CC Flashcards

Question

The PUREST TYPE OF REAGENT WATER is: Type I Type II Type III All are equal

Answer 1

USP and NF chemical grade

Answer 2

Kilogram 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 3

pH 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 4

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

Answer 5

Class C 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 6

1 and 2 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 7

Shock Liquid nitrogen is probably one of the most widely used cryogenic fluids (liquefied 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 8

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 9

Turn instrument off and unplug it 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 10

Pull the person away from the electrical source 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 11

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

Answer 12

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

Answer 13

Photomultiplier 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 14

Tungsten–halogen lamp Slide technology depends on reflectance spectrophotometry. For colorimetric determinations, the light source is a tungsten–halogen lamp.

Answer 15

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

Answer 16

1 and 2 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 17

Inversely proportional

Answer 18

Increase in fluorescence

Answer 19

Nephelometry

Answer 20

Scintillation counter

Answer 21

Continuous flow analysis

Answer 22

Discrete analyzers 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 23

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

Answer 24

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

Answer 25

Coefficient of variation Range Standard deviation 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 26

Fluctuations in line voltage Reagent lot variability Wear and tear of instrument 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 27

Reagent dispensing Variation in handling techniques: pipetting, mixing, timing Variation in operator 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 28

Mode 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 29

Constant systematic error 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 30

Proportional systematic error 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 31

Bias 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 32

Diagnostic sensitivity 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 33

Diagnostic specificity 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 34

Analytic sensitivity 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 35

Analytic specificity 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 36

Chance of an individual having a given disease or condition if the test is abnormal. 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 37

Chance an individual does not have a given disease or condition if the test is within the reference interval.

Answer 38

95.45% 68.26% will lie within ±1 s 95.45% will lie within ±2 s 99.74% will lie within ±3 s

Answer 39

2:2S 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 40

Two controls in the same run are greater than 4s units apart 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 41

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

Answer 42

Random error 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 reflecting 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 43

Deterioration of the reagent

Answer 44

Levy–Jennings 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 45

Tonks–Youden 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 46

Cusum 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 47

Accuracy 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 48

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

Answer 49

Reliability 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 50

Student’s t test 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 significant difference in means. The F test is the ratio of variances and determines if one method is significantly less precise.

Answer 51

120 minutes (2 hours)

Answer 52

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

Answer 53

Glucose oxidase Glucose oxidase is the most specific 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 54

Glucose-6-phosphate dehydrogenase 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 55

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

Answer 56

False decrease 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 57

Type 1 diabetes mellitus

Answer 58

Type 2 diabetes mellitus

Answer 59

Data represents an impaired glucose status 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 60

6.5% If the result is 6.5% or more, the treatment plan should be adjusted to achieve a lower level, and the test performed every 3 months until control is improved.

Answer 61

Red blood cell life span 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 62

Glycosylated hemoglobin (HbA1c) 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 63

Fructosamine 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 64

Gluconeogenesis 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 65

Glucagon 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 66

Insulin 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 67

Hyperglycemia CORTISOL INCREASES BLOOD GLUCOSE.

Answer 68

Below 50 mg/dL

Answer 69

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

Answer 70

Dilution = 2:10 Ratio = 2:8

Answer 71

Moles = g/MW = 75g/ 58g/mol = 1.29 moles = 1.3 moles

Answer 72

all of the above

Answer 73

according to their chemical properties and classification

Answer 74

a. Impermeable lab coat with eye/ face protection and appropriate disposable gloves Nitrile gloves used on organic chemicals

Answer 75

UV light and microwaves - BSC, Spectro Most common UV light source - Mercury lamp/ deuterium lamp UV in CC = VERY SHORT

Answer 76

b. Alert and evacuate those in the immediate area out of harms way

Answer 77

b. Nuclear magnetic resonance spectroscopy

Answer 78

tungsten light bulb light source for UV spectrum: MXDHH entrance slit: prevents stray light exit slit: selects specific band pass

