Clinical Chemistry

Front 1

Which of the following expenses incurred by the clinical laboratory is BEST classified as both a direct and a variable cost?
a. Analyzer purchase
b. Salaries for laboratory staff performing the tests
c. Proficiency testing materials
d. Reagents
e. Utility expenses

Back 1

d.
Variable costs change proportionately with the test volume. Reagent costs grow with increasing number of tests performed. Fixed
costs are considered constant and therefore do not vary with the volume of tests performed. Except for reagents, all of the
expenses listed are fixed costs. Direct costs can be directly linked to an end product (i.e., billable test). Reagents and technologist
time are examples of direct costs. While indirect costs are not directly linked to a billable test, they are essential for laboratory
function. Indirect costs are also known as overhead

Front 2

Which financial management-related term best describes the condition or diagnosis of a patient?
a. International Classification of Disease, 9th Revision with Clinical Modifications (ICD-9-CM)
b. Current Procedural Terminology (CPT) codes
c. Diagnostic Related Groups (DRGs)
d. Healthcare Financing Administration Common Procedural Coding System (HCPCS)

Back 2

a.
Before medical claims are paid, the claim must describe the patient's medical condition or diagnosis in addition to the list of
services and/or tests performed. This information is translated to a standard coding system recognized by all government and
non-government organizations. HCPCS codes provide a description of the tests or services performed. The ICD-9-CM codes
describe the patient's condition or diagnosis. These standards facilitate communication between health care providers and thirdparty
organizations. CPT codes are a component of HCPCS that are used to identify clinical laboratory tests and medical services.
DRGs classify patients to facilitate reimbursement of hospital costs for Medicare patients. The DRG does not cover physician
services.

Front 3

Which of the following is a laboratory-related governmental agency?
a. American Society of Clinical Pathology (ASCP)
b. College of American Pathologists (CAP)
c. Clinical and Laboratory Standards Institute (CLSI)
d. Joint Commission ( JC)
e. Centers for Medical and Medicaid Services (CMS)

Back 3

e.
Choices A-D are all considered non-governmental organizations. The ASCP offers certification for various specialties. JC is a nonprofit
organization based on setting quality standards and may substitute for federal Medicare and Medicaid surveys. JC meets
licensure and insurers' requirements. CAP provides a proficiency survey program that is accompanied with a peersurveyed
laboratory accreditation program that has CLIA-deemed status and is recognized by JC as meeting laboratory standards. CLSI
(formerly known as NCCLS) is a professional peer group with standard criteria directed laboratory practices (retrieved from:
http://www.clsi.org). CMS (formerly known as HCFA) sets quality standards and reimbursement rates for laboratory tests and
services that are considered standards for use by third-party payers.

Front 4

Which of the following is LEAST correct about fecal porphyrins?
a. Fecal porphyrins can be used to distinguish variegate porphyria from coproporphyria.
b. Increases in fecal porphyrin excretion up to threefold the upper reference limit may be seen in healthy individuals.
c. Fecal porphyrins are usually increased in acute intermittent porphyria.
d. The main components of fecal porphyrins are coproporphyrin and protoporphyrin.
e. Diet can influence the amount of fecal porphyrin excretion.

Back 4

c.
Coproporphyrin, protoporphyrin, and other dicarboxylic porphyrins make up fecal porphyrins. One of the most important
applications of fecal porphyrins is to distinguish between variegate porphyria (coproporphyrin and protoporphyrin) and
coproporphyria (coproporphyrin only). Fecal porphyrins are usually increased in all of the porphyrias except acute intermittent
porphyria. The amount of fecal porphyrins excreted is a function of diet and the anaerobic flora of the colon. Therefore, healthy individuals may demonstrate variability in fecal porphyrin excretion as much as three times the upper reference limit.

Front 5

Which statement about zinc protoporphyrin is LEAST correct?
a. Zinc protoporphyrin, measured as free erythrocyte protoporphyrin, provides an assessment of iron available for hemoglobin production.
b. Free erythrocyte protoporphyrin is usually decreased in response to both iron deficiency (absolute lack of iron) and chronic disease
(impaired use of iron).
c. Lead's interference with ferrochelatase usually results in increased free erythrocyte protoporphyrin.
d. The zinc protoporphyrin heme ratio reflects iron status within bone marrow because zinc can substitute for iron within the marrow.
e. Zinc protoporphyrin regulates heme catabolism via competitive inhibition of heme oxygenase.

