SM_167a: Lung Pathology & Restrictive Lung Disease Flashcards
What are features of normal lungs on gross anatomy?
- Pleura that are smooth or glistening
- Red color (but not overly red)
- Consistency of a wet, firm sponge
- Airways enlarged and patent
What are features of diseased lungs on gross anatomy?
- Rough or dull pleura
- Gray color (fibrosis, consolidation) or overly red splotchy color
- Too firm (fibrosis, consolidation) or too soft (emphysema)
- Lots of enlarged air spaces (emphysema)
_______ and ________ indicates this a bronchus
Cartilaginous ring and submucosal gland indicate this is a bronchus
(Ciliated columnar epithelium lining airway, submucosa sparsely populated with collagenous tissue and smooth muscles)
How can you tell that this bronchus is normal?
- Ciliated columnar epithelium lining airway, then loose connective tissue, then cartilage
- Submucosa sparsely populated with collagenous tissue and smooth muscles
How can you tell this alveolus is normal?
- Nothing in the alveolar spaces
- Alveolar septae (single layer of epithelium on both sides with capillary between them) are thin and delicate
What are the characteristics of obstructive lung disease?
- Most involve airway
- Increased resistance to airflow
- Do not generally progress to honeycomb lung
What are the characteristics of restrictive lung disease?
- Most involve lung parenchyma
- Decreased lung capacity
- Reduced expansion of lung parenchyma
- May progress to end stage honeycomb lung
Most obstructive lung diseases involve the ______, while most restrictive lung diseases involve the ______
Most obstructive lung diseases involve the airway, while most restrictive lung diseases involve the lung parenchyma
Obstructive lung diseases involve increased ______, while restrictive lung diseases involve decreased ______
Obstructive lung diseases involve increased resistance to flow, while restrictive lung diseases involve decreased lung capacity and reduced expansion of lung parenchyma
Obstructive lung diseases ____ progress to honeycomb lung, while restrictive lung diseases ____ progress to end-stage honeycomb lung
Obstructive lung diseases do not generally progress to honeycomb lung, while restrictive lung diseases may progress to end-stage honeycomb lung
What are examples of obstructive lung disease?
Obstructive lung disease
- COPD (emphysema, chronic bronchitis)
- Asthma
- Bronchiectasis
What are examples of restrictive lung disease?
Restrictive lung disease
- Usual interstitial pneumonia
- Nonspecific interstitial pneumonia
- Hypersensitivity pneumonitis
- Sarcoidosis
Restrictive lung disease patterns include ______ and ______
Restrictive lung disease patterns include usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP)
Specific disease entities causing restrictive lung disease include ______ and ______
Specific disease entities causing restrictive lung disease include sarcoidosis and hypersensitivity pneumonitis
What are common causes of usual interstitial pneumonia?
- Idiopathic pulmonary fibrosis
- Connective tissue diseases
- Asbestosis
- Chronic hypersensitivity pneumonia
Pathology of usual interstitial pneumonia involves ________ and _______ heterogeneity
Pathology of usual interstitial pneumonia involves temporal and geographic heterogeneity
- Geographic heterogenity: normal areas immediately adjacent to areas of fibrosis
- Temporal heterogeneity: areas of young fibrosis (fibroblastic foci) adjacent to areas of old (eosinophilic, hypocellar foci)
- More severe in subpleural regions
Geographic heterogeneity in usual interstitial pneumonia is _______
Geographic heterogeneity in usual interstitial pneumonia is normal areas immediately adjacent to areas of fibrosis
Temporal heterogeneity in usual interstitial pneumonia is _______
Temporal heterogeneity in usual interstitial pneumonia is areas of young fibrosis (fibroblastic foci) adjacent to areas of old (eosinophilic, hypocellular) fibrosis
Geographic and temporal heterogeneity in usual interstitial pneumonia are more severe in _______ regions
Geographic and temporal heterogeneity in usual interstitial pneumonia are more severe in subpleural regions
What are common causes of nonspecific interstitial pneumonia?
