Article(id=1207751282580885980, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1207751280789921836, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.07.0723, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1631462400000, receivedDateStr=2021-09-13, revisedDate=null, revisedDateStr=null, acceptedDate=1636560000000, acceptedDateStr=2021-11-11, onlineDate=1765879944700, onlineDateStr=2025-12-16, pubDate=1658937600000, pubDateStr=2022-07-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765879944700, onlineIssueDateStr=2025-12-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765879944700, creator=13701087609, updateTime=1765879944700, updator=13701087609, issue=Issue{id=1207751280789921836, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='7', pageStart='639', pageEnd='744', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1765879944274, creator=13701087609, updateTime=1765879944274, updator=13701087609, preIssue=null, nextIssue=null, ext=null, issueFiles=null}, startPage=723, endPage=730, ext={EN=ArticleExt(id=1207751283767874021, articleId=1207751282580885980, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Pathogenesis and clinical features of pleural effusion related to pulmonary hypertension, columnId=1190243275882729994, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Review, runingTitle=null, highlight=null, articleAbstract=

Pulmonary hypertension is a clinical syndrome with progressive abnormal increase of pulmonary artery pressure resulting from multiple factors, which eventually leads to patient death by right heart failure. Patients with pulmonary hypertension are often accompanied by pleural effusion clinically and the pleural effusion produced by patients with different types of pulmonary hypertension has its own characteristics. At present, it is widely acknowledged that the occurrence of pleural effusion is closely related to left heart failure, while the relationship between right heart failure and pleural effusion remains controversial. Pulmonary hypertension is an ideal model to study the effects of isolated right heart failure on the development of pleural effusion. This article summarizes the research results of domestic and foreign scholars on pleural effusion related to various types of pulmonary hypertension in recent years, concludes the clinical characteristics, diagnosis and treatment of pleural effusion caused by pulmonary hypertension, describes the hemodynamics, pathophysiology and other mechanisms of pleural effusion and explores the association between the development of pleural effusion and right heart failure. Hoping to be helpful for the diagnosis and treatment of pulmonary hypertension and the study of the relationship between right heart failure and pleural effusion.

, correspAuthors=Ran Wang, authorNote=null, correspAuthorsNote=
*E-mail:
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肺动脉高压是多种原因引起的肺动脉压进行性异常升高的临床综合征,最终可导致患者右心衰竭而死亡。临床上,肺动脉高压常伴发胸腔积液,且不同类型的肺动脉高压患者产生的胸腔积液有其各自的特点。目前被学界广泛认同的是胸腔积液的发生与左心衰竭密切相关,而胸腔积液与右心衰竭的关系一直存在争议。肺动脉高压是研究孤立性右心衰竭影响胸腔积液发展的理想模型。本文总结近年来国内外学者对各类型肺动脉高压相关胸腔积液的研究成果,归纳由肺动脉高压所致胸腔积液的临床特征及其相应的诊断与治疗措施,并对胸腔积液产生的血流动力学、病理生理学等机制进行阐述,探讨胸腔积液的发展与右心衰竭之间的联系,以期为肺动脉高压的诊疗以及研究右心衰竭与胸腔积液的关系提供帮助。

