Assessment CC Flashcards

Question

Extremely inert, excellent temperature tolerance and chemical resistance; used for stir bars, stopcocks and tubing: A. Polyethylene B. Polycarbonate C. Polystyrene D. Teflon

Answer 1

D. Teflon ## Footnote POLYETHYLENE - Widely used in plastic ware, too, including test tubes, bottles, graduated tubes, stoppers, disposable transfer pipets, volumetric pipets, and test tube racks. - May bind or absorb proteins, dyes, stains, and picric acid POLYCARBONATE - Used in tubes for centrifugation, graduated cylinders, and flasks - Usable temperature range is broad: –100° C to +160° C - Very strong plastic but is not suitable for use with strong acids, bases, and oxidizing agents - May be autoclaved but with limitations POLYSTYRENE - Rigid, clear type of plastic that should not be autoclaved - Used in an assortment of tubes, including capped graduated tubes and test tubes - Not resistant to most hydrocarbons, ketones, and alcohols TEFLON - Widely used for manufacturing stirring bars, tubing, cryogenic vials, and bottle cap liners - Almost chemically inert and is suitable for use at temperatures ranging from –270° C to +255° C - Resistant to a wide range of chemical classes, including acids, bases, alcohol, and hydrocarbons

Answer 2

B. Fixed-angle head centrifuge

Answer 3

C. Swinging bucket centrifuge ## Footnote HORIZONTAL-HEAD OR SWINGING BUCKET CENTRIFUGE * HORIZONTAL WHEN MOVING OR SPINNING * VERITICAL WHEN NOT MOVING Cups holding the tubes of material to be centrifuged occupy a vertical position when the centrifuge is at rest but assume a horizontal position when the centrifuge revolves

Answer 4

C. Ultracentrifuge ## Footnote ULTRACENTRIFUGE - High-speed centrifuges used to separate layers of different specific gravities - Commonly used to separate lipoproteins - Usually refrigerated to counter heat produced through friction

Answer 5

D. Cytocentrifuge ## Footnote CYTOCENTRIFUGE - Uses a very high-torque and low-inertia motor to spread monolayers of cells rapidly across a special slide for critical morphologic studies - Used for blood, urine, body fluid, or any other liquid specimen that can be spread on a slide

Answer 6

A. Tachometer

Answer 7

C. Every 3 months (quarterly) ## Footnote Photoelectric tachometer or strobe tachometer CAP recommends that the number of revolutions per minute for a centrifuge used in chemistry laboratories be checked every 3 months

Answer 8

B. Weekly ## Footnote Calibration of centrifuges is customarily performed every 3 months, and the appropriate relative centrifugal force for each setting is recorded. Centrifuges are routinely disinfected on a weekly basis.

Answer 9

B. Standard ## Footnote A standard may differ from a control in its overall composition and in the way it is handled in the test. Standards are the best way to measure ACCURACY. Standards are used to establish reference points in the construction of graphs (e.g., manual hemoglobin curve) or to calculate a test result.

Answer 10

A. Control ## Footnote The value of a control specimen is known. Control specimens are tested in exactly the same way as the patient specimen and are tested daily or in conjunction with the unknown (patient) specimen. Controls are the best measurements of PRECISION and may represent normal or abnormal test values.

Answer 11

A. Deionized water

Answer 12

USP and NF chemical grade

Answer 13

B. Kilogram ## Footnote BASE QUANTITY 1. Length (meter) 2. Mass (kilogram) 3. Time (second) 4. Electric current (ampere) 5. Thermodynamic temperature (Kelvin) 6. Amount of substance (mole) 7. Luminous intensity (Candela)

Answer 14

A. pH ## Footnote The properties of osmotic pressure, vapor pressure, freezing point, and boiling point are called COLLIGATIVE PROPERTIES. When a solute is dissolved in a solvent, these colligative properties change in a predictable manner for each osmole of substance present: - FREEZING POINT IS LOWERED by −1.86°C - VAPOR PRESSURE IS LOWERED by 0.3 mm Hg or torr - OSMOTIC PRESSURE IS INCREASED by a factor of 1.7 × 104 mm Hg or torr - BOILING POINT IS RAISED by 0.52°C

Answer 15

B. Moderate ## Footnote DEGREE OF HAZARD 0: NO OR MINIMAL 1: SLIGHT 2: MODERATE 3: SERIOUS 4: EXTREME

Answer 16

C. Class C ## Footnote Fires have been divided into four classes based on the nature of the combustible material and requirements for extinguishment: Class A: ordinary combustible solid materials, such as paper, wood, plastic, and fabric Class B: flammable liquids/gases and combustible petroleum products Class C: energized electrical equipment Class D: combustible/reactive metals, such as magnesium, sodium, and potassium

Answer 17

A. 1 and 2 ## Footnote TYPE OF EXTINGUISHER (Bishop page 47) Class A: Pressurized water and dry chemical Class B: Dry chemical and carbon dioxide Class C: Dry chemical, carbon dioxide and halon Class D: Metal X

Answer 18

C. Shock ## Footnote Liquid nitrogen is probably one of the most widely used cryogenic fluids (liquefi ed gases) in the laboratory. There are, however, several hazards associated with the use of any cryogenic material: fire or explosion, asphyxiation, pressure buildup, embrittlement of materials, and tissue damage similar to that of thermal burns.

Answer 19

C. Ergonomic hazards ## Footnote ERGONOMIC HAZARDS The primary contributing factors associated with repetitive strain disorders are position/posture, applied force, and frequency of repetition. Remember to consider the design of hand tools (e.g., ergonomic pipets), adherence to ergonomically correct technique, and equipment positioning when engaging in any repetitive task. Chronic symptoms of pain, numbness, or tingling in extremities may indicate the onset of repetitive strain disorders. Other hazards include acute musculoskeletal injury. Remember to lift heavy objects properly, keeping the load close to the body and using the muscles of the legs rather than the back. Gradually increase force when pushing or pulling, and avoid pounding actions with the extremities.

Answer 20

B. Turn instrument off and unplug it ## Footnote Before REPAIR OR ADJUSTMENT of electrical equipment The following should be done (1) unplug the equipment (2) make sure the hands are dry (3) remove jewelry.

Answer 21

A. Pull the person away from the electrical source ## Footnote When an accident involving electrical shock occurs: The electrical source must be removed immediately. TURNING OFF THE CIRCUIT BREAKER, UNPLUGGING THE EQUIPMENT, or moving the equipment using a nonconductive glass or wood object are safe procedures to follow

Answer 22

B. Incandescent tungsten or tungsten-iodide lamp ## Footnote The most common source of light for work in the visible and near-infrared regions is the incandescent tungsten or tungsten-iodide lamp.

Answer 23

A. Deuterium discharge lamp and mercury arc lamp ## Footnote The lamps most commonly used for ultraviolet (UV) work are the deuterium discharge lamp and the mercury arc lamp.

Answer 24

A. Photomultiplier ## Footnote Because of this amplification, the PM tube is 200 times more sensitive than the phototube. PM tubes are used in instruments designed to be extremely sensitive to very low light levels and light flashes of very short duration.

Answer 25

B. Tungsten–halogen lamp ## Footnote Slide technology depends on refl ectance spectrophotometry. For colorimetric determinations, the light source is a tungsten–halogen lamp.

Answer 26

A. Hollow-cathode lamp ## Footnote The usual light source, known as a hollow-cathode lamp, consists of an evacuated gastight chamber containing an anode, a cylindrical cathode, and an inert gas, such as helium or argon.

Answer 27

C. 1 and 2 ## Footnote Nephelometry and turbidimetry are used to measure the concentrations of large particles (such as antigen–antibody complexes, prealbumin, and other serum proteins) that because of their size cannot be measured by absorption spectroscopy.

Answer 28

B. Inversely proportional

Answer 29

A. Increase in fluorescence

Answer 30

C. Nephelometry

Answer 31

C. Scintillation counter

Answer 32

A. Continuous flow analysis

Answer 33

A. Discrete analyzers ## Footnote All three can use batch analysis (i.e., large number of specimens in one run), but only discrete analyzers offer random-access, or stat, capabilities.

Answer 34

C. Function verification ## Footnote Function verification includes monitoring temperature, setting electronic parameters, calibrating instruments and analyzing control data.

Answer 35

D. Vigorously shaking the blood tube to prevent clotting ## Footnote Vigorously mixing can cause hemolysis.

Answer 36

C. 95% ## Footnote The probability of an observation having a value within ± 2 standard deviations of the mean in a normal distribution is 95%.

Answer 37

B. 5 ## Footnote The probability of an observation having a value of 2 SD from the mean in a normal distribution is 95.5%. Therefore, 5 control values out of 100 would be out of control due to random error.

Answer 38

C. Monitors patient sample day by day ## Footnote The delta check method compares current results from automated analyzers with the result from the most recent, previous values for the same patient.

Answer 39

C. 5.50 to 6.10 mg/dL ## Footnote Standard deviation is a measure of the dispersion of data around the mean.

Answer 40

Mean Median Mode ## Footnote The three most commonly used descriptions of the center of a dataset are the mean, the median, and the mode.

Answer 41

Coefficient of variation Range Standard deviation ## Footnote The spread represents the relationship of all the data points to the mean. There are three commonly used descriptions of spread: (1) range (2) standard deviation (SD), and (3) coefficient of variation (CV).

Answer 42

Fluctuations in line voltage Reagent lot variability Wear and tear of instrument ## Footnote Reference: Clinical Chemistry: A Laboratory Perspective [Arneson] A SYSTEMATIC ERROR, on the other hand, will be seen as a trend in the data. Control values gradually rise (or fall) from the previously established limits. This type of error includes improper calibration, deterioration of reagents, sample instability, instrument drift, or changes in standard materials. All the Westgard rules that indicate trends identify systematic errors. 2(2S), 4(1S) and 10(x) rule. SYSTEMATIC ERRORS MAY BE DUE TO: * Aging reagents * Aging calibrators * Instrument components * Optical changes * Fluctuations in line voltage * Wear and tear of instrument * Reagent lot variability * Calibration differences * Technologist interactions

Answer 43

Reagent dispensing Variation in handling techniques: pipetting, mixing, timing Variation in operator ## Footnote Reference: Clinical Chemistry: A Laboratory Perspective [Arneson] RANDOM ERROR is one with no trend or means of predicting it. Random errors include such situations as mislabeling a sample, pipetting errors, improper mixing of sample and reagent, voltage fluctuations not compensated for by instrument circuitry, and temperature fluctuations. Violations of the 1(2S), 1(3S) and R(4S) Westgard rules are usually associated with random error. To assess the situation, the sample is assayed using the same reagents. If a random error occurred, the same mistake may not be made again, and the result will be within appropriate control limits. RANDOM ERRORS MAY BE DUE TO: * Reagent dispensing * Sample evaporation * Temperature of analyzer * Electro-optical mechanism * Calibrator reconstitution * Environmental conditions * Instability of instrument * Variation in handling techniques: pipetting, mixing, timing * Variation in operators

Answer 44

C. Mode ## Footnote The mode is the most frequently occurring value in a dataset. Although it is seldom used to describe data, it is referred to when in reference to the shape of data, a bimodal distribution, for example.

Answer 45

A. Constant systematic error ## Footnote Constant error: Type of systemic error in the sample direction and magnitude; the magnitude of change is constant and not dependent on the amount of analyte. Proportional error: Type of systemic error where the magnitude changes as a percent of the analyte present; error dependent on analyte concentration.

Answer 46

B. Proportional systematic error ## Footnote Constant error: Type of systemic error in the sample direction and magnitude; the magnitude of change is constant and not dependent on the amount of analyte. Proportional error: Type of systemic error where the magnitude changes as a percent of the analyte present; error dependent on analyte concentration.

Answer 47

A. Bias ## Footnote Bias: Difference between the observed mean and the reference mean. Negative bias indicates that the test values tend to be lower than the reference value, whereas positive bias indicates test values are generally higher. Bias is a type of constant systematic error.

Answer 48

C. Diagnostic sensitivity ## Footnote Analytic sensitivity: Ability of a method to detect small quantities of an analyte. Analytic specificity: Ability of a method to detect only the analyte it is designed to determine. Diagnostic sensitivity: Ability of a test to detect a given disease or condition. Diagnostic specificity: Ability of a test to correctly identify the absence of a given disease or condition.

Answer 49

D. Diagnostic specificity ## Footnote Analytic sensitivity: Ability of a method to detect small quantities of an analyte. Analytic specificity: Ability of a method to detect only the analyte it is designed to determine. Diagnostic sensitivity: Ability of a test to detect a given disease or condition. Diagnostic specificity: Ability of a test to correctly identify the absence of a given disease or condition.

Answer 50

A. Analytic sensitivity ## Footnote Analytic sensitivity: Ability of a method to detect small quantities of an analyte. Analytic specificity: Ability of a method to detect only the analyte it is designed to determine. Diagnostic sensitivity: Ability of a test to detect a given disease or condition. Diagnostic specificity: Ability of a test to correctly identify the absence of a given disease or condition.

Answer 51

B. Analytic specificity ## Footnote Analytic sensitivity: Ability of a method to detect small quantities of an analyte. Analytic specificity: Ability of a method to detect only the analyte it is designed to determine. Diagnostic sensitivity: Ability of a test to detect a given disease or condition. Diagnostic specificity: Ability of a test to correctly identify the absence of a given disease or condition.

Answer 52

C. Chance of an individual having a given disease or condition if the test is abnormal. ## Footnote Positive predictive value: Chance of an individual having a given disease or condition if the test is abnormal. Negative predictive value: Chance an individual does not have a given disease or condition if the test is within the reference interval.

Answer 53

D. Chance an individual does not have a given disease or condition if the test is within the reference interval. ## Footnote Positive predictive value: Chance of an individual having a given disease or condition if the test is abnormal. Negative predictive value: Chance an individual does not have a given disease or condition if the test is within the reference interval.

Answer 54

C. 95.45% ## Footnote 68.26% will lie within ±1 s 95.45% will lie within ±2 s 99.74% will lie within ±3 s

Answer 55

B. 2:2S ## Footnote Westgard multirule is a control procedure that utilizes control rules to assess numerical quality control data; the control rules establish the limits for data rejection in a system with two controls. Other rules apply when three controls are used. 1:2s = 1 control value exceeds the mean ±2 standard deviations; warning rule that triggers inspection of control values using the other rejection rules that follow; only rule that is not used to reject a run; results are reportable 1:3s = 1 control value exceeds the mean ±3 standard deviations; detects random error 2:2s = 2 consecutive control values exceed the same 2 standard deviation limit (same mean +2 s or same mean -2 s); detects systematic error R:4s = 1 control value in a group exceeds the mean +2 s and a second control value exceeds the mean -2 s, creating a 4 standard deviation spread; detects random error 4:ls = 4 consecutive control values are recorded on one side of the mean and exceed either the same mean +1 s or the same mean -1 s; detects systematic error 10:x =10 consecutive control values are recorded on one side of the mean (either above or below the mean); detects systematic error

Answer 56

B. Two controls in the same run are greater than 4s units apart ## Footnote The R:4s rule is applied to two control levels within the same run. The rule is violated when the algebraic difference between them (level 1 – level 2) exceeds 4s. The R:4s rule detects random error (error due to poor precision).

