• Pregnancy is associated with an increase in blood volume and cardiac output and a de-crease in systemic vascular resistance and mean arterial pressure; heart rate gradually increases d
Trang 1sure and therefore cannot be responsible for
the increased sympathetic drive when
hy-potension accompanies chronic heart failure
In addition, not all patients in chronic heart
failure are hypotensive; therefore, it is not
clear what drives the characteristic increase in
sympathetic activity in heart failure
Important humoral changes occur duringheart failure to help compensate for the re-
duction in cardiac output Arterial
hypoten-sion, along with sympathetic activation,
stimu-lates renin release, leading to the formation of
angiotensin II and aldosterone Vasopressin
(antidiuretic hormone) release from the
pos-terior pituitary is also stimulated Increased
vasopressin release seems paradoxical because
right atrial pressure is often elevated in heart
failure, which should inhibit the release of
sopressin (see Chapter 6) It may be that
va-sopressin release is stimulated in heart failure
by sympathetic activation and increased
an-giotensin II
These changes in neurohumoral status strict resistance vessels, which causes an in-
con-crease in systemic vascular resistance to help
maintain arterial pressure Venous
capaci-tance vessels constrict as well This increased
venous tone further increases venous
pres-sure Angiotensin II and aldosterone, along
with vasopressin, increase blood volume by
in-creasing renal reabsorption of sodium and
wa-ter This contributes to a further increase in
venous pressure, which increases cardiac
pre-load and helps to maintain stroke volumethrough the Frank-Starling mechanism.Increased right atrial pressure stimulates thesynthesis and release of atrial natriuretic peptide to counter-regulate the renin-angiotensin-aldosterone system These neuro-humoral responses function as compensatorymechanisms, but they can aggravate heart fail-ure by increasing ventricular afterload (whichdepresses stroke volume) and increasing pre-load to the point at which pulmonary or sys-temic congestion and edema occur
Exercise Limitations Imposed
by Heart Failure
Heart failure can severely limit exercise pacity In early or mild stages of heart failure,cardiac output and arterial pressure may benormal at rest because of compensatorymechanisms When the person in heart failurebegins to perform physical work, however, themaximal workload is reduced and he or sheexperiences fatigue and dyspnea at less thannormal maximal workloads
ca-A comparison of exercise responses in anormal person and in a heart failure patient isshown in Table 9-4 In this example, the de-gree of heart failure is moderate to severe Atrest, the person with congestive heart failure(CHF) has reduced cardiac output (decreased29%) caused by a 38% decrease in stroke volume Mean arterial pressure is slightly CARDIOVASCULAR INTEGRATION AND ADAPTATION 209
TABLE 9-4 COMPARISON OF CARDIOVASCULAR FUNCTION IN A NORMAL
PERSON AND A PATIENT WITH MODERATE-TO-SEVERE CONGESTIVE HEART FAILURE (CHF) AT REST AND AT MAXIMAL (MAX) EXERCISE
Trang 2con-decreased, and resting heart rate is elevated.
Whole-body oxygen consumption is normal at
rest, but the reduced cardiac output results in
an increase in the arterial-venous oxygen
dif-ference as more oxygen is extracted from the
blood because organ blood flow is reduced At
a maximally tolerated exercise workload, the
CHF patient can increase cardiac output by
only 50%, compared to a 221% increase in the
normal person The reduced cardiac output is
a consequence of the inability of the left
ven-tricle to augment stroke volume as well as a
lower maximal heart rate The CHF patient
has a significant reduction in arterial pressure
during exercise in contrast to the normal
per-son’s increase in arterial pressure Arterial
pressure falls because the increase in cardiac
output is not sufficient to maintain arterial
pressure as the systemic vascular resistance
falls during exercise The maximal whole-body
oxygen consumption is greatly reduced in the
CHF patient because reduced perfusion of
the active muscles limits oxygen delivery and
therefore the oxygen consumption of the
mus-cles The CHF patient experiences substantial
fatigue and dyspnea during exertion, which
limits the patient’s ability to sustain the
physi-cal activity
Some of the neurohumoral compensatory
mechanisms that operate to maintain resting
cardiac output in heart failure contribute to
limiting exercise capacity The chronic
in-crease in sympathetic activity to the heart
down-regulates 1-adrenoceptors, which
re-duces the heart’s chronotropic and inotropic
responses to acute sympathetic activation
dur-ing exercise Increased sympathetic activity
(and possibly circulating vasoconstrictors) to
the skeletal muscle vasculature limits the
de-gree of vasodilation during muscle
contrac-tion This limits oxygen delivery to the
work-ing muscle and leads to increased oxygen
extraction (increased arterial-venous oxygen
difference), enhanced lactic acid production
(and a lower anaerobic threshold), and muscle
fatigue at lower workloads The increase in
blood volume, although helping to maintain
stroke volume at rest through the
Frank-Starling mechanism, decreases the reserve
ca-pacity of the heart to increase preload duringexercise
Physiologic Basis for Therapeutic Intervention
Therapeutic goals in the pharmacologic ment of heart failure include (1) reducing theclinical symptoms of edema and dyspnea; (2)improving cardiovascular function to enhanceorgan perfusion and increase exercise capac-ity; and (3) reducing mortality
treat-Four pharmacologic approaches are taken
