CPAT3201 - Lectures 11-14

What is the functional definition of Chronic Obstructive Airways Disease (COAD)?

COAD is defined by expiratory airflow obstruction caused by reduced airway diameter (e.g., asthma, chronic bronchitis) or reduced parenchymal elasticity (e.g., emphysema).

What causes reduced functional airway diameter in COAD?

conditions like asthma, chronic bronchitis, and bronchiectasis

What causes reduced elasticity of lung parenchyma in COAD?

emphysema

What is atopic asthma?

a type I hypersensitivity reaction involving allergen sensitisation, immune activation, and mast cell degranulation upon re-exposure

What cells and mediators are involved in the pathogenesis of atopic asthma?

IgE, mast cells, eosinophils; mediators like histamine, leukotrienes, prostaglandins

What histological changes occur in asthma?

increased mucus, thickened basement membrane, immune cell infiltration, smooth muscle hypertrophy/hyperplasia, and sub-epithelial fibrosis

What is emphysema?

abnormal enlargement of distal air spaces and destruction of alveolar walls

What are key causes of emphysema?

smoking and α1-antitrypsin deficiency

What is the pathogenesis of emphysema?

protease-antiprotease imbalance → destruction of elastin/collagen → loss of alveolar walls and elastic recoil

What histological changes occur in emphysema?

loss of alveolar walls, enlarged air spaces, reduced surface area for gas exchange

What defines chronic bronchitis clinically?

productive cough lasting >3 months/year for at least 2 consecutive years

What histological changes occur in chronic bronchitis?

goblet cell metaplasia, thickened basement membrane, epithelial damage, submucosal gland hypertrophy, neutrophilic inflammation

What is the Reid Index and its relevance?

the ratio of submucosal gland thickness to bronchial wall thickness; >40% indicates chronic bronchitis

What complications are associated with chronic bronchitis?

mucociliary dysfunction, squamous metaplasia, infections, cor pulmonale, and right heart failure

What common functional losses occur in both emphysema and chronic bronchitis?

loss of air exchange surface, loss of elastic recoil, and reduced functional airway diameter

What is a restrictive airway disease?

a condition with reduced total lung capacity due to chest wall or lung interstitial issues, while airflow may remain near-normal.

What are pneumoconioses?

interstitial lung diseases caused by inhalation of dusts like coal (CWP), silica (silicosis), and asbestos (asbestosis)

What particle size is most problematic in pneumoconiosis?

1-5 μm particles, which reach alveoli and are poorly cleared

What is the pathogenesis of coal workers' pneumoconiosis (CWP)?

inhaled coal dust is engulfed by macrophages → chronic inflammation → stellate scars and centrilobular emphysema

What is a key histological feature of CWP?

stellate scarring and surrounding blood vessel fibrosis

What is the hallmark of silicosis pathogenesis?

macrophage death and chronic inflammation caused by silica dust → large fibrotic onion ring scars and panlobular emphysema

What histological feature distinguishes silicosis?

fibrotic onion ring-like lesions with macrophages and fibroblasts

What is the pathogenesis of asbestosis?

inhaled asbestos fibres reach alveoli → macrophage activation → diffuse fibrotic scarring and chronic inflammation

What distinguishes the scarring in asbestosis?

patchy, diffused fibrotic scars (not onion-ring like)

What is a shared pathogenic mechanism in CWP, silicosis, and asbestosis?

chronic inflammation due to persistent dust particles leading to fibrosis and impaired gas exchange

What are common complications of pneumoconioses?

pulmonary hypertension, right/left heart failure, fibrosis, emphysema, pleural adhesions, infections, and cancer

What is pneumonia?

inflammation of the lung parenchyma, most often due to infection (bacterial, viral, fungal, TB), but can also be non-infective (e.g., aspiration, toxins)

What are the anatomical types of pneumonia?

lobar pneumonia (diffuse and confluent) and bronchopneumonia (patchy)

What is the main difference between lobar pneumonia and bronchopneumonia?

lobar affects entire lobes, usually in healthy individuals; bronchopneumonia is patchy, bilateral, and occurs in debilitated individuals

What determines whether pneumonia is lobar or bronchopneumonia?

the organism involved, the immune response, and the timing of treatment

What are the 4 stages of lobar pneumonia progression?

