Respiratory System Pathology: Lung Structure

• Notes cover Systemic Pathology - Respiratory System Pathology

Lung Structure and Function

• Lungs facilitate gas exchange between air and blood as their primary function.
• Bronchi have firm cartilaginous walls for structural support
• The columnar ciliated epithelium and subepithelial glands impede entry of microbes.
• Bronchioles lack cartilage and submucosal glands, directing air to alveoli.
• Acinus is composed of the respiratory bronchiole, alveolar ducts, and alveolar sacs, supporting gas exchange.
• Anastomosing capillary networks bring blood for gas exchange.
• Alveolar walls contain a basement membrane and interstitium to support tissue
• Type 1 pneumocytes are flat, cover 95% of the alveolar surface for gas exchange.
• Type 2 pneumocytes synthesize surfactant and can differentiate to type 1 cells to repair damage.
• Alveolar macrophages are loosely attached or free inside alveolar spaces.

Congenital Lung disorders

• Congenital lung disorders are rare overall
• Pulmonary hypoplasia is a decreased lung size due to defects during development, like congenital diaphragmatic hernia or oligohydramnios.
• Foregut cysts result from abnormal detachment of the primitive foregut and may cause symptoms via compression/infection.
• Pulmonary sequestration is lung tissue disconnected from airways with blood supply from the aorta/branches, either extralobar or intralobar.
• Miscellaneous disorders include tracheal/bronchial anomalies.

Atelectasis

• Atelectasis refers to incomplete lung expansion or collapse of previously inflated lung, resulting in poorly aerated tissue
• Poorly aerated lung tissue reduces oxygenation and increases infection risk
• Atelectasis is typically reversible unless caused by fibrosis

Resorption Atelectasis

• Resorption atelectasis arises from airway obstruction (mucus, foreign bodies, tumors)
• Air from distal alveoli is resorbed, leading to collapse
• Mediastinum shifts towards the affected lung due to volume reduction

Compression Atelectasis

• Compression atelectasis develops due to fluid, air, or tumors in the pleural cavity
• Mediastinum shifts away from the affected lung

Contraction Atelectasis

• Contraction atelectasis happens because of focal or generalized pulmonary or pleural fibrosis

Pulmonary Edema

• Pulmonary edema involves excessive interstitial fluid in the alveoli, impairing respiratory function and increasing infection risk.
• It is caused by haemodynamic disturbances or increased capillary permeability due to alveolar wall injury

Hemodynamic Edema

• Increased hydrostatic pressure is common, primarily affects lower lobes
• Increased pulmonary venous pressure is a result of left-sided heart failure, volume overload, or pulmonary vein obstruction
• Histology presents engorged alveolar capillaries, intra-alveolar transudate, and haemosiderin-laden macrophages.
• Long-standing edema leads to fibrosis, thickened alveolar walls and brown induration of lungs.
• Decreased oncotic pressure is less common, caused by hypoalbuminemia, nephrotic syndrome, liver issues, or protein-losing enteropathies.
• Lymphatic obstruction is a rare cause of pulmonary edema.

Edema Caused by Alveolar Wall Injury

• Damage to alveolar microvasculature or epithelium leads to inflammatory exudate in the interstitium, which extends to the alveoli in severe cases.
• This is a major component of acute respiratory distress syndrome.
• Direct injuries come from infections like bacterial pneumonia, inhaled gases, liquid aspiration, radiation, or lung trauma.
• Indirect injuries arise from systemic inflammatory response syndrome or exposure to drugs/chemicals.

Acute Lung Injury and ARDS

• Acute lung injury (ALI) is an abrupt onset of hypoxemia and bilateral pulmonary edema without cardiac failure.
• Acute respiratory distress syndrome (ARDS) is a severe manifestation of ALI and a clinical syndrome of progressive respiratory insufficiency.
• Diffuse alveolar damage (DAD) is the histologic manifestation of ALI

Acute Lung Injury (ALI) Causes

• Pulmonary and systemic disorders are causes of acute lung injury
• Sepsis, diffuse pulmonary infections, gastric aspiration, and mechanical trauma (including head injuries) are causes of more than 50% of cases
• Other causes include burns or trauma, inhaled irritants, or transfusion-associated lung injury

Pathogenesis of ALI

• Pneumocyte and pulmonary endothelium injury initiates a cycle of inflammation and pulmonary damage, impairing gas exchange
• Hypoxemia is worsened by ventilation-perfusion mismatch due to uneven lesion distribution.
• Endothelial activation occurs early as inflammation causes increased vascular permeability and edema and releases inflammatory mediators in cases of tissue injury/sepsis. Alveolar macrophages secrete TNF that activate endothelium.
• Neutrophil adhesion and extravasation into interstitium/alveoli occur; neutrophils release inflammatory mediators/extracellular traps for more inflammation/lung damage.
• Intra-alveolar fluid accumulates and hyaline membranes form because endothelial activation/injury leads to leaky capillaries - Surfactant abnormalities happen due to Type II pneumocyte damage. Hyaline membranes result from protein rich edema fluid organization

Clinical findings of ALI

• Severe dyspnea and tachypnea proceed respiratory failure, hypoxemia, and cyanosis.
• Loss of surfactant stiffens lungs, which necessitates intubation and high ventilatory pressures.
• Radiology presents diffuse bilateral infiltrates.
• The clinical course has a moderate mortality rate or chronic lung disease in a minority of survivors.
• Gross exam shows heavy, firm, red, boggy lungs.
• Microscopy reveals diffuse alveolar damage, congestion, edema, inflammation, fibrin deposition, and hyaline membranes. Proliferation or organization occurs in stage II
• Late development of fibrosis occurs when the granulation tissue doesn't resolve

Obstructive Lung Disease

• Obstructive lung disease involves diffuse airway issues that increase resistance to airflow (FEV1/FVC <0.7).

Restrictive Lung Disease

• Restrictive lung disease stems from diseases that reduce lung parenchyma expansion, decreasing total lung capacity (normal FEV1/FVC).
• Chronic interstitial, infiltrative lung diseases, and chest wall disorders characterize restrictive lung disease.

Obstructive Lung Disease Overview

• Obstructive lung disease includes COPD, asthma, and bronchiectasis, which can overlap in reversibility of bronchospasm.

Chronic Obstructive Pulmonary Disease (COPD)

• COPD features ongoing respiratory symptoms and airflow limitation from airway and/or alveolar abnormalities caused by exposure to noxious particles/gases.
• Risk factors include smoking, poor lung development, pollutants, airway hyperresponsiveness, and genetic polymorphisms.
• Emphysema and chronic bronchitis are two major clinicopathologic manifestations often found together.
• Emphysema involves airspace enlargement distal to the terminal bronchiole, with wall destruction and small airway fibrosis.
• Classification based on anatomic distribution includes centriacinar, panacinar, paraseptal, and irregular types.
• Centriacinar (95%) and panacinar cause clinically significant airflow obstruction.
• Centriacinar occurs in heavy smokers with COPD and involves the upper lung lobes.
• Panacinar occurs with a1-antitrypsin deficiency, exacerbated by smoking, and involves the lower zones.
• Paraseptal manifests as pneumothorax in young adults, while irregular is clinically insignificant.
• Pathogenesis is injury from inhaled smoke damaging respiratory epithelium, causing inflammation/oxidative stress, and parenchymal destruction.
• An imbalance in proteases from inflammatory cells versus antiproteases may also lead to parenchymal destruction

Emphysema mechanism

• Airway obstruction stems from elastic loss in alveolar walls surrounding respiratory bronchioles, causing decreased radial traction and respiratory bronchiole collapse during expiration.
• Gross exam shows voluminous lungs which may overlap the heart anteriorly, with air spaces forming apical blebs/bullae in advanced disease.
• Microscopy shows abnormally large alveoli separated by thin septa with focal centriacinar fibrosis and small airway inflammation/vascular changes.

Emphysema Notes and Chronic Bronchitis

• Emphysema can also occur through compensatory hyperinflation after lung removal, obstructive overinflation due to airway obstruction, bullous emphysema, or interstitial emphysema.
• Chronic bronchitis presents with ongoing cough and sputum production for 3 months in 2 consecutive years without an identifiable cause.
• Pathogenesis is initiated by exposure to inhaled substances (e.g., cigarette smoke) causing mucus hypersecretion that obstructs airways.
• Gross exam shows hyperemia, swelling, mucous membrane edema, and secretions
• Microscopy includes chronic inflammation, smooth muscle hypertrophy, peribronchiolar fibrosis, goblet cell hyperplasia, and enlargement of submucosal glands.
• Clinical findings include slowly increasing dyspnea, chronic productive cough (worse in the morning) in a patient with a smoking history

