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Flashcards in Obstructive & Restrictive Lung Disease Deck (66):


Loss of lung volume caused by inadequate expansion of airspaces
Results in shunting of inadequately oxygenated blood from pulmonary arteries to the pulmonary veins
-Ventilation-perfusion imbalance


Atelectasis 3 forms

Resorption Atelectasis
Compression Atelectasis
Contraction Atelectasis


Resorption Atelectasis

Obstruction prevents air from reaching distal airways
Most common cause is a mucous or mucopurulent plug in a bronchus
-Postoperatively; also asthma, bronchiectasis, chronic bronchitis, or aspiration of a foreign body


Compression Atelectasis

Mechanical collapse of the lung
Usually associated with accumulation or fluid, blood, or air in the pleural cavity
Elevated diaphragm: Bedridden, ascites, surgery


Contraction Atelectasis

Caused by fibrotic changes
Hamper expansion or increase elastic recoil


Acute Lung Injury

Encompasses a spectrum of pulmonary lesions that can be initiated by numerous conditions
-Acute onset of dyspnea
-Bilateral pulmonary infiltrates on radiographs
-No clinical evidence of primary left-sided heart failure
An example of non-cardiogenic pulmonary edema
Most severe manifestation of ALI is Acute Respiratory Distress Syndrome (ARDS)


Acute Respiratory Distress Syndrome

ARDS is a clinical syndrome caused by diffuse alveolar capillary and epithelial damage
-Rapid onset of life-threatening respiratory insufficiency
-Severe hypoxemia refractory to oxygen therapy
-May progress to multisystem organ failure
May be caused by direct or indirect injury to the lung
Histological manifestation of ARDS is known as Diffuse Alveolar Damage


ARDS Pathogenesis

The blood-air barrier is compromised by endothelial injury, epithelial injury, or most commonly both
-Leads to increased vascular permeability and alveolar flooding, loss of diffusing capacity, and widespread surfactant abnormalities
Lung injury is caused by an imbalance of pro-inflammatory and anti-inflammatory mediators
-Neutrophils are thought to have an important role in the pathogenesis of ARDS


ARDS clinical

Mortality rate: 60%
Poor prognosis: Advanced age, bacteremia (sepsis), multisystem failure
Chronic sequelae: may develop diffuse interstitial fibrosis and have continued compromise of respiratory function
In most patients who survive normal respiratory function returns within 6-12 months


Obstructive disease (airway disease)

Limitation of airflow resulting from an increase in resistance caused by partial or complete obstruction at any level


Restrictive disease

Reduced expansion of lung parenchyma accompanied by decreased total lung capacity


Major diffuse obstructive disorders

Emphysema, chronic bronchitis, bronchiectasis, and asthma
Hallmark is decreased expiratory flow rate
Measured by FEV1
Obstruction is the result of anatomic narrowing or decreased elastic recoil


Diffuse restrictive diseases

FEV1 is normal or proportionally reduced
-Chest wall disorders in the presence of normal lungs
*Obesity, pleural disease, neuromuscular disorders
-Acute or chronic interstitial lung diseases
*Acute: ARDS
*Chronic: pneumoconioses, idiopathic pulmonary fibrosis, infiltrative conditions (e.g., sarcoidosis)


Obstructive Pulmonary Disease

Emphysema and chronic bronchitis can exist one without the other, but they usually coexist
-Both have a common trigger—cigarette smoking, especially long-term, heavy tobacco exposure
Often emphysema and chronic bronchitis are grouped together clinically as Chronic Obstructive Pulmonary Disease (COPD)
-Affects >10% of the adult population in the US
-Fourth leading cause of death in the US



Abnormal permanent enlargement of the airspaces, distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis
Emphysema is classified by its anatomic distribution within the lobule
-Centriacinar, panacinar, distal acinar, and irregular
-Only the first two cause clinically significant airway obstruction
-Centriacinar is 20 times more common than panacinar


Centriacinar (Centrilobular) Emphysema

Central or proximal part of acini involved; distal alveoli spared
More common and severe in the upper lobes
In severe cases, the distal acinus can become involved
Most commonly seen as a consequence of cigarette smoking


Panacinar (Panlobular) Emphysema

Acini uniformly enlarged from respiratory bronchiole to terminal blind alveoli
More common in the lower lung zones
Occurs in α1-antitrypsin deficiency (genetic deficiency)


Distal Acinar (Paraseptal) Emphysema

Distal acinus involved; proximal part normal
Most striking near pleura, along lobular septa, and margins of lobules
Adjacent to areas of fibrosis, scarring, or atelectasis
More severe in upper half of lungs
Sometimes spaces merge and further enlarge into bullae
Associated with spontaneous pneumothorax in young people


