Two major lung diseases Two major lung diseases 1. Obstructive 1. Obstructive – airway disease a) limitations of airflow i) partial or complete obstruction at any level major causes a) asthma – obstructive b) emphysema – loss of elastic recoil c) chronic bronchitis d) Bronchiectasis e) cystic fibrosis f) bronchiolitis
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Two major lung diseasesTwo major lung diseases
1. Obstructive1. Obstructive – airway diseasea) limitations of airflow
i) partial or complete obstruction at any level major causes
a) asthma – obstructiveb) emphysema – loss of elastic recoilc) chronic bronchitisd) Bronchiectasise) cystic fibrosisf) bronchiolitis
1. Obstructive (con’t)1. Obstructive (con’t)
In these diseases:• TLC and FVC are normal or slightly increased• Marked by decreased expiratory flow (FEV1)• Ratio of FEV1 to FVC is decreased
2. Restrictive diseases2. Restrictive diseasesa) FVC is reducedb) ratio of FEV1 to FVC is increased or near normal
1.- Extrapulmonary disordersa) disorders which affect
chest to act as a bellows
b) examples: neuromuscal disordersi) Guillan-Barre Syndrome
a) interstitial lung disease !!interstitial lung disease !!i) interstitial fluid or fibrosis cause lung
to be stiff which decrease lung compliance• Acute
a) edema (pulmonary; ARDS)b) inflammation
• Chronic (involvement of connective tissue)
a) fibrosis• Most diseases are idiopathic
• S & SS & Sa) dyspneab) tachycardiac) end expiratory “crackles”d) cyanosise) no “wheezing” or evidence of airway obstructionf) Cor pulmonale
• FeaturesFeaturesa) CO diffusing capacityb) TLCc) compliance
• Frequency of diseaseFrequency of diseasea) environmental diseases (~ 25%)b) sarcoidosis (~ 20%)c) IPF (~ 15%)d) collagen vascular disease (~ 10%)e) et al. (~ 30% - more than 100
PneumoconiosesPneumoconioses • ““Non neoplastic lung reaction to Non neoplastic lung reaction to inhalation of mineral dusts, organic, inhalation of mineral dusts, organic, inorganic particulates and chemical inorganic particulates and chemical fumes and vapors encountered in the fumes and vapors encountered in the workplace”workplace”
• Most dangerous particles range Most dangerous particles range from 1-5from 1-5 m diameter.m diameter.
a) reach terminal small airways and alveoli
i) settle in liningii) alveolar macrophages clear
small to moderate amounts• Solubility and cytotoxicity Solubility and cytotoxicity
a) smaller the particlesi) reach pulmonary fluids and
induce toxicity more quicklyii) small particles induce acute
lung injuryiii) large particles induce fibrosing
collagenous pneumoconiosis-Silicosis
b) particles stimulate fibroblasts scarring
i) may travel via lymphatics and induce systemic organ pathology
c) tobacco smokei) worsens affects of inhaled dust - e.g., asbestos toxicity
significantly magnified by tobacco smoke
• Only small % of people develop Only small % of people develop diseasedisease
a) many diseases listed in table are rare
b) a select few to induce pulmonary fibrosis at increased frequency
• contaminating silica in coal dust contaminating silica in coal dust favorfavor
progression of disease (anthracosis)progression of disease (anthracosis)• carbon dust is primary culpritcarbon dust is primary culprit• VariationsVariations
a) asymptomaticb) simple CWP little or no
pulmonary dysfunctionc) complicated CWP progressing to “progressive massive fibrosis”
(PMF)• In absence of smoking In absence of smoking no no
evidenceevidence that CWP lead to cancer !!that CWP lead to cancer !!
2. 2. SilicosisSilicosis• inhalation of crystalline silicone inhalation of crystalline silicone dioxidedioxide (silica)(silica)• it is the most prevalent chronicit is the most prevalent chronic occupational disease in the world !!occupational disease in the world !!
a) presents as slowly progressing nodular fibrosing pneumoconiosis• Quartz most implicated in SilicosisQuartz most implicated in Silicosis• inhaled particles:inhaled particles:
a) activation and release of alveolar macrophage mediators
i) IL-1, TNF, fibronectin, ROS and fibrogenic cytokines
ii) TNF most implicated
• Quartz mixed with other minerals Quartz mixed with other minerals has has toxicity (i.e., toxicity (i.e., fibrogenic activity) fibrogenic activity)
• Silicosis first observed Silicosis first observed asymptomaticallyasymptomatically in upper zones of lungsin upper zones of lungs
• Silicosis Silicosis susceptibility to TB susceptibility to TB
• Crystalline silica from occupationalCrystalline silica from occupational sources is carcinogenic in humanssources is carcinogenic in humans
3. 3. Asbestos – related diseaseAsbestos – related disease• family of crystalline hydrated family of crystalline hydrated silicates silicates form fibersform fibers• occupational exposure causes:occupational exposure causes:
a) fibrous plaquesb) pleural effusionsc) lung CAd) mesotheliomae) laryngeal and colon CA ?
• 2 forms of asbestos2 forms of asbestosa) serpentine (i.e., curly and flexible)
i) most of asbestos used in industry
b) amphibole (i.e., straight, stiff and brittle)
i) more pathogenic - malignant mesothelioma
c) both forms are fibrogenicd) dose is associated with incidence
of all asbestos related diseasesi) except that only amphibole
exposure correlates with mesothelioma
• correlation of asbestos induced CA and smoking
Complications of therapyComplications of therapy• Drug – induced lung diseaseDrug – induced lung disease
a) acute (i.e., ARDS)b) chronic alterations in lung structure/function
i) most likely to develop pulmonary fibrosis (PPF)
• Granulomas preferentially involveGranulomas preferentially involve interstitium rather than air spacesinterstitium rather than air spaces a) localize around bronchioles and
pulmonary venules
• Erythema nodosum (raised tender red nodules on anterior aspects of legs)
a) hallmark skin lesion in acute sarcoidosis
• Another skin lesiona) lupus pernia
i) discoloration in region of nose, cheeks and lips
a) affects alveoli (allergic alveolitis)b) often is occupational disease
i) inhaled irritantsc) early diagnosis prevents PPF by
removal from antigen• Evidence for immune mediatedEvidence for immune mediated
a) MIP-1 and IL-8 in bronchoalveolar fluid
b) CD4+ and CD8+ T lymphocytes present
c) most patients have specific Antibodies (type III hypersensitivityimmune)
d) non caseating granuloma suggest delayed type IV hypersensitivity
• HP therefore is an immune HP therefore is an immune mediatedmediated disease innitiated by an extrinsic disease innitiated by an extrinsic antigenantigen that involves both type III and type that involves both type III and type IVIV hypersensitivity reactionshypersensitivity reactions
• Rare diseaseRare disease• presence of acellular surfactant inpresence of acellular surfactant in intraalveolar and bronchiolar intraalveolar and bronchiolar spacesspaces• Three classes:Three classes:
a) acquired PAPi) etiology unknownii) no familial predispositioniii) > 90% of all types of PAPiv) autoimmune disorder
b) Congenital PAPi) causes neonatal respiratory
distress syndromeii) fatal disorder w/out lung
transplant w/in 3-6 months
c) secondary PAPi) immune deficient disorderii) malignanciesiii) lysinuric protein intoleranceiv) acute silicosisv) other inhalation syndromes,
etc.
Pulmonary InfectionsPulmonary Infections• Pneumonia infections account for Pneumonia infections account for 1/6 of1/6 of all deaths in USA each yearall deaths in USA each year
a) epithelial surfaces of lung constantly exposed to contaminated air
b) nasopharyngeal flora normally aspirated during sleep
c) other lung parenchymal diseases render lung vulnerable to virulent organisms
• Pneumonia is a generic term Pneumonia is a generic term refers to refers to inflammation and consolidation (i.e. inflammation and consolidation (i.e. solidification)solidification)
a) Traditional bacterial pneumonia classified i) lobar - - consolidation of entire lobe
ii) bronchopneumonia - - scattered foci within same or several lobes
common cause of deathiii) today, these differences have
little clinical relevanceb) Bacterial pneumonias occur in 3
associated pneumonia”)d) strep. Pneumoniae NOT major strep. Pneumoniae NOT major
pathogenpathogen
4.4. Aspiration pneumoniaAspiration pneumoniaa) occur in severely debilitated
patients (unconscious e.g., following stroke), or during repeated vomiting
i) have abnormal gag and swallowing reflexes
b) pneumonia partly chemical (gastric or chemical irritant) plus bacterial
i) anerobes and aerobesc) necrotising frequent cause of deathd) patients who survive usually
develop abscess
• Lung Abcessa) Localized area of suppurative
necrosis within pulmonary parenchyma. Causative organism may be introduced into lung by many mechanisms
i) Aspiration of infected material- teeth (carious)- infected sinuses, tonsils- oral surgery
ii) aspiration of gastric contentsiii) septic embolismsiv) neoplasias (e.g., malignancies)
causing obstructions to the bronchopulmonary
segment.
b) Anaerobic bacteria are present in almost all lung abscesses
i) primarily those found on oral cavity
ii) most common aerobes are:- S. aureus- Nocardia- β – hemolytic strep.
5.5. Opportunistic pneumoniaeOpportunistic pneumoniaea)a) more common since advent of more common since advent of
immunosuppressive and cytotoxic immunosuppressive and cytotoxic therapy therapy b)b) AIDS epidemic AIDS epidemic
i)i) Pneomocyctic carinii (fungus) Pneomocyctic carinii (fungus)ii)ii) most common bacteria are most common bacteria are E. E.
colicoli and and Pseudomonas aeruginosaPseudomonas aeruginosa - - E.coli E.coli complication of complication of
bacteremia, cancer patients given bacteremia, cancer patients given chemotherapy, chronic heart and lung chemotherapy, chronic heart and lung disease. RESPONDS POORLY TO disease. RESPONDS POORLY TO TREATMENT !!TREATMENT !!
P. AeruginosaP. Aeruginosa (Con’t) (Con’t)
- P. aeruginosa often seen in burn patients, cystic fibrosis and immunocompromised pts.
- prior history of antibiotic treatment for another
infection is common- infectious vasculitis often
result in pulmonary infarction- ANTIBIOTIC TREATMENT IS USUALLY UNSSATISFACTORY