病理学-呼吸系统

1、呼吸系统疾病 The Respiratory System第四章快速气体交换 Rapid gas exchange VentilationPerfusion Diffusion 清洁空气 肺的结构与功能 MucosaSubmucosaCartilageMusclesBronchusBronchial epithelium Kulchitsky cells Bronchial Submucosal Glands Alveoli The respiratory membrane 病原体 Pathogen 空气 contaminated air exposure 鼻咽部菌群 nasopharynge

2、al flora aspiration宿主防御功能下降 Compromised defense mechanisms 肺部疾病 other common lung disease免疫缺陷 Immunodeficiency生活方式 Life style肺部感染 Pulmonary Infections分类 Classification 根据解剖和影像学 Anatomy and radiography根据病因 Etiology根据在哪获得 Setting in which they arise Community-Acquired Hospital-acquired (nosocomial )一、

3、细菌性肺炎 大叶性肺炎 （95%肺炎链球菌） 小叶性肺炎 军团菌性肺炎 （肺炎+全身毒血症状）小叶性肺炎大叶性肺炎 患者杨某，男，20岁，学生。酗酒后遭雨淋，于当天晚上突然起病，寒颤、高热、呼吸困难、胸痛，继而咳嗽，咳铁锈色痰，其家属急送当地医院就诊。听诊，左肺下叶有大量湿性啰音；触诊语颤增强；血常规：WBC：17X109/L；X线检查，左肺下叶有大片致密阴影。典型病例1入院经抗生素治疗，病情好转，各种症状逐渐消失；X线检查，左肺下叶的大片致密阴影缩小2/3面积。病人于入院后第7天自感无症状出院。冬季征兵体检，X线检查左肺下叶有约3cmX2cm大小不规则阴影，周围边界不清，怀疑为“支气管肺癌”

4、。在当地医院即做左肺下叶切除术。病理检查，肺部肿块肉眼为红褐色肉样，镜下为肉芽组织。大叶性肺炎大叶性肺炎大叶性肺炎In the era before antibiotics 充血水肿期 Hyperemia and edema红肝期 Red hepatization灰肝期 Gray hepatization溶解消散期 Resolution (hopefully)Hyperemia and edema，12-24 hours Red hepatization 2-3 daysGray hepatization，3-4 days并发症 complications肺脓肿，脓胸，脓气胸败血症，脓毒败血症

5、，感染性休克肺肉质变小叶性肺炎小叶性肺炎Filled with exudateAerated lung小叶性肺炎小叶性肺炎并发症 Complications 心力衰竭、呼吸衰竭肺脓肿、脓胸、脓毒败血症 支气管扩张Organization Abscess formation Abscess formation Purulent pleuritisHemorrhagic Pneumoniaby Pseudomonas aeruginosaPseudomonas pneumonia Klebsiella pneumonia二、病毒性肺炎/三、支原体性肺炎 轻者为急性间质性肺炎，旧称不典型性肺炎aty

6、pical缺乏实变体征 WBC轻度升高 重者为急性呼吸窘迫症ARDS肺泡弥漫性损伤透明膜形成Viral pneumoniaAtypical pneumonia Severe Acute Respiratory Syndrome (SARS) Pneumonia in the Immunocompromised Host 机会致病原 opportunistic agents常为多重感染 bacteria (P. aeruginosa, Mycobacterium spp., L. pneumophila, and Listeria monocytogenes)viruses (cytomegal

7、ovirus and herpesvirus)fungi (P. jiroveci, Candida spp., Aspergillus spp., and Cryptococcus neoformans)CMV infections in situ hybridizationSputum cytology from an AIDS patient(Papanicolaou) (Giemsa) Pneumocystis Pneumonia (silver stain)Pneumocystis Pneumonia (silver stain)Pneumocystis Pneumonia Pneu

8、mocystis carinii in bronchial lavage from an AIDS patient (Grocotts silver)(Papanicolaou) (Immunostaining)慢性阻塞性肺病 (COPD) Chronic Obstructive Pulmonary Diseaselimitation of airflow usually resulting from an increase in resistance caused by partial or complete obstruction at any level肺气肿 Emphysema慢性支气

