Tin's Chem I Set 18,22,33,24,36,3,4,8,19,14,23,9,21,35,24,36,20,26,27,28,29,20 (for Final)

Select the order of mobility of lipoproteins electrophoresed on cellulose acetate or agarose at pH 8.6.

A. - Chylomicrons→pre-β →β→α+

B. - β→pre-β→α→chylomicrons +

C. - Chylomicrons →β→pre-β→α +

D. - α→β→pre-β→chylomicrons +

C. - Chylomicrons →β→pre-β→α +

The protein composition of HDL is what percentage by weight?

A. Less than 2%

B. 25%

C. 50%

D. 90%

C. 50%

Which apoprotein is inversely related to risk of coronary heart disease?

A. Apoprotein A-I

B. Apoprotein B100

C. Apoprotein C-II

D. Apoprotein E4

A. Apoprotein A-I

Which of the following statements is correct?

A. Both HDL and LDL are homogenous

B. There are several subfractions of LDL but not HDL C. There are several subfractions of HDL but not LDL D. There are several subfractions of both HDL and LDL

D. There are several subfractions of both HDL and LDL

The presence of C-reactive protein in the blood is an indication of:

a. a recent steptococcal infection

b. recovery from a pneumococcal infection

c. an inflammatory process

d. a state of hypersensitivity

c. an inflammatory process

1. In uncontrolled diabetes mellitus, excess ketones are present in the blood and urine because of:

a. decreased lipid formation.

b. increased glycolysis.

c. increased breakdown of lipids (lipolysis).

d. increased glucose uptake into cells.

ANS: C

In uncontrolled diabetes, the low insulin concentration result in increased lipolysis and decreased reesterification, thereby increasing plasma free fatty acids. In addition, the increased glucagon/insulin ratio enhances fatty acid oxidation in the liver. Increased counter-regulatory hormones also augment lipolysis and ketogenesis in fat and liver, respectively. Thus increased hepatic ketone production and decreased peripheral tissue metabolism lead to acetoacetate accumulation in the blood.

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4. Glycated hemoglobins are formed by the addition of glucose to the ___-terminal _____ residue.

a. C; valine

b. N; valine

c. C; alanine

d. N; alanine

ANS: B

Hb A1c is formed by the condensation of glucose with the N-terminal valine residue of either β-chain of Hb A to form an unstable Schiff base.

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6. The role of the clinical laboratory in diagnosis of diabetes mellitus involves initial diagnostic criteria. For many years, the only diagnostic criterion required was demonstration of hyperglycemia in two or more fasting plasma glucose tests. What other laboratory analysis is now considered to be useful as a diagnostic criterion?

a. Demonstration of impaired glucose tolerance in the OGTT

b. Consistent hyperglycemia after a 72-hour fast

c. Presence of ketones in urine on more than one occasion

d. Demonstration of elevated hemoglobin A1c

ANS: D

Several influential clinical organizations now include hemoglobin A1c (Hb A1c), which reflects long-term blood glucose concentrations, as a diagnostic criterion for diabetes. This analysis is particularly useful in the diagnosis of type 2 diabetes when hyperglycemia often is not severe enough for an individual to notice symptoms of diabetes.

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7. The syndrome that is considered a collection of associated clinical and laboratory findings that include insulin resistance, hyperinsulinemia, obesity, high triglyceride and low high-density lipoprotein (HDL) cholesterol, and hypertension is the:

a. glucotoxic syndrome.

b. type 1A diabetes mellitus syndrome.

c. glucose counter-regulatory syndrome.

d. insulin resistance syndrome.

ANS: D

The insulin resistance syndrome (also known as syndrome X, or the metabolic syndrome) is a constellation of associated clinical and laboratory findings, consisting of insulin resistance, hyperinsulinemia, obesity, dyslipidemia (high triglyceride and low high-density lipoprotein [HDL] cholesterol), and hypertension. Individuals with this syndrome are at increased risk for cardiovascular disease.

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Which of the following serum constituents is unstable if a blood specimen is left standing at room temperature for 8 hours before processing?

A. cholesterol

B. triglyceride

C. creatinine

D. glucose

D

A mother brings her obese, 4-year-old child who is a known type 1 diabetic to the laboratory for a blood workup. She states that the boy has been fasting for the past 12 hours. After centrifugation the tech notes that the serum looks turbid. The specimen had the following results: blood glucose = 150 mg/dL, total cholesterol = 250 mg/dL, HDL cholesterol = 32 mg/dL, triglyceride = 395 mg/dL. What best explains these findings? The boy...

A. Is a low risk for coronary artery disease

B. Is a good candidate for a 3-hour oral glucose tolerance test

C. Has secondary hyperlipidemia due to the diabetes

D. Was not fasting when the specimen was drawn

C.

Explanation: In this case, the child fits the description of a suspected hyperlipemic patient. He is known to have diabetes mellitus, and the mother has assured the laboratory that the boy has followed the proper fasting protocol before the test. Hyperlipoproteinemia can be secondary to diabetes mellitus. The boy has a relatively high risk to develop CAD, and, as a known diabetic, should never undergo an oral 3-hour glucose tolerance test.

Bile acids that are synthesized in the liver are derived from what substance?

A. Bilirubin

B. Fatty acid

C. Cholesterol

D. Triglyceride

C. Cholesterol

C. Bile acids are synthesized in the hepatocytes of the liver. They are C24 steroids that are derived from cholesterol. With fat ingestion, the bile salts are released into the intestines, where they aid inthe emulsification of dietary fats. Thus bile acids also serve as a vehicle for cholesterol excretion. A majority of the bile acids, however, are reabsorbed from the intestines into the enterohepatic circulation for reexcretion into the bile. The two principal bile acids are cholic acid and chenodeoxycholic acid. These acids are conjugated with one of two amino acids, glycine or taurine. Measurement of bile acids is possible via immunotechniques and may aid in the diagnosis of some liver disorders such as obstructive jaundice, primary biliary cirrhosis, and viral hepatitis.

The turbid, or milky, appearance of serum after fat ingestion is termed postprandial lipemia, which is caused by the presence of what substance?

A. Bilirubin

B. Cholesterol

C. Chylomicron

D. Phospholipid

C. Chylomicron

C. After fat ingestion, lipids are first degraded, then reformed, and finally incorporated by the intestinal mucosal cells into absorbable complexes known as chylomicrons. These chylomicrons enter the blood through the lymphatic system, where they impart a turbid appearance to serum. Such lipemic plasma specimens frequently interfere with absorbance or cause achange in absorbance measurements, leading to invalid results.

Cholesterol ester is formed through the esterification of the alcohol cholesterol with what substance?

A. Protein

B. Triglyceride

C. Fatty acid

D. Digitonin

C. Fatty acid

C. Total cholesterol consists of two fractions, free cholesterol and cholesteryl ester. In the plasma, cholesterol exists mostly in the cholesteryl ester form. Approximately 70% of total plasma cholesterol is esterfied with fatty acids. The formation of cholesteryl esters is such that a transferase enzyme catalyzes the transfer of fatty acids from phosphatidylcholine to the carbon-3 alcohol function position of the free cholesterol molecule. Laboratories routinely measure total cholesterol by first using the reagent cholesterol esterase to break the ester bonds with the fatty acids.

Which of the following tests would most likely be included in a routine lipid profile?

A. Total cholesterol, triglyceride, fatty acid, chylomicron

B. Total cholesterol, triglyceride, HDL cholesterol, phospholipid

C. Triglyceride, HDL cholesterol, LDL cholesterol, chylomicron

D. Total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol

D. Total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol

D. A "routine" lipid profile would most likely consist of the measurement of total cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol. These measurements are most easily adapted to today's multichannel chemistry analyzers. Both total cholesterol and triglyceride use enzymatic techniques to drive the reaction to completion. HDL cholesterol and LDL cholesterol are commonly requested tests to help determine patient risk for coronary heart disease. The HDL is separated from other lipoproteins using a precipitation technique, immunotechniques, and/or polymers and detergents. The nonprecipitation techniques are preferred because they can give better precision, be adapted to an automated chemistry analyzer, and be run without personnel intervention. LDL cholesterol may be calculated using the Friedewald equation, or it may be assayed directly using selective precipitation methods or direct homogeneous techniques.

To produce reliable results, when should blood specimens for lipid studies be drawn?

A. Immediately after eating

B. Anytime during the day

C. In the fasting state, approximately 2 to 4 hours after eating

D. In the fasting state, approximately 9 to 12 hours after eating

D. In the fasting state, approximately 9 to 12 hours after eating

D. Blood specimens for lipid studies should be drawn in the fasting state at least 9 to 12 hours after eating. Although fat ingestion only slightly affects cholesterol levels, the triglyceride results are greatly affected. Triglycerides peak at about 4 to 6 hours after a meal, and thse exogenous lipids should be cleared from the plasma before analysis. The presence of chylomicrons, as a result of an inadequate fasting period, must be avoided because of their interference in spectrophotometric analyses.

Which of the following lipid tests is least affected by the fasting status of the patient?

A. Cholesterol

B. Triglyceride

C. Fatty acid

D. Lipoprotein

A. Cholesterol

A. Total cholesterol screenings are commonly performed on nonfasting individuals. Total cholesterol is only slightly affected by the fasting status of the individual, whereas triglycerides, fatty acids, and lipoproteins are greatly affected. Following a meal, chylomicrons would be present, which are rich in triglycerides and fatty acids and contain very little cholesterol. The majority of cholesterol is produced by the liver and other tissues. High levels of exogenous triglycerides and/or fatty acids will interfere with the measurement of lipoproteins. Chylomicrons are normally cleared from the body 6 hours after eating

What compound is a crucial intermediary in the metabolism of triglyceride to form energy?

A. Bile

B. Acetyl-coenzyme A

C. Acetoacetate

D. Pyruvate

B. Acetyl-coenzyme A

B. The long-chain fatty acids of triglycerides can be broken down to form energy through the process of beta/oxidation, also known as the fatty acid cycle. In this process, two carbons at a time are cleaved from long-chain fatty acids to form acetyl-coenzyme A. Acetyl-coenzyme A, in turn, can enter the Krebs cycle to be converted to energy or be converted to acetoacetyl-Co-A and converted to energy by an alternate pathway, leaving behind the acidic by-product ketones composed of beta-hydroxybutyrate, acetoacetate, and acetone. Under proper conditions, pyruvate can be converted to acetyl-coenzyme A at the end of glycolysis of glucose. Bile is a breakdown product of cholesterol used in the digestion of dietary cholesterol.

The kinetic methods for quantifying serum triglyceride employ enzymatic hydrolysis. The hydrolysis of triglyceride may be accomplished by what enzyme?

A. Amylase

B. Leucine aminopeptidase

C. Lactate dehydrogenase

D. Lipase

D. Lipase

D. The kinetic methods used for quantifying serum triglycerides use a reaction system of coupling enzymes. It is first necessary to

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

Enzymatic methods for the determination of total cholesterol in serum utilize a cholesterol oxidase-peroxidase method. In this method, cholesterol oxidase reacts specifically with what?

A. Free cholesterol and cholesteryl ester

B. Free cholesterol and fatty acid

C. Free cholesterol only

D. Cholesteryl ester only

C. Free cholesterol only

C. In the enzymatic method for quantifying total cholesterol in serum, the serum specimen must initially be treated with cholesteryl ester hydrolase. This enzyme hydrolyzes the cholesteryl esters into free cholesterol and fatty acids. Both the free cholesterol, derived from the cholesteryl ester fraction, and any free cholesterol normally present in serum may react in the cholesterol oxidase/peroxidase reactions for total cholesterol. The hydrolysis of the cholesteryl ester fraction is necessary because cholesterol oxidase reacts only with free cholesterol.

Exogenous triglycerides are transported in the plasma in what form?

A. Phospholipids

B. Cholesteryl esters

C. Chylomicrons

D. Free fatty acids

C. Chylomicrons

C. Chylomicrons are protein-lipid complexes composed primarily of triglycerides and containing only small amounts of cholesterol, phospholipids, and protein. After food ingestion, the chylomicron complexes are formed in the epithelial cells of the intestines. From the epithelial cells, the chylomicrons are released into the lymphatic system, which transports chylomicrons to the blood. The chylomicrons may then carry the triglycerides to adipose tissue for storage, to organs for catabolism, or to the liver for incorporation of the triglycerides into very-low-density lipoproteins (VLDLs). Chylomicrons are normally cleared from plasma within 6 hours after a meal.

Ketone bodies are formed because of an excessive breakdown of fatty acids. Of the following metabolites, which may be classified as a ketone body?

A. Pyruvic acid

B. beta-Hydroxybutyric acid

C. Lactic acid

D. Oxaloacetic acid

B. beta-Hydroxybutyric acid

B. Beta-hydroxybutyric acid, acetoacetic acid, and acetone are collectively referred to as ketone bodies. They are formed as a result of the process of beta-oxidation in which liver cells degrade fatty acids with a resultant excess accumulation of acetyl-coenzyme A (CoA). The acetyl-CoA is the parent compound from which ketone bodies are synthesized through a series of reactions.

Which of the following is most associated with the membrane structure of nerve tissue?

A. Cholesterol

B. Triglyceride

C. Phospholipids

D. Sphingolipids

D. Sphingolipids

D. Sphingolipids, most notably sphingomyelin, are the major lipids of the cell membranes of the central nervous system (i.e., the myelin sheath). Like phospholipids, Sphingolipids are amphipathic and contain a polar, hydrophilic head and a nonpolar, hydrophobic tail, making them excellent membrane formers. Although sometimes considered a subgroup of phospholipids, sphingomyelin is derived from the amino alcohol sphingosine instead of glycerol

Each lipoprotein fraction is composed of varying amounts of lipid and protein components. The beta-lipoprotein fraction consists primarily of which lipid?

A. Fatty acid

B. Cholesterol

C. Phospholipid

D. Triglyceride

B. Cholesterol

B. All the lipoproteins contain some amount of triglyceride, cholesterol, phospholipid, and protein. Each of the lipoprotein fractions is distinguished by its unique concentration of these substances. The beta-lipoprotein fraction is composed of approximately 50% cholesterol, 6% triglycerides, 22% phospholipids, and 22% protein. The beta-lipoproteins, which are also known as the low-density lipoproteins (LDLs), are the principal transport vehicle for cholesterol in the plasma. Both the chylomicrons and the prebeta-lipoproteins are composed primarily of triglycerides. The chylomicrons are considered transport vehicles for exogenous triglycerides. In other words, dietary fat is absorbed through the intestine in the form of chylomicrons. After a meal, the liver will clear the chylomicrons from the blood and use the triglyceride component to form the prebeta-lipoproteins. Therefore, in the fasting state triglycerides are transported in the blood primarily by the prebeta-lipoproteins. The prebeta-lipoproteins are composed of approximately 55% triglycerides.

What substance is the precursor to all steroid hormones?

A. Fatty acid

B. Cholesterol

C. Triglyceride

D. Phospholipid

B. Cholesterol

B. The 27-carbon, ringed structure of cholesterol is the backbone of steroid hormones. The nucleus is called the cyclopentanoperhydrophenanthrene ring. The steroid hormones having this ring include estrogens (18 carbons), androgens (19 carbons), glucocorticoids (21 carbons), and mineralocorticoids (21 carbons).

The term "lipid storage diseases" is used to denote a group of lipid disorders, the majority of which are inherited as autosomal recessive mutations. What is the cause of these diseases?

A. Excessive dietary fat ingestion

B. Excessive synthesis of chylomicrons

C. A specific enzyme deficiency or nonfunctional enzyme form

D. An inability of adipose tissue to store lipid materials

C. A specific enzyme deficiency or nonfunctional enzyme form

C. The majority of the lipid (lysosomal) storage diseases are inherited as autosomal recessive mutations. This group of diseases is characterized by an accumulation of Sphingolipids in the central nervous system or some other organ. Such lipid accumulation frequently leads to mental retardation or progressive loss of central nervous system functions. The cause of such lipid accumulation has been attributed either to specific enzyme deficiencies or to nonfunctional enzyme forms that inhibit the normal catabolism of the Sphingolipids.

Several malabsorption problems are characterized by a condition known as steatorrhea. Steatorrhea is caused by an abnormal accumulation of what substance in the feces?

A. Proteins

B. Lipids

C. Carbohydrates

D. Vitamins

B. Lipids

B. Pancreatic insufficiency, Whipple disease, cystic fibrosis, and tropical sprue are diseases characterized by the malabsorption of lipids from the intestines. This malabsorption results in an excess lipid accumulation in the feces that is known as steatorrhea. When steatorrhea is suspected, the amount of lipid material present in the feces may be quantified. A 24- or 72-hour fecal specimen should be collected, the latter being the specimen of choice. The lipids are extracted from the fecal specimen and analyzed by gravimetric or titrimetric methods.

What is the sedimentation nomenclature associated with alpha-lipoprotein?

A. Very-low-density lipoproteins (VLDLs)

B. High-density lipoproteins (HDLs)

C. Low-density lipoproteins (LDLs)

D. Chylomicrons

B. High-density lipoproteins (HDLs)

B. A double nomenclature exists for the five principal lipoprotein fractions. The nomenclature is such that the various fractions have been named on the basis of both the electrophoretic mobilities and the ultracentrifugal sedimentation rates. The chylomicrons are known as chylomicrons by both methods. The chylomicrons are the least dense fraction, exhibiting a solvent density for isolation of less than 0.95 g/mL, and have the slowest electrophoretic mobility. The HDLs, also known as the alpha-lipoproteins, have the greatest density of 1.063-1.210 g/mL and move the fastest electrophoretically toward the anode. The VLDLs, also known as the prebeta-lipoproteins, move slightly slower electrophoretically than the alpha fraction. The VLDLs have a density of 0.95-1.006 g/mL. The IDLs, intermediate-density lipoproteins, have a density of 1.006-1.019 g/mL and migrate as a broad band between beta- and prebeta-lipoproteins. The LDLs, also known as the beta-lipoproteins, have an electrophoretic mobility that is slightly slower than that of the IDL fraction. The LDLs have an intermediate density of 1.019-1.063 g/mL, which is between the IDLs and the HDLs. To summarize the electrophoretic mobilities, the alpha-lipoprotein fraction migrates the farthest toward the anode from the origin, followed in order of decreasing mobility by the prebeta-lipoprotein, broad band between beta and prebeta-lipoprotein, beta-lipoprotein, and chylomicron fractions. The chylomicrons remain more cathodic near the point of serum application

The quantification of the high-density lipoprotein cholesterol level is thought to be significant in the risk assessment of what disease?

A. Pancreatitis

B. Cirrhosis

C. Coronary artery disease

D. Hyperlipidemia

C. Coronary artery disease

C. The quantification of the HDL cholesterol level is thought to contribute in assessing the risk that an individual may develop coronary artery disease (CAD). There appears to be an inverse relationship between HDL cholesterol and CAD. With low levels of HDL cholesterol, the risk of CAD increases. It is thought that the HDL facilitates the removal of cholesterol from the arterial wall, therefore decreasing the risk of atherosclerosis. In addition, LDL cholesterol may be assessed, because increased LDL cholesterol and decreased HDL cholesterol are associated with increased risk of CAD.

The VLDL fraction primarily transports what substance?

A. Cholesterol

B. Chylomicron

C. Triglyceride

D. Phospholipid

C. Triglyceride

C. The VLDL fraction is primarily composed of triglycerides and lesser amounts of cholesterol and phospholipids. Protein components of VLDL are mostly apolipoprotein B-100 and apolipoprotein C. VLDL migrates electrophoretically in the prebeta region.

A 54-year-old male, with a history of type 2 diabetes mellitus for the past 8 years, is seen by his family physician. The patient indicates that during the past week he had experienced what he described as feeling lightheaded and faint. He also indicated that he became out of breath and had experienced mild chest pain when doing heavy yard work, but the chest pain subsided when he sat down and rested. The physician performed an ECG immediately, which was normal, and he ordered blood tests. The patient fasted overnight and had blood drawn the next morning. The laboratory test values follow:

Test/Patient's Values/ Reference Ranges

Glucose, fasting/ 175 mg/dL / 74-99 mg/dL

Hemoglobin Alc/ 8.1% / 4-6%

Total cholesterol / 272 mg/dL / <200 mg/dL

HDL cholesterol / 30 mg/dL / >40 mg/dL

LDL cholesterol / 102 mg/dL / <130 mg/dL

Triglyceride / 250 mg/dL / <150 mg/dL

hs-CRP/ 6.2 mg/l / 0.3-8.6 mg/L, < 1.0 mg/L low risk

Based on

A. LDL cholesterol

A. The patient is a known diabetic who has been experiencing chest pain and shortness of breath with activity. The ECG was normal. The most likely diagnosis is angina pectoris. The LDL cholesterol result does not correlate with the other lipid results, and it appears to be less than what would be expected. Using the formula LDL cholesterol = total cholesterol - [HDL cholesterol + triglycerides/5], the calculated LDL cholesterol would be 192 mg/dL. The total cholesterol, HDL cholesterol, and triglyceride results con-elate and indicate hyperlipidemia. The elevated fasting glucose indicates poor carbohydrate metabolism, and the elevated hemoglobin Ajc indicates a lack of glucose control during the previous 2 to 3 months. The elevated glucose and lipid results support an increased risk of coronary artery disease, as does the hs-CRP value, which falls in the high risk range (>3.0 mg/L).

Name a commonly used precipitating reagent to separate HDL cholesterol from other lipoprotein cholesterol fractions.

A. Zinc sulfate

B. Trichloroacetic acid

C. Heparin-manganese

D. Isopropanol

C. Heparin-manganese

C. Either a dextran sulfate-magnesium chloride mixture or a heparin sulfate-manganese chloride mixture may be used to precipitate the LDL and VLDL cholesterol fractions. This allows the HDL cholesterol fraction to remain in the supernatant. An aliquot of the supernatant may then be used in a total cholesterol procedure for the quantification of the HDL cholesterol level.

What is the principle of the "direct" or "homogeneous" HDL cholesterol automated method, which requires no intervention by the laboratorian? The direct HDL method

A. Quantifies only the cholesterol inHDL, whereas the precipitation HDL

method quantifies the entire lipoprotein

B. Utilizes polymers and detergents that make the HDL cholesterol soluble while keeping the other lipoproteins insoluble

C. Uses a nonenzymatic method to measure cholesterol, whereas the other methods use enzymes to measure cholesterol

D. Uses a column chromatography step to separate HDL from the other

lipoproteins, whereas the other methods use a precipitation step

B. Utilizes polymers and detergents that make the HDL cholesterol soluble while keeping the other lipoproteins insoluble

B. Both the direct and the heparin sulfatemanganese chloride precipitation methods measure HDL cholesterol. The direct or homogeneous method for HDL cholesterol uses a mixture of polyanions and polymers that bind to LDL and VLDL and chylomicrons, causing them to become stabilized. The polyanions neutralize ionic charges on the surface of the lipoproteins, and this enhances their binding to the polymer. When a detergent is added, HDL goes into solution, whereas the other lipoproteins remain attached to the polymer/polyanion complexes. The HDL cholesterol then reacts with added cholesterol enzyme reagents while the other lipoproteins remain inactive. The reagents, polymer/polyanions, and detergent can be added to the specimen in an automated way without the need for any manual pretreatment step. Furthermore, the direct HDL cholesterol procedure has the capacity for better precision than the manual precipitation methods. Both the adaptability to automated instalments and the better precision make the direct method a preferred choice for quantifying HDL cholesterol

Which of the following results would be the most consistent with high risk for coronary heart disease?

A. 20 mg/dL HDL cholesterol and 250 mg/dL total cholesterol

B. 45 mg/dL HDL cholesterol and 210 mg/dL total cholesterol

C. 50 mg/dL HDL cholesterol and 180 mg/dL total cholesterol

D. 55 mg/dL HDL cholesterol and 170 mg/dL total cholesterol

A. 20 mg/dL HDL cholesterol and 250 mg/dL total cholesterol

A. A number of risk factors are associated with developing coronary heart disease. Notable among these factors are increased total cholesterol and decreased HDL cholesterol levels. Although the reference ranges for total cholesterol and HDL cholesterol vary with age and sex, reasonable generalizations can be made: An HDL cholesterol less than 40 mg/dL and a total cholesterol value >240 mg/dL are undesirable and the individual is at greater risk for coronary heart disease. Total cholesterol values between 200 and 239 mg/dL are borderline high.

A patient's total cholesterol is 300 mg/dL, his HDL cholesterol is 50 mg/dL, and his triglyceride is 200 mg/dL. What is thispatient's calculated LDL cholesterol?

A. 200

B. 210

C. 290

D. 350

B. 210

B. Once the total cholesterol, triglyceride, and HDL cholesterol are known, LDL cholesterol can be quantified by using the Friedewald equation LDL cholesterol = Total cholesterol — (HDL cholesterol + Triglyceride/5)

In this example, all results are in mg/dL:

LDL cholesterol = 300 - (50 + 200/5)

= 300 - (90)

= 210 mg/dL

This estimation of LDL cholesterol has been widely accepted in routine clinical laboratories and can be easily programmed into laboratory computers. In addition, LDL methods are available for direct measurement of serum levels. Note: The equation should not be used with triglyceride values exceeding 400 mg/dL because the VLDL composition is abnormal, making the [triglyceride/5] factor inapplicable.

A patient's total cholesterol/HDL cholesterol ratio is 10.0. What level of risk for coronary heart disease does this result indicate?

A. No risk

B. Half average risk

C. Average risk

D. Twice average risk

D. Twice average risk

D. Both total cholesterol and HDL cholesterol are independent measurable indicators of risk of coronary heart disease (CHD). By relating total and HDL cholesterol in a mathematical way, physicians can obtain valuable additional information in predicting risk for CHD. Risk of CHD can be quantified by the ratio of total cholesterol to HDL cholesterol along the following lines:

Ratio/ Risk CHD

3.43/ half average

4.97 /average

9.55 /two times average

24.39/ three times average

Thus this patient shows approximately twice the average risk for CHD. Risk ratios for CHD can easily be calculated by instrument and/or laboratory computers given the total and HDL cholesterol values. Reports indicating level of risk based on these results can be programmed by the laboratory and/or manufacturer.

Which of the following techniques can be used to quantify apolipoproteins?

A. Spectrophotometric endpoint

B. Ion-selective electrode

C. Immunonephelometric assay

D. Refractometry

C. Immunonephelometric assay

C. A number of immunochemical assays can be used to quantify the apolipoproteins. Some of the techniques that can be used include immunonephelometric assay, enzyme-linked immunosorbent assay (ELISA), and immunoturbidimetric assay. Commercial kits are available for the quantification of Apo A-I and Apo B-100. Measuring the apolipoproteins can be of use in assessing increased risk for coronary heart disease.

Which of the following may be described as a variant form of LDL, associated with increased risk of atherosclerotic cardiovascular disease?

A. Lp(a)

B. HDL

C. ApoA-I

D. ApoA-II

A. Lp(a)

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

In what way is the "normal" population reference interval for total cholesterol in America different from that of other clinical chemistry parameters (i.e., protein, sodium, BUN, creatinine, etc.)?

A. Established units for total cholesterol are mg/dL; no other chemistry test has these units.

B. Reference interval is artificially set to reflect good health even though

Americans as a group have "normally" higher total cholesterol levels.

C. Total cholesterol reference interval must be interpreted in line with

triglyceride, phospholipid, and sphingolipid values.

D. Total cholesterol reference interval is based on a manual procedure, whereas all other chemistry parameters are based on automated procedures.

B. Reference interval is artificially set to reflect good health even though

Americans as a group have "normally" higher total cholesterol levels.

B. Historically, total cholesterol levels of Americans have been below 300 mg/dL. Other countries, however, have relatively lower population cholesterol levels. The prevalent diet of these countries, however, may be vegetarian or fish, as opposed to meat, oriented. Higher total cholesterol resulting from a meat diet has been established. Clinical studies have also shown an increased risk of CAD in individuals with total cholesterol greater than 200 mg/dL. Thus, the upper reference interval of acceptable total cholesterol was artificially lowered to 200 mg/dL to reflect the lower risk of CAD associated with it.

Your lab routinely uses a precipitation method to separate HDL cholesterol. You receive a slightly lipemic specimen for HDL cholesterol. The total cholesterol and triglyceride for the specimen were 450 and 520 mg/dL, respectively. After adding the precipitating reagents and centrifuging, you notice that the supernatant still looks slightly cloudy. What is your next course of action in analyzing this specimen?

A. Perform the HDL cholesterol test; there is nothing wrong with this specimen.

B. Take off the supernatant and recentrifuge.

C. Take off the supernatant and add another portion of the precipitating reagent to it and recentrifuge.

D. Send specimen to a lab that offers other techniques to separate more effectively the HDL cholesterol.

D. Send specimen to a lab that offers other techniques to separate more effectively the HDL cholesterol.

D. The Abell-Kendall assay is commonly used to separate HDL cholesterol from other lipoproteins. In this precipitation technique a heparin sulfate-manganese chloride mixture is used to precipitate the LDL and VLDL cholesterol fractions. This technique works well as long as there is no significant amount of chylomicrons or lipemia in the specimen and/or the triglyceride is under 400 mg/dL. Incomplete sedimentation is seen as cloudiness or turbidity in the supernatant after centrifugation. It indicates the presence of other lipoproteins and leads to over estimation of HDL cholesterol. The lipemic specimens may be cleared and the HDL cholesterol separated more effectively by using ultrafiltration, extraction, latex immobilized antibodies, and/or ultracentrifugation. These techniques are usually not available in a routine laboratory.

A 46-year-old known alcoholic with liver damage is brought into the emergency department unconscious. In what way would you expect his plasma lipid values to be affected?

A. Increased total cholesterol, triglyceride, LDL, and VLDL

B. Increased total cholesterol and triglyceride, decreased LDL and

VLDL

C. Decreased total cholesterol, triglyceride, LDL, and VLDL

D. Normal lipid metabolism, unaffected by the alcoholism

A. Increased total cholesterol, triglyceride, LDL, and VLD

A. Hyperlipoproteinemia can be genetically inherited or secondary to certain diseases such as diabetes mellitus, hypothyroidism, or alcoholism. If the alcoholism has advanced to the state where there is liver damage, the liver can become inefficient in its metabolism of fats, leading to an increase of total cholesterol, triglyceride, LDL, and/or VLDL in the bloodstream. The elevation of these lipids along with the previous liver damage (e.g., cirrhosis) leads to a poor prognosis for the patient.

A healthy, active 10-year-old boy with no prior history of illness comes to the lab after school for a routine chemistry screen in order to meet requirements for summer camp. After centrifugation, the serum looks cloudy. The specimen had the following results: blood glucose = 135 mg/dL, total cholesterol =195 mg/dL, triglyceride =185 mg/dL. What would be the most probable explanation for these findings? The boy

A. Is at risk for coronary artery disease

B. Has type 1 diabetes mellitus that is undiagnosed

C. Has an inherited genetic disease causing a lipid imbalance

D. Was most likely not fasting when the specimen was drawn

D. Was most likely not fasting when the specimen was drawn

D. In evaluating lipid profile results, it is important to start with the integrity of the sample. From the case history, it is doubtful that a 10-year-old healthy, active boy would be suffering from a lipid or glucose disorder manifesting these kinds of results. Furthermore, the boy came in for testing after school. It is improbable that a 10-year old boy would be able to maintain a 9- to 12-hour fast during the school day. In this case, the boy should have been thoroughly interviewed by the laboratory staff before the blood test to determine if he was truly fasting. Specimen integrity is the first thing that must be ensured before running any glucose or lipid tests

A mother brings her obese, 4-year-old child who is a known type 1 diabetic to the laboratory for a blood workup. She states that the boy has been fasting for the past 12 hours. After centrifugation the tech notes that the serum looks turbid. The specimen had the following results: blood glucose = 150 mg/dL, total cholesterol = 250 mg/dL, HDL cholesterol = 32 mg/dL,triglyceride = 395 mg/dL. What bestexplains these findings? The boy

A. Is a low risk for coronary artery disease

B. Is a good candidate for a 3-hour oral glucose tolerance test

C. Has secondary hyperlipidemia due to the diabetes

D. Was not fasting when the specimen was drawn

C. Has secondary hyperlipidemia due to the diabetes

C. In this case, the child fits the description of a suspected hyperlipemic patient. He is known to have diabetes mellitus, and the mother has assured the laboratory that the boy has followed the proper fasting protocol before the test. Hyperlipoproteinemia can be secondary to diabetes mellitus. The boy has a relatively high risk to develop CAD, and, as a known diabetic, should never undergo an oral 3-hour glucose tolerance test.

35. High levels of which lipoprotein class are associated with decreased risk of accelerated atherosclerosis?

a. chylomicrons

b. VLDL

c. LDL

d. HDL

d. HDL

High-density lipoprotein (HDL) is the smallest and most dense lipoprotein. Its role in lipid metabolism involves removing

cholesterol from the peripheral cells and transporting it to the liver for further metabolism. Because of these actions, HDLis thought to be anti-atherogenic. Increased

levels of LDL, VLDL and chylomicrons are associated with atherosclerosis.

36. The most consistent analytical error involved in the routine determination of H D L-cholesterol is caused by:

a. incomplete precipitation of LDL-cholesterol

b. coprecipitation of HDL- and LDL-cholesterol

c. inaccurate protein estimation of HDL-cholesterol

d. a small concentration of apoB-containing lipoproteins after precipitation

D. a small concentration of apoB-containing lipoproteins after precipitation

Serum HDL has been routinely measured indirectly by a 2-step

procedure. Precipitation of all of the non-H DL lipoproteins with a polyaniondivalent cation combination reagent and

centrifugation to obtain the supernatant containing only HDL. The cholesterol bound to HDL is measured as HDL. One challenge

regarding the method has been the selection of a precipitating reagent that would precipitate the apoB containing lipoproteins.

Dextran sulfate with magnesium has proven to be very effective.

37. If the LDL- cholesterol is to be calculated by the Friedewald formula, what are the 2 measurements that need to be carried out by the same chemical procedure?

a. total cholesterol and H DL-cholesterol

b. total cholesterol and triglyceride

c. triglyceride and chylomicrons

d. apolipoprotein A and apolipoprotein B

a. total cholesterol and H DL-cholesterol

In the indirect measurement of LDL using the Friedewald equation, values are needed for the total cholesterol, HDL cholesterol a n d triglyceride. Because LDL and HDL are measured based on their cholesterol content, it is necessary

to determine the total choles terol

and HDL cholesterol using the same cholesterol procedure.

