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28 Cards in this Set
- Front
- Back
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Cellular defense mechanisms of lung
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Neutrophils- 40% of blood PMNs are marginated or in transit through the lung; leukotrienes, complement fragments, NADPH oxidase-dependent reactive oxygen species
Mast cells- TNF proteases, histamine proteoglycans Dendritic cells- Toll-like receptors Macrophages- phagocytosis, leukotrienes, IL8, activation of T4 cells |
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Acute pneumonia: pathology
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Diffuse consolidation with pallor of parenchyma
Neutrophilic infiltrate with varying degrees of associated necrosis, edema Late stage may include diffuse alveolar damage or abscesses |
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Diffuse alveolar damage: clinical
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Clinical
-Acute onset of dyspnea; usually need for mechanical ventilation -Diffuse pulmonary infiltrates -Changes all at same stage -Rapid respiratory failure with mortality rate of 40-60% -Multiple underlying causes Pathologic Pattern of Diffuse Acute Lung Injury -Correlation with clinical label of “adult respiratory distress syndrome” Idiopathic variant -Known as Acute Interstitial Pneumonia (AIP) (Hammon-Rich Syndrome) |
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Pathophysiology of diffuse alveolar damage
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Lung toxin causes epithelial and endothelial injury
Endothelial injury causes leaky capillaries Epithelial injury causes necrosis of type 1 cells Both epithelial and endothelial injury cause edema, hyaline membranes (acute stage) Can lead to interstitial connective tissue (organizing stage) -alveolar collapse and fibrosis -or can lead to resolution |
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Histologic features of diffuse alveolar damage (acute interstitial pneumonia)
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Diffuse distribution
Uniform temporal appearance Diffuse alveolar septal thickening (cellular or fibroblastic) Hyaline membranes (exudative phase) Organizing pneumonia (organizing phase) Pertinent negative features- Lack of granulomas, abscess or necrosis No evidence of infection No marked increase in eosinophils |
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Diffuse alveolar damage pathologic features
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Exudative Stage
- Interstitial edema - Type I pneumocyte sloughing - Hyaline membranes - Rigid, heavy, hemorrhagic, beefy red Organizing Stage (1 week later) -Proliferating type II pneumocytes -Interstitial fibroblasts -(focal airspace organization) - Firm, consolidated, pale gray |
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Diffuse alveolar damage: exudative stage histology
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Type 1 pneumocytes and endothelial cells:
- Edema and exudation of plasma proteins into alveolar interstitium and spaces Type 1 pneumocytes: - Undergo extensive necrosis - Slough off alveolar surface Underlying Basement Membrane: - Denudation - Becomes surface of attachment for hyaline membranes and fibrin Eosinophilic “membranes”: - Line alveolar surfaces - Consist of precipitated plasma proteins and cytoplasmic and nuclear debris from sloughed epithelial cells |
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Diffuse alveolar damage: proliferative (early organizing) stage histology
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Proliferation of loose, organizing type of connective tissue (early fibrosis) in the alveolar septal walls
Prominent lining of hyperplastic type 2 pneumocytes |
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Diffuse alveolar damage: late organizing stage histology
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Can't see alveolar spaces
Many type 2 pneumocytes Thickened septa from collagenous fibrosis |
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Acute interstitial pneumonia: overview, radiographic and pathologic features, mortality rate
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Clinicopathologic term:
-Widespread DAD of unknown etiology -Uncommon -Rapidly progressive clinical course -Occurring at a mean age of 50 years -No sex predilection -Acute respiratory failure often following an illness of less than 3 weeks' duration -Resembles an upper respiratory tract infection Radiographic and pathologic features: -Identical to those of organizing stage of DAD Mortality rate: -Varies from 33% to 74% -Most deaths occurring within 1 to 2 months -For survivors, recurrences and chronic interstitial disease may develop |
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Organizing pneumonia pattern: etiology
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Histologic pattern may be part of Cryptogenic Organizing Pneumonia (COP)
Pattern may be present after infections, in collagen vascular diseases, drug reactions (amiodarone) , adjacent to neoplasms, or part of graft vs. host disease following bone marrow transplant |
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Organizing pneumonia: clinical findings
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Short prodrome duration (2-3 months)
5th-6th decade; males=females More common in nonsmokers Patchy unilateral or bilateral airspace consolidation; reticulonodular pattern; lower lung zones more frequently involved Very responsive to corticosteroids |
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Organizing pneumonia: key histologic features and pertinent negatives
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Key Histologic Features:
-Organizing pneumonia: intraluminal organizing fibrosis in distal airspaces (bronchioles, alveolar ducts, and alveoli) (loose organizing plug) -Patchy distribution -Preservation of lung architecture in intervening areas -Temporally uniform appearance -Mild chronic interstitial inflammation Pertinent Negatives: -Lack of interstitial fibrosis (except for incidental scars or apical fibrosis) -Absence of granulomas -Lack of neutrophils or abscesses -Absence of necrosis -Lack of hyaline membranes or prominent airspace fibrin -Lack of prominent infiltration of eosinophils -Absence of vasculitis |
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Differences between DAD and OP
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DAD:
More diffuse More fulminant course Hyaline membranes present Interstitial fibrosis Type 2 pneumocyte hyperplasia pronounced Fibrin thrombi often present OP: Patchy distribution Prodrome of a few months No hyaline membranes Intraluminal fibrous plugs Type 2 pneumocyte hyperplasia less common Sparse or no fibrin thrombi |
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Asthma: cause
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Obstructive pulmonary disorder
Role of cytokines, chemokines in eosinophil differentiation and airway hyperreactivity (esp. IL5, eotaxin II) produced by T helper (1 and 2) lymphocytes Atopic (type I, extrinsic) asthma vs. nonatopic (type II, intrinsic) asthma Aspirin sensitivity in nonatopic variety |
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Asthma: pathophysiology
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Hyperinflated lungs with areas of atelectasis
Mucous plugging, sometimes with bronchiectasis in upper lobes Hyperplasia of goblet cells and bronchial and bronchiolar smooth muscle with thickened basement membrane Submucosal glandular hypertrophy; Reid index normal Peribronchiolocentric mononuclear inflammation with eosinophils |
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Asthma: histology
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Eosinophilic infiltrate
Curschmann spirals Charcot-leyden crystals |
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Eosinophilic bronchitis
Eosinophilic pneumonia Allergic bronchopulmonary aspergillosis |
All eosinophilic pulmonary diseases
Eosinophilic bronchitis- no airway hyperresponiveness Eosinophilic pneumonia- secondary to infection/toxin, associated with other diseases like Churg-Strauss) or idiopathic (acute vs. chronic forms) Allergic Bronchopulmonary Aspergillosis- associated with cystic fibrosis, asthma |
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Sarcoidosis: clinical features
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Multiorgan disease
Most frequently affects: -Lungs (90-95%) -Lymphatic system -Liver, spleen, eyes and other organs Wide variety of signs and symptoms -Asymptomatic (most common presentation) --Incidental finding on a routine CXR -Symptomatic --Dyspnea with or without exertion --Nonproductive cough --Nonspecific chest pain |
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Sarcoidosis: epidemiology
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Young adults 20-40 (most common)
Slight female predominance >> in African-Americans (US) - 10x higher than Caucasians >> Irish and Scandinavians (outside US) Rare Chinese and Southeast Asians |
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Sarcoidosis: diagnosis
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Clinical and radiologic findings supported by interstitial noncaseating granulomas in a lymphatic and bronchovascular distribution
Exclusion of other disorders which cause granulomatous disease |
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Sarcoidosis: etiology/pathogenesis
