1、Obstructive Lung DiseasesRobert W.AllanDepartment of PathologyObstructive Lung Diseases-“You cant get air out”-Chronic Obstructive Pulmonary Diseases(COPD)Emphysema Chronic Bronchitis Asthma BronchiectasisObstructive Lung Diseases-“You cant get air out”-Share features of dyspnea and chronic(recurren
2、t)obstruction to airflow Usually occur in combinations,with one predominating Cigarette smoking,is common to chronic bronchitis and emphysemaEmphysema-Four major types Centriacinar(centrilobular)Panacinar(panlobular)Paraseptal(distal acinar)IrregularI will only discuss Centriacinar and Panacinar Emp
3、hysemaEmphysemaCentriacinar Emphysema-In this type of emphysema the central or proximal parts of the acini,formed by respiratory bronchioles,are affected,whereas distal alveoli are spared-Thus,both emphysematous and normal airspaces exist within the same acinus and lobule.The lesions are more common
4、 and usually more severe in the upper lobes,particularly in the apical segments.-Inflammation around bronchi and bronchioles is common.In severe centriacinar emphysema,the distal acinus may also be involved,and differentiation from panacinar emphysema becomes difficult.-Centriacinar emphysema occurs
5、 predominantly in heavy smokers,often in association with chronic bronchitis.Centriacinar EmphysemaAirspace Enlargement in Center of AcinusUpper lobe predominantInvolves mainly the central portion of the acinus-there are intact alveoli at the periphery of the acinusPanacinar Emphysema-In this type,t
6、he acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli-The prefix“pan”refers to the entire acinus but not to the entire lung.-In contrast to centriacinar emphysema,panacinar emphysema tends to occur more commonly in the lower zones and in the anter
7、ior margins of the lung,and it is usually most severe at the bases.-This type of emphysema is associated with 1-antitrypsin(1-AT)deficiencyPanacinar EmphysemaDiffuse Enlargement of AcinusLower lobe predominantInvolves whole acinus I cant find any normalPathogenesis EmphysemaEmphysema-clinical-The cl
8、inical manifestations of emphysema do not appear until at least one third of the functioning pulmonary parenchyma is damaged-Dyspnea is usually the first symptom;it begins insidiously but is steadily progressive.In some patients,cough or wheezing is the chief complaint,easily confused with asthma.-W
9、eight loss is common and can be so severe as to suggest a hidden malignant tumor.Classically,the patient is barrel-chested and dyspneic,with obviously prolonged expiration,sits forward in a hunched-over position,and breathes through pursed lips.-Expiratory airflow limitation,best measured through sp
10、irometry,is the key to diagnosis.Emphysema-clinical-In individuals with severe emphysema,cough is often slight,overdistention is severe,diffusion capacity is low,and blood gas values are relatively normal at rest.Such patients may overventilate and remain well oxygenated,and therefore are somewhat i
11、ngloriously designated pink puffers-Development of cor pulmonale and eventually congestive heart failure,related to secondary pulmonary vascular hypertension,is associated with a poor prognosis.Death in most patients with emphysema is due to(1)respiratory acidosis and coma,(2)right-sided heart failu
12、re,and(3)massive collapse of the lungs secondary to pneumothorax.-Treatment options include bronchodilators,steroids,bullectomy,and,in selected patients,lung volume reduction surgery and lung transplantation.Chronic Bronchitis-Chronic bronchitis is defined clinically as persistent cough with sputum
13、production for at least 3 months in at least 2 consecutive years,in the absence of any other identifiable cause.-The primary or initiating factor in the genesis of chronic bronchitis seems to be long-standing irritation by inhaled substances such as tobacco smoke(90%of patients are smokers)-The earl
14、iest feature of chronic bronchitis is hypersecretion of mucus in the large airways,associated with hypertrophy of the submucosal glands in the trachea and bronchi.-Proteases released from neutrophils,such as neutrophil elastase and cathepsin,and matrix metalloproteinases,stimulate this mucus hyperse
15、cretion.-As chronic bronchitis persists,there is also a marked increase in goblet cells of small airwayssmall bronchi and bronchiolesleading to excessive mucus production that contributes to airway obstruction.-Infections seem to be secondary and may lead to exacerbations-smoking(as discussed)leads
16、to increased susceptibility to infectionsChronic BronchitisChronic bronchitis-marked increased in the number of submucosal mucus glandsChronic BronchitisGoblet cell metaplasia and an increase in chronic inflammatory cells(lymphocytes and plasma cells)COPD-comparisonPredominant BronchitisPredominant
17、EmphysemaAge40-45 years50-75 yearsDyspneaMild,lateSevere,earlyCoughEarly,copious sputumLate,scanty sputumInfectionsCommonOccasionalRespiratory insufficiencyRepeatedTerminalCor PulmonaleCommonRare(terminal)Airway resistanceIncreasedNormalElastic recoilNormalLowChest radiographProminent vessels,large
18、heartHyperinflation,small heartAppearanceBlue BloaterPink PufferCOPD-comparisonMany patients will have a combination of both featuresMr.Pink PufferMr.Blue BloaterCOPD-comparisonLecture/Lab-Obstructive Lung Diseases-Emphysema Predominant-Destruction of airspaces distal to the terminal bronchiole(i.e.
