Oedema Kuliah

7/30/2019 Oedema Kuliah

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OEDEMA

Sutikno Tanuwidjaja

Subbagian Kardiologi Bagian Ilmu Penyakit Dalam

FK UNDIP/RS Dr. Kariadi Semarang


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Major body fluid compartments with average volumes indicated for a 70-kg human.Total body water is about 60% of body weight.

LUNGS

RIGHT

HEART

LEFT

HEART

BODY ORGANS

Circulating plasma

- 3 L

Intracellular space

- 30 L

Interstitial space

(internal environment

- 12 L

CAPILLARIES

CELLS


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BERAT BADAN TOTAL (70 KG)

AIR TUBUH TOTAL (42L)

ICV (28L) ECV (14L)

SDM PV

(3 L)

Vol darah 5 L

IF = ECV - PV

Volume distribusi air mencakup volume

intraselular (ICV) dan ekstraselular (ECV).


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Diffusion of fluid and dissolved substances between the

capillary and interstitial space

BLOOD CAPILLARYArterial

endVenous

end

LYMPHATIC CAPILLARY


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Alveolar

epithelium

Epithelialbasementmembrane

Interstitialspace

Capillarybasementmembrane

Capillaryendothelium

REDBLOODCELL

CAPILLARYALVEOLUS

Diffusion of oxygen

Diffusion of carbon dioxide

The structures of thealveolar-capillary

membrane over whichreciprocal diffusion of

oxygen and carbondioxide occurs


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LUNGS

LEFT HEART PUMPRIGHT HEART PUMP

HEART MUSCLE

BRAIN

SKELETAL MUSCLE

GASTROINTESTINAL SYSTEM, SPLEEN

LIVER

KIDNEY

SKIN

OTHER

BONE

VEINS ARTERIES

100%100%

100%

3%

14%

15%

5%

21%

6%

22%

6%

8%


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Definition of Heart Failure

Heart failure is the pathophysiologicalstate in which the heart is unable to pumpblood at a rate commensurate with therequirements of the metabolizing tissues

or can do so only from an elevated fillingpressure.

Heart failure is a complex clinical

syndrome that can result from anystructural or functional cardiac disorderthat impairs the ability of ventricle to fillwith or eject blood.


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Mechanism of death

Sudden death 40%

Worsening CHF 40%

Other 20%

Further damage

Excessive wall stressNeurohormonal activation

Myocardial ischemia

Progression

Annual mortality


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FRAMINGHAM HEART STUDY

Incidence of heart failure by age and sex

(Kannel & Belanger, 1981)

100

90

80

70

60

50

40

30

20

10

045-54 55-64 65-74 75-84 85-94

Age (yr)

Rate

per1000

Males

Females


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EVOLVING MODELS OF HEART FAILURE

Cardiorenal Hemodynamic Neurohormonal

Digitalis and

Diuretic to Perfuse

kidneys

Vasodilators or

positive inotropes to

relieve ventricular

wall stress

ACE-I, -blockers

and other agents to

block neurohormonal

activation

1940s 1960s 1970s 1990s - 2000


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LV dilatation

Activation of Neurohormonal Pathways in HF

Coronary Disease Cardiomyopathy Cardiac Overload

Left Ventricular Dysfunction

Neurohormonal Activation Cathecholamines

RAS AVP Endothelin

Cardiac RemodellingPeripheral OrganBlood Flow

Vasoconstriction

skeletalmuscle flow

RBFNa+ retention

LV hypertrophy

Arrhythmias

Exercise Intolerance Edema, Congestion Sudden Death Pump Failure

Ruffolo, J Cardiovasc, Pharmachol, 1998


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The multiple effects of left ventricular (LV) dysfunction

Autonomic NS Metabolic

Renal

Hepatic Skeletal muscle

Other

Neuroendocrine

Vascular tone/structure

Peripheral

Coronary

LV Dysfunction

Electrical

substrate

dennervation

chemical milieu

Mechanical

cell death

fibrosis

Heart


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The Role of Angiotensin II in the progression of Heart Failure

