人感染高致病性禽流感病毒H5N1的病理学观察

Histopathologic study of avian influenza H5N1 infection in humans

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。

Objective To identify histopathologic changes of major organs and to correlate clinical symptoms in patients infected by avian influenza H5N1. Methods Autopsy study was performed in two patients died of avian influenza H5N1 infection, following conventional protocols and strict safety procedures. Tissue samples from all major organs of two cases and lung samples of one case were collected and fixed in 4% formaldehyde. Histupatholagic changes were evaluated by light microscope. Results Diffuse alveolar damage （DAD） of the lung was seen in both cases. Lesions at various stages of development were seen involving different areas of the lung. At the early stages, the lungs exhibited exudative changes, including capillary congestion, necrosis of alveolar epithelial cells, and intra-alveolar edema. Hyaline membranes were prominent and diffusely distributed along alveoli. In the middle-late stages of the disease, the lungs exhibited proliferative and fibrotic changes, including proliferation of pneumocytes and bronchial epithelium, fibrosis of the interstitium and alveolar spaces. Lung biopsy tissue of one case showed DAD and interstitial fibrosis in a background of bronchiectasis. Lymph nodes and spleens showed quantity reduction of lymphocytes and active hemophagocytosis. Other changes in major organs included interstitial carditis in one case and acute renal tubular necrosis in one case. In one case, the brain showed edema with cytoplasmic eosinophilia, loss of structure, axon welling and focal necrosis around ventricle. Multiple loci of trophoblastic necrosis with dystrophic calcification were observed in placenta of one pregnant patient. Acute necrotizing deciduitis was found focally. Sections of fetal lung showed edema and scattered interstitial neutrophils were consistent with acute interstitial pneumonitis. Condusions The respiratory tract is the major target of avian influenza A H5N1 virus infection. The changes of DAD in the lungs resulted in hypoxia, leading to multiple organ failure and death.