Heart Failure( 心力衰竭 )

Department of Pathophysiology

病理生理教研室 刘金保1999,5,20

临床医学（本）、医学检验（本）、医学影像学（本）适用

Concept ( 概念 )

Heart failure(pump failure) may be defined as the condition in which the heart is no longer able to pump an adequate supply of blood for the metabolic needs of the body,provided there is adequate veneous blood.

Concept( 概念 )

Myocardial failure( 心肌衰竭 ) refers to the heart failure which is caused by a defect in myocardium itself. Congestive heart failure( 充血性心衰 ) has a chronic course with an abnormal accumulation of fluid,which results in the expansion of intravascular blood volume

Cardiac insufficiency( 心功能不全 )

Causes of Heart Failure ( 心衰的病因 )

• Dysfunction of myocardium ( 心肌结构破坏 ) diffuse myocardial damage: myocardial infarction;cardiopathies; myocarditi; myocardial ischemia and hypoxia: coronary heart disease;severe anemia;hypotension;shock;myocardial hypertrophy;vitamin B1 deficiency

Causes of Heart failure( 心衰的病因 )• Overload for myocardium

( 心脏负荷过重 ) Pressure overload(afterload): systemic hypertension;pulmonary hypertension;aortic stenosis;pulmonary stenosis; Volume overload(preload): mitral and aortic regurgitation for left ventricles;tricuspid and pulmonary regurgitation for right ventricles

Causes of heart failure ( 心衰的病因 )

• Conditions that restrict ventricular filling ( 心室充盈受限 ) mitral stenosis,constrictive pericarditis, restrictive cardiomyopathy

Precipitating factors ( 诱因 )

• Infection

• arrhythmias

• pulmonary embolism

• pregnancy

• water,eletrolytes disturbances

• acid-base disturbances

• emotion

Infection

fever tach

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a hyp

oxia toxin

emi

aIncreased

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Arrhythmias( 心律失常 )

• Reduce the time period available for ventricular filling and coronary perfusion

• increase the demand for myocardial oxygen

• the dissociation between atrial and ventricular contractions

Acidosis and heart failure ( 酸中毒和心力衰竭 )

• Compete with Ca2+ for combination of troponin

• Influence the Ca2+ trigger mechanism-reduce the sensitivity of the sarcoplasmic reticulum to the local concentrations of Ca2+; result in a reduced release of Ca2+ from the SR

Compensatory mechanism in heart failure ( 心衰的代偿机制 )

1. The Frank-starling mechanism(tonogenic dilatation)

2. Increased release of catecholamines

3. Myocardial hypertrophy

4. Increase of blood volume and redistribution of blood flow

1.The Frank-starling mechanism

Sarcomere length(micron)

Ten

sion

2.2

Relationship between myofilament length andtension development in cardiac muscle

3.65

2.Increased release of catecholamines ( 儿茶酚胺释放增加 )

• Augment myocardial contractility(the positive inotropic effect)

• increase heart rate(the positive chrotropic effect)

• elevate the peripheral vascular resistance

• pressure receptor,volume receptor,chemical receptor

3.Myocardial hypertrophy ( 心肌肥大 )

• Volume overload eccentric hypertrophy

• Pressure overload concentric hypertrophy

Myocardial hypertyophy heart failure• Increased formation of a myosin isozyme,V3• uptake and release of Ca2+ by SR may be impar

ied• diminished activity of sympathetic nervous syste

m• proliferation of mitochondria and capillaries

myofilament proliferation• increased collagen in hypertrophic myocardium

can lead to a reduced ventricular compliance and interfere with the filling of ventricles

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4.increase of blood volume and redistribution of blood flow ( 血容量增加和血流重分布 )

Water and sodium retension

Redistribution of blood flow

Classification of heart failure ( 心力衰竭的分类 )

• Right-sided versus left-sided heart failure

• acute versus chronic heart failure

• high-output versus low-output heart failure

• high out-put heart failure:hyperthyrodism, anemia,arterioveneous fistulas and beriberi(any other factors that decrease the total resistance chronically will also increase the cardiac output)

beriberi

• Lack of this vitamin causes diminished ability of the tissues to utilize cellular neutrients,which in turn causes marked peripheral vasodilation.The total peripheral resistance decreases sometimes to as little as one-half normal.consequently,the long time level of cardiac output also increases to as much as 2 times normal.