to achieve these goals The first approach is toreduce venous pressure to decrease edema andhelp relieve the patient of dyspnea Diureticsare routinely used to reduce blood volume byincreasing renal excretion of sodium and water.Drugs that dilate the venous vasculature (e.g.,angiotensin-converting enzyme inhibitors) alsocan reduce venous pressure Judicious use ofthese drugs to decrease blood volume and ve-nous pressure does not significantly reducestroke volume because the Frank-Starlingcurve associated with systolic failure is rela-tively flat at left ventricular end-diastolic pres-sures above 15 mm Hg (see Fig 9-8)
The second approach is to use drugs thatreduce afterload on the ventricle by dilatingthe systemic vasculature Drugs such as an-giotensin-converting enzyme inhibitors andangiotensin receptor blockers have proven to
be useful in this regard for patients withchronic heart failure Decreasing the afterload
on the ventricle can significantly enhancestroke volume and ejection fraction, whichalso reduces ventricular end-diastolic volume(preload) Because arterial vasodilators en-hance cardiac output in heart failure patients,the reduction in systemic vascular resistancedoes not usually lead to an unacceptable fall inarterial pressure
The third approach is to use drugs thatstimulate ventricular inotropy A commonlyused drug is digitalis, which inhibits the
Na/K- ATPase and thereby increases cellular calcium (see Chapter 2) This drug,however, has not been shown to reduce mor-tality associated with heart failure Drugs that
intra-210 CHAPTER 9
Trang 3stimulate 1-adrenoceptors (e.g., dobutamine)
or inhibit cAMP-dependent
phosphodi-esterase (e.g., milrinone) are sometimes used
as inotropic agents (see Chapter 3) With the
exception of digitalis, inotropic drugs are used
only in acute heart failure and end-stage
chronic failure because their long-term use
has been shown to be deleterious to the heart
The fourth therapeutic approach involvesusing -blockers Although this might seem
counterintuitive, many recent clinical trials
have clearly demonstrated the efficacy of
newer generation -blockers (e.g., carvedilol)
The mechanism of their efficacy is not clear,
but it is known that long-term sympathetic
ac-tivation of the heart is deleterious Therefore,
-blockers probably work by reducing the
deleterious actions of long-term sympathetic
activation Beta-blockers (as well as
an-giotensin-converting enzyme inhibitors)
pro-vide long-term benefit through ventricular
remodeling (e.g., reducing ventricular
hyper-trophy or dilation) Furthermore, -blockers
such as carvedilol significantly reduce ity in heart failure
mortal-It should be noted that the therapeutic proaches described above are nearly alwaysused in combination with a diuretic
ap-SUMMARY OF IMPORTANT CONCEPTS
• Dynamic exercise such as running is ated with a large fall in systemic vascularresistance owing to metabolic vasodilation
associ-in active skeletal muscle (i.e., active emia) To maintain (and elevate) arterialpressure, sympathetic activation increasescardiac output and constricts blood vessels
hyper-in the gastrohyper-intesthyper-inal tract, nonactive cles, and kidneys Skin blood flow increases
mus-to facilitate heat loss
• Adrenal release of catecholamines and tivation of the renin-angiotensin-aldo-sterone system contribute directly or indi-rectly to the cardiac stimulation and
ac-CARDIOVASCULAR INTEGRATION AND ADAPTATION 211
A patient is diagnosed with dilated cardiomyopathy The echocardiogram shows stantial left ventricular dilation (end-diastolic volume is 240 mL) and an ejection frac- tion of 20%; the arterial pressure is 115/70 mm Hg Calculate the stroke volume and end-systolic volume How would combined therapy with an angiotensin-converting en- zyme (ACE) inhibitor and diuretic alter ventricular volumes, ejection fraction, and arte- rial pressure?
sub-Given that the ejection fraction is 20% and the end-diastolic volume is 240 mL, thestroke volume is 48 mL/beat using the following relationship: stroke volume ejectionfraction x end-diastolic volume The end-systolic volume is the end-diastolic volume mi-nus the stroke volume, which equals 192 mL The administration of a diuretic woulddecrease the end-diastolic volume by decreasing blood volume The ACE inhibitorwould reinforce the effects of the diuretic on the kidney and also cause dilation of re-sistance and capacitance vessels These actions would further decrease end-diastolicpressure by decreasing venous pressure, and would reduce the afterload This latter ef-fect enhances stroke volume by decreasing the end-systolic volume and increasing thecardiac output The increased stroke volume and decreased end-diastolic volume wouldcause the ejection fraction to increase Although the ACE inhibitor would decrease sys-temic vascular resistance, the increased cardiac output might prevent arterial pressurefrom falling, or at least partially offset the pressure-lowering effect of systemic vasodi-lation
C A S E 9 - 3
Trang 4changes in vascular resistance that occur
during exercise
• Cardiovascular responses to exercise are
significantly influenced by the type of
exer-cise (dynamic versus static), body posture,
physical conditioning, altitude,
tempera-ture, age, and gender
• The skeletal muscle and abdominothoracic
pump systems, along with increased
ve-nous tone, facilitate veve-nous return during
exercise and prevent preload from falling
as heart rate and inotropy increase, thereby
enabling cardiac output to increase
• Pregnancy is associated with an increase in
blood volume and cardiac output and a
de-crease in systemic vascular resistance and
mean arterial pressure; heart rate gradually
increases during pregnancy
• Hypotension is most commonly caused by
a reduction in cardiac output, which can
result from heart failure, cardiac
arrhyth-mias, hemorrhage, dehydration, or
chang-ing from supine to standchang-ing position
Impaired baroreceptor reflexes (e.g.,
auto-nomic dysfunction associated with
dia-betes) or reduced systemic vascular
resis-tance as occurs in circulatory shock (e.g.,
septic shock) can also cause hypotension