Back 5

b.
Free erythrocyte protoporphyrin is often used as a screen for iron deficiency because it usually increases in both iron deficiency
and chronic disease. Zinc protoporphyrin level increases in response to decreased iron and is often measured as free erythrocyte protoporphyrin. Lead interferes with ferrochelatase, the final step in heme synthesis. Zinc protoporphyrin regulates heme
catabolism by competition with heme oxygenase, the rate limiting enzymatic step in heme degradation to biliverdin followed by
biliverdin reductase conversion of biliverdin to bilirubin. Because zinc protoporphyrin can assess bilirubin formation, it may also
be used to monitor hyperbilirubinemia in neonates.

Front 6

A defect in which of the following enzymes results in the only autosomal recessive porphyria? This porphyria is also the only one
whose tissue expression is in erythroid cells.
a. Uroporphyrinogen III synthase
b. Protoporphyrinogen oxidase
c. Ferrochelatase
d. Porphobilinogen deaminase
e. Coproporphyrinogen oxidasen

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a.
Congenital erythropoietic porphyria is the result of an enzyme defect in uroporphyrinogen III synthase and is the only porphyria
with an autosomal recessive mode of inheritance. The others are autosomal dominant. A defect in protoporphyrinogen oxidase
results in variegate porphyria. A defect in ferrochelatase results in erythropoietic protoporphyria. A defect in porphobilinogen
deaminase results in acute intermittent porphyria. A defect in coproporphyrinogen oxidase results in hereditary coproporphyria.
Tissue expression for protoporphyria can be both erythroid cells and liver; congenital erythropoietic porphyria is the only one with
only erythroid cell expression. Tissue expression for the other porphyrias are liver only.

Front 7

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

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

Front 8

Which of the following neuroendocrine tumors would most likely be associated with gallstones, diabetes, diarrhea, and
hypochlorhydria?
a. Carcinoid
b. Gastrinoma
c. Insulinoma
d. VIPomas
e. Somatostatinoma

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e.
Somatostatin inhibits a number of intestinal and pancreatic hormones. It causes diabetes through inhibition of insulin and
hypochlorhydria due to inhibition of gastrin. Diarrhea is at least partially due to inhibition of pancreatic enzyme production, and
gallstones may be due to inhibition of CCK production. While diarrhea can be seen with carcinoid and gastrinoma, the other
findings are rare, while insulinomas only cause hypoglycemia and none of the other manifestations.

Front 9

Which of the following assays generates the highest sensitivity for diagnosing a pheochromocytoma?
a. Plasma-free metanephrines
b. Plasma catecholamines
c. Urine catecholamines
d. Urine total metanephrines
e. Urine vanillylmandelic acid

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a.
Measurement of plasma-free metanephrines is between 97% and 99% sensitive for diagnosing hereditary and sporadic
pheochromocytomas and has the highest sensitivity among the choices listed for diagnosing a pheochromocytoma; however,
specificity is relatively low (85%). Specificity is highest for measurement of fractionated metanephrines or catecholamines in urine.

Front 10

Which of the following disorders is associated with increased renin levels?
a. Cushing syndrome
b. Liddle syndrome
c. Addison disease
d. Primary hyperaldosteronism
e. Dexamethasone-suppressible hyperaldosteronism

Back 10

c.
Addison disease is associated with elevated levels of renin. Primary hyperaldosteronism and Cushing and Liddle syndromes are
conditions associated with decreased renin levels. Additionally, decreased renin levels are associated with dexamethasonesuppressible
hyperaldosteronism.

