[MCQs] Cardiology and Pulmonology Quiz (20 test)

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Cardiovascular and Respiratory Systems - Cardiology and Pulmonology (20 test)

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Question 1

A 22-year-old Hispanic male college student with a normal medical history collapses during an intramural soccer game. His friends think he is joking, then notice his blue color and call an ambulance. Resuscitation is unsuccessful and the autopsy reveals dilated cardiac chambers with increased thickness of the ventricular walls (hypertrophic, dilated cardiomyopathy). Electron microscopy of the heart muscle shows abnormal thick filaments, and the pathologist suspects a genetic disorder. Genes encoding which of the following proteins would be most likely to reveal the causative mutation?

A	Keratin
B	Lamin
C	Myosin
D	Peripherin
E	Vimentin

Question 1 Explanation:

Incorrect answers a-b and d-e are intermediate filament proteins that anchor the cytoskeleton. Cardiac and skeletal muscles are similar in that both are striated and contain two kinds of interacting protein filaments. The thick filaments (15 nm in diameter) contain primarily myosin, while the thin filaments (7 nm in diameter) contain actin, troponin, and tropomyosin. The thick and thin filaments slide past one another during muscle contraction. Myosins are a family of proteins with heavy and light chains, and muscle myosins function as ATPases that bind to thin filaments during contraction. A particular cardiomyopathy (MIM*160760) is caused by mutations in the myosin heavy chain 7 gene, one of many causes of acute lifethreatening events (ALTEs) that can affect previously asymptomatic adults. ALTE are adult equivalents of sudden infant death syndrome (SIDS) or, more inclusively, sudden unexplained death syndrome (SUDS) that affect children. Congenital defects in muscle filaments, potassium channels, and the like, that affect cardiac contractility are substantial contributors to these tragic and unexpected disease categories—important reasons for annual and transitional (sports, precollege) physical examinations.

Question 2

A 65-year-old obese Caucasian male presents with pain radiating down the left arm and shortness of breath. A serum lactate dehydrogenase (LDH) level is obtained to evaluate possible myocardial infarction, and its activity is only slightly elevated. Shortly thereafter the laboratory calls, saying that a more detailed analysis of LDH does suggest myocardial damage. The managing physician knows that lactate dehydrogenase is composed of two different polypeptide chains arranged in the form of a tetramer. Which of the following is the likely correlation between LDH measures and the likelihood of myocardial infarction?

A	LDH is an enzyme specific to the endocardium.
B	LDH is mainly localized in liver, and its elevation in cardiac disease occurs because of heart failure.
C	LDH isozymes are composed of different subunit combinations, some released during inflammation following heart attacks.
D	LDH isozymes are composed of different subunit combinations, some specific for heart and released with myocardial damage.
E	LDH isozymes are composed of different subunit combinations, some specific for vascular endothelium and released with infarction.

Question 2 Explanation:

Isozymes are multiple forms of a given enzyme that occur within a given species. Since isozymes are composed of different proteins, analysis by electrophoretic separation can be done. Lactate dehydrogenase is a tetramer composed of any combination of two different polypeptides, H and M. Thus, the possible combinations are H4, H3M1, H2M2, H1M3, and M4. Although each combination is found in most tissues, M4 predominates in the liver and skeletal muscle, whereas H4 is the predominant form in the heart. White and red blood cells as well as brain cells contain primarily intermediate forms. The M4 forms of the isozyme seem to have a higher affinity for pyruvate compared with the H4 form. Following a myocardial infarction, the H4 (LDH1) type of lactate dehydrogenase rises and reaches a peak approximately 36 hours later. Elevated LDH1 levels (increased H4 relative to other isoforms) may signal myocardial disease even when the total lactate dehydrogenase level is normal.

Question 3

A 28-year-old Caucasian female presents to her obstetrician at week 23 of pregnancy, complaining of extreme fatigue. Evaluations of serum iron level and fetal well-being are normal, but the nurse notices a weak and irregular pulse. Chest x-ray reveals an enlarged heart and the electrocardiogram reveals a short PR interval and prolonged QRS interval, including a slurred-up stroke of the R wave called a delta wave. The ECG is read as showing Wolff-Parkinson-White syndrome, a condition with risks for paroxysmal supraventricular tachycardia. The physician considers treatment with calcium channel regulators, balancing their risks to mother and fetus. Contraction of cardiac and skeletal muscle is initiated by the binding of calcium to which of the following substances?

A	Actin
B	Actomyosin
C	Myosin
D	Tropomyosin
E	Troponin

Question 3 Explanation:

Calcium ions are the regulators of contraction of skeletal muscle. Calcium is actively sequestered in sarcoplasmic reticulum by an ATP pump during relaxation of muscle. Nervous stimulation leads to the release of calcium into the cytosol and raises the concentration from less than 1 mM to about 10 mM. The calcium binds to troponin C. The calcium-troponin complex undergoes a conformational change, which is transmitted to tropomyosin and causes tropomyosin to shift position. The shift of tropomyosin allows actin to interact with myosin and contraction to proceed. Mutations affecting proteins involved in muscle contraction can present with low muscle tone and developmental delay in childhood, as chronic muscle cramps or fatigue, or with cardiomyopathies due to weakened heart muscle. Since cardiac muscle contraction is coordinated by electrical conduction from the sinus and atrioventricular nodes, muscle protein abnormalities can also interfere with cardiac rhythm. A specific mutation in troponin I can cause cardiomyopathy and the irregular cardiac rhythm known as Wolff-Parkinson-White syndrome (MIM*600858).

