Self-assessment Q&A in Clinical Laboratory Science, III

By Alan H.B. Wu

Self-assessment Q&A in Clinical Laboratory Science, III, adds a variety of subject matter that addresses new concepts and emerging technology, particularly in the areas of kidney biomarkers, cancer biomarkers, molecular diagnostics, multiple myeloma, pharmacogenomics, novel cardiovascular biomarkers and biomarkers of neurologic diseases. The field of Clinical Laboratory Science continues to evolve and editor Alan Wu has once again brought together experts in the field to cover the contemporary topics that are being tested today. This updated bank of questions and answers is a must-have to sharpen knowledge and skills.

• Contains nearly 800 multiple choice questions with correct answer explanations
• Assists readers in determining knowledge gaps so they can better study for certification examinations and remain current in this rapidly changing field
• Provides a format that is conducive to quick learning in digestible segments
• Includes beneficial citations for additional study

• Language: English
• Publisher: Elsevier Science
• Release date: Aug 29, 2020
• ISBN: 9780128220948

Book preview

Self-assessment Q&A in Clinical Laboratory Science, III

First Edition

Alan H.B. Wu

Professor of Laboratory Medicine, School of Medicine, San Francisco, CA, United States

Table of Contents

Cover image

Title page

Copyright

Contributors

Reviewers

Preface

Section A: General clinical chemistry

Chapter 1: Antiquated and novel clinical laboratory tests

Chapter 2: Cardiac markers

Chapter 3: Cardiovascular disease markers

Chapter 4: Oncology

Chapter 5: Tumor markers

Chapter 6: Sepsis tests

Chapter 7: Serum proteins and electrophoresis

Chapter 8: Interference and HIL indices

Chapter 9: Clinical cases

Chapter 10: Blood gases, electrolytes, and iron

Chapter 11: Pancreatic markers, GI absorption, vitamins

Chapter 12: Endocrinology

Chapter 13: Adrenal, thyroid hormones, and pregnancy

Section B: Therapeutic drug monitoring and toxicology

Chapter 14: Clinical toxicology

Chapter 15: Forensic toxicology

Chapter 16: Mass spectrometry

Chapter 17: Metal testing

Chapter 18: Pharmacogenomics and therapeutic drug monitoring

Chapter 19: Transplant therapeutic drug monitoring

Section C: Molecular diagnostics and infectious diseases

Chapter 20: Molecular diagnostics—Basics

Chapter 21: Molecular diagnostics—Genetic diseases

Chapter 22: Molecular microbiology

Chapter 23: Infectious disease serology and molecular diagnostics for infectious diseases

Chapter 24: Microbiology

Section D: Other clinical laboratory sections

Chapter 25: Hematology and coagulation

Chapter 26: Immunology and autoimmune disease

Chapter 27: Liquid biopsy

Chapter 28: Urinalysis and stool testing

Chapter 29: Flow cytometry

Chapter 30: Clinical chemistry of neurological and psychiatric diseases

Chapter 31: Newborn screening

Section E: General laboratory topics

Chapter 32: Preanalytical factors and test interferences

Chapter 33: Reference ranges

Chapter 34: Laboratory statistics

Chapter 35: Regulations and lab administration

Chapter 36: Lab medicine informatics

Chapter 37: Point-of-care testing

Index

Copyright

Elsevier

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This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

About AACC

Dedicated to achieving better health through laboratory medicine, AACC brings together more than 50,000 clinical laboratory professionals, physicians, research scientists, and business leaders from around the world focused on clinical chemistry, molecular diagnostics, mass spectrometry, translational medicine, lab management, and other areas of progressing laboratory science. Since 1948, AACC has worked to advance the common interests of the field, providing programs that advance scientific collaboration, knowledge, expertise, and innovation. For more information, visit www.aacc.org.

Library of Congress Cataloging-in-Publication Data

A catalog record for this book is available from the Library of Congress

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library

ISBN: 978-0-12-822093-1

For information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Stacy Masucci

Senior Editorial Project Manager: Susan Ikeda

Production Project Manager: Stalin Viswanathan

Cover Designer: Miles Hitchen

Typeset by SPi Global, India

Contributors

Numbers in parentheses indicate the pages on which the authors' contributions begin.

Zane D. Amenhotep     University of California, San Francisco, CA, United States

Wayne B. Anderson     University of Rochester, Rochester, NY, United States

Jason M. Baron     Massachusetts General Hospital, Boston, MA, United States

Carey-Ann D. Burnham     Washington University School of Medicine, St. Louis, MO, United States

Jing Cao     Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Janine D. Cook     Substance Abuse Mental Health Services Administration, Rockville, MD, United States

Gyorgy Csako     National Institute of Health, Washington, DC, United States

Sarah Delaney     Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States

Anand S. Dighe     Massachusetts General Hospital, Boston, MA, United States

Shu-Ling Fan     UMass Memorial Medical Center, Worcester, MA, United States

Wieslaw Furmaga

Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX

University of California, San Francisco, CA, United States

Putuma P. Gqamana     University of Rochester, Rochester, NY, United States

Dina N. Greene     Kaiser Permanente, Seattle, WA, United States

Neil Harris     University of Florida, Gainesville, FL, United States

Ibrahim Hashim     University of Texas Southwestern, Dallas, TX, United States

Erika M. Hissong     Weill Cornell Medicine, New York, NY, United States

Paul J. Jannetto     Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States

Michael Karasick     University of Rochester, Rochester, NY, United States

Adil I. Khan     Temple University, Philadelphia, PA, United States

Rasoul A. Koupaei     California Department of Public Health, Richmond, CA, United States

Kent Lewandrowski     Massachusettes General Hospital, Boston, MA, United States

Chuanyi Mark Lu     University of California, San Francisco, CA, United States

Maximo J. Marin     Department of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States

Yvette McCarter     University of Florida, Jacksonsville, FL, United States

Qing H. Meng     MD Anderson Cancer Center, Houston, TX, United States

James H. Nichols     Vanderbilt University, Nashville, TN, United States

Anthony Okorodudu     University of Texas Medical Branch, Galveston, TX, United States

Octavia M. Peck Palmer     University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Hanna Rennert     Weill Cornell Medicine, New York, NY, United States

Luke Rodda     Office of the Chief Medical Examiners, San Francisco, CA, United States

Lusia Sepiashvili     Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

Christine L.H. Snozek     Mayo Clinic Arizona, Scottsdale, AZ, United States

Carole A. Spencer     University of Southern California, Los Angeles, CA, United States

John Toffaletti     Duke University, Durham, NC, United States

Nam Tran     University of California, Davis, CA, United States

Greg Tsongalis     Dartmouth Hitchock Hospital, Hanover, NH, United States

Priya D. Velu     Weill Cornell Medicine, New York, NY, United States

Jeffrey Whitman     University of California, San Francisco, CA, United States

Xander M.R. van Wijk

Department of Pathology, Pritzker School of Medicine, The University of Chicago

The University of Chicago Medicine and Biological Sciences, Chicago, IL, United States

Alison Woodworth     University of Kentucky, Lexington, KY, United States

Alan H.B. Wu     University of California, San Francisco, CA, United States

Melanie L. Yarbrough     Washington University School of Medicine, St. Louis, MO, United States

He Sarina Yang     Weill Cornell Medicine, New York, NY, United States

Brandy Young     University of Rochester, Rochester, NY, United States

Y. Victoria Zhang     University of Rochester, Rochester, NY, United States

Zhen Zhao     Weill Cornell Medicine, New York, NY, United States

Reviewers

Justin Volk, Office of the Chief Medical Examiners, San Francisco, CA, United States

Kelsa West, Office of the Chief Medical Examiners, San Francisco, CA, United States

A.S. Danielle Dhari, Office of the Chief Medical Examiners, San Francisco, CA, United States

Jirair Gevorkyan, Office of the Chief Medical Examiners, San Francisco, CA, United States

Sue Pearring, Office of the Chief Medical Examiners, San Francisco, CA, United States

Ruben Luo, University of California, San Francisco, CA, United States

Yu Jada Zhang, University of California, San Francisco CA, United States

Preface

Alan H.B. Wu, San Francisco, CA

Since the First Edition of Clinical Chemistry Self-Assessment was published by the American Association for Clinical Chemistry (AACC) in 1982 by Marge A. Brewster, a clinical chemist at the University of Arkansas. I joined Dr. Brewster and Charles Turley for authorship of the Second Edition in 1989. When I joined the staff at Hartford Hospital, I convinced (coerced) my colleagues there (Robert Moore, Greg Tsongalis, and Robert Burnett) to coauthor the Third Edition in year 2000. The title of this edition was changed from Clinical Chemistry to Clinical Laboratory Science, to reflect questions that cover more of the field of laboratory medicine and to include emerging topics. In 2008 rather than a publish a Fourth Edition, we decided to add new questions to complement those found in the Third Edition, and labeled the book Self-Assessment in Clinical Laboratory Science II.

Now, more than a decade later, I found it appropriate to produce what is essentially the Fifth Edition, entitled, Self-Assessment Q&A in Clinical Laboratory Science III. As the AACC is dropped out of the book publishing business, this edition is produced by Elsevier Science. Like the Fourth Edition, this book is written by an army of content experts in our field. Some chapters on general clinical chemistry have been reproduced from prior editions with updated references. These questions reflect the ever increasing scope and range of topics that we as clinical laboratory professionals have to deal with on a regular basis.

Section A

General clinical chemistry

Chapter 1: Antiquated and novel clinical laboratory tests

Alan H.B. Wu    University of California, San Francisco, CA, United States

1.Which of the following tests may be unnecessary in light of grain supplementation that occurs in North America?

a.mean corpuscular volume

b.vitamin B12

c.serum folate

d.homocysteine

e.methylmalonic acid

2.Which of the following test is largely obsolete with regards to pancreatic disease?

a.amylase

b.lipase

c.serum trypsin

d.CA19-9

e.secretin

3.Which test is most appropriate for testing fetal lung maturity, replacing all of the others listed?

a.lecithin:sphingomyelin ratio

b.foam stability index

c.phosphatidyl glycerol

d.lamellar body count

e.FLM test (surfactant-to-albumin ratio)

4.Which cardiac marker is largely antiquated?

1.myoglobin

2.creatine kinase-MB

3.lactate dehydrogenase isoenzymes

4.total creatine kinase

a.1,2,3

b.1,3

c.2,4

d.4 only

e.all of the above

5.Which of the following is recommended for vitamin D testing?

a.general population screening

b.routine measurement of both hydroxy and dihydroxyvitamin D

c.use of mass spectrometry for D2 and D3 speciation to monitor the effect of supplementation

d.analysis of the C-3 25(OH)D3 epimer in neonates

e.analysis of the C-3 25(OH)D3 epimer in adults

6.Which of the following analytes is not yet standardized by a recognized body?

a.creatinine

b.hemoglobin A1c

c.cholesterol

d.glucose

e.parathyroid hormone

7.Which of the following is correct regarding the differences between the MDRD and CKD-EPI equations for estimated glomerular filtration rate?

a.The CKD-EPI equation is more accurate at 60 mL/min.

b.The CKD-EPI equation accounts for Asians and Hispanics.

c.The CKD-EPI equation uses cystatin C.

d.The MDRD equation significantly overestimates GFR among individuals with normal kidney function.

e.Neither equation has biases for patients with renal transplant.

8.The MDRD and CKD-EPI use a correction factor for subjects who are African American. On average, this is because African Americans

a.have larger kidneys

b.have larger muscle mass

c.have large fat volume

d.eat more red meat

e.have higher likelihood of reduced kidney function

9.What of the following is true regarding prostatic acid phosphatase today (PAP)?

a.It is synonymous with prostate-specific antigen (PSA).

b.Ratio of PAP/PSA better separates benign prostatic hypertrophy from prostate cancer.

c.Recent data suggests that PAP may be better than PSA for screening.

d.Recent data suggests that PAP may be better than PSA for predicting metastatic disease.

e.No recurring role for PAP.

10.Which of the following is true regarding the use of the erythrocyte sedimentation rate (ESR) vs C-reactive protein (CRP)?

a.Results are concordant 95% of the time, obviating the need for both testing.

b.ESR is more sensitive as an early marker of inflammation.

c.ESR is less sensitive than CRP in patients with bacterial infections.

d.CRP results from an increase in fibrinogen.

e.CRP has a longer half-life.

11.Which of the following tests is rarely used regarding a workup of pernicious anemia?

a.Schilling test

b.methylmalonic acid

c.mean corpuscular volume

d.serum B12 level

e.red cell folate level

12.Which of the following statements do not provide rationale for measuring methylmalonic acid (MMA) and homocysteine for megaloblastic anemia?

a.MMA is an early indicator of B12 deficiency.

b.Serum vitamin B12 levels do not represent functional stores.

c.Homocysteine is elevated in B12 deficiency.

d.MMA concentrations decline with vitamin B12 treatment.

e.MMA is not increased in folate deficiency.

13.Which of the following has not been studied as a marker for traumatic brain injury?

a.S100b

b.myelin basic protein

c.ubiquitin C-terminal hydrolase L1

d.CK-MM Isoenzyme

e.brain-derived neurotrophic factor

14.Which of the following traumatic brain injury markers is released as the result of microvascular injury?

a.glial fibrillary acidic protein

b.neuron specific enolase

c.matrix metalloproteinase

d.tau protein

e.αII-spectrin

15.What may the role of detecting autoantibodies to brain proteins after traumatic brain injury (TBI)?

a.early detection

b.differentiation between health and mild TBI

c.the presence of autoantibodies themselves produce adverse events

d.predicting onset of TBI-induced Parkinson syndrome

e.their absence excludes the need for a head CT scan

16.Which of the following is not a clinical application of measuring anti-Müllerian hormone levels?

a.prediction the age of menopause

b.aid in the diagnosis of polycystic ovary syndrome

c.assessment of ovarian function before and after gynecologic surgeries

d.prediction of ectopic pregnancy

e.predicting the risk for developing ovarian hyperstimulation syndrome

17.Which of the following is true regarding anticyclic citrullinated peptide antibodies with regards to rheumatoid arthritis?

a.is highly specificity

b.arrive late after rheumatoid arthritis onset

c.do not contribute to the pathophysiology

d.are positive in all cases

e.increases are more prevalent among the younger patients

18.What is the medical utility of fetal fibronectin testing?

a.fetal lung maturity

b.prediction of spontaneous preterm birth

c.ectopic pregnancy

d.diagnosis of endometriosis

e.diagnosis of polycystic ovary syndrome

19.What is the value of measuring total bile salts during pregnancy?

a.detection of congenital heart malformations

b.identification of Down syndrome

c.intrauterine malignancy

d.identification of preeclampsia

e.detection of obstetric cholestasis

20.What is hepcidin?

a.transport protein for iron

b.iron regulatory hormone for gut absorption and release from storage sites

c.major iron storage protein

d.hormone that stimulates reabsorption from the renal tubule

e.drug used to treat iron deficiency

21.What is the medical value of hepcidin measurements?