Irregular Emphysema

Acinus is irregularly involved
Associated with scarring
Most common form of emphysema
-Clinically asymptomatic


Emphysema Pathogenesis

Current opinion favors two critical imbalances
-Protease-antiprotease imbalance
-Oxidant-antioxidant imbalance
Almost always coexist
-Additive effect in producing tissue damage
Protease-antiprotease imbalance hypothesis
-Genetic deficiency of α1-antitrypsin has a marked tendency to develop emphysema that is compounded by cigarette smoking


Protease-antiprotease imbalance hypothesis

Neutrophils are normally sequestered in the pulmonary capillaries; a few gain access to the alveolar spaces
Any stimulus that increases number of leukocytes or release of protease containing granules increases proteolytic activity
With low levels of α1-antitrypsin, elastic tissue destruction is unchecked resulting in emphysema


Cigarette smoking contributes to both protease-antiprotease and oxidant-antioxidant imbalance hypotheses

Neutrophils and macrophages accumulate in alveoli
Neutrophils are activated
Macrophage elastase activity is enhanced
Tobacco smoke contains abundant reactive oxygen species
Activated neutrophils generate reactive oxygen species
Oxidative injury inactivates native antiproteases


Clinical of “pure” emphysema

Dyspnea is usually first symptom; steadily progressive
Weight loss
Reduced FEV1


Emphysema Classic presentation

Barrel-chested and dyspneic, prolonged expiratory interval, sitting hunched forward squeezing the air out of lungs with each breath
Severe airspace enlargement and low diffusing capacity, dyspnea and hyperventilation is prominent until very late in the disease, gas exchange is adequate and blood gases are near normal
Referred to as “Pink puffers” (see later picture)


Emphysema clinical course

Secondary pulmonary hypertension develops gradually
-Hypoxia-induced vascular spasm
-Loss of pulmonary capillary surface area
-Pulmonary failure
-Right-sided heart failure


Emphysema That’s Not Emphysema

Compensatory emphysema
-loss of parenchyma
Obstructive overinflation
Bullous emphysema
Mediastinal (interstitial) emphysema


Chronic Bronchitis clinical diagnosis

Persistent productive cough for at least 3 months in at least 2 consecutive years
Caused by cigarette smoking and air pollutants


Chronic Bronchitis 3 forms

Simple chronic bronchitis
-Airflow not obstructed
Chronic asthmatic bronchitis
-Hyperresponsive airways with intermittent bronchospasm and wheezing
Chronic obstructive bronchitis
-Chronic outflow obstruction usually with associated emphysema
-Heavy cigarette smokers


Chronic Bronchitis pathogenesis

Hypersecretion of mucus is a distinctive feature
-Cigarette smoking and air pollutants induce:
*Hypertrophy of mucous glands in the trachea and bronchi
*Marked increase in goblet cells in smaller bronchi and bronchioles
*Inflammation and infiltration by CD8+ T cells, macrophages, and neutrophils (eosinophils are lacking unless asthmatic bronchitis)
Airflow obstruction is due to peripheral involvement
-Small airway disease
*Goblet cell metaplasia with mucous plugging, inflammation, and bronchiolar wall fibrosis
*Causes early and mild airflow obstruction
-Coexistent emphysema
*Cause of significant airflow obstruction
Microbial infection has a secondary role
-Maintains inflammation
-Exacerbates symptoms


Chronic Bronchitis clinical

Prominent cough with production of sputum
With chronic outflow obstruction,
Hypercapnia, hypoxemia, cyanosis
Secondary pulmonary hypertension and right-sided heart failure
Often seek medical attention when CHF develops
Referred to as “Blue bloaters” (see picture later)
Recurrent infections and respiratory failure are constant threats



Chronic inflammatory disorder of the airways
-Recurrent episodes of wheezing, breathlessness, chest tightness, and cough
-Particularly at night or early morning
Caused by repeated immediate hypersensitivity and late-phase reactions
Triad of:
-Intermittent and reversible airway obstruction
-Chronic bronchial inflammation with eosinophils
-Bronchial smooth muscle hypertrophy and hyperreactivity


Asthma classification

70% extrinsic or atopic asthma
-IgE and TH2-mediated immune responses to environmental antigens
30% intrinsic or non-atopic asthma
-Non-immune triggers
-Aspirin, viral infections, cold, exercise, inhaled irritants, psychological stress


Asthma Etiologic factors

Genetic predisposition to type I hypersensitivity
Acute and chronic airway inflammation
Bronchial hyperresponsiveness


Asthma Inflammation

Many cell types and mediators, especially important are TH2 cells
TH2 cells: IgE, eosinophil recruitment, mucus production
Epithelial activation: more TH2 cells and eosinophils, other leukocytes, amplifying inflammatory reaction


