Unit 0.4: Treatment of Heart Failure Flashcards
what is heat failure
when heart is unable to pump enough blood
- the delivery of blood or CO is inadequate for oxygen and the nutritional needs of the body
what are the causes of heart failure?
- myocardial damage (>80%), hypertension, infection, genetric/congential abnormality and chemical toxicity
what are the two types of heart failure
- systolic heart failure: reduced contractility of the heart
- Diastolic heart failure: reduced filling of the heart
how does the body compensate for decreases in CO
- inc SNS activity, activate the renin angiotensin system inc force on contraction of the heart and centricular hypertrophy
how does the SNS compensate for heart failure
- decrease in CO is monitored by baroreceptors and signals an inc in SNS and dec in PSNS activity
- changes result in an increase in HR, force of contraction and peripheral vascular resistance
- compensatory mechansisms contribute to some of the symptoms of heart failure like tachycardia and sweating
- also results in fluid retnetnion via renin-angiotensin system
Describe the renin angiotensin system
- decrease in CO and SNS medicated vasoconstriction causes a decrease in blood flow to the kidneys
- this decreases glomerular filtration
- SNS activity activates β1 receptors in the kidneys, inc renin relase and conversion of angiotensin I to angiotensin II
- results in decrease in fluid removed from blood and dec in urine output
*occurs bc of an increase in vasocontriction and sodium and water rentention - BP and PVR are increased
describe the neurohumoral effects of heart failure
- Compromised cardiac function -> dec arterial BP -> Baroreceptor reflex -> inc sympathetic outlfow (α and β Adrenergic sympathetic outflow)
- α: vasoconstriction -> INC afterload -> greater pressure against which the heart must contract -> inc myocardial demand
- β: inc juxtaglomerular cell release of renin -> inc AT II (directly acts as vasoconstrictor but also) ->inc aldosterone synthesis and secretion -> inc collecting duct Na+ reabsorption eading to intravascular volume expansion and inc preload
*net is inc afterload and preload which inc myocardial O2 demand - if heart if already compromised this inc stress can lead to worsening heart failure
How does contractility compensate for heart failure
- fluid retnetion combined with vasocontriction = increased contractility
- when blood volume increases in veins there is an increase in pressure in blood returning to heart
* cardiac muscle stretching to increase strength of contraction called Frank-Starling Law
describe the frank starling relationship in heart failure and treatment with positive inotrope
*left panel
normal frank starling relatinship shows a steep increase in CO w/ increasing ventricular end-diastolic pressure (preload)
point A = the end diastolic pressure and CO of a normal HR at rest
- contractile dysfunction (untreated HR), cardiac output falls (B_ and frank starling curve flatterns - increasing preload translated to only modest inc in CO
- inc in CO acompanied by dyspnea
= treatment with positive inotrope shifts curve upwards and CO increases - imporvement in myocardial contractility supports a sufficient reduction in preload that the venous congestion is relieved (E)
how does afterlad reduction and preload reduction influence the stank starling curve
- afterload reduction (ACE inhibitors) (F) inc CO at any given preload - elevate the frank-starling relationship
- Preload reduction (G) alleviates congestive symptoms by decreasing ventricular end diastolic pressure along same rnak starling curve
what is ventircular hypertrophy
thickening of ventricular cell calls
- results if damage to heart causes a decrease in CO or the heart is chronically stressed and cardiac muscle cells increase in size to compensate
- heart can function normally at rest but can fail due to exercise or stress
- if compensatory mechansims return CO to normal levels then renal output also reutnrs to normal - if does not return to norma levels end result is decompensated heart failure
what is a decompensated heart
- severely damaged heart that cannot be compensated by SNS activity, renin-angiotensin system or ventricular hypertrophy
- excessive stretching of heart muscle weakens heart further and excess fluid in venous system can leak into tissues (ie fluid in lungs = pulmonary edema)
- decompensated heart combined with edema is reffered to as congestive heart failure
what is congestive heart failure
- insufficient CO to supply the organs in the body with nutrients and oxygen
- fluid accumulation in extremities and/or lungs (which results in decreased oxygenation of blood) is also contributing factor
- when normal CO cannot be achieved, reflex mechanisms that are used to compensate for heart failure decrease cardiac function even more
- body canot respond to CHF - there is a high mortality rate associated with the disease
what are symptoms of CHF caused by compensatory responses to decrease CO
- tachycardia, shortness of breath, sweating, peripheral/pulmonary edema, decreased exercise tolerance, enlargement of heart (cardiomegaly), hypotension and urine retention
- therapeutic strategies are aimed at reducing the work load of the heart
how is heart failure treated
- reccomend lifestyle changes - decreasing activity level, weight and stress. restrict sodium instake from diet and stop smoking
- use of pharmacological agenets like diuretics, ACH inhibitors/ARBs, cardiac glycosides, beta-blockers and vasodilators
*patients with severe HR usually requrie combination therapy (diuretic, ACE inhibitor and cardiac glycoside)
describe calss 1 heart failure
mild
No limitation of physical activity
Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath).
