Enzymes and Cardiac Markers

Which of the following statements is true? A. Apoenzyme + prosthetic group = holoenzyme B. A coenzyme is an inorganic molecule required for activity C. Cofactors are as tightly bound to the enzyme as prosthetic groups D. All enzymes have optimal activity at pH 7.00

A A coenzyme is an organic molecule required for full enzyme activity. A prosthetic group is a coenzyme that is tightly bound to the apoenzyme and is required for activity. Cofactors are inorganic atoms or molecules needed for full catalytic activity. Pyridoxyl- 5´-phosphate is a prosthetic group for ALT and AST. Consequently, patients with low levels of pyridoxal- 5´-phosphate (P-5´-P) (vitamin B6 deficiency) may have reduced transaminase activity in vitro. Enzymes can have diverse pH (and temperature) optimas. Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

Which of the following statements describes a nonkinetic enzyme assay? A. Initial absorbance is measured followed by a second reading after 5 minutes B. Absorbance is measured at 10-second intervals for 100 seconds C. Absorbance is monitored continuously for 1 minute using a chart recorder D. Reflectance is measured from a xenon source lamp pulsing at 60 Hz

A A kinetic assay uses several evenly spaced absorbance measurements to calculate the change in absorbance per unit time. A constant change in absorbance per unit of time occurs only when the rate of the reaction is zero order (independent of substrate concentration). Enzyme activity is proportional to rate only under zero-order conditions. Harr, Robert R. Medical Laboratory Science Review (Page 263). F.A. Davis Company. Kindle Edition.

In which liver disease is the DeRitis ratio (ALT:AST) usually greater than 1.0? A. Acute hepatitis B. Chronic hepatitis C. Hepatic cirrhosis D. Hepatic carcinoma

A ALT prevails over AST in hepatitis; however, AST is greater than ALT in carcinoma, alcoholic liver disease, and cirrhosis of the liver. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

Which definition best describes the catalytic activity of amylase? A. Hydrolyzes second α1-4 glycosidic linkages of starch, glycogen, and other polyglucans B. Hydrolyzes all polyglucans completely to produce glucose C. Oxidatively degrades polysaccharides containing glucose D. Splits polysaccharides and disaccharides by addition of water

A Amylase in humans is a hydrolase that splits the second α 1-4 glycosidic bonds of polyglucans forming maltose. There are two major types of amylase: P-type derived from the pancreas and S-type derived from the salivary glands. These can be differentiated by both electrophoresis and immunoassay. In healthy persons, the principal form in plasma is the salivary isoenzyme. There are several genetic variants of the salivary isoenzyme, which in part accounts for the broad reference range. Harr, Robert R. Medical Laboratory Science Review (Page 277). F.A. Davis Company. Kindle Edition.

Which statement regarding bone-specific ALP is true? A. The bone isoenzyme can be measured immunochemically B. Bone ALP is increased in bone resorption C. Bone ALP is used for the diagnosis of osteoporosis D. There are two distinct bone isoenzymes

A Bone ALP assays (Ostase and Alkphase-B) use monoclonal antibodies to measure the bone isoenzyme in mass units. The assays may be used to monitor bone remodeling by osteoblasts in osteoporosis, and thus, are useful for following treatment. Bone specific ALP is not sufficiently sensitive to diagnose osteoporosis, and antibodies may cross-react with other ALP isoenzymes, depending on their source. Harr, Robert R. Medical Laboratory Science Review (Page 275). F.A. Davis Company. Kindle Edition.

Which of the following conditions is associated with a high level of S-type amylase? A. Mumps B. Intestinal obstruction C. Alcoholic liver disease D. Peptic ulcers

A Both salivary and pancreatic amylases designated S-type and P-type, respectively, are present in normal serum. High amylase occurs in mumps, ectopic pregnancy, biliary obstruction, peptic ulcers, alcoholism, malignancies, and other nonpancreatic diseases. Isoenzymes can be separated by electrophoresis (S-type is faster than P-type), but more commonly immunoinhibition of S-type amylase is used to rule out mumps, malignancy, and ectopic pregnancy, which give rise to high S-type amylase. Harr, Robert R. Medical Laboratory Science Review (Page 278). F.A. Davis Company. Kindle Edition.

Which statement about the clinical utility of plasma or serum lipase is true? A. Lipase is not increased in mumps, malignancy, or ectopic pregnancy B. Lipase is not increased as dramatically as amylase in acute pancreatitis C. Increased plasma or serum lipase is specific for pancreatitis D. Lipase levels are elevated in both acute and chronic pancreatitis

A Lipase elevation is of greater magnitude (2-50 × N) and duration than amylase in acute pancreatitis. When the lipase method is optimized by inclusion of colipase and bile salts, the test is more sensitive and specific than serum amylase for detection of acute pancreatitis. However, lipase is also increased in peptic ulcers, renal insufficiency, and intestinal obstruction. Lipase levels are often low in chronic pancreatitis, and are low in cystic fibrosis. Harr, Robert R. Medical Laboratory Science Review (Page 279). F.A. Davis Company. Kindle Edition.

In which type of liver disease would you expect the greatest elevation of LD? A. Toxic hepatitis B. Alcoholic hepatitis C. Cirrhosis D. Acute viral hepatitis

A Liver disease produces an elevated LD-4 and LD-5. Levels may reach up to 10 times the URL in toxic hepatitis and in hepatoma. However, LD levels are lower in viral hepatitis (2-5 × URL), only slightly elevated in cirrhosis (2-3 × URL) and not significantly elevated in alcoholic liver disease. Harr, Robert R. Medical Laboratory Science Review (Page 265). F.A. Davis Company. Kindle Edition.

Which of the following statements about enzymatic reactions is true? A. NADH has absorbance maximas at 340 and 366 nm B. Enzyme concentration must be in excess to achieve zero-order kinetics C. Rate is proportional to substrate concentration in a zero-order reaction D. Accumulation of the product increases the reaction rate

A Most enzymes are measured by monitoring the rate of absorbance change at 340 nm as NADH is produced or consumed. This rate will be proportional to enzyme activity when substrate is in excess. When the enzyme is present in excess, the initial reaction rate will be proportional to substrate concentration. This condition, called a first-order reaction, is needed when the enzyme is used as a reagent to measure a specific analyte. Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

In a nonmyocardial as opposed to a myocardial cause of an increased serum or plasma CK-MB, which would be expected? A. An increase in CK-MB that is persistent B. An increase in the percent CK-MB as well as concentration C. The presence of increased TnI D. A more modest increase in total CK than CK-MB

A Plasma CK-MB becomes abnormal 4 hours postinfarction, peaks in 16-20 hours, and usually returns to normal within 48 hours. In some noncardiac causes of elevated plasma CK-MB such as muscular dystrophy, there is a persistent elevation of both total CK and CK-MB. TnI and TnT are cardiac-specific markers. They become elevated slightly before CK-MB when a CK-MB URL of 4 μg/L is used, remain elevated for 7-10 days following an AMI, and are not increased in muscular dystrophy, malignant hyperthermia, or crush injuries that are associated with an increase in the concentration of CK-MB. Absolute CK-MB increases are evaluated cautiously, when CK-MB is less than 2.5% of total enzyme because noncardiac sources may be responsible. Harr, Robert R. Medical Laboratory Science Review (Page 268). F.A. Davis Company. Kindle Edition.