- Idiopathic
- Autoimmune disease
Pathology of nonspecific interstitial pneumonia involves ______ and ______ _____ fibrosis
Pathology of nonspecific interstitial pneumonia involves temporally and geographically uniform fibrosis
- What is sarcoidosis?
Granulomatous disease of unknown etiology
- More common in adults <40, females, and African Americans
- Extrapulmonary involvement (eyes, skin, spleen) common
- Most cases regress with or without treatment but some progress to pulmonary fibrosis
Pathology of sarcoidosis involves _______ typically along _______
Pathology of sarcoidosis involves well formed granulomas without lymphoid inflammation or necrosis (naked granulomas) typically along bronchovascular structures
What must you rule out when considering a diagnosis of sarcoidosis?
Infectious etiology
A naked granuloma is a granuloma _______
A naked granuloma is a granuloma without inflammation or necrosis
What is hypersensitivity pneumonia?
Hypersensitivity pneumonia
- Caused by prolonged exposure to inhaled organic antigens (animal proteins, bacteria, or plants)
- Symptoms may be acute (fever, cough, dyspnea) or chronic (progressive respiratoru failure) depending on exposure
Pathology of hypersensitivity pneumonia involves ________
Pathology of hypersensitivity pneumonia involves poorly formed non-necrotizing granulomas accompanied by lymphocytes and plasma cells, typically around airways
Chronic hypersensitivity pneumonia demonstrates a ______ pattern of injury
Chronic hypersensitivity pneumonitis demonstrates a usual interstitial pneumonia pattern of injury
What is honeycomb lung?
Honeycomb lung
- End stage form of fibrosis associated with restrictive lung disease (most commonly associated with usual interstitial pneumonia)
- Can be identified in CT scans and pathologic specimens
Pathology of honeycomb lung involves ______ on gross examination and ______ on pathological examination
Pathology of honeycomb lung involves fibrosis and cystic dilated spaces on gross examination and dense fibrosis with loss of normal lung architecture and cystic spaces lined by columnar bronchial epithelial cells on pathological examination
Describe the characteristics of obstructive lung disease
Obstructive lung diseases
- Produce decreased flow in large and small airways
- Generally increase lung volumes due to air trapping and overexpansion
- Generally decreased elastic recoil
_______, _______, and _______ are examples of obstructive lung disease
COPD (emphysema, chronic bronchitis), asthma, and bronchiectasis are examples of obstructive lung disease
COPD includes ______ and ______
COPD includes emphysema and chronic bronchitis
(irreversible, related to long term damage from smoking)
Emphysema is a disease of the ______, with ______ airway involvement
Emphysema is a disease of the lung parenchyma, with minimal airway involvement
Describe emphysema
Emphysema
- Enlargement of alveolar spaces due to parenchymal destruction
- Loss of elastic connective tissue around airways results in airway collapse during expiration (obstruction)
- Protease-antiprotease imbalance
- Smoking is most common etiology
Pathology of emphysema involves _______ and _______
The pathology of emphysema involves large overinflated lungs and enlarged alveolar spaces w/ floating spaces
A lung affected by emphysema shows ______ on gross inspection
A lung affected by emphysema shows enlarged alveolar spaces on gross inspection
(large and overinflated)
A lung affected by emphysema shows _______ on pathology
A lung affected by emphysema shows enlarged alveolar spaces w/ floating septae on pathology
Describe the variants of emphysema
- Centriacinar: most common, smoking related
- Distal acinar: involves areas of scarring
- Panacinar: usually related to A1AT deficiency
Describe chronic bronchitis
Chronic bronchitis
- Disease of larger airways
- Smoking related
- Clinical diagnosis: productive cough for msot days in 3 consecutive months for 2 consecutive years
- Predisposes to infection
Pathology of chronic bronchitis involves _______ and _______
The pathology of chronic bronchitis involves chronic airway inflammation and mucus gland hypertrophy
Reid index is defined as _______
Reid index is defined as ratio of mucus gland size to distance from epithelium to cartilage
( > 0.4 for chronic bronchitis)
Contrast emphysema and chronic bronchitis
Emphysema: disease lung parenchyma, does not require lots of inflammation, protease/antiprotease imbalance
Chronic bronchitis: larger airways, usually has more significant inflammatory component, airway irritation results in inflammation and mucus hypersecretion