Answer 79

HAXI horizontal axis/ x axis abscissa independent variable VOYD vertical axis/ ordinate y-axis dependent variable

Answer 80

Diabetes monitoring

Answer 81

fixed angle/ angle-head centri - swinging bucket/ horizontal-head centri = horizontal when rotating, vertical when at rest most rapid = ultracentrifuge

Answer 82

presumptive test

Answer 83

definitive test

Answer 84

all of these

Answer 85

Calcium Best = Total proteins

Answer 86

200mg/dl = clear 300mg/dl = turbid/ hazy 400mg/dl = lactascent 600mg/dl = MILKY/ OPAQUE

Answer 87

1, 2, 3, 4

Answer 88

Diagnosis of monoclonal gammopathies

Answer 89

All of these

Answer 90

Proteinuria

Answer 91

Negatively, anode

Answer 92

BCG (Bromcresol green)

Answer 93

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

Answer 94

Dehydration

Answer 95

Prolonged tourniquet application

Answer 96

Microalbuminuria

Answer 97

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

Answer 98

Tyrosine 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 99

Albumin 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 100

Prealbumin 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 101

A decreased level of prealbumin

Answer 102

Prealbumin 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 103

Down syndrome Conditions associated with an elevated AFP level include spina bifida, 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 104

Alpha2-macroglobulin 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 105

Alpha1-acid glycoprotein 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 106

Beta2-microglobulin 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 107

Fibronectin

Answer 108

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

Answer 109

Crosslinked C-telopeptides (CTX) 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 110

Beta-trace protein 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 verified 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 111

Cystatin C

Answer 112

Amyloid β42 (Aβ42) and Tau protein In a symptomatic patient, low Aβ42 along with high Tau reflects an increased likelihood of Alzheimer disease, but it does not mean that the person definitely 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 113

Myoglobin 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 114

Troponin 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 115

hs-CRP 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 116

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

Answer 117

BNP and echocardiogram 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 118

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

Answer 119

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

Answer 120

Greater than 600 mg/dL 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 121

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

Answer 122

In the fasting state, approximately 12 hours after eating 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 123

Cholesterol 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 124

Lipase 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 125

Chylomicrons 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 126

HDL 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 127

LpX 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 esterifies cholesterol.

Answer 128

Chylomicrons 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 129

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

Answer 130

Cholesterol 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 131

50% 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 132

High-density lipoproteins (HDLs) 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 133

Coronary artery disease The quantification 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 134

HDL-C concentration < 40 mg/dL 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 135

Apoprotein A-I 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 136

Apo-B100 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 137

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

Answer 138

Heparin-manganese 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 139

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

Answer 140

210 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 141

Triglycerides over 400 mg/dL 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 142

– Chylomicrons →β→pre-β→α + 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 143

B-VLDL β-VLDL (‘floating 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 144

Lp(a) 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 145

Lp(a) 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

Answer 146

Elevated VLDL and presence of chylomicrons 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 147

Pre-renal azotemia

Answer 148

Renal azotemia

Answer 149

Post-renal azotemia

Answer 150

The catabolism of proteins and amino acids 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 151

Oxidation of creatine

Answer 152

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

Answer 153

Creatinine

Answer 154

Cystatin C

Answer 155

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

Answer 156

Ammonia 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 157

Hepatic coma 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 158

Urea 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 159

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

Answer 160

64 mg/dL 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 161

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

Answer 162

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

Answer 163

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

Answer 164

The patient had two cigarettes 15 minutes prior to blood draw. 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 165

Glomerular filtration rate is decreased by at least 50% 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 166

Creatinine 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 167

Uric acid Uric acid may be quantified by reacting it with phosphotungstic acid reagent in alkaline solution.

Answer 168

Chronic renal failure 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 169

Uric acid 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 170

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

Answer 171

Uric acid 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 172

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

Answer 173

Azobilirubin 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 174

Uridine diphosphate glucuronyltransferase 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 175

Urobilin 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 176

Albumin 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 177

Jaundice 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 178

Brain 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 179

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

Answer 180

Specimen refrigeration 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 181

Delta Four bilirubin fractions represented by Greek letters have been identified: unconjugated (alpha), monoconjugated (beta), diconjugated (gamma), and conjugated 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.

Answer 182

Spleen 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 183

Insoluble in water 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 184

Conjugated bilirubin 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 185

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

Answer 186

Caffeine-sodium benzoate 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 caffeine-sodium benzoate to solubilize it before proceeding with the diazo reaction. Note: EVELYN-MALLOY: methanol JENDRASSIK-GROF: caffeine-sodium benzoate

Answer 187

Obstructive jaundice "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 backflow 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 backflow of conjugated bilirubin.

Answer 188

Unconjugated serum bilirubin level increased 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 189

Deficiency in the bilirubin conjugation enzyme system 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 190

Gilbert syndrome 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 191

Deficiency of the enzyme system required for conjugation of bilirubin Both Crigler-Najjar syndrome and neonatal jaundice, a physiological disorder, are due to a deficiency in the enzyme-conjugating system. With a deficiency 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 192

Inability to conjugate bilirubin 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 193

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

Answer 194

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

Answer 195

Cirrhosis 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 196

Cirrhosis Cirrhosis is defined as destruction of the liver’s architecture. The leading cause of this condition is alcohol abuse.

Answer 197

B1 and B2 Hemolytic jaundice: unconjugated bilirubin (B1) Hepatic jaundice: unconjugated and conjugated bilirubin (B1 and B2) Obstructive jaundice: conjugated bilirubin (B2)

Answer 198

Tissue damage and necrosis 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 199

Lower than expected 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 specific 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 200

Enzymes are protein catalysts of biological origin. 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 specific chemical reaction by lowering the activation energy needed for the reaction to proceed.

Answer 201

Lock-and-key theory by Emil Fischer 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 202

First-order kinetics 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 203

Zero-order kinetics 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 204

Kinetic assay 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 specific time intervals (usually every 30 or 60 seconds) or continuously by a continuous- recording spectrophotometer.

Answer 205

Coenzyme 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 206

Activator 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 207

Transferases 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 208

Aldolase 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 209

Oxidoreductases

Answer 210

Ligases In addition to naming enzymes, the IUB system identifies 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 contains 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 211

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

Answer 212

Pernicious anemia and hemolytic disorders The highest levels of total LD are seen in pernicious anemia and hemolytic disorders.

Answer 213

LD-5 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 214

Paget's disease 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 215

Bone disease 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 216

Creatine kinase 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 217

CK, AST, LD 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 218

Cholinesterase Normal serum levels of cholinesterase are quite high, reflecting its continual synthesis and release by the liver. Decreased values are considered abnormal.

Answer 219

Amylase 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 220

G6PD 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 221

Nuclear matrix protein

Answer 222

Potassium 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 223

Bicarbonate 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 224

Calcium and magnesium 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 225

Bicarbonate, potassium and chloride

Answer 226

Potassium 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 227

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

Answer 228

Less than 135 mmol/L Hyponatremia is defined 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 significant. Hyponatremia can be assessed by the cause for the decrease or with the osmolality level.

Answer 229

Diuretic use Causes Of Hyponatremia 1. Increased Sodium Loss Hypoadrenalism Potassium deficiency 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 230

Plasma/serum osmolality Hyponatremia can also be classified 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 231

Pseudohyponatremia 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 232

Urine osmolality 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 233

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

Answer 234

Potassium 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 235

Vomiting 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 236

Alkalosis 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 237

Chloride 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 238

Cystic fibrosis 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 239

Bicarbonate 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 240

Magnesium 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 241

Hypomagnesemia 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 242

Parathyroid hormone, vitamin D and calcitonin 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 243

