Obstructive Lung Diseases PDF

# OBSTRUCTIVE LUNG DISEASES ## pathology2 Dr. Motaz Natsheh by: Eman turkman PPU University 2024-2025 ## Obstructive Lung Diseases Obstructive lung (airway) diseases include four main disorders: 1. Emphysema 2. Chronic bronchitis 3. Asthma 4. Bronchiectasis ## Emphysema Emphysema is a lung condit...

# OBSTRUCTIVE LUNG DISEASES ## pathology2 Dr. Motaz Natsheh by: Eman turkman PPU University 2024-2025 ## Obstructive Lung Diseases Obstructive lung (airway) diseases include four main disorders: 1. Emphysema 2. Chronic bronchitis 3. Asthma 4. Bronchiectasis ## Emphysema Emphysema is a lung condition characterized by the permanent enlargement of air spaces distal to terminal bronchioles, along with the destruction of their walls, occurring without significant fibrosis. This damage reduces the lungs' ability to exchange gases effectively, leading to breathing difficulties. - Destruction of alveolar air sacs - Loss of elastic recoil ### Types of Emphysema: * Centriacinar (centrilobular) * Panacinar (panlobular) * Distal acinar (paraseptal) ## Normal Acinus * Respiratory bronchioles * Alveolar duct * Alveoli * Septum ## Centriacinar (Centrilobular) Emphysema - **Definition:** A type of emphysema affecting the central or proximal parts of the acini (respiratory bronchioles), while sparing the distal alveoli. - **Distribution:** Lesions are more common and severe in the upper lobes, particularly in the apical segments. - **Progression:** In severe cases, the distal acinus may also be affected, making it hard to distinguish from panacinar emphysema. - **Risk Factor:** Most frequently occurs in cigarette smokers. - **Association:** with chronic bronchitis. ## Panacinar (panlobular) emphysema - **Definition:** Panacinar emphysema is characterized by uniform enlargement of the acini, affecting the respiratory bronchioles, alveolar ducts, and terminal alveoli. - **Distribution:** It predominantly affects the lower lung zones. - **Association:** Strongly linked to alpha-1 antitrypsin deficiency (a genetic condition that leads to reduced protection of the lung tissue from enzyme damage) ## Distal acinar (paraseptal) emphysema - **Definition:** Is a form of emphysema that predominantly affects the distal parts of the acinus, while the proximal portion remains normal. - **Location:** More prominent near the pleura, along lobular connective tissue septa, and at the margins of lobules. - **Distribution:** Usually more severe in the upper half of the lungs. - **Association:** Often occurs adjacent to areas of fibrosis, scarring, or atelectasis. - **Cause:** unknown - **Association:** Commonly seen in young adults and frequently linked to spontaneous pneumothorax. - **Appearance:** Characterized by multiple, contiguous, enlarged air spaces ranging from less than 0.5 mm to more than 2.0 cm, which can form bullae. ## Pathogenesis of Emphysema * Smoking or air pollutant + genetic predisposition * Congenital a1-anti-trypsin deficiency * Oxidative stress, increased apoptosis and senescence * Inflammatory cells, release of inflammatory mediators * Protease-anti-protease imbalance ### Protease-Anti-Protease Imbalance Protease release from inflammatory cells breaks down connective tissue, with insufficient anti-protease protection, such as alpha-1 antitrypsin deficiency. ### Oxidative Stress Cigarette smoke and inflammatory cells generate reactive oxygen species (ROS) causing further tissue damage. ### Inflammatory Cells and Mediators Cigarette smoke increases inflammatory mediators, like IL-8, tumor necrosis factor (TNF), attracting neutrophils, macrophages, and T cells, leading to inflammation and structural damage. ## Morphology of emphysema Emphysema is characterized by destruction of alveolar walls without fibrosis, leading to enlarged air spaces and reduced alveolar capillaries. In severe cases, loss of elastic tissue causes small airway collapse during expiration, contributing to airflow obstruction. ## Conditions Related to Emphysema ### Bullous Emphysema Formation of large subpleural bullae (>1 cm), which can rupture and lead to pneumothorax. ## Chronic