Front 11

Which of the following causes of congenital adrenal hyperplasia is most likely to result in increased levels of 11-deoxycortisol?
a. 21-hydroxylase deficiency
b. 11 beta-hydroxylase deficiency
c. 3 beta-hydroxylase deficiency
d. 3 beta-hydroxysteroid dehydrogenase deficiency
e. 17 alpha-hydroxylase deficiency

Back 11

b.
11 beta-hydroxylase converts 11-deoxycortisol to cortisol in the glucocorticoid pathway (
zona fasciculata
) in the adrenal cortex. Congenital adrenal hyperplasia (CAH) associated with elevated levels of 11-deoxycortisol will likely be
caused by a deficiency in 11 beta-hydroxylase. This enzyme defect represents approximately 5% of all cases of CAH, while 21-
hydroxylase deficiency represents almost all of the remaining 95% of CAH cases. Much rarer causes include deficiencies of
enzymes further “upstream” in the glucocorticoid and mineralocorticoid cascade.

Front 12

A 24-hour urine sample was submitted to the laboratory from a 32-year-old man who is being evaluated for a possible
pheochromocytoma. The catecholamines that were ordered were determined to be 145 μg/day (reference range = 90-150 μg/day). The
printout indicated that the creatinine was 0.5 g/day. Which of the following is most appropriate for the technician to take?
a. Check the urine pH to verify that it has been acidified correctly (pH < 2).
b. Report the catecholamines as grams of creatinine.
c. Measure metanephrines and cancel the order for catecholamines.
d. Request a plasma sample to obtain corresponding plasma catecholamine levels.
e. Cancel the order and request a new 24-hour urine sample.

Back 12

e.
A urine creatinine much less than 0.9 g/day likely means that the sample collection was incomplete. These values would lead to a
misinterpreted catecholamine result.

Front 13

For these questions, use the following reference limits: Total T4, 4.5-12.5 mcg/dL, Total T3 80-220 ng/dL, Free T4 0.7-1.7 ng/dL, T3 uptake 22%
to 33%, TSH 0.45-4.8 mIU/L, thyroglobulin 2.0-35 ng/mL. Anti-thyroglobulin and anti-thyroid peroxidase <1.0 relative units, thyroid-stimulating
immunoglobulin 70% to 130%.
A 53-year-old woman is admitted with hypotension, fever, and abdominal pain and is found to have a perforated colon. Because of
concerns for coexisting thyroid disease, a full panel of thyroid tests was ordered, including total T4 6.7 mcg/dL, total T3 45 ng/dL, T3
uptake 28%, and TSH 4.4 mIU/L. The surgeon is concerned and has called for your assistance in interpreting these results. The correct
interpretation would be:
a. No interpretation is possible, since thyroid tests are always misleading in the setting of acute illness.
b. The high ratio of T4 to T3 suggests early hyperthyroidism, and could be due to a TSH-producing tumor, since TSH is not suppressed.
c. These results are typical for “euthyroid sick syndrome,” or nonthyroidal illness, and do not indicate underlying thyroid disease.
d. This patient likely has early hypothyroidism, and should have measurement of TPO antibodies.
e. This patient likely has a decreased level of thyroid binding proteins due to the surgery, which causes the observed results.

Back 13

c.
The normal T4, T3 uptake, and TSH with low T3 are typical of “euthyroid sick syndrome,” or nonthyroidal illness. In acute illness,
peripheral conversion of T4 to T3 (by the type I monodeiodinase) is impaired, while pituitary conversion of T4 to T3 (by the type 2
monodeiodinase) is normal, preventing an increase in TSH. Those who are acutely ill may actually have abnormal TSH due to the
effects of a number of factors (cortisol, dopamine, cytokines) that impact TSH production, often making it hard to evaluate actual
thyroid status in acute illness.

Front 14

A 35-year-old woman complained of feeling tired, and so had thyroid function tests ordered. Results included total T4 14.3 mcg/dL,
total T3 280 ng/dL, T3 uptake 18%, TSH 2.5 mIU/L. Her primary care physician asked for your input in interpreting these results. The
correct interpretation would be:
a. A heterophile antibody is likely present, causing falsely increased T4 and T3 and falsely low T3 uptake.
b. These results are typical for euthyroid sick syndrome, or nonthyroidal illness, and do not indicate underlying thyroid disease.
c. These results indicate increased thyroid-binding proteins, most likely due to increased estrogenic effect; you are told the woman is taking
oral contraceptives.

Back 14

c.
These results, with increased levels of total thyroid hormones, low T3 uptake, and normal TSH, are typical of increased levels of
thyroid-binding proteins, especially TBG. Common causes for this are pregnancy, use of oral contraceptives, exposure to other
drugs that increase TBG (such as phenothiazines, antidepressants, and opiates), and active liver injury. Hyperthyroidism should
cause increases in both thyroid hormones and T3 uptake, as well as suppressed TSH. Euthyroid sick syndrome should cause low
T3 but normal T4, T3 uptake, and TSH. Heterophile antibodies typically interfere in sandwich assays (such as are used for TSH
measurement) and should not increase T3 and T4 (which are measured by competitive immunoassays) and would not affect T3
uptake (which is not an immunoassay at all).

Front 15

A 75-year-old man presents with acute shortness of breath and is found to be in atrial fibrillation with a rate of 150 beats/minute.
Thyroid function tests include free T4 of 1.6 ng/dL, Total T3 of 530 ng/dL, TSH <0.01 mIU/L. Thyroid peroxidase antibodies are 25.3 units,
and thyroid stimulating antibodies are 420%. The most likely diagnosis is:
a. Euthyroid sick syndrome (nonthyroidal illness)
b. Euthyroid with increased thyroid-binding globulins due to medications
c. Hyperthyroidism due to Graves disease
d. Hyperthyroidism due to thyroid adenoma
e. Hyperthyroidism from thyroid damage in Hashimotos thyroiditis

Back 15

c.
The normal free T4 with even increased T3 and suppressed TSH is typical for hyperthyroidism, particularly that due to Grave
disease. The overactive thyroid cells in this state tend to produce proportionally more T3 and proportionally less T4 per cell,
resulting in earlier increases in T3 than in T4, and earlier return of T4 to normal with treatment. This impression is confirmed by
the presence of thyroid-stimulating immunoglobulins (TSI), which are highly specific for Grave disease. While thyroid peroxidase
antibodies are used as a test for Hashimoto thyroiditis, they are present in 85% of those with Grave disease. Thyroid adenoma can
cause hyperthyroidism, as can Hashimoto disease, but in both conditions T4 is increased to a greater extent than T3 and TSI
should be absent. In euthyroid sick syndrome, T3 should be low, not high; while TSH may be lower than normal, it is not
undetectable. With increased TBG, total thyroid hormones are increased while free hormone levels are normal; however, TSH
would be normal and thyroid autoantibodies would be absent

Front 16

A 56-year-old woman was diagnosed with hypothyroidism after presenting with tiredness, cold intolerance, and weight gain; her
initial thyroid function test results included free T4 of 0.3 ng/dL and TSH 75 mIU/L. She has started on thyroxine therapy and has
repeated thyroid function tests performed 10 days later; free T4 is 0.5 ng/dL and TSH is 56 mIU/L. What is the most likely interpretation
for these results?
a. The patient is hypothyroid, but an inadequate dose of thyroid hormone was given, and the dose should be increased with repeat thyroid
function tests performed in another 10 days.
b. The patient is hypothyroid, but free T4 is not the correct thyroid function test to monitor treatment, since it is not the active hormone; free
or total T3 should be followed instead.
c. The patient is hypothyroid, but TSH is falsely elevated because of a heterophile antibody, and only free T4 should be used to guide
treatment.
d. The patient is hypothyroid, but repeat thyroid function tests were performed too soon after starting treatment; at least 5 to 6 weeks is
needed to reach steady state on replacement hormone.
e. These results indicate a high likelihood of interference from heterophile antibodies in both TSH and free T4 assays, and a repeat analysis
after incubation with neutralizing mouse serum would likely result in normal results for both tests.

