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PATHOPHYSIOLOGY OF PATHOPHYSIOLOGY OF HEART FAILUREHEART FAILURE
Jianzhong Sheng MD Jianzhong Sheng MD PhDPhD
Notes to heart Notes to heart physiologyphysiology
• Essential functions of the heartEssential functions of the heart
• to cover metabolic needs of body tissueto cover metabolic needs of body tissue (oxygen, substrates) by adequate blood (oxygen, substrates) by adequate blood supplysupply
• to receive all blood coming back from the tissue to receive all blood coming back from the tissue to the heartto the heart
• Essential conditions for fulfilling these functionsEssential conditions for fulfilling these functions
• normal structure and functions of the heartnormal structure and functions of the heart
• adequate filling of the heart by bloodadequate filling of the heart by blood
Essential functions of the heart are secured Essential functions of the heart are secured by integration of electrical and mechanicalby integration of electrical and mechanical
functions of the heartfunctions of the heart
Cardiac output (CO) = heart rate (HR) x stroke vol.(SV)Cardiac output (CO) = heart rate (HR) x stroke vol.(SV)
- - changes of the heart ratechanges of the heart rate
- changes of stroke volume- changes of stroke volume
• Control of HR:Control of HR:- autonomic nervous system- autonomic nervous system
- - hormonal(humoral) controlhormonal(humoral) control
• Control of SVControl of SV:: - preload- preload
- contractility- contractility
- afterload- afterload
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 R–A–A system
Causes leading to changes of number and size of
cardiomyocytes
PreloadPreloadStretching the myocardial fibers during diastole by Stretching the myocardial fibers during diastole by
increasing end-diastolic volume increasing end-diastolic volume force of contraction force of contraction
during systole = during systole = Starling´s lawStarling´s law
preloadpreload = = diastolic muscle sarcomere length leading to increased diastolic muscle sarcomere length leading to increased tension in muscle before its contraction tension in muscle before its contraction (Fig. 2,3)(Fig. 2,3)
- venous return to the heart is important venous return to the heart is important end-diastolic end-diastolic volume is influenced
- stretching of the sarcomere maximises the number stretching of the sarcomere maximises the number of actin-myosin bridges responsible for development of actin-myosin bridges responsible for development of forceof force
- - optimal sarcomere length optimal sarcomere length 2.2 2.2 mm
Myocardial contractilityMyocardial contractility
Contractility of myocardiumContractility of myocardium CChanges in hanges in ability of myocardium to ability of myocardium to developdevelop the the force force by contraction that occurby contraction that occur independently onindependently on the the changes in myocardial fibchanges in myocardial fibrre lengthe length
Mechanisms involved in changes of contractilityMechanisms involved in changes of contractility
• amount of created cross-bridges in the sarcomereamount of created cross-bridges in the sarcomere by by of of Ca Ca ++++ii concentration concentration
-- catecholamines catecholamines CaCa++++ii contractility contractility
- - inotropic drugs inotropic drugs CaCa++++ii contractility contractility
contractilitycontractility shifting the entire ventricular function shifting the entire ventricular function curve upward and to the leftcurve upward and to the left
contractilitycontractility shiffting the entire ventricular functionshiffting the entire ventricular function curve (hypoxia, acidosis) downward and to the righcurve (hypoxia, acidosis) downward and to the rightt
The pressure – volume loop
• It is the relation between ventricular volume and pressure
• This loop provides a convenient framework for understanding
the 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
Pressure – volume loops recorded under different
conditions
It It is expressed as tension which must be developedis expressed as tension which must be developed in in the wall of ventricles during systole to open the the wall of ventricles during systole to open the semilunar valvesemilunar valvess and eject blood to and eject blood to aorta/pulmunary aorta/pulmunary arteryartery
Laplace law:Laplace law:
intraventricular pressure x radius of ventricleintraventricular pressure x radius of ventriclewall tension = --------------------------------------------------------wall tension = --------------------------------------------------------
2 x2 x ventricular wall thickness ventricular wall thickness
afterloadafterload:: due to - elevation of arterialdue to - elevation of arterial resistance resistance - - ventricular size ventricular size - myocardial hypotrophy- myocardial hypotrophy
afterloadafterload:: due to - due to - arterial arterial resistance resistance - myocardial hypertrophy- myocardial hypertrophy - - ventricular size ventricular size
AfterloadAfterload
Heart failureHeart failure
DefinitionDefinition
It is the pathophysiological process in whichIt is the pathophysiological process in which
the heart as a pump is unable to meetthe heart as a pump is unable to meet
the metabolic requirements of the tissue for the metabolic requirements of the tissue for
oxygen and substrates despite the venousoxygen and substrates despite the venous
returnreturn to heart to heart is either normal or increased is either normal or increased
Explanation of the Explanation of the termsterms
• Myocardial failureMyocardial failure == abnormalities reside in the abnormalities reside in the myocardiummyocardium and lead and lead
to to inability of inability of myocardium myocardium to fulfilling its to fulfilling its function function
• Circulatory failureCirculatory failure = = any abnormality of the circulationany abnormality of the circulation responsible for the inadequacy in bodyresponsible for the inadequacy in body tissuetissue perfusion, e.g. decreased blood volume, perfusion, e.g. decreased blood volume, changeschanges of vascular tone, heart of vascular tone, heart functiones functiones disordersdisorders
• Congestive heart failureCongestive heart failure = clinical syndrome which is = clinical syndrome which is developed developed due to due to accumulation of the blood inaccumulation of the blood in frontfront
of the left or right parts of the of the left or right parts of the
heartheart
General pathomechanisms General pathomechanisms involved in heart failure involved in heart failure
developmentdevelopment
Cardiac mechanical dysfunction can developCardiac mechanical dysfunction can develop as as
a a consequence in preload, contractility and afterload consequence in preload, contractility and afterload
disordersdisorders
Disorders of preloadDisorders of preload
preloadpreload length of sarcomere is more than optimal length of sarcomere is more than optimal strength of contractionstrength of contraction
preloadpreload length of sarcomere is well below thelength of sarcomere is well below the optioptimalmal strength of contractionstrength of contraction
Important:Important: failing ventricle requires higher end-diastolicfailing ventricle requires higher end-diastolic volume volume
to achieve the same improvement of CO that to achieve the same improvement of CO that
normalnormal
ventricle achievesventricle achieves with lower ventricular with lower ventricular
volumesvolumes Disorders of contractilityDisorders of contractility
In In the the most forms of heart failure the contractility ofmost forms of heart failure the contractility of myocardium myocardium
is decreased (ischemia, hypoxiais decreased (ischemia, hypoxia,, acidosis, acidosis, inflammation, toxins, inflammation, toxins,
metabolic disordersmetabolic disorders...... ) )
Disorders of afterloadDisorders of afterload due to: due to:
• fluid retentionfluid retention in the body in the body
• arterial resistancearterial resistance
• valvular heart diseases ( stenosisvalvular heart diseases ( stenosis ))
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
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 period
of passive filling)
end-diastolic ventricular pressure is increased
Causes of heart pump failureCauses of heart pump failure
A. MECHANICAL ABNORMALITIESA. MECHANICAL ABNORMALITIES
1. Increased pressure load1. Increased pressure load
– – ccentral (aortic stenosisentral (aortic stenosis, aortic coarctation..., aortic coarctation...))
