6.6 Enzymes and Cardiac Markers

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 URI in acute viral and toxic hepatitis. Both transaminases are moderately increased (5-10 x URL) in infectious mononucleosis, diffuse intrahepatic obstruction, lymphoma, and cancer of the liver, and slightly increased (2-5 x URL) in cirrhosis and extrahepatic obstruction.

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 fullenzyme activity. A prosthetic group is a coenzyme that is tightly bound to the apoenzyme and is required for activity. Cofactors are inorganic or molecules needed for full catalytic activity atoms Pyridoxyl-5-phosphate (P-5"-P) is a prosthetic group for ALT and AST. Consequently, patients with low levels (vitamin Bg deficiency) may have reduced transaminase activity in vitro. Enzymes can have diverse pH (and temperature) optima

Which of the following measurement modes does not allow for continuous monitoring of enzyme activity? 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.

Which substrate concentration is needed to achieve zero-order conditions? A. Greater than 99 x K B. [S] = Km C. Less than 10 x Km D. [S] = 0

A A zero-order reaction rate is independent of substrate concentration because there is sufficient substrate to saturate the enzyme. V= Vmax X[S/Km + (S) where V= velocity, Vmax = maximum velocity, [S] = substrate concentration, and Km = substrate concentration required to give 1/2 Vmax If (S] >>> Km then the Km can be ignored. V= Vmar X[S/IS) = VmaxX[S]° or velocity approaches maximum and is independent of substrate concentration. When [S] is 10x K velocity will be greater than 90% of Vmar

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 cirrhosis of the liver,

Which definition best describes the catalytic activity of amylase? A. Hydrolyzes second a-1-4 glycosidic linkages B. Hydrolyzes all polyglucans completely to of starch, glycogen, and other polyglucans produce glucose C. Oxidatively degrades polysaccharides containing glucose D. Splits polysaccharides and disaccharides by addition of water

A Amylase in hunans is a hydrolase that splits the second a-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, and P-type amylase in plasma can be measured by immunoinhibition of S-type. 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.

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. Three bone isoforms of ALP can be detected in serum.

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.

SITUATION: An EDTA sample for cTnl assay gives a result of 40 ng/L (reference range 0-13 ng/L). The test is repeated 30 minutes later on a new specimen, and the result is 4 ng/L. A third sample collected 1 hour later gives a result of 5 ng/L. What is the most likely explanation? A false-positive result occurred as a result of matrix interference B. Heparin should have been used instead of EDTA, which causes false-positive results C. The patient has suffered a heart attack D. The patient has had an ischemic episode without cardiac injury

A EDTA is the additive of choice for troponin assays because it avoids microclots that can lead to false- positive results when serum or heparinized plasma is used. False-positive results caused by matrix effects usually revert to normal when the test is repeated on a new sample, An AMI will cause cTnl to increase in serial tests. Although cTnl can be high as a result of cardiac injury and noncardiac conditions, such as chronic kidney disease, the level should remain elevated in samples taken so closely together.

What is the typical time course for high-sensitivity (guideline compliant) cardiac troponin I (cTnl) or cardiac troponin T (CTNT) following an AMI? A. Abnormal within 1 hour; peak within 24 hours; return to normal in 7 to 10 days B. Abnormal within 4 hours; peak within 18 hours; return to normal in 48 hours C. Abnormal within 4 hours; peak within 24 hours: return to normal in 3 days D. Abnormal within 6 hours; peak within 36 hours: return to normal in 5 days

A High-sensitivity cTnl and CTNT exceed the 99th percentile of a healthy population within 1 hour after a heart attack and remain elevated for about 1 week. Some triage protocols use this to rule out MI within 1 hour of arrival at the ED in patients wie symptoms of angina, However, a rise and fall ofr sea measurements must be documented to establisno diagnosis of MI when the test exceeds the URL established for the assay.

Which statement about the clinical utility of plasma or serum lipase is true? A. Lipase is not increased in mumps, breast cancer, 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 x 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.

