Thorough Pathophysiology

dr. T. M. Haykal Putra

Heart Failure

Definition of Heart FailureFrank – Starling Relationship

(Preload-Afterload-Contractility)Cardiac OutputPressure-Volume LoopSystolic & Diastolic DysfunctionNeurohormonal AlterationRemodellingClinical Manifestation

Milestones

Leonard S. LillyInability of the heart to pump blood forward at sufficient

rate to meet the metabolic demands of the body (forward failure)

The ability to do so if the cardiac filling pressures are abnormally high (backward failure)

ESCAn abnormality of cardiac structure or function leading to

failure of the heart to deliver oxygen at a rate commensurate with the requirements of the metabolizing tissue, despite normal filling pressure.

Definition

Basic PhysiologyCardiac Output (CO)

Volume of blood ejected from the ventricle every minute

Stroke Volume (SV) Volume of blood ejected from

the ventricle during systole (every beat)

CO = SV x HR

Cardiac Output

Heart Rate Stroke Volume

Preload Afterload Contractility

If the muscle is passively stretched and then stimulated to contracts The force would be augmentedOptimization of myosin & actin interaction Increased sensitivity of myofilament to calcium

Clinical ImplicationThe larger ventricular volume during diastole, the more

fibers are stretchedGreater force of contraction

Stretch of the muscle ~ Preload

Frank-Starling Relationship (I)

The Force of contraction is directly related to the magnitude of the loadThe force is independent of the muscle length before

contraction (stretch)

Clinical ImplicationThe pressure generated by the ventricle depend on the

load (afterload) againts which the ventricle contracts

Magnitude of the load ~ afterload

Frank-Starling Relationship (II)

Myocardial contractility (inotropic) is independent of initial fiber length (preload) & load against which it contracts (afterload)

Contractility reflects chemical & hormonal influences on cardiac contractionEx. Exposure to cathecolamines

Frank-Starling Relationship (III)

Cardiac Output

CO

HR SV

Preload Afterload Contractility

+ +-

The ventricular wall tension at the end of diastoleThe stretch on the ventricular fiber just before the

contraction“Tekanan pengisian ventrikel”

The more ventricle is filled with blood, the greater the volume ejected

Preload is measured as EDVInfluenced by intravascular volume

Decreased in dehydration or hemorrhageIncreased in hypervolemia or water retention

Preload

The ventricular wall tension during contractionThe resistance that must be overcome for the ventricle to ejectVentricular wall stress that develops during systolic ejection “Tekanan Pengosongan Ventrikel”

Measured as wall stress

Wall stress based on Laplace’s relationship Influenced by pressure load (P) Influenced by increased chamber size (r) Influenced by wall thickness (h)

Afterload

Pressure – Volume Loop

Preload – Afterload

Contractility

Cardiac Output

CO

HR SV

Preload Afterload Contractility

+ +-

1. Systolic Dysfunction Abnormality of ventricular emptying “Reduced Ejection Fraction” (EF<50%)

2. Diastolic disfunction Abnormality of ventricular relaxation (ventricular

filling) “Preserved Ejection Fraction” (EF>50%)

Ejection Fraction(stroke volume)/(end-diastolic volume)

Systolic & Diastolic Dysfunction

Diminished capacity to eject blood because of impaired myocardial contractility or pressure overloadContractilityAfterload

Compensatory mechanismIncreased preloadThe volume remains in the ventricle because of

incomplete emptying result in volume accumulation (increased EDV)

Maintain SV via Frank-Starling mechanism

Systolic Dysfunction

Abnormality of vetricular diastolic function either impaired diastolic relaxation (energy-dependent process) or increased stiffness of the ventricular wallIschemia or passive property of the heart (hypertrophy,

fibrosis, etc.)