Answer 57

B. Systematic error ## Footnote Systemic error: Error always in one direction. Random error: Error varies from sample to sample.

Answer 58

A. Random error ## Footnote Random errors are deviations from the true value caused by unavoidable errors inherent in laboratory measurements. The standard error of the mean is a statistical concept refl ecting sampling variation. It is the standard deviation of the entire population. Parametric statistics refer to a Gaussian (normal) distribution of data. Nonparametric statistics are more general and require no assumptions.

Answer 59

A. Deterioration of the reagent

Answer 60

A. Levy–Jennings ## Footnote 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.

Answer 61

B. Tonks–Youden ## Footnote 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.

Answer 62

C. Cusum ## Footnote 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.

Answer 63

C. Accuracy ## Footnote The accuracy of an analytical result is the closeness with which the measured value agrees with the true value. Precision is reproducibility. Accuracy and precision are independent, but it is the goal of the clinical laboratory to design methods that are both precise and accurate.

Answer 64

B. Precision ## Footnote Accuracy is easy to define but difficult to establish and maintain. Precision is relatively easy to measure and maintain.

Answer 65

A. Reliability ## Footnote The reliability of an analytical procedure is its ability to maintain accuracy and precision over an extended period of time during which supplies, equipment, and personnel in the laboratory may change. It is often used interchangeably with the term "consistency." It is the goal of every clinical laboratory to produce reliable results.

Answer 66

A. Student’s t test ## Footnote T TEST: COMPARES MEANS, ACCURACY F TEST: COMPARES S.D., PRECISION Student’s t test is the ratio of mean difference to the standard error of the mean difference (bias/random error) and tests for a signifi cant difference in means. The F test is the ratio of variances and determines if one method is significantly less precise.

Answer 67

A. Glucose

Answer 68

D. 120 minutes (2 hours)

Answer 69

B. 5 to 15 mg/dL ## Footnote Glucose measurements can be 5 to 15 mg/dL erroneously higher by reducing methods than by more accurate enzymatic methods.

Answer 70

A. Glucose oxidase ## Footnote Glucose oxidase is the most specifi c enzyme reacting with only beta D-glucose. Glucose oxidase converts beta D-glucose to gluconic acid. Mutarotase may be added to the reaction to facilitate the conversion of alpha-D-glucose to beta-D-glucose.

Answer 71

C. Glucose-6-phosphate dehydrogenase ## Footnote The hexokinase method is considered more accurate than the glucose oxidase methods because the coupling reaction using glucose-6-phosphate dehydrogenase is highly specific; therefore, it has less interference than the coupled glucose oxidase procedure.

Answer 72

B. Hemolysis ## Footnote Hemolyzed samples require a serum blank correction (subtraction of the reaction rate with hexokinase omitted from the reagent).

Answer 73

B. False decrease ## Footnote Generally accepted as the reference method, hexokinase method is not affected by ascorbic acid or uric acid. Gross hemolysis and extremely elevated bilirubin may cause a false decrease in results.

Answer 74

A. Type 1 diabetes mellitus

Answer 75

B. Type 2 diabetes mellitus

Answer 76

B. Data represents an impaired glucose status ## Footnote Resting plasma glucose NORMAL <140 IMPAIRED 140 – 199 DIAGNOSTIC ≥ 200 mg/dL Fasting plasma glucose NORMAL <100 IMPAIRED 100 – 125 DIAGNOSTIC ≥ 126 mg/dL 2-hour OGTT NORMAL <140 IMPAIRED 140 – 199 DIAGNOSTIC ≥ 200 mg/dL HbA1c NORMAL <5.7 % IMPAIRED 5.7 – 6.4% DIAGNOSTIC ≥ 6.5%

Answer 77

B. 6.5% ## Footnote 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.

Answer 78

B. Red blood cell life span ## Footnote Two factors determine the glycosylated hemoglobin levels: the average glucose concentration and the red blood cell life span. If the red blood cell life span is decreased because of another disease state such as hemoglobinopathies, the hemoglobin will have less time to become glycosylated and the glycosylated hemoglobin level will be lower.

Answer 79

A. Glycosylated hemoglobin (HbA1c) ## Footnote Long-term estimation of glucose concentration can be followed by measuring glycosylated hemoglobin (Hb A1c). A level of 8% or less is considered “good” glycemic control. Because the average red blood cell lives approximately 120 days, the glycosylated hemoglobin level at any one time reflects the average blood glucose level over the previous 2 to 3 months. Therefore, measuring the glycosylated hemoglobin provides the clinician with a time-averaged picture of the patient’s blood glucose concentration over the past 3 months.

Answer 80

B. Fructosamine ## Footnote FRUCTOSAMINE: GLYCOSYLATED ALBUMIN Fructosamine assays are the most widely used to assess short-term (3 to 6 weeks) glycemic control because the average half-life of the proteins is 2–3 weeks.

Answer 81

B. Gluconeogenesis ## Footnote Glycolysis Metabolism of glucose molecule to pyruvate or lactate for production of energy Gluconeogenesis Formation of glucose-6-phosphate from noncarbohydrate sources Glycogenolysis Breakdown of glycogen to glucose for use as energy Glycogenesis Conversion of glucose to glycogen for storage Lipogenesis Conversion of carbohydrates to fatty acids Lipolysis Decomposition of fat

Answer 82

B. Glucagon ## Footnote Glucagon is the primary hormone responsible for increasing glucose levels. It is synthesized by the ALPHA-cells of islets of Langerhans in the pancreas and released during stress and fasting states. ACTION OF GLUCAGON Increases glycogenolysis: glycogen → glucose Increases gluconeogenesis: fatty acids → acetyl-CoA → ketone, proteins → amino acids

Answer 83

D. Insulin ## Footnote Insulin is the only hormone that decreases glucose levels and can be referred to as a hypoglycemic agent. Insulin is the primary hormone responsible for the entry of glucose into the cell. It is synthesized by the beta cells of islets of Langerhans in the pancreas. It decreases plasma glucose levels by increasing the transport entry of glucose in muscle and adipose tissue by way of nonspecific receptors. It also regulates glucose by increasing glycogenesis, lipogenesis, and glycolysis and inhibiting glycogenolysis. ACTION OF INSULIN * Increases glycogenesis and glycolysis: glucose → glycogen → pyruvate → acetyl-CoA * Increases lipogenesis * Decreases glycogenolysis

Answer 84

A. Hyperglycemia ## Footnote CORTISOL INCREASES BLOOD GLUCOSE.

Answer 85

A. Below 50 mg/dL

Answer 86

A. Type 1 DM

Answer 87

B. Type 2 DM

Answer 88

B. 50 grams ## Footnote ORAL LACTOSE TOLERANCE TESTS, measuring the increase in plasma glucose or galactose following ingestion of lactose, have been used to diagnose lactase defi ciency.

Answer 89

A. Apo-A1 ## Footnote Apo-A1 is the predominant apoprotein associated with the high-density lipoprotein (HDL) molecule, activates (lecithin cholesterol acyltransferase [LCAT]), and is associated with reverse cholesterol transport. As a result, it is protective against coronary artery disease.

Answer 90

C. Pancreatitis ## Footnote Marked increases in triglyceride levels, between 1000 and 2000 mg/dL have been associated with increased risk for the development of pancreatitis.

Answer 91

A. IgM ## Footnote Waldenström’s primary macroglobulinemia (WM), or simply macroglobulinemia, is a B cell disorder characterized by the infiltration of lymphoplasmacytic cells into bone marrow and the presence of an IgM monoclonal gammopathy.

Answer 92

D. Serum-free light chain immunoassay ## Footnote Measurement of free light chains is recommended along with protein electrophoresis when testing for myeloma. Free light chains are normally present in serum because L chains are made at a faster rate than H chains.

Answer 93

D. Measurement of serum-free light chains ## Footnote Unlike electrophoresis methods, serum free light chain assays are quantitative and an increase in free light chain production with an abnormal kappa:lambda ratio occurs earliest in recurrence of myeloma.

Answer 94

D. Diagnosis of monoclonal gammopathies

Answer 95

D. All of these

Answer 96

C. Proteinuria

Answer 97

A. Negatively, anode

Answer 98

B. BCG (Bromcresol green)

Answer 99

B. Bromcresol purple (BCP) ## Footnote BCP is more specific for albumin than BCG.

Answer 100

C. Dehydration

Answer 101

A. Prolonged tourniquet application

Answer 102

A. Microalbuminuria

Answer 103

A. Glutamine ## Footnote Glutamine is the most abundant amino acid in the body, being involved in more metabolic processes than any other amino acid.

Answer 104

D. Tyrosine ## Footnote Tyrosine is a precursor of the adrenal hormones epinephrine, norepinephrine, and dopamine and the thyroid hormones, including thyroxine. It is important in overall metabolism, aiding in the functions of the adrenal, thyroid, and pituitary glands.

Answer 105

A. Albumin ## Footnote Albumin is responsible for nearly 80% of the colloid osmotic pressure (COP) of the intravascular fluid, which maintains the appropriate fluid balance in the tissue.

Answer 106

A. Prealbumin ## Footnote A low prealbumin level is a sensitive marker of poor nutritional status. When a diet is deficient in protein, hepatic synthesis of proteins is reduced, with the resulting decrease in the level of the proteins originating in the liver, including prealbumin, albumin, and β-globulins. Because prealbumin has a short half-life of approximately 2 days, it decreases more rapidly than do other proteins.

Answer 107

A. A decreased level of prealbumin

Answer 108

D. Prealbumin ## Footnote Prealbumin is the transport protein for thyroxine and triiodothyronine (thyroid hormones); it also binds with retinol-binding protein to form a complex that transports retinol (vitamin A) and is rich in tryptophan.

Answer 109

B. Emphysema

Answer 110

D. Down syndrome ## Footnote Conditions associated with an elevated AFP level include spina bifi da, neural tube defects, abdominal wall defects, anencephaly (absence of the major portion of the brain), and general fetal distress. Low levels of maternal AFP indicate an increased risk for Down syndrome and trisomy 18, while it is increased in the presence of twins and neural tube defects.

Answer 111

A. Alpha2-macroglobulin ## Footnote In nephrosis, the levels of serum α2-macroglobulin may increase as much as 10 times because its large size aids in its retention. The protein is also increased in diabetes and liver disease. Use of contraceptive medications and pregnancy increase the serum levels by 20%.

Answer 112

D. Alpha1-acid glycoprotein ## Footnote α1-Acid Glycoprotein (Orosomucoid) α1-Acid glycoprotein (AAG), a major plasma glycoprotein, is negatively charged even in acid solutions, a fact that gave it its name. This protein is produced by the liver and is an acute-phase reactant.

Answer 113

B. Beta2-microglobulin ## Footnote β2-microglobulin is a single polypeptide chain that is the light chain component of human leukocyte antigens (HLAs). It is found on the surface of nucleated cells and is notably present on lymphocytes. Increased plasma levels of β2-microglobulin are associated with renal failure, lymphocytosis, rheumatoid arthritis, and systemic lupus erythematosus.

Answer 114

C. Fibronectin

Answer 115

D. Fetal fibronectin ## Footnote Fetal fibronectin (fFN) is a glycoprotein used to help predict the short-term risk of premature delivery.

Answer 116

B. Crosslinked C-telopeptides (CTX) ## Footnote Cross-linked C-telopeptides (CTXs) are proteolytic fragments of collagen I formed during bone resorption (turnover). CTX is a biochemical marker of bone resorption that can be detected in serum and urine.

Answer 117

A. Beta-trace protein ## Footnote β-Trace protein (BTP; synonym prostaglandin D synthase) is a 168–amino acid, low-molecular-mass protein in the lipocalin protein family. Recently, it was verifi ed that BTP was established as an accurate marker of CSF leakage. It has also been reported recently as a potential marker in detecting impaired renal function, although no more sensitive than cystatin C.

Answer 118

D. Cystatin C

Answer 119

A. Amyloid β42 (Aβ42) and Tau protein ## Footnote In a symptomatic patient, low Aβ42 along with high Tau refl ects an increased likelihood of Alzheimer disease, but it does not mean that the person defi nitely has Alzheimer disease. If a patient does not have abnormal levels of these proteins, then the dementia is more likely due to a cause other than Alzheimer disease.

Answer 120

D. Myoglobin ## Footnote As a cardiac biomarker, myoglobin has been used in conjunction with troponin to help diagnose or rule out a heart attack. When striated muscle is damaged, myoglobin is released, elevating the blood levels. In an AMI, this increase is seen within 2 to 3 hours of onset and reaches peak concentration in 8 to 12 hours. Myoglobin is a small molecule freely filtered by the kidneys, allowing levels to return to normal in 18 to 30 hours after the AMI. Because of the speed of appearance and clearance of myoglobin, it is also a useful marker for monitoring the success or failure of reperfusion.

Answer 121

D. Troponin ## Footnote ACUTE CORONARY SYNDROME/MYOCARDIAL INFARCTION Cardiac troponin (cTn) represents a complex of regulatory proteins that include troponin I (cTnI) and troponin T (cTnT) that are specific to heart muscle. cTnI and cTnT are the “gold standard” in the diagnosis of acute coronary syndrome (ACS). cTn should be measured in all patients presenting with symptoms suggestive of ACS, in conjunction with physical examination and ECG.

Answer 122

B. hs-CRP ## Footnote HIGH-SENSITIVITY CRP Considered a GOOD PREDICTOR TEST for assessing cardiovascular risk CK-MB, TROPONIN AND MYOGLOBIN Used to assess if a myocardial infarction HAS OCCURRED

Answer 123

B. B-type natriuretic peptide ## Footnote B-type (brain) natriuretic peptide (BNP) is used to determine if physical symptoms are related to congestive heart failure.

Answer 124

B. BNP and echocardiogram ## Footnote DIAGNOSIS OF CONGESTIVE HEART FAILURE: Until recently, this condition was diagnosed strictly on the basis of symptomatology and/or as a result of procedures such as echocardiography, but more recently a biomarker for this condition is the brain form or B-type natriuretic peptide (BNP), which has been approved as a definitive test for this condition and appears to be an excellent marker for early heart failure.

Answer 125

A. Albumin cobalt binding ## Footnote Albumin cobalt binding is a test that measures ischemia-modified albumin, which is a marker for ischemic heart disease.

Answer 126

C. Chylomicron ## Footnote These chylomicrons enter the blood through the lymphatic system, where they impart a turbid appearance to serum.

