心力衰竭（英文）ppt課件
Heart Failure,Department of pathophysiology Xiangrong Sun,Fundamental knowledge,Heart is one of the most important organs in body. The main function of heart is to providing impetus for circulation of blood.,volume：like left fist weight：500g Ejection of blood： 70ml/SV70/min 60min24h 7056 L/d 10.8萬(wàn)次/天,Histology of myocardium,Intercalated disc,2019/4/1,mitochondrion,Ca2+,Ca2+ 10-7mol/L,Ca2+ 10-5mol/L,Release of Ca2+,tropomyosin,contraction,（粗）myosin,（細(xì)）actin,troponin,Ca2+,Ca2+ 10-5mol/L,SR,mitochondrion,Ca2+,Ca2+ 10-7mol/L,Reuptake of Ca2+,relaxation,tropomyosin,（粗）myosin,（細(xì)）actin,troponin,Ca2+,2019/4/1,AP and contraction of cardiac myocyte,冠心病 (CHD) 高血壓 (Hypertension) 心肌病 (Cardiomyopathy) 瓣膜疾病 (Valvular heart disease),What causes heart failure?,In addition to those causes above, the following factors also can play a role in determining if heart failure will affect you: family history of heart disease(家族史） diabetes（糖尿?。?marked obesity（肥胖） heavy consumption of alcohol, or tobacco（酗酒、 吸煙） 5.large salt intake in diet （高鹽飲食）,Other factors,heart failure is the pathological process in which the systolic or/and diastolic function of the heart impaired, and as result , cardiac output decrease and is unable to meet the metabolic demands of body,Concept of heart failure,the systolic or/and diastolic function of the heart impaired,heart failure,2019/4/1,Determinants of cardiac function,Etiology,Decreased myocyte contractility,pressure overload (afterload),Overload for myocardium,volume overload （preload ）,etiology of heart failure,2019/4/1,Restriction of filling,output,low-output heart failure high-output heart failure (*compared with healthy adult),Classification,Low output heart failure,before high output heart failure,high output heart failure,Normal output,health adult,onset,acute heart failure chronic heart failure,Location,left-sided heart failure right-sided heart failure whole heart failure,2019/4/1,法洛氏四聯(lián)征,Compensatory responses,increased heart rate,cardiac dilation,myocardial hypertrophy,Cardiac compensation,(一) Increased heart rate,Mechanism,pressure receptor volume receptor,advantage,This adaptation may increase the cardiac output And maintain the perfusion of heart and brain,disadvantage,If heart rate 180times/min, it will: Increase the consumption of oxygen of heart Reduce the duration for ventricular filling Inadequate flow of the coronary artery (squeeze, lumen, narrow),(二) cardiac dilatation,Frank-Starling law: The more a myocyte or ventricular chamber is stretched ,the more it will contract,2019/4/1,tonicity dilation: the volume of ventricle increases due to the sarcomere dilation, accompanying the increased cardiac contractility and stoke volume,myocardiogenic dilation: the stretch of