, correspAuthors=王苒, authorNote=null, correspAuthorsNote=
王苒,E-mail:
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王恩泽,硕士研究生,主要从事肺动脉高压方面的研究

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王恩泽,硕士研究生,主要从事肺动脉高压方面的研究

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王恩泽,硕士研究生,主要从事肺动脉高压方面的研究

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肺动脉高压相关胸腔积液的临床特点及机制研究进展
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王恩泽 1 , 孙鹏 1 , 周思静 2 , 王苒 1, *
解放军医学杂志 | 综述 2022,47(7): 723-730
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解放军医学杂志 | 综述 2022, 47(7): 723-730
肺动脉高压相关胸腔积液的临床特点及机制研究进展
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王恩泽1, 孙鹏1, 周思静2, 王苒1, *
作者信息
  • 1安徽医科大学第一附属医院呼吸与危重症医学科,安徽合肥 230022
  • 2安徽医科大学合肥第三临床学院职业病科,安徽合肥 230001
  • 王恩泽,硕士研究生,主要从事肺动脉高压方面的研究

通讯作者:

王苒,E-mail:
Pathogenesis and clinical features of pleural effusion related to pulmonary hypertension
En-Ze Wang1, Peng Sun1, Si-Jing Zhou2, Ran Wang1, *
Affiliations
  • 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
  • 2Department of Occupational Medicine, Hefei Third Clinical College of Anhui Medical University, Hefei, Anhui 230001, China
出版时间: 2022-07-28 doi: 10.11855/j.issn.0577-7402.2022.07.0723
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肺动脉高压是多种原因引起的肺动脉压进行性异常升高的临床综合征,最终可导致患者右心衰竭而死亡。临床上,肺动脉高压常伴发胸腔积液,且不同类型的肺动脉高压患者产生的胸腔积液有其各自的特点。目前被学界广泛认同的是胸腔积液的发生与左心衰竭密切相关,而胸腔积液与右心衰竭的关系一直存在争议。肺动脉高压是研究孤立性右心衰竭影响胸腔积液发展的理想模型。本文总结近年来国内外学者对各类型肺动脉高压相关胸腔积液的研究成果,归纳由肺动脉高压所致胸腔积液的临床特征及其相应的诊断与治疗措施,并对胸腔积液产生的血流动力学、病理生理学等机制进行阐述,探讨胸腔积液的发展与右心衰竭之间的联系,以期为肺动脉高压的诊疗以及研究右心衰竭与胸腔积液的关系提供帮助。

肺动脉高压  /  胸腔积液  /  右心衰竭  /  机制  /  进展

Pulmonary hypertension is a clinical syndrome with progressive abnormal increase of pulmonary artery pressure resulting from multiple factors, which eventually leads to patient death by right heart failure. Patients with pulmonary hypertension are often accompanied by pleural effusion clinically and the pleural effusion produced by patients with different types of pulmonary hypertension has its own characteristics. At present, it is widely acknowledged that the occurrence of pleural effusion is closely related to left heart failure, while the relationship between right heart failure and pleural effusion remains controversial. Pulmonary hypertension is an ideal model to study the effects of isolated right heart failure on the development of pleural effusion. This article summarizes the research results of domestic and foreign scholars on pleural effusion related to various types of pulmonary hypertension in recent years, concludes the clinical characteristics, diagnosis and treatment of pleural effusion caused by pulmonary hypertension, describes the hemodynamics, pathophysiology and other mechanisms of pleural effusion and explores the association between the development of pleural effusion and right heart failure. Hoping to be helpful for the diagnosis and treatment of pulmonary hypertension and the study of the relationship between right heart failure and pleural effusion.