• Negative feedback compensatory
mecha-nisms are triggered by hypotension, and
they help to restore arterial pressure
These mechanisms include baroreceptor
reflexes, renin-angiotensin-aldosterone
sys-tem activation, increased circulating
vaso-pressin (antidiuretic hormone), adrenal
re-lease of catecholamines, and enhanced
capillary fluid reabsorption
• Severe hypotension activates positive
feed-back mechanisms that can lead to
irre-versible shock and death These
mecha-nisms include cardiac depression caused by
myocardial ischemia and acidosis, vascular
escape from sympathetic vasoconstriction,
autonomic depression resulting from
cere-bral ischemia, rheological factors that
im-pair organ perfusion, and systemic
inflam-matory responses that damage tissues and
impair perfusion
• Hypertension can result from increases in
cardiac output or systemic vascular
resis-tance Impaired sodium and water tion by the kidneys, leading to increases inblood volume and cardiac output, appears
excre-to be a major facexcre-tor in the development ofessential hypertension, although increases
in systemic vascular resistance occur as thedisease progresses Conditions causing sec-ondary hypertension include renal arterystenosis, renal disease, primary hyperaldos-teronism, pheochromocytoma, aorticcoarctation, pregnancy, hyperthyroidism,and Cushing’s syndrome
• Hypertension can be controlled by drugsthat (1) reduce cardiac output (e.g., -block-ers, calcium-channel blockers); (2) decreasesystemic vascular resistance (e.g., -adreno-ceptor antagonists, calcium-channel block-ers, angiotensin-converting enzyme in-hibitors, angiotensin receptor blockers); and(3) reduce blood volume (e.g., diuretics)
• Heart failure occurs when the heart is able to supply adequate blood flow andthus oxygen delivery to peripheral tissuesand organs, or when it is able to do so only
un-at elevun-ated filling pressures It may involvesystolic dysfunction (depressed ventricularinotropy) or diastolic dysfunction The lat-ter is associated with reduced ventricularcompliance, often caused by hypertrophy
or impaired relaxation; this leads to paired filling
im-• Heart failure is associated with the ing cardiovascular changes and clinicalsymptoms: reduced stroke volume, re-duced ejection fraction (systolic dysfunc-tion), increased ventricular and atrial fillingpressures, increased blood volume, venouscongestion, pulmonary or systemic edema,increased systemic vascular resistance, hy-potension (depending upon severity),shortness of breath, fatigue, and reducedexercise capacity
follow-• The following compensatory mechanismsare activated during heart failure: sympa-thetic nervous system, renin-angiotensin-aldosterone system, atrial natriuretic pep-tide, and vasopressin The overall effect ofthese mechanisms is an increase in bloodvolume and systemic vascular resistance tohelp maintain arterial pressure
212 CHAPTER 9
Trang 5• Pharmacologic management of heart
fail-ure is directed toward the following: (1) ducing blood volume, venous congestion,and edema by using diuretics; (2) dilatingthe systemic vasculature to reduce after-load on the ventricle and thereby improvestroke volume and reduce preload; (3)stimulating the heart with positive in-otropic drugs to increase stroke volumeand reduce preload (particularly in acuteheart failure); and (4) reducing the delete-rious effects of chronic sympathetic activa-tion by using -blockers
re-Review Questions
Please refer to appendix for the answers to
the review questions.
For each question, choose the one best
answer:
1 During a moderate level of whole-body
exercise (e.g., running),
a Arterial pulse pressure decreasesowing to the elevated heart rate
b Sympathetic-mediated tion occurs in the skin
vasoconstric-c Systemic vascular resistance creases owing to sympathetic activa-tion
in-d Vagal influences on the sinoatrialnode are inhibited
2 One important reason why stroke
vol-ume is able to increase during runningexercise is that
a Central venous pressure decreases
b Heart rate increases
c The rate of ventricular relaxation creases
de-d Venous return is enhanced by themuscle pump system
3 Maximal cardiac output during exercise
a Decreases with age because of creased maximal heart rate andstroke volume
de-b Increases by exercise training owing
to increased maximal heart rates
c Is higher when exercising in a ing than in a supine position
stand-d Is higher with static than dynamicexercise
4 In an exercise study, the subject’s ing heart rate and left ventricularstroke volume were 70 beats/min and
rest-80 mL/beat, respectively While thesubject was walking rapidly on a tread-mill, the heart rate and stroke volumeincreased to 140 beats/min and 100mL/beat, respectively; ejection frac-tion increased from 60% to 75% Thesubject’s mean arterial pressure in-creased from 90 mm Hg at rest to 110
mm Hg during exercise One can clude that
con-a Cardiac output doubled
b Compared to rest, the cardiac put increased proportionately moreduring exercise than systemic vascu-lar resistance decreased
out-c Ventricular end-diastolic volume creased
in-d The increase in mean arterial sure during exercise indicates thatsystemic vascular resistance in-creased
pres-5 During pregnancy,
a Systemic vascular resistance is creased
in-b Heart rate is decreased
c Cardiac output is decreased
d Blood volume is increased
6 The baroreceptor reflex in hemorrhagicshock
a Decreases venous compliance
b Decreases systemic vascular tance
resis-c Increases vagal tone on the SA node
d Stimulates angiotensin II releasefrom the kidneys
7 Long-term recovery of cardiovascularhomeostasis following moderate hemor-rhage involves
a Aldosterone inhibition of renin lease
re-b Enhanced renal loss (excretion) ofsodium
c Increased capillary fluid filtration.CARDIOVASCULAR INTEGRATION AND ADAPTATION 213
Trang 6d Vasopressin-mediated water sorption by the kidneys.