sarcomere does not accompany the increased cardiac contractility.,(三) Myocardial hypertrophy,concentric hypertrophy,eccentric hypertrophy,2019/4/1,Concentric hypertrophy: is the response to pressure overload. It is associated with increased number of sarcomere arranged in parallel. The increase in wall thickness reduces wall tension and cardiac compliance without increasing the internal chamber size.,eccentric hypertrophy: the response to volume overload is characterized by dilation of chamber size, as well as relative decreased wall thickness. It is thought to result from increased number of sarcomere arranged in series.,concept,GPCR,胞膜,Ca2+,離子通道,Ca2+,IP3,DAG,Gq,PLC,PKC,Biologic responses in hypertrophy,CA, Ang等,Gs,R,R,肌鈣蛋白結(jié)合,興奮-收縮偶聯(lián),心肌收縮,基因表達(dá)增加，心肌和血管平滑肌增生,cAMP,PKA,細(xì)胞內(nèi) Ca2+庫(kù),MAPK家族/NHE-1,CaM-K,2019/4/1,Significance of myocardial hypertrophy Enhancing the contractility of heart Decreasing wall tension and oxygen consumption,2019/4/1,Reduced in the concentration of NE and 1-adrenergic receptor (Tyrosine hydroxylase ),Decreased oxygen and blood supply,Altered of energy metabolism and utilization,Dysfunction of excitation-contraction coupling,Excessive cardiac hypertrophy,Decreased compliance (collagen),(四) Increased ability of cells to use oxygen,Systemic compensation,Increased blood volume,機(jī)制,1.腎小球?yàn)V過(guò)率（ CA ，AGII , PGE2 ,腎血流),2.腎小管對(duì)水鈉的重吸收 腎內(nèi)血流重分布：皮質(zhì)髓質(zhì)水鈉的重吸收 腎小球?yàn)V過(guò)分?jǐn)?shù)=腎小球?yàn)V過(guò)率/腎血流量. 促進(jìn)水鈉重吸收的激素（醛固酮ADH ） 抑制水鈉重吸收的激素（PGE2 利鈉素）,交感腎上腺髓質(zhì)系統(tǒng)激活 (activation of sympathetic-adrenal medulla system),腎素-血管緊張素-醛固酮系統(tǒng)激活 (activation of renin-angiotensin-aldosterone system, RAAS),Neurohumoral compensation,血流重新分布,Renin-angiotensin system and concept of its inhibitory action,Angiotensinogen,Angiotensin ,Angiotensin ,Vascular contraction,Angiotension II Receptor antangonists,ACE Inhibitors,Angiotensin converting enzyme (ACE),Renin,Renin inhibitors,etc.,etc.,etc.,Receptor,心力衰竭與機(jī)體的代償模式圖,心力衰竭,機(jī)體代償,心臟,HR,心臟緊張?jiān)葱詳U(kuò)張,心肌肥大,收縮力,舒縮功能,心外,血容量,血液重分配,紅細(xì)胞、肌紅蛋白,心血供,有效循環(huán)血量,供血供氧,利用氧能力,細(xì)胞線粒體數(shù) 、呼吸酶活性,SV,CO,心肌舒縮功能降低,R x SV = CO,組織細(xì)胞缺血缺氧,神經(jīng)-體液,交感-腎上腺髓質(zhì)系統(tǒng),ARRS,血容量,血液重分配,收縮力,2019/4/1,infection ( pulmonary infection),precipitating factors,Precipitating factors,2019/4/1,infection,2019/4/1,cardiac dysrhythmia,precipitating factors,2019/4/1,尤其是快速型心律失常 心率 舒張期縮短 心肌耗氧量 冠脈血流 心肌缺血、缺氧 心室充盈 心泵功能 心輸出量,房室活動(dòng)協(xié)調(diào)性紊亂,2019/4/1,water-electrolytes and acid-base disturbance,precipitating factors,Ca2+ inflow , SR released Ca2+ binding to troponin activity of ATP enzyme sensitivity of Cap to CA ,myocardial conductibility,autorhythmicity,cardiac contractility,myocardial excitability,2019/4/1,pregnancy and