Lung Diseases PDF

Lung diseases Dr Zehra Affan The Lung microanatomy  The respiratory acinus It is the fundamental unit of the lung. It is the portion of lung...

Lung diseases Dr Zehra Affan The Lung microanatomy  The respiratory acinus It is the fundamental unit of the lung. It is the portion of lung tissue formed by the branching of a single terminal bronchiole (the part of the lung distal to the terminal bronchiole) Pulmonary acini are composed of respiratory bronchioles that proceed into alveolar ducts, which immediately branch into alveolar sacs, whose walls are formed entirely of alveoli Microscopic structure of the alveolar wall  ATELECTASIS (COLLAPSE) Atelectasis is loss of lung volume caused by inadequate expansion of air spaces. Atelectasis is classified into three forms: 1. Obstruction atelectasis (Resorption atelectasis): It occurs when an obstruction prevents air from reaching distal airways. Air present distal to the obstruction is gradually absorbed, leading to alveolar collapse. Causes: ✓Postoperative intrabronchial mucous or mucopurulent plugs (most common cause) ✓Foreign body aspiration (particularly in children) ✓Bronchial asthma, Bronchiectasis, Chronic bronchitis ✓Intrabronchial tumor (it may be the first sign of malignancy) 2. Compression atelectasis: It is caused by the accumulation of fluid, blood, or air within the pleural cavity. ✓Pleural effusions in the setting of CHF (a frequent cause) ✓Pneumothorax: Leakage of air into the pleural cavity (pneumothorax) 3. Contraction atelectasis (or cicatrization atelectasis): It occurs when local or diffuse pulmonary or pleural fibrosis hampers lung expansion. Atelectasis (except when caused by contraction) is potentially reversible and should be treated promptly to prevent hypoxemia and superimposed infection of the collapsed lung.  ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME Acute lung injury (ALI): is characterized by the abrupt onset of hypoxemia and bilateral pulmonary edema in the absence of cardiac failure (noncardiogenic pulmonary edema) If severe, ALI may lead to acute respiratory distress syndrome (ARDS). Both ARDS and ALI are associated with inflammation-induced increases in pulmonary vascular permeability, edema, and epithelial cell death. The histologic manifestation of these conditions is diffuse alveolar damage.  ARDS is a clinical syndrome caused by diffuse alveolar capillary and epithelial damage with rapid onset of; - Life-threatening respiratory insufficiency - Cyanosis - Severe arterial hypoxemia - May progress to multisystem organ failure. ARDS may occur in a multitude of clinical settings and is associated with primary pulmonary diseases and severe systemic inflammatory disorders such as sepsis. The most frequent triggers of ARDS are pneumonia (35%-45%) and sepsis (30%- 35%) followed by aspiration of gastric contents, trauma (including brain injury, abdominal surgery, and multiple fractures), pancreatitis, and transfusion reactions.  Pathogenesis: ⑳ The underlying basis of ARDS is injury to - the epithelial and endothelial linings of the alveolar-capillary membrane. => Most research suggests that ARDS stems from an inflammatory reaction initiated by the release of factors such ⑳ as IL-1 and TNF that leads to endothelial & activation & activation of neutrophils in pulmonary capillaries. - ② Neutrophils are thought to have an -important role in the pathogenesis of ARDS. - Activated neutrophils release a variety of products (e.g., ROS, proteases) that damage the alveolar epithelium and endothelium. => This results in vascular leakiness ⑳ & (edema), a loss of surfactant that - stiffens the alveolar unit and hyaline membrane - formation. - & 00 membranes, particularly lining the distended alveolar ducts (arrow) - ⑧ A) In the acute phase of ARDS: The most characteristic finding is the presence of bright pink hyaline ⑳ - Such membranes consist of fibrin-rich edema fluid admixed with remnants of necrotic epithelial cells. ② => B) In the organizing stage: type II pneumocytes proliferate vigorously in an attempt to regenerate the alveolar lining (arrows) & Complete resolution is unusual; more commonly, the fibrin-rich exudates undergo organization, leading to fibrosis and alveolar septal thickening. = OBSTRUCTIVE AND RESTRICTIVE PULMONARY DISEASES  Diffuse pulmonary diseases can be classified into two categories: 1) Obstructive (airway) disease: 2) Restrictive disease: Characterized by an a increase in resistance to air Marked by reduced expansion of lung parenchyma = and decreased total lung capacity. flow caused by partial or complete obstruction at any level Restrictive diseases fall into two broad categories: The major diffuse obstructive disorders are: 1. Disorders of chest wall in the presence of ✓ Emphysema normal lungs: (e.g., severe obesity, diseases of the pleura, and neuromuscular disorders, such ✓ Chronic bronchitis as the Guillain-Barré syndrome) ✓ Bronchiectasis 2. Acute or chronic interstitial lung diseases: ✓ Asthma The classic acute restrictive disease is ARDS, In patients with these diseases, the expiratory Chronic restrictive diseases include the flow rate, measured as the forced expiratory pneumoconioses, interstitial fibrosing disorders, and infiltrative conditions such as sarcoidosis. volume at 1 second (FEV1), is significantly decreased, whereas forced vital capacity (FVC) is In diffuse restrictive diseases, FVC is reduced, and the expiratory flow rate is normal or reduced either normal or slightly decreased. proportionately. Thus, the FEV1/FVC ratio is decreased. Hence, FEV1/FVC ratio is near normal. OBSTRUCTIVE LUNG DISEASES  Chronic Obstructive Pulmonary Diseases (COPD) Affect more than 10% of the U.S. adult population over the age of 40 years. They are the 4th leading cause of death in the U.S. and the third leading cause of death worldwide Include; Emphysema and Chronic bronchitis. - - Although chronic bronchitis may exist without demonstrable emphysema, and ⑧ almost pure emphysema may occur, the two diseases usually coexist. & - This is almost certainly because the major cause—cigarette smoking—is common to both disorders. - In view of their propensity to coexist, emphysema and chronic bronchitis often are clinically grouped together under the rubric of chronic obstructive pulmonary disease (COPD).  