20.2
心力衰竭 II：病理生理学
收缩性心力衰竭与代偿机制
收缩性心力衰竭（亦称射血分数降低的心力衰竭，HFrEF）是最常见的心力衰竭类型。该病表现为心室射出血量减少。主动脉弓和颈动脉窦内的压力感受器感知血压下降，从而激活交感神经系统（SNS）释放肾上腺素和去甲肾上腺素。该反应初期旨在通过提高心率与心肌收缩力以支持功能受损的心肌。
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收缩性心力衰竭的病理生理学始于左心室泵出的血量减少。
主动脉弓和颈动脉窦中的压力感受器可检测到这种下降，从而激活交感神经系统释放肾上腺素和去甲肾上腺素，进而提高心率和心肌收缩力。
交感神经刺激还会引起皮肤、胃肠道和肾脏的血管收缩。
心输出量降低和交感神经激活导致肾灌注减少，从而触发肾素释放。
肾素将血管紧张素原转化为血管紧张素I。随后，血管紧张素I在肺部通过血管紧张素转换酶转化为血管紧张素II。
血管紧张素II可升高血压和后负荷，并刺激醛固酮释放，导致钠和液体潴留。
此外，由过度扩张的心腔释放的利钠肽可促进血管扩张和利尿，但其作用常不充分。
最终，心脏负荷增加会降低心肌收缩力，导致心室扩张、肥厚、重构以及早期心肌细胞死亡，进而引起舒张性心力衰竭。
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Q1: What triggers the sympathetic nervous system response in systolic heart failure?
Baroreceptors in the aortic arch and carotid sinuses detect reduced blood pressure from decreased cardiac output. This triggers the sympathetic nervous system to release epinephrine and norepinephrine, which increase heart rate and contractility to support the weakened myocardium and restore blood pressure.
Q2: How does reduced renal perfusion activate the renin-angiotensin-aldosterone system?
Low cardiac output and sympathetic activation cause vasoconstriction in the kidneys, reducing renal perfusion. This triggers renin release, which converts angiotensinogen to angiotensin I. Angiotensin-converting enzyme in the lungs then converts angiotensin I to angiotensin II, a potent vasoconstrictor that raises blood pressure and afterload.
Q3: What role does aldosterone play in fluid overload during heart failure?
Angiotensin II stimulates the adrenal cortex to release aldosterone, which causes renal tubules to retain sodium and fluid. This increases blood volume and preload, contributing to the fluid overload characteristic of heart failure and further burdening the weakened heart muscle.
Q4: Why are natriuretic peptides insufficient to counteract heart failure progression?
Natriuretic peptides like BNP and ANP are released from distended cardiac chambers to promote vasodilation and diuresis. However, their effects are typically insufficient to counteract the adverse effects of prolonged sympathetic activation, renin-angiotensin-aldosterone system activation, and other neurohormonal mechanisms driving heart failure.
Q5: How does increased cardiac workload lead to ventricular dilation and hypertrophy?
As myocardial contractility decreases, end-diastolic blood volume increases, stretching myocardial fibers and causing ventricular dilation. The heart responds to increased workload by thickening its muscle, a process called ventricular hypertrophy. These structural changes constitute ventricular remodeling, which further impairs cardiac function.
Q6: What is the vicious cycle of heart failure and how does it progress?
Low cardiac output triggers compensatory mechanisms that increase the heart's workload, worsening the condition. Neurohormones like angiotensin II promote myocardial hypertrophy and fibrosis, causing cell death and loss of contractility. This cycle eventually leads to diastolic heart failure, where a stiff ventricle resists filling and decreases cardiac output.
Q7: What adverse effects result from prolonged sympathetic nervous system activation?
Prolonged sympathetic activation causes vasoconstriction in the skin, gastrointestinal tract, and kidneys, reducing perfusion to vital organs. This triggers renin release and activates the renin-angiotensin-aldosterone system, leading to increased blood pressure, fluid retention, and elevated preload and afterload that further stress the failing heart.