Clinical Chemistry (Lipids and Lipoproteins) Flashcards
179-211 (33 cards)
Bile acids that are synthesized in the liver are derived from what substance?
A. Bilirubin
B. Fatty acid
C. Cholesterol
D. Triglyceride
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 in the 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
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 a change 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
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
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
Blood specimens for lipid studies should be drawn in the fasting state at least 9 to 12 hours after eating. Although fat ingestion only slightly
affects cholesterol levels, the triglyceride results are greatly affected. Triglycerides peak at about 4 to 6 hours after a meal, and these exogenous lipids should be cleared from the plasma before analysis. 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
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
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
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
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 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. B-Hydroxybutyric acid
C. Lactic acid
D. Oxaloacetic 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, 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
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
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
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
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
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
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 surfactant/albumin ratio by fluorescence polarization is performed to assess what physiological state?
A. Hyperlipidemia
B. Coronary artery disease
C. Hemolytic disease of the newborn
D. Fetal lung maturity
D
Respiratory distress syndrome (RDS), also referred to as hyaline membrane disease, is commonly seen in preterm infants. A deficiency of pulmonary surfactant causes the infant’s alveoli to collapse during expiration, resulting in improper oxygenation of capillary blood in the alveoli. Currently, the surfactant/albumin ratio by fluorescence polarization is performed using amniotic fluid to assess fetal lung maturity. The amniotic fluid is mixed with a fluorescent dye. When the dye binds to albumin there is a high polarization, and when the dye binds to surfactant there is a low polarization. Thus the surfactant/albumin ratio is determined. The units are expressed as milligrams of surfactant per gram of albumin, with fetal lung maturity being sufficient with values greater than 50 mg/g. Older methodologies have employed the determinations of phosphatidylglycerol, foam stability, and lecithin/sphingomyelin (L/S) ratio. The L/S ratio is based on the physiological levels of lecithin and sphingomyelin. Lecithin is a surfactant that prepares lungs to expand and take in air. Sphingomyelin is incorporated into the myelin sheath of the central nervous system of the fetus. The amounts of lecithin and sphingomyelin produced during the first 34 weeks of gestation are approximately equal; however, after the 34th week, the amount of lecithin synthesized greatly exceeds that of sphingomyelin. At birth, an L/S ratio of 2:1 or greater would indicate sufficient lung maturity
The VLDL fraction primarily transports what substance?
A. Cholesterol
B. Chylomicron
C. Triglyceride
D. Phospholipid
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 175mg/dL 74-99 mg/dL
HbA1C 8.1% 4-6%
Total cholesterol 272 mg/dL <200mg/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/dL 0.3-8.6 mg/L,
<1.0 mg/L low risk
Based on the patient’s test results, history,
and symptoms, which of the laboratory
values in the chart above does not support
the patient’s diagnosis?
A. LDL cholesterol
B. HDL cholesterol
C. Hemoglobin Ai c
D. hs-CRP
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
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 in HDL, 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
Both the direct and the heparin sulfate manganese 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
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.
