致死的严重急性呼吸综合征的病理变化及发病机制探讨

Pathological changes and pathogenesis of fatal severe acute respiratory syndrome

目的 研究严重急性呼吸综合征 (SARS)患者的各系统的病理变化 ,探讨SARS发病机制。方法 对北京市 6例SARS死亡病例进行系统尸体解剖 ,并进行肉眼、常规HE组织学、免疫组织化学、电子显微镜、原位杂交检查。结果 电镜和原位杂交显示SARS CoV侵犯多种器官的多种组织 ,SARS CoV样的病毒颗粒可见于包括血管内皮细胞、Ⅱ型肺泡上皮细胞、淋巴细胞、巨噬细胞、肠上皮细胞和远端肾小管上皮细胞等。原位杂交显示气管和支气管上皮细胞、Ⅱ型肺泡上皮细胞、淋巴细胞、巨噬细胞、血管内皮细胞、肠上皮细胞、远端肾小管上皮细胞等都有SARS CoV的基因存在。致死的SARS对呼吸系统和免疫系统损害最严重。弥漫性肺泡损伤是肺内的主要病变 ,表现为渗出性、增生性和纤维化三种病变的混杂。渗出性病变是早期改变 ,肺泡腔内大量蛋白性液体渗出 ,部分肺泡内多量纤维蛋白渗出 ,并可见多量红细胞 ;肺泡壁蛋白性透明膜形成。增生性病变为中期改变 ,主要表现为脱屑性肺泡炎。纤维化病变为晚期改变 ,在透明膜和纤维蛋白渗出的基础上 ,肌纤维母细胞增生 ,胶原纤维沉积 ,肺泡内逐渐发生纤维化 ;肺间质明显增宽 ,其内纤维组织和毛细血管增生。脾和淋巴结的淋巴组织萎缩 ,T细胞和B细胞大量减少 ,以T细胞减少更明显。淋巴滤泡和生发?

Objective To study the pathological changes and pathogenesis of fatal severe acute respiratory syndrome (SARS). Methods Complete autopsy was performed in 6 SARS cases in Beijing. Systemic examinations were carried out by naked eyes, light microscopy, immunohistochemistry, electron microscopy, and in situ hybridization. Results It was found that SARS-CoV attack different tissues in various organs, including endothelial cells of capillaries, pulmonary alvolar type Ⅱ pneumocytes, lymphocytes and macrophages in lymph node and spleen, epithelial cells of renal tubule (especial distal tubule), mucosal epithelial cells and lymphocytes of alimentary tract, cardiac myocytes by electron microscopy. SARS-CoV genome were identified in epithelial cells of trachea and bronchus, pulmonary alveolar type Ⅱ pneumocytes, lymphocytes and macrophages in lymph node and spleen, endothelial cells of capillaries, mucosal epithelial cells and lymphocytes of alimentary tract, epithelial cells of distal renal tubule by in situ hybridization. Respiratory system and immune system were most severely damaged in fatal SARS patients. Diffuse alveolar damage (DAD) was basic pathological finding in fatal SARS patients. Exudation, proliferation and fibrosis were observed in the involved lungs. Exudation seemed to occur in early stage. In this stage, air spaces were filled with inflammatory exudates (including protein, fibrin, mononuclear cells, lymphocytes, even red cells), hyaline membrane was formed along the alveolar walls. Proliferation changes happened subsequently, desquamative alveolitis was the characteristic changes in the stage. Fibrosis was the late change. The organization of protein exudates and hyaline membrane resulted in intra-alveolar fibrosis and thickening of the alveolar septa. Atrophy of lymphoid tissues was the obvious changes in spleens and lymph nodes. Both T cell and B cell, especially T cell, ppoulations were decreased greatly. The germinal centers were burnt-out. Some activated atypical cells, positive by in situ hybridization, were observed in spleens and lymph nodes. However, the immune phenotype were unknown. Such specials were named SARS by us. Degeneration and even necrosis of cardiac myocytes occurred in 2 cases. Fatty degeneration of the central area in liver lobules occurred in all cases, but only 2 cases with necrosis in the same area were found. Aspergillosis in the lungs were founded in 3 cases.Conclusions Fatal SARS is a respiratory infectious disease involved different tissues in multiple organs in which respiratory system and immune system were most severely damaged.