Which of the statements below regarding the methods of Henry for AST and ALT is correct? A. Hemolysis will cause positive interference in both AST and ALT assays B. Loss of activity occurs if samples are frozen at -20°C C. The absorbance at the start of the reaction should not exceed 1.0 A D. Reaction rates are unaffected by addition of P-5´-P to the substrate

A RBCs are rich in AST and to a lesser extent in ALT. Hemolysis causes positive interference in both assays, although the effect on AST is greater. Samples are stable for up to 24 hours at room temperature and up to 3 days at 4°C, and should be frozen if kept longer. The starting absorbance should be at least 1.5 A for both assays. Substrates with lower concentrations of NADH are subject to NADH depletion during the lag phase due to side reactions or high transaminase activity. When P-5'-P is added, a significant increase in activity sometimes occurs because some of the enzyme in the serum is in the inactive apoenzyme form. Harr, Robert R. Medical Laboratory Science Review (Page 273). F.A. Davis Company. Kindle Edition.

A patient has a plasma CK-MB of 14 μg/L at admission and a total CK of 170 IU/L. Serum myoglobin is 130 μg/L and TnI is 1.6 μg/L. Three hours later, the TnI is 3.0 μg/L. Which statement best describes this situation? A. This patient has had an AMI and further testing is unnecessary B. A second CK-MB and myoglobin test should have been performed at 3 hours postadmission to confirm AMI C. These results are consistent with skeletal muscle damage associated with a crush injury that elevated the CK-MB D. Further testing 6-12 hours postadmission is required to establish a diagnosis of AMI

A Results on admission indicate strongly that the patient has suffered an MI. The 3-hour TnI confirms this and rules out the possibility of a sample collection or transcription error for the admission sample. Repeat testing of other cardiac markers at 3 hours was not necessary because admission results were significantly increased for all three markers. Skeletal muscle damage or crush injury does not cause an increase in cardiac TnI. Harr, Robert R. Medical Laboratory Science Review (Page 270). F.A. Davis Company. Kindle Edition.

Which condition produces the highest elevation of serum lactate dehydrogenase? A. Pernicious anemia B. Myocardial infarction C. Acute hepatitis D. Muscular dystrophy

A Serum LD levels are highest in pernicious anemia, reaching 10-50 times the upper reference limit (URL) as a result of intramedullary hemolysis. Moderate elevations (5-10 × URL) usually are seen in acute myocardial infarction, necrotic liver disease, and muscular dystrophy. Slight increases (2-3 × URL) are sometimes seen in obstructive liver disease. Harr, Robert R. Medical Laboratory Science Review (Page 265). F.A. Davis Company. Kindle Edition.

Which substrate is used in the Bowers-McComb method for ALP? A. p-Nitrophenyl phosphate B.β-Glycerophosphate C. Phenylphosphate D.α-Naphthylphosphate

A The method of Bowers-McComb (Szasz modification) is the IFCC-recommended method for ALP. This method uses 2-amino-2-methyl-1-propanol, pH 10.15, and measures the increase in absorbance at 405 nm as p-nitrophenyl phosphate is hydrolyzed to p-nitrophenol. Harr, Robert R. Medical Laboratory Science Review (Page 276). F.A. Davis Company. Kindle Edition.

In which condition would an elevated serum alkaline phosphatase be likely to occur? A. Small cell lung carcinoma B. Hemolytic anemia C. Prostate cancer D. Acute myocardial infarction

A The primary diagnostic utility of ALP is to help differentiate necrotic jaundice (↑ALT) from obstructive jaundice (↑ALP). ALP is also increased in several bone diseases. Large increases are seen in Paget's disease, moderate increases in bone cancer, and slight increases in rickets. Total ALP may be slightly increased in osteoporosis but often it is not. In addition to obstructive jaundice and bone diseases, alkaline phosphatase is a tumor marker. In most cases, the alkaline phosphatase is the product of fetal gene activation, and resembles placental ALP (e.g., hepatoma, small cell carcinoma of the lung, ovarian cancer). Leukemia and Hodgkin's disease may cause an elevated leukocyte or bone-derived ALP. Harr, Robert R. Medical Laboratory Science Review (Page 276). F.A. Davis Company. Kindle Edition.

Which condition gives rise to the highest serum level of transaminases? A. Acute hepatitis B. Alcoholic cirrhosis C. Obstructive biliary disease D. Diffuse intrahepatic cholestasis

A The transaminases usually reach 20-50 times the URL in acute viral and toxic hepatitis. Both transaminases are moderately increased (5-10 × URL) in infectious mononucleosis, toxic hepatitis, diffuse intrahepatic obstruction, lymphoma, and cancer of the liver, and slightly increased (2-5 × URL) in cirrhosis and extrahepatic obstruction. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

The reference method for lipase uses olive oil as the substrate because: A. Other esterases can hydrolyze triglyceride and synthetic diglycerides B. The reaction product can be coupled to NADH generating reactions C. Synthetic substrates are less soluble than olive oil in aqueous reagents D. Triglyceride substrates cause product inhibition

A Triglycerides may be hydrolyzed by nonspecific esterases in serum as well as lipase. Lipase acts only at an interface of oil and H2 O and requires bile salts and colipase for activity. Colipase is a protein secreted by the pancreas. Harr, Robert R. Medical Laboratory Science Review (Page 279). F.A. Davis Company. Kindle Edition.

Which of the following statements about the aminotransferases (AST and ALT) is true? A. Isoenzymes of AST and ALT are not found in humans B. Both transfer an amino group to α-ketoglutarate C. Both require NADP+ as a coenzyme D. Both utilize four carbon amino acids as substrates

B ALT catalyzes the transfer of an amino group from alanine, a three-carbon amino acid, to α-ketoglutarate (2-oxoglutarate), forming pyruvate. AST catalyzes the transfer of an amino group from aspartate (four carbons) to α-ketoglutarate, forming oxaloacetate. The reactions are highly reversible and regulate the flow of aspartate into the urea cycle. Both transaminases require P-5'-P as an intermediate amino acceptor (coenzyme). Cytoplasmic and mitochondrial isoenzymes are produced but are not differentiated in clinical practice. Harr, Robert R. Medical Laboratory Science Review (Page 272). F.A. Davis Company. Kindle Edition.

