industry in electroplating, (2) in the production of rechargeable batteries, (3) as a common pigment in organic-based paints, and (4) in tobacco products. Chronic exposure to Cd causes accumulated renal damage, while breathing the fumes of Cd vapors leads to nasal epithelial deterioration and pulmonary congestion resembling chronic emphysema.

DIF:

1

REF: Page 598

OBJ: 4

6. Which one of the following is a toxic metal that produces Mees’ lines upon overdose exposure by denaturing keratin in fingernails? a. Aluminum b. Arsenic c. Chromium d. Gadolinium ANS: B Several weeks after exposure to As, transverse white striae, called Mees’ lines, may appear in the fingernails of the exposed individual caused by denaturation of keratin by metals such as As, Cd, Pb, and Hg. DIF:

1

REF: Page 597

OBJ: 1 | 4

7. Lead produces a serious toxic effect when ingested because it: a. irreversibly binds to heme iron in hemoglobin. b. vasoconstricts cardiac blood vessels and vasodilates peripheral vessels. c. depresses the central nervous system and induces coma. d. does not allow for the incorporation of heme into the porphyrin molecule.

ANS: D Lead inhibits aminolevulinic acid dehydratase (ALAD), one of the enzymes that catalyze synthesis of heme from porphyrin. ALAD is also referred to as ferrochelatase and is important in incorporating heme into protoporphyrin.

DIF:

1

REF: Page 601

OBJ: 4

8. What is the specimen of choice for determining arsenic exposure in an individual and why? a. Urine is the specimen of choice because arsenic is concentrated in and excreted predominantly by kidneys. b. Whole blood is the specimen of choice because blood concentrations remain elevated for at least 48 hours after exposure. c. Serum is the specimen of choice because arsenic moves into the serum phosphate pool and is easily measured with phosphate. d. Plasma is the specimen of choice because arsenic attaches to coagulation factors and affects clotting times best assayed in a plasma sample.

ANS: A Urine is the specimen of choice for As analysis because As is excreted predominantly by the kidney, where it becomeT s cEoSnT ceB ntAraNteKdS .B odEiR s. thC eO leM ast useful specimen for identifying ElLoL As exposure because blood As concentrations are elevated for only a short time after administration and rapidly disappear into the large body phosphate pool.

DIF:

2

REF: Page 598

OBJ: 5

9. Both mercury and arsenic produce their symptoms of toxicity in a similar way. This includes: a. deposition in bone causing interruption of physiological calcium exchange. b. strong acid formation when dissolved in water leading to tissue toxicity. c. binding to the sulfhydryl groups of protein causing loss of protein activity. d. formation of protein adducts leading to protein denaturation in alveoli.

ANS: C Arsenic also binds with any hydrated sulfhydryl group on protein, distorting the three-dimensional configuration of the protein, thus causing it to lose activity. Mercury avidly reacts with sulfhydryl groups of protein, causing a change in the tertiary structure of the protein with subsequent loss of the biological activity associated with that protein.

DIF:

2

REF: Page 597

OBJ: 4

10. A four-member family of fish-loving vegetarians has become ill and visits their family practitioner. Their symptoms include stumbling (ataxia), visual field loss, and urinary difficulties. No Mees’ lines are observed. Being environmentally conscious, they have their home examined for toxic gases. All tests are negative. Based on their history and symptoms, what toxic metal might be to blame? a. Cadmium b. Iron c. Arsenic d. Mercury ANS: D The symptoms listed here, including ataxia, vision problems, and renal failure, all indicate possible methylmercury poisoning. The most common source of mercury in the diet is through the aquatic food chain, and humans are exposed to mercury through eating contaminated fish.

DIF:

2

REF: Page 603

OBJ: 4 | 6

11. A four-member family of vegetarians has become ill and visits their family practitioner.

Their symptoms include stumbling (ataxia), visual field loss, and urinary difficulties. No Mees’ lines are observed. Based on their symptoms and knowledge of the correct metal involved, what is the best therapy? a. British anti-Lewisite (BAL) b. Erythropoietin c. Chelation therapy d. Keratin ANS: A Treatment with BAL or penicillamine will mobilize mercury, allowing for its excretion in the urine.

DIF:

1

REF: Page 604

OBJ: 1 | 4

12. All of the following factors must be demonstrated before metal toxicity is considered a diagnosis except: a. A source of metal exposure must be evident. b. More than two organ systems must be affected. c. Typical metal overdose signs and symptoms must be shown. d. Abnormal metal concentration in the appropriate tissue must be evident.

ANS: B The number of organ systems affected is not a critical consideration in this case. Diagnosis of metal toxicity requires demonstration of all of the following factors: (1) a source of metal exposure must be evident, (2) the patient must demonstrate signs and symptoms typical of the metal, and (3) abnormal metal concentration in the appropriate tissue must be evident.

DIF:

1

REF: Page 593

OBJ: 2

13. When reporting the results of a urine metal analysis, such as urine chromium, how are the results reported?

a. b. c. d.

In millimoles of drug per liter of urine per 24 hours As micrograms of metal per milliliter of urine in a random specimen In concentration units of the metal of interest per gram of creatinine As milligrams of metal/deciliter of urine

ANS: C The most common sample used is a random urine sample, and results are expressed in concentration units for the metal of interest per gram of creatinine to normalize for excretion volume variances.

DIF:

1

REF: Page 594

OBJ: 5

14. Certain metals are essential for life at low concentrations and typically function as protein cofactors required for enzymatic reactions. These particular elements are located in which group(s) and row(s) of the periodic table? a. Groups 6 through 12, row 4 b. Groups 1 and 2, rows 3 and 4 c. Group 1, row 5 d. Groups 13 through 16, rows 4 through 6 ANS: A Elements in groups 6 through 12 in row 4 are essential for life but are required at low concentrations; many are protein cofactors required for enzymatic activity. The gastrointestinal tract and the dermis regulate intake of these to some degree, but overload will induce passive diffusion that can lead to excessive concentrations and toxicity.

Elements in rows 5 and below are classified as nonessential.

DIF:

2

REF: Page 594

OBJ: 3

MATCHING Match the metal with the analytical issue that could alter the results of analysis. a. Reduced to a nontoxic form in biological specimens b. Blood specimens are not especially useful; urine is best c. Requires a lymphocyte proliferation test; serum or urine quantification is not useful d. To examine erythrocytes, EDTA-anticoagulated blood is specimen of choice 1.

2.

3.

4.

Arsenic Lead Chromium Beryllium

1. ANS: B DIF: 2 REF: Page 597 OBJ: 5 MSC: Blood is the least useful specimen for identifying As exposure, because blood As concentrations are elevated for only a short time after administration and rapidly disappear into the large body phosphate pool.

2. ANS: D DIF: 2 REF: Page 602 OBJ: 5 MSC: Because Pb is concentrated in the erythrocytes, blood containing

ethylenediaminetetraacetic acid (EDTA) as an anticoagulant is the specimen of choice for Pb analysis.

3. ANS: A DIF: 2 REF: Page 599 OBJ: 5 MSC: When measuring chromium in biological specimens, it is quickly reduced to a nontoxic form.

4. ANS: C DIF: 2 REF: Page 598 OBJ: 5 MSC: Blood and lung cells from CBD patients proliferated when exposed to Be in culture.

This assay has been refined and is offered as the Be lymphocyte proliferation test.

Chapter 33: Diabetes Test Bank MULTIPLE CHOICE 1. In uncontrolled diabetes mellitus, excess ketones are present in the blood and urine because of: a. decreased lipid formation. b. increased glycolysis. c. increased breakdown of lipids (lipolysis). d. increased glucose uptake into cells.

ANS: C In uncontrolled diabetes, the low insulin concentration result in increased lipolysis and decreased reesterification, thereby increasing plasma free fatty acids. In addition, the increased glucagon/insulin ratio enhances fatty acid oxidation in the liver. Increased counter-regulatory hormones also augment lipolysis and ketogenesis in fat and liver, respectively. Thus increased hepatic ketone production and decreased peripheral tissue metabolism lead to acetoacetate accumulation in the blood.

DIF:

1

REF: Page 613

OBJ: 16

2. Glucagon is made by the -cells in the pancreas and when released causes elevated blood glucose. By what mechanism does glucagon promote hyperglycemia? a. Glucagon promotes hypoglycemia, not hyperglycemia. b. Glucagon stimulates T inEsuSliTnBreAleNaK seS. ELLER.COM c. Glucagon promotes glycogenesis in all cells. d. Glucagon stimulates glycogenolysis and gluconeogenesis.

ANS: D Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.

DIF:

1

REF: Page 613

OBJ: 1 | 5

3. Which of the following is characteristic of type 1A diabetes mellitus? a. Normal blood insulin levels b. Lack or decrease of functional insulin receptors on cells c. Circulating autoantibodies formed against pancreatic insulin-secreting cells. d. Individuals with this type of diabetes are not prone to ketosis.

ANS: C Immune-mediated diabetes or type 1A is caused by cellular-mediated autoimmune destruction of the insulin-secreting cells of pancreatic -cells, typically mediated by T cells.

DIF:

2

REF: Page 616

OBJ: 1 | 2

4. Glycated hemoglobins are formed by the addition of glucose to the residue.

-terminal

a. b. c. d.

C; valine N; valine C; alanine N; alanine

ANS: B Hb A1c is formed by the condensation of glucose with the N-terminal valine residue of either -chain of Hb A to form an unstable Schiff base.

DIF:

1

REF: Page 625

OBJ: 1 | 17

5. Determining urinary albumin excretion (UAE) is critical in type 1 and type 2 diabetics because: a. this indicates increased attachment of glucose to proteins, lipids, and nucleic acids that contribute to the microvascular complications of diabetes. b. UAE increase indicates increased glycation of serum albumin that forms fructosamine and leads to ketoacidosis. c. increased UAE is highly predictive of and is thought to precede diabetic nephropathy and end-stage renal disease. d. it assesses the long-term blood glucose concentration in a diabetic to monitor glucose control over an 8- to 12-week period.

ANS: C The presence of increased UAE denotes an increase in the transcapillary escape rate of albumin and therefore is a marker of microvascular disease. Increased UAE precedes and is highly predictive of diabetic nephropathy, end-stage renal disease, cardiovascular mortality, and total mortality in patT ieE ntS sT wB itA hN diK abSeE teL s.LER.COM DIF:

2

REF: Page 629

OBJ: 22

6. The role of the clinical laboratory in diagnosis of diabetes mellitus involves initial diagnostic criteria. For many years, the only diagnostic criterion required was demonstration of hyperglycemia in two or more fasting plasma glucose tests. What other laboratory analysis is now considered to be useful as a diagnostic criterion? a. Demonstration of impaired glucose tolerance in the OGTT b. Consistent hyperglycemia after a 72-hour fast c. Presence of ketones in urine on more than one occasion d. Demonstration of elevated hemoglobin A1c ANS: D Several influential clinical organizations now include hemoglobin A1c (Hb A1c), which reflects long-term blood glucose concentrations, as a diagnostic criterion for diabetes. This analysis is particularly useful in the diagnosis of type 2 diabetes when hyperglycemia often is not severe enough for an individual to notice symptoms of diabetes.

DIF:

1

REF: Page 618

OBJ: 10

7. The syndrome that is considered a collection of associated clinical and laboratory findings that include insulin resistance, hyperinsulinemia, obesity, high triglyceride and low high-density lipoprotein (HDL) cholesterol, and hypertension is the:

a. b. c. d.

glucotoxic syndrome. type 1A diabetes mellitus syndrome. glucose counter-regulatory syndrome. insulin resistance syndrome.

ANS: D The insulin resistance syndrome (also known as syndrome X, or the metabolic syndrome) is a constellation of associated clinical and laboratory findings, consisting of insulin resistance, hyperinsulinemia, obesity, dyslipidemia (high triglyceride and low high-density lipoprotein [HDL] cholesterol), and hypertension. Individuals with this syndrome are at increased risk for cardiovascular disease.

DIF:

1

REF: Page 617

OBJ: 1 | 8

8. Type 2 diabetes mellitus: a. is associated with resistance to the action of insulin. b. is often initially observed in an individual with ketoacidosis. c. is also referred to as gestational diabetes. d. occurs less frequently than type 1 diabetes.

ANS: A At least two major identifiable pathological defects have been reported in individuals with type 2 diabetes. One is a decreased ability of insulin to act on peripheral tissue. This is called insulin resistance and is thought by many to be the primary underlying pathological process. Type 2 is the most prevalent type of diabetes.

DIF:

2

RETFE: ST PaBgA eN 61K7SELLOEBRJ. : C2OM

9. A pregnant woman at 27 weeks gestation is screened for gestational diabetes mellitus.

Plasma venous glucose was measured at 1 hour following a 50 g oral glucose load. What value must this glucose be above or equal to for a glucose tolerance test to be performed? a. The value must be remain within healthy glucose reference interval. b. The value must be 140 mg/dL glucose. c. The value must be 200 mg/dL glucose. d. The value must be 500 mg/dL glucose.

ANS: B See Table 33-2. A plasma glucose value greater than or equal to 140 mg/dL (7.7 mmol/L) at 1 hour after glucose ingestion indicates the necessity for definitive testing. Approximately 15% of pregnant women meet this criterion and require a full OGTT. DIF:

1

REF: Page 619, Table 33-2

OBJ: 1 | 11

10. Insulin regulates blood glucose levels by: a. enhancing glycogenolysis, gluconeogenesis, and ketogenesis in the liver. b. stimulating gluconeogenesis and increasing the breakdown of protein and fat. c. inhibiting release of growth hormone from the pituitary and inhibiting secretion of glucagon by the pancreas. d. stimulating the translocation of a glucose transporter and promoting glucose uptake into skeletal muscle and fat.

ANS: D After a meal, the pancreas releases insulin, which stimulates the translocation of GLUT4 to the plasma membrane, thereby promoting glucose uptake into skeletal muscle and fat.

DIF:

1

REF: Page 613

OBJ: 4 | 6

11. Factors identified as associated with (and possibly causing) type 1 diabetes mellitus include all of the following except: a. autoimmune reaction. b. insulin resistance. c. genetic factors. d. absolute deficiency of insulin.

ANS: B Insulin resistance is a decreased ability of insulin to act on the receptors in the peripheral tissue and is thought to be the primary underlying pathological process in type 2 diabetes, not type 1 diabetes.

DIF:

2

REF: Page 617

OBJ: 2

12. A woman visits her physician with a complaint of polyuria and polydipsia. She has a family history of type 2 diabetes mellitus and is concerned that she is developing the disease. The physician notes that her previous hemoglobin A1c (Hb A1c) value was 6% (considered within healthy reference interval in the physician’s practice) with a fasting plasma glucose of 95 mg/dL. At this visit, her Hb A1c value is 8.5%. Why would the physician be correct to order an oral glucose tolerance test (OGTT) for this individual? teT s tBhA atNgK lyScaEtiLoL nE ofRp.roCteOiM ns has increased producing a. The Hb A1c result indTicEaS elevated advanced glycation end products and the possible onset of type 2 diabetes.

An OGTT would help to confirm this. b. The Hb A1c result indicates that diabetic nephropathy is occurring, signaling the possible onset of type 2 diabetes. An OGTT would help to confirm this. c. The Hb A1c result indicates an increase in average blood glucose and possible onset of type 2 diabetes. An OGTT would help to confirm this. d. The physician would not be correct in ordering an OGTT because there is no indication that there is an onset of type 2 diabetes from the given laboratory values.

ANS: C Because each 1% change in Hb A1c represents an approximate 30 mg/dL change in average blood glucose, the woman’s average glucose might be or have been elevated to over 170 mg/dL. Fasting blood glucose concentration of 126 mg/dL is one of the diagnostic criteria for diabetes mellitus as are specific results of an OGTT. DIF:

2

REF: Page 628

OBJ: 10 | 18

13. Hb A1c makes up approximately what percentage of total Hb A1? a. 10% b. 25% c. 50% d. 80%

ANS: D Chromatographic analysis of Hb A identifies several minor hemoglobins, namely, Hb A1a, Hb A1b, and Hb A1c, which are collectively referred to as Hb A1. Hb A1c is the major fraction, constituting approximately 80% of Hb A1.

DIF:

1

REF: Page 625

OBJ: 17

14. Retinopathy, neuropathy, microvascular, and macrovascular changes are all chronic complications of both type 1 and type 2 diabetes mellitus. One theory as to the cause of these chronic problems is the elevation of advance glycation end (AGE) products. These AGE products consist of: a. glucose transporter proteins that promote the uptake of glucose from the lumen of the small bowel. b. hemoglobin that has a glucose attached to the N-terminal valine residue of either -chain of hemoglobin A. c. proteins that have been irreversibly modified by nonenzymatic attachment of glucose. d. glycated genes that contribute to the development of diabetes and the formation of diabetogenes.

ANS: C AGE products are proteins that have been irreversibly modified by nonenzymatic attachment of glucose and may contribute to the chronic complications of diabetes.

DIF:

1

REF: Page 629

OBJ: 1 | 2

15. Insulin deficiency in diabTeE teS sT mB elA liN tuK sS wE illLcLauEsR e:.COM a. increased insulin resistance and hyperglycemia. b. increased glucose uptake by cells leading to hyperglycemia and cell death. c. decreased lipolysis leading to ketosis. d. increased glucagon concentration, which contributes to hyperglycemia and ketosis.

ANS: D Increased glucagon concentrations, secondary to insulin deficiency, are believed to contribute to the hyperglycemia and ketosis of diabetes. Low insulin concentrations result in increased lipolysis and decreased reesterification of fatty acids into triglycerides, and increased plasma-free fatty acids.

DIF:

2

REF: Page 613

OBJ: 1 | 5

16. Which one of the following 2-hour plasma glucose oral glucose tolerance test (OGTT) results would be classified as diagnostic for impaired glucose tolerance if an individual’s fasting blood glucose value is 120 mg/dL (healthy glucose reference interval is 74 to 99 mg/dL)? a. 195 mg/dL b. 105 mg/dL c. 130 mg/dL d. 75 mg/dL ANS: A

Impaired glucose tolerance is diagnosed in people who have fasting blood glucose concentrations less than those required for a diagnosis of diabetes, but have a plasma glucose response during the OGTT between normal and diabetic states. The 2-hour postload plasma glucose following an OGTT is 140 to 199 mg/dL for this classification. An OGTT is required to assign a patient to this class.

DIF:

3

REF: Page 611

OBJ: 3

17. A fingerstick glucose value was 120 mg/dL. If unhemolyzed serum or plasma were tested from the same individual at the same time, what might the glucose value be? a. Approximately 132 mg/dL b. Approximately 100 mg/dL c. Approximately 60 mg/dL d. There would be no difference.

ANS: A Because whole blood glucose concentrations are approximately 10% to 15% lower than plasma or serum concentrations, a fingerstick value of 120 mg/dL + 10% of 120 would equal approximately 132 mg/dL. DIF:

3

REF: Page 622

OBJ: 13

18. The development of ketoacidosis in an uncontrolled diabetic is caused by the: a. elevated presence of lactic acid. b. increased formation of -hydroxybutyric acid. c. loss of regulation of certain diabetogenes. d. decreased number ofTinEsS ulT inBrA ecNeK ptS orEs L onLE ceR rt. aiC nO ceMlls.

ANS: B In uncontrolled diabetes, increased hepatic ketone production and decreased peripheral tissue ketone metabolism leads to acetoacetate accumulation in the blood. A small fraction undergoes spontaneous decarboxylation to form acetone, but the majority is converted to -hydroxybutyrate. These elevated ketone bodies are the major contributors to the metabolic acidosis that occurs in individuals with diabetic ketoacidosis.

DIF:

2

REF: Page 624

OBJ: 1 | 16

19. An individual with a severe, uncontrolled case of type 1 diabetes mellitus will exhibit all of the following laboratory results except: a. hyperlipidemia. b. hyperglycemia. c. hyperinsulinemia. d. decreased blood pH with increased ketone bodies.

ANS: C Individuals with uncontrolled type 1 diabetes typically have hypoinsulinemia, which leads to elevated lipids, glucose, and ketones.

DIF:

1

REF: Page 610

OBJ: 2 | 12

20. As a counter-regulator of glucose metabolism in a healthy individual, epinephrine has the effect of blood glucose. a. breaking down glucose to form glycogen to increase b. inducing liver gluconeogenesis to decrease c. increasing glucose uptake by cells to decrease d. stimulating glycogenolysis to increase ANS: D Epinephrine, a catecholamine secreted by the adrenal medulla, stimulates glucose production (glycogenolysis) and decreases glucose use, thereby increasing blood glucose concentration. It also stimulates glucagon secretion and inhibits insulin secretion by the pancreas.

DIF:

2

REF: Page 614

OBJ: 1 | 5

21. High albuminuria is defined as: a. a large albumin molecule that is present only in urine and that is measured by the lab in preclinical screening for diabetes. b. an albumin molecule that is larger and less functional because of the effects of hyperglycemia that is measured by the laboratory in the clinical diagnosis of diabetes. c. increased urinary albumin excretion between the range of 20 to 200 µg/min that is measured by the laboratory in the chronic management of diabetes mellitus. d. a long-lived glycated albumin molecule found in the urine of a type 2 diabetic and measured by the laboratory in the acute management of a diabetic.

ANS: C Before the detection of persistent proteinuria (a urinary albumin excretion, UAE, rate 200 µg/min) observed in overt diabetic nephropathy, a stage of increased UAE occurs that is not detected by routine methods. This range of 20 to 200 µg/min is termed high albuminuria.

The clinical laboratory has a vital role in both the diagnosis and management of diabetes.

Laboratory detection of and monitoring complications as part of the chronic management of diabetes is achieved by assaying creatinine, urine albumin, and serum lipids. See Table 33-3.

DIF:

2

REF: Page 621, Table 33-3

OBJ: 1 | 12 | 22

22. Although not a routine clinical laboratory screening test, measurement of insulin secretion in a potential diabetic is important because: a. an increase in insulin indicates the onset of hypoglycemia and the presence of advanced glycation end products. b. increased insulin leads to retinopathy, nephropathy, and neuropathy. c. a decrease in insulin will cause overstimulation of the GLUT4 transporter and low blood glucose. d. a decrease in glucose-stimulated insulin secretion is the first functional abnormality in both types of diabetes.

ANS: D

A decrease in glucose-stimulated insulin secretion is the first functional abnormality in both type 1 and type 2 diabetes; however, tests of insulin secretion are not currently recommended for routine clinical use.

DIF:

1

REF: Page 621, Table 33-3

OBJ: 2 | 12

23. The hyperglycemia observed in a diabetic causes many toxic effects such as retinopathy and nephropathy. Although it is unclear how these outcomes are caused by elevated blood sugar, it is thought that hyperglycemia: a. causes increased serum osmolarity, which leads to decreased blood flow in the microvascular compartments in peripheral tissues. b. causes increased production of advanced glycation end products, which might contribute to microvascular complications. c. induces secretion of glucagon, which antagonizes insulin secretion and leads to destruction of the microvessels in the retina and kidney. d. causes a hemolytic disease with shortened red blood cell survival, thus not providing enough oxygen to peripheral tissues.

ANS: B The molecular mechanism by which hyperglycemia produces toxic effects is unknown, but glycation of tissue proteins may be important. Hyperglycemia accelerates the formation of protein-bound AGE, and patients with diabetes thus have more AGE than healthy subjects.

Through effects on the functional properties of protein and extracellular matrix, AGE may contribute to the microvascular and macrovascular complications of diabetes.

DIF:

2

REF: Page 629

OBJ: 21

24. Which one of the following antibodies is found most commonly in over 90% of children who develop type 1 diabetes before 5 years old? a. Islet cell cytoplasmic antibodies b. Insulin autoantibodies c. Insulinoma-associated antigens d. Zinc transporter ZnT8 ANS: B Insulin autoantibodies are present in more than 90% of children who develop type 1 diabetes before 5 years old, but in less than 40% of individuals who develop diabetes after age 12 years.

DIF:

1

REF: Page 616

OBJ: 7

MATCHING Match the substance with the effect it has on blood glucose concentration. a. Increases b. Decreases c. Has no effect 1. Exercise 2. C-peptide

3. Somatostatin 1. ANS: A DIF: 2 REF: Page 613 OBJ: 5 | 9 MSC: Exercise induces glucagon release and glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.

2. ANS: C DIF: 2 REF: Page 612 OBJ: 5 | 9 MSC: C-peptide is devoid of biological activity but appears necessary to ensure the correct structure of insulin.

3. ANS: B DIF: 2 REF: Page 614 OBJ: 5 | 9 MSC: Somatostatin is referred to as “growth hormone inhibiting hormone” and indirectly decreases glucose by inhibiting the effects of growth hormone.

Chapter 34: Cardiovascular Disease Test Bank MULTIPLE CHOICE 1. Which one of the following cardiac biomarkers is elevated about 50 times the upper limit of normal at 24 hours after onset of an acute myocardial infarction? a. Total CK b. CK-2 (CKMB) c. Myoglobin d. Troponin ANS: D See Figure 34-5. In this figure, note the increased value of troponin compared with the other biomarkers. An increased value of cardiac troponin (cTn) is required in the appropriate clinical setting with values that manifest a rising pattern for the diagnosis of acute myocardial infarction.

DIF:

1

REF: Page 641, Figure 34-5

OBJ: 7

2. Why would high-sensitivity C-reactive protein (CRP) be an indicator of a potential myocardial infarction? a. It is an acute phase reactant plasma protein that rises in response to inflammation and the atherosclerotic process. b. CRP levels rise in response to decreased ATP generation in the heart.

LuEsRcl.e CcoOnMtraction through interaction c. It is a myocardial proTteEinStT haBtAreNgK ulSatEesLm with myosin and actin. d. It is an enzyme found in skeletal muscle and cardiac muscle that is released upon muscle damage.

ANS: A C-reactive protein (CRP) is an acute-phase reactant that was initially developed to evaluate patients with infection. It now appears that concentrations below those seen in infection but above healthy values (as measured by so-called high-sensitivity CRP, or hsCRP, assays) are biomarkers of the atherosclerotic process.

DIF:

2

REF: Page 647

OBJ: 9

3. An ideal cardiac marker should be elevated in the circulation for how long following a cardiac event? a. At least several days b. 1 to 2 months c. 1 to 3 hours d. 1 to 3 years ANS: A The ideal biomarker of myocardial injury would persist in the circulation for several days to provide a late diagnostic time window for patients who arrive late after the event.

DIF:

1

REF: Page 637

OBJ: 4

4. A 55-year-old man is taken to a hospital emergency department by helicopter following a rural automobile accident that occurred approximately 3 hours ago. The man, who is having difficulty speaking to the EMTs, is clutching his chest. Upon the man’s arrival, the emergency room physician orders a cardiac marker panel that includes serum CK, CK-2 (CK-MB), troponin, and myoglobin. The CK-2 value was less than 2% of total CK, which was slightly increased; troponin was normal; and the myoglobin was increased 3 times the upper limit of normal. The physician has asked the laboratory to explain the findings. Which of the following represents the lab’s explanation? a. The assays used to determine these results were nonspecific and not sensitive enough to detect the troponin. b. Trauma caused by the accident with possible crush injury to the chest caused elevated myoglobin with normal troponin and CK-MB. c. The use of serum as a specimen interfered with troponin and CK-MB immunoassays giving falsely low results. d. It is expected that in someone who has had a myocardial infarction in the past that all cardiac biomarker values except myoglobin to have returned to normal.

ANS: B See Figure 34-5. If an acute myocardial infarction had occurred within the past 24 hours, troponin values and CK-MB would be elevated. Cardiac troponins are specific proteins found in cardiac muscle, while increases in serum myoglobin occur after trauma to either skeletal or cardiac muscle, as in crush injuries or AMI. Even minor injury to skeletal muscle may result in increased serum concentrations of myoglobin, creating a potential for misinterpretation as myocardial injury. In addition, the proportion of CK-MB is much lower in the surrounding normaTl E arSeaTsBoA fN tisKsuSeEtL haLnEinRi.nC faO rcM ted myocardium in humans.