delivery,precipitating factors,2019/4/1,妊娠期血容量（臨產(chǎn)期） 分娩時(shí)疼痛、精神緊張、 稀釋性貧血 交感一腎上腺髓質(zhì)系統(tǒng)興奮 高動(dòng)力循環(huán)狀態(tài) 靜脈回流 小血管收縮 心臟前負(fù)荷 （左室）后負(fù)荷 心肌耗氧量和冠脈流量 心輸出量,2019/4/1,Excessively labor and spiritual burden; infusion,precipitating factors,2019/4/1,(一) loss of cardiomyocyte,(二) metabolic dysfunction of myocardium,(三) dysfunction of excitation-contraction coupling,Pathogenesis,Decreased myocardial contractility,(一) loss of cardiomyocyte,Decreased myocardial contractility,contractility decreased,myocardial cell apoptosis : apoptotic index 35.5%,(二) metabolic dysfunction of myocardium,impaired energy production reduced energy reserve impaired energy utilization,Decreased myocardial contractility,1.impaired energy production,myocardial ischemia hypoxia,Disorder of myocardial energy metabolism,2. reduced energy reserve,CP,Disorder of myocardial energy metabolism,3. impaired energy utilization,Disorder of myocardial energy metabolism,能量生成,能量利用,脂肪酸 乳酸 丙酮酸 葡萄糖 氨基酸,三羧酸循環(huán),氧化磷酸化,ATP,ADP+Pi,Ca2+,與肌鈣 蛋白結(jié)合,心肌收縮,心衰時(shí)的能量代謝障礙,CP,能量?jī)?chǔ)存,ATPase,乙酰 CoA,(三) dysfuncion of excitation-contraction coupling,Decreased myocardial contractility,1. Altered of Sarcoplasmic reticulum (SR) handling Ca2+,2. Reduced influx of extracellular Ca2+,3. Dysfunction of Ca2+ binding to troponin,1.Sarcoplasmic reticulum (SR) mishandling Ca2+,Impaired excitation-contraction coupling,SR mishandling Ca2+,Reduced Ca2+ released by SR Ryanodin receptor (Ry-R) or Ry-R mRNA decreased Acidosis reduced release of Ca2+ by SR,SR mishandling Ca2+,2. Reduced influx of extracellular Ca2+,Ca2+ inflow,voltage dependence,- receptor dependence,Na+/Ca2+ exchange,Impaired excitation-contraction coupling,L型通道亞單位,胞外 Ca2+內(nèi)流障礙,Na+/Ca2+ exchange： Depolarization Na+ outward Ca2+ inward Repolarization Na+ inward Ca2+ outward,Reduced influx of extracellular Ca2+,K+ impaired influx of Ca2+ (Hyperkalemia),Reduction of 1-receptor density,Norepinephrine depletion,H+ depress the sensitivity of receptor,Causes of Ca2+ influx decreased in heart failure:,Reduced influx of extracellular Ca2+,Acidosis decrease the m，L-Ca2+ cannel ,3. Dysfunction of Ca2+ binding to troponin,troponin,Impaired excitation-contraction coupling,Reduced in the concentration of NE and 1-adrenergic receptor,Decreased oxygen and blood supply,Altered of energy metabolism and utilization,Dysfunction of excitation-contraction coupling,Excessive cardiac hypertrophy,Decreased compliance,Delayed reposition of Ca2+ Ca2+ 10-5 mol/L 10-7 mol/L,Diastolic dysfunction,Affinity of Ca2+ and Ca2+-Na+ Ca2+ excretion,Delayed reposition of Ca2+,Impaired dissociation of the actin-myosin complex,Impaired myocardial diastolic properties,ATP,Decreased ventricular diastolic potential,Impaired myocardial diastolic