SARS肺间质血管病变的病理观察

目的 观察分析严重急性呼吸综合征(severe acute respiratory syndrome，SARS)肺间质血管病变的病理形态学特征。方法 对3例行尸体解剖的SARS病例肺组织进行常规HE染色、组织化学染色和免疫组织化学染色，并探讨其病理形态学特征。结果 死亡的SARS病人肺部病变除弥漫性的肺部损伤(肺泡腔内可见细颗粒样或泡状水肿液、脱落的肺泡上皮细胞；肺泡间隔内表面可见透明膜覆盖，有的区域肺泡腔内出现机化性改变等)外，肺间质内的毛细血管簇状增生及血管壁出现明显的损伤性改变。结论 SARS的肺部血管病变是一个特征性病理形态学变化，可能与SARS病毒的蛋白导致的剧烈免疫反应有关。     

SARS肺的病理鉴别诊断

目的 分析严重急性呼吸综合征(severe acute respiratory syndrome，SARS)肺部病变的临床病理形态学特征及与其他肺部炎性疾病的鉴别诊断。方法 对3例行尸体解剖的SARS病例的肺组织进行组织形态学、免疫组织化学和电镜下超微结构的观察，对其临床表现、病理形态学特征及主要鉴别诊断进行探讨，并与病理资料完整的16例病毒性肺炎、13例间质性肺炎的肺部病变进行鉴别诊断。结果 死亡的SARS病人肺部病变主要表现为弥漫性的肺部损伤，但是各处病变轻重不一。肺泡腔内可见细颗粒样或泡状水肿液，其中可见脱落的肺泡上皮细胞。肺泡间隔表面可见透明膜覆盖，有的区域肺泡腔内出现机化性改变，肺泡腔和肺问质内可见大量的巨噬细胞浸润。同时，肺间质内的小动脉壁出现明显的损伤性改变。结论 SARS的肺部病理形态学特征可与其他肺部炎症性疾病鉴别。     

危重型手足口病3例尸检临床病理分析

目的 探讨危重型手足口病死亡患者各脏器的病理改变特点,并分析其死亡原因.方法 对3例危重型手足口病死亡病例作尸体解剖,镜检各脏器的病理改变,并分析主要脏器的病理改变与临床症状和体征的关系,探讨导致患者死亡的病变基础.结果 危重型手足口病起病急,进展快,病程短,临床表现为发热、手足口疱疹、神经系统症状和突发性呼吸窘迫.病变累及的关键脏器是延髓、脑干和肺脏.延髓和脑干的病理改变是神经元变性坏死、脑软化灶形成、出现血管周围炎细胞浸润和噬神经细胞现象,呈病毒性脑炎改变.肺的病理改变是肺泡间隔毛细血管扩张充血,并大量单核细胞浸润;肺泡腔内大量单核细胞渗出,填满肺泡腔,致局部肺实变;局部肺透明膜形成;局部肺组织出血性梗死;局部肺泡腔内有大量水肿液;呈严重病毒性肺炎和急性肺水肿改变.此外,淋巴结和脾脏的结构破坏,淋巴小结萎缩,淋巴滤泡的生发中心细胞核碎裂,呈生发中心烧毁现象.结论 危重型手足口病病毒侵犯患者肺、延髓、脑干和免疫器官,导致病毒性肺炎、病毒性脑炎和免疫器官损害.其中,延髓和脑干呼吸中枢的损害与肺部本身的严重病变协同作用引起的呼吸衰竭,是病人死亡的主要原因.     

严重急性呼吸综合征的病理改变

目的 探讨严重急性呼吸综合征(SARS)的主要脏器的病理改变特点及发病机制。方法 详细检查7例SARS患者的肺、心、脾、肝、肾等标本的大体特点及用常规方法研究光镜下SARS累及各脏器的病变特点。结果 7例中,病程短(5d)的患者肺部表现以肺水肿为主。与通常的肺水肿相比,其水肿液中纤维素成分多,可见透明膜形成。5例病程超过3周的患者出现肺泡内机化及肺泡间隔内的纤维母细胞增生,造成肺泡的实变和闭塞。6例可见到肺小血管内的微血栓。7例均可见到散在的肺出血、小叶性肺炎、肺泡上皮脱落、增生等病变。2例可见真菌感染,1例累及左全肺及右肺部分区域,还累及心脏和肾脏,1例出现在肺门淋巴结。肺门淋巴结多表现为充血、出血及淋巴组织减少,窦组织细胞增多。5例心脏有明显的肥大,2例有心内血栓,1例有灶性心肌炎,1例为真菌性心肌炎。7例中有1例为结节性肝硬化,另1例出现广泛的肝细胞带状坏死。脾内均有白髓变小或消失,红髓明显充血和出血。1例腹腔内淋巴结肿大,但其内淋巴滤泡亦减少,有明显充血和出血及窦组织细胞增生。结论 SARS的主要病变为肺,以各期弥漫性肺泡损伤的病变为基本特征。发病机制可能为病毒造成肺泡上皮及毛细血管的严重损伤导致肺水肿及肺泡及细支气管的纤维素性渗出性炎,出现透明膜,继而出现肺泡内机化及肺泡间隔的纤维化,导致肺泡萎陷,最终形成纤维化、实变。脾和淋巴结的淋巴组织减少是此病影响免疫系统的形态学表现。     

从SARS患者肺部病变的病理特点探讨SARS的损伤机理

目的 根据严重急性呼吸道综合征(severe acute respiratory syndrome，SARS)患者肺部病变的病理特点探讨SARS的损伤机理。方法 在3500例尸体解剖材料中，找出死亡时有肺部炎症的共842例。对其中病毒性肺炎16例、Good-Pasture综合征2例、自身免疫疾病2例、SARS1例，共21例进行肺部病变的病理组织学的比较观察。结果 病毒性肺炎的肺部病变主要的病理变化表现为间质性肺炎；自身免疫性疾病病人的肺部病理变化有肺泡表面透明膜形成，肺泡腔内脱落的细胞团，肺泡腔内机化等；SARS病人尸体解剖的肺部病变主要为肺泡腔内细颗粒样或泡状肺水肿，脱屑性肺炎以及机化性肺炎的表现。同时，肺间质内的小动脉出现明显的结构改变，形态学上与自身免疫性疾病的肺损伤相似。结论 机体的变态反应可能是SARS的损伤机理之一。     

严重急性呼吸综合征临床病理分析

目的 探讨严重急性呼吸综合征(Severe acute respitatory syndrome，SARS)的病理形态学特点。方法 3例SARS标本为患者支气管镜穿刺活检和切取的肺组织，经HE染色，光镜观察，并用免疫组化S-P法检测SARS患者肺组织CK、CD34、Ⅳ型胶原、CD68、Mac387的表达。结果 SARS患者肺组织病理形态表现为肺泡上皮广泛破坏，Ⅱ型上皮细胞增生。肺泡壁毛细血管内皮细胞肿胀。大部分肺泡腔及肺泡管内透明膜形成。间质有较多的炎细胞浸润，成纤维细胞增生。结论 SARS是一种伴透明膜形成的急性非特异性间质性肺炎。     

SARS尸检组织的病理变化和超微结构观察

目的 研究严重急性呼吸综合征(SARS)尸检组织的临床病理和超微结构特征。方法 对1例SARS死亡患者做即刻肺穿刺和12h后尸检,进行病理形态和超微结构的观察;用Macchiavello法做病毒包涵体染色;并对淋巴结、脾脏、结肠、小肠及骨髓组织行CD20、CD45RO(UCHL-1)、CD4、CD8、CD68、CD34免疫组织化学标记。结果 SARS肺的主要病变为急性弥漫性全小叶性间质性炎,可见肺泡腔内透明膜形成和增生及脱落的肺泡上皮,偶见胞质内病毒包涵体样结构,病毒包涵体染色阳性,肺内小血管增生、扩张,呈血管炎性改变。淋巴结、脾脏结构破坏,淋巴滤泡消失,脾小体萎缩,淋巴细胞明显减少,组织细胞增生;结肠、小肠孤立和集合淋巴结淋巴滤泡消失;骨髓增生减低,巨核细胞增多。免疫组织化学染色：淋巴结、脾脏B细胞CD20弥漫散在阳性,CD45RO(UCHL-1)散在阳性,CD4辅助T细胞显著减少,CD8毒性T细胞稍增加,CD4／CD8比例明显小于0．5。电镜观察：肺泡内的单核巨噬细胞、肺泡上皮胞质内可见病毒样颗粒,大小80～160nm,有光晕或花环状包膜。结论 肺部明显急性弥漫性全小叶性间质性炎,肺泡腔透明膜形成,肺外淋巴造血系统明显损害,尤T细胞明显;内脏器官出血、坏死和血管炎改变等为急性SARS的形态特征;肺内所见病毒样颗粒可能为新型冠状病毒,推测其为此次SARS流行的主要病原体。     