DIF:

3

REF: Page 641, Figure 34-5

OBJ: 7 | 10

5. Which one of the following cardiac markers is elevated for the longest period of time after a myocardial infarction? a. Troponins b. hs-CRP c. CK-2 (CK-MB) d. Myoglobin ANS: A See Figure 34-5. Cardiac troponins remain elevated for a much longer time after the onset of an AMI (up to 5 days).

DIF:

1

REF: Page 641, Figure 34-5

OBJ: 4

6. Which one of the following is considered to be the most specific marker for adverse ventricular remodeling following an acute myocardial infarction? a. CK-2 b. Troponin c. Myoglobin d. Brain natriuretic peptide (BNP)

ANS: D Early studies have demonstrated that BNP secretion reflects regional wall stress in the ventricles and is thus associated with adverse ventricular remodeling and poor prognosis after AMI. DIF:

1

REF: Page 646

OBJ: 1 | 7

7. In regard to cardiac anatomy, the myocardium: a. is the outermost layer of the cardiac wall. b. is composed of two upper chambers, the right and left atria. c. contains bundles of striated muscle fibers. d. is the sac that encloses the heart.

ANS: C The heart is enclosed in a sac called the pericardium. The cardiac wall is composed of three layers: the epicardium (the outermost layer), a middle layer, and an inner layer called the endocardium. The heart has four chambers. The two upper chambers are termed the right and left atria. The myocardium contains bundles of striated muscle fibers.

DIF:

1

REF: Page 633-634

OBJ: 1 | 2

8. Which one of the following specimen types and collection methods is best for laboratory assessment of brain natriuretic peptide (BNP) in the evaluation of congestive heart failure? a. Serum in glass blood collection tubes only b. EDTA-anticoagulated whole blood or plasma in plastic blood collection tubes only c. Heparinized plasma in any type of blood collection tube d. Urine in sterile collecTtiE onST coBnA taN inK erSfE orLaLnE alR ys.isCoOf M BNP metabolites only ANS: B For BNP, EDTA-anticoagulated whole blood or plasma appears to be the only acceptable specimen choice. For NT-proBNP, serum, heparin plasma, and EDTA plasma (reads 10% lower) appear acceptable. Plastic blood collection tubes are necessary for BNP analysis.

DIF:

2

REF: Page 644

OBJ: 7

9. Laboratory measurements for brain natriuretic peptide (BNP) be reported in: a. millimoles/liter. b. grams/deciliter. c. nanograms/liter. d. picomoles/milliliter.

ANS: C For both BNP and NT-proBNP, in the interim until a primary reference material is defined for either assay for appropriate calibration of assays, measurements should be reported in ng/L, not in pmol/mL. DIF:

1

REF: Page 646

OBJ: 8

10. A cardiac marker that increases progressively with increasing severity of disease and is not increased (or decreased) in conditions that mimic congestive heart failure is:

a. b. c. d.

troponin I. CK-2.

B-type natriuretic peptide. myoglobin.

ANS: C B-type natriuretic peptide (BNP) is a sensitive biomarker for changes in ventricular physiology; therefore concentrations of BNP in CHF patients reflect severity of CHF. CHF is defined as ineffective pumping of the heart and BNF is affected by changes in cardiac volume and performance. Circulating concentrations of BNP and NT-proBNP depend on age and sex. In addition, they are increased in chronic heart failure and are correlated with its severity.

DIF:

2

REF: Page 633-634

OBJ: 1 | 7

11. The most common laboratory method used to assess brain natriuretic peptides is: a. HPLC. b. serum electrophoresis. c. nephelometry. d. immunoassay.

ANS: D Generally, the concentrations of BNP and NT-proBNP are measured by immunoassay. A number of different immunoassays are available that use antibodies directed to different epitopes located on the antigen molecules.

DIF:

1

RETFE: ST PaBgA eN 64K4SELLOEBRJ. : C7OM

12. Which one of the following troponins appears as uncomplexed or free following myocardial injury? a. Cardiac troponin I b. Cardiac troponin T c. Cardiac troponin C d. Ternary complex of T-I-C ANS: A Following myocardial injury, multiple forms of troponin appear both in tissue and in blood.

These include (1) the complexes of cardiac troponins T, I, and C (T-I-C or ternary complex); (2) complexes of I and C (I-C binary complex); and (3) free I. DIF:

1

REF: Page 639

OBJ: 5

13. In a point-of-care (POC) test for a cardiac biomarker used in the evaluation of an individual with possible acute coronary syndrome, which one of the following is a Laboratory Medicine Practice guideline of the National Academy of Clinical Biochemistry (NACB)? a. POC testing must be performed with a maximum turnaround time of 24 hours. b. POC assays should provide quantitative results. c. Quality control and quality assurance are not required when using POC assays. d. Laboratories that use qualitative POC biomarker assays should confirm results with a quantitative biomarker test.

ANS: B The guidelines set by the NACB include the requirement for quality assurance, a turnaround time for a biomarker test of 1 hour from blood collection to results reporting, and a POC assay that provides quantitative results.

DIF:

1

REF: Page 640

OBJ: 6

14. Chest pain that is associated with a decrease in oxygen supply to the heart muscle but that exhibits no cellular necrosis based on cardiac troponin value and is considered a less severe event is referred to as: a. angina. b. acute myocardial infarction. c. congestive heart failure. d. thrombolysis.

ANS: A Other events of lesser severity may be missed entirely or be called angina, which ranges from stable to unstable angina. The ischemic events in the heart, ranging from angina (no cell death) to acute myocardial infarction (cell death), are known as acute coronary syndromes (ACS).

DIF:

1

REF: Page 633-634

OBJ: 1

15. In the process of atherosclerotic plaque formation, what is the typical precipitating event? a. Increased concentration of circulating coagulation factors b. Cellular involvement and clot formation TBoA c. Damage to the endotT heEliS um f cNaK rdSiaEcLbL loE odRv.eCssOeM ls d. Release of tissue factor leading to coagulability ANS: C Atherosclerosis, a disease process that causes plaque formation, is a chronic inflammatory disease that results after some event damages the internal lining cells (endothelium) of blood vessels, which facilitates the passage of lipid into the subendothelial space.

DIF:

1

REF: Page 636

OBJ: 1 | 3

16. The protein in cardiac muscle fibers that regulates contraction is: a. actin. b. myosin. c. B-type natriuretic peptide. d. troponin.

ANS: D The work of the heart is generated by the alternating contraction and relaxation of the striated muscle fibers of the heart. The fibers contain the contractile proteins actin and myosin, and also contain the troponins that regulate contraction.

DIF:

1

REF: Page 634

OBJ: 1 | 7

17. Regarding assessment of congestive heart failure, NT-proBNP can be measured. This protein is: a. the C-terminal portion of the prepro-hormone natriuretic peptide (BNP). b. the N-terminal fragment of pro-BNP. c. an isoenzyme that migrates separately from BNP on an electrophoresis. d. degraded by circulating proteases to form the final form of BNP. ANS: B Circulating proteases are capable of cleaving the N-terminal from the active BNP moiety.

The major circulating forms are the N-terminal portion (or fragment) of proBNP (NT-proBNP) and BNP. DIF:

2

REF: Page 643

OBJ: 1 | 7

18. In your clinical chemistry laboratory, you use an immunoassay to detect blood levels of NT-proBNP. You receive a filled green-top anticoagulant-containing plastic blood collection tube with a request for NT-proBNP. What is your next step? a. Because this is an incorrect specimen type, contact the physician/nurse immediately and request a serum specimen. b. Proceed, because this tube contains heparin and provides plasma after centrifugation, which is acceptable for the NT-proBNP assay. c. Proceed, because this tube will provide serum after centrifugation, which is acceptable for the NT-proBNP assay. d. Because only whole blood is acceptable, go ahead and run the test on the green-top tube.

ANS: B For NT-proBNP, serum, heparin plasma, and EDTA plasma (reads 10% lower) appear acceptable. A green-top blood collection tube contains heparin.

DIF:

2

REF: Page 644

OBJ: 10

19. What are the laboratory results for CK-MB and cardiac troponin in the following conditions: muscular dystrophy, polymyositis, and extreme physical activity? a. CK-MB elevated, troponin normal b. CK-MB elevated, troponin elevated c. CK-MB normal, troponin elevated d. CK-MB normal, troponin normal ANS: A Elevations of serum CK-MB resulting from chronic muscle disease occur in (1) patients with muscular dystrophy, (2) patients with end-stage renal disease, (3) patients with polymyositis, and (4) healthy subjects who undergo extreme exercise or physical activities.

In all these cases, cardiac troponin has been shown to be normal when the myocardium is not injured.

DIF: MATCHING

2

REF: Page 647

OBJ: 7 | 10

For each of the cardiac biomarkers, match the biochemical classification. a. BNP b. CK-MB c. Troponin d. Myoglobin 1.

2.

3.

4.

Protein involved in muscle fiber contraction Protein hormone Enzyme isoform Oxygen-binding protein

1. ANS: B DIF: 1 REF: Page 643 OBJ: 7 | 9 MSC: Creatine kinase (CK) is an enzyme present in (1) heart muscle, (2) skeletal muscle, and (3) the brain, and CK-2 (CK-MB) is sometimes called the cardiac isoenzyme.

2. ANS: C DIF: 1 REF: Page 646 OBJ: 7 | 9 MSC: Muscle fibers also contain the troponins that regulate contraction.

3. ANS: A DIF: 1 REF: Page 634 OBJ: 7 | 9 MSC: B-type natriuretic peptide (BNP) is a hormone that is mainly released from the myocardial ventricles.

4. ANS: D DIF: 1 REF: Page 647 OBJ: 7 | 9 MSC: Myoglobin is an oxygen-binding protein of cardiac and skeletal muscle.

Chapter 35: Kidney Disease Test Bank MULTIPLE CHOICE 1. A 36-year-old individual visits her physician with a complaint of nausea, loss of appetite,

weakness, and an inability to concentrate. Laboratory results indicate increased serum urea and creatinine, increased potassium, reduced glomerular filtration rate (GFR), low blood pH, anemia (low red blood cell count), and hypocalcemia. What is the likely diagnosis? a. IgA nephropathy b. Chronic kidney disease c. Uremia d. Nephrotic syndrome ANS: C

The classic signs of uremia (azotemia) include (1) progressive weakness and fatigue easily, (2) loss of appetite followed by (3) nausea and vomiting, (4) muscle wasting, (5) tremors, (6) abnormal mental function, (7) frequent but shallow respirations, and (8) metabolic acidosis.

The most characteristic laboratory findings are increased concentrations of nitrogenous compounds in plasma, such as urea and creatinine, as a result of reduced GFR and decreased tubular function. Retention of these compounds and of metabolic acids is followed by progressive (1) hyperphosphatemia, (2) hypocalcemia, and (3) potentially dangerous hyperkalemia.

DIF: 3

REF: Page 670

OBJ: 1 | 8 | 10

2. The portion of a nephron considered the most metabolically active and that is involved in the

reabsorption of 60% to 80% of the glomerular filtrate and that secretes 90% of hydrogen ion excreted by the kidney is the: a. glomerulus. b. proximal tubule. c. loop of Henle. d. distal tubule.

ANS: B

The proximal tubule is the most metabolically active part of the nephron, facilitating the reabsorption of 60% to 80% of the glomerular filtrate volume; it secretes 90% of the hydrogen ion excreted by the kidney.

DIF: 1

REF: Page 654

OBJ: 1 | 2

3. A patient with elevated serum nitrogen compounds, markedly reduced GFR, increased serum

sodium and potassium, and metabolic acidosis is diagnosed with acute kidney injury (AKI).

Which one of the following is a likely cause? a. -Hemolytic streptococcal infection b. Decreased cardiac output c. Urinary tract infection d. Pyelonephritis ANS: B

The definition of AKI, endorsed by the Kidney Disease Improving Global Outcomes (KDIGO) during 2012, is the occurrence of any one of the following: (1) increase of plasma creatinine by 0.3 mg/dL ( 26 µmol/L) within 48 hours; (2) increase in plasma creatinine to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; and (3) reduction in urine output. Metabolic acidosis is the most common acid-base disorder in patients with AKI. Reduced renal excretion of potassium and the effects of acidosis on the generation of extracellular potassium may lead to a very high concentration of potassium in the plasma.

DIF: 3

REF: Page 665

OBJ: 8 | 10

4. Which of the following laboratory results would point to a diagnosis of acute nephritic

syndrome in an individual who exhibits hypertension and edema? a. Increased serum protein, increased GFR, hematuria b. Increased white blood cells (WBCs) in the urine, bacteriuria, decreased GFR, proteinuria c. Hematuria, sodium retention, decreased GFR, proteinuria d. Normal serum urea and creatinine, increased GFR, massive proteinuria ANS: C

This disorder is characterized by the rapid onset of (1) hematuria, (2) proteinuria, (3) reduced GFR, and (4) sodium and water retention, with resulting hypertension and localized peripheral edema.

DIF: 2

REF: Page 672

OBJ: 8 | 10

5. The functional unit of the kidney is the: a. b. c. d.

lobule. bladder. glomerulus. nephron.

ANS: D

The functional unit of the kidney is the nephron. Each kidney may contain up to 1 million nephrons. The nephron consists of a (1) glomerulus, (2) proximal tubule, (3) loop of Henle, (4) distal tubule, and (5) collecting duct.

DIF: 1

REF: Page 653

OBJ: 1

6. If a physician requests a creatinine clearance on an individual, what is the physician

attempting to determine? a. Glomerular filtration rate (GFR) b. Random urine output volume c. Serum creatinine level d. Urine creatinine level ANS: A

Because creatinine is endogenously produced and released into body fluids at a constant rate, its clearance has been measured as an indicator of GFR. DIF: 1

REF: Page 660

OBJ: 1 | 5

7. Which one of the following components of the renal system is most important for regulation

of plasma electrolytes and acid-base balance? a. Bladder b. Loop of Henle c. Proximal convoluted tubule d. Distal convoluted tubule ANS: D

The distal tubule is functionally the most active region of the nephron for the homeostatic regulation of plasma electrolytes and plasma acid-base concentrations.

DIF: 1

REF: Page 657

OBJ: 2

8. In homeostatic regulation of plasma acid-base concentrations, sodium is both actively and

passively exchanged in the tubules for which one of the following ions? a. Bicarbonate b. Carbon dioxide c. Hydrogen d. Potassium ANS: C

It is in the distal tubule that exchange of H+ for Na+ (which is reabsorbed) fine-tunes the balance between H+ loss and retention.

DIF: 1

REF: Page 657

OBJ: 2

9. Which one of the following statements regarding creatinine is correct? a. Serum creatinine levelsTaEreSeTleBvA atNedKS eaErlL yL inEaRll.rC enOalMdisease. b. Normal plasma creatinine does not always indicate normal kidney function. c. Creatinine levels fluctuate in a diurnal manner. d. Creatinine is completely reabsorbed by the renal tubules.

ANS: B

Since plasma creatinine is derived from creatine and phosphocreatine breakdown in muscle, the reference interval encompasses the variety of muscle mass observed in the population.

This contributes to the insensitivity of creatinine as a marker of diminished GFR. Although an elevated plasma creatinine concentration does generally equate with impaired kidney function, a normal plasma creatinine does not necessarily equate with normal kidney function.

DIF: 2

REF: Page 660

OBJ: 5

10. Secretion of renin and aldosterone is induced by low blood pressure and volume. Renin is

synthesized in the and aldosterone is made in the a. kidney; adrenal gland b. kidney; brain c. adrenal gland; brain d. adrenal gland; kidney ANS: C

.

The juxtaglomerular apparatus plays an important part in maintaining systemic blood pressure through regulation of the circulating intravascular blood volume and sodium concentration through synthesis of the proteolytic enzyme renin. Renin acts on the plasma protein angiotensinogen to generate angiotensin I, converted in the lungs by angiotensin converting enzyme (ACE) to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release from the adrenal gland.

DIF: 2

REF: Page 655

OBJ: 2 | 6

11. Secretion of renin and aldosterone is induced by low blood pressure and volume. What other

hormone would be released in the event of low blood pressure and volume? a. 1,25(OH2) Vitamin D3 b. Growth hormone c. Erythropoietin d. Antidiuretic hormone ANS: D

Vasoconstriction and aldosterone release (with increased distal tubular sodium retention) act in concert with the other action of AII, to increase the release of antidiuretic hormone (ADH, vasopressin) and to increase proximal tubular sodium reabsorption, intravascular volume, and pressure.

DIF: 1

REF: Page 655

OBJ: 6

12. A 45-year-old man visits his physician with complaints of insatiable thirst, sudden onset of

fatigue, polydipsia, and polyuria. Laboratory results indicate a normal fasting blood sugar.

Serum sodium was slightly elevated. Urine was clear and had low specific gravity (hypotonic). The most likeT lyEcS auTsB eA ofNtK heSsE eL syL mEpR to. mCs O anMd laboratory results would be: a. diabetes mellitus. b. acute tubular necrosis. c. polycystic kidney disease. d. diabetes insipidus.

ANS: D

Diabetes insipidus is a disorder in which there is an abnormal increase in urine output, fluid intake, and often thirst. Diabetes insipidus is due to the absence of an ADH effect, either because of impaired or failed secretion (cranial or central DI) or lack of end-organ response to ADH. DIF: 3

REF: Page 674

OBJ: 1 | 8 | 10

13. Upon microscopic examination, an individual’s urine shows many bacteria, white blood cells,

and cellular casts composed of polymorphonuclear leukocytes. It is likely that this individual has: a. pyelonephritis. b. rapidly progressing glomerulonephritis. c. urinary tract infection. d. end-stage renal disease.

ANS: A

A variety of chemical, bacterial, and immunological injuries to the kidney cause either generalized or localized changes that primarily affect the tubulointerstitium rather than the glomerulus. Pyelonephritis is the term associated with a bacterial infection that causes this kind of damage and is the most common of the interstitial nephritides. Acute allergic interstitial nephritis presents with AKI and marked inflammation of the interstitium. White cells or casts imply the presence of white cells in the tubules. Blood cells that are prominent upon inspection include (1) lymphocytes, (2) polymorphonuclear cells, and (3) eosinophils.

DIF: 2

REF: Page 672

OBJ: 8

14. If an individual has a normal GFR and a hyperchloremic normal anion gap metabolic acidosis

with a freshly voided early morning urine specimen which has a pH of 6.5, what is the likely diagnosis? a. The pH It is increased above the reference interval due to the conversion of urea to ammonia. b. This pH is within the healthy reference interval for this specimen. c. The pH has decreased below the reference interval due to the urea content. d. There is likely the onset of distal renal tubular acidosis (RTA).

ANS: D

The renal tubular acidoses are characterized by a (1) hyperchloremic, (2) normal anion gap, (3) metabolic acidosis, (3) urinary bicarbonate, or (4) hydrogen ion excretion inappropriate for the plasma. Measurement of urinary pH in a fresh, early morning urine sample should be performed, and the finding of a urine pH greater than 5.5 in the presence of a systemic acidosis supports the diagnosis of distal RTA. DIF: 2

REF: Page 673

J: 8 | 10 TESTBANKSOEBL LER.COM

15. Damage to the glomerulus would be suspected when the urine sediment contains: a. proteinaceous casts. b. red blood cell casts. c. visible proteins. d. crystals.

ANS: B

An increase in red cells or casts implies hematuria, possibly caused by glomerular disease.

DIF: 1

REF: Page 665

OBJ: 2

16. Why is bone disease a consequence of chronic kidney disease (CKD)? a. The juxtaglomerular apparatus no longer synthesizes renin in CKD, which keeps

calcium phosphate complexes from mineralizing. b. The basement membrane in Bowman capsule is damaged and calcium is lost in the

glomerular filtrate. c. When glomerular filtration declines, vitamin D activation decreases resulting in

reduced calcium, which further leads to resorption of calcium from bone. d. The synthesis of erythropoietin by peritubular fibroblasts because of reduced red

blood cell survival.

ANS: C

Bone disease as a consequence of CKD has long been recognized. As GFR declines, renal activation of vitamin D decreases and plasma phosphate concentration rises resulting in reduced ionized calcium. Consequently, the parathyroid glands increase the production of PTH. This increased secretion of PTH stimulates resorption of calcium and phosphate from the bone, the body’s major calcium reservoir.

DIF: 2

REF: Page 669

OBJ: 8

17. You have been asked what laboratory tests should be requested to assess the electrolyte

balance regulatory function of an individual’s kidneys. Which of the following is your reply? a. Serum creatinine, serum urea, serum uric acid, and creatinine clearance b. Serum sodium and potassium, and arterial blood pH c. Serum renin and erythropoietin d. Serum and urine protein ANS: B

The distal tubule is functionally the most active region of the nephron for the homeostatic regulation of plasma electrolytes and plasma acid-base concentrations. Here a combination of secretion and reabsorption takes place among Na+, K+, and H+. Although excess plasma hydrogen ions are secreted all along the tubule, it is in the distal tubule that exchange of H+ for Na+ (which is reabsorbed) fine-tunes the balance between H+ loss and retention. Potassium ions are also secreted in the distal tubule.

DIF: 2

REF: Page 657

OBJ: 4

18. The major artery that expands into the capillary bed that forms the glomerulus is the: a. renal artery. b. nephronic artery. c. vasa recta. d. arcuate artery.

ANS: A

The renal artery divides into posterior and anterior elements, which then divide into interlobar, arcuate, interlobular, and ultimately afferent arterioles, which expand into the capillary bed that forms the glomerulus.

DIF: 1

REF: Page 655

OBJ: 3

19. The most common glomerular disease worldwide is: a. acute proliferative glomerulonephritis. b. acute pyelonephritis. c. IgA nephropathy. d. chronic kidney disease.

ANS: C

IgA nephropathy is the most common type of glomerulonephritis worldwide.

DIF: 1

REF: Page 672

OBJ: 8

20. A 46-year-old patient visits her physician with a complaint of chest pain, blood in her urine,

and oliguria. She states that these symptoms have gotten worse over the past 2 to 3 months.

Urine and blood samples are collected. Urine GFR is calculated to be 40 mL/min/1.73 m2 and hemoglobin is 8 g/dL. Urine protein was elevated, with the presence of red blood cell casts.

Upon review of her health history, it was noted that she was a cigarette smoker with hypertension. The most likely diagnosis in this case would be: a. nephrotic syndrome. b. chronic kidney disease (CKD). c. end-stage renal disease. d. chronic pyelonephritis.

ANS: B

CKD is defined as abnormalities of kidney structure or function, present for greater than 3 months, with implications for health. A GFR of less than 60 mL/min/1.73 m2 is considered decreased and a GFR of less than 15 mL/min/1.73 m2 is considered kidney failure. Kidney damage is defined by structural abnormalities or functional abnormalities other than decreased GFR and may include (1) albuminuria, (2) urine sediment abnormalities, and (3) electrolyte and other abnormalities due to tubular and other disorders.

DIF: 3

REF: Page 668

OBJ: 1 | 8 | 10

21. In an individual with chronic kidney disease, what might be the predominant cause of the low

hemoglobin value and anemia? a. Decreased erythropoietin synthesis b. Decreased iron absorption c. Bone loss from decreased 1,25(OH2) vitamin D3 synthesis d. Folate deficiency ANS: A

Failure of peritubular fibroblasts to produce EPO leads to decreased numbers of red cells and concomitant concentrations of hemoglobin and anemia.

DIF: 2

REF: Page 670

OBJ: 2 | 8

22. An individual presents to his physician with generalized weakness and fatigue. Blood is

collected and an elevated WBC count with lymphocytosis is noted. Serum protein is moderately decreased, but the urine reagent dipstick does not indicate proteinuria. Upon confirmatory testing with a precipitation test, the urine protein is 4+. Based on other symptoms, the physician suspects multiple myeloma. What might be the cause of the discrepancy in urine protein values? a. Increased WBCs will interfere with urine protein dipstick values. b. The urine reagent dipsticks are outdated and must be discarded. c. The precipitation test was performed without controls. d. Reagent dipsticks respond mostly to urine albumin and not to other proteins.

ANS: D

The reagent on the urine dipstick protein reagent pad is most sensitive to albumin and less sensitive to globulins, Bence Jones protein, mucoproteins, and hemoglobin.

DIF: 3

REF: Page 665

OBJ: 6 | 7

23. In multiple myeloma, what protein is likely causing an elevated value in the urine protein

confirmatory test? a. Tamm-Horsfall protein b. Bence Jones protein c. Haptoglobin d. Mucoprotein ANS: B

In multiple myeloma complete monoclonal immunoglobulins (usually IgG or IgA) are accompanied in the plasma by variable concentrations of free light chains that appear in the urine as Bence Jones proteins.

DIF: 2

REF: Page 675

OBJ: 1 | 7

24. The volume of plasma from which a substance is completely removed by the kidneys per unit

of time is the definition of: a. renal threshold. b. prerenal acute kidney injury. c. glomerular filtration rate. d. clearance.

ANS: D

Glomerular filtration rate measurements may be based on either the urinary or plasma clearance of a marker. The renal clearance of a substance is defined as “the volume of plasma from which the substance is completely cleared by the kidneys per unit of time.”

DIF: 1

REF: Page 658

OBJ: 1

25. Which one of the following is the correct formula for determining glomerular filtration rate? a. GFR = ([urine concentration of the substance]  volume)/[plasma concentration of

the substance] b. GFR = ([plasma concentration of the substance]  volume)/[urine concentration of

the substance]

c. GFR = ([urine concentration of the substance]  volume)  [plasma concentration

of the substance] d. GFR = ([urine concentration of the substance]  volume) + [plasma concentration of the substance] ANS: A

The amount of that substance filtered at the glomerulus is equal to the amount excreted in the urine. The amount of S filtered at the glomerulus is equal to the GFR multiplied by plasma S concentration: GFR  [PS]. The amount of S excreted equals the urine S concentration (US) multiplied by the urinary flow rate (V, volume excreted per unit of time). The term ([US]  V)/[PS] is defined as the clearance of substance S and is an accurate estimate of GFR. DIF: 1

REF: Page 658

OBJ: 5

Chapter 36: Physiology and Disorders of Water, Electrolyte, and Acid-Base Metabolism Test Bank MULTIPLE CHOICE 1. An individual is brought to the emergency department of a local hospital with signs of narcotic overdose and respiratory depression. What acid-base status would this individual have? a. Respiratory acidosis b. Respiratory alkalosis c. Metabolic acidosis d. Metabolic alkalosis ANS: A Any condition that decreases elimination of carbon dioxide through the lungs results in an increase in PCO2 (hypercapnia) and dCO2 (respiratory acidosis). Thus respiratory acidosis occurs only through decreased elimination of CO2. Causes of decreased CO2 elimination are listed in Box 36-2. These conditions may be separated into those caused by factors that directly depress the respiratory center (such as centrally acting drugs, CNS trauma, or infection).

DIF:

2

REF: Page 697

OBJ: 7 | 10

2. A person suspected of having chloride responsive metabolic alkalosis caused by prolonged vomiting would exhibit which one of the following? a. Primary bicarbonate deficit b. Primary bicarbonate excess c. Primary cdCO2 deficit d. Primary cdCO2 excess ANS: B Alkalosis occurs when excess base is added to the system, base elimination is decreased, or acid-rich fluids are lost in excess as in prolonged vomiting. Most causes of Cl– responsive metabolic alkalosis occur as a result of hypovolemia (see Box 36-1). When the ECF is severely depleted, the resulting acid-base disorder is often referred to as contraction alkalosis. Common causes of contraction alkalosis include prolonged vomiting.

DIF:

2

REF: Page 696, Box 36-1

OBJ: 7 | 9 | 10

3. In regard to respiration, peripheral chemoreceptors located in the carotid arteries and aorta are stimulated by: a. HCO3 content of arterial blood. b. PO2 content of blood only. c. pH only. d. pH and PO2 content of blood.

ANS: D

Peripheral chemoreceptors are stimulated by a fall in pH caused by accumulation of CO2 or by a decrease in PO2.

DIF:

1

REF: Page 690

OBJ: 6

4. An overweight 55-year-old single woman from a rural farming area was brought to the emergency department by her neighbor. The woman had a large abscess on the bottom of her foot; she was irritable and complained of blurred vision and of being thirsty. Her breathing was rapid. The neighbor said that the only medication the woman was using was for blood pressure and sometimes an aspirin. Blood and urine samples were collected.