pulmonary hypertension  /  pleural effusion  /  right heart failure  /  mechanism  /  progress
王恩泽, 孙鹏, 周思静, 王苒. 肺动脉高压相关胸腔积液的临床特点及机制研究进展. 解放军医学杂志, 2022 , 47 (7) : 723 -730 . DOI: 10.11855/j.issn.0577-7402.2022.07.0723
En-Ze Wang, Peng Sun, Si-Jing Zhou, Ran Wang. Pathogenesis and clinical features of pleural effusion related to pulmonary hypertension[J]. Medical Journal of Chinese People’s Liberation Army, 2022 , 47 (7) : 723 -730 . DOI: 10.11855/j.issn.0577-7402.2022.07.0723
肺动脉高压(pulmonary hypertension,PH)是指由多种异源性疾病(病因)及不同发病机制所致肺血管结构或功能改变,引起肺血管阻力(pulmonary vascular resistance,PVR)及肺动脉压力升高的临床及病理生理综合征。PH易发展成右心衰竭甚至导致死亡[1]。近年来,PH对所有年龄段的人群尤其是老年人的影响显著增加。据估计,PH的全球患病率约为1%,而在65岁以上人群中可高达10%,且约80%的患者生活在发展中国家[2]。胸腔积液是PH较常见的临床表现之一,了解胸腔积液产生的机制及表现对PH的诊断和治疗有较大帮助。本文主要对PH合并胸腔积液的发生机制及临床特点进行综述。
正常成年人静息状态下的肺动脉平均压(mean pulmonary artery pressure,mPAP)为(14.0±3.3) mmHg(1 mmHg=0.133 kPa),其上限不超过20 mmHg[3]。PH是指在海平面、静息状态下,经右心导管检查测定的mPAP≥25 mmHg[4]。临床上将PH分为五大类:(1)动脉性PH;(2)左心疾病所致PH;(3)肺部疾病和(或)低氧所致PH;(4)慢性血栓栓塞性PH和(或)其他肺动脉阻塞性病变所致PH;(5)未明和(或)多因素所致PH[1]
胸膜包括脏层胸膜及壁层胸膜,两层胸膜之间的间隙称为胸膜腔。正常情况下,胸膜腔内存在少量的液体,起到润滑作用,其分泌及吸收处于一种动态平衡的状态,当这种动态平衡被打破时,会产生过多的胸腔积液[5]。胸腔积液的发生机制主要有胸膜毛细血管静水压增高、通透性增加、胶体渗透压降低及壁层胸膜淋巴回流障碍。疾病可以导致胸腔积液的发生,最常见的原因是充血性心力衰竭、肺癌、肺炎及肺栓塞。
PH患者产生胸腔积液的原因尚不清楚。由于不同类型的PH发病机制不尽相同,并不是所有伴发胸腔积液的PH患者产生胸腔积液的原因都与PH有关。国外报道1例患者因肺炎引起右侧大量胸腔积液,压迫肺组织产生PH,行肺炎治疗及胸腔积液穿刺引流后,PH随之消失[6]
IPAH与FPAH的病理学改变基本类似,主要是由于肺循环中的小动脉及细小动脉病变,使肺动脉压力及肺血管阻力不断增加,右心压力升高,最终导致进行性右心衰竭。虽然胸腔积液常见于左心衰竭患者,但研究表明,在无明显左心疾病的情况下,孤立性右心衰竭也会导致胸腔积液的发生[7]。动物实验显示其发生机制主要有两种:其一,右心衰竭时,平均右心房压(mean right atrial pressure,mRAP)升高导致上腔静脉压升高,可机械性阻碍壁层胸膜的淋巴引流;其二,右心衰竭引起全身静脉压力增加,支气管及胸壁静脉静水压也会升高,胸膜毛细血管静水压增高使液体进入胸膜腔,同时,升高的mRAP还可直接导致心包积液的发生[7]。