Question 4

A 43-year-old Caucasian male is rushed to the hospital with crushing chest pain radiating to his left arm and a probable heart attack. His cholesterol is 420 mg/dL despite prior use of statin medicines and he has familial hypercholesterolemia (MIM*143890). Which of the following treatments should be considered?

A	A platelet transfusion
B	Heparin infusion
C	Thrombin infusion
D	Fibrinogen infusion
E	Tissue plasminogen activator infusion

Question 4 Explanation:

Many enzymes interact to regulate blood clotting. Plasmin is activated by proteolytic cleavage of its zymogen, plasminogen. The activating protease is called tissue plasminogen activator (tPA). Plasmin hydrolyzes fibrin clots to form soluble products and is used to dissolve clots in coronary arteries that cause myocardial infarction. Platelets, thrombin, and fibrinogen promote clotting through the intrinsic pathway and would be contraindicated in myocardial infarction. Platelets form a plug at the site of bleeding and bind prothrombin to facilitate its conversion to thrombin. Fibrinogen is the substrate acted on by thrombin to yield the fibrin mesh of blood clots. Heparin is a mucopolysaccharide that terminates clot formation by interfering with a number of steps in the coagulation cascade. Heparin inhibits the formation of clots, but cannot dissolve clots that have already formed.

Question 5

After a term uncomplicated gestation, normal delivery, and unremarkable nursery stay, a 10-day-old African American girl is readmitted to the hospital because of poor feeding, weight loss, and rapid heart rate. Antibiotics are started as a precaution against sepsis, and initial testing indicates an unusual echocardiogram with a very short PR interval and a large heart on x-ray. Initial concern about a cardiac arrhythmia changes when a large tongue is noted, causing concern about glycogen storage disease type II (Pompe disease—MIM*232300). Which of the following best explains why Pompe disease is more severe and lethal compared to other glycogen storage diseases?

A	The deficiency is a degradative rather than synthetic enzyme
B	The deficiency involves a liver enzyme
C	The deficiency involves a lysosomal enzyme
D	The deficiency causes associated neutropenia
E	The deficiency involves a serum enzyme

Question 5 Explanation:

Pompe disease has an early and severe onset compared to the other glycogen storage diseases listed in High-Yield Facts, Table 3 because the defective α-glucosidase is a lysosomal enzyme. Accumulation of substances in the lysosome often leads to a more severe and progressive course, illustrated by the mucopolysaccharidoses like Hurler syndrome (MIM*607014) or the neurolipi doses like Tay-Sachs disease (MIM*272800). Patients with Pompe disease exhibit lysosomal glycogen accumulation in muscle (muscle weakness or hypotonia), brain (with developmental retardation), and heart (with a short PR interval and heart failure). The other glycogen storage diseases lead to glycogen accumulation in liver or muscle with correspondingly milder symptoms.

Question 6

A 35-year-old African American male has avoided health care but presents to his physician because his father recently died of a heart attack at age 55. The physician obtains a serum cholesterol of 320 mg/dL and a serum lipoprotein profile. Which of the following describes the order of lipoproteins from lowest to highest density along with the likely levels (↑ = elevated, ↓ = decreased) in this patient if his blood is drawn 30 minutes after breakfast?

A	HDLs ↓ LDLs ↑ IDLs ↑ VLDLs ↑ chylomicrons ↓
B	Chylomicrons ↑ VLDLs ↑ IDLs ↑ LDLs ↑ HDLs ↓
C	VLDLs ↓ IDLs ↓ LDLs ↓ chylomicrons ↓ HDLs ↓
D	HDLs ↑ Chylomicrons ↑ IDLs ↑ VLDLs T LDLs ↑
E	LDLs ↑ VLDLs ↑ IDLs ↑ chylomicrons ↑ HDLs ↑

Question 6 Explanation:

Serum lipoproteins bind lipids and transport various lipid components from intestine and liver to peripheral tissues. Chylomicrons have the highest fat content and thus the lowest density, followed by very low density (VLDL), intermediate-density (IDL), lowdensity (LDL), and several high/very high density (HDL/VHDL) lipoproteins (incorrect answers a, c-e). Chylomicrons transport triglycerides and other lipids absorbed from the intestine and thus are elevated after a meal (incorrect answers a, c). Very low density lipoproteins (VLDLs) are triglyceride- and cholesterolcontaining particles from the liver; removal of triglycerides from VLDLs leads to formation of intermediate forms (IDLs) and finally to a cholesterol-enriched small particle, the low-density lipoprotein (LDL). VLDL, IDL, and LDL fractions all contain cholesterol and will be elevated in patients with hypercholesterolemia (incorrect answer c). Table 4 in the High-Yield Facts summarizes the characteristics of these plasma lipoproteins.

