OBSTRUCTIVE LUNG DISEASES

ROSHNI SANKARA SUBRAMANIAN

OBSTRUCTIVE DISEASES
Obstructive lung disease is a category of respiratory disease characterized by airway obstruction inflamed and easily collapsible airways obstruction to airflow problems exhaling

OBSTRUCTIVE DISEASES

In these diseases:
TLC and FVC are normal or slightly increased Marked by decreased expiratory flow (FEV1) Ratio of FEV1 to FVC is decreased

OBSTRUCTIVE CONDITIONS

Asthma Emphysema Chronic bronchitis Bronchiectasis Bronchiolitis

COPD

ASTHMA

Characterized by episodic, reversible bronchospasm resulting from broncho constriction in response to various stimuli

ASTHMA

Triggers
Allergens Exercise Respiratory infections Drugs and food additives Nose and sinus problems GERD Emotional stress

Inflammation causes obstruction of airways by: Acute bronchoconstriction Swelling of bronchial wall Chronic production of mucous Remodeling of airways walls

Two main processes are seen in the pathophysiology of asthma in the airways. 1. Inflammatory reaction 2. Remodeling

Cells involved in chronic allergic inflammation 1. Eosinophils 2. Mast cells 3. T-lymphocytes 4. Neutrophils 5. Basophils

ASTHAMA- pathology

Early phase response: 30 60 minutes

Allergen or irritant activates mast cells

Inflammatory mediators are released

histamine, bradykinin, leukotrienes, prostaglandins, plateletactivating-factor, chemotactic factors, cytokines

Intense inflammation occurs

Bronchial smooth muscle constricts Increased vasodilation and permeability Epithelial damage Increased mucus secretion Edema

Bronchospasm

ASTHAMA- pathology

Late phase response: 5 6 hours

Characterized by inflammation
Eosinophils and neutrophils infiltrate Mediators are released mast cells release histamine and additional mediators Self-perpetuating cycle Lymphocytes and monocytes invade as well Future attacks may be worse because of increased airway reactivity that results from late phase response

Individual becomes hyperresponsive to specific allergens and non-specific irritants such as cold air and dust Specific triggers can be difficult to identify and less stimulation is required to produce a reaction

 Airway remodeling

thickening of basement membrane edema size of submucosal glands

muscular hypertrophy
inflammatory infiltrate in bronchial walls

Asthma: Early Clinical Manifestations

Expiratory & inspiratory wheezing Dry or moist non-productive cough Chest tightness Dyspnea Anxious &Agitated Prolonged expiratory phase Increased respiratory & heart rate Decreased PEFR

Asthma: Early Clinical Manifestations

Wheezing Chest tightness Dyspnea Cough Prolonged expiratory phase [1:3 or 1:4]

Asthma: Severe Clinical Manifestations

Hypoxia Confusion Increased heart rate & blood pressure Respiratory rate up to 40/minute & pursed lip breathing Use of accessory muscles Diaphoresis(excessive sweating) & pallor Cyanotic nail beds Flaring nostrils

COPD

Chronic Obstructive Pulmonary Disease: COPD

Disease of airflow obstruction that is not totally reversible
Chronic

Bronchitis Emphysema

Chronic Bronchitis Common in smokers (> 90%), passive inhalation of smoke and smog-ridden cities Definition: Based on clinical grounds. persistent productive cough for at least 3 consecutive months and at least 2 consecutive years Occurrence: (Increased mucus production) a) simple chronic bronchitis i) raises mucoid sputum ii) airflow not obstructed b) chronic mucopurulent bronchitis i) mucus and pus ii) from secondary infection

c) chronic asthmatic bronchitis i) bronchitis with intermittent hypersensitivity and asthmatic constriction (difficult to diagnose from atopic asthma) d) chronic obstructive bronchitis i) difficult outflow as measured by pulmonary function test

Pathogenesis Hypersecretion of mucus a) beginning in large airways b) smoking single most important causative factor Increased transcription of mucin gene (MUC5AC) by cigarette smoke a) enlargement of mucus secreting glands (major consequence) b) hyperplasia and hypertrophy of mucus secreting cells and increase proportion of mucus to serous secretions. i) Reid index size of mucus glands