50 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 244

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

Answer 245

Ammonium molybdate Serum inorganic phosphate concentrations are determined most commonly by reacting with ammonium molybdate reagent. The molybdenum-phosphate complexes can be quantified 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 246

Hypernatremia Ketoacidosis Lactic acidosis Methanol, ethanol, ethylene glycol poisoning Uremia/renal failure 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 247

Hypoalbuminemia Hypercalcemia

Answer 248

Serum 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 249

92 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 250

2(Na) + (glucose ÷ 18) + (BUN ÷ 2.8)

Answer 251

Ferritin 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 252

Lithium heparin; dry 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 253

pO2 and pH increase; pCO2 decreases 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 254

pO2 decreases, pCO2 increases, pH decreases 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 255

Bicarbonate/carbonic acid 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 256

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

Answer 257

Carbon dioxide

Answer 258

Will decrease pO2 by 7% Fever will decrease pO2 by 7% Fever will increase pCO2 by 3%

Answer 259

Will increase pCO2 by 3% Fever will decrease pO2 by 7% Fever will increase pCO2 by 3%

Answer 260

Kidney function 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 261

Lung function 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 262

Metabolic alkalosis 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 263

pH 7.66 HCO3- 22 mmol/L pCO2 20 mm Hg 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 264

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

Answer 265

Metabolic alkalosis 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 classification is metabolic alkalosis, partially compensated by increased pCO2.

Answer 266

pH, pCO2 and pO2 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 267

Occasionally 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 268

Respiratory acidosis

Answer 269

Pituitary gland

Answer 270

Anterior pituitary gland

Answer 271

Posterior pituitary gland

Answer 272

ACTH FSH LH TSH

Answer 273

GH Prolactin

Answer 274

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

Answer 275

Oral glucose loading

Answer 276

Amino acids

Answer 277

Anterior pituitary gland

Answer 278

Vasopressin deficiency

Answer 279

TSH assay 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 280

Primary hyperthyroidism 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 281

Primary hyperthyroidism

Answer 282

All of these

Answer 283

Aldosterone 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 284

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

Answer 285

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

Answer 286

Excess secretion of pituitary ACTH 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 287

Serum ACTH 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 288

Overnight low-dose dexamethasone suppression test

Answer 289

Cholesterol

Answer 290

Estradiol (E2 )

Answer 291

Testosterone

Answer 292

Acute toxicity

Answer 293

Chronic toxicity

Answer 294

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

Answer 295

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

Answer 296

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

Answer 297

Marijuana 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 298

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

Answer 299

Cocaine 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 300

Cocaine 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 301

Whole blood 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 302

Arsenic ARSENIC Toxins may BIND SULFHYDRYL GROUPS IN KERATIN FOUND IN HAIR AND FINGERNAILS

Answer 303

Cyanide overdose 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 304

Arsenic toxicity ODOR OF BITTER ALMONDS: CYANIDE POISONING ODOR OF GARLIC, METALLIC TASTE: ARSENIC POISONING

Answer 305

Ethanol 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 306

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 modification of the drug by cells 5. Excretion is the process by which the drug and its metabolites are removed from the body

Answer 307

Varies with the drug, depending on its rate of absorption 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 308

Shortly before drug administration 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 309

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

Answer 310

Salicylate The Trinder reaction or modification is used almost routinely in the determination of salicylate and is based on the colorimetric reaction with ferric ions.

Answer 311

Liver 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 312

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

Answer 313

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

Answer 314

Theophylline 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 315

3 and 4 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. Digoxin - cardiac glycoside, CHF Phencyclidine - hallucinogen

Answer 316

Caffeine 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 confirmed by HPLC or immunoassay methods.

Answer 317

Lithium 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 318

Vancomycin 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 319

Ethosuximide (Zarontin) 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 320

1, 2 and 3 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 321

Osmolar gap

Answer 322

Phosphomolybdic acid 'FoFo' Aresenomolybdic acid = Nelson somogyi O-toluidine = aromatic rings Ferric chloride = inverse colorimetry (+) colorless Obsolete = 6C, Inc 5-15mg/dl Only non-obsolete = O-toluidine

Answer 323

Glycolysis (EMP) glycogenolysis = glycogen to glucose gluconeogenesis = form glucose from other substances (AA, glycerol, pyruvate) glycogenesis = glucose to glycogen

Answer 324

FBS (8-12 hours fast) 75g OGTT = pregnant GDM

Answer 325

Transthyretin (prealbumin) transport thyroxine and retinol Albumin = indicator of nutritional status B-trace protein = indicator of CSF leakage Transferrin = transport iron in ferric state

Answer 326

Blanking technique: REAGENT blank Patient blank = hemolyzed, lipemic, icteric spx

Answer 327

Water CO2 = Class B and C Dry chemical = A, B, C Halon = B and C Metal X = D

Answer 328

B. migration of lymphocytes = chronic a. inc capillary permeability = acute c. release of haptoglobin = acute d. CRP release (and SAA) = acute -- inc 1000x

Answer 329

c. B-hCG threatened abortion: placenta is still intact; vaginal bleeding a. AFP - amniotic fluid not vaginal secretion; inc in spina bifida/ neural tube defect, dec in down syndrome b. fetal fibronectin - dec when pregnant is threatened, inc in pregnancy; detect pre-term labor

Answer 330

c. fibronectin (also albumin) Adiponectin = marker for obesity (dec levels) Recent studies have shown an inverse correlation between body mass index and adiponectin values. Lower levels of adiponectin correlate with an increased risk of heart disease, type 2 diabetes, metabolic syndrome, and obesity

Answer 331

HDL LDL - highest cholesterol content VLDL - endogenous TAG CM - exogenous TAG

Answer 332

40 above years old 20-200-220

Answer 333

Chylomicrons

Answer 334

ApoB = LDL, VLDL, IDL, CM ApoA = HDL - activates LCAT ApoC = cofactor for LPL ApoE = ligand for LDL-R

Answer 335

post renal azotemia pre-renal azotemia = BUN:CREA ratio is >20:1

Answer 336

1 and 2 dx sensi = positive dx speci = negative accuracy and precision = QA

Answer 337

Fixed angle

Answer 338

Cystatin C = Indirect GFR = BEST BUN and CREA = direct GFR B2 - microglobulin = tubular function

Answer 339

Sensitivity Specificity = all negative

Answer 340

b. cirrhosis, nephrotic syndrome, MM Reverse A:G ratio = dec albumin, inc globulin immunodeficiency = dec globulin cirrhosis = dec albumin nephrotic syndrome = dec albumin, inc alpha-2 gamma glo MM = inc gamma globulin hypogammaglobulinemia = dec globulin

Answer 341

b. creatinine creatinine -- PO4 +ADP -CK> creatinine +ATP Urea - (catabolism) protein Uric acid (catabolism) nucleic acid Glucose - (anabolism) proteins and NA --gluconeogenesis (ana) > glucose

Answer 342

Cystatin C - marker for kidney function

Answer 343

c. factor assay = not all a. bilirubin = metabolic b. enzymes = hepatic injury and obstruction d. prothrombin = synthetic 1st factor affected: FVII (extrinsic pathway PT)

Answer 344

b. bilirubin = bile acid and bile salt a. prothrombin time = synthetic c. albumin = synthetic d. transaminases = injury

Answer 345

c. transaminases a. prothrombin time = synthetic b. bilirubin = metabolic, excretory, synthetic d. albumin = synthetic

Answer 346

C. activator = inorganic cofactor - important part in enzyme function b. coenzyme = inorganic factor

Answer 347

1, 2 1. Catalyzes the transfer of chemical or functional group from one substance to another = TRANFERASE 2. Catalyzes intramolecular rearrangement of the substrate compound = ISOMERASE 3. Increased activity EXTRACELLULARLY when red cells are damaged (hemolysis) INC LD INC AST INC CK