properties,Reduced ventricular compliance myocardial hypertrophy; fibrosis; edema dv/dp,Impaired myocardial diastolic properties,心室順應(yīng)性(ventricular compliance)：心室在單位壓力變化下所引起的容積改變(Dv/dp),PV曲線左移,V稍有增加 P增加很多,2019/4/1,三、 Inconsistent behavior in systolic and diastolic function of the heart,Summary of the etiology of heart failure,Heart failure,Contractility,Loss of cardiomyocyte,Metabolic dysfunction,Dysfunction of excitation-contraction coupling,Altered of SR handling Ca2+,Reduced influx of extracellular Ca+,Dysfunction of Ca+ binding to troponin,Diastolic dysfunction,Delay of Ca+ reposition,Impaired dissociation of actin-myocin complex,Cardiac diastolic potential energy,Impaired ventricular compliance,Inconsistent behavior in systolic and diastolic function,Questions:,(一) 肺循環(huán)淤血 (Pulmonary congestion),當(dāng)PCWP18 mmHg時(shí)，即出現(xiàn)肺循環(huán)淤血征，見于左心衰竭。,Clinical manifestations,左心衰竭能導(dǎo)致肺淤血、肺水腫；因此主要的 臨床表現(xiàn)是呼吸困難,肺水腫,心力衰竭細(xì)胞,1、呼吸困難 (dyspnea),勞力性呼吸困難的發(fā)生機(jī)制:,回心血量增多，加重肺淤血 心率加快，舒張期縮短 機(jī)體活動(dòng)時(shí)需氧量增加,睡眠時(shí),1) 毛細(xì)血管壓 左心衰左室舒張末期壓力肺毛細(xì)血管壓 超過(guò)其代償能力肺水腫 2) 毛細(xì)血管通透性,肺循環(huán)淤血 肺泡通氣血流失調(diào)缺氧 毛細(xì)血管通透性 肺水腫 肺泡表面活性物質(zhì)破壞肺泡表面張力 毛細(xì)血管通透性 肺水腫,2、肺 水 腫,(二) 體循環(huán)淤血 (Systemic congestion),當(dāng)CVP16 cmH2O時(shí)，即出現(xiàn)體循環(huán)淤血征，見于右心衰竭及全心衰竭。,主要表現(xiàn) 頸靜脈充盈或怒張 肝腫大及肝功能損害 胃腸道淤血所致的食欲不振等 消化道癥狀 心性水腫,體循環(huán)淤血,體征：,肝大 水腫 頸靜脈怒張,食欲不振、惡心、腹脹,肝頸靜脈返流征,皮下水腫、腹水、胸水,全心 左心衰右心衰,檳榔肝,(三) 心輸出量不足,(low cardiac output ),心輸出量 (cardiac output,CO)減少 心臟指數(shù) (cardiac index,CI)降低 射血分?jǐn)?shù) (ejection fraction)降低 心室充盈(ventricular filling)受損 心率(heart rate)增快,亦稱低排出量綜合征 (syndrome of low output)或前向衰竭( forward failure) 特點(diǎn)為:,臨床表現(xiàn),疲乏無(wú)力、失眠、嗜睡,皮膚蒼白或發(fā)紺,尿量減少,心源性休克,表現(xiàn)形式,防治基本病因、消除誘因,改善心臟舒縮功能,減輕心臟前、后負(fù)荷,控制水腫,增強(qiáng)心肌收縮功能,改善心臟舒張功能,降低心臟后負(fù)荷,調(diào)整心臟前負(fù)荷,防治的病理生理基礎(chǔ),Pathophysiologic basis of prevention and treatment,著眼點(diǎn) 從傳統(tǒng)的改善血流動(dòng)力學(xué)，減輕癥狀“強(qiáng)心、利尿、擴(kuò)血管” 到改善預(yù)后，降低總死亡率針對(duì)過(guò)度激活的神經(jīng)、內(nèi)分泌系統(tǒng)（交感神經(jīng)、腎素-血管緊張素-醛固酮系統(tǒng)），進(jìn)行“修復(fù)” 藥物 強(qiáng)心甙地位 利尿劑、轉(zhuǎn)化酶抑制劑、-阻滯劑地位,2003年在法國(guó)召開的以心衰為主題的國(guó)際會(huì)議上，歐洲心臟學(xué)會(huì)心衰指南委員會(huì)的主席之一K. Swedberg建議：應(yīng)向醫(yī)生們廣泛宣傳阻滯劑在心衰治療中的效用 2006在西班牙召開的國(guó)際會(huì)議上再次被強(qiáng)調(diào),病史：患風(fēng)濕性心臟病10余年。近3月來(lái)出現(xiàn)心慌、悶氣, 伴浮腫、腹脹，不能平臥。 體查：重病容, 半坐臥位, 頸靜脈怒張, 呼吸36次/分, 兩肺底可聞濕性羅音。心界向左右兩側(cè)擴(kuò)大, 心率130次/分, 血壓(110/80mmHg) 。,Clinical example,心尖部可聞IV級(jí)收縮期吹風(fēng)樣及舒張期雷鳴樣雜音。肝臟在右肋下6cm可觸及，有壓痛，腹部有移動(dòng)性濁音，骶部及下肢明顯凹陷性水腫。 試分析患者發(fā)生了哪些病理生理變化？其發(fā)生機(jī)制是什么?,111,掌握心力衰竭概念;心力衰竭發(fā)生機(jī)制;心力衰竭時(shí)心臟的代償方式（包括幾個(gè)重要概念） 熟悉心力衰竭原因及分類;心力衰竭時(shí)心外代償反應(yīng)；心力衰竭臨床表現(xiàn)的病理生理基礎(chǔ) 了解心力衰竭時(shí)神經(jīng)-體液的代償反應(yīng)，防治原則,本章要求,