38. The chemical composition of HDL-cholesterol corresponds to:

Tri glyceride Cholesterol Protein

a. 60% 15% 10%

b. 10% 45% 25%

c. 5% 15% 50%

d. 85% 5% 2 %

c. 5% 15% 50%

High-density lipoprotein (HDL) is the smallest and most dense of the lipoproteins. This is evidenced by its lipid content of 20% and protein concentration of 50%.

39. In familial hypercholesterolemia, the hallmark finding is an elevation of:

a. low-density lipoproteins

b. chylomicrons

c. high-density lipoproteins

d. apolipoprotein A1

a. low-density lipoproteins

Familial hypercholesterolemia is a

genetic condition characterized by elevated serum cholesterol levels. In homozygotes and heterozygotes, the elevated cholesterol is associated with an increased LDL level. The lack or deficiency of the LDL receptors

prevents the metabolism of LDL cholesterol, resulting in an increased LDL level.

40. Premature atherosclerosis can occur when which of the following becomes elevated?

a. chylomicrons

b. prostaglandins

c. low-density lipoproteins

d. high-density lipoproteins

c. low-density lipoproteins

Atherosclerosis is characterized by a thickening and hardening of the arterial walls by cholesterol plaques in the lining of the arteries. Elevated levels of cholesterol

are associated with the development of the plaques. One of the roles of LDL is to transport cholesterol esters to the

cells for metabolism. Elevated LDL levels are also associated with development of atherosclerosis.

41. Transportation o f 60%-75% of the plasma cholesterol is performed by:

a. chylomicrons

b. very low-density lipoproteins

c. low-density lipoproteins

d. high-density lipoproteins

c. low-density lipoproteins

Low-density lipoprotein (LD L) transports about 70% of the total plasma cholesterol. HDL transports only 30% ofthe cholesterol. Chylomicrons and VLDL

transport triglycerides.

42. Which of the following diseases results from a familial absence of high density lipoprotein?

a. Krabbe disease

b. Gaucher disease

c. Tangier disease

d. Tay-Sachs disease

c. Tangier disease

Tangier disease results from a defect in the catabolism of Apo A-I, an essential apoprotein for H D L . In homozygotes, the plasma level for HDL is practically zero. The reduced HDL levels result from

increased HDL catabolism.

43.A 1-year-old girl with a hyperlipoproteinemia and lipase deficiency has the following lipid profile:

cholesterol: 300 mg/dl (7.77 mmoi/L)

LDL: increased

HDL: decreased

triglycerides: 200 mg/dl (2.26 mmoi/L)

chylomicrons: present

A serum specimen from this patient that was refrigerated overnight would most likely be:

a. clear

b. cloudy

c. creamy layer over cloudy serum

d. creamy layer over clear serum

d. creamy layer over clear serum

Lipid analysis using overnight

refrigeration involves incubating the sample at 4oC overnight. The chylomicrons, present as a thick homogenous cream layer, may be

observed floating at the plasma surface.

44. Which of the following lipid results would be expected to be falsely elevated on a serum specimen from a non fasting patient?

a. cholesterol

b. triglyceride

c. H D L

d. LDL

b. triglyceride

Food intake can cause a transient increase in the triglyceride level by 50%. The LDL and HDL levels may be decreased by 10%-15 % depending on the fat content

of the meal.

45. A 9-month-old boy from Israel has gradually lost the ability to sit up, and develops seizures. He

has an increased amount of a phospholipid called GMrganglioside in his neurons, and he lacks

the enzyme hexosaminidase A in his leukocytes. These findings suggest:

a. Neimann-Pick disease

b. Tay-Sachs disease

c. phenylketonuria

d. Hurler syndrome

b. Tay-Sachs disease

Tay-Sachs disease is a rare inherited disorder characterized by the near-total deficiency of the enzyme N-acetylbeta hexosaminidase A. The enzyme is responsible for the hydrolysis of the beta (1,4)-glycosidic bond between N-acetylgalactosamine and galactose in GM2 ganglioside. Neimann-Pick disease and

Hurler's syndrome are lysosomal disorders as is Tay-Sachs. Phenylketonuria results

from an absent enzyme, but is an inborn error of metabolism.

46. In amniotic fluid, the procedure used to determine fetal lung maturity is:

a. lecithin/sphingomyelin ratio

b. creatinine

c. measurement of absorbance at 450 nm

d. alpha-fetoprotein

a. lecithin/sphingomyelin ratio

The historical method to evaluate fetal lung maturity is the lecithin/sphingomyelin

(LIS) ratio. Measurement of pulmonary surfactant is done to evaluate fetal lung maturity. Lecithin is the major component

of the lung surfactant. Sphingomyelin, a non-lung phospholipid, has no role in the

surfactant system. I t serves as a control for the increase in lecithin that occurs around the 34-36th week of gestation. Other amniotic fluid evaluations include measurement of creatinine for fetal age; alpha-fetoprotein for neural tube disorder and absorbance at 450nm-bilirubin for fetal distress.

47. Refer to the following illustration:

The class of phospholipid surfactants represented by the dotted line on the amniotic fluid analysis show above is thought to originate in what fetal organ system?

A) cardiovascular

B) pulmonary

C) hepatic

D) placental

B) pulmonary

48. A fasting serum sample from an asymptomatic 43-year-old woman is examined visually and chemically with the following results:

initial appearance of serum:

milky appearance of serum after overnight refrigeration: cream layer over turbid serum

triglyceride level: 2,000 mg/dl (22.6 mmoi/L)

cholesterol level: 550 mg/dl (14.25 mmoi/L)

This sample contains predominantly:

a. chylomicrons, alone

b. chylomicrons and very low-density lipoproteins (VLDL)

c. very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL)

d. high-density lipoproteins (HDL)

b. chylomicrons and very low-density lipoproteins (VLDL)

Mixed hyperlipoproteinemia or type V hyperlipoproteinemia occurs primarily in adulthood and is characterized by markedly elevated triglycerides, elevated

very low-density lipoproteins (VLDL) and chylomicrons. Because of the markedly increased triglyceride level, the specimen integrity is milky, and overnight

refrigeration shows a creamy layer over turbid serum due to the chylomicrons and triglycerides.

49. Chylomicrons are present in which of the following dyslipidemias?

a. familial hypercholesterolemia

b. hypertriglyceridemia

c. deficiency in lipoprotein lipase activity

d. familial hypoalphalipoproteinemia

c. deficiency in lipoprotein lipase activity

Lipoprotein lipase hydrolyzes

triglycerides and chylomicrons during normal lipid metabolism. A deficiency in lipoprotein lipase results in markedly increased serum chylomicrons and triglycerides.

50. The function of the major lipid components of the very low-density lipoproteins (VLDL) is to transport:

a. cholesterol from peripheral cells to the liver

b. cholesterol and phospholipids to peripheral cells

c. exogenous triglycerides

d. endogenous triglyceride

d. endogenous triglyceride

In the endogenous pathway for lipid metabolism the hepatocytes can synthesize triglycerides from carbohydrates and fatty acids. The triglycerides are packaged

in VLDL, and ultimately delivered to the circulation in that form. Exogenous triglycerides are transported primarily by

chylomicrons. HDL transports cholesterol from peripheral cells to the liver. LDL transports cholesterol and phospholipids to

peripheral cells.

51. Turbidity in serum suggests elevation of:

a. cholesterol

b. total protein

c. chylomicron

d. albumin

c. chylomicron

Elevated levels of chylomicrons in serum or plasma will result in a turbid specimen. The large size of the chylomicron will reflect

the light, causing a turbid appearance.

52 A lipemic serum is separated and frozen at -20C for assay at a later date. One week later, prior to performing an assay for triglycerides, the specimen should be:

A) warmed to 37C and mixed thoroughly

B) warmed to 15C and centrifuged

C) transfered to a glycerated test tube

D) discarded and a new specimen obtained

A) warmed to 37C and mixed thoroughly

53. As part of a hyperlipidemia screening program, the following results were obtained on a 25-year-old woman 6 hours after eating:

test results:

triglycerides 260 mg/dL (2.86 mmol/L)

cholesterol 120 mg/dL (3.12 mmol/L)

Which of the following is the best interpretation of these results?

A. both results are normal, and not affected by the recent meal

B. cholesterol is normal, but triglycerides are elevated, which may be attributed to the recent meal

C. both results are elevated, indicating a metabolic problem in addition to the nonfasting state

D. both results are below normal despite the recent meal, indicating a metabolic problem

B. cholesterol is normal, but triglycerides are elevated, which may be attributed to the recent meal

54. Blood was collected in a serum separator tube on a patient who has been fasting since midnight. The time of collection was 7 am. The laboratory test which should be recollected is:

A. triglycerides

B. iron

C. LD

D. sodium

A. triglycerides

- Triglycerides are affected by recent ingestion (<8h) of food

- Fasting over 10-14h is the optima fasting around which to standardize blood collection, including lipids.