Describe bronchiectasis
Bronchiectasis
- Irreversible dilatation of the airways
- Vicious cycle of obstruction, infection, and bronchial wall destruction - caused by cystic fibrosis (thick secretions), Kartagener’s syndrome (ciliary dysmotility), repeated infections
- Can cause chronic productive cough w/ foul-smelling sputum
The pathology of bronchiectasis involves ______ and ______
The pathology of bronchiectasis involves dilated bronchi and plugging of bronchi with mucus containing acute and chronic inflammatory cells
Asthma involves _____, _____, and _____
Asthma involves reversible episodic obstruction, airway hyperreactivity, and chronic inflammation
- Reversible episodic obstruction: smooth muscle contraction, mucosal edema, mucus secretion
- Airway hyperreactivity
- Chronic inflammation: cytokine secreting TH2 lymphocytes, eosinophils (MBP), and leukotrienes are center
Asthma has an ______ and ______ phase
Asthma has an early and late phase
Early phase of asthma is mediated by ______
Early phase of asthma is mediated by soluble factors
- Airway constriction, vascular permeability, edema
- Mediated by leukotrienes, prostaglandins, histamine, etc
Late phase of asthma is mediated by ______
Late phase of asthma is mediated by inflammatory cells
- Recruitment of inflammatory cells: eosinophils, lymphocytes, etc
Atopic asthma is a ______, while non-atopic can occur from _____
Atopic asthma is a Type I hypersensitivity, while non-atopic asthma may occur due to something like cold weather
Acute pathology of asthma involves ______, ______, and ______
Acute pathology of asthma involves eosinophils (Charcot-Leyden crystals), mucus plugging, Churchman spiral
Chronic pathology of asthma involves ______ and ______
Chronic pathology of asthma involves basement membrane thickening and smooth muscle hypertrophy and airway fibrosis
_______ in asthma involves smooth muscle hyperplasia, mucus gland hyperplasia, and epithelial damage
Airway remodeling in asthma involves smooth muscle hyperplasia, mucus gland hyperplasia, and epithelial damage
What is this?
What condition is this seen in?
Basement membrane thickening in asthma
What is this?
What condition is this seen in?
Charcot-Leyden crystals in asthma
What is this?
What condition is this seen in?
Mucus plugging in asthma
What is this?
What condition is this seen in?
Churchman’s spirals in asthma
Describe acute lung injury
Acute lung injury
- Abrupt onset of hypoxemia and bilateral pulmonary infiltrates
- Set of clinical symptoms, not a disease, caused by infection, physical injury, inhaled irritants, chemical injury
- Pathogenesis related to pneumocyte/endothelial injury which triggers endothelial activation and inflammation
Common etiologies of bacterial pneumonia are ______, ______, ______, and ______
Common etiologies of bacterial pneumonia are
- S. pneumoniae
- H. influenza
- M. catarrhalis
- S. aureus
(may be community or hospital acquired)
Pathology of acute lung injury involves _____, characterized by _____ and _____
Pathology of acute lung injury involves diffuse alveolar damage, characterized by intra-alveolar dense pink hyaline membranes and increased inflammatory cells
Common etiologies of viral pneumonia include
- Immunocompetent:
- Immunocompromised:
Common etiologies of viral pneumonia include
- Immunocompetent: influenza A and B, RSV, adenovirus
- Immunocompromised: CMV, herpes
Pathology of bacterial pneumonia involves ______, ______, and ______
Pathology of bacterial pneumonia involves
- May be patchy (bronchopneumonia) or diffuse (lobar pneumonia)
- Parenchyma that are firm, congested and consolidated (hepatization)
- Numerous neutrophils and hyaline membranes within alveolar spaces
Pathology of viral pneumonia involves ______ and ______
Pathology of viral pneumonia involves lymphoid infiltrate within alveolar septae and interstitium and viral inclusions (CMV) or glassy chromatin (herpes)
Pneumonia caused by CMV is characterized by ______
Pneumonia caused by CMV is characterized by viral inclusions
Pneumonia caused by herpes is characterized by ______
Pneumonia caused by herpes is characterized by glassy chromatin
(cytopathic effect)
Chronic granulomatous infection common etiologies are _____ and _____
Chronic granulomatous infection common etiologies are mycobacterial and fungal (histoplasmosis, blastomycoses, coccidiodomycosis)
(asymptomatic or subacute in healthy individuals)
Pathology of chronic granulomatous infections involves ______
Which stains are used?