Question 7

Which of the following best explains why statin therapy is effective for individuals with hypercholesterolemia?

A	Statins inhibit HMG-CoA reductase, a key regulator of cholesterol synthesis.
B	Statins inhibit HMG-CoA synthase, key step for synthesis of mevalonate that inhibits fatty acid synthesis.
C	Stains stimulate thiolase, thus making more malonyl-CoA for inhibition of the tricarboxylic acid cycle.
D	Statins bind to LDL receptor, displacing cholesterol and inhibiting cholesterol synthesis.
E	Statins stimulate synthesis of trans-unsaturated fatty acids.

Question 7 Explanation:

Cholesterol is formed in five steps. The first step, biosynthesis of mevalonate, is catalyzed by three enzymes—acetyl-CoA thiolase, HMG-CoA synthase, and HMG-CoA reductase. Thiolase catalyzes the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA. HMG-CoA synthase catalyzes the addition of a third molecule of acetyl-CoA to form HMG-CoA. This compound is reduced to mevalonate by HMG-CoA reductase. This enzyme is the rate-limiting and thus principal regulatory step in the pathway. In the second step of cholesterol synthesis, mevalonate is phosphorylated and decarboxylated to produce isopentyl diphosphate. Six of these isoprenoid units are condensed to form squalene in the third step. Lanosterol is formed in the fourth step and is subsequently converted to cholesterol. Malonyl-CoA is a 3-carbon acyl-CoA that condenses with acetyl-CoA to initiate fatty acid synthesis. Malonate does inhibit the Krebs tricarboxylic acid cycle at the step from succinate to fumarate and may have an important role in diabetes mellitus.

Question 8

Coronary artery disease is a multifactorial disorder involving occlusion of the coronary artery with atherosclerotic plaques. Several Mendelian disorders affecting lipid metabolism increase susceptibility for heart attacks, while environmental factors include smoking and high-fat diets. A 45-year-old Caucasian male has a mild heart attack and is placed on diet and mevastatin therapy. Which of the following will be the most likely result of this therapy?

A	Low blood glucose
B	Low blood LDLs
C	High blood cholesterol
D	High blood glucose
E	Low oxidation of fatty acids

Question 8 Explanation:

The lowering of cholesterol by mevastatin lowers amounts of the lipoprotein that transports cholesterol to the peripheral tissues, low-density lipoprotein (LDL). Mevastatin, an analogue of mevalonic acid, acts as a feedback inhibitor of 3′-hydroxy-3′-methylglutaryl-CoA (HMG-CoA) reductase, the regulated enzyme of cholesterol synthesis. Effective treatment with mevastatin, along with a low-fat diet, decreases levels of blood cholesterol and will not have immediate effects on glucose levels or fatty acid oxidation (incorrect answers a, c-e). Because lipids like cholesterol and triglycerides are insoluble in water, they must be associated with lipoproteins for transport and salvage between their major site of synthesis (liver) and the peripheral tissues. Those lipoproteins associated with more insoluble lipids thus have lower density during centrifugation, a technique that separates the lowest-density chylomicrons from very low density lipoproteins (VLDLs with pre-β-lipoproteins), low-density lipoproteins (LDLs with β- lipoproteins), intermediate density lipoproteins (IDLs), and high-density lipoproteins (HDLs with α-lipoproteins). Each type of lipoprotein has typical apolipoproteins such as the apo B-100 and apo B-48 (translated from the same messenger RNA) in LDL. LDL is involved in transporting cholesterol from the liver to peripheral tissues, whereas HDL is a scavenger of cholesterol. The ratio of HDL to LDL is thus a predictor of cholesterol deposition in blood vessels, the cause of myocardial infarctions (heart attacks). The higher the HDL/LDL ratio, the lower the rate of heart attacks.

Question 9

A 6-year-old African American boy is evaluated for respiratory distress from refractory asthma and improves after albuterol inhalation therapy He is discharged with instructions to continue albuterol nebulizer treatments and is given 2 mg/kg oral prednisolone as a 5-day burst. This therapy avoids the side effects of chronic steroid therapy (obesity, hypertension, and shock susceptibility) by using short bursts of oral therapy or inhaled steroids that affect nasal/bronchial membranes without systemic absorption. Steroid therapies impact which of the following processes?

A	Conversion of membrane arachidonyl-triglyceride to arachidonic acid
B	Conversion of arachidonic acid to leukotrienes
C	Conversion of arachidonic acid to prostaglandins
D	Peroxidation of prostaglandin precursor
E	Dietary absorption of arachidonic acid

Question 9 Explanation:

Anti-inflammatory steroids act at many metabolic sites that include inhibition of phospholipase A2 (incorrect answers b-e). This enzyme is responsible for hydrolyzing arachidonyl-glycerol ester that is found at the second position of some membrane glycerophospholipids. Corticosteroids induce the phospholipase A2-inhibitory protein lipocortin and inhibit production of all of the derivatives of arachidonic acid (lipoxins, leukotrienes, thromboxanes, and prostaglandins). Steroids also inhibit inflammatory signal transduction pathways as shown in Fig. 20 of the High-Yield facts. Arachidonic acid liberated from membrane phospholipids (stimulated by epinephrine, angiotensin II, etc) or absorbed from the diet is converted to prostaglandin by cyclooxygenase components of prostaglandin synthase. (COX I, II—inhibited by nonsteroidal anti-inflammatory drugs [NSAIDs] such as aspirin, indomethacin, and ibuprofen.) The prostaglandin precursor can be converted to thromboxanes active in platelets or prostacyclins. Alternatively, lipoxygenases act on arachidonic acid to produce lipoxins and leukotrienes.