但是这两种机制尚未在人体试验中得到证实。Ajakumar Menon等[8]在临床病例研究中提出了一种新的机制——右心衰竭导致了充血性肝病的发生,所生成的腹水通过横膈膜移动至胸膜腔,最终形成胸腔积液,这个过程类似于肝硬化患者肝性胸腔积液的形成。此外,Kataoka[9]从分子生物学角度对心力衰竭引起胸腔积液的机制提出了一种新的理论——氯理论。在正常生理状况下,人体电解质的分布明显不同,体内的每个腔室中氯离子浓度均存在相当大的差异,由于道南效应或带负电荷的糖胺聚糖网络,肺间质的氯离子浓度远高于血清,同时由于胸膜液的正常转运,胸膜腔内的氯离子浓度较低,因此肺间质较为潮湿,而胸膜腔较为润滑,液体较少。心力衰竭时胸膜液的转运不畅,胸膜腔内的氯离子浓度明显升高,这预示氯可能是调节体液或水在不同体腔内分布的关键电解质。然而,由右心衰竭引起胸腔积液的病例在临床上毕竟少见,单纯右心衰竭与随后产生的胸腔积液之间的相关性仍存在争议[10]
PAH相关胸腔积液的量通常较少,传统的体格检查时容易被忽略,因此需要借助其他非侵入性检测手段进行诊断,临床上常使用胸部CT支持胸腔积液的确诊。CT肺动脉成像(CT pulmonary angiography,CTPA)可见肺叶内不规则斑片状影、“马赛克”征、小叶中心性磨玻璃样结节影、纵隔淋巴结肿大及支气管动脉扩张[11]。然而在PAH的诊疗过程中,连续使用胸部CT增加了患者长期暴露于辐射的风险,此时,超声检查成为了一种有效、快速、低成本、无创的胸腔积液检测手段,有助于PAH的纵向风险评估[12]。Tang等[13]调查了147例IPAH患者(128例)及FPAH患者(19例),伴发胸腔积液者31例(21.1%,31/147),其中19例与右心衰竭有关。与无胸腔积液的患者相比,有胸腔积液的右心衰竭患者mRAP显著升高,且常伴发腹水及心包积液。右心衰竭引起的胸腔积液大多数为少量,发生在右侧或双侧,接受胸腔穿刺术的5例患者中4例为渗出液。Chandel等[12]统计了IPAH及FPAH患者共52例,其中13例(25%)出现胸腔积液,积液通常较少,位于双侧。另外,他们还发现在治疗期间胸腔积液的发展与患者的总体存活率降低有关,这种影响独立于其他重要的临床风险因素,且伴发胸腔积液的PH患者中右心房高压更为常见。
由于PAH伴发胸腔积液的机制与右心衰竭密切相关,且积液量通常较少,因此临床上主要针对病因进行干预,降低右心室后负荷是治疗的关键,使用前列环素类似物、内皮素受体拮抗剂、磷酸二酯酶5抑制剂等针对PAH的靶向治疗药物对右心衰竭同样有效,当病因得到控制后,临床症状将明显缓解,胸腔积液也会减少或消失[14]
PVOD是PAH分类中的另一种罕见疾病,预后比IPAH更差,且死亡通常发生在确诊后的1年内[15]。PVOD特征性的组织病理学表现为肺毛细血管后的小静脉重塑、阻塞,而大静脉相对正常[16]。这导致了PVOD具有独特的血流动力学特征:肺动脉压升高而肺毛细血管楔压正常或降低[17]。血栓、药物或者化疗等病因引起肺内小静脉内膜纤维化,可使静脉腔变窄、静脉压力增加、毛细静脉阻塞,毛细血管网继发扩张,从而引起以下改变:一方面,胸膜毛细血管内静水压升高超过血液渗透压,导致液体渗透到胸膜腔;另一方面,液体渗出到肺间质,导致胸膜下及小叶间隔淋巴管充血扩张,淋巴回流障碍,产生胸腔积液。