9、管炎 Chronic bronchitis支气管扩张 Bronchiectasis哮喘 AsthmaFEV1 / FVCClinical TermAnatomic SiteMajor Pathologic ChangesEtiologySigns/SymptomsChronic bronchitisBronchusBronchioleMucus gland hyperplasia, hypersecretionInflammatory scarringTobacco smoke, air pollutantsCough, sputum productionCough, dyspneaBronc

10、hi-ectasisBronchusAirway dilation and scarringPersistent or severe infectionsCough, purulent sputum, feverAsthmaBronchusSmooth muscle hyperplasia, excessive mucus, inflammationImmunologic or undefined causesEpisodic wheezing, cough, dyspneaEmphysemaAcinusAirspace enlargement,wall destructionTobacco

11、smokeDyspnea 我国国家“十五”课题最新统计数据（2005年公布）显示40岁以上人口COPD患病率为8%。估计全国有2500万人罹患此病，每年因COPD死亡的人数达100万，致残人数达5001000万，COPD居我国疾病负担的首位。慢性支气管炎 Chronic bronchitisA persistent cough productive of sputum for at least 3 months, in at least 2 consecutive years单纯型 Simple 喘息型 Asthmatic 阻塞型 obstructive 病 因 etiology吸烟和空气污染

12、 Cigarette smoking and air pollutants感染 Microbial infection Secondary role使炎症持续，加重症状 maintaining the inflammation and exacerbating symptoms发病机制 Pathogenesis 多痰粘液分泌亢进 Hypersecretion of mucus 大气道病变 large bronchial involvement 粘液腺增生，杯状细胞分泌亢进 Hypertrophy of mucous glands and a marked increase in mucin-

13、secreting goblet cells 气道阻塞 Airflow obstruction小气道炎症和管壁纤维化 inflammation, bronchiolar wall fibrosis 杯状细胞化生，细支气管痰栓形成 goblet cell metaplasia with mucus plugging of the bronchiolar lumen并发肺气肿 coexistent emphysema 发病机制 Pathogenesis inner perichondriumbasal laminaChronic bronchitisNormal bronchusChronic b

14、ronchitis Chronic bronchitis Chronic bronchiolitis luminal and mucuschronic inflammation肺气肿 Emphysema Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis 指呼吸性细支气管、肺泡管、肺泡囊、肺泡因组织弹性减弱而过度充气伴有肺泡间隔破坏，致使肺容积增大

15、的病理状态病理类型 腺泡(小叶)中央型 Centriacinar 全腺泡(小叶)型 Panacinar腺泡(小叶)周围型 Distal acinar不规则型 IrregularobstructionSpontaneous pneumothoraxasymptomatic发病机理 Pathogenesis Centriacinar emphysemaBullous emphysemaCentriacinar emphysema Inadequate ventilation Less perfusion Narrowed bronchioleConditions Related to Emphys

16、ema 间质性肺气肿 Mediastinal (interstitial) emphysema 代偿性肺气肿 Compensatory emphysema阻塞性过充气 Obstructive overinflation 瘢痕旁肺气肿 Paracicatrical emphysema老年性肺气肿 Senile emphysema COPD的临床表现Respiratory failureRight heart failurePink puffer桶状胸 Barrel chest 支气管扩张症 BronchiectasisPermanent dilation of bronchi and bronc

17、hioles caused by destruction of the muscle and elastic supporting tissue resulting from or associated with chronic necrotizing infections 继发于持续性感染或阻塞 Secondary to persisting infection or obstruction 诊断依靠病史和影像学Predisposing conditions 支气管阻塞 Bronchial obstruction肿瘤 Tumor异物 Foreign bodies 先天性或遗传性疾病 Cong

18、enital or hereditary conditions Cystic fibrosis Kartagener syndrome坏死性化脓性肺炎 Necrotizing, or suppurative, pneumonia Cystic Fibrosis (CF)Cystic Fibrosis (CF)Bronchiectasis57 year old woman with a long history of recurrent respiratory tract infections and episodes of hemoptysis Bronchiectasis Bronchiec

