Pulmonary Pathology RESTRICT AND INFECTION 3.ppt
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Pulmonary Pathology RESTRICT AND INFECTION 3.ppt

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Pulmonary Pathology RESTRICT AND INFECTION 3.ppt Pulmonary Pathology RESTRICT AND INFECTION 3.ppt Presentation Transcript

  • Two major lung diseases 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
    • 1. Obstructive (con’t)
    • In these diseases:
    • TLC and FVC are normal or slightly increased
    • Marked by decreased expiratory flow (FEV 1 )
    • Ratio of FEV 1 to FVC is decreased
  • 2. Restrictive diseases a) FVC is reduced b) ratio of FEV 1 to FVC is increased or near normal 1.- Extrapulmonary disorders a) disorders which affect chest to act as a bellows b ) examples: neuromuscal disorders i) Guillan-Barre Syndrome
  • 2. Restrictive diseases (con’t) 2.- acute or chronic interstitial lung disease a) classic – ARDS (ie, shock lung, wet lung) b) chronic disease – idiopathic pulmonary fibrosis, pneumoconiosis, sarcoidosis
    • RESTRICTIVE LUNG DISEASE
    • reduced expansion (Decreased TLC)
    • reduced compliance !!
    • a) 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 & S
    • a) dyspnea
    • b) tachycardia
    • c) end expiratory “crackles”
    • d) cyanosis
    • e) no “wheezing” or evidence of airway obstruction
    • f) Cor pulmonale
    • Features
    • a)  CO diffusing capacity
    • b)  TLC
    • c)  compliance
    • Frequency of disease
    • a) environmental diseases (~ 25%)
    • b) sarcoidosis (~ 20%)
    • c) IPF (~ 15%)
    • d)  collagen vascular disease (~ 10%)
    • e) et al. (~ 30% - more than 100 causes)
    • Alveolitis
    • a) earliest common S & S of interstitial disease
    • i)  inflammatory and immune cells
    • - stimulate fibrosis via mediator release
    • - and initiates end-stage fibrotic lung disease
    • Chronic Restrictive Lung Disease (interstitial lung disease)
    • Some diseases also have alveolar component
    • Decreased FVC (forced vital capacity)
    • Decreased FEV1
    • Ratio of FEV1/FVC is not reduced as was the
    • case with obstructive pulmonary disease
    • (increased or normal)
    • ~15% of noninfections pulmonary disease
  • Idiopathic Pulmonary Fibrosis (IPF) (usual interstitial pneumonia - UIP) a) diffuse interstitial fibrosis b) males more affected c) > 2/3 cases, patients older than 60 years d) recurrent cycles of lung injury (alveolitis) i) current concept ii) wound healing  fibroblast foci, a characteristic finding of IPF - Tx might be directed to  fibroblast replication iii) with time, fibrosis causes a “honey- comb” fibrosis
  •  
  • - collapse of alveolar wall - formation of cystic spaces filled with type II pneumocytes and bronchiolar epithelial iv) secondary PH e) begins with some alveolar wall injury f) Hypothesized that immune mechanisms are trigger i) IL-8 and leukotrienes recruit and activate neutrophils! ii) injure alveolar epithelial cells and degrade connective tissue
    • Clinical course
    • a) nonproductive cough
    • b) progressive dyspnea
    • c) cor pulmonale, cyanosis and peripheral edema may be present (later stages of disease); “clubbing”
    • d) abnormal chest x-ray
    • e) surgical lung biopsy is “Gold Standard” for diagnosing
    • f) treatment aimed at suppressing inflammatory insult
    • i) glucocorticoids
    • g) IPF so progressive 2 to 4 year survival after diagnosis; Tx  lung transplant for
    • Non specific interstitial pneumonia (NSIP)
    • lung biopsy does not fit any other type of
    • interstitial disease
    • a) “waste basket” type of diagnosis
    • b) better outcome vs. IPF
    • Types
    • a) fibrosing
    • b) cellular
    • i) better outcome than fibrosing
    • Cryptogenic organising pneumonia(COP) or (BOOP; “bronchiolitis obliterans-organising pneumonia”)
    • Characterized by:
    • a) polypoid plugs of loose connective tissue w/in alveoli and bronchioles
    • b) no interstitial fibrosis
    • c) no honeycomb lung
    • d) some pts. recover spontaneously
    • i) most require steroids for > 6 months for recovery
    • e) COP w/intraalveolar fibrosis seen in response to:
    • i) infection, drugs, inhaled toxins
    • Collagen vascular disease
    • Diseases:
    • a) SLE
    • b) RA
    • c) scleroderma
    • d) dermatomyositis – polymyositis
    • e) mixed connective tissue disease
    • Pneumoconioses
    • “ Non neoplastic lung reaction to inhalation of mineral dusts, organic, inorganic particulates and chemical fumes and vapors encountered in the workplace”
  •  
    • Most dangerous particles range from 1-5
    •  m diameter.
    • a) reach terminal small airways and alveoli
    • i) settle in lining
    • ii) alveolar macrophages clear small to moderate amounts
    • Solubility and cytotoxicity
    • a) smaller the particles
    • i) reach pulmonary fluids and induce toxicity more quickly
    • ii) small particles induce acute lung injury
    • iii) large particles induce fibrosing collagenous pneumoconiosis- Silicosis
    • b) particles stimulate fibroblasts scarring
    • i) may travel via lymphatics and induce systemic organ pathology
    • c) tobacco smoke
    • i) worsens affects of inhaled dust
    • - e.g., asbestos toxicity significantly magnified by tobacco smoke
    • Only small % of people develop disease
    • a) many diseases listed in table are rare
    • b) a select few to induce pulmonary fibrosis at increased frequency
    • Coal workers pneumoconiosis (CWP)
    • contaminating silica in coal dust favor
    • progression of disease (anthracosis)
    • carbon dust is primary culprit
    • Variations
    • a) asymptomatic
    • b) simple CWP  little or no pulmonary dysfunction
    • c) complicated CWP  progressing to “progressive massive fibrosis” (PMF)
    • In absence of smoking  no evidence
    • that CWP lead to cancer !!
    • 2. Silicosis
    • inhalation of crystalline silicone dioxide
    • (silica)
    • it is the most prevalent chronic
    • occupational disease in the world !!
    • a) presents as slowly progressing nodular fibrosing pneumoconiosis
    • Quartz most implicated in Silicosis
    • 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 has 
    • toxicity (i.e.,  fibrogenic activity)
    • Silicosis first observed asymptomatically
    • in upper zones of lungs
    • Silicosis  susceptibility to TB
    • Crystalline silica from occupational
    • sources is carcinogenic in humans
    • Read file entitled “Silicosis”
    • 3. Asbestos – related disease
    • family of crystalline hydrated silicates 
    • form fibers
    • occupational exposure causes:
    • a) fibrous plaques
    • b) pleural effusions
    • c) lung CA
    • d) mesothelioma
    • e) laryngeal and colon CA ?
    • 2 forms of asbestos
    • a) 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 fibrogenic
    • d)  dose is associated with  incidence of all asbestos related diseases
    • i) except that only amphibole exposure correlates with mesothelioma
    •  correlation of asbestos induced CA and
    • smoking
    • Complications of therapy
    • Drug – induced lung disease
    • a) acute (i.e., ARDS)
    • b) chronic alterations in lung structure/function
    • i) bronchospasm
    • ii) edema
    • iii) DAD
    • iv) COP
    • v) eosinophilic pneumonia
    • vi) interstitial fibrosis
    • c) cancer chemotherapeutic drugs
    • i) bleomycin
    • - direct toxic effects, fibrosis
  •  
    • Radiation – induced lung disease
    • a) radiation pneumonitis
    • i) Tx w/ steroids  recovery
    • ii) progression  chronic pneumonitis
    • b) initial causes
    • i) lymphocytic alveolitis
    • ii) hypersensitivity pneumonitis
    • - pulmonary fibrosis
    • c) DAD
    • i) hyperplasia of type II pneumocytes
    • ii) “ “ fibroblasts
    • iii) presence of foam cells
    • Sarcoidosis
    • Is a multisystem disease
    • a) unknown etiology
    • b) characterized by:
    • i) non caseating (i.e., “hard”) granulomas
    • - other diseases such as mycobacterial and fungal infrections, and berylliosis sometimes produce noncaseating granulomas, therefore diagnosis  one of exclusion !!
