Pathophysiology of Heart Failure

Question 1

Heart failure my be viewed as a _____ disorder that is initiated after a(n) ______ that is either abrupt or insidious in onset.

Answer 1

progressive
index event

Question 2

The compensatory mechanisms that help maintain cardiovascular function in the setting of heart failure include activation of the ______ nervous systemic system and the ______ system, which are responsible for maintains cardiac output through increased retention of salt and water; peripheral arterial _____ and increased _____; and ______ mediators that are responsible for cardiac repair and remodeling.

Answer 2

adrenergic
renin-angiotensin (RAS)
vasoconstriction
contractility
inflammatory

Question 3

Many of the so-called classic “neurohormones” such as norepinephrine and angiotensin II are synthesized directly within the _____ by _____ and thus act in a(n) ____ and _____ manner.

Answer 3

myocardium
myocytes
autocrine
paracrine

Question 4

One of the most important adaptations in early heart failure is the _____ of the sympathetic (adrenergic). This is accompanied by a concomitant ______ of parasympathetic tone.

Answer 4

activation
withdrawal

Question 5

Under normal conditions, _____ inputs from high-pressure carotid sinus and aortic arch baroreceptors and the low-pressure cardiopulmonary mechanoreceptors are the principal ____ of sympathetic outflow, whereas discharge from the nonbaroreflex peripheral chemoreceptors and from muscle metaboreceptors are the major ____ inputs to sympathetic outflow.

Answer 5

inhibitory
inhibitors
excitatory

Question 6

Healthy persons display _____ sympathetic discharge at rest and have a ____ heart rate variability. In patients with HF, _____ input from baroreceptors and mechanoreceptors _____ and excitatory input ______. The net result is generalized _____ in sympathetic nerve traffic and _____ parasympathetic nerve traffic, leading to _____ of heart rate variability and ______ peripheral vascular resistance.

Answer 6

low
high
inhibitory
decreases
increases
increase
decreased
loss
increased

Question 7

In heart failure, there is a(n) ______ in circulating norepinephrine.

Answer 7

increase

Question 8

In patients with moderate HF, the coronary sinus NE concentration is ______ than the arterial concentration, indicating _______ adrenergic stimulation of the heart. However, as HF progresses, there is a significant _____ in the myocardial concentration of NE. This may relate to an _____ phenomenon in advanced HF.

Answer 8

greater
increased
decrease
“exhaustion”

Question 9

Heightened activity of the adrenergic nervous system in HF also leads to _____ of myocardial alpha1-adrenergic receptors, which elicits a modest ____ inotropic effect, as well as peripheral arterial ______.

Answer 9

positive
vasoconstriction

Question 10

In contrast with the sympathetic nervous system, the Renin-Angiotensin II (RAS) system is activated comparatively ____ in HF.

Answer 10

later

Question 11

The presumptive mechanisms for RAS activation in HF include renal _____, _____ filtered sodium reaching the macula dense in the distal tubule, and _____ sympathetic stimulation of the kidney, leading to ____ renin release from the juxtaglomerular apparatus.

Answer 11

hypoperfusion
decreased
increased
increased

Question 12

Complete the RAS cycle.
Renin causes ______ to turn into the biologically ______ angiotensin I. _____ then causes angiotensin I to turn into the biologically ______ angiotensin II.

Answer 12

angiotensinogen
inactive
ACE
active

Question 13

Angiotensin II can be synthesized using renin-independent pathways through the enzymatic conversion of angiotensinogen to angiotensin I by ______ and _____. The tissue production of angiotensin II also may occur along ACE-independent pathways through the activation of _____.

Answer 13

kallikrein
cathepsin G
chymase

Question 14

Angiotensin II exerts its effects by binding to two GPCRs, the ____ and _____ receptors

Answer 14

Angiotensin type 1 (AT1)
Angiotensin type 2 (AT2)

Question 15

The predominant angiotensin receptor in the vasculature is the ____ receptor

Answer 15

AT1

Question 16

Although both AT1 and AT2 receptor subtypes are present in the myocardium, the ____ receptor predominates in a __ to __ ratio.