- Iron is subject to circadian rhythm and is best analyzed on specimen draw in the morning, however a specific time of fasting is not as critical.

- LD and sodium are not affected by recent ingestion of food

55. Which of the following is the formula for calculating absorbance given the percent transmittance (%T) of a solution?

A. 1- log(%T)

B. log(%T)/2

C. 2(log(%T))

D. 2-log(%T)

D. 2-log(%T)

56 .The substance that is measured to estimate the serum concentration of triglycerides by most methods is:

A. phospholipids

B. glycerol

C. fatty acids

D. pre-beta lipoprotein

B. glycerol

57. Which of the following methods for quantitation of high-density lipoprotein is most suited for clinical laboratory use?

A. Gomori procedure

B. homogeneous

C. column chromatography

D. agarose gel electrophoresis

B. homogeneous

42.Select the order of mobility of lipoproteins electrophoresed on cellulose acetate or agarose at pH 8.6.

A. - Chylomicrons→pre-β →β→α+

B. - β→pre-β→α→chylomicrons +

C. - Chylomicrons →β→pre-β→α +

D. - α→β→pre-β→chylomicrons +

C. - Chylomicrons →β→pre-β→α +

C Although pre-β lipoprotein is lower in density than β lipoprotein, it migrates faster on agarose or cellulose acetate owing to its more negative apoprotein composition. When lipoproteins are

separated on polyacrylamide gel, pre-β moves slower than β lipoprotein. Molecular sieving causes migration to correlate with lipoprotein density when PAGE is used.

43.Following ultracentrifugation of plasma, which fraction correlates with pre-β lipoprotein?

A. Very low-density lipoprotein (VLDL)

B. Low-density lipoprotein (LDL)

C. High-density lipoprotein (HDL)

D. Chylomicrons

A. Very low-density lipoprotein (VLDL)

A The VLDL (very low-density lipoprotein) migrates in the pre-β zone. The VLDL is about 50% triglyceride, whereas LDL is only 10% triglyceride by weight. LDL is formed from VLDL in the circulation. The process is initiated by apoC-II on VLDL activating peripheral lipoprotein lipase. Hydrolysis of triglycerides and transfer of apoproteins from VLDL to HDL result in formation of IDL. Larger IDLs are returned to the liver as remnant lipoproteins. Further hydrolysis of triglycerides, transfer cholesterol esters from HDL, and transfer of apoproteins to HDL convert IDL to LDL.

44.Select the lipoprotein fraction that carries most of the endogenous triglycerides.

A. VLDL

B. LDL

C. HDL

D. Chylomicrons

A. VLDL

A The VLDL is formed in the liver largely from chylomicron remnants and hepatic-derived triglycerides. Therefore, the VLDL transports the majority of endogenous triglycerides, while the triglycerides of chylomicrons are derived entirely from dietary absorption.

45. The protein composition of HDL is what percentage by weight?

A. Less than 2%

B. 25%

C. 50%

D. 90%

C. 50%

C About 50% of the weight of HDL is protein, largely apo A-I and apo A-II. The HDL is about 30% phospholipid and 20% cholesterol by weight. The HDL binds and esterifies free cholesterol from cells and transports it to the liver, where it can be eliminated in the bile.

46. Which apoprotein is inversely related to risk of coronary heart disease?

A. Apoprotein A-I

B. Apoprotein B100

C. Apoprotein C-II

D. Apoprotein E4

A. Apoprotein A-I

A Apoprotein A-I and apo A-II are the principal apoproteins of HDL, and low apo A-I has a high correlation with atherosclerosis. Conversely, apo-B100 is the principal apoprotein of LDL, and an elevated level is a major risk factor in developing coronary heart disease. Apoprotein assays are not recommended as screening tests because they are not as well standardized as LDL cholesterol assays. However, apo-B100 assay is more sensitive than LDL cholesterol in predicting coronary artery disease risk. Apo-B100 may be abnormal in persons with increased small dense LDL. Small dense LDL is more atherogenic than large LDL molecules. In addition, persons with hyperapobetalipoproteinemia overproduce apo-B100 without having significantly elevated LDL cholesterol

47. In familial β dyslipoproteinemia (formerly

type III hyperlipoproteinemia), which lipoprotein accumulates?

A. Chylomicrons

B. VLDL

C. IDL

D. HDL

C. IDL

C IDLs have roughly equal amounts of cholesterol and triglyceride. The IDL has a density of about 1.006-1.020, causing it to float on the 1.063 density potassium bromide solution used to recover LDL by ultracentrifugation. IDL has faster electrophoretic mobility on agarose than beta lipoprotein. These observations gave rise to the terms "floating beta" and "broad beta," respectively. Familial dysbetalipoproteinemia is in part caused by a polymorphism of apoE (apo E2) that has poor affinity for the apo-E receptor on hepatocytes. Not all persons with the homozygous polymorphism develop the disease; thus, other factors are necessary for the accumulation of IDL.

48. Which of the following mechanisms accounts for the elevated plasma level of β lipoproteins seen in familial hypercholesterolemia (formerly type II hyperlipoproteinemia)?

A. Hyperinsulinemia

B. ApoB-100 receptor defect

C. ApoC-II activated lipase deficiency

D. ApoE3 deficiency

B. ApoB-100 receptor defect

B The production of excess insulin leads to hypertriglyceridemia and is one mechanism responsible for familial endogenous

hypertriglyceridemia. ApoC-II is an activator of lipoprotein lipase, and a homozygous deficiency results in high plasma chylomicrons and VLDL. ApoE3 deficiency is synonymous with inheritance of two apo-E2 alleles that lead to β dyslipoproteinemia. Familial hypercholesterolemia is inherited as an autosomal dominant trait. The classical form results from one of many mutations affecting the LDL receptor that cause it to have a lower affinity for LDL.

A related hypercholesterolemia common in people of European ancestry results from a mutation of the apo-B100 gene that causes LDL to have a lower affinity for the LDL receptor. Together, they make familial hypercholesterolemia the most common inherited hyperlipoproteinemia with a frequency over 1:500.

49. Which enzyme deficiency is most commonly associated with familial hypertriglyceridemia associated with fasting plasma cholomicrons (formerly type I hyperlipoproteinemia)?

A. β Glucocerebrosidase deficiency

B. Post-heparin-activated lipoprotein lipase deficiency

C. Apo-B deficiency

D. Apo-C-III deficiency

B. Post-heparin-activated lipoprotein lipase deficiency

B Deficiency of capillary endothelial lipase is the most common cause of fasting chylomicronemia. This lipase is also known as post heparinactivated lipase and apo C-II-activated lipase. β Glucocerebrosidase deficiency results in accumulation of glucocerebrosides and is the cause of Gaucher's disease. ApoC-II deficiency results in decreased activity of peripheral and hepatic lipases and is associated with hypertriglyceridemia. Apo-B deficiency resulting from a point mutation in the apo-B gene, is responsible for hypobetalipoproteinemia, and is inherited as an autosomal dominant trait. LDL levels are about half normal in heterozygotes, and this reduces their risk of coronary artery disease.

50. Which of the following conditions is most consistently associated with secondary hypercholesterolemia?

A. Hypothyroidism

B. Pancreatitis

C. Oral contraceptive therapy

D. Diabetes mellitus

A. Hypothyroidism

A The conditions listed are very commonly encountered causes of secondary hyperlipoproteinemia. Oral contraceptives, pregnancy, and estrogens may cause secondary hypertriglyceridemia owing to increased VLDL and endogenous triglycerides. Hypothyroidism and obstructive hepatobiliary diseases are usually associated with secondary hypercholesterolemia owing to high LDL. Diabetesmellitus and chronic pancreatitis may produce hypertriglyceridemia, chylomicronemia, or mixed hyperlipidemia

51.Which of the following is associated with Tangier disease?

A. Apoprotein C-II deficiency

B. Homozygous apo-B100 deficiency

C. Apoprotein C-II activated lipase

D. Apoprotein A-I deficiency

D. Apoprotein A-I deficiency

D Deficiency of apo A-I is seen in Tangier disease, a familial hypocholesterolemia. Heterozygotes have about half of the normal level of HDL (familial hypoalphalipoproteinemia) and homozygotes have almost no detectable HDL. Tangier disease is caused by a mutation of the ATP-binding cassette gene. The deficient gene prevents apo A-I from binding lipids, and it israpidly catabolized. Abetalipoproteinemia results from defective hepatic transport of apo-B100, and is also inherited as an autosomal recessive condition. LDL is absent, and the condition is associated with hemolytic anemia and central nervous system damage

52. Which of the following statements is correct?

A. Both HDL and LDL are homogenous

B. There are several subfractions of LDL but not HDL

C. There are several subfractions of HDL but not LDL

D. There are several subfractions of both HDL and LDL

D. There are several subfractions of both HDL and LDL

D There are 7 subfractions of LDL and 10 subfractions of HDL. These are grouped into subclasses defined by their molecular sizes. In general, the small, dense LDL subclasses contain more oxidized LDL and are more atherogenic than the larger LDL molecules. The larger HDL subfractions comprising the HDL-3 subclass are associated with a lower risk of coronary artery disease.

