Shock (1)

休克(1)

Shock is a state of organ hypoperfusion with resultant cellular dysfunction and death. Mechanisms may involve decreased circulating volume, decreased cardiac output, and vasodilation, sometimes with shunting of blood to bypass capillary exchange beds. Symptoms include altered mental status, tachycardia, hypotension, and oliguria. Diagnosis is clinical, including BP measurement. Treatment is with IV fluids, correction of underlying disorder, and sometimes vasopressors.

休克是因器官灌注不足，导致细胞机能障碍和死亡的一种状态。休克生理机制涉及循环容量减少、心排量降低和血管扩张，有时伴血液分流，绕过毛细管交换床。症状包括精神状态改变、心动过速、低血压和少尿。临床诊断包括量血压。治疗采静脉输液、纠正潜在疾病，有时使用血管升压类药物。

Pathophysiology

病理生理学

The fundamental defect in shock is reduced perfusion of vital tissues. Once perfusion declines so that O2 is inadequate for aerobic metabolism, cells shift to anaerobic metabolism with increased production of CO2 and accumulation of lactic acid. Cellular function declines, and if shock persists, irreversible cell damage and death occur.

休克的主要问题是生命组织灌注的减少。一旦组织灌注减少，细胞有氧代谢所需的氧气就会不足，转入无氧代谢，致使二氧化碳和乳酸积累压增加，细胞功能下降。持续休克时就会发生不可逆的细胞损害和死亡。

During shock, both the inflammatory and clotting cascades may be triggered in areas of hypoperfusion. Hypoxic vascular endothelial cells activate WBCs, which bind to the endothelium and release directly damaging substances (eg, proteolytic enzymes) and inflammatory mediators (eg, cytokines, leukotrienes, tumor necrosis factor [TNF]). Some of these mediators bind to cell surface receptors and activate nuclear factor kappa B (NFκB), which leads to production of additional cytokines and also nitric oxide (NO), a potent vasodilator. Septic shock may be more proinflammatory than other forms because of the actions of bacterial toxins, especially endotoxin.

休克期间，可在组织灌注不足部位引发炎症性和凝血性连锁反应。低氧血管上皮细胞激活WEC，粘附在内皮上，直接释放出破坏性物质（如蛋白水解酶)和炎症介质（如细胞活素、白三烯、肿瘤坏死因子[TNF])。有些介质与细胞表面受体结合，活化核因子卡巴B(NFkB)，造成细胞活素和氧化亚氮（NO)生产增多。NO有强烈的血管扩张效果。由于细菌毒素的作用，尤其是内毒素，败血症性休克的促炎症性反应强于其他休克。

Vasodilation of capacitance vessels leads to pooling of blood and hypotension because of “relative” hypovolemia (ie, too much volume to be filled by the existing amount of blood). Localized vasodilation may shunt blood past the capillary exchange beds, causing focal hypoperfusion despite normal cardiac output and BP. Additionally, excess NO is converted to peroxynitrite, a free radical that damages mitochondria and decreases ATP production.医学全在线www.med126.com

容量血管扩张导致血液瘀积和因血容量“相对”减少（即现有血量充盈过度)而形成的低血压，局部血管扩张使血液从毛细管交换床分流，造成局部血流灌注不足，但心排量和血压均正常。此外，过多的NO被转化成可破坏线粒体、降低APT生产的游离基――过亚硝酸盐。

Blood flow to microvessels including capillaries is reduced even though large-vessel blood flow is preserved in settings of septic shock. Mechanical microvascular obstruction may, at least in part, account for such limiting of substrate delivery. Leukocytes and platelets adhere to the endothelium, and the clotting system is activated with fibrin deposition.

败血症性休克发作时，即使大血管血流未受影响，但微血管包括毛细管的血流却减少了。微血管的机械性阻塞，至少可以部分说明酶解物输送的受限原因。粒细胞和血小板粘附于内皮，凝血系统得以激活，纤维素沉积。

Multiple mediators, along with endothelial cell dysfunction, markedly increase microvascular permeability, allowing fluid and sometimes plasma proteins to escape into the interstitial space. In the GI tract, increased permeability possibly allows translocation of the enteric bacteria from the lumen to the blood stream, potentially leading to sepsis or metastatic infection.

多种介质，再加上内皮细胞功能障碍，明显增加了微血管的渗透性，使液体及血浆蛋白溢入细胞间隙。胃肠道渗透性的增加致使肠道细菌易位，由腔体进入血流，并可能导致败血症或代谢性感染。

Neutrophil apoptosis may be inhibited, enhancing the release of inflammatory mediators. In other cells, apoptosis may be augmented, increasing cell death and thus worsening organ function.

嗜中性粒细胞的吞噬作用被抑制，炎症介质释放得到加强。也增强了其他细胞的吞噬作用，细胞死亡增多，从使器官功能恶化。

BP is not always low in the early stages of shock (although hypotension eventually occurs if shock is not reversed). Similarly, not all patients with “low” BP have shock. The degree and consequences of hypotension vary with the adequacy of physiologic compensation and the patient's underlying diseases. Thus, a modest degree of hypotension that is well tolerated by a young, relatively healthy person might result in severe cerebral, cardiac, or renal dysfunction in a patient with significant arteriosclerosis.