Answer 16

AT2
2:1 ratio

Question 17

Cellular localization of the AT1 receptor is most abundant in nerves distributed in the _____, whereas the AT2 receptor is localized more specifically in ____ and the _____.

Answer 17

myocardium
fibroblasts
interstitium

Question 18

Activation of the AT1 receptor leads to ___? (list 4)
Activation of the AT2 receptor leads to ___? (list 4)

Answer 18

AT1 receptor: vasoconstriction, cell growth, aldosterone secretion and catecholamine release
AT2 receptor: vasodilation, inhibition of cell growth, natriuresis and bradykinin release

Question 19

Sustained expression of angiotensin II is maladaptive, leading to ____ of the heart, kidneys, and other organs.

Answer 19

fibrosis

Question 20

Sustained expression of aldosterone may provoke ____ and ____ within the vasculature and myocardium, contributing to _____ vascular compliance and _____ ventricular stiffness.

Answer 20

hypertrophy
fibrosis
reduced
increased

Question 21

Oxidative stress is _____ both systemically and in the myocardium in patients with HF

Answer 21

increased

Question 22

In HF, falling cardiac output or redistribution of the circulating blood volume is sensed by _____ in the _____, _____, _____ and _____. The loss of inhibitory input from arterial or cardiopulmonary _____ reflexes leads to sustained _____ of the SNS and the RAS.

Answer 22

baroreceptors
left ventricle, aortic arch, carotid sinus and renal afferent arterioles
baroreceptor
activation

Question 23

Describe the results of the BeAT-HF trial

Answer 23

BeAT-HF was a multi-center, prospective, RCT where subjects received either baroreflex activation therapy (BAT) plus optimal medical management or optimal medical management alone. BAT was found to be safe, significantly improved quality of life, exercise capacity and NT-proBNP measurements

Question 24

Renal sympathetic stimulation in HF can also lead to release of arginine vasopressin (AVP), which reduces the excretion of ____ and contributes to worsening peripheral _____, as well as increased _____ production.

Answer 24

free water
vasoconstriction
endothelin (ET)

Question 25

Angiotensin II facilitates retention of sodium and water by multiple renal mechanisms, including a direct _____ effect as well as through activation of aldosterone, which leads to increased sodium resorption in the _____.

Answer 25

proximal tubular
distal tubule

Question 26

Under physiologic conditions, ANP and BNP function as natriuretic peptides that are released in response to increases in atrial and myocardial _____, often secondary to excessive ____ intake.

Answer 26

stretch
sodium

Question 27

Once released, the cardiac peptides (ANP and BNP) act on the _____ and peripheral _____ to unload the heart, through increased excretion of ____ and ____, while inhibiting the release of _____ and _____.

Answer 27

kidneys
circulation
sodium
water
renin
aldosterone

Question 28

The renal effects of the natriuretic peptides (ANP and BNP) appear to become _____ with advancing HF, leaving the effects of RAS _____.

Answer 28

blunted
unopposed

Question 29

ANP is principally produced in the cardiac ____ whereas BNP is primarily produced in the cardiac _____

Answer 29

atria
ventricles

Question 30

Both ANP and BNP are secreted in response to increasing ______

Answer 30

cardiac wall tension/stretch

Question 31

Whereas ANP is secreted in ____ bursts in response to ____ changes in atrial pressure, the activation of BNP is regulated transcriptionally in response to _____ increases in atrial/ventricular pressure.

Answer 31

short
acute
chronic

Question 32

Neprilysin (NEP) degrades both _____ and _____. However inhibition of NEP increases urinary ____ levels which may contribute to its natriuretic effects.

Answer 32

natriuretic peptides
vasoactive peptides
kinin