reab-8 A mechanism that may contribute to
ir-reversible, decompensated hemorrhagic
shock is
a Diminished sympathetic-mediatedvasoconstriction
b Increased capillary fluid tion
reabsorp-c Myocardial depression by metabolicalkalosis
d Increased renin release by kidneys
9 Hypertension may result from
a Excessive nitric oxide production byvascular endothelium
b Low plasma concentrations of cholamines
cate-c Low plasma renin activity
d Decreased renal sodium excretion
10 One mechanism by which a -blocker
lowers blood pressure in a patient with
essential hypertension is by
a Dilating the systemic vasculature
b Increasing plasma renin activity
c Increasing ventricular preload
d Reducing heart rate
11 Left ventricular systolic failure is usually
associated with
a Decreased systemic vascular tance
resis-b Increased ejection fraction
c Increased left ventricular diastolic volume
end-d Reduced pulmonary capillary sures
pres-12 Compared to the maximal exercise
re-sponses of a normal subject, a patient
with moderate-to-severe heart failure
during maximal exercise will have a
a Lower arterial pressure
b Lower arterial-venous oxygen tion
extrac-c Higher ejection fraction
d Similar maximal oxygen tion
consump-13 Reducing afterload with an arterial sodilator in a patient diagnosed withheart failure
va-a Improves ventricular ejection tion
frac-b Increases stroke volume by ing preload
increas-c Reduces organ perfusion
d Reduces preload and cardiac output
SUGGESTED READINGS
Chapman AB, Abraham WT, Zamudio S, et al Temporal relationships between hormonal and hemodynamic changes in early human pregnancy Kidney Int 1998;54:2056–2063.
Chobanian AV, Bakris GL, Black HR, et al Joint National Committee on prevention, detection, evalu- ation, and treatment of high blood pressure: The JNC 7 report JAMA 2003;289:2560–2572.
Elkayam U Pregnancy and cardiovascular disease In Braunwald E, ed Heart Disease 5th Ed.
Philadelphia: W.B Saunders Company, 1997 Janicki JS, Sheriff DD, Robotham JL, Wise RA Cardiac output during exercise: contributions of the cardiac, circulatory, and respiratory systems In Rowell LB, Shepherd JT, eds Handbook of Physiology; Exercise: Regulation and Integration of Multiple Systems New York: Oxford University Press, 1996.
Hall JE The kidney, hypertension, and obesity Hypertension 2003;41:625–633.
Laughlin MH, Korthius RJ, Duncker DJ, Bache RJ Control of blood flow to cardiac and skeletal muscle during exercise In Rowell LB, Shepherd JT, eds Handbook of Physiology; Exercise: Regulation and Integration of Multiple Systems New York: Oxford University Press, 1996.
Lilly LS Pathophysiology of Heart Disease 3rd Ed Philadelphia: Lippincott Williams & Wilkins, 2003 Rowell LB, O’Leary DS, Kellogg DL: Integration of car- diovascular control systems in dynamic exercise In Rowell LB, Shepherd JT, eds Handbook of Physiology; Exercise: Regulation and Integration of Multiple Systems New York: Oxford University Press, 1996.
Wei JY Age and the cardiovascular system N Engl J Med 1992;327:1735–1739.
214 CHAPTER 9
Trang 7CHAPTER 1
1 The correct answer is “a” because blood
flow carries heat from the deep organswithin the body to the skin where the heatenergy can be given off to the environ-ment Choice “b” is incorrect because thepulmonary and systemic circulations are
in series Choice “c” is incorrect becausecarbon dioxide is transported from the tis-sues to the lungs Choice “d” is incorrectbecause blood transports oxygen from thelungs to the tissues
2 The correct answer is “d” because when
the volume per beat (stroke volume) ismultiplied by the number of beats perminute (heart rate), the units become vol-ume per minute, which is the flow out ofthe heart (cardiac output) Choice “a” isincorrect because the pulmonary veinsempty into the left atrium Choice “b” isincorrect because the left ventricle gener-ates much higher pressures than the rightventricle during contraction Choice “c” isincorrect because the right and left ven-tricles are in series
3 The correct answer is “a” because when a
person stands up, blood pools in the legs,reducing the filling of the heart, whichleads to a fall in cardiac output and arter-ial pressure Choice “b” is incorrect be-cause increased blood volume leads to anincrease in cardiac output and arterialpressure Choice “c” is incorrect becauseincreased cardiac output increases arterialpressure Choice “d” is incorrect becauseincreases in circulating angiotensin II andaldosterone increase arterial pressure byconstricting systemic blood vessels (an-giotensin II) and by acting on the kidneys
to increase blood volume (angiotensin IIand aldosterone)
CHAPTER 2
