Chapter 13

Cardiac insufficiency

Introduction

The heart, by virtue of contractile activity of its muscular walls, propels blood throughout the body so as to deliver nutrients to and remove wastes from each of organs. The heart also provides for the transport of hormones and other regulatory substances between various regions of the body. The function of heart as a pump interposed between two interlocking circuits. The overall function of the circulation depends on the satisfactory performance of both cardiac muscle and heart valves. Severe dysfunction of the myocardium may lead to heart failure.

Concept

Heart failure may be defined as the pathological process or syndrome which absolute or relative decrease of cardiac output, namely, to weaken the function of heart pump, by dysfunction of myocardial systole and/or diastole under action of various etiological factors results in being no longer able to meet the metabolic needs of body tissues.

Congestive heart failure usually has a chronic course with an abnormal accumulation of fluid, which results in increase of blood volume, congestion of vein, increase of interstitial fluid and presents edema obviously in clinic.

Myocardial failure refers to the heart failure which is caused by primary dysfunction of myocardial systole and/or diastole.

Heart failure is not a disease; it is a consequence of diseases that impair the ability of heart to function as a pump. Heart failure is a clinical syndrome that may result from a wide spectrum of diseases.

The relationship between heart failure and cardiac insufficiency:

Heart failure belongs to decompensatory phase of CI and cardiac insufficiency includes all courses from complete compensatory to decompesatory phase of the heart. There is no intrinsical difference between them.

Section 1

Etiological causes, Predisposing causes

and Classification of HF

1.1, Etiological Causes

1, Primary dysfunction of myocardial systole and diastole

1) Myocardial damage

For example, Myocarditis, Cardiomyopathies, Myocardial infarction

2) Myocardial ischemia and hypoxia

For example, Coronary heart diseases, Anemia, Hypotension, etc..

2, Overload for myocardium

1) Pressure overload or Excess of after load

For example, Hypertension, aortic stenosis----Pressure overload of left ventricle; Pulmonary hypertension, Pulmonary stenosis, pulmonary embolism, COPD, etc.----- Pressure overload of right ventricle

2) Volume overload or Excess of preload

For example, Mitral and aortic regurgitation for left ventricle; Tricuspid and pulmonary incompetence for right ventricle

1.2, Predisposing causes

90 of patients in HF have predisposing causes. The common predisposing causes i﹪nclude:

1, Infection-----Specially infection of superior respiratory tract is the most common PC.

Mechanism of predisposing HF

1) Fever excitation of sympathetic nerve increase rate of metabolism

enlargement of heart load

2) Endotoxin can directly despress myocardial systole

3) Tachycardia induces increase of oxygen consumption and ischemia and hypoxia in myocardium.

4) The infection of respiratory tract increases heart load and influences supplement of blood and oxgen.

2, Disturbance of acid-base balance and electrolyte metabolism

1) Acidosis

2) Hyperkalemia

a) H+ inhibtes Ca2+ to combine with troponin, internal flow of Ca2+ and decreases Ca2+ release from SR

b) H+ restrains activity of ATP enzyme of myosin

c) H+ induces relaxation of precapillary sphincter and declines blood volume returned to heart and then reduces cardiac output.

a) Hyperkalemia and acidosis depress internal flow of Ca2+ in repolarization and then decline contractibility of myocardium

b) Hyperkalemia results in decrease of myocardial conductibility and then take places arrhythmia

3, Arrhythmia-----especially tachycardia

4, Pregnancy and delivery

a) Tachycardia conduces to shortening of relaxing period of heart and blood supplement of coronary artery declines

b) Tachycardia induces to increase oxygen consumption of myocardium

c) Tachycardia leads to lack of perfusion of heart ventricle and decrease of cardiac output

Increase of blood volume in the stage of pregnancy

Excess of preloada)

b)

Exitation of sympathetico-adrenomedullary system because of pain, anxiety

Increase of backflow of vein Excess of preload

Vasoconstriction of peripheral vessels and increase of resistance

Excess of after load

1.3, Classification 1, According to the time of development

1) Acute heart failure----developed from hours to days, and no enough time for compensatory mechanisms. E.g. acute myocardial infarction, severe myocarditis etc..

2) Chronic heart failure---- developed from weeks to months or years, and fully compensatory mechanisms developed. E.g. hypertension, multivalvular heart diseases, cor pulmonale, etc..