–– pperipheral (systemic hypertension)eripheral (systemic hypertension)
2. Increased volume load2. Increased volume load– – valvular regurgitationvalvular regurgitation
– hypervolemia
3. Obstruction to ventricular filling3. Obstruction to ventricular filling –– valvular stenosisvalvular stenosis
–– pericardial restrictionpericardial restriction
B. MYOCARDIAL DAMAGEB. MYOCARDIAL DAMAGE
1. Primary1. Primary
a) a) ccardiomyopathyardiomyopathy
b) b) mmyocarditisyocarditis
c) c) ttoxicity (oxicity (e.g. e.g. alcohol)alcohol)
d) d) mmetabolic abnormalities (etabolic abnormalities (e.g. e.g. hyperthyroidismhyperthyroidism))
2. Secondary2. Secondary
a) a) ooxygen deprivation (xygen deprivation (e.g. e.g. coronary heart disease)coronary heart disease)
b) b) iinflammation (nflammation (e.g. e.g. increased metabolic demands)increased metabolic demands)
c) c) cchronic obstructive lung diseasehronic obstructive lung disease
C. ALTERED CARDIAC RHYTHMC. ALTERED CARDIAC RHYTHM
1. 1. vventricular entricular flutter and flutter and fibrilationfibrilation
2. 2. eextreme tachycardiasxtreme tachycardias
3. 3. eextreme bradycardiasxtreme bradycardias
Pathomechanisms involved in heart failurePathomechanisms involved in heart failure
A. Pathomechanisms involved in myocardial failureA. Pathomechanisms involved in myocardial failure
1.1. Damage of cardiomyocytesDamage of cardiomyocytes contractility, contractility, compliancecompliance
Consequences:Consequences: defect in ATP production and utilisationdefect in ATP production and utilisation
changes in contractile proteinschanges in contractile proteins
uncoupling of excitation – contraction processuncoupling of excitation – contraction process
number of cardiomyocytesnumber of cardiomyocytes
impairment of relaxation of cardiomyocytes withimpairment of relaxation of cardiomyocytes with decrease decrease compliance of myocardiumcompliance of myocardium
impaired of sympato-adrenal system (SAS) impaired of sympato-adrenal system (SAS) numbernumber of of 11-adrenergic receptors on the surface of -adrenergic receptors on the surface of
cardiomycytescardiomycytes
2. Changes of neurohumoral control of the heart 2. Changes of neurohumoral control of the heart functionfunction
• Physiology:Physiology: •• SNSSNS contractili contractilityty
HRHR
activactivity of ity of physiologic physiologic pacemakerspacemakers
Mechanism:Mechanism: sympathetic activity sympathetic activity cAMP cAMP Ca Ca ++++ii contractilitycontractility
sympathetic activity sympathetic activity influenceinfluence of parasympathetic system onof parasympathetic system on thethe heartheart
•• Pathophysiology:Pathophysiology: normal neurohumoral control isnormal neurohumoral control is
changed and creationchanged and creation of of
pathologicpathologic
neurohumoral mechanismsneurohumoral mechanisms are are
presentpresent
Chronic heart failure (CHF) is characterized by Chronic heart failure (CHF) is characterized by an imbalance of neurohumoral adaptive an imbalance of neurohumoral adaptive mechanisms with a net results of excessive mechanisms with a net results of excessive vasoconstriction andvasoconstriction and salt and water retentionsalt and water retention
Catecholamines :Catecholamines : - concentration in blood :- concentration in blood :
- norepinephrin – 2-3x norepinephrin – 2-3x higher at the rest than in healthy subjectshigher at the rest than in healthy subjects
- - circulating norepinephrin is increased much more circulating norepinephrin is increased much more during equal load in patients suffering from CHF than during equal load in patients suffering from CHF than in in healthy subjecthealthy subject
- number of beta 1 – adrenergic receptors number of beta 1 – adrenergic receptors sensitivity ofsensitivity of cardiomyocytes to catecholamines cardiomyocytes to catecholamines contractilitycontractility
System rennin – angiotensin – aldosteronSystem rennin – angiotensin – aldosteron
hheart failureeart failure CO CO kidney perfusion kidney perfusion stim stim.. Of Of RAA RAA systemsystem
Important:Important:
Catecholamines and system RAA = compensatory mechanisms
heart function and arterialheart function and arterial BPBP
The role of angiotensin II in development of heart The role of angiotensin II in development of heart failurefailure
vasoconstriction ( in resistant vesels)vasoconstriction ( in resistant vesels)
retention of Na retention of Na blood volume blood volume
releasing of arginin – vasopresin peptide (AVP ) releasing of arginin – vasopresin peptide (AVP ) fromfrom neurohypophysisneurohypophysis
sensitivity of vessel wall to norepinephrinesensitivity of vessel wall to norepinephrine
mitogenic effect on smooth muscles in vessels and mitogenic effect on smooth muscles in vessels and
onon cardiomyocytes cardiomyocytes hypertrophy hypertrophy
constriction of vas efferens ( in glomerulus )constriction of vas efferens ( in glomerulus )
sensation of thirstsensation of thirst
secretion of aldosteron from adrenal glandsecretion of aldosteron from adrenal gland
mesangial conctraction mesangial conctraction glomerular filtration rateglomerular filtration rate
facilitation of norepinephrine releasing from facilitation of norepinephrine releasing from sympatheticsympathetic nerve endingsnerve endings
Pathophysiology of diastolic Pathophysiology of diastolic heart failureheart failure
systolic heart failuresystolic heart failure = = failure of ejecting function of the heartfailure of ejecting function of the heart
diastolic heart failurediastolic heart failure = = failure of filling the ventricles,failure of filling the ventricles,
resistanceresistance to filling to filling of ventricles of ventricles
But,But, wwhich of the cardiac cycle ishich of the cardiac cycle is real real diastole ? diastole ?
Diastolic failure is a widely recognized clinical entity
Definition of diastolic heart failureDefinition of diastolic heart failure
It is pathophysiological process characterized by symptoms It is pathophysiological process characterized by symptoms
and signs of congestive heart failure, which is caused byand signs of congestive heart failure, which is caused by
increased filling resistance of ventricles and increased filling resistance of ventricles and iincreasedncreased
intraventricular diastolic pressureintraventricular diastolic pressure
Primary diastolic heart failurePrimary diastolic heart failure
- no signs and symptoms of systolic dysfunctionno signs and symptoms of systolic dysfunction is present is present
-- ! up to 40% ! up to 40% of of patients suffering from heart failure!patients suffering from heart failure!
Secondary diastolic heart failureSecondary diastolic heart failure
- diastolic dysfunction is the consequence of- diastolic dysfunction is the consequence of primary primary systolic systolic dysfunctiondysfunction
Main causes and pathomechanisms of diastolicMain causes and pathomechanisms of diastolic heart failureheart failure
1.1. structural disordersstructural disorders passive chamber stiffnesspassive chamber stiffness
a)a) intramyocardialintramyocardial
– – e.g. myocardial fibrosis, amyloidosis,e.g. myocardial fibrosis, amyloidosis, hypertrophy, hypertrophy,
myocardial ischemiamyocardial ischemia......
b) extramyocardialb) extramyocardial – e.g. constrictive pericarditis – e.g. constrictive pericarditis
2. functional disorders2. functional disorders relaxation of chambers relaxation of chambers e. g. myocardial e. g. myocardial
ischemia, advanced hypertrophy of ventricles,ischemia, advanced hypertrophy of ventricles,
failing myocardium, asynchronyfailing myocardium, asynchrony in heart in heart
functionsfunctions
Causes and mechanism participating on impairedCauses and mechanism participating on impaired ventricular relaxationventricular relaxation
a)a) physiological changesphysiological changes in chamber relaxation in chamber relaxation due todue to: :
– – prolonged ventricular contraction prolonged ventricular contraction
Relaxation of ventricles is not impairedRelaxation of ventricles is not impaired !