Question 10

Congestive heart failure can be caused by intrinsic defects of the heart muscle/valves or by pumping against increased pressure as with prolonged hypertension. Which of the following effects of the steroid digitalis is observed after treatment of congestive heart failure?

A	Decrease in cytosolic sodium levels
B	Inhibition of Na+, K+-ATPase
C	Decrease in the force of heart muscle contraction
D	Stimulation of the plasma membrane ion pump
E	Decrease in cytosolic calcium

Question 10 Explanation:

Treatment of patients with congestive heart failure is often based on the use of cardiotonic steroids such as digitalis. Digitalis is derived from the foxglove plant and has been used as a herbal treatment for heart problems since ancient times. Digitalis and ouabain are cardiotonic steroids that inhibit the Na+, K+-ATPase pump located in the plasma membrane of cardiac muscle cells. They specifically inhibit the dephosphorylation reaction of the ATPase when the cardiotonic steroid is bound to the extracellular face of the membrane. Because of inhibition of the pump, higher levels of sodium are left inside the cell, leading to a diminished sodium gradient. This results in a slower exchange of calcium by the sodium-calcium exchanger. Subsequently, intracellular levels of calcium are maintained at a higher level and greatly enhance the force of contraction of cardiac muscle.

Question 11

A 40-year-old Caucasian female is stung by a bee and rushed into the emergency room with a variety of symptoms including increasing difficulty in breathing due to nasal and bronchial constriction. Although your subsequent treatment is to block the effects of histamine and other acute-phase reactants released by most cells, you must also block the slow-reacting substance of anaphylaxis (SRS-A), which is the most potent constrictor of the muscles enveloping the bronchial passages. An SRS-A is composed of which of the following?

A	Thromboxanes
B	Interleukins
C	Complement
D	Leukotrienes
E	Prostaglandins

Question 11 Explanation:

Leukotrienes C4, D4, and E4 together compose the slow-reacting substance of anaphylaxis (SRSA), which is thought to be the cause of asphyxiation in individuals not treated rapidly enough following an anaphylactic shock. SRS-A is up to 1000 times more effective than histamines in causing bronchial muscle constriction. Anti-inflammatory steroids are usually given intravenously to end chronic bronchoconstriction and hypotension following a shock. The steroids block phospholipase A2 action, preventing the synthesis of leukotrienes from arachidonic acid. Acute treatment involves epinephrine injected subcutaneously, initially, and then intravenously. Antihistamines such as diphenhydramine are administered intravenously or intramuscularly.

Question 12

A 23-year-old Caucasian female with cystic fibrosis (MIM*219700) marries her first cousin. What is the risk that their first child will have cystic fibrosis?

A	1/2
B	1/4
C	1/8
D	1/16
E	1/32

Question 12 Explanation:

The McKusick number for cystic fibrosis (MIM*219700) begins with 2, indicating an autosomal recessive disorder. The genotype of the affected female with cystic fibrosis is therefore best represented as the two lowercase letters cc. Her parents are obligate carriers for the disorder (genotypes Cc), and one of her grandparents must also be a carrier (barring new mutations). Her first cousin then has a one-fourth chance of being a carrier, since one of their common grandparents is a carrier, one of his parents has a one-half chance of being a carrier, and he has a one-half chance of inheriting the c allele from his parent. The affected female can only transmit c alleles to her fetus, while her cousin has one-half chance of transmitting his c allele if it is present. Thus, the probability that the first child will have cystic fibrosis is one-fourth (cousin is carrier) × one-half (cousin transmits c allele) = one-eighth (fetus has cc genotype).

Question 13

A 23-year-old Caucasian male whose brother has cystic fibrosis (MIM*219700) wants to know his risk of having an affected child. The prevalence of cystic fibrosis is 1 in 1600 individuals. Which of the following is the risk in this case?

A	1/8
B	1/16
C	1/60
D	1/120
E	1/256

Question 13 Explanation:

According to the Hardy-Weinberg equilibrium, where p is the frequency of the normal allele and q that of the abnormal, p = q = 1, and thus the combinations of gametes p and q will be (p + q)2 = p2 + 2pq + q2 also = 1. The frequency of heterozygotes (2pq) is twice the square root of the rare homozygote frequency (q2). The male in the question has a two-thirds chance of being a carrier. His wife has a one-twentieth chance of being a carrier. The rare homozygote frequency is 1/600, so the square root is 1/40 and the frequency of heterozygotes is thus 2 × 1/40 = 1/20. His risk for an affected child is 2/3 × 1/20 × ¼ = 1/20.