Arterial blood gas results were: pH 7.2; PCO2 47 mm Hg; HCO3 8 mmol/L. Blood glucose was 340 mg/dL and a high anion gap was calculated. Urine glucose and ketones were markedly increased. Based on the laboratory values, what state of acid-base balance is this patient in? a. Respiratory acidosis b. Respiratory alkalosis c. Metabolic acidosis d. Metabolic alkalosis ANS: C Metabolic acidosis is a pathological process that leads to the accumulation of acid that lowers the bicarbonate concentration and decreases the pH. A high anion gap indicates the presence of organic acids, such as acetoacetate and -hydroxybutyrate, which indicate an acidotic state. Urine values confirm the presence of high glucose and ketone bodies.

DIF:

3

REF: Page 681

OBJ: 7 | 8 | 10

5. An overweight 55-year-old single woman from a rural farming area was brought to the emergency department by her neighbor. The woman had a large abscess on the bottom of her foot; she was irritable and complained of blurred vision and of being thirsty. Her breathing was rapid. The neighbor said that the only medication the woman was using was for blood pressure and sometimes an aspirin. Blood and urine samples were collected.

Arterial blood gas results were: pH 7.2; PCO2 47 mm Hg; HCO3 8 mmol/L. Blood glucose was 340 mg/dL and a high anion gap was calculated. Urine glucose and ketones were markedly increased. Based on the laboratory values and symptoms of the woman, what is the most likely cause of her acid-base disorder? a. Abscess formation and infection b. Diabetic ketoacidosis c. Pneumonia d. Hysteria ANS: B Because of the elevated blood and urine glucose and elevated anion gap, the symptoms of irritability and thirst, the presence of an abscess on her foot, and the lack of hypoglycemic agents in her pharmacy regimen, it is likely that she has been developing type 2 diabetes mellitus. Uncontrolled DM type 2 leads to overproduction of ketones and increase of intermediate organic acids such as -hydroxybutyrate, which are normally metabolized to carbon dioxide and water. In a diabetic, however, they may accumulate to a significant extent resulting in acidemia.

DIF:

3

REF: Page 693

OBJ: 7 | 8 | 10

6. Hypernatremia commonly occurs with: a. decreased synthesis of antidiuretic hormone (ADH). b. decreased aldosterone. c. edema. d. hyperkalemia.

ANS: A Tubular permeability to H2O is under the influence of antidiuretic hormone (ADH). When blood volume decreases, ADH keeps water and sodium in the system. Hypernatremia can be caused by decreased or total lack of ADH. Excess (as opposed to decreased) aldosterone also results in excess Na+ and water retention. Edema produces a dilutional hyponatremia.

DIF:

2

REF: Page 683

OBJ: 3

7. Hypokalemia may be seen in all of the following except: a. decreased dietary intake. b. renal loss. c. gastrointestinal loss. d. decreased glucocorticoid concentration in blood.

ANS: D Renal losses of K+ may occur during the diuretic (recovery) phase of acute tubular necrosis and during states of excess mineralocorticoid (primary or secondary aldosteronism) or glucocorticoid (Cushing syndrome) when the distal tubules increase Na+ reabsorption and K+ excretion.

DIF:

2

REF: Page 686

OBJ: 3

8. What is the anion gap given the following serum electrolyte data: Na = 132 mmol/L, Cl– = 90 mmol/L, HCO3– = 22 mmol/L, K = 4 mmol/L? a. 10 mmol/L b. 18 mmol/L c. 20 mmol/L d. 60 mmol/L ANS: C Anion gap is measured by subtracting the chloride plus bicarbonate sum from the sodium value. In this case, 132 − (90 + 22) = 20 mmol/L. DIF:

2

REF: Page 693

OBJ: 8

9. Determine the anion gap given the following serum electrolyte data: Na = 132 mmol/L, Cl− = 90 mmol/L, HCO3– = 22 mmol/L, K = 4 mmol/L. Is the anion gap you calculated within the healthy reference interval? a. Yes b. No ANS: B The healthy reference interval for anion gap is 7 to 16 mmol/L.

DIF:

2

REF: Page 693

OBJ: 8

10. Which of the following conditions will cause an increased anion gap? a. Salicylate intoxication b. Controlled diabetes mellitus c. Decreased albumin concentration d. Severe diarrhea ANS: A See Table 36-4. Salicylate, itself an unmeasured anion, alters peripheral metabolism, leading to the production of various organic acids without dominance of any specific acid. These processes eventually result in a metabolic acidosis with a high anion gap.

DIF:

1

REF: Page 696

OBJ: 8

11. All of the following are causes of hyponatremia with concomitant decreased plasma osmolality and normal volume status except: a. decreased serum aldosterone. b. hypothyroidism. c. diarrhea. d. decreased serum antidiuretic hormone (ADH).

ANS: C See Figure 36-1. In hyponatremia with a normal volume status, the most common causes are the syndrome of inappropriate ADH (SIADH), causing increased serum ADH, primary polydipsia, hypothyroidiT sm ndBaAdN reKnS alEinLsL ufE fiR ci. enCcO yM (decreased cortisol and/or E,SaT aldosterone). SIADH is usually a result of ectopic or otherwise “inappropriate” increased ADH production arising from a variety of conditions.

DIF:

3

REF: Page 681, Figure 36-1

OBJ: 2

12. Metabolic organic acidoses typically present with an increased anion gap. In contrast to these, inorganic acidosis with a normal anion gap is typically caused by: a. uncontrolled diabetes mellitus. b. loss of bicarbonate-rich fluid via the kidneys or gastrointestinal tract. c. an acquired defect in enzymes involved in gluconeogenesis. d. production of glycolic and oxalic acids.

ANS: B In contrast to high anion gap acidosis, in which bicarbonate is consumed from buffering excess H+, the cause of acidosis in the presence of a normal anion gap is the loss of bicarbonate-rich fluid from the kidney or the gastrointestinal tract.

DIF:

2

REF: Page 695

OBJ: 7 | 8

13. An individual visits a physician with the complaint of nausea, mental confusion, and needing an excessive amount of salt all the time. Laboratory results indicate decreased serum sodium and low serum osmolality. Physical examination reveals hypovolemia with low orthostatic blood pressure and tachycardia. A urine sodium analysis was suggested by a laboratorian and urine sodium was found to be increased; the physician diagnoses a salt-losing nephropathy (a renal tubule disease). What type of electrolyte disorder is this? a. Dilutional hyponatremia b. Depletional hyponatremia c. Hypernatremia d. Metabolic acidosis ANS: B Typically, when plasma Na+ concentration is low, calculated or measured osmolality will also be low. This type of hyponatremia can be due to excess loss of Na+ (depletional hyponatremia). If urine Na+ is elevated, renal loss of Na+ is likely. Renal loss of Na+ occurs with (1) osmotic diuresis, (2) use of diuretics that inhibit reabsorption of Cl– and Na+ in the ascending loop, (3) adrenal insufficiency (no aldosterone or cortisone prevents distal tubule reabsorption of Na+), or (4) salt wasting nephropathies, as can occur after acute tubular necrosis or obstructive nephropathy.

DIF:

3

REF: Page 683

OBJ: 1 | 3 | 10

14. A hospitalized patient in the ICU has cirrhosis. After a period of time, the heart and kidneys begin to fail and the patient develops edema. What type of electrolyte disorder would develop from this situation? a. Dilutional hyponatremia EiSaTBANKSELLER.COM b. Depletional hyponatrT em c. Hypernatremia d. There would be no electrolyte disorder.

ANS: A Dilutional hyponatremia is a result of excess H2O retention and often can be detected during the physical examination as edema. In advanced renal failure, water is retained because of decreased filtration and H2O excretion. When ECF is increased but the blood volume is decreased, as occurs in congestive heart failure (CHF), hepatic cirrhosis, or nephrotic syndrome, the kidneys reabsorb Na+ and H2O in response to increased aldosterone and ADH in an attempt to restore the blood volume, but this simply results in further increases in ECF and further dilution of Na+.

DIF:

3

REF: Page 683

OBJ: 1 | 3 | 10

15. How do healthy kidneys compensate for the excess hydrogen ions and concurrent low pH observed in metabolic acidosis? a. Releasing bicarbonate into urine b. Stimulating hyperventilation c. Decreasing urinary excretion of ammonia d. Increasing excretion of acid ANS: D

Various compensatory mechanisms attempting to reestablish the normal ratio of cHCO3– /cdCO2 may result in changes in bicarbonate concentration, dissolved CO2 concentration, or both. If possible in metabolic acidosis, the kidneys respond to restore thenormal pH through increased excretion of acid and preservation of base (increased rate of Na+-H+ exchange, increased ammonia formation, and increased reabsorption of bicarbonate).

DIF:

1

REF: Page 689

OBJ: 1 | 6 | 7

16. How do healthy lungs compensate for the decrease in pH in a state of metabolic acidosis? a. Releasing bicarbonate into urine b. Stimulating hyperventilation c. Decreasing urinary excretion of acid d. Increasing excretion of acid ANS: B Various compensatory mechanisms attempting to reestablish the normal ratio of cHCO3– /cdCO2 may result in changes in bicarbonate concentration, dissolved CO2 concentration, or both. The decrease in pH in metabolic acidosis stimulates hyperventilation(Kussmaul respiration), which results in the elimination of carbonic acid as CO2.

DIF:

1

REF: Page 689

OBJ: 1 | 6 | 7

17. Physiologically important buffers maintaining body pH include all of the following except: a. bicarbonate. b. albumin. c. phosphate. d. lactate.

ANS: D The most important buffer of plasma is the bicarbonate/carbonic acid pair, while the total concentration of H2PO4– in both erythrocytes and plasma accounts for about 5% of the nonbicarbonate buffer value of plasma. Proteins, especially albumin, account for the greatest portion (>90%) of the nonbicarbonate buffer value of plasma. Hemoglobin accounts for the major part of the nonbicarbonate buffers in erythrocyte fluid.

DIF:

1

REF: Page 690

OBJ: 5

18. At physiological pH of 7.4, which one of the following contributes most to the total serum CO2 (think about the equilibrium of the reaction in the formula)? a. Dissolved CO2 b. Carbaminohemoglobin c. HCO3– d. Carbonic acid ANS: D HCO3– + H+ H2CO3 CO2 + H2O; in this formula, H+ will react with HCO3– to form more H2CO3 and subsequently CO2 and H2O. DIF:

2

REF: Page 698

OBJ: 5

19. Hypokalemia (<3.0 mmol/L) is considered a serious health threat because: a. the heart rate increases, leading to weakness, difficulty in breathing, and eventual cardiac arrest. b. the heart rate slows because of the lowered excitability of cardiac smooth muscle, leading to possible cardiac standstill. c. the body gains water through the kidney reabsorption, leading to severe edema. d. arterial pH will decrease (increased H+ concentration), leading to metabolic acidosis.

ANS: A Plasma K+ concentrations less than 3.0 mmol/L are associated with serious neuromuscular symptoms and indicate a critical degree of intracellular depletion. At lower concentrations, tachycardia and specific cardiac conduction effects are apparent by electrocardiographic examination and can lead to cardiac arrest.

DIF:

1

REF: Page 685

20. The most important buffer of plasma is the a. bicarbonate/carbonic acid b. protein/albumin c. phosphoric acid/phosphate d. hemoglobin erythrocyte

OBJ: 3 system.

ANS: A The most important buffer of plasma is the bicarbonate/carbonic acid pair.

DIF:

1

REF: Page 689

OBJ: 5

21. The metabolic component of acid-base regulation is the renal system. Which one of the following statements concerning this component is incorrect? a. Renal tubule cells reabsorb sodium and bicarbonate to affect bicarbonate concentration. b. Sodium and bicarbonate are important in the exchange of excess H+ ions, thus altering blood pH. c. The renal system acts to remove excess H+ ions by combining them with HPO4. d. In the metabolic component, the renal system responds immediately to a change in acid-base status.

ANS: D The respiratory component responds quickly to a change in acid-base status, while the metabolic component responds much more slowly.

DIF:

1

REF: Page 690

OBJ: 6

22. Which one of the following hormones is an active regulator of water retention/reabsorption in the kidney? a. Aldosterone b. Erythropoietin c. Antidiuretic hormone

d. Renin ANS: C Water regulation in the kidney occurs from the distal tubule through the collecting duct, where tubular permeability to H2O is under the influence of antidiuretic hormone (ADH).

DIF:

1

REF: Page 683

OBJ: 1 | 2

23. Which one of the following hormones is an active regulator of sodium (and passive controller of water) in the kidney? a. Aldosterone b. Erythropoietin c. Antidiuretic hormone d. Renin ANS: A At the level of the distal tubule, the first of the two primary Na+/H2O regulating processes occurs. Here, aldosterone stimulates the cortical collecting ducts to reabsorb Na+ (with water following passively) and secrete K+ (and to a lesser extent, H+) to maintain electrical neutrality.

When the kidneys are hypoperfused (as occurs when blood volume decreases, or when the renal arteries are obstructed), the distal tubules, under the influence of aldosterone, reclaim Na+.

DIF:

1

REF: Page 683

OBJ: 1 | 2

24. A 17-year-old woman wT asEbS roTuB ghAtNbK yS heErLfrL ieEnR ds.tC oO thM e emergency room in an agitated state. She stated that she had broken up with her boyfriend and he had threatened her. Her temperature was 101° F, and she was breathing rapidly. She claimed that she could not slow her breathing down despite attempts to have her breathe deeply. An arterial blood gas revealed a pH of 7.54, HCO3 of 18 mmol/L, and PCO2 of 28 mm Hg. What is occurring in this patient? a. Excess retention of acid via the renal route b. Excess elimination of acid via the renal route c. Excess elimination of acid via the respiratory route d. Excess retention of bicarbonate via the respiratory route ANS: C The basic cause of respiratory alkalosis is excess elimination of acid via the respiratory route. Excessive elimination of carbon dioxide reduces the PCO2 and causes an increase in the cHCO3–/cdCO2 ratio (due to decrease in cdCO2).

DIF:

3

REF: Page 698

OBJ: 7 | 10

MATCHING Match the action of acid-base balance regulation with the correct component of acid-base balance. a. Metabolic component b. Respiratory component

c. Both components 1. Hydrogen ions are exchanged for sodium or potassium 2. Hydrogen ions are attached to hemoglobin 3. Can alter blood pH 1. ANS: A DIF: 2 REF: Page 692 OBJ: 5 | 6 | 7 MSC: Excess carbonic acid present in blood is to a great extent buffered by the hemoglobin and protein buffer systems.

2. ANS: B DIF: 2 REF: Page 697 OBJ: 5 | 6 | 7 MSC: The H+ is excreted by the kidney and reacts with HCO3- to form H2CO3 and subsequently CO2 and H2O (catalyzed by carbonic anhydrase, in the brush border of the proximal tubular cells and alveolar cells).

3. ANS: C DIF: 2 REF: Page 690 OBJ: 5 | 6 | 7 MSC: Both metabolic and respiratory components can alter blood pH through the buffering systems.

Chapter 37: Liver Disease Test Bank MULTIPLE CHOICE 1. The major risk factor for development of hepatocellular carcinoma is: a. infection with hepatitis A virus. b. infection with hepatitis B or C viruses. c. hepatorenal syndrome. d. hepatic encephalopathy.

ANS: B The major risk factor for development of hepatocellular carcinoma (HCC) is infection with hepatitis B virus or hepatitis C virus.

DIF:

1

REF: Page 720

OBJ: 10

2. In chronic liver failure, such as cirrhosis, there is a significant impairment of normal ammonia metabolism and eventual hyperammonemia. Elevated ammonia can lead to: a. hepatocellular carcinoma. b. hepatic encephalopathy. c. chronic hepatitis. d. cholestasis.

ANS: B Severe or chronic liver faTilEuS reT(aBsAoN ccKuS rsEinLL fuE lm naCnO t hMepatitis and cirrhosis, respectively) Ri. leads to a significant impairment of normal ammonia metabolism. Reye syndrome, which is primarily a central nervous system disorder with minor hepatic dysfunction, is also associated with hyperammonemia. Animal and human studies have shown that an elevated concentration of ammonia (hyperammonemia) exerts toxic effects on the central nervous system. Hepatic encephalopathy, in the cirrhotic patient, is often precipitated by GI bleeding that enhances ammonia production.

DIF:

2

REF: Page 707

OBJ: 3 | 8

3. The functional unit of the liver is the: a. nephron. b. cord. c. glomerulus. d. acinus.

ANS: D The functional anatomic unit of the liver is the acinus, adjacent to the portal triad. Each acinus is a diamond-shaped mass of liver parenchyma that is supplied by a terminal branch of the portal vein and of the hepatic artery and drained by a terminal branch of the bile duct.

DIF:

1

REF: Page 703

OBJ: 1 | 2

4. You operate a laboratory that receives many serum specimens from the Billy Rubin Memorial Liver Clinic next door. The patients who go to this clinic have serious acute and chronic liver diseases. Would you expect to see increased or decreased plasma albumin from the liver patients who go to this clinic? a. Increased b. Decreased ANS: B Albumin is synthesized exclusively by the liver. With liver disease, hypoalbuminemia is noted primarily in cirrhosis, autoimmune hepatitis, and alcoholic hepatitis. Plasma albumin concentration is decreased in chronic liver disease. However, its utility for this purpose is somewhat limited, as the plasma albumin concentration is also decreased in severe acute liver disease.

DIF:

2

REF: Page 705

OBJ: 8 | 11

5. Bilirubin that is attached to albumin before it is transported across the hepatocyte membrane is called: a. unconjugated bilirubin. b. conjugated bilirubin. c. jaundice. d. urobilinogen.

ANS: A Bilirubin is carried to the liver, loosely bound to albumin, in its native, unconjugated form.

DIF:

1

RETFE: ST PaBgA eN 70K4SELLOEBRJ. : C3OM

6. The type of RNA virus that is considered to be the cause of the most common type of acute hepatitis that does not lead to chronic hepatitis is: a. hepatitis A virus. b. hepatitis B virus. c. hepatitis C virus. d. Reye syndrome.

ANS: A Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in North America. There is no chronic form of hepatitis A. See Table 37-1.

DIF:

1

REF: Page 711, Table 37-1

OBJ: 7

7. A 53-year-old man notices the whites of his eyes seem a bit yellow, there is swelling in his abdomen, and he is often fatigued. He tells his physician that he enjoys “a few” martinis every night and sometimes more on the weekend. Upon physical examination, the physician notes decreased weight, elevated blood pressure, jaundice, and ascites, and laboratory results indicate decreased albumin, low platelet count, increased prothrombin time, and increased serum liver enzymes with AST activity higher than ALT. All viral hepatitis and cholestasis testing is negative. What is the likely diagnosis? a. Pancreatitis b. Primary sclerosing cholangitis

c. Chronic alcoholic hepatitis transitioning to cirrhosis d. Nonalcoholic fatty liver disease ANS: C In the early stages of transition from chronic hepatitis to cirrhosis, termed compensated cirrhosis, there may be no signs or symptoms of liver damage. Laboratory abnormalities usually appear before clinical findings begin to develop. The latter include (1) ascites, (2) gynecomastia, (3) palmar erythema, and (4) portal hypertension. The earliest laboratory abnormalities are (1) fall in platelet count, (2) increase in prothrombin time, (3) decrease in the albumin to globulin ratio to 1, and (4) increase in the AST/ALT activity ratio to 1.

DIF:

3

REF: Page 719

OBJ: 8 | 11

8. In the liver, ammonia is metabolized to form: a. amino acids. b. ketoacids. c. urea. d. glucuronic acid.

ANS: C Under normal circumstances, most ammonia is metabolized to urea in hepatocytes in the Krebs-Henseleit urea cycle.

DIF:

1

REF: Page 706

OBJ: 3

9. An autoimmune disease caused by an antibody directed toward the mitochondria of biliary epithelial cells that resultTs E inShTeB paAtiN cK inSflE am atR io. nC anOdMportal hypertension is: Lm LE a. autoimmune hepatitis. b. fatty liver. c. fulminant hepatitis. d. primary biliary cirrhosis.

ANS: D In primary biliary cirrhosis (PBC), at least 95% of patients have antimitochondrial antibodies that react against the dihydrolipoamide acyltransferase component of the pyruvate decarboxylase complex on the apical surface of biliary epithelial cells, suggesting a role for this antigen as an immune target. PBC progresses slowly in most patients and ultimately leads to portal hypertension.

DIF:

2

REF: Page 719-720

OBJ: 8

10. The first protein marker to appear approximately 1 to 2 months after infection with the hepatitis B virus and also the last marker to disappear is the: a. antihepatitis B core antigen. b. antihepatitis B surface antigen. c. hepatitis B surface antigen. d. hepatitis B immune globulin.

ANS: C

HBsAg is produced in excess by the hepatitis B virus and is used as a laboratory test to detect current HBV infection. It is typically present with both acute and chronic infection.

HBsAg is the first serological marker to appear (1 to 2 months after infection, before evidence of hepatitis) and is the last protein marker to disappear.

DIF:

1

REF: Page 712

OBJ: 7

11. Which one of the following is not a consequence of portal hypertension in an individual? a. Bleeding esophageal varices b. Increased prothrombin time c. Altered estrogen metabolism d. Hemochromatosis ANS: D Portal hypertension is an increase in the portal vein (in the liver) pressure due to anatomic or functional obstruction to blood flow in the portal venous system. As portal hypertension worsens, it compromises many of the metabolic functions of the liver. One such abnormality is altered estrogen metabolism. Synthetic functions are also impaired, resulting in decreased concentration of most plasma protein including clotting factors. The most life-threatening consequence of portosystemic shunting is the development of varices most common in the esophagus and stomach. Hemochromatosis is a genetic disorder that presents as chronic hepatitis.

DIF:

2

REF: Page 707

OBJ: 1 | 4

12. A new intern calls the laboratory to ask which liver enzymes would be best to assess to differentiate between hepTaE toS ceTllBuA laN r aKnS d EchLoLleEstRat.icCdOisMease. You respond: a. ALP, GGT, and LD. b. AST, ALT, and ALP. c. ALP and GGT only. d. AST and ALT only.

ANS: B Serum activities of aminotransferases and alkaline phosphatase are the most useful tests, because they allow differentiation of hepatocellular disease from cholestatic disease. AST and ALT are both mitochondrial and cytosolic isoenzymes in hepatocytes and other cells containing these enzymes. In contrast, ALP and GGT are membrane-bound glycoprotein enzymes. The most important location of both enzymes is on the canalicular (biliary) membrane of hepatocytes.

DIF:

2

REF: Page 721

OBJ: 5 | 8 | 11

13. Which type of hepatitis is a leading cause of chronic hepatitis and is caused by a mutating RNA virus? a. Hepatitis A b. Fulminant hepatitis c. Hepatitis B d. Hepatitis C ANS: D

The hepatitis C virus (HCV) is the most common cause of chronic hepatitis in (1) North America, (2) Europe, and (3) Japan. HCV is an RNA flavivirus, with a high rate of spontaneous mutation.

DIF:

1

REF: Page 712

OBJ: 7

14. Which one of the following is considered a mechanism by which a membrane-bound enzyme, such as alkaline phosphatase, is released from a hepatocyte into blood? a. Bile acids solubilize membrane-bound enzymes. b. Cell injury allows leakage of the enzyme into blood. c. Decreased expression of the enzyme causes release from the membrane. d. Alcohol fragments membranes and causes release of the membrane-bound enzyme.

ANS: A The mechanism of release of membrane-bound enzymes, such as GGT and ALP, into the circulation appears to be caused by (1) increased synthesis, (2) membrane fragmentation by bile acids, and (3) solubilization of membrane-bound enzymes by the action of bile acids.

DIF:

2

REF: Page 710-711

OBJ: 4 | 5

15. A 30-year-old man sees his physician with complaints of pruritus, fever, and pain around his abdomen and right side that he says “have been there a while but suddenly got really bad.”

Laboratory results on his blood sample indicate elevated conjugated and unconjugated bilirubin and elevated alkaline phosphatase activity. There are no signs of chronic hepatitis or ascites. Gallstones are ruled out, and the physician notes that a previous diagnosis of ulcerative colitis had beeT nEmSaT deB. A WNhK atSisEtL heLlEikRe. lyCcO urMrent diagnosis? a. Primary sclerosing cholangitis b. Acute hepatitis attack from fulminant hepatitis c. Hemolytic anemia caused by tumor d. Liver injury caused by obstruction of the portal vein ANS: A Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree, most commonly affecting extrahepatic bile ducts. PSC has a male predominance and a median age at onset of 30 years. The clinical presentation of PSC includes elevated activities of ALP found during routine laboratory screening with symptoms of pruritus and intermittent abdominal pain, but fever may also occur. In 80% of patients, PSC is associated with ulcerative colitis, which usually (but not always) precedes onset of PSC. DIF:

3

REF: Page 720

OBJ: 8 | 11

16. Prognosis in cirrhosis is based on a MELD score, which is also used to prioritize cases for liver transplantation. Which of the following laboratory values are used to calculate the MELD score of an individual? a. Plasma albumin, bilirubin, and liver enzymes b. Liver enzyme activities and prothrombin time c. Bilirubin, creatinine, and INR d. Creatinine, urea, and ammonia

ANS: C MELD score = [3.8 + ln bilirubin concentration (mg/dL)] + [11.2 ln International Normalized Ratio] + [9.6 ln creatinine concentration (mg/dL)] + 6.4 etiology score (0 if alcohol or obstruction, 1 for all other causes).

DIF:

1

REF: Page 719

OBJ: 1 | 9

17. Liver disease is classified as either acute or chronic. Acute liver disease takes the general form of either acute hepatitis or: a. cirrhosis. b. cholestasis. c. hepatocellular carcinoma. d. portal hypertension.

ANS: B The two major acute liver diseases are acute hepatitis and cholestasis. Chronic liver injury generally takes the clinical form of chronic hepatitis; its long-term complications include cirrhosis and HCC. DIF:

1

REF: Page 710-711

OBJ: 6

MATCHING Match the disorder with the correct cause of that condition. a. Decreased flow of bile b. Inflammation of bile ducts c. Gallstones in bile ducts d. Fibrosis of the liver 1.

2.

3.

4.

Cirrhosis Choledocholithiasis Cholestasis Cholangitis

1. ANS: D DIF: 2 REF: Page 703 OBJ: 1 | 8 MSC: Cirrhosis is formation of fibrotic scars in the liver, choledocholithiasis is the appropriate name for bile duct blockage by gallstones, cholestasis is defined as a decrease in the flow of bile, and cholangitis is inflammation of the biliary tree.

2. ANS: C DIF: 2 REF: Page 719 OBJ: 1 | 8 MSC: Cirrhosis is formation of fibrotic scars in the liver, choledocholithiasis is the appropriate name for bile duct blockage by gallstones, cholestasis is defined as a decrease in the flow of bile, and cholangitis is inflammation of the biliary tree.

3. ANS: A DIF: 2 REF: Page 719 OBJ: 1 | 8 MSC: Cirrhosis is formation of fibrotic scars in the liver, choledocholithiasis is the appropriate name for bile duct blockage by gallstones, cholestasis is defined as a decrease in the flow of bile, and cholangitis is inflammation of the biliary tree.

4. ANS: B DIF: 2 REF: Page 719 OBJ: 1 | 8 MSC: Cirrhosis is formation of fibrotic scars in the liver, choledocholithiasis is the appropriate name for bile duct blockage by gallstones, cholestasis is defined as a decrease in

the flow of bile, and cholangitis is inflammation of the biliary tree.

TRUE/FALSE 1. The most common cause of toxic hepatitis in North America leading to direct damage of hepatocytes is acetaminophen overdose.

ANS: T Toxic hepatitis refers to direct damage of hepatocytes by a toxin or toxic metabolite. Toxic reactions are usually predictable, and are directly related to the dose of the agent ingested. In North America and Europe, the most common cause of toxic hepatitis is acetaminophen.