Which statement accurately describes serum transaminase levels in AMI? A. ALT is increased 5- to 10-fold after an AMI B. AST peaks 24-48 hours after an AMI and returns to normal within 4-6 days C. AST levels are usually 20-50 times the upper limit of normal after an AMI D. Isoenzymes of AST are of greater diagnostic utility than the total enzyme level

B ALT may be slightly elevated after an AMI. AST levels can be up to 5-10 times the URL after AMI, but elevations of this range are also seen in patients with muscular dystrophy, crush injury, pulmonary embolism, infectious mononucleosis, and cancer of the liver. Harr, Robert R. Medical Laboratory Science Review (Page 273). F.A. Davis Company. Kindle Edition.

Select the products formed from the forward reaction of AST. A. Alanine and α-ketoglutarate B. Oxaloacetate and glutamate C. Aspartate and glutamine D. Glutamate and NADH

B AST forms oxaloacetate and glutamate from aspartate and α-ketoglutarate (2-oxoglutarate). Both transaminases use α-ketoglutarate and glutamate as a common substrate and product pair. Both aspartate and alanine can be used to generate glutamate in the central nervous system, where it acts as a neurotransmitter. Harr, Robert R. Medical Laboratory Science Review (Page 272). F.A. Davis Company. Kindle Edition.

Which statement about methods for measuring LD is true? A. The formation of pyruvate from lactate (forward reaction) generates NAD+ B. The pyruvate-to-lactate reaction proceeds at about twice the rate as the forward reaction C. The lactate-to-pyruvate reaction is optimized at pH 7.4 D. The negative-rate reaction is preferred

B Although the rate of the reverse reaction (P →L) is faster, the L →P reaction is more popular because it produces a positive rate (generates NADH), is not subject to product inhibition, and is highly linear. The pH optimum for the forward reaction is approximately 8.8. Harr, Robert R. Medical Laboratory Science Review (Page 265). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding the diagnosis of pancreatitis is correct? A. Amylase and lipase are as predictive in chronic as in acute pancreatitis B. Diagnostic sensitivity is increased by assaying both amylase and lipase C. Measuring the urinary amylase:creatinine ratio is useful only when patients have renal failure D. Serum lipase peaks several hours before amylase after an episode of acute pancreatitis

B Amylase is not increased in all persons with pancreatitis and can be increased in several nonpancreatic conditions. Lipase adds both sensitivity and specificity to the diagnosis of acute pancreatitis. Plasma or serum lipase becomes abnormal within 6 hours, peaks at approximately 24 hours, and remains abnormal for about 1 week following an episode of acute pancreatitis. In acute pancreatitis, the rate of urinary amylase excretion increases, and the amylase:creatinine clearance ratio is helpful in diagnosing some cases of pancreatitis. The normal A:C clearance ratio is 1%-4%. In acute pancreatitis, the ratio is usually above 4% and can be as high as 15%. In chronic pancreatitis, acinar cell degeneration often occurs, resulting in loss of amylase and lipase production. This lowers the sensitivity of amylase and lipase in detecting chronic disease to below 50%. Patients with chronic disease have pancreatic insufficiency giving rise to increased fecal fat, and decreased pancreatic digestive enzymes such as trypsin, chymotrypsin, and elastin. Harr, Robert R. Medical Laboratory Science Review (Page 278). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding amylase methods is true? A. Requires sulfhydryl compounds for full activity B. Activity will vary depending on the method used C. Amyloclastic methods measure the production of glucose D. Overrange samples are diluted in deionized water

B Chloride and Ca 2+ ions are required for amylase activity. Samples with high activity should be diluted with NaCl to prevent inactivation. Lipase and CK require sulfhydryl activators. Saccharogenic methods measure the production of glucose, while amyloclastic methods measure the degradation of starch. Starch is a polymer of α-D glucose subunits linked together by both α 1-4 and α 1-6 glycosidic bonds. Different lots may have more or less branching owing to the number of α 1-6 bonds. Since amylase hydrolyzes at the α 1-4 sites only, the amount of product measured is influenced by the extent of branching. Harr, Robert R. Medical Laboratory Science Review (Page 278). F.A. Davis Company. Kindle Edition.

Which of the following enzymes is a transferase? A. ALP B. CK C. Amylase D. LD

B Enzymes are identified by a numeric system called the EC (Enzyme Commission) number. The first number refers to the class of the enzyme. There are six classes; in order, these are oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases. Dehydrogenases are oxidoreductases, whereas kinases and transaminases are transferases. CK is EC number 2.7.3.2, which distinguishes it from other kinases. Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

Which enzyme is measured in whole blood? A. Chymotrypsin B. Glucose-6-phosphate dehydrogenase C. Glycogen phosphorylase D. Lipase

B Glucose-6-phosphate dehydrogenase deficiency is the most common inherited RBC enzyme deficiency and is X linked. The enzyme is measured on a wholeblood hemolysate using glucose-6-phosphate as the substrate, and forms 6-phosphogluconate as NADP+ is converted to NADPH. Persons with the deficiency are prone to a hemolytic episode upon exposure to certain oxidative drugs and fava beans and as a result of infections. Heinz bodies form in the RBCs, bite cells are seen in the circulation, and plasma haptoglobin is reduced in severe cases. Harr, Robert R. Medical Laboratory Science Review (Page 281). F.A. Davis Company. Kindle Edition.

Which statement best describes the clinical utility of plasma homocysteine? A. Levels are directly related to the quantity of LDL cholesterol in plasma B. High plasma levels are associated with atherosclerosis and increased risk of thrombosis C. Persons who have an elevated plasma homocysteine will also have an increased plasma Lp(a) D. Plasma levels are increased only when there is an inborn error of amino acid metabolism

B Homocysteine includes the monomeric amino acid as well as the dimers such as homocystine that contain homocysteine. Plasma levels are measured as an independent risk factor for coronary artery disease. High levels of homocysteine are toxic to vascular endothelium and promote inflammation and plaque formation. Plasma levels are independent of LDL and other cholesterol fractions and help explain why approximately 35% of people with first-time AMI have LDL cholesterol levels < 130 mg/dL. Harr, Robert R. Medical Laboratory Science Review (Page 272). F.A. Davis Company. Kindle Edition.