Coronary artery disease

Pressure overload Cardiomyopathy

Left ventricular dysfunction

Arterial blood pressure

Renin release

Angiotensin II

Na+

and water retention

Aldosterone release

Vasoconstriction

Edema

Vascular and cardiac

hypertrophy

Peripheral organ blood flow

Renalblood flow

Skeletal muscleBlood flow

Exercise intolerance

Cardiac remodelling

Left ventricular

dilation & hypertrophy

Pump failure


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Vasodilatation

Diuresis

Antimitogenic

VasoconstrictionSalt and water

retention

Apoptosis

Hypertrophy

Myocardial

dysfunction

Prostaglandins Natriureticpeptides No

Free radicals

Cytokines

Growth

hormoneEndothelins

Catecholamines

All

ReninAVP

Aldosterone

Many different neurohormonal pathways are stimulated following myocardial dysfunction


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Humoral

RAAS

Epinephrine

EndothelinGrowth factors

Myocyte

slippage

Myocyte

hypertrophy

Interstitial

fibrosis

Stretch

Increased

myocardial

volume

Increased

myocardial

mass

Remodeling

Increased

stroke volume

(Starling)

Decreased

Wall stress

(Laplace)

Adaptive Mal-

adaptive

Increased

O2 demand

Ischemia

Impaired

Contractility

Arrhythmo-

genesis

Factors influencing myocardial remodelling in HF


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CARDIAC REMODELING

Cardiac remodeling may be defined as genome expression,

molecular, cellular and interstitial changes that are

manifested clinically as changes in size, shape and

function of the heart after cardiac injury.

Remodeling encompasses cellular changes including

myocyte hypertrophy, necrosis, apoptosis, fibrosis,

increased fibrillar collagen and fibroblast

proliferation.

(Cohn et al, 2000)


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Disease progression in heart failure. LV = left ventricular.( Elchorn & Young , 2001)

Asymptomatic Symptomatic

LVEjectionFraction

0.60

0.20

Index Event (myocardial injury)


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NEUROHUMORAL EFFECTS OF HEART FAILURE

Poor organperfusion

kidneyLow BP

FORWARD FAILURELOW BLOOD PRESSURE

Baroreflexes

Adrenergic stimulation

RENIN

Angiotensin

Aldosterone

ANP

Na+ loss Na+ retension

Edema

EXCESSBLOOD VOLUME

low renal

blood flow

EXCESSAFTERLOAD

Increasing

forward

failure

Increasing

preload

heartINCREASINGBACKWARD

FAILURE

big liveredema

Leftventricle

back

ward

pressure

RVLA

RV failure

JVP

BACKWARD FAILUREINTO LUNGS & RV

ACE inhibitors for congestive heart failure

(Opie, 1994)


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DETERMINANTS OF

VENTRICULAR FUNCTION

CONTRACTILITY

PRELOAD

Synergistic LV contraction

LV wall integrity

Valvular competence

CARDIAC OUTPUT

HEART

RATE

STROKE

VOLUME

AFTERLOAD


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Major Criteria

Paroxysmal nocturnal dyspnea

Neck vein distention

Rales

Radiographic cardiomegalyAcute pulmonary edema

S3 gallop

Central venous pressure > 16 cm H2O

Circulation time > 25 sec

Hepatojugular reflux

Pulmonary edema, visceral congestion, or cardiomegaly at autopsyWeight loss > 4.5 kg in 5 days in response to treatment of congestive heart failure

Minor Criteria

Bilateral ankle edema

Nocturnal cough

Dyspnea on ordinary exertion

HepatomegalyPleural effusion

Decrease in vital capacity by one third from maximal value recorded

Tachycardia (rate > 120 beats min)

FRAMINGHAM CRITERIA FOR CONGESTIVE HEART FAILURE

( Ho KL, et al., 1993 )

The diagnosis of CHF in this study required that two major

or one major and two minor criteria be present concurrently, Minor Criteria

were acceptable only if they could not be attributed to another medical condition.


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Clinical Clues to the Differential Diagnosis of

Congestive Heart Failure

Systolic CHF Diastolic CHF

History

Myocardial infarction XX XHypertension X XX

Physical examination

Displaced PMI XS3 gallop X

S4 gallop X

Chest radiograph

Cardiomegaly XX X

Pulmonary congestion XX XX

Electrocardiogram

Q waves XX X

Left ventricular hypertrophy X XX

(Goldsmith & Dick, 1993)


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Neurohormonal stimulation

Endothelial dysfunction

Vasoconstriction

Renal sodium retention

Progression of Cardiovascular DiseaseCoronary

arterydisease

HypertensionArrhythmia

Left ventricularremodeling

RemodelingLow ejection

fractionDeath

Pump

failureCardiomyopathyValvular

disease

(Abraham, 2000)

Noncardiac

factors

Symptoms:

Dyspnea

Fatigue

Edema

Chronic

heart

failure


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HEART FAILURE SPECTRUMRisk

Factors

Symptoms

NYHA II-III SymptomsNYHA - IV

Symptoms

ECHO / LV dysfunction

BNP?