  • ii) bilateral hilar lymphadenopathy present in > 90% cases !! iii) next in frequency is eye and skin involvement (~ 25% of cases) iv) one of few pulmonary diseases where incidence is higher in non smokers !! v) 10x  in American blacks vs. whites, and in Southeast regions vi) Danish and Swedish  incidence vii)  incidence in women vii)  incidence in young adults < 40
    • Pathogenesis
    • immune disorder is highly suggestive
    • a) CD4+ helper T cells
    • i)  intra alveolar and interstitial
    • ii)  T cell derived cytokines
    • - IL-2
    • - IFN- 
    • iii)  IL-8, TNF and MIP-1 
    • - favors recruitment of T cells
    • - contributes to formation of granuloma
    • iv) TNF  at high levels in bronchoalveolar fluid
    • - marker for disease
    • Environmental/genetic factors
    • a) infectious agents  no evidence of causal relationship
    • b) familial and racial clustering
    • i) HLA association (class I)
    • - HLA - A1; HLA – B8
    • Clinical
    • a) ~ 70% recover with little affect
    • b) ~ 20% have permanent loss of some lung function or visual impairment
    • c) ~ 10-15% die of cardiac or CNS damage
    • i) most die of progressive pulmonary fibrosis and Cor Pulmonale
  • d) patients with hilar lymphadenopathy alone  best prognosis; next is… e) lymphadenopathy plus pulmonary infiltrates; poorest outcome is… c) pulmonary disease alone i) most likely to develop pulmonary fibrosis (PPF)
  •  
    • Granulomas preferentially involve
    • interstitium 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 lesion
    • a) lupus pernia
    • i) discoloration in region of nose, cheeks and lips
  •  
  • -
    • Hypersensitivity Pneumonitis (HP)
    • Immune induced inflammatory lung disease
    • a) affects alveoli (allergic alveolitis)
    • b) often is occupational disease
    • i) inhaled irritants
    • c) early diagnosis prevents PPF by removal from antigen
    • Evidence 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 hypersensitivity  immune)
    • d) non caseating granuloma suggest delayed type IV hypersensitivity
    • HP therefore is an immune mediated
    • disease innitiated by an extrinsic antigen
    • that involves both type III and type IV
    • hypersensitivity reactions
    • Acute reaction
    • a) fever
    • b) cough
    • c) dyspnea
    • Chronic disease
    • a) cough
    • b) dyspnea
    • c) malaise
    • d) weight loss
    • Most often inhaling dust containing
    • spores
    • a) thermophilic bacteria/byproducts
    • b) true fungi, animal proteins
    • c) names:
    • i) Farmers lung (humid, warm hay)
    • ii) bird feeders lung (bird fanciers disease)
    • iii) air conditioning lung
    • Unlike bronchial asthma
    • a) HP presents as restrictive lung disease
    • i) Decreased diffusion capacity
    • ii) Decreased lung compliance
    • iii) Decreased TLC
    • Pulmonary Eosinophilia
    • Variety of disease, usually immunologic
    • in origin
    • a) eosinophil attractant  IL-5
    • i) seen in alveoli in several diseases
    • Groups:
    • a) acute eosinophilic pneumonia with respiratory disease
    • b) simple pulmonary eosinophilia (Löffler)
    • c) tropical eosinophilia-microfilarial infection
    • d) secondary (asthma, HP, drugs, etc)
    • e) idiopathic chronic eosinophilic pneumonia
    • Good response to glucocorticoid Tx
    • Pulmonary alveolar proteinosis (PAP)
    • Rare disease
    • presence of acellular surfactant in
    • intraalveolar and bronchiolar spaces
    • Three classes:
    • a) acquired PAP
    • i) etiology unknown
    • ii) no familial predisposition
    • iii) > 90% of all types of PAP
    • iv) autoimmune disorder
  • b) Congenital PAP i) causes neonatal respiratory distress syndrome ii) fatal disorder w/out lung transplant w/in 3-6 months c) secondary PAP i) immune deficient disorder ii) malignancies iii) lysinuric protein intolerance iv) acute silicosis v) other inhalation syndromes, etc.
    • Pulmonary Infections
    • Pneumonia infections account for 1/6 of
    • all 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  refers to
    • inflammation and consolidation (i.e.