19、tasisDue to pneumoniaBronchiectasisBronchiectasis Purulent exudation in the lumenDestruction of lining epitheliumScarring of the bronchial wallHRCT scans of bronchiectasis 支气管扩张症的临床表现咳嗽，咳脓臭痰 Severe, persistent cough with mucopurulent sputum, sometimes fetid咯血 Flecks of blood in sputum or frank hemop

20、tysis 严重病例及合并症肺间质疾病 ILD肺弥漫性纤维化肺顺应性减弱，容量减小 已知病因和特发性间质性肺炎Selected causes of chronic interstitial lung disease Occupational and environmental exposureAsbestosisSilicosisHypersensitivity pneumonitisDrug or treatment relatedChemotherapeutic agentsIonizing irradiationOxygenImmunologic lung diseaseSarcoido

21、sisWegner granulomatosisCollagen vascular diseaseGoodpasture syndromeMiscellaneousPost acute respiratory distress syndromeIdiopathic pulmonary fibrosis杵状指（趾）Clubbing of digitsHoneycomb lung矽 肺 Silicosis职业病 Occupational diseases 吸入二氧化硅粉尘引起 Inhalation of crystalline silica致残和致死 Disabling and fatal病理：硅

22、结节形成 广泛的肺纤维化 发病机制 Pathogenesis 直径5m的硅尘沉积于肺间质肺泡巨噬细胞引发和持续肺损伤和纤维化 Alveolar macrophage is a key cellular element in the initiation and perpetuation of lung injury and fibrosisSilicosis a slice of lung from a 61 yo ceramics worker矽结节 Silicosis临床表现 Clinical course早期常为体检发现 usually detected in routine chest

23、 radiographs晚期表现：呼吸困难 shortness of breath肺心病 cor pulmonale合并TB increased susceptibility to TB可能致癌 carcinogenic (controversial) Silicosis 急性呼吸窘迫征 (ARDS) Acute Respiratory Distress Syndrome进行性呼吸衰竭 Acute onset of Dyspnea Hypoxemia Bilateral pulmonary infiltrates (X-ray)No evidence of left-sided heart f

24、ailure病理：弥漫性肺泡损伤 Diffuse Alveolar Damage (DAD)常伴多器官衰竭 Multiple Organ Dysfunction Syndrome (MODS)Direct Lung InjuryIndirect Lung InjuryCommon CausesPneumoniaSepsisAspiration of gastric contentsSevere trauma with shockUncommon CausesPulmonary contusionCardiopulmonary bypassFat embolismAcute pancreatit

25、isNear-drowningDrug overdoseInhalational injuryTransfusion of blood productsReperfusion injury afterlung transplantationUremiaClinical Disorders Associated with developing ARDS发病机制 Pathogenesis 广泛内皮和肺泡I型、II型上皮损伤 Endothelial and epithelial (I and II) damage肺水肿 alveolar flooding气体交换丧失 loss of diffusio

26、n capacity 表面活性物质异常 surfactant abnormalities 促炎和抗炎介质的失衡 Imbalance of pro-inflammatory and anti-inflammatory mediators 病理变化 Morphology急性渗出期 Acute Exudative Stage 水肿 Edema (interstitial and alveolar) 透明膜形成 Hyaline membranes 肺泡塌陷 Many alveoli collapse 增生期 Proliferative Stage II型肺泡上皮增生肺泡内机化 Intra-alveol

27、ar fibrosis widening of the interstitium ARDS Hyaline membranesHyaline membranes Hyaline membranes Healing stage Healing stage suviving patient ARDS临床表现 Clinical features肺顺应性差 Poor pulmonary compliance难治性低氧血症 Poor response to oxygen血管床进行性减少 Pulmonary vascular bed is progressively obliterated 易感染 Pro

28、ne to bacteria infection预后 Prognosis Depends successfully treatements before extensive fibrosis 40-70% mortalityHigh-dose steroids failedConservative therapy helpsConsiderable interest in the quality of survivals LUNG TUMORS Metastatic tumorsPrimary tumorsBRONCHOGENIC CARCINOMAOthers bronchial carci