2, According to the cardiac output1) Low output heart failure----caused by hypertension, ischemic heart failure, valvular heart disease and myocarditis. The cardiac output is lower than usuall normal output.

2) High output heart failure---- caused by anemia, beriberi(severe lack of Vit B1), arterio-venous shunting, hyperthyroidism, pregnancy, etc.. The cardiac output is greater than normal but lower than the output before failure.

3, According to the side of disorder

1) Left heart failure----causing obstruction to systemic blood flow, and producing overfilling of pulmonary veins. E.g. coronary heart disease, myocardiopathy, hypertension and mitral incompetence, etc..

2) Right heart failure----causing obstruction to pulmonary blood flow, and producing overfilling of systemic veins. E.g. pulmonary embolism, Pulmonary hypertension, COPD, mitral stenosis, etc..

3) Whole heart failure----right and left sides both are of failure. E.g. rheumatic myocarditis and severe anemia, etc..

4, According to disturbance of systole and diastole of myocardium

1) Heart failure of insufficiency of myocardial systole----e.g. hypertensive heart disease, coronary heart disease, etc..

2) Heart failure of insufficiency of myocardial diastole----e.g. mitral and tricuspid stenosis, constrictive pericarditis, hypertrophic myocardiopathy, etc..

Section 2

Compensation of body in HF

Grade of cardiac compensation;

1) Complete compensation

2) Incomplete compensation

3) decompensation

The cardiac output by compensatory reaction of body suffice a need of normal work and life. The clinical manifestation of HF cannot occur provisionally.

The cardiac output by compensatory reaction of body only suffice a need of body under tranquil and resting condition. The patients have shown mild degree of HF.

The cardiac output by compensatory reaction of body cannot suffice a need of body under tranquil and resting condition. The patients have shown obvious symptoms and sign of HF.

Heart failure

Cardiac insufficiency

2.1, Compensation of heart

1, Increased heart rate

It is a rapid compensatory reaction for elevation of cardiac output, but it is not economical.

Compensatory mechanism include;

1) Role of pressure receptor in carotid sinus and aortic arch

2) Effect of volume receptor in atrium and vena cava

3) Function of chemical receptor in carotid body and aortic body

Limitation –i.e. to be not economical;

1) Increased heart rate results in high oxygen consumption.

2) Heart rate of more than 180 per minute can induce inadequate perfusion of coronary artery and filling of ventricle.

2, Cardiac dilation

It is an important mechanism of regulation for acute hemodynamic change, and as well as called heterometric autoregulation. It conform to law of Frank-Starling.

Initial length of sarcomere

Ten

sion

of

sarc

omer

e

2.2μm 3.65 μm1.7 μm2.1μm

Relation between initial length and tension development in cardiac muscle

There are two kinds of cardiac dilation in HF.

1) Tonic cardiac dilation refers to cardiac relaxation with increase of myocardial contraction. It is compensatory.

2) Myogenic cardiac dilation refers to cardiac relaxation without increase of myocardial contraction. It is decompensatory.

3, Myocardial hypertrophy----long-term adaptation to increased myocardial work

Myocardial hypertrophy refers to aggrandizement of cubage and increase weight in myocardial cell. Exceeding critical value(heart weight more than 500g, or weight of left ventricle more than 200g) induces increase in number of myocardial cell.

Myocardial hypertrophy is divided into two types

1) Concentric hypertrophy

2) Eccentric hypertrophy

Hypertension etc. Increase of Pressure load

Parallel hyperplasia of sarcomere

Increase of thickness of ventricular wall

Without cardiac chamber dilation

Aortic incompetence etc..