b) pathological changesb) pathological changes inin chamber relaxation chamber relaxation due todue to: : IImpaired relaxation processmpaired relaxation process
delayed relaxation (retarded)delayed relaxation (retarded)
incomplete (slowed) relaxationincomplete (slowed) relaxation
Consequences of impaired ventricular relaxationConsequences of impaired ventricular relaxation
- filling of ventricles isfilling of ventricles is more dependent on diastasis more dependent on diastasis and onand on thethe systolesystole of atrias than in healthy subjects of atrias than in healthy subjects
SSymptoms and signs:ymptoms and signs:
exercise intoleranceexercise intolerance = = early sign of diastolic failureearly sign of diastolic failure
coronary blood flow during diastolecoronary blood flow during diastole
Causes and mechanisms involved in developmentCauses and mechanisms involved in development of ventricular stiffnessof ventricular stiffness
ventricular complianceventricular compliance = passive property of ventricle= passive property of ventricle
Source of compliance: Source of compliance: cardiomyocytes and other heart cardiomyocytes and other heart
tissue to stretching tissue to stretching
VVentricular compliance is caused by structuralentricular compliance is caused by structural abnormalities abnormalities
localized in myocardium and in extramyocardial tissuelocalized in myocardium and in extramyocardial tissue
a) a) Intramyocardial causesIntramyocardial causes : myocardial fibrosis, hypertrophy of : myocardial fibrosis, hypertrophy of ventricular wall, restrictive cardiomyopathyventricular wall, restrictive cardiomyopathy
b. Extramyocardial causesb. Extramyocardial causes :: constrictive pericarditis constrictive pericarditis
The role of myocardial remodelling in genesis ofThe role of myocardial remodelling in genesis of heart failureheart failure
adaptive remodelling of the heartadaptive remodelling of the heart
pathologic remodelling of the heartpathologic remodelling of the heart
Main causes and mechanisms involved Main causes and mechanisms involved in in
pathological remodelation of the heartpathological remodelation of the heart1. Increased amount and size1. Increased amount and size of myocytesof myocytes == hypertrophyhypertrophy
Due to:Due to: - - volume and/or pressure load volume and/or pressure load (excentric, concentric hypertrophy(excentric, concentric hypertrophy))
- hormonal stimulation of cardiomyocytes by - hormonal stimulation of cardiomyocytes by norepinephrine, angiotenzine IInorepinephrine, angiotenzine II
2. Increased 2. Increased % % ofof non-myocytnon-myocyticic cells cells iin myocardiumn myocardium and and their their influenceinfluence on structure and function of heart on structure and function of heart
a.a. endothelial cellsendothelial cells – – endothelins :endothelins : mitogenic ability mitogenic ability stimulation growth of smooth muscle cells of vessels, fibroblastsstimulation growth of smooth muscle cells of vessels, fibroblasts
b.b. fibroblastsfibroblasts - - production of kolagens production of kolagens
Symptoms and signs of heart failureSymptoms and signs of heart failure
1.1. forward failure:forward failure: symptoms result from inability of the heart to pump enough symptoms result from inability of the heart to pump enough
blood to the peripheryblood to the periphery (from(from left heart), or to the lungs (from left heart), or to the lungs (from
the right heart)the right heart)
a) forward failure of left heart:a) forward failure of left heart:-- muscle weakness, fatigue, muscle weakness, fatigue, dyspepsia, oliguriadyspepsia, oliguria........
generalgeneral mechanism mechanism:: tissue hypoperfusiontissue hypoperfusion
b) forward failure of right heartb) forward failure of right heart:: - hypoperfusion of the - hypoperfusion of the lungs lungs disorders of gas disorders of gas exchangeexchange
- decreased blood supply decreased blood supply to the left heartto the left heart
2. backward failure:2. backward failure: – symptoms result from inability of the heart to accept symptoms result from inability of the heart to accept
the blood comthe blood commming from periphery and from lungsing from periphery and from lungs
a.a. backward failure of left heart:backward failure of left heart:
– – increased pulmonary capillary pressureincreased pulmonary capillary pressure dyspnoea dyspnoea
and tachypnoea, pulmonary edema (cardiac asthma) and tachypnoea, pulmonary edema (cardiac asthma)
arterial arterial hypoxhypoxemiaemia and hypercapnia and hypercapnia........
b. backward failure of right heart:b. backward failure of right heart:
– increased pressure in increased pressure in systemic systemic venous systemvenous system
peripheral edemas, hepatomegaly, ascites peripheral edemas, hepatomegaly, ascites nocturnalnocturnal diuresisdiuresis........
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