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 x URL), only slightly elevated in cirrhosis (2-3 x URL) and not significantly elevated in alcoholic liver disease.

Which of the following statements about enzymatic reactions is true? A. NADH has absorbance maxima 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 k produced or consumed. This rate will be propotional 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.

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 troponin I (Tnl) D. A more modest increase in total CK than CK-MB

A Plasma CK-MB becomes abnormal 4 hours post infarction, peaks in 16 to 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. Tnl and troponin T (TnT) are cardiac- specific markers. They become elevated before CK-MB even when a CK-MB URL of 4 ug/L is used, remain elevated for 7 to 10 days after 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.

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.

Which of the following conditions will interfere with the measurement of LD? A. Slight hemolysis during sample collection B. Storage at 4°C for 3 days C. Storage at room temperature for 16 hours D. Use of plasma collected in heparin

A RBCS are rich in LD-1 and LD-2, and even slight hemolysis will falsely elevate results. Hemolytic, megaloblastic, and pernicious anemias are associated with LD levels of 10 to 50 times the URL, LD is stable 2 days at room temperature or 1 week at 4"C: however, freezing causes deterioration of LD-5. The activity of LD is inhibited by EDTA, which binds divalent cations; serum or heparinized plasma should be used.

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

A Serum LD levels are highest in pernicious anemia, reaching 10 to 50 times the upper reference limit (URL) as a result of intramedullary hemolysis. Moderate elevations (5-10 x URL) usually are seen in acute myocardial infarction (AMI), necrotic liver disease, and muscular dystrophy. Slight increases (2-3 x URL) are sometimes seen in obstructive liver disease.

In the Oliver-Rosalki method, the reverse reaction is used to measure CK activity. The enzyme(s) used in the coupling reactions is (are): A. Hexokinase and G-6-PD B. Pyruvate kinase and LD C. Luciferase D. Adenylate kinase

A The Oliver-Rosalki method for CK is based upon the formation of ATP from creatine phosphate. Hexokinase (HK) catalyzes the phosphorylation of glucose by ATP. This produces glucose-6-PO, and adenosine diphosphate (ADP). Glucose-6-PO, is oxidized to 6-phosphogluconate as NADP+ is reduced to NADPH.

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

In which condition would an elevated serum ALP 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 (TALT) from obstructive jaundice (T ALP). ALP is also increased in several bone diseases. Large increases are seen in Paget 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, ALP is a tumor marker. In most cases, the ALP 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 disease may cause an elevated leukocyte or bone- derived ALP,

In the Oliver-Rosalki method for CK, AMP is added to the substrate to: A. Inhibit adenylate kinase B. Block the oxidation of glutathione C. Increase the amount of ADP that is available D. Block the action of diadenosine pentaphosphate

A Positive interference in the Oliver-Rosalki method can Occur when adenylate kinase is present in the serum from hemolysis or damaged tissue. Adenylate kinase hydrolyzes ADP, forming adenosine monophosphate (AMP) and ATP (2 ADP --> AMP + ATP), This reaction is inhibited by adding AMP and diadenosine pentaphosphate (Ap,A) to the substrate.

Which statement best describes the clinical significance of a single cTnl or CTNT result that is slightly above the limit of detection? A. A positive test in the absence of laboratory error is diagnostic of MI B. A positive test in the absence of laboratory error or in vitro false positive result indicates cardiac injury C. Serial increases indicate necrosis caused by plaque rupture or thrombosis D. Serial increases indicate S-T segment elevated myocardial infarction (STEMI)

B A true-positive Tnl or TnT result at a low level is diagnostic of cardiac damage but not necessarily MI. The diagnosis of MI requires demonstration of a rise and subsequent fall in serial measurements and clinical signs of ischemic heart disease. Cardiac troponins can be increased in the absence of necrosis when heart muscle cell membrane permeability increases. Static increases can occur in chronic kidney disease, congestive heart failure, left ventricular hypertrophy, pulmonary embolism myocarditis, rhabdomyolysis involving the heart, and unstable angina. Cardiac troponins cannot differentiate between STEMIl and non-S-T segment elevated myocardial infarction (NSTEMI).