    • solidification)
    • a) Traditional bacterial pneumonia classified i) lobar - - consolidation of entire lobe
    • ii) bronchopneumonia - - scattered foci within same or several lobes  common cause of death
    • iii) today, these differences have little clinical relevance
    • b) Bacterial pneumonias occur in 3 settings
    • i) community-acquired pneumonia
    • ii) nosocomial pneumonia
    • iii) opportunistic pneumonia
  •  
  •  
  •  
  • c) broadly defined as any infection in the lungs d) classification based on specific etiologic agent or clinical setting e) evolution of lobar pneumococcal pneumonia i) congestion – edema, exudate fluid ii) red hepatization – alveoli packed with neutrophils, RBC, fibrin iii) gray hepatization – dry, firm, color due to lysed RBC, exudate persist iv) resolution – exudate enzymatically digested and resorbed
  •  
  • 1. Community-acquired acute pneumonia a) bacterial in origin i) usually follows viral upper respiratory infection ii) Streptococcus pneumoniae (i.e., pneumococcus)  most common cause of community-acquired pneumonia b) patients present with abrupt: i) high fever ii) shaking chills iii) productive cough (mucopurulent) iv) pleuritic chest pain
  • c) These infections occur with increased frequency in patients i) underlying chronic disease (CHF, COPD, diabetes) ii) immunodeficiency (AIDS) iii) decreased splenic function (organ responsible for removing strep pneumoniae from the blood) – seen in sickle cell disease or post splenectomy !! iv) aspiration of S. pneumonia with impaired epiglottic reflex - alcohol intoxication - cold, anesthesia
  • d) Other organisms commonly implicated in community-acquired pneumonia i) Hemophilus influenza - most common bacteria cause of acute exacerbation of COPD - is a pediatric emergency with high mortality rate 1. Causes meningitis 2. Pinkeye in children -  ciliary movement - destroys IgA; main class of antibody secreted into airways
  • ii) Staph aureus - high incidence of complications (empyema and lung abscess) - important in nosocomial infections - important cause of secondary bacterial pneumonia following viral respiratory illness 1. Measels 2. Influenza - IV drug users at high risk
  • iii) Klebsiella pneumonia - most frequent cause of gram (-) bacterial pneumonia - commonly associated with alcoholism 1. debilitated 2. malnourished - only other organism which causes lobar pneumonia - accounts for only ~ 1 % of all CAP
  • iv) Legionella pneumophila - flourishes in artificial aquatic environments such as AC, water towers, water tubing for drinking, water, etc. - common in people with predisposing condition (heart, renal, immunologic, blood) - organ transplant patients  risk v) Moraxella catarrhalis (in elderly) - 1 of the 3 (i.e., S. pneumoniae, H. influenza) most common causes of otitis media in children
  • e) S. pneumoniae normal inhabitant of nasopharynx - - false positive cultures i) blood cultures more reliable - resistant strains to penicillin - sensitivity test OTHER a) Chlamydia psittaci i) causes Psittacosis ii) inhaled in dust contaminated with excreta from birds, usually parrots ! iii) other pets as well b) Pontiac fever (mainly febrile illness; Legionella sp.;
    • COMPLICATIONS following
    • pneumococcal pneumonia
    • a) pleuritis (pneumonia extends to pleura)
    • b) pleural effusion
    • c) empyema (pus in thorax)
    • d) pyothorax (infection of pleural effusion)
    • e) bacteremia
    • i) > 25% of patients in early stage of pneumococcal pneumonia
    • - may lead to endocarditis or meningitis
    • - patients w/out spleen  usually die !!!
    • f) pulmonary fibrosis (rare)
  • 2. Community-acquired atypical pneumonias (mycoplasma + viruses) a) most common organisms is mycoplasma pneumoniae (others include viruses, chlamydiae and rickettsiae) b) sputum production, WBC modest increase, bacteria and influenza A viruses not found c) Chlamydia pneumonia increasing prevalence and important cause of this type pneumonia
  • d) Can produce some alveolar fluid accumulation, thus minimizing bacterial pneumoniae e) secondary bacterial infections f) mycoplasma infections common in children and young adults i ) sporadic outbreaks in close communities (schools, military camps, prisons) g) viral infections of lower respiratory tract – influenza A and B i) most common in adults h ) adenovirus pneumoniae i) common in young army recruits
    • Atypical pneumonia (con’t)
    • i) More serious lower respiratory tract infections in infancy, old age, malnourished, alcoholism and immunosuppression
        • j) Viruses and mycoplasmas frequently
        • involved in outbreaks in hospitals
        • (nosocomial)
        • k) SARS “severe acute respiratory
        • syndrome”
        • i) coronavirus pathogen
        • - unlike other coronaviruses, SARS infects lower resp. tract and spreads to rest of body
  • 3. Nosocomial pneumonia a) pseudomonas sp. Most common gram (-) rods (also Enterobacteriaceia) i) gram(+) cocci – staph aureus b) Pulmonary infections acquired in the course of a hospital stay c) Common in patients with severe underlying disease, immunosupression, antibiotic therapy, invasive devices such as catheters i) mechanical ventilator increase incidence (“ventilator-associated pneumonia”) d) strep. Pneumoniae NOT major pathogen
  • 4. Aspiration pneumonia a) 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 aerobes c) necrotising frequent cause of death d) patients who survive usually develop abscess
    • Lung Abcess
    • a) 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 contents
    • iii) septic embolisms
    • iv) 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. Opportunistic pneumoniae a) more common since advent of immunosuppressive and cytotoxic therapy b) AIDS epidemic i) Pneomocyctic carinii (fungus) ii) most common bacteria are E. coli and Pseudomonas aeruginosa - E.coli  complication of bacteremia, cancer patients given chemotherapy, chronic heart and lung disease. RESPONDS POORLY TO TREATMENT !!
