北京大學醫(yī)學院《病理學》呼吸系統(tǒng)

1、呼吸系統(tǒng)疾病Diseases of Respiratory SystemAnatomy and Histology The Upper Respiratory Tract the nose, pharynx and larynx Cricoid cartilage The Lower Respiratory Tract the trachea, bronchi and lungsTrachea Bronchus Lobar bronchus Segmental bronchus Bronchiole Terminal bronchiole Respiratory bronchiole Alve

2、olar ductAlveolar sac Alveolus Trachea & Bronchial treeLobuleAcinusLobeTracheaEpitheliumLamina propriaSubmucosaAdventitiaBrush cell Goblet cell basal cell ciliated cell small granular cellPseudostratified ciliated columnar epithelium0.5-2cmLobuleLungPulmonary veinRespiratory bronchioleAlveolar ductA

3、lveolar sac Pulmonary alveolus終末細支氣管Alveolar sacTerminal bronchiole Pulmonary arteryType II alveolar cellType I alveolar cellcapillaryAlveolar septummacrophageBloodair BarrierAlveolar pore (Kohns pore)Heart failure cell:Definition:Alveolar macrophages containing hemosiderin are seen in cardiac failu

4、re.The alveolar spaces contain macrophages which show brownish discoloration of their cytoplasm due to the hemosiderin content .正常肺組織Diseases of Respiratory System1）Obstructive Lung Diseases: Chronic bronchitis, Emphysema, Bronchiectasis Asthma2）Restrictive Lung Diseases： acuteARDS ，chronicSilicosis

5、3）Chronic cor pulmonale 4）Pulmonary Infections: Community-Acquired Acute and Atypical pneumonias Tuberculosis Primary, Secondary5）Tumor： Lung cancer, Nasopharyngeal carcinomaA group of diseases characterized by limitation of airflow, usually resulting from an increase in resistance from partial or c

6、omplete obstruction at any level Major symptom dyspnea Major disordersChronic bronchitisEmphysemaBronchiectasisAsthmaObstructive Lung DiseasesDefinition: a persistent productive cough for at least 3 consecutive months in at least 2 consecutive yearsThe diagnosis is made on clinical groundsA common d

7、isease in middle-aged heavy smokersMay progress to emphysema and chronic cor pulmonaleChronic BronchitisEtiology & PathogenesisChronic irritation by inhaled substancesCigarette smoking predisposes to infectionInterfere with ciliary actionCause direct damage to epitheliumInhibit leukocytes functionAi

8、r pollutants（SO2, NO2)Cold airMicrobiologic infectionsRecurrent viral infections Secondary bacterial infectionsChronic BronchitisPathological ChangeFrom trachea to bronchi and bronchiolesDamage of epithelium: cilium Squamous metaplasia Goblet cell hyperplasiaMucous glands hyperplasia and hypertrophy

9、Chronic inflammatory cells infiltrationSmooth muscle hypertrophy (asthmatic)Fibrosis of bronchiolar wall (persistent)Chronic BronchitisSquamous metaplasiaSquamous metaplasiaMucous glands hyperplasia and hypertrophyChronic bronchitis Goblet cell hyperplasiaClinical CourseMiddle-aged heavy smokersPers

10、istent cough productive of copious sputumWheezing in asthmatic typePulmonary function damage with complicationLead to emphysema, cor pulmonale when persistChronic BronchitisChronic BronchitisDefined clinically as cough and sputum for 3 months in 2 consecutive yearsMucus hypersecretion with bronchial

11、 mucous gland hypertrophyRespiratory bronchiolitisMost cases caused by smokingPulmonary Emphysema DefinitionA pathological condition of the lung characterized by permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious f

12、ibrosis. Pulmonary Emphysema正常肺腺泡中心型肺氣腫Pathogenesis Etiology Cigarette smokingObstruction of small airways1-antitrypsin (1 -AT) genetic deficiency Pulmonary EmphysemaDegeneration of elastin1ATElastase & metallo-proteinasesMacrophageNeutrophilFree radicalsProtease-antiprotease imbalance hypothesisCla

13、ssificaion & Pathological ChangeIn terms of anatomic distribution alveolar emphysemacentriacinar emphysemapanacinar emphysemaperiacinar emphysemaOther types Interstitial , Senile Compensatory Obstructive Overinflation Pulmonary Emphysema腺泡中央型肺氣腫呼吸性細支氣管囊狀擴張，而肺泡管、肺泡囊和肺泡不擴張因呼吸性細支氣管位于肺腺泡的中央，故得名。正常肺腺泡中心型

14、肺氣腫吸煙者的肺氣腫，腺泡中央型。全腺泡型肺氣腫肺氣腫均勻地累及全部腺泡呼吸性細支氣管、肺泡管、肺泡囊和肺泡彌漫性擴張與1-AT有關全腺泡型肺氣腫全腺泡型肺氣腫全腺泡型肺氣腫腺泡周圍型肺氣腫也稱隔旁肺氣腫，因小葉間隔受牽拉或炎癥所致；多累及鄰近胸膜和小葉周邊間隔的肺泡。腺泡周圍型肺氣腫間質性肺氣腫由于肺泡間隔或細支氣管壁破裂使空氣進入肺間質所致；氣體在小葉間隔和肺膜下形成囊球狀小氣泡。Pathological ChangeGross ExaminationThe basis of diagnosis and classification Pale and voluminous lung in

15、advanced casesPanacinar type more voluminous than centriacinar typeUpper 2/3 of lung more severely affectedPulmonary Emphysemaa smoker, centriacinar emphysemaPanacinar emphysema Periacinar emphysemaMicroscopic examination Destruction of alveoli wallsAdjacent alveoli fuseDeformation or compression of

16、 vasculature of lungWith or without bronchitis or bronchiolitisPathological ChangePulmonary EmphysemaPulmonary Emphysemabullae lung2cm in diameterAdjacent to pleuraCause spontaneous pneumothorax in young adultsPulmonary EmphysemaPathological ChangeClinical CourseProgressively dyspnea with prolonged

17、expiration Barrel-chestPulmonary function damage: slowing of forced expirationRecurrent infection in patients with chronic bronchitisComplication: pneumothorax, cor pulmonalePulmonary EmphysemaEmphysemaDefined anatomically as enlargement of alveolar airspaces with destruction of elastin in wallsFreq

18、uent association with chronic bronchitisBronchiectasisDefinition: a chronic necrotizing infection of the bronchi and bronchiole leading to permanent dilation of these airways Clinical manifestation: cough with large amounts of foul-smelling purulent or bloody sputumBronchiectasisEtiologyBronchial ob

19、structionDiffused obstructive lung diseasesTumorForeign bodiesNecrotizing or suppurative pneumoniaCongenital or hereditary conditionsCystic fibrosisImmunodeficiencyKartagener syndromeBronchiectasisObstructionChronic persistent infectionPermanent dilation of bronchi and bronchiolesPathogenesisPeribro

20、nchial fibrosis and scarring traction on the wallBronchial walls damageClearance mechanisms Accumulation of exudatePathological ChangeLower lobes, bilateralCylindroid and saccular dilated airwaysDilated airway direct out to the pleural surfacesDamage of epitheliumAirway walls destruction and fibrosi

21、s Acute and Chronic inflammatory exudationBronchiectasisBronchiectasisMacroscopic:Diffuse or localized enlarged, fibrotic cartilaginous airwaysDilated airways extend to pleural surfaceCommonly filled with mucopurulent materialMicroscopicEctatic, dilated airwaysChronically inflamed wallFollicular bro

22、nchitis may be presentAcute and organizing pneumonia is commonBronchiectasisBronchiectasis Definition: Asthma is characterized by episodic, reversible bronchospasm resulting from an exaggerated bronchoconstrictor response to various stimuli.Clinically manifested by episodic dyspnea, cough and wheezi

23、ng TypesExtrinsic asthmaIntrinsic asthmaBronchial asthmaBronchial asthmaEtiology & PathogenesisEtiologyVarious stimuliExaggerated bronchoconstrictor responsePathogenesisImmediate reactionLate-phase reactionBronchial asthmaBronchial asthma Immediate reaction Antigen-induced cross-linking of IgE Bronc

24、hospasm last-phase reaction Recruited inflammatory cells Damage to the epitheliumPathological changesOverdistention of the lungsBronchi and bronchiolesOcclusion by thick, tenacious mucus plugsCharcot-Leyden crystalsCurschmann spiralsEdema and inflammation in walls with prominent eosinophilsPatchy ne

25、crosis and shedding of epithelium cellsHyperplasia of mucous glands or increased numbers of goblet cellsThickened basement membraneHypertrophy and hyperplasia of the smooth muscleBronchial asthmaBronchial asthmaMacroscopicMucous plugging of airwaysOverdistention with abundant air trapping Restrictiv

26、e Lung Diseases Characterized by reduced complianceInterstitial fluid or fibrosis produced a “stiff lung”Abnormalities in the ventilation-perfusion ratioTypesAcute: Adult Respiratory Distress Syndrome (ARDS)Chronic Occupational and Environmental silicosisDrug or treatment related Immunologic sarcoid

27、osisIdiopathic idiopathic pulmonary fibrosis (IPF)Adult Respiratory Distress Syndrome (ARDS)(Diffuse Alveolar Damage)Definition A syndrome caused by diffuse alveolar capillary damageCharacterized clinically by acute life-threatening respiratory insufficiency, severe arterial hypoxemia that is refrac

28、tory to oxygen therapy and that may progress to extrapulmonary multisystem organ failure. Synonyms Shock lung / Traumatic wet lungs / Adult respiratory failureARDSEtiology & PathogenesisARDSDirect lung injuryEndothelial and/or epithelial injuryVascular permeabilityImbalance of proinflammatory and an

29、ti-inflanmmatory cytokinesIL-8,IL-1,TNF,TGF, PDGFIndirect lung injuryLoss of diffusion capacityAlveolar floodingNeutrophils & macrophages activationHyaline membranes formationPathological ChangeGrosslyAcute edematous stage (0-7 days)heavy, firm, red, boggy, airlessProliferative phase (1-3 weeks)Fibr

30、otic phaseARDSMicroscopicCongestion, edema and fibrin exudationHyaline membranes Fibrin-rich edema fluid & Remnants of necrotic epitheliums Proliferation of type II pneumocytes phagocytosis of hyaline membranes by macrophagesOrganization and pulmonary fibrosisARDSPathological ChangeAcute edematous s

31、tageProliferative phaseSilicosisDefinition: A lung disease caused by inhalation of crystalline silicon dioxide (silica, SiO2), characterized by progressive silicotic nodules and diffuse pulmonary fibrosis. Currently the most prevalent chronic occupational disease in the worldPneumoconiosis includes

32、diseases induced by organic particulates and chemical fumes and vaporsSilicosisInvolving pulmonary tissue, pleura and lymph nodesSilicotic nodule2-3mm , round, well-demarcatedcollagenous scars with central cavityProgressive massive fibrosisSilicosisPathological ChangePathological Change Silicotic no

33、duleconcentric layers of hyalinzed collagenPolarized microscopy: birefringent silica particles Diffused interstitial fibrosisSilicosisChronic cor pulmonaleDefinition Cor pulmonale is the disease of the right-sided cardiac chambers caused by pulmonary hypertension resulting from chronic pulmonary par

34、enchymal or pulmonary vascular disease. May be acute or chronicThe average incidence is 0.46%Cor pulmonaleDisorders that predispose to cor pulmonaleChronic lung diseases COPD: most commonChronic restrictive lung diseasesDiseases of pulmonary vesselsPulmonary embolism: acutePrimary pulmonary artery h

35、ypertensionDisorders affecting chest movementCor pulmonalePathologenesisCor pulmonalePulmonary resistanceArteriolar spasmDecrease in capillary bedRemodeling of vascular structureThrombosisRestriction of chest movementPulmonary hypertensionPathological ChangeRight ventricular (and/or atrium) progress

36、ively hypertrophy (compensation) & dilation (decompensation)Heart enlargement with blunting of the apexWeight 300gRight ventricular wall 0.5cmCor pulmonalePathological ChangePrimary pulmonary diseases Thickening Alterations of pulmonary arteriole wall Intimal hyperplasiaMedial hypertrophySecondary t

37、hrombosis and organizationCor pulmonaleClinical CourseThe symptoms and signs of primary chronic pulmonary diseasesRespiratory failureRight-sided congestive heart failureHepatic congestionAscitesEdema of the lower extremitiesComplication Pulmonary encephalopathyCor pulmonaleCor pulmonalePneumoniaDefi

38、nition: Acute Exudative inflammation of lung, Commonly seenEtiology Infective: Bacterial/ Viral/ Fungal/ Mycoplasmal Physical/ Chemical/ AllergicPathological change 1) Location: Alveolar/Interstitial 2) Range: Lobar / Segment/ Lobular 3) Feature: Serous/ Fibrinous/ Suppurative/ Hemorrhagic/ Granulom

39、aPneumoniaPneumoniaLobar PneumoniaAn acute bacterial infection of a large portion of a lobe or an entire lobe Caused by streptococcus pneumoniaeCharacterized by diffused fibrinous exudative inflammation of alveoli. Common in young menClassic case is now infrequent owing to effective antibiotics appl

40、ication. Lobar PneumoniaDefinitionAn acute bacterial infection of a large portion of a lobe or an entire lobe Etiology and PathogenesisEtiologic agent Streptococcus pneumonia (type1，3，7) 90-95%, Predisposed agent (Imparied resistance of airway) Smoking, Flu, Alcoholic, Fatigue, ImmunodeficiencyA lob

41、ar distribution appears merely to be a function of the virulence of the organism and the vulnerability of the hostLobar PneumoniaPathological ChangeWide-spread Fibrinous inflammation of alveoli within an entire lobeFour stages: Consistency of exudationCongestion (1-2 days)Red hepatization Gray hepat

42、izationResolution (7-10days)Lobar Pneumonia3-7 daysRed hepatizationGray hepatizationCongestionGrosslyHeavy, Boggy and RedMicroscopic Serous exudation with few neutrphilsVascular engorgement Numerous bacteriaLobar PneumoniaRed hepatizationGrosslyRed/ Firm/ Airless Liver-like MicroscopicMassive conflu

43、ent exudation filling the alveolar spaces Red cells/ Neutrophils/ Fibrin Lobar PneumoniaGrey hepatization GrosslyGrayish brownDry surfaceLiver-likeMicroscopic Disintegration of red cells Persistence of fibrinosuppurative exudationLobar PneumoniaResolutionGrossly Soften of consolidation MicroscopicGr

44、anular, semifluid debris in alveoli The exudate is resorbed, ingested by macrophages, or coughed upNo structure damageLobar PneumoniaYoung men, Malaise, fever Cough productive of sputumPleuritic pain (accompanied by pleuritis)Characteristic radiology: radiopaque, well-circumscribed lobeClinical pict

45、ure is significantly modified by the administration of antibioticsClinical CourseLobar PneumoniaComplicationCarnificationPulmonary abscessPurulent pleuritisSepticemiaInfective shockLobar PneumoniaPulmonary CarnificationAdhesive pleuritisPurulent pleuritisabscessLobular PneumoniaBronchopneumonia0.5-2

46、cmlobuleDefinitionAcute suppurative inflammation of bronchiole and around pulmonary tissueGenerally bilateral, multilocated, based on lobuleCommonly seen in children and old people Etiology and Pathogenesis Etiologic agent Staphylococci/ pneumococci / Streptococci / H. influenzae Predisposed agent I

47、mpaired resistance of airway, commonly seen as a complicationUsually secondary to pre-existing disease.Lobular Pneumonia Bronchopneumonia Grossly bilateral, multilobar basal, patchy distribution consolidation 1-2 cm in diameterCentred on bronchioles or bronchiPathological ChangeLobular Pneumonia Bro

48、nchopneumoniaLobular Pneumonia BronchopneumoniaPathological ChangeMicroscopicSuppurative inflammation of bronchioles Neutrophil-rich exudation within alveolar spacesDestruction of alveolar walls Lobular Pneumonia BronchopneumoniaMicroscopicVariable exudation Neutrophils, Serous fluid, fibrin, macrop

49、hage, RBC小葉性肺炎：病灶壞死融合abscess小葉性肺炎Viral and Mycoplasmal PneumoniaPrimary Atypical PneumoniaInterstitial PneumoniaDefinitionCharacterized by inflammatory changes confined to the alveolar septa and pulmonary interstitiumAtypical denotes the lack of alveolar exudateCaused by variable viruses, mycoplasma

50、 and uncertain agentWith variety pathological change and clinical courseInterstitial Pneumoniaviral pneumoniaPathological ChangeMicroscopicDepends on the severity of the diseaseThe septa are widened and edematous.Chronic inflammation confined within the walls of the alveoli.Lymphocytes and mononucle

51、ar cell infiltration, widen alveolar septa.Interstitial PneumoniaPathological ChangeMicroscopicAlveolar spaces are remarkably free of cellular exudate.In severe cases, diffuse alveolar damage with pink hyaline membranes may develop. Interstitial PneumoniaViral Inclusions:Affected cells are strikingl

52、y enlarged, and they show cellular and Nuclear polymorphism, Prominent intranuclear basophilic inclusionsspanning half the nuclear diameter are usually set off from the nuclear membrane by a clear halo.Pathological Change病毒包涵體是診斷病毒性肺炎的依據(jù)。在增生的支氣管上皮細胞、支氣管腺體上皮細胞、肺泡上皮細胞或多核巨細胞內見到的一種圓形或橢圓形紅染球形小體，約紅細胞大小，周圍

53、有透明暈。本質是多量病毒顆粒聚集而成。viral pneumonia呼吸道合胞病毒包涵體：在上皮細胞胞漿內呼吸道合胞病毒包涵體：在上皮細胞胞漿內麻疹病毒包涵體在細胞核和胞漿中禽流感病毒Lung cancer GrosslyCentral type 50% cases take origin from first to third-order bronchiLung cancerPathological ChangeLung cancerCentral typeLarge squamous cell carcinoma extending into the pleura and associat

54、ed with central cavitation. Pathological ChangeGrosslyPeripheral type 30-40%Arise in the periphery of the lungs, from the alveolar cells or terminal bronchiolesLung cancerGrosslyDiffuse type2-5%Lung cancerPathological ChangeHistological ChangeClassification Squamous carcinoma: 25-30% Adenocarcinoma

55、: 30-35% Large cell carcinoma: 10-15% Small cell carcinoma (SCLC): 20-25%Lung cancerMost common in menClosely related with smokingCentral typeVary from small to large, obstructive lesions, commonly cavitate.Usually found in segmental or subsegmental bronchi.Incidence: 1/3Squamous cell carcinomaLung

56、cancerOrigin: Squamous metaplasiaAtypical hyperplasiaIn situ carcinomaHistologically, these tumors range from well-differentiated squamous cell neoplasms showing keratin pearls and intercellular bridges to poorly differentiated neoplasms.Squamous cell carcinomaAdenocarcinoma Most common in women Per

57、ipheral typeDesmoplasia can be prominent(“scar carcinomas”) Prognosis worse than SC 80% contain mucin Incidence: 1/3Lung cancerGlandular differentiation presentDifferent growth patterns:LepidicPapillaryAcinarmicropapillarySolidAdenocarcinoma MicroscopicPrimary pulmonary adenocarcinoma with signet ri

58、ng cells, a most unusual finding in this location. ALK 免疫抑制劑治療有效Large cell carcinomaClinical:10%-20% of lung carcinomasAn anaplastic carcinomaStrongly associated with smoking.Highly malignantLung cancerLarge cell carcinomaMacroscopic:Central or peripheral.Typically large, with pleural invasion.Lung

59、cancerLarge cell carcinomaSheets and nests growth pattern with extensive necrosis.Large cells, usually anaplastic,and have large vesicular nuclei with prominent nucleoli.Lack definitive evidence of squamous or glandular differentiation by light microscope.Can have giant cell, clear cell, or spindle

60、cell changes.Lung cancerLung cancerSmall cell carcinoma Young or middle-aged men Strong relationship to smoking arise from Kulchitsky cellsIncidence : 1/4Highly malignant, with earlymetastases; chemotherapy responsive.Lung cancerSmall cell carcinoma: Macroscopic Most are central type, 70% of cases p