Post on 03-Apr-2018
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PATHOPHYSIOLOGY OF
HEART FAILUREProf. J. Hanacek
Technical co-operation: L. urinov
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Notes to heart physiology Essential functions of the heart
to cover metabolic needs of body tissue(oxygen, substrates) by adequate blood supply
to receive all blood comming back from the tissueto the heart
Essential conditions for fulfilling these functions
normal structure and functions of the heartadequate filling of the heart by blood
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Essential functions of the heart are securedby integration of electrical and mechanical
functions of the heartCardiac output (CO) = heart rate (HR) x stroke vol.(SV)
- changes of the heart rate
- changes of stroke volume Control of HR:- autonomic nervous system
- hormonal(humoral) control
Control of SV:
- preload
- contractility
- afterload
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Adaptive mechanisms of the heart
to increased load
Frank - Starling mechanism
Ventricular hypertrophy increased mass of contractile elements strength
of contraction
Increased sympathetic adrenergic activity increased HR, increased contractility
Incresed activity of RAA system
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Causes leading to changes of number and size
of cardiomyocytes
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Preload
Stretching the myocardial fibers during diastole by increasing end-
diastolic volume force of contraction during systole =Starlings law
preload = diastolic muscle sarcomere length leading to increased
tension in muscle before its contraction (Fig.2,3)
-venous return to the heart is important end-diastolicvolume is influenced
-stretching of the sarcomere maximises the numberof actin-myosin bridges responsible for development of force
- optimal sarcomere length 2.2 m
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Myocardial contractility
Contractility of myocardium
Changes in ability of myocardium to develop the forceby contraction that occur independently on thechanges in myocardial fibre length
Mechanisms involved in changes of contractility
amount of created cross-bridges in the sarcomereby ofCa ++i concentration
- catecholamines Ca++i contractility- inotropic drugs Ca++i contractility
contractilityshifting the entire ventricular functioncurve upward and to the left
contractilityshiffting the entire ventricular functioncurve (hypoxia, acidosis) downward and to the right
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The pressure volume loop
It is the relation between ventricular volume and pressure
This loop provides a convenient framework for understandingthe response of individual left ventricular contractions
to alterations in preload, afterload, and contractility
It is composed of 4 phases:
- filling of the ventricle- isovolumic contraction of ventricle
- isotonic contraction of ventricle(ejection of blood)
- isovolumic relaxation of ventricle
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Pressure volume loops recorded under differentconditions
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It is expressed as tension which must be developed in the wall
of ventricles during systole to open the semilunar valves andeject blood to aorta/pulmunary arteryLaplace law:
intraventricular pressure x radius of ventriclewall tension = --------------------------------------------------------
2 x ventricular wall thickness
afterload:due to - elevation of arterial resistance- ventricular size- myocardial hypotrophy
afterload:due to - arterial resistance- myocardial hypertrophy
- ventricular size
Afterload
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Heart failure
Definition
It is the pathophysiological process in whichthe heart as a pump is unable to meet
the metabolic requirements of the tissue for
oxygen and substrates despite the venous
return to heart is either normal or increased
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Explanation of the terms
Myocardial failure = abnormalities reside in the myocardium and leadto inability of myocardium to fulfilling its function
Circulatory failure= any abnormality of the circulationresponsible for the inadequacy in body tissueperfusion, e.g. decreased blood volume, changesof vascular tone, heart functiones disorders
Congestive heart failure= clinical syndrome which is developeddue to accumulation of the blood in front
of the left or right parts of the heart
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General pathomechanisms involved in heartfailure development
Cardiac mechanical dysfunction can develop asa consequence in preload, contractility and afterload
disorders
Disorders of preload
preloadlength of sarcomere is more than optimal strength of contraction preloadlength of sarcomere is well below the optimal strength of contraction
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Important:failing ventricle requires higher end-diastolic volumeto achieve the same improvement of CO that normal
ventricle achieves with lower ventricular volumes
Disorders of contractility
In the most forms of heart failure the contractility of myocardium
is decreased (ischemia, hypoxia, acidosis, inflammation, toxins,
metabolic disorders... )
Disorders of afterload due to:
fluid retention in the body
arterial resistancevalvular heart diseases ( stenosis)
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Characteristic features of systolic dysfunction
(systolic failure)
ventricular dilatation
reducing ventricular contractility (either generalized
or localized)
diminished ejection fraction (i.e., that fraction of end-diastolic
blood volume ejected from the ventricle during each systolic
contraction les then 45%)
in failing hearts, the LV end-diastolic volume (or pressure)
may increse as the stroke volume (or CO) decreases
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Characteristic features of diastolic dysfunctions
(diastolic failure)
ventricular cavity size is normal or small
myocardial contractility is normal or hyperdynamic
ejection fraction is normal (>50%) or supranormal
ventricle is usually hypertrophied
ventricle is filling slowly in early diastole (during the periodof passive filling)
end-diastolic ventricular pressure is increased
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Causes of heart pump failure
A. MECHANICAL ABNORMALITIES
1. Increased pressure load
central (aortic stenosis, aortic coarctation...)