Lung Complications and Clinical Findings

• Progressive lung dysfunction can cause hypertension, cor pulmonale, or death due to heart failure.
• Death can occur due to acute respiratory failure from superimposed infections or fatal pneumothorax from rupture of subpleural blebs.
• Management includes smoking cessation, oxygen therapy, bronchodilators, corticosteroids, antibiotics/physical therapy/bullectomy/lung transplant
• Picture depends on proportions of emphysematous versus bronchitic changes.
• People with bronchitis are "blue bloaters" and younger
• People with emphysema are "pink puffers" and older

Asthma

• Asthma is marked by reversible bronchoconstriction due to airway hyperresponsiveness, inflammation, expiratory airflow obstruction, and episodic wheezing/cough/chest tightness Symptoms
• Triggers include respiratory infections, irritants, cold air, stress, and exercise.

Clinical Phenotypes

• Atopic
• Non-atopic
• Drug-induced
• Occupational
• Pathogenesis of atopic asthma involves a Th2-mediated IgE response to environmental allergens.
• Airway inflammation releases inflammatory mediators, causing bronchoconstriction and airway remodeling.
• Histamine, prostaglandin D2, platelet-activating factor, IL-4, IL-5, IL-13, TNF, and chemokines are contributors to clinical findings
• Genetic susceptibility is commonly associated with other allergic disorders.
• Asthma can develop in industrialized societies due to airborne pollutants that trigger exposure to microbial antigens
• Acute attack symptoms manifest through chest tightness, dyspnea, wheezing, and coughing, Clinical course resolves with bronchodilators, glucocorticoids, leukotriene antagonists.

Asthma Gross and Microscopic Features

• Gross exam shows overinflated lungs with areas of atelectasis, plus mucus plugs occluding bronchi.
• Microscopy shows mucus plugs containing shed epithelium, eosinophils, Charcot Leyden crystals, and evidence of airway remodelling.

Bronchiectasis Description and Causes

• Bronchiectasis results from inflammatory destruction of the bronchi
• Congenital/hereditary diseases, severe pneumonia, obstruction/immune disorders can cause these
• Caused by obstruction interfering with secretion drainage
• Infections are a key factor with conditions such as cystic fibrosis, primary ciliary dyskinesia, and allergic bronchopulmonary aspergillosis

Clinical Aspects

• Severe productive cough with foul-smelling sputum, dyspnea, orthopnea, and potential hemoptysis.
• Involves lung infection(abscesses)
• Gross exam shows dilated airways filled with mucopurulent secretions mostly in the lower lobes.
• Microscopy can show necrosis

Chronic Diffuse Interstitial Diseases

• Show inflammation and fibrosis
• Clinical findings: dyspnea and eventual cyanosis
• Imaging: bilateral disease with small nodules
• Complications: pulmonary hypertension

Pneumonia

• Infection of lunch parenchyma
• Caused by microbial infections overwhelm mechanisms
• Can be caused by: impaired local mechanisms, or lowered systematic resistance
• Healthcare, acquired outside the hospital, or required in the hospital.

Pneumonia Key Features

• Associated with underlying disease, immunosuppression, antibiotic therapy, and mechanical ventilation.
• Risks: patients with abnormal gag and swallowing reflexes
• In immunocompetent patients
• From gram positive cocci

Pulmonary Embolism

• More common than pulmonary thrombosis
• Patients at risk of thrombophilia
• Fat, air and bone marrow can cause emboli to the lungs
• Depends on cardio health of the patient
• Hemodynamic compromise can cause sudden death of acute Cor pulmonale

Histologic Adenocarcinomas

• The most common type in never-smokers
• Squamous is most associated with smoking
• Small is always smoking related
• Classification is based on histologic types
• Arising in lung periphery and smaller
• With glandular differentiation or mucin production

Tumour Spread

• It spreads by local and regional means
• Clinical features - patients are >50
• Arising from mesothelial cells
• Presents with chest pain

Pleural Effusion

• Accumulation of fluid in the pleural space
• Caused by infection or inflammatory diseases
• Occurs due to increased systematic pressure(heart failure, renal failure, liver cirrhosis)
• Malignant tumour with chest pain

Overview of the respiratory system which facilitates gas exchange. Includes the structure and function of bronchi, bronchioles, acinus, alveolar walls, pneumocytes, alveolar macrophages and congenital lung disorders.