Week 9 Content

Respiratory pathophysiology: disorders of ventilation and gas exchange (restrictive)+

Restrictive Lung Diseases

Group of pulmonary conditions that restrict the expansion of the lungs. Leads to decreased total lung volume, alterations of lung parenchyma, pleura, chest wall, and neuromuscular structures.

Interstitial Lung Diseases (ILDs) (Lung parenchyma)

• Umbrella term for restrictive diseases that affect lung parenchyma as opposed to airways characterised by decreased compliance of lung tissue.

• casued by inflammation or fibrosis; other causes of chronic mucous production have been excluded.

ILDs- Aetiology

• Occupational/environmental (asbestosis, silicosis), Treatment/drug-induced, Connective tissue disorders, Idiopathic

ILDs- Clinical Manifestations

• Dyspnoea (progressive with exertion), exertional intolerance, persistent nonproductive cough, Haemoptysis, abnormal chest imaging, lung function abnormalities on PFTs

Occupational Lung Diseases/Pneumoconiosis

Caused by inhalation of dust, fumes, smoke, biological agents (e.g. occupational asthma, asbestosis, silicosis, anthracosis)

Pneumoconiosis-pathogenesis

Fine particles deposit in lung tissue→macrophages engulf particles and become dust-laden macrophages.

Neutrophils, T-cells, B-cells/plasma cells recruited→ triggers inflammatory cascade→causes pneumoconiosis

Pneumoconiosis- Investigations

• CXR: varies with severity; micronodular mottling and haziness

• HRCT: better characterises pattern and extent of parenchymal involvement

Pneumoconiosis- Lung volumes

Restrictive defect with decrease in TLC, FRC, and RV

Spirometry- decrease in FVC, FEV1

Pneumoconiosis- ABGs

Hypoxaemia caused by diffusion limitation, V/Q ratio mismatching, and abnormalities of pulmonary vasculature

Pneumoconiosis- PFT

Decreased DLCO, diffuse alveolar capillary damage, and loss of aerated alveoli

Asbestosis

pneumoconiosis caused by asbestos fibre inhalation.

Manifestations: progressive exertional dyspnoea, weakness, finger clubbing, pleural thickening and plaque development

2 Layers of Pleural Space

Parietal: Lines chest cavity

Visceral: lines lungs

Potential space: 5-15ml of fluid

Peural Cavity: negative pressure

-8 cmH2O during inspiration

-4 cmH2O during expiration

Pneumothorax

Air in pleural space (between visceral and parietal pleurra)

Pneumothorax- Aetiology

Spontaneous; pre-existing pulmonary disease; tension pneumothorax

Pneumothorax- Pathophysiology

Disruption to the negative pressure in IPS, rupture of subpleural cyst. Visceral pleura separates from parietal, air enters IPS, air pushes/collapses the lung down

Pneumothorax- Clinical Manifestations

normal to diaphoretic and unwell

Pneumothorax- Investigations

• CXR: visible separation between lung edge and pleura (visceral pleural line)

• ABG: ↓ PaO₂; acute respiratory alkalosis if respiratory rate is elevated

• PFTs: not routinely performed

Pleural Effusion

Pathologic collection of fluid or pus in pleural cavity

Pleural Effusion- aetiology

transudates, exudates, empyema attributable to infection in the pleural space, haemothorax or haemorrhagic pleural effusions, chylothorax or lymphatic pleural effusions

Pleural Effusion- pathophysiology

Pleural fluid rate exceeds lympatic removal rate in the pleural cavity

Pleural Effusion-pathogenesis (transudates)

Transudates - systemic factors that alter the pressure and fluid balance in the body.

Pleural Effusion- Pathogenesis (exudates)

caused by inflammation or injury to the pleura itself; associated with increased production of

fluid result of increased permeability of the pleural membrane (inflammation) or impaired lymphatic drainage

Pleural Effusion- Clinical Manifestations

Dysnopea, pleuritic pain that is sharp and worsens with inspiration, dry cough, decreased chest wall movement, absence of breath sounds. Dependent on size and cause.