Congestion → Red hepatization → Grey hepatization → Resolution

What happens during the congestion stage of lobar pneumonia?

bacteria multiply, blood vessels become engorged, and fluid begins to enter alveoli (transudate → exudate), with early neutrophil infiltration

What characterises red hepatization in pneumonia?

lung becomes firm and red, exudate fills alveoli, RBCs extravasate, and neutrophils + fibrin are present

What happens during grey hepatization?

fewer RBCs, continued exudate and neutrophil presence, lung appears grey-brown and firm

What occurs during the resolution stage of pneumonia?

macrophages remove debris and digest fibrin, restoring normal lung architecture if no complications arise

How does bronchopneumonia differ in progression from lobar pneumonia?

it follows a similar inflammatory process but is more focal and patchy, potentially confluent, and often secondary

What are common bacterial organisms causing pneumonia?

Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, coliforms, Pseudomonas aeruginosa.

Which organism causes 95% of lobar pneumonia?

Streptococcus pneumoniae

What factors govern whether lobar or bronchopneumonia develops?

organism virulence, dose, host immune status

What are complications of pneumonia?

abscess formation, pleurisy, empyema, fibrosis, septicaemia, ARDS, secondary infections

What distinguishes viral (atypical) pneumonia from bacterial (typical)?

viral pneumonia is interstitial with less exudate, few neutrophils, more lymphocytes/monocytes, and minimal alveolar filling

What are common causes of viral pneumonia?

influenza, RSV, adenovirus, SARS-CoV-2, and Mycoplasma pneumoniae

What is a key complication of viral pneumonia?

secondary bacterial infection and progression to ARDS

What are the three major vascular-related lung conditions?

pulmonary embolism, pulmonary hypertension, pulmonary oedema/ARDS

What causes pulmonary embolism?

a thrombus (usually from leg veins) travels to and blocks a pulmonary artery

What factors influence the outcome of a pulmonary embolism?

size and location of the embolus, pulmonary circulation status, and pre-existing lung disease

What is pulmonary hypertension?

pulmonary arterial pressure >25% of aortic pressure; normally it is ~12.5%

What causes pulmonary hypertension?

increased blood flow, vascular resistance, left heart failure, or destruction of vessels (e.g., COAD, fibrosis)

What is the outcome of progressive pulmonary hypertension?

Cor pulmonale (right-sided heart failure)

What are haemodynamic causes of pulmonary oedema?

increased hydrostatic pressure (e.g., left heart failure), decreased oncotic pressure (e.g., hypoalbuminemia), and volume overload

What are microvascular causes of pulmonary oedema?

capillary damage causing increased permeability, leading to protein-rich fluid leakage and ARDS

What are signs of pulmonary oedema?

engorged vessels, fluid in lower lobes, hemosiderin-laden macrophages, and pink frothy sputum

What is Acute Respiratory Distress Syndrome (ARDS)?

severe lung injury marked by diffuse alveolar damage, inflammation, and impaired gas exchange

What causes ARDS?

sepsis, viral infection (e.g., COVID-19), toxins, radiation, trauma

What histological features are seen in ARDS?

hyaline membranes, interstitial mononuclear infiltrates, and Type II pneumocyte hyperplasia

What is the Berlin Definition of ARDS?

acute diffuse lung injury with increased permeability, lung weight, reduced aeration, hypoxemia, and bilateral radiographic opacities

How does SARS-CoV-2 cause lung damage?

infects epithelial and endothelial cells → triggers innate immune response → cytokine storm → vascular leakage and inflammation.

What are the consequences of COVID-19 lung infection?

pulmonary oedema, thrombosis, impaired gas exchange, ARDS, and multi-organ failure

What are extracellular vesicles (EV), and what is their role in ARDS?

small vesicles (e.g., exosomes) released by cells that mediate communication; elevated in ARDS and contribute to inflammation and thrombosis

What is the impact of ARDS on lung function?

poor compliance, V/Q mismatch, fibrosis, low oxygenation

What are the three zones affected in ARDS?

infiltrated, consolidated, and collapsed lung regions