DIF:

1

REF: Page 714

OBJ: 6 | 8

2. Alkaline phosphatase is a soluble enzyme localized in the cytosol of hepatocytes.

ANS: F ALP is a membrane-bound glycoprotein enzyme. The most important location of this enzyme is on the canalicular membrane of hepatocytes.

DIF:

1

REF: Page 710-711

OBJ: 5

Chapter 38: Gastrointestinal and Pancreatic Diseases Test Bank MULTIPLE CHOICE 1. Regarding the gastrointestinal (GI) tract, the function of gastrin is to: a. stimulate release of GI hormones, such as secretin and insulin. b. regulate contraction of the gallbladder. c. stimulate intestinal motility. d. induce absorption of digested food products across the intestinal wall.

ANS: A

Gastrin causes HCl release from parietal cells and stimulates (1) antral motility, (2) the secretion of pepsinogens and pancreatic fluid rich in enzymes, and (3) the release of GI hormones, such as secretin, insulin, acetylcholine, somatostatin, and pancreatic polypeptide (PP).

DIF: 1

REF: Page 729

OBJ: 3 | 5

2. Which one of the following peptide hormones acts to increase intestinal motility and stimulate

gallbladder contractions? a. Secretin b. Glucagon c. Insulin d. Cholecystokinin (CCK) ANS: D

See Table 38. Cholecystokinin’s principal actions are stimulation of gallbladder contraction; secretion of enzymes, bicarbonate, insulin, and glucagon from the pancreas; and stimulation of intestinal motility and stomach contraction.

DIF: 2

REF: Page 728

OBJ: 5

3. Which one of the following substances is not synthesized by the pancreas? a. Gastrin b. Somatostatin c. Vasoactive intestinal polypeptide (VIP) d. Insulin ANS: C

VIP is not found in the mucosal endocrine cells of the GI tract. It is believed to be a neurotransmitter limited to peripheral and central nervous tissue. VIP-containing nerve fibers are found throughout the GI tract from the esophagus to the colon.

DIF: 1

REF: Page 729

OBJ: 3 | 5 | 17

4. Extremely elevated serum levels of gastrin are typically indicative of: a. insulinoma. b. diabetes mellitus. c. Zollinger-Ellison syndrome.

d. cystic fibrosis.

ANS: C

Zollinger-Ellison syndrome is a condition resulting from a gastrin-producing tumor (gastrinoma) of the pancreatic islet cells further resulting in an overproduction of gastric acid, leading to ulceration of the esophagus, stomach, duodenum, and jejunum, and causing hypergastrinemia, diarrhea, and steatorrhea.

DIF: 1

REF: Page 731

OBJ: 10

5. What special specimen requirements must be met when collecting and preparing a sample for

gastrin analysis? a. Whole blood is the specimen of choice, collected in EDTA-containing tubes, placed on ice, and then refrigerated immediately upon receipt in the lab. b. Blood must be collected into a heparin-containing tube, separated in a refrigerated centrifuge, and frozen within 15 minutes of collection. c. Serum is the specimen of choice and must be collected into non-anticoagulant-containing tubes and kept warm until analysis is complete. d. A 12-hour overnight collection of gastric juice must be assessed for gastrin.

ANS: B

Due to the action of proteolytic enzymes, samples should be collected into tubes containing heparin as anticoagulant and aprotinin to prevent proteolysis. Samples should be mixed by inversion and transported rapidly on ice to the laboratory, and the plasma should be separated in a refrigerated centrifuge. The plasma should be frozen at approximately 20° C within 15 minutes of venipuncture.

DIF: 2

REF: TPE agSe T 73B1ANKS OE BL J: LE 10R.COM

6. Which one of the following statements concerning secretin is correct? a. Secretin is produced by the parietal cells in the stomach. b. The release of secretin is controlled by the presence of glucose in the blood. c. The function of secretin is to relax smooth muscle of the gut. d. Secretin stimulates release of pancreatic hormones.

ANS: D

See Table 38-1. Secretin is a hormone secreted by the mucosal granular S cells located in the duodenum but present throughout the small intestine. It stimulates pancreatic, pepsin, and bile secretion, and inhibits gastric acid secretion.

DIF: 2

REF: Page 728

OBJ: 4 | 5

7. A problem with the use of noninvasive testing for assessing pancreatic exocrine function is

that this type of testing: a. is uncomfortable for the patient compared with invasive testing. b. is expensive and time-consuming for the patient and provider. c. is only useful for adults with early pancreatic disease. d. lacks the clinical sensitivity and specificity for early disease detection.

ANS: D

A number of invasive and noninvasive laboratory tests are available to measure exocrine function in the investigation of pancreatic insufficiency. Invasive tests require GI intubation to collect pancreatic samples, which is (1) uncomfortable for the patient, (2) time-consuming, and (3) expensive. Noninvasive tests are simpler and less expensive to perform, but none has adequate clinical sensitivity for reliably detecting early pancreatic disease.

DIF: 2

REF: Page 736

OBJ: 22

8. An autoimmune disorder produced by ingestion of gluten and characterized by inflammatory

damage to intestinal lining cells and malabsorption is: a. Crohn disease. b. ulcerative colitis. c. lactose intolerance. d. celiac disease.

ANS: D

Celiac disease is an autoimmune intestinal disorder found in genetically susceptible individuals caused by the destructive interaction of glutens, the complex group of proteins present in wheat, with the intestinal mucosa, causing malabsorption.

DIF: 1

REF: Page 732

OBJ: 11

9. The use of the urea breath test for detection of H. pylori involves: a. titration of bacterial free acid in breath with sodium hydroxide to a pH end point of

3.5 compared with a urea standard. b. immunoassay measurement of deficiency of IgA-class transglutaminase in breath

using tissue transglutaminase as an antigen.

c. bacterial hydrolysis of T inEgS esT teB dAlaNbK elS edEuLrL eaEpRro.dC ucOinMg labeled bicarbonate, which

is absorbed into the blood and exhaled as 14CO2 or 13CO2. d. production of hydrogen by bacterial metabolism that is absorbed into the systemic circulation and exhaled in the breath as urea.

ANS: C

To determine the presence of H. pylori as the causative factor in peptic ulcer disease, urea labeled with either 14C or 13C is given orally as a drink or a capsule to swallow with water; urease from gastric H. pylori rapidly hydrolyzes the ingested urea to produce labeled bicarbonate, which is absorbed into the blood and exhaled as 14CO2 or 13CO2.

DIF: 2

REF: Page 731

OBJ: 9

10. A consequence of Crohn disease is bacterial overgrowth of the small bowel that normally

contains few bacteria. Bacterial overgrowth further leads to: a. bile salt deficiency and fat malabsorption. b. excess hydrogen in the intestine and acid reflux disease. c. lactase deficiency. d. chronic pancreatitis and pancreatic islet destruction.

ANS: A

Colonization of the upper small bowel is described as bacterial overgrowth and occurs as a consequence of other abnormalities of the small intestine such as Crohn disease. Bacteria colonizing the small bowel (such as Escherichia coli and Bacteroides species) deconjugate and dehydroxylate bile salts, leading to conjugated bile salt deficiency, which causes fat malabsorption.

DIF: 2

REF: Page 734

OBJ: 15 | 16

11. Secondary acquired lactose intolerance can occur from reduced lactase activity following

diffuse intestinal damage caused by, for example, inflammatory bowel disease (IBD). Which one of the following IBDs affects the large bowel in particular? a. Celiac disease b. Ulcerative colitis c. Crohn disease d. Peptic ulcer disease ANS: B

Secondary lactose intolerance may occur as a result of reduced enzyme activity following diffuse intestinal damage from ulcerative colitis. Inflammatory bowel disease (IBD) includes Crohn disease and ulcerative colitis, and ulcerative colitis is confined to the large bowel.

DIF: 2

REF: Page 733

OBJ: 12 | 16

12. During the gastric phase of the digestive process, HCl will be released from parietal cells

following the a. release b. inhibition

of gastrin from the mucosal endocrine cells in the stomach.

ANS: A

HCl is released during the gastric phase of digestion. HCl release is caused in part from the release of gastrin, which is stimulated by the near neutralization (pH 5 to 7) of gastric HCl by ingested food entering the pyloric zone.

DIF: 2

REF: Page 726-727

OBJ: 3 | 5

13. Chronic pancreatic damage leads to pancreatic insufficiency. In children, this is most

commonly associated with: a. accidental alcohol ingestion. b. cystic fibrosis. c. gallstones. d. pancreatic tumors.

ANS: B

Pancreatic insufficiency is the inability of the pancreas to produce and/or transport enough digestive enzymes to metabolize food in the intestine and allow its absorption. It is most frequently associated with cystic fibrosis in children and with chronic pancreatitis in adults.

DIF: 1

REF: Page 735

OBJ: 19 | 20

14. A peptide secreted by the upper intestinal mucosa that causes gallbladder contraction and

release of digestive enzymes from the pancreas, and is also localized in the nervous system, is: a. secretin.

b. VIP. c. insulin. d. CCK. ANS: D

See Table 37-1. CCK is found in the cells of the upper small intestinal mucosa. CCK regulates gallbladder contraction and increases small intestinal motility. CCK is widely distributed throughout both the central and peripheral nervous systems, with the highest concentrations in the cerebral cortex.

DIF: 1

REF: Page 728, Table 37-1

OBJ: 5

15. Mucosal inflammation of the stomach that is associated with peptic ulcer disease or gastric

carcinoma is referred to as: a. celiac disease. b. Zollinger-Ellison syndrome. c. nonerosive gastritis. d. erosive gastritis.

ANS: C

Gastritis is the term used to denote mucosal inflammation of the stomach. Nonerosive gastritis (chronic gastritis) is associated with peptic ulcer disease or gastric carcinoma, while erosive gastritis occurs in individuals after severe trauma or severe burns and in those who chronically ingest drugs, such as corticosteroids, ethanol, or aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs).

DIF: 2

REF: Page 732

OBJ: 1

16. Fecal osmotic gap measurements are done to: a. assess the functional mass of pancreatic tissue. b. distinguish between osmotic and secretory diarrhea. c. determine lactose tolerance. d. assess the amount of protein lost in stool.

ANS: B

Measurement of fecal osmotic gap enables an estimate to be made of the contribution of electrolytes or nonelectrolytes to the retention of water in the bowel and therefore assists in distinguishing between secretory and osmotic diarrhea.

DIF: 1

REF: Page 738

OBJ: 24

17. Gastrointestinal neuroendocrine tumors are either carcinoid tumors of enterochromaffin cells

or, as in the case of somatostatinoma, tumors of the: a. gastric parietal cells. b. cells in the brush border of the small intestine. c. small bowel mucosal cells. d. pancreatic endocrine cells.

ANS: D

GI neuroendocrine tumors are either endocrine pancreatic tumors or carcinoid tumors arising from enterochromaffin cells, which occur throughout the GI tract. Tumors arising from pancreatic islet cells have clinical syndromes associated with excessive hormone production.

This group of tumors includes (1) insulinomas, (2) gastrinomas, (3) VIPomas, (4) glucagonomas, and (5) somatostatinomas.

DIF: 2

REF: Page 737

OBJ: 23

18. A 23-year-old man visits his physician with symptoms of abdominal discomfort and diarrhea.

The man states that the diarrhea has been present off and on for approximately 6 weeks. He especially notes symptoms after a breakfast of wheat cereal and milk. His physician considers the possibility of two disorders, celiac disease and lactose intolerance. Which of the following pairs of laboratory tests would provide a definitive answer? a. Analysis of tissue transglutaminase IgA antibodies and breath hydrogen testing b. Serum gastrin and fecal alpha1-antitrypsin analysis c. Breath hydrogen testing and fecal osmotic gap determination d. Fecal elastase-1 and tissue transglutaminase IgA antibody analysis ANS: A

See Table 38-3. Immunoglobulin A (IgA) antibodies are used to diagnose celiac disease, and antitissue transglutaminase is now the antibody of choice for serological testing. Noninvasive breath-hydrogen testing is now the technique of choice for diagnosing lactase deficiency.

DIF: 3

REF: Page 739, Table 38-3

OBJ: 11 | 14

19. Which one of the following statements concerning insulin is incorrect? a. Insulin release from the pancreas is stimulated by gastrin.

EIRP. b. Glucose-dependent insT ulE inSoT troBpAicNpKeS ptE idLeL(G ) iCnO hiM bits insulin release. c. An insulinoma belongs to a group of tumors arising from pancreatic islet cells. d. Secretion of insulin is one of the principal actions of CCK. ANS: B

See Table 38-1. The effects of GIP, which is released from the jejunum and duodenum, are to stimulate insulin release and to inhibit gastrin secretion. For food components to stimulate GIP release, they must be absorbed by the intestinal mucosa.

DIF: 2

REF: Page 728, Table 38-1

OBJ: 5 | 23

20. A test that is considered diagnostic for cystic fibrosis in infants over the age of 2 weeks and

for other assessment of pancreatic insufficiency is: a. fecal elastase-1. b. an invasive test, such as the secretin stimulation test. c. a pancreatic enzyme test, such as amylase or lipase. d. gastrin analysis.

ANS: A

See Box 38-7. The measurement of pancreatic elastase-1 in feces is a reliable test for pancreatic insufficiency in infants over the age of 2 weeks with cystic fibrosis and in older children at diagnosis of the disorder. The test also is used to detect the onset of pancreatic insufficiency in those previously pancreatic sufficient.

DIF: 1

REF: Page 736, Table 736

OBJ: 20 | 22

Chapter 39: Disorders of Bone and Mineral Metabolism Test Bank MULTIPLE CHOICE 1. The primary physiological regulator of parathyroid hormone (PTH) synthesis and secretion is: a. PTH releasing hormone from the pituitary gland. b. the concentration of free calcium in blood or extracellular fluid. c. the concentration of PTH in blood. d. PTH stimulating hormone.

ANS: B

The concentration of free calcium in blood or extracellular fluid is the primary physiological regulator of PTH synthesis and secretion. Free calcium is sensed by a calcium-sensing receptor in the plasma membrane of parathyroid cells.

DIF: 1

REF: Page 753

OBJ: 3

2. Rickets is sometimes associated with deficiency of which one of the following vitamins? a. B12 b. A c. D d. C ANS: C

Deficiency of vitamin D results in impaired formation of bone, specifically interruption in the development and mineralizTaE tioSnToBf A thNeKgS roE wL thLpElaRte., C anOdMproduces rickets in children and osteomalacia in adults.

DIF: 1

REF: Page 755

OBJ: 8 | 10

3. Hypoparathyroidism is most commonly caused by: a. resistance to parathyroid hormone. b. adenoma of the parathyroid gland. c. pseudohypoparathyroidism. d. parathyroid gland destruction.

ANS: D

Hypoparathyroidism is due most commonly to parathyroid gland destruction during neck surgery (90%).

DIF: 1

REF: Page 745

OBJ: 6

4. What makes up the organic matrix component of bone? a. Calcium, protein, and collagen b. Cells and collagen only c. Minerals and cells only d. Cells only ANS: A

The matrix of bone is primarily type I collagen with lesser amounts of other proteins, including osteocalcin. The matrix is mineralized primarily by the deposition of inorganic calcium and phosphate.

DIF: 1

REF: Page 743

OBJ: 1 | 2

5. In bone: a. calcium is complexed with bicarbonate. b. the collagen component is type II collagen. c. osteoclasts are responsible for bone formation. d. osteoblasts are the bone-forming cells.

ANS: D

Osteoclasts resorb bone, whereas osteoblasts synthesize new bone.

DIF: 2

REF: Page 743

OBJ: 2

6. The major cause of the decrease in total bone mass in an aging osteoporotic woman is: a. being postmenopausal and estrogen deficient. b. lack of vitamin D. c. severe hypocalcemia. d. increased PTH. ANS: A

See Box 38-11. Most often the cause of osteoporosis is attributed to age (senile osteoporosis), postmenopausal osteoporosis, or both.

DIF: 1

REF: TPE agSe T 76B5A ,B 8-L 11LER.COM NoKxS3E

OBJ: 10

7. An individual’s serum phosphate level is decreased but his physician cannot determine a

physiological basis for this abnormal result. What could possibly have caused this result? a. Individual not fasting when blood was drawn b. Specimen hemolysis c. Use of IV carbohydrate therapy to stimulate insulin secretion d. Diurnal variation ANS: C

Injected insulin and carbohydrate-induced stimulation of insulin secretion increase the transport of phosphate and glucose into cells and thus are common causes of hypophosphatemia.

DIF: 2

REF: Page 750

OBJ: 4

8. Telopeptides: a. are released from type I collagen during bone resorption. b. are enzymes that become elevated during bone growth. c. are proteins found in bone whose serum level can reflect bone formation. d. is the most abundant noncollagenous protein in bone.

ANS: C

Cross-linked telopeptides are released from type I collagen during bone resorption. Increased urinary telopeptides and deoxypyridinoline have been reported in osteoporosis, Paget disease of bone, primary and secondary hyperparathyroidism, hyperthyroidism, and other diseases with increased bone resorption or osteolysis.

DIF: 1

REF: Page 764

OBJ: 9

9. An individual has the following laboratory test results: increased serum calcium, decreased

serum phosphorus, increased parathyroid hormone. This individual most likely has: a. hyperparathyroidism. b. hypoparathyroidism. c. hyperthyroidism. d. renal failure.

ANS: A

Primary hyperparathyroidism is most often caused by excessive secretion of PTH by a solitary adenoma of the parathyroid glands. Primary hyperparathyroidism is also the most common cause of hypercalcemia in outpatients. The counterbalance between calcium and phosphorus leads to decreased phosphorus in hyperparathyroidism.

DIF: 2

REF: Page 745

OBJ: 6 | 11

10. Total serum calcium: a. consists of an equal mix of free and protein-bound calcium. b. contains a 10% fraction that is complexed to small anions. c. is 80% bound to albumin. d. contains a 25% fraction that is free and unbound.

ANS: B

Calcium exists in three physiochemical states in plasma, of which approximately (1) 50% is free (ionized), (2) 40% is bound to plasma proteins, primarily albumin, and (3) 10% is complexed with small anions.

DIF: 1

REF: Page 744

OBJ: 5

11. In a case of severe osteomalacia, would bone-specific alkaline phosphatase be increased,

decreased, or remain unchanged? a. Increased b. Decreased c. Remain unchanged ANS: A

In severe osteomalacia, bone-specific alkaline phosphatase may be markedly increased without an increase in bone mineralization because of a mineralizing defect.

DIF: 1

REF: Page 763

OBJ: 5 | 10

12. A noncollagenous protein marker of bone formation that is released from bone during bone

resorption, regulated by 1,25-dihydroxyvitamin D, and synthesized by osteoblasts and that regulates insulin secretion and sensitivity is: a. n-telopeptide. b. deoxypyridinoline.

c. hydroxyproline. d. osteocalcin.

ANS: D

1,25-dihydroxyvitamin D regulates the synthesis of bone alkaline phosphatase and osteocalcin. Osteocalcin has a small role in bone mineralization, and is released from the bone matrix during bone resorption. Osteocalcin (about 20% of total) is regarded as an osteoblast-secreted hormone, regulating insulin secretion and sensitivity.

DIF: 2

REF: Page 763

OBJ: 8 | 9

13. Hypercalcemia occurs in humoral hypercalcemia of malignancy (HHM) because: a. tumors synthesize parathyroid hormone (PTH), which increases calcium levels in

blood. b. metastasizing cells synthesize calcium and release it into the circulation. c. PTH-related protein (PTHrP) is synthesized by tumors and stimulates bone resorption. d. osteoclasts bind tumor marker proteins and the process of bone remodeling becomes unregulated.

ANS: C

Tumors most commonly cause hypercalcemia by producing PTHrP, which is secreted into the circulation and stimulates bone resorption. PTHrP binds to the PTH receptor and is the principal mediator of humoral hypercalcemia of malignancy (HHM).

DIF: 2

REF: Page 746

OBJ: 4

lcS itT onBinAm eaS suErL em t i. s:COM 14. The clinical usefulness of cTaE NK LeEnR a. in the assessment of primary hyperparathyroidism. b. in the determination of sources of vitamin D deficiency. c. the differential diagnosis of multiple endocrine neoplasia (MEN). d. as a tumor marker for medullary thyroid carcinoma.

ANS: D

Calcitonin is secreted by the parafollicular or C cells, which are distributed throughout the thyroid gland. These cells are included in the APUD (amine precursor uptake and decarboxylation) family, associating them with medullary thyroid carcinoma (a tumor of the C cells) and other tumors of the APUD family in MEN type-2A and type-2B. DIF: 1

REF: Page 759

OBJ: 5

15. Which one of the following diseases is characterized by a loss in bone mass? a. Osteoporosis b. Osteomalacia c. Rickets d. Bone cancer ANS: A

Osteoporosis is a condition characterized by reduction in bone mass, leading to fractures with minimal trauma.

DIF: 1

REF: Page 742

OBJ: 10

16. Which one of the following analytes is most useful in distinguishing primary from secondary

hyperparathyroidism? a. Parathyroid hormone b. Serum calcium c. Vitamin D d. Serum phosphorus ANS: C

Vitamin D insufficiency is observed in individuals with secondary hyperparathyroidism but is elevated in primary hyperparathyroidism. This occurs because of parathyroid hormone activation of the hydroxylase enzyme in the kidney, which forms active vitamin D. DIF: 2

REF: Page 745

OBJ: 8

17. In a case of osteomalacia related to vitamin D deficiency, would serum calcium be increased,

decreased, or remain unchanged? a. Increased b. Decreased c. Remain unchanged ANS: B

Osteomalacia caused by vitamin D deficiency is uncommon in the United States. The disorder is caused by defective mineralization of bone and insufficiency of vitamin D. In rickets and osteomalacia, calcium may be low-normal or low in vitamin D deficiency.

DIF: 2

REF: Page 755

OBJ: 3 | 8 | 10

18. A blood specimen is collected in a heparin-containing tube for calcium and magnesium

determination. Upon centrifugation, the plasma appeared hemolyzed. How would this affect the magnesium value? a. There would be no effect on the magnesium value. b. The magnesium would form complexes with the hemoglobin and the results would indicate a false negative value. c. The magnesium would be incorporated into the bilirubin molecule, leading to a false negative value. d. Because erythrocytes contain magnesium, hemolysis would increase its apparent value.

ANS: D

Because erythrocytes contain higher concentrations of magnesium than serum or plasma, hemolyzed specimens are unacceptable.

DIF: 2

REF: Page 753

OBJ: 5 | 11

19. Hypophosphatemia is seen in all of the following except: a. intravenous glucose administration. b. vitamin D deficiency. c. hyperparathyroidism. d. malabsorption.

ANS: C

Hypophosphatemia is commonly caused by carbohydrate-induced stimulation of insulin secretion, lowered renal threshold as in hyperparathyroidism, intestinal loss, malabsorption, or acidosis. Vitamin D deficiency is typically associated with hypocalcemia.

DIF: 2

REF: Page 745

OBJ: 3 | 4

20. Magnesium: a. concentration is present mostly in the complexed state. b. decrease produces neuromuscular excitability. c. is the second most abundant intracellular cation. d. concentration is decreased with excessive intake of antacids.

ANS: B

Magnesium competitively inhibits the entry of calcium into neurons through its inhibitory action on glutamate-receptor mediation of calcium, thereby producing neuromuscular excitability.

DIF: 2

REF: Page 751

OBJ: 4

21. Hypermagnesia may be observed in all of the following except: a. excessive intake of antacids. b. gastrointestinal disorders. c. administration of magnesium in the presence of renal disease. d. enemas.

ANS: B

See Box 39-7. Decreased magnesium (hypomagnesia) occurs because of gastrointestinal loss and renal loss. The remainT inE gS chToBicAesNaKreSaEllLcLaE usR es.oCfOhM ypermagnesia.

DIF: 1

REF: Page 752,Box 39-7

OBJ: 3

22. A factor that would alter protein binding of calcium and its redistribution among the three

plasma pools would be: a. a change in an individual’s posture. b. liver disease. c. increased citrate concentration. d. an altered anion gap.

ANS: B

Liver disease will affect synthesis of proteins; 40% of calcium is bound to plasma proteins, particularly albumin. An altered anion gap and citrate concentration would alter the complexed calcium pool. Postural changes are preanalytical factors that would cause an increase in total calcium.

DIF: 2

REF: Page 744

OBJ: 3 | 4

23. Which of the following is a recognized clinical feature of hypercalcemia? a. Muscle tetany b. Muscle weakness c. Dementia d. Mental retardation

ANS: B

Most clinical symptoms related to elevated serum calcium are nonspecific and related to the neuromuscular system. Calcium is required for neurotransmission and muscle contraction, and when present in increased amounts, reduces neuromuscular excitability and causes weakness.

DIF: 1

REF: Page 745-746

OBJ: 4

24. Specimen requirements for assessing free calcium using ion-selective electrode methodology

include: a. heparinized whole blood. b. heparinized plasma. c. serum. d. all of the above.

ANS: D

Free calcium is measured in heparinized whole blood, heparinized plasma, or serum. Heparin does not involve calcium in the process of anticoagulation and does not interfere with free calcium measurement.

DIF: 1

REF: Page 748

OBJ: 5

25. Pseudohypoparathyroidism is characterized by tissues that are resistant to the effects of

circulating levels of parathyroid hormone (PTH). Which one of the following sets of values presents expected laboratory findings in this disorder? a. Calcium, phosphorus, and PTH within healthy reference intervals b. Elevated calcium, decreased phosphorus, normal PTH c. Decreased calcium, elevated phosphorus, elevated PTH MH d. Elevated calcium, elevT atE edSpThB osApN hoKrS usE, L deLcE reR as.eC dO PT ANS: C

Moderate increases of serum phosphate occur in individuals with PTH resistance (pseudohypoparathyroidism). Because of feedback mechanisms and interaction between calcium, PTH level increases in the circulation while calcium decreases.

DIF: 2

REF: Page 750

OBJ: 6

Chapter 40: Disorders of the Pituitary Test Bank MULTIPLE CHOICE 1. The release of thyrotropin-releasing hormone from the hypothalamus stimulates thyrotropin

release from the pituitary, which further leads to synthesis and secretion of thyroid hormone from the thyroid gland. When the concentration of thyroid hormone in the blood turns off the release of thyrotropin from the pituitary, this is referred to as what type of feedback? a. Open loop feedback b. Negative feedback c. Positive feedback d. Inhibitory feedback ANS: B

The effect of negative feedback is typically opposite to that of the initial stimulus. For example, an elevated concentration of cortisol (initial stimulus) reduces the synthesis and release of CRH, resulting in decreased secretion of ACTH and, ultimately, reduced secretion of cortisol (final response). Such feedback control maintains an optimal concentration of hormone in the blood under a variety of circumstances.

DIF: 2

REF: Page 772

OBJ: 3 | 4

2. The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are important in the

reproductive function of the male and female and are released in response to: a. gonadotropin-releasingThEoS rmToBnA eN (GKnSREHL).LER.COM b. corticotrophin-releasing hormone (CRH). c. TSH. d. oxytocin.

ANS: A

GnRH stimulates the secretion of FSH and LH. However, a separate and distinct releasing factor for FSH has not yet been established, although negative feedback control of this gonadotropin is affected by inhibin, a peptide of gonadal origin.

DIF: 1

REF: Page 772

OBJ: 3 | 4

3. A 35-year-old man visits his physician with complaints of sudden onset of fatigue, polydipsia,

and polyuria. Laboratory results indicate a normal fasting blood sugar. Serum sodium was slightly elevated. The most likely cause of these symptoms and laboratory results would be: a. diabetes mellitus due to insulin deficiency. b. secondary hypothyroidism. c. pituitary adenoma. d. diabetes insipidus due to hypothalamic dysfunction.

ANS: D

Deficient secretion of antidiuretic hormone (ADH) results in polyuria caused by the failure of the renal tubules to reabsorb solute-free water. If the thirst response is normal, increased ingestion of fluid (polydipsia) will follow. Hypothalamic diabetes insipidus is caused by a failure of the pituitary gland to secrete normal amounts of ADH in response to osmoregulatory factors.