  • P. Aeruginosa (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 !!
    • Tuberculosis
    • Communicable chronic granulomatous disease
    • a) Mycobacterium tuberculosis
    • b) lungs are predominant target but also involves other organs
    • i) occurs in medically and economically deprived populations
    • c) leading cause of death worldwide !
    • d) ~ 2 billion infected worldwide
    • i) 8-10 million new cases/yr
    • ii) 3 million deaths/yr
    • iii) 6% of all deaths worldwide
    • e) in 1984, in US there was increased incidence due to HIV-infected persons, Since 1992, incidence of TB is decreased
    • f) In US, TB is disease of elderly (decreased immunity) and immigrants
    • Higher incidence induced by other diseases
    • i) diabetes
    • ii) Hodgkin disease
    • iii) chronic lung disease (e.g., silicosis)
    • iv) malnutrition
    • v) alcoholism
    • vi) immunosuppression (i.e., HIV/AIDS)
    • Most infections acquired
      • a) direct person-to-person contact
      • b) delayed hypersensitivity (PPD [Purified Protein Derivative] test; mantoux test; tuberculin test)
      • i) false negative reactions
      • - other viral infections
      • - sarcoidosis
      • - Hodgkin’s disease
      • - malnutrition
      • ii) false positive reactions
      • - atypical mycobacterium
      • c) contaminated milk (M. bovis) causing intestinal tuberculosis (rare in USA)
    • Primary TB
    • a) develops in previously unexposed (unsensitized) person
    • i) source of the organism is exogenous
    • ii) ~ 5% of newly infected people develop significant disease
    • b) chief implications
    • i) induces hypersensitivity (type iv)
    • ii) increased resistance to organisms
    • iii) may be nidus for reactivation when host defenses are decreased
    • iv) may develop without interruption
    • - Progressive primary TB (immunocompromised)
  • c) Eskimos more prone to develop progressive primary TB d) Lymphohematogenous dissemination severe complication i) tuberculosis meningitis ii) miliary TB (organisms drain through lymphatics and into central veins then to lungs – almost all organs are “seeded”) (liver, spleen, bone marrow, meningitis) e) hallmark of TB is caseating granulomas and cavitation (secondary)
  • i) implant in distal airways - lower part of upper lobe or - upper part of lower lobe ii) as sensitization develops - gray-white consolidation emerges  “GHON FOCUS” (parenchymal lesion and nodal involvement  GHON COMPLEX ) iii) center of GHON focus undergoes caseous necrosis iv) GHON COMPLEX undergoes progressive calcification  RANKE COMPLEX (detectable by x-ray)
  •  
    • Secondary TB (post primary)
    • a) Pattern of disease that arises in previously sensitized host
    • i) may follow shortly after 1  TB
    • ii) more commonly arise from dormant (reactivation) primary lesions many years (decades) after initial infection
    • b) Only few patients (~5%) with primary disease usually develop secondary TB
    • c) Classically localized to the apex of one or both upper lobes of the lungs
    • i) lymph nodes not as affected early vs. 1  TB
    • ii) cavitation does occur readily
  • - erodes along airway and becomes source of infection  pt. Raises sputum containing bacilli ! d) HIV patients i) less severe immunosupression – “usual” secondary TB (apical disease with cavitation) ii) more severe immunosuppression – clinical picture resembling “progressive primary TB” (lower and middle lobes, hilar lymphadenopathy, non cavitating)
  •  
  •  
    • Clinical (secondary)
    • a) malaise
    • b) weight loss
    • c) low grade fever
    • i) appearing late each afternoon then remitting
    • d) night sweats
    • e) pleuritic pain
    • f) hemoptysis
    • Nontuberculosis Mycobacterial Disease
    • a) Chronic pulmonary disease in immunocompetent people is most common localized disease caused by nontuberculosis mycobacteria
    • Fungal Infections
    • a) Molds and yeast
      • b) Histoplasma
      • c) Aspergillus
      • d) Candida – most frequent disease causing fungus
      • e) Cryptococcus