Bronchitis A long-term condition defined by a productive cough that lasts for at least 3 months in two consecutive years, frequently affecting smokers and those living in polluted environments, such as sulfur dioxide or nitrogen dioxide. ### Key Feature Hypertrophy of mucous glands. Increased & goblet cells lead to mucus hypersecretion (large airways). ## Normal histology of bronchioles: * **MUCOSA** * **EPITHELIUM** * Ciliated pseudostratified columnar epithelial cells * Goblet cell - makes mucus * **LAMINA PROPRIA** * Basement membrane * Loose connective tissue * **SUBMUCOSA** * Smooth muscle * Connective tissue * Bronchial mucous glands * **(BRONCHI ONLY) CARTILAGE** * Stiffens bronchus ## Pathogenesis of Chronic Bronchitis ### Inflammation Environmental irritants cause inflammation with infiltration of macrophages, neutrophils, and lymphocytes. Eosinophils are typically absent. ### Inflammatory Mediators Airway epithelial cells release inflammatory mediators, like interleukin-8, in response to toxic and infectious stimuli. ### Cytokine Mediators IL-13 from T cells and innate lymphoid cells mediate effects of irritants on the respiratory epithelium. ## Airflow Obstruction 1. **Small airway disease (chronic bronchiolitis):** Contributes to early, mild airflow obstruction. 2. **Significant airflow obstruction in chronic bronchitis:** Is almost always associated with emphysema. ## Morphology of Chronic Bronchitis 1. Squamous metaplasia and dysplasia of epithelium 2. Loss of ciliary activity 3. Hypertrophy of submucosal smooth muscle 4. Hyperplasia of submucosal glands of trachea/bronchi ## Reid Index * **THICKNESS OF GLANDS** * **THICKNESS OF WALL** * **NORMAL:** < 40% * **CHRONIC BRONCHITIS:** > 40% ## Complication of Chronic Bronchitis Chronic bronchitis is often referred to as "blue bloaters." This term describes patients who typically exhibit hypoxia and cyanosis due to poor oxygenation, along with a tendency to retain carbon dioxide. ### Secondary Polycythemia Vera Increased red blood cell production due to chronic hypoxemia. ### Pulmonary Hypertension Elevated blood pressure in the pulmonary arteries caused by reactive vasoconstriction from prolonged hypoxemia. ### Cor Pulmonale Right-sided heart failure resulting from chronic pulmonary hypertension ## Asthma * Is a chronic inflammatory disorder of the airways. * Characterized by: Recurrent episodes of wheezing, breathlessness, chest tightness, cough, particularly at night and early in the morning. * It involves reversible airway obstruction, increased mucus production, and inflammation primarily involving eosinophils and mast cells. ### Bronchial Asthma * **Extrinsic (Allergic)** * Children * Hypersensitivity to type I * +ve family history * Regression * Atopic * **Intrinsic (Non-allergic)** * Adults * Associated with bronchitis, drugs * No family history * Progression * Non-atopic ## **Types of Asthma:** 1. Atopic Asthma (The most common type) 2. Non-Atopic Asthma 3. Drug-Induced Asthma 4. Occupational Asthma ## Atopic Asthma (Allergic Asthma) **Definition:** Most common form of asthma, characterized by IgE-mediated hypersensitivity to allergens. **Onset:** Typically begins in childhood. **Family History:** Commonly associated with a family history of atopy or asthma. **Triggers:** Allergens (dust, pollen, animal dander, food) and respiratory infections. **Symptoms:** Recurrent wheezing, breathlessness, chest tightness, and cough. **Diagnosis:** Confirmed by skin tests (wheal-and-flare reaction) or serum tests (RAST for allergen-specific IgE). ## Non-Atopic (non-allergic) Asthma **Definition:** A form of asthma without evidence of allergen sensitization; skin tests are usually negative. **Family History:** Less common in patients compared to atopic asthma. **Common Triggers:** * Viral respiratory infections (e.g., rhinovirus, parainfluenza virus). * Inhaled pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide). **Mechanism:** Viral inflammation may lower the threshold for irritants affecting the respiratory mucosa. ## Drug-Induced Asthma **Triggers:** By pharmacologic agents, primarily