Presentation on theme: "Chronic Obstructive Pulmonary Diseases"— Presentation transcript:
1 Chronic Obstructive Pulmonary Diseases Chronic BronchitisEmphysemaBronchiectasisBronchial AsthmaSmall Air way disease Bronchiolitis
2 PathogenesisProlonged exposure to cigarette smoke and/or other air pollutants.Airway obstructionat times may result in a check-valve mechanismleading to overdistension and rupture of alveolar septa, especially if the latter are inflamed and exposed to high positive pressure (i.e. barotrauma).With loss of alveolar surface in emphysema, there is a decrease in surface tension, resulting in expiratory airway collapse.Additional investigative work continues in an effort to link disease states to pathogenesis
3 EtiologyBy far the most common etiological cause of COPD remains smoking. Even after the client quits smoking, the disease process continues to worsen.Air pollutionand occupation also play an important role in COPD.Smog and second-hand smoke contribute to worsening of the disease.
4 Cont.Occupational exposure to irritating fumes and dusts may aggravate COPD.Silicosis and other pneumonoconioses may bring about lung fibrosis and focal emphysema.Exposure to certain vegetable dusts, such as cotton fiber, molds and fungi in grain dust, may increase airway resistance and sometimes produce permanent respiratory impairment.
5 Cont.Exposures to irritating gases, produce pulmonary edema, bronchiolitis and at times permanent parenchymal damage.ChlorineOxides of nitrogen and sulfur,Repeated bronchopulmonary infections can also intensify the existing pathological changes, playing a role in destruction of lung parenchyma and the progression of COPD.
6 Chronic BronchitisDefinition: Chronic bronchitis is a clinical syndrome defined by chronic sputum productionPersistent coughwith sputum productionfor at least 3 monthsin at least 2 consecutive yearsAnatomic siteBronchus
7 Morphology Hyperemia and edema of mm of lungs Mucinous secretions or casts filling in the air waysIncrease in the size and numbers of mucous secreting glandsBronchial or bronciolar mucous plugging, fibrosis, inflammation and fibrosisSquamous metaplaisa or dysplasia of bronchial epithelium
8 Chronic Bronchitis Pathophysiology Cilia DamagedChronic inflammationHypertrophy & hyperplasia of bronchial glands that secrete mucusIncrease number of goblet cellsCilia are destroyed
9 Chronic Bronchitis Pathophysiology Narrowing of airwayStarting w/ bronchi smaller airwaysairflow resistancework of breathingHypoventilation & CO2 retention hypoxemia & hypercapnea
10 Chronic Bronchitis Pathophysiology Bronchospasm often occursEnd resultHypoxemiaHypercapneaPolycythemia (increase RBCs)CyanosisCor pulmonale (enlargement of right side of heart
11 Cartilage damage in long standing cases Degenerative changes, atrophy and loss of bronchial cartilage were common features of most chronic bronchitic specimensThis usually being related to intrinsic changes in the chondrocyte phenotype, including proliferative and matrix-degrading properties.Mast cells and macrophages were often observed in close association with the bronchial cartilage,suggesting that inflammatory cells may also contribute to the mechanisms of bronchial cartilage degradation and loss
12 Inflammatory CellsStudies 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, and of an increased proportion of CD8+ T-lymphocytesMast cells
15 This inflammatory process consists predominantly of neutrophils and macrophages, and of an increased proportion of CD8+ T-lymphocytes andMast Cells
16 Pathogenesis Chronic irritation of airways SmokingDustAir pollutants etcThe major risk factor for the development of chronic bronchitis is cigarette smokingInfective agents Secondary factorThese irritants causeHypersecretions of mucousSubsequent hypertrophy of mucous glandsMetaplasiainflammation
17 EmphysemaPulmonary emphysema is described in clinical, radiological and physiologic terms, but the condition is best defined morphologicallyDefinition:Abnormal enlargement of airspaces distal to the terminal bronchioles with destruction of their wallIt is characterized by destruction and enlargement of alveoli
18 Cont.Although the normal lung has about 35,000 terminal bronchioles and their total internal cross-sectional area is at least 40 times as great as that of the lobar bronchi but the bronchioles are more delicate and vulnerable.
19 ContBronchioles may be obstructed partially or completely, temporarily or permanently, by thickening of their walls, by collapse due to loss of elasticity of the surrounding parenchyma, or by influx of exudates.
20 ContIn advanced emphysema, the lungs are large, pale, and relatively bloodless.They do not readily collapse.They many contain many superficial blebs or bullae, which occasionally are huge.The right ventricle of the heart is often enlarged (cor pulmonale), reflecting pulmonary arterial hypertension.
21 Emphysema: Pathophysiology Structural changesHyperinflation of alveoliDestruction of alveolar & alveolar-capillary wallsSmall airways narrowLung elasticity decreases
22 EmphysemaLoss of Lung Surface Area for Gas Exchange and Oxygen TransportLoss of Lung Surface area is due to death of Lung Endothelial CellsPolycyclic aromatic hydrocarbons (PAHs) in Cigarette Smoke and in Environmental Pollution may cause endothelial cell death
23 Emphysema: Pathophysiology Mechanisms of structural changeObstruction of small bronchiolesProteolytic enzymes destroy alveolar tissueElastin & collagen are destroyedSupport structure is destroyed“paper bag” lungs
24 Emphysema: Pathophysiology The end result:Alveoli lose elastic recoil, then distend, & eventually blow out.Small airways collapse or narrowAir trappingHyperinflationDecreased surface area for ventilation
25 Emphysema: Clinical Manifestations Early stagesDyspneaNon productive coughDiaphragm flattensA-P diameter increases“Barrel chest”Hypoxemia may occurIncreased respiratory rateRespiratory alkalosisProlonged expiratory phaseTripod position
26 Emphysema: Clinical Manifestations Later stagesHypercapneaPurse-lip breathingMuscle retractionUse of accessory muscles to breatheUnderweightNo appetite & increase breathing workloadLoss of subcutaneous fatLung sounds diminished
28 Classification Anatomical Distribution Cetriacinar Panacinar ParaseptalIrregular
29 Pathogenesis Protease anti Protease Theory Pollutants in environment Hereditary deficiency of the major protease inhibitorsLaurell and Eriksson –1963 – deficiency of α1-antitrypsin and emphysemaPollutants in environmentsmoking of cigarettesexhalations from cars, dust from grainRecruitment of neutrophilsstimulation of macrophages and epithelial cells to produce TNF- α, IL-8 and LTB4Elastase release from leukocytes and tissue macrophagesInactivation of α1-antitrypsin by oxidants in tobacco smoke or free radicals released from the neutrophils
31 Diseases in which misfolding of a given protein results in improper trafficking
32 Diseases in which misfolding of a given protein results in improper trafficking polymers of alpha1 antitrypsin molecules will form. These will be retained in the liver (where alpha1 antitrypsin is produced) and will not reach the lungs
33 increased lung lucency hyper aerationincreased lung lucencydecreased vessel sizeFlattening of the DiaphragmIncreased Lung HeightDecreased Peripheral Vascular Markings
34 Chest X-Ray Changes in Emphysema: The two primary findings are:Increased Lung Volumes, i.e., hyperaeration or overinflation.Lung Destruction (bullae or decreased vascularity which gives increased lung lucency and decreased vessel size ).In end-stage disease, emphysema and chronic obstructive pulmonary disease can result in pulmonary arterial hypertension and eventually cor pulmonale (cp) - which causes an increase in the pulmonary arterial size, as well as right ventricular enlargement and cardiomegaly.
40 Other types of Emphysema 1 Bullous Emphysema (also known as Bullous Lung Disease): Bullous emphysema is so named when there are multiple large bullae associated with a compromise in pulmonary function. It is usually associated with concomitant emphysema, although occasionally, it can be familial
41 Bullous Emphysema Subpleural Type: These subpleural bullae contain only gas with no alveolar remnants or blood vessels. They are often located in the apex of the upper lung zone, and along the costophrenic rim of the middle lobe and lingua, but may be seen in the vicinity of parenchymal scars.Superficial Type: These bullae are found along the anterior edge of the upper and/or middle lung zones, or lingula, and over the diaphragms. They contains blood vessels and strands of partially-destroyed lung.Deep Type: These bullae are found within the lung substance and contain strands of partially-destroyed lung tissue and blood vessels.
42 2.Giant Bullous Emphysema: ("Vanishing Lung Syndrome" or "Primary Bullous Disease of the Lungs") It is usually associated with young males who show large progressive upper lung zone bullae that are often asymmetric.The giant bullous lesions occupy greater than or equal to one-third of the hemithorax.
43 Cont.3.Focal Dust Emphysema ( This is focal emphysema surrounding silicotic nodules.4.Congenital Lobar Emphysema (CLE) 5.Interstitial Emphysema
44 BronchiectasisBronchiectasis is a chronic lung disease that is characterized by permanent dilatation of the bronchi and fibrosis of the lung.It is defined as the pathological, irreversible dilation of bronchi , due to destruction of the bronchilal walls and their supporting tissuesIt is highly associated with chronic bacterial infectionOften looked at, as the final common pathway of many injurious processes
46 Cont.Bronchiectasis , although uncommon,bears the potential to cause severe illness , including repeated respiratory infections , disabling cough, purulent sputum, shortness of breath,chest pain and occasionally hemoptysis, with significant impact on the health and the quality of life of the affected person
47 Types of Bronchiectasis Bronchiectasis means irreversible dilation and distortion of the bronchi and bronchioles.Pathologically, bronchiectasis can be divided into four types
51 Cylindrical Bronchiectasis The first type, cylindrical bronchiectasis, is characterized by uniform dilatation of bronchi, that extends into the lung periphery, without tapering.Tubular bronchiectasis is simply the absence of normal bronchial tapering and is usually a manifestation of severe chronic bronchitis rather than of true bronchial wall destruction
53 Varicose Bronchiectasis The second type is called varicose bronchiectasis and is characterized by irregular and beaded outline of bronchi, with alternating areas of constriction and dilatation.
54 Saccular Bronchiectasis. The third type is called cystic or saccular bronchiectasis and is the most severe form of the disease.The bronchi dilate, forming large cysts, which are usually filled with air and fluid.Saccular bronchiectasis is the classic advanced form characterized by irregular dilatations and narrowing.The term cystic is used when the dilatations are especially large and numerous
56 Follicular Bronchiectasis The fourth type of bronchiectasis is called follicular and is characterized by extensive lymphoid nodules within the bronchial walls.It usually occurs following childhood infections
57 Cont. Repeated or prolonged episodes of pneumonitis, Inhaled foreign objects orNeoplasms have been known to cause bronchiectasis.When the bronchiectatic process involves most or all of the bronchial tree, whether in one or both lungs, it is believed to be genetic or developmental in origin
58 ASTHMADefinitionAsthma is a chronic inflammatory disorder of airways.Many cells and mediators are involved in this process – eosinophils, mast cells and T-lymphocytes.
59 Asthma Reversible inflammation & obstruction Intermittent attacks Sudden onsetVaries from person to personSeverity can vary from shortness of breath to death
60 Bronchial Hypersensitivity Chronic inflammation is connected with bronchial hyperreactivityand leads to episodes of wheezing,coughing,tightness in the chest,breathlessness,shortage of breath specially at night and in the morning.This episodes are usually connected with variable obstruction which is reversible spontaneously or by treatment.
61 Types A) Allergic asthma B) Non-allergic asthma asthma induced by immunological mechanisms.IgE induced asthmaIgE antibodies triggers early and late-phase of response,T- lymphocytes late and opožděné responses.B) Non-allergic asthmaasthma induced by non-immunological triggers Intermittent and persistent
62 Response of Inflammation Inflammation causes obstruction of airways by:Acute bronchoconstrictionSwelling of bronchial wallChronic production of mucousRemodeling of airways walls
63 Risk factors: Individual predisposition Environment genetic variability – 5. a 11. chromosomeatopy,bronchial hyperreactivity,male or female,nationEnvironmentexposition to allergensprofessional chemicals which lead to sensitivity,viral and bacterial infection,food,smoking,social and economic society,number of family members,psychosomatic influence
64 Asthma: Pathophysiology Swelling of mucus membranes (edema)Spasm of smooth muscle in bronchiolesIncreased airway resistanceIncreased mucus gland secretion
65 Asthma: Pathophysiology Early phase response: 30 – 60 minutesAllergen or irritant activates mast cellsInflammatory mediators are releasedhistamine, bradykinin, leukotrienes, prostaglandins, platelet-activating- factor, chemotactic factors, cytokinesIntense inflammation occursBronchial smooth muscle constrictsIncreased vasodilation and permeabilityEpithelial damageBronchospasmIncreased mucus secretionEdema
66 Late phase response: 5 – 6 hours Characterized by inflammationEosinophils and neutrophils infiltrateMediators are released mast cells release histamine and additional mediatorsSelf-perpetuating cycleLymphocytes and monocytes invade as wellFuture attacks may be worse because of increased airway reactivity that results from late phase responseIndividual becomes hyperresponsive to specific allergens and non-specific irritants such as cold air and dustSpecific triggers can be difficult to identify and less stimulation is required to produce a reaction
69 Pathogenesis Acute inflammation Remodeling of airways Chronic inflammationSymptomsof bronchoconstrictionExacerbationnonspecific hyperreactivityOngoingobstruction of airway
70 Remodelingdestruction of brush epithelium in airwaysswelling of the bronchial wallstimulation of proliferation of fibroblastsdeposition of collagen in lamina reticularis of basal membranehypertrophy of smooth muscleshyperplasia of goblet cells
71 The process of remodeling is involved by: Th2 lymphocytes (CD25+, production of IL-4,13,5,6,10)antigen presenting cellsmast cells (tryptase-converting angiotensin I to angiotensin II,hypertrophy of smooth muscles, histamin – fibrogenetic effect)eosinophils (long-living in epithelium and submucoses, createlipids –PAF, LTC4,LTD4, LTB4, peptides, cytokines, TGF-α,TGF-β, IL-1,3, GM-CSF, ECP)alveolar macrophages (production of TNF-α, IL-6)epithelial cells (desquamation of epithelium, lost of integrity,TGF-β, IGF-1, KGF- β, alteration of differentiation andproliferation of epithelial cells, apoptosis)endothelial cells
72 Cont. myocytes (proliferation of myocytes - after stimulation with IL- 11, which is produced by mezenchymal cells after stimulationwith allergen, PGDF, EGF, the effect of gelatinase A (MMP-2)and B (MMP-9), production of IL-6,8, eotaxin, PGE2, RANTES,MCP-1,2,3, expression of ICAM-1, VCAM-1, production of NO,GM-CSF, IL-5)fibroblasts (activation of fibroblasts, creation ofmyofibroblasts, release of GM-CSF and TGF-β, increasing proinflammatoryactivity of eosinophils)
73 Subepithelial structures: thickness of basal membraneincreasing deposition of extracellular matrix under epitheliumdeposition of collagen I., III., IV., V. and VII. in reticular membraneincreasing deposition of proteoglycans (lumican, biblycan,decorin, fibromodulin, hyaluron, versica)tenascin (corresponds with activity of chronic inflammation)fibronectin