53.What is the lipid testing protocol for adults recommended by the National Cholesterol Education Program (NCEP) to evaluate risk for atherosclerosis beginning at age 20?

A. Total cholesterol, fasting or nonfasting every year

B. Total cholesterol, fasting, every 2 years

C. Lipid profile, fasting, every 5 years

D. LDL cholesterol, fasting, every 2 years

C. Lipid profile, fasting, every 5 years

C Because LDL cholesterol, HDL cholesterol, VLDL cholesterol, and triglycerides are all risk factors for coronary artery disease, NCEP recommends a fasting lipid profile to include triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol be performed every 5 years beginning at age 20. However, because LDL cholesterol is the target of treatment, therapeutic goals are based on the LDL cholesterol. New guidelines recommend an LDL cholesterol goal below 70 mg/dL for the highest-risk persons

54.What is the most appropriate fasting procedure when a lipid study of triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol tests are ordered?

A. 8 hours; nothing but water allowed

B. 10 hours; water, smoking, coffee, tea (no sugar or cream) allowed

C. 12 hours; nothing but water allowed

D. 16 hours; water, smoking, coffee, tea (no sugar or cream) allowed

C. 12 hours; nothing but water allowed

C Lipid orders that include triglyceride and LDL cholesterol should always be performed using a plasma or serum specimen collected after a 12-14 hour fast. The patient should be instructed to drink nothing but water during this period.Fasting specimens are preferred for total and HDL cholesterol as well, but nonfasting specimens may be used for initial screening purposes.

55. Treatment recommendations for patients with coronary heart disease are based upon measurement of which analyte?

A. HDL cholesterol

B. Apo-B100

C. LDL cholesterol

D. Total cholesterol

C. LDL cholesterol

C NECP has identified LDL cholesterol as the target of therapy for reducing the risk of heart attack because lowering LDL cholesterol has proven to be an effective intervention. The greater the risk of coronary heart disease, the lower the cutpoint for intervention. For persons at high risk (a 10-year risk of heart attack > 20%) the cutpoint is ≥ 100 mg/dL for initiation of statin therapy. For highest-risk persons (those that have acute coronary syndrome, and multiple or uncontrolled risk factors) the treatment goal is LDL cholesterol below 70 mg/dL

56. What is the HDL cholesterol cutpoint recommend by NCEP?

A. <30 mg/dL

B. <40 mg/dL

C. <30 mg/dL for males and < 40 mg/dL for females

D. <45 mg/dL for males and < 50 mg/dL for females

B. <40 mg/dL

B The HDL cholesterol cutpoint recommended by NCEP is < 40 mg/dL regardless of sex. A result below 40 mg/dL counts as a risk factor for coronary artery disease. Conversely, if the HDL cholesterol is ≥ 60 mg/dL, then one risk factor is subtracted from the total number. The therapeutic goal for someone with low HDL cholesterol is still reduction of LDL cholesterol (if elevated), weight loss, and increased exercise.

57. An EDTA blood sample is collected from a nonfasting person for a CBC. The physician collected the sample from the femoral vein because venipuncture from the arm was unsuccessful. He called the lab 15 minutes after the sample arrived and requested a lipid study including triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol. Which test results should be used to evaluate the patient's risk for coronary artery disease?

A. Total cholesterol and LDL cholesterol

B. LDL cholesterol and triglyceride

C. Total cholesterol and HDL cholesterol

D. Total cholesterol and triglyceride

C. Total cholesterol and HDL cholesterol

C NCEP recommends a 12-hour fasting sample when screening persons for risk of coronary artery disease. However, if a fasting sample is unavailable, NCEP recommends performing the total cholesterol and HDL cholesterol because these tests are least affected by recent ingestion of food. If the total cholesterol is ≥ 200 mg/dL or the HDL cholesterol is < 40 mg/dL, then testing for LDL cholesterol and triglycerides should be performed when a fasting sample can be obtained. An EDTA plasma sample is acceptable for mostenzymatic cholesterol and triglyceride assays.

58. Which of the following diseases is caused by a deficiency of sphingomyelinase?

A. Gaucher disease

B. Fabry disease

C. Niemann-Pick disease

D. Tay-Sachs disease

C. Niemann-Pick disease

C The diseases mentioned result from inborn errors of lipid metabolism (lipidoses) caused by deficiency of an enzyme needed for lipid degradation. Specific lipids accumulate in the lysosomes. Niemann-Pick disease results from a deficiency of sphingomyelinase; Gaucher disease from β-glucocerebrosidase ; Fabry disease (sex linked) from α-galactosidase A; and Tay-Sachs from N acetylglucosaminidase A

59. Which method is considered the candidate reference method for triglyceride measurement?

A. Glycerol kinase-ultraviolet

B. CDC modification of van Handel and Zilversmit

C. Hantzsch condensation

D. Glycerol kinase coupled to peroxidase

B. CDC modification of van Handel and Zilversmit

B Enzymatic methods for triglyceride measurement are widely used because they eliminate the need for extraction and saponification. However, they are subject to positive interference from endogenous glycerol and variations in the efficiency of lipase, which can result in under- or overestimation of triglycerides. The most accurate method for triglyceride assay is the nonenzymatic method based upon reaction of formaldehyde with chromotropic acid. In this method, extraction with silicic acid and chloroform separates triglycerides from lipoproteins, phospholipids, and glycerol. Saponification with alcoholic potassium hydroxide (KOH) produces glycerol, which is oxidized to formaldehyde by periodate. The formaldehyde reacts with chromotropic acid to form a pink product.

60. Which of the following enzymes is common to all enzymatic methods for triglyceride measurement?

A. Glycerol phosphate oxidase

B. Glycerol phosphate dehydrogenase

C. Glycerol kinase

D. Pyruvate kinase

C. Glycerol kinase

C All enzymatic triglyceride methods require lipase to hydrolyze triglycerides, and glycerol kinase to phosphorylate glycerol, forming glycerol-3 phosphate. The most common method couples glycerol kinase with glycerol phosphate oxidase and peroxidase.

1. Triglyceride + H2O -Lipase-> glycerol + fatty acids

2. Glycerol + ATP -GK-> glycerol-3-phosphate + ADP

3. Glycerol-3-phosphate + O2 -GPO-> dihydroxyacetone phosphate + H2O2

H2O2 + phenol + 4-aminophenazone -Px -> quinoneimine dye + H2O

GK = glycerol kinase; GPO = glycerol phosphate oxidase; Px = peroxidase

61. Select the reagent needed in the coupling enzyme reaction used to generate a colored product in the cholesterol oxidase method for cholesterol.

A. Cholestahexaene

B. H2O2

C. 4-Aminoantipyrine

D. Cholest-4-ene-3-one

C. 4-Aminoantipyrine

C In the cholesterol oxidase method, cholesterol ester hydrolase converts cholesterol esters to free cholesterol by hydrolyzing the fatty acid from the C3-OH group. Cholesterol oxidase catalyzes the oxidation of free cholesterol at the C3-OH group forming cholest-4-ene-3-one and hydrogen peroxide. The peroxide is used in a peroxidase reaction to oxidize a dye (e.g., 4-aminoantipyrine), which couples to phenol, forming a red quinoneimine complex.

62. What is the purpose of the saponification step used in the Abell-Kendall method for cholesterol measurement?

A. Remove phospholipids

B. Reduce sterol molecules structurally similar to cholesterol

C. Convert cholesterol esters to free cholesterol

D. Remove proteins that can interfere with color formation

C. Convert cholesterol esters to free cholesterol

C The Abell-Kendall method is the reference method for cholesterol assay because differences in esterase activity and interference in the peroxidase step are potential sources of error in enzymatic assays. Saponification is performed to hydrolyze the fatty acid esters of cholesterol, forming free cholesterol. This is required because the reagents react more intensely with cholesterol esters than with free cholesterol. Saponification is followed by extraction

of cholesterol in petroleum ether to separate it from

proteins and interfering substances. The extract is

reacted with sulfuric acid, acetic anhydride, and acetic

acid (Liebermann-Burchard reagent), which oxidizes

the cholesterol and forms a colored product.