Answer 127

D. Greater than 600 mg/dL ## Footnote The appearance of the plasma or serum can be observed and noted after a minimum 12- hour fast. If the plasma is clear, the triglyceride level is probably less than 200 mg/dL. When the plasma appears hazy or turbid, the triglyceride level has increased to greater than 300 mg/dL, and if the specimen appears opaque and milky (lipemic, from chylomicrons), the triglyceride level is probably greater than 600 mg/dL. Note: 1. Clear plasma: TAG < 200 mg/dL 2. Hazy or turbid plasma: TAG > 300 mg/dL 3. Opaque or milky plasma: TAG > 600 mg/dL

Answer 128

D. Total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol ## Footnote A "routine" lipid profile would most likely consist of the measurement of total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol.

Answer 129

D. In the fasting state, approximately 12 hours after eating ## Footnote Blood specimens for lipid studies should be drawn in the fasting state at least 9 to 12 hours after eating. Although fat ingestion only slightly affects cholesterol levels, the triglyceride results are greatly affected. Triglycerides peak at about 4 to 6 hours after a meal, and these exogenous lipids should be cleared from the plasma before analysis.

Answer 130

A. Cholesterol ## Footnote Total cholesterol screenings are commonly performed on nonfasting individuals. Total cholesterol is only slightly affected by the fasting status of the individual, whereas triglycerides, fatty acids, and lipoproteins are greatly affected.

Answer 131

D. Lipase ## Footnote It is first necessary to hydrolyze the triglycerides to free fatty acids and glycerol. This hydrolysis step is catalyzed by the enzyme lipase. The glycerol is then free to react in the enzyme-coupled reaction system that includes glycerokinase, pyruvate kinase, and lactate dehydrogenase or in the enzyme-coupled system that includes glycerokinase, glycerophosphate oxidase, and peroxidase.

Answer 132

D. Chylomicrons ## Footnote Chylomicrons, which contain apo B-48, are the largest and the least dense of the lipoprotein particles. HDL, the smallest and most dense lipoprotein particle, is synthesized by both the liver and the intestine.

Answer 133

B. HDL ## Footnote Chylomicrons, which contain apo B-48, are the largest and the least dense of the lipoprotein particles. HDL, the smallest and most dense lipoprotein particle, is synthesized by both the liver and the intestine.

Answer 134

D. LpX ## Footnote Lipoprotein X is an abnormal lipoprotein present in patients with biliary cirrhosis or cholestasis and in patients with mutations in lecithin:cholesterol acyltransferase (LCAT), the enzyme that esterifi es cholesterol.

Answer 135

C. Chylomicrons ## Footnote From the epithelial cells, the chylomicrons are released into the lymphatic system, which transports chylomicrons to the blood. The chylomicrons may then carry the triglycerides to adipose tissue for storage, to organs for catabolism, or to the liver for incorporation of the triglycerides into very-low-density lipoproteins (VLDLs). Chylomicrons are normally cleared from plasma within 6 hours after a meal.

Answer 136

A. VLDL ## Footnote VLDL transports the majority of endogenous triglycerides, while the triglycerides of chylomicrons are derived entirely from dietary absorption.

Answer 137

B. Cholesterol ## Footnote The beta-lipoprotein fraction is composed of approximately 50% cholesterol, 6% triglycerides, 22% phospholipids, and 22% protein. The beta-lipoproteins, which are also known as the low-density lipoproteins (LDLs), are the principal transport vehicle for cholesterol in the plasma.

Answer 138

C. 50% ## Footnote About 50% of the weight of HDL is protein, largely apo A-I and apo A-II. The HDL is about 30% phospholipid and 20% cholesterol by weight.

Answer 139

B. High-density lipoproteins (HDLs) ## Footnote The HDLs, also known as the alpha-lipoproteins, have the greatest density of 1.063-1.210 g/mL and move the fastest electrophoretically toward the anode.

Answer 140

C. Coronary artery disease ## Footnote The quantifi cation of the HDL cholesterol level is thought to contribute in assessing the risk that an individual may develop coronary artery disease (CAD). There appears to be an inverse relationship between HDL cholesterol and CAD. With low levels of HDL cholesterol, the risk of CAD increases.

Answer 141

C. HDL-C concentration < 40 mg/dL ## Footnote POSITIVE (INCREASED) RISK FACTORS * Age: ≥ 45 y for men; ≥ 55 y or premature menopause for women * Family history of premature CHD * Current cigarette smoking * Hypertension (blood pressure ≥ 140/90 mm Hg or taking antihypertensive medication) * LDL-C concentration ≥ 160 mg/dL (≥ 4.1 mmol/L), with ≤ 1 risk factor * LDL-C concentration ≥ 130 mg/dL (3.4 mmol/L), with ≥ 2 risk factors * LDL-C concentration ≥ 100 mg/dL (2.6 mmol/L), with CH D or risk equivalent * HDL-C concentration < 40 mg/dL (< 1.0 mmol/L) * Diabetes mellitus = CH D risk equivalent * Metabolic syndrome (multiple metabolic risk factors) NEGATIVE (DECREASED) RISK FACTORS * HDL-C concentration ≥ 60 mg/dL (≥ 1.6 mmol/L) * LDL-C concentration < 100 mg/dL (< 2.6 mmol/L)

Answer 142

A. Apoprotein A-I ## Footnote Apoprotein A-I and apo A-II are the principal apoproteins of HDL, and low apo A-I has a high correlation with atherosclerosis. Conversely, apo-B100 is the principal apoprotein of LDL, and an elevated level is a major risk factor in developing coronary heart disease.

Answer 143

C. Apo-B100 ## Footnote LDL primarily contains apo B-100 and is more cholesterol rich than other apo B–containing lipoproteins. Note: Apo-AI, Apo-AII = HDL Apo-B100 = LDL, VLDL Apo-B48 = chylomicrons

Answer 144

C. Triglyceride ## Footnote The VLDL fraction is primarily composed of triglycerides and lesser amounts of cholesterol and phospholipids.

Answer 145

C. Heparin-manganese ## Footnote Either a dextran sulfate-magnesium chloride mixture or a heparin sulfate-manganese chloride mixture may be used to precipitate the LDL and VLDL cholesterol fractions. This allows the HDL cholesterol fraction to remain in the supernatant.

Answer 146

D. Apoprotein A-I deficiency ## Footnote Deficiency of apo A-I is seen in Tangier disease, a familial hypocholesterolemia.

Answer 147

B. 210 ## Footnote Once the total cholesterol, triglyceride, and HDL cholesterol are known, LDL cholesterol can be quantified by using the Friedewald equation LDL cholesterol = Total cholesterol — (HDL cholesterol + Triglyceride/5) In this example, all results are in mg/dL: LDL cholesterol = 300 - (50 + 200/5) = 300 - (90) = 210 mg/dL

Answer 148

D. Triglycerides over 400 mg/dL ## Footnote LDL cholesterol may be calculated or measured directly: 1. Friedewald formula Indirect, not valid for triglycerides over 400mg/dL LDL cholesterol = total cholesterol — [HDL cholesterol + triglyceride/5] 2. Homogeneous assay uses detergents to block HDL and VLDL from reacting with the dye to form a colored chromogen product. An enzymatic cholesterol analysis is performed with only LDL cholesterol able to react.

Answer 149

C. – Chylomicrons →β→pre-β→α + ## Footnote Although pre-β lipoprotein is lower in density than β lipoprotein, it migrates faster on agarose or cellulose acetate owing to its more negative apoprotein composition. LIPOPROTEINS 1. By electrophoresis From the origin: chylomicrons > beta (LDL) > prebeta (VLDL) > alpha (HDL) Anode 2. By ultracentrifugation From the least dense and largest: chylomicrons > VLDL > LDL > HDL most dense and smallest

Answer 150

B. B-VLDL ## Footnote β-VLDL (‘fl oating β’ lipoprotein) is an abnormal lipoprotein that accumulates in type 3 hyperlipoproteinemia. It is richer in cholesterol than VLDL and apparently results from the defective catabolism of VLDL. The particle is found in the VLDL density range but migrates electrophoretically with or near LDL.

Answer 151

A. Lp(a) ## Footnote Lp(a) has a density similar to LDL, but migrates similarly to VLDL on electrophoresis. Thus it can be detected when the d > 1.006 g/mL protein is examined electrophoretically. When Lp(a) is present in concentrations exceeding 20-30 mg/dL (i.e., when it contributes more than about 10 mg/dL to the LDL-C measurement) an additional band with pre-β mobility is also observed in the d > 1.006 kg/L fraction (hence the name sinking pre-β-lipoprotein).

Answer 152

A. Lp(a) ## Footnote Lipoprotein (a) is an apolipoprotein that is more commonly referred to as Lp(a). Although it is related structurally to LDL, Lp(a) is considered to be a distinct lipoprotein class with an electrophoretic mobility in the prebeta region. Lp(a) is believed to interfere with the lysis of clots by competing with plasminogen in the coagulation cascade, thus increasing the likelihood of atherosclerotic cardiovascular disease.

Answer 153

D. Elevated VLDL and presence of chylomicrons ## Footnote BLOOD LIPOPROTEIN PATTERNS IN PATIENTS WITH HYPERLIPOPROTEINEMIA Type I: Extremely elevated TG due to the presence of chylomicrons Type IIa: Elevated LDL Type IIb: Elevated LDL and VLDL Type III: Elevated cholesterol, TG; presence of B-VLDL Type IV: Elevated VLDL Type V: Elevated VLDL and presence of chylomicrons

Answer 154

A. Pre-renal azotemia

Answer 155

B. Renal azotemia

Answer 156

C. Post-renal azotemia

Answer 157

A. The catabolism of proteins and amino acids ## Footnote Urea is generated by deamination of amino acids. Most is derived from the hepatic catabolism of proteins. Uric acid is produced by the catabolism of purines. Oxidation of pyrimidines produces orotic acid.

Answer 158

A. Oxidation of creatine

Answer 159

A. Alkaline picrate ## Footnote The classic Jaffe reaction involves complexing of creatinine with an alkaline picrate solution to produce a red complex (Janovski complex).

Answer 160

B. Creatinine

Answer 161

B. Cystatin C

Answer 162

B. Catabolism of purines ## Footnote Uric acid is the principal product of purine (adenosine and guanosine) metabolism.

Answer 163

B. Ammonia ## Footnote Severe liver disease is the most common cause of altered ammonia metabolism. Therefore the monitoring of ammonia levels may be used to determine prognosis.

Answer 164

C. Hepatic coma ## Footnote Hepatic coma is caused by accumulation of ammonia in the brain as a result of liver failure. The ammonia increases central nervous system pH and is coupled to glutamate, a central nervous system neurotransmitter, forming glutamine. Blood and cerebrospinal fluid ammonia levels are used to distinguish encephalopathy caused by cirrhosis or other liver disease from nonhepatic causes and to monitor patients with hepatic coma.

Answer 165

D. Urea ## Footnote UREA > AMINO ACIDS > URIC ACID > CREATININE > CREATINE > AMMONIA Constituents in the plasma that contain the element nitrogen are categorized as being protein- or nonprotein-nitrogen compounds. The principal substances included among the nonprotein-nitrogen compounds are urea, amino acids, uric acid, creatinine, creatine, and ammonia. Of these compounds, urea is present in the plasma in the greatest concentration, comprising approximately 45% of the nonprotein-nitrogen fraction.

Answer 166

B. 2.14 ## Footnote BUN is multiplied by 2.14 to give the urea concentration in mg/dL.

Answer 167

D. 64 mg/dL ## Footnote 30 x 2.14 = 64.2 mg/dL When it is necessary to convert urea nitrogen values to urea, the concentration may be calculated easily by multiplying the urea nitrogen value by 2.14. This factor is derived from the molecular mass of urea (60 daltons) and the molecular weight of its two nitrogen atoms (28):

Answer 168

B. Sodium fluoride ## Footnote With the urease reagent systems for the quantifi cation of urea, the use of sodium fluoride must be avoided because of its inhibitory effect on this system.

Answer 169

B. Urea ## Footnote In the diacetyl method, acidic diacetyl reacts directly with urea to form a yellow-diazine derivative.

Answer 170

D. Diabetes mellitus ## Footnote Diseases associated with elevated blood ammonia levels include Reye syndrome, renal failure, chronic liver failure, cirrhosis, and hepatic encephalopathy.

Answer 171

A. The patient had two cigarettes 15 minutes prior to blood draw. ## Footnote Cigarette smoking by the patient is a significant source of ammonia contamination. It is recommended that patients do not smoke for several hours before a specimen is collected.

Answer 172

A. Glomerular filtration rate is decreased by at least 50% ## Footnote The assay for urea is only a rough estimate of renal function and will not show any significant level of increased concentration until the glomerular filtration rate is decreased by at least 50%. A more reliable single index of renal function is the test for serum creatinine. Contrary to urea concentration, creatinine concentration is relatively independent of protein intake (from the diet), degree of hydration, and protein metabolism.

Answer 173

D. Creatinine ## Footnote The quantity of creatinine formed daily is a relatively constant amount because it is related to muscle mass. Therefore, it has been customary to quantify the creatinine present in a 24-hour urine specimen as an index of the completeness of the collection.

Answer 174

D. Uric acid ## Footnote Uric acid may be quantifi ed by reacting it with phosphotungstic acid reagent in alkaline solution.

Answer 175

A. Chronic renal failure ## Footnote As renal function continues to be lost over time, chronic renal failure develops. Chronic renal failure is manifested by loss of excretory function, inability to regulate water and electrolyte balance, and increased production of parathyroid hormone, all of which contribute to the abnormal laboratory findings. The decreased production of erythropoietin causes anemia to develop.

Answer 176

D. Uric acid ## Footnote Gout is a pathological condition that may be caused by a malfunction of purine metabolism or a depression in the renal excretion of uric acid. Two of the major characteristics of gout are hyperuricemia and a deposition of uric acid as monosodium urate crystals in joints, periarticular cartilage, bone, bursae, and subcutaneous tissue.

Answer 177

A. Lesch-Nyhan syndrome ## Footnote Lesch-Nyhan syndrome is an X-linked genetic disorder (seen only in males) caused by the complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, an importantenzyme in the biosynthesis of purines.

Answer 178

A. Uric acid ## Footnote An increase in serum uric acid levels may be seen during chemotherapy for leukemia. The cause of this is the accelerated breakdown of cell nuclei in response to the chemotherapy. Other proliferative disorders that may respond similarly are lymphoma, multiple myeloma, and polycythemia. It is important that serum uric acid be monitored during chemotherapy to avoid nephrotoxicity.

Answer 179

D. Biliverdin ## Footnote It is biliverdin that is the immediate precursor of bilirubin formation. Mesobilirubinogen and urobilinogen represent intestinal breakdown products of bilirubin catabolism.

Answer 180

B. Azobilirubin ## Footnote Diazo reagent is a mixture of sulfanilic acid, sodium nitrite, and hydrochloric acid. The mixing of sodium nitrite with hydrochloric acid forms nitrous acid, which in turn reacts with sulfanilic acid to form a diazonium salt. This diazotized sulfanilic acid mixture, when mixed with solubilized bilirubin, forms a red azobilirubin complex.

Answer 181

C. Uridine diphosphate glucuronyltransferase ## Footnote In order for the bilirubin-albumin complex to reach the parenchymal cells of the liver, the complex must be transported from the sinusoids to the sinusoidal microvilli and into the parenchymal cell. The microsomal fraction of the parenchymal cell is responsible for the conjugation of bilirubin. It is here that bilirubin reacts with uridine diphosphate glucuronate in the presence of the enzyme uridine diphosphate glucuronyltransferase to form bilirubin diglucuronide.

Answer 182

B. Urobilin ## Footnote In the colon, a portion of the urobilinogen is oxidized by the action of microorganisms to urobilin, which is excreted in the feces as an orange-brown pigment

Answer 183

A. Albumin ## Footnote Albumin acts as the transport vehicle for unconjugated bilirubin in the blood, with each mole of albumin capable of binding two moles of bilirubin.

Answer 184

A. Jaundice ## Footnote Jaundice may be caused by an increase in either the unconjugated or conjugated form of bilirubin. Such increases in bilirubin levels may be caused by prehepatic, hepatic, or posthepatic disorders.

Answer 185

A. Brain ## Footnote Kernicterus refers to the accumulation of bilirubin in brain tissue that occurs with elevated levels of unconjugated bilirubin. This condition is most commonly seen in newborns with hemolytic disease resulting from maternal-fetal Rh incompatibility. Newborns afflicted with kernicterus will exhibit severe neural symptoms.

Answer 186

B. Urobilinogen ## Footnote In the small intestine, urobilinogen is formed through the enzymatic reduction process of anaerobic bacteria on bilirubin.

Answer 187

D. Specimen refrigeration ## Footnote Bilirubin will deteriorate when exposed to either white or UV light. This deterioration is also temperature sensitive. Thus, specimens for bilirubin analysis should be stored in the dark at refrigerator temperature until the assay can be performed. Lipemia should be avoided, due to its interference with spectrophotometric analyses. Because hemoglobin reacts with diazo reagent, use of hemolyzed specimens should be avoided. Hemolysis will cause bilirubin results to be falsely low.

Answer 188

C. Delta ## Footnote Four bilirubin fractions represented by Greek letters have been identifi ed: unconjugated (alpha), monoconjugated (beta), diconjugated (gamma), and unconjugated bilirubin covalently bound to albumin (delta). Delta-bilirubin is normally present in low concentration in the blood, and it is known to react directly with diazotized sulfanilic acid. Increased serum levels of delta-bilirubin are associated with liver-biliary disease. According to Bishop: DELTA bilirubin is CONJUGATED bilirubin that is covalently bound to albumin.

Answer 189

A. Spleen ## Footnote The cells of the reticuloendothelial system are responsible for the removal of old red blood cells from the peripheral circulation. As the red blood cells reach the end of their 120-day life span, the specialized cells mainly of the spleen phagocytize the aged cells and convert the released hemoglobin into the excretory pigment bilirubin.

Answer 190

A. Insoluble in water ## Footnote Direct bilirubin was so named because of its ability in the van den Bergh method to react directly with diazotized sulfanilic acid without the addition of alcohol. Such a direct reaction is possible because direct bilirubin is conjugated in the liver with glucuronic acid, thereby making it a polar, water-soluble compound. Because conjugated bilirubin is both water soluble and not protein bound, it may be filtered through the glomerulus and excreted in the urine of jaundiced patients.

Answer 191

A. Conjugated bilirubin ## Footnote Because conjugated bilirubin is both water soluble and not protein bound, it may be filtered through the glomerulus and excreted in the urine of jaundiced patients.

Answer 192

C. Diazo ## Footnote Ehrlich's DIAZO REAGENT consists of sulfanilic acid, hydrochloric acid, and sodium nitrite.

Answer 193

C. Caffeine-sodium benzoate ## Footnote Unlike direct bilirubin, indirect-reacting bilirubin is insoluble in deionized water and dilute hydrochloric acid. Indirect-reacting bilirubin must first be mixed with methanol or caffeinesodium benzoate to solubilize it before proceeding with the diazo reaction. Note: EVELYN-MALLOY: methanol JENDRASSIK-GROF: caffeine-sodium benzoate

Answer 194

D. Obstructive jaundice ## Footnote "Obstructive jaundice" is a term applied to conditions in which the common bile duct is obstructed because of gallstone formation, spasm, or neoplasm. Such an obstruction blocks the flow of bile from the gallbladder into the small intestine. This impedance of bile flow will result in a backfl ow of bile from the gallbladder into the sinusoids of the liver and ultimately into the peripheral circulation. Because the liver is not initially involved and the disorder is of posthepatic origin, the increased levels of bilirubin in the blood are caused by the backfl ow of conjugated bilirubin.

Answer 195

A. Unconjugated serum bilirubin level increased ## Footnote Hemolytic jaundice is also referred to as prehepatic jaundice. It is caused by excessive destruction of erythrocytes at a rate that exceeds the conjugating ability of the liver. As a result, increased levels of unconjugated bilirubin appear in the blood.

Answer 196

D. Deficiency in the bilirubin conjugation enzyme system ## Footnote The enzyme uridine diphosphate glucuronyltransferase catalyzes the conjugation of bilirubin with glucuronic acid. In newborns, especially premature infants, this liver enzyme system is not fully developed or functional. Because of this deficiency in the enzyme system, the concentration of unconjugated bilirubin rises in the blood, because only the conjugated form may be excreted through the bile and urine. The increased levels of unconjugated bilirubin will cause the infant to appear jaundiced. Generally, this condition persists for only a short period because the enzyme system usually becomes functional within several days after birth.

Answer 197

D. Gilbert syndrome ## Footnote Gilbert syndrome is a preconjugation transport disturbance. In this disorder the hepatic uptake of bilirubin is defective because the transportation of bilirubin from the sinusoidal membrane to the microsomal region is impaired.

Answer 198

B. Deficiency of the enzyme system required for conjugation of bilirubin ## Footnote Both Crigler-Najjar syndrome and neonatal jaundice, a physiological disorder, are due to a deficiency in the enzyme-conjugating system. With a defi ciency in uridine diphosphate glucuronyltransferase, the liver is unable to conjugate bilirubin, and both of these conditions are characterized by increased levels of unconjugated bilirubin. Unlike Crigler-Najjar syndrome, which is a hereditary disorder, neonatal physiological jaundice is a temporary situation that usually corrects itself within a few days after birth.

Answer 199

C. Inability to conjugate bilirubin ## Footnote In Dubin-Johnson syndrome, the transport of conjugated (direct) bilirubin from the microsomal region to the bile canaliculi is impaired. In this rare familial disorder, plasma conjugated bilirubin levels are increased because of defective excretion of bilirubin in the bile. Because conjugated bilirubin is water soluble, increased amounts of bilirubin are found in the urine.

Answer 200

B. Hepatic cirrhosis ## Footnote Gamma spike: multiple myeloma Beta-gamma bridging: hepatic cirrhosis α1 globulin flat curve: juvenile cirrhosis (AATdefi ciency) Α2 globulin band spike: nephrotic syndrome Spikes in α1, α2 and β: inflammation

Answer 201

A. Hepatitis ## Footnote HEPATITIS: less than 80% liver damage High: AST, ALT, LD, ALP, bilirubin Normal: Total protein, albumin, ammonia

Answer 202

B. Cirrhosis ## Footnote CIRRHOSIS: 80% liver tissue damage Death of liver cells with regeneration leads to fibrosis, scarring and destruction of the normal liver architecture Low: Total protein, albumin High: Bilirubin, ammonia Normal to slightly high: ALP Normal: AST, ALT and LD

Answer 203

A. Cirrhosis ## Footnote Cirrhosis is defi ned as destruction of the liver’s architecture. The leading cause of this condition is alcohol abuse.

Answer 204

C. B1 and B2 ## Footnote Hemolytic jaundice: unconjugated bilirubin (B1) Hepatic jaundice: unconjugated and conjugated bilirubin (B1 and B2) Obstructive jaundice: conjugated bilirubin (B2)

Answer 205

C. Tissue damage and necrosis ## Footnote The majority of serum enzymes that are of interest clinically are of intracellular origin. These enzymes function intracellularly, with only small amounts found in serum as a result of normal cellular turnover. Increased serum levels are due to tissue damage and necrosis, where the cells disintegrate and leak their contents into the blood. Thus, elevated serum levels of intracellular enzymes are used diagnostically to assess tissue damage.

Answer 206

A. Lower than expected ## Footnote Factors that affect enzyme assays include temperature, pH, substrate concentration, and time of incubation. For each clinically important enzyme, the optimum temperature and pH for its specifi c reaction are known. When lower than optimum temperature or pH is employed, the measured enzyme activity will be lower than the expected activity value. As temperature increases, the rate of the reaction increases.

Answer 207

B. Enzymes are protein catalysts of biological origin. ## Footnote Enzymes are protein in nature. Like all proteins, they may be denatured with a loss of activity as a result of several factors (e.g., heat, extreme pH, mechanical agitation, strong acids, and organic solvents). Enzymes act as catalysts for the many chemical reactions of the body. Enzymes increase the rate of a specifi c chemical reaction by lowering the activation energy needed for the reaction to proceed.

Answer 208

C. Lock-and-key theory by Emil Fischer ## Footnote LOCK-AND-KEY (EMIL FISCHER) The shape of the key (substrate) must fit into the lock (enzyme) INDUCED-FIT (DANIEL KOSHLAND) Substrate binding to the active site of the enzyme

Answer 209

A. First-order kinetics ## Footnote In 1913, Michaelis and Menten hypothesized the role of substrate concentration in formation of the enzyme–substrate (ES) complex. According to their hypothesis, the substrate readily binds to free enzyme at a low-substrate concentration. With the amount of enzyme exceeding the amount of substrate, the reaction rate steadily increases as more substrate is added. The reaction is following first-order kinetics because the reaction rate is directly proportional to substrate concentration. Eventually, however, the substrate concentration is high enough to saturate all available enzyme, and the reaction velocity reaches its maximum. When product is formed, the resultant free enzyme immediately combines with excess free substrate. The reaction is in zero-order kinetics, and the reaction rate depends only on enzyme concentration.

Answer 210

B. Zero-order kinetics ## Footnote In 1913, Michaelis and Menten hypothesized the role of substrate concentration in formation of the enzyme–substrate (ES) complex. According to their hypothesis, the substrate readily binds to free enzyme at a low-substrate concentration. With the amount of enzyme exceeding the amount of substrate, the reaction rate steadily increases as more substrate is added. The reaction is following first-order kinetics because the reaction rate is directly proportional to substrate concentration. Eventually, however, the substrate concentration is high enough to saturate all available enzyme, and the reaction velocity reaches its maximum. When product is formed, the resultant free enzyme immediately combines with excess free substrate. The reaction is in zero-order kinetics, and the reaction rate depends only on enzyme concentration.

Answer 211

B. Kinetic assay ## Footnote One of two general methods may be used to measure the extent of an enzymatic reaction: (1) fixed-time and (2) continuous-monitoring or kinetic assay. 1. In the fixed time method, the reactants are combined, the reaction proceeds for a designated time, the reaction is stopped (usually by inactivating the enzyme with a weak acid), and a measurement is made of the amount of reaction that has occurred. The reaction is assumed to be linear over the reaction time; the larger the reaction, the more enzyme is present. 2. In continuous-monitoring or kinetic assays, multiple measurements, usually of absorbance change, are made during the reaction, either at specifi c time intervals (usually every 30 or 60 seconds) or continuously by a continuous- recording spectrophotometer

Answer 212

B. Coenzyme ## Footnote A nonprotein molecule, called a cofactor, may be necessary for enzyme activity. Inorganic cofactors, such as chloride or magnesium ions, are called activators. A coenzyme is an organic cofactor, such as nicotinamide adenine dinucleotide (NAD). When bound tightly to the enzyme, the coenzyme is called a prosthetic group. The enzyme portion (apoenzyme), with its respective coenzyme, forms a complete and active system, a holoenzyme.

Answer 213

A. Activator ## Footnote A nonprotein molecule, called a cofactor, may be necessary for enzyme activity. Inorganic cofactors, such as chloride or magnesium ions, are called activators. A coenzyme is an organic cofactor, such as nicotinamide adenine dinucleotide (NAD). When bound tightly to the enzyme, the coenzyme is called a prosthetic group. The enzyme portion (apoenzyme), with its respective coenzyme, forms a complete and active system, a holoenzyme.

Answer 214

D. Transferases ## Footnote There are six major classes of enzymes. The International Commission of Enzymes of the International Union of Biochemistry has categorized all enzymes into one of these classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Transferases are enzymes that catalyze the transfer of groups, such as amino and phosphate groups, between compounds. Transferases frequently need coenzymes, such as pyridoxal-5'- phosphate (P-5-P), for the amino transfer reactions. Aspartate and alanine aminotransferases, creatine kinase, and gamma-glutamyltransferase are typical examples.

Answer 215

B. Aldolase ## Footnote Hydrolases are enzymes that split molecules with the addition of water—for example, amylase, lipase, alkaline phosphatase, acid phosphatase, 5'-nucleotidase, and trypsin. They do not usually require coenzymes but often need activators. Aldolase and carbonic anhydrase are examples of the class of enzymes known as the lyases. Lyases are enzymes that split molecules between carbon-to-carbon bonds without the addition of water. The resulting products usually contain carbon double bonds.

Answer 216

C. Oxidoreductases

Answer 217

D. Ligases ## Footnote In addition to naming enzymes, the IUB system identifi es each enzyme by an EC numerical code containing four digits separated by decimal points. The first digit places the enzyme in one of the following six classes: 1. Oxidoreductases. Catalyze an oxidation–reduction reaction between two substrates 2. Transferases. Catalyze the transfer of a group other than hydrogen from one substrate to another 3. Hydrolases. Catalyze hydrolysis of various bonds 4. Lyases. Catalyze removal of groups from substrates without hydrolysis; the product ontains double bonds 5. Isomerases. Catalyze the interconversion of geometric, optical, or positional isomers 6. Ligases. Catalyze the joining of two substrate molecules, coupled with breaking of the pyrophosphate bond in adenosine triphosphate (ATP) or a similar compound

Answer 218

A. Decreasing the activation energy ## Footnote Enzymes catalyze physiologic reactions by lowering the activation energy level that the reactants (substrates) must reach for the reaction to occur.

Answer 219

B. Pernicious anemia and hemolytic disorders ## Footnote B. Pernicious anemia and hemolytic disorders

Answer 220

E. LD-5 ## Footnote LD-5 is the most labile isoenzyme. Loss of activity occurs more quickly at 4°C than at 25°C. Serum samples for LD isoenzyme analysis should be stored at 25°C and analyzed within 24 hours of collection.

Answer 221

D. Paget's disease ## Footnote Elevated ALP levels may be observed in various bone disorders. Perhaps the highest elevations of ALP activity occur in Paget’s disease (osteitis deformans). Other bone disorders include osteomalacia, rickets, hyperparathyroidism, and osteogenic sarcoma.

Answer 222

D. Bone disease ## Footnote Increased serum creatine kinase (CK), formerly called creatine phosphokinase (CPK), values are caused primarily by lesions of cardiac muscle, skeletal muscle, or brain tissue. CK increases in the early stages of Duchenne-type progressive muscular dystrophy. Assays of total CK and CK isoenzymes are commonly used in the diagnosis of myocardial infarction. Hypothyroidism causes a moderate increase in CK values. Elevation of this enzyme also occurs after vigorous muscular activity, in cases of cerebrovascular accidents (stroke), and after repeated intramuscular injections.

Answer 223

A. Creatine kinase ## Footnote To aid in the diagnosis of skeletal muscle disease, measurement of creatine kinase would be most useful. CK yields the most reliable information when skeletal muscle disease is suspected. Other enzymes that are also useful to measure are aspartate aminotransferase and lactate dehydrogenase. Both of these enzymes will be moderately elevated, whereas CK is significantly increased.

Answer 224

C. CK, AST, LD ## Footnote When an AMI occurs, CK is the first enzyme to become elevated in the blood, rising within 4 to 6 hours following chest pain. AST exhibits a rise in the serum level within 6 to 8 hours. LD shows an increase in 8 to 12 hours following infarction. Measurement of these three enzymes to assess acute myocardial infarction has been replaced by cardiac troponin, myoglobin, and CK-MB.

Answer 225

C. Cholinesterase ## Footnote Normal serum levels of cholinesterase are quite high, refl ecting its continual synthesis and release by the liver. Decreased values are considered abnormal.

Answer 226

A. Amylase ## Footnote AMYLASE is the smallest enzyme, with a molecular weight of 50,000 to 55,000 Da. Because of its small size, it is readily filtered by the renal glomerulus and also appears in the urine.

Answer 227

E. G6PD ## Footnote Macroenzymes are high-molecular-mass forms of the serum enzymes (ACP, ALP, ALT, AMY, AST, CK, GGT, LD, and LPS) that can be bound to either an immunoglobulin (macroenzyme type 1) or a nonimmunoglobulin substance (macroenzyme type 2). Macroenzymes are usually found in patients who have an unexplained persistent increase of enzyme concentrations in serum. The presence of macroenzymes can also increase with increasing age.

Answer 228

A. p-Nitrophenyl phosphate ## Footnote The method of Bowers–McComb (Szasz modifi cation) is the IFCC-recommended method for ALP. This method uses 2-amino-2-methyl-1-propanol, pH 10.15, and measures the increase in absorbance at 405 nm as p-nitrophenyl phosphate is hydrolyzed to p-nitrophenol.

Answer 229

C. 2-Amino-2-methyl-1-propanol ## Footnote The method of Bowers–McComb (Szasz modifi cation) is the IFCC-recommended method for ALP. This method uses 2-amino-2-methyl-1-propanol, pH 10.15, and measures the increase in absorbance at 405 nm as p-nitrophenyl phosphate is hydrolyzed to p-nitrophenol.

Answer 230

A. Linear phase ## Footnote Enzyme assays are recommended to be performed during the linear phase, so that a consistent change over time can be used to calculate the enzyme concentration.

Answer 231

B. Copper ## Footnote Copper is found in the plasma mainly in two forms: a minor fraction loosely bound to albumin and the majority, representing about 80-95%, firmly bound to the enzyme ceruloplasmin, an alpha2-globulin, which is important in the oxidation of iron from the ferrous to the ferric state.

Answer 232

A. Chromium ## Footnote Cr(3+) is an essential dietary element and plays a role in maintaining normal metabolism of glucose, fat, and cholesterol. Glucose tolerance factor (GTF), the biologically active form of chromium, is an essential dietary agent that potentiates the action of insulin and thereby functions in regulating carbohydrate metabolism.

Answer 233

A. Parkinson's disease ## Footnote Chronic manganese toxicity resembles Parkinson’s disease with akinesia, rigidity, tremors, and mask-like faces.

Answer 234

C. Molybdenum ## Footnote Molybdenum is vital to human health through its inclusion in at least three enzymes: xanthine oxidase, aldehyde oxidase, and sulfite oxidase. The active site of these enzymes binds molybdenum in the form of a cofactor “molybdopterin".

Answer 235

B. CA-15-3

Answer 236

C. HER-2/neu

Answer 237

C. Nuclear matrix protein

Answer 238

A. Hepatoma

Answer 239

C. Potassium

Answer 240

C. Potassium ## Footnote As the primary intracellular cation, potassium is an integral part of the transmission of nerve impulses. Movement of potassium across the nerve tissue membrane permits the neural signal to move down the nerve fiber. Potassium also seems to be involved in synaptic processes, where the impulse "jumps" from one nerve fiber to another.

Answer 241

C. Chloride

Answer 242

B. Chloride

Answer 243

A. Bicarbonate ## Footnote Bicarbonate is the second most abundant anion in the extracellular fluid. It is a major component of the blood buffering system, accounts for 90% of total blood carbon dioxide, and maintains charge neutrality in the cell.

Answer 244

B. Magnesium

Answer 245

B. Calcium and magnesium ## Footnote Electrolytes are an essential component in numerous processes, including: 1. Volume and osmotic regulation (sodium [Na+], chloride [Cl−], potassium [K+]) 2. Myocardial rhythm and contractility (K+, magnesium [Mg2+], calcium [Ca2+]) 3. Cofactors in enzyme activation (e.g., Mg2+, Ca2+, zinc [Zn2+]) 4. Regulation of adenosine triphosphatase (ATPase) ion pumps (Mg2+) 5. Acid–base balance (bicarbonate HCO3−, K+, Cl−) 6. Blood coagulation (Ca2+, Mg2+) 7. Neuromuscular excitability (K+, Ca2+, Mg2+) 8. Production and use of ATP from glucose (e.g., Mg2+, phosphate PO4−)

Answer 246

C. Bicarbonate, potassium and chloride

Answer 247

B. Potassium ## Footnote Hemolysis of blood specimens because of physiological factors is often difficult to differentiate from hemolysis produced by the blood collection itself. In either case, the concentration of potassium will be increased in the serum because of the release of the very high level of intracellular potassium from the erythrocytes into the plasma. When hemolysis is present, the serum concentrations of sodium, bicarbonate, chloride, and calcium will be decreased because their concentrations are lower in erythrocytes than in plasma.

Answer 248

D. Sodium ## Footnote Na+ is the most abundant cation in the ECF, representing 90% of all extracellular cations, and largely determines the osmolality of the plasma.

Answer 249

D. Less than 135 mmol/L ## Footnote Hyponatremia is defi ned as a serum/plasma level less than 135 mmol/L. Hyponatremia is one of the most common electrolyte disorders in hospitalized and nonhospitalized patients. Levels below 130 mmol/L are clinically signifi cant. Hyponatremia can be assessed by the cause for the decrease or with the osmolality level.

Answer 250

C. Diuretic use ## Footnote Causes Of Hyponatremia 1. Increased Sodium Loss Hypoadrenalism Potassium defi ciency Diuretic use Ketonuria Salt-losing nephropathy Prolonged vomiting or diarrhea Severe burns 2. Increased Water Retention Renal failure Nephrotic syndrome Hepatic cirrhosis Congestive heart failure 3. Water Imbalance Excess water intake SIADH Pseudohyponatremia

Answer 251

C. Plasma/serum osmolality ## Footnote Hyponatremia can also be classifi ed according to plasma/serum osmolality. Because Na+ is a major contributor to osmolality, both levels can assist in identifying the cause of hyponatremia. There are three categories of hyponatremia—low osmolality, normal osmolality, or high osmolality. Most instances of hyponatremia occur with decreased osmolality.

Answer 252

C. Pseudohyponatremia ## Footnote Pseudohyponatremia can occur when Na+ is measured using indirect ion-selective electrodes (ISEs) in a patient who is hyperproteinemic or hyperlipidemic. An indirect ISE dilutes the sample prior to analysis and as a result of plasma/serum water displacement; the ion levels are falsely decreased.

Answer 253

D. Urine osmolality ## Footnote The measurement of urine osmolality is necessary to evaluate the cause of hypernatremia. With renal loss of water, the urine osmolality is low or normal. With extrarenal fluid losses, the urine osmolality is increased.

Answer 254

A. Hypernatremia ## Footnote Any condition that increases water loss, such as fever, burns, diarrhea, or exposure to heat, will increase the likelihood of developing hypernatremia.

Answer 255

C. Potassium ## Footnote Potassium (K+) is the major intracellular cation in the body, with a concentration 20 times greater inside the cells than outside. Many cellular functions require that the body maintain a low ECF concentration of K+ ions. As a result, only 2% of the body’s total K+ circulates in the plasma. Functions of K+ in the body include regulation of neuromuscular excitability, contraction of the heart, ICF volume, and H+ concentration.

Answer 256

D. Vomiting ## Footnote Causes Of Hypokalemia 1. Gastrointestinal Loss Vomiting Diarrhea Gastric suction Intestinal tumor Malabsorption Cancer therapy—chemotherapy, radiation therapy Large doses of laxatives 2. Renal Loss Diuretics—thiazides, mineralocorticoids Nephritis Renal tubular acidosis Hyperaldosteronism Cushing’s syndrome Hypomagnesemia Acute leukemia 3. Cellular Shift Alkalosis Insulin overdose 4. Decreased Intake

Answer 257

B. Alkalosis ## Footnote K+ concentration also affects the H+ concentration in the blood. For example, in hypokalemia (low serum K+), as K+ is lost from the body, Na+ and H+ move into the cell. The H+ concentration is, therefore, decreased in the ECF, resulting in alkalosis. CAUSES OF HYPERKALEMIA 1. Decreased Renal Excretion Acute or chronic renal failure (GFR < 20 mL/min) Hypoaldosteronism Addison’s disease Diuretics 2. Cellular Shift Acidosis Muscle/cellular injury Chemotherapy Leukemia Hemolysis 3. Increased Intake Oral or intravenous potassium replacement therapy 4. Artifactual Sample hemolysis Thrombocytosis Prolonged tourniquet use or excessive fist clenching

Answer 258

B. Chloride ## Footnote Chloride (Cl−) is the major extracellular anion. It is involved in maintaining osmolality, blood volume, and electric neutrality. In most processes, Cl− shifts secondarily to a movement of Na+ or HCO3 −.

Answer 259

C. Cystic fibrosis ## Footnote Measuring the concentration of chloride in sweat is a commonly used diagnostic procedure for determining the disorder of cystic fibrosis (CF). The majority of patients with CF will present with increased concentrations of sodium and chloride in their sweat.

Answer 260

A. Bicarbonate ## Footnote Bicarbonate is the second most abundant anion in the ECF. Total CO2 comprises the bicarbonate ion (HCO3−), H2CO3, and dissolved CO2, with HCO3− accounting for more than 90% of the total CO2 at physiologic pH. Because HCO3− composes the largest fraction of total CO2, total CO2 measurement is indicative of HCO3− measurement.

Answer 261

D. Magnesium ## Footnote Magnesium (Mg2+) is the fourth most abundant cation in the body and second most abundant intracellular ion. The average human body (70 kg) contains 1 mol (24 g) of Mg2+. Approximately 53% of Mg2+ in the body is found in bone, 46% in muscle and other organs and soft tissue, and less than 1% is present in serum and RBCs.

Answer 262

A. Hypomagnesemia ## Footnote Hypomagnesemia is most frequently observed in hospitalized individuals in intensive care units (ICUs) or those receiving diuretic therapy or digitalis therapy. These patients most likely have an overall tissue depletion of Mg2+ as a result of severe illness or loss, which leads to low serum levels. Hypomagnesemia is rare in nonhospitalized individuals.

Answer 263

D. Parathyroid hormone, vitamin D and calcitonin ## Footnote Three hormones, PTH, vitamin D, and calcitonin, are known to regulate serum Ca2+ by altering their secretion rate in response to changes in ionized Ca2+.

Answer 264

C. 50 ## Footnote Free ionized calcium normally accounts for about 50% of total serum calcium, with the remainder being made up of complexed calcium (about 10%) and calcium bound to proteins (about 40%).

Answer 265

A. Cresolphthalein complexone ## Footnote Total serum calcium concentration is often determined by the spectrophotometric quantification of the color complex formed with cresolphthalein complexone.

Answer 266

B. Ammonium molybdate ## Footnote Serum inorganic phosphate concentrations are determined most commonly by reacting with ammonium molybdate reagent. The molybdenum-phosphate complexes can be quantifi ed at 340 nm. Alternately, treatment of the phosphomolybdate compound formed with a reducing agent leads to the formation of molybdenum blue, which can be measured spectrophotometrically.

Answer 267

* Hypernatremia * Ketoacidosis * Lactic acidosis * Methanol, ethanol, ethylene glycol poisoning * Uremia/renal failure ## Footnote An elevated AG may be caused by uremia/renal failure, which leads to PO4 and SO4 retention; ketoacidosis, as seen in cases of starvation or diabetes; methanol, ethanol, ethylene glycol, or salicylate poisoning; lactic acidosis; hypernatremia; and instrument error. Low AG values are rare but may be seen with hypoalbuminemia (decrease in unmeasured anions) or severe hypercalcemia (increase in unmeasured cations).

Answer 268

* Hypercalcemia * Hypoalbuminemia ## Footnote An elevated AG may be caused by uremia/renal failure, which leads to PO4 and SO4 retention; ketoacidosis, as seen in cases of starvation or diabetes; methanol, ethanol, ethylene glycol, or salicylate poisoning; lactic acidosis; hypernatremia; and instrument error. Low AG values are rare but may be seen with hypoalbuminemia (decrease in unmeasured anions) or severe hypercalcemia (increase in unmeasured cations).

Answer 269

A. Serum ## Footnote Osmolality may be measured in serum or urine. Major electrolyte concentrations, mainly sodium, chloride, and bicarbonate, provide the largest contribution to the osmolality value of serum. Plasma use is not recommended because osmotically active substances may be introduced into the specimen from the anticoagulant.

Answer 270

D. 92 ## Footnote For monovalent cations or anions the contribution to osmolality is approximately 92%. Other serum electrolytes, serum proteins, glucose, and urea contribute to the remaining 8%.

Answer 271

C. 2(Na) + (glucose ÷ 18) + (BUN ÷ 2.8)

Answer 272

C. Ferritin ## Footnote In adults the total body iron content averages 3-4 g. The majority of this iron is found in the active pool as an essential constituent of hemoglobin, with a much lesser amount being an integral component of myoglobin and a number of enzymes. Approximately 25% of the body iron is found in inactive storage forms. The major storage form of iron is ferritin, with a lesser amount being stored as hemosiderin.

Answer 273

A. Lithium heparin; dry ## Footnote Evacuated collection tubes are not appropriate for blood gases. While both dry (lyophilized) and liquid heparin are acceptable anticoagulants, the liquid form is not recommended because excessive amounts can dilute the sample and possibly alter the sample due to equilibration with room air.

