Clinical Chemistry

Front 1

A 55-year-old man presents with acute mental status changes. Electrolytes: Na 137 mmol/L, K 5.1 mmol/L, Cl 87 mmol/L, CO2 42
mmol/L, BUN 18 mmol/L, creatinine 1.3 mg/dL, glucose 92 mg/dL, pH 7.37, pCO2 75 mm Hg, pO2 65 mm Hg.

Back 1

Respiratory acidosis
This is a typical panel of tests in a patient with chronic obstructive lung disease leading to respiratory acidosis that is fairly well
compensated, although pH is at the low end of normal.

Front 2

A 23-year-old woman passed out at work. Electrolytes: Na 139 mmol/L, K 2.1 mmol/L, Cl 90 mmol/L, CO2 39 mmol/L, BUN 21
mmol/L, creatinine 1.0 mg/dL, glucose 75 mg/dL, pH 7.46, pCO2 51 mm Hg, pO2 91 mm Hg.

Back 2

Metabolic alkalosis
These results indicate a metabolic alkalosis, accompanied by hypokalemia; compensation is not complete, so pH is above normal.
Rarely, as in this case, a person with bulimia may have severe enough alkalosis and hypokalemia to require medical attention.

Front 3

A 61-year-old man is admitted with tense ascites and jaundice; asterixis is present. Electrolytes: Na 125 mmol/L, K 2.7 mmol/L, Cl
103 mmol/L, CO2 18 mmol/L, BUN 14 mmol/L, creatinine 1.8 mg/dL, glucose 82 mg/dL, pH 7.46, pCO2 21 mm Hg, pO2 75 mm Hg.

Back 3

Respiratory alkalosis
Persistent respiratory alkalosis occurs in persons with chronic hypoxemia when there is either impaired oxygen exchange across
the alveolar wall (interstitial fibrosis, inflammation, or edema), or with right to left shunting of blood (intrinsic cardiac defects,
pulmonary hypertension, cirrhosis). In this case, the clinical presentation is typical for decompensated chronic liver disease with portal hypertension.

Front 4

A 24-year-old man with a history of depression is found unconscious. Electrolytes: Na 140 mmol/L, K 6.3 mmol/L, Cl 105 mmol/L,
CO2 11 mmol/L, BUN 35 mmol/L, creatinine 2.3 mg/dL, glucose 89 mg/dL, pH 7.16, pCO2 24 mm Hg, pO2 94 mm Hg.

Back 4

Anion gap metabolic acidosis
The anion gap is 24 mmol/L in the presence of a significant decrease in bicarbonate and pH. The history of depression with an
anion gap metabolic acidosis should suggest the possibility of a suicide attempt; common agents to produce metabolic acidosis
include ethylene glycol, methanol, and salicylates.

Front 5

A 54-year-old woman with no prior medical problems is seen for weakness. Electrolytes: Na 137 mmol/L, K 2.5 mmol/L, Cl 111
mmol/L, CO2 17 mmol/L, BUN 15 mmol/L, creatinine 0.9 mg/dL, glucose 86 mg/dL. Urine electrolytes: Na 21 mmol/L, K 7 mmol/L, Cl 75
mmol/L. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to starvation ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 5

d.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (9 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. Hyperventilation due to anxiety does not cause chronic
respiratory alkalosis, and respiratory alkalosis does not typically cause hypokalemia. Type 4 renal tubular acidosis (RTA) causes
hyperkalemia, and can be excluded. While both type 2 RTA and GI losses of bicarbonate can cause non-anion gap metabolic
acidosis with hypokalemia, the urine electrolytes are conclusive: the urine anion gap (the difference between the sum of [Na + K]
and Cl) is typically a positive number in RTA (and respiratory alkalosis) reflecting increased bicarbonate loss, while in GI losses of
bicarbonate the urine anion gap is strongly negative, as in this case. This woman, on further questioning, had chronic diarrhea
and was found to have a large villous adenoma of the colon.

Front 6

A 75-year-old man has a history of diabetes and hypertension. He presents with weakness and lethargy, and peaked T waves are
noted on his ECG. Laboratory results include: Na 135 mmol/L, K 7.2 mmol/L, Cl 109 mmol/L, CO2 16 mmol/L, BUN 45 mmol/L, creatinine
3.2 mg/dL, glucose 246 mg/dL. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to diabetic ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 6

b.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (10 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. While diabetes can cause ketoacidosis, the anion gap should
be increased. Hyperventilation due to anxiety does not cause chronic respiratory alkalosis, and respiratory alkalosis does not
typically cause hyperkalemia. Type 2 renal tubular acidosis and GI bicarbonate losses would be expected to produce hypokalemia.
Type 4 renal tubular acidosis is common in persons with moderate renal insufficiency, particularly that due to diabetes, where
production of renin is often decreased. In this patient, hypertension was treated by an ACE inhibitor (which is also indicated in
diabetes to minimize progression of diabetic nephropathy), but which may exacerbate hyperkalemia and metabolic acidosis in a
few patients.

Front 7

A 61-year-old man is admitted with tense ascites and jaundice; asterixis is present. Electrolytes: Na 125 mmol/L, K 2.7 mmol/L, Cl
103 mmol/L, CO2 18 mmol/L, BUN 14 mmol/L, creatinine 1.8 mg/dL, glucose 82 mg/dL, pH 7.46, pCO2 21 mm Hg, pO2 75 mm Hg.

Back 7

Respiratory alkalosis
Persistent respiratory alkalosis occurs in persons with chronic hypoxemia when there is either impaired oxygen exchange across
the alveolar wall (interstitial fibrosis, inflammation, or edema), or with right to left shunting of blood (intrinsic cardiac defects,
pulmonary hypertension, cirrhosis). In this case, the clinical presentation is typical for decompensated chronic liver disease with portal hypertension.

Front 8

49-year-old man with no prior medical history presented in a coma. Laboratory findings included Na 143 mmol/L, K 5.9 mmol/L, Cl
102 mmol/L, CO2 9 mmol/L, BUN 24 mmol/L, creatinine 1.6 mg/dL, glucose 92 mg/dL. Serum osmolality was 336 mosm/kg. Urine dipstick
was negative. The most likely cause of this picture is:
a. Diabetic ketoacidosis
b. Ethylene glycol ingestion
c. Lactic acidosis
d. Starvation ketoacidosis
e. Uremia

Back 8

b.
The basic metabolic panel shows a low bicarbonate and an anion gap of 22 mmol/L, which is diagnostic for a metabolic acidosis.
All of the choices could cause an increased anion gap, but not an increased osmotic gap. The combination suggests ingestion of
ethylene glycol, methanol, or paraldehyde. Uremia is ruled out by the only minimally increased BUN, while diabetic ketoacidosis is
ruled out by the normal glucose. Starvation ketoacidosis is ruled out by the negative urine dipstick (no ketones are present).
Lactic acidosis does not produce an increased osmotic gap.

Front 9

A 24-year-old man with a history of depression is found unconscious. Electrolytes: Na 140 mmol/L, K 6.3 mmol/L, Cl 105 mmol/L,
CO2 11 mmol/L, BUN 35 mmol/L, creatinine 2.3 mg/dL, glucose 89 mg/dL, pH 7.16, pCO2 24 mm Hg, pO2 94 mm Hg.

Back 9

Anion gap metabolic acidosis
The anion gap is 24 mmol/L in the presence of a significant decrease in bicarbonate and pH. The history of depression with an
anion gap metabolic acidosis should suggest the possibility of a suicide attempt; common agents to produce metabolic acidosis
include ethylene glycol, methanol, and salicylates.

Front 10

A 54-year-old woman with no prior medical problems is seen for weakness. Electrolytes: Na 137 mmol/L, K 2.5 mmol/L, Cl 111
mmol/L, CO2 17 mmol/L, BUN 15 mmol/L, creatinine 0.9 mg/dL, glucose 86 mg/dL. Urine electrolytes: Na 21 mmol/L, K 7 mmol/L, Cl 75
mmol/L. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to starvation ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 10

d.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (9 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. Hyperventilation due to anxiety does not cause chronic
respiratory alkalosis, and respiratory alkalosis does not typically cause hypokalemia. Type 4 renal tubular acidosis (RTA) causes
hyperkalemia, and can be excluded. While both type 2 RTA and GI losses of bicarbonate can cause non-anion gap metabolic
acidosis with hypokalemia, the urine electrolytes are conclusive: the urine anion gap (the difference between the sum of [Na + K]
and Cl) is typically a positive number in RTA (and respiratory alkalosis) reflecting increased bicarbonate loss, while in GI losses of
bicarbonate the urine anion gap is strongly negative, as in this case. This woman, on further questioning, had chronic diarrhea
and was found to have a large villous adenoma of the colon.

Front 11

A 75-year-old man has a history of diabetes and hypertension. He presents with weakness and lethargy, and peaked T waves are
noted on his ECG. Laboratory results include: Na 135 mmol/L, K 7.2 mmol/L, Cl 109 mmol/L, CO2 16 mmol/L, BUN 45 mmol/L, creatinine
3.2 mg/dL, glucose 246 mg/dL. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to diabetic ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 11

b.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (10 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. While diabetes can cause ketoacidosis, the anion gap should
be increased. Hyperventilation due to anxiety does not cause chronic respiratory alkalosis, and respiratory alkalosis does not
typically cause hyperkalemia. Type 2 renal tubular acidosis and GI bicarbonate losses would be expected to produce hypokalemia.
Type 4 renal tubular acidosis is common in persons with moderate renal insufficiency, particularly that due to diabetes, where
production of renin is often decreased. In this patient, hypertension was treated by an ACE inhibitor (which is also indicated in
diabetes to minimize progression of diabetic nephropathy), but which may exacerbate hyperkalemia and metabolic acidosis in a
few patients.

Front 12

49-year-old man with no prior medical history presented in a coma. Laboratory findings included Na 143 mmol/L, K 5.9 mmol/L, Cl
102 mmol/L, CO2 9 mmol/L, BUN 24 mmol/L, creatinine 1.6 mg/dL, glucose 92 mg/dL. Serum osmolality was 336 mosm/kg. Urine dipstick
was negative. The most likely cause of this picture is:
a. Diabetic ketoacidosis
b. Ethylene glycol ingestion
c. Lactic acidosis
d. Starvation ketoacidosis
e. Uremia

Back 12

b.
The basic metabolic panel shows a low bicarbonate and an anion gap of 22 mmol/L, which is diagnostic for a metabolic acidosis.
All of the choices could cause an increased anion gap, but not an increased osmotic gap. The combination suggests ingestion of
ethylene glycol, methanol, or paraldehyde. Uremia is ruled out by the only minimally increased BUN, while diabetic ketoacidosis is
ruled out by the normal glucose. Starvation ketoacidosis is ruled out by the negative urine dipstick (no ketones are present).
Lactic acidosis does not produce an increased osmotic gap.

Front 13

A 61-year-old man is admitted with tense ascites and jaundice; asterixis is present. Electrolytes: Na 125 mmol/L, K 2.7 mmol/L, Cl
103 mmol/L, CO2 18 mmol/L, BUN 14 mmol/L, creatinine 1.8 mg/dL, glucose 82 mg/dL, pH 7.46, pCO2 21 mm Hg, pO2 75 mm Hg.

Back 13

Respiratory alkalosis
Persistent respiratory alkalosis occurs in persons with chronic hypoxemia when there is either impaired oxygen exchange across
the alveolar wall (interstitial fibrosis, inflammation, or edema), or with right to left shunting of blood (intrinsic cardiac defects,
pulmonary hypertension, cirrhosis). In this case, the clinical presentation is typical for decompensated chronic liver disease with portal hypertension.

Front 14

A 24-year-old man with a history of depression is found unconscious. Electrolytes: Na 140 mmol/L, K 6.3 mmol/L, Cl 105 mmol/L,
CO2 11 mmol/L, BUN 35 mmol/L, creatinine 2.3 mg/dL, glucose 89 mg/dL, pH 7.16, pCO2 24 mm Hg, pO2 94 mm Hg.

Back 14

Anion gap metabolic acidosis
The anion gap is 24 mmol/L in the presence of a significant decrease in bicarbonate and pH. The history of depression with an
anion gap metabolic acidosis should suggest the possibility of a suicide attempt; common agents to produce metabolic acidosis
include ethylene glycol, methanol, and salicylates.

Front 15

A 54-year-old woman with no prior medical problems is seen for weakness. Electrolytes: Na 137 mmol/L, K 2.5 mmol/L, Cl 111
mmol/L, CO2 17 mmol/L, BUN 15 mmol/L, creatinine 0.9 mg/dL, glucose 86 mg/dL. Urine electrolytes: Na 21 mmol/L, K 7 mmol/L, Cl 75
mmol/L. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to starvation ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 15

d.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (9 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. Hyperventilation due to anxiety does not cause chronic
respiratory alkalosis, and respiratory alkalosis does not typically cause hypokalemia. Type 4 renal tubular acidosis (RTA) causes
hyperkalemia, and can be excluded. While both type 2 RTA and GI losses of bicarbonate can cause non-anion gap metabolic
acidosis with hypokalemia, the urine electrolytes are conclusive: the urine anion gap (the difference between the sum of [Na + K]
and Cl) is typically a positive number in RTA (and respiratory alkalosis) reflecting increased bicarbonate loss, while in GI losses of
bicarbonate the urine anion gap is strongly negative, as in this case. This woman, on further questioning, had chronic diarrhea
and was found to have a large villous adenoma of the colon.

Front 16

A 75-year-old man has a history of diabetes and hypertension. He presents with weakness and lethargy, and peaked T waves are
noted on his ECG. Laboratory results include: Na 135 mmol/L, K 7.2 mmol/L, Cl 109 mmol/L, CO2 16 mmol/L, BUN 45 mmol/L, creatinine
3.2 mg/dL, glucose 246 mg/dL. The most likely diagnosis is:
a. Anion gap metabolic acidosis due to diabetic ketoacidosis
b. Non-anion gap metabolic acidosis due to type 4 renal tubular acidosis
c. Non-anion gap metabolic acidosis due to type 2 renal tubular acidosis
d. Non-anion gap metabolic acidosis due to GI losses of bicarbonate
e. Respiratory alkalosis due to chronic hyperventilation from anxiety

Back 16

b.
The laboratory results indicate a low bicarbonate and high chloride and a normal anion gap (10 mmol/L), which could either
represent non-anion gap metabolic acidosis or respiratory alkalosis. While diabetes can cause ketoacidosis, the anion gap should
be increased. Hyperventilation due to anxiety does not cause chronic respiratory alkalosis, and respiratory alkalosis does not
typically cause hyperkalemia. Type 2 renal tubular acidosis and GI bicarbonate losses would be expected to produce hypokalemia.
Type 4 renal tubular acidosis is common in persons with moderate renal insufficiency, particularly that due to diabetes, where
production of renin is often decreased. In this patient, hypertension was treated by an ACE inhibitor (which is also indicated in
diabetes to minimize progression of diabetic nephropathy), but which may exacerbate hyperkalemia and metabolic acidosis in a
few patients.

Front 17

49-year-old man with no prior medical history presented in a coma. Laboratory findings included Na 143 mmol/L, K 5.9 mmol/L, Cl
102 mmol/L, CO2 9 mmol/L, BUN 24 mmol/L, creatinine 1.6 mg/dL, glucose 92 mg/dL. Serum osmolality was 336 mosm/kg. Urine dipstick
was negative. The most likely cause of this picture is:
a. Diabetic ketoacidosis
b. Ethylene glycol ingestion
c. Lactic acidosis
d. Starvation ketoacidosis
e. Uremia

Back 17

b.
The basic metabolic panel shows a low bicarbonate and an anion gap of 22 mmol/L, which is diagnostic for a metabolic acidosis.
All of the choices could cause an increased anion gap, but not an increased osmotic gap. The combination suggests ingestion of
ethylene glycol, methanol, or paraldehyde. Uremia is ruled out by the only minimally increased BUN, while diabetic ketoacidosis is
ruled out by the normal glucose. Starvation ketoacidosis is ruled out by the negative urine dipstick (no ketones are present).
Lactic acidosis does not produce an increased osmotic gap.

Front 18

A 63-year-old woman is admitted with severe shortness of breath and hypotension. She is noted to have a respiratory rate of 32
and cyanosis. Laboratory findings include Na 135 mmol/L, K 6.1 mmol/L, Cl 94 mmol/L, CO2 23 mmol/L, BUN 18 mmol/L, creatinine 1.4
mg/dL, glucose 116 mg/dL, pH 7.21, pCO2 65, pO2 71, osmolality 281 mosm/kg. The most likely cause of this laboratory picture is:
a. Diabetic ketoacidosis plus respiratory alkalosis
b. Lactic acidosis plus respiratory acidosis
c. Lactic acidosis plus metabolic alkalosis
d. Metabolic alkalosis plus respiratory alkalosis
e. Uncompensated respiratory acidosis

Back 18

b.
The pH indicates acidemia is present. The increased anion gap (18 mmol/L) indicates the presence of a metabolic acidosis, while
the high pCO2 in an acidemic patient indicates a respiratory acidosis. While a variety of conditions may cause increased anion
gap, the normal glucose rules out diabetic ketoacidosis, while normal osmolality and osmotic gap would rule out an ingestion
(except for salicylates) as a cause. In the setting of hypotension, lactic acidosis is likely. Looked at another way, uncompensated
respiratory acidosis would have low pH, high pCO2, and normal bicarbonate, as seen in this case, but would not give an increased
anion gap.

Front 19

Which of the following would be the likely diagnosis in a patient with an acidosis accompanied by hypochloremia?
a. Diabetic ketoacidosis
b. Diarrhea
c. Lactic acidosis
d. Renal tubular acidosis
e. Respiratory acidosis

Back 19

e.
In all acid-base disorders except for anion gap acidosis, chloride changes in the opposite direction to bicarbonate, but by the
same amount. In metabolic acidosis with a normal anion gap (such as caused by diarrhea or renal tubular acidosis), chloride
would be increased. In anion gap acidosis, chloride is typically normal. The only acidosis with a high bicarbonate, and low
chloride, is respiratory acidosis

Front 20

In a patient with metabolic alkalosis, which of the following findings would suggest mineralocorticoid excess as its cause?
a. Decreased potassium
b. Hypernatremia
c. Increased bicarbonate
d. Increased BUN and creatinine with high BUN/ creatinine ratio
e. Urine chloride of 45 mmol/L

Back 20

e.
The most common causes of metabolic alkalosis are vomiting and dehydration. In these disorders, urine chloride is typically quite
low (below detection limits or ≤10 mmol/L), while mineralocorticoid excess is usually associated with high urine chloride. Low
potassium and increased bicarbonate are seen in all forms of alkalosis. Hypernatremia is rare in mineralocorticoid excess and
most commonly occurs with dehydration, as would increased BUN and creatinine with a high BUN/creatinine ratio.

Front 21

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

Back 21

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 22

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?

Back 22

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 23

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 23

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 24

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 24

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 25

A clinician questions the results on an hCG value on a female patient. She had undergone D & C of a complete hydatidiform mole
approximately six months previously, and had normal hCG levels at another hospital; your lab reported an hCG of 240 IU/mL. The
patient had gone to the other hospital for further treatment, but their laboratory had measured hCG as <0.5 IU/mL. A repeat sample in
your laboratory one month later gave an hCG of 236 IU/mL, but was again negative at the other laboratory. By accident, a technologist in
your laboratory had also performed a PSA on the sample, and a value of 6.2 ng/mL was obtained. Which of the following is the most
likely explanation for these values?
a. Different calibrators are used by the two assays, and this represents common methodological differences in results.
b. Heterophile antibodies are present and are causing false elevations of both PSA and hCG.
c. The sample contains beta core fragment, which is not detected by all serum hCG assays.
d. The sample contains free alpha subunits, a known cause for discrepant results in hCG assays.
e. Tumor recurrence is present, and the tumor is also causing ectopic production of PSA.

Back 25

b.
Heterophile antibodies are a common cause of erroneous results in sandwich immunoassays, which are used to measure most
tumor markers, peptide hormones, cardiac markers, and a number of other compounds. These antibodies react with
immunoglobulins from other species, which may generate a signal in the immunoassay that is read as the presence of the analyte.
While manufacturers take steps to minimize heterophile antibody interference, they vary in their effectiveness (even within different
assays from the same manufacturer), so discrepant results are common in samples containing high titer heterophile antibodies.
While fragments of hCG may also cause discrepant hCG results, they would not explain the positive PSA in a female, and ectopic
PSA production has not been reported in trophoblastic tumors. Use of different calibrators may also cause slight differences
between assays, but not to this degree.

Front 26

Matrix effects:
a. Are most commonly seen with chemical assays for substances such as glucose, urea, and electrolytes
b. Are most commonly seen with tandem mass spectrometric methods
c. Can be prevented by using purified standards rather than calibrators for determining the relationship between concentration and machine
response
d. Describes differences in measured concentration of a substance between samples of different composition that actually have the same
concentration
e. Occur in most methods when aqueous controls are used to evaluate method performance

Back 26

d.
Matrix effects are defined as differences in apparent concentration between samples with different composition (e.g., serum and
urine). Matrix effects are common for substances that are poorly soluble in water (such as lipids) or in which there is a complex
interaction between the sample and the reagents (such as enzyme assays and immunoassays). This creates problems in use of
pure standards, which often have a very different matrix than serum samples. The solution to matrix effects is to use calibrators,
solutions similar in composition to the samples being tested in which the concentration has been determined. Either calibrators or

Front 27

The Beer-Lambert law (Beer's law):
a. Applies only to pure solutions and cannot be used in biologic samples
b. Can be expressed by the formula A = abc, where A is absorbance, a is a constant for the compound, b is path length, and c is
concentration
c. Describes the direct relationship between amount of light transmitted through a solution and the concentration of a substance present
d. Is used to determine the amount of current needed to produce adequate separation of compounds in an electrophoretic apparatus
e. Represents the relationship between number of drinks and blood alcohol concentration

Back 27

b.
The Beer-Lambert law is the basis for photometric measurement, which is the underlying principle for most chemical assays. It
describes a linear relationship between amount of light absorbed and the concentration of a compound in a solution. While
biologic samples have a variety of other compounds within them, use of chemical reactions specific for the compound of interest
allows use of this relationship in the clinical laboratory. Transmittance has an inverse relationship to absorbance (light that was
not absorbed is transmitted through a solution), so there is an inverse relationship between transmittance and concentration.

Front 28

In evaluating method performance, which of the following terms and corresponding method of determination is defined
INCORRECTLY?
a. Carryover - running a low sample before and after a very high sample
b. Linearity - use of samples with known concentration and comparison of measured concentration to known concentration
c. Precision - multiple measurements of the same sample
d. Sensitivity - multiple measurements of the zero calibrator or standard
e. Within-run variation - comparison of results from the same sample over the course of 2 weeks, using the same calibrators

Back 28

e.
Within-run variation is a measure of repeatability of results over a single set-up of an instrument, typically during the course of a
single shift, when a single operator sets up the instrument and performs a group of tests. The description given would apply to
betweenrun variation, which is generally a larger number.

Front 29

Coefficient of variation:
a. Can be calculated by measuring samples from multiple persons used for reference range studies
b. Defines the variation observed in a person over a period of time
c. Is calculated as (standard deviation * 100)/mean value
d. Should typically be about 5% for serum sodium
e. Should typically be about 10% for serum glucose

Back 29

c.
Coefficient of variation is a measure of the repeatability for a test, calculated as the percentage of the mean represented by the
standard deviation of measurement. It is calculated by making multiple measurements of the same sample, either a control or a
single patient. Coefficient of variation should be for electrolyte measurements, and in general is in the range of 2% to 5% for most
tests. However, it may be as much as 10% for enzyme activity measurements, measurement of substances in very low
concentrations, and for some immunoassays. For very complicated assays, it may be even higher. It is ideal that measurement
variation be significantly lower than the variation within a person over time, so that changes in condition can be detected as
changes in laboratory test results.

Front 30

Comparing nephelometry and turbidimetry, which of the following statements is INCORRECT?
a. Both are most often used in the laboratory to measure antigen-antibody complexes to determine the amount of an antigen present.
b. Both are typically performed on large analyzers used for routine clinical chemistry testing.
c. In nephelometry, the detector is at an angle to the incident light.
d. In turbidimetry, the detector is in a straight line with the incident light.
e. Triglycerides are a major source of interference with both measurement principles.

Back 30

b.
Turbidimetry and nephelometry are often used to measure the amounts of antigens (often proteins) that are present in
concentrations of mg/dL or higher by measuring the number of antigen-antibody complexes present. The complexes form particles
that prevent light from traveling in a straight line to a detector, instead causing the photons to be sent off at an angle to the
incident light. This produces turbidity in a solution. Turbidimetry measures the decrease in light in the straight line path from the
light source to the detector, while nephelometry places a detector at an angle to the incident light and measures the amount
reaching the detector. Common applications are measurement of immunoglobulins, C-reactive protein, haptoglobin, and hemoglobin
A1c. Anything else that causes turbidity in a sample, most commonly triglycerides, will interfere with measurement. Turbidimetry
can be run using the same instrumental setup as spectrophotometry, which is used for most routine chemistry tests;
nephelometry requires an instrument with a detector at an angle to the light source and is commonly done on dedicated
instruments.

Front 31

A patient with metastatic prostate cancer has an initial PSA measurement of 345.7 ng/mL. After his first course of chemotherapy, a
repeat sample has a PSA result of 952 ng/mL. The oncologist questions the initial PSA result. When the initial sample is retrieved (it had
been stored frozen) and run in dilution, the PSA result on the 1:10 dilution is 1157 ng/mL, yielding an apparent PSA concentration in the
initial sample of 11,570 ng/mL. The second sample is also run in a 1:10 dilution, with a result of 96.3 ng/mL. What is the most likely
explanation for the initial result on the first sample?
a. A high-dose hook effect was present, causing falsely low formation of antigen-antibody complexes in the presence of very large amounts
of antigen.
b. An inhibitor of PSA's enzymatic activity was present, but was removed by dilution.
c. Heterophile antibodies were present in the initial sample, causing falsely low results, but the antibody was removed by sample dilution.
d. The high enzymatic activity of PSA caused substrate depletion, which resulted in a falsely low activity measurement.
e. The technologist performing the initial run mixedup the samples, and ran the wrong patient.

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a.
High-dose hook effect is seen in immunometric assays for substances that have very large ranges of concentration, most
commonly tumor markers. When the range of assay concentration seen in samples exceeds 4-5 logs (for PSA, from <0.05 to over
5000, for example), there is the possibility of such an effect occurring. Since what is measured in immunometric assays is the
number of antigen-antibody complexes, and this decreases with great antigen excess, a falsely low concentration results. Such
samples can have extremely low apparent concentrations when the result is 6-7 logs above the usual measured concentration
(e.g., for hCG measurements). PSA is not measured by its enzymatic activity, so those choices could not be correct. Heterophile
antibodies typically cause falsely increased results, and would not be expected to disappear in the short period of time between
diagnosis and first round of chemotherapy. While sample mix-up is always a possibility, it would be unusual to have another
patient with the very high PSA value seen in the initial result.