病理學(xué)-呼吸系統(tǒng)

1、呼吸系統(tǒng)疾病 The Respiratory System第四章快速氣體交換 Rapid gas exchange VentilationPerfusion Diffusion 清潔空氣 肺的結(jié)構(gòu)與功能 MucosaSubmucosaCartilageMusclesBronchusBronchial epithelium Kulchitsky cells Bronchial Submucosal Glands Alveoli The respiratory membrane 病原體 Pathogen 空氣 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分類 Classification 根據(jù)解剖和影像學(xué) Anatomy and radiography根據(jù)病因 Etiology根據(jù)在哪獲得 Setting in which they arise Community-Acquired Hospital-acquired (nosocomial )一、

3、細(xì)菌性肺炎 大葉性肺炎 （95%肺炎鏈球菌） 小葉性肺炎 軍團(tuán)菌性肺炎 （肺炎+全身毒血癥狀）小葉性肺炎大葉性肺炎 患者楊某，男，20歲，學(xué)生。酗酒后遭雨淋，于當(dāng)天晚上突然起病，寒顫、高熱、呼吸困難、胸痛，繼而咳嗽，咳鐵銹色痰，其家屬急送當(dāng)?shù)蒯t(yī)院就診。聽(tīng)診，左肺下葉有大量濕性啰音；觸診語(yǔ)顫增強(qiáng)；血常規(guī)：WBC：17X109/L；X線檢查，左肺下葉有大片致密陰影。典型病例1入院經(jīng)抗生素治療，病情好轉(zhuǎn)，各種癥狀逐漸消失；X線檢查，左肺下葉的大片致密陰影縮小2/3面積。病人于入院后第7天自感無(wú)癥狀出院。冬季征兵體檢，X線檢查左肺下葉有約3cmX2cm大小不規(guī)則陰影，周圍邊界不清，懷疑為“支氣管肺癌”

4、。在當(dāng)?shù)蒯t(yī)院即做左肺下葉切除術(shù)。病理檢查，肺部腫塊肉眼為紅褐色肉樣，鏡下為肉芽組織。大葉性肺炎大葉性肺炎大葉性肺炎In the era before antibiotics 充血水腫期 Hyperemia and edema紅肝期 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并發(fā)癥 complications肺膿腫，膿胸，膿氣胸?cái)⊙Y，膿毒敗血癥

5、，感染性休克肺肉質(zhì)變小葉性肺炎小葉性肺炎Filled with exudateAerated lung小葉性肺炎小葉性肺炎并發(fā)癥 Complications 心力衰竭、呼吸衰竭肺膿腫、膿胸、膿毒敗血癥 支氣管擴(kuò)張Organization Abscess formation Abscess formation Purulent pleuritisHemorrhagic Pneumoniaby Pseudomonas aeruginosaPseudomonas pneumonia Klebsiella pneumonia二、病毒性肺炎/三、支原體性肺炎 輕者為急性間質(zhì)性肺炎，舊稱不典型性肺炎aty

6、pical缺乏實(shí)變體征 WBC輕度升高 重者為急性呼吸窘迫癥ARDS肺泡彌漫性損傷透明膜形成Viral pneumoniaAtypical pneumonia Severe Acute Respiratory Syndrome (SARS) Pneumonia in the Immunocompromised Host 機(jī)會(huì)致病原 opportunistic agents常為多重感染 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肺氣腫 Emphysema慢性支氣

9、管炎 Chronic bronchitis支氣管擴(kuò)張 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 我國(guó)國(guó)家“十五”課題最新統(tǒng)計(jì)數(shù)據(jù)（2005年公布）顯示40歲以上人口COPD患病率為8%。估計(jì)全國(guó)有2500萬(wàn)人罹患此病，每年因COPD死亡的人數(shù)達(dá)100萬(wàn)，致殘人數(shù)達(dá)5001000萬(wàn)，COPD居我國(guó)疾病負(fù)擔(dān)的首位。慢性支氣管炎 Chronic bronchitisA persistent cough productive of sputum for at least 3 months, in at least 2 consecutive years單純型 Simple 喘息型 Asthmatic 阻塞型 obstructive 病 因 etiology吸煙和空氣污染