74 Decrease of elasticity of the wall Inflammation Increasing number of mucous glandsIncreasing number of smooth muscles fibresSever bronchospasms during exacerbationIncrease of mucous secretion duringRelease of fibrogenetic factorsOngoing of inflammatory cellsElastolysisDeposition of collagen in basal and Epithelial membranesDecrease of elasticity of the wallInflammation
75 Cytokines involved in pathogenesis of asthma IL-4- cross-linking of immunoglobulines in B lymphocytes – production of IgE andIgG4- increases of expression of VCAM-1 and mucous secretion- inhibits of activation of Th1 and production of IFNγIL-13- induces production of IgE a IgG4- activates mast cells- increases bronchial hyperreactivity and contractility of smooth muscles, affectsthe differentiation of cilia- induces the production of eotaxin, VCAM-1- suppress production of pro-inflammatory cytokines
76 Cont.IL-5- produced by mast cells and Th2 lymphocytes, epithelial cells and eosinophils- affects the proliferation and the differentiation of B lymphocytes- induces expression of IL-2R- proliferating and differentiating factor for eosinophilsIL-12- produced by macrophages, dendritic cells and monocytes- decreases production of Th2 cytokines and then production of IgE and IgG1- decreases number of eosinophils in peripheral blood and in sputum
77 Cont. IL-10 - large immunosupressive and anti-inflammatory effect - decreases expression of iNOS, COX2decreases release of IL-2, expression of MHC class II., CD80, CD86 andCD32 on the surface of APC and then presentation of allergen, RANTES, IL-5- correlation with asthma severity
78 Cont. - IFNγ - low levels in atopic people - stimulatory effects on Th1 cells, inhibitory effects on Th2 cells- the nebulissation of IFNγ decreases the number of eosinophils in BAL but this effect is not significantTGF-β- remodeling- induction of expression of Fas receptor on the surface of epithelial cells,activation of apoptosis, phagocytosis by macrophages, exudation of plasma,fibrosis
79 Etiological Classification of asthma: A. Atopic (allergic) asthma- in combination with allergic rhinitis, atopic dermatitis, genetic predisposition- confirmation of spec. IgE antibodies, prick tests, inhalation challengeB. Endogenous asthma- without specific known influence, obviously in women after exposition to coldweather, refract to the standard therapyC. Exercise induced asthma- physical exercising, provocation by inhalation of chemicals, cold or hotweather
80 Cont. D. Aspirin induced asthma - typical triads-nasal polyps, urticaria and asthma induced by application ofaspirin- other drugsE. Allergic bronchopulmonary aspergillosis- aspergillus acts as an allergen challenge in atopic people and inducesaspergillus asthma or alergic bronchopulmonary aspergillosis- in the chest radiography are intermitent infiltrates in lungs, the viscosity ofmucous is increased and mucous plugs, bronchiectasia
81 Cont. F. Gastroesophageal reflux - bronchospasm induced by reflex G. Sinobronchial syndrome- combination of sinusitis with nasal polyps and with asthmaH. Professional asthma- induced by inhalation and exposition to industry chemicalsCH. Asthmatic equivalent- dry cough, irritating, without breathlessness
82 Classification of grading of asthma Grade 1. Intermitent asthma- rare symptoms < than 1x per week, short episodes of worsening- night symptoms 2x monthly- no symptoms between attacks- PEF or FEV1 > 80%, variability < 20%Grade 2. Mild persistent asthma- symptoms <1x per day >1x per week- night symptoms > 2x per month- exacerbation can affect daily activity or sleeping- PEF or FEV1 > 80%, variability 20-30%
83 Cont. Grade 3. Moderate persistent asthma - Everyday symptoms - Exacerbation affects daily activity and sleeping- Night symptoms > 1x per week- Everyday use of releasing drugs- PEF or FEV1 between %, variability > 30%Grade 4. Severe persistent asthma- Continuous symptoms- Frequent exacerbation- Physical activity is decreased- Frequent night symptoms- PEF or FEV1 < 60%, variability > 30%