Increase of volume load

series hyperplasia of sarcomere

Increase of length of myocardial fiber

With cardiac chamber dilation

Significance of hypertrophy

1) Increased myocardial contraction

2) Decreased tension of ventricular wall and myocardial oxygen consumption

According to Laplace law;

T ＝p×r

2h

T---Tension of ventricular wall

P--- Pressure within ventricular chamber

R---Semidiameter of cardiac chamber

H---Thickness of ventricular wall

2.2, Compensatory reaction outside heart

1, Increase of blood volume

1) Decreased GFR(glomerular filtration rate)

HF Decreased cardiac output

Decline of arterial pressure

Excitation of sympathetico-adrenomedullary system

Vasoconstriction of renal vessels

Activation of renin-angiotensin-aldosterone system, RAAS

Reduced blood volume in kidney

Fall of synthesization and release of PGE2

2) Increased reabsorption of water and natrium ion in renal tubule

(1) Redistribution of blood flow within kidney

(2) Increased glomerular filtration fraction(FF)

(3) Increased hormones promoting reabsorption of water and natrium ion

For example enhanced renin-angiotensin-aldosterone system, RAAS

(4) Decreased hormones inhibiting reabsorption of water and natrium ion

For example reduced PGE2 and ANP

2, Redistribution of blood flow

3, Increase of red blood cells

4, Increased ability of oxygen utilization in tissue cells

2.3, Adverse influence of long-term compensatory reaction on body

1, Increased pressure load and volume load of heart

2, Increased oxygen consumption

3, Arrhythmia

4, Role of injury of cytokines

5, Oxidative stress

6, Myocardial remodelling

7, Retention of sodium and water

Section 3

Pathogenesis of Heart Failure

肌节中粗细肌丝的组成

3.1, Normal courses of myocardial contraction

肌丝滑行过程

Pathogenesis of Heart Failure

Depressed myocardial contractility

Abnormality of ventricular diastole

Disharmony in contraction and relaxation of heart

3.2, Depressed myocardial contractility

1, Damage of contractive proteins of myocardium

1) Necrosis of myocardial cells----caused by ischemia and hypoxia, bacteria, virus, poisoning(antimony锑 , adriamycin阿霉素 ) , etc..

2) Apoptosis of myocardial cells----caused by

(1) Oxidative stress

(2) Cytokines

(3) Imbalance of homeostasis of Ca2+

(4) Abnormality of mitochondrial function

The most common factor is the acute myocardial infarction.

2, Disorder of energy metabolism of myocardium

1) Disorder in production of energy

2) Disorder in utilization of energy

The most common factor is myocardial ischemia and hypoxia, e.g. ischemic heart diseases, severe anemia, myocardial hypertrophy, lack of VitB1etc..

The most common cause is myocardial hypertrophy in which activity of ATP enzyme in myosin declines

The causes decreased activity of ATP enzyme in myosin are alteration of the structure of peptide chain of ATP enzyme from high active V1(consisting of a couple of -peptide chain) to low active V3 (a couple of -peptide chain)

3, Dysfunction of excitation-contraction coupling

1) Disorder of disposal of Ca2+ in sarcoplasmic reticulum(SR)

(1) Weakened uptake of Ca2+ by SR

HF

Ischemia and hypoxia of myocardium

Decrease of ATP and Ca2+ pump ATPase

Decrease of noradrenalin in myocardium and down-regulation of β-receptor

Weakened uptake of Ca2+ by SR

Bated phosphorylation of PLN

PLN(phospholamban) is a protein of low molecular weight in myocardium, smooth muscle and skeletal muscle. PLN of non-phosphorylation has an inhibition for Ca2+ pump in SR and PLN of phosphorylation can make activity of Ca2+ pump increased.

(2) Reduced reserve of Ca2+ in SR----caused by

(3) Declined release of Ca2+ in SR

a) Weakened uptake of Ca2+ by SR

b) Increased uptake of Ca2+ by mitochondrion

Reduced reserve of Ca2+ in SR

Decreased RyR protein in SR and RyRmRNA

Acidosis to enhance affinity between Ca2+ and calcium store protein in SR

HFDeclined release of Ca2+ in SR

Normal

HF

2) Disorder of Ca2+ inward flow from outside of myocardial cells

There are two paths of Ca2+ inward flow in the myocardial cells. They are channel of Ca2+ inward flow and Na+- Ca2+ exchange.

(1) Ca2+ channel----it included two kinds of channels

a) Voltage-dependent calcium channel(VDC)

b) Receptor-operated calcium channel(ROC)

It is adjusted by membrane potential. When potential within membrane is positive in depolarization VDC opens and Ca2+ outside cells enter into the cytoplasm along the concentration degree. When potential within membrane is negative in repolarization VDC closes up and stops inward flow of Ca2+.