大鼠液压冲击脑损伤急性肺水肿的病理观察

我们研究于脑损伤后大鼠急性肺水肿的肺微循环改变.用显微观察方法(H.E、透射电子显微镜)观察液压冲击脑损伤大鼠出现急性肺水肿的肺微循环改变情况.其结果为光镜下肺泡腔有富含蛋白的液体,并有局灶性的出血区,可见透明膜、白细胞及其他组织碎片.电镜下见Ⅰ型肺泡上皮明显肿胀,线粒体肿胀、嵴消失,内质网扩张,Ⅱ型细胞的板层体消失;基底膜肿胀;在出血区多数毛细血管肺泡呼吸膜严重破坏,有严重的不可逆性细胞损伤;肺毛细血管壁松散、断裂、出血及大量血浆蛋白颗粒渗出.结论为液压冲击脑损伤大鼠神经原性肺水肿与脑损伤后肺微循环病理改变有密切关系.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

人感染高致病性禽流感病毒H5N1的病理学观察

目的 观察人感染高致病性禽流感病毒H5N1后各主要脏器的病理改变.方法 按传染病尸体解剖要求对2例死亡病例系统解剖,并获得心、肝、脾、肺和肾等主要脏器,对1例重症患者行肺大泡切除术,组织常规HE和免疫组织化学染色,光学显微镜下观察.结果 2例肺组织主要呈弥漫性肺泡损伤改变.早期呈渗出性改变,肺泡上皮坏死脱落,肺泡腔内见大量均匀粉染渗出液伴广泛透明膜形成.中晚期主要呈增生性和纤维化性改变,肺泡上皮和支气管上皮增生,肺泡腔内渗出物和肺间质纤维化.1例在慢性支气管扩张症基础上伴弥漫性肺泡损伤和肺间质纤维化.免疫器官改变:全身淋巴组织萎缩伴活跃的噬血现象.其他脏器病变:1例心脏有间质性心肌炎;1例肾脏有急性肾小管坏死;1例有脑水肿伴脑实质内神经细胞嗜酸性变,轴突肿胀,粗细不均.脑室旁见灶状坏死.1例孕妇胎盘内多灶状滋养叶细胞坏死伴营养不良性钙化,有急性坏死性蜕膜炎.胚胎肺脏有肺水肿和肺炎改变.结论 人感染高致病性禽流感病毒H5N1后首先出现呼吸系统症状,广泛弥漫性肺泡损伤致低氧血症是病理学基础,患者最终因多器官功能衰竭致呼吸、循环衰竭死亡.     

严重急性呼吸综合征的临床病理及发病机制研究

目的　研究严重急性呼吸综合征 (SARS)的病理学特征及临床治疗的病理学基础 ,并探讨SARS的发病机制。方法　采用光、电镜观察 ,对 2例SARS系统尸检病例和 4例多器官多部位穿刺标本进行病理学观察 ;应用免疫组化标记并分析肺组织及免疫器官中各淋巴亚群的分布及数量变化 ;核酸原位杂交结合电镜观察 ,作SARS冠状病毒 (SARS CoV)在体病原学定位及定量检测。结果　 6例SARS肺组织均呈弥漫性肺泡上皮损伤 ,2例尸检肺组织呈急性间质性炎和区域性肺水肿 ,2例尸检和1例穿刺肺组织中肺泡腔内透明膜形成 ,1例尸检和 2例穿刺肺组织呈脱屑性终末细支气管炎及肺泡炎 ,2例穿刺病例见早期肺纤维化及肺泡腔机化。SARS肺外器官 ,2例病程 <12dSARS病例免疫器官呈较广泛的出血坏死性炎 ,组织细胞及单核细胞样免疫母细胞反应性增生 ,骨髓组织内单核 粒细胞系统相对抑制 ,而 4例病程 >2 1dSRAS病例脾脏中央动脉周围T淋巴细胞增生 ,骨髓像大致正常。体内SARS CoV存在多种感染靶细胞和靶器官 ,其中肺脏为主要靶器官 ,支气管、肾、肾上腺、心肌、胃肠道、淋巴组织及睾丸等也为靶器官。肺组织内以CD8+ 细胞浸润为主 ,杂以少数CD4 + 细胞 ;淋巴结及脾脏中CD3+ 、CD4 + 、CD8+ 和CD2 0 + 淋巴细胞亚群呈不同程度减少及比例失衡 ,而     

Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP)

BACKGROUND/AIMS: The pathogenesis of idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), a chronic and incurable human respiratory disease, is not well established. This study was designed to investigate whether the apoptosis of type II pneumocytes could be the precipitating factor in the pathogenesis of IPF. METHODS: Nineteen specimens obtained by retrospective review of the medical and pathological records of 55 patients with IPF, four normal subjects, and 10 disease control lungs were analysed. The selected specimens had normal alveoli with intervening patchy scarring of the lung parenchyma, fulfilling the pathological criteria for UIP. To identify individual cells undergoing apoptosis in the normal alveoli, electron microscopy and in situ end labelling of fragmented DNA were performed on paraffin was embedded sections using digoxigenin-11-dUTP and the enzyme terminal deoxynucleotidyl transferase. RESULTS: Apoptosis was detected in the normal alveoli of 17 of the 19 patients with IPF/UIP and was absent in the controls. Electron microscopy demonstrated apoptotic changes in type II pneumocytes. These results indicate that apoptotic type II pneumocyte death occurs in normal alveoli of IPF/UIP and could be the principal cause of several events that account for the histological, clinical, and functional alterations seen in IPF/UIP. CONCLUSIONS: In conclusion, numerous type II pneumocytes from the normal alveoli of most patients with IPF/UIP actively undergo programmed cell death. This finding may shed new light on the pathogenesis of this disease, with implications mainly for the treatment of affected patients.     