peripheral (systemic hypertension)
2. Increased volume load valvular regurgitation
hypervolemia
3. Obstruction to ventricular fillingvalvular stenosis
pericardial restriction
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B. MYOCARDIAL DAMAGE
1. Primary
a) cardiomyopathy
b) myocarditis
c) toxicity (e.g. alcohol)
d) metabolic abnormalities (e.g. hyperthyreoidism)
2. Secondary
a) oxygen deprivation (e.g. coronary heart disease)
b) inflammation (e.g. increased metabolic demands)
c) chronic obstructive lung disease
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C. ALTERED CARDIAC RHYTHM
1. ventricular flutter and fibrilation
2. extreme tachycardias
3. extreme bradycardias
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Pathomechanisms involved in heart failure
A. Pathomechanisms involved in myocardial failure
1. Damage of cardiomyocytescontractility, complianceConsequences:
defect in ATP production and utilisationchanges in contractile proteins
uncoupling of excitation contraction process
number of cardiomyocytes impairment of relaxation of cardiomyocytes with decrease
compliance of myocardium
impaired of sympato-adrenal system (SAS) number of1-adrenergic receptors on the surface of cardiomycytes
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2. Changes of neurohumoral control of the heartfunction
Physiology:SNS contractility HR activity of physiologic pacemakersMechanism: sympathetic activity cAMP Ca ++icontractility
sympathetic activity influenceof parasympathetic system on the heart
Pathophysiology: normal neurohumoral control ischanged and creation of pathologic
neurohumoral mechanisms are present
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Chronic heart failure (CHF) is characterized by an imbalance ofneurohumoral adaptive mechanisms with a net results of excessive
vasoconstriction and salt and water retention
Catecholamines :- concentration in blood :-norepinephrin 2-3x higher at the rest than in healthy subjects
- circulating norepinephrin is increased much moreduring equal load in patients suffering from CHF thanin healthy subject
- number of beta 1 adrenergic receptors sensitivity of cardiomyocytes to catecholamines contractility
System rennin angiotensin aldosteron
heart failure CO kidney perfusion stim. Of RAA system
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Important:Catecholamines and system RAA = compensatory mechanisms
heart function and arterialBP
The role of angiotensin II in development of heartfailure
vasoconstriction ( in resistant vesels) retention of Na blood volume releasing of arginin vasopresin peptide (AVP )
from neurohypophysis
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sensitivity of vessel wall to norepinephrinemitogenic effect on smooth muscles in vessels and
on cardiomyocytes hypertrophy constriction of vas efferens ( in glomerulus ) sensation of thirst secretion of aldosteron from adrenal glandmesangial conctraction glomerular filtration rate
facilitation of norepinephrine releasing fromsympathetic nerve endings
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Pathophysiology of diastolic heart failure
systolic heart failure = failure of ejecting function of the heart
diastolic heart failure = failure of filling the ventricles, resistance to filling of ventricles
But, which of the cardiac cycle is real diastole ?
Diastolic failure is a widely recognized clinical entity
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Definition of diastolic heart failure
It is pathophysiological process characterized by symptoms andsigns of congestive heart failure, which is caused by increased filling
resistance of ventricles and increased intraventricular diastolic
pressure
Primary diastolic heart failure
-no signs and symptoms of systolic dysfunction is present
- ! up to 40% of patients suffering from heart failure!
Secondary diastolic heart failure
- diastolic dysfunction is the consequence of primarysystolic dysfunction
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Main causes and pathomechanisms of diastolicheart failure
1. structural disorderspassive chamber stiffness
a) intramyocardial
e.g. myocardial fibrosis, amyloidosis, hypertrophy,
myocardial ischemia...
b) extramyocardial e.g. constrictive pericarditis
2. functional disorders relaxation of chambers e. g. myocardialischemia, advanced hypertrophy of ventricles,
failing myocardium, asynchrony in heart
functions
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Causes and mechanism participating on impairedventricular relaxation
a)physiological changesin chamber relaxation due to: prolonged ventricular contraction
Relaxation of ventricles is not impaired!
b) pathological changesin chamber relaxation due to:
Impaired relaxation process delayed relaxation (retarded) incomplete (slowed) relaxation
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Consequences of impaired ventricular relaxation-filling of ventricles ismore dependent on diastasisand onthesystole of atrias than in healthy subjects
Symptoms and signs: exercise intolerance = early sign of diastolic failure coronary blood flow during diastole
Causes and mechanisms involved in development
of ventricular stiffness ventricular compliance= passive property of ventricleSource of compliance: cardiomyocytes and other heart
tissue to stretching
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Ventricular compliance is caused by structural abnormalitieslocalized in myocardium and in extramyocardial tissue
a) Intramyocardial causes : myocardial fibrosis, hypertrophy of
ventricular wall,restrictive cardiomyopathy
b. Extramyocardial causes : constrictive pericarditis
The role of myocardial remodelling in genesis ofheart failure
adaptive remodelling of the heart pathologic remodelling of the heart
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Main causes and mechanisms involved inpathological remodelation of the heart
1.Increased amount and size of myocytes=hypertrophyDue to:- volume and/or pressure load
(excentric, concentric hypertrophy)
- hormonal stimulation of cardiomyocytes by
norepinephrine, angiotenzine II
2. Increased % ofnon-myocytic cellsin myocardium
and their influence on structure and function of heart
a.endothelial cellsendothelins : mitogenic ability stimulation growth of smooth muscle cells of vessels, fibroblasts
b.fibroblasts - production of kolagens
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Symptoms and signs of heart failure
1. forward failure:symptoms result from inability of the heart to pump enough
blood to the periphery (from left heart), or to the lungs (from
the right heart)
a) forward failure of left heart:-muscle weakness, fatigue,dyspepsia, oliguria....
general mechanism:tissue hypoperfusionb) forward failure of right heart:- hypoperfusion of thelungs disorders of gas
exchange
-decreased blood supplyto the left heart
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2. backward failure:symptoms result from inability of the heart to accept
the blood comming from periphery and from lungs
a. backward failure of left heart:
increased pulmonary capillary pressure dyspnoea
and tachypnoea, pulmonary edema (cardiac asthma)
arterial hypoxemia and hypercapnia....
b. backward failure of right heart:increased pressure in systemic venous system peripheral edemas, hepatomegaly, ascites nocturnal diuresis....