1.differentiate between iron deficiency and anemia of chronic disease

2.iron refractory iron deficiency anemia

3.aid in the diagnosis of hemochromatosis

4.sickle cell disease

a.1,3

b.1,2,3

c.2,4

d.4 only

e.all of the above

22.Which of the following is not used as a serologic test for celiac disease?

a.antigliadin antibodies

b.antiendomysial antibodies

c.antitransglutaminase antibodies

d.antimitochondrial antibodies

e.deamidated gliadin peptides

23.Which of the following conditions is not a cause of false positive results for use of celia antibodies?

a.chronic liver disease

b.Patient is not on a gluten-free diet when tested.

c.enteric infections

d.hypergammaglobulinemia

e.congestive heart failure

24.Which of the following is not a test for acute kidney injury (AKI)?

a.neutrophil gelatinase-associated lipocalin

b.miRNA-122

c.proenkephalin

d.kidney injury molecule-1

e.metalloproteinases-2 and insulin-like growth factor-binding protein

25.Which of the following is an essential attribute for a biomarker of acute kidney injury?

a.increased 24–48 h before creatinine

b.equations available for estimating glomerular filtration rate

c.predicts the need for renal transplant

d.no difference in results between ancestry

e.predicts renal transplant rejection

26.Creatinine testing is performed prior to contrast imaging with gadolinium to reduce the risk of

a.systemic nephrogenic fibrosis

b.acute kidney injury

c.lupus nephritis

d.scleroderma

e.anaphylactic reactions

27.What is the best rationale for intraoperative parathyroid hormone analysis?

a.Prediction of postsurgical parathyroid hormone function.

b.Determine that additional tumor is present.

c.PTH assays are more analytically accurate when conducted at the point-of-care.

d.Eliminates the need for repeat surgical resection.

e.Supersedes the need for a frozen biopsy of the excised gland.

28.Which parathyroid hormone testing criteria is used to determine that the procedure was successful?

a.a reduce ratio of intact to N-terminal PTH

b.a 90% reduction of PTH within 10 min of resection relative to baseline

c.a 90% reduction of PTH within 30 min of resection relative to baseline

d.a 50% reduction of PTH within 10 min of resection of PTH relative to baseline

e.depends on the number of glans removed

Answers

1.c. Folate deficiency is rare after the supplementation of grain, even among the homeless. McMullin MF. Homocysteine and methylmalonic acid as indicators of folate and vitamin B12 deficiency in pregnancy. Clin Lab Haematol 2001;23:161–5. Joelson DW, et al. Diminished need for folate measuremens among indigent populations in the post folic acid supplementation era. Arch Pathol Lab Med 2007;131:477–80.

2.a. Amylase is less specific than lipase and is largely redundant. CA19-9 is a pancreatic tumor marker. Secretin and trypsin are useful for some diseases that affect the pancreas including steatorrhea and as cystic fibrosis. Barbieri JS, et al. Amylase testing for acute pancreatitis. J Hosp Med 2016;5:366–8.https://doi.org/10.1002/jhm.2544.

3.d. The lamellar body count can be measured using a hematology analyzer. All of the others are largely no available or should not be used. Lu J, et al. Lamellar body counts performed on automated hematology analyzers to assess fetal lung maturity. Lab Med 2008;38:419–23.

4.a. Total creatine kinase can be used to determine reinfarction and detection of skeletal muscle disease. Wu AHB, et al. Antiquated tests within the clinical pathology laboratory. Am J Manag Care 2010;https://www.ajmc.com/journals/issue/2010/2010-09-vol16-n09/ajmc_10sep_wu_xcl_e220to227.

5.c. General population screening is not recommended. The 1,25(OH)2 testing is recommended only for those who have renal disease. The D3 epimer is largely inactive and present in low concentrations in adults but higher in neonates. Either vitamin D2 or D3 can be supplemented. Karras SN, et al. The road no so travelled: should measurement of vitamin D epimers during pregnancy affect our clinical decisions? Nutrients 2017;9:90.https://doi.org/10.3390/nu9020090.

6.e. Standardization enables interpretation of test results generated from different assays and laboratories. PTH is currently not standardized. American Association for Clinical Chemistry. The need to harmonize clinical laboratory test results July 2015. White paper.

7.a. The CKD-EPI is more accurate between 60 and 100 mL/min whereas with the MDRD, no value should be given if the eGFR is > 60 mL/min. Murata K, et al. Relative performance of the MDRD and CKD-EPI equations for estimating glomerular filtration rate among patients with varied clinical presentations. Clin J Am Soc Nephrol 2011;6:1963–72.

8.b. Muscle mass affects the creatinine concentration, which on the average, is higher for African Americans. Delanaye P, et al. Are the creatinine-based equations accurate to estimate glomerular filtration rate in African American populations? Clin J Am Soc Nephrol 2011;6:906–12.

9.e. Recent data have shown prognostic value of PAP, especially after surgery. But there are no clinical practice groups that have recommended revival of PAP testing. Xu H, et al. Prostatic acid phosphastase (PAP) predicts prostate cancer progress in a population-based study: the renewal of PAP? Dis Mark 2019;10.https://doi.org/10.1155/2019/7090545.

10.c. ESR and CRP are both markers of inflammation but CRP is considered more sensitive and therefore overall, more useful especially for infections. CRP declines faster than ESR in blood. Bray C, et al. Erythrocyte sedimentation rate and C-reactive protein measurements and their relevance in clinical medicine. Wisc Med J 2016;115:317–21.

11.a. Pernicious anemia is caused by a deficiency of vitamin B12 due to poor dietary absorption due to the absence of intrinsic factor. The Schilling test involves injection of radiolabeled B12 and measuring urinary excretion, but is not widely available. Ramphul K, et al. Schilling Test. [Updated 2019 Jun 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK507784/.

12.e. Vitamin B12 is a cofactor required in the conversion of methylmalonyl CoA to succinyl CoA. An increase in MMA is an early indicator of vitamin B12 deficiency and folate deficiency. MMA is falsely increased in renal disease. Hannibal L et al. Biomarkers and algorithms for the diagnosis of vitamin B12 deficiency. Front Mol Biosci 2016;2.https://doi.org/10.3389/fmolb.2016.00027.

13.d. The CK-BB isoenzyme is being investigated as a TBI marker but not the MM isoenzyme that originates from skeletal muscles. Gan ZS, et al. Blood biomarkers for traumatic brain injury: a quantitative assessment of diagnostic and prognostic accuracy. Front Neurol 2019;10:446.https://doi.org/10.3389/fneur.2019.00446.

14.a. Traumatic brain injury triggers a complex array of events beginning from disruption of metabolism, microvessels and synaptic membrane dysfunction, cell leakage, cellular necrosis, and cerebral ischemia. GFAB is released from microvesicles and is one of the earlier biomarkers of TBI. Dambinova,et al. Gradual return to play: potential role of neurotoxicity biomarkers in assessment of concussions severity. J Mol Biom Diag 2013, s3.https://doi.org/10.4172/2155-9929.S3-003.

15.c. One theory is that exposure of proteins from the central nervous system may illicit an autoimmune response and may produce injury in a similar manner as in autoimmune diseases. Raad M, et al. Autoantibodies in traumatic brain injury and central nervous system trauma. Neurosci 2014;281:16–23.

16.d. Anti-Mullerian is a glycoprotein hormone related to inhibin and actin from the transforming growth factor beta family. Oh SR, et al. Anti- Müllerian hormone is a peptide growth factor and a marker of ovarian reserve. Clinical application of serum anti-Müllerian hormone in women. Clin Exp Reprod Med 2019;46:50–59.

17.a. Anti-CCP antibodies are highly specific, early indicator, and cause bone and joint damage, but there are rheumatoid arthritis patients who have negative results. Cader MZ, et al. The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis. BMC Musculoskelet Disord 2010;11:187.https://doi.org/10.1186/1471-2474-11-187.

18.b. During pregnancy, the presence of vaginal fetal fibronectin is an indicator of disruption of the maternal-fetal interface, and the initial onset of labor. Kiefer DG, et al. The utility of fetal fibronectin in the prediction and prevention of spontaneous preterm birth. Ref Ostet Gynecol 2008;1:106–12.

19.d. Bile salts are end products of cholesterol catabolism. When present, it can cause postpartum hemorrhage, preterm labor, intrapartum fetal distress, and stillbirth. Egan N, et al. Reference standard for serum bile acids in pregnancy. Brit J Obstet Gynecol 2012;119:493–8.

20.b. Hepcidin regulates the rate of iron efflux into plasma. During iron overload, hepcidin is upregulated preventing release of iron from enterocytes. Ganz T, et al. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003;102:783–8.

21.c. Hepcidin is useful for both iron overload and deficiency. Iron refractory iron deficiency anemia is due to a mutation and patients do not respond to iron treatment. Girelli D, et al. Hepcidin in the diagnosis of iron disorders. Blood 2016;127:2809–13.

22.d. Antimitochondrial antibodies are useful for diagnosis of biliary cirrhosis. Singh A, et al. Non-invasive biomarkers for celiac disease. J Clin Med 2019;8:885.https://doi.org/10.3390/jcm8060885.

23.b. Patients on a gluten-free or reduced-gluten diet will produce a false negative result for many of these antibodies. Singh A, et al. J Clin Med 2019;8:885.https://doi.org/10.3390/jcm8060885.

24.b. miRNA-122 is a specific liver injury marker. Each of the others has been studied as AKI markers. Konukoglu D, et al. Biomarkers for acute kidney injury. Int J Med Biochem 2018;1:80–7.

25.a. Creatinine is a renal function marker that rises within 1-2 days after acute kidney injury. AKI biomarkers are useful if they are increased within the first few hours after AKI. Konukoglu D, et al. Biomarkers for acute kidney injury. Int J Med Biochem 2018;1:80–7.

26.a. Patients with reduced clearance of gadolinium can produce systemic nephrogenic fibrosis that produces thickening and hardening of the skin and is similar in appearance to scleroderma. Acute kidney injury occurs with iodide contrast imaging and less so with gadolinium. Anaphylactic reactions can occur with contrast injection but is not predicted by creatinine measurement. Schieda N, et al. Gadolinium-based contrast agents in kidney disease: a comprehensive review and clinical practice guideline issued by the Canadian Association of Radiologists. Can J Kidney Health Dis 2018;5.https://doi.org/10.1177/2054358118778573.

27.b. Due to the short half-life of PTH in blood, estimated to be 3–5 min, residual activity indicates the presence of residual tumor that should be resected. Carter AB, et al. Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Path Lab Med 2003;127:1424–42.

28.d. If there is substantial residual PTH, a full bilateral exploration of the neck is warranted to search for additional tumors. Carter AB, et al. Intraoperative testing for parathyroid hormone: a comprehensive review of the use of the assay and the relevant literature. Arch Path Lab Med 2003;127:1424–42.

Chapter 2: Cardiac markers

Alan H.B. Wu    University of California, San Francisco, CA, United States

1.NT-pro BNP is

a.inactive metabolite of BNP

b.active metabolite of BNP

c.inactive metabolite of proBNP

d.active metabolite of proBNP

e.inactive metabolite of atrial natriuretic peptide (ANP)

2.Which of the following is true regarding BNP and NT-proBNP?

a.Compensated heart failure have higher values than decompensated

b.Increased to the same extent in chronic obstructive pulmonary disease

c.Diastolic failure lower than systolic failure

d.No age- or sex-related differences in healthy subjects

e.No correlation to the 6-minute walk test

3.Which of the following is the most accurate regarding the origin of the natriuretic peptides (BNP and ANP) in blood?

a.BNP originates from the brain and cardiac ventricles

b.BNP originates from the cardiac ventricles, ANP from the cardiac atria

c.BNP originates from the left ventricles, ANP from the right ventricles

d.BNP originates from the cerebral ventricles

e.BNP originates from the heart, ANP from the kidneys

4.What is true regarding the use of neprilysin inhibitors in an HF patient?

a.BNP increased, NT-proBNP decreased

b.BNP decreased, NT-proBNP increased

c.Both are increased

d.Both are decreased

e.Both stay the same

5.Which of the following is true regarding the use of BNP/NT-proBNP to guide heart failure treatment for heart failure patients?

a.This has become part of standard practice

b.BNP is effective but NT-proBNP is not

c.Guided therapy is limited to angiotensin-converting enzyme inhibitors

d.Various randomized trials have produced mixed result

e.Must be used in conjunction with high-sensitivity cardiac troponin

6.Which of the following is not part of the diagnostic criteria for acute myocardial infarction according to the 4th Universal Definition?

a.rising or falling pattern of cardiac troponin

b.electrocardiographic changes

c.intimal thickness of the carotid artery

d.pathologic findings

e.evidence of occlusion upon angiography

7.Which of the following is not correct regarding types of AMIs?

a.Type I is associated with plaque rupture

b.Cocaine use can produce a type II AMI

c.Cardiac troponin testing can be used to differentiate between types

d.Type 1 and type 2 are treated differently

e.Demand ischemia characterizes type 2 AMI

8.Which of the following are the criteria for determining if a troponin assay qualifies as high sensitivity?

a.Values at the 99th percentile produce a 10% imprecision

b.Values at the 99th percentile produce a 20% imprecision

c.At least 50% of healthy subjects detected above the assay’s limit of detection

d.At least 90% of healthy subjects detected above the assay’s limit of detection

e.99% of patients with AMI detected

9.Which of the following is the biggest advantage for implementing high-sensitivity troponin?

a.more accurate risk stratification for adverse cardiac events

b.more accurate diagnosis of ST-segment elevation myocardial infarction

c.obviates the need for testing the natriuretic peptides

d.earlier rule out of myocardial infarction

e.aid in the selection of the most appropriate therapy

10.Biological variation studies have shown that cardiac troponin has a low index of individuality. Which of the following cannot be concluded?

a.Reference ranges for troponin will be of limited value

b.Serial testing will be essential for interpretation of results for AMI diagnosis

c.An individual’s own baseline value during health could be useful if there were standardization among troponin assays

d.CK-MB is more valuable for AMI rule out

e.Either a delta change or absolute change in troponin over time can be used

11.Which of the following is least likely to cause an increase in troponin in the absence of cardiac injury?

a.renal failure

b.cardiac failure

c.pulmonary embolus

d.sepsis

e.untreated cancer

12.What is the value of measuring troponin in a patient who presents to the emergency department with chest and has an ST-segment elevation on an electrocardiogram?

a.No value for acute testing

b.Troponin determines whether or not a cardiac catheterization is required

c.Troponin differentiates between types I and II AMI

d.Troponin is useful for 30-day risk stratification for future adverse events

e.Troponin determines the likelihood of the patient developing chronic heart failure

13.Which of the following is correct regarding recommendations for the reporting units for cardiac troponin?

a.report results of all assays in ng/mL

b.report results of all assays in ng/L

c.report high sensitivity in ng/L, conventional assays in ng/mL

d.report point-of-care troponin in ng/mL, high sensitivity in ng/L

e.dependent on the manufacturer’s recommendations

14.According to the International Federation of Clinical Chemistry, which epitopes within the troponin protein should the antibodies be directed toward?

a.Two antibodies directed toward the central part

b.One antibody directed toward the C-terminus and one toward the N-terminus

c.One antibody directed toward the C-terminus and one toward the central part

d.One antibody directed toward the N-terminus and one toward the central part

e.Three antibodies, one at the C-terminus, N-terminus, and one toward the central part

15.Which of the following describes the clearance kinetics of cardiac markers in successful versus unsuccessful revascularization?

a.No change in the marker vs time profile

b.Earlier release in successful than unsuccessful reperfusion

c.Earlier release in unsuccessful reperfusion is due to periprocedural MI

d.Release kinetics dependent on the type of AMI (type I vs II)

e.Early release in unsuccessful reperfusion is due to reperfusion injury

16.What is the current state of standardization for cardiac troponin assays?

a.Troponin T and troponin I are standardized to each other

b.There is no standardization of cTnI, but results are harmonized to each other

c.Standardization will not be possible as there are no industry-wide agreement on antibodies used (epitopes or number of antibodies)

d.There is standardization between point-of-care and the central lab cTnI within a company

e.Although there is no standardization, troponin I results between manufacturers are currently within 20% of each other

17.The following electrocardiogram was obtained from a patient who presents to an emergency department with chest pain. This patient went straight to the cardiac catheterization laboratory for revascularization. Which of the following is false?