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 2-oxogluterate (a-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 2-oxogluterate (a-ketoglutarate), forming pyruvate. AST catalyzes the transfer of an amino group from aspartate (four carbonsi to 2-oxogluterate, 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.

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.

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

B AST forms oxaloacetate and glutamate from aspartate and 2-oxogluterate (a-ketoglutarate). Both transaminases use 2-oxogluterate and glutamate as common substrate and product pair. Both aspartate and alanine can be used to generate glutamate in the CNS, where it acts as a neurotransmitter.

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 LP reaction is more popular because it produces a positive rate (generates NADH), is not subject to product inhibition, and is highly linear. The optimal pH for the forward reaction is approximately 8.8.

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 pancreara and can be increased in several nonpancreatic conditions. Lipase adds both sensitivity and specificity to the diagnosis of acute pancreatitis. Plasma or senm 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 5096. Patients with chronic disease have pancreatic insufficiency giving rise to fatty stools, and decreased pancreatic digestive enzymes such as trypsin, chymotrypsin, and elastin.

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. Over-range samples are diluted in deionized water

B Chloride and Ca+ 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 methodos measure the production n of of glucose, while amyloclastic methods measure the degradation of starch. Starch is a polymer of a-D glucose subunits linked together by both a 1-4 and a 1-6 glycosidic bonds. Different lots may have more or less branching owing to the number of a 1-6 bonds. Since amylase hydrolyzes at the a 1-4 sites only, the amount of product measured is influenced by the extent of branching.

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

B Enzymes are identified by a numeric system called the EC (Enzyme refers to the class of the enzyme. There are six classe Commission) number. The first numbe in order, these are oxidoreductases, transferases hydrolases, lyases, isomerases, and ligases. kinases and transaminases are transferases. CK B Dehydrogenases are oxidoreductases, whereas EC number 2.7.3.2, which distinguishes it from o kinases,

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

B G-6-PD deficiency is the most common inherited RBC enzyme deficiency and is X linked. The enzyme is measured on a whole-blood hemolysate using glucose-6-PO, 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 haptoqlobin is reduced in severe cases.

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 acit well as the dimers formed when two homocysteiner are linked by a disulfide bond (homocystine) or homocysteine joins to cysteine. Plasma levels are measured as an independent risk factor for coronary artery disease. High levels of homocysteine are toxic to vascular endothelium and promote inflammationn an plaque formation. Plasma levels are independent of in and other cholesterol fractions and help explain why approximately 35% of people with first-time AMI have LDL cholesterol levels less than 130 mg/dL. Increased plasma homocysteine occurs when there is a block in the conversion of methionine to cysteine. This can occur in homocystinuria, or deficiency of vitamins B, B,, or folic acid.

Which of the following enzymes is activated by calcium ions? А. СК 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 analyss The substrate must also contain anions required (e.g. C for amylase) and should not contain inhibiting cations or anions (e.g. Zn+2 and Mn+2 for CK):

Which statement best describes the clinical utility of plasma or serum myoglobin? A. Levels greater than 100 ug/L are diagnostic of AMI B. Levels below 100 ug/L on admission and 2 to 4 hours after admission help exclude a diagnosis of AMI C. Myoglobin peaks after the cardiac troponins but is more sensitive D. The persistence of myoglobin greater than 110 ug/L for 3 days after 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 ug/L for males and 75 ug/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 greater than 110 ug/L). However, specificity is approximately 75% to 85% as a result of skeletal muscle injury or renal insufficiency. For this reason, a plasma myoglobin below the cutoff on admission. and within the first 3 hours after chest pain helps rule out AMI, A value above the cutoff must be confirmed using a cardiac-specific assay, such as Tnl or TnT.

What is the purpose of LD in the 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.

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

B Persons with unstable angina (angina at rest) who have an elevated cTnT or cTnl are at eight times greater risk of having an MI within the next 6 months. This property is used to identify patients who have short-term risk and should be considered for coronary angioplasty. The reference range for cTnT is very low (approximately 0-14 ng/L) but differs with the assay used, gender, and age. Persons with unstable angina and a positive cardiac troponin test result are likely to have a cTnT or cTnl near the cutoff. CK-MB and myoglobin have not been useful in the risk assessment of unstable angina.

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 (IFC) recommended method employs 2-amino-2-methyl-1-propanol, a buffer that binds P.

How soon following acute abdominal pain due to pancreatitis is the serum amylase expected to peak? 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

A patient's CK-MB isoenzyme concentration is reported as 18 ug/L and the total CK as 560 IU/L. What is the CK relative index (CKI)? A. 0.10% B. 3.2% C. 10.0% D. 30.0%

B The CKI is an expression of the portion of the total CK that is attributed to CK-MB. The reference range is 0% to 2.5%. Values above 2.5% point to an increase in CK-MB from cardiac muscle.

In which condition is the measurement of acid phosphatase clinically useful? A. Measuring the prostatic isoenzyme to screen for prostate cancer B. Measuring the enzyme in a vaginal swab extract C. The diagnosis of hemolytic anemia D. As a marker for bone regeneration

B The PSA test is clinically more sensitive than prostatic acid phosphatase in detecting prostatic cancer. The clinical use of prostatic acid phosphatase is confined to the investigation of sexual assault. Acid phosphatase activity greater than 50 IU/L establishes the presence of seminal fluid in the vaginal sample. Tartrate-resistant acid phosphatase is used as a cytochemical marker for hairy-cell leukemia, and may be measured in serum to identify diseases with increased osteoclast activity. particularly malignancies involving bone.

What protocol is needed to rule out an MI with a high-sensitivity troponin assay? A. A single sample at arrival and 30 minutes later B. Serial samples for up to 3 hours after arrival C. Serial samples for up to 6 hours after arrival D. A minimum of four samples over 4 hours

B The high-sensitivity cTnl and cTnT tests obviate the need for either myoglobin or CK-MB to rule out an AMI, Evidence-based protocols have shown that these tests have at least a 999% negative predictive value for ruling out AMIS at 3 hours after arrival at the hospital by using a críterion of less than 14 ng/L when there is no significant change in serial measurements during that time. A single sample protocol using a cutoff of 6 ng/L has also been shown to have a negative predictive value greater than 99%. However, this protocol is associated with more false-positive results, which are eliminated by serial testing. Assays that do not meet high sensitivity criteria but have a CV in the 10% to 20% range are still clinically acceptable but require serial testing over 6 hours to conclusively rule out AMI.

Select the coupling enzyme used in the AST reaction of Henry. A. LD B. Malate dehydrogenase (MD) C. GLD D. G-6-PD

B The method of Henry for AST uses malate dehydrogenase (MD) to reduce oxaloacetate to malate. The electrons come from NADH forming NAD+.

A patient has a plasma cTnT of 10 ng/L at admission. One hour later, the CTNT is 34 ng/L, and 3 hours later 120 ng/L. Electrocardiography (ECG) showed no change over this time. 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

B These results are consistent with a type 2 heart attack These are characterized by a serial rise in cardiac troponin with clinical signs of ischemia but the absence of typical ECG changes, such as S-T segment elevation or O-wave.

Which statement best describes cardiac troponin I and T? A. An enzyme embedded in the endocardium released after MI B. Two polypeptides that regulate the sliding of contractile proteins in cardiac muscle C. A peptide that is released in response to ventricular stretching D. A prohormone released from the pericardium in response to injury

B Troponin is a complex of three polypeptides that function as a regulator of actin and tropomyosin, The three subunits are designated TnC, Tnl, and TnT. All are present in both cardiac and some skeletal muscles, but cardiac and skeletal isoforms of Tnl and TnT can be differentiated by specific antisera.cTnl and cTnT (cardiac isoforms) are not detectable in the plasma of 50% of healthy persons and are at near zero concentration in the remaining 50%. They can be detected within 1 hour after MI, peak within 24 hours, and usually remain elevated for 7 to 10 days. CTNT and cTnl have the same sensitivity and specificity. Both are elevated in chronic kidney disease, unstable angina (chest pain while at rest), and cardiac ischemia.

