Obstructive & Restrictive Lung Disease

Question 1

Atelectasis

Answer 1

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
-Hypoxia

Question 2

Atelectasis 3 forms

Answer 2

Resorption Atelectasis
Compression Atelectasis
Contraction Atelectasis

Question 3

Resorption Atelectasis

Answer 3

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

Question 4

Compression Atelectasis

Answer 4

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

Question 5

Contraction Atelectasis

Answer 5

Caused by fibrotic changes

Hamper expansion or increase elastic recoil

Question 6

Acute Lung Injury

Answer 6

Encompasses a spectrum of pulmonary lesions that can be initiated by numerous conditions
Clinically
-Acute onset of dyspnea
-Hypoxemia
-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)

Question 7

Acute Respiratory Distress Syndrome

Answer 7

ARDS is a clinical syndrome caused by diffuse alveolar capillary and epithelial damage
-Rapid onset of life-threatening respiratory insufficiency
-Cyanosis
-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

Question 8

ARDS Pathogenesis

Answer 8

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

Question 9

ARDS clinical

Answer 9

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

Question 10

Obstructive disease (airway disease)

Answer 10

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

Question 11

Restrictive disease

Answer 11

Reduced expansion of lung parenchyma accompanied by decreased total lung capacity

Question 12

Major diffuse obstructive disorders

Answer 12

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

Question 13

Diffuse restrictive diseases

Answer 13

FEV1 is normal or proportionally reduced
Causes
-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)

Question 14

Obstructive Pulmonary Disease

Answer 14

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

Question 15

Emphysema

Answer 15

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

Question 16

Centriacinar (Centrilobular) Emphysema

Answer 16

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

Question 17

Panacinar (Panlobular) Emphysema

Answer 17

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

Question 18

Distal Acinar (Paraseptal) Emphysema

Answer 18

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

Question 19

Irregular Emphysema

Answer 19

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

Question 20

Emphysema Pathogenesis

Answer 20

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

Question 21

Protease-antiprotease imbalance hypothesis

Answer 21

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

Question 22

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

Answer 22

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

Question 23

Clinical of “pure” emphysema

Answer 23

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

Question 24

Emphysema Classic presentation

Answer 24

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)

Question 25

Emphysema clinical course

Answer 25

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

Question 26

Emphysema That’s Not Emphysema

Answer 26

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

Question 27

Chronic Bronchitis clinical diagnosis

Answer 27

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

Question 28

Chronic Bronchitis 3 forms

Answer 28

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

Question 29

Chronic Bronchitis pathogenesis

Answer 29

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

Question 30

Chronic Bronchitis clinical

Answer 30

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

Question 31

Asthma

Answer 31

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

Question 32

Asthma classification

Answer 32

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

Question 33

Asthma Etiologic factors

Answer 33

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

Question 34

Asthma Inflammation

Answer 34

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

Question 35

Asthma Airway remodeling

Answer 35

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

Question 36

Atopic Asthma

Answer 36

``` Usually begins in childhood History of atopy Triggered by environmental allergens Model -Sensitization -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 ```

Question 37

Non-Atopic Asthma

Answer 37

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

Question 38

Asthma attack

Answer 38

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

Question 39

Status asthmaticus

Answer 39

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

Question 40

Bronchiectasis

Answer 40

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

Question 41

Bronchiectasis pathogenesis

Answer 41

Obstruction | Chronic persistent infection

Question 42

Bronchiectasis clinical

Answer 42

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

Question 43

Diffuse Interstitial (Restrictive) Lung Disease

Answer 43

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)

Question 44

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

Answer 44

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

Question 45

Diffuse Interstitial (Restrictive) Lung Disease Pathogenesis

Answer 45

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

Question 46

Idiopathic Pulmonary Fibrosis

Answer 46

Cryptogenic fibrosing alveolitis M>F 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

Question 47

Idiopathic Pulmonary Fibrosis Clinical

Answer 47

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

Question 48

Nonspecific Interstitial Pneumonia

Answer 48

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 Prognosis -Cellular pattern better than fibrosing pattern -Fibrosing pattern better than UIP

Question 49

Cryptogenic Organizing Pneumonia

Answer 49

Bronchiolitis obliterans organizing pneumonia (BOOP) Present with cough and dyspnea; radiographs show patchy areas of airspace consolidation Histologically -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

Question 50

Pulmonary Involvement in Collagen Vascular Disease

Answer 50

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

Question 51

Pneumoconioses

Answer 51

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

Question 52

Pneumoconioses path

Answer 52

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

Question 53

Coal Workers’ Pneumoconiosis (CWP) spectrum

Answer 53

Asymptomatic anthrocosis Simple coal workers’ pneumoconiosis Complicated CWP or progressive massive fibrosis (PMF)

Question 54

Asymptomatic anthrocosis

Answer 54

Pigment accumulates without perceptible cellular reaction

Question 55

Simple coal workers’ pneumoconiosis

Answer 55

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

Question 56

Complicated CWP or progressive massive fibrosis (PMF)

Answer 56

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

Question 57

Coal Workers’ Pneumoconiosis clinical

Answer 57

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

Question 58

Silicosis

Answer 58

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

Question 59

Silicosis morphology

Answer 59

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

Question 60

Silicosis clinical

Answer 60

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

Question 61

Asbestos Related Diseases

Answer 61

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

Question 62

Asbestos Related Diseases path

Answer 62

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

Question 63

Asbestos probably also functions as a tumor initiator and promoter

Answer 63

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

Question 64

Asbestosis morphology

Answer 64

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

Question 65

Asbestos Related Diseases

Answer 65

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 Mesothelioma -1000 fold increased risk -Not increased with cigarette smoking

Question 66

Drug and Radiation Induced Pulmonary Diseases

Answer 66

Cause pneumonitis and interstitial fibrosis -Bleomycin -Amiodarone 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