12、 Cigarette smoking and air pollutants感染 Microbial infection Secondary role使炎癥持續(xù)，加重癥狀 maintaining the inflammation and exacerbating symptoms發(fā)病機(jī)制 Pathogenesis 多痰粘液分泌亢進(jìn) Hypersecretion of mucus 大氣道病變 large bronchial involvement 粘液腺增生，杯狀細(xì)胞分泌亢進(jìn) Hypertrophy of mucous glands and a marked increase in mucin-

13、secreting goblet cells 氣道阻塞 Airflow obstruction小氣道炎癥和管壁纖維化 inflammation, bronchiolar wall fibrosis 杯狀細(xì)胞化生，細(xì)支氣管痰栓形成 goblet cell metaplasia with mucus plugging of the bronchiolar lumen并發(fā)肺氣腫 coexistent emphysema 發(fā)病機(jī)制 Pathogenesis inner perichondriumbasal laminaChronic bronchitisNormal bronchusChronic b

14、ronchitis Chronic bronchitis Chronic bronchiolitis luminal and mucuschronic inflammation肺氣腫 Emphysema Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis 指呼吸性細(xì)支氣管、肺泡管、肺泡囊、肺泡因組織彈性減弱而過(guò)度充氣伴有肺泡間隔破壞，致使肺容積增大

15、的病理狀態(tài)病理類型 腺泡(小葉)中央型 Centriacinar 全腺泡(小葉)型 Panacinar腺泡(小葉)周圍型 Distal acinar不規(guī)則型 IrregularobstructionSpontaneous pneumothoraxasymptomatic發(fā)病機(jī)理 Pathogenesis Centriacinar emphysemaBullous emphysemaCentriacinar emphysema Inadequate ventilation Less perfusion Narrowed bronchioleConditions Related to Emphys

16、ema 間質(zhì)性肺氣腫 Mediastinal (interstitial) emphysema 代償性肺氣腫 Compensatory emphysema阻塞性過(guò)充氣 Obstructive overinflation 瘢痕旁肺氣腫 Paracicatrical emphysema老年性肺氣腫 Senile emphysema COPD的臨床表現(xiàn)Respiratory failureRight heart failurePink puffer桶狀胸 Barrel chest 支氣管擴(kuò)張癥 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 繼發(fā)于持續(xù)性感染或阻塞 Secondary to persisting infection or obstruction 診斷依靠病史和影像學(xué)Predisposing conditions 支氣管阻塞 Bronchial obstruction腫瘤 Tumor異物 Foreign bodies 先天性或遺傳性疾病 Cong

18、enital or hereditary conditions Cystic fibrosis Kartagener syndrome壞死性化膿性肺炎 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 支氣管擴(kuò)張癥的臨床表現(xiàn)咳嗽，咳膿臭痰 Severe, persistent cough with mucopurulent sputum, sometimes fetid咯血 Flecks of blood in sputum or frank hemop

20、tysis 嚴(yán)重病例及合并癥肺間質(zhì)疾病 ILD肺彌漫性纖維化肺順應(yīng)性減弱，容量減小 已知病因和特發(fā)性間質(zhì)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杵狀指（趾）Clubbing of digitsHoneycomb lung矽 肺 Silicosis職業(yè)病 Occupational diseases 吸入二氧化硅粉塵引起 Inhalation of crystalline silica致殘和致死 Disabling and fatal病理：硅

22、結(jié)節(jié)形成 廣泛的肺纖維化 發(fā)病機(jī)制 Pathogenesis 直徑5m的硅塵沉積于肺間質(zhì)肺泡巨噬細(xì)胞引發(fā)和持續(xù)肺損傷和纖維化 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矽結(jié)節(jié) Silicosis臨床表現(xiàn) Clinical course早期常為體檢發(fā)現(xiàn) usually detected in routine chest

23、 radiographs晚期表現(xiàn)：呼吸困難 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進(jìn)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：彌漫性肺泡損傷 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發(fā)病機(jī)制 Pathogenesis 廣泛內(nèi)皮和肺泡I型、II型上皮損傷 Endothelial and epithelial (I and II) damage肺水腫 alveolar flooding氣體交換喪失 loss of diffusio

26、n capacity 表面活性物質(zhì)異常 surfactant abnormalities 促炎和抗炎介質(zhì)的失衡 Imbalance of pro-inflammatory and anti-inflammatory mediators 病理變化 Morphology急性滲出期 Acute Exudative Stage 水腫 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內(nèi)機(jī)化 Intra-alveol