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.

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

D The LD activity of body fluids is normally less than half that of serum, and a fluid:serum LD ratio greater than 1:2 is highly suggestive of an exudative process. Elevated LD in chest fluid is often caused by lung malignancy, metastatic carcinoma, Hodgkin disease, and leukemia.

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.

76. In which condition would amylase but not lipase be elevated? A. Pancreatic cancer B. Peptic ulcer C. Macroamylasemia D. Renal failure

C Approximately 196-2% of older adults have elevated plasma amylase due to macroamylasemia. This is an elevated blood amylase caused by formation of a complex between IgG and amylase. The aggregated molecule is too large to pass through the glomerulus resulting in a high plasma amylase. Lipase and urinary amylase are within normal limits, and there is no pathology associated with macroamylasemia.

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-Nucieotidase is increased primarily in obstructive liver disease and liver cancer. When elevated along with ALP, It identifies the liver as the source of ALP GLD is increased in necrotic liver diseases along wit transaminases, but because of its distribution it is elevated to a greater extent in toxic hepatitis and therefore is useful as a (anesthesia) toxicity. marker for halothane Aldolase is found in all tissues including MI, V and is increased in many conditions hepatitis, and myelocytic leukemia. the greatest increase is seen wasting disease such as muscular dystrophies. in skeletal muscle- However, like CN

What requirements must be met for a troponin assay to be considered a high-sensitivity test? A. Must have a detection limit of 30 ng/L B. Must be able to give a value for 100% of the healthy population who have a concentration above the limit of detection C. Must have a coefficient of variation (CV) of less than 10% at the 99th percentile of the healthy population D. Must have a clinical specificity of 99% or greater

C A troponin test qualifies as high sensitivity (guideline compliant) if it has a CV less than 10% at the 99th percentile of healthy persons, and gives a measurable result in at least 50% of the healthy population who have a troponin concentration above the limit of detection (LOD). The 99th percentile is method dependent but for a high-sensitivity assay is approximately13 ng/L (0.013 ng/mL).

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 rissues, Some differ mainly in carbohydrate content and cannot be identified by immunologic methodk Highest levels of ALP are seen in Paget disease of bone, where ALP can be as high as 25 times the LIR GGT in serum is derived from the hepatobiliary System and is increased in alcoholic hepatitis, hepatobiliary obstruction, and hepatic cancer. 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.

Which condition is associated with a decrease in ALP activity? A. Pregnancy B. VDDR C. Hypophosphatasia D. Bone fracture

C ALP must be evaluated with age- and gender-specific reference ranges. Hypophosphatasia is a rare genetic disease caused by a mutation in the TNSALP gene causing diminished expression of tissue nonspecific ALP. Substrates such as pyridoxyl-5'-phosphate, pyrophosphate (diphosphate salts), and phosphoethanolamine accumulate in blood and tissues Bone mineralization is blocked and both calcium and phosphorus are elevated in plasma. Bone, muscle, and vital organs are affected and the mortality rate is very high. The diagnosis is suspected when ALP is low and vitamin B, is high, but can be missed if adult reference ranges for ALP are used.

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 persons with hepatitis

C ALTI 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, Elevation of ALT occurs early in hepatitis B; therefore, elevated ALT (e.g., greater than 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.

Which statement best describes the clinical utility of BNP? A. Abnormal levels may be caused by obstructive lung disease B. A positive test result indicates prior myocardial damage caused by AMI that occurred within the last 3 months C. A normal test result (less than 100 pg/mL) helps rule out CHF in persons with symptoms associated with coronary insufficiency D. A level greater than 100 pg/mL is not significant if evidence of CHF 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 that is not physiologically active. Both BNP and NT-proBNP are increased.in persons with CHF. Levels are notG 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 less than 100 pg/ml the BNP test is effective in ruling out CHF. Diagnostic accuracy in distinguishing CHF from non- CHF ranges from 83% to 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.

