1 / 63

Pathophysiology of Heart Failure

Heart Disease Braunwald. CV R4 李威廷醫師 Supervisor: 劉秉彥醫師. Pathophysiology of Heart Failure. Myocardial failure: myocardial infarction, acute myocarditis Heart failure: myocardial failure, acute AR, constrictive pericarditis Circulatory failure:

kali
Download Presentation

Pathophysiology of Heart Failure

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Heart Disease Braunwald CV R4 李威廷醫師 Supervisor: 劉秉彥醫師 Pathophysiology of Heart Failure

  2. Myocardial failure: myocardial infarction, acute myocarditis Heart failure: myocardial failure, acute AR, constrictive pericarditis Circulatory failure: heart failure, hypovolemic shock, septic shock

  3. Adaptive mechanisms • Frank-starling mechanism: preload (short-term) • Neuroendocrine system: norepinephrine (short-term) • Myocardial remodeling: with or without chamber dilatation (chronic or long-term)

  4. Frank-starling mechanism: LVEDPv.s.ventricular performance

  5. Vascular redistribution • Increase vasoconstrictor activity sympathetic nervous system renin-angiotensin system endothelin system keep adequate oxygen to vital organs (brain, heart) • Endothelial dysfunction ischemic- and exercise- induced vasodilation attenuated L-arginine, NO

  6. Peripheral hypoperfusion • Non-vital organs: Anaerobic metabolism, lactic acidosis • Skin: cold, dry turger • Muscle: weakness • Kidney: sodium and nitrogen retention • Gut: decreased GI motility, GI upset • Liver: hepatic dysfunction

  7. Chronic myocardial remodeling (1) • Pressure overload: increase ventricular wall thickness (concentric hypertrophy) (isometric) • Volume overload: mild increase ventricular wall thickness (eccentric hypertrophy)(counterbalance the increased radius) (isotonic)

  8. Left ventricular wall thickness vs Chamber radius

  9. Apoptosis and necrosis

  10. Molecular mechanism of myocardial remodeling and failure(Myocyte Loss) • Necrosis: deprived of oxygen or energy  loss of membrane integrity  influx of ECF  cellular swelling  release of proteolytic enzymes  cellular disruption (subendocardial area) (acute myocarditis, DCM, myocardial infarction) • Apoptosis: specific genetic program  molecular cascade of degradation of nuclear DNA (angiotensin II, NO, inflammatory cytokines, mechanical strain)

  11. Molecular mechanism of myocardial remodeling and failure(Excitation-Contraction coupling alternation) • Ca: contraction and relaxation; • Force-frequency relationship: contractile force decrease, rates of stimulation increase • Sarcoplasmic reticulum Ca-ATPase & phospholamban: Ca reuptake system (SERCA2) • Na-Ca exchanger: removal Ca in diastole • Ca free channel, voltage-dependent Ca channel: • Calsequestrin: major Ca binding protein in SR

  12. Molecular mechanism of myocardial remodeling and failure(Contractile apparatus alternation) • Reduction of myosin ATPase activity: qualitative, quantitative • Myosin isoform changes: fetal and neonatal form • Altered regulatory proteins: troponin-T1  T2

  13. Molecular mechanism of myocardial remodeling and failure(Matrix alternation) • Regulation of interstitial collagen: • Collagen strut depletion: • Interstitial matrix accumulation:

  14. ACEI

  15. Vicious cycles in the overloaded heart

  16. Pathophysiology of diastolic heart failure • Altered ventricular relaxation relaxation: inactivation of contraction isovolemic relaxation and early ventricular filling  SERCA2 and calcium pump  ischemia, elevated afterload • Altered ventricular filling wall stiffness diastolic asynergy: regional abnormal relaxation diastolic asynchony: no relaxation  ischemia, pericardial disease

  17. Diastolic dysfunction mechanism

  18. Neurohormonal, autocrine, & paracrine adjustments (1) • Response to inadequate arterial volumesystolic HF • Adrenergic • Renin-angiotensin-aldosterone • Vasopressin and endothelin • Atrial natriuretic peptide (ANP)

  19. Neuroendocrine, autocrine, & paracrine adjustments (2) • Autonomic nervous system Increased sympathetic activity: bloodnorepinephrine, abnormalbaroreflex (?) Decreased parasympathetic activity: Cardiac norepinephrine depletion: not clear Beta1-adrenergic receptor density decrease, G protein: local NE concentration, beta1-antagonist Gs (stimulation), Gi (inhibition): adenynyl cyclase