DIF: 3

REF: Page 780

OBJ: 1 | 5 | 8

4. Which one of the following hormones is classified as a glycoprotein? a. Growth hormone b. Adrenocorticotropic hormone c. Prolactin d. Follicle-stimulating hormone ANS: D

The glycoprotein hormones of the pituitary (LH, FSH, and TSH) are composed of two peptide chains (usually referred to as - and -subunits), each with carbohydrate substituent groups attached.

DIF: 1

REF: Page 778

OBJ: 4

5. An example of a hypothalamic hormone would be: a. growth hormone (GH). b. thyroid-stimulating hormone (TSH). c. antidiuretic hormone (ADH). d. adrenocorticotropic hormone (ACTH).

ANS: C

Arginine vasopressin (AVP) is formed by neuronal cells of hypothalamic nuclei and stored in the neurohypophysis. Arginine vasopressin is also called antidiuretic hormone and vasopressin.

DIF: 1

REF: Page 779

OBJ: 4

6. The insulin tolerance test is used to assess which one of the following hormones? a. Growth hormone b. Thyrotropin c. Adrenocorticotropic hormone d. Prolactin ANS: A

To interpret meaningful GH concentrations, a number of provocative tests have been established to stimulate or suppress GH release. The insulin tolerance test, which produces a transient hypoglycemia to provoke GH release, is the most common stimulation test used to assess adequacy of GH secretion.

DIF: 1

REF: Page 775

OBJ: 7

7. Inhibition of growth hormone (GH) occurs through the action of: a. acetylcholine. b. somatostatin release-inhibiting hormone.

c. norepinephrine. d. gonadotropin-releasing inhibiting hormone.

ANS: B

The release of GH is thought to be controlled by hypothalamic growth hormone releasing hormone and somatostatin release-inhibiting hormone. The former stimulates GH release and the latter inhibits GH release.

DIF: 2

REF: Page 773

OBJ: 3 | 4

8. The anterior portion of the pituitary gland synthesizes many protein hormones. Another name

for this part of the pituitary gland is the: a. hypothalamus. b. neurohypophysis. c. hypophysis. d. adenohypophysis.

ANS: D

The pituitary gland is anatomically divided into the anterior (adenohypophysis) and the posterior (neurohypophysis) lobes.

DIF: 1

REF: Page 770

OBJ: 1

9. The hypothalamic hormone that inhibits prolactin is referred to as prolactin-inhibiting

hormone but is actually: a. thyrotropin. b. dopamine. c. adrenaline. d. interleukin 1.

ANS: B

PRL-inhibiting hormone (PIH) is actually the neurotransmitter dopamine. Prolactin is unique among the adenohypophyseal hormones in that the primary control of its secretion is inhibitory via dopamine.

DIF: 1

REF: Page 772

OBJ: 3

10. Which one of the following is not a function of thyrotropin? a. Action as a carrier protein of circulating thyroid hormones b. Induction of iodine uptake by the thyroid gland c. Stimulation of the growth of thyroid follicular cells d. Stimulation of the release of thyroid hormones from thyroglobulin ANS: A

Thyroglobulin is a carrier protein of circulating thyroid hormones. All other functions listed are roles of thyrotropin.

DIF: 1

REF: Page 779

OBJ: 4

11. Which one of the following statements concerning hormonal regulation via the feedback loop

is correct? a. The feedback loop is composed of two endocrine organs, the hypothalamus and the

pituitary gland. b. Negative feedback occurs when a structure secretes a hormone in response to a

stimulating hormone released from the pituitary. The initial hormone then induces more hormones to be released from the pituitary gland. c. When a stimulating hormone induces production of a hormone, elevated levels of that hormone shut off further release of the stimulating hormone. This is referred to as negative feedback. d. In the case of a pituitary adenoma that increases TSH levels, for example, thereby increasing thyroid release of T4 and T3, the increased thyroid hormones can easily shut off the release of TSH. ANS: C

See Figure 40-2. Control of the functional relationship between the pituitary gland and its target organs is based on the principle of feedback control, which is primarily negative between the blood concentration of circulating hormones and the pituitary gland and hypothalamus. The effect of negative feedback is typically opposite to that of the initial stimulus.

DIF: 2

REF: Page 772

OBJ: 3

12. Which one of the following statements regarding FSH/LH is incorrect? a. FSH, secreted by the anterior pituitary, induces growth of the ovum in the follicle

of the ovary. b. LH triggers release of the ovum from the ovarian follicle and produces an initial

decrease in estrogen. c. Progesterone produced by the ruptured follicle (the corpus luteum) causes LH levels to increase. d. In the male, FSH increases the number of LH receptors on Leydig cells.

ANS: B

LH in females causes ovulation and release of the ovum from the ovarian follicle, which has previously ripened under the influence of FSH, and causes luteinization of the ruptured follicle to form the corpus luteum.

DIF: 2

REF: Page 778

OBJ: 4

13. The most common hypothalamic-pituitary disorder in clinical endocrinology is: a. hyperprolactinemia. b. hyperthyroidism. c. Cushing disease. d. infertility.

ANS: A

Hyperprolactinemia is the most common hypothalamic-pituitary disorder encountered in clinical endocrinology. Also prolactinomas are the most common secretory tumors of the pituitary gland.

DIF: 1

REF: Page 776

OBJ: 4 | 7 | 8

14. A 45-year-old female complains of fatigue, heat intolerance, and hair loss. Serum thyroxine is

abnormally low. What test would confirm that this might be a pituitary disorder?

a. b. c. d.

Free T3 Thyroid binding globulin (TBG) Thyroid hormone binding ratio (THBR) Thyrotropin

ANS: D

Because TSH stimulates the synthesis and secretion of thyroid hormones from the thyroid gland, its measurement is used to distinguish primary from secondary hypothyroidism.

Decreased TSH leads to decreased thyroxine in secondary hypothyroidism, while elevated TSH with decreased thyroxine indicates an issue with the thyroid gland itself.

DIF: 2

REF: Page 779

OBJ: 4 | 8

15. Which one of the following hormones is responsible for normal development of cartilage and

bone, mobilizing fat stores, and stimulation of protein synthesis? a. ADH b. ACTH c. GH d. Prolactin ANS: C

Growth hormone affects carbohydrate, lipid, and protein metabolism. The overall physiological effect of GH is to promote growth in soft tissue, cartilage, and bone. This action results from stimulation of protein synthesis.

DIF: 1

REF: Page 770

OBJ: 4

16. Oxytocin is: a. synthesized by the somatotropic cells of the adenohypophysis and is stored within

intracellular granules. b. released upon stimulation of cell bodies in the hypothalamic paraventricular

nucleus. c. found in the pituitary gland but is mostly localized in the

catecholamine-synthesizing cells of the adrenal medulla. d. the principal hormone that controls the initiation and maintenance of lactation.

ANS: B

Stimulation of tactile receptors located around the nipples of the breasts initiates an action potential that propagates along afferent nerve fibers through the spinal cord and midbrain to the hypothalamus. The cell bodies in the paraventricular nucleus are then stimulated, resulting in release of oxytocin.

DIF: 2

REF: Page 781-782

OBJ: 3

17. A 28-year-old man and his wife visit a fertility clinic. His sperm count is low, but his wife’s

tests (LH/FSH, estrogen, etc.) all fall within the healthy reference intervals. His history indicates that he had a motor vehicle accident one year previously and was suffering from visual problems. What might be the cause of his oligospermia? a. Decreased prolactin (PRL) b. Elevated FSH c. Decreased LH

d. Elevated GH ANS: A

PRL excess in men is frequently manifested as oligospermia or impotence or both. In addition, men with PRL-secreting pituitary adenomas more often have macroadenomas along with visual field disturbances as a result of a larger tumor pressing on the optic chiasm. In both men and women, increased PRL can result in infertility.

DIF: 3

REF: Page 776

OBJ: 4 | 8

18. Use of the cosyntropin stimulation test: a. determines whether the hypothalamic-pituitary-thyroid axis is intact and

functional. b. involves measurement of serum gonadotropins and sex steroid hormones. c. is indicated when a morning cortisol result is low in addition to indications of

adrenal insufficiency. d. assesses adequacy of GH secretion.

ANS: C

The cosyntropin (a potent analogue of ACTH) stimulation test is used when the morning cortisol results are low or equivocal or when there is a strong clinical suspicion of adrenal insufficiency.

DIF: 2

REF: Page 782

OBJ: 7

19. The most common assay used to assess serum concentration of adenohypophyseal hormones

is: a. b. c. d.

chromatography. immunoassay. electrophoresis. spectrometry.

ANS: B

Assessment of anterior pituitary hormones typically involves immunoassay that is available commercially as part of an immunoassay kit or on automated immunoassay instruments.

DIF: 1

REF: Page 775

OBJ: 4

20. An individual using antidepressants visited her physician with a complaint of water retention.

Laboratory results indicated decreased urine volume, low serum sodium, low plasma osmolality, decreased serum uric acid, and urea. Antidiuretic hormone was measured and found to be elevated. What is the likely diagnosis? a. Acromegaly b. Hypothyroidism c. Diabetes insipidus d. Syndrome of inappropriate ADH secretion (SIADH) ANS: D

In SIADH a primary excess of ADH coupled with unrestricted fluid intake promotes increased reabsorption of free water by the kidney. The result is a decreased urine volume and an increased urine sodium concentration and urine osmolality. As a consequence of water retention, these patients become modestly volume expanded. Also both serum uric acid and blood urea nitrogen are decreased from free water retention.

DIF: 3

REF: Page 781-782

OBJ: 1 | 4 | 8

Chapter 41: Disorders of the Adrenal Cortex Test Bank MULTIPLE CHOICE 1. Which of the following steroid hormones is (are) synthesized and secreted by the zona

reticularis of the adrenal cortex? a. Cortisol b. Estradiol c. Androstenedione d. All of the above ANS: C

See Table 41-1. The adrenal cortex and the gonads share many metabolic pathways in the synthesis of steroid hormones because both are embryologically derived from nearby mesodermal anlagen.

DIF: 1

REF: Page 787, Table 41-1

OBJ: 3 | 4

2. Following multiple-day cosyntropin stimulation, an individual with Addison disease (primary

adrenal insufficiency) will: a. show markedly elevated cortisol production. b. fail to demonstrate increased cortisol production. c. demonstrate markedly elevated serum aldosterone.

ANS: B

CC OTMH stimulation test) is designed to See Figures 41-5 and 41-6T . TEhSeTcoBsA ynNtK roS piEnLteLstE(R an.A assess the functional capacity of the adrenal glands to synthesize cortisol. Cosyntropin is a potent stimulator of cortisol secretion, and failure to demonstrate increased cortisol production in response to multiple-day cosyntropin stimulation supports the diagnosis of Addison disease (primary adrenal insufficiency).

DIF: 2

REF: Page 792-794, Table 41-4,41-6

3. The most reliable screening test for a. Cushing syndrome b. Addison disease c. Conn syndrome d. adrenal tumor

OBJ: 5 | 6

is measurement of 24-hour urinary free cortisol.

ANS: A

Three screening tests are available for detecting Cushing syndrome: measurement of 24-hour urinary free cortisol (UFC), the overnight dexamethasone suppression test, and midnight measurements of salivary or serum/plasma cortisol. The most reliable test is the 24-hour UFC. DIF: 1

REF: Page 798

4. The primary glucocorticoid is: a. glucose. b. cortisol.

OBJ: 6 | 9

c. aldosterone. d. epinephrine.

ANS: B

Cortisol is the major glucocorticoid synthesized from cholesterol in the zona fasciculata and reticularis of the human adrenal cortex. Glucocorticoids are named as such because they have major effects on carbohydrate, protein, and lipid metabolism.

DIF: 1

REF: Page 788

OBJ: 4

5. During an evaluation of adrenal function, a patient had plasma cortisol determinations in the

morning after awakening and in the evening at approximately 7:30 PM. Laboratory results indicated that the evening value was approximately half as high as the morning concentration.

This is indicative of: a. a normal finding. b. Cushing syndrome. c. adrenal gland tumor. d. ectopic hormone production.

ANS: A

Serum cortisol concentrations are highest in the early morning hours and vary from 7 to 25 µg/dL between 4 AM and 12 PM. Late afternoon concentrations are about half the morning concentrations and frequently are less than 5 µg/dL between 10 PM and 2 AM. DIF: 2

REF: Page 802

OBJ: 7

6. The adrenal cortical hormone that promotes sodium resorption and potassium and hydrogen

ion excretion by the renal tTuE buSleTsBaA ndNtK huSsEaL ffL ecEtsRw.aCteOr M balance in the body is: a. androstenedione. b. cortisol. c. aldosterone. d. calcium.

ANS: C

Mineralocorticoids bind to a cytoplasmic mineralocorticoid receptor (MR) in the distal convoluted tubule and collecting duct of the nephron, the colon, and the salivary glands to promote sodium reabsorption, and potassium and hydrogen ion excretion.

DIF: 1

REF: Page 788

OBJ: 4

7. Glucocorticoids: a. decrease blood glucose concentration. b. repress inflammatory genes. c. stimulate erythropoiesis. d. stimulate lipogenesis.

ANS: B

Glucocorticoids are powerful antiinflammatory hormones that repress proinflammatory genes, such as cyclo-oxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), various interleukins (IL-1, IL-2, and IL-6), tumor necrosis factor-alpha, interferon-gamma, and E-selectin.

DIF: 1

REF: Page 790

OBJ: 1 | 4

8. A patient with Cushing syndrome has plasma cortisol measured at 8 AM. The nighttime

cortisol level will be a. increased b. decreased c. unchanged

from the 8 AM value.

ANS: C

Diurnal variation in plasma cortisol leads to a blood concentration at 8 PM being approximately 50% of the concentration obtained at 8 AM. However, the morning to night difference is lost in patients with Cushing syndrome so that the nocturnal concentrations are inappropriately raised from normal and will be closer to the 8 AM value.

DIF: 2

REF: Page 801

9. Renin is synthesized in the

OBJ: 6 | 7 | 10

and stimulates the production of angiotensin I, which

eventually leads to _. a. kidney; lowering of the blood pressure and volume b. adrenal gland; an increase in blood pressure and volume c. kidney; stimulation of aldosterone production d. adrenal gland; stimulation of cortisol production ANS: C

Upon stimulation of the juxtaglomerular apparatus, renin is released into the circulation, where it hydrolyzes its substrate, angiotensinogen, to produce a decapeptide known as angiotensin I, which is then converted into angiotensin II. Angiotensin II stimulates the cells of the zona glomerulosa toTpE roSdT ucBeAaN ldK osSteErL onLeE . R.COM DIF: 2

REF: Page 791

OBJ: 1 | 4

10. The major site of cortisol synthesis is the a. zona glomerulosa b. zona fasciculata c. zona reticularis d. medulla

of the adrenal gland.

ANS: B

See Table 41-1. Cortisol is the major glucocorticoid synthesized from cholesterol with the zona fasciculata being the major site of synthesis.

DIF: 1

REF: Page 787, Table 41-1

OBJ: 3 | 4

11. Which one of the following statements concerning cortisol is incorrect? a. Cushing syndrome is the syndrome of hypercortisolism. b. A cortisol-secreting tumor can lead to Cushing disease. c. Plasma cortisol levels show a diurnal variation, with the highest level present in

the morning and the lowest level in the late afternoon. d. Hypocortisolism due to primary adrenal disease is referred to as Addison disease.

ANS: B

In Cushing disease, hypersecretion of ACTH by a pituitary tumor (e.g., a microadenoma or a macroadenoma) leads to bilateral adrenal hyperplasia and cortisol overproduction.

DIF: 2

REF: Page 797-798

OBJ: 6

12. A hypertensive, hypokalemic patient with increased aldosterone production and decreased

plasma renin activity likely has: a. Cushing syndrome. b. Addison disease. c. Conn syndrome. d. congenital adrenal hyperplasia.

ANS: C

Primary hyperaldosteronism, commonly referred to as Conn syndrome, is a syndrome of hypersecretion of aldosterone. In primary hyperaldosteronism, excessive aldosterone production originates within the adrenal gland and produces the syndrome, which is characterized by low renin, hypokalemic alkalosis, and hypertension.

DIF: 2

REF: Page 798

OBJ: 6

13. Deficiency of which of the following enzymes can lead to congenital adrenal hyperplasia

(CAH)? a. 21-Alpha-hydroxylase b. 11-Beta-hydroxylase c. 17-Ketosteroidase d. Both a and b ANS: C

The most common cause of congenital adrenal hyperplasia (CAH) is a deficiency in the 21-hydroxylase enzyme (CYP21), which converts 17-hydroxyprogesterone (17-OHP) to 11-desoxycortisol. 17-OHP may also elevated in CYP11B1 (11-beta-hydroxylase)–deficient CAH. DIF: 2

REF: Page 798

OBJ: 6

14. How would CAH affect cortisol and adrenal androgen levels in blood? a. Cortisol increased, adrenal androgens increased b. Cortisol decreased, adrenal androgens increased c. Cortisol increased, adrenal androgens decreased d. Cortisol decreased, adrenal androgens decreased ANS: B

CAH presents a mixed picture of cortisol deficiency (hypofunction) and adrenal androgen overproduction (hyperfunction).

DIF: 2

REF: Page 798

OBJ: 6

15. Which one of the following statements concerning androstenedione is incorrect? a. In adrenal carcinoma, cortisol is greatly elevated, but androstenedione is greatly

decreased. b. The precursor molecule in the formation of androstenedione is

dihydroepiandrostenedione (DHEA). c. Androstenedione metabolites are measured as 17-ketosteroids. d. 11-Hydroxylase deficiency leads to elevated plasma androstenedione.

ANS: A

Adrenal carcinomas are rare, with an incidence of only 1 per million population, and occur more commonly in women than in men by a 2.5:1.0 ratio. Most adrenal carcinomas are functional, producing glucocorticoids alone or both glucocorticoids and androgens. Plasma DHEA-S, DHEA, and androstenedione concentrations are markedly elevated in patients with functional adrenal carcinomas.

DIF: 2

REF: Page 798

OBJ: 4

16. In the classic plasma renin activity assay that measures the main function of the enzyme and

uses inhibitors of angiotensinase, what is actually measured at the end of the assay? a. Plasma renin b. Angiotensin-converting enzyme c. Angiotensin I d. Angiotensin II ANS: C

In the classic PRA method, inhibitors of angiotensinase and angiotensin-converting enzyme (ACE) are added to prevent the conversion of angiotensin I to angiotensin II, the specimen is incubated at 37° C, and production of angiotensin I is measured.

DIF: 1

REF: Page 803

OBJ: 9

17. Because of the biochemicaT lE prS opTeBrtA ieN sK ofSsE teL roLidEhRo.rm CoOnMes, the majority of these hormones, at

physiological concentration: a. are bound with high affinity to a carrier protein in the circulation. b. remain free in the circulation. c. are conjugated to glucuronides. d. are bound with low affinity to albumin.

ANS: A

At physiological concentrations, about 90% to 98% of steroid hormones circulate bound to albumin or a carrier protein, usually with high affinity for a binding globulin, such as corticosteroid-binding globulin (CBG) and sex hormone–binding globulin (SHBG).

DIF: 1

REF: Page 792-793

OBJ: 4

18. The urinary metabolite of cortisol and adrenal androgens is: a. renin. b. 17-hydroxyprogesterone. c. 11-desoxycortisol. d. 17-ketosteroid.

ANS: D

The urinary metabolites of 17-hydroxyprogesterone, 11-desoxycortisol, and cortisol are 17-ketogenic steroids. In addition, the urinary excretion of 17-ketosteroids (the breakdown products of adrenal androgens) increases as an early sign that puberty will begin in the coming 3 to 5 years.

DIF: 1

REF: Page 802-803

OBJ: 4 | 9

19. In the corticotropin-releasing hormone stimulation test, an individual with secondary adrenal

insufficiency (pituitary ACTH deficiency) will have which of the following laboratory test results? a. Plasma ACTH peak at 30 minutes and serum cortisol peak at 60 minutes b. Decreased plasma ACTH and decreased serum cortisol response times c. Prolonged ACTH response time and decreased cortisol response time d. Excessive increase in plasma response ANS: B

In the interpretation of the CRH stimulation test, normal subjects show a plasma ACTH concentration peak 30 minutes after CRH injection and a serum cortisol peak at 60 minutes.

Individuals with pituitary ACTH deficiency (secondary adrenal insufficiency) have decreased ACTH and cortisol responses.

DIF: 2

REF: Page 793

OBJ: 5 | 6

TRUE/FALSE 1. The principal site of steroid metabolism is the liver.

ANS: T

The liver is the major site of steroid metabolism via P-450 enzyme systems, with the kidney playing less of a metabolic role but an important excretory role.

DIF: 1

TESTBANKSOEBL LER.COM J: 2

REF: Page 793

Chapter 42: Thyroid Disorders Test Bank MULTIPLE CHOICE 1. Thyroid-stimulating hormone (TSH) receptor antibodies can be detected in serum of patients

having which of the following? a. Multinodular goiter b. Thyroid tumors c. Thyrotoxicosis d. Graves disease ANS: D

Graves disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones. It results from agonistic autoantibodies that bind to, and activate, the TSH receptor, producing hyperthyroidism.

DIF: 2

REF: Page 816

OBJ: 6

2. What causes the total thyroxine (T4) levels to be increased in pregnant women? a. Inappropriate iodine metabolism b. hCG-induced thyrotoxicosis c. Altered glucose metabolism d. Change in thyroglobulin synthesis ANS: B

hCG-induced hyperthyroidTisEmSiT sB obAsN erK veSdEiL nL (1E )R ge.sC taO tioMnal transient thyrotoxicosis, (2) TSH receptor hypersensitivity to appropriate hCG concentrations during pregnancy, and (3) hCG-secreting tumors.

DIF: 1

REF: Page 817

OBJ: 5

3. Serum thyroid-stimulating hormone (TSH) level is decreased in individuals with: a. hyperthyroidism. b. primary hypothyroidism. c. secondary hyperthyroidism. d. primary hyperparathyroidism.

ANS: A

See Table 42-2. The biochemical picture of primary hyperthyroidism shows increases in concentrations of T4 and T3, with the quantities of TSH suppressed to undetectable concentrations.

DIF: 1

REF: Page 812, Table 42-2

OBJ: 4 | 5

4. An amorphous material enclosed within each follicle of the thyroid gland and that is

composed mainly of thyroglobulin is: a. thyroxine. b. iodine. c. colloid.

d. goiter.

ANS: C

Each follicle has an outer layer of epithelial cells that enclose an amorphous material called colloid. Colloid is mainly composed of thyroglobulin (Tg) and small quantities of iodinated thyroalbumin.

DIF: 1

REF: Page 808

OBJ: 1 | 2

5. Which one of the following is not a function of the thyroid hormones? a. Control of metabolic rate b. Removal of defective RBCs c. Increasing cholesterol synthesis and breakdown d. Stimulation of neural development ANS: B

The functions of thyroid hormones include (1) control of the basal metabolic rate and calorigenesis, (2) enhancement of mitochondrial metabolism, (3) stimulation of neural development and normal growth, (4) promotion of sexual maturation, (5) stimulation of adrenergic activity with increased heart rate and myocardial contractility, (6) stimulation of protein synthesis and carbohydrate metabolism, (7) increasing synthesis and degradation of cholesterol and triglycerides, (8) increasing the requirement for vitamins, (9) increasing the calcium and phosphorus metabolism, and (10) enhancing the sensitivity of adrenergic receptors to catecholamines.

DIF: 1

REF: Page 808-809

OBJ: 2

esE, S thT eB prAim seL crLetEoR ry.pCroOdM uct of the normal thyroid gland is in 6. Regarding thyroid hormonT NaKrySE the form of: a. free thyroxine (T4). b. free triiodothyronine (T3). c. iodine. d. thyroglobulin (Tg).

ANS: A

Free (unbound) T4 (FT4) is the primary secretory product of the normal thyroid gland. T4 undergoes peripheral deiodination of the outer ring at the 5' position to yield T3.

DIF: 1

REF: Page 810

OBJ: 2 | 3

7. Thyroid hormones are derived from the amino acid: a. phenylalanine. b. threonine. c. theophylline. d. tyrosine.

ANS: D

The biosynthesis of thyroid hormones involves the (1) trapping of circulating iodide by the thyroid gland, (2) incorporation of iodine into tyrosine, and (3) coupling of iodinated tyrosyl residues to form the thyronines (T4 and T3) within the protein backbone of the thyroglobulin protein in the follicular lumen.

DIF: 1

REF: Page 809

OBJ: 3

8. A 45-year-old woman visits her physician with complaints of fatigue, heat intolerance, goiter,

and unusual hair loss. Blood is collected and serum T4 value is below the healthy reference interval. What laboratory assay would confirm that this might be a pituitary disorder? a. Free T3 b. Thyroid-binding globulin (TBG) c. Thyrotropin-releasing hormone (TRH) d. Thyroid-stimulating hormone (TSH) ANS: D

TSH is synthesized in the anterior pituitary gland and stimulates (1) the “iodide pump,” (2) thyroglobulin synthesis, and (3) colloidal uptake by follicular cells. A decreased TSH concentration can lead to decreased circulating thyroxine. An elevated concentration of TSH is also an important laboratory finding, particularly in the early detection of thyroid failure. In mild or subclinical hypothyroidism, thyroid hormone concentrations remain within the healthy reference interval, but the TSH concentration is elevated.

DIF: 2

REF: Page 810

OBJ: 4 | 5 | 9

9. Which one of the following statements is correct regarding reverse T3 (rT3)? a. rT3 is physiologically active, but less so than T3. b. rT3 is formed in the blood by central deiodination of T4. c. rT3 is decreased in patients with the “euthyroid sick syndrome.” d. Renal failure is associated with elevated rT3 concentrations.

ANS: B

rT3 is biologically inert andTE isSaTcaBtaAbNoK litS eE ofLTL4E . rRT. inOsM erum is present almost entirely as a 3C result of its generation from T4 in peripheral tissues by 5'-deiodinases. Renal failure is associated with low rT3 concentrations while increased rT3 can be associated with the euthyroid sick syndrome.

DIF: 2

REF: Page 807

OBJ: 1 | 3

10. Increased TSH, decreased T3, and decreased T4 with the presence of goiter indicate: a. primary hypothyroidism. b. secondary hypothyroidism. c. tertiary hypothyroidism. d. pseudohypothyroidism.

ANS: A

Primary hypothyroidism occurs when the synthesis of T4 and T3 is impaired, either because of an extrinsic factor or because of an intrinsic, inherited defect in thyroid hormone biosynthesis.

As a result, the feedback loop causes compensatory thyroid enlargement (goiter) through the hypersecretion of thyrotropin-releasing hormone (TRH) and TSH. DIF: 2

REF: Page 812-813

OBJ: 4 | 5 | 9

11. An individual’s thyroid-binding globulin (TBG) concentration is 2.8 mg/dL, T3 value is 10.5

µg/dL, and T4 value is 12.5 µg/dL. What is the estimate of free T4 value? a. 37.5

b. 4.3 c. 1.35 d. The approximate free T4 value cannot be determined from the given values.

ANS: B

See Table 42-1. Measurements of serum TBG concentration are used two ways in the diagnosis of thyroid disease. In one, the T4:TBG (T4/TBG) ratio is calculated. Such indices are used to approximate FT4 concentrations. In this case, 12.5/3 = 4.18.

DIF: 3

REF: Page 808, Table 42-1

OBJ: 8

12. Another term used to describe hyperthyroidism is: a. goiter. b. euthyroid sick syndrome. c. thyrotoxicosis. d. cretinism.

ANS: C

Some clinicians prefer the general term thyrotoxicosis rather than hyperthyroidism to define the hypermetabolic state associated with increased amounts of thyroid hormone in the circulation.