Select the products formed from the forward reaction for measurement of ALT, A. Aspartate and alanine B. Alanine and a-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 2-oxogluterate.

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 (20-50x URL). Levels are moderately elevated (5-10x URL) in hepatic cancer. They are slightly elevated (2-5 x URL) in chronic hepatitis, hepatic cirrhosis, alcoholic hepatitis, and obstructive jaundice.

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.

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 types 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 URL. LD is also increased in crush injury and muscular dystrophies as a result of skeletal muscle damage, and in pulmonary infarction resulting from embolism formation. Amylase is increased in a majority of persons with acute appendicitis, but LD is not.

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 ALP. The order from cathode to anode is: - Renallntestinal-BonePlacental-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 acid content of the bone isoenzyme, causing it to migrate at a slower rate.

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 a-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.

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.

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.

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-nitropheny phosphate, and continuously monitors the formation of p-nitrophenol at 405 nm. AMP buffer chelates phosphorus, preventing product inhibition; Zn and Mg+2 are added to the substrate to activate AL HEDTA is used to chelate the excess Znt2, which is inhibitory at high concentrations.

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

C The international unit is a rate expressed in micromoles per minute. Activity is reported as international units per liter (IU/L) or milli-international units per milliliter (miU/mL). The Sl unit for enzyme activity is katal (1 katal converts 1 mole of substrate to product in 1 second).

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 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

SITUATION: A specimen for CK performed on an automated analyzer using an optimized Oliver- Rosalki method gives an error flag indicating substrate depletion. The sample is diluted 1:2 and 1:4 by the serial dilution technique and reassayed. After correcting for the dilution, the results are as follows: 1:2 Dilution = 3,000 IU/L 1:4 Dilution = 3,600 IU/L Dilutions are made a second time and assayed again but give identical results. What is the most likely explanation? A. The serum became contaminated prior to making the 1:4 dilution B. The wrong pipet was used to make one of the dilutions C. An endogenous competitive inhibitor is present in the serum D. An error has been made in calculating the enzyme activity of one of the two dilutions

C When a competitive inhibitor is present in serum, a dilution of the sample will cause an increase in the reaction rate by reducing the concentration of the inhibitor. Dilution of serum frequently increases the activity of CK and amylase. The same effect will occur when a smaller volume of serum is used in the assay because less inhibitor will be present in the reaction mixture.

Which of the following laboratory tests is a marker for ischemic heart disease? A. Oxidized LDL B. F2 isoprostanes C. Albumin cobalt binding D. Free fatty acid binding protein

C When the heart muscle suffers reversible damage as à result of oxygen deprivation, free radicals are released from the cells and bind to circulating albumin, 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 (GP-BB)is marker for ischemia because it is released from heart muscle during an ischemic episode. Oxidized LDL and F2 isoprostanes are markers for risk of progression to ACS and thus are markers for early stage atherosclerotic disease.

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

Which of the following enzymes is considered most tissue specific? А. СК B. Amylase C. ALP D. ADH

D No enzyme is truly tissue specific and diagnostic accuracy depends on 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 isoenzymels) released, and the concomitant changes of other enzymes. ALT and ADH are primarily increased in necrotic liver disease.

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 Age- and gender-specific reference intervals should be used when evaluating ALP levels. 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.

Which of the following cardiac markers is derived from neutrophils and predicts an increased risk for MI? A. Lipoprotein-associated phospholipase A, (Lp-PLA,) B. Glycogen phosphorylase-BB (GP-BB) C. Cystatin C 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. CystatinC is a serine protease found in all nucleated cells that is a marker for early stage glomerular disease. Both high plasma cystatin Cand microalbuminuria double the risk of AMI since persons with renal impairment are at higher risk for CVD. Lp-PLA, 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.

