Respiratory System Pathology 3rd Year PDF

College of Medicine & Health Sciences Histopathology Department Respiratory system-pathology For 3rd year Medical student  Objectives At the end of this lecture you must be able to: - Define emphysema and chronic bronchitis - Classify emphysema - Describe th...

College of Medicine & Health Sciences Histopathology Department Respiratory system-pathology For 3rd year Medical student  Objectives At the end of this lecture you must be able to: - Define emphysema and chronic bronchitis - Classify emphysema - Describe the various clinical forms of emphysema. - Discuss the etiology, pathogenesis, morphology and clinical features of emphysema and chronic bronchitis Chronic Obstructive Pulmonary Diseases (COPD) Chronic bronchitis Emphysema Bronchiectasis Asthma  What IS Chronic Obstructive Pulmonary Disease? Patient is greater than age 45 Respiratory symptoms of cough, shortness of breath History of cigarette smoking and/or other pollutants What happens? Air Trapping & Poor Gas Exchange Small airway (obstruction) And parenchyma destruction (emphysema) Chronic obstructive pulmonary disease (COPD) Is characterized by poorly reversible airflow obstruction and an abnormal inflammatory response in the lungs. The latter represents the innate and adaptive immune responses to long term exposure to noxious particles and gases, particularly cigarette smoke.  Disorders Associated with Airflow Obstruction The Spectrum of Chronic Obstructive Pulmonary Disease Clinical Term Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms Mucous gland hyperplasia, Tobacco smoke, air Cough, sputum Chronic bronchitis Bronchus hypersecretion pollutants production Persistent or severe Cough, purulent sputum, Bronchiectasis Bronchus Airway dilation and scarring infections fever Smooth muscle hyperplasia, Immunologic or Episodic wheezing, Asthma Bronchus excess mucus, inflammation undefined causes cough, dyspnea Airspace enlargement; wall Emphysema Acinus Tobacco smoke Dyspnea destruction Small airway Inflammatory Tobacco smoke, air disease, * Bronchiole Cough, dyspnea scarring/obliteration pollutants, miscellaneous bronchiolitis Emphysema and chronic bronchitis are the two most common conditions that contribute to COPD. These two conditions usually occur together and can vary in severity among individuals with COPD.  Chronic bronchitis Is inflammation of the lining of the bronchial tubes, which carry air to and from the air sacs (alveoli) of the lungs. It's characterized by daily cough and mucus (sputum) production.  Chronic bronchitis Is defined clinically. It is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause.  Chronic bronchitis -It is common among cigarette smokers and affect 20-25% of men in the 40-65 years-old. Heavy smokers patients develop chronic bronchitis usually with associated emphysema.  Pathogenesis of chronic bronchitis. Environmental irritants (smoking) induced: 1. Hypersecretion of mucous glands in the trachea and main bronchi then small bronchi and bronchioles. 2. Inflammation with infiltration by lymphocytes, macrophages and neutrophils. 3. Chronic obstructive component results from small airway disease (chronic bronchiolitis) and coexistent emphysema.  Mechanism of mucus accumulation in COPD Mucus hypersecretion and chronic productive cough is a feature of CB. The primary mechanisms responsible for excessive mucus production in CB in COPD are the overproduction and hypersecretion by goblet cells, and the decreased elimination of mucus. There is also hypertrophy of the submucosal glands that Reid described with a ratio of the thickness of the submucosal glands and the thickness between the epithelium and cartilage that covers the bronchi. The size of the submucosal glands correlates with the degree of airway inflammation Mechanism of mucus accumulation in COPD  Morphology of chronic bronchitis. Grossly Airway hyperemic and swollen, covered by mucopurulent secretion. Histologically – Chronic inflammation of the airways (predominantly lymphocytes) – Enlargement of the mucus-secreting glands in the trachea and larger bronchi. – Inflammatory cells, largely mononuclear but sometimes admixed with neutrophils – Goblet cell metaplasia, mucus plugging, inflammation, and fibrosis (small airway disease, (bronchiolitis obliterans)  Morphology of chronic bronchitis. This photomicrograph demonstrates a bronchus with increased numbers of chronic inflammatory cells in the submucosa.  