Pathogenesis of heart failure ( 心力衰竭的发生机制 )

Sarcomere

Thick filament

Thin filament

MyosinActin TropomyosinTroponin

Basic structure of sarcomere

TnC

TnITnT

Myosin

Troponin Actin

Tropomyosin

Myocardial filament sliding

Pathogenesis of heart failure ( 心力衰竭的发生机制 )

• Depressed myocardial contractility

• altered diastolic properties of ventricles

• asymmetry and asynchronism in ventricular contraction and relaxation

1.Depressed myocardial contractility ( 心肌收缩功能降低 )

• Myocardial cellular injuries

• Myocardial metabolic dysfunction

• Dysfunction of excitation-contraction coupling

• Alterations of the adrenergic nervous system in the failing myocardium

The relationship between ventricular dysfunction and prognosis

Myocardial infarted size

Cardiacindex Mortality

5-10% Normal 2%

10-20% Slightly decreased 10%

20-40% Decreased 22%

>40% Markedly decreased 60%

Energy liberation(ischemia)

energy storageenergy storage

energy utilization(hypertrophy)

Myocardial metabolic dysfunction ( 心肌代谢障碍 )

• Disorders in liberation of energy ischemic heart disease;shock;severe anemia;hypoxia

• Disorders in utilization of energy myocardial hypertrophy

Dysfunction of excitation-contraction coupling ( 兴奋和收缩偶联障碍 )

• Reduced uptake and release of Ca2+ by sarcoplasmic reticulum(SR)

• Mitochondria Ca2+ is greatly increased

• Extracellular Ca2+ inward movement

• Diturbed combination with troponin

Alterations of the adrenergic nervous system in the failing myocadium ( 交感神经系统变化 )

• Norepinephrine depletion

• Dowmregulation of belta 1-receptors

• Uncoupling of belta 2-receptors

Receptor-operated channels

2.Altered diastolic properties of ventricles( 舒张功能改变 )

• Dysfunction of ventricular relaxation--increased cytosol Ca2+ concentration; low levels of ATP

• Reduced ventricular compliance-- Myocardialhypertrophy;inflammation; edema;fiberosis

3.Asymmetry and asynchronism in ventricular contraction and relaxation( 心肌收缩舒张不协调 )

• Hypokinesis or akinesis

• dyskinesis

• asynchronism

Functional and metabolic alterations in heart failure ( 功能代谢

变化 )

1.Alterations in cardiac function

2.Blood pressure change

3.Respiratory distress

Alterations in cardiac function

1. Decreased cardiac output and cardiac index(CI) 2. Decreased ejection fraction(EF): stroke volume/end diastolic volume3. Increased intracardiac pressure: LVEDP-PCWP;RVEDP-CVP4. Alterations in myocardial contractility and its diastolic properties: Vmax and dp/dt max5. Blood pressure change

Respiratory distress( 呼吸困难 )

• Dyspnea- exertional dyspnea

• Orthopnea- reduced pooling of fluid in the extremities and abdomen;elevation of diaphragm

• Paroxysmal nocturnal dyspnea- reduced adrenergic drive to the left ventricle during sleep;elevation of thracic blood volume during recunbency;normal nocturnal depression of the respiratory center;elevation of diaphragm

病例 患者，女， 36 岁。主诉心慌，气闷，浮肿，腹胀三月余。患者有风湿性心脏病十年病史。近三月来又出现心慌气闷加重，不能平卧而住院治疗。检查：重病容，半卧位，颈静脉怒张，呼吸 36 次/ 分，两肺底闻湿性罗音，心界向两侧扩大，心率130 次分，血压 14.6/10.7kPa, 心尖部可闻及收缩期吹风样杂音和舒张期雷鸣样杂音Ⅲ级，肝脏在右侧锁骨中线肋下 6 厘米，压痛，腹部有移动性浊音，骶部及下肢明显指压性水肿，腹腔抽出液体，为漏出液，血浆蛋白 22g/L, 球蛋白 15g/L 。1. 临床诊断 ? 心衰属何种类型 ? 发生机制 ?2. 水肿及腹水发生机制 ? 端坐呼吸 ? 心界扩大 , 心率 130次 / 分 , 血压正常 , 为什么 ?

Myocardial hypertrophy heart failure?

• Organic?

• Histological?

• Cellular?

• Molecular?

Myocardial hypertyophy heart failure• Molecular: Increased formation of a myosin iso

zyme--V3• Cellular and subcellular: uptake and release of

Ca2+ by SR ; mitochondriaproliferation;uptake and release of Ca2+ by mitochondria

• histological: diminished activity of sympathetic nervous system and capillaries

• organic: increased collagen in hypertrophic myocardium can lead to a reduced ventricular compliance and interfere with the filling of ventricles

?

Coronary heart disease

heart failure