PVOD患者常表现为进行性呼吸困难、乏力、运动耐量降低,杵状指在IPAH中并不常见,但在PVOD中多发;其临床体征与其他PAH相似,包括右心室隆起、三尖瓣反流引起的收缩期杂音以及明显的右心衰竭征象,随着PH的恶化,将出现肺充血和(或)胸腔积液[18-19]。有研究回顾性分析国内外86例PVOD患者的临床资料,发现在77例使用肺部CT检查的患者中,17例(22.1%)出现了胸腔积液[20]。肺动脉扩张和突出的小叶间隔线(Kerley B)是PVOD患者胸部X线表现的主要特征,而肺静脉直径与左心房及左心室的轮廓显示正常,有时会观察到胸腔积液[17]。高分辨率CT是PVOD最常用的检查手段,可见肺部结节状磨玻璃样影,纵隔线增厚,淋巴结肿大,以及液体在气腔内及塌陷肺泡的凹槽处聚集[15]
PH是结缔组织病的常见并发症。在我国,CTD-PAH患者以系统性红斑狼疮为主,约占49%,其他依次为干燥综合征、大动脉炎、混合性结缔组织病、系统性硬化症等[21]
CTD-PAH引起胸腔积液的机制十分复杂,虽然一些积液可能是由于原发病直接侵袭胸膜腔或免疫机制(如抗心磷脂抗体与肺动脉内皮细胞间的相互作用使血管重塑以及抗U1小核糖核蛋白抗体参与的自身免疫过程等)导致毛细血管通透性增加所致,但文献表明这些炎症过程不能解释所有CTD-PAH患者的胸腔积液[22]。通常干燥综合征患者并不常见胸腔积液,然而Luo等[23]发现,约50%的干燥综合征相关肺动脉高压患者会发生胸腔积液。与IPAH相比,CTD-PAH的肺血管也会产生一些相似的原发性病变,如细支气管动脉内膜纤维化,肺动脉内侧肥大[24],不断升高的mRAP及PVR引起右侧充盈压力缓慢升高,导致右心衰竭及胸腔积液的发生。但是,CTD-PAH的发病机制也有其独特之处:Dorfmüller等[25]检查了8例不同类型CTD-PAH患者的肺组织,发现有6例出现肺静脉及小静脉闭塞性病变,且静脉病变的血管数量明显多于动脉病变的血管数量,CTD-PAH的病理学改变与PVOD十分类似。另一项心内膜心肌活检研究表明,16例系统性红斑狼疮患者中有15例(94%)的心肌胶原沉积异常,而不伴左心或右心疾病症状[26],即CTD-PAH患者不仅可能因肺动脉压升高而发生继发性心功能障碍,还可能因心肌纤维化损害而发生原发性心脏受累[27]
CTD-PAH常见临床表现包括雷诺现象、心包积液、胸腔积液、多关节炎及肺间质病变[28]。低一氧化碳弥散量、胸腔积液及伴发糖尿病是CTD-PAH患者死亡的独立预测因子,而抗U1小核糖核蛋白抗体阳性提示预后良好[29]。此外,在血清免疫学指标中,补体C3降低,C反应蛋白、循环免疫复合物(CIC)和(或)红细胞沉降率(ESR)升高可作为早期诊断CTD-PAH的依据[28]。胸腔积液常为渗出液,积液内蛋白质、乳酸脱氢酶、白细胞(以淋巴细胞为主)升高,在系统性红斑狼疮患者中可以检测出抗核抗体阳性,在干燥综合征患者中可检测出类风湿因子、抗Ro抗体、抗La抗体及免疫复合物水平升高[30-32]。Chandel等[12]发现,在PH患者中,与结缔组织病有关的患者胸腔积液发生率与结缔组织病无关者无明显差异(31.1% vs. 24.7%,P=0.45),且积液量少,发生部位常为双侧。Luo等[23]调查了89例不同类型的CTD-PAH患者,其中35例(39.1%)出现胸腔积液。同时,他们还发现与没有伴发胸腔积液的患者相比,伴发胸腔积液的患者mRAP及PVR明显升高,心包积液及腹水的发生率增高,病死率显著上升,心输出量及心脏指数明显降低,但两组mPAP无明显差异,这可能提示单纯的PH并不是胸腔积液产生的原因,胸腔积液是由PH导致的右心衰竭引起的。
PoPH是指与门静脉高压症相关的PAH。最近,来自法国的数据显示,PoPH约占所有PAH患者的15%,且随着筛查规模的扩大,这一比例可能会继续增高[33]。PoPH的病理学改变与IPAH相似,两者均存在内膜增生、中膜肥大、肌动脉外膜纤维化及丛状动脉病变[34]。但二者在血流动力学及患者的生存率方面有较大差异。Krowka等[35]发现,PoPH患者的mPAP及PVR普遍低于IPAH患者,但PoPH患者的生存率明显较低,这可能与治疗方式及肝病的影响有关。