Answer 348

a. isomerase = rearrangement b. ligase = joins with 2 ATP c. transferase = transfer d. oxireductase = redox

Answer 349

d. AST LDH = least specific

Answer 350

b. acute pancreatitis

Answer 351

200mg/dl - 400mg/dl = unacceptably large

Answer 352

apo-B48 = CM apo-B100 = VLDL, LDL, IDL HDL = apo AI and apo AII

Answer 353

d. A and C For kidney function and GFR

Answer 354

Glucose: 160-180 Sodium: 120 mmol/L (110-130mmol/L)

Answer 355

c. organic mercury - animal, soil, plant; can reach BBB a. elemental mercury = not readily absorbed b. inorganic mercury = Hg and Hg2+

Answer 356

Fluid retention and low serum sodium ADH - prevent urine formation *SIADH - syndrome of inappropriate ADH secretion

Answer 357

c. renal failure a. diuretic use - Na, K, Cl, HCO3, Mg b. hypokalemia - water retention

Answer 358

b. irreversible reversible = acute irreversible = chronic

Answer 359

130 mmol/L

Answer 360

Serum and urine osmolality

Answer 361

2 and 3 - chloride shift *should be 1, 2, 3

Answer 362

c. detect osmolal gap - ethanol poisoning - detect anion gap: metabolic acidosis

Answer 363

2 x [NA] + [Glucose] + [BUN] (mmol/L)

Answer 364

c. 1,2,3 (also hemolysis) Thrombocytosis = inc clotting = inc K+ Thrombocythemia = dec K+

Answer 365

Osmolality

Answer 366

CHLORIDE!!

Answer 367

All of the above (A,B,C)

Answer 368

3, 4 severe burn = excess Na loss CHF = H2O retention

Answer 369

c. hemosiderosis = minimal or no tissue damage, inc TIBC a. sideroblastic anemia = defective heme synthesis leading to iron overload in erythroblasts (Dimorphic population of RBCs) b. hemochromatosis = dec TIBC, there is tissue damage d. chron's disease = inflammatory bowel disease

Answer 370

a. Phosphate

Answer 371

b. kidneys = HCO3 lungs = CO2 pH = 6.1 + log (HCO3/H2CO3) H2CO3 = PCO2 x 0.03

Answer 372

1. Uncompensated respiratory alkalosis 2. Fully compensated metabolic alkalosis

Answer 373

A. Glucose loading GH = hyperglycemic hormone

Answer 374

a. low Stress = starvation = dec TBG, albumin, prealbumin Thyroxine - neo, gly, glucose absorption

Answer 375

a. thyroiditis

Answer 376

1. T7 2. TSH 3. TBG 4. rT3 (inc) 5. T3 uptake

Answer 377

d. myxedema = severe hypothyroidism (edema throughout the body) a. hirsutism = hair growth b. infertility = impaired ovulation c. obesity = hormonal imbalance

Answer 378

d. skin - Vit. D and estrogen * if B is a major endocrine gland, skin is secondary site of hormone production Liver - TPO, angiotensinogen Pancreas - glucagon, insulin, somatostatin

Answer 379

Secreted by the posterior pituitary gland Synthesized by the hypothalamus

Answer 380

Calcitonin - tumor marker (medullary thyroid carcinoma) Thyroglobulin (thyroid tissue)

Answer 381

None of the above LH Female = stimulates progesterone Male = stimulates testosterone All hormones have a specific function LH is produced by anterior pituitary gland Sertoli cells: produce (nourish) sperm cells

Answer 382

a. progesterone

Answer 383

1. Valproic acid 2. Ethosuximide (zarotin) - measured by immunoassays

Answer 384

1, 2 = bronchodilator digoxin and procainamide - cardioactive

Answer 385

a. CNS depressant

Answer 386

methamphetamine aka designer drugs

Answer 387

c. methotrexate - anti-neoplastic (anti-cancer chemo drug) a. barbiturates - anti-convulsant b. benzodiazepines - anti-convulsant d. cannabinoids - drug of abuse (addiction)

Answer 388

C. cocaine - CNS stimulant

Answer 389

d. Anti-depressant - TCA Lithium - mania and depression (bipolar disorder)

Answer 390

d. marijuana

Answer 391

a. whole blood b. hair - arsenic, keratin

Answer 392

B. Mercury

Answer 393

d. arsenic = Mee's lines (fingernails)

Answer 394

Oral Oral administration is the most common route of delivery.

Answer 395

Intravenous Intravenous (IV) administration into the circulatory system offers the most direct route with effective delivery to their sites of action.

Answer 396

Rectal Rectal delivery (suppository) is commonly used in infants and in situations in which oral delivery is unavailable.

Answer 397

Rise Serum concentrations rise when the rate of absorption exceeds distribution and elimination. The concentration declines as the rate of elimination and distribution exceeds absorption. The rate of elimination can only be determined after absorption and distribution are complete.

Answer 398

Declines Serum concentrations rise when the rate of absorption exceeds distribution and elimination. The concentration declines as the rate of elimination and distribution exceeds absorption. The rate of elimination can only be determined after absorption and distribution are complete.

Answer 399

Timing of specimen collection Timing of specimen collection is the single most important factor in TDM. In general, trough concentrations for most drugs are drawn right before the next dose; peak concentrations are drawn 1 hour after an orally administered dose.

Answer 400

Serum or plasma Serum or plasma is the specimen of choice for the determination of circulating concentrations of most drugs. Heparinized plasma is suitable for most drug analysis. The calcium-binding anticoagulants add a variety of anions and cations that may interfere with analysis or cause a drug to distribute differently between cells and plasma. As a result, ethylenediaminetetracetic acid (EDTA), citrated and oxalated plasma are not usually acceptable specimens.

Answer 401

Aminoglycoside Aminoglycosides are a group of chemically related antibiotics used for the treatment of infections with gram-negative bacteria that are resistant to less toxic antibiotics.

Answer 402

Phenobarbital

Answer 403

Phenytoin Phenytoin (Dilantin) is a commonly used treatment for seizure disorders.

Answer 404

Methotrexate

Answer 405

Xenobiotics

Answer 406

Greater than 2.0

Answer 407

Isopropyl alcohol

Answer 408

Decrease amount of oxygen delivered to tissue

Answer 409

100% oxygen therapy

Answer 410

Hepatotoxicity

Answer 411

Methylenedioxymethylamphetamine Methylenedioxymethylamphetamine (MDMA) is an illicit amphetamine derivative that is commonly referred to as “ecstasy.”

Answer 412

8 to 9 hours Half-life of ecstasy: 8 to 9 hours Half-life of THC: 1 day after a single use and 3 to 5 days in chronic, heavy consumers Half-life of cocaine: 0.5 to 1 hour Half-life of benzoylecgonine: 4 to 7 hours

Answer 413

0.5 to 1 hour Half-life of ecstasy: 8 to 9 hours Half-life of THC: 1 day after a single use and 3 to 5 days in chronic, heavy consumers Half-life of cocaine: 0.5 to 1 hour Cocaine’s short half-life is a result of rapid hepatic hydrolysis to inactive metabolites. Half-life of benzoylecgonine: 4 to 7 hours

Answer 414

Heroin OPIATES: The naturally occurring substances include opium, morphine, and codeine. Heroin, hydromorphone (Dilaudid), and oxycodone (Percodan) are chemically modified forms of the naturally occurring opiates. Meperidine (Demerol), methadone (Dolophine), propoxyphene (Darvon), pentazocine (Talwin), and fentanyl (Sublimaze) are the common synthetic opiates.