a.ST-segment elevation in leads V2 through V5

b.ST-depression in leads III and afF

c.indicative of an anterolateral AMI

d.prolongation of the QT interval

e.absence of a left bundle branch block

18.Which of the following is a marker of early myocardial infarction?

a.soluble ST2

b.CD40 ligand

c.growth differentiation factor-15

d.pregnancy-associated plasma protein-A

e.copeptin

19.Some have opined that troponin should replace the need for CK-MB testing. Which of the following might counter that argument?

a.Since troponin remains increased for many days after CK-MB, the latter could be used to detect the presence of a reinfarction

b.It is more accurate to measure the size of infarcted tissue with CK-MB

c.CK-MB has more sensitivity for AMI than troponin

d.CK-MB is more stable than troponin in vitro

e.Reagents for troponin assays are substantially more expensive than CK-MB

20.The following figure is a plot of cardiac biomarker release vs time after myocardial infarction. Label the curves appropriately.

a.A = myoglobin, B = CK-MB, C = troponin I, D = lactate dehydrogenase, E = troponin T

b.A = CK-MB, B = myoglobin, C = lactate dehydrogenase, D = troponin I, E = troponin T

c.A = myoglobin, B = CK-MB, C = troponin I, D = troponin T, E = lactate dehydrogenase

d.A = lactate dehydrogenase, B = aspartate aminotransferase, C = CK-MB, D = troponin I, E = troponin T

e.A = CK-MB, B = myoglobin, C = troponin C, D = troponin I, E = lactate dehydrogenase

21.The following figure represents the thin filament of muscle fiber. What is the correct labeling?

a.A = actin, B = troponin complex, C = tropomyosin

b.A = myosin, B = troponin complex, C = tropomyosin

c.A = actin, B = myosin, C = troponin complex

d.A = troponin complex, B = myosin, C = actin

e.A = troponin complex, B = tropomyosin, C = actin

22.Galectin-3 and soluble ST-2 are novel heart failure biomarkers. Unlike the natriuretic peptides, they are not influenced by volume overload. Which of the following medical applications would this attribute give these markers an advantage?

a.aid in the diagnosis of acute myocardial infarction

b.outpatient monitoring for success of antiheart failure medications

c.diagnosis of heart failure from the emergency department

d.risk stratification for future adverse cardiac events

e.as a replacement for the echocardiogram

23.After intensive discussion with ED resident about all possible interpretation of cardiac markers results, he asks you to summarize the most important information about laboratory diagnosis of cardiac diseases. What is considered to be true about cardiac markers?

a.In myocardial infarct LD is flipped and LD2 > LD1

b.In the normal heart, CK-MB consists of 15%–20% of the total CK and this percentage is greater in the right than in the left ventricle

c.In patient with myocardial infarct even small secondary increase in cTnI after initial diagnostic peak is interpreted as a reinfarction

d.The concentrations of cTnT and cTnI must be at least two times higher than 99th percentile to indicate damage to myocytes and myocardial infarct

24.Following are angiograms of patient undergoing an elective cardiac catheterization. The Before image shows a major blockage of the left anterior descending (LAD) coronary artery. Two minor collaterals are present near the blockage that forms as a compensatory mechanism to supply blood to that portion of the heart. The interventional cardiologist decides to open the artery with a balloon catheter. The After image shows a patent LAD artery. One of the collateral arteries is now blocked.

Before

After

Which of the following is true?

a.This patient has suffered postprocedural myocardial infarction

b.This is sufficient to release a small amount of cardiac troponin that can be detected with a high-sensitivity assay

c.This will stimulate release of B-type natriuretic peptide

d.CK-MB but not troponin will be increased

e.A postprocedural electrocardiogram will demonstrate significant changes

Answers

1.c. Both BNP (active) and NT-proBNP (inactive) are cleaved from proBNP and released into the circulation in equimolar concentrations. Mair, J. Biochemistry of B-type natriuretic peptide: where are we now? Clin Chem Lab Med 2008;46(11):1507–14.

2.c. In diastolic failure, now labeled as heart failure with preserved ejection fraction (HFpEF), BNP levels are lower than in systolic failure, now labeled as heart failure with reduced ejection fraction (HFrEF). Are of the others are false. Harada E, et al. B-type natriuretic Peptide in heart failure with preserved ejection fraction: relevance to age-related left ventricular modeling in Japanese. Circ J 2017;81:1006–13.

3.b. BNP originates from both ventricles and ANP from both atria. While the original name for BNP was brain natriuretic peptide, blood concentrations originate from the heart. Weber M, et al. Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart 2006;92(6):843–9.

4.a. Neprilysin inhibitors affect the metabolism of BNP, therefore values are slightly higher immediately after treatment. This leads to improvement of heart function, as reflected by a decrease in NT-proBNP. Mair J. Clinical utility of BNP for monitoring patients with chronic HF treated with sacubitril-valsartan. Am Coll Cardiol, Latest in cardiology.https://www.acc.org/latest-in-cardiology/articles/2016/12/19/08/06/clinical-utility-of-bnp-for-monitoring-patients-with-chronic-hf-treated-with-sacubitril-valsartan.

5.d. A meta-analysis has shown that BNP/NT-proBNP can be used to guide therapy but this has not been clinically adopted. Porapakkham P, et al. B-type natriuretic peptide-guided heart failure therapy. A meta-analysis. Arch Intern Med 2010;170:507–14.