胸腔积液与PoPH发生发展的关系仍有待探索,其产生积液的机制可能有以下几个方面[36]:(1)肝脏合成白蛋白减少,引起低白蛋白血症,降低了血浆胶体渗透压;(2)门静脉压力增高,导致奇静脉及半奇静脉压力同时升高,壁层胸膜毛细血管静水压升高;(3)腹腔积液通过横膈淋巴管及横膈局部缺损进入胸膜腔,产生胸腔积液;(4)PH导致右心房压力升高,全身静脉阻力升高,促进了胸腔积液的发生。
在没有其他潜在心肺源性疾病的肝硬化患者中,只有5%~10%会发展为肝性胸腔积液,表现为渗出性胸腔积液,积液量通常大于500 ml,绝大多数出现在右侧[37]。然而,Luo等[38]发现,33例PoPH患者中有12例(36.4%)出现胸腔积液,其中7例被诊断为右心衰竭,积液量通常较少,位于双侧,且几乎所有伴发胸腔积液的患者均有不同程度的腹水。肝硬化及门脉高压症患者的mRAP通常较低,但伴发胸腔积液者的mRAP及血清脑利钠肽水平明显升高,6 min步行试验的距离更短,提示右心衰竭与胸腔积液的发生密切相关。
PH-LHD是最常见的PH类型,具有独特的血流动力学特点,主要特征是毛细血管后性肺动脉高压,可进一步分为孤立性毛细血管后性肺动脉高压及毛细血管前-后混合性肺动脉高压。在大多数PH-LHD患者中,肺动脉压力的升高往往是被动的,左心室收缩或舒张功能障碍及主动脉和(或)二尖瓣狭窄和(或)关闭不全提高了左室充盈压力,进而提高了左心房压力,左心房压力通过肺静脉传递至肺血管,引起肺血管内膜肥厚及纤维化,导致肺血管阻力升高及PH[39]。而充血性心力衰竭是胸腔积液最常见的原因,由于解剖及功能的关系,充血性心力衰竭患者发生胸腔积液主要与左心衰竭有关,故胸腔积液在PH-LHD患者中多见[40]
大部分胸腔积液通过壁层胸膜淋巴管引流,脏层胸膜上无淋巴孔结构,其淋巴管与间皮细胞间由一层连接组织分隔,故脏层胸膜在胸腔积液的吸收中不起任何作用。然而新的研究发现,肺淋巴管直接起源于脏层胸膜表面的间皮细胞,且脏层胸膜与壁层胸膜一起促进胸膜腔内液体的循环,在胸腔积液的形成中起重要作用[41]。左心衰竭时,增加的肺静脉压力可形成压力梯度,驱使液体从脏层胸膜毛细血管流向胸膜腔,而脏层胸膜淋巴引流作用减弱;同时,PH引起的右心房压力升高导致壁层胸膜毛细血管静水压及滤过率增高,淋巴引流减少。此外,左心室充盈压及肺静脉压力的持续升高将伴随肺循环内的叠加效应,包括一氧化氮利用率降低、内皮素-1增加、利钠肽诱导肺血管舒张效应降低、炎性细胞浸润等,引起内脏充血、胸膜缺血缺氧,使胸膜毛细血管通透性增加,进一步促进液体向胸膜腔渗透[42]。在这几种因素的共同作用下,淋巴引流速度无法跟上胸膜液产生的速度,从而产生胸腔积液。
胸腔积液的位置大多是双侧的,若出现在单侧积液则常见于右侧[43]。对于这一现象,目前有几种理论可以解释:第一种是奇静脉理论,右心扩张对右肺门施加压力,随后奇静脉受压,而奇静脉引流右肺胸膜壁层的一部分,其受压增加了壁层胸膜毛细血管的静水压,并产生胸腔积液。第二种理论认为,右心房及左心房的扩张会撞击肺静脉,右心房的解剖位置及结构使右肺静脉的压迫可能比左肺静脉的压迫更常见。第三种理论提出,由于左心室与肺的解剖关系,心力衰竭患者卧床时倾向于右侧卧位,长此以往,右肺静脉压力往往会高于左肺静脉压力。
心力衰竭引起的胸腔积液通常为漏出液,pH值大于7.4,以淋巴细胞浸润为主。有研究表明,相比于无胸腔积液的PH-LHD患者,伴发胸腔积液者舒张末期左心室容积指数升高、内径增大、射血分数降低,故胸腔积液的发生可能意味着左心室功能的损害,此外,该研究还发现胸腔积液与患者的病死率密切相关[44]
目前,临床上对于心源性胸腔积液的治疗主要是在纠正心力衰竭的基础上给予强心、利尿等药物支持,以及胸腔穿刺抽液等,但是胸腔积液常随着病情的反复而复发,因此控制患者心力衰竭是避免心源性胸腔积液发生的有效手段[45]。一般不推荐在PH-LHD中使用PAH的靶向药物。但对于有明显的毛细血管前肺动脉高压的PH-LHD患者,可以根据临床情况制定特殊的治疗方案[46]。需要注意的是,在心力衰竭的治疗中,使用利尿剂会增加胸膜液中蛋白质、乳酸脱氢酶及脂质的浓度,此时,若根据Light标准易将积液误诊为渗出液[30]。近年来,胸腔积液中N端B型利钠肽前体(N-terminal pro-B-type natriuretic peptide,NT-proBNP)已被提倡用于心力衰竭引起的胸腔积液的诊断。NT-proBNP是心力衰竭的敏感生物标志物,其在血液中的浓度与胸腔积液中的浓度密切相关,即使发现积液为渗出液,NT-proBNP水平升高也可能提示胸腔积液的发生与心力衰竭有关[47]
慢性肺部疾病患者到了疾病晚期常会伴发PH,包括慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)、特发性肺纤维化及结节病等。长期存在的慢性肺部疾病及缺氧等可导致缺氧诱导因子激活,炎性因子及细胞增殖因子聚集,腺苷等缩血管物质升高,内皮细胞向间质细胞转化,引起肺血管广泛病变,包括肺血管收缩重塑,肺小动脉粥样斑块形成,肌性动脉内膜层增生、中外膜层纤维化增厚,非肌性动脉管腔狭窄、张力增加,肺静脉管腔闭塞、管壁增厚,最终形成PH[48]
由于CLD-PH患者本身肺部已存在病变,由PH引起的临床症状(如呼吸困难)及体征(如第二心音肺成分增强、三尖瓣反流所致全收缩期杂音等)很难与原发病区分,此时,若出现胸腔积液往往提示患者可能有肺动脉高压的病变[49]。调查发现,COPD患者伴发胸腔积液的主要原因包括低蛋白血症、肺部感染及右心衰竭,当合并PH时,其胸腔积液发生的频率及程度将明显增快或加重[50]。国内学者使用CTPA检查COPD导致PH的患者80例,其中53例轻、中度患者中有4例(8%)伴有胸腔积液,而37例重症患者中有10例(27%)伴有胸腔积液[51]。这可能是由于PH导致右心室肥大重塑,最终演变为右心衰竭所致。事实上,慢性肺部疾病患者的右心室在亚临床水平的mPAP升高时就已经出现病变。Hilde等[52]的研究表明,即使静息时mPAP略有上升,右心室的肥大及扩张也会适应性地大幅增加,当临床确诊为肺动脉高压(mPAP>25 mmHg)时,表明至少50%的肺血管床已受损,右心功能已经出现严重损害,临床症状可表现为乏力、下肢水肿、气喘、胸腔积液、活动明显受限、晕厥[53]
CLD-PH的治疗主要针对原发性肺部疾病,并不推荐使用常规的血管扩张剂或PAH靶向药物,因为这些药物可能会抑制低氧导致的肺血管收缩,损害气体交换功能[54]。同时,由于CLD-PH患者产生胸腔积液的原因各不相同,当积液量较少时,针对不同的病因采取相应的治疗措施后,积液即可自行吸收;而产生中到大量胸腔积液,造成压迫性肺不张及呼吸衰竭时,需要紧急使用无创呼吸机辅助通气联合胸腔闭式引流,以迅速解除积液对肺组织的压迫,有效改善患者的肺通气状态[55]
CTEPH通常被视为抗凝治疗无效的急性肺栓塞患者罕见的晚期并发症[56]。美国及欧洲的调查结果显示,肺动脉栓塞后肺动脉高压的发生率为0.1%~9.1%[57]。但不能简单地认为CTEPH是急性肺栓塞自然病程的延续。研究发现,CTEPH患者不仅近端动脉有机械性阻塞,其远端肌性肺动脉、肺小动脉及小静脉也会发生血管重塑。一方面,由于长期暴露于高压及剪切应力,肺血流在未闭塞的肺动脉中重新分布,导致血管内皮功能障碍;另一方面,支气管动脉与阻塞后的肺动脉之间形成广泛吻合支,虽然有助于维持梗阻下游缺血组织的灌注,但也会使肺循环暴露于高压的体循环中,引起栓塞远端肺血管重构;最终导致肺血管内膜增厚、血管重塑及纤维化,肺血管阻力增加,从而产生PH[56]
CTEPH的早期症状及体征缺乏特异性,常见症状为劳力性呼吸困难及运动耐量下降,可以通过房性奔马律、三尖瓣反流性杂音等判断PH的存在,若出现颈静脉扩张、周围水肿、胸腹腔积液,则提示右心功能已严重受损[58]。CTPA是CTEPH常用的检查技术,既能观察到肺动脉分支减少、血管壁不规则、各级肺动脉管腔充盈缺损等直接征象,也可显示出肺窗马赛克征(局限性肺纹理分布不均匀或稀疏)、右心室增大、胸腔积液等间接征象[59]。国内有学者使用CTPA检查了30例CTEPH患者,其中4例(13.3%)并发胸腔积液,且积液量少[60];而另一项研究检查了80例CTEPH患者,其中8例(10%)产生胸腔积液[61],与上述结果基本一致,故推测CTEPH患者胸腔积液的发生率约为10%。
肺动脉血栓内膜剥脱术是无禁忌证的CTEPH患者首选的治疗方法,对于不能进行手术的患者,可采取肺动脉球囊扩张成形术这一新兴的介入治疗方式,此外,抗凝剂、利尿剂的支持治疗以及PAH靶向药物治疗也被广泛使用[62]。CTEPH患者的病情得到控制后,其血流动力学状况会明显改善,胸腔积液等临床症状也会得到相应缓解。
PH患者常伴发胸腔积液,由于不同类型PH的发病机制各异,产生胸腔积液的机制及特点往往各不相同。胸腔积液的发生与右心衰竭密切相关,单独的右心房压力升高可能会导致胸腔积液的产生,但仍存在争议。心力衰竭引起胸腔积液的机制十分复杂,现有的研究大多关注于血流动力学方面,主要为胸膜毛细血管静水压及滤过率增高,淋巴引流减少所致。而PH与右心衰竭所致胸腔积液发生发展关系的病理生理学机制及分子机制仍需进一步探索。
总的来说,相较于未伴发胸腔积液的PH患者,伴发胸腔积液者常合并腹水及心包积液,且mRAP与PVR明显升高,病死率显著上升,这强化了诊断肺动脉高压后对患者进行胸腔积液及右心衰竭筛查的必要性。临床医师可通过辨识胸腔积液的性质及性状辅助判断肺动脉高压的类型。当发现肺动脉高压患者伴发胸腔积液时,临床医师应意识到其临床恶化的风险,需要尽早进行干预。
  • 国家自然科学基金(81970051)
  • 合肥市卫生健康应用医学研究项目(hwk2021zd008)
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2022年第47卷第7期
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doi: 10.11855/j.issn.0577-7402.2022.07.0723
  • 接收时间:2021-09-13
  • 首发时间:2025-12-16
  • 出版时间:2022-07-28
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  • 收稿日期:2021-09-13
  • 录用日期:2021-11-11
基金
National Natural Science Foundation of China(81970051)
国家自然科学基金(81970051)
Applied Medical Research Project of Hefei Health Commission(hwk2021zd008)
合肥市卫生健康应用医学研究项目(hwk2021zd008)
作者信息
    1安徽医科大学第一附属医院呼吸与危重症医学科,安徽合肥 230022
    2安徽医科大学合肥第三临床学院职业病科,安徽合肥 230001

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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