1、Chronic BronchitisDefinition:Chronic and unspecific inflammation of bronchi and the surrounding tissue.A clinical syndrome defined -chronic sputum production -Persistent cough -for at least 3 months -in at least 2 consecutive years Anatomic site -Bronchus 3PathogenesisChronic irritation of airwaysSm
2、okingDust Air pollutants The major risk factor for the development of chronic bronchitis is cigarette smokingInfective agents-secondary factornChronic inflammation nHypertrophy&hyperplasia of bronchial glands that secrete mucusnIncrease number of goblet cellsnCilia are destroyedChronic Bronchitis Pa
3、thophysiologyCilia DamagedInflammatory Cells Studies show that smokers with symptoms of chronic bronchitis have an increased number of inflammatory cells in their bronchial glands when compared with asymptomatic smokers.This inflammatory process consists predominantly of neutrophils and macrophages,
4、and of an increased proportion of CD8+T-lymphocytes.MacrophagesNeutrophilsMast cellsLymphocytes7Chronic Bronchitis-pathological sectionNarrowing of airway airflow resistancework of breathChronic Bronchitis Pathophysiology9Chronic Bronchitis PathophysiologyBronchospasm often occursEnd resultHypoxemia
5、HypercapneaPolycythemia(increase RBCs)Clinical manifestation Main symptoms:cough:chronic,long term,repeatedly expectoration:mucoid sputum,purulent sputum when infection wheezing:seen in some patientsClinical manifestation Sign:1.no obvious sign in early stage2.sometimes moist rales and rhonchi Diagn
6、osis Chronic cough and sputum production for 3 consecutive months in at least 2 successive years（3m/y2y）excluding other chronic lung diseasesEmphysema15Definition Pulmonary emphysema is described in clinical,radiological and physiologic terms,but the condition is best defined morphologically.It mean
7、s abnormal enlargement of airspaces distal to the terminal bronchioles with destruction of their wall.It is characterized by destruction and enlargement of alveoli.Etiology Environment FactorsCigarette smoking(In industrialized countries,cigarette smoking accounts for most cases of COPD)environmenta
8、l pollutantsOccupational dusts and chemicalsHost FactorsGenes:Alpha1-antitrypsin deficiencyLow birth weight is also a risk of COPDIn old person,the ability of the immune system is decrease,therefore bronchitis is more common in old people.Emphysema:PathophysiologyStructural changesHyperinflation of
9、alveoliDestruction of alveolar&alveolar-capillary wallsLung elasticity decreases18Loss of Lung Surface Area for Gas Exchange and Oxygen TransportLoss of Lung Surface area is due to death of Lung Endothelial CellsCigarette Smoke and Environmental Pollution may cause endothelial cell deathEmphysema:Pa
10、thophysiology19Pathology feature Alveolar walls become thinnerAlveolar sacs enlargementRupture of alveoli and formation of bleb20 Severe destruction of small airways can lead to the formation of large air pockets-known as bullae-that replace lung tissue.This form of disease is called bullous emphyse
11、mamicroscope21Bullous Emphysema Univ of AL at Birmingham,Dept.of Path.Dissection22A lateral chest x-ray of a person with emphysema.Note the barrel chest and flat diaphragm23CT image of the lung of a person with bullous emphysema.24Types of Emphysemacentrilobular emphysema panacinar emphysemaIn centr
12、ilobular emphysema,respiratory bronchioles are selectively and dominantly involved.26In panacinar emphysema,the enlargement and destruction of air space involve the acinus more or less uniformly.27emphysema is only a description of lung changes rather than a disease itself28Chronic Obstructive Pulmo
13、nary Disease(COPD)What is COPD?Global Strategy for Diagnosis,Management and Prevention of COPDnDefinitionnDiagnosis and AssessmentnTherapeutic OptionsnManage Stable COPDnManage ExacerbationsnManage ComorbiditiesREVISED 2011What is COPD?COPD,a common preventable and treatable disease,is characterized
14、 by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response to noxious particles or gases.COPD is a type of obstructive lung disease in which chronic incompletely reversible poor airflow(airflow limitation)and inability to breathe out f
15、ully(air trapping)exist.The poor airflow is the result of breakdown of lung tissue(known as emphysema)and small airways disease(known as obstructive bronchiolitis).The relative contributions of these two factors vary between people.33Relationship of COPD and Chronic bronchitis,Asthma or Emphysema34W
16、hy COPD is Important?COPD is the chronic disease that is showing progressive upward trend in both mortality and morbidityWHO predicts that COPD will become the third leading cause of death worldwide by 2030.Worldwide,COPD affects 329 million people or nearly 5 percent of the population.In 2013,it re
17、sulted in 2.9 million deaths,up from 2.4 million deaths in 1990.The number of deaths is projected to increase because of higher smoking rates and an aging population in many country.EconomicsGlobally,as of 2010,COPD is estimated to result in economic costs of$2.1 trillion,half of which occurring in
18、the developing world.Of this total an estimated$1.9 trillion are direct costs such as medical care,while$0.2 trillion are indirect costs such as missed workGlobal Strategy for Diagnosis,Management and Prevention of COPDRisk Factors for COPDLung growth and development肺的生物自然过程 Gender性别Age 年龄Respirator
19、y infections呼吸系统感染Socioeconomic status社会经济地位Asthma/Bronchial hyperreactivity哮喘/气道高反应性Chronic Bronchitis慢性支气管炎Genes遗传因素Exposure to particles粉尘暴露 Tobacco smoke吸烟 Occupational dusts,organic and inorganic有机、无机职业粉尘 Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings室
20、内空气污染（尤其是在通风不良的室内燃烧生物燃料做饭）Outdoor air pollution室外空气污染Risk Factors for COPDPathogenesisTobacco smoking is the most common cause of COPD,with a number of other factors such as air pollution and genetics playing a smaller role.In the developing world,one of the common sources of air pollution is poorly
21、 vented cooking and heating fires.Long-term exposure to these irritants causes an inflammatory response in the lungs resulting in narrowing of the small airways and breakdown of lung tissue,known as emphysema.41PathogenesisInflammationsImbalance of proteinases and antiproteinases in the lungsOxidati
22、ve stress are also important in the pathogenesis of COPD.Noxious particles and gasesLung inflammationHost factorsCOPD pathologyProteinasesOxidative stressAnti-proteinasesAnti-oxidantsRepair mechanisms43Mechanisms Underlying Airflow Limitation in COPDSmall Airways Disease小气道病变Airway inflammation气道炎症A
23、irway fibrosis纤维化Increased airway resistance气道阻力增大Parenchymal Destruction肺实质的破坏Loss of alveolar attachments肺泡减少Decrease of elastic recoil弹力下降AIRFLOW LIMITATION44On the left is a diagram of the lungs and airways of normal bronchioles and alveoli.On the right is lungs damaged by COPD,bronchiole loose
24、their shape and clogged by mucus.The walls of alveoli are destroyed forming larger alveoli.Pathological change46Airway in COPDNon-smokerCOPDSaetta.199847COPD PathophysiologyHypoventialtion-PaCO2 -Airflow obstruction/airway narrowingHyperinflation:air trappingGas exchange defects-PaO2 Destruction of
25、alveolar wall/alveolar-capillary membraneV/Q mismatch 49COPD PathophysiologySystemic effects of COPD Muscular weakness Impaired salt&water excretion leading to peripheral oedema.Altered fat metabolism contributing to weight lossIncreased prevalence of osteoporosis.Increased circulating inflammatory
26、markers.【医生】COPD的病理_标清.mp4The most common symptoms of COPD are sputum production,dyspnea,and a productive cough.These symptoms are present for a prolonged period of time and typically worsen over time.Clinical manifestationSigns and symptomsClinical manifestationSymptom1.Cough and Expectoration A ch
27、ronic cough is often the first symptom to develop.It is characteristically accompanied by mucoid sputum.Some people with COPD attribute the symptoms to a smokers cough.Those with COPD often have a history of common colds that last a long time.Clinical manifestationSymptom2.Dyspnea:Progressive,persis
28、tent and characteristically worse with exercise.Many people with more advanced COPD breathe through pursed lips and this action can improve shortness of breath in some.Symptom3.Other featuresProlonged expiratory phase.In COPD,it may take longer to breathe out than to breathe in.Chest tightness may o
29、ccur.Systemic wastingSignificant weight lossanxiety disorder and depression Clinical manifestationSign:1.not obvious in early stage2.typical sign:barrel chestdecreased chest movementdiminished tactile fremitusprolong expiration Wheezefingernail clubbing is not specific to COPDbarrel chestthoracic an
30、tero-posteral-diameter/transverse-diameterExaminationPulmonary function test (SpirometrySpirometry)DiagnosisAssessing Monitoring progressionIncompletely reversible airflow limitation is the necessary criteria to diagnose COPD(after inhaled bronchodilator FEV1/FVC 70%59Spirometry:Normal and COPD05142
31、3Liter165432FVCFVCFEV1FEV1NormalCOPD3.9005.2002.3504.15080%60%NormalCOPDFVCFEV1FVCFEV1/Seconds forced expiratory volume in 1 second(FEV1)forced vital capacity(FVC)60Chest X-rayBlood gas：to detect respiratory failureBlood routine and sputum examination ExaminationChest X-rayIntercostal space widening
32、Diaphragm are low and flatShadow of the heart narrowing62Complications of COPD1.Chronic respiratory failure Type 2 2.Spontanous pneumothorax 3.Cor pulmonale Global Strategy for Diagnosis,Management and Prevention of COPD nDefinitionnDiagnosis and Therapeutic OptionsnManage Stable COPDnManage Exacerb
33、ationsnManage ComorbiditiesREVISED 2011Diagnosis 1、Smoking history2、Symptom:cough,sputum production,gradually progressive dyspnea3、Sign：emphysema4、PFT:airway flow limitationDiagnosis:Key PointsA clinical diagnosis of COPD should be considered in any patient who has dyspnea,chronic cough or sputum pr