Back 16

d.
These results are typical of primary hypothyroidism at baseline. Thyroxine (thyroid hormone) has a half-life of 1 week, and it takes
five half-lives to reach about 95% of steady-state levels for any drug. It is common for nonspecialist physicians to repeat thyroid
function tests too soon after beginning treatment and to incorrectly modify therapy based on those results. While heterophile
antibodies may cause falsely increased TSH, one would expect results to be similar on repeat testing rather than decrease as
observed; heterophile antibodies do not typically affect free T4 measurements, since these are not measured using sandwich
assays. T3 is not monitored in hypothyroidism because it is not a sensitive test of thyroid dysfunction, and since most T3 comes
from metabolism of T4, levels reflect thyroxine levels closely.

Front 17

Which of the following cardiac markers would best be used to identify plaque destabilization?
a. Interleukin 6
b. Soluble CD40 ligand
c. Myeloperoxidase
d. NT-proBNP
e. Cardiac troponin I

Back 17

c.
IL-6 is an indicator of proinflammatory cytokines. Soluble CD40 ligand indicates plaque rupture. NT-proBNP is a good indicator of
myocardial dysfunction, and cardiac troponins T and I indicate myocardial necrosis. Myeloperoxidase is a granulocyte enzyme that
converts hydrogen peroxide into hyporchlorus acid (bleach) and is a good indicator for plaque destabilization.

Front 18

Which of the following cardiac injury markers would remain elevated longest after an acute myocardial infarction?
a. Myoglobin
b. CK-MB
c. Troponin C
d. Troponin I
e. Troponin T

Back 18

e.
Myoglobin is cleared by the kidney and remains elevated only about 24 hours. CK MB has a half-life of about 12 hours and
generally remains elevated 24-36 hours. Troponin C is not measured, as it is not cardiac specific. Because detection limits are
lower for troponin T than for troponin I, it generally remains elevated for up to 10 to 14 days (depending on the size of the infarct),
several days longer than that for troponin I.

Front 19

Which of the following has the greatest CK-MB activity (i.e., IU/g)?
a. Skeletal muscle
b. Heart
c. Brain.
d. GI tract
e. Lungs

Back 19

b.
The distribution of total CK is significantly grater in skeletal muscle than any in other tissue. However, CK-MB activity represents
only 1% to 2% of skeletal muscle and is even greater in neonates. Cardiac muscle contains, on average, 10% to 20% CK MB. The
brain, GI tract, and lungs have predominantly CK BB.¶


Front 20

Which of the following is the most accurate statement describing the recommended use of CK-MB or cardiac troponin (cTn) to
evaluate patients presenting to the ER with chest pain?
a. CK-MB is the reference biomarker for myocardial infarction detection and risk stratification in acute myocardial infarction diagnosis.
b. In an acute coronary syndrome patient, three consecutive, nonfluctuating, elevated cTn results are diagnostic of acute myocardial
infarction.
c. The 99th percentile of troponin values from healthy adults is the generally accepted cutoff level used by most hospitals.
d. CK-MB values greater than the 20% CV of the assay defines the reference range for a “normal” population.
e. cTn values greater than the 20% CV of the assay defines the reference range for a “normal” population.

Back 20

c.
Cardiac troponin is the reference biomarker for myocardial infarction (MI) and risk stratification in acute MI. A rise and fall in
troponin is considered diagnostic of myocardial infarction. The cutoff value used to diagnose MI is the 99th percentile of values
from healthy individuals, or where the CV of the assay is 10%, whichever value is higher. If cTn values remain constant, the
elevated result may be due to an interfering antibody or to another condition, such as renal failure (which causes chronic
elevation in troponin). CK MB is less sensitive and less specific than troponin, and is no longer considered the reference marker
for diagnosis of myocardial infarction; however, it is still used if troponin is not available.

Front 21

Which statement regarding B-type natriuretic peptide (BNP) is most accurate?
a. NT-proBNP and BNP are released from the cardiac myocyte in a 1:1 ratio.
b. The circulating levels of NT-proBNP are generally lower than circulating BNP.
c. NT-ProBNP is significantly more accurate in predicting heart failure than BNP.
d. BNP levels are about equal for population-matched men and women.
e. Measuring serum Prepro-BNP is a good predictor of heart failure within the subsequent six months for patients diagnosed with congestive
heart failure.