It is controled by β-receptor on the cellular membrane and some of hormones. When NE integrate with β-receptor adenylate cyclases are activated and make ATP into cAMP.The latter activates ROC and Ca2+ outside cells enter into the cytoplasm. When the amounts of NE reduces and activity of AC declines ROC closes up and stops inward flow of Ca2+.

(2) Na+- Ca2+ exchange

Na+- Ca2+ exchange is also protein on the cellular membrane. Its efficiency of exchange is far higher than Ca2+ pump. When potential within membrane is positive Na+ is outward flow and Ca2+ inward flow.

The role of Ca2+ inward flow is not only enhancing concentration of Ca2+ in cytoplasm but also inducing SR to release Ca2+ .

Myocardial hypertrophy

Acidosis

Decrease of β-receptor and NE

Declined sensitivity of β-receptor to NE

Hyperkalemia K+inhibiting inward flow of Ca2+ competetively

Decrease of Ca2+ inward flow

Dysfunction of excitation-contraction coupling

3) Disorder of combination between Ca2+ and troponin

Acidosis

Ca2+ replaced by H+ to combine with troponin

Decreasing Ca2+ release from SR

Ischemia and hypoxia

Decrease of ATPFall of uptake and release in SR

Decline of Ca2+ concentration in cytoplasm

Dysfunction of excitation-contraction coupling

4, Imbalance growth of myocardial hypertrophy In chronic heart failure excessive hypertrophy of myocardium results in disproportion between increase of myocardial weight and elevation of cardiac function, I.e. Imbalance growth of myocardial hypertrophy and ultimately induces HF.

Mechanism is

1) Increase of myocardial weight exceeding growth of neuraxon in cardiac sympathetic neuron induces fall of distributing density of sympathetic nerve.

3) The amount of capillaries increasing disproportionably with hypertrophy or perfusion disturbance of microcirculation frequently arise ischemia and hypoxia of myocardium

2) The amount of mitochondrion increasing disproportionably with hypertrophy results in insufficiency of energy production of myocardial hypertrophy.

4) Decrease of activity of myosin ATPase in hypertrophy leads to disorder of utilization of energy

5) Disorder of disposal of Ca2+ of SR in hypertrophy conduces dysfunction of excitation-contraction coupling

3.3, Abnormality of ventricular diastole

It is coequal importance for normal cardiac output that both myocardial systole and diastole are all normal. The patients with HF induced by disorder of relaxation may account for 30% of the sum of HF.

1, Delayed restoration of calcium ions

HF

Ischemia of myocardium, severe anemia etc.. Decrease of

ATP

Ca2+ pump not to transport Ca2+ from cytoplasm to the SR and outside the cell adequately

Incomplete relaxation of myocardium

Decrease of affinity between Na+- Ca2+ exchange and Ca2+

Fall of Ca2+

elimination

Disorder of dissociation between Ca2+ and troponin

2, Disorder of disassociation of myosin-actin complex

The myocardial diastole requires not only Ca2+ detaching from troponin but also disassociation of myosin-actin complex. The disassociation of myosin-actin complex is a course of expending energy, I.e.

Myosin-actin complex+ATP

Myosin-ATP + Actin

Decrease of ATP by various factors

Disorder of disassociation of myosin-actin complex

Disturbance of diastole

HF

Thereby;

3, Weakened diastolic potential energy in ventricle of heart

The diastolic potential energy of ventricle is from condition of ventricular systole. The better ventricle contract, the bigger diastolic potential energy of ventricle is. Moreover filling and perfusion of coronary artery in diastole is an concernful factor to promote relaxation of ventricle. Therefore;

Decrease of myocardial contractility by various factors

Stenosis of coronary artery by atherosclerosis or thrombosis

Excessive high pressure within ventricle

Excessive tension in ventricular wall

Reduced perfusion of coronary artery

Disturbance of diastole

Diminished change of geometry structure in heart

4, Declined ventricular compliance

The term of ventricular compliance is defined as the ratio of the change in volume to the change in pressure, “dv/dp”. The ventricular stiffness is the inverse of compliance, I.e., “dp/dv”.

P-V curve can reflect relationship between ventricular compliance and stiffness.

图 心室压力 一 容积（ p-V ）曲线

N

Causes of decreased compliance have incrassation of ventricular wall by hypertrophy, myocarditis, edema, fibrosis and hyperplasia of stroma, etc..

The clinical significance of decreased compliance is that restricted ventricular relaxation and filling may result in fall of cardiac output and then may induce heart failure.

3.4, Disharmony in contraction and relaxation of heart

Disharmony in contraction and relaxation of heart results in disorder of heart pump and decrease of cardiac output.

The most common cause is arrhythmia.

Section 4

Functional and Metabolic Alteration

in Heart Failure

4.1, Congestion of pulmonary circulationThe congestion of pulmonary circulation is frequently caused by left heart failure. Dyspnea and pulmonary edema are the main representation.

1, Dyspnea1) Exertional dyspneaIt refers to that the patients show dyspnea with increasing movement of physical force and dyspnea can lighten or disappear after a rest.

Causes ;Increased oxygen requirement during movement of physical force

(1) Aggravating hypoxia and CO2 retention

Stimulating respiratory center

(2) Quickened heart rate

Shortened diastole

Fall of perfusion in coronary artery

Hypoxia of cardiac muscle

Decrease of filling in left ventricle

Embittered congestion of lung

(3)Increased blood volume returned to heart

Embittered congestion of lung

Declined compliance of lung

Enhanced resistance of ventilation

Dyspnea

2) Orthopnea

This symptom may be defined as dyspnea that develops in the supine position and is relieved by sitting or recumbent position

Causes of mitigating dyspnea;

(1)

(2)

(3)

Sitting positionA part of blood flow transfering to the lower extremities by gravity

Lightened congestion of lung

Sitting position

Sitting position

Downward movement of diaphragmatic muscle

Increase of vital capacity

Decreased absorption of edematous fluid from the lower extremities

Lightened congestion of lung

3) Paroxysmal nocturnal dyspnea

The patients awakens with a feeling of extreme suffocation during sleep, sits bolt upright, and grasps for breath. When accompanies with wheezing sound it is called “cardiac asthma”. It is a typical manifestation of left heart failure.

Causes ;

(1)

(2)

(3)

The patients by supine position

Dereased volume of thoracic cavity

Fall of ventilation

During sleep Excitation of vagus Contraction of bronchus

Increased resistance of respiratory tract

During sleep Correspondingly depressing of CNS

Dulling of respiratory center

2, Pulmonary edema

It is the most severe manifestation for acute left heart failure.

Mechanism ;1) Rise of capillary pressure----＞ 30mmHg(4kPa)

2) Increase of permeability in capillaries

Caused by left heart failure or improper fluid transfusion during LHF

Caused by hypoxia

4.2, Congestion of systemic circulation

It is induced by whole or right heart failure.

1, Venous congestion and increase of venous pressure

The main representations are jugular venous engorgement, positive hepatojugular reflux test, etc..

2, Edema

Cardiac edema

3, Hepatomegaly and abnormality of liver function

The patients of hepatomegaly almost account to 95-99% of sum in right heart failure. The chronic right HF may result in cardiogenic hepatocirrhosis.

4.2, Insufficiency of cardiac output

1, Pale of skin or cyanosis

2, Fatigue and adynamia, insomnia, lethargy

3, Decrease of urine volume

4, Cardiogenic shock

Section 5

Treatment Principle of HF

5.1, Preventing and Treating causes, Removing predisposing causes

5.2, Improving function of systole and diastole

1, Elevating function of systole in myocardium

2, Meliorating function of diastole in myocardium

Usage of foxglove, dopamine etc..

Application of calcium antagonism, β-receptor retarder, etc..

5.3, Lightened preload and afterload of heart

1, Reducing afterload of heart

Usage of drug of vasodilatation, e.g., hydralazine, ACEI , calcium antagonism, etc..

2, Modulating preload of heart

Usage of drug of venous vasodilatation, e.g., glonoin, etc..

5.4, Control edema

4, Declined ventricular compliance

The term of ventricular compliance is defined as the ratio of the change in volume to the change in pressure, “dv/dp”. The ventricular stiffness is the inverse of compliance, I.e., “dp/dv”.

P-V curve can reflect relationship between ventricular compliance and stiffness.

Diastolic P

ressure

Diastolic Volume

ab c

A—decline of compliance

B--- normal of compliance

C--- elevation of compliance

Diagrammatic representation of P-V curve in ventricular diastole