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Heart Failure,Department of pathophysiology Xiangrong Sun,Fundamental knowledge,Heart is one of the most important organs in body. The main function of heart is to providing impetus for circulation of blood.,volume：like left fist weight：500g Ejection of blood： 70ml/SV70/min 60min24h 7056 L/d 10.8萬(wàn)次/天,Histology of myocardium,Intercalated disc,2019/4/1,mitochondrion,Ca2+,Ca2+ 10-7mol/L,Ca2+ 10-5mol/L,Release of Ca2+,tropomyosin,contraction,（粗）myosin,（細(xì)）actin,troponin,Ca2+,Ca2+ 10-5mol/L,SR,mitochondrion,Ca2+,Ca2+ 10-7mol/L,Reuptake of Ca2+,relaxation,tropomyosin,（粗）myosin,（細(xì)）actin,troponin,Ca2+,2019/4/1,AP and contraction of cardiac myocyte,冠心病 (CHD) 高血壓 (Hypertension) 心肌病 (Cardiomyopathy) 瓣膜疾病 (Valvular heart disease),What causes heart failure?,In addition to those causes above, the following factors also can play a role in determining if heart failure will affect you: family history of heart disease(家族史） diabetes（糖尿病） marked obesity（肥胖） heavy consumption of alcohol, or tobacco（酗酒、 吸煙） 5.large salt intake in diet （高鹽飲食）,Other factors,heart failure is the pathological process in which the systolic or/and diastolic function of the heart impaired, and as result , cardiac output decrease and is unable to meet the metabolic demands of body,Concept of heart failure,the systolic or/and diastolic function of the heart impaired,heart failure,2019/4/1,Determinants of cardiac function,Etiology,Decreased myocyte contractility,pressure overload (afterload),Overload for myocardium,volume overload （preload ）,etiology of heart failure,2019/4/1,Restriction of filling,output,low-output heart failure high-output heart failure (*compared with healthy adult),Classification,Low output heart failure,before high output heart failure,high output heart failure,Normal output,health adult,onset,acute heart failure chronic heart failure,Location,left-sided heart failure right-sided heart failure whole heart failure,2019/4/1,法洛氏四聯(lián)征,Compensatory responses,increased heart rate,cardiac dilation,myocardial hypertrophy,Cardiac compensation,(一) Increased heart rate,Mechanism,pressure receptor volume receptor,advantage,This adaptation may increase the cardiac output And maintain the perfusion of heart and brain,disadvantage,If heart rate 180times/min, it will: Increase the consumption of oxygen of heart Reduce the duration for ventricular filling Inadequate flow of the coronary artery (squeeze, lumen, narrow),(二) cardiac dilatation,Frank-Starling law: The more a myocyte or ventricular chamber is stretched ,the more it will contract,2019/4/1,tonicity dilation: the volume of ventricle increases due to the sarcomere dilation, accompanying the increased cardiac contractility and stoke volume,myocardiogenic dilation: the stretch of sarcomere does not accompany the increased cardiac contractility.,(三) Myocardial hypertrophy,concentric hypertrophy,eccentric hypertrophy,2019/4/1,Concentric hypertrophy: is the response to pressure overload. It is associated with increased number of sarcomere arranged in parallel. The increase in wall thickness reduces wall tension and cardiac compliance without increasing the internal chamber size.,eccentric hypertrophy: the response to volume overload is characterized by dilation of chamber size, as well as relative decreased wall thickness. It is thought to result from increased number of sarcomere arranged in series.,concept,GPCR,胞膜,Ca2+,離子通道,Ca2+,IP3,DAG,Gq,PLC,PKC,Biologic responses in hypertrophy,CA, Ang等,Gs,R,R,肌鈣蛋白結(jié)合,興奮-收縮偶聯(lián),心肌收縮,基因表達(dá)增加，心肌和血管平滑肌增生,cAMP,PKA,細(xì)胞內(nèi) Ca2+庫(kù),MAPK家族/NHE-1,CaM-K,2019/4/1,Significance of myocardial hypertrophy Enhancing the contractility of heart Decreasing wall tension and oxygen consumption,2019/4/1,Reduced in the concentration of NE and 1-adrenergic receptor (Tyrosine hydroxylase ),Decreased oxygen and blood supply,Altered of energy metabolism and utilization,Dysfunction of excitation-contraction coupling,Excessive cardiac hypertrophy,Decreased compliance (collagen),(四) Increased ability of cells to use oxygen,Systemic compensation,Increased blood volume,機(jī)制,1.腎小球?yàn)V過(guò)率（ CA ，AGII , PGE2 ,腎血流),2.腎小管對(duì)水鈉的重吸收 腎內(nèi)血流重分布：皮質(zhì)髓質(zhì)水鈉的重吸收 腎小球?yàn)V過(guò)分?jǐn)?shù)=腎小球?yàn)V過(guò)率/腎血流量. 促進(jìn)水鈉重吸收的激素（醛固酮ADH ） 抑制水鈉重吸收的激素（PGE2 利鈉素）,交感腎上腺髓質(zhì)系統(tǒng)激活 (activation of sympathetic-adrenal medulla system),腎素-血管緊張素-醛固酮系統(tǒng)激活 (activation of renin-angiotensin-aldosterone system, RAAS),Neurohumoral compensation,血流重新分布,Renin-angiotensin system and concept of its inhibitory action,Angiotensinogen,Angiotensin ,Angiotensin ,Vascular contraction,Angiotension II Receptor antangonists,ACE Inhibitors,Angiotensin converting enzyme (ACE),Renin,Renin inhibitors,etc.,etc.,etc.,Receptor,心力衰竭與機(jī)體的代償模式圖,心力衰竭,機(jī)體代償,心臟,HR,心臟緊張?jiān)葱詳U(kuò)張,心肌肥大,收縮力,舒縮功能,心外,血容量,血液重分配,紅細(xì)胞、肌紅蛋白,心血供,有效循環(huán)血量,供血供氧,利用氧能力,細(xì)胞線粒體數(shù) 、呼吸酶活性,SV,CO,心肌舒縮功能降低,R x SV = CO,組織細(xì)胞缺血缺氧,神經(jīng)-體液,交感-腎上腺髓質(zhì)系統(tǒng),ARRS,血容量,血液重分配,收縮力,2019/4/1,infection ( pulmonary infection),precipitating factors,Precipitating factors,2019/4/1,infection,2019/4/1,cardiac dysrhythmia,precipitating factors,2019/4/1,尤其是快速型心律失常 心率 舒張期縮短 心肌耗氧量 冠脈血流 心肌缺血、缺氧 心室充盈 心泵功能 心輸出量,房室活動(dòng)協(xié)調(diào)性紊亂,2019/4/1,water-electrolytes and acid-base disturbance,precipitating factors,Ca2+ inflow , SR released Ca2+ binding to troponin activity of ATP enzyme sensitivity of Cap to CA ,myocardial conductibility,autorhythmicity,cardiac contractility,myocardial excitability,2019/4/1,pregnancy and delivery,precipitating