Pleural Effusion- Investigations

• CXR: visible when >200 ml — blunting of costophrenic angle; meniscus sign (concave fluid line)

• ABG: can worsen gas exchange → hypoxaemia (↓ PaO₂)

• PFTs: not usually assessed acutely; classified as a restrictive disorder

Haemothorax

collection of blood in the space between visceral and parietal pleura

Haemothorax- Aetiology

traumatic injury, aortic rupture, myocardial rupture, injuries to hilar structures, injuries to lung parenchyma and intercostal or mammary blood vessels, disruption of intercostal vessels

Haemothorax- Clinical Manifestations

Respiratory distress and tachypnoea

Haemothorax- Pathophysiology

• Bleeding into hemithorax from diaphragmatic, mediastinal, pulmonary, chest wall or abdominal injuries

• Blood in pleural space → ↓ functional vital capacity (FVC)

• → alveolar hypoventilation, V/Q mismatch, anatomic shunting

Haemothorax- Severity factors and clinical features

• Severity depends on: location of injury, patient's functional reserve, volume of blood, rate of accumulation

• Clinical features: respiratory distress, tachypnoea

Scoliosis

lateral displacement/curvature of the spine in the coronal plane. Severe rib distortion occurs with moderate-to-severe scoliosis

Scoliosis Aetiology

Idiopathic (most common), de novo, congenital vertebral anomalies, connective tissue disorders, NMD, Marfan syndrome

Clinical Manifestations- Scoliosis

Dyspnoea on exertion, rapid shallow breathing, thoracic cage deformity

Scoliosis- Investigations

PFTs: Restrictive pattern- ↓ TLC and VC, preserved RV; RV/TLC ratio ↑

ABG: Alveolar hypoventilation (hypercapnia and hypoxaemia)

Kyphosis

A/P anguaton of spine. Severe rib distortion when: angulation is excessive, moderate-severe scoliosis

Kyphosis- Aetiology

Trauma, developmental problems or degenerative diseases

Kyphosis- clinical manifestations

Dyspnoea on exertion, rapid shallow breathing, chest wall deformity

Kyphosis- Investigations

Restrictive ventilation impairment, ↑ kyphosis, ↓ FVC, ↓FEV1

ABG: hypoxaemia: V/Q mismatch, alveolar hypoventilation

Scoliosis- Pathogeneis

paediatric-adolescent-adulthood development, compression of growth plates, asymmetric loading, higher loads on chondrocytes (concave side)

Pathogenesis- Kyphosis

Vertebral compression fractures, low bone density, scheuermann's disease, degenerative disc disease, postural changes

Ankylosing Spondylitis

chronic inflammation at the site of ligamentous insertion into the spine or sacroiliac joints

Ankylosing Spondylitis- Aetiology

enetic and environmental factors, HLA-B27 Gene, hereditary component

Ankylosing Spondylitis- Clinical manifestations

Lower back pain, stiffnes after prolonged rest-decreases with exercise, limited flexibility of back and neck

Ankylosing Spondylitis- Investigations

PFTs- Restrictive lung dysfunction (Thorax, ILD), bronchiectasis develops- obstructive also

Ankylosing Spondylitis- Pathogenesis

• inflammatory process affects articular processes, costovertebral joints, and sacroiliac joints

• induce a fibrotic response→leads to joint calcification, ligament ossification, and skeletal immobility

Ankylosing Spondylitis- Pathophysiology

• starts with inflammation at the entheses→over time chronic inflammation causes bone erosion and new bone formation→can lead to fusion of vertebrae

Congenital and Childhood Abnormalities- Pectus Excavatum

concave depression; broad shallow defect or narrow central pocket

Aetiology: no consensus

Clinical manifestations: mild dyspnoea on exertion during exercise and pain in rib deformity area

Investigations: normal – restrictive PFTs (severity dependent)

Congenital and Childhood Abnormalities- Pectus Carinatum

protrusion of the sternum and costal cartilages (pigeon chest)

Aetiology: Unknown

Clinical manifestations: exertional dyspnoea, frequent respiratory infections

Investigations: normal PFTs

Disorders of Obesity

an excess of body-fat mass

BMI > 30kg/m2

Complex disease: environmental influences with obesity-risk genetic allelic variants

Disorders of obesity- Pathogenesis

• (energy intake > energy expenditure)

• resetting of the body weight “set point” at an increased value

• Excess calorie intake

• environmental factors

Obesity- Investigations

ABGs: Hypoventilation: hypoxemia and hypercapnia

PFTs:

• Static lung volumes: decreased chest wall compliance, VC, TLC, and expiratory reserve.

• Spirometry: Obstruction ,

• Airway hyperresponsiveness

Neuromuscular diseases (NMDs)

Not due to lung parenchyma; external factors. Diseases progress, lung volumes decline- limited inspiration and cough effectively

Neuromuscular disease- Investigations

ABGs: Hypercapnia

PFTs: degree of pulmonary dysfunction correlates with severity of respiratory muscle weakness.

• Reduced FEV₁ and FVC, normal FEV₁/FVC ratio, reduced TLC, and slow VC.

poliomyelitis

Inflammation of the spinal cord caused by an enