MLS Review Harr: Clinical Chemistry

In most circumstances, when two controls within a run are both greater than ±2s from the mean, what action should be taken first? A. Recalibrate, then repeat controls followed by selected patient samples if quality control is acceptable B. Repeat the controls before taking any corrective action C. Change the reagent lot, then recalibrate D. Prepare fresh standards and recalibrate

A When a 22s rule is broken an SE is present and corrective action is required (repeating just the QC will not correct the problem). If recalibration yields acceptable QC results, both sets of QC results and the corrective action taken are documented in the QC log. If the magnitude of the error is large enough to be medically significant, then all patient samples since the last previously acceptable QC should be repeated. If in question, the magnitude of the error can be evaluated by repeating abnormal patient samples. If the average difference between results before and after recalibration is > 2s, then all samples should be repeated since the last acceptable QC.

Which of the following quality control (QC) rules would be broken 1 out of 20 times by chance alone? A. 12s B. 22s C. 13s D. 14s

A. 12s A The notation 12S means that one control is outside ±2 standard deviation units. QC results follow the bellshaped curve called the Gaussian (normal) distribution. If a control is assayed 100 times, 68 out of 100 results would fall within +1 s and -1 s of the mean. Ninetyfive (95.4) out of 100 results would fall within +2 s and -2 s. This leaves only 5 out of 100 results (1:20) that fall outside the ±2 s limit. Also, 99.7 out of 100 results fall within ±3 s of the mean.

Given the following data, calculate the coefficient of variation for glucose. Analyte / Mean / Std Deviation Glucose / 76mg/dL / 2.3 A. 3.0% B. 4.6% C. 7.6% D. 33.0%

A. 3.0% A The coefficient of variation is calculated by dividing the standard deviation by the mean and multiplying by 100. % CV = s/X × 100 = 2.3/76 × 100 = 3.0% The CV is the most appropriate statistic to use when comparing the precision of samples that have different means. For example, when comparing the precision of the level 1 control to the level 2 control, the coefficient of variation normalizes the variance to be independent of the mean. The control with the lower CV is the one for which the analysis is more precise.

What is the recommended cutoff for the early detection of chronic kidney disease in diabetics using the test for microalbuminuria? A. >30 mg/g creatinine B. >80 mg/g creatinine C. >200 mg/g creatinine D. >80 mg/L

A. >30 mg/g creatinine A Microalbuminuria is the excretion of small quantities of albumin in the urine. In diabetics, excretion of albumin that is within allowable limits for healthy persons may signal the onset of chronic kidney disease. The term microalbuminuria is defined as albumin excretion ≥ 30 mg/g creatinine but ≤ 300 mg/g creatinine. The use of the albumin to creatinine ratio is preferred to measures of albumin excretory rate (μg/min) because the latter is subject to error associated with timed specimen collection. ADA recommends the test be done annually for all type 2 diabetics and type 1 diabetics who have had the disease for > 5 years

Bilirubin is transported from reticuloendothelial cells to the liver by: A. Albumin B. Bilirubin-binding globulin C. Haptoglobin D. Transferrin

A. Albumin A Albumin transports bilirubin, haptoglobin transports free Hgb, and transferrin transports ferric iron. When albumin binding is exceeded, unbound bilirubin, called free bilirubin, increases. This may cross the blood-brain barrier, resulting in kernicterus.

Which of the following statements regarding the TIBC assay is correct? A. All TIBC methods require addition of excess iron to saturate transferrin B. All methods require the removal of unbound iron C. Measurement of TIBC is specific for transferrin-bound iron D. The chromogen used must be different from the one used for measuring serum iron

A. All TIBC methods require addition of excess iron to saturate transferrin A All TIBC methods require addition of excess iron to saturate transferrin. Excess iron is removed by ion exchange or alumina gel columns or precipitation with MgCO3 and the bound iron is measured by the same procedure as is used for serum iron. Alternatively, excess iron in the reduced state can be added at an alkaline pH. Under these conditions, transferrin will bind Fe2+ and the unbound Fe2+ can be measured directly.

Which statement regarding bilirubin metabolism is true? A. Bilirubin undergoes rapid photo-oxidation when exposed to daylight B. Bilirubin excretion is inhibited by barbiturates C. Bilirubin excretion is increased by chlorpromazine D. Bilirubin is excreted only as the diglucuronide

A. Bilirubin undergoes rapid photo-oxidation when exposed to daylight A Samples for bilirubin analysis must be protected from direct sunlight. Drugs may have a significant in vivo effect on bilirubin levels. Barbiturates lower serum bilirubin by increasing excretion. Other drugs that cause cholestasis, such as chlorpromazine, increase the serum bilirubin. Although most conjugated bilirubin is in the form of diglucuronide, some monoglucuronide and other glycosides are excreted. In glucuronyl transferase deficiency, some bilirubin is excreted as sulfatides.

Which of the following assays has the poorest precision? Analyte / Mean (mmol/L) / Std Deviation A. Ca / 2.5 / 0.3 B. K / 4.0 / 0/4 C. Na / 140 / 4.0 D. Cl / 100 / 2.5

A. Ca / 2.5 / 0.3 A Although calcium has the lowest s, it represents the assay with poorest precision. Relative precision between different analytes or different levels of the same analyte must be evaluated by the coefficient of variation (CV) because standard deviation is dependent upon the mean. CV = s × 100/Mean. This normalizes standard deviation to a mean of 100. The CV for calcium in the example is 12.0%.

A trend in QC results is most likely caused by: A. Deterioration of the reagent B. Miscalibration of the instrument C. Improper dilution of standards D. Electronic noise

A. Deterioration of the reagentA A trend occurs when six or more consecutive quality control results either increase or decrease in the same direction; however, this is not cause for rejection until a multirule is broken. Trends are systematic errors (affecting accuracy) linked to an unstable reagent, calibrator, or instrument condition. For example, loss of volatile acid from a reagent causes a steady pH increase, preventing separation of analyte from protein. This results in lower QC results each day.

Which of the following statements about carbohydrate intolerance is true? A. Galactosemia results from deficiency of galactose-1-phosphate (galactose-1-PO4) uridine diphosphate transferase B. Galactosemia results in a positive glucose oxidase test for glucose in urine C. Urinary galactose is seen in both galactosemia and lactase deficiency D. A galactose tolerance test is used to confirm a diagnosis of galactosemia

A. Galactosemia results from deficiency of galactose-1-phosphate (galactose-1-PO4) uridine diphosphate transferase A Galactose is metabolized to galactose-1-PO4 by the action of galactokinase. Galactose-1-PO4 uridine diphosphate (UDP) transferase converts galactose-1-PO4 to glucose. Deficiency of either enzyme causes elevated blood and urine galactose. Lactase deficiency results in the presence of urinary lactose because it is not broken down to glucose and galactose. Tests for reducing sugars employing copper sulfate are used to screen for galactose, lactose, and fructose in urine. Nonglucose-reducing sugars are not detected by the glucose oxidase reaction. A positive test is followed by TLC to identify the sugar, and demonstration of the enzyme deficiency in RBCs. The galactose tolerance test is used (rarely) to evaluate the extent of liver failure since the liver is the site of galactose metabolism.

Identify the enzyme deficiency responsible for type 1 glycogen storage disease (von Gierke's disease). A. Glucose-6-phosphatase B. Glycogen phosphorylase C. Glycogen synthetase D. β-Glucosidase

A. Glucose-6-phosphatase A Type 1 glycogen storage disease (von Gierke's disease) is an autosomal recessive deficiency of glucose-6 phosphatase. Glycogen accumulates in tissues, causing hypoglycemia, ketosis, and fatty liver. There are seven types of glycogen storage disease, designated type 1 through type 7, involving deficiency of an enzyme that acts on glycogen. Types 1, 4, and 6 cause deficient glycogen breakdown in the liver. Types 2, 5, and 7 involve skeletal muscle and are less severe. Type 3 usually involves both liver and muscle, although an uncommon subtype (3B) involves only the liver

Select the coupling enzyme used in the hexokinase method for glucose. A. Glucose-6-phosphate dehydrogenase B. Peroxidase C. Glucose dehydrogenase D. Glucose-6-phosphatase

A. Glucose-6-phosphate dehydrogenase A The hexokinase reference method uses a protein-free filtrate prepared with barium hydroxide (BaOH) and zinc sulfate (ZnSO4). Hexokinase catalyzes the phosphorylation of glucose in the filtrate using ATP as the phosphate donor. Glucose-6-phosphate (glucose-6-PO4) is oxidized to 6-phosphogluconate and NAD+ is reduced to NADH using G-6-PD. The increase in absorbance at 340 nm is proportional to glucose concentration. Although hexokinase will phosphorylate some other hexoses including mannose, fructose, and glucosamine, the coupling reaction is entirely specific for glucose-6-PO4 eliminating interference from other sugars.

Which of the following would cause an increase in only the unconjugated bilirubin? A. Hemolytic anemia B. Obstructive jaundice C. Hepatitis D. Hepatic cirrhosis

A. Hemolytic anemia A Conjugated bilirubin increases as a result of obstructive processes within the liver or biliary system or from failure of the enterohepatic circulation. Hemolytic anemia (prehepatic jaundice) presents a greater bilirubin load to a normal liver, resulting in increased bilirubin excretion. When the rate of bilirubin formation exceeds the rate of excretion, the unconjugated bilirubin rises.

A neonatal bilirubin assay performed at the nursery by bichromatic direct spectrophotometry is 4.0 mg/dL. Four hours later, a second sample assayed for total bilirubin by the Jendrassik-Grof method gives a result of 3.0 mg/dL. Both samples are reported to be hemolyzed. What is the most likely explanation of these results? A. Hgb interference in the second assay B. δ-Bilirubin contributing to the result of the first assay C. Falsely high results from the first assay caused by direct bilirubin D. Physiological variation owing to premature hepatic microsomal enzymes

A. Hgb interference in the second assay A The Jendrassik-Grof method is based upon a diazo reaction that may be suppressed by Hgb. Because serum blanking and measurement at 600 nm correct for positive interference from Hgb, the results may be falsely low when significant hemolysis is present. Direct spectrophometric bilirubin methods employing bichromatic optics correct for the presence of Hgb. These are often called "neonatal bilirubin" tests. A commonly used approach is to measure absorbance at 454 nm and 540 nm. The absorbance contributed by Hgb at 540 nm is equal to the absorbance contributed by Hgb at 454 nm. Therefore, the absorbance difference will correct for free Hgb. Neonatal samples contain little or no direct δ-bilirubin. They also lack carotene pigments that could interfere with the direct spectrophotometric measurement of bilirubin.

Which of the following is associated with low serum iron and high total iron-binding capacity (TIBC)? A. Iron deficiency anemia B. Hepatitis C. Nephrosis D. Noniron deficiency anemias

A. Iron deficiency anemia A Iron-deficiency anemia is the principal cause of low serum iron and high TIBC because it promotes increased transferrin. Pregnancy without iron supplementation depletes maternal iron stores and also results in low serum iron and high TIBC. Iron-supplemented pregnancy and use of contraceptives increase both iron and TIBC. Nephrosis causes low iron and TIBC due to loss of both iron and transferrin by the kidneys. Hepatitis causes increased release of storage iron, resulting in high levels of iron and transferrin. Noniron deficiency anemias may cause high iron and usually show low TIBC and normal or high ferritin.

Which of the following statements regarding urobilinogen is true? A. It is formed in the intestines by bacterial reduction of bilirubin B. It consists of a single water-soluble bile pigment C. It is measured by its reaction with p-aminosalicylate D. In hemolytic anemia, it is decreased in urine and feces

A. It is formed in the intestines by bacterial reduction of bilirubin A Urobilinogen is a collective term given to the reduction products of bilirubin formed by the action of enteric bacteria. Urobilinogen excretion is increased in extravascular hemolytic anemias and decreased in obstructive jaundice (cholestatic disease). Urobilinogen is measured using Ehrlich's reagent, an acid solution of p-dimethylaminobenzaldehyde.

Which of the following is a characteristic of conjugated bilirubin? A. It is water soluble B. It reacts more slowly than unconjugated bilirubin C. It is more stable than unconjugated bilirubin D. It has the same absorbance properties as unconjugated bilirubin

A. It is water soluble A Conjugated bilirubin refers to bilirubin mono- and diglucuronides. Conjugated bilirubin reacts almost immediately with the aqueous diazo reagent without need for a nonpolar solvent. Historically, conjugated bilirubin has been used synonymously with direct-reacting bilirubin, although the latter includes the δ-bilirubin fraction when measured by the Jendrassik-Grof method. Conjugated bilirubin is excreted in both bile and urine. It is easily photo-oxidized and has very limited stability. For this reason, bilirubin standards are usually prepared from unconjugated bilirubin stabilized by the addition of alkali and albumin.

Which statement about glucose in cerebrospinal fluid (CSF) is correct? A. Levels below 40 mg/dL occur in septic meningitis, cancer, and multiple sclerosis B. CSF glucose is normally the same as the plasma glucose level C. Hyperglycorrhachia is caused by dehydration D. In some clinical conditions, the CSF glucose can be greater than the plasma glucose

A. Levels below 40 mg/dL occur in septic meningitis, cancer, and multiple sclerosis A High glucose in CSF is a reflection of hyperglycemia and not central nervous system disease. The CSF glucose is usually 50%-65% of the plasma glucose. Low levels are significant and are most often associated with bacterial or fungal meningitis, malignancy in the central nervous system, and some cases of subarachnoid hemorrhage, rheumatoid arthritis, and multiple sclerosis.

Which statement regarding measurement of Hgb A1c is true? A. Levels do not need to be done fasting B. Both the labile and stable Hgb A1c fractions are measured C. Samples should be measured within 2 hours of collection D. The assay must be done by chromatography

A. Levels do not need to be done fasting A Since Hgb A1C represents the average blood glucose 2-3 months prior to blood collection, the dietary status of the patient on the day of the test has no effect upon the results. Refrigerated whole-blood samples are stable for up to 1 week. Hgb A1C is assayed by cation exchange high-performance liquid chromatography or immunoassay (immunoturbidimetric inhibition) because both methods are specific for stable Hgb A1C, and do not demonstrate errors caused by abnormal hemoglobins, temperature of reagents, or fractions other than A1c.

Which of the following plots is best for detecting all types of QC errors? A. Levy-Jennings B. Tonks-Youden C. Cusum D. Linear regression

A. Levy-Jennings A The Levy-Jennings plot is a graph of all QC results with concentration plotted on the y axis and run number on the x axis. The mean is at the center of the y axis, and concentrations corresponding to -2 and +2s are highlighted. Results are evaluated for multirule violations across both levels and runs. Corrective action for shifts and trends can be taken before QC rules are broken.

The D-xylose absorption test is used for the differential diagnosis of which two diseases? A. Pancreatic insufficiency from malabsorption B. Primary from secondary disorders of glycogen synthesis C. Type 1 and type 2 diabetes mellitus D. Generalized from specific carbohydrate intolerance

A. Pancreatic insufficiency from malabsorption A Xylose is a pentose that is absorbed without the help of pancreatic enzymes and is not metabolized. In normal adults, more than 25% of the dose is excreted into the urine after 5 hours. Low blood or urine levels are seen in malabsorption syndrome, sprue, Crohn's disease, and other intestinal disorders, but not pancreatitis.

One of two controls within a run is above +2s and the other control is below -2s from the mean. What do these results indicate? A. Poor precision has led to random error (RE) B. A systematic error (SE) is present C. Proportional error is present D. QC material is contaminated

A. Poor precision has led to random error (RE) A When control results deviate from the mean in opposite directions, the run is affected by RE, which results from imprecision. An analytical run is rejected when two controls within the same run have an algebraic difference in excess of 4s (R4s). The R4S rule is applied only to controls within a run (Level 1 - Level 2), never across runs or days.

When referring to quality control (QC) results, what parameter usually determines the acceptable range? A. The 95% confidence interval for the mean B. The range that includes 50% of the results C. The central 68% of results D. The range encompassed by ±2.5 standard deviations

A. The 95% confidence interval for the mean A The acceptable range for quality control results is usually set at the 95% confidence interval. This is defined as the range between -1.96s and +1.96s. This means that we can expect a QC result to fall within this range 95 out of 100 times. For practical purposes, this is the same as ±2 s (95.4 out of 100 results should fall within ±2 s of the mean on the basis of chance).

Which of the following is a characteristic of obstructive jaundice? A. The ratio of direct to total bilirubin is greater than 1:2 B. Conjugated bilirubin is elevated, but unconjugated bilirubin is normal C. Urinary urobilinogen is increased D. Urinary bilirubin is normal

A. The ratio of direct to total bilirubin is greater than 1:2 A Obstruction prevents conjugated bilirubin from reaching the intestine, resulting in decreased production, excretion, and absorption of urobilinogen. Conjugated bilirubin regurgitates into sinusoidal blood and enters the general circulation via the hepatic vein. The level of serum direct (conjugated) bilirubin becomes greater than unconjugated bilirubin. The unconjugated form is also increased because of accompanying necrosis, deconjugation, and inhibition of UDP-glucuronyl transferase

Which statement regarding total and direct bilirubin levels is true? A. Total bilirubin level is a less sensitive and specific marker of liver disease than the direct level B. Direct bilirubin exceeds 3.5 mg/dL in most cases of hemolytic anemia C. Direct bilirubin is normal in cholestatic liver disease D. The ratio of direct to total bilirubin exceeds 0.40 in hemolytic anemia

A. Total bilirubin level is a less sensitive and specific marker of liver disease than the direct leve A Direct bilirubin measurement is a sensitive and specific marker for hepatic and posthepatic jaundice because it is not elevated by hemolytic anemia. In hemolytic anemia, the total bilirubin does not exceed 3.5 mg/dL, and the ratio of direct to total is less than 0.20. Unconjugated bilirubin is the major fraction in necrotic liver disease because microsomal enzymes are lost. Unconjugated bilirubin is elevated along with direct bilirubin in cholestasis because some necrosis takes place and some conjugated bilirubin is hydrolyzed back to unconjugated bilirubin.

Which of the following conditions is cause for rejecting an analytical run? A. Two consecutive controls greater than 2 s above or below the mean B. Tree consecutive controls greater than 1 s above the mean C. Four controls steadily increasing in value but less than ±1 s from the mean D. One control above +1 s and the other below -1 s from the mean

A. Two consecutive controls greater than 2 s above or below the mean A Rejecting a run when three consecutive controls fall between 1 and 2 s or when a trend of four increasing or decreasing control results occurs would lead to frequent rejection of valid analytical runs. Appropriate control limits are four consecutive controls above or below 1 s (41s ) to detect a significant shift, and a cusum result exceeding the ±2.7 s limit to detect a significant shift or trend. When controls deviate in opposite directions, the difference should exceed 4s before the run is rejected.

In the enzymatic assay of bilirubin, how is measurement of both total and direct bilirubin accomplished? A. Using different pH for total and direct assays B. Using UDP glucuronyl transferase and bilirubin reductase C. Using different polarity modifiers D. Measuring the rate of absorbance decrease at different time intervals

A. Using different pH for total and direct assays A Enzymatic methods use bilirubin oxidase to convert bilirubin back to biliverdin, and measure the decrease in absorbance that results. At pH 8, both conjugated, unconjugated, and delta bilirubin react with the enzyme, but at pH 4 only the conjugated form reacts.

What is the pH of a solution of HNO3, if the hydrogen ion concentration is 2.5 × 10-2 M? A. 1.0 B. 1.6 C. 2.5 D. 2.8

B. 1.6 B For a strong acid, the pH is equal to the negativelogarithm of the hydrogen ion concentration. pH = -Log H+ pH = -Log 0.025 pH = 1.6

According to American Diabetes Association criteria, which result is consistent with a diagnosis of impaired fasting glucose? A. 99 mg/dL B. 117 mg/dL C. 126 mg/dL D. 135 mg/dL

B. 117 mg/dL B Impaired fasting glucose is defined as a plasma glucose ≥100 but <126 mg/dL. A fasting glucose of 126 or higher on two consecutive occasions indicates diabetes. A fasting glucose of 99 mg/dL is considered normal.

A glycerol kinase method for triglyceride calls for a serum blank in which normal saline is substituted for lipase in order to measure endogenous glycerol. Given the following results, and assuming the same volume of sample and reagent are used for each test, calculate the triglyceride concentration in the patient's sample. Std Concentration : 125mg/dL Absorbance of RB: 0.000 Abs of Std: 0.62 Abs of Pt Serum: 0.750 Abs of Serum Blank: 0.100 A. 119 mg/dL B. 131 mg/dL C. 156 mg/dL D. 180 mg/dL

B. 131 mg/dL B The serum blank absorbance is subtracted from the result for the patient's serum before applying the ratiometric formula to calculate concentration. Cu = [(Au - ASB)/As] × Cs where ASB = absorbance of serum blank = (0.750-0.100)/0.620 × 125 mg/dL = 131 mg/dL

A procedure for cholesterol is calibrated with a serum-based cholesterol standard that was determined by the Abell-Kendall method to be 200.0 mg/dL. Assuming the same volume of sample and reagent are used, calculate the cholesterol concentration in the patient's sample from the following results. Standard Concentration /Absorbance of Reagent Blank / Absorbance of Standard/ Absorbance of Patient Serum 200 mg/dL/ 0.00 /0.860/ 0.740 A. 123 mg/dL B. 172 mg/dL C. 232 mg/dL D. 314 mg/dL

B. 172 mg/dL B Cu = Au/As × Cs where Cu = concentration of unknown, Au = absorbance of unknown, As = absorbance of standard, and Cs = concentration of standard. Cu = 0.740/0.860 × 200 mg/dL = 172 mg/dL

How many significant figures should be reported when the pH of a 0.060 M solution of nitric acid is calculated? A. 1 B. 2 C. 3 D. 4

B. 2 B When zeros appear by themselves to the left of the decimal point, they are not significant. When they are to the left of the decimal point and are preceded by a number, they are significant. Zeros after the decimal point preceding a number are not significant. However, they are significant if they follow another number or are between two numbers. Therefore, 0.060 M has only two significant figures (the underlined digits). In laboratory practice, most analytes are reported with two significant figures. Routine analytes that are exceptions are pH, which includes three significant figures, and analytes with whole numbers above 100 such as sodium, cholesterol, triglycerides, and glucose

What is the pH of a buffer containing 40.0 mmol/L NaHC2O4 and 4.0 mmol/L H2C2O4? (pKa = 1.25) A. 1.35 B. 2.25 C. 5.75 D. 6.12

B. 2.25 B The Henderson-Hasselbalch equation can be used to determine the pH of a buffer containing a weak acid and a salt of the acid. pH = pKa + log salt / Acid = 1.25 + log 40.0 mmol/L / 4.0 mmol/L = 1.25 + log 10 = 2.25

A solvent needed for HPLC requires a 20.0 mmol/L phosphoric acid buffer, pH 3.50, made by mixing KH2PO4 and H3PO4. How many grams of KH2PO4 are required to make 1.0 L of this buffer? Formula weights: KH2PO4 = 136.1; H3PO4 = 98.0; pKa H3PO4 = 2.12 A. 1.96 g B. 2.61 g C. 2.72 g D. 19.2 g

B. 2.61 g B The Henderson-Hasselbalch equation is used to calculate the ratio of salt to acid needed to give a pH of 3.50. pH = pKa + log(salt/acid) 3.50 = 2.12 + log(KH2PO4/H3PO4) 1.38 = log(KH2PO4/H3PO4) antilog 1.38 = KH2PO4/H3PO4 KH2PO4/H3PO4 = 23.99 Rearranging gives KH2PO4 = 23.99 × H3PO4. Because the phosphate in the buffer is 20.0 mmol/L, then H3PO4 + KH2PO4 must equal 20. Because KH2PO4 = 23.99 × H3PO4 then: H3PO4 + (23.99 × H3PO4) = 20.0 mmol/L 24.99 × H3PO4 = 20.0 mmol/L H3PO4 = 20.0/24.99 = 0.800 mmol/L KH2PO4 = 20.0-0.800 = 19.2 mmol/L (0.0192 M)

What is the pH of a 0.05 M solution of acetic acid? Ka = 1.75 × 10-5, pKa = 4.76 A. 1.7 B. 3.0 C. 4.3 D. 4.6

B. 3.0 B Weak acids are not completely ionized, and pH must be calculated from the dissociation constant of the acid (in this case 1.75 × 10-5). Ka = [H+] × [Ac-]/[HAc] 1.75 x 10^-5 = [H+] × [Ac-]/5.0 x 10^-2 Since [H+] = [Ac-] X2 = (1.75 × 10^-5 ) × (5.0 × 10^-2 ) = 8.75 × 10^-7 x = √8.75 × 10^-7 = [H+] = 9.35 × 10^-4 M pH = -Log 9.35 × 10^-4 M = 3.0 Alternatively, pH = 1/2 (pKa - Log HA) pH = 1/2 (4.76 - Log 5.0 × 10^-2) = 1/2 (4.76 + 1.30) = 3.0

What is the American Diabetes Association recommended cutoff value for adequate control of blood glucose in diabetics as measured by glycated hemoglobin? A. 5% B. 6.5% C. 9.5% D. 11%

B. 6.5% B The ADA recommends that 6.5% be used as the cutoff for determining the adequacy of treatment for diabetes. A glycated hemoglobin test should be performed at the time of diagnosis and every 6 months thereafter if the result is < 6.5%. If the result is 6.5% or more, the treatment plan should be adjusted to achieve a lower level, and the test performed every 3 months until control is improved.

How many milliliters of a 2,000.0 mg/dL glucose stock solution are needed to prepare 100.0 mL of a 150.0 mg/dL glucose working standard? A. 1.5 mL B. 7.5 mL C. 15.0 mL D. 25.0 mL

B. 7.5 mL B To calculate the volume of stock solution needed, divide the concentration of working standard by the concentration of stock standard, then multiply by the volume of working standard that is needed. C1 × V1 = C2 × V2, where C1 = concentration of stock standard V1 = volume of stock standard C2 = concentration of working standard V2 = volume of working standard 2000.0 mg/dL × V1 = 150.0 mg/dL × 100.0 mL V1 = (150.0 ÷ 2000.0) × 100.0 mL V1 = 7.5 mL

Point-of-care-tests (POCTs) for whole-blood glucose monitoring are based mainly on the use of: A. Glucose oxidase as the enzyme B. Amperometric detection C. Immunochromatography D. Peroxidase coupling reactions

B. Amperometric detection B All POCT devices for monitoring blood glucose use either glucose dehydrogenase (GDH) or glucose oxidase and are amperometric. For glucose oxidase methods, the electrons derive from the oxidation of hydrogen peroxide. For GDH, the electrons are transferred from one of several coenzymes that are reduced when glucose is oxidized, FAD+, NAD+, or PQQ (pyrroloquinoline quinone). Interferences depend upon which enzyme/coenzyme pair are used. For example, maltose and xylose interference can be pronounced with GDH/PQQ-based strips, but not with other GDH or glucose oxidase strips. Uric acid depresses glucose oxidase reactions but has no effect on GDH reactions.

Which of the following processes occurs when iron is in the oxidized (Fe3+) state? A. Absorption by intestinal epithelium B. Binding to transferrin and incorporation into ferritin C. Incorporation into protoporphyrin IX to form functional heme D. Reaction with chromogens in colorimetric assays

B. Binding to transferrin and incorporation into ferritin B Intestinal absorption occurs only if the iron is in the reduced (Fe+2) state. After absorption, Fe+2 is oxidized to Fe+3 by gut mucosal cells. Transferrin and ferritin bind iron efficiently only when in the oxidized state. Iron within Hgb binds to O2 by coordinate bonding, which occurs only if the iron is in the reduced state. Likewise, in colorimetric methods, Fe+2 forms coordinate bonds with carbon and nitrogen atoms of the chromogen.

When preparing a patient for an oral glucose tolerance test (OGTT), which of the following conditions will lead to erroneous results? A. The patient remains ambulatory for 3 days prior to the test B. Carbohydrate intake is restricted to below 150 g/day for 3 days prior to test C. No food, coffee, tea, or smoking is allowed 8 hours before and during the test D. Administration of 75 g of glucose is given to an adult patient following a 10-12-hour fast

B. Carbohydrate intake is restricted to below 150 g/day for 3 days prior to test B Standardized OGTTs require that patients receive at least 150 grams of carbohydrate per day for 3 days prior to the test in order to stabilize the synthesis of inducible glycolytic enzymes. The 2-hour OGTT test is no longer recommended for screening and should be reserved for confirmation of diabetes in cases that are difficult to diagnose, such as persons who lack symptoms and signs of fasting hyperglycemia.

Which stationary phase is used for the measurement of hemoglobin A1c by high performance liquid chromatography? A. Octadecylsilane (C18) B. Cation exchanger C. Anion exchanger D. Polystyrene divinylbenzene

B. Cation exchanger B HPLC methods for measuring Hgb A1c are performed by diluting whole blood with an acid buffer that hemolyzes the sample. Normal hemoglobin A has a weak positive charge at an acidic pH and binds weakly to the resin. Glycated hemoglobin has an even weaker positive charge and is eluted before hemoglobin A. Abnormal hemoglobin molecules S, D, E, and C have a higher positive charge than hemoglobin A and are retained longer on the column. Elution is accomplished by increasing the ionic strength of the mobile phase. Cations in the buffer displace the hemoglobin pigments from the column.

Which statement about iron methods is true? A. Interference from Hgb can be corrected by a serum blank B. Colorimetric methods measure binding of Fe2+ to a ligand such as ferrozine C. Atomic absorption is the method of choice for measurement of serum iron D. Serum iron can be measured by potentiometry

B. Colorimetric methods measure binding of Fe2+ to a ligand such as ferrozine B Atomic absorption is not the method of choice for serum iron because matrix error and variation of iron recovered by extraction cause bias and poor precision. Most methods use HCl to deconjugate Fe3+ from transferrin followed by reduction to Fe2+. This reacts with a neutral ligand such as ferrozine, tripyridyltriazine (TPTZ), or bathophenanthroline to give a blue complex. Anodic stripping voltammetry can also be used to measure serum iron. Hemolysis must be avoided because RBCs contain a much higher concentration of iron than does plasma.

When establishing QC limits, which of the following practices is inappropriate? A. Using last month's QC data to determine current target limits B. Exclusion of any QC results greater than ±2s from the mean C. Using control results from all shifts on which the assay is performed D. Using limits determined by reference laboratories using the same method

B. Exclusion of any QC results greater than ±2s from the mean B Data between ±2 and ±3s must be included in calculations of the next month's acceptable range. Elimination of these values would continuously reduce the distribution of QC results, making "out-of-control" situations a frequent occurrence. Generally, QC results greater than 3s are not used to calculate next month's mean.

In hepatitis, the rise in serum conjugated bilirubin can be caused by: A. Secondary renal insufficiency B. Failure of the enterohepatic circulation C. Enzymatic conversion of urobilinogen to bilirubin D. Extrahepatic conjugation

B. Failure of the enterohepatic circulation B Conjugated bilirubin is increased in hepatitis and other causes of hepatic necrosis due to failure to re-excrete conjugated bilirubin reabsorbed from the intestine. Increased direct bilirubin can also be attributed to accompanying intrahepatic obstruction, which blocks the flow of bile.

Which of the following hormones promotes hyperglycemia? A. Calcitonin B. Growth hormone C. Aldosterone D. Renin

B. Growth hormone B Growth hormone and cortisol promote gluconeogenesis and epinephrine stimulates glycogenolysis. Excess thyroid hormone causes hyperglycemia by increasing glucagon and inactivation of insulin, thereby promoting both gluconeogenesis and glycogenolysis. An increase in any of these hormones can cause hyperglycemia. Calcitonin opposes the action of parathyroid hormone. Aldosterone is the primary mineralocorticoid hormone and stimulates sodium reabsorption and potassium secretion by the kidneys. Renin is released from the kidney due to ineffective arterial pressure and promotes activation of angiotensinogen and aldosterone secretion.

Which of the following is a potential source of error in the hexokinase method? A. Galactosemia B. Hemolysis C. Sample collected in fluoride D. Ascorbic acid

B. Hemolysis B The hexokinase method can be performed on serum or plasma using heparin, EDTA, citrate, or oxalate. RBCs contain glucose-6-PO4 and intracellular enzymes that generate NADH, causing positiveinterference. Therefore, hemolyzed samples require a serum blank correction (subtraction of the reaction rate with hexokinase omitted from the reagent).

Which of the following is the reference method for measuring serum glucose? A. Somogyi-Nelson B. Hexokinase C. Glucose oxidase D. Glucose dehydrogenase

B. Hexokinase B The hexokinase method is considered more accurate than glucose oxidase methods because the coupling reaction using glucose-6-phosphate dehydrogenase (G-6-PD) is highly specific. The hexokinase method may be done on serum or plasma collected using heparin, EDTA, fluoride, oxalate, or citrate. The method can also be used for urine, cerebrospinal fluid, and serous fluids.

Which statement best characterizes serum bilirubin levels in the first week following delivery? A. Serum bilirubin 24 hours after delivery should not exceed the upper reference limit for adults B. Jaundice is usually first seen 48-72 hours postpartum in neonatal hyperbilirubinemia C. Serum bilirubin above 5.0 mg/dL occurring 2-5 days after delivery indicates hemolytic or hepatic disease D. Conjugated bilirubin accounts for about 50% of the total bilirubin in neonates

B. Jaundice is usually first seen 48-72 hours postpartum in neonatal hyperbilirubinemia B Bilirubin levels may reach as high as 2-3 mg/dL in the first 24 hours after birth owing to the trauma of delivery, such as resorption of a subdural hematoma. Neonatal hyperbilirubinemia occurs 2-3 days after birth due to increased hemolysis at birth and transient deficiency of the microsomal enzyme, UDP-glucuronyl transferase. Normally, levels rise to about 5-10 mg/dL but may be greater than 15 mg/dL, requiring therapy with UV light to photo-oxidize the bilirubin. Neonatal jaundice can last up to 1 week in a mature neonate and up to 2 weeks in prematures babies. Neonatal bilirubin is almost exclusively unconjugated

Which form of jaundice occurs within days of delivery and usually lasts 1-3 weeks, but is not due to normal neonatal hyperbilirubinemia or hemolytic disease of the newborn? A. Gilbert syndrome B. Lucey -Driscoll syndrome C. Rotor syndrome D. Dubin-Johnson syndrome

B. Lucey -Driscoll syndrome B Lucey-Driscoll syndrome is a rare form of jaundice caused by unconjugated bilirubin that presents within 2-4 days of birth and can last several weeks. It is caused by an inhibitor of UDP-glucuronyl transferase in maternal plasma that crosses the placenta. Jaundice is usually severe enough to require treatment.

Which statement best describes the use of the Hgb A1C test? Peak / Calibrated % Area / % Area / Retention Time / Peak Area Alb / 0.60/ 0.25/ 12500 F/ 0.50/ 0.50/ 11300 LA1c/ 0.75/ 0.70/ 15545 A1c/ 6.2/ 0.90/ 45112 P3/ 2.6 /1.60 /57489 Ao /48.0/ 1.8/ 994813 C/ 43.0 /2.00/ 926745 A. Should be used for monitoring glucose control only B. May be used for both diagnosis and monitoring C. Should be used only to monitor persons with type 1 diabetes D. May be used only to monitor persons with type 2 diabetes

B. May be used for both diagnosis and monitoring B The ADA now recommends that the hemoglobin A1c test be used for both diagnosis and monitoring blood glucose levels. The cutpoint for diabetes is an A1c of 6.5. Persons with an A1c of 5.7%-6.4% are classified as being at high risk for diabetes within 5 years. An A1c between 4.0%-5.5% is defined as within normal limits

Which of the following processes is part of the normal metabolism of bilirubin? A. Both conjugated and unconjugated bilirubin are excreted into the bile B. Methene bridges of bilirubin are reduced by intestinal bacteria forming urobilinogens C. Most of the bilirubin delivered into the intestine is reabsorbed D. Bilirubin and urobilinogen reabsorbed from the intestine are mainly excreted by the kidneys

B. Methene bridges of bilirubin are reduced by intestinal bacteria forming urobilinogens B Most of the conjugated bilirubin delivered into the intestine is deconjugated by β-glucuronidase and then reduced by intestinal flora to form three different reduction products collectively called urobilinogens. The majority of bilirubin and urobilinogen in the intestine are not reabsorbed. Most of that which is reabsorbed is re-excreted by the liver. The portal vein delivers blood from the bowel to the sinusoids. Hepatocytes take up about 90% of the returned bile pigments and secrete them again into the bile. This process is called the enterohepatic circulation

Which statement about colorimetric bilirubin methods is true? A. Direct bilirubin must react with diazo reagent under alkaline conditions B. Most methods are based upon reaction with diazotized sulfanilic acid C. Ascorbic acid can be used to eliminate interference caused by Hgb D. The color of the azobilirubin product is independent of pH

B. Most methods are based upon reaction with diazotized sulfanilic acid B Unconjugated bilirubin is poorly soluble in acid, and therefore, direct bilirubin is assayed using diazotized sulfanilic acid diluted in weak HCl. The direct diazo reaction should be measured after no longer than 3 minutes to prevent reaction of unconjugated bilirubin, or the diazo group can be reduced using ascorbate or hydroxylamine preventing any further reaction.

In peroxidase-coupled glucose methods, which reagent complexes with the chromogen? A. Nitroprusside B. Phenol C. Tartrate D. Hydroxide

B. Phenol B The coupling step in the Trinder glucose oxidase method uses peroxidase to catalyze the oxidation of a dye by H2O2. Dyes such as 4 aminophenozone or 4-aminoantipyrine are coupled to phenol to form a quinoneimine dye that is red and is measured at about 500 nm.

Which formula provides the best estimate of serum TIBC? A. Serum transferrin in mg/dL × 0.70 = TIBC (µg/dL) B. Serum transferrin in mg/dL × 1.43 = TIBC (µg/dL) C. Serum iron (µg/dL)/1.2 + 0.06 = TIBC (µg/dL) D. Serum Fe (µg/dL) × 1.25 = TIBC (µg/dL)

B. Serum transferrin in mg/dL × 1.43 = TIBC (µg/dL) B Transferrin, a β-globulin, has a molecular size of about 77,000. Transferrin is the principal iron transport protein, and TIBC is determined by the serum transferrin concentration. One mole of transferrin binds two moles of Fe+3, so the transferrin concentration can be used to predict the TIBC. Since the direct measurement of TIBC requires manual pretreatment to remove the excess iron added and is prone to overestimation if all of the unbound iron is not removed, some labs prefer to measure transferrin immunochemically and calculate TIBC. This formula may underestimate TIBC because albumin and other proteins will bind iron when the percent iron saturation of transferrin is abnormally high.

Polarographic methods for glucose analysis are based upon which principle of measurement? A. Nonenzymatic oxidation of glucose B. The rate of O2 depletion C. Chemiluminescence caused by formation of adenosine triphosphate (ATP) D. The change in electrical potential as glucose is oxidized

B. The rate of O2 depletion B Polarographic glucose electrodes measure the consumption of O2 as glucose is oxidized. Glucose oxidase in the reagent catalyzes the oxidation of glucose by O2 under first order conditions, forming hydrogen peroxide (H2O2). As the dissolved O2 decreases, less is reduced at the cathode, resulting in a decrease in current proportional to glucose concentration. It is important that the H2O2 not breakdown to re-form O2. This is prevented by adding molybdate and iodide that react with H2O2, forming iodine and water, and by adding catalase and ethanol that react with H2O2, forming acetaldehyde and water

Which of the following plots is best for comparison of precision and accuracy among laboratories? A. Levy-Jennings B. Tonks-Youden C. Cusum D. Linear regression

B. Tonks-Youden B The Tonks-Youden plot is used for interlaboratory comparison of monthly means. The method mean for level 1 is at the center of the y axis and mean for level 2 at the center of the x axis. Lines are drawn from the means of both levels across the graph, dividing it into four equal quadrants. If a laboratory's monthly means both plot in the lower left or upper right, then systematic error (SE) exists in its method

The term R4S means that: A. Four consecutive controls are greater than ±1 standard deviation from the mean B. Two controls in the same run are greater than 4s units apart C. Two consecutive controls in the same run are each greater than ±4s from the mean D. There is a shift above the mean for four consecutive controls

B. Two controls in the same run are greater than 4s units apart B The R4s rule is applied to two control levels withinthe same run. The rule is violated when the algebraic difference between them (level 1 - level 2) exceeds 4s. The rule is never applied across different runs. The R4s rule detects random error (error due to poor precision).

Which enzyme is responsible for the conjugation of bilirubin? A. β-Glucuronidase B. UDP-glucuronyl transferase C. Bilirubin oxidase D. Biliverdin reductase

B. UDP-glucuronyl transferase B UDP-glucuronyl transferase esterifies glucuronic acid to unconjugated bilirubin, making it water soluble. Most conjugated bilirubin is diglucuronide; however, the liver makes a small amount of monoglucuronide and other glycosides. β Glucuronidase hydrolyzes glucuronide from bilirubin, hormones, or drugs. It is used prior to organic extraction to deconjugate urinary metabolites (e.g., total cortisol). Biliverdin reductase forms bilirubin from biliverdin (and heme oxygenase forms biliverdin from heme). Bilirubin oxidase is used in an enzymatic bilirubin assay in which bilirubin is oxidized back to biliverdin and the rate of biliverdin formation is measured at 410 nm.

Which of the following findings is characteristic of all forms of clinical hypoglycemia? A. A fasting blood glucose value below 55 mg/dL B. High fasting insulin levels C. Neuroglycopenic symptoms at the time of low blood sugar D. Decreased serum C peptide

C Clinical hypoglycemia can be caused by insulinoma, drugs, alcoholism, and reactive hypoglycemia. Neuroglycopenic symptoms at the time of low blood sugar C. Reactive hypoglycemia is characterized by delayed or excessive insulin output after eating and is very rare. Fasting insulin is normal but postprandial levels are increased. High fasting insulin levels (usually > 6 μg/L) are seen in insulinoma, and patients with insulinoma almost always display fasting hypoglycemia, especially when the fast is extended to 48 72 hours. C peptide is a subunit of proinsulin that is hydrolyzed when insulin is released. In hypoglycemia, low levels indicate an exogenous insulin source, whereas high levels indicate overproduction of insulin.

How many milliliters of HNO3 (purity 68.0%, specific gravity 1.42) are needed to prepare 1.0 L of a 2.0 N solution? Atomic weights: H = 1.0; N = 14.0; O = 16.0 A. 89.5 mL B. 126.0 mL C. 130.5 mL D. 180.0 mL

C. 130.5 mL C The molecular weight of HNO3 is 63.0 g. Because the valance of the acid is 1 (1 mol of hydrogen is produced per mole of acid), the equivalent weight is also 63.0 g. The mass is calculated by multiplying the normality (2.0 N) by the equivalent weight (63.0 g) and volume (1.0 L); therefore, 126.0 g of acid are required. Because the purity is 68.0% and the specific gravity 1.42, the amount of HNO3 in grams per milliliter is 0.68 × 1.42 g/mL or 0.9656 g/mL. The volume required to give 126.0 g is calculated by dividing the mass needed (grams) by the grams per milliliter. mL HNO3 = 126.0 g ÷ 0.9656 g/mL = 126.0 g × 1.0 mL/0.9656 g = 130.5 mL

A biuret reagent requires preparation of a stock solution containing 9.6 g of copper II sulfate (CuSO4) per liter. How many grams of CuSO4 • 5H2O are needed to prepare 1.0 L of the stock solution? Atomic weights: H = 1.0; Cu = 63.6; O = 16.0; S = 32.1 A. 5.4 g B. 6.1 g C. 15.0 g D. 17.0 g

C. 15.0 g C Determine the mass of CuSO4 • 5H2O containing 9.6 g of anhydrous CuSO4. First, calculate the percentage of CuSO4 in the hydrate, then divide the amount needed (9.6 g) by the percentage. % CuSO4 = molecular weight CuSO4 ÷ molecular weight CuSO4 • 5H2O × 100 = (159.7 ÷ 249.7) × 100 = 63.96% Grams CuSO4 • 5H2O = 9.6 g ÷ 0.6396 = 15.0 g A convenient formula to use is: g hydrate = (MW hydrate ÷ MW anhydrous salt) × g anhydrous salt

Which of the following 2-hour glucose challenge results would be classified as impaired glucose tolerance (IGT)? Two-hour serum glucose: A. 130 mg/dL B. 135 mg/dL C. 150 mg/dL D. 204 mg/dL

C. 150 mg/dL C With the exception of pregnant females, impaired glucose tolerance is defined by the ADA as a serum or plasma glucose at 2 hours following a 75-g oral glucose load of ≥140 mg/dL and < 200 mg/dL. Persons who have a fasting plasma glucose of ≥100 but < 126 mg/dL are classified as having impaired fasting glucose (IFG). Both IGT and IFG are risk factors for developing diabetes later in life. Such persons are classified as having prediabetes and should be tested annually.

Convert 2.0 mEq/L magnesium (atomic weight = 24.3) to milligrams per deciliter. A. 0.8 mg/dL B. 1.2 mg/dL C. 2.4 mg/dL D. 4.9 mg/dL

C. 2.4 mg/dL C To convert from milliequivalent per liter to milligrams per deciliter, first calculate the milliequivalent weight (equivalent weight expressed in milligrams), which is the atomic mass divided by the valence. Because magnesium is divalent, each mole has the charge equivalent of 2 mol of hydrogen. Then, multiply the milliequivalent per liter by the milliequivalent weight to convert to milligrams per liter. Next, divide by 10 to convert milligrams per liter to milligrams per deciliter. Milliequivalent weight Mg = 24.3 ÷ 2 = 12.15 mg/mEq 2.0 mEq/L × 12.15 mg/mEq = 24.3 mg/L 24.3 mg/L × 1.0 L/10.0 dL = 2.4 mg/dL

Convert 10.0 mg/dL calcium (atomic weight = 40.1) to International System of Units (SI). A. 0.25 B. 0.40 C. 2.5 D. 0.4

C. 2.5 C The SI unit is the recommended method of reporting clinical laboratory results. The SI unit for all electrolytes is millimole per liter. To convert from milligrams per deciliter to millimoles per liter, multiply by 10 to convert to milligrams per liter, then divide by the atomic mass expressed in milligrams. 10.0 mg/dL × 10.0 dL/1.0 L = 100.0 mg/L 100.0 mg/L × 1.0 mmol/40.1 mg = 2.5 mmol/L

Select the most appropriate adult reference range for fasting blood glucose. A. 40-105 mg/dL (2.22-5.82 mmol/L) B. 60-140 mg/dL (3.33-7.77 mmol/L) C. 65-99 mg/dL (3.61-5.50 mmol/L) D. 75-150 mg/dL (4.16-8.32 mmol/L)

C. 65-99 mg/dL (3.61-5.50 mmol/L) C Reference ranges vary slightly depending upon method and specimen type. Enzymatic methods specific for glucose have an upper limit of normal no greater than 99 mg/dL. This is the cutoff value for impaired fasting plasma glucose (prediabetes) recommended by the American Diabetes Association. Although 65 mg/dL is considered the 2.5 percentile, a fasting level below 50 mg/dL is often seen without associated clinical hypoglycemia, and neonates have a lower limit of approximately 40 mg/dL owing to maternal insulin

How many grams of sodium hydroxide (NaOH) are required to prepare 150.0 mL of a 5.0% w/v solution? A. 1.5 g B. 4.0 g C. 7.5 g D. 15.0 g

C. 7.5 g C A percent solution expressed in w/v (weight/volume) refers to grams of solute per 100.0 mL of solution. To calculate, multiply the percentage (as grams) by the volume needed (mL), then divide by 100.0 (mL) (5.0 g × 150.0 mL) ÷ 100.0 mL = 7.5 g

Calculate the pH of a solution of 1.5 × 10-5 M NH4OH. A. 4.2 B. 7.2 C. 9.2 D. 11.2

C. 9.2 C First, calculate the pOH of the solution. pOH = -Log [OH-] pOH = - Log 1.5 x 10-5 = 4.82 pH = 14 - pOH pH = 14 - 4.8 = 9.2

The term δ-bilirubin refers to: A. Water-soluble bilirubin B. Free unconjugated bilirubin C. Bilirubin tightly bound to albumin D. Direct-reacting bilirubin

C. Bilirubin tightly bound to albumin C HPLC separates bilirubin into four fractions: α = unconjugated, β = monoglucuronide, γ = diglucuronide, and δ = irreversibly albumin bound. δ Bilirubin is a separate fraction from the unconjugated bilirubin, which is bound loosely to albumin. δ Bilirubin and conjugated bilirubin react with diazo reagent in the direct bilirubin assay

Which reagent is used in the Jendrassik-Grof method to solubilize unconjugated bilirubin? A. 50% methanol B. N-butanol C. Caffeine D. Acetic acid

C. Caffeine C A polarity modifier is required to make unconjugated bilirubin soluble in diazo reagent. The Malloy-Evelyn method uses 50% methanol to reduce the polarity of the diazo reagent. Caffeine is used in the Jendrassik-Grof method. This method is recommended because it is not falsely elevated by hemolysis and gives quantitative recovery of both conjugated and unconjugated bilirubin.

Which form of hyperbilirubinemia is caused by an inherited absence of UDP-glucuronyl transferase? A. Gilbert's syndrome B. Rotor syndrome C. Crigler-Najjar syndrome D. Dubin-Johnson syndrome

C. Crigler-Najjar syndrome C Crigler-Najjar syndrome is a rare condition that occurs in two forms. Type 1 is inherited as an autosomal recessive trait and causes a total deficiency of UDP-glucuronyl transferase. Life expectancy is less than 1 year. Type 2 is an autosomal dominant trait and is characterized by lesser jaundice and usually the absence of kernicterus. Bilirubin levels can be controlled with phenobarbital, which promotes bilirubin excretion. Gilbert's syndrome is an autosomal recessive condition characterized by decreased bilirubin uptake and decreased formation of bilirubin diglucuronide. It is the most common form of inherited jaundice. UDP glucuronyl transferase activity is reduced owing to an increase in the number of AT repeats in the promoter region of the gene. Dubin-Johnson and Rotor syndromes are autosomal recessive disorders associated with defective delivery of bilirubin into the biliary system.

Which plot will give the earliest indication of a shift or trend? A. Levy-Jennings B. Tonks-Youden C. Cusum D. Histogram

C. Cusum C Cusum points are the algebraic sum of the difference between each QC result and the mean. The y axis is the sum of differences and the x axis is the run number. The center of the y axis is 0. Because QC results follow a random distribution, the points should distribute about the zero line. Results are out of control when the slope exceeds 45° or a decision limit (e.g., ±2.7s) is exceeded.

Which of the following is likely to occur first in iron deficiency anemia? A. Decreased serum iron B. Increased TIBC C. Decreased serum ferritin D. Increased transferrin

C. Decreased serum ferritin C Body stores must be depleted of iron before serum iron falls. Thus, serum ferritin falls in the early stages of iron deficiency, making it a more sensitive test than serum iron in uncomplicated cases. Ferritin levels are low only in iron deficiency. However, concurrent illness such as malignancy, infection, and inflammation may promote ferritin release from the tissues, causing

Which condition is caused by deficient secretion of bilirubin into the bile canaliculi? A. Gilbert's disease B. Neonatal hyperbilirubinemia C. Dubin-Johnson syndrome D. Crigler-Najjar syndrome

C. Dubin-Johnson syndrome C Dubin-Johnson syndrome is an autosomal recessive condition arising from mutation of an ABC transporter gene. It produces mild jaundice from accumulation of conjugated bilirubin that is not secreted into the bile canaliculi. Total and direct bilirubin are elevated, but other liver function is normal. Rotor syndrome is an autosomal recessive condition that also results in retention of conjugated bilirubin. The mechanism in Rotor syndrome is unknown, and like Dubin-Johnson syndrome it is commonly asymptomatic. It can be differentiated from Dubin-Johnson syndrome by the pattern of urinary coproporphyrin excretion and because it produces no black pigmentation in the liver.

A lab measures total bilirubin by the Jendrassik-Grof bilirubin method with sample blanking. What would be the effect of moderate hemolysis on the test result? A. Falsely increased due to optical interference B. Falsely increased due to release of bilirubin from RBCs C. Falsely low due to inhibition of the diazo reaction by hemoglobin D. No effect due to correction of positive interference by sample blanking

C. Falsely low due to inhibition of the diazo reaction by hemoglobin C The sample blank measures the absorbance of the sample and reagent in the absence of azobilirubin formation and corrects the measurement for optical interference caused by hemoglobin absorbing the wavelength of measurement. However, hemoglobin is an inhibitor of the diazo reaction and will cause falsely low results in a blank corrected sample. For this reason, direct bichromatic spectrophotometric methods are preferred when measuring bilirubin in neonatal samples, which are often hemolyzed.

Which of the following is characteristic of type 2 diabetes mellitus? A. Insulin levels are consistently low B. Most cases require a 3-hour oral glucose tolerance test to diagnose C. Hyperglycemia is often controlled without insulin replacement D. The condition is associated with unexplained weight loss

C. Hyperglycemia is often controlled without insulin replacement C. Hyperglycemia is often controlled without insulin replacement C Type 2, or late-onset diabetes, is associated with a defect in the receptor site for insulin. Insulin levels may be low, normal, or high. Patients are usually obese and over 40 years of age, although the incidence is increasing in both children and young adults. The American Diabetes Association (ADA) recommends screening all adults for diabetes who are overweight and have one additional risk factor and all adults over age 45, and to retest them every 3 years, if negative. Patients do not require insulin to prevent ketosis and hyperglycemia can be controlled in most patients by diet and drugs that promote insulin release. Type 2 accounts for 80%-90% of all diabetes mellitus.

Which condition is associated with the lowest percent saturation of transferrin? A. Hemochromatosis B. Anemia of chronic infection C. Iron deficiency anemia D. Noniron deficiency anemia

C. Iron deficiency anemia C Percent saturation = Serum Fe × 100/TIBC. Normally, transferrin is one-third saturated with iron. In iron deficiency states, the serum iron falls but transferrin rises. This causes the numerator and denominator to move in opposite directions, resulting in very low percent saturation (about 10%). The opposite occurs in hemochromatosis and sideroblastic anemia, resulting in an increased percent saturation

Which testing situation is appropriate for the use of point-of-care whole-blood glucose methods? A. Screening for type 2 diabetes mellitus B. Diagnosis of diabetes mellitus C. Monitoring of blood glucose control in type 1 and type 2 diabetics D. Monitoring diabetics for hyperglycemic episodes only

C. Monitoring of blood glucose control in type 1 and type 2 diabetics C The ADA does not recommend the use of whole-blood glucose monitors for establishing a diagnosis of diabetes or screening persons for diabetes. The analytical measurement range of these devices varies greatly, and whole blood glucose is approximately 10% lower than serum or plasma glucose. In addition, analytical variance is greater and accuracy less than for laboratory instruments. Whole blood glucose meters should be used by diabetics and caregivers to monitor glucose control and can detect both hyper- and hypoglycemic states that result from too little or too much insulin replacement. Therefore, postprandial monitoring with such a device is recommended for all persons who receive insulin therapy.

What is the principle of the transcutaneous bilirubin assay? A. Conductivity B. Amperometric inhibition C. Multiwavelength reflectance photometry D. Infrared spectroscopy

C. Multiwavelength reflectance photometry C Measurement of bilirubin concentration through the skin requires the use of multiple wavelengths to correct for absorbance by melanin and other light-absorbing constituents of skin and blood. More than 100 wavelengths and multiple reflectance measurements at various sites may be used to derive the venous bilirubin concentration in mg/dL. Such devices have been shown to have a high specificity. They can be used to identify neonates with hyperbilirubinemia, and to monitor treatment.

Which statement regarding glycated (glycosylated) Hgb (G-Hgb) is true? A. Has a sugar attached to the C-terminal end of the β chain B. Is a highly reversible aminoglycan C. Reflects the extent of glucose regulation in the 8- to 12-week interval prior to sampling D. Will be abnormal within 4 days following an episode of hyperglycemia

C. Reflects the extent of glucose regulation in the 8- to 12-week interval prior to sampling C G-Hgb results from the nonenzymatic attachment of a sugar such as glucose to the N-terminal valine of the β chain. The reaction is nonreversible and is related to the time-averaged blood glucose concentration over the life span of the RBCs. There are three G-Hgb fractions designated A1a, A1b, and Alc. Hemoglobin A1c makes up about 80% of glycated hemoglobin, and is used to determine the adequacy of insulin therapy. The time-averaged blood glucose is approximated by the formula (G-Hgb × 33.3) - 86 mg/dL, and insulin adjustments can be made to bring this level to within reference limits. Also, glycated protein assay (called fructosamine) provides similar data for the period between 2 and 4 weeks before sampling.

Which of the following statements regarding iron metabolism is correct? A. Iron absorption is decreased by alcohol ingestion B. Normally, 40%-50% of ingested iron is absorbed C. The daily requirement is higher for pregnant and menstruating women D. Absorption increases with the amount of iron in the body stores

C. The daily requirement is higher for pregnant and menstruating women C For adult men and nonmenstruating women, approximately 1-2 mg/day of iron is needed to replace the small amount lost mainly by exfoliation of cells. Because 5%-10% of dietary iron is absorbed normally, the daily dietary requirement in this group is 10-20 mg/day. Menstruating women have an additional requirement of 1 mg/day and pregnant women 2 mg/day. Absorption efficiency will increase in iron deficiency and decrease in iron overload. Iron absorption is enhanced by low gastric pH and is increased by alcohol ingestion.

Which glucose method is subject to falsely low results caused by ascorbate? A. Hexokinase B. Glucose dehydrogenase C. Trinder glucose oxidase D. Polarography

C. Trinder glucose oxidase C Although glucose oxidase is specific for β-D-glucose, the coupling (indicator) reaction is prone to negative interference from ascorbate, uric acid, acetoacetic acid, and other reducing agents. These compete with the chromogen (e.g., o-dianisidine) for peroxide, resulting in less dye being oxidized to chromophore. The choice of chromogen determines the specificity and linearity. 4-aminophenazone and phenol is more resistant to interference from azo compounds and proteins than is o-dianisidine.

. A procedure for aspartate aminotransferase (AST) is performed manually because of a repeating error code for nonlinearity obtained on the laboratory's automated chemistry analyzer; 0.05 mL of serum and 1.0 mL of substrate are used. Te reaction rate is measured at 30°C at 340 nm using a 1.0 cM light path, and the delta absorbance (-∆A) per minute is determined to be 0.382. Based upon a molar absorptivity coefficient for NADH at 340 nm of 6.22 X 103 M-1 cM-1 L-1, calculate the enzyme activity in international units (IUs) per liter. A. 26 IU/L B. 326 IU/L C. 1228 IU/L D. 1290 IU/L

D. 1290 IU/L D An IU is defined as 1 μmol of substrate consumed or product produced per minute. The micromoles of NADH consumed in this reaction are determined by dividing the change in absorbance per minute by the absorbance of 1 μmol of NADH. Because 1 mol/L/cm would have an absorbance of 6.22 X 103 absorbance units, then 1 μmol/mL/cm would produce an absorbance of 6.22. Therefore, dividing the δA per minute by 6.22 gives the micromoles of NADH consumed in the reaction. This is multiplied by the dilution of serum to determine the micromoles per milliliter, and multiplied by 1,000 to convert to micromoles per liter. IU/L = ∆A/min x TV(mL) × 1,000 mL/L 6.22(A/μmol/mL/cM) x 1 cm x SV(mL) = ∆A/min × 1.05 x 1,000 6.22 X 0.05 = ∆A/min × 1,050 0.311 = ∆A/min × 3,376 = 0.382 × 3376 = 1,290 IU/L

Two consecutive controls are both beyond -2s from the mean. How frequently would this occur on the basis of chance alone? A. 1:100 B. 5:100 C. 1:400 D. 1:1,600

D. 1:1,600 D QC results follow a Gaussian or normal distribution. Ninety-five percent of the results fall within ±2s of the mean; therefore, 2.5 out of 100 (1:40) are above +2s and 2.5 out of 100 are below -2s. The probability of two consecutive controls being beyond -2s is the product of their individual probabilities. 1/40 × 1/40 = 1/1,600 trials by chance.

How many milliliters of glacial acetic acid are needed to prepare 2.0 L of 10.0% v/v acetic acid? A. 10.0 mL B. 20.0 mL C. 100.0 mL D. 200.0 mL

D. 200.0 mL D The expression percent v/v refers to the volume of one liquid in mL present in 100.0 mL of solution. To calculate, multiply the percentage (as mL) by the volume required (mL), then divide by 100 (mL). (10.0 mL × 2000.0 mL) ÷ 100.0 mL = 200.0 mL To prepare 2.0 L of a 10.0% v/v solution of acetic acid, add approximately 1.0 L of deionized H2O to a 2.0-L volumetric flask. Add 200.0 mL of glacial acetic acid and mix. Then, add sufficient deionized H2O to bring the meniscus to the 2.0-L line and mix again

Which statement regarding the diagnosis of iron deficiency is correct? A. Serum iron levels are always higher at night than during the day B. Serum iron levels begin to fall before the body stores become depleted C. A normal level of serum ferritin rules out iron deficiency D. A low serum ferritin is diagnostic of iron deficiency

D. A low serum ferritin is diagnostic of iron deficiency D Serum iron levels are falsely elevated by hemolysis and subject to diurnal variation. Levels are highest in the morning and lowest at night, but this pattern is reversed in persons who work at night. A low ferritin is specific for iron deficiency. However, only about 1% of ferritin is in the vascular system. Any disease that increases ferritin release may mask iron deficiency

In addition to polarography, what other electrochemical method can be used to measure glucose in plasma? A. Conductivity B. Potentiometry C. Anodic stripping voltammetry D. Amperometry

D. Amperometry D In some critical care analyzers, amperometric measurement of glucose is used. The glucose oxidaseis impregnated into the membrane covering the electrode. It reacts with glucose in the sample, forming H2O2. This diffuses across the membrane to the anode of the electrode, where it is oxidized to O2. The electrons produced are used to reduce oxygen at the cathode, completing the current path. At the anode (usually platinum), 2H2O2 → 4e- + 2O2 + 4H+. At the cathode (usually silver), O2 + 4H+ + 4e- → 2H2O. The net equation is 2H2O2 → O2 + 2H2O.

In addition to measuring blood glucose, Hgb A1c, and microalbumin, which test should be done on diabetic persons once per year? A. Urine glucose B. Urine ketones C. Plasma fructosamines D. Estimated glomerular filtration rate

D. Estimated glomerular filtration rate D While urinary glucose can identify persons who may have diabetes, it is not sensitive enough to manage glucose control on a daily basis, and has been replaced by whole-blood glucose monitoring or continuous glucose monitoring. While the urinary ketone test is a useful screening test for diabetic and other forms of ketosis, the plasma β hydroxybutyrate test should be used to identify and monitor ketosis in diabetic persons. Fructosamine is a useful adjunct to Hgb A1c to identify poor control of blood glucose in the past 2-4 weeks, but has not been recommended for routine use in all diabetic patients.

Which statement regarding the measurement of bilirubin by the Jendrassik-Grof method is correct? A. The same diluent is used for both total and direct assays to minimize differences in reactivity B. Positive interference by Hgb is prevented by the addition of HCl after the diazo reaction C. The color of the azobilirubin product is intensified by the addition of ascorbic acid D. Fehling's reagent is added after the diazo reaction to reduce optical interference by hemoglobin

D. Fehling's reagent is added after the diazo reaction to reduce optical interference by hemoglobin D The Jendrassik-Grof method uses HCl as the diluent for the measurement of direct bilirubin because unconjugated bilirubin is poorly soluble at low pH. Total bilirubin is measured using an acetate buffer with caffeine added to increase the solubility of the unconjugated bilirubin. After addition of diazotized sulfanilic acid and incubatiion, the diazo group is reduced by ascorbic acid, and Fehling's reagent is added to alkalinize the diluent. At an alkaline pH the product changes from pink to blue, shifting the absorbance maximum to 600 nm where Hgb does not contribute significantly to absorbance.