1 The correct answer is “d” because the colemmal Na/K-ATPase is an electro-genic pump that generates hyperpolariz-ing currents; inhibition of this pumpresults in depolarization Furthermore,inhibition of the pump leads to an in-crease in intracellular sodium and a de-crease in intracellular potassium, both ofwhich cause depolarization Choices “a”and “b” are incorrect because decreasedcalcium and sodium conductance reducesthe inward movement of positive chargesthat normally depolarize the membrane.Choice “c” is incorrect because increasedpotassium conductance hyperpolarizesthe membrane (see Equations 2-4 and 2-5)
sar-2 The correct answer is “c” because slowdepolarization leads to closure of the h-gates, which inactivates the fast sodiumchannels Choice “a” is incorrect becausethe m-gates open at the onset of phase 0,which activates the fast sodium channels.Choice “b” is incorrect because it is theclosure of the h-gates that inactivates thechannel Choice “d” is incorrect becauseL-type (long-lasting) calcium channelshave a prolonged phase of activation be-fore they become inactivated
3 The correct answer is “d” because themembrane potential during phase 4 is pri-marily determined by the high potassiumconductance Choices “a,” “b,” and “c” areincorrect because the overall potassiumconductance is reduced during phases 0
A P P E N D I X
Answers to Review Questions
215
Trang 8through 2, and it begins to recover only
during early phase 3
4 The correct answer is “a” because one
ef-fect of 1-adrenoceptor activation is to
in-crease If, which enhances the rate of
spontaneous depolarization Choice “b” is
incorrect because fast sodium channels
are inactivated in SA nodal cells; inward
calcium currents are responsible for
phase 0 Choice “c” is incorrect because
potassium conductance is lowest during
phase 0 Choice “d” is incorrect because
vagal stimulation reduces pacemaker
fir-ing rate, in part, by decreasfir-ing the slope
of phase 4
5 The correct sequence of activation and
conduction within the heart is choice “a”
6 The correct answer is “b” because
acetyl-choline released by the vagus nerve binds
to M2receptors, which decreases
conduc-tion velocity Removal of vagal tone
through the use of a muscarinic receptor
antagonist (e.g., atropine) leads to an
in-crease in conduction velocity Choice “a”
is incorrect because blocking
1-adreno-ceptors would decrease the influence of
sympathetic nerves on the AV node and
lead to a decrease in conduction velocity
Choice “c” is incorrect because
depolar-ization of the AV node, which occurs
dur-ing hypoxic conditions, decreases
conduc-tion velocity Choice “d” is incorrect
because L-type calcium channel blockers
(e.g., verapamil) reduce conduction
ve-locity by decreasing the rate of calcium
entry into the cells during depolarization,
which decreases the slope of phase 0 in
AV nodal cells
7 The correct answer is “c” because the T
wave represents repolarization of the
ven-tricular muscle Choice “a” is incorrect
because the normal P-R interval is
be-tween 0.12 and 0.20 seconds Choice “b”
is incorrect because the duration of the
ventricular action potential is most closely
associated with the Q-T interval Choice
“d” is incorrect because the duration of
the QRS complex is normally less than 0.1
seconds
8 The correct answer is “a” because thepositive electrode is on the left arm andthe negative electrode in on the right armfor lead I Choices “b” and “d” are incor-rect because lead II and aVFhave the pos-itive electrode on the left leg Choice “c”
is incorrect because the positive electrode
is on the right arm for aVR
9 The correct answer is “a” because whenlead II is biphasic, the mean electrical axismust be perpendicular to that lead, andtherefore it is either –30º or 150º.Because aVLis positive, the mean electri-cal axis must be –30º because that is theaxis for aVL All the other choices aretherefore incorrect
10 The correct answer is “c” because a plete dissociation between P waves andQRS complexes indicates a complete(third-degree) AV nodal block Fur-thermore, the rate of ventricular depolar-izations and the normal shape and dura-tion of the QRS complexes suggest thatthe pacemaker driving ventricular depo-larization lies within the AV node or bun-dle of His so that conduction follows nor-mal ventricular pathways Choice “a” isincorrect because a first-degree AV nodalblock increases only the P-R interval.Choice “b” is incorrect because some ofthe QRS complexes would still be pre-ceded by a P wave in a second-degreeblock Choice “d” is incorrect becausepremature ventricular complexes nor-mally have an irregular discharge rhythmand the QRS is abnormally shaped andhas a longer-than-normal duration
com-CHAPTER 3
1 The correct answer is “b” because myosinlight chain kinase is involved in myosinphosphorylation in both types of muscle.Choice “a” is incorrect because densebodies are specialized regions found onlywithin vascular smooth muscle cellswhere bands of actin filaments are joinedtogether Choices “c” and “d” are incor-rect because these structures are found in
216 APPENDIX
Trang 9cardiac muscle cells, not smooth musclecells.