Answer 274

A. pO2 and pH increase; pCO2 decreases ## Footnote Note: OPEN TUBE (ENTRY OF OXYGEN) ⬆️ Increased pO2 ⬇️ Deceased pCO2 (H2CO3) ⬆️ Increased pH (ALKALINE) CLOSED TUBE (OXYGEN UTILIZED BY CELLS) ⬇️ Decreased pO2 ⬆️ Increased pCO2 (H2CO3) ⬇️ Decreased pH (ACIDIC)

Answer 275

C. pO2 decreases, pCO2 increases, pH decreases ## Footnote Note: OPEN TUBE (ENTRY OF OXYGEN) ⬆️ Increased pO2 ⬇️ Deceased pCO2 (H2CO3) ⬆️ Increased pH (ALKALINE) CLOSED TUBE (OXYGEN UTILIZED BY CELLS) ⬇️ Decreased pO2 ⬆️ Increased pCO2 (H2CO3) ⬇️ Decreased pH (ACIDIC)

Answer 276

A. Bicarbonate/carbonic acid ## Footnote Because of its high concentration in blood, the bicarbonate/carbonic acid pair is the most important buffer system in the blood. This buffer system is also effective in the lungs and in the kidneys in helping to regulate body pH. The other buffers that also function to help maintain body pH are the phosphate, protein, and hemoglobin buffer systems.

Answer 277

B. 20:1 ratio of bicarbonate to carbonic acid ## Footnote When the ratio of the concentrations of bicarbonate to carbonic acid is 20:1, the pH is 7.4.

Answer 278

B. Carbon dioxide

Answer 279

C. Will decrease pO2 by 7% ## Footnote Fever will decrease pO2 by 7% Fever will increase pCO2 by 3%

Answer 280

B. Will increase pCO2 by 3% ## Footnote Fever will decrease pO2 by 7% Fever will increase pCO2 by 3%

Answer 281

A. Kidney function ## Footnote The role of the lungs and kidneys in maintaining pH is depicted with the Henderson-Hasselbalch equation. The numerator (HCO3−) denotes kidney functions, and the denominator (pCO2) denotes lung function.

Answer 282

B. Lung function ## Footnote The role of the lungs and kidneys in maintaining pH is depicted with the Henderson-Hasselbalch equation. The numerator (HCO3−) denotes kidney functions, and the denominator (pCO2) denotes lung function.

Answer 283

D. Metabolic alkalosis ## Footnote An excess of bicarbonate without a change in pCO2 will increase the ratio of bicarbonate to carbonic acid. Therefore, the pH will increase; that is, the plasma becomes more alkaline.

Answer 284

B. pH 7.66 HCO3- 22 mmol/L pCO2 20 mm Hg ## Footnote TIPS FOR EVALUATING ACID-BASE DISORDERS 1. Look at the pH: determine if acidosis or alkalosis 2. Compare pCO2 and HCO3- A. pCO2 going opposite to pH – RESPIRATORY Abnormal pCO2 respiratory [↓pH ↑pCO2 respiratory acidosis] [↑pH ↓pCO2 respiratory alkalosis] B. HCO3- going same direction as pH - METABOLIC Abnormal HCO3- metabolic [↓pH ↓HCO3- metabolic acidosis] [↑ pH ↑ HCO3- metabolic alkalosis] 3. If pH is normal, full compensation occurred 4. If main compensatory mechanism kicked in, but pH still out of normal range, partial compensation has occurred

Answer 285

A. pH 7.25 HCO3- 15 mmol/L pCO2 37 mm Hg

Answer 286

D. Metabolic alkalosis ## Footnote A pH above 7.45 corresponds with alkalosis. Both bicarbonate and pCO2 are elevated. Bicarbonate is the conjugate base and is under metabolic (renal) control, while pCO2 is an acid and is under respiratory control. Increased bicarbonate (but not increased CO2) results in alkalosis; therefore, the classifi cation is metabolic alkalosis, partially compensated by increased pCO2.

Answer 287

A. Anxiety

Answer 288

C. pH, pCO2 and pO2 ## Footnote pH, pCO2, and pO2 are measured directly from the specimen by utilizing electrodes. The pH and PCO2 electrodes are potentiometric where the voltage produced across a semipermeable membrane to hydrogen ions or CO2 gas is proportional to the "activity" of those ions in the patient's sample. Activity is measured in voltage whose value can be presented in terms of concentration. pO2 is measured similarly, but using an amperometric electrode. Note: pH and pCO2 = POTENTIOMETRY pO2 = AMPEROMETRY

Answer 289

B. Occasionally ## Footnote Mixed respiratory and nonrespiratory disorders occasionally arise from more than one pathologic process and represent the most serious of medical conditions as compensation for the primary disorder is failing.

Answer 290

A. Respiratory acidosis

Answer 291

C. Pituitary gland

Answer 292

A. Anterior pituitary gland

Answer 293

B. Posterior pituitary gland

Answer 294

* ACTH * FSH * LH * TSH

Answer 295

* GH * Prolactin

Answer 296

B. GH ## Footnote Growth hormone (GH), also called somatotropin, is structurally related to prolactin and human placental lactogen.

Answer 297

A. Oral glucose loading

Answer 298

D. Amino acids

Answer 299

A. Anterior pituitary gland

Answer 300

A. Vasopressin deficiency

Answer 301

D. TSH assay ## Footnote TSH is produced by the anterior pituitary in response to low levels of free T4 or T3. A normal TSH rules out thyroid disease. TSH is low in primary hyperthyroidism and high in primary hypothyroidism.

Answer 302

A. Primary hyperthyroidism ## Footnote In primary hyperthyroidism, the TSH will be within a range of 0–0.02 mU/mL, while in nonthyroid illnesses it will be 0.03 mU/mL or higher.

Answer 303

A. Primary hyperthyroidism

Answer 304

D. All of these

Answer 305

A. Aldosterone ## Footnote Zona glomerulosa (G-zone) cells (outer 10%) synthesize mineralocorticoids (aldosterone) critical for sodium retention (volume), potassium, and acid–base homeostasis. They have low cytoplasmic-to-nuclear ratios and small nuclei with dense chromatin with intermediate lipid inclusions.

Answer 306

B. Cortisol ## Footnote Zona fasciculata (F-zone) cells (middle 75%) synthesize glucocorticoids, such as cortisol and cortisone critical to blood glucose homeostasis and blood pressure.

Answer 307

B. Catecholamine ## Footnote Medullary catecholamine products serve as firstresponders to stress by acting within seconds (cortisol takes 20 min) to promote the fight-or-fl ight response, which increases cardiac output and blood pressure, diverts blood toward muscle and brain, and mobilizes fuel from storage.

Answer 308

A. Excess secretion of pituitary ACTH ## Footnote Cushing’s disease refers to adrenal hyperplasia resulting from misregulation of the hypothalamic–pituitary axis. It is usually caused by small pituitary adenomas. Cushing’s syndrome may be caused by Cushing’s disease, adrenal adenoma or carcinoma, ectopic ACTH-producing tumors, or excessive corticosteroid administration. The cause of Cushing’s syndrome can be differentiated using the ACTH and dexamethasone suppression tests.

Answer 309

C. Serum ACTH ## Footnote Serum ACTH assays are very helpful in distinguishing the cause of Cushing’s syndrome. Patients with adrenal tumors have values approaching zero. Patients with ectopic ACTH tumors have values greater than 200 pg/dL. Fifty percent of patients with Cushing’s disease have high 8 a.m. ACTH levels (between 100–200 pg/dL). The high-dose dexamethasone suppression test is also used.

Answer 310

A. Overnight low-dose dexamethasone suppression test

Answer 311

A. Cholesterol

Answer 312

B. Estradiol (E2)

Answer 313

D. Testosterone

Answer 314

A. Gastrin

Answer 315

C. Hirsutism

Answer 316

A. Acute toxicity

Answer 317

B. Chronic toxicity

Answer 318

D. Cigarette smokers ## Footnote Cigarette smokers exhibit levels of 8-9% carboxyhemoglobin, but occasionally saturations of greater than 16% have been reported in heavy smokers.

Answer 319

B. Morphine ## Footnote Heroin (diacetylmorphine), an abused drug, is a derivative of morphine. The morphine used in its synthesis is generally obtained from opium.

Answer 320

B. Marijuana ## Footnote THC (tetrahydrocannabinol) is the principal active component of marijuana.

Answer 321

D. Marijuana ## Footnote Marijuana is stored in fatty tissue and is metabolized slowly. In persons who use marijuana several times per week, cannabinoids can be detected several weeks after last use. For chronic daily users, this extends to months after discontinuation

Answer 322

B. Ecstacy

Answer 323

A. 0.5 to 1 hour ## Footnote The half-life of the circulating cocaine is brief: 0.5 to 1 hour. BISHOP

Answer 324

B. Cocaine ## Footnote Cocaine is an abused drug and not available for therapeutic use. After absorption, cocaine in the blood is rapidly converted into ecgonine and benzoylecgonine.

Answer 325

C. Cocaine ## Footnote COCAINE IS A CNS STIMULANT. CNS STIMULANTS Cocaine and its metabolite, benzoylecgonine, and amphetamines and methamphetamines CNS DEPRESSANTS Barbiturates; methaqualone; benzodiazepines including Valium; and oxycodone and other opiates, including morphine, heroin (which metabolizes to morphine), codeine (methylmorphine), and methadone HALLUCINOGENS OR PSYCHOACTIVES Cannabinoids and phencyclidine (PCP) ANTIDEPRESSANTS Lithium, tricyclic antidepressants

Answer 326

C. Whole blood ## Footnote After absorption, lead is distributed into an active pool in the blood and soft tissue and a storage pool in bone, teeth, and hair. In blood, the majority is found in erythrocytes, with only minor quantities in plasma or serum. Lead is mainly excreted by the kidney; hence urine or whole blood would be appropriate specimens for determining lead exposure.

Answer 327

A. Arsenic ## Footnote ARSENIC Toxins may BIND SULFHYDRYL GROUPS IN KERATIN FOUND IN HAIR AND FINGERNAILS

Answer 328

C. Cyanide overdose ## Footnote The principal symptoms of cyanide overdose are tachypnea (initially), followed by respiratory depression and cyanosis, hypotension, convulsions, and coma. Death may occur in a matter of minutes because cyanide is a fast-acting toxin. Diagnosis may be difficult, and a high index of suspicion is needed to make the correct diagnosis. Clues include the odor of bitter almonds, the occurrence of an altered mental status and tachypnea in the absence of cyanosis, and an unexplained metabolic acidosis (with an increased anion gap).

Answer 329

A. Arsenic toxicity ## Footnote ODOR OF BITTER ALMONDS: CYANIDE POISONING ODOR OF GARLIC, METALLIC TASTE: ARSENIC POISONING

Answer 330

B. Ethanol ## Footnote Ethanol is probably the most common drug of abuse and is frequently responsible for the presentation of patients with altered mental status to hospitals and emergency rooms.

Answer 331

C. Liberation, absorption, distribution, metabolism, excretion ## Footnote LADME: Liberation, absorption, distribution, metabolism and excretion 1. Liberation is the release of the drug 2. Absorption is the transport of drug from the site of administration to the blood 3. Distribution refers to the delivery of the drug to the tissues 4. Metabolism is the process of chemical modifi cation of the drug by cells 5. Excretion is the process by which the drug and its metabolites are removed from the body

Answer 332

A. Varies with the drug, depending on its rate of absorption ## Footnote The peak concentration of a drug is the highest concentration obtained in the dosing interval. For oral drugs, the time of peak concentration is dependent upon their rates of absorption and elimination and is determined by serial blood measurements. Peak levels for oral drugs are usually drawn 1–2 hours after administration of the dose. For drugs given intravenously, peak levels are measured immediately after the infusion is completed.

Answer 333

C. Shortly before drug administration ## Footnote When peak levels of the drug are required, the blood sample must be drawn at a specified time after drug administration. Trough levels are most reliably determined by collecting the blood sample before the next drug administration.

Answer 334

D. Intravenous ## Footnote When a drug is administered intravenously, all the drug enters the bloodstream.

Answer 335

C. Salicylate ## Footnote The Trinder reaction or modifi cation is used almost routinely in the determination of salicylate and is based on the colorimetric reaction with ferric ions.

Answer 336

D. Liver ## Footnote Paracetamol, also known as acetaminophen. Hepatotoxicity is common in acetaminophen overdose. It is particularly important to be able to determine the acetaminophen serum level rapidly so that the elimination half-life of the drug can be estimated. Hepatic necrosis is more common when the half-life exceeds 4 hours and is very likely when it exceeds 12 hours.

Answer 337

B. Kidney ## Footnote Tobramycin and gentamicin are examples of aminoglycoside antibiotics. Their use has been associated with both nephrotoxicity and ototoxicity.

Answer 338

C. Tacrolimus ## Footnote Tacrolimus (Prograf) is an antibiotic that functions as an immunosuppressant in organ transplantation, especially in liver transplants.

Answer 339

A. Theophylline ## Footnote Theophylline is a bronchodilator that is used to treat asthma. The therapeutic range is 10- 20 ug/mL, and use must be monitored to avoid toxicity. Use of theophylline has been replaced where possible with beta-adrenergic agonists, which are available in the inhaled form.

Answer 340

D. 3 and 4 ## Footnote Anti-asthmatic drugs, such as THEOPHYLLINE and THEOBROMINE, are used for treatment of neonatal breathing disorders or of respiratory conditions that affect adults or children, such as asthma.

Answer 341

B. Caffeine ## Footnote Theophylline, a xanthine with bronchodilator activity, is widely used in the treatment of asthma. Because of its availability and potential toxicity, it can also be subject to accidental overdose. Chromatographic methods are effective in separating theophylline from caffeine and theobromine, which are two commonly occurring and potentially interfering xanthines. However, most clinical thin-layer chromatographic methods are relatively insensitive to the xanthines, and suspected theophylline overdose should be confi rmed by HPLC or immunoassay methods.

Answer 342

B. Lithium ## Footnote Lithium is used in the treatment of manic depression. Because of the small difference between therapeutic and toxic levels in the serum, accurate measurements of lithium concentrations are essential.

Answer 343

D. Vancomycin ## Footnote The major toxicities of vancomycin are red man syndrome, nephrotoxicity, and ototoxicity. Red man syndrome is characterized by an erythemic flushing of the extremities. The renal and hearing effects are similar to those of the aminoglycosides.

Answer 344

B. Ethosuximide (Zarontin) ## Footnote HENRY: Ethosuximide is the drug of choice for absence (petit mal) seizures unaccompanied by other types of seizures. It is preferred over valproic acid, at least initially, because hepatotoxicity is a rare but serious side effect of valproic acid.

Answer 345

D. 1, 2 and 3 ## Footnote Most analgesics, such as salicylates, acetaminophen, and ibuprofen, do not require TDM because physicians and pharmacists are able to achieve and maintain therapeutic levels with standardized dosing intervals. Because of the presumed safety of these medications, they are available without a prescription and sold as OVER-THE-COUNTER medications.