19、respiratory bronchiole outward)-This results in a loss of the elastic recoil of the lungs on expiration-This also results in loss of tethering or support of the most distal portions of the airway leading to collapse on expirationNormalElastic RecoilAirway supported by connective tissueDecreased Elas
20、tic Recoil=Lower FlowLoss of support=Airway collapses=Air gets trapped in lungLecture/Lab-Obstructive Lung Diseases-Chronic Bronchitis predominant-Airway obstruction is the main problem-Lots of work to breath and body“decides”to compensate by decreased ventilation with increase in cardiac output-Bod
21、y adapts to elevated PaCO2(central control in brain)and relies on the peripheral O2 sensor to drive respirationNormalElastic RecoilAirway supported by connective tissueChronic BronchitisElastic RecoilIncreased airway resistance due to thickened wall and secretionsAsthmaAsthma is a chronic inflammato
22、ry disorder of the airways that causes recurrent episodes of wheezing,breathlessness,chest tightness,and cough,particularly at night and/or in the early morning.Associated with bronchoconstriction and airflow limitation that is at least partly reversible,either spontaneously or with treatment.The ha
23、llmarks of the disease are:increased airway responsiveness to a variety of stimuli,resulting in episodic bronchoconstriction inflammation of the bronchial walls increased mucus secretion.Some of the stimuli that trigger attacks in patients would have little or no effect in subjects with normal airwa
24、ysAsthma Atopic(allergic)Non-atopic No evidence of allergen,usually post-infectious,may be due to airway hyperirritability Sometimes induced by exercise-particularly in cold-air Drug induced Aspirin in certain individuals,inhibiting the cyclooxygenase pathway of arachidonic acid metabolism without a
25、ffecting the lipoxygenase route tips the balance toward elaboration of the bronchoconstrictor leukotrienes Occupational(fumes,organic dusts,chemicals)Not well understood,Type I?,other hypersensitivity?C,Inhaled allergens(antigen)elicit a TH2-dominated response favoring IgE production and eosinophil
26、recruitment(priming or sensitization).D,On re-exposure to antigen(Ag),the immediate reaction is triggered by Ag-induced cross-linking of IgE bound to IgE receptors on mast cells.These cells release preformed mediators.Collectively,either directly or via neuronal reflexes,the mediators induce broncho
27、spasm,increased vascular permeability,and mucus production,and recruit additional mediator-releasing cells from the blood.E,The arrival of recruited leukocytes(neutrophils,eosinophils,and basophils;lymphocytes and monocytes)signals the initiation of the late phase of asthma and a fresh round of medi
28、ator release from leukocytes,endothelium,and epithelial cells.Factors,particularly from eosinophils(e.g.,major basic protein,eosinophil cationic protein),also cause damage to the epithelium.GM-CSF,granulocyte-macrophage colony-stimulating factor.Robbins 8th ed 2009Asthma vs.normalAtopic AsthmaBronch
29、ial biopsy specimen from an asthmatic patient showing eosinophilic inflammation,and muscle hyperplasiaBronchiectasisBronchiectasis is a disease characterized by permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue,resulting from or associated with chro
30、nic necrotizing infections.Associated conditions(things that lead to bronchiectasis)Congenital or hereditary conditions,including cystic fibrosis,intralobar sequestration of the lung,immunodeficiency states,and primary ciliary dyskinesia and Kartagener syndromes Postinfectious conditions,including n
31、ecrotizing pneumonia caused by bacteria(Mycobacterium tuberculosis,Staphylococcus aureus,Haemophilus influenzae,Pseudomonas),viruses(adenovirus,influenza virus,and fungi(Aspergillus species)Bronchial obstruction,due to tumor,foreign bodies,and occasionally mucus impaction,in which the bronchiectasis
32、 is localized to the obstructed lung segment Other conditions,including rheumatoid arthritis,systemic lupus erythematosus,inflammatory bowel disease,and post-transplantation(chronic lung rejection,and chronic graft-versus-host disease after bone marrow transplantation)Bronchiectasis-clinicalBronchie
33、ctasis causes severe,persistent cough;expectoration of foul-smelling,sometimes bloody sputum;dyspnea and orthopnea in severe cases;and occasional life-threatening hemoptysis.Episodic and are precipitated by upper respiratory tract infections or the introduction of new pathogenic agents.Paroxysms of
34、cough are particularly frequent when the patient rises in the morning,when changes in position lead to drainage of collections of pus and secretions into the bronchi.Obstructive respiratory insufficiency can lead to marked dyspnea and cyanosis.Bronchiectasis-pathogenesis Infection leading to obstruc
35、tion leading to airway damage Cystic fibrosis patients are the best example(have thick viscous secretions due to defect in ion transport)Bacterial infections(often chronic)lead to airway damage with destruction of the supporting tissue of the airway leading to dilatation and bronchiectasisBronchiect
36、asis-Notice the cystically dilated airways that are much to big to be present in the periphery of the lung-Microscopically these areas would contain abundant acute inflammatory cells,chronic inflammation and mucusBronchiectasis-Notice the enlarged airways on the right compared to the normal on the l
37、eft-One airway is highlighted to show how large it is at this level in the normal the airways are difficult to make outObstructive Lung Diseases-SUMMARY-DISEASEIMPORTANT POINTSEmphysemaCentriacinar most common SmokingPink PufferChronic bronchitisCough,sputum productionBlue bloaterAtopic asthmaType I,recurrent reversible airway constriction,Other types of asthmaGenerally not atopic(not type I hypersensitivity),aspirin,post-infectious,airway irritabilityBronchiectasisDilatation of airways leads to obstruction,recurrent infections,CF