A Study of Human Interstitial Lung Diseases with Special Reference to Immune Complexes and Hyaline Membrane

To evaluate the pathogenetic roles of immune complexes and alveolar hyaline membrane in idiopathic interstitial pneumonia (IIP), immunohistological and ultrastructural studies of the kidney and lung were performed in 23 cases of IIP, 19 cases of autoimmune diseases, 17 cases of interstitial pneumonia other than IIP, and 11 cases of bronchopneumonia as a control group. None of the cases of IIP or interstitial pneumonia other than IIP showed immune complexes in the alveolar and glomerular capillary walls. On the other hand, one case of SLE was positive for IgG and components of complement along the alveolar and glomerular capillary walls. The alveolar hyaline membrane in the present cases revealed immunoglobulins as well as components of complement, which were poorly soluble in chaotropic solution or acidic buffer. These results indicate that circulating immune complexes play a minor role in the pathogenesis of IIP and other types of interstitial pneumonia, and that there is no relationship between immune complex deposition in alveoli and the alveolar hyaline membrane. It is necessary to further investigate factors other than immune complexes involved in alveolar tissue damage and to clarify the significance of the hyaline membrane in the processes occurring from acute changes to pulmonary fibrosis in IIP.     

Pathological post‐mortem findings in lungs infected with SARS‐CoV‐2

Italy was the first European nation to be massively infected by SARS‐CoV‐2. Up to the end of May 2020, more than 33,000 deaths had been recorded in Italy, with a large prevalence among males, those over 75 years of age, and in association with co‐morbidities. We describe the lung pathological and immunohistochemical post‐mortem findings at the autopsy of nine patients who died of SARS‐CoV‐2‐associated disease. We found in the lung tissues of all patients histological changes consistent with diffuse alveolar damage in various evolution phases ranging from acute exudative to acute proliferative to fibrotic phase. Alveolar damage was associated with prominent involvement of the vascular component in both the interstitial capillaries and the mid‐size vessels, with capillary fibrin micro‐thrombi, as well as organized thrombi even in medium‐sized arteries, in most cases not related to sources of embolism. Eosinophilic infiltrate was also seen, probably reactive to pharmacological treatment. Viral RNA of SARS‐CoV‐2 was detected from the lung tissues of all the nine patients. Immunohistochemistry for the receptor of the SARS‐CoV‐2, ACE2, and its priming activator TMPRSS2 revealed that both proteins co‐localize in airway cells. In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD). Pneumocytes, but not endothelial cells, also expressed TMPRSS2. There are no distinctive histological features of SARS‐CoV‐2 infection with respect to SARS‐CoV‐1 and other DAD with different aetiology. The identification of the cause of death in the course of SARS‐CoV‐2 infection is more likely multi‐factorial. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A study of human interstitial lung diseases with special reference to immune complexes and hyaline membrane

To evaluate the pathogenetic roles of immune complexes and alveolar hyaline membrane in idiopathic interstitial pneumonia (IIP), immunohistological and ultrastructural studies of the kidney and lung were performed in 23 cases of IIP, 19 cases of autoimmune diseases, 17 cases of interstitial pneumonia other than IIP, and 11 cases of bronchopneumonia as a control group. None of the cases of IIP or interstitial pneumonia other than IIP showed immune complexes in the alveolar and glomerular capillary walls. On the other hand, one case of SLE was positive for IgG and components of complement along the alveolar and glomerular capillary walls. The alveolar hyaline membrane in the present cases revealed immunoglobulins as well as components of complement, which were poorly soluble in chaotropic solution or acidic buffer. These results indicate that circulating immune complexes play a minor role in the pathogenesis of IIP and other types of interstitial pneumonia, and that there is no relationship between immune complex deposition in alveoli and the alveolar hyaline membrane. It is necessary to further investigate factors other than immune complexes involved in alveolar tissue damage and to clarify the significance of the hyaline membrane in the processes occurring from acute changes to pulmonary fibrosis in IIP.     

The spectrum of pathological changes in severe acute respiratory syndrome (SARS)

AIMS: To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease. METHODS AND RESULTS: Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy. CONCLUSIONS: The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.