Back 21

a.
The following figure () illustrates release of BNP from a cardiac muscle cell. Inside the cardiac myocyte, pre-pro-BNP (a 134 amino
acid peptide) is cleaved to a signal peptide (a 26 amino acid peptide) and pro-BNP (a 108 amino acid peptide). Pro-BNP is
cleaved and released into the blood as equal molar amounts of NT-pro-BNP (amino acids 1 through 76 of pro-BNP) and BNP
(amino acids 77 through 108 of pro-BNP). Once in the blood, NT-pro-BNP has a longer half-life and is therefore present at higher
levels than BNP. The utility of both analytes is about equal in predicting heart failure, and the major differences are manufacturer
specific with respect to reagents, reference ranges, and proprietary rights. Other differences include: BNP is lower in obese
individuals, and NT-proBNP is higher in the presence of renal failure.

Front 22

The following figure illustrates release of BNP from a cardiac muscle cell. Inside the cardiac myocyte, pre-pro-BNP (a 134 amino
acid peptide) is cleaved to a signal peptide (a 26 amino acid peptide) and pro-BNP (a 108 amino acid peptide). Pro-BNP is
cleaved and released into the blood as equal molar amounts of NT-pro-BNP (amino acids 1 through 76 of pro-BNP) and BNP
(amino acids 77 through 108 of pro-BNP). Once in the blood, NT-pro-BNP has a longer half-life and is therefore present at higher
levels than BNP. The utility of both analytes is about equal in predicting heart failure, and the major differences are manufacturer
specific with respect to reagents, reference ranges, and proprietary rights. Other differences include: BNP is lower in obese
individuals, and NT-proBNP is higher in the presence of renal failure.ure.

Back 22

Front 23

Which of the following is directly measured/detected by the ischemia modified albumin assay?
a. Albumin
b. Copper
c. Ascorbic acid
d. Cobalt
e. Superoxide dismutase°

Back 23

d.
This assay is also called the albumin-cobalt binding test. Exogenous cobalt used in the reagent is unable to bind to modified
albumin in the location where copper can also bind. During the assay procedure when modified albumin is removed from the
analytical reaction cell, all unbound cobalt remains and is spectrophotometrically measured. Because all cobalt bound to
nonmodified albumin is no longer present, the level of modified albumin is calculated from the remaining unbound cobalt.

Front 24

Which statement is FALSE regarding cardiac troponin I (cTnI) assays?
a. The signal is determined by using a microparticle that fluoresces and sends a signal read by the instrument.
b. Capture antibodies are designed to detect specific epitopes of cTnI.
c. Capture antibodies are attached to the manufacturer's microparticles.
d. Manufacturers use capture antibodies to improve cTn assay sensitivity.

Back 24

a.
The signal is generated by acridinium ester that directly binds to cTnI via another antibody. illustrates possibilities of how different
components of cTnI can generate signal in an assay.

Front 25

Which of the following are causes of an
oxyhemoglobin dissociation curve with a right
shift? (K-type)
1. acidosis
2. increased pCO2.
3. increased 2,3 DPG
4. increased pO2

Back 25

A (1,2,3) When the oxygen dissociation curve shifts
to the right, there is less saturation at a given pO2; this
increases oxygen delivery to tissues. Increases in
hydrogen ion concentration (decreases in pH), carbon
dioxide (pCO2), temperature, and 2,3 DPG all shift the
curve to the right. Decreases in these parameters shift
the curve to the left.

Front 26

What is/are the cause of an oxyhemoglobin
dissociation curve with a left shift (K-type)?
1. alkalosis
2. increased carboxyhemoglobin
3. decreased pCO2
4. increased methemoglobin

Back 26

E (1, 2, 3 4) As discussed in the answer to question
1, decreases in hydrogen ion (increases in pH), pCO2,
temperature, and 2,3 DPG all decrease oxygen delivery
to tissues and shift the dissociation curve to the left. In
addition, carboxyhemoglobin (in carbon monoxide
poisoning) and methemoglobin also impair oxygen
delivery to tissues, as do high affinity hemoglobin variants including fetal hemoglobin.

Front 27

True or false: pH has a direct relationship to
the oxygen affinity of hemoglobin.