Asymptomatic

LV Dysfunction

Heart disease


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Aims of treatment

Preventiona) Prevention and/or controlling of diseases

leading to cardiac dysfunction and heart failure

b) Prevention of progression to heart failure once

cardiac dysfunction is established

MorbidityMaintenance or improvement in quality of life

MortalityIncreased duration of life

Guidelines for the diagnosis and treatment of chronic heart failure

European Heart Journal (2001) 22, 1527-1560

Ch i C ti H t F il


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Cortex

Medulla

ThiazidesInhibit active exchange of Cl-Na

in the cortical diluting segment of the

ascending loop of Henle

K-sparingInhibit reabsorption of Na in thedistal convoluted and collecting tubule

Loop diuretics

Inhibit exchange of Cl-Na-K inthe thick segment of the ascendingloop of Henle

Loop of HenleCollecting tubule

DIURETICS

Chronic Congestive Heart Failure


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LOW VS HIGH CEILING DIURETICS

High-ceiling

Loop diuretics

Low-ceiling

Thiazides

K+ -sparing

DOSE

EFFICACY

Opie (2001)

Dose foroliguria

Dose for

severe CHF

Dose for

mild CHF

Dose for

hypertension


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Low-outputsymptoms

Left ventricular filling pressure

Congestiveand low-

outputsymptoms

Diureticonly

Stro

kevolume

Inotropic agent+ vasodilator+ diuretic

Inotropic agent+ vasodilator

Vasodilatoronly

Inotropicagent only

Congestivesymptoms

(Smith & Kelly, 1991)


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Myocardial Insult

and/or

Excessive Load

LV Dilation

and

Hypertrophy

Myocyte Loss,

Elongation or

Slippage

DecreasedLV Reserve

Increased

Afterload

GISSI-3CONSENSUS-2SMILEISIS-4

SAVESOLVD (prev.)TRACE

V-HeFT-1V-HeFT-2SOLVD (treat.)CONSENSUS-1AIRE

CHF

INITIAL EVENT LV REMODELING CLINICAL

SYNDROMEAII

M.R.

Diastolic WallStress

Energy SupplyPATHOPHYSIOLOGY

TRIALS

The pathophysiology of heart failure progressing

with time from the initial event. (Lejemtel et al, 2001)


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INOTROPIC, VAGAL & SYMPATHOLYTIC EFFECTS OF DIGOXIN

Vasodilation

Diuresis

RASinhibition

E

NE

Sympatho-inhibitoreffects

Vagomimeticeffect

Baroreceptors

Adrenergicactivationin CHF

CHF

AVSA

+

Positive inotropic effect

3 Na+

Digoxin Na+

Na+ rises

2K+

+Ca2+

Digitalis has both neural and myocardial cellular effects. Opie (2001)

Toxic arrhythmias


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Bisoprolol pooled (2 trials)

Bucindolol pooled (4 trials)

Carvedilol pooled (5 trials)

Metoprolol pooled (9 trials)

5 small trials

Overall (25 trials)

0.1 0.2 0.5 1 2 5 10

Pooled odds ratios (and 95% confidence intervals) describing the effectof blockers on mortality in patients with heart failure (fixed effects model)

(Cleland et al, 1999)


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Adrenergic

Directcardiotoxicity

Renin-angiotensin

?

Vasoconstriction

Volumeoverloaded

Increasedheart rate andcontractility

IncreasedMVO2

Increasedwall stress

Myocytedamage Hypertrophy

Decreased contractility

(Bristow, 1993)

Betablocker and beta adrenergic

receptor in heart failure


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Vascular

smooth

muscle

cells

Endothelial cell of

intramyocardial

coronary artery

Tissue fluid

of interstitium

Myocyte

Fibrillar

collagen

Endothelial

cell ofcapillary

Cardiac

fibrolast

ofinterstitial

space

Myocyte and nonmyocyte constituents of the heart.


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Pulmonary capillary fluid dynamics (Adapted from Wilson RF: Cardiovascular

physiology. In Critical care manual, ed 2, Philadelphia, 1992, Davis)

PULMONARY CAPILLARY FLUID DYNAMICSHydrostatic forces at either end of the pulmonary capillary favor a

driving pressure through the capillary bed of approximately 4 mm

Hg. The normal mean forces acting at the pulmonary capillary are

as follows :

AVERAGE FORCES TENDING TO PUSH FLUID OUT OF

THE PULMONARY VASCULAR SPACE

Mean pulmonary capillary hydrostatic pressure 8.0 mm Hg

Subatmospheric pulmonary interstitial hydrostatic

pressure (drawing fluid into the lung) -10.0 mm Hg

Interstitial oncotic pressure +12.0 mm Hg

Net Forces Directing Fluid Outward 30.0 mm Hg

AVERAGE FORCES TENDING TO PUSH FLUID INTO

THE PULMONARY VASCULAR SPACE

Plasma oncotic pressure 28.0 mm Hg

Net Forces Dircted Inward 28.0 mm Hg

Net forces : Outward 30.0 mm HgInward -28.0 mm Hg

AVERAGE FORCES DIRECTING FLUID INTO

THE PULMONARY TISSUE SPACE 2.0 mm Hg

Arteriole

Venule

Laters

titialspace

Alveolus


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PRESSURES CAUSING FLUID MOVEMENT

Hydrostatic and osmotic forces at the capillary (left) and alveolar membrane (right) of

the lungs. Also shown is a lymphatic (center) that pumps fluid from the pulmonary

interstitial spaces. (Modified from Guyton, Taylor, and Granger : Dynamics of the

Body Fluids. Philadelphia, W. B. Saunders Company, 1975)

Osmoticpressure

Netpressure

Hydrostaticpressure

Capillary Alveolus

( Surfacetensionat pore )

( Evaporation )

+7

-28 -14

-8

(+1)-5000

-8 -8

-5000-8

-4

( 0 )

Lymphatic pump


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Various causes of edema


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Pathophysiology of CHF

Injury to myocytesand EC matrix

Electrical, vascular, renal,

pulmonary, muscle effects

CHF

Ventricular

remodelling

Neurohumoral activationIncreased cytokines

Immune andinflammatory changes

altered fibrinolysis

Oxidative stressApoptosis

Altered geneExpressionEnergy starvation

McMurray J, Pfeffer M. Circulation. 2002 (in press)


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CAPILLARY (NUTRIENT) BED

ARTERY

VEIN

Venules

Capillary

(nutrient) bed

Metarterioles

Arterioles


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Determinants of stroke volume and cardiac output

MUSCULAR SYNCHRONY

CONTRACTILITY

AFTERLOAD

PRELOAD

HEART RATE

STROKE VOLUME

CARDIAC OUTPUT


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Starlings law of the heart

Ventricular end-diastolic volume

stro

kevolume


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E A

AO

mmHg120

80

40

0

ml120

80

40

0

cm/s80

40

0

Factors

influencing

LV diastole

M-mode

achocardio-

graphy

Dopplerecho

ECG

LV Volume

LV Pressure

AortaLV

LA

RV

sv

P

R

T P

Q S

(Stork et al, 1995)

MI

Cardiac Cycle

Relaxation

Passive stiffness

Elastic recoil

Atrial reserve


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Diagram showing the interrelationship of influences on ventricular end-diastolic

Volume (EDV) through stretching of the myocardium and the contractile stase

Of the myocardium.

Stretching of

myocardium

Dyspnea

Ventricular EDVPul. edema

Fatal

myocardial

depression

Exercise

Heart failureRest

Contractile stateof myocardium

Normal-rest

Normal-exerciseMaximal

activity

Walking

Rest

Ventricularperformance

B

A

D

3

3

4E

1

2 C


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Treating Hemodynamic profiles

DRYWETWARM

A B

CL

Vasodilators

Natriuretic peptides

Nitroprusside

nitroglycerin

COLDInotropic drugs

Dobutamine

Milrinone

(levosimendan)

(enoxinune)

Suggestions for how the hemodynamic profiles may be used to conceptualize initial

therapy for patients with advanced heart failure, patients who are wet and warm

(profile B) generally can be dried out without complex intervention. patients who

are cold and wet (profile C) often require addition of other therapy to Warm up

before they can dry out.Concepts are further discussed in text and in Ref [30].