aspirin. **Symptoms:** Recurrent rhinitis, nasal polyps, urticaria, bronchospasm. **Likely involves:** Abnormal prostaglandin metabolism due to cyclooxygenase inhibition. ## Occupational Asthma **Triggers:** Caused by exposure to fumes, epoxy resins, organic dust (e.g., wood, cotton), and chemicals, like toluene. **Onset:** Symptoms usually develop after repeated exposure to specific antigens. ## Pathogenesis of Asthma **Inflammatory Response**: Activation of Type 2 Helper T (TH2) cells in asthma lead to produce many cytokines, for example: 1. **IL-4:** * Promotes IgE antibody production. * IgE coats mast cells leading to release of histamine, causes bronchoconstriction and increased mucus, leukotrienes, and prostaglandins, contribute to airway narrowing. 2. **IL-5:** * Stimulates eosinophil activation and survival. * Eosinophils release mediators that can damage lung endothelium. 3. **IL-13:** * Increases mucus production in airways. * Contributes to airway hyperreactivity, making airways more sensitive. ## **Molecular Pathway Leading to Asthma:** Is often initiated by environmental triggers. * **Eosinophils:** Cytokines and leukotrienes * **TH2:** IL-4 * **Mast Cells:** IgE antibodies * **Type 1 Hypersensitivity** ## Phases of Reaction in Asthma ### Early-Phase Reaction Immediate symptoms (mins to few hrs) due to mediator release. **Characteristics:** * **Bronchoconstriction:** Who triggered by: * Mediators released from mast cells: Histamine, prostaglandin (D2), and leukotrienes (LTC4, D4, and E4). * Reflex neural pathways. * **Increased mucus production** * **Vasodilation** ### Late-Phase Reaction (Inflammatory in nature) Begins 4-12 hrs after allergen exposure due to inflammatory cell influx. * **Where:** Inflammatory mediators trigger epithelial cells to release chemokines like eotaxin. * **Eotaxin:** Acts as a strong attractant and activator for eosinophils, leading to the recruitment of T2 cells, eosinophils, and other leukocytes. * **Which:** Further intensifies the inflammatory response initiated by resident immune cells. ## Morphology of Asthma Thick, tenacious mucous plugs containing whorls of shed epithelium (Curschmann spirals). Numerous eosinophils and Charcot-Leyden crystals (crystalloids made up of the eosinophil protein galectin-10) also are present. ## Airway Remodeling in Asthma **Caused by:** Repeated bouts of inflammation **Structural changes in the bronchial wall, includes:** 1. **Thickening of the airway wall**: Increased smooth muscle mass and collagen deposition. 2. **Mucous hypersecretion**: Enlarged mucus glands leading to excess mucus production. 3. **Epithelial cell changes**: Alterations in epithelial cell structure and function. 4. **Airway narrowing**: Reduced lumen size, making airflow difficult. 5. **Vascular changes**: Increased blood vessel formation and vascular permeability. 6. **Immune cell infiltration**: Persistent presence of inflammatory cells, like eosinophils and T cells. ## Bronchiectasis **Permanent dilation of bronchi and bronchioles:** Caused by destruction of smooth muscle and elastic tissue. Typically linked to (associated) chronic necrotizing infections. * It is not a primary disorder as it always occurs secondary to persistent infection or obstruction caused by a variety of conditions. * Affects lower lobes bilaterally, especially vertical air passages. ### Chronic Inflammation ### Airflow ## Symptoms * **Wheezing & coughing:** Comes and goes, worse during pneumonia. * **Shortness of breath** * **Foul-smelling mucus** * **Long-term hypoxia** * **Digital clubbing** ## Conditions Predisposing to Bronchiectasis * **Bronchial Obstruction** * **Congenital/Hereditary Conditions:** * Cystic Fibrosis: Thick mucus, secondary infections * Immunodeficiency: Recurrent bacterial infections * Primary Ciliary Dyskinesia (Autosomal recessive disease) * **Necrotizing (suppurative) Pneumonia:** Caused by virulent organisms * Staphylococcus aureus * Klebsiella * **Post-tuberculosis** ## Morphology of Bronchiectasis Bronchi and bronchioles can be dilated up to four times their normal diameter. Visible almost to the pleural surface.