Reduced chamber complianceThe ease or difficulty with which the chamber can be

filledVentricular filling is at higher pressure

Diastolic Dysfunction

Frank-Starling MechanismNeurohormonal AlterationRemodelling

Compensatory Mechanism

1. Adrenergic Nervous System2. Renin-Angiotensin-Aldosteron System (RAA system)3. Antidiuretic Hormone (ADH)

To maintain arterial perfusion to vital organs (BP)BP = CO x SVRSVR Systemic Vascular Resistance

Moreover, neurohormonal activation results in salt and water retention Which maximizing SV via Frank-Sarling Mechanism

Neurohormonal Alteration (I)

The fall in CO is sensed as decreased pressure by baroreceptors in the carotid sinus and aortic arch

Signal is transmitted to CV control in the MedullaThe result is diminished parasympathetic tone and

increased sympathetic tone

Effect of sympathetic tone:Increased HRIncreased ventricular contractilityVasoconstriction veins & arteries

Adrenergic Nervous System (I)

Adrenergic Nervous System (II)

Augmented CO Increased HR Increased contractility

Vasoconstriction of veins augments blood return to the

heart which increase preload (frank-starling mechanism)

Vasoconstriction of arteries Increased SVR to maintain BP

BP

SVR CO

HR SV

Preload Afterload Contractility

+ +-

RAA system

Vasopressin is secreted by posterior pituitary through baraoreceptors and angiotensin II

Clinical importanceIncreased Intravascular volume (promotes water

retention in the distal nephron)

ADH

Neurohormonal Alteration (II)

Initially beneficial However, continue activation typicaly proves harmful

Increased circulating volume and augmented venous return increase the afterload Against which the failing LV contracts Will impair SV

Increased metabolic demand Further reduce the performance of the failing heart

Chronically elevated AII & aldosterone provoke the production of cytokines Resulting in remodelling and cellular dysfunction

Neurohormonal Alteration (III)

A sustained increase in wall stress (afterload) along with neurohormonal and cytokine stimulate the development of myocardial hypertrophy and deposition of extracellular matrixIs actually compensatory mechanism to counteract wall

stress

However the hypertrophic wall is stiffDiastolic ventricular pressure will be higherThe pressure will be directed backwards to LA &

pulmonary vasculature

Remodelling (I)

Pressure Directed Backwards

There will be myocite loss, cellular dysfunction & deposition of extracellular matrixApoptosisPhagocytosis without inflammatory responseTriggered by Catecholamines, AII, Cytokines &

mechanical strains

Remodelling (II)

Alteration in MyociteBeta-adrenergic desensitizationHypertrophy

Myocardial ChangesMyocite loss (apoptosis)Matrix degradationMyocardial Fibrosis

Alteration in LV GeometryLV dilationLV wall thinningMV incompetence

Remodelling (III)

Clinical Manifestation (I)DOE (dyspneu on

effort/dyspnea on exertion)Decreased COManifestation of

pulmonary venous congestionTransudation of fluid into

pulmonary interstisial increased greater effort of respiration

Juxtacapillary receptor are stimulated and mediate rapid shallow breathing

OrthopneaLabored breathing while

lying flat and relieved by sitting upright

Assessed by the number of pillow being used during sleeping

Results from redistribution of intravascular volume from abdomen & lower extremities towards the lungs

Clinical Manifestation (II)Paroxysmal Nocturnal

Dyspnea (PND)Severe breathlessness

that awakens the patient from sleep 2 to 3 hours after bed

Results from gradual reabsoprtion into circulation of lower extremity intterstisial edema after lying downSubsequent expansion of

intravascular volume

Weight gainAccumulation of

interstitial fluid

Abdominal dyscomfort Engorged liver and

stretched capsule

Diaphoretic Increased sympathetic

activity

ReferrenceLilly LS. Pathophysiology of heart disease. 5th ed. USA:

Williams & Wilkins; 2011.Libby P, Bonow RO, Mann DL, Zipes DP. Braunwald’s

heart disease. 8th ed. USA: elseviers; 2007.McMurray JV, Adamopoulos S, Anker SD, Auricchio A,

Bohmm M, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. European Heart Journal 2012; 33: 1787-1847.

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