Answer 346

A. 0.01 ## Footnote Immunoglobulin conversion factors: mg/dL to g/L: 0.01 mg/dL to mg/L: 10

Answer 347

C. 0.2 mg per mL

Answer 348

D. Densitometry

Answer 349

D. Prealbumin

Answer 350

C. Prealbumin

Answer 351

A. EDTA plasma sample ## Footnote Ethylenediaminetetraacetic acid (EDTA) (1 mg/1 mL blood) plasma preferred for analysis of lipoproteins (EDTA preserves lipoproteins); separate plasma within 2 hours.

Answer 352

B. Bassen-Kornzweig syndrome

Answer 353

B. 30 to 50%

Answer 354

B. Increases unconjugated bilirubin measured as direct bilirubin

Answer 355

D. Placental ALP

Answer 356

D. Obstructive jaundice

Answer 357

D. Osteitis deformans (Paget disease)

Answer 358

A. Acute hepatitis

Answer 359

D. Malate dehydrogenase

Answer 360

C. Lactate dehydrogenase

Answer 361

B. Amylase

Answer 362

B. Down syndrome ## Footnote Conditions associated with an elevated AFP level include spina bifi da, neural tube defects, abdominal wall defects, anencephaly (absence of the major portion of the brain), and general fetal distress. Low levels of maternal AFP indicate an increased risk for Down syndrome and trisomy 18, while it is increased in the presence of twins and neural tube defects.

Answer 363

A. pH 7.25 HCO3- 15 mmol/L pCO2 37 mm Hg ## Footnote TIPS FOR EVALUATING ACID-BASE DISORDERS 1. Look at the pH: determine if acidosis or alkalosis 2. Compare pCO2 and HCO3- pCO2 going opposite to pH – RESPIRATORY Abnormal pCO2 respiratory ↓pH ↑pCO2 respiratory acidosis ↑pH ↓pCO2 respiratory alkalosis HCO3- going same direction as pH - METABOLIC Abnormal HCO3- metabolic ↓pH ↓HCO3- metabolic acidosis ↑ PH ↑ HCO3- METABOLIC ALKALOSIS 3. If pH is normal, full compensation occurred 4. If main compensatory mechanism kicked in, but pH still out of normal range, partial compensation has occurred

Answer 364

A. Ferriman-Gallwey scale

Answer 365

A. Primary hypothyroidism

Answer 366

A. Fluorescent polarization immunoassay (FPIA)

Answer 367

B. Fluorescent substrate-labeled inhibition immunoassay

Answer 368

0.5 to 1 hour

Answer 369

D. Potable water

Answer 370

B. Root beer

Answer 371

A. Quality assessment/assurance (QA)

Answer 372

D. Quality systems

Answer 373

E. Communicate

Answer 374

B. Green belts

Answer 375

E. Elimination

Answer 376

B. PPE, administrative controls, engineering controls, substitution, elimination

Answer 377

Albumin and calcium ## Footnote An upright position increases hydrostatic pressure, causing a reduction of plasma volume and increased concentration of proteins. Albumin and calcium levels may become elevated as one changes position from supine to upright. Elements that are affected by postural changes are albumin, total protein, enzymes, calcium, bilirubin, cholesterol, triglycerides, and drugs bound to proteins.

Answer 378

Iron ## Footnote Cortisol: Peaks 4-6 AM; lowest 8 PM–12 AM; 50% lower at 8 PM than at 8 AM; increased with stress Adrenocorticotropic hormone: Lower at night; increased with stress Plasma renin activity: Lower at night; higher standing than supine Aldosterone: Lower at night Insulin: Lower at night Growth hormone: Higher in afternoon and evening Acid phosphatase: Higher in afternoon and evening Thyroxine: Increases with exercise Prolactin: Higher with stress; higher levels at 4 and 8 AM and at 8 and 10 PM Iron: Peaks early to late morning; decreases up to 30% during the day Calcium: 4% decrease supine

Answer 379

Nepholometry and turbidimetry ## Footnote Nephelometry and turbidimetry are used to measure the concentrations of large particles (such as antigen–antibody complexes, prealbumin, and other serum proteins) that because of their size cannot be measured by absorption spectroscopy.

Answer 380

Potentiometry ## Footnote Potentiometry The measurement of potential (voltage) between two electrodes in a solution forms the basis for a variety of procedures for measuring analyte concentration.

Answer 381

Mass spectrometry

Answer 382

Crystal scintillation counter ## Footnote Crystal scintillation generally is used to detect gamma radiation. When a gamma ray penetrates the sodium iodide (NaI) crystal, which contains 1% thallium, it excites the electrons of iodide atoms and raises them to higher energy states. Liquid scintillation is primarily used to count radionuclides that emit beta particles.

Answer 383

Nuclear magnetic resonanance ## Footnote Nuclear magnetic resonance spectroscopy (NMR) is a technique for determining the structure of organic compounds. Unlike mass spectroscopy (MS), NMR is nondestructive, although it does require a larger sample volume than MS. Although NMR is widely used as a diagnostic imaging technique, it has been adapted for only a limited number of clinical laboratory analyses, the most popular being lipoprotein particle measurements. It also has the unique capability of performing chemical analysis in vivo.

Answer 384

Syndrome of inappropriate ADH (SIADH) secretion ## Footnote HYPONATREMIA: Syndrome of Inappropriate ADH (SIADH) Secretion In this condition, secondary to head trauma, seizures, other CNS diseases, and neoplastic conditions, especially lung, breast, and ovarian cancers that secrete ADH-like hormones, the serum sodium is depressed due to the excess retention of water in the collecting ducts.

Answer 385

Low ## Footnote In all forms of hyponatremia, the chloride ion concentration is also generally low because chloride is the chief counterion for sodium.

Answer 386

Hypoalbuminemia, hypercalcemia and multiple myeloma ## Footnote Low AG values are rare but may be seen with hypoalbuminemia (decrease in unmeasured anions) or severe hypercalcemia (increase in unmeasured cations). HENRY: Persistently low anion gaps are a serious sign of possible malignancy—for example, multiple myeloma.

Answer 387

More than 80% ## Footnote Because in panhepatic cirrhosis there is destruction of more than 80% of liver tissue, with no regeneration of damaged liver tissue, the AST/ALT aminotransferases and LD levels (all from the regenerating nodules) tend to be normal or low, or occasionally mildly elevated. However, the total protein and albumin are both abnormally low. In hepatitis, much less than 80% of the liver is destroyed, total regeneration will occur, and enough tissue is present to enable adequate levels of protein synthesis and ammonia fixation as urea. Therefore, the total protein and albumin and ammonia levels remain normal.

Answer 388

B-type natriuretic peptide ## Footnote Diagnosis of Congestive Heart Failure Until recently, this condition was diagnosed strictly on the basis of symptomatology and/or as a result of procedures such as echocardiography, but more recently a biomarker for this condition is the brain form or B-type natriuretic peptide (BNP), which has been approved as a definitive test for this condition and appears to be an excellent marker for early heart failure.

Answer 389

Urea ## Footnote Urea is the main waste product of nitrogen-containing chemicals in the body.

Answer 390

Beta2-microglobulin ## Footnote Beta-2 microglobulin, a polypeptide with a molecular weight of 11.6 kDa with a length of 99 amino acids, is a component of the MHC (major histocompatibility complex) class I molecule. The protein appears in the urine when reabsorption is incomplete because of the proximal tubular damage as in acute kidney injury.

Answer 391

Acute glomerular nephritis

Answer 392

Slower developing disease and may be idiopathic, and is characterized by gradual uremia and loss of functioning nephrons ## Footnote Chronic glomerular nephritis is a slower developing disease and may be idiopathic, and is characterized by gradual uremia and loss of functioning nephrons.

Answer 393

Buffer ## Footnote A buffer, the combination of a weak acid or weak base and its salt, is a system that resists changes in pH. The effectiveness of a buffer depends on the pKa of the buffering system and the pH of the environment in which it is placed. In plasma, the bicarbonate–carbonic acid system, having a pKa of 6.1, is one of the principal buffers.

Answer 394

Kidney function ## Footnote The role of the lungs and kidneys in maintaining pH is depicted with the HendersonHasselbalch equation. The numerator (HCO3−) denotes kidney functions, and the denominator (Pco2) denotes lung function.

Answer 395

Lung function ## Footnote The role of the lungs and kidneys in maintaining pH is depicted with the HendersonHasselbalch equation. The numerator (HCO3−) denotes kidney functions, and the denominator (Pco2) denotes lung function.

Answer 396

Respiratory acidosis

Answer 397

Calcium ## Footnote Calcium is the fifth most common element and is the most prevalent cation in the human body. A healthy adult contains approximately 1 to 1.3 kg of calcium, and 99% of this is in the form of hydroxyapatite in the skeleton. The remaining 1% is contained in the extracellular fluid (ECF) and soft tissues. Additionally, less than 1% of the skeletal content of calcium is in bone fluid and exchanges freely with the ECF.

Answer 398

Type 1 diabetes mellitus

Answer 399

Fructosamine ## Footnote Fructosamine assays are the most widely used to assess short-term (3- to 6-week) glycemic control because the average half-life of the proteins is 2 to 3 weeks

Answer 400

HDL ## Footnote HDL plays a key role in reverse cholesterol transport, the process by which excess cholesterol is returned from tissues to the liver, where it is reused or excreted in bile.

Answer 401

LpX lipoprotein ## Footnote LpX is an abnormal lipoprotein found in patients with obstructive biliary disease and in patients with familial lecithin/cholesterol acyltransferase (LCAT) deficiency.

Answer 402

Chylomicrons and VLDL ## Footnote VLDL and chylomicrons are the most lipid-rich lipoprotein classes in human blood. This fact leaves them as the most buoyant in plasma. These lipoproteins have a density of less than 1.006 kg/L (density measurement). LDL particles are smaller in size and in lipid content, causing their density to range from 1.006 to 1.063 kg/L. HDL, the densest lipoprotein, ranges from 1.063 to 1.210 kg/L.

Answer 403

Tangier disease ## Footnote Tangier disease is a rare autosomal recessive disorder characterized by complete absence of HDL due to a mutation in the ABCA1 gene on chromosome 9. In the homozygous state, patients present with low or undetectable HDL in plasma, hepatosplenomegaly, peripheral neuropathy, orange tonsils, and premature coronary disease.

Answer 404

Prealbumin ## Footnote Prealbumin plays a significant role in the metabolism of vitamin A by complexing with the retinol-binding protein (RBP), which, in turn, complexes with vitamin A to transport it through the body.

Answer 405

Alpha1-acid glycoprotein

Answer 406

Iron deficiency anemia ## Footnote A striking elevation of transferrin in the β-region sometimes occurs in patients suffering from iron deficiency anemia. The increase in transferrin corresponds to increased IBC, and the percent saturation is low.

Answer 407

Lower ## Footnote Enzymes lower the activation energies of the chemical reactions that they catalyze, so as to cause greatly enhanced rates of reaction. They do not become modified in these reactions and do not affect the equilibrium between reactants and products in the reaction.

Answer 408

Isoenzymes ## Footnote Many enzymes have isoenzymes, called isozymes, of different forms that catalyze the same reaction. These different forms occur because of differences in the amino acid sequences of enzymes. Despite these differences in sequence, the enzymes fold to the same three-dimensional structures and frequently exhibit similar affinities for and catalytic rates with substrates.

Answer 409

Cofactors ## Footnote In addition to the basic enzyme structure, a nonprotein molecule, called a cofactor, may be necessary for enzyme activity. Inorganic cofactors, such as chloride or magnesium ions, are called activators. A coenzyme is an organic cofactor, such as NAD.

Answer 410

Catalytic mechanism

Answer 411

LD4 and LD5 ## Footnote In myocardial damage, the predominant isozymes that become elevated in serum are LD1 and LD2; in liver or skeletal muscle disease, the LD4 and LD5 isozymes become elevated predominantly in serum.

Answer 412

LD6 ## Footnote Another band detected in electrophoresis and termed LD6 can be seen; this probably represents alcohol dehydrogenase, which can also metabolize lactate.

Answer 413

Hemolysis Gilbert's syndrome Crigler-Najjar syndrome

Answer 414

Dubin-Johnson syndrome Biliary obstruction

Answer 415

Fall below normal references ranges due to inadequate protein feeding ## Footnote The common recommendation for neonatal testing is that specimens are collected when the newborn is at least 3 days old and after 24 hours of protein feeding in order to adequately supply nutrients to produce thyroid hormones. Given the common practice of dismissing mother and newborn baby within 48 hours of the mother’s admission, it is likely that thyroxine levels may occasionally fall below normal reference ranges due to inadequate protein feeding rather than congenital hypothyroidism.

Answer 416

Acute toxicity ## Footnote Acute toxicity is usually associated with a single, short-term exposure to a substance, the dose of which is sufficient to cause immediate toxic effects.

Answer 417

Chronic toxicity ## Footnote Chronic toxicity is usually associated with repeated frequent exposure for extended periods for greater than 3 months and possibly years, at doses that are insufficient to cause an immediate acute response. In many instances, chronic exposure is related to an accumulation of the toxicant or the toxic effects within the individual. Chronic toxicity may affect different systems than those associated with acute toxicity.

Answer 418

Phencyclidine ## Footnote PHENCYCLIDINE Used almost exclusively as a drug of abuse, this drug is traded on the streets under the name of angel dust or angel hair

Answer 419

Lysergic acid diethylamide ## Footnote Lysergic acid diethylamide (LSD) is a semisynthetic indolalkylamine and a hallucinogen. LSD toxicity levels are low, and deaths are generally due to trauma secondary to errors in the user’s judgment. Panic reactions—a bad trip—are the most common adverse reactions.

Answer 420

Ethosuximide (Zarontin) ## Footnote Ethosuximide is the drug of choice for absence (petit mal) seizures unaccompanied by other types of seizures. It is preferred over valproic acid, at least initially, because hepatotoxicity is a rare but serious side effect of valproic acid.

Answer 421

Theophylline and theobromine ## Footnote Anti-asthmatic drugs, such as theophylline and theobromine, are used for treatment of neonatal breathing disorders or of respiratory conditions that affect adults or children, such as asthma.

Answer 422

Ethanol ## Footnote Ethanol is probably the most common drug of abuse and is frequently responsible for the presentation of patients with altered mental status to hospitals and emergency rooms. Peak plasma concentrations are usually reached within 1 hour after ingestion.

Answer 423

Whole blood ## Footnote Unlike many other toxins, lead is generally measured in whole blood rather than in serum or plasma, because most of the circulating lead is bound within the blood cells.

Answer 424

Quality systems ## Footnote Quality assessment (QA) in the laboratory, a program that monitors the total testing process with the aim of providing the highest quality patient care; formerly called quality assurance. Quality control (QC) a system that verifies the reliability of analytical test results through the use of standards, controls, and statistical analysis. Quality systems (QS) in an institution, a comprehensive program in which all areas of operation are monitored to ensure quality with the aim of providing the highest quality patient care.