  20. Neuroendocrine, autocrine, & paracrine adjustments (3) • Renin-angiotensin system (RAS) Juxtaglomerular beta1-receptor: renin Renal vascular baroreceptor: renin Adrenergic nervous system: NE • Tissue RAS: 90—99% Early activation than blood RAS • Angiotensin receptor: AT1, AT2

  21. Neuroendocrine, autocrine, & paracrine adjustments (4) • Arginine vasopressin (AVP): V1 receptor, cathecholamine • Natriuretic peptides: Atrial-NP, Brain-NP, C-NP • Endothelin: pulmonary vasoconstrictor, Killip stage • Inflammatory cytokine: TNF-a, IL-1b; Ca & myocardium • Nitric oxide: inhibit inflammatory cytokines, apoptosis • Oxidative stress: (animal study)

  22. Clinical Aspects of heart failure: high-output heart failure; pulmonary edema CV R4 李威廷醫師 Supervisor: 劉秉彥醫師 Nov 6th, 2003

  23. Backward heart failure hypothesis • Right ventricular failure as a sequence of left ventricular failure • Ventricle failed to discharge its contents • Increase LVEDP • Blood accumulation and pressure arises in atrium and venous system • The atrium contracts more vigorously • Venous and capillary pressure arise • Fluid transudation from capillary bed to interstitial space

  24. Forward heart failure hypothesis • Reduced cardiac output, then diminished perfusion of vital organs • Sodium and water retention • Increased extracellular fluid • Congestion of organs and tissues • Massive myocardial infarction  both forward and backward heart failure hypothesis

  25. Low output versus high output heart failure • Low output heart failure congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic heart failure • High output heart failure thyrotoxicosis, arteriovenous fistula, anemia, beriberi disease, Paget’s disease of bone

  26. Causes of heart failure • Underlying disease: structural, vessel, or valvular • Fundamental causes: increased hemodynamic burden or reduction in oxygen delivery • Precipitating causes: specific causes or incidents (avoidance of a precipitating cause can prevent heart failure)

  27. Precipitating causes of heart failure (1) • Inapposite reduction of therapy: Na, water, diuretics • Arrhythmia: tachycardia, bradycardia, abnormal conduction • Myocardial ischemia or infarction • Systemic infection: esp. pulmonary • Pulmonary embolism • Physical, emotional, and environmental stress • Cardiac infection and inflammation: myocarditis • Development of an unrelated illness: ARF

  28. Precipitating causes of heart failure (2) • Cardiac depressant of salt-retaining drug: beta- blocker, isoptin, diltiazm, doxorubicin, cyclophosphamide • Cardiac toxins: alcohol, cocaine • High-output status: valvular heart disease, anemia, pregnancy • A second form of heart failure: HCVD + AMI

  29. Symptoms of heart failure • Respiratory distress • Reduced exercise capacity • Physical findings • Laboratory findings • CXR

  30. Respiratory distress • Exertional dyspnea: the degreeof activity necessary tp induce the symptom • Orthopnea: dyspnea at recumbent position, relieving by elevation of the head with pillows (not-specific) • Paroxysmal nocturnal dyspnea: interstitial pulmonary edema  bronchospasm  wheezing (cardiac asthma) • Dyspnea at rest • Acute pulmonary edema

  31. Pulmonary & Cardiac Dyspnea • Cough v.s. sitting up relief • Smoking history • Bronchodilator agent v.s. diuretics

  32. Reduced exercise capacity (1) • Mechanism Pulmonary vascular congestion Inadequate blood flow to exercise muscle Deconditioning of skeletal and respiratory muscles Attenuated peripheral blood vessel resistance Abnormal skeletal metabolism Patient anxiety

  33. Reduced exercise capacity (2) • Exercise testing Maximal exercise capacity: treadmill test (total oxygen uptakes) reflecting central hemodynamic response adequacy Submaximal exercise capacity: 6-minute walk test reflecting regulation of blood flow to the skeletal muscle • Other organs symptoms Brain (confusion, insomnia), urinary tract (nocturia)

  34. Reduced exercise capacity (3) • Functional classification: (New York Heart Association) I: no limitation II: slight limitation III: marked limitation IV: inability for any work without discomfort • Quality of life: reduce symptoms, prolong survival, and improve quality of life

  35. Physical findings • General appearance: orthopnea, malnutrition, cyanosis • Increased adrenergic activity: pallor, cold, diaphoresis • Pulmonary rales • Systemic venous hypertension: JVE, Kussmaul’s sign • Hepatojugular reflux: right side heart • Congestive hepatomegaly • Edema: extracelluar fluid gain >4L • Pleural effusion: R’t ± L’t • Ascites: long-term systemic venous hypertension

More Related