Answer 415

By lowering the activation energy Enzymes accelerate reactions by lowering the activation energy needed to overcome the transition state on the way to product formation.

Answer 416

Hyperventilation

Answer 417

Hyperventilation

Answer 418

p02 and pH increase, pC02 decreases

Answer 419

4 pyrrole rings bound to an iron molecule

Answer 420

The total amount of iron that can be bound by transferrin

Answer 421

Multiple myeloma

Answer 422

Alpha-fetoprotein

Answer 423

Chylomicron

Answer 424

Red blood cell hemolysis

Answer 425

Serum lipase

Answer 426

Cholesterol

Answer 427

Myasthenia gravis

Answer 428

Peripheral neuropathy

Answer 429

Very low or absent HDL

Answer 430

Tacrolimus Tacrolimus (proprietary name: Prograf) is used to prevent rejection of heart, allogenic liver and kidney transplants.

Answer 431

Theophyliine Theophylline (proprietary name: Theo-Dur) is used to treat moderate or severe asthma.

Answer 432

Diazepam Diazepam (proprietary name: Valium) is in a class of drugs called benzodiazepines, which are sedative-hypnotics.

Answer 433

It is associated with an insufficient amount of insulin secreted by the pancreas

Answer 434

Can develop type 2 diabetes at a later date

Answer 435

The serum should be observed for hemolysis; hemolysis of the red cells will shift potassium from the cells into the serum, resulting in a falsely elevated potassium value

Answer 436

Test in the electrolyte profile (sodium, potassium, chloride and bicarbonate)

Answer 437

Bicarbonate ions

Answer 438

Very low; renal glomerular filtration is not functioning normally Late stages of renal failure show increased serum potassium and phosphorus and decreased serum calcium and urinary potassium. Creatinine clearance decreases, often to less than 50 mL/min compared with reference ranges.

Answer 439

21 mg/dL 10 mg/dL x 2.14 = 21.4 mg/dL

Answer 440

Increased creatinine

Answer 441

Triglycerides Serum or plasma specimens collected from patients in blood collection tubes who have fasted for at least 12 hours are required for triglyceride testing.

Answer 442

HDL cholesterol < 35 mg/dL

Answer 443

The cholesterol is normal, but the triglyceride test is elevated; retest using a 12-hour fasting specimen, because the triglyceride test is affected by the recent meal

Answer 444

Hemolytic anemia in which his red blood cells are being destroyed

Answer 445

Potassium 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 446

Bicarbonate 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 447

Gluconeogenesis Gluconeogenesis is the formation of glucose from amino acids and lipids that occurs when carbohydrate intake decreases. Glycogenesis is the process of glycogen formation by enzyme action on glucose to eventually form glycogen. Glycogenolysis is the breakdown of glycogen, with the eventual formation of glucose-6-phosphate or free glucose that can be used for energy production. Glycolysis is the catabolism of glucose to pyruvate or lactate for adenosine triphosphate (ATP) production (Embden-Meyerhof pathway and Krebs’ cycle).

Answer 448

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

Answer 449

Increased INCREASED ANION GAP 1. Uremia/renal failure, which leads to PO4- and SO42- retention 2. Ketoacidosis, as seen in cases of starvation or diabetes 3. Methanol, ethanol, ethylene glycol poisoning, or salicylate 4. Lactic acidosis 5. Hypernatremia 6. Instrument error DECREASED ANION GAP 1. Hypoalbuminemia (decrease in unmeasured anions) 2. Severe hypercalcemia (increase in unmeasured cations)

Answer 450

Viral hepatitis

Answer 451

4 to 6 hours

Answer 452

Decreased, increased, increased

Answer 453

Normal T3 T4, increased TSH In subclinical hypothyroidism, the TSH is minimally increased while the free T4 stays within the normal range. Likewise, in subclinical hyperthyroidism, the TSH is suppressed while the free T4 is normal.