Emphysema Emphysema is characterized by permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls but without significant fibrosis. There are four patterns of emphysema (according to the anatomic distribution): (1) Centriacinar (2) Panacinar (3) Distal acinar (4) Irregular Only the first two types are associated with COPD, with centriacinar emphysema being about 20 times more common than panacinar disease. 1) Centriacinar (centrilobular) emphysema: - The distinctive feature of centriacinar emphysema is involvement of the central or proximal parts of the acini with sparing of the distal alveoli. => Thus, both emphysematous and normal air spaces exist within the same acinus and lobule. sa The lesions are more common and severe in the upper lobes, particularly in the apical segments. Centroacinar emphysema is most common in individuals who smoke cigarettes, in whom it is often accompanied by chronic bronchitis. 2) Panacinar (panlobular) emphysema: In panacinar emphysema, the acini are uniformly enlarged, from the level of the respiratory bronchiole to the terminal blind alveoli. In contrast to centriacinar emphysema, panacinar emphysema occurs more commonly in the lower lung zones and is associated with α1- antitrypsin deficiency. 3) Distal acinar (paraseptal) emphysema: & In this form of emphysema, the part of the acinus distal to the respiratory bronchiole is primarily affected. - It tends to be found near the pleura, adjacent to areas of fibrosis, scarring, or atelectasis - - The characteristic finding is multiple enlarged air spaces ranging in diameter from less than 0.5 mm to more than 2.0 cm, sometimes forming cystic structures, that with further enlargement & give rise to bullae. # The cause is unknown; it comes to attention most often in young adults who present with spontaneous pneumothorax. 4) Irregular emphysema: Irregular emphysema, so named because the acinus is irregularly involved, Es It is almost invariably associated with scarring In most cases it occurs in small foci and is clinically insignificant.  Pathogenesis of emphysema: Due to an imbalance between protease (elastase) and anti-protease (anti- elastase) activities in lung - - - > => => # - & Protease-mediated damage of extracellular matrix has a central role in the airway obstruction = seen in emphysema. e Expiratory obstruction in emphysema results from loss of elastic recoil, which leads to & functional airflow obstruction in the absence of mechanical obstruction. - -  Hereditary α1-antitrypsin deficiency accounts for a small subgroup of cases of emphysema. It is caused by variants in the pi (proteinase inhibitor) gene, localized to chromosome 14. The& piZ allele codes for a structural alteration in the protein that interferes with its hepatic secretion - = = The homozygous state (piZZ) is associated with markedly decreased serum levels of α1-anti-trypsin and panacinar emphysema = Bullous emphysema: 9 Refers to large subpleural blebs or bullae (spaces >1 cm in diameter in the distended state) - emphysema & Such blebs stem from a localized accentuation of one of the four forms of pulmonary => & & - Most often the blebs are subpleural and prone to rupture, leading to pneumothorax.  Histologic examination: reveals destruction of alveolar walls without fibrosis, leading to enlarged air spaces Due to alveolar loss, the number of alveolar capillaries is diminished.  e The classic presentation of emphysema with no “bronchitic” component: Dyspnea (progressive) - Barrel-shaped chest. The patient has obviously prolonged expiration, sitting- leaning forward with his lips pursed to facilitate his breathing. * = Development of pulmonary hypertension and right-side heart failure (Cor > pulmonale) > - Pulmonary function tests reveal reduced FEV1 with normal or near-normal = FVC. Hence, the FEV1 to FVC ratio is reduced. & Imaging studies show hyperinflated lungs that “flatten” the diaphragm -  Chronic Bronchitis Chronic bronchitis is defined by the presence of a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Thus its definition is based on clinical features, as opposed to emphysema which is defined anatomically. In early stages of chronic bronchitis, the cough produces mucoid sputum, but airflow is not obstructed.  Pathogenesis: The distinctive feature of chronic bronchitis is hypersecretion of mucus, beginning in the large airways. Although the most important cause is cigarette smoking, other air pollutants, such as sulfur dioxide and nitrogen dioxide, may contribute. These environmental irritants induce: (1) Hypertrophy & hyperplasia of mucous glands in the trachea and bronchi (2) An increase in mucin-secreting goblet cells in the epithelial surfaces of smaller bronchi and bronchioles (3) Inflammation marked by the infiltration of macrophages, neutrophils, and lymphocytes. Whereas the mucus hypersecretion primarily involves the large bronchi, the airflow obstruction in chronic bronchitis results from: ─ small airway disease (chronic bronchiolitis) induced by mucous plugging of the bronchiolar lumen, inflammation, and bronchiolar wall fibrosis.  Microscopic: The diagnostic feature of chronic bronchitis in the trachea and larger bronchi is enlargement of the mucus-secreting glands The magnitude of the increase in size is assessed by the ratio of the thickness of the submucosal gland layer to that of the bronchial wall (The Reid index-normally 0.4). Epithelial changes as hyperplasia and squamous cell metaplasia (arrow) are common. Variable numbers of inflammatory cells, largely lymphocytes & MQ but sometimes also admixed PNLs, are frequently seen in the bronchial mucosa. Chronic bronchiolitis (small airway disease), characterized by goblet cell metaplasia, mucus plugging, inflammation, & fibrosis, is also seen.