DIF: 1

REF: Page 815

OBJ: 1

13. A 30-year-old man visits his physician for an annual health check. He complains that he has

been feeling fatigued of late and has lost weight. Blood is collected and the following laboratory results are noted: total T3, elevated; total T4, elevated; free T4, elevated; TSH, slightly elevated. MagneticTrE esSoT naBnA ceNiK mSaE giL ngLiEnR di. caCteOsMa mass in the area of his pituitary gland. What disorder do the results suggest? a. Central hyperthyroidism b. Graves disease c. Secondary hypothyroidism d. TSH-secreting pituitary tumor ANS: A

Endogenous disorders causing hyperthyroidism include (1) intrinsic thyroid disease (primary hyperthyroidism), (2) ectopic thyroid tissue (struma ovarii), and (3) disorders of the hypothalamus or pituitary causing excess TSH secretion (central hyperthyroidism).

TSH-secreting anterior pituitary adenomas have been observed. Their diagnosis is suggested by (1) clinical hyperthyroidism, (2) elevated concentrations of FT4, (3) normal to elevated TSH concentration, and (4) evidence of a pituitary mass on computed tomography (CT) scan or magnetic resonance imaging (MRI).

DIF: 3

REF: Page 815

OBJ: 4 | 5 | 9

14. Severe hypothyroidism that develops during the newborn period is referred to as: a. thyrotoxicosis. b. myxedema. c. cretinism. d. euthyroid sick syndrome.

ANS: C

Cretinism is the term used to describe severe hypothyroidism that develops in the newborn period.

DIF: 1

REF: Page 812

OBJ: 1

15. Which of the following hormones require transport proteins to move them through the

circulation and are more than 99% bound to these proteins? a. TSH b. Thyrotropin-releasing hormone c. Calcitonin d. T3 and T4 ANS: D

See Figure 42-7. T4 and T3 in the circulation are bound reversibly and almost completely to carrier proteins. Circulating T4 is highly (>99.9%) protein bound, and the fraction that is bound to protein is biologically inactive. The carrier proteins include TBG, transthyretin, and albumin. The remaining hormones are peptide hormones that travel mostly unbound in the circulation.

DIF: 1

REF: Page 811, Figure 42-7

OBJ: 3

16. Myxedema is a skin and tissue mucopolysaccharide disorder caused by severe and prolonged: a. Graves disease. b. hypothyroidism. c. hyperthyroidism. d. thyrotoxicosis.

ANS: B

Myxedema is a severe form of hypothyroidism in which there is accumulation of mucopolysaccharides in the skin and other tissue, leading to a thickening of facial features and a doughy induration of the skin.

DIF: 1

REF: Page 812

OBJ: 5

17. What is required for normal thyroxine synthesis? a. Iodine b. Iodine and thyroglobulin c. Iodine and thyroid-binding globulin d. TSH, iodine, and thyroglobulin ANS: D

T4 is the principal hormone secreted by the thyroid, and its circulating concentration is under the influence of TSH. Each step in the synthesis of thyroid hormones is regulated by pituitary TSH, which stimulates (1) the “iodide pump,” (2) thyroglobulin synthesis, and (3) colloidal uptake by follicular cells. T4 is synthesized from tyrosine residues on iodinated thyroglobulin in the colloid of the thyroid gland.

DIF: 2

REF: Page 810

OBJ: 3

18. The limited clinical information that is available from the results of a total T4 measurement is

due to: a. interferences with circulating autoantibodies directed against the colloid.

b. the formation of fibrin clots during the preparation of the blood sample. c. the fact that total T4 measurements reflect inactive, protein-bound hormone. d. the fact that circadian rhythms are not determined.

ANS: C

Because it reflects mostly inactive (protein-bound) hormone, the quantity of total T4 alone provides limited clinical information. For this reason, FT4 measurements are preferred over total T4 measurements for routine testing.

DIF: 2

REF: Page 820

OBJ: 7

19. The secretory unit of the thyroid gland is the: a. colloid. b. thyroid follicle. c. parafollicular cell. d. thymus.

ANS: B

The thyroid follicle or acini (see Figure 42-1) is the secretory unit of the thyroid gland.

DIF: 1

REF: Page 808

OBJ: 1 | 2

20. A woman with thyroid cancer has her thyroglobulin (Tg) level checked to assess return of

thyroid function following surgery. The Tg value was markedly decreased. Her physician calls the laboratory asking for an explanation of the result. You respond that: a. this is a typical value for someone with thyroid cancer and that Tg can be used as a tumor marker, so decreased values are better than increased values. b. Tg is probably being inTteErfSeT reB dA wN itK hS byEtL heLiEmRm.uCnO ogMlobulins that are involved in the healing postsurgery process. c. your laboratory uses a Tg assay that likely has been interfered with by Tg autoantibodies, which limits the accurate measurement of Tg. d. thyroid cancer obliterates all colloid in the thyroid gland and therefore Tg will not be present in a blood sample.

ANS: C

A major difficulty in most immunoassays for Tg is interference due to endogenous anti-Tg antibodies (TGA) that are present in about 15% to 35% of thyroid cancer patients. This limits the accurate measurement of Tg. Consequently, it is standard practice to search for TGAs whenever Tg is measured.

DIF: 3

REF: Page 822

OBJ: 6 | 7 | 9

Chapter 43: Reproduction-Related Disorders Test Bank MULTIPLE CHOICE 1. Which one of the following hormones causes the hypothalamus to trigger the surge of luteinizing hormone (LH) from the anterior pituitary just before ovulation? a. Estrogen b. Progesterone c. Follicle-stimulating hormone (FSH) d. Gonadotropin-releasing hormone (GnRH) ANS: A Just before ovulation, estrogen secretion by the follicle increases dramatically; this positively stimulates the hypothalamus and triggers the LH surge. The LH surge is a reliable predictor of ovulation.

DIF:

2

REF: Page 835

OBJ: 3 | 4

2. What would the laboratory results be in a male patient exhibiting characteristic symptoms of hypogonadotropic hypogonadism? a. Elevated testosterone, decreased FSH b. Decreased testosterone, decreased FSH c. Elevated testosterone, elevated FSH d. Decreased testosterone, elevated FSH ANS: B Decreased concentrations of testosterone (<200 ng/dL) and decreased concentrations of FSH (<10 mIU/mL) are suggestive of hypogonadotropic hypogonadism.

DIF:

1

REF: Page 842

OBJ: 5 | 7

3. During the luteal phase, which hormone, when decreased in the absence of conception, releases its inhibition on pituitary gland synthesis and release of FSH? a. Chorionic gonadotropin b. Progesterone c. Estrone d. Estradiol ANS: D FSH is suppressed by negative feedback from E2 during the luteal phase. In the absence of conception, the corpus luteum resolves, resulting in a decrease in estrogen and progesterone concentrations. The decrease in negative feedback from E2 on the anterior lobe of the pituitary gland triggers the FSH surge that begins the development of an ovarian follicle for the next cycle.

DIF:

2

REF: Page 835

OBJ: 4

4. Which one of the following hormones shuts off synthesis and release of LH from the male pituitary gland? a. FSH b. Testosterone c. Prolactin d. Inhibin ANS: B Sex steroids and inhibin provide negative feedback control of LH and FSH secretion, respectively. LH secretion is inhibited by testosterone and by its metabolites, estradiol and dihydrotestosterone (DHT).

DIF:

1

REF: Page 827

OBJ: 3

5. Laboratory assessment of which of the following hormones is used to evaluate ovulation? a. FSH b. Estradiol c. Progesterone d. All of the above ANS: C Measurement of the concentration of serum progesterone is the primary assay used for the evaluation of ovulation.

DIF:

1

REF: Page 842-843

OBJ: 3 | 6

6. Which of the following sTtaEteSmTeB ntA sN coKnS ceErnLiL ngEaRm.eC noOrM rhea is (are) correct? a. One cause of primary amenorrhea is Turner syndrome, in which there is no estrogen production by the ovaries. b. Hirsutism is a typical side effect of amenorrhea caused by androgen excess. c. Primary amenorrhea is defined as the absence of menstrual bleeding in women who have never menstruated. d. All of the above are correct.

ANS: D Amenorrhea, the absence of menstrual bleeding, is traditionally categorized as primary (women who have never menstruated) or secondary (women in whom menstruation is present for a variable time and then ceases). About 40% of phenotypic females who have primary amenorrhea have Turner syndrome (45,X karyotype). Patients with androgen excess often will have acne, obesity, and variable degrees of excess hair on the face, chest, abdomen, and thighs.

DIF:

2

REF: Page 837

OBJ: 1 | 5

7. A typical characteristic in a woman with polycystic ovary disease (PCOS) includes: a. markedly increased serum FSH concentration. b. decreased serum androstenedione concentration. c. increased serum LH concentration. d. persistent ovulation.

ANS: C

Relatively low FSH and disproportionately high LH concentrations are common in PCOS. Serum androstenedione and testosterone concentrations (total and free concentrations) are elevated.

DIF:

1

REF: Page 839

OBJ: 1 | 6

8. In nonpregnant women, progesterone is synthesized and secreted by the: a. corpus luteum. b. placenta. c. pituitary gland. d. Both a and b are correct.

ANS: A After ovulation, the granulosa and thecal cells of the follicle become the corpus luteum.

These luteal cells produce estrogen and progesterone. If fertilization and pregnancy occur, the corpus luteum persists and continues to produce estrogen and progesterone. If pregnancy does not occur, the corpus luteum regresses and is eventually replaced by scar tissue.

DIF:

1

REF: Page 832

OBJ: 3 | 4

9. Typical findings in a woman in menopause include: a. increased progesterone. b. decreased serum LH/FSH. c. hirsutism. d. decreased estrogen and inhibin.

ANS: D Menopause is the permanent cessation of menstruation resulting from loss of ovarian follicular activity. The ovaries fail to produce adequate amounts of estrogen and inhibin, and gonadotropin production then increases in a continued attempt to stimulate the ovary.

DIF:

1

REF: Page 836

OBJ: 1 | 6

10. Which one of the following statements regarding FSH/LH is incorrect? a. LH acts to stimulate Leydig cells in the testes to synthesize testosterone. b. FSH, secreted by the anterior pituitary, induces follicular maturation. c. FSH acts on the cells of the follicle to increase responsiveness of LH receptors. d. Progesterone produced by the corpus luteum causes LH levels to increase.

ANS: D In the luteal phase of the menstrual cycle, there is increasing production of progesterone and estrogen from the corpus luteum with consequent gradual lowering of LH and FSH concentrations.

DIF:

2

REF: Page 835

OBJ: 3 | 4

11. Dehydroepiandrosterone sulfate (DHEA-S): a. concentrations exhibit a circadian rhythm that reflects the secretion of adrenocorticotropic hormone (ACTH). b. is an important screening test used to evaluate women with hirsutism and

virilization. c. concentration is increased in 17-hydroxylase deficiency-caused amenorrhea. d. analysis is performed using heparinized plasma.

ANS: B The two most important screening tests used in the evaluation of women for hirsutism and virilization are serum total or free testosterone and DHEA-S. Elevation of DHEA-S concentration suggests an adrenal origin of androgens, whereas elevations in testosterone indicate an adrenal or ovarian source. DHEA-S in circulation originates primarily from the adrenal glands, although in men some may be derived from the testes. None is produced by the ovaries.

DIF:

2

REF: Page 840

OBJ: 1 | 6

12. Early activation of the hypothalamic-pituitary-gonadal axis in a young child will lead to: a. GnRH-dependent precocious puberty. b. GnRH-independent precocious puberty. c. pseudoprecocious puberty. d. pseudohermaphroditism.

ANS: A Precocious puberty has been classified as GnRH dependent or independent.

GnRH-dependent precocious puberty is due to precocious activation of the hypothalamic-pituitary-gonadal axis. GnRH-independent precocious puberty (also called pseudoprecocious puberty) refers to precocious sex steroid secretion that is independent of pituitary gonadotropin release.

DIF:

2

REF: Page 837

OBJ: 1 | 5

13. In measurement of testosterone in blood: a. assessment of serum 17-ketosteroids is included. b. specimens must be collected in EDTA anticoagulant. c. morning specimens are preferred because of the diurnal release of testosterone. d. 5-androstenediol derivatives are actually measured.

ANS: C Testosterone is subject to a diurnal variation, reaching a peak concentration between 4 and 8 AM. Therefore morning specimens are preferred.

DIF:

1

REF: Page 844

OBJ: 6

14. The peptide hormone responsible for the discharge of the gonadotropins from the anterior pituitary gland, which causes Kallmann syndrome when deficient, is: a. FSH. b. gonadotropin-releasing hormone. c. testosterone. d. DHEA-S. ANS: B

Gonadotropin-releasing hormone (GnRH) is a decapeptide synthesized in the hypothalamus and transported to the anterior pituitary gland, where it stimulates the release of both FSH and LH. Kallmann syndrome, the most common form of hypogonadotropic hypogonadism, results from a deficiency of GnRH in the hypothalamus.

DIF:

1

REF: Page 826-827

OBJ: 2 | 5

15. Inhibin: a. augments release of LH from the male pituitary gland. b. promotes synthesis of testosterone by the Sertoli cells. c. inhibits release of FSH from the male pituitary gland. d. increases in males with elevated GnRH. ANS: C Inhibin is a protein that is released by seminiferous tubules of Sertoli cells and acts to inhibit FSH release by cells of the anterior pituitary. It serves as the negative feedback control.

DIF:

2

REF: Page 826-827

OBJ: 1 | 2

16. A 14-year-old male comes to his physician with infantile genitalia and the lack of development of any secondary sex characteristics. The patient is short in stature. Upon discussion of family history, it was discovered that several male relatives had similar defects in testicular development. Based on this information, laboratory results would indicate: a. decreased testosterone and decreased follicle-stimulating hormone (FSH)/luteinizing hormone (LH). b. decreased testosterone and elevated FSH/LH. LH E.R.COM c. elevated testosteroneTaE ndSeTleBvA atN edKS FSEHL/L d. elevated testosterone and decreased FSH/LH. ANS: B Patients with primary testicular failure have elevated concentrations of LH and FSH and decreased concentrations of testosterone. One cause for primary hypogonadism is chromosomal defects, such as Klinefelter syndrome (47, XXY).

DIF:

3

REF: Page 830

OBJ: 2 | 5 | 7

17. A 30-year-old female visits her physician with a complaint of excess facial and body hair, weight gain, and oligomenorrhea. She has read online that her symptoms indicate possible Cushing syndrome. Laboratory values indicate plasma cortisol levels within the reference intervals, elevated estrogen and LH, and decreased FSH. What other disorder might this patient have? a. Polycystic ovarian syndrome (PCOS) b. Conn syndrome c. Ovarian tumor d. Adult onset congenital adrenal hyperplasia ANS: A

PCOS is considered to be a hypothalamic disorder. It is clinically defined by hyperandrogenism with chronic anovulation in women without underlying disease of the adrenal or pituitary glands. This syndrome is characterized by infertility, hirsutism, obesity, and various menstrual disturbances ranging from amenorrhea to irregular bleeding.

Relatively low FSH concentrations and high LH concentrations are common in PCOS. PCOS patients have substantial estrogen production because of the peripheral conversion of androgens to estrogens.

DIF:

3

REF: Page 839

OBJ: 1 | 6 | 7

18. The benign growth of glandular breast tissue in men is referred to as: a. galactorrhea. b. glanduloma. c. andropause. d. gynecomastia.

ANS: D Gynecomastia, the benign growth of glandular breast tissue in men, is a common finding among males of varied ages.

DIF:

1

REF: Page 830

OBJ: 1

19. Regarding the phases of the menstrual cycle, the suppression of luteinizing hormone synthesis by progesterone occurs during which one of the following phases? a. Follicular phase b. Luteal phase c. Ovulation d. Both a and b ANS: B LH production is suppressed during the luteal phase by negative feedback from progesterone combined with estradiol.

DIF:

2

REF: Page 836

OBJ: 4

MATCHING Match the specific hormone with its clinical usefulness. a. Occurrence of ovulation b. Assesses ovarian function c. Screens for fetal Down syndrome d. Assesses amenorrhea 1.

2.

3.

4.

Estriol (E3) Prolactin Estradiol (E2) LH

1. ANS: C DIF: 2 REF: Page 833 OBJ: 3 MSC: Estriol measurements are used as part of the maternal screens for Down

syndrome-affected fetuses.

2. ANS: D DIF: 2 REF: Page 839 OBJ: 3 MSC: Hyperprolactinemia is a common cause of amenorrhea.

3. ANS: B DIF: 2 REF: Page 832 OBJ: 3 MSC: The most potent estrogen secreted by the ovary is 17-beta-estradiol. Because it is derived almost exclusively from the ovaries, its measurement is often considered sufficient to evaluate ovarian function.

4. ANS: A DIF: 2 REF: Page 842 OBJ: 3 MSC: Measurement of the LH surge is indicative of the occurrence of ovulation.

Match the hormone with the disease or condition produced by that hormone’s hypersecretion or hyposecretion. a. Precocious puberty b. Polycystic ovary syndrome c. Galactorrhea d. Inability to maintain endometrium 5.

6.

7.

8.

Prolactin Testosterone Progesterone LH

5. ANS: C DIF: 2 REF: Page 830 OBJ: 1 | 3 MSC: Prolactin is involved in milk production, and hyperprolactinemia causes galactorrhea, especially in men.

6. ANS: A DIT FE : ST 2 BANKSELLREERF. : CPOaM ge 837 OBJ: 1 | 3 MSC: Testosterone hypersecretion is implicated in precocious puberty in prepubertal males and in PCOS. 7. ANS: D DIF: 2 REF: Page 831 OBJ: 1 | 3 MSC: Decreased progesterone leads to a failure to produce or maintain a normal endometrial lining.

8. ANS: B DIF: 2 REF: Page 846 OBJ: 1 | 3 MSC: Elevated LH is used to diagnose PCOS (which is a hypothalamic disorder).

TRUE/FALSE 1. To evaluate ovulation, basal body temperature can be recorded. If ovulation has occurred, a rapid decrease in body temperature is noted throughout the luteal phase and is caused by progesterone.

ANS: F Ovulation is associated with a rapid rise in body temperature, by 0.5° F, which persists through the luteal phase. The rise in temperature is due to the increased concentration of progesterone.

DIF:

1

REF: Page 843

OBJ: 3

Chapter 44: Pregnancy and Prenatal Testing Test Bank MULTIPLE CHOICE 1. Which one of the following statements concerning maternal endocrine changes during the first

12 weeks (first trimester) of pregnancy is correct? a. Cortisol gradually decreases b. Free thyroxine values remain unchanged c. TSH remains unchanged d. 1,25-Dihydroxyvitamin D decreases ANS: C

See Table 44-2. The absolute plasma concentrations of both total and free cortisol are several times higher during pregnancy. Baseline concentrations of other pituitary hormones, such as thyroid-stimulating hormone (TSH), remain nearly unchanged. High concentrations of thyroxine-binding globulin raise the concentration of total thyroxine (T4) and triiodothyronine (T3). During pregnancy, 1,25-dihydroxyvitamin D is increased and promotes increased intestinal calcium absorption.

DIF: 2

REF: Page 853, Table 44-2

OBJ: 5

2. The placental peptide hormone that has exceptional homology with growth hormone and that

has aldosterone-stimulating effects is: a. estriol. b. chorionic gonadotropinT. ESTBANKSELLER.COM c. progesterone. d. estrone.

ANS: B

The major protein hormones are chorionic gonadotropin and placental lactogen (PL). The structure of PL is exceptionally homologous (96%) with growth hormone, and PL has many biological activities, including (1) lactogenic, (2) metabolic, (3) somatotropic, (4) luteotropic, (5) erythropoietic, and (6) aldosterone-stimulating effects.

DIF: 1

REF: Page 851

OBJ: 1

3. In a preterm infant, the lack of pulmonary surfactant in immature lungs will produce which of

the following symptoms? a. Red blood cell hemolysis b. Unconjugated hyperbilirubinemia c. Respiratory distress d. Metabolic acidosis ANS: C

Respiratory distress syndrome (RDS) is the most common critical problem encountered in clinical management of preterm newborns. The disorder is caused by a deficiency of pulmonary surfactant.

DIF: 1

REF: Page 859

OBJ: 8

4. The presence of bilirubin in amniotic fluid is an indicator of: a. fetal erythroblastosis. b. respiratory distress. c. Down syndrome. d. eclampsia.

ANS: A

The presence of bilirubin in amniotic fluid is an indicator of fetal erythroblastosis. Hemolytic disease of the newborn (HDN) is a fetal hemolytic disorder caused by maternal antibodies directed against antigen on fetal erythrocytes. Erythroblastosis is severe HDN. DIF: 1

REF: Page 867

OBJ: 4 | 8

5. When the gradual replacement of hemoglobin F by hemoglobin A does not occur normally,

what is the result? a. Increased oxygen affinity to hemoglobin F b. Hyperbilirubinemia and a jaundiced baby c. Overactive embryonic hemoglobin and fetal death d. A lack of surfactant and respiratory distress ANS: A

With the switch of erythropoiesis to the fetal liver and spleen, fetal hemoglobin (Hb F) production begins. The difference between fetal and adult hemoglobin is very significant because Hb F has a higher affinity for oxygen than does Hb A. This means oxygen is not given up to the tissues by hemoglobin F as easily as hemoglobin A. DIF: 2

REF: TPE agSe T 85B5ANKS OE BL J: LE 7 R.COM

6. Fetal lung maturity: a. is complete at 20 weeks gestation. b. can be accelerated by administration of corticosteroids before birth. c. is indicated by an L/S ratio less than 2.0. d. can be assessed by measuring maternal inhibin A serum concentration.

ANS: B

If the fetal lungs are immature, conservative management with close fetal monitoring is necessary in conjunction with antibiotic therapy and administration of corticosteroids to accelerate lung development.

DIF: 2

REF: Page 859

OBJ: 7

7. The primary function of amniotic fluid is to: a. provide nourishment to the fetus. b. facilitate oxygen and carbon dioxide exchange in fetal lungs. c. synthesize hormones before the brain develops. d. provide protection, constant temperature, and moisture for the fetus.

ANS: D

Throughout intrauterine life, the fetus lives within an amniotic fluid-filled compartment that (1) provides a medium in which a fetus readily moves, (2) cushions it against possible injury, and (3) helps maintain a constant temperature.

DIF: 1

REF: Page 852

OBJ: 3 | 4

8. The trophoblast cells that surround the developing blastocyst: a. form the amnion and amniotic fluid. b. synthesize glucose for the fetus. c. are the major blood-forming organs in early fetal life. d. invade the endometrium and form the placenta.

ANS: D

The cells on the exterior wall of the blastocyst, trophoblasts, synergistically invade the uterine endometrium and develop into chorionic villi, creating the placenta.

DIF: 1

REF: Page 851

OBJ: 2

9. The cells that form surfactant in fetal lungs are the: a. type II pneumocytes. b. placental trophoblasts. c. fetal hepatocytes. d. maternal lung cells.

ANS: A

Specialized alveolar cells called type II granular pneumocytes synthesize pulmonary surfactant and package it into laminated storage granules called lamellar bodies.

DIF: 1

REF: Page 854

OBJ: 1

10. A pregnant woman, who hT asEbSeT enBpAreNvK ioSuE slL yL diE agRn. oC seO dM with preeclampsia, develops edema,

headaches, and nausea over several weeks. She complains about a band of pain around the upper part of her abdomen. Her eyes and skin are yellow. Her obstetrician orders a full blood workup, including coagulation studies, CBC, liver enzyme profile, and electrolyte panel. Her serum appears hemolyzed. If this woman was diagnosed with preeclampsia originally, what might these laboratory results reveal? a. Elevated liver enzymes, abnormal coagulation results, low platelet count, elevated sodium b. Normal liver enzymes, elevated red blood cell count, elevated white blood cell count, normal coagulation studies, hypoproteinemia c. Decreased liver enzymes, decreased albumin, decreased bilirubin, normal electrolytes, abnormal coagulation times d. These symptoms are normal in a pregnant woman, so all lab results would be within healthy reference intervals.

ANS: A

The HELLP (hemolysis, elevated liver enzymes, and low platelet counts in association with preeclampsia) syndrome includes thrombocytopenia and disseminated intravascular coagulation. Most cases occur between the twenty-seventh and thirty-sixth weeks of pregnancy. Women typically exhibit (1) epigastric or right upper quadrant pain, (2) malaise, (3) nausea, (4) vomiting, and (5) headache. Jaundice occurs in 5% of patients. Lactate dehydrogenase may be very high, and other liver enzyme activities are usually 2 to 10 times their upper reference limit.

DIF: 3

REF: Page 856-857

OBJ: 8 | 10

11. In the second trimester of pregnancy, maternal serum inhibin A concentration is: a. very high in a normal pregnancy. b. very low in the presence of twins. c. high in the presence of Down syndrome and low in trisomy 18. d. undetectable in disorders related to any trisomy.

ANS: C

See Table 44-3. Prenatal screening studies have found that fetal trisomy 18 has a distinctive triple marker pattern that is different from the Down syndrome pattern, including a marked difference in inhibin A concentration.

DIF: 2

REF: Page 861, Table 44-3

OBJ: 6

12. The maternal screening tests that are considered to be part of the “quadruple test” for

estimating Down syndrome risk include: a. alpha-fetoprotein, alpha1-antitrypsin, bilirubin, and chorionic gonadotropin. b. unconjugated estriol, chorionic gonadotropin, inhibin A, and inhibin B. c. alpha-fetoprotein, amniotic bilirubin, inhibin A, and unconjugated estriol. d. alpha-fetoprotein, unconjugated estriol, chorionic gonadotropin, and inhibin A. ANS: D

The use of alpha-fetoprotein measurements in screening programs for Down syndrome was begun in 1984. Subsequently, (1) unconjugated estriol, (2) chorionic gonadotropin, and (3) inhibin A were added to screening panel. This resulted in the use of the “quadruple test” being commonly offered and found to provide a detection rate of approximately 80% for Down syndrome.

DIF: 2

REF: Page 860

OBJ: 9

13. A pregnant woman was tested for fetal fibronectin (fFN) using vaginal secretions as the

specimen. The fFN result indicated a concentration of 55 ng/mL. What information does this analyte’s value provide? a. It indicates that the risk of preterm delivery is two to four times greater than normal. b. It indicates that the fetal Down syndrome risk is 10 times higher than in a normal pregnancy. c. It indicates a deficiency of placental sulfatase and likely delayed labor and delivery. d. This value is within the reference interval and indicates that the gestational age of the pregnancy is 24 weeks.

ANS: A

fFN concentration in cervical and vaginal secretions is a test that aids in predicting preterm delivery. When labor begins and the cellular adhesion between the placenta and the uterine wall is disrupted, the fFN concentration in cervical and vaginal secretions increases. Women with a positive result (>50 ng/mL) are at a twofold to fourfold higher risk for preterm delivery.

DIF: 3

REF: Page 867

OBJ: 5

14. Early in gestation, amniotic fluid has a composition similar to: a. intracellular fluid. b. extracellular fluid. c. urine. d. water.

ANS: B

See Table 44-1. Early in gestation, the sodium and potassium values in particular indicate a similarity between amniotic fluid and extracellular fluid.

DIF: 2

REF: Page 852, Table 44-1

OBJ: 4

15. A pregnant woman in her second trimester visits her obstetrician with elevated blood pressure.

A urine sample reveals normal glucose, elevated protein, and a small number of red and white blood cells. The woman is recommended for bed rest for the remaining term of her pregnancy.

This condition is known as: a. eclampsia. b. preeclampsia. c. hydramnios. d. oligohydramnios.

ANS: B

Preeclampsia is characterized by hypertension, proteinuria, and edema, usually occurring late in the second trimester or early in the third trimester.

DIF: 2

REF: Page 856-857

OBJ: 8 | 10

16. During embryonic development of the brain and spinal cord, failure of the neural tube to close

with resultant fetal protein leaking into the amniotic fluid is referred to as: a. hydrops fetalis. b. Down syndrome. c. anencephaly. d. trisomy 18.

ANS: C

Failure of neural tube fusion during embryonic development leads to permanent developmental defects of the brain (anencephaly) or spinal cord (meningomyelocele). Almost all cases of anencephaly and about 95% of meningomyeloceles are open, with no overlying skin; therefore, they are in direct communication with the amniotic fluid.