SITUATION: A single heparinized plasma sample measured for troponin was found to have a concentration exceeding the laboratory's upper reportable limit. However, the patient had a normal ECG result and was stable without showing any classic signs of MI and had no history of arteriosclerotic cardiovascular disease. What is the most likely cause? A. Chronic renal failure B. Recent angioplasty C. Non-transmural MI D. False positive troponin

D Although chronic kidney disease, recent angioplast and non-transmural MI (necrosis involving only part of the heart wall) can cause a positive cTnl result they would not cause a level that exceeds the reportable range of the assay. False-positive troponins have been caused by heterophile antibodies; microfibrin clots in the sample; autoantibodies, such as rheumatoid factor, immune complexes, microparticles; and a markedly increased ALP. The other likely cause would be sample misidentification.

The most commonly employed method of assay for plasma or serum lipase is based on: A. Hydrolysis of olive oil B. Rate turbidimetry C. Immunoassay D. Peroxidase coupling

D Although olive oil is the natural and most specifi substrate for lipase, the most commonly used method for lipase assay is based upon the hydrolysis of a synthetic diglyceride substrate yielding 2-monoglyceride. This is hydrolyzed and forms glycerol, which is phosphorylated and forms glycerol-3-phosphate. This is oxidized by glycerophosphate oxidase, yielding H,0,

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 polymer is covalently linked to p-nitrophenol and the other is linked to 4,6 ethylidine (EPS) to prevent its hydrolysis by a-glucosidase. Amylase hydrolyzes the substrate from both ends producing fragments of 2, 3, and 4 glucose subunits. a-Glucosidase hydrolyzes the subunits containing p-nitrophenyl groups, forming glucose and p-nitrophenol. The increase absorbance at 405 nm is proportional to amylase activity.

SITUATION: A physician calls to request a CK on a sample already sent to the laboratory for coagulation studies. The sample is 2-hour-old citrated blood and has been stored at 4°C. The plasma shows very slight hemolysis. What is the best course of action and the reason for it? A. Perform the CK assay on the sample because no interferent is present B. Reject the sample because it is slightly hemolyzed C. Reject the sample because it has been stored too long D. Reject the sample because the citrate will interfere

D CK activity is lost with excessive storage, the most labile isoenzyme being CK-1. However, CK in serum is to 1 week at 4°C, provided that an optimized method stable at room temperature for about 4 hours and up is used. Slight hemolysis does not interfere because CK is absent from RBCS. More significant hemolysis may cause positive interference by contributing ATP, glucose-6-PO, and adenylate kinase to the serum. Calcium chelators remove magnesium as well as calcium and should not be used.

Which statement about enzymes is true? A. An enzyme alters the Gibbs 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 Km D. A competitive inhibitor will alter the apparent Km 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.

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.

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.

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 on tissue perfusion, enzyme half-life, molecular size, and location of the enzyme within the cell. Most enzymes are liberated by necrosis, but a few are produced and secreted at a greater rate, such as ALP and y-glutamyltransferase in obstructive liver disease.

Which test becomes abnormal earliest in the progression of ACS? A Proprotein convertase subtilisin/kexin type 9 (PCSK9) B. B-type natriuretic peptide (BNP) C. Myoglobin D. High-sensitivity CRP

D The term acute coronary syndrome (ACS) refers to the evolution of cardiac ischemia (unstable angina, NSTEMI, and ultimately STEMI). CAD begins with formation of a plaque comprising lipid from dead endothelium that proliferated 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. High-sensitivity C-reactive protein (hs-CRP) is an ultrasensitive CRP assay that accurately measures CRP levels less than 1 mg/L. CRP is an acute-phase protein increased in inflammation. Levels of CRP between 3.2 and 10 mg/L signal low-grade inflammation, which occurs in the asymptomatic phase of arteriosclerotic disease. Such inflammation occurs when coronary artery plaques become disrupted, and therefore, persons with CAD who have mildly increased CRP are at high risk of disease progression.

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

D YAlthough 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.