Answer 425

Trend ## Footnote TREND: an indication of error in the analysis, detected by a progressive drift of control values in one direction for at least 5 consecutive runs SHIFT: an abrupt change from the established mean indicated by the occurrence of all control values on one side of the mean ------ Assaying control specimens and standards along with patient specimens serves several major functions: 1. Provides a guide to the functioning of equipment, reagents, and individual technique 2. Confirms the accuracy of testing when compared with reference values 3. Detects an increase in the frequency of both high and low minimally acceptable values (dispersion) 4. Detects any progressive drift of values to one side of the average value for at least 3 days (trends) 5. Demonstrates an abrupt shift or change from the established average value for 3 days in a row (shift)

Answer 426

Swinging-bucket centrifuge Fixed-angle centrifuge ## Footnote Fixed angle–head centrifuges are used when rapid centrifugation of solutions containing small particles is needed; an example is the microhematocrit centrifuge. Ultracentrifuges are high-speed centrifuges generally used for research projects, but for certain clinical uses, a small air-driven ultracentrifuge is available that operates at 90,000 to 100,000 rpm and generates a maximum RCF of 178,000 g. Ultracentrifuges are often refrigerated.

Answer 427

All of these ## Footnote COMPONENTS OF A QUALITY SYSTEMS PROGRAM A comprehensive quality systems program is designed to follow a specimen all the way through the testing process, from the time a test is ordered, through specimen collection and testing to reporting, charting, and delivery and use of results. The scope of QS programs differs among laboratories, but in general QS programs are broad, ongoing, and encompass evaluation of: 1. Personnel qualifications, training, and competency 2. Quality Assessment components including preanalytical (before test) factors, analytical factors and QC methods and postanalytical (after test) factors 3. Proficiency testin

Answer 428

Instrument maintenance and calibration ## Footnote Analytical Factors Affecting Laboratory Test Results Quality assessment programs also evaluate analytical factors that can affect the actual test procedure. Many of these factors fall under the umbrella of QC. Analytical factors include: 1. Instrument maintenance and calibration 2. Use of standards and procedural controls 3. Techniques and test components associated with performing the test procedure (reagents, laboratory water, pipetting, timing, etc.) 4. Interfering substances or conditions 5. Statistical analysis of control results An example of an analytical error is inaccurate sampling caused by problems with an instrument’s automatic sampler, perhaps because of dirt or protein buildup in the sampling probe. The error might be detected when control values show an abrupt or steady change. Such an error can usually be prevented by performing recommended maintenance tasks.

Answer 429

Proficiency testing ## Footnote Proficiency testing (PT) is another component of laboratory quality programs. Laboratories that perform nonwaived procedures are required to subscribe to an external PT program. At regular intervals during the year, the PT agency sends blind samples to the laboratory. These are samples that have been assayed multiple times by the PT agency. The subscribing laboratory analyzes these blind samples and sends the results to the PT agency. The subscribing laboratory’s results are then compared to the PT agency’s assayed values and to the results of peer laboratories participating in the PT program. Participating laboratories receive a report evaluating their performance

Answer 430

Presumptive test ## Footnote Presumptive test A procedure with minimal complexity, instrumentation, and personnel requirements so that the results can be quickly determined.

Answer 431

Definitive test ## Footnote Definitive test Highly sensitive and specific test in which results can be used as legal evidence

Answer 432

Turbidimetry ## Footnote Turbidimetry measures light blocked as a decrease in the light transmitted through the solution; dependent on particle size and concentration.

Answer 433

Very short wavelengths ## Footnote Ultraviolet (UV) light has very short wavelengths and infrared (IR) light has very long wavelengths. When all visible wavelengths of light (400-700 nm) are combined, white light results

Answer 434

Increased specificity and increased sensitivity ## Footnote Fluorometric methods are extremely sensitive and highly specific. Because of this extreme sensitivity, reagents used must be of a higher degree of purity than is required for spectroscopy, because even slight traces of impurities may fluoresce.

Answer 435

Mie scatter ## Footnote Mie scatter - large particles scattering light predominantly a in the forward direction Raleigh scatter - small particles scattering light in all directions with maximum scatter forward and backward

Answer 436

Raleigh scatter ## Footnote Mie scatter - large particles scattering light predominantly a in the forward direction Raleigh scatter - small particles scattering light in all directions with maximum scatter forward and backward

Answer 437

Fluorescence intensity decreases ## Footnote In general, fluorescence intensity decreases with increasing temperature by approximately 1 to 5% per degree Celsius.

Answer 438

Volumetric transfer pipettes

Answer 439

Ostwald-Folin transfer pipettes

Answer 440

Ultracentrifuge

Answer 441

Cytocentrifuge ## Footnote This type of preparation can be used for blood, urine, body fluid, or any other liquid specimen that can be spread on a slide. An advantage of this technology is that only a small amount of sample is used, producing evenly distributed cells that can then be stained for microscopic study. The slide produced can be saved and examined at a later time, in contrast to “wet” preparations, which must be examined immediately.

Answer 442

Increased potassium and calcium ## Footnote Fist pumping during venipuncture ↑ K+, lactic acid, Ca2+, phosphorus; ↓ pH Pumping of the fist before venipuncture should be avoided because it causes an increase in plasma potassium, phosphate, and lactate concentrations. Lowering of blood pH by accumulation of lactate causes the plasma ionized calcium concentration to increase.

Answer 443

20 mg/dL ## Footnote Hemolysis is generally a preanalytical problem that can be avoided. It is graded based on visible presence of hemoglobin, when greater than 20 mg/dL, and it is often graded as mild, moderate, or gross hemolysis.

Answer 444

5 to 15 mg/dL erroneously higher ## Footnote Glucose measurements can be 5 to 15 mg/dL erroneously higher by reducing methods than by more accurate enzymatic methods that are highly specific for glucose.

Answer 445

Colorimetric: endpoint

Answer 446

Colorimetric

Answer 447

Five bands ## Footnote Standard SPE separates the protein into 5 distinct bands but, by modifying the electrophoretic parameters, proteins can be further separated into as many as 12 bands. The modification, known as high-resolution protein electrophoresis (HRE), uses a higher voltage coupled with a cooling system in the electrophoretic apparatus and a more concentrated buffer.

Answer 448

Deficiency in the bilirubin conjugation enzyme system ## Footnote The increased levels of unconjugated bilirubin will cause the infant to appear jaundiced. Generally, this condition persists for only a short period because the enzyme system usually becomes functional within several days after birth. Neonatal physiological jaundice resulting from an enzyme deficiency is hepatic in origin.

Answer 449

Celite ## Footnote Support media that may be used for electrophoretic separations include agarose gel, starch gel, cellulose acetate, and acrylamide. Celite provides the inert supporting phase in gas-liquid chromatography

Answer 450

Ponceau S ## Footnote Amido black 10B, Coomassie brilliant blue, and Ponceau S are dyes that are used to stain serum proteins after electrophoresis. Oil red O and fat red 7B are dyes that are used to stain lipoproteins following electrophoresis.

Answer 451

Albumin ## Footnote Using standard SPE methods, serum proteins appear in five bands: albumin travels farthest to the anode, followed by α1-globulins, α2-globulins, β-globulins, and γ-globulins, in that order.

Answer 452

Bisalbuminemia ## Footnote Bisalbuminemia is a congenital disorder that does not exhibit any clinical manifestations. The only sign of this disorder is the splitting of albumin into two distinct bands when serum is subjected to electrophoresis.

Answer 453

Ceruloplasmin ## Footnote CERULOPLASMIN - ALPHA2-GLOBULIN

Answer 454

Bromcresol purple (BCP) ## Footnote BCP is more specific for albumin than BCG. However, BCG is the method used most often. One reason for this is that renal dialysis patients produce an organic acid that competes with BCP for the binding site on albumin, causing a falsely low result.

Answer 455

Fetal fibronectin ## Footnote The level of fetal fibronectin increases in the secretions of the cervix and vagina. When this occurs prematurely, the increase in fetal fibronectin is used to predict risk of premature birth. Inhibin A, alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol are used together in the quadruple test to assess risk for such disorders as Down syndrome.

Answer 456

Down syndrome ## Footnote An increased AFP level in maternal serum is associated with such disorders as neural tube defects, spina bifida, and fetal distress. A decreased AFP level in maternal serum is characteristic of Down syndrome.

Answer 457

Progesterone ## Footnote SCREENING FOR BIRTH DEFECTS 1. Triple test: AFP, HCG and ESTRIOL 2. Quadruple (QUAD) screen: AFP, HCG, ESTRIOL and INHIBIN-A

Answer 458

Mancini or the endpoint RID ## Footnote The endpoint method requires that all Ag diffuse from the well and the concentration of the Ag is related to the square of the diameter of the precipitin ring; the standard curve is plotted and a line of the best fit is computed. To ensure that all of the Ag has diffused, the incubation time is 48 to 72 hours, depending on the molecular weight of the Ag; for example, IgG quantitation requires 48 hours, and IgM requires 72 hours. For those performing RID, the endpoint method is favored because of its stability and indifference to temperature variations; however, turnaround time is longer compared with the kinetic method.

Answer 459

Fahey-McKelvey or the kinetic RID ## Footnote The kinetic method requires that all rings be measured at a fixed time of 18 hours; a sample with a greater concentration will diffuse at a faster rate and will be larger at a fixed time. The diameter of the precipitin ring is plotted against the Ag concentration on a logarithmic scale.

Answer 460

In the fasting state, approximately 12 hours after eating

Answer 461

Uptake ## Footnote The FTI has been largely replaced by the direct measurement of free T4 by immunoassay, dialysis, or ultrafiltration.

Answer 462

> 200 mg/dL, > 400 mg/dL ## Footnote Errors in LDL-C become noticeable at triglyceride levels >2.26 mmol/L (200 mg/dL) and become unacceptably large at triglyceride levels >4.52 mmol/L (400 mg/dL).

Answer 463

Over 400 mg/dL ## Footnote The equation should not be used with triglyceride values exceeding 400 mg/dL because the VLDL composition is abnormal, making the [triglyceride/5] factor inapplicable

Answer 464

Competitive inhibitors ## Footnote Competitive inhibitors: compete with the substrate for the active site of the enzyme and prevent formation of product, but have a higher Km than the preferred substrate and can be overcome by addition of more substrate. Noncompetitive inhibitors: bind on a different active site of the enzyme than the substrate and so cannot be overcome by addition of more substrate, but prevent formation of product despite the enzyme-substrate complex. Uncompetitive inhibitors: bind to the enzyme-substrate complex and prevent the formation of product. This type of inhibition is also reversible.

Answer 465

Noncompetitive inhbitors ## Footnote Competitive inhibitors: compete with the substrate for the active site of the enzyme and prevent formation of product, but have a higher Km than the preferred substrate and can be overcome by addition of more substrate. Noncompetitive inhibitors: bind on a different active site of the enzyme than the substrate and so cannot be overcome by addition of more substrate, but prevent formation of product despite the enzyme-substrate complex. Uncompetitive inhibitors: bind to the enzyme-substrate complex and prevent the formation of product. This type of inhibition is also reversible.

Answer 466

Uncompetitive inhibitors ## Footnote Competitive inhibitors: compete with the substrate for the active site of the enzyme and prevent formation of product, but have a higher Km than the preferred substrate and can be overcome by addition of more substrate. Noncompetitive inhibitors: bind on a different active site of the enzyme than the substrate and so cannot be overcome by addition of more substrate, but prevent formation of product despite the enzyme-substrate complex. Uncompetitive inhibitors: bind to the enzyme-substrate complex and prevent the formation of product. This type of inhibition is also reversible.

Answer 467

Fixed-time method ## Footnote In the fixed-time method, the reactants are combined, the reaction proceeds for a designated time, the reaction is stopped (usually by inactivating the enzyme with a weak acid), and a measurement of the amount of reaction that has occurred is made.

Answer 468

Kinetic method ## Footnote In continuous-monitoring or kinetic assays, multiple measurements, usually of absorbance change, are made during the reaction, either at specific time intervals (usually every 30 or 60 seconds) or continuously by a continuous-recording spectrophotometer.

Answer 469

LD-5 ## Footnote LD-5 is the most labile isoenzyme. Loss of activity occurs more quickly at 4°C than at 25°C. Serum samples for LD isoenzyme analysis should be stored at 25°C and analyzed within 24 hours of collection.

Answer 470

Para-nitrophenylphosphate ## Footnote ALP catalyzes the hydrolysis of para-nitrophenyl phosphate forming phosphate and free 4- nitrophenyl (4-NPP) which, under alkaline conditions has very intense yellow color.

Answer 471

92% ## Footnote For monovalent cations or anions the contribution to osmolality is approximately 92%. Other serum electrolytes, serum proteins, glucose, and urea contribute to the remaining 8%

Answer 472

Hyponatremia due to increased water retention

Answer 473

Hypernatremia due to excess water loss

Answer 474

Sample hemolysis, thrombocytosis, prolonged tourniquet use or excessive fist clenching

Answer 475

Parathyroid hormone, calcitonin and vitamin D

Answer 476

Angiotensin II

Answer 477

Fluid retention, low serum sodium

Answer 478

Increased unmeasured cations or decreased unmeasured anions ## Footnote Decreased anion gaps of less than 10 mmol/L: either an increase in unmeasured cations (Ca2+, Mg2+) or a decrease in the unmeasured anions Anion gap exceeds 16 mmol/L Indication of increased concentrations of the unmeasured anions (PO4 3−, SO4 2−, protein ions)

Answer 479

10 mOsm/kg ## Footnote The degree of increase in osmolality due to ethanol is expressed as the difference between the measured and the calculated osmolality; the difference is called the osmolar gap. Serum osmolality increases by about 10 mOsm/kg for each 60 mg/dL increase in serum ethanol.

Answer 480

On ice, no clots, no air bubbles ## Footnote Specimen requirements for blood gas analysis include the following. 1. Arterial blood is collected in a glass or plastic syringe. Capillary specimens can also be used (blood must be “arterialized”). 2. Lyophilized or liquid heparin is the preferred anticoagulant. 3. No air bubbles should exist in the sample because they lower the pCO2 value. 4. The specimen must be placed on ice and transported to the laboratory in 15 minutes at 4◦C and tested immediately. Otherwise, pH values decrease, and pCO2 values increase. 5. Blood clots are unacceptable

Answer 481

pO2 will fall 7% and pCO2 will rise 3%

Answer 482

Thyroxine ## Footnote T4 is the predominant form of the thyroid hormones secreted into the circulation, having a concentration in the plasma significantly greater than T3. However, in terms of physiological activity, T3 must be considered because it is four to five times more potent than T4.

Answer 483

Thyroid-stimulating hormone (TSH) ## Footnote TSH is the American Thyroid Association’s recommended screening test.

Answer 484

No decrease in serum growth hormone concentration 90 minutes after oral glucose administration ## Footnote Following an overnight fast, a 100-gram oral glucose load will cause a large drop in serum growth hormone in a normal individual, but will not suppress in patients with acromegaly.

Answer 485

Single-stranded DNA ## Footnote The target DNA must be denatured to single-stranded DNA before it can serve as a template for the PCR reaction.

Answer 486

42.5 grams

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