Question 14

A 22-year-old Caucasian female who married her first cousin wants to know the risk of having a child with cystic fibrosis (MIM*219700) because her grandmother, who is also her husband’s grandmother, died of cystic fibrosis. Which of the following is her risk?

A	1/8
B	1/16
C	1/60
D	1/120
E	1/256

Question 14 Explanation:

The grandmother has cystic fibrosis, so her children are obligate carriers. Each cousin therefore has a onehalf chance of being a carrier. The female’s risk is ½ × ½ × ¼ = 1/16 chance of having an affected child. This illustrates the effects of consanguinity.

Question 15

A 32-year-old Caucasian male of Scandinavian origin exhibits increased fatigue with shortness of breath during his usual jogging routine. His physician suspects early-onset emphysema and performs protein electrophoresis for analysis of α1-antitrypsin (AAT) deficiency (MIM*107400). The result shows two electrophoretic bands that react with AAT, one at the normal position, and one at an abnormal position. Which of the following best describes this result?

A	The male is homozygous and has normal AAT activity
B	The male is heterozygous and has normal AAT activity
C	The male is homozygous and has deficient AAT activity
D	The male is homozygous and has an altered AAT protein
E	The male is heterozygous and has an altered AAT protein

Question 15 Explanation:

Serum protein electrophoresis separates proteins according to their structure and charge. Two bands for AAT (α1-antitrypsin deficiency-MIM*107400) in this male imply that two types of AAT protein with different structures or charges are present. The electrophoresis does not reveal whether the abnormal AAT protein has normal or abnormal activity (incorrect answers a-c). The McKusick number indicates that AAT deficiency is an autosomal dominant, single gene disorder, implying paired alleles at a single AAT locus. The male is thus heterozygous, one allele encoding a normal and the other an abnormal protein (incorrect answer d). The AAT locus is located on chromosome 14 within a family of protease inhibitors called serpins. Altered AAT proteins termed M, S, or Z variants have normal inhibitory activity but are defective in their rates of secretion across the liver membrane into the blood. Lower levels of AAT protein apparently expose lung proteins to damage, causing emphysema. Heterozygotes are usually not affected, so the male may have emphysema because of cigarette smoking or other factors. Homozygous ZZ individuals may have liver disease in addition to lung disease because the abnormally secreted AAT accumulates in liver cells.

Question 16

A 45-year-old male is hospitalized for treatment of myocardial infarction. His father and a paternal uncle also had heart attacks at an early age. His cholesterol is elevated, and lipoprotein electrophoresis demonstrates an abnormally high ratio of low- to high-density lipoproteins (LDL to HDL). Which of the following is the most likely explanation for this problem?

A	Mutant HDL is not responding to high cholesterol levels.
B	Mutant LDL is not responding to high cholesterol levels.
C	Mutant caveolae proteins are not responding to high cholesterol levels.
D	Mutant LDL receptors are deficient in cholesterol uptake.
E	Intracellular cholesterol is increasing the number of LDL receptors.

Question 16 Explanation:

This male has familial hypercholesterolemia (MIM*143890), an autosomal dominant phenotype defined by studying males who experienced heart attacks at young ages. Mutations in the LDL receptor lead to decreased cellular cholesterol uptake and increased serum cholesterol. Since LDL has a high cholesterol content, the LDL fraction is elevated compared to the HDL fraction on lipoprotein electrophoresis. In normal individuals, the LDL is taken up by its specific receptor and imported via caveolae to the cell interior. Cholesterol then produces feedback inhibition on the rate-limiting enzyme of cholesterol synthesis (hydroxymethylglutaryl-CoA reductase) and also leads to a decrease in the number of LDLreceptors. In rare cases, two individuals with familial hypercholesterolemia marry and produce a child with homozygous familial hypercholesterolemia. These children develop severe atherosclerosis and xanthomas (fatty tumors) at an early age.

Question 17

A patient with myocardial infarction is treated with nitroglycerin to dilate his coronary arteries. Which of the following best describes the action of nitroglycerin?

A	Methylation occurs to produce S-adenosylmethionine.
B	GTP hydrolysis accomplishes oxidation of LDL proteins.
C	Arginine is converted to a neurotransmitter that activates guanyl cyclase.
D	Acetyl-CoA and choline are condensed to form a neurotransmitter.
E	Tyrosine is converted to serotonin.

Question 17 Explanation:

Nitroglycerin causes release of nitric oxide (NO), which activates guanyl cyclase, produces cyclic GMP, and causes vasodilation. NO is formed from one of the guanidino nitrogens of the arginine side chain by the enzyme nitric oxide synthase. NO has a short half-life, reacting with oxygen to form nitrite and then nitrates that are excreted in urine. Coronary vasodilation caused by nitroglycerin is thus short-lived, making other measures necessary for long-term relief of coronary occlusion. The neurotransmitter formed by condensation of acetyl-CoA and choline is acetylcholine, which does not play a role in dilation of coronary arteries.

Question 18

A male is evaluated for mild liver disease, arthritis, fatigue, and grayish skin pigmentation. A liver biopsy shows marked increase in iron. Which of the following laboratory values is most likely?