休克初期，血压并不总是很低的（尽管休克若不被逆转，最终会发生低血压)。同样，并不是所有的“低”血压病人都会休克。低血压程度及其后果与生理代偿是否充足及病人潜在疾病有关。因此，相对健康的年轻人可以忍受的轻度低血压若发生在严重动脉硬化者向上，就可能导致严重的脑、心、或肾功能障碍。

Compensation: Initially, when O2 delivery (DO2) is decreased, tissues compensate by extracting a greater percentage of delivered O2. Current guidelines provide for interventions that will maintain mixed-venous O2 saturation above 30%. Additionally, low arterial pressure triggers an adrenergic response with sympathetic-mediated vasoconstriction and often increased heart rate. Initially, vasoconstriction is selective, shunting blood to the heart and brain. Circulating β-adrenergic amines (epinephrine, norepinephrine) also increase cardiac contractility and trigger release of corticosteroids from the adrenal gland, renin from the kidney, and glucose from the liver. Increased glucose may overwhelm ailing mitochondria, causing further lactate production.

代偿：一开始，当输氧（DO2)减少，组织通过增加氧气提取量得到代偿。现有指南提供了一些措施，它可以使混合静脉氧气饱和度保持在30%以上。而且，低动脉压触发肾上腺素能反应，导致交感神经介导性血管收缩，常会使心率加快。开始时，血管收缩是选择性的，血液被分流到心脏和大脑。循环系统中的β肾上腺素能胺（肾上腺素、去甲肾上腺素)也会增加心肌收缩性，触发肾上腺释放皮质激素，肾脏释放肾素，肝脏释放葡萄糖。葡糖增加可压制虚弱的线粒体，导致乳酸盐的进一步分泌。

Reperfusion: Reperfusion of ischemic cells can cause further injury. As substrate is reintroduced, neutrophil activity may heighten, increasing production of damaging superoxide and hydroxyl radicals. After blood flow is restored, inflammatory mediators may be circulated to other organs.

再灌注：缺血细胞再灌注可造成进一步伤害。再次导入酶解物，嗜中性细胞活动增强，增加破坏性超氧游离基和羟基的生产。血流恢复后，炎症介质可能被循环到其他器官部位。

Multiple organ dysfunction syndrome (MODS): The combination of direct and reperfusion injury may cause MODS—the progressive dysfunction of 2 or more organs consequent to life-threatening illness or injury. MODS can follow any type of shock but is most common when infection is involved; organ failure is one of the defining features of septic shock. MODS also occurs in > 10% of patients with severe traumatic injury and is the primary cause of death in those surviving > 24 h.

多器官功能障碍综合征（MODS)：直接损伤与再灌注损伤结合在一起就可能造成MODS――某个致命性疾病或损伤引起两个或多个器官的进行性功能障碍。任何一种休克后都可发生MODS，但以感染型最常见，器官衰竭是败血症性休克的典型特征之一。10%以上的严重外伤病人也会得MODS，它也是存活＞24小时病人死亡的主要原因。

Any organ system can be affected, but the most frequent target organ is the lung, in which increased membrane permeability leads to flooding of alveoli due to capillary leaks. Progressive hypoxia may be increasingly resistant to supplemental O2 therapy. This condition is termed acute lung injury or, if severe, acute respiratory distress syndrome (ARDS).

可累及任何器官系统，最常见的靶器官有肺，肺膜渗透性增加导致毛细管渗漏，造成肺泡溢水。渐进性缺氧可逐步增强对补氧疗法的阻力，这种情况被称为急性肺损伤，严重时则为急性呼吸窘迫综合征（ARDS)

The kidneys are injured when renal perfusion is critically reduced, leading to acute tubular necrosis and renal insufficiency manifested by oliguria and progressive rise in serum creatinine.

肾灌注严重减少则伤肾，导致急性肾小管坏死和肾机能不全，表现为少尿和血清肌酸酐的不断上升。

In the heart, reduced coronary perfusion and mediators (including TNF and IL-1) may depress contractility, worsen myocardial compliance, and down-regulate β-receptors. These factors decrease cardiac output, further worsening both myocardial and systemic perfusion and causing a vicious circle often culminating in death.

若涉及心脏，冠状动脉灌注减少和介质减少（包括TNF和IL－1)可抑制血管收缩性，心肌顺应性变差，β受体功能下降。这些因素又会减少心排量，进一步恶化心肌和系统灌注，造成恶性循环，最终导致死亡。

The GI tract can develop ileus and submucosal hemorrhage. Liver hypoperfusion can produce focal or extensive hepatocellular necrosis, transaminase elevation, and decreased production of clotting factors.

胃肠道会发展成肠梗阻和粘膜下出血，肝脏灌注不足可产生局部性或广泛性肝细胞坏死、转氨酶升高及凝血因子产量减少。