Asthma Airway remodeling

Hypertrophy of bronchial smooth muscle
Deposition of subepithelial collagen
Inherited predisposition and mast cells


Atopic Asthma

Usually begins in childhood
History of atopy
Triggered by environmental allergens
-Immediate response on re-exposure
*Within minutes
*Bronchoconstriction, edema, mucus secretion
-Late-phase reaction
*4-8 hours later
*Eosinophils are particularly important
*Amplify and sustain the inflammatory response


Non-Atopic Asthma

Triggered by viral respiratory tract infections and inhaled air pollutants
Mechanism less clear for the bronchial inflammation and hyperresponsiveness
Common end pathway with atopic asthma
-Treated the same way


Asthma attack

severe dyspnea and wheezing
Chief difficulty lies in exhalation
Progressive hyperinflation (air trapped distal to the bronchi)
Attacks last 1 to several hours
Treat with bronchodilators and corticosteroids


Status asthmaticus

severe attack that doesn’t respond to therapy
May last days or even weeks
Associated with hypercapnia, acidosis, severe hypoxemia
May be fatal



Permanent dilation of bronchi and bronchioles due to destruction of muscle and elastic supporting tissue
Predisposing conditions
-Bronchial obstruction
-Congenital or hereditary conditions
*Cystic fibrosis, immunodeficiency states, Kartagener syndrome
-Necrotizing pneumonia


Bronchiectasis pathogenesis

Chronic persistent infection


Bronchiectasis clinical

Severe, persistent cough with expectoration of mucopurulent sputum
Often episodic
-Upper respiratory tract infection or new pathogen introduced
May have clubbing of fingers
Significant obstructive ventilatory defects develop in severe cases


Diffuse Interstitial (Restrictive) Lung Disease

Heterogeneous group of disorders characterized predominantly by diffuse and usually chronic involvement of the pulmonary connective tissue
Many have unknown cause and pathogenesis
Some have intraalveolar as well as interstitial components
Frequent overlap of histological features
Hallmark is reduced lung compliance (stiff lungs)


Diffuse Interstitial (Restrictive) Lung Disease Similar clinical signs, symptoms, radiographic findings, and pathophysiology

Increased breathing effort (dyspnea)
Damage to epithelium and vasculature leads to ventilation-perfusion abnormalities and hypoxia
Radiographs show diffuse infiltrates
Progress to respiratory failure often with pulmonary hypertension
-End stage is often diffuse pulmonary interstitial fibrosis


Diffuse Interstitial (Restrictive) Lung Disease Pathogenesis

Alveolitis is an early common manifestation
Persistent inflammation leads to cellular interactions involving lymphocytes, macrophages, and neutrophils with parenchymal injury, proliferation of fibroblasts, and progressive interstitial fibrosis
Activation of pulmonary macrophages is a key event in the pathogenesis of interstitial fibrosis


Idiopathic Pulmonary Fibrosis

Cryptogenic fibrosing alveolitis
2/3 of patients > 60 years of age at presentation
Histological pattern: Usual interstitial pneumonia (UIP)
-Patchy interstitial fibrosis that varies in intensity and with time
-End stage results in honeycombing
Other known causes must be ruled out


Idiopathic Pulmonary Fibrosis Clinical

Presents insidiously
Non-productive cough and progressive dyspnea
Dry crackles on inspiration
Cyanosis, cor pulmonale, and edema may develop late
Relentless progression
-Mean survival is 3 years or less
-Lung transplant is only definitive therapy


Nonspecific Interstitial Pneumonia

Diffuse fibrosing interstitial lung disease
Histology different from UIP
-Cellular pattern
-Fibrosing pattern
*Patchy fibrosis without temporal heterogeneity
Present with dyspnea and cough of several months duration
-Cellular pattern better than fibrosing pattern
-Fibrosing pattern better than UIP


Cryptogenic Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP)
Present with cough and dyspnea; radiographs show patchy areas of airspace consolidation
-Polypoid plugs of loose, organizing connective tissue within alveoli, alveolar ducts, and often bronchioles
-Connective tissue is same age
-Underlying lung architecture is normal
Most patients require steroid treatment of 6 months or longer
Must rule out known causes of organizing pneumonia


Pulmonary Involvement in Collagen Vascular Disease

Many collagen vascular diseases may involve the lung
Many patterns are possible
-UIP, NSIP, vascular sclerosis, organizing pneumonia, bronchiolitis are most common
-Pleural involvement may be present
Pulmonary involvement in these diseases is usually associated with a poor prognosis
-Still better than IPF