Morphology of chronic bronchitis. The lumen of the bronchus is above. Note the marked thickening of the mucous gland layer (approximately twice normal) and squamous metaplasia of the epithelium. Clinical features. 1. Common among smokers, and accounts for 20-25% of men in the age of 40 to 65-years-old. 2. Prominent cough with sputum production. 3. Chronic obstructive lung disease with outflow obstruction. 4. Hypercapnia. 5. Hypoxemia. 6. cyanosis. 7. Coexistent with emphysema. Complications: Emphysema Cor pulmonale Bronchiectasis Bronchopneumonia Bronchogenic carcinoma of lung SUMMARY Chronic bronchitis is defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Cigarette smoking is the most important underlying risk factor; air pollutants also contribute. Chronic obstructive component largely results from small airway disease (chronic bronchiolitis) and coexistent emphysema. Histology demonstrates enlargement of mucussecreting glands, goblet cell metaplasia, and bronchiolar wall fibrosis.  Emphysema Definition – Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis.  Emphysema The chest cavity is opened at autopsy to reveal numerous large bullae apparent on the surface of the lungs in a patient dying with emphysema. Bullae are large dilated airspaces that bulge out from beneath the pleura. Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that there is permanent dilation of airspaces.  Types of Emphysema: According to its anatomic distribution within the lobule Four major types: 1- Centriacinar 2- Panacinar 3- Paraseptal 4- Irregular Only the first two cause clinically significant airflow obstruction.  Pathogenesis of emphysema A consequence of two critical imbalances: 1 – The protease-antiprotease imbalance 2 – Oxidant-antioxidant imbalance  Protease-Antiprotease Imbalance Hypothesis Genetic deficiency of the antiprotease α1-antitrypsin The effect of cigarette smoking in the development of emphysema Increased elastase availability and decreased antielastase activity occur in smokers. Smoking enhances elastase activity in macrophages.  Oxidant-Antioxidant Imbalance Tobacco smoke contains abundant reactive oxygen species (free radicals), which deplete these antioxidant mechanisms, thereby inciting tissue damage. Tissue breakdown is enhanced as a consequence of inactivation of protective antiproteases by reactive oxygen species in cigarette smoke  Pathogenesis of emphysema The protease-antiprotease imbalance and oxidant-antioxidant imbalance are additive in their effects and contribute to issue damage. α1-antitrypsin (α1-AT) deficiency can be either congenital or "functional" as a result of oxidative inactivation.  Morphology of emphysema. Gross: Pale voluminous lung. Microscopic: Destruction of the alveolar walls without fibrosis, leading to enlarged air spaces Lung with dilated airspaces ( left). Loss of alveolar walls with dilation of remaining airspaces (right ). Clinical features: 1. Dyspnea with prolonged expiration ( hyperventilation). 2. Reduced pulmonary functional test FEV1 to FVC. 3. Barrel-chest. 4. Development of secondary pulmonary hypertension. 5. Respiratory acidosis, hypoxia and coma. Complications: - Cor pulmonale - Pneumothorax - Respiratory failure SUMMARY Emphysema is a chronic obstructive airway disease characterized by permanent enlargement of airspaces distal to terminal bronchioles. Subtypes include centriacinar (most common; smoking related), panacinar (seen in α1-antitrypsin deficiency), distal acinar, and irregular. The two key pathogenic mechanisms are an excess of cellular proteases with low antiprotease levels (protease-antiprotease imbalance), and an excess of reactive oxygen species (oxidant-antioxidant imbalance). Most individuals with emphysema demonstrate elements of chronic bronchitis concurrently, since cigarette smoking is an underlying risk factor for both. Anatomic distribution of pure chronic bronchitis and pure emphysema. In chronic bronchitis the small-airway disease (chronic bronchiolitis) results in airflow obstruction, while the large-airway disease is primarily responsible for the mucus hypersecretion. you might want to think twice about smoking…. 32 See you in the next lecture