Which of the following enzymes is activated by calcium ions? A. CK B. Amylase C. ALP D. LD

B Most enzymes require metals as activators or cofactors. CK and ALP require Mg +2 for full activity, and amylase requires Ca +2. Metals required for activity should be components of the substrate used for enzyme analysis. The substrate must also contain anions required (e.g., Cl -for amylase) and should not contain inhibiting cations or anions (e.g., Zn +2 and Mn +2 for CK). Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

Which statement best describes the clinical utility of plasma or serum myoglobin? A. Levels greater than 100 μg/L are diagnostic of AMI B. Levels below 100 μg/L on admission and 2-4 hours postadmission help to exclude a diagnosis of AMI C. Myoglobin peaks after the cardiac troponins but is more sensitive D. The persistence of myoglobin > 110 μg/L for 3 days following chest pain favors a diagnosis of AMI

B Myoglobin is a heme-containing pigment in both skeletal and cardiac muscle cells. The upper limit of normal is approximately 90 μg/L for males and 75 μg/L for females. The plasma myoglobin is a sensitive marker for AMI. Over 95% of affected persons have a value higher than the cutoff (typically >110 μg/L). However, specificity is approximately 75%-85% owing to skeletal muscle injury or renal insufficiency. For this reason, a plasma myoglobin below the cutoff on admission, and within the first 3 hours following chest pain helps to rule out AMI. A value above the cutoff must be confirmed using a cardiac specific assay such as TnI or TnT. Harr, Robert R. Medical Laboratory Science Review (Page 268). F.A. Davis Company. Kindle Edition.

What is the purpose of LD in the kinetic method of Henry for AST? A. Forms NADH, enabling the reaction to be monitored at 340 nm B. Rapidly exhausts endogenous pyruvate in the lag phase C. Reduces oxaloacetate, preventing product inhibition D. Generates lactate, which activates AST

B Patients with liver disease often have high levels of pyruvate and LD. The LD can catalyze the reaction of pyruvate with NADH in the substrate, forming NAD+ and lactate. This would give a falsely high rate for AST because NAD+ is the product measured. Adding LD to the substrate causes pyruvate to be depleted in the first 30 seconds, before AST and MD reactions reach steady state. Harr, Robert R. Medical Laboratory Science Review (Page 273). F.A. Davis Company. Kindle Edition.

Which of the following cardiac markers is consistently increased in persons who exhibit unstable angina? A. Troponin C B. Troponin T C. CK-MB D. Myoglobin

B Persons with unstable angina (angina at rest) who have an elevated TnT or TnI are at eight times greater risk of having an MI within the next 6 months. This property is being used to identify short-term risk patients who should be considered for coronary angioplasty. The reference range for troponin is very low (0-0.03 ng/mL); persons with unstable angina usually have values between 0.04 and 0.1 ng/mL without clinical evidence of AMI. CK-MB and myoglobin have not been useful in identifying persons with unstable angina. Harr, Robert R. Medical Laboratory Science Review (Page 269). F.A. Davis Company. Kindle Edition.

Which of the following statements about the phosphatases is true? A. They hydrolyze adenosine triphosphate and related compounds B. They are divided into two classes based upon pH needed for activity C. They exhibit a high specificity for substrate D. They are activated by Pi

B Phosphatases are classified as either alkaline or acid depending upon the pH needed for optimum activity. The phosphatases hydrolyze a wide range of monophosphoric acid esters. ALP is inhibited by phosphorus (product inhibition). The International Federation of Clinical Chemistry (IFCC) recommended method employs 2-amino-2-methyl-1-propanol, a buffer that binds Pi Harr, Robert R. Medical Laboratory Science Review (Page 275). F.A. Davis Company. Kindle Edition.

How soon following acute abdominal pain due to pancreatitis is the serum amylase expected to rise? A. 1-2 hours B. 2-12 hours C. 3-4 days D. 5-6 days

B Serum amylase usually peaks 2-12 hours following acute abdominal pain resulting from pancreatitis. Levels reach 2-6 times the URL and return to normal within 3-4 days. Urinary amylase peaks concurrently with serum but rises higher and remains elevated for up to 1 week. Harr, Robert R. Medical Laboratory Science Review (Page 277). F.A. Davis Company. Kindle Edition.

What is the recommended troponin T and I cutoff (upper limit of normal) for detecting myocardial infarction? A. The cutoff varies with the method of assay but should be no lower than 0.2 ng/mL B. The upper 99th percentile or lowest level that can be measured with 10% CV C. The concentration corresponding to the lowest level of calibrator used D. The highest value fitting under the area of the curve for the 95% confidence interval

B The American College of Cardiology recommends the cutoff for an abnormal troponin test be set at the 99th percentile of the normal population, 0.013 ng/mL, or if the assay precision at this level is >10% then the cutoff should be the lowest value measurable with a CV of 10% (typically 0.03 ng/mL). An abnormal result (0.04 ng/mL or higher) in a patient with other evidence of ischemic changes indicates cardiac damage. This typically occurs when a pattern of increasing troponin concentration is seen over the first 6 hours after initial testing. Harr, Robert R. Medical Laboratory Science Review (Page 269). F.A. Davis Company. Kindle Edition.

Which enzyme is most likely to be elevated in the plasma of a person suffering from a muscle wasting disorder? A. 5´-Nucleotidase B. Pseudocholinesterase C. Aldolase D. Glutamate dehydrogenase

C 5'-Nucleotidase is increased primarily in obstructive liver disease and liver cancer. When elevated along with ALP, it identifies the liver as the source of ALP. Glutamate dehydrogenase is increased in necrotic liver diseases along with transaminases, but because of its distribution it is elevated to a greater extent in toxic hepatitis and therefore is useful as a marker for halothane (anesthesia) toxicity. Aldolase is found in all tissues and is increased in many conditions including myocardial infarction, viral hepatitis, and myelocytic leukemia. However, like CK, the greatest increase is seen in skeletal muscle-wasting disease such as muscular dystrophies. Harr, Robert R. Medical Laboratory Science Review (Page 280). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding ALP is true? A. All isoenzymes of ALP are antigenically distinct and can be identified by specific antibodies B. Highest serum levels are seen in intrahepatic obstruction C. Elevated serum ALP seen with elevated GGT suggests a hepatic source D. When jaundice is present, an elevated ALP suggests acute hepatitis