29、noidsmesenchymal malignancies Lymphomasa few benign lesions 95%5%慢性肺动脉高压症和肺心病（自学）概念病因发病机制病理变化临床病理联系思考题：试述慢性支气管炎并发肺心病的发病机制。肺 癌 癌症死因第一位 cause of cancer-related deaths 发病率随年龄和烟龄增长 pack-years smoked. 确诊的病人一半以上已有远处转移 distant metastatic disease5年生存率约为15%5-year survival肺癌的临床病理分型肺小细胞癌 Small cell lung cancer

30、 (SCLC)肺非小细胞癌 Non-small-cell lung cancer (NSCLC) 鳞癌 Squamous cell carcinoma 腺癌 Adenocarcinomas大细胞癌 Large cellcarcinomas SCLCKulchitsky cell起源hADH (hyponatremia/ water intoxication)ACTH (Cushings syndrome)中央型 Centrally located masses 坏死常见 Necrosis is invariably present and may be extensive 燕麦细胞癌 Oat

31、cell carcinomaSCLCOat cell carcinomaSCLCOat cell carcinomaSCLC鳞状细胞癌病人大多有吸烟史 Closely correlated with a smoking history 中央型 Tend to arise centrally in major bronchi 常见空洞 Cavitation is not uncommon副癌综合征 Preneoplastic lesions Squamous cell carcinomaSquamous cell carcinomaSquamous cell carcinomaSquamous

32、cell carcinomaSquamous cell carcinomaMetaplaisa? Anaplasia? Dysplasia?腺 癌 Adenocarcinoma 周围型多见 peripherally located是女性和非吸烟者常见的肺癌类型常发生自肺周边部疤痕处 arising in relation to peripheral lung scars 生长缓慢但早期转移支气管肺泡干细胞起源 Bronchioalveolar stem cells origin Adenocarcinoma Adenocarcinoma Adenocarcinoma 细支气管肺泡癌(BAC)

33、Bronchioloalveolar carcinomaA distinct subtype of adenocarcinoma弥漫型多见multiple diffuse nodules Growing along preexisting structures and preservation of alveolar architecture 分为粘液型和无粘液型 mucinous/nonmucinous subtypesBACBACBACPrecursor lesions of ADCAAHBAC低分化癌，排除SCLC, SCC or ADCCells are not-columnar in

34、 shapeDo not contain mucousDo not show squamous differentiation Do not have neuroendocrine properties or small cell characteristics 可发生与任何部位 arise anywhere in lungs大部分与吸烟有关，预后差 smoking-related, cures are rare大细胞癌 Large cell carcinoma 肺癌的临床表现 原发灶引起的症状 Symptoms due to primary tumor原发灶蔓延引起的症状 Symptoms

35、due to locoregional spread转移引起的问题 Metastatic disease副肿瘤综合征 Paraneoplastic syndromes 中央型肺癌 Central tumors cough, dyspnea, 肺不张atelectasis, 阻塞后肺炎，喘息 咯血hemoptysis 周围型肺癌 Peripheral tumors cough, dyspnea胸水pleural effusion疼痛severe painDue to primary tumorDue to locoregional spread上腔静脉综合征 Superior vena cava

36、 obstruction声音嘶哑 Hoarseness肩膀和上臂疼痛Horners syndrome吞咽困难 Dysphagia 心包积液 Pericardial effusion 眼球内陷 a sunken eyeball (enophthalmia) 瞳孔缩小，对光反射异常 上睑下垂 droopy upper eyelid 患侧面部无汗Horners SyndromeNormal Abnormal Metastatic disease脑 brain (mental or neurologic changes)肝 liver (hepatomegaly)骨 bones (pain) Para

37、neoplastic syndromesHypercalcemiaCushing syndromeHyponatremia Neuromuscular syndromesHematologic manifestationsClubbing of the fingersBlindness and dementia3% to 10% of all patientsMetastatic carcinomadilated lymphatic channelTransesophageal Echocardiogram6/22, 8 days before death, showed thickening of the lea