A	Low serum iron
B	High serum copper
C	Low saturation of transferrin
D	High serum ferritin
E	Low serum haptoglobin

Question 18 Explanation:

The male has symptoms of hemochromatosis (MIM*235200), an autosomal recessive disorder with increased iron absorption from the small intestine. There is increased serum iron, higher saturation of transferrin, and increased amounts of ferritiniron complex so that it appears in serum. The red cell lifetime is normal in hemochromatosis, resulting in normal release of hemoglobin and normal serum haptoglobin. Hemochromatosis is caused by mutations at a locus in the histocompatibility region of chromosome 6; the protein product is localized to the small intestine and influences iron absorption by an unknown mechanism.

Question 19

The regulation of transferrin receptors is studied in tissue culture. There is increased synthesis of transferrin receptor protein with no changes in transferrin mRNA transcription. Which of the following is the most plausible explanation?

A	Change in amounts or types of transcription factors
B	Allosteric regulation of transferrin receptor function
C	Activation of transferrin receptor function by a protein kinase
D	Stabilization of transferrin mRNA
E	Increased GTP levels to accelerate protein elongation

Question 19 Explanation:

The regulation of mammalian gene expression is selective: specific genes are up- or down-regulated by controls at the gene dosage, mRNA transcription, mRNA splicing, mRNA stability, or protein function levels. Under conditions of iron deficiency, transferrin receptor mRNA is stabilized so that more protein is synthesized. Regulation thus occurs at the protein translation level, without changes in transferrin mRNA transcription through transcription factors or transferrin receptor activity through interaction with small molecules (allostery) or through phosphorylation by protein kinases. Overall increases in rates of RNA transcription or protein elongation are not employed for gene regulation by mammalian cells.

Question 20

The development of DNase therapy has dramatically improved survival and therapy of lung infections in children with cystic fibrosis (MIM*219700). Early diagnosis also allows supplementation of missing pancreatic enzymes with better lipid absorption and improved IQ measures. Over 97 common mutant alleles for Caucasians with cystic fibrosis have now been characterized at the DNA level, allowing screening of pregnant couples with high sensitivity. Which of the following techniques is used to screen couples and newborns for cystic fibrosis?

A	Fluorescent in situ hybridization (FISH) for deletions surrounding the disease locus
B	Subtelomeric FISH analysis
C	Multiplex PCR with high sensitivity
D	Southern analysis to display mutant alleles
E	Comparative genomic hybridization (CGH)-microarray analysis

Question 20 Explanation:

Multiple polymerase chain reaction (PCR) primers targeting regions of the cystic fibrosis gene known to contain mutations (multiplex PCR) are used for cystic fibrosis screening of adults and newborns. Comparative genomic hybridization (CGH), also known as microarray analysis, uses DNA arrays or chips containing 40-100,000 DNA segments affixed to microbeads or glass slides, hybridized in duplicate to control and patient DNAs, and passed through machines for reading of excess hybridization (duplicated DNA segments) or deficiencies (deleted DNA segments—incorrect answer e). Microarray analysis essentially provides a high-resolution karyotype and is defining subtle chromosome aberrations in patients with disorders like autism or learning disabilities. Fluorescent in situ hybridization may employ control and test labeled DNA probe to highlight their specific locus on a chromosome, showing two signals for individuals with paired autosomes. An absence of test signal on one chromosome when the control signal is present shows there is a submicroscopic deletion as in the DiGeorge or Williams syndromes (incorrect answer a). Subtelomere FISH analysis extends this to many DNA probes, highlighting all 44 autosome and the two X chromosome ends—subtle rearrangements will shift the position of the FISH signal, and deletions or duplications involving a target region will yield a missing or extra signal (incorrect answer b). Southern analysis is labor intensive and has limited use in this era of automated allele detection and DNA sequencing (incorrect answer d). Advances in rapid DNA sequencing may soon allow screening for multiple genetic diseases in patients, detecting DNA markers of risk or mutations that cause disease—an example is the threefold coverage of DNA pioneer James Watson’s DNA in several weeks for a million dollars (50 years from discovering DNA structure to a genome sequence for the discoverer’). Complicating the clinical applications of total genomic sequencing (personalized medicine, prenatal or newborn screening) is the enormous amount of variation; distinguishing diseases from traits and false from true positives will be enormously difficult. Another problem is exemplified by current expanded newborn screening where as many as 60 inborn errors of metabolism can be detected, many of which cannot be treated effectively. Such detection violates the prime justification for screening: early or presymptomatic diagnosis should benefit the patient through treatment or planning.

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II. Preview all questions below

1. A 22-year-old Hispanic male college student with a normal medical history collapses during an intramural soccer His friends think he is joking, then notice his blue color and call an ambulance. Resuscitation is unsuccessful and the autopsy reveals dilated cardiac chambers with increased thickness of the ventricular walls (hypertrophic, dilated cardiomyopathy). Electron microscopy of the heart muscle shows abnormal thick filaments, and the pathologist suspects a genetic disorder. Genes encoding which of the following proteins would be most likely to reveal the causative mutation?

Keratin
Lamin
Myosin
Peripherin
Vimentin

2. A 65-year-old obese Caucasian male presents with pain radiating down the left arm and shortness of breath. A serum lactate dehydrogenase (LDH) level is obtained to evaluate possible myocardial infarction, and its activity is only slightly Shortly thereafter the laboratory calls, saying that a more detailed analysis of LDH does suggest myocardial damage. The managing physician knows that lactate dehydrogenase is composed of two different polypeptide chains arranged in the form of a tetramer. Which of the following is the likely correlation between LDH measures and the likelihood of myocardial infarction?

LDH is an enzyme specific to the
LDH is mainly localized in liver, and its elevation in cardiac disease occurs because of heart
LDH isozymes are composed of different subunit combinations, some released during inflammation following heart
LDH isozymes are composed of different subunit combinations, some specific for heart and released with myocardial
LDH isozymes are composed of different subunit combinations, some specific for vascular endothelium and released with

3. A 28-year-old Caucasian female presents to her obstetrician at week 23 of pregnancy, complaining of extreme Evaluations of serum iron level and fetal well-being are normal, but the nurse notices a weak and irregular pulse. Chest x-ray reveals an enlarged heart and the electrocardiogram reveals a short PR interval and prolonged QRS interval, including a slurred-up stroke of the R wave called a delta wave. The ECG is read as showing Wolff-Parkinson-White syndrome, a condition with risks for paroxysmal supraventricular tachycardia. The physician considers treatment with calcium channel regulators, balancing their risks to mother and fetus. Contraction of cardiac and skeletal muscle is initiated by the binding of calcium to which of the following substances?

Actin
Actomyosin
Myosin
Tropomyosin
Troponin

4. A 43-year-old Caucasian male is rushed to the hospital with crushing chest pain radiating to his left arm and a probable heart attack. His cholesterol is 420 mg/dL despite prior use of statin medicines and he has familial hypercholesterolemia (MIM*143890). Which of the following treatments should be considered?

A platelet transfusion
Heparin infusion
Thrombin infusion
Fibrinogen infusion
Tissue plasminogen activator infusion

5. After a term uncomplicated gestation, normal delivery, and unremarkable nursery stay, a 10-day-old African American girl is readmitted to the hospital because of poor feeding, weight loss, and rapid heart rate. Antibiotics are started as a precaution against sepsis, and initial testing indicates an unusual echocardiogram with a very short PR interval and a large heart on x-ray. Initial concern about a cardiac arrhythmia changes when a large tongue is noted, causing concern about glycogen storage disease type II (Pompe disease—MIM*232300). Which of the following best explains why Pompe disease is more severe and lethal compared to other glycogen storage diseases?

The deficiency is a degradative rather than synthetic enzyme
The deficiency involves a liver enzyme
The deficiency involves a lysosomal enzyme
The deficiency causes associated neutropenia
The deficiency involves a serum enzyme

6. A 35-year-old African American male has avoided health care but presents to his physician because his father recently died of a heart attack at age The physician obtains a serum cholesterol of 320 mg/dL and a serum lipoprotein profile. Which of the following describes the order of lipoproteins from lowest to highest density along with the likely levels (↑ = elevated, ↓ = decreased) in this patient if his blood is drawn 30 minutes after breakfast?

HDLs ↓ LDLs ↑ IDLs ↑ VLDLs ↑ chylomicrons ↓
Chylomicrons ↑ VLDLs ↑ IDLs ↑ LDLs ↑ HDLs ↓
VLDLs ↓ IDLs ↓ LDLs ↓ chylomicrons ↓ HDLs ↓
HDLs ↑ Chylomicrons ↑ IDLs ↑ VLDLs T LDLs ↑
LDLs ↑ VLDLs ↑ IDLs ↑ chylomicrons ↑ HDLs ↑

7. Which of the following best explains why statin therapy is effective for individuals with hypercholesterolemia?

Statins inhibit HMG-CoA reductase, a key regulator of cholesterol
Statins inhibit HMG-CoA synthase, key step for synthesis of mevalonate that inhibits fatty acid
Stains stimulate thiolase, thus making more malonyl-CoA for inhibition of the tricarboxylic acid
Statins bind to LDL receptor, displacing cholesterol and inhibiting cholesterol
Statins stimulate synthesis of trans-unsaturated fatty

8. Coronary artery disease is a multifactorial disorder involving occlusion of the coronary artery with atherosclerotic Several Mendelian disorders affecting lipid metabolism increase susceptibility for heart attacks, while environmental factors include smoking and high-fat diets. A 45-year-old Caucasian male has a mild heart attack and is placed on diet and mevastatin therapy. Which of the following will be the most likely result of this therapy?

Low blood glucose
Low blood LDLs
High blood cholesterol
High blood glucose
Low oxidation of fatty acids

9. A 6-year-old African American boy is evaluated for respiratory distress from refractory asthma and improves after albuterol inhalation therapy He is discharged with instructions to continue albuterol nebulizer treatments and is given 2 mg/kg oral prednisolone as a 5-day This therapy avoids the side effects of chronic steroid therapy (obesity, hypertension, and shock susceptibility) by using short bursts of oral therapy or inhaled steroids that affect nasal/bronchial membranes without systemic absorption. Steroid therapies impact which of the following processes?