Non-neoplastic lung reaction to inhalation of mineral dusts
-Extended to include organic particulates
-Some also include fume and vapor induced disease
Most common mineral dust pneumoconioses
-Coal dust, silica, and asbestos
-Nearly all result from workplace exposure
-Asbestos cancer risk extends to family members and exposure outside the workplace


Pneumoconioses path

Lung reaction depends on size, shape, solubility, and reactivity of the particles
-Particles 1-5 microns are the most dangerous; lodge at the distal airways
-Macrophages accumulate and endocytose the trapped particles
-Macrophages are the key cellular element in initiating and perpetuating lung injury and fibrosis
-Lymphatic drainage and macrophage migration may amplify and extend the local reaction
Tobacco smoking worsens the effects of all inhaled mineral dusts, especially asbestos


Coal Workers’ Pneumoconiosis (CWP) spectrum

Asymptomatic anthrocosis

Simple coal workers’ pneumoconiosis

Complicated CWP or progressive massive fibrosis (PMF)


Asymptomatic anthrocosis

Pigment accumulates without perceptible cellular reaction


Simple coal workers’ pneumoconiosis

Accumulation of macrophages in macules and nodules
Little or no pulmonary dysfunction
Upper lung zones are more affected
Centrilobular emphysema can occur


Complicated CWP or progressive massive fibrosis (PMF)

Extensive fibrosis and compromised lung function
< 10% of simple CWP progresses to PMF
Requires years to develop
Scars > 2 cm
PMF can also be seen in silicosis and asbestosis
Coal containing trace metals, inorganic minerals, and silica is associated with higher risk of CWP


Coal Workers’ Pneumoconiosis clinical

CWP is usually a benign disease
If PMF develops,
-Increasing pulmonary dysfunction, pulmonary hypertension, and cor pulmonale
Progression linked to exposure level and total dust burden
PMF tends to progress even in the absence of further exposure
No increased risk of bronchogenic carcinoma



Most prevalent chronic occupational disease in the world
Caused by the inhalation of crystalline silica
-Crystalline > amorphous silica
-Quartz is most commonly associated with silicosis
-Quartz mixed with other minerals has a reduced fibrogenic effect
Inhaled silica particles cause activation and release of mediators by pulmonary macrophages


Silicosis morphology

Silicotic nodules
-Concentrically arranged hyalinized collagen fibers
-Weakly birefringent silica by polarized microscopy
-More prevalent in upper lung zones
Nodules may coalesce into hard collagenous scars
May progress to PMF
Fibrotic lesions may occur in lymph nodes
-“Eggshell” calcification of hilar lymph nodes


Silicosis clinical

Usually detected in routine chest radiographs of asymptomatic workers
-Fine nodularity in upper lung zones
If PMF develops,
-Progressive without further exposure
-Dyspnea, pulmonary hypertension, cor pulmonale
Increased susceptibility to tuberculosis
Crystalline silica is considered to be carcinogenic


Asbestos Related Diseases

Asbestos is a family of crystalline hydrated silicates with a fibrous geometry
Exposure is linked to:
Parenchymal interstitial fibrosis (asbestosis)
Localized fibrous plaques or rarely diffuse pleural fibrosis
Pleural effusions
Bronchogenic carcinoma
Malignant pleural and peritoneal mesotheliomas
Laryngeal carcinoma


Asbestos Related Diseases path

Concentration, size, shape, and solubility of the different forms dictate whether disease will occur
-Serpentine: curly, flexible, and more soluble
-Amphiboles: straight, stiff, brittle, less soluble
-Amphiboles are less prevalent but more pathogenic
-Both types cause disease
Asbestos causes fibrosis by interacting with lung macrophages


Asbestos probably also functions as a tumor initiator and promoter

Free radical generation
Toxic chemicals absorb onto the fibers
-Synergy of tobacco smoke and asbestos in bronchogenic carcinoma


Asbestosis morphology

Diffuse pulmonary interstitial fibrosis with the presence of asbestos bodies
-Begins in lower lobes and subpleurally


Asbestos Related Diseases

Progressive dyspnea appears 10-20 years after exposure
Accompanied by productive cough
May be static or progress to CHF, cor pulmonale, and death
Bronchogenic carcinoma
-5 fold increased risk
-Concomitant cigarette smoking: 55 fold increased risk
-1000 fold increased risk
-Not increased with cigarette smoking


Drug and Radiation Induced Pulmonary Diseases

Cause pneumonitis and interstitial fibrosis
Acute radiation pneumonitis
-1-6 months after therapy
-Fever, out of proportion dyspnea, pleural effusion, pulmonary infiltrates in irradiated area
-May resolve with steroids
Chronic radiation pneumonitis
-Progression of acute radiation pneumonitis
-Associated with pulmonary fibrosis