DIF: 2

REF: Page 858

OBJ: 8

17. Concerning alpha-fetoprotein (AFP), which one of the following statements is correct? a. A decrease in AFP in a pregnant woman’s serum indicates the presence of possible

spina bifida in the fetus. b. An appropriate time to measure AFP in maternal serum is at 16 weeks gestation

when it is approximately 3.5 µg/dL. c. An increase in AFP in a pregnant woman’s serum indicates the presence of Down syndrome in the fetus. d. AFP in maternal serum rapidly decreases to a low point at 11 weeks and then

increases to reach a second maximum at 13 weeks.

ANS: B

AFP is first detectable in maternal serum at about the tenth week of gestation. A typical 16-week concentration is approximately 35 µg/L. This value is also stated as 3.5 µg/dL. DIF: 2

REF: Page 865

OBJ: 1 | 6

18. A hormone that is monitored to assess conditions associated with intrauterine (vs. ectopic)

fetal growth is: a. progesterone. b. placental lactogen (PL). c. estrogen. d. chorionic gonadotropin (CG).

ANS: D

Serial CG testing may be helpful. In normal intrauterine pregnancy, a rapid increase in CG follows. During the second through fifth weeks, the CG doubles in about 1.5 days. After 5 weeks of gestation, the doubling time gradually lengthens to 2 to 3 days. In cases of ectopic pregnancies or spontaneous abortions, the CG concentrations rise more slowly or often decrease.

DIF: 1

REF: Page 863

OBJ: 2 | 6

19. In the second trimester, maternal age along with a screening serum analysis of

alpha-fetoprotein, inhibin A, unconjugated estriol, chorionic gonadotropin, and which of the following are assessed as the “integrated test” testing panel for Down syndrome risk estimate? a. Nuchal translucency (NTTE)San anEcyL-L asEsoRc. iaCteOdMplasma protein A (PAPP-A) TdBpAreNgKnS b. Placental lactogen and NT c. PAPP-A and placental lactogen d. Estrone and PAPP-A ANS: A

In the integrated test, measurements of NT and PAPP-A are made in the first trimester but are usually not interpreted or acted upon until testing in the second trimester is complete. In the second trimester, a second blood sample is collected and a quadruple test performed. Results from all six tests, (1) NT, (2) PAPP-A, (3) AFP, (4) uE3, (5) hCG, and (6) inhA, are then combined into a single risk estimate.

DIF: 2

REF: Page 861

OBJ: 6 | 9

20. Greenish amniotic fluid indicates the presence of: a. fetal meconium. b. hemolysis. c. increased surfactant. d. fetal death.

ANS: A

If severely stressed, a fetus may defecate in utero and produce meconium. This heterogeneous material contains many bile pigments and therefore stains the amniotic fluid green.

DIF: 1

REF: Page 853

OBJ: 1 | 4

Chapter 45: Newborn Screening and Inborn Errors of Metabolism Test Bank MULTIPLE CHOICE 1. Newborn screening is considered a public health activity that aims to identify and treat

possible deadly conditions early in an infant’s life. Which one of the following characteristics must be met before a disease can be part of a screening program? a. The disease must be rare. b. Genetic counseling and treatment for the disease must be available. c. The natural history of the disease must be unclear. d. Screening for the disease must only be offered to those who would benefit most from it.

ANS: B

Newborn screening tests must fit specific criteria that evaluate the characteristics of the disease, the test used to screen for it, and the newborn screening program. The disease to be screened must be serious; fairly common; its natural history understood; and helpful treatment or genetic counseling (in the case of genetic disease) must be available. In addition, the screening test must be (1) acceptable to the public, (2) reliable, (3) valid, and (4) affordable.

DIF: 1

REF: Page 873

OBJ: 3

2. What is the basic setup of a tandem mass spectrometry analyzer? a. Tandem mass spectrometry uses a UV laser to ionize small amounts of matrix and

analyte that are directeT dE toS wT arBdAmNaK ssSaE nal yzEeR r. .COM LL b. Tandem mass spectrometry is primarily for complex compound analysis, while tandem mass spectrometry is used for elemental analysis only. c. Tandem mass spectrometry uses an ion trap designed to trap ions in three dimensions instead of two dimensions as in a typical beam type of mass spectrometer. d. Two beam type mass spectrometers are arranged sequentially in tandem mass spectrometry, with a “collision cell” placed between the two instruments.

ANS: D

Refer to Chapter 13. Tandem mass spectrometry measures the ratio of the mass (m) of a chemical to its charge (z). Two mass spectrometers are used in tandem to separate and analyze mixtures of compounds, such as amino acids and acylcarnitines. After the ions are separated by the first mass spectrometer, they enter the “collision cell” where they are broken down into fragments by collision with a neutral gas. The fragments pass through a second mass spectrometer that separates them according to their mass to charge (m/z) ratio. Each molecule has a characteristic fragmentation pattern and classes of compounds will fragment in a similar way.

DIF: 3

REF: Page 882

OBJ: 7

3. Hyperphenylalaninemia due to classic phenylketonuria (PKU) is accompanied by all the

following except: a. elevation of blood tyrosine. b. elevation in urinary phenylketones.

c. elevation in blood phenylalanine correctable by dietary phenylalanine restriction. d. mental retardation if left untreated.

ANS: A

Primary or secondary (due to a deficiency of the cofactor) impairment of phenylalanine hydroxylase causes accumulation of (1) phenylalanine, (2) phenylketones, and (3) phenylamines, and a deficiency of tyrosine.

DIF: 2

REF: Page 875

OBJ: 6

4. An autosomal recessive disorder: a. is characterized by a 50% chance of an individual having the disease phenotype if

the parents are heterozygous for the trait. b. is defined as one in which there is a mutation in both alleles encoding for a specific

enzyme/transporter. c. affects males approximately 25% more than females because the allele is present

on the X chromosome. d. is one in which parents of diseased offspring are carriers of the condition in that

they carry two mutant alleles.

ANS: B

In the case of an autosomal recessive disorder, affected individuals have a mutation in both alleles encoding for a specific enzyme/transporter. Parents of children with one of these metabolic conditions are carriers of the condition in that they carry one normal allele and one mutant allele, and they do not show clinical signs of the condition.

DIF: 2

REF: Page 872

OBJ: 2

5. The disorder that is identified by increased serum carnitine and urine glutaric acid on newborn

screening is: a. PKU. b. tyrosinemia. c. glutaric acidemia type 1. d. glycine encephalopathy.

ANS: C

Glutaric acidemia type I is an autosomal recessive disorder of (1) lysine, (2) hydroxylysine, and (3) tryptophan metabolism caused by deficiency of glutaryl-CoA dehydrogenase. In this condition, glutaric acid (GA) and 3-hydroxyglutaric acid (3-OH-GA), formed in the catabolic pathway of the above amino acids, accumulate especially in urine. This disorder is also identified by an increased concentration of glutaryl (C5DC) carnitine on newborn screening.

DIF: 2

REF: Page 879

OBJ: 6

6. The disorder that is identified by increased serum carnitine and urine glutaric acid on newborn

screening is characterized by dysfunctional metabolism of: a. hydroxylysine and phenylalanine. b. tyrosine and tryptophan. c. tryptophan, hydroxylysine, and lysine. d. cystine and hydroxylysine.

ANS: C

See Figure 45-8. This disorder is identified by an increased concentration of glutaryl (C5DC) carnitine on newborn screening.

DIF: 2

REF: Page 879, Figure 45-8

OBJ: 6

7. A newborn screening test using a dried blood spot is positive for congenital adrenal

hyperplasia (CAH). What laboratory testing would be done next? a. No next step as this test is the confirmatory analysis b. DNA analysis of genetic mutation c. A stimulating hormone test d. A second-tier test for CAH, such as an MS/MS steroid profile ANS: D

Second-tier tests involve further analysis of the same blood spot that produced an abnormal result targeting different, more specific analytes and, often, using a methodology different from the one used in the primary screening test. They include DNA analysis for cystic fibrosis, MS/MS steroid profile for congenital adrenal hyperplasia, and thyroid-stimulating hormone testing for congenital hypothyroidism.

DIF: 1

REF: Page 873

OBJ: 1 | 6 | 8

8. What is the advantage of tandem mass spectrometry (MS/MS) multiplex analysis? a. It eliminates the need for second-tier testing by providing a built-in confirmatory

test. b. Multiple metabolites are detected simultaneously in one blood sample to allow for

detection of several disorders at once. c. Tests are performed singly so a single disorder is tested for with a single specimen. d. It allows for screening T ofEaSlT arB gA eN nuKmSbE erLoLf E inRfa.nC tsOnM ot only for PKU, but also for

other disorders of amino acid metabolism using different growth antagonists.

ANS: B

The advantage of MS/MS is that multiple metabolites can be detected simultaneously in the same blood spot (multiplex analysis), allowing for the identification of several disorders at once.

DIF: 1

REF: Page 882

OBJ: 1 | 7

9. Of the following, what is the inborn error of metabolism for maple syrup urine disease? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: B

See Table 45-1. Maple syrup urine disease is an aminoacidopathy caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids leucine, isoleucine, and valine and their toxic ketoacids in the blood and urine.

DIF: 2

REF: Page 874, Table 45-1

OBJ: 1 | 5

10. Of the following, what is the inborn error of metabolism for medium chain acyl-CoA

dehydrogenase deficiency? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: A

See Table 45-1. MCAD is a disorder of fatty acid oxidation that is indicated by DNA analysis and urine organic acid and acylglycine analysis showing excess hexanoylglycine and a plasma acylcarnitine profile (confirming elevated C6-, C8-, and C10:1 carnitine).

DIF: 2

REF: Page 874, Table 45-1

OBJ: 1 | 5

11. Of the following, what is the inborn error of metabolism for glutaric acidemia type 1? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: C

See Table 45-1. Glutaric acidemia type 1 is an autosomal recessive disorder of (1) lysine, (2) hydroxylysine, and (3) tryptophan metabolism caused by deficiency of glutaryl-CoA dehydrogenase. In this condition, glutaric acid (GA) and 3-hydroxyglutaric acid (3-OH-GA), formed in the catabolic pathway of the above amino acids, accumulate—especially in urine.

DIF: 2

REF: Page 874, Table 45-1

OBJ: 1 | 5

12. Of the following, what is the inborn error of metabolism for glycogen storage disease? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: D

See Table 45-1. Disorders of carbohydrate metabolism include the (1) glycogen storage diseases, (2) glucose-6-phosphate dehydrogenase [G-6-PD] deficiency, and (3) classic galactosemia due to the absence of galactose-1-phosphate uridyl transferase.

DIF: 2

REF: Page 874, Table 45-1

OBJ: 5

13. Of the following, what is the inborn error of metabolism for alkaptonuria? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: B

See Table 45-1. Alkaptonuria is a genetic disorder due to deficiency of the enzyme homogentisic acid (HGA) dioxygenase. Deficiency of this enzyme leads to the presence of homogentisic acid and its oxide, called alkapton, in the urine.

DIF: 2

REF: Page 874, Table 45-1

OBJ: 1 | 5

14. Of the following, what is the inborn error of metabolism for propionic acidemia? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Disorder of carbohydrate metabolism ANS: B

See Table 45-1. Propionic acidemia is an organic acidemia caused by deficiency of an enzyme involved in amino acid and fatty acid catabolism. It is characterized by excess of propionic acid and glycine in the blood and urine.

DIF: 2

REF: Page 874, Table 45-1

OBJ: 1 | 5

15. A newborn infant is observed to have symptoms of poor feeding, vomiting, lethargy, and

irritability. Screening tests reveal elevated ornithine and ammonia in the infant’s blood. What type of disorder do these symptoms indicate? a. Disorder of fatty acid oxidation b. Aminoacidopathy c. Organic acidemia d. Urea cycle disorder ANS: D

In a newborn, hyperammonemia and the accumulation of glutamine in the brain lead to (1) poor feeding, (2) vomiting, (3) lethargy, or (4) irritability progressing to coma and death. The urea cycle disposes of the nitrogen groups of amino acids before their carbon skeleton is TB KiSnoEaLcLidEs)Ro.r CkeOtM metabolized to gluconeogeTnE icS(m osA tN am ogenic precursors (leucine and lysine), or both (isoleucine, phenylalanine, tyrosine, and tryptophan). This cycle requires the combined action of different enzymes and deficiency of any of these enzymes or transporters will impair the function of the urea cycle, causing hyperammonemia.

DIF: 3

REF: Page 878

OBJ: 6 | 10

16. Dietary restriction of foods containing the branched-chain amino acids is one of the treatments

required for individuals with: a. phenylketonuria. b. glutaric acidemia type 1. c. maple syrup urine disease. d. alkaptonuria.

ANS: C

Cornerstones of treatment for individuals with maple syrup urine disease include diets with restricted branched-chain amino acids contents, including supplementation with high-dose (1) thiamine, (2) valine, and (3) isoleucine.

DIF: 2 TRUE/FALSE

REF: Page 878

OBJ: 6

1. An example of a confirmatory laboratory test used to verify a borderline abnormal newborn

screening test result in an asymptomatic individual would be gas chromatography combined with mass spectrometry, particularly for organic acid analysis.

ANS: T

In asymptomatic patients, the confirmation of diagnosis relies on specific tests, such as gas chromatography-mass spectrometry (GC-MS) for organic acids analysis. The combination of these tests is the key in the confirmation of abnormal newborn screening results, especially for those with borderline values.

DIF: 1

REF: Page 882

OBJ: 9

Chapter 46: Pharmacogenetics Test Bank MULTIPLE CHOICE 1. You have been asked to direct a pharmacogenetics testing laboratory in a hospital with many

transplant patients who receive mercaptopurine derivatives to control transplant rejection.

Which of the following enzyme phenotyping or genotyping services would be the highest priority to establish initially? a. N-acetyltransferase genotyping b. Thiopurine methyltransferase (TPMT) genotyping c. CYP1A1 genotyping d. CYP2D6 phenotyping ANS: B

TPMT is a phase II metabolic enzyme that catalyzes the inactivation of 6-mercaptopurine (6-MP) by S-methylation. Numerous studies have shown that TPMT-deficient patients are at high risk for severe and sometimes fatal toxicity. Genotyping is valid anytime, as long as the patient genotype is detected by the analytical technique employed. The influence of TPMT genotype on hematopoietic toxicity is most dramatic for homozygous variant patients, but is also of clinical relevance for heterozygous individuals.

DIF: 3

REF: Page 894

OBJ: 3 | 5 | 7

2. You are appointed director of the county hospital cardiac laboratory and have been asked to

identify individuals that mT igE htSnToB t rAesNpK onSdEw atO elM et-inhibiting, clot-destroying drugs.

LeLllEtoRp.lC Which of the following polymorphic genes would you be most interested in having genotyped to discover these individuals? a. TPMT b. UGT1A1 c. CYP2C19 d. CYP2D6 ANS: C

CYP2C19 is involved in the metabolism of a number of therapeutic drugs, including clopidogrel, a drug used to dissolve clots in coronary arteries. There are two common alleles, CYP2C19*2 and CYP2C19*3, that account for nearly all poor metabolizers of this drug.

Approximately one-third of patients do not respond to clopidogrel. One explanation for drug resistance is based on the fact that clopidogrel is a prodrug that requires metabolism of the active metabolite, prasugrel. Carriers of the CYP2C19*2 and *3 alleles have reduced formation of the active metabolite, and have a higher incidence of major thrombotic events.

DIF: 2

REF: Page 893

OBJ: 3 | 5 | 7

3. Bilirubin is an important endogenous substrate of which one of the following enzymes? a. N-acetyltransferase b. Thiopurine methyltransferase c. UGT1A1 d. CYP3A4

ANS: C

The UGT1 and UGT2 families are most efficient at glucuronidation of drugs and toxicants in humans. The primary goal of glucuronidation is to increase the water solubility of a compound (such as bilirubin), which typically inactivates that compound and promotes its elimination. An important endogenous substrate for UGT1A1 is bilirubin.

DIF: 1

REF: Page 895

OBJ: 5

4. Regarding pharmacogenetics, a phase 1 enzyme metabolizes drugs by: a. conjugating an acetyl group to a drug compound. b. transferring a methyl group to a drug substrate. c. conjugating an amine group to a drug substrate. d. oxidizing a drug substrate.

ANS: D

Most phase 1 reactions are oxidative and mediated by the cytochrome P-450 enzymes.

DIF: 1

REF: Page 889

OBJ: 4

5. A combination of alleles that are located closely together on the same chromosome and are

inherited together is the definition of: a. haplotype. b. pseudogene. c. allelic diversity. d. genotype.

ANS: A

Definition: a haplotype is aTcEoS mTbB inA atN ioK nSoE f aLllLelEesR(.foCrOdM ifferent genes) that are located closely together on the same chromosome and that tend to be inherited together.

DIF: 1

REF: Page 885

OBJ: 1

6. Tamoxifen is a drug that is used to prevent or treat some forms of breast cancer. Before it can

have a physiological effect, tamoxifen must be metabolized to an active metabolite called endoxifen. Tamoxifen is therefore considered to be a: a. metabolizer. b. prodrug. c. transferase. d. cytochrome.

ANS: B

An inactive or less active drug that must be first metabolized to the active form of the drug to elicit the desired therapeutic effect is a prodrug. Tamoxifen is a prodrug and must be metabolized to the active metabolite attributed with most of its therapeutic response to endoxifen, which is formed largely by a reaction mediated by CYP2D6.

DIF: 2

REF: Page 891

OBJ: 1

7. A drug substrate for the metabolizing enzyme UGT1A1 is: a. tamoxifen. b. codeine. c. diazepam

d. irinotecan.

ANS: D

A thoroughly studied example of a pharmacogenetic application for UGT1A1*28 genotyping is seen with irinotecan. Irinotecan is a prodrug widely used in metastatic colorectal cancer and in other tumors, such as lung and liver. A major route for inactivation of SN-38 (the active metabolite) is formation of the glucuronide conjugate by UGT1A1.

DIF: 1

REF: Page 895

OBJ: 5

8. A drug substrate for the metabolizing enzyme CYP2D6 is: a. tamoxifen. b. codeine. c. diazepam. d. irinotecan.

ANS: A

The metabolite of tamoxifen attributed with most of its therapeutic response is endoxifen, which is formed largely by a reaction mediated by CYP2D6.

DIF: 1

REF: Page 891

OBJ: 5

9. The metabolizing enzyme that catalyzes the transfer of an acetyl moiety from acetyl-CoA to

homocyclic and heterocyclic arylamines and hydrazines in, for example, substrates related to cigarette smoke is: a. CYP2C6. b. CYP2D9. c. NAT1. d. UGT1A1.

ANS: C

NAT1 and NAT2 are two thoroughly characterized isoforms that catalyze the transfer of an acetyl moiety from acetyl-CoA to homocyclic and heterocyclic arylamines and hydrazines.

NAT substrates also have been related to (1) cigarette smoking, (2) some medications, and (3) occupational exposures.

DIF: 1

REF: Page 894

OBJ: 5

10. Which two of the following metabolizing enzymes are involved in metabolism of warfarin? a. TPMT and CYP2D9 b. CYP2D9 and CYP2D19 c. VKORC1 and CYP2C9 d. NAT1 and VKORC1 ANS: C

VKOR converts vitamin K epoxide to vitamin K and is the primary site of action for the commonly used oral anticoagulant warfarin. Examples of drugs metabolized by CYP2C9 include warfarin. Genetic variants of VKORC1, representing sensitivity in response to warfarin, and of CYP2C9, representing pharmacokinetics of warfarin inactivation, are thought to account for approximately one-third of the variability among individuals and their response to warfarin.

DIF: 2

REF: Page 896

OBJ: 5

11. The enzyme that metabolizes 5-fluorouracil is: a. DPD. b. TMPT. c. CYP2D6. d. NAT1.

ANS: A

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the three-step pathway of uracil and thymidine catabolism. Under typical metabolic conditions, approximately 80% of 5-fluorouracil is inactivated by DPD. DIF: 2

REF: Page 896

OBJ: 5

12. A limitation of using genotyping in pharmacogenetic testing would be: a. the lack of gene variants to actually test for. b. interindividual variation in gene expression. c. a strong genotype-phenotype correlation. d. the lack of good positive controls.

ANS: B

There are limitations to genotyping that include possible misinterpretation between the genotype and phenotype relationship and the inability to test all variants of a gene. Limitations in testing and the possibility of false negative results due to the targeted nature of most pharmacogenetic testing may also reduce the clinical utility of genotyping, as will interindividual variation in gene expression, and nongenetic factors, such as drug-drug or drug-food interactions.

DIF: 2

REF: Page 888

OBJ: 3

13. A pharmacogenetic drug-gene target would be most successful when clinically implemented

when it: a. is associated with a clinically significant effect on the relationship between drug dose and plasma concentration. b. does not involve a major metabolic pathway but instead is involved in alternate pathways. c. indicates alternative drugs that are much more efficient than conventional drugs in producing a dose-response. d. allows for an extended period of time for changes to be made in drug dosing.

ANS: A

Based on successful applications to date, pharmacogenetic targets are most likely to be successful clinically when they are associated with a clinically significant and actionable effect on the relationship between dose and plasma drug concentration or a measurable biomarker.

DIF: 2

REF: Page 887

OBJ: 2

14. Which one of the following metabolizing enzymes is considered a phase 1 enzyme? a. CYP2C6

b. VKORC1 c. NAT1 d. UGT1A1 ANS: A

Most phase 1 reactions are oxidative and are mediated by cytochrome P-450 enzymes (CYPs).

DIF: 1

REF: Page 889

OBJ: 5

15. The HLA gene and its variants that have been associated most closely with drug

hypersensitivity and that can be assessed in a laboratory is HLA-: a. A. b. B. c. C. d. D. ANS: B

It is the HLA-B gene, and in particular, the HLA-B*5701 allele, that has been best characterized from the perspective of pharmacogenetics, based on association of variants with drug hypersensitivity phenotypes. HLA-B gene variants are also associated with risk of disease, particularly immune-mediated inflammatory disease.

DIF: 1

REF: Page 896

OBJ: 6

Chapter 47: Principles of Molecular Biology Test Bank MULTIPLE CHOICE 1. The most basic level of chromatin organization that is present as repeated units along the full

length of each chromosome is represented by the: a. histone. b. nucleosome. c. purine. d. spliceosome.

ANS: B

The nucleosome represents the most basic level of chromatin organization and is present as repeated units along the full length of each chromosome.

DIF: 1

REF: Page 904

OBJ: 6

2. The main goal of the ENCODE Project is to: a. identify all functional elements within the human genome. b. catalog and interpret genome-wide DNA methylation patterns. c. decipher the 3 billion base pairs that make up the human genome. d. study heritable variations across the human genome.

ANS: A

The Encyclopedia of DNA Elements (ENCODE) Project aims to identify all functional NKfeSaE elements within the humanTgEeS noTmBeA .A siL biL litEyRst.uC dyOtM argeting 1% of the human genome has been done.

DIF: 1

REF: Page 913

OBJ: 12

3. DNA replication is referred to as semiconservative because: a. only some DNA sequences are duplicated during the cell cycle. b. certain amino acids can be synthesized by more than one codon. c. newly duplicated DNA molecules are composed of one parent and one daughter

strand. d. it can only occur in the 5' to 3' direction.

ANS: C

In replication, each of the two parent strands of a double-stranded (ds) DNA molecule serves as the template for the synthesis of a daughter strand. The process is called semiconservative because each of the duplicated dsDNA molecules produced in this manner is composed of one parent (conserved) strand and one daughter strand.

DIF: 2

REF: Page 906

OBJ: 1 | 2 | 7

4. The protective nucleotide sequences that are located on the end of a chromosome and make up

part of constitutive heterochromatin is referred to as the: a. centromere. b. nucleosome

c. acromere. d. telomere.

ANS: D

Telomeres contain repetitive nucleotide sequences that are located on and protect the ends of chromosomes. Genomic regions that remain condensed during the cell cycle, such as centromeres, telomeres, and the inactivated X chromosome in female cells, are termed constitutive heterochromatin.

DIF: 1

REF: Page 906

OBJ: 1 | 5

5. If 30% of the nucleotides in a genome are A (adenine), what would be the percentage of

nucleotides that are G (guanine)? a. 20% b. 30% c. 40% d. 60% ANS: B

The purines are adenine (A) and guanine (G), and the pyrimidines are cytosine (C) and thymine (T). When in the proper orientation, adenine forms two hydrogen bonds with thymine, and guanine forms three hydrogen bonds with cytosine. Sequences of each molecule must be such that A:T and G:C hydrogen bonds are always formed (base pairing). If 30% of nucleotides are A, then 30% must be T, which equals 60% of nucleotides; therefore, the remaining 40% of the total must be G:C, so 20% are G and 20% are C. DIF: 2

REF: Page 902

OBJ: 4

6. DNA and RNA differ, in part, because of their sugar molecules. What is missing on the DNA

sugar that is present on the RNA sugar? a. Phosphate group b. Hydrogen c. Hydroxyl group d. Methyl group ANS: C

RNA is chemically very similar to DNA but differs in important ways. The sugar unit is ribose with an added hydroxyl group at the 2' position, and the methylated pyrimidine uracil (U) replaces thymine.

DIF: 1

REF: Page 903

OBJ: 3

7. DNA methylation as a means of regulating gene expression is restricted to which of the

following bases? a. Guanine bases in the dinucleotide sequence GC b. Cytosine bases in the base pair CG c. Cytosine bases in the dinucleotide sequence CG d. Guanine bases in the base pair GC ANS: C

See Figure 47.7. DNA methylation is possibly the most widely studied epigenetic phenomenon. It refers to the addition of a methyl group to the fifth carbon position of cytosine residues in CpG dinucleotides.

DIF: 2

REF: Page 909, Figure 47-7

OBJ: 9

8. In regard to replication, the “parent” strand of deoxyribonucleic acid (DNA): a. is completely excised by exonuclease enzymes when replication of the strand is

complete. b. has a sequence that is complementary (opposite) to the daughter strand being

replicated. c. is also referred to as the “leading” strand. d. will be copied by DNA polymerase I to form a new daughter DNA strand.

ANS: B

Owing to the laws of base pairing, the sequence of a single strand of DNA dictates the sequence of its complementary strand, which during replication is the “daughter” strand.

DIF: 2

REF: Page 906

OBJ: 7

9. In regard to the components of the genetic code, a “codon” is a: a. sequence of nucleotides that codes for a protein. b. polymeric molecule composed of nucleic acids. c. phosphate group, a ribose sugar, and nitrogen. d. sequence of three nucleotides.

ANS: D

Each amino acid is encodeT dE byST aB triA plNeK t nSuE clL eoLtiEdR e. coCdO e,Mwhich is three nucleotides in length.

This triplet code is referred to as a “codon.”

DIF: 1

REF: Page 902

OBJ: 1

10. The conversion of mRNA nucleotide sequences and the tRNA-attached amino acids into a

polypeptide is referred to as: a. replication. b. transcription. c. translation. d. restriction.

ANS: C

Translation is the process whereby the mRNA codon sequence directs amino acid sequence during protein synthesis. Translation takes place on ribosomes, which bind to the initiation site on mRNA. During synthesis, codons are “read” by transfer RNA (tRNA), and anticodons are bound to the amino acid molecule specified by the codon.

DIF: 1

REF: Page 902

OBJ: 7

11. In regard to DNA, an exon is defined as a: a. segment of DNA that is represented in a mature strand of mRNA and is translated

into protein. b. sequence of nucleotides recognized by RNA polymerase as the initiation point of

transcription.

c. segment of DNA that is transcribed but removed from mRNA by excision and is

not translated into protein. d. sequence of three base pairs that signal initiation or termination of replication.

ANS: A

The coding region of a gene is divided into segments called exons, and coding regions specify the amino acid sequence of a protein.

DIF: 1

REF: Page 908

OBJ: 1 | 7

12. During replication, the addition of bases occurs: a. in the 5' to 3' direction. b. in the 3' to 5' direction. c. in both the 5' to 3' and 3' to 5' direction. d. only at the methylated end of a DNA strand.

ANS: A

DNA polymerase synthesizes a daughter strand only in this direction because nucleotides can only be added to the 3' carbon end.

DIF: 1

REF: Page 906

OBJ: 8

13. Which one of the following sequences contains a signal that indicates the end of a protein? a. 5' GUG ACU AGG UGG CGA CCC UAU 3' b. 5' AAC CGA CUC AUC CAG GUA UAA 3' c. 5' ACC CGA CCA UCC AGG CUG AGG 3' d. 5' AGC CGA CUC AUC AGG UUU GAU 3' ANS: B

One codon, UAA, does not code for amino acids but always signals termination of protein synthesis (a stop codon). UGA codes for a stop or for selenocysteine, and UAG codes for a stop or for pyrrolysine, depending on adjacent sequences or RNA-binding proteins.

DIF: 2

REF: Page 908

OBJ: 1 | 7

14. Transfer RNA (tRNA): a. contains the anticodon region that binds to mRNA codon in the ribosome. b. is a macromolecular complex containing ribosomal RNA. c. contains the codon sequence that synthesizes an amino acid. d. is a noncoding RNA. ANS: A

A three-nucleotide codon within an mRNA will bind to its anticodon on a specialized transfer RNA molecule, which then carries the attached amino acid to a ribosome to be added to a growing peptide chain.

DIF: 1

REF: Page 908

OBJ: 3

15. In regard to transcription, an example of a core promoter sequence on a DNA strand is the

TATA box. Core promoters are: a. codons that signal specific enzymes to terminate replication. b. segments of DNA that are represented in mature RNA and are translated into

protein. c. sequences of nucleotides that are recognized by RNA polymerase II and that

control the initiation of transcription. d. codons that signal the initiation of replication.

ANS: C

For transcription, the polymerase is RNA polymerase II, which first binds to specific sequences in the promoter, called the core promoter, upon initiation of gene expression. Core promoters that have been identified to date generally occur within a hundred bases around the initiation site of transcription, known as the transcription start site, where the first ribonucleotide unit is paired with the template DNA. DIF: 2

REF: Page 907

OBJ: 7

16. A woman inherits a specific allele from her mother and develops a specific disease syndrome.

Another woman receives the same specific allele from her father and develops a much milder form of the disease. This is likely an example of: a. genometastisis. b. genomic imprinting. c. histone deacetylation. d. mitochondrial mutation.

ANS: B

Genomic imprinting refers to the phenomenon whereby the function of each of the two alleles of a gene is determined by its parental origin. Differential methylation of the imprinted locus from the time of germ cell development allows recognition of the parental origin of imprinted alleles by cellular processes.

DIF: 3

REF: Page 910

OBJ: 9

17. Which one of the following statements concerning the difference between DNA and RNA is

correct? a. The four nucleotide building blocks of RNA include thymosin, cytosine, guanine, and adenine. b. RNA exists typically as a single-stranded polymer that is much shorter than DNA. c. DNA is composed of a sugar unit, ribose, with an added hydroxyl group at the 2' position. d. DNA molecules can interact to form complex tertiary structures related to the novel functions of DNA. ANS: B

RNA exists in various functional forms but mostly as a single-stranded polymer that is much shorter than DNA. DIF: 2

REF: Page 903

OBJ: 3

18. The expressed function or biological effect of a gene product is termed a: a. genotype. b. promoter. c. codon. d. phenotype.

ANS: D

The primary nucleotide sequences of the two gene alleles form the genotype, whereas the expressed function or biological effect of the gene product is termed the phenotype. Thus one could study a human disease or trait at the genetic level through determination of the allelic sequence of a gene (i.e., genotyping) or at the functional level (i.e., phenotyping).

DIF: 1

REF: Page 902

OBJ: 1 | 2

19. Which one of the following statements concerning mitochondrial DNA (mtDNA) is

incorrect? a. Pseudogenes are DNA segments that share significant homology with mtDNA. b. mtDNA is circular and contains approximately 16,500 base pairs. c. mtDNA is transmitted by maternal inheritance. d. The mutation rate of mtDNA is 20 times lower than that of nuclear DNA. ANS: D

The mutation rate of mitochondrial DNA is 10 to 20 times higher than that of nuclear DNA. This high rate has been viewed as resulting from the poor fidelity of mitochondrial DNA polymerase.

DIF: 2

REF: Page 912

OBJ: 11

20. A noncoding RNA is one that: a. is involved in the synthesis of protein by acting as an intermediate. b. encodes for amino acids only. c. has a biological function but does not code for a protein. d. contains an anticodon.

ANS: C

RNA molecules that serve a direct biological function without coding for a protein are collectively termed noncoding or ncRNAs. DIF: 1

REF: Page 902

OBJ: 10

21. Regarding transcription, the proteins that help to position eukaryotic RNA polymerase II at

the core promoter region are referred to as: a. activators. b. elongation factors. c. general transcription factors. d. site-specific positioning proteins.

ANS: C

To initiate transcription, a series of protein cofactors, known as general transcription factors, is required to bind to RNA polymerase II to form an assembly known as the preinitiation complex, which, in turn, acts on the gene by interacting with the core promoter.

DIF: 2

REF: Page 907

OBJ: 7

22. The proteins that wrap DNA tightly to condense it into nucleosomes are called: a. histones. b. hormones. c. lysosomes.

d. nucleotides.

ANS: A

See Figure 47-3. Each chromosome is a highly ordered structure of a single dsDNA molecule, compacted many times with the aid of structural DNA-binding proteins, for example, histones. Histones are an integral part of nucleosomes, the basic repeating structural unit of chromatin.

DIF: 1

REF: Page 905, Figure 47-3

OBJ: 6

23. In regard to DNA structure, a sugar/phosphate group with its attached base is referred to as

a(n): a. base pair. b. codon. c. anticodon. d. nucleotide.

ANS: D

Nucleotides are composed of the sugar deoxyribose, a phosphate residue, and a purine or pyrimidine base.

DIF: 1

REF: Page 902

OBJ: 1 | 4

24. The conversion of an mRNA sequence into a string of covalently bonded amino acids is a

process referred to as: a. translation. b. transcription. c. redundancy. d. promotion.

ANS: A

Translation is the process whereby the mRNA sequence directs the amino acid sequence during protein synthesis.

DIF: 1

REF: Page 908

OBJ: 7

25. In regard to excision of introns and splicing of exons in a primary RNA transcript, the

spliceosome is made up of: a. noncoding RNAs. b. small nuclear ribonucleoprotein particles. c. histone proteins and DNA. d. ribosomal RNA. ANS: B

Excision or splicing of the noncoding introns is carried out by a molecular complex termed a spliceosome. These complexes are composed of multiple small nuclear ribonucleoprotein particles. Spliceosomes mediate the cleavage and ligation of RNA at specific recognition sequences.

DIF: 2

REF: Page 908

OBJ: 7

Chapter 48: Nucleic Acid Techniques and Applications Test Bank MULTIPLE CHOICE 1. You have prepared a restriction enzyme digest of DNA from an individual who might have a

genetic disorder. On the gel, you note that the digest from this individual produces one fragment, whereas the digest from a normal healthy individual produces two fragments. All controls worked correctly and you used the same reagents for all testing. What is your interpretation? a. The enzymes were not working. b. The diseased individual’s DNA is missing a restriction site. c. You must have skipped the amplification step. d. The normal individual’s DNA is missing a restriction site.

ANS: B

See Figure 48-8. Many sequence alterations are on fragments that, when amplified by polymerase chain reaction (PCR), make RFLP analysis very simple. After PCR the products are digested with one or more restriction enzymes and analyzed by electrophoresis. If a sample has a variant that disrupts an enzyme recognition site, this is distinguished from a sample that does not have the variant by producing one uncut PCR fragment when the mutation is present and two shorter fragments when the mutation is absent.

DIF: 3

REF: Page 926, Figure 48-8

OBJ: 8 | 12

2. The purpose of restriction T frE agSmTeB ntApNoK lyS mE orLpL hiE sm R.anCaOlyMsis (RFLP) is to: a. determine the purity of DNA isolation. b. evaluate the integrity of isolated genomic DNA. c. assess the exonuclease activity of DNA polymerase. d. identify the presence of mutations or sequence changes.

ANS: D

Restriction endonucleases cut DNA into fragments and the same enzyme produces the same fragments in different specimens if the specimens contain the same DNA sequence. If an alteration in the DNA abolishes or creates a cleavage site recognized by the enzyme (or changes the spacing between two cleavage sites), then the digested fragments will have different lengths.

DIF: 1

REF: Page 926, Figure 48-8

OBJ: 8

3. You want to determine the accuracy of hybridization of a probe to a Southern blot to eliminate

binding of the probe to incorrect target sequences. Which one of the following would be an appropriate positive control to assess assay sensitivity? a. Sequences complementary to the probe b. Sequences that are not complementary to the probe c. Water d. Sequences from a housekeeping gene such as beta actin ANS: A

Both positive and negative controls are necessary for validation of the analytical phase of hybridization assays. Positive controls contain sequences complementary to the probe that are used to assess assay sensitivity, and ensure that the probe will hybridize to the target under the assay conditions. Negative controls without target sequence assess assay specificity and will detect positive contamination if present.

DIF: 2

REF: Page 932-933

OBJ: 9 | 12

4. What is the key enzyme used in a polymerase chain reaction (PCR)? a. Restriction enzyme b. Lysozyme c. Polymerase d. Transcriptase ANS: C

PCR requires (1) a thermostable DNA polymerase, (2) deoxynucleotides of each base, (3) the target sequence, and (4) a pair of oligonucleotides (referred to as primers) complementary to opposite strands flanking the sequence to be amplified.

DIF: 1

REF: Page 919

OBJ: 2 | 4

5. In the dideoxy-termination sequencing method, what causes the termination of the newly

synthesized DNA strand? a. Addition of a dideoxynucleotide b. Deletion of a deoxyribonucleotide c. Addition of a deoxyribonucleotide d. Addition of a ribonucleotide ANS: A

See Figures 48-10 and 48-11. This reaction (also referred to as the Sanger reaction) generates fragments that are terminated at various lengths by the incorporation of one of the four dideoxynucleotide base analogs during extension from the sequencing primer.

DIF: 1 OBJ: 8

REF: Page 927-928, Figures 48-10, 48-11

6. In real-time PCR: a. an isolated mRNA and Thermus thermophilus is used. b. one can observe amplified nucleic acid fragments as they are synthesized. c. RNA:DNA hybrids are bound to a solid phase. d. RNA targets are used in an isothermal reaction.

ANS: B

When operating in the real-time PCR mode, data elements are collected during the nucleic acid amplification step rather than at the end of it.

DIF: 1

REF: Page 937

OBJ: 10

7. False positive results in molecular testing are most likely caused by which one of the

following? a. Inhibitors present in the sample b. Contamination with amplicon

c. Lengthy specimen prep time d. Lengthy patient prep time ANS: B

Because PCR is able to detect a single molecule of target sequence, a small amount of contamination in a sample easily produces a false positive result. The greatest potential for contamination comes from the product of the amplification reaction, referred to as the amplicon.

DIF: 1

REF: Page 922

OBJ: 1 | 4 | 12

8. Which of the following procedures can be used to avoid contamination with PCR reaction

product (amplicon) when performing a PCR procedure? a. Use of positive displacement pipettes b. Use of closed-tube methods c. Physical separation of preamplification and postamplification rooms d. All of the above ANS: D

The use of physically separated areas for preamplification and postamplification steps, positive-displacement pipettes to minimize aerosol contamination, and the use of prealiquoted reagents, as well as methods that perform amplification, detection, and characterization in a closed tube eliminate the risk of product contamination.

DIF: 1

REF: Page 922

OBJ: 4

9. Which one of the following statements regarding DNA gel electrophoresis is true? a. It is the charge of the pT yrEim inA esNiK nS thEe LDLNEARm SiTdB .oCleOcMule that gives DNA its net

negative charge and ability to migrate on a gel. b. Agarose gel can resolve 1 bp differences in DNA fragments and is best to use for

DNA sequencing. c. Polyacrylamide gel can separate smaller fragments of DNA with high resolution

and is best for single-stranded nucleic acid separation. d. Because of the negative charge of DNA, it will migrate toward the negative

electrode during electrophoresis.

ANS: C

Polyacrylamide polymers are suited for high-resolution separation (down to about a 0.1% size difference) of short molecules (up to about 2 kb) and are the primary polymer for single-stranded nucleic acid separation, such as DNA sequencing.

DIF: 2

REF: Page 925

OBJ: 7

10. The annealing step in a PCR involves: a. binding of the primers to the single-stranded DNA. b. unwinding and separating the double-stranded DNA. c. adding nucleotides to primed sites of the DNA strands. d. making a cDNA from an mRNA strand.

ANS: A

See Figure 48-1. In a PCR, primers provided in great excess specifically anneal to complementary sequences on the target. Once the primers are annealed, the action of the polymerase synthesizes two additional DNA strands containing the primers.

DIF: 1

REF: Page 920

OBJ: 4

11. When performing a PCR procedure, what is the best control to run to assess the presence of

amplicon? a. Positive control b. Blank control c. Oligoligated control d. dTTP control ANS: B

A negative control or blank (all reactants minus target DNA) is one of the most important controls for PCR. If the blank demonstrates DNA bands, the master mix has likely been contaminated with PCR reaction product.

DIF: 1

REF: Page 922

OBJ: 4

12. An example of a signal amplification technique (as opposed to a target or probe amplification

technique) would be: a. polymerase chain reaction. b. branched-chain amplification. c. ligase chain reaction. d. real-time PCR. ANS: B

Signal amplification techniques use nucleic acids to magnify the detection signal. In branched-chain signal amplification, hybridization to a series of (1) “extender,” (2) “preamplifier,” and (3) amplifier probes produce a final, highly branched amplifier probe that includes multiple copies of signal-generating enzymes that act on a chemiluminescent substrate to produce light.

DIF: 1

REF: Page 923

OBJ: 3

13. How does a dideoxynucleotide (ddNTP) that is used in DNA sequencing methods differ from

a typical deoxynucleotide (dNTP) present in normal DNA? a. ddNTPs have a hydroxyl group at the 2' carbon b. ddNTPs have a hydroxyl group at the 3' carbon c. ddNTPs lack a hydroxyl group at the 3' carbon d. ddNTPs lack a hydroxyl group at the 5' carbon ANS: C

Dideoxy-termination sequencing generates fragments that are terminated at various lengths by the incorporation of one of the four dideoxynucleotide bases during extension from the sequencing primer. Dideoxynucleotides lack the 3' hydroxyl group (OH) on the pentose ring.

Because DNA chain growth requires the addition of deoxynucleotides to the 3' OH, incorporation of a dideoxynucleotide terminates chain growth.

DIF: 1

REF: Page 827

OBJ: 8

14. In a pyrosequencing reaction, the incorporation of a nucleotide releases

. Eventually,

visible light is produced by an enzyme reaction. a. pyrophosphate b. ATP c. luciferase d. a primer ANS: A

After a sequencing primer is hybridized to a single-stranded template, enzymes and substrate are added. Next, one of the four dNTPs is added. If the base is complementary to the template strand, DNA polymerase catalyzes its incorporation and releases pyrophosphate (PPi). PPi release generates visible light through linked enzyme reactions.

DIF: 1

REF: Page 930

OBJ: 8

15. Which one of the following statements regarding single-stranded conformational

polymorphism (SSCP) analysis is incorrect? a. SSCP is used to assess a specimen for the presence of unknown variants in a nucleic acid sequence. b. SSCP distinguishes altered gene sequences by detecting a change in the three-dimensional structure of a piece of single-stranded DNA. c. SSCP is a polyacrylamide gel electrophoresis procedure. d. In SSCP, separation of a PCR product is performed with a gel that includes a concentration gradient of denaturants.

ANS: D

SSCP analysis is dependent on the change in the three-dimensional structure of altered single-stranded nucleic aciT dsE; S grTaB diA enNt K geSlsEaLreLtEhR e. haCllO mMark of denaturing gradient gel electrophoresis (DGGE) and not SSCP. DIF: 2

REF: Page 927

OBJ: 8

16. If RNA is to be used in a PCR amplification procedure, what is the initial step that must be

performed? a. The RNA must be denatured to form single strands for annealing to primers. b. RNA should never be used in a PCR reaction because thermostable enzymes cannot synthesize strands to anneal to it. c. A reverse transcription procedure must be performed to form cDNA. d. RNA must first be treated with RNases to remove interfering substances from the target.

ANS: C

In vitro, reverse transcriptase is used to make complementary DNA (cDNA) copies of RNA and may be used for cloning, probe preparation, and nucleic acid assays.

DIF: 2

REF: Page 919

OBJ: 2

17. The increase in the quantifiable signal observed early on in real-time PCR is dependent upon

the: a. amount of fluorescent dye added to the reaction. b. initial amount of fluorescent primer added.

c. amount of fluorescent quenching. d. initial amount of target DNA. ANS: D

Real-time PCR monitors the amount of product formed each cycle by systematically quantifying the fluorescence signal. The fluorescence signals depend on the amount of target DNA present in the sample.

DIF: 2

REF: Page 937

OBJ: 10

18. What type of assay is hybrid capture? a. Solid-phase hybridization b. Signal amplification c. Transcription-mediated amplification d. Solution-phase hybridization ANS: D

Hybrid capture methods are solution-phase hybridization methods that use a bound antibody that is specific for RNA-DNA hybrid molecules that are formed during the hybridization of a DNA sample and an unlabeled RNA probe.

DIF: 1

REF: Page 936

OBJ: 9

19. When combined with real-time PCR, melting curve analysis is done to: a. examine a single nucleotide variant genotype in a short amount of time. b. quickly quantify the amplified target. c. detect nucleic molecules at a specific wavelength. d. examine the size of a frTaE gm prN odKuSceEdLbLyERRF. LC P.OM SeTnBt A ANS: A

Real-time PCR with melting curve analysis allows (1) amplification, (2) detection, (3) quantification, and (4) genotyping to be performed quickly. Genotyping is preferably performed in the same tube by monitoring the melting (separation) of hybridized duplexes (probe plus DNA sequence) during controlled heating, producing a melting curve signature for the duplex. SNV genotyping compares the melt temperature of a normal DNA strand hybridized to a reporter probe with that obtained when a mutant allele is mismatched to a reporter probe.

DIF: 2

REF: Page 942

OBJ: 11

20. Gene expression microarrays quantify: a. a single copy of a nucleic acid target. b. relative amounts of different messenger RNAs in samples. c. RNA promoter regions that are adjacent to an inserted DNA sequence. d. the number of specific base pairs in a DNA target.

ANS: B

Gene expression microarrays quantify the relative amounts of different messenger RNAs in test and reference samples. Because the human genome is completely sequenced, mRNA probes are usually directly synthesized on microarrays. Modern gene expression arrays have been used to measure the mRNA transcribed from all human genes in one experiment.

Microarrays are used to assess numerous disease conditions.

DIF: 1

REF: Page 935

OBJ: 1 | 9

21. Regarding detection methods, the most common and preferred sequence-specific label for

probes used in nucleic acid analysis is a(n) a. enzyme b. radioactive c. fluorescent d. colorimetric

label.

ANS: C

Advances in oligonucleotide synthesis and fluorescence detection have made fluorescence-labeled probes the preferred reporter for nucleic acid analysis. Many fluorescent labels are now available, allowing color multiplexing for applications such as (1) DNA sequencing, (2) fragment length analysis, (3) DNA arrays, and (4) real-time PCR. DIF: 1

REF: Page 924

OBJ: 1 | 6

22. Which one of the following is the name given to the probe types used in real-time PCR that

change fluorescence through fluorescence resonance energy transfer (FRET) upon duplex formation? a. Hybridization b. Hydrolysis c. Mixed mechanism d. Primer ANS: A

When probes reversibly chT anEgSeTflB uoArN esKceSnE ceLoLnEdRu. plC exOfMormation, they are called hybridization probes. These probes change fluorescence upon hybridization, usually by fluorescence resonance energy transfer.

DIF: 1

REF: Page 938

OBJ: 10

23. In a PCR, a control nucleic acid sequence that is different from the target sequence is added to

each sample to: a. control for the presence of amplicon contamination. b. bind aerosols. c. control for the presence of inhibitors in the sample that might inhibit polymerase activity. d. compare with an internal standard for quantitative analysis.

ANS: C

Clinical samples may contain unpredictable amounts of impurities that could inhibit polymerase activity. Typically, a control nucleic acid sequence, usually different from the target, is added to the sample (or to nucleic acid extracted from the sample). Failure to amplify this control indicates that further purification of the sample is required to remove inhibitors of the reaction.

DIF: 1

REF: Page 922

OBJ: 4

24. What is the purpose of the labeled oligonucleotide probe used in hybridization assays? a. To stabilize the assay

b. To cut the DNA into smaller-size fragments c. To reduce the background of the assay d. To detect the presence of a specific nucleotide sequence ANS: D

A probe is similar to an antibody in an immunoassay. Therefore in a hybridization assay, a probe is the nucleic acid whose sequence is known and is used to reveal the identity, location, or abundance of a target.

DIF: 2

REF: Page 932

OBJ: 7

25. An enzyme that hydrolyzes one or more phosphodiester bonds in nucleic acid polymers is

called a: a. polymerase. b. nuclease. c. ligase. d. reverse transcriptase.

ANS: B

Nucleases are enzymes that hydrolyze one or more phosphodiester bonds in nucleic acid polymers. Nucleases may require a free hydroxyl end (exonucleases), with specificity for the 3' or 5' end, or may act only on internal bonds (endonucleases).

DIF: 1

REF: Page 918

OBJ: 2

Chapter 49: Genomes and Nucleic Acid Alterations Test Bank MULTIPLE CHOICE 1. A single nucleotide variant (SNV) that produces a misplaced termination codon in a

polypeptide chain is called a: a. missense variant. b. transposon. c. copy number variant. d. nonsense variant.

ANS: D

Most SNVs that cause disease are missense and result in an amino acid substitution, whereas significantly fewer are nonsense variants that result in a termination codon and premature polypeptide chain termination.

DIF: 1

REF: Page 948

OBJ: 4

2. A single nucleotide variant that produces a misplaced termination codon in a polypeptide

chain results in: a. a frameshift mutation. b. premature polypeptide chain termination. c. chromosomal translocation. d. a trinucleotide repeat.

ANS: B

Most SNVs that cause disease are missense and result in an amino acid substitution, whereas significantly fewer are nonsense variants that result in a termination codon and premature polypeptide chain termination.

DIF: 1

REF: Page 948

OBJ: 4

3. Polymorphic DNA sequences that are short tandem repeats 1 to 13 base pairs in length are

referred to as: a. microsatellites. b. minisatellite DNA. c. long tandem repeats. d. transposable elements.

ANS: A

Intergenic DNA also carries most of the simple sequence repeats (SSRs) present in the genome. These repeats are known as microsatellites or short tandem repeats (STRs) when the repeat unit is 1 to 13 bases in length.

DIF: 1

REF: Page 947

OBJ: 2

4. On average, how much of a gene sequence is removed as introns, leaving the exons to be

spliced together and translated into protein? a. 100%

b. 95% c. 50% d. 1% ANS: B

The primary RNA transcript is processed by splicing to retain exons that are interspersed throughout the gene and have a higher GC content than noncoding regions. On average, 95% of a gene is removed as introns, retaining a mean of 10.4 exons, of which 9.1 are translated into proteins.

DIF: 1

REF: Page 947

OBJ: 1

5. Which one of the following is a similarity between bacterial and human genomes? a. Number of chromosomes b. Structure of chromosomes c. Number of genes d. Presence of double-stranded DNA ANS: D

Although the chromosome number (1), structure (circular), and the amount of DNA that codes for protein is different in the bacterial genome, the double helix remains the basic structure of genomic DNA. DIF: 2

REF: Page 949

OBJ: 5

6. Polymorphic repeated DNA sequences that are sometimes referred to as minisatellite

sequences and are between 14 and 500 base pairs in length are called: a. transposons. b. a variable number of tandem repeats. c. a restriction endonuclease. d. short tandem repeats.

ANS: B

Intergenic DNA also carries most of the simple sequence repeats (SSRs) present in the genome. If the repeat length is between 14 and 500 base pairs, the sequence is called a minisatellite sequence or a variable number of tandem repeats.

DIF: 1 7.

REF: Page 949

OBJ: 2

Which one of the following statements regarding the human genome below is correct? a. Mobile genetic elements (transposons) comprise almost half of the human genome. b. An intron is located within a transposon segment of a chromosome. c. Genes that contain instructions for making proteins are located in transposons. d. Unique sequences that code for protein make up only 10% of the human genome.

ANS: A

Three quarters of human DNA is intergenic or between genes. More than 60% of this intergenic sequence consists of “parasitic” DNA regions of transposable elements 100 to 11,000 bases in length. Between 2 million and 3 million of these transposons are present in each copy of the genome.

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8. If you were interested in studying plasmid structure, which one of the following cell types

would be appropriate for you to examine? a. Human cells b. Fungal cells c. Bacterial cells d. All cell types ANS: C

In addition to the large circular chromosome that carries essential genes, bacteria also carry accessory genes in smaller circles of double-stranded DNA known as plasmids. Plasmids range in size from 1000 to more than 1 million base pairs. Plasmids are important in molecular diagnosis of bacterial infections.

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9. In the following sequences, the normal amino acid sequence is given first followed by a

sequence that is produced by a sequence alteration. Identify the type of sequence alteration that most likely causes the altered amino acid sequence.

Normal Sequence: Phe-Asn-Pro-Thr-Arg Mutated Sequence: Phe-Asn-Pro What type of sequence alteration most likely caused the mutation? a. Indel b. Missense c. Nonsense d. There is no alteration.

ANS: C

An amino acid substitution that results in a termination codon is referred to as a nonsense mutation. The sequence in mutation 1 is truncated prematurely.

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10. In the following sequences, the normal amino acid sequence is given first followed by the

sequence that is produced by a sequence alteration. Identify the type of sequence alteration that most likely causes the altered amino acid sequence.

Normal Sequence: Phe-Asn-Pro-Thr-Arg Mutated Sequence: Phe-His-Pro-Thr-Arg What type of sequence alteration most likely caused the mutation? a. Indel b. Missense c. Nonsense d. There is no alteration.

ANS: B

A single nucleotide polymorphism that causes an amino acid substitution is referred to as a missense mutation.

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11. A virus does not need as much nucleic acid for the production of protein as bacteria do

because: a. viruses use the DNA of the cells that they infect to produce protein. b. viruses contain high sequence variation. c. there are no introns in the viral genome. d. it uses plasmids to synthesize protein instead of DNA. ANS: A

Because a virus will infect a cell by injecting its own RNA or DNA into that cell, it requires less of its own genes for protein synthesis, using that of the infected cell instead.

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12. Approximately what percentage of genomic DNA is required to maintain the structure of

chromosomes as centromeres and telomeres? a. 75% b. 50% c. 20% d. 2% ANS: D

Approximately 2% of DNA is required to maintain the structure of chromosomes and is located at chromosome centers (centromeres) and ends (telomeres).

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13. The major difference between single nucleotide variants (SNVs) and copy number variants

(CNVs) is that: a. SNVs are duplicated in tandem and involve complex gains or losses of homologous sequences, whereas CNVs involve simple sequence changes. b. CNVs occur in stretches of DNA ranging from 100 to millions of bases in size, whereas SNVs involve single base changes. c. SNVs are always associated with disease, whereas CNVs are not. d. SNVs are involved in gene amplification by producing more than two functional genes in a genome.

ANS: B

Copy number variants occur in stretches of DNA that may range from 100 bases up to several Mb (megabases, or million bases) in size, whereas the most common single nucleotide variants are single base changes. CNVs may be duplicated in tandem or may involve complex gains or losses of homologous sequences at multiple sites in the genome.

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14. An example of epigenetic variation that affects gene expression would be: a. heteroplasmy. b. chromosomal translocation. c. copy number alteration. d. histone modifications.

ANS: D

Since DNA is associated with proteins in nucleosomes, gene expression can be altered by histone phosphorylation, acetylation, and methylation.

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15. Copy number variants comprise approximately what percent of the human genome? a. 75% b. 50% c. 10% d. 0.5% ANS: C

See Table 49-1. CNV regions exist in every chromosome and involve 5% to 12% of the human genome.

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