34、oduction,and/or a history of exposure to risk factors for the disease.Spirometry is required to make the diagnosis;the presence of a post-bronchodilator FEV1/FVC 0.780I:Mild COPD80II:Moderate COPD0.750-80III:Severe COPD0.730-50IV:Very severe COPD0.730Clinical Features of COPD Patients of different s
35、everityMild COPD:no abnormal signs,smokers cough,little or no breathlessnessModerate COPD:breathlessness with/without wheezing,cough with/without sputumSevere COPD:breathlessness on any exertion/at rest,wheeze and cough prominent,lung inflation usual,cyanosis,peripheral edema,and polycythemia in adv
36、anced diseaseStage of diseaseAcute ExacerbationsStableAcute exacerbations of COPD Acute exacerbations of COPD are characterised by an increase in symptoms and deterioration in lung function.They become more common as the disease progresses and may be caused by bacteria,viruses or a change in air qua
37、lity.They may be accompanied by the development of respiratory failure and/or fluid retention and represent an important cause of death79This may present with signs of increased work of breathing such as fast breathing,a fast heart rate,sweating,active use of muscles in the neck and even a bluish ti
38、nge to the skin in very severe exacerbations.Crackles may also be heard.During exacerbations,airway inflammation is also increased,resulting in increased hyperinflation,reduced expiratory airflow and worsening of gas transfer.This can also lead to insufficient ventilation and,eventually,low blood ox
39、ygen levelsCauses:75%infectiousVirusBacteria20%environmental5%Other:MI/CHFSurgeryAspiration.Pulmonary embolism(20%in one study!)caution-select patient populationCOPD ExacerbationsGlobal Strategy for Diagnosis,Management and Prevention of COPD nDefinitionnDiagnosis and AssessmentnTherapeutic Optionsn
40、Manage Stable COPDnManage ExacerbationsnManage ComorbiditiesREVISED 2011Global Strategy for Diagnosis,Management and Prevention of COPDTherapeutic Options:Key Points Smoking cessation has the greatest capacity to influence the natural history of COPD.Health care providers should encourage all patien
41、ts who smoke to quit.Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates.All COPD patients benefit from regular physical activity and should repeatedly be encouraged to remain active.Appropriate pharmacologic therapy can reduce COPD symptoms,reduce the frequ
42、ency and severity of exacerbations,and improve health status and exercise tolerance.None of the existing medications for COPD has been shown conclusively to modify the long-term decline in lung function.Influenza and pneumococcal vaccination should be offered depending on local guidelines.Global Str
43、ategy for Diagnosis,Management and Prevention of COPDTherapeutic Options:Key PointsCOPD:TherapySmoking cessationMedicationsLong term oxygen therapyRehabilitationManagement of COPDTherapeutic Options:Smoking Cessation Keeping people from starting smoking is a key aspect of preventing COPD.Counseling
44、delivered by physicians and other health professionals significantly increases quit rates over self-initiated strategies.Smoking bans in public areas and places of work are important measures to decrease exposure to secondhand smoke.Therapeutic Options:Risk ReductionTherapeutic Options:COPD Medicati
45、onsBeta2-agonists Short-acting beta2-agonists Long-acting beta2-agonistsAnticholinergicsCombination beta2-agonists+anticholinergic in one inhaler TheophyllineInhaled corticosteroids Combination beta2-agonists+corticosteroids in one inhalerSystemic corticosteroidsBronchodilatorsTherapeutic Options:Br
46、onchodilatorsTherapeutic Options:Bronchodilators The principal action of 2-agonists is to relax airway smooth muscle by stimulating 2-adrenergic receptors,which increases cyclic AMP and produces functional antagonism to bronchoconstriction.Inhaled 2-agonists have a relatively rapid onset of bronchod
47、ilator effect although this is probably slower in COPD than in asthmaBronchodilators：2-agonist bronchodilatorsRapid-acting 2-agonists(SABA)Agents such as salbutamol(ventolin 万托林)terbutalineThe bronchodilator effects of shoracting 2-agonists usually wear off within 4 to 6 hours.Use this prnminimal ri
48、sk of side effectsBronchodilators：2-agonist bronchodilators-Long acting 2-agonists(LABA)Agents such as salmeterol,formoterolshow a duration of effect of 12 hours or more with no loss of effectiveness overnight or with regular use in COPD patientsThe benefit for longtime usingpatients activity and QO
49、L The most important effect of anticholinergic medications,in COPD patients appears to be blockage of acetylcholines effect on M3 receptors.Current short-acting drugs also block M2 receptors and modify transmission at the pre-ganglionic junction,although these effects appear less important in COPD.T
50、herapy-BronchodilatorsAnticholinergic bronchodilatorsAgents such as Ipratropium,Tiotropium:Ipratropium is a short-acting agent while tiotropium is long-acting.Regular therapyTherapy-BronchodilatorsAnticholinergicSymptomatic benefits,decrease in exacerbations and improved quality of lifeSide effects:
