lecture 18 - physiology/ pharmacology management of heart failure

Question 1

what is the definition of heart failure?

Answer 1

characterised by impaired cardiac pumping such that heart is unable to pump adequate amount of blood to meet metabolic needs

Question 2

what are signs and symptoms of heart failure?

Answer 2

shortness of breath, excessive tiredness, leg swelling

Question 3

what are the underlying causes and risk factors for heart failure?

Answer 3

ischemic heart disease

hypertension

myocardial infarction

valvular heart disease

congenital heart disease

dilated cardiomyopathy

Question 4

describe the normal function of the heart

Answer 4

the left ventricle pumps the blood via aorta to most organs in the body (oxygenated). the blood then returns via the inferior vena cava and superior vena cava. the right ventricle pumps the blood to the lungs via pulmonary arteries (deoxygenated)

Question 5

where and how does congestive heart failure occur in the heart structure?

Answer 5

left-sided failure

• most common form
• blood backs up through the left atrium into the pulmonary veins - pulmonary congestion and edema

Question 6

what is cardiac output defined by

Answer 6

heart rate times stroke volume

Question 6

what is cardiac output defined by

Answer 6

heart rate times stroke volume

Question 7

what are factors affecting cardiac output?

Answer 7

heart rate

preload

afterload

contractility

Question 8

how does heart failure affect cardiac output ?

Answer 8

heart failure - in general the higher the heart rate, the higher the cardiac output - but only up to a point. with excessively high heart rates, diastolic filling time begins to fall, causing stroke volume and thus CO to fall.

Question 9

how does preload affect cardiac output?

Answer 9

the amount of fibre stretch in the ventricles at the end diastole (ie before the next contraction)

• preload is directly related to ventricular filling
  –> a higher end-diastolic volume implies higher preload

Question 10

what does preload increase with?

Answer 10

increase in blood volume

vasoconstriction (‘squeezes’ blood from vascular system into atrium)

Question 11

what does preload decrease with ?

Answer 11

loss in blood volume

vasodilation (able to ‘hold’ more blood, therefore less restrunign to atrium)

Question 12

what does starlings law describe?

Answer 12

the relationship between preload and cardiac output

Question 13

what does excessive preload equal?

Answer 13

excessive stretch which leads to reduced contraction and reduced stroke volume or cardiac output

Question 14

how does afterload affect cardiac output?

Answer 14

the resiatnce against which the ventricle must pump. excessive after load leads to difficult to pump blood which causes reduced stroke volume or cardiac output

Question 15

what does afterload increase with?

Answer 15

hypertension

vasoconstriction

Question 16

what does afterload decrease with?

Answer 16

vasodilation

Question 17

how does contractility affect cardiac output - what is it?

Answer 17

ability of the heart muscle to contract

relates to the strength of contraction

Question 18

what does contractility decease with ?

Answer 18

infarcted tissue - no contractile strength

ischemci tissue - reduced contractile strength

Question 19

what does contractility increase with?

Answer 19

positive ionotropes (medications that increase contractility, such as digoxin, sympathomimetics)

Question 20

what is the pathophysiology of congestive heart failure?

Answer 20

pump fails which leads to a decreased stroke volume or cardiac output

compensatory mechanisms attempt to increase cardiac output
- sympathetic nerve stimulation leads to a release of epinephrine/ norepinephrine
- increase HR
-increase contractility
-peripheral vasoconstriction (increases afterload)

myocardial hypertrophy: walls of heart thicken o provide more muscle mass which leads to stringer contraction

Question 21

what is the hormonal response to pathophysiology of congestive heart failure?

Answer 21

decreased renal perfusion interpreted by juxtaglomerular apparatus as hypovolemia thus:
- kidneys release renin, which stimulates conversion of angiotensin I to angiotensin II which causes
- aldosterone release so sodium retention and water ration via ADH secretion
- peripheral vasoconstriction

Question 22

how does vasoconstriction decrease cardiac output?

Answer 22

increases the resistance against which heart has to pump (.e. increases afterload), and may therefore decrease CO

Question 23

how does sodium ions and water retention decrease cardiac output?

Answer 23

increases fluid volume, which increases preload. If too much “stretch” (too much fluid) there will be a decreased strength of contraction and decreased CO

Question 24

how does excessive tachycardia cause reduced sv and co ?

Answer 24

Excessive tachycardia → decreases diastolic filling time → decreasing ventricular filling → decreasing SV and CO

Question 25

what drugs are. used in chronic congestive heart failure pharmacotherapy?

Answer 25

ace inhibitors

beta adrenergic blockers

aldosterone antagonists

diuretics

vasodilators

new drugs ie neprilysin anatagonists

Question 26

what is the core pathophysiology of heart failure?

Answer 26

the raas

Question 27

describe ace inhibitors and how the work

Answer 27

relaxes blood vessels, lower arteriolar resiatnce nd increases venous capacity; decrease cardiac output, stroke work, and volume;

lowers reisatnce inLowers resistance in blood vessels in the kidneys; and leads to increased natriuresis (excretion of sodium in the urine).

Reduces secretion of aldosterone, reducing reabsorption of sodium

Question 28

describe how beta blockers reduce co

Answer 28

Reduce excessive sympathetic stimulation which causes
Tachycardia, increase myocardial oxygen demand

Cardiac remodeling effects caused by catecholamines

Reduce heart rate, decrease force of contraction

Question 29

describe how aldosterone antagonist work

Answer 29

Aldosterone, a steroid hormone produced by adrenal cortex, is essential for sodium conservation mainly via mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron.

Drugs that interfere with the secretion or action of aldosterone (e.g., Spironolactone)reduce sodium and water retention which decreases intravascular volume by releasing fluid from the body

Pharmacological effects:
Reduce preload
Reduce afterload
Relieve symptoms of congestion

Question 30

describe how diuretics affect co

Answer 30

Loop diuretics (Furosemide, bumetanide)

Act at the ascending limb of the loop of Henle in the kidney to inhibit sodium, chloride and potassium reabsorption, so that there is less osmotic driving force for water has to leave the collecting duct system

Decreases intravascular volume
Reduces preload
Improves LV function
by reducing venous return

Question 31

describe how vasodilators affect co

Answer 31

Hydralazine plus Nitrates
Hydralazine (smooth muscle relaxant)
Isosorbide dinitrate (smooth muscle relaxant)

Question 32

describe how new drugs Ie neprilysin antagonists affect co

Answer 32

In response to elevated wall stress (from increased preload and afterload) the heart releases several natriuretic peptides.

These peptides promote vasodilation and natriuresis …..i.e. have exactly the opposite function of RAAS system

Neprilysin is an enzyme that cleaves natriuretic peptides reducing their beneficial effects in a failing heart.

Neprilysin inhibitors are used to prevent the breakdown of natriuretic peptides maintaining their ability to decrease intravascular volume and vasodilation.