2 The correct answer is “b” because myosin
is the major component of the thick ment Choices “a,” “c,” and “d” are incor-rect because they are all components ofthe thin filament
fila-3 The correct answer is “c” because a
myosin binding site is exposed on theactin after calcium binds to TN-C
Choices “a” and “b” are incorrect becausecalcium binds to TN-C, not myosin orTN-I Choice “d” is incorrect becauseSERCA pumps calcium back into the sar-coplasmic reticulum
4 The correct answer is “d” because
phos-phorylation of the L-type calcium nels by protein kinase A increases the per-meability of the channel to calcium,thereby permitting more calcium to enterthe cell during depolarization, which trig-gers the release of calcium by the sar-coplasmic reticulum Choice “a” is incor-rect because Gi-protein activationdecreases cAMP formation, thereby de-creasing inotropy Choice “b” is incorrectbecause calcium binding to TN-C en-hances inotropy Choice “c” is incorrectbecause it is the calcium that is released
chan-by the terminal cisternae of the mic reticulum that binds to TN-C leading
sarcoplas-to contraction
5 The correct answer is “d” because
2-adrenoceptor activation in vascular smoothmuscle increases cAMP, which inhibitsphosphorylation of myosin light chains bymyosin light chain kinase Choice “a” is in-correct because activation of myosin lightchain kinase leads to myosin phosphoryla-tion and contraction Choice “b” is incor-rect because 2-adrenoceptor activationcauses smooth muscle relaxation Choice
“c” is incorrect because 2-adrenoceptoractivation increases cAMP
6 The correct answer is “c” because
an-giotensin II receptors (AT1) are coupled
to the Gq-protein and phospholipase C,which increases IP3 when activated
Choice “a” is incorrect because
an-giotensin II activates the Gq-protein.Choice “b” is incorrect because the Gq-protein stimulates IP3 formation, notcAMP Choice “d” is incorrect becausethe increase in IP3stimulates calcium re-lease from the sarcoplasmic reticulum
7 The correct answer is “b” because dothelin-1 (ET-1) acts through the Gq-protein pathway to increase IP3, whichleads to contraction Choices “a” and “c”are incorrect because increased nitric ox-ide stimulates the formation of cGMP,which leads to relaxation Choice “d” is in-correct because prostacyclin (PGI2)causes smooth muscle relaxation by actingthrough the Gs-protein and stimulatingthe formation of cAMP
en-CHAPTER 4
1 The correct answer is “c” because the tral valve is open throughout ventricularfilling Choice “a” is incorrect because S4,when heard, is associated with atrial con-traction and frequently is heard in hyper-trophied hearts Choice “b” is incorrectbecause the aortic valve is open only dur-ing ventricular ejection Choice “d” is in-correct because the ventricular pressure
mi-is higher than aortic pressure only duringthe phase of rapid ejection
2 The correct answer is “c” because moretime is available for filling at reducedheart rates (diastole is lengthened); there-fore, preload is increased at reducedheart rates Choices “a,” “b,” and “d” areincorrect because decreased atrial con-tractility, blood volume, and ventricularcompliance lead to reduced ventricularfilling and therefore reduced preload
3 The correct answer is “a” because creased preload causes length-dependentactivation of actin and myosin, which in-creases active tension development This
in-is the basin-is for the Frank-Starling nism Choice “b” is incorrect becausechanges in inotropy are independent
mecha-of sarcomere length Choice “c” is rect because an increase in preload, byANSWERS TO REVIEW QUESTIONS 217
Trang 10incor-definition, is an increase in sarcomere
length Choice “d” is incorrect because an
increase in preload increases the velocity
of shortening by shifting the
force-velocity curve to the right
4 The correct answer is “d” because
ven-tricular hypertrophy reduces venven-tricular
compliance, which results in elevated
end-diastolic pressures when the
ventri-cle fills Choice “a” is incorrect because
decreased afterload leads to a reduction
in end-systolic volume, which results in a
secondary fall in end-diastolic volume and
pressure Choice “b” is incorrect because
decreased venous return decreases
ven-tricular filling, which decreases
ventricu-lar end-diastolic volume and pressure
Choice “c” is incorrect because increased
inotropy reduces end-systolic volume,
which results in a secondary fall in
end-diastolic volume and pressure
5 The correct answer is “a” because
de-creased inotropy diminishes the ability of
the ventricle to develop pressure and
eject blood Choice “b” is incorrect
be-cause increased venous return increases
stroke volume by the Frank-Starling
mechanism Choice “c” is incorrect
be-cause reduced afterload enhances the
ability of the ventricle to eject blood and
therefore increases stroke volume
Choice “d” is incorrect because a reduced
heart rate provides more time for filling,
which increases preload and stroke
vol-ume by the Frank-Starling mechanism
6 The correct answer is “c” because a
de-crease in inotropy causes a reduction in
stroke volume, which increases the
end-systolic volume Choice “a” is incorrect
because a sudden increase in aortic
pres-sure increases the afterload on the
ventri-cle, which reduces stroke volume and
in-creases end-systolic volume Choice “b” is
incorrect because end-diastolic volume,
by definition, is the ventricular volume at
the end of filling, whereas the end-systolic
volume is that which is left in the
ventri-cle after ejection Choice “d” is incorrect
because increasing preload alone does not
change end-systolic volume
7 The correct answer is “a” because adrenoceptors are coupled to the Gs-pro-tein, which increases cAMP (see Chapter3) Choice “b” is incorrect because an in-crease in heart rate leads to an increase ininotropy (Bowditch effect), probably ow-ing to an increase in intracellular calcium.Choice “c” is incorrect because calciummovement into the cell during the actionpotential triggers the release of calciumfrom the sarcoplasmic reticulum, whichleads to contraction (see Chapter 3).Therefore, decreased calcium entry intothe cell results in less calcium release bythe sarcoplasmic reticulum and decreasedinotropy Choice “d” is incorrect becausevagal activation decreases inotropy
1-8 The correct answer is “b” because an crease in inotropy increases stroke vol-ume, which is the width of the pressure-volume loop Choice “a” is incorrectbecause increased inotropy increasesstroke volume and reduces the end-systolic volume Choice “c” is incorrectbecause increased inotropy causes a sec-ondary reduction in end-diastolic volumebecause of the reduced end-systolic vol-ume Choice “d” is incorrect because in-creased inotropy shifts the force-velocitycurve to the right so that for any given af-terload, an increase in muscle fiber short-ening velocity occurs
in-9 The correct answer is “b” Choices “a”and “c” are incorrect because increas-ing afterload decreases ejection velocityand stroke volume, which leads to
an increase in end-systolic volume.Choice “d” is incorrect because Vmax,which is the y-intercept of the force-velocity relationship, changes only whenthere are changes in inotropy
10 The correct answer is “b” because an crease in end-diastolic volume will in-crease stroke volume; however, strokevolume changes are about one-fourth aseffective in changing myocardial oxygenconsumption as are changes in heart rate,mean arterial pressure, or ventricular ra-dius because of the relationships betweenoxygen consumption, wall stress, ventric-
in-218 APPENDIX
Trang 11ular pressure, and ventricular radius Forthis reason, choices “a,” “c,” and “d” areincorrect.