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Unknown
Disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents Three contributory factors: -Immunological -Genetic -Environmental |
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Sarcoidosis: etiology/pathogenesis immunological contributory factor
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Immunological contributory factor:
-Heightened/exaggerated helper T-cell type 1 (Th1) immune response to unidentified antigen (self or foreign) at sites of disease -Depression of cutaneous delayed-type hypersensitivity --Anergy to common skin test antigens such as Candida or tuberculosis purified protein derivative (PPD) -Elevated circulating immune complexes & signs of B-cell hyperactivity --Manifestation of helper T-cell dysregulation Granulomatous reaction (affected sites): -T- cell expansion and macrophage activation -Increased levels of T cell–derived TH1 cytokines (IL-2 and IFN-γ), resulting in T-cell expansion and macrophage activation, respectively -Increased local environment cytokine levels --IL-8, TNF, macrophage inflammatory protein 1α --Favor recruitment of additional T cells and monocytes for granuloma formation -Intra-alveolar and interstitial accumulation of CD4+ T cells --CD4/CD8 T-cell ratios ranging from 5:1 to 15:1 --Oligoclonal expansion of T-cell subsets ---Determined by T-cell receptor rearrangement analysis ---Suggesting antigen-driven proliferation |
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Sarcoidosis: etiology/pathogenesis genetic and environmental contributory factors
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Genetic contributory factor:
Certain HLA genotypes -HLA-A1 -HLA-B8 Environmental contributory factor: Possibly the most tenuous of all associations Suspicion (no unequivocal evidence) for microbes -Mycobacteria -Propionibacterium acnes -Rickettsia species |
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Sarcoidosis: laboratory tests
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No specific lab test
Serum level of angiotensin converting enzyme (ACE): -Elevated (2/3 of patients) 24-hour urine calcium excretion: -Frequently increased Hyperglobulinemia: -Nonspecific polyclonal activation of B cells by helper T cells -Typical of active sarcoidosis Bronchoalveolar fluid TNF concentration: -Released at high levels by activated alveolar macrophages -Marker of disease activity |
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Sarcoidosis: xray, gross
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Xray:
Marked, symmetric, bilateral hilar and mediastinal lymphadenopathy Mild reticulonodular interstitial infiltrate in the perihilar regions Gross: Small nodules which have irregular margins and are located mainly along the pulmonary vessels (arrows) and bronchi Late stage: -Interstitial fibrosis -Cavitary lesions -Honeycomb change -Subpleural cysts (especially apex of this upper lobes) |
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Sarcoidosis: histology
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Major Features
-Noncaseating granulomas --with multinucleated giant cells --epitheliod histiocytes -Characteristics: well formed or tightly packed, may become hyalinized -Distribution: along lymphatic routes—bronchovascular bundles, pleura, and septa Minor Features -Vasculitis in up to 2/3 of open lung biopsies -Punctate necrosis in up to 1/3 of open lung biopsies -Inclusions --Schaumann bodies --Asteroid bodies --Birefringent calcium carbonate or calcium oxalate crystals --Microcalcifications --Hamazaki-Wesenberg bodies Pertinent Negatives -Lack of organisms on cultures or special stains -Lack of exposure to mineral dust such as beryllium, talc, or aluminum -Paucity of interstitial chronic inflammation Complications -Interstitial fibrosis with honeycombing in advanced stages -Cavitation/cystic changes -Aspergillomas |
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Sarcoidosis: treatment and prognosis
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Mortality secondary to sarcoidosis occurs
-1 to 5 percent of patients -Usually secondary to lung, central nervous system, or cardiac involvement Deciding when to treat sarcoidosis can be difficult -Almost 50 percent spontaneously remit Corticosteroids -Severe symptoms, persistent pulmonary opacities, hypoxemia, and severe lung function impairment -Extrapulmonary manifestations including ocular disease, hypercalcemia, cardiac dysrhythmia, neurologic involvement, arthritis, and disfiguring skin lesions -Aspergilloma is complication which may result in life-threatening pulmonary hemorrhage Alternative treatments -Immunosuppressive, cytotoxic, and antimalarial drugs -Radiation -Organ transplantation (for end stage problems) |