C ALP isoenzymes can result from different genes or from modification of a common gene product in the tissues. Some differ mainly in carbohydrate content and cannot be identified by immunologic methods. Highest levels of ALP are seen in Paget's disease of bone, where ALP can be as high as 25 times the URL. GGT in serum is derived from the hepatobiliary system and is increased in alcoholic hepatitis and hepatobiliary obstruction. It is not increased in diseases of bone or in pregnancy. When the increase in GGT is twofold higher than the increase in ALP, the liver is assumed to be the source of the elevated ALP. Serum ALP is a sensitive marker for extrahepatic obstruction, which causes an increase of approximately 10 times the URL. A lesser increase is seen in intrahepatic obstruction. ALP is only mildly elevated in acute hepatitis as a result of accompanying obstruction. Harr, Robert R. Medical Laboratory Science Review (Page 276). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding transaminases is true? A. ALT is often increased in muscular disease, pancreatitis, and lymphoma B. ALT is increased in infectious mononucleosis, but AST is usually normal C. ALT is far more specific for liver diseases than is AST D. Substrate depletion seldom occurs in assays of serum from hepatitis cases

C ALT is far more specific for liver disease than AST. High ALT may result from nonhepatic causes such as AMI, muscle injury or disease, and severe hemolysis, but nonhepatic sources can be ruled out by a high direct bilirubin. Elevated ALT (e.g., >65 IU/L) is used along with immunologic tests for hepatitis to disqualify blood donors. AST is increased in muscle disease, MI, pancreatitis, and lymphoma. Both transaminases are moderately increased in infectious mononucleosis. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

What is the typical time course for plasma myoglobin following an AMI? A. Abnormal before 1 hour; peaks within 3 hours; returns to normal in 8 hours B. Abnormal within 3 hours; peaks within 6 hours; returns to normal in 18 hours C. Abnormal within 2 hours; peaks within 12 hours; returns to normal in 36 hours D. Abnormal within 6 hours; peaks within 24 hours; returns to normal in 72 hours

C After AMI, myoglobin usually rises above the cutoff within 1-2 hours, peaks within 8-12 hours and returns to normal within 36 hours. Typically, levels reach a peak concentration that is 10-fold the upper reference limit. Since myoglobin is the first marker to become abnormal after an AMI, it should be measured on admission and if negative, again 2 hours later. If both samples are below the cutoff, the probability of an AMI having occurred is low. If the myoglobin is above the cutoff, a cardiac specific marker such as TnI, or TnT must be performed at some point to confirm the diagnosis. Harr, Robert R. Medical Laboratory Science Review (Page 268). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding enzymatic reactions is true? A. The enzyme shifts the equilibrium of the reaction to the right B. The enzyme alters the equilibrium constant of the reaction C. The enzyme increases the rate of the reaction D. The enzyme alters the energy difference between reactants and products

C An enzyme will accelerate the rate of a reaction, reducing the time required to reach equilibrium. The concentration of reactants and products at equilibrium will be the same with or without the enzyme. Harr, Robert R. Medical Laboratory Science Review (Page 263). F.A. Davis Company. Kindle Edition.

Which statement best describes the clinical utility of B-type natriuretic peptide (BNP)? A. Abnormal levels may be caused by obstructive lung disease B. A positive test indicates prior myocardial damage caused by AMI that occurred within the last 3 months C. A normal test result (<100 pg/mL) helps rule out congestive heart failure in persons with symptoms associated with coronary insufficiency D. A level above 100 pg/mL is not significant if evidence of congestive heart failure is absent

C B-type natriuretic peptide is a hormone produced by the ventricles in response to increased intracardiac blood volume and hydrostatic pressure. It is formed in the heart from a precursor peptide (preproBNP) by enzymatic hydrolysis, first forming proBNP followed by BNP and NT (N-terminal) proBNP which is not physiologically active. Both BNP and NT-proBNP are increased in persons with congestive heart failure (CHF). Levels are not increased in pulmonary obstruction, hypertension, edema associated with renal insufficiency, and other conditions that cause physical limitation and symptoms that overlap CHF. At a cutoff of <100 pg/mL the BNP test is effective in ruling out CHF. Diagnostic accuracy in distinguishing CHF from nonCHF ranges from 83%-95%. In addition, persons with ischemia who have an increased BNP are at greater risk for MI. The NTpro-BNP assay is similar in clinical value, and can be used for persons being treated with nesiritide, a recombinant form of BNP used to treat CHF. Harr, Robert R. Medical Laboratory Science Review (Page 271). F.A. Davis Company. Kindle Edition.

Select the products formed from the forward reaction of ALT. A. Aspartate and alanine B. Alanine and α-ketoglutarate C. Pyruvate and glutamate D. Glutamine and NAD+

C Because glutamate is a common product for transaminases, pyruvate (a three-carbon ketoacid) and glutamate would be generated from the transamination reaction between alanine and α-ketoglutarate. Harr, Robert R. Medical Laboratory Science Review (Page 272). F.A. Davis Company. Kindle Edition.

Which of the following liver diseases produces the highest levels of transaminases? A. Hepatic cirrhosis B. Obstructive jaundice C. Hepatic cancer D. Alcoholic hepatitis

C Elevation of transaminases is greatest in acute hepatitis (20-50 × URL). Levels are moderately elevated (5-10 × URL) in hepatic cancer. They are slightly elevated (2-5 × URL) in chronic hepatitis, hepatic cirrhosis, alcoholic hepatitis, and obstructive jaundice. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

Which substance is used in the CK assay to activate the enzyme? A. Flavin adenine dinucleotide (FAD) B. Imidazole C. N-acetylcysteine D. Pyridoxyl-5´-phosphate

C In addition to Mg +2, CK requires a thiol compound to reduce interchain disulfide bridges and bind heavy metals that inactivate the enzyme. N-acetylcysteine is an activator of CK used for this purpose in the IFCC recommended method. Pyridoxyl-5´-phosphate is a prosthetic group of AST and ALT. FAD is a prosthetic group of glucose oxidase. Imidazole is used to buffer the CK reagent. Harr, Robert R. Medical Laboratory Science Review (Page 266). F.A. Davis Company. Kindle Edition.

In which condition is the LD most likely to be within normal limits? A. Hepatic carcinoma B. Pulmonary infarction C. Acute appendicitis D. Crush injury

C LD is increased slightly to moderately in most causes of liver disease. Smallest elevations are seen in obstructive jaundice and highest in hepatic carcinoma and toxic hepatitis, where levels can reach 10-fold the upper reference limit. LD is also increased in crush injury and muscular dystrophies due to skeletal muscle damage, and in pulmonary infarction owing to embolism formation. Amylase is increased in a majority of persons with acute appendicitis, but LD is not. Harr, Robert R. Medical Laboratory Science Review (Page 265). F.A. Davis Company. Kindle Edition.