Conversion of membrane arachidonyl-triglyceride to arachidonic acid
Conversion of arachidonic acid to leukotrienes
Conversion of arachidonic acid to prostaglandins
Peroxidation of prostaglandin precursor
Dietary absorption of arachidonic acid

10. Congestive heart failure can be caused by intrinsic defects of the heart muscle/valves or by pumping against increased pressure as with prolonged Which of the following effects of the steroid digitalis is observed after treatment of congestive heart failure?

Decrease in cytosolic sodium levels
Inhibition of Na+, K+-ATPase
Decrease in the force of heart muscle contraction
Stimulation of the plasma membrane ion pump
Decrease in cytosolic calcium

11. A 40-year-old Caucasian female is stung by a bee and rushed into the emergency room with a variety of symptoms including increasing difficulty in breathing due to nasal and bronchial constriction. Although your subsequent treatment is to block the effects of histamine and other acute-phase reactants released by most cells, you must also block the slow-reacting substance of anaphylaxis (SRS-A), which is the most potent constrictor of the muscles enveloping the bronchial passages. An SRS-A is composed of which of the following?

Thromboxanes
Interleukins
Complement
Leukotrienes
Prostaglandins

12. A 23-year-old Caucasian female with cystic fibrosis (MIM*219700) marries her first cousin. What is the risk that their first child will have cystic fibrosis?

½
¼
1/8
1/16
1/32

13. A 23-year-old Caucasian male whose brother has cystic fibrosis (MIM*219700) wants to know his risk of having an affected The prevalence of cystic fibrosis is 1 in 1600 individuals. Which of the following is the risk in this case?

1/8
1/16
1/60
1/120
1/256

14. A 22-year-old Caucasian female who married her first cousin wants to know the risk of having a child with cystic fibrosis (MIM*219700) because her grandmother, who is also her husband’s grandmother, died of cystic Which of the following is her risk?

1/8
1/16
1/60
1/120
1/256

15. A 32-year-old Caucasian male of Scandinavian origin exhibits increased fatigue with shortness of breath during his usual jogging His physician suspects early-onset emphysema and performs protein electrophoresis for analysis of α1-antitrypsin (AAT) deficiency (MIM*107400). The result shows two electrophoretic bands that react with AAT, one at the normal position, and one at an abnormal position. Which of the following best describes this result?

The male is homozygous and has normal AAT activity
The male is heterozygous and has normal AAT activity
The male is homozygous and has deficient AAT activity
The male is homozygous and has an altered AAT protein
The male is heterozygous and has an altered AAT protein

16. A 45-year-old male is hospitalized for treatment of myocardial infarction. His father and a paternal uncle also had heart attacks at an early His cholesterol is elevated, and lipoprotein electrophoresis demonstrates an abnormally high ratio of low- to high-density lipoproteins (LDL to HDL). Which of the following is the most likely explanation for this problem?

Mutant HDL is not responding to high cholesterol
Mutant LDL is not responding to high cholesterol
Mutant caveolae proteins are not responding to high cholesterol
Mutant LDL receptors are deficient in cholesterol
Intracellular cholesterol is increasing the number of LDL

17. A patient with myocardial infarction is treated with nitroglycerin to dilate his coronary Which of the following best describes the action of nitroglycerin?

Methylation occurs to produce S-adenosylmethionine.
GTP hydrolysis accomplishes oxidation of LDL
Arginine is converted to a neurotransmitter that activates guanyl
Acetyl-CoA and choline are condensed to form a
Tyrosine is converted to

18. A male is evaluated for mild liver disease, arthritis, fatigue, and grayish skin pigmentation. A liver biopsy shows marked increase in Which of the following laboratory values is most likely?

Low serum iron
High serum copper
Low saturation of transferrin
High serum ferritin
Low serum haptoglobin

19. The regulation of transferrin receptors is studied in tissue There is increased synthesis of transferrin receptor protein with no changes in transferrin mRNA transcription. Which of the following is the most plausible explanation?

Change in amounts or types of transcription factors
Allosteric regulation of transferrin receptor function
Activation of transferrin receptor function by a protein kinase
Stabilization of transferrin mRNA
Increased GTP levels to accelerate protein elongation

20. The development of DNase therapy has dramatically improved survival and therapy of lung infections in children with cystic fibrosis (MIM*219700). Early diagnosis also allows supplementation of missing pancreatic enzymes with better lipid absorption and improved IQ measures. Over 97 common mutant alleles for Caucasians with cystic fibrosis have now been characterized at the DNA level, allowing screening of pregnant couples with high Which of the following techniques is used to screen couples and newborns for cystic fibrosis?

Fluorescent in situ hybridization (FISH) for deletions surrounding the disease locus
Subtelomeric FISH analysis
Multiplex PCR with high sensitivity
Southern analysis to display mutant alleles
Comparative genomic hybridization (CGH)-microarray analysis

[MCQs] Cardiology and Pulmonology Quiz (20 test)

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Cardiovascular and Respiratory Systems - Cardiology and Pulmonology (20 test)

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