Back 27

TRUE. As pH increases (alkalemia), the oxygen
dissociation curve is shifted to the left which results in
increased affinity of hemoglobin for oxygen and
oxygen saturation, which causes decreased dissociation
and oxygen delivery to tissues. The opposite changes
occur with pH decreases (acidemia).

Front 28

Which of the following does not have a direct
effect on P(A)-aD O2
a. barometric pressure
b. inspired O2
c. arterial pO2
d. inspired CO2
e. arterial pCO2

Back 28

D The alveolar-arterial difference in pO2 (P(A)-aD
O2) requires calculation of alveolar pO2 using the
following formula:
[(P atm - P H20) * %O2] - alveolar pCO2
Calculation of this requires knowledge of atmospheric
barometric pressure (in mm of Hg), inspired pO2
percentage, and humidity (normally about 50 mm Hg).
Alveolar pCO2 is estimated at approximately 80% of
arterial pCO2. The difference (alveolar pO2 - arterial
pO2) requires knowledge of arterial pO2. Inspired
pCO2 is assumed to be essentially zero and is not
needed in the calculation.

Front 29

A 56-year-old man with papillary thyroid carcinoma had a thyroglobulin level (measured by competitive immunoassay) of 5.7 ng/mL
after total thyroidectomy. A therapeutic dose of radioactive iodine is administered, and a repeat thyroglobulin measurement is performed
4 weeks later and is 5.6 ng/mL. A postablation radioactive iodine scan had been done after the treatment, and no foci of iodine uptake
were identified. What is the most likely interpretation of these results?
a. An ectopic source of thyroglobulin is likely present; a search for another tumor should be performed.
b. No residual thyroid carcinoma is present; these values are within the reference range.
c. Residual thyroid cancer is likely present, and the tumor does not take up iodine indicating a poorly differentiated carcinoma.
d. There was a remnant of normal thyroid tissue present after surgery that was not destroyed by the administered radioactive iodine.
e. The persistent increase in thyroglobulin suggests the presence of thyroglobulin antibodies; if confirmed, thyroglobulin levels should not be
done to follow the patient in the future.

Back 29

e.
Thyroglobulin antibodies are common in the general population and are even more common in persons with thyroid cancer; some
studies suggest as many as one third of those with differentiated thyroid cancer have thyroglobulin antibodies. These antibodies
cause falsely increased thyroglobulin with competitive immunoassay and falsely decreased results with the more commonly used
sandwich immunoassays. The presence of thyroglobulin antibodies invalidates its measurement, preventing its use to monitor
residual thyroid cancer; however, with successful destruction of all thyroid tissue, thyroglobulin antibody titers should fall over
time and ultimately disappear in many cases, so that decrease in titer indicates a good prognosis. After total thyroidectomy, and
especially destruction of any thyroid remnant by radioactive iodine, thyroglobulin levels should be undetectable; reference ranges
from persons who have intact thyroid glands are inappropriate comparison ranges for monitoring a person following total
thyroidectomy. The negative scan indicates that there was no significant residual thyroid tissue, either normal or neoplastic,
remaining. Ectopic production of thyroglobulin is extremely rare and generally only occurs in teratomas (which actually have
thyroid tissue within them).

Front 30

The graph illustrates the difference between results of the old and new methods displayed as a function of the value for
BUN obtained using the current method using a bias (Bland-Altman) plot. Which of the following statements is correct?
a. There is a proportional bias between the new and old methods at values above 20 mg/dL.
b. There is a constant bias of about 3 mg/dL at values below 20 mg/dL.
c. There is a proportional bias of about 3% at values below 20 mg/dL.
d. There is a constant bias of about 1 mg/dL at all values.
e. There is a proportional bias of 2% at all values.

Back 30

b.
Bias (Bland-Altman) plots are the most sensitive way to detect biases, particularly those that occur only in part of the
measurement range. Bias plots can use either the absolute difference or the percent difference. When using either, the goal is to
have the points centered on the zero line, with about half above and half below. Values that are consistently on one side of the
zero line represent bias in that part of the measurement range.