6.c. Imaging is part of the Universal Definition of AMI but not of the carotid artery. Thygesen K, et al. Fourth universal definition of myocardial infarction. Eur Heart J 2018;40:237–69.

7.c. Troponin is increased in both types of AMIs although the concentrations in type 1 are usually higher than type 2. Thygesen K, et al. Fourth universal definition of myocardial infarction. Eur Heart J 2018;40:237– 69.

8.c. The designation of high sensitivity is an analytical determination from healthy subjects. Prior generation of troponin assays was inadequately sensitive enough to detect troponin in blood of healthy subjects. Apple FS. A new season for cardiac troponin assays: it’s time to keep a score card. Clin Chem 2009;55:1303–6.

9.d. High-sensitivity assays enable rule out of myocardial infarction earlier, even with the admission specimen only. Body R, et al. Diagnostic accuracy of a high-sensitivity cardiac troponin assay with a single serum test in the emergency department. Clin Chem 2019;65:1006–14.

10.d. The index of individuality is the ratio of the intra-individual divided by the inter-individual variation. A low index of < 0.6 indicates that reference values will not be useful and serial testing becomes important. Very low values for troponin are useful for AMI rule out on the admission sample. Wu AHB, et al. Short- and long-term biological variation in cardiac troponin I with a high-sensitivity assay: implications for clinical practice. Clin Chem 2009;55:52–8.

11.e. Certain chemotherapeutic such as doxorubicin can cause cardiac injury. However, cancer by itself, unless it has metastasized to the heart, should not increase troponin. Wu AHB, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: use of cardiac troponin and the natriuretic peptides for etiologies other than acute coronary syndromes and heart failure. Clin Chem 2007;53:2086–96.

12.e. There is no value in patients with an STEMI for diagnosis and minimal value for risk stratification. These individuals should be sent for emergent cardiac catheterization. Cediel G, et al. Prognostic value of new-generation troponins in ST-segment-elevation myocardial infarction in the modern era: the RUTI-STEMI Study. J Am Heart Assoc 2017;6(12):e007252. Published 2017 Dec 23. doi:10.1161/JAHA.117.007252.

13.c. According to the Academy of the American Association for Clinical Chemistry, the reporting units should be dependent on the generation of the assay. Since high-sensitivity troponin produces the lowest results, the ng/L should be used with values reported in whole numbers. Wu AHB, et al. Clinical laboratory practice recommendations for use of cardiac troponin in acute coronary syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardio Bio-markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem 2018;64:645–55.

14.a. Troponin degrades when released into the circulation at the C-terminal and N-terminal ends of the protein. Therefore most assays use antibodies that are directed toward the central portion. Some commercial troponin assays do use three antibodies, but not one directed at the N-terminus. Panteghini M, et al. Quality specifications for cardiac troponin assays. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Clin Chem Lab Med 2001;39:174–8.

15.b. In patients with successful reperfusion, such as angioplasty, revascularization facilitates egress directly into the circulation and a washout of cardiac biomarkers. Tanasijevic MJ, et al. Myoglobin, creatine-kinase-MB and cardiac troponin-I 60-minute ratios predict infarct-related artery patency after thrombolysis for acute myocardial infarction: results from the Thrombolysis in Myocardial Infarction study (TIMI) 10B. J Am Coll Cardiol. 1999;34(3):739–47.

16.c. Standardization of cTnI assays will not occur unless all manufacturers agree on the antibodies used in their assay, which is highly unlikely. Apple FS. Counterpoint: Standardization of cardiac troponin I assays will not occur in my lifetime. Clin Chem. 2012 Jan;58(1):169–71. doi:10.1373/clinchem.2011.166165.

17.d. The yellow highlighted areas indicate ST elevation myocardial infarction (STEMI) and blue areas indicate ST-segment depression indicative of myocardial ischemia and MI when it exceeds 5 mm (as in this case). STEMIs do not require troponin testing. ST segment elevations in leads V3 and V4 are indicative of an anterolateral AMI. A left bundle branch block can indicate underlying heart disease. Prolongation of the QT interval can cause arrhythmias. Akbar H. Acute myocardial infarction ST elevation (STEMI). StatPearls [Internet].https://www.ncbi.nlm.nih.gov/books/NBK532281/Image courtesy of Wikimedia commons.

18.e. Copeptin is the C-terminal portion of arginine vasopressin and is released before troponin after myocardial infarction. owever, the peptide is not as specific. Maisel AS, et al. Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN Trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction). J Am Coll Cardiol 2013;62:150–60.

19.a. In theory, reinfarctions can be more readily detected with CK-MB than troponin because CK-MB returns to baseline, although published cases have suggested that a secondary rise is observed with troponin as well. Apple FS, et al. Cardiac troponin and creatine kinase MB monitoring during in-hospital myocardial reinfarction. Clin Chem 2005;51:460–3.

20.c. Myoglobin is the smallest of the cardiac biomarkers and is released and cleared the fastest. LDH is larger and is released slower than myoglobin and CK-MB. The troponins have a prolonged biphasic release (cytosolic and structural component) with troponin T producing higher results. Jaffe AS, et al. Biomarkers in acute cardiac disease–the present and the future. J Am Coll Cardiol 2006;48:1–11.

21.a. The troponin complex of C, T, and I subunits resides on the tropomyosin strand of the actin thin filament. It regulates contraction by