Pathology of chronic granulomatous infections involves granulomatous inflammation (typically necrotizing)
- Silver stain to highlight fungal organisms
- Acid fast bacillus stain to highlight mycobacteria
_____ stain is used to highlight fungal organisms in chronic granulomatous infection
Silver stain is used to highlight fungal organisms in chronic granulomatous infection
_____ stain is used to highlight mycobacteria in chronic granulomatous infection
Acif fast bacillus stain is used to highlight mycobacteria in chronic granulomatous infections
Describe the categorization of tumors affecting the lung
- Lung tumors
- Non-small cell lung carcinoma: adenocarcinoma, squamous cell carcinoma, large cell carcinoma
- Small cell carcinoma
- Carcinoid
- Pleural tumors: malignant mesothelioma
Describe adenocarcinoma
Adenocarcinoma
- Type of non-small cell carcinoma
- Most common form of lung carcinoma and in non-smokers
- Often peripheral tumors
- Molecular testing for driver mutations used to guide therapy in unresectable cases
Pathology of adenocarcinoma involves _____, _____, and _____
Pathology of adenocarcinoma involves gland formation, mucin production, and immunoreactive for TTF1
What pathologic changes is occuring?
Which condition is this?
Gland formation in adenocarcinoma
What pathologic changes is occuring?
Which condition is this?
Mucin production in adenocarcinoma
What pathologic changes is occuring?
Which condition is this?
TTF1 immunoreactivity in adenocarcinoma
Describe squamous cell carcinoma
Squamous cell carcinoma
- Type of non-small cell carcinoma
- Almost always occurs in smokers
- Usually large centrally placed masses
- Different set of driver mutation than adenocarcinoma, none of which have an associated drug
Pathology of squamous cell carcinoma involves _____, _____, and _____
Pathology of squamous cell carcinoma involves keratinization, intracellular bridges, and TTF1 negative
What pathologic changes is occuring?
Which condition is this?
Keratinization in squamous cell carcinoma
What pathologic changes is occuring?
Which condition is this?
Intracellular bridges in squamous cell carcinoma
Describe large cell carcinoma
Large cell carcinoma
- Wastebasket category
- Non-small cell carcinoma with no evidence of squamous or glandular differentiation
- Tend to be poorly differentiated tumors
Describe small cell carcinoma
Small cell carcinoma
- Invariably associated with smoking
- Vast majority of cases are unresectable bulky mediastinal disease
- Distant metastases are common
- Demonstrate neuroendocrine differnetiation (neurosecretory granules)
Pathology of small cell carcinoma involves ______, ______, and ______
Pathology of small cell carcinoma involves high nuclear/cytoplasmic ratios, lots of mitotic figures, and dark granular chromatin w/o nucleoli
Describe carcinoid tumors
Carcinoid tumors
- Often not associated with smoking
- Usually very indolent but metastasize occassionally
- Usually centrally placed tumors - often endobronchial
- Neuroendocrine differentiation (neurosecretory granules)
Pathology of carcinoid tumors involves ______, ______, and ______
Pathology of carcinoid tumors involves low nuclear cytoplasmic ratios, nested growth, granular “salt and pepper” chromatin
Describe malignant mesothelioma
Malignant mesothelioma
- Arises from mesothelial cells lining pleural and peritoneal surfaces
- Frequently associated with asbestos exposure
- Bad prognosis
Pathology of malignant mestholioma involves ______
Pathology of malignant mestholioma involves resembling adenocarcinoma or a malignant spindle cell tumor