factors,2019/4/1,妊娠期血容量（臨產(chǎn)期） 分娩時(shí)疼痛、精神緊張、 稀釋性貧血 交感一腎上腺髓質(zhì)系統(tǒng)興奮 高動(dòng)力循環(huán)狀態(tài) 靜脈回流 小血管收縮 心臟前負(fù)荷 （左室）后負(fù)荷 心肌耗氧量和冠脈流量 心輸出量,2019/4/1,Excessively labor and spiritual burden; infusion,precipitating factors,2019/4/1,(一) loss of cardiomyocyte,(二) metabolic dysfunction of myocardium,(三) dysfunction of excitation-contraction coupling,Pathogenesis,Decreased myocardial contractility,(一) loss of cardiomyocyte,Decreased myocardial contractility,contractility decreased,myocardial cell apoptosis : apoptotic index 35.5%,(二) metabolic dysfunction of myocardium,impaired energy production reduced energy reserve impaired energy utilization,Decreased myocardial contractility,1.impaired energy production,myocardial ischemia hypoxia,Disorder of myocardial energy metabolism,2. reduced energy reserve,CP,Disorder of myocardial energy metabolism,3. impaired energy utilization,Disorder of myocardial energy metabolism,能量生成,能量利用,脂肪酸 乳酸 丙酮酸 葡萄糖 氨基酸,三羧酸循環(huán),氧化磷酸化,ATP,ADP+Pi,Ca2+,與肌鈣 蛋白結(jié)合,心肌收縮,心衰時(shí)的能量代謝障礙,CP,能量?jī)?chǔ)存,ATPase,乙酰 CoA,(三) dysfuncion of excitation-contraction coupling,Decreased myocardial contractility,1. Altered of Sarcoplasmic reticulum (SR) handling Ca2+,2. Reduced influx of extracellular Ca2+,3. Dysfunction of Ca2+ binding to troponin,1.Sarcoplasmic reticulum (SR) mishandling Ca2+,Impaired excitation-contraction coupling,SR mishandling Ca2+,Reduced Ca2+ released by SR Ryanodin receptor (Ry-R) or Ry-R mRNA decreased Acidosis reduced release of Ca2+ by SR,SR mishandling Ca2+,2. Reduced influx of extracellular Ca2+,Ca2+ inflow,voltage dependence,- receptor dependence,Na+/Ca2+ exchange,Impaired excitation-contraction coupling,L型通道亞單位,胞外 Ca2+內(nèi)流障礙,Na+/Ca2+ exchange： Depolarization Na+ outward Ca2+ inward Repolarization Na+ inward Ca2+ outward,Reduced influx of extracellular Ca2+,K+ impaired influx of Ca2+ (Hyperkalemia),Reduction of 1-receptor density,Norepinephrine depletion,H+ depress the sensitivity of receptor,Causes of Ca2+ influx decreased in heart failure:,Reduced influx of extracellular Ca2+,Acidosis decrease the m，L-Ca2+ cannel ,3. Dysfunction of Ca2+ binding to troponin,troponin,Impaired excitation-contraction coupling,Reduced in the concentration of NE and 1-adrenergic receptor,Decreased oxygen and blood supply,Altered of energy metabolism and utilization,Dysfunction of excitation-contraction coupling,Excessive cardiac hypertrophy,Decreased compliance,Delayed reposition of Ca2+ Ca2+ 10-5 mol/L 10-7 mol/L,Diastolic dysfunction,Affinity of Ca2+ and Ca2+-Na+ Ca2+ excretion,Delayed reposition of Ca2+,Impaired dissociation of the actin-myosin complex,Impaired myocardial diastolic properties,ATP,Decreased ventricular diastolic potential,Impaired myocardial diastolic properties,Reduced ventricular compliance myocardial hypertrophy; fibrosis; edema dv/dp,Impaired myocardial diastolic properties,心室順應(yīng)性(ventricular compliance)：心室在單位壓力變化下所引起的容積改變(Dv/dp),PV曲線左移,V稍有增加 P增加很多,2019/4/1,三、 Inconsistent behavior in systolic and diastolic function of the heart,Summary of the etiology of heart failure,Heart failure,Contractility,Loss of cardiomyocyte,Metabolic dysfunction,Dysfunction of excitation-contraction coupling,Altered of SR handling Ca2+,Reduced influx of extracellular Ca+,Dysfunction of Ca+ binding to troponin,Diastolic dysfunction,Delay of Ca+ reposition,Impaired dissociation of actin-myocin complex,Cardiac diastolic potential energy,Impaired ventricular compliance,Inconsistent behavior in systolic and diastolic function,Questions:,(一) 肺循環(huán)淤血 (Pulmonary congestion),當(dāng)PCWP18 mmHg時(shí)，即出現(xiàn)肺循環(huán)淤血征，見于左心衰竭。,Clinical manifestations,左心衰竭能導(dǎo)致肺淤血、肺水腫；因此主要的 臨床表現(xiàn)是呼吸困難,肺水腫,心力衰竭細(xì)胞,1、呼吸困難 (dyspnea),勞力性呼吸困難的發(fā)生機(jī)制:,回心血量增多，加重肺淤血 心率加快，舒張期縮短 機(jī)體活動(dòng)時(shí)需氧量增加,睡眠時(shí),1) 毛細(xì)血管壓 左心衰左室舒張末期壓力肺毛細(xì)血管壓 超過(guò)其代償能力肺水腫 2) 毛細(xì)血管通透性,肺循環(huán)淤血 肺泡通氣血流失調(diào)缺氧 毛細(xì)血管通透性 肺水腫 肺泡表面活性物質(zhì)破壞肺泡表面張力 毛細(xì)血管通透性 肺水腫,2、肺 水 腫,(二) 體循環(huán)淤血 (Systemic congestion),當(dāng)CVP16 cmH2O時(shí)，即出現(xiàn)體循環(huán)淤血征，見于右心衰竭及全心衰竭。,主要表現(xiàn) 頸靜脈充盈或怒張 肝腫大及肝功能損害 胃腸道淤血所致的食欲不振等 消化道癥狀 心性水腫,體循環(huán)淤血,體征：,肝大 水腫 頸靜脈怒張,食欲不振、惡心、腹脹,肝頸靜脈返流征,皮下水腫、腹水、胸水,全心 左心衰右心衰,檳榔肝,(三) 心輸出量不足,(low cardiac output ),心輸出量 (cardiac output,CO)減少 心臟指數(shù) (cardiac index,CI)降低 射血分?jǐn)?shù) (ejection fraction)降低 心室充盈(ventricular filling)受損 心率(heart rate)增快,亦稱低排出量綜合征 (syndrome of low output)或前向衰竭( forward failure) 特點(diǎn)為:,臨床表現(xiàn),疲乏無(wú)力、失眠、嗜睡,皮膚蒼白或發(fā)紺,尿量減少,心源性休克,表現(xiàn)形式,防治基本病因、消除誘因,改善心臟舒縮功能,減輕心臟前、后負(fù)荷,控制水腫,增強(qiáng)心肌收縮功能,改善心臟舒張功能,降低心臟后負(fù)荷,調(diào)整心臟前負(fù)荷,防治的病理生理基礎(chǔ),Pathophysiologic basis of prevention and treatment,著眼點(diǎn) 從傳統(tǒng)的改善血流動(dòng)力學(xué)，減輕癥狀“強(qiáng)心、利尿、擴(kuò)血管” 到改善預(yù)后，降低總死亡率針對(duì)過(guò)度激活的神經(jīng)、內(nèi)分泌系統(tǒng)（交感神經(jīng)、腎素-血管緊張素-醛固酮系統(tǒng)），進(jìn)行“修復(fù)” 藥物 強(qiáng)心甙地位 利尿劑、轉(zhuǎn)化酶抑制劑、-阻滯劑地位,2003年在法國(guó)召開的以心衰為主題的國(guó)際會(huì)議上，歐洲心臟學(xué)會(huì)心衰指南委員會(huì)的主席之一K. Swedberg建議：應(yīng)向醫(yī)生們廣泛宣傳阻滯劑在心衰治療中的效用 2006在西班牙召開的國(guó)際會(huì)議上再次被強(qiáng)調(diào),病史：患風(fēng)濕性心臟病10余年。近3月來(lái)出現(xiàn)心慌、悶氣, 伴浮腫、腹脹，不能平臥。 體查：重病容, 半坐臥位, 頸靜脈怒張, 呼吸36次/分, 兩肺底可聞濕性羅音。心界向左右兩側(cè)擴(kuò)大, 心率130次/分, 血壓(110/80mmHg) 。,Clinical example,心尖部可聞IV級(jí)收縮期吹風(fēng)樣及舒張期雷鳴樣雜音。肝臟在右肋下6cm可觸及，有壓痛，腹部有移動(dòng)性濁音，骶部及下肢明顯凹陷性水腫。 試分析患者發(fā)生了哪些病理生理變化？其發(fā)生機(jī)制是什么?,111,掌握心力衰竭概念;心力衰竭發(fā)生機(jī)制;心力衰竭時(shí)心臟的代償方式（包括幾個(gè)重要概念） 熟悉心力衰竭原因及分類;心力衰竭時(shí)心外代償反應(yīng)；心力衰竭臨床表現(xiàn)的病理生理基礎(chǔ) 了解心力衰竭時(shí)神經(jīng)-體液的代償反應(yīng)，防治原則,本章要求,
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