27、ar fibrosis widening of the interstitium ARDS Hyaline membranesHyaline membranes Hyaline membranes Healing stage Healing stage suviving patient ARDS臨床表現(xiàn) Clinical features肺順應(yīng)性差 Poor pulmonary compliance難治性低氧血癥 Poor response to oxygen血管床進(jìn)行性減少 Pulmonary vascular bed is progressively obliterated 易感染 Pro

28、ne to bacteria infection預(yù)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%慢性肺動(dòng)脈高壓癥和肺心?。ㄗ詫W(xué)）概念病因發(fā)病機(jī)制病理變化臨床病理聯(lián)系思考題：試述慢性支氣管炎并發(fā)肺心病的發(fā)病機(jī)制。肺 癌 癌癥死因第一位 cause of cancer-related deaths 發(fā)病率隨年齡和煙齡增長(zhǎng) pack-years smoked. 確診的病人一半以上已有遠(yuǎn)處轉(zhuǎn)移 distant metastatic disease5年生存率約為15%5-year survival肺癌的臨床病理分型肺小細(xì)胞癌 Small cell lung cancer

30、 (SCLC)肺非小細(xì)胞癌 Non-small-cell lung cancer (NSCLC) 鱗癌 Squamous cell carcinoma 腺癌 Adenocarcinomas大細(xì)胞癌 Large cellcarcinomas SCLCKulchitsky cell起源hADH (hyponatremia/ water intoxication)ACTH (Cushings syndrome)中央型 Centrally located masses 壞死常見(jiàn) Necrosis is invariably present and may be extensive 燕麥細(xì)胞癌 Oat

31、cell carcinomaSCLCOat cell carcinomaSCLCOat cell carcinomaSCLC鱗狀細(xì)胞癌病人大多有吸煙史 Closely correlated with a smoking history 中央型 Tend to arise centrally in major bronchi 常見(jiàn)空洞 Cavitation is not uncommon副癌綜合征 Preneoplastic lesions Squamous cell carcinomaSquamous cell carcinomaSquamous cell carcinomaSquamous

32、cell carcinomaSquamous cell carcinomaMetaplaisa? Anaplasia? Dysplasia?腺 癌 Adenocarcinoma 周圍型多見(jiàn) peripherally located是女性和非吸煙者常見(jiàn)的肺癌類型常發(fā)生自肺周邊部疤痕處 arising in relation to peripheral lung scars 生長(zhǎng)緩慢但早期轉(zhuǎn)移支氣管肺泡干細(xì)胞起源 Bronchioalveolar stem cells origin Adenocarcinoma Adenocarcinoma Adenocarcinoma 細(xì)支氣管肺泡癌(BAC)

33、Bronchioloalveolar carcinomaA distinct subtype of adenocarcinoma彌漫型多見(jiàn)multiple diffuse nodules Growing along preexisting structures and preservation of alveolar architecture 分為粘液型和無(wú)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 可發(fā)生與任何部位 arise anywhere in lungs大部分與吸煙有關(guān)，預(yù)后差 smoking-related, cures are rare大細(xì)胞癌 Large cell carcinoma 肺癌的臨床表現(xiàn) 原發(fā)灶引起的癥狀 Symptoms due to primary tumor原發(fā)灶蔓延引起的癥狀 Symptoms

35、due to locoregional spread轉(zhuǎn)移引起的問(wèn)題 Metastatic disease副腫瘤綜合征 Paraneoplastic syndromes 中央型肺癌 Central tumors cough, dyspnea, 肺不張atelectasis, 阻塞后肺炎，喘息 咯血hemoptysis 周圍型肺癌 Peripheral tumors cough, dyspnea胸水pleural effusion疼痛severe painDue to primary tumorDue to locoregional spread上腔靜脈綜合征 Superior vena cava

36、 obstruction聲音嘶啞 Hoarseness肩膀和上臂疼痛Horners syndrome吞咽困難 Dysphagia 心包積液 Pericardial effusion 眼球內(nèi)陷 a sunken eyeball (enophthalmia) 瞳孔縮小，對(duì)光反射異常 上瞼下垂 droopy upper eyelid 患側(cè)面部無(wú)汗Horners SyndromeNormal Abnormal Metastatic disease腦 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