63. Which of the following methods for HDL cholesterol is the reference method?

A. Manganese-heparin

B. Magnesium-phosphotungstate

C. Magnesium-dextran

D. Ultracentrifugation

D. Ultracentrifugation

D Ultracentrifugation of plasma in a potassium bromide solution with a density of 1.063 is used to separate HDL from LDL and VLDL. The HDL fraction is transferred from the bottom of the tube and assayed for cholesterol content by the Abell-Kendall method. The remaining three methods rely upon selective precipitation of lipoproteins containing apoprotein B using a polyanionic solution. All of these methods are subject to interference by very high triglycerides and vary somewhat in specificity depending on the efficiency of precipitation.

64. Cholesterol esterase is used in enzymatic assays to:

A. Oxidize cholesterol to form peroxide

B. Hydrolyze fatty acids bound to the third carbon atom of cholesterol

C. Separate cholesterol from apoproteins A-I and A-II by hydrolysis

D. Reduce NAD+ to NADH

B. Hydrolyze fatty acids bound to the third carbon atom of cholesterol

B Approximately two-thirds of the serum cholesterolhas a fatty acid esterified to the hydroxyl group ofthe third carbon atom of the cholesterol molecule. Cholesterol esterase hydrolyzes fatty acids and is required because cholesterol oxidase cannot utilize esterified cholesterol as a substrate

65. Which of the following reagents is used in the direct HDL cholesterol method?

A. Sulfated cyclodextrin

B. Magnesium sulfate and dextran sulfate

C. Anti-apoA-I

D. Manganese heparin

A. Sulfated cyclodextrin

A The direct HDL cholesterol method most commonly employed uses cholesterol esterase and oxidase enzymes conjugated to polyethylene glycol. In the presence of sulfated cyclodextrin, the enzymes do not react with non-HDL cholesterol molecules. Anti-apoA-I binds to HDL and is not used in HDL assays

66.What do "direct" or homogenous methods for LDL cholesterol assay have in common?

A. They are inaccurate when plasma triglyceride is above 250 mg/dL

B. All use a detergent to facilitate selective reactivity with reagent enzymes

C. All use monoclonal antibodies to apo A1 and C

D. All are free of interference from abnormal lipoproteins

B. All use a detergent to facilitate selective reactivity with reagent enzymes

B The direct LDL cholesterol assays are all detergent based methods. One commonly used method employs a polyanionic detergent to release cholesterol from HDL, chylomicrons, and VLDL. The detergent binds to LDL and blocks its reaction with the esterase and oxidase enzymes in the reagent. Cholesterol oxidase oxidizes the non-LDL cholesterol, forming H2O2, and peroxidase catalyzes the oxidation of an electron donor by the H2O2,which does not result in color formation. A second nonionic detergent and chromogen is added. The second detergent removes the first from the LDL, allowing it to react with the enzymes. The resulting H2O2 reacts with the chromogen, forming a colored product

67. Lipoprotein (a), or Lp(a), is significant when elevated in serum because it:

A. Is an independent risk factor for atherosclerosis

B. Blocks the clearance of VLDLs

C. Displaces apo-AI from HDLs

D. Is linked closely to a gene for obesity

A. Is an independent risk factor for atherosclerosis

A Lp(a) is a complex of apo-B100 and protein (a) formed by a disulfide bridge. The complex is structurally similar to plasminogen and is thought to promote coronary heart disease by interfering with the normal fibrinolytic process. Lp(a) is measured by immunoassay; however, the measurement will vary depending on the type of antibodies used and their epitope specificity.

68.Which type of dietary fatty acid is not associated with an increase in serum LDL cholesterol production?

A. Monounsaturated trans fatty acids

B. Saturated fatty acids

C. Monounsaturated cis fatty acids

D. Monounsaturated trans Ω-9 fatty acids

C. Monounsaturated cis fatty acids

C Polyunsaturated and cis monounsaturated fatty acids are not associated with increased production of LDL cholesterol. On the other hand, saturated and trans monounsaturated fatty acids are both associated with increased LDL. Cis fatty acids are those in which the H atoms belonging to the double-bonded carbons are on the same side of the molecule. Ω-9 (n-9) fatty acids are those with a double bond located 9 carbons from the terminal methyl group. Ω Fatty acids are associated with increased cholesterol, if the hydrogens attached to the double-bonded carbons are in the trans position.

69.SITUATION: A lipemic specimen collected from an adult after a 12-hour fast was assayed for total cholesterol, triglycerides, and HDL cholesterol using a direct HDL method. Following are the

results:

Total cholesterol = 220 mg/dL

HDL cholesterol = 40 mg/dL

Triglyceride = 420 mg/dL

The physician requests an LDL cholesterol assay after receiving the results. How should the LDL cholesterol be determined?

A. Dilute the specimen 1:10 and repeat all tests; calculate LDL cholesterol using the Friedewald equation

B. Perform a direct LDL cholesterol assay

C. Ultracentrifuge the sample and repeat the HDL cholesterol on the infranate. Use the new result to calculate the LDL cholesterol

D. Repeat the HDL cholesterol using the manganese heparin precipitation method. Use the new result to calculate the LDL cholesterol

B. Perform a direct LDL cholesterol assay

B An accurate LDL cholesterol can be reported, if thedirect (detergent) method for LDL cholesterol is employed. These methods are not subject to interference by triglycerides at a concentration below 700 mg/dL.

70.A person has a fasting triglyceride level of 240 mg/dL. The physician wishes to know the patient's non-HDL cholesterol level. What cholesterol fractions should be measured?

A. Total cholesterol and HDL cholesterol

B. Total cholesterol and LDL cholesterol

C. HDL cholesterol and LDL cholesterol

D. Total cholesterol and chylomicrons

A. Total cholesterol and HDL cholesterol

A When the HDL cholesterol is subtracted from the total cholesterol, the result is called the non-HDL cholesterol. This result, the sum of LDL cholesterol and VLDL cholesterol, represents the fraction with atherogenic remnant lipoproteins as well as LDL cholesterol. People who have a fasting triglyceride ≥ 200 mg/dL are at increased risk for coronary artery disease owning to atherogenic VLDL remnants, and the treatment goal is to have a non-HDL cholesterol no more than 30 mg/dL greater than the LDL cholesterol.

1. A 46-year-old man visits his physician complaining of fatigue and chest pains. His family history reveals that his father and grandfather both died of heart attacks at the age of 50. Laboratory results indicated elevated total cholesterol, elevated low-density lipoprotein (LDL), and normal triglyceride. He is eventually diagnosed with familial hypercholesterolemia and atherosclerosis. What is the likely cause?

a. Genetic lack of LDL receptors on cell surfaces

b. Insulin deficiency

c. Lipoprotein lipase deficiency

d. Tangier disease

ANS: A

Familial hypercholesterolemia is caused by defects in the LDL receptor pathway, which binds and removes LDL from the circulation. LDL thus accumulates in the plasma, resulting in its increased deposition in the skin, tendons, and in arteries where it causes atherosclerosis. LDL particles tend to be larger, carrying increased amounts of cholesterol. The majority of these patients have gene defects in the

LDL receptor itself.

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2. The lipoprotein with the smallest diameter and that has a 50:50 lipid:lipoprotein ratio is the:

a. LDL.

b. chylomicron.

c. HDL.

d. VLDL.

ANS: C

See Table 23-4. HDL has a diameter of 4 to 10 nm and a 50:50 ratio of lipid to lipoprotein.

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3. In the small intestine, _____ is (are) solubilized by emulsification to form micelles.

a. lipase

b. cholesterol

c. starch

d. monosaccharides

ANS: B

Cholesterol is first solubilized through a process called emulsification, which occurs by the formation of micelles that contain unesterified cholesterol, fatty acids, monoglycerides, phospholipids, and conjugated bile acids.

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4. Cholesterol is esterified to form a cholesteryl ester by acylcholesterol acyltransferase in the cell. In the circulation, cholesteryl esters are formed by the action of which one of the following enzymes?

a. HMG CoA reductase

b. Cholesterol oxidase

c. Lecithin cholesterol acyltransferase

d. Fatty acid hydrolase

ANS: C

Cholesteryl esters also are formed in the circulation by the action of a plasma enzyme called lecithin cholesterol acyltransferase (LCAT) bound to lipoproteins, particularly high-density lipoproteins (HDL).

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5. Recognized abnormalities of fatty acid catabolism associated with uncontrolled diabetes mellitus include the development of ketone formation. This ketosis is caused by:

a. loss of apolipoprotein receptors on the surfaces of cells.

b. dysbetalipoproteinemia.

c. destruction of mitochondria within cells.

d. excess acetyl-CoA being diverted to form ketone bodies.

ANS: D

During prolonged starvation or when the carbohydrate metabolism is impaired, such as in uncontrolled diabetes mellitus, the formation of acetyl-CoA exceeds the supply of oxaloacetate. The resulting acetyl- CoA excess is diverted to an alternative pathway in the mitochondria for the formation of (1) acetoacetic acid, (2) b-hydroxybutyric acid, and (3) acetone, the three compounds known collectively as ketone bodies.

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