CHAPTER 5
1 The correct answer is “c” because these
vessels are the most permeable to fluid
Choice “a” is incorrect because ies, not arterioles, have the highest indi-vidual resistance because of their smalldiameter Choice “b” is incorrect becausethe large number of parallel capillaries re-duces their overall resistance as a group ofvessels Choice “d” is incorrect becausethe small arteries and arterioles are theprimary sites for pressure and flow regu-lation
capillar-2 The correct answer is “a” because any
fac-tor that reduces stroke volume will crease pulse pressure Choice “b” is in-correct because increased inotropyincreases stroke volume, which increasespulse pressure Choice “c” is incorrect be-cause aortic compliance decreases withage Choice “d” is incorrect because theperfusion pressure for the systemic circu-lation is aortic pressure minus right atrialpressure
de-3 The correct answer is “c;” “a” and “b” are
incorrect because reducing heart rate by10% without changing stroke volume de-creases cardiac output by 10% Becausemean arterial pressure is also reduced by10% and mean arterial pressure equalscardiac output times systemic vascular re-sistance (when central venous pressure iszero), systemic vascular resistance is notchanged Choice “d” is incorrect becausesystemic vascular resistance changes if thesystemic vasculature dilates
4 The correct answer is “d” because a 50%
increase in diameter will increase flow byabout five-fold because flow is propor-tional to radius (or diameter) to the fourthpower in a single vessel segment (assum-ing that the pressure gradient does notchange appreciably) Choice “a” is incor-rect because decreasing temperature in-creases blood viscosity, which decreases
flow Choice “b” is incorrect because creasing perfusion pressure by 100% in-creases flow by about 100% Choice “c” isincorrect because flow is inversely related
in-to blood viscosity
5 The correct answer is “a” because temic vascular resistance equals arterialminus venous pressure (mm Hg) divided
sys-by cardiac output (mL/min)
6 The correct answer is “b” because the nal artery is the distributing artery to thekidney, which is in series with the renalartery Although decreasing the diameter
by 50% increases the resistance of the nal artery sixteen-fold, the total renal re-sistance increases only about 15% be-cause the renal artery resistance is about1% of total renal resistance Therefore,flow will decrease about 13%
re-7 The correct answer is “a” because aforced expiration against a closed glottis(Valsalva maneuver) increases in-trapleural pressure, which compressesthe vena cava and increases central ve-nous pressure Choice “b” is incorrect be-cause increasing cardiac output decreasesvenous blood volume, which decreasescentral venous pressure Choice “c” is in-correct because increasing venous com-pliance decreases venous pressure.Choice “d” is incorrect because gravita-tional forces associated with standingcauses blood to pool in the legs, which de-creases central venous volume and pres-sure
8 Choice “d” is correct because inspirationreduces intrapleural pressure, which ex-pands the right atrium, lowers its pres-sure, and thereby enhances venous re-turn Choice “a” is incorrect because anincrease in cardiac output must increasevenous return because the circulatory sys-tem is closed Choice “b” is incorrect be-cause decreased sympathetic activation ofthe veins causes them to relax, which in-creases their compliance This reducespreload on the heart, which leads to a re-duction in cardiac output and venous re-turn Choice “c” is incorrect because aValsalva maneuver increases intrapleuralANSWERS TO REVIEW QUESTIONS 219
Trang 12pressure, compresses the vena cava, and
reduces venous return
9 Choice “a” is correct because decreased
venous compliance shifts the systemic
function curve to the right, which
in-creases the mean circulatory filling
pres-sure (value of the x-intercept) Choice “b”
is incorrect because changes in systemic
vascular resistance alter the slope of the
systemic function curve, but not its
x-in-tercept Choice “c” is incorrect because a
decrease in blood volume causes a
paral-lel shift in the systemic function curve to
the left, which decreases mean circulatory
filling pressure Choice “d” is incorrect
because mean circulatory filling pressure,
by definition, is the intravascular pressure
when cardiac output is zero, and
there-fore it is independent of cardiac output
10 The correct answer is “b” because a
de-crease in systemic vascular resistance
in-creases the slope of the systemic function
curve Choices “a” and “d” are incorrect
because decreased blood volume and
in-creased venous compliance decrease right
atrial pressure and cardiac output by
causing a leftward parallel shift in the
sys-temic function curve Choice “c” is
incor-rect because increased heart rate
in-creases cardiac output a small amount
and decreases right atrial pressure
CHAPTER 6
1 The correct answer is “c” because this
re-gion of the brainstem contains cell bodies
for both sympathetic and parasympathetic
neurons; choices “a” and “b” are therefore
incorrect Choice “d” is incorrect because
the nucleus tractus solitarius is the region
in the medulla that receives afferent
fibers from peripheral sensors (e.g.,
baroreceptors) and then sends excitatory
or inhibitory fibers to sympathetic and
parasympathetic neurons within the
medulla
2 The correct answer is “b” because
norepi-nephrine binds to 1-adrenoceptors located
on vascular smooth muscle to stimulate
vasoconstriction Choice “a” is incorrect
be-cause norepinephrine preferentially binds
to 1-adrenoceptors in the heart Choice
“c” is incorrect because prejunctional adrenoceptors facilitate norepinephrine re-lease (prejunctional 2-adrenoceptors in-hibit release) Choice “d” is incorrectbecause norepinephrine stimulates reninrelease through 1-adrenoceptors
