深和节律的改变Dyspneaonexertion劳力性呼吸困难Orthopnea端

1、深和节律的改变深和节律的改变Dyspneaonexertion劳劳力性呼吸困难力性呼吸困难Orthopnea端端 Concept 概念概念 Pathogenesis 发病机制发病机制 Effect（important）and mechanisms 影响及机制影响及机制 Outline大纲大纲 Background 背景背景 Definition and explaining the definition 定义定义 pathogenesis 机制机制 Content 内容内容 心为君主之官，脏腑百骸，惟所是命，聪明智慧，莫不由之心为君主之官，脏腑百骸，惟所是命，聪明智慧，莫不由之 The hea

2、rt is more deceitful than anything. It is The heart is more deceitful than anything. It is incurable who can know it?incurable who can know it? Jeremiah 17:9-10 Heart failure 心衰心衰-Background Heart failure 心衰心衰-Background Cats look down on us. Dogs look up to us. Pigs treat us as equalsHeart failure

3、心衰心衰-Background What kill us?Background 2010年中国心血管病报告年中国心血管病报告 1/5 adults suffer from cardiovascular disease 3 million die from cardiovascular disease account for 41% of death number China death 1/11.6s America death 1/34.0s equivalent to once Wen chuan big earthquake Backgroundthe report of cardiov

4、ascular disease in china 2010 hypertension 高血压高血压 2亿人亿人 myocardial infarction 心肌梗心肌梗 200万人万人 pulmonary heart disease 肺心病肺心病 500万人万人 rheumatic heart disease 风心病风心病 250万人万人 congenital heart disease 先心病先心病 200万人万人 heart failure 心衰竭心衰竭 420万人万人2010年中国心血管病报告年中国心血管病报告the report of cardiovascular disease in

5、 china 2010BackgroundWe Face an epidemic of HF Affecting 0.4-2% of total population， 8-10% of elderly The global HF patients have up to 2250 million， increasing at 200 million per year The prognosis of HF similar to cancer or even worse The 20% patients with HF readmission after discharged from hosp

6、ital in 30 days Less than 50% patients survival 5 years from the diagnosis of heart failure Average survival time is 16 month ， in hospital only 25% survival 5 years Background0 02020404060608080100100Heart diseaseCerebrovascular malignancyaccidentalrespiratory gastrointestinalcommunicableUrinary sy

7、stem Neuropsychosis EndocrinosisLife styleBiogentics Environmental factorsHealth careTop 10 cause of death in China and the main risk factors %Forecasting the future of cardiovascular disease in the United States Circulation 2011;123(8):933-944Estimated direct and indirect cost of major cordial dise

8、ase In united state in 2010The Economic Burden Of Cardiovascular DiseasesCoronary heart disease Hypertensive disease Stroke Heart failure$53.9$34.4 Cost in billion $105.9 $93.5 Clinical intervention 生生 死死Low riskstateDangerous state Early changeDifferent prognosisClinicdiseaseSub-clinic symptoms Pre

9、vent interventionHypertension hyperlipidmia smoking diabetes obey hereditary psychological intervention National standard life style drug operation physics Backgroundheath sub-health sub-clinic diseaseRisk FactorsEndothelial DysfunctionAtherosclerosisCoronary artery disease Myocardial IschemiaCorona

10、ry ThrombosisMyocardial InfarctionArrhythmia & Loss of MuscleRemodelingVentricular DilationCongestive Heart FailureEnd stage Heart Disease The Progressive Development of Chronic Cardiovascular Disease 慢性心血管疾病渐进式发展慢性心血管疾病渐进式发展心功不全心功不全 insufficiencyHeart functionPhysicalActivitylimitationSymptoms

11、at rest DescriptionINono almost as normal personII Mild Slight noCan withstand heavier physical activityIIImoderateobviousnoCan with lighter physical activityIVsevereobviousyesLose labor ability completely Life-threating 分级分级: The New York Heart Association Functional Class (NYHA-FC) 心肌收缩力因各种心肌收缩力因各

12、种病因病因减弱（原发或继发），不能将减弱（原发或继发），不能将静脉回心血量等量搏出，因而使静脉回心血量等量搏出，因而使心输出量心输出量绝对或相对绝对或相对减减少，少，使体循环和使体循环和/或肺循环静脉系统或肺循环静脉系统淤血淤血，动脉系统，动脉系统供血供血不足不足，不能满足人体在静息状态或一般活动时代谢的的需，不能满足人体在静息状态或一般活动时代谢的的需要，从而出现一系列的心脏循环障碍的要，从而出现一系列的心脏循环障碍的症状和体征症状和体征。大循环大循环 心功心功 临床临床 心肌衰竭心肌衰竭：原发性心肌病变，如心肌炎，心肌梗塞：原发性心肌病变，如心肌炎，心肌梗塞 Myocardial fail

13、ure： primary myocardial lesions ，myocarditiis 心力衰竭心力衰竭：不仅仅是心脏问题，如缩窄性心包炎：不仅仅是心脏问题，如缩窄性心包炎Heart failure：not only heart problem，contractive pericarditis 充血性心衰充血性心衰： 慢性经过，血容量增加，出现水肿慢性经过，血容量增加，出现水肿 Congestive heart failure：chronic，blood，edema 心肌收缩力因各种心肌收缩力因各种病因病因减弱（原发或继发）减弱（原发或继发） Expounding Myocardial c

14、ontractility is impaired by various causes （primary or secondary).fibrinous pericarditis心肌收缩力因各种心肌收缩力因各种病因病因减弱（原发或继发）减弱（原发或继发） Expounding The factors influence CO Basic causesExample Contractility 收缩性（力收缩性（力)Myocardial abnormalitiescoronary heart diseaseload负荷负荷OverloadValvular stenosis, valvular in

15、sufficiencySynergy 协同性协同性 Disharmony Rhythm 节律节律Arrhythmia Underlying Causes of HF 心衰的基本病因心衰的基本病因 CAD the commonest 2/3Hypertension in 4%Toxic injury in 2%-4%Valve diseases in 4%Unknown in 20% Common Causes of HF 心衰的常见病因心衰的常见病因诱因诱因 precipitation cause （Aggravating Factors） Infections Arrhythmias (AF

16、) Pregnancy and childbirth be heated with passion too fast to transfusionp any factor that increase cordial load or injure heartp precipitation is not always precipitation Attention Expounding 心输出量绝对或相对降低心输出量绝对或相对降低A AV V瘘瘘 贫贫血血 甲甲亢亢 脚脚气气病病Hyperdynamic status Increased ventricular preloadATP consump

17、tion increased and production decreased high cardiac output HF（1%） low cardiac output HF notes：other classification self-study cardiac output reduce absolutely or relatively,dermatophytosis barbiers = beriberipanneuritis epidemica dietetic neuritis endemic neuritis脚气与脚气病脚气与脚气病香港脚香港脚 Hong Kong foot 运

18、动员脚运动员脚 athlete footburning, itching，cracking糖代谢脱羧酶的辅酶糖代谢脱羧酶的辅酶Coenzyme of decarboxylase in Sugar metabolism参与参与 -酮酸的氧化脱羧酮酸的氧化脱羧Participate in - keto acid oxidative decarboxylation VitB1(thiamin 硫胺素硫胺素) ：葡萄糖葡萄糖 glucose 酵解酵解glycolysis 乳酸乳酸Lactic acid丙酮酸丙酮酸 pyruvic acidTCA循环循环乙酰辅酶乙酰辅酶A丙酮酸丙酮酸NADHNAD+NA

19、DHNAD+发酵发酵 ferment呼吸链递氢呼吸链递氢NADHNAD+VitB1丙酮酸脱氢酶系丙酮酸脱氢酶系参与参与 -酮酸的氧化脱羧酮酸的氧化脱羧 丙酮酸丙酮酸 乳酸堆积乳酸堆积CO2, H+Beriberi： comes from a Sinhalese phrase Meaning： “weak, weak” or “I can not, I can not”,备急千金要方备急千金要方考诸经方往往有考诸经方往往有脚弱脚弱之论，而古人之论，而古人少有此疾。自永嘉南渡，衣缨士人，少有此疾。自永嘉南渡，衣缨士人，多有遭者。风毒中人，随处皆得，多有遭者。风毒中人，随处皆得，作病何偏着于脚也？答

20、曰作病何偏着于脚也？答曰 夫人有夫人有五脏，心肺二脏，经络所起在手十五脏，心肺二脏，经络所起在手十指；肝肾与脾三脏，经络所起在足指；肝肾与脾三脏，经络所起在足十趾。夫十趾。夫风毒之气，皆起于地风毒之气，皆起于地。地。地之寒暑风湿皆作蒸气，足常履之，之寒暑风湿皆作蒸气，足常履之，所以风毒之中人也所以风毒之中人也必先中脚必先中脚；久而；久而不瘥，遍及四肢腹背头项也；微时不瘥，遍及四肢腹背头项也；微时不觉，痼滞乃知。经云不觉，痼滞乃知。经云 次传、间次传、间传是也。传是也。 东晋、六朝时叫脚弱东晋、六朝时叫脚弱孙思邈称为风毒脚气孙思邈称为风毒脚气内经内经诸病源候论诸病源候论脚气病治法总要脚气病治法总

21、要 Dry beriberiWaste beriberiDifficulty in walkingPeripheral edemaTingling or numbnessIncreased heart rateparalysis of the lower legsDyspnea on exertionMental confusion/speech difficultiesParoxysmal nocturnal dyspneanystagmusVasodilation leading to increased arteriovenous shuntPeripheral or center le

22、sion Cardiovascular system infant beriberi crying, but not loudly and without tears. Maybe fatal . Types of beriberi Expounding 心功下降，静脉淤血，动脉缺血心功下降，静脉淤血，动脉缺血 Causes Cardiac function impairment 代代 偿偿 Cardiac output Venous congestion引起病理性损害，出现临床症状和体征引起病理性损害，出现临床症状和体征Arterials ischemiavenous system cong

23、estion arterial system insufficient blood supplyCardiac outputIschemia and Hypoxia heart Rate sympathetic stroke sympathetic Frank-Starling law hypertrophy- remodeling Blood redistribution neurohumoral (NE, RAAS) 心衰时机体的适应和代偿心衰时机体的适应和代偿 adaption and compensationCardiac output CO =stroke/min X heart R

24、ateCardiac（ventricular） remodeling 心肌重塑（构）心肌重塑（构）心肌受损，代偿与适应心肌受损，代偿与适应 出现结构、代谢和功能改变出现结构、代谢和功能改变 生物学：心肌细胞，非心肌细胞、细胞外基质生物学：心肌细胞，非心肌细胞、细胞外基质 基因表达基因表达 ？几何学：心肌肥大，心室扩大等几何学：心肌肥大，心室扩大等 Normal Centripetal Centrifugal Load postload preload Myofibers hyperplasia parallel tandem Ventricular Wall thickness thicken

25、ing slight thickening Heart Chamber expansion no obvious obvious Myocardial hypertrophy significant myofibre disarray and interstitial fibrosis in HCM. Heart Rate 180 Scarometers 2.2 Excessive hypertrophy organ interstitium tissue cap, sympathetic density cell surface area, mitochondria molecular V3

26、imbalance growth and increase Limitation of myocardial compensationAbstractIt has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of 14C, generated by nucle

27、ar bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from1% turning over annually at the age of 20 to 0.3% at the age of 75. Less than 50% of cardiomyocytes are exchanged during a normal lifespan. T

28、he capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work towards the development of therapeutic strategies aiming to stimulate this process in cardiac pathologies. were myocardial cells post-mitotic cells?Science 324: 98, 2009.Expounding 4：症状和体征：症状和体征

29、signs and symptomsCardiac output Arterials perfusion Venous stagnation renal FatigueCardiac shock Sudden death liver-gut lung skin Edema Dyspnea CyanosisDyspnea 呼吸困难呼吸困难Respiratory become labored 呼吸费力呼吸费力 Respiratory frequency depth and rhythm 呼吸频率、深度和节律的改变呼吸频率、深度和节律的改变 Dyspnea on exertion 劳力性呼吸困难劳力

30、性呼吸困难Orthopnea 端坐呼吸端坐呼吸Paroxysmal nocturnal dyspnea 夜间阵发性呼吸困难夜间阵发性呼吸困难Dyspnea 呼吸困难呼吸困难 Fatigue Activities limited Chest congestion Edema or ankle swelling Shortness of breathThe Major signs and symptoms of CHF?Think FACES. 疲乏疲乏 活动受限活动受限 胸闷胸闷 水肿或脚踝肿胀水肿或脚踝肿胀 气促气促“Evolution” of Our Understanding of CHF

31、慢性心衰的认识演变慢性心衰的认识演变 cardio-renal model 心肾模型心肾模型 Na-water retention Hemodynamic disorder 血流动力学紊乱血流动力学紊乱 reduced cardiac output and excessive vasoconstriction Neurohormonal model 神经体液模型神经体液模型Actin myosin troponinThick & thin myofilament 10-5 10-7 Tropomyosin肌球蛋白肌球蛋白肌动蛋白肌动蛋白肌纤蛋白肌纤蛋白肌凝蛋白肌凝蛋白阻凝蛋白阻凝蛋白亲

32、凝蛋白亲凝蛋白原肌球蛋白原肌球蛋白原肌凝蛋白原肌凝蛋白向肌球蛋白向肌球蛋白Woe？！？！ “ pump ” Basic mechanisms Cell1. Systole proteins Ca+ transfer ATP 1. Contraclity abnormalities degeneration, necrosis, apoptosis excitation constration Ca influx (channel) Ca binding to troponin SR lease ATP production/utilization2. Diastole 2. Disorder

33、diastolic properties Ca+ restoration efflux and SR Actin & myosin dissociationgross3.Synergy Anatomies Compliance Coordination synchronism symmetry 3 dysynergy Gross anatomy anomalies Ventricular wall thick？ ! Altered Compliance Changed in Coordination Paradoxical:？! asynchronism asymmetry “ pump ” Basic mechanisms 图图3-1-4 心脏反常收缩示意图心脏反常收缩示意图 正常心脏正常心脏 受损心脏变薄受损心脏变薄 室压室压，膨突，膨突Heart failure 心衰心衰-Background Cats look down on us. Dogs look up to us. Pigs treat us as equalsHeart failure 心衰心衰-Background CAD the commonest 2/3Hyperten