Which isoenzyme of ALP migrates farthest toward the anode when electrophoresed at pH 8.6? A. Placental B. Bone C. Liver D. Intestinal

C Liver ALP isoenzymes migrate farthest toward the anode, but fast and slow variants occur. The slow liver ALP band is difficult to distinguish from placental and bone ALP. The order from cathode to anode is: - Renal→Intestinal→Bone→Placental→Liver + Improved separation of bone and liver isoenzymes can be achieved by incubating the serum with neuraminidase prior to electrophoresis. The enzyme reduces the sialic content of the bone isoenzyme, causing it to migrate at a slower rate. Harr, Robert R. Medical Laboratory Science Review (Page 275). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding amylase methods is true? A. Dilution of serum may result in lower than expected activity B. Methods generating NADH are preferred because they have higher sensitivity C. Synthetic substrates can be conjugated to p-nitrophenol (PNP) for a kinetic assay D. The reference range is consistent from method to method

C Many endogenous inhibitors of amylase, such as wheat germ, are found in serum. Diluted samples often show higher than expected activity caused by dilution of the inhibitor. Units of amylase activity vary widely depending upon the method of assay and calibration. Synthetic substrates such as maltotetrose or 4-nitrophenyl maltohepatoside can be used for kinetic assays. Maltotetrose is hydrolyzed to maltose by amylase, and the maltose hydrolyzed by α-glucosidase or maltose phosphorylase, forming glucose or glucose-1-phosphate, respectively. These can be measured by coupling to NADH-generating reactions. Antibodies to the salivary isoenzyme can be added to synthetic substrate assays to inhibit S-type amylase. Harr, Robert R. Medical Laboratory Science Review (Page 279). F.A. Davis Company. Kindle Edition.

Which of the following enzymes is usually depressed in liver disease? A. Elastase-1 B. GLD C. Pseudocholinesterase D. Aldolase

C Pseudocholinesterase is found mainly in the liver and functions to hydrolyze acetylcholine. It is depressed by organophosphate insecticides and drugs that function as cholinesterase inhibitors and the serum assay is used to presumptively identify cases of insecticide poisoning. Levels of pseudocholinesterase are decreased in patients with liver disease as a result of depressed synthesis. In cirrhosis and hepatoma, there is a 50%-70% reduction in serum level and a 30%-50% reduction in hepatitis. Elastase-1 is a pancreatic digestive enzyme that breaks down connective tissue protein. Its level in feces is reduced in persons with pancreatic insufficiency. GLD is increased in necrotic jaundice, and aldolase in necrotic jaundice and muscle disease. Harr, Robert R. Medical Laboratory Science Review (Page 280). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding the naming of transaminases is true? A. Serum glutamic oxaloacetic transaminase (SGOT) is the older abbreviation for ALT B. Serum glutamic pyruvic transaminase (SGPT) is the older abbreviation for AST C. SGPT is the older abbreviation for ALT D. SGOT is the newer abbreviation for AST

C SGOT refers to the products measured in the in vitro reaction, and is more correctly named AST for the four-carbon amino acid substrate aspartate. SGPT is the older name referring to the products of the reaction for ALT. SGPT is more correctly named ALT for the three-carbon amino acid substrate alanine. Harr, Robert R. Medical Laboratory Science Review (Page 273). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding the clinical use of CK-MB (CK-2) is true? A. CK-MB becomes elevated before myoglobin after an AMI B. CK-MB levels are usually increased in cases of cardiac ischemia C. CK-MB is more specific than myoglobin D. An elevated CK-MB is always accompanied by an elevated total CK

C Serum myoglobin becomes abnormal within 1-2 hours after an acute myocardial infarction (AMI) before troponin and CK-MB. CK-MB becomes abnormal shortly after troponin I (TnI) or troponin T (TnT) when a URL of 4 μg/L is used, and peaks at around the same time following AMI. However, cardiac troponins remain elevated significantly longer than CK-MB after AMI, are not increased in crush injuries. There is less than 5 μg/L CK-MB in the serum of healthy adults, while the total CK ranges from 10-110 U/L. Consequently, an abnormal CK-MB can occur in the absence of an elevated total CK. Harr, Robert R. Medical Laboratory Science Review (Page 267). F.A. Davis Company. Kindle Edition.

Which of the following is the most effective serial sampling time for ruling out AMI using both myoglobin and a cardiac specific marker in an emergency department environment? A. Admission and every hour for the next 3 hours or until positive B. Admission, 2 hours, 4 hours, and 6 hours or until positive C. Admission, 3 hours, 6 hours, and a final sample within 12 hours D. Admission and one sample every 8 hours for 48 hours

C Since the time between the onset of symptoms and arrival in the emergency department is often speculative, serial measurement of cardiac markers is required in order to rule out AMI. Since myoglobin is the first marker to rise after AMI, if used it should be measured on admission. Since TnI, TnT, and CK-MB are more cardiac specific, at least one should be measured starting at 3 hours postadmission, and again at 6 hours postadmission. If all results are negative to this point, a final assay should be performed 6-12 hours postadmission to conclusively rule out the possibility of AMI and evaluate the short-term risk of AMI. Harr, Robert R. Medical Laboratory Science Review (Page 269). F.A. Davis Company. Kindle Edition.

An international unit (IU) of enzyme activity is the quantity of enzyme that: A. Converts 1 μmol of substrate to product per liter B. Forms 1 mg of product per deciliter C. Converts 1 μmol of substrate to product per minute D. Forms 1 μmol of product per liter

C The IU is a rate expressed in micromoles per minute. Activity is reported as IUs per liter (IU/L) or mIU/mL. The SI unit for enzyme activity is the katal (1 katal converts 1 mol of substrate to product in 1 second). Harr, Robert R. Medical Laboratory Science Review (Page 263). F.A. Davis Company. Kindle Edition.

Which of the following buffers is used in the IFCC recommended method for ALP? A. Glycine B. Phosphate C. 2-Amino-2-methyl-1-propanol D. Citrate

C The Szasz modification of the Bowers-McComb method measures the hydrolysis of p-nitrophenyl phosphate, and continuously monitors the formation of p-nitrophenol at 405 nm. AMP buffer chelates phosphorus, preventing product inhibition; Zn +2 and Mg +2 are added to the substrate to activate ALP. HEDTA is used to chelate the excess Zn +2, which is inhibitory at high concentrations. Harr, Robert R. Medical Laboratory Science Review (Page 276). F.A. Davis Company. Kindle Edition.

The reference method for serum lipase is based upon: A. Assay of triglycerides following incubation of serum with olive oil B. Rate turbidimetry C. Titration of fatty acids with dilute NaOH following controlled incubation of serum with olive oil D. Immunochemical assay

C The reference method of Cherry and Crandall is based upon the titration of fatty acids formed by the hydrolysis of an emulsion of olive oil after incubation for 24 hours at 37°C. Because most of the activity occurs within the first 3 hours, the incubation time may be shortened to as little as 1 hour without loss of clinical utility. Harr, Robert R. Medical Laboratory Science Review (Page 279). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding total CK is true? A. Levels are unaffected by strenuous exercise B. Levels are unaffected by repeated intramuscular injections C. Highest levels are seen in Duchenne's muscular dystrophy D. The enzyme is highly specific for heart injury

C Total CK is neither sensitive nor specific for AMI. An infarct can occur without causing an elevated total CK. Exercise and intramuscular injections cause a significant increase in total CK. Crush injuries and muscular dystrophy can increase the total CK up to 50 times the URL. Harr, Robert R. Medical Laboratory Science Review (Page 267). F.A. Davis Company. Kindle Edition.

What is the typical time course for plasma TnI or TnT following an AMI? A. Abnormal within 3 hours; peaks within 12 hours; returns to normal in 24 hours B. Abnormal within 4 hours; peaks within 18 hours; returns to normal in 48 hours C. Abnormal within 4 hours; peaks within 24 hours; returns to normal in 1 week D. Abnormal within 6 hours; peaks within 36 hours; returns to normal in 5 days

C Troponin is a complex of three polypeptides that function as a regulator of actin and tropomyosin. The three subunits are designated TnC, TnI, and TnT. All are present in both cardiac and some skeletal muscles, but cardiac and skeletal isoforms of TnI and TnT can be differentiated by specific antiseras. TnI and TnT cardiac isoforms in plasma will at least double within 4-6 hours after MI, peak within 24 hours and usually remain elevated for 7-10 days. TnT and TnI have the same sensitivity, but TnT is more commonly elevated in renal failure patients. Both are increased slightly in unstable angina (chest pain while at rest) and cardiac ischemia. Harr, Robert R. Medical Laboratory Science Review (Page 268). F.A. Davis Company. Kindle Edition.

Which of the following laboratory tests is a marker for ischemic heart disease? A. CK-MB isoforms B. Myosin light chain 1 C. Albumin cobalt binding D. Free fatty acid binding protein

C When heart muscle suffers reversible damage as a result of oxygen deprivation, free radicals are released from the cells and bind to circulating albumin. The albumin is modified at the N-terminus, causing a reduced ability to bind certain metals. This ischemia-modified albumin can be measured by its inability to bind cobalt. An excess of cobalt is incubated with plasma followed by addition of dithiothreitol. The sulfhydryl compound complexes with the free cobalt, forming a colored complex. The absorbance of the reaction mixture is directly proportional to the ischemia-modified albumin concentration. In addition to ischemia-modified albumin, glycogen phosphorylase-BB is a marker for ischemia because it is released from heart muscle during an ischemic episode. Myosin light chains and fatty acid-binding protein are released from necrotic heart tissue in the early stages of AMI. Harr, Robert R. Medical Laboratory Science Review (Page 270). F.A. Davis Company. Kindle Edition.

Which of the following enzymes is considered most tissue specific? A. Creatine kinase (CK) B. Amylase C. Alkaline phosphatase (ALP) D. Alcohol dehydrogenase (ADH)

D No enzyme is truly tissue specific and diagnostic accuracy depends upon recognizing changes in plasma levels that characterize different diseases. This includes the mass or activity of enzyme released, its rise, peak, and return to normal, the isoenzyme(s) released, and the concomitant changes of other enzymes. Alanine aminotransferase and alcohol dehydrogenase are primarily increased in necrotic liver disease. Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

Which isoenzyme of ALP is most heat stable? A. Bone B. Liver C. Intestinal D. Placental

D Placental ALP and tumor-associated isoenzymes such as the Regan isoenzyme associated with lung cancer are the only isoenzymes that retain activity when serum is heated to 65° C for 10 minutes. Heat inactivation is used primarily to distinguish liver ALP from bone ALP. If less than 20% activity remains after heating serum to 56°C for 10 minutes, then bone ALP is most likely present. Harr, Robert R. Medical Laboratory Science Review (Page 275). F.A. Davis Company. Kindle Edition.

Which condition is least likely to be associated with increased serum ALP? A. Osteomalacia B. Biliary obstruction C. Hyperparathyroidism and hyperthyroidism D. Osteoporosis

D ALP is elevated in osteomalacia (rickets), bone cancer, and bone disease secondary to hyperthyroidism and hyperparathyroidism, but total ALP it is high in less than 30% of osteoporosis patients. Pancreatic disease associated with biliary obstruction, such as cancer at the head of the pancreas, is associated with elevated ALP. Harr, Robert R. Medical Laboratory Science Review (Page 276). F.A. Davis Company. Kindle Edition.

Which of the following statements regarding ALP is true? A. In normal adults, the primary tissue source is fast-twitch skeletal muscle B. Geriatric patients have a lower serum ALP than other adults C. Serum ALP levels are lower in children than in adults D. Pregnant women have a higher level of serum ALP than other adults

D ALP is higher in children than in adults due to bone growth. Children and geriatric patients have higher serum ALP due to increased bone isoenzyme. Serum ALP levels are often two- or threefold higher than the URL in the third term of pregnancy. In nonpregnant normal adults, serum ALP is derived from liver and bone. Liver, bone, placental, renal, and intestinal isoenzymes of ALP can be separated by electrophoresis, and many other ALP isoenzymes have been identified by isofocusing. Harr, Robert R. Medical Laboratory Science Review (Page 275). F.A. Davis Company. Kindle Edition.

Which of the following cardiac markers derived from neutrophils predicts an increased risk for myocardial infarction? A. Phospholipase A2 (PLA2 ) B. Glycogen phosphorylase BB (GPBB) C. Soluble CD40 ligand (sCD40l) D. Myeloperoxidase (MPO)

D All of the answer choices are markers for acute coronary syndrome and increased risk of AMI. MPO is released from neutrophils and is thought to destabilize the arterial plaque by oxidizing both LDL and HDL and reducing nitric oxide levels in the coronary arteries. Levels in the upper third quartile predict an increased risk of a coronary event even when troponin is normal. GPBB is released from myocytes early in an ischemic episode and becomes abnormal about 2 hours after an AMI. sCD40l is released from activated platelets and indicates an unstable plaque. PLA2 is produced by the arterial wall. It removes a fatty acid from phospholipids and increases the amount of oxidized LDL, leading to foam cell formation. Like hs-CRP, it is a marker for an inflamed plaque. Harr, Robert R. Medical Laboratory Science Review (Page 272). F.A. Davis Company. Kindle Edition.