2-3 The correct answer is “d” because the gus nerve is parasympathetic cholinergicand therefore releases acetylcholine.Choice “a” is incorrect because efferentright vagal stimulation primarily affectsthe sinoatrial node and has no significantdirect effects on the systemic vasculature.Choice “b” is incorrect because vagalstimulation decreases atrial inotropy.Choice “c” is incorrect because right vagalstimulation reduces heart rate by decreas-ing the slope of phase 4 of the pacemakeraction potential
va-4 The correct answer is “c” because creased carotid artery pressure stimulatesthe firing of carotid sinus baroreceptors(therefore, choice “a” is incorrect), whichleads to a reflex activation of vagal effer-ents to slow the heart rate (therefore,choice “d” is incorrect) Choice “b” is in-correct because the baroreceptor reflexwould attempt to reduce arterial pressure
in-by withdrawing sympathetic tone on thesystemic vasculature
5 The correct answer is “b” because creased blood pCO2stimulates chemore-ceptors, which activate the sympatheticnervous system to constrict the systemicvasculature and raise arterial pressure.Choice “a” is incorrect because submerg-ing the face in cold water elicits the “div-ing reflex,” which causes bradycardia.Choice “c” is incorrect because increasedcarotid sinus firing (usually caused by ele-vated arterial pressure) causes a reflex decrease in heart rate brought about byvagal activation and sympathetic with-drawal Choice “d” is incorrect becausethe vasovagal reflex causes vagal activa-tion and bradycardia
in-6 The correct answer is “d” because thisdose of epinephrine binds to both 2and
1-adrenoceptors on blood vessels.Therefore, if the 2-adrenoceptors (which
220 APPENDIX
Trang 13produce vasodilation) are blocked, the adrenoceptors can produce vasoconstric-tion unopposed by the 2-adrenoceptors.
1-Choice “a” is incorrect because the posed -adrenoceptor activation in-creases arterial pressure Choice “b” is in-correct because epinephrine binds toboth and -adrenoceptors Choice “c” isincorrect because the increase in arterialpressure will cause a reflex bradycardia
unop-7 The correct answer is “c” because
acetyl-choline dilates blood vessels, which ers arterial pressure and causes a barore-ceptor-mediated increase in heart ratebrought about by sympathetic activation
low-Choice “a” is incorrect because tion of muscarinic receptors on the sinoa-trial node induces bradycardia Choice
stimula-“b” is incorrect because the hypotensioncauses decreased carotid sinus firing
Choice “d” is incorrect because reflex temic vasodilation can occur only if arte-rial pressure is elevated and baroreceptorfiring increases
sys-8 The correct answer is “b” because
in-creased angiotensin II acts directly on thekidney and indirectly by increasing aldo-sterone secretion (therefore, choice “c” isincorrect) to increase sodium reabsorption,which leads to an increase in blood volume
Choice “a” is incorrect because angiotensin
II enhances sympathetic activity by tating the release of norepinephrine fromsympathetic nerves and decreasing norepi-nephrine re-uptake Choice “d” is incorrectbecause angiotensin II stimulates the re-lease of atrial natriuretic peptide
facili-9 The correct answer is “c” because atrial
natriuretic peptide is counter-regulatory
to the renin-angiotensin-aldosterone tem (therefore, choices “a” and “b” are in-correct) Choice “d” is incorrect becausedepression of the renin-angiotensin-aldosterone system leads to enhancedsodium loss, hypovolemia, and a subse-quent reduction in cardiac output
sys-CHAPTER 7
1 The correct answer is “c.” Choice “a” is
incorrect because elevated pCO2 causes
vasodilation in most organs; therefore decreased pCO2 would cause vasocon-striction Choice “b” is incorrect becauseincreased tissue pO2causes vasoconstric-tion Choice “d” is incorrect because en-dothelin-1 is a vasoconstrictor
2 The correct answer is “a” because in sponse to a reduction in perfusion pres-sure and blood flow, the kidney undergoesautoregulation through dilation of the af-ferent arterioles Choice “b” is incorrect.When the pressure is first reduced, bloodflow will fall by about 30%, but after 2minutes the blood flow will be near nor-mal owing to the autoregulation Choice
re-“c” is incorrect because afferent arteriolarvasodilation reduces renal vascular resis-tance Choice “d” is incorrect because au-toregulation, by maintaining blood flow,protects the kidney against ischemia andhypoxia
3 The correct answer is “c” because the crease in flow (reactive hyperemia) fol-lowing release of the occlusion causes aflow-dependent release of nitric oxide bythe vascular endothelium, which furthercontributes to the increase in blood flow.Choice “a” is incorrect because active hyperemia is associated with increasedtissue metabolic activity and not withpostischemic hyperemia Choice “b” is in-correct because vasodilation occurs dur-ing ischemia Choice “d” is incorrect be-cause increased interstitial adenosinedilates coronary arterioles
in-4 The correct answer is “c.” Choice “a” isincorrect because the brain responds little
to sympathetic activation Although thecoronary vasculature in the heart (choice
“b”) is capable of responding to thetic activation, concurrent stimulation
sympa-of heart rate and inotropy lead to bolic vasodilation Choice “d” is incorrectbecause sympathetic control of the skincirculation is primarily related to ther-moregulation; therefore, the barorecep-tor reflex associated with standing has lit-tle influence on cutaneous blood flow
meta-5 The correct answers are “f” and “i”
6 The correct answers are “b” and “d”
7 The correct answer is “e”
ANSWERS TO REVIEW QUESTIONS 221