Two Minute Assessment of Hemodynamic Profile


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NO

NO

Two Minute Assessment of Hemodynamic Profile

Congestion at rest?

YES

Warm & Dry Warm & Wet

A B

Low perfusion

Evidence forCongestion

Orthopnea

Elevated JVP

Edema (25%)

Pulsatile hepatomegaly

AscitesRales (rare in chronic

HF)

Louder S3

P2 radiation leftward

Abdomino-jugular reflex

Valsalva square wave

at rest?YES

Cold & Dry Cold & Wet

L C

Evidence for low perfusion

Narrow pulse pressure8

Cool extremities*

May be sleepy, obtundedSuspect from ACEI hypotension

And low serum Sodium

One cause of worsening renal fn

* Most helpful


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+

Normal

AFTERLOADREDUCTION

PRELOAD REDUCTION

Inotropic

Decreased pulmonary wedge pressureDecreased dyspnea

Theoretical Frank-Starling curves in CHF.(Opie, 2001)

Decreased

fatigue

Increasedcar

diacoutput

HEMODYNAMICS OF VASODILATORS IN CHF


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Pathophysiology of CHF

Injury to myocytesand EC matrix

Electrical, vascular, renal,

pulmonary, muscle effects

CHF

Ventricular

remodelling

Neurohumoral activationIncreased cytokines

Immune andinflammatory changes

altered fibrinolysis

Oxidative stressApoptosis

Altered geneExpressionEnergy starvation

McMurray J, Pfeffer M. Circulation. 2002 (in press)


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HIPOTESA STARLING


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HIPOTESA STARLING


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AVERAGE FORCES TENDING TO PUSH FLUIDArteriole


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Systemic capillary fluid dynamics (Adapted from Wilson RF: Cardiovascular

physiology. In Critical care manual, ed 2, Philadelphia, 1992, Davis)

AVERAGE FORCES TENDING TO PUSH FLUID

OUT OF THE SYSTEMIC VASCULAR SPACE

AVERAGE FORCES TENDING TO PUSH FLUID INTOTHE SYSTEMIC VASCULAR SPACE

Mean capillary hydrostatic pressure 17.0 mm Hg

Subatmospheric interstitial hydrostatic

pressure (acting as a vacuum drawingfluid into the interstitium) -6.0 mm Hg

Interstitial oncotic pressure +5.3 mm Hg

Net Forces Directing Fluid Outward 28.3 mm Hg

Plasma oncotic pressure 28.0 mm Hg

Net Forces Dircted Inward 28.0 mm Hg

Net forces : Outward 28.3 mm Hg

Inward -28.0 mm Hg

AVERAGE FORCE DIRECTING FLUID INTO

THE BODY TISSUE SPACE 0.3 mm Hg

Arteriole

Venule

Interstitial

space

Systemic

cell

Capillary

Overload/

Myocyte lossPreload Energy supply:

demand ratio


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Cellular Altered collagen

hypertropy matrix

Remodelling

Cardiac outputBaroreflex

response

Neurohormonal

activation

Arrhythmias

Sudden death

demand ratio

Afterload

Inotropy

Ca2- Renin-angiotensin-aldosterone

Sympatheticnervous system

Endothelin Arginine vasopressin

Natriureticpeptides

Prostaglandins Bradykinin

Response

to stress

Fluid & salt

retention

Altered skeletal muscle

blood flow and metabolism

Vasoconstriction, vascular remodelling, endothelial dysfunction

maintains blood pressure

redistributes cardiac outputperfusion

of vital

organs

Dyspnea, edema, fatigue

The pathophysiology of heart failure involves the interaction of intrinsic cardiac function wit neurohormonal activation, peripheral

vasoconstriction and volume expansion. Neurohormonal activation may increase vasoconstriction and lead to a vicious cycle of

worsening cardiac function. Natriuretic peptides and other hormones with vasodilating properties may have potentially beneficial

effects on vasoconstriction and volume expansion. This complex model is influenced by numerous factors, including age of patient,

Peripheral

resistance

Oedema Kuliah

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