 Cough with sputum may last indefinitely without respiratory obstruction usually accompanies emphysema Some patients develop COPD with outflow obstruction a) hypercapnia b) hypoxemia c) exertional dyspnea d) cyanosis blue-bloaters Progression of disease a) pulmonary hypertension (Cor Pulmonale) b) cardiac failure Metaplasia of bronchial epithelium

2. Emphysema Permanent enlargement of airspaces distal to terminal bronchioles and is accompanied by destruction of their walls

Types of emphysema a) Panacinar (panlobular) emphysema i) uniformly enlarged acini ii) lower lung zones iii) 1-antitrypsin definciency b) Centrilacinar emphysema i) dilation upstream with normal distal portions ii) more common than panacinar (~ 95% of cases) iii) seen in heavy smokers, often in association with chronic bronchitis

c) Distal Acinar (paraseptal) emphysema i) proximal acini normal and distal part most involved ii) upper half of lungs/near pleura d) irregular i) acini irregularly involved ii) airspace enlargement with fibrosis iii) most are asymptomatic and not clinically significant
Centriacinar and panacinar are the ones that cause clinical airflow obstruction

Incidence Centrilobular most common and severe in men Clear association with cigarette smoking 2 Theories i) protease-antiprotease imbalance ii) oxidant-antioxidant imbalance

 Protease-antiprotease Hypothesis a) patients with deficiency of antiprotease, 1-antitrypsin (AAT) have increased tendency to develop emphysema b) about 1% of all patients have this defect c) 1-antitrypsin major inhibitor of proteases, particularly elastase d) homozygous patients with genetic AAT deficiency develop emphysema

 Sequence: a) neutrophils (primary source of proteases) sequestered in pulmonary capillaries (lower zones primarily) i) smoking neutrophils & macrophages ii) CD8+ T cells cause direct damage and/or recruit macrophages b) few gain access to alveolar space c) release of proteolytic enzymes + ROS (reactive oxygen species) d) low levels of 1-antitrypsin damage to elastin (via elastase) e) emphysema ensues

 Oxidant-antioxidant hypothesis Lung has antioxidants a) superoxide dismutase b) glutathione Smoke has many oxidant species which deplete these normal scavengers a) activated neutrophils also has ROS Oxidative injury depletes or destroys native antiproteases a) Functional 1- antitrypsin definciency even though blood enzyme is not deficient

 Signs: a) Barrel chested and dyspneic b) Hyperventilation c) Normal blood gases (- pink puffers) Some patients have other pulmonary disease a) do not hyperventilate and become cyanotic i) blue-bloaters (chronic bronchitis) b) death from Right CHF, coma, acidosis, pulmonary fatigue

Bronchiectasis Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic supporting tissue resulting or associated with chronic necrotizing infection. Is not primary disease but secondary to persisting infection or obstruction caused by variety of conditions. Cough and purulent sputum Irreversible Bronchial dilation

 Most often caused by: a) bronchial obstruction i) tumors ii) foreign bodies iii) localized to obstructed lung segment b) congenital or hereditary condition i) cystic fibrosis ii) immunodeficiency states (IgE deficiency) repeated infections iii) Kartagener syndrome (Structural abnormalities of cilia (decreased mucocilliary clearance) - Sterility in males/females

c) necrotizing pneumonia (S. aureus, K. pneumoniae) i) post tubercular bronchiectasis significant cause of morbidity

Bronchiolitis

Bronchiolitis is an acute inflammatory injury of the bronchioles that is usually caused by a viral infection. severe symptoms are usually only evident in young infants Bronchiolitis usually affects children younger than 2 years, with a peak in infants aged 3-6 months Bronchioles are small airways, less than 2 mm in diameter, and lack cartilage and submucosal glands

Bronchiolitis - Pathophysiology

Bronchiolitis is very contagious. The virus that causes it is spread from person to person by direct contact with nasal secretions, airborne droplets, and fomites. The effects of bronchiolar injury include the following: Increased mucus secretion Bronchial obstruction and constriction Alveolar cell death, mucus debris, viral invasion

Bronchiolitis - Pathophysiology

Air trapping Atelectasis Reduced ventilation that leads to ventilation/perfusion mismatch Labored breathing Ninety percent of cases are caused by respiratory syncytial virus (RSV)

Bronchiolitis- signs & symptoms

Cough Dyspnea Wheezing Poor feeding Hypothermia or hyperthermia Wheezing Hypoxia Nasal flaring