Select the enzyme that is most specific for β-D-glucose. A. Hexokinase B. G-6-PD C. Phosphohexisomerase D. Glucose oxidase

D. Glucose oxidase D Glucose oxidase is the most specific enzyme reacting with only β-D-glucose. However, the peroxida coupling reaction used in the glucose oxidase method is subject to positive and negative interference. Therefore, hexokinase is used in the reference method.

In the liver, bilirubin is conjugated by addition of: A. Vinyl groups B. Methyl groups C. Hydroxyl groups D. Glucuronyl groups

D. Glucuronyl groups D The esterification of glucuronic acid to the propionyl side chains of the inner pyrrole rings (I and II) makes bilirubin water soluble. Conjugation is required before bilirubin can be excreted via the bile.

Which of the following is classified as a mucopolysaccharide storage disease? A. Pompe's disease B. von Gierke disease C. Hers' disease D. Hurler's syndrome

D. Hurler's syndrome D Hurler's syndrome is an autosomal recessive disease resulting from a deficiency of iduronidase. Glycosaminoglycans (mucopolysaccharides) accumulate in the lysosomes. Multiple organ failure and mental retardation occur, resulting in early mortality. Excess dermatan and heparin sulfate are excreted in urine. Other mucopolysaccharidoses (MPS storage diseases) are Hunter's, Scheie's, Sanfilippo's, and Morquio's syndromes.

Which of the following abnormal laboratory results is found in von Gierke's disease? A. Hyperglycemia B. Increased glucose response to epinephrine administration C. Metabolic alkalosis D. Hyperlipidemia

D. Hyperlipidemia D Von Gierke's disease (type 1 glycogen storage disease) results from a deficiency of glucose-6-phosphatase. This blocks the hydrolysis of glucose-6-PO4 to glucose and Pi, preventing degradation of glycogen to glucose. The disease is associated with increased triglyceride levels because fats are mobilized for energy and lactate acidosis caused by increased glycolysis. A presumptive diagnosis is made when intravenous galactose administration fails to increase serum glucose, and can be confirmed by demonstrating glucose-6-phosphatase deficiency or decreased glucose production in response to epinephrine.

Which statement regarding gestational diabetes mellitus (GDM) is correct? A. Is diagnosed using the same oral glucose tolerance criteria as in nonpregnancy B. Converts to diabetes mellitus after pregnancy in 60%-75% of cases C. Presents no increased health risk to the fetus D. Is defined as glucose intolerance originating during pregnancy

D. Is defined as glucose intolerance originating during pregnancy D Control of GDM reduces perinatal complications such as respiratory distress syndrome, high birth weight, and neonatal jaundice. Women at risk are usually screened between 24 and 28 weeks' gestation. The screening test can be performed nonfasting and consists of an oral 50-g glucose challenge followed by serum or plasma glucose measurement at 1 hour. A result ≥ 140 mg/dL is followed by a 2-hour or 3-hour oral glucose tolerance test to confirm gestational diabetes. For the 3-hour test, a 100-g dose of glucose is used and at least two of the following cutoffs must be exceeded: fasting, ≥ 95 mg/dL or higher; 1 hour, ≥ 180 mg/dL or higher; 2 hour ≥ 155 mg/dL or higher; 3 hour, ≥ 140 mg/dL or higher. The same cutpoints are used for the 2-hour test except that a 75-g dose is used. GDM converts to diabetes mellitus within 10 years in 30%-40% of cases. ADA recommends testing persons with GDM for diabetes 6-12 weeks after delivery

Which of the following statements regarding the metabolism of bilirubin is true? A. It is formed by hydrolysis of the α methene bridge of urobilinogen B. It is reduced to biliverdin prior to excretion C. It is a by-product of porphyrin production D. It is produced from the destruction of RBCs

D. It is produced from the destruction of RBCs D Synthesis of porphyrins results in production of heme and metabolism of porphyrins other than protoporphyrin IX yields uroporphyrins and coproporphyrins, not bilirubin. Reticuloendothelial cells in the spleen digest Hgb and release the iron from heme. The tetrapyrrole ring is opened at the α methene bridge by heme oxygenase, forming biliverdin. Bilirubin is formed by reduction of biliverdin at the γ methene bridge. It is complexed to albumin and transported to the liver.

What effect does hematocrit have on POCT tests for whole-blood glucose monitoring? A. Low hematocrit decreases glucose readings on all devices B. High hematocrit raises glucose readings on all devices C. The effect is variable and dependent on the enzyme/coenzyme system D. Low hematocrit raises readings and high hematocrit lowers readings unless corrected

D. Low hematocrit raises readings and high hematocrit lowers readings unless corrected D Hematocrit affects POCT glucose measurements. High hematocrit lowers the glucose because RBC glucose concentration is lower than plasma concentration. Other factors include binding of oxygen to hemoglobin and the slower diffusion of glucose onto the solid phase—both of which occur when the hematocrit is high. Bias due to an abnormal hematocrit can be avoided by simultaneously measuring the conductivity of the sample. The hematocrit is calculated and used to mathematically correct the glucose measurement.

Which condition is most often associated with a high serum iron level? A. Nephrosis B. Chronic infection or inflammation C. Polycythemia vera D. Noniron deficiency anemias

D. Noniron deficiency anemias D Anemia associated with chronic infection causes a low serum iron, but unlike iron deficiency, causes a low (or normal) TIBC and does not cause low ferritin. Noniron deficiency anemias such as pernicious anemia and sideroblastic anemia produce high serum iron and low TIBC. Nephrosis causes iron loss by the kidneys. Polycythemia is associated with increased iron within the RBCs and depletion of iron stores.

Which of the following results falls within the diagnostic criteria for diabetes mellitus? A. Fasting plasma glucose of 120 mg/dL B. Two-hour postprandial plasma glucose of 160 mg/dL C. Two-hour plasma glucose of 180 mg/dL following a 75 g oral glucose challenge D. Random plasma glucose of 250 mg/dL and presence of symptoms

D. Random plasma glucose of 250 mg/dL and presence of symptoms D The American Diabetes Association recommends the following criteria for diagnosing diabetes mellitus: fasting glucose ≥ 126 mg/dL, casual (random) glucose ≥ 200 mg/dL in the presence of symptoms (polyuria, increased thirst, weight loss), glucose ≥ 200 mg/dL at 2 hours after an oral dose of 75 g of glucose, and hemoglobin A1c ≥ 6.5%. A diagnosis of diabetes mellitus is indicated if any one or combination of these four criteria is met on more than a single testing event. The fasting plasma glucose test requires at least 8 hours with no food or drink except water. The 2-hour postloading test should be conducted according to the oral glucose tolerance guidelines currently recommended by the World Health Organization

Which of the following is characteristic of type 1 diabetes mellitus? A. Requires an oral glucose tolerance test for diagnosis B. Is the most common form of diabetes mellitus C. Usually occurs after age 40 D. Requires insulin replacement to prevent ketosis

D. Requires insulin replacement to prevent ketosis D Type 1, or juvenile, diabetes is also called insulindependent diabetes because patients must be given insulin to prevent ketosis. Type 1 accounts for only about 10%-20% of cases of diabetes mellitus, and is usually diagnosed by a fasting plasma glucose. Two consecutive results ≥126 mg/dL is diagnostic. Approximately 95% of patients produce autoantibodies against the beta cells of the pancreatic islets. Other autoantibodies may be produced against insulin, glutamate decarboxylase, and tyrosine phosphorylase IA2. There is genetic association between type 1 diabetes and human leukocyte antigens (HLA) DR3 and DR4.

Evaluate the following chromatogram of a whole-blood hemolysate, and identify the cause and best course of action. A. Result is not reportable because hemoglobin F is present and interferes B. The result is not reportable because hemoglobin C is present and interferes C. The result is not reportable because labile hemoglobin A1c is present D. The result is reportable; neither hemoglobin F or C interfere

D. The result is reportable; neither hemoglobin F or C interfere D The chromatogram is from a person with hemoglobin AC; however, hemoglobin C is completely separated from Hgb A1c and does not interfere. Hgb F is also present, but does not interfere unless its concentration is > 30%. Labile hemoglobin is formed initially when the aldehyde of glucose reacts with the N-terminal valine of the β globin chain. This Shiff base is reversible but is converted to Hgb A1c by rearrangement to a ketoamine. It is called labile A1c and produces a peak (LA1c) after HgF and before Hgb A1c. Therefore, it does not interfere.

Which of the following biochemical processes is promoted by insulin? A. Glycogenolysis B. Gluconeogenesis C. Lipolysis D. Uptake of glucose by cells

D. Uptake of glucose by cells D Insulin reduces blood glucose levels by increasing glucose uptake by cells. It promotes lipid and glycogen production, induces synthesis of glycolytic enzymes, and inhibits formation of glucose from pyruvate and Krebs cycle intermediates.