describe class II heart failure
Slight limitation of physical activity
Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea.
Describe class III heart failure
moderate
Marked limitation of physical activity
Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.
describe class IV heart failure
severe
Unable to carry out any physical activity without discomfort.
Symptoms of cardiac insufficiency at rest.
If any physical activity is undertaken, discomfort is increased
how is mild heart failure treated? Patients with left ventricular dysfunction but no edema? left ventricular dysfunction with edema?
- ACE inhibitors (enalapril), ARBs (lorartan), thaizide diuretics or loop diuretic (furosemide) if a more powerful agent is required
- patients with elft venticular dysfunction but no edema can receieve ACE inhibitiors (enalarpil) or ARBs (lorartain) and those with edema require vasodilators or diuretics.
what are patients with excessive tachycardiac prescribed
low dose beta-blockers (metoprolol) but must be monitored closely to ensure sufficient cardiac output
how are patients with CHF combined with atrial fibrillation or an enlarged/dysfunctional left ventricle
- require cardiac glycosides (digoxin)
- absorbed and dsitrbuted well and has direct and indirect cardiovascular effects on heart and baroreceptors respectively
what is the mechanism of action of Digoxin: direct pathway
- inhibition of Na+/K+ ATPase
- for the direct pathway the concentration of Na+ inc inside cardiac muscle cells due to inhibition of Na+/K+ ATPase
*result = decrease in Ca2+ efflu via Na+/Ca+ exchanger
- intracellualr Ca2+ builds up which inc interaction between actin and myosin
*overall effect is an increase in cardiac contractility
describe the mechanism of digoxin - indirect pathway
- increase PSNS activity and decreases SNS actiivty
- increased force and decreased rate of contraction
*occurs at least in part from the imporved CO )detected by baroreceptors
digoxin treatment - half life, therapeutic index, dosing, administration, side effects
- long half life ~ 40 hours and narrow therapeutic index (0.5-1.5 ng/mL)
- toxicity observed at >2 ng/mL
- pateints given large initial dose (digitalization) and then daily maintenance doses - maintenace doses adjusted per pateints by monitoring plasma digoxin levels
- toxicities associated include adverse cardiac and GI effects
- can develop arrhythmias from pateints with decrease K+ levels (from diuretics or diarrhea) can lead to tachycardia and fibrilation
- GI toxicity includes anorexia, nausea, vomiting and diarrhea
what is quinidine
anti-arrhythmic
reduces digoxin clearance and therefore increases toxicity if administered in tandem with digoxin
GI toxicity includes anorexia, nausea, vomiting and diarrhea.
describe the poritive inotropic mechanism of digoxin
- digoxin selectively binds to and inhibits Na+/K+-ATPase.
- Dec Na+ extrusion (dashed arrows) -> increased concentration of cytosolic Na+
- Inc intracellular Na+ decreases teh driving force for the Na+/Ca2+ exchanger
- leads to decreased extrusion of Ca2+ from cardiac myocyte into extracellular space and to increase cytoslic Ca2+
- ince Ca2+ is pumped by SERCA Ca2+ ATPase into sarcoplasmic reticulum
- creates a net increase in Ca2+ that is available for release during subsequnt contractions
- During each contraction, the increased Ca2+ release from SR leads to increased myofibril contraction =? INC cardiac inotropy