Select the most sensitive marker for alcoholic liver disease. A. GLD B. ALT C. AST D.γ-Glutamyltransferase (GGT)

D Although AST and ALT are elevated in alcoholic hepatitis, GGT is a more sensitive indicator of alcoholic liver disease. Levels of GGT can reach in excess of 25 times the URL in alcoholic hepatitis. It is also markedly elevated in obstructive jaundice; a high GGT supports the inference that liver is the tissue source of an elevated ALP. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

Which of the following amylase substrates is recommended by the IFCC? A. Starch B. Maltodextrose C. Maltotetrose D. Blocked maltohepatoside

D Amylase is commonly measured using synthetic substrates. In the IFCC-recommended method, p-nitrophenyl maltohepatiside is used. One end of the polymer is covalently linked to p-nitrophenol and the other is linked to 4,6 ethylidine to prevent its hydrolysis by α-glucosidase. Amylase hydrolyzes the substrate from both ends producing fragments of 2, 3, and 4 glucose subunits. α-Glucosidase hydrolyzes the subunits containing p-nitrophenyl groups, forming glucose and p-nitrophenol. The increase absorbance at 405 nm is proportional to amylase activity. Harr, Robert R. Medical Laboratory Science Review (Page 277). F.A. Davis Company. Kindle Edition.

Which statement about enzymes is true? A. An enzyme alters the Gibb's free energy of the reaction B. Enzymes cause a reaction with a positive free energy to occur spontaneously C. An enzyme's natural substrate has the highest K m D. A competitive inhibitor will alter the apparent K m of the reaction

D Enzymes alter the energy of activation by forming a metastable intermediate, the enzyme substrate complex. Enzymes do not alter the free energy or direction of a reaction. Competitive inhibitors bind to the active site where the enzyme binds substrate and are overcome by increasing the substrate concentration. Harr, Robert R. Medical Laboratory Science Review (Page 263). F.A. Davis Company. Kindle Edition.

Which enzyme is least useful in differentiating necrotic from obstructive jaundice? A. GGT B. ALT C. 5' Nucleotidase D. LD

D GGT and 5´ nucleotidase are markedly elevated in both intra- and posthepatic obstruction. ALT is slightly elevated in obstructive jaundice but is markedly elevated in necrotic jaundice. Although LD is usually greater in necrotic jaundice than in obstructive jaundice, elevations in these conditions overlap frequently and result from many other causes. Harr, Robert R. Medical Laboratory Science Review (Page 274). F.A. Davis Company. Kindle Edition.

A serum ALP level greater than twice the elevation of GGT suggests: A. Misidentification of the specimen B. Focal intrahepatic obstruction C. Acute alcoholic hepatitis D. Bone disease or malignancy

D In obstructive jaundice, GGT is elevated more than ALP. A disproportionate increase in ALP points to a nonhepatic source of ALP, often bone disease. GGT is the most sensitive marker of acute alcoholic hepatitis, rising about fivefold higher than ALP or transaminases. Harr, Robert R. Medical Laboratory Science Review (Page 277). F.A. Davis Company. Kindle Edition.

Which test becomes abnormal in the earliest stage of the acute coronary syndrome? A. Myosin light chain 1 B. CK-MB isoforms C. Myoglobin D. High-sensitivity C-reactive protein

D The acute coronary syndrome (ACS) refers to the evolution of coronary artery events that lead up to AMI. Coronary artery disease (CAD) begins with formation of a plaque comprised of lipid from dead endothelium that proliferates into the artery lumen. The plaque becomes disrupted and the vessel wall inflamed in the asymptomatic stage of CAD. If platelet activation occurs and results in thrombosis, blood flow becomes significantly reduced, resulting in angina. This signals the transition to more advanced disease in which ischemia to heart muscle occurs and eventually to AMI. Myoglobin and CK-MB isoforms are not increased until the end stage of ACS. High-sensitivity C-reactive protein (hs-CRP) is an ultrasensitive CRP assay that accurately measures CRP below 1 mg/L. CRP is an acute-phase protein increased in inflammation. Levels of CRP between 3.2-10 mg/L signal low-grade inflammation, which occurs in the asymptomatic phase of ACS. Such inflammation occurs when coronary artery plaques become disrupted, and therefore, persons with CAD who have a mildly increased CRP are at high risk of disease progression. Glycogen phosphorylase-BB and albumin cobalt binding are increased by ischemia. Troponins are increased when there is unstable angina and ischemic injury, and indicate an increased risk for AMI. Harr, Robert R. Medical Laboratory Science Review (Page 271). F.A. Davis Company. Kindle Edition.

The increase in the level of serum enzymes used to detect cholestatic liver disease is caused mainly by: A. Enzyme release from dead cells B. Leakage from cells with altered membrane permeability C. Decreased perfusion of the tissue D. Increased production and secretion by cells

D The amount of enzyme in the serum can be increased by necrosis, altered permeability, secretion, or synthesis. It is also dependent upon tissue perfusion, enzyme half-life, molecular size, and location of the enzyme within the cell. Most enzymes are liberated by necrosis, but a few, such as ALP and γ-glutamyltransferase, are produced and secreted at a greater rate in obstructive liver disease. Harr, Robert R. Medical Laboratory Science Review (Page 264). F.A. Davis Company. Kindle Edition.

The LD pleural fluid:serum ratio for a transudative fluid is usually: A. 3:1 or higher B. 2:1 C. 1:1 D. 1:2 or less

D The lactate dehydrogenase activity of body fluids is normally less than serum, and a fluid to serum LD ratio greater than 1:2 is highly suggestive of an exudative process. Elevated lactate dehydrogenase in chest fluid is often caused by lung malignancy, metastatic carcinoma, Hodgkin's disease, and leukemia. Harr, Robert R. Medical Laboratory Science Review (Page 265). F.A. Davis Company. Kindle Edition.

A patient has a plasma myoglobin of 10 μg/L at admission. Three hours later, the myoglobin is 14 μg/L and the troponin I is 0.02 μg/L (reference range 0-0.03 μg/L). These results are consistent with which condition? A. Skeletal muscle injury B. Acute myocardial infarction C. Unstable angina D. No evidence of myocardial or skeletal muscle injury

D This person displays very low plasma myoglobin (reference range for females is approximately 17-75 μg/L). The TnI result is also within normal limits. These results are consistent with baseline levels and no evidence of cardiac or skeletal muscle injury. TnI cutpoints for diagnosis of AMI are dependent upon the method, and may be higher than the upper limit of normal. Troponin results above the upper reference limit but below the cutpoint for AMI indicate myocardial injury and increased risk for AMI. Harr, Robert R. Medical Laboratory Science Review (Page 269). F.A. Davis Company. Kindle Edition.