《病理学》教学课件：6 呼吸系统疾病

1、Diseases of Respiratory System,呼吸系统疾病 2016.4,Aantomy and Function,Upper respiratory tract nasopharynx(鼻咽), larynx(喉) Lower respiratory tract trachea(气管), bronchi(支气管) Right bronchus diverging at a lesser angle, foreign material more frequently aspirated Lobar, segmental, lobular,1. Bronchial tree (通

2、气） conducting portion from main bronchi to terminal bronchioles 2. Terminal lung unit (gas exchange) respiratory portion from respiratory bronchiole to alveoli,Bronchial tree 1.Mucosa pseudostratified ciliated column cell goblet cell, producing mucus basal cell-stem cell small granules cell highly s

3、pecialized bronchial lining cells, containing neurosecretory granules 2.Submucosal gland serous and mucus 3.Wall smooth muscle contractile elastic fibers, provide flexibility cartilage plate, for support,Bronchioles 1mm 1.Mucosa ciliated epithelial cell Clara cell (non-ciliated secretory cell) 2.Wal

4、l smooth muscle no gland no cartilage,Respiratory membrane Alveoli type I cells 95% of the surface gas permeable Alveoli type II cells 5% of the surface producing surfactant, lowering the surface tension Involved in the repair of alveolar epithelium Capillary network 85%95% of the surface Arranged i

5、deally for gas exchange,Pulmonary vasculature Double blood supply, protecting from ischemia Pulmonary circulation: functional Bronchial system: nutrient Pulmonary lymph circulation Deep and superficial network draining to the hilum lymph nodes No lymphatics in most alveolar walls,Location,Host Defen

6、se Mechanism,Upper Airways Nasopharynx Oropharynx,Nasal hair Turbinates Mucociliary apparatus IgA secretion Saliva Sloughing of epithelial cells Local complement production Interference from resident flora,Defense mechanisms,Conducing Airways Trachea, bronchi Lower Respiratory Tract Terminal airways

7、, alveoli,Cough, epiglottic reflexes Sharp-angled branching of airways Mucociliary apparatus Immunoglobulin production(IgG, IgM, IgA) Alveolar lining fluid(surfactant, immunoglobulin, complement, fibronectin) Cytokines(IL-1, TNF) Alveolar macrophages Polymorphonuclear leukocytes Cell-mediated immuni

8、ty,Lung defense mechanisms,Remarks 1. Respiratory system is communicating with external enviroment, from which pathogens, noxious gas or particles,so it is susceptible to the diseases. 2.All blood from the body will pass through the lung and the biological pathogens (e.g bacterial, neoplasmic) embol

9、us etc. can be trapped in the lung.,Remarks 3. The lung is closely related to the heart, not only by their location but also by the pulmonary circulation. 4. Damage and disturbance to the specialized structures and function of the lung will lead to the development of the diseases specific to the lun

10、g. (e.g damage to the wall of bronchial tree, obstruction of bronchioles and disintegration of alveolar/capillary membrane),silicosis,I. Pneumonia 肺 炎,Pulmonary infections 1/6 of all deaths in the U.S.A Causes Epithelial surface exposed to contaminated air Nasopharyngeal flora aspirated during sleep

11、 Lung parenchyma vulnerable to virulent organisms Defects in innate immunity and humoral immunodeficiency Cell-mediated immune defects Lifestyle factors (eg. cigarette smoke, alcohol) caused Facilitating infections,Pneumonia can be very broadly defined as any infection in the lung Acute, fulminant o

12、r chronic Histologic spectrum Fibrinopurulent alveolar exudate acute bacterial pneumonias Mononuclear interstitial infiltrates viral and other atypical pneumonias Granulomas and cavitation chronic pneumonias,Acute Bacterial Pneumonias Lobar pneumonia Consolidation of an entire lobe Lobular pneumonia

13、 (Bronchopneumonia) Scattered solid foci in the same or several lobes,Lobar Pneumonia,Contiguous airspaces of part or all of a lobe are homogeneously filled with an exudate that can be visulized on radiographs as a lobar or segmental consolidation. A disease of acute exudative inflammation,Pathogene

14、sis Healthy adult Host defenses depressed Normal inhabitants of the oropharynx and Nasopharynx, Pneumococcus Aspiration of pharyngeal flora Lower lobes or the right middle lobe most frequently involved,Pathology and clinical features A rather clear cut 4 staged battle in the affected lung in a perio

15、d about 7-8 days A complete and unsloppy recovery,Four stages a. Congestion b. Red hepatization c. Gray hepatization d. Resolution,Congestion (1-2d) GrossHeavy, red, boggy LMVascular congestion Proteinaceous fluid containing numerous pneumococci filling the alveoli Scattered neutrophils Clinical fea

16、ture Acute, fever, chill Crepitation, moist rale Chest radiograph dim, uniform shadow,Red hepatization (3-4d) GrossA liver-like consistency A fibrinous or fibrinopurulent exudate of pleura LMIntra-alveolar hemorrhage Massive neutrophils Fibrin packing within alveolar spaces Numerus pneumococci detec

17、ted Clinical feature Hemoptysis (rusty) Chest radiograph: a solid appearance extending to entire lobes or segments Dyspnea, debility, chest pain,Gray hepatization (4-6d) “A turning point” GrossDry, gray, firm, granular LM Red cells lysed Fibrinous exudate persisting within alveoli No pneumococci det

18、ected Clinical feature,Resolution Gross Pleural resolved or organized fibrous thickening or permanent adhesions LM Exudates within alveoli enzymatically digested either resorbed or expectorated Clinical featuresrecovery,Complications Not common Death rate: 3-5% Carnification (肺肉化, organizing pneumon

19、ia) Pulmonary abscess and pyothorax Septicemia Toxic pneumonia,Lobular pneumonia (Bronchopneumonia),Resulting from an initial infection of the bronchi and bronchioles with extension into the adjacent alveoli A purulent inflammation A patchy distribution of inflammation that generally involves more t

20、han one lobe Most frequently bilateral and basal,Pathogenesis Organisms Relatively avirulent Pneumococcus, staphylococcus, and streptococcus, etc. “Opportunistic infection” Often a secondary disease Terminally ill patients, infants and taking immunosuppressive drugs, etc. A common cause of death “ t

21、erminal pneumonia ” Aspiration pneumonia,Pathology and clinical features Gross In the lower and posterior portions Because of the tendency for secretions to gravitate into the lower lobes 3-4cm, gray to yellow Confluence of foci the appearance of a lobar consolidation Hyperemic and edematous surroun

22、ding areas Scattered irregular foci of pneumonia are centered on terminal bronchioles and respiratory bronchioles,LM Focal suppurative exudate filling the brochi, bronchioles and adjacent alveolar spaces clinical features,Complications Common Poor in prognosis “ terminal pneumonia ” Abscess formatio

23、n Empyema Meningitis, arthritis, infective endocarditis Respiratory insufficient Cardiac insufficient,Comparison between lobar and lobular pneumonia,lobar lobular,Primary A definite disease entity,Secondary Not a definite entity,Primary or secondary,Age distribution,A disease of healthy adults,Often

24、 infants and the elderly,Causative organisms,Mostly pneumococcus,At least 20 different agents, often commensals or relatively avirulent,Prognosis & recovery,A complete recovery,Poor in prognosis, “terminal pneumonia” Multiple complications,lobar lobular,Pathologic features,An acute exudative inflamm

25、ation,A purulent inflammation,Frequently bilateral and basal,Lower lobes or the right middle lobe,Gross,Liver-like, or gray, dry, firm, granular,A pachy distribution,LM,A fibrinous exudate,Centrally located bronchioles which are intensely inflammed and filled with pus,Interstitial pneumonia Atypical

26、 pneumonia Modest sputum production No physical findings of consolidation White cell count moderately elevated Mononuclear inflammatory infiltration in pulmonary interstitium,Pathogenesis Mycoplasma the most common cause Viruses, Chlamydiae and Rickettsiae, etc. A primarily upper respiratory tract i

27、nfection with coryza, pharyngitis, laryngitis and tracheobronchitis, Damage to/denudation of the epithelium Children & young adults frequently attacked Sporadically or as local epidemics Viral infections at any age Influenza viruses A and B adults,-,Mucociliary clearance,+,Secondary bacterial infect

28、ions,Pathology GrossPatchy, involving whole lobes bilaterally or unilaterally Red-yellow, congested and subcrepitant LMInflammatory reaction largely confined within the walls of alveoli Septa widened and edematous A mononuclear inflammatory infiltrate Free of cellular exudate Full-blown diffuse alve

29、olar damage with hyaline membranes in severe cases A mixed histologic picture with secondary infection,Clinical course Extremely varied a severe upper respiratory tract infection chest radiographs transient, ill-defined patches mainly in the lower lobes physical findings characteristically minimal P

30、rognosis good, complete recovery Most serious infections complicated by bacterial superinfection poor in prognosis,SARS (Severe acute respiratory syndrome),First identified in November 2002 in China SARS coronavirus Laboratory diagnostic criteria Serological test of anti-SARS CoV Clinical features F

31、ulminant, fever, contagious Rapidly progressing to sever respiratory syndrome Pathological feature Severe atypical pneumonia,Atelectasis (肺不张/肺萎陷）,Loss of lung volume caused by inadequate expansion of airspaces Categories: Resorpation Atelectasis A mucous or mucopurulent plug, foreign body, tumors,

32、enlarged lymph nodes, vascular aneurysms, etc. Compression Atelectasis Accumulation of fluid,blood,or air within the pleural cavity Elevated position of diaphragm,Microatelectasis Loss of surfactant, postsurgical atelectasis Contraction Atelectasis Local or generalized fibrotic changes in the lung o

33、r pleura,Atelectasis (肺不张/肺萎陷）, Adult Respiratory Distress Syndrome (ARDS),Brief introduction Diffuse alveolar damage Injury of alveolar epithelial, basement membrane and capillary endothelial cells (the respiratory membrane) Developing rapidly progressive respiratory failure Accompanied by Decrease

34、d lung compliance Hypoxemia (cyanosis) Extensive radiological opacities in both lungs (“white-out”),Pathogenesis induced by a large variety of insults Pulmonary Respiratory tract infections, aspiration of gastric contents, inhalation of toxic gases, near-drowning, radiation pneumonitis, a large asso

35、rtment of drugs and other chemicals Out of pulmonary Sepsis, shock, DIC, etc. Injuries of respiratory membrane,Oxygen radicals Hydrolytic enzymes Cytokines,Activation of the complement system,Sequestration of neutrophils and macrophage,Damage to the capillary endothelium Damage to the epithelial jun

36、ctions,Exudation of fluid and proteins from the interstitium into the alveolar spaces,Pathology Gross Early stage Wine, liver-like, large, heavy Cut surface consolidation, dim fluid 1 week later-Diffuse gray, lustering,3 phases Exudative phase (1-3d) Edema, exudation of plasma proteins Hyperemia, he

37、morrhage Accumulation of inflammatory cells Hyaline membranes Damage to both endothelial cells and type I pneumocytes Sloughing of type I cells & appearance of denuded basement membranes Fibrin thrombi in capillaries and arterioles,Proliferative phase (3-10d) Proliferation of type II pneumocytes and

38、 fibroblasts Alveolar septa thickened Fibrotic phase Diffuse interstitial fibrosis “Honeycomb lung” Multiple cyst-like spaces throughout the lung Remodeling of the lung architecture,Clinical feature Tachypnea, dyspnea, cyanotic, etc. Radiologically bilateral diffuse shadow Prognosis Poor, progressiv

39、e, 50% died in acute phase Scarred lungs, respiratory dysfunction, pulmonary hypertension, etc. Recovering normal pulmonary function 46 months later,Idiopathic pulmonary fibrosis,characteristics: patchy fibroblast expansion tissue remodeling excessive accumulation of the extracellular matrix classfi

40、cation usual interstitial pneumonia Desquamative Interstitial Pneumonia Respiratory Bronchiolitis Interstial Lung Disease Acute Interstitial Pneumonia Nonspecific Interstitial Pneumonia, Chronic Obstructive Pulmonary Diseases (COPD) 慢性阻塞性肺部疾病,Conception A group of diseases in which fundamental disor

41、der is the increase resistance to respiratory airflow caused by diseases affecting the conducting airway and/or lung parenchyma Including Chronic bronchitis Emphysema Bronchiectasis Asthma,Air flow can be reduced in two ways By increasing the resistance to air flow Narrowed airways-chronic bronchiti

42、s or asthma By reducing the outflow pressure Loss of elastic recoil - emphysema Small airway disease Obstruction of small bronchioles2mm narrow channel thin wall lack of cartilage less ciliated cells,Chronic bronchitis Chronic inflammation of bronchi and bronchioles Defined clinically as the presenc

43、e of a persistent productive cough without a discernible cause for at least 3 consecutive months in at least 2 consecutive years,Pathogenesis Physical and chemical factors cold, humid primarily a disease of cigarette smoking, air pollution (SO2, NO2, Cl2, etc.) Infections Bacteria, virus inflammatio

44、n,Mucous epithelium injured Destruction of ciliated columnar cell, interfering of cilia movement, Metaplasia of the bronchial epithelium Inflammation extending deeply into the wall Hypersecretion of the bronchial mucous glands, hypertrophy of mucous glands, smooth muscle and elastic fibers injured i

45、nvolvement of bronchioles Mucus plugging, thickening of the wall resulting in narrowing and obstruction of the lumen incapability of IgA synthesis or phagocytosis,Pathology Gross Mucous membrane dusky red (hyperemic) and swollen by edema fluid Lumen filled with mucus and pus Dilated bronchial gland

46、ducts “Pits” on the surface of the bronchial epithelium,LM Epithelial damage Alternation of cilia Epithelial cell-degenerative, proliferative Increased number of goblet cells Squamous metaplasia Hypertrophy of mucinous glands “ The reid index” A measure of the increase in the size of the mucous glan

47、ds,inflammation in the wall Infiltration of lymphocytes and macrophage Destruction of smooth muscle (hypertrophy, hyperplasia) Destruction of elastic fibers Fibrosis Destruction of cartilage Atrophy, degeneration Expiratory outflow obstruction,Clinical course A prominent cough and the production of

48、sputum More severe in the winter months From hibernal to perennial Accompanied by hypercapnia, hypoxemia, cyanosis and emphysema Complicated by pulmonary hypertension & cardiac failure (cor pulmonale) Recurrent infections and respiratory failure Treatments Stoping smoking, prompt antibiotic treatmen

49、t, administration of bronchodilator drugs, etc.,Emphysema (肺气肿) Defined as a state of pathologically increased inflation of terminal lung unit Permanent enlargement of the acinus with destruction of their walls but without fibrosis Overinflation without destruction of wall A clear association betwee

50、n heavy cigarette smoking and emphysema,Types and pathology According to its distribution in the lobule and acinus Acinus Distal to the terminal bronchiole including: the respiratory bronchiole, alveolar ducts, alveoli A lobule A cluster of three to five acini three types centriacinar panacinar dist

51、al acinar,Centriacinar type Central or proximal parts of the acini affected while distal alveoli spared More common and severe in the upper lobes, particularly in the apical segments Severe cases: Distal acinus also involved A sequence of cigarette smoking,Panacinar type Entire Acini enlarged from t

52、he respiratory bronchiole to the terminal blind alveoli More commonly in the lower lung zones Pale and voluminous lungs often obscuring the heart in autopsy 1-antitrypsin deficiency,Distal acinar (paraseptal) type Distal part of the acinus dominantly involved Distribution along the lobular septa At

53、the margins of the lobules and adjacent to the pleura Adjacent to areas of fibrosis, scarring, or atelectasis More severe in the upper half of the lungs Characteristic findings multiple, contiguous, enlarged airspaces that range in diameter from 2.0cm, sometimes forming cystlike structures (bullae),

54、 Cause of the cases of spontaneous pneumothorax in young adults,LM Thinning and destruction of alveolar walls Marked enlargement of airspaces Fibrosis of respiratory bronchioles Collapsing during expiration,Pathogenesis Incomplete obstruction or narrow of bronchiole chronic bronchiolitis obstruction

55、 of the lumen destruction of the wall and the adjacent alveoli increasing the resistance to the expiratory airflow Injury of alveolar wall, The protease-antiprotease imbalance A genetic deficiency of 1-antitrypsin Neutrophils and macrophages releaseing protease-containing granules Elastic tissue des

56、truction Destructive effect of high protease activity in subjects with low antiprotease acitivity,Normally present in serum, tissue fluids, and macrophages, a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation,Clinical features Dyspnea: the usual first s

57、ymptom Respiratory acidosis Barrel-chest Prolonged expiration, hyperventilation A chronic bronchitis Cyanotic, cor pulmonale, edema, secondary pulmonary hypertension,Bronchiectasis (支气管扩张症) Definition The permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic s

58、upporting tissue, resulting from or associated with chronic necrotizing infections.,Not a primary disease but secondary to persisting infection or obstruction A characteristic symptom complex dominated by cough and expectoration of copious amounts of purulent sputum Common in older children and youn

59、g adults,Pathogenesis Bronchial obstruction Tumors, foreign bodies, impaction of mucus Localized to the obstructed lung segment Congenital or hereditary conditions Cystic fibrosis, immunoglobulin deficiencies, Kartagener syndrome Necrotizing or suppurative pneumonia Childhood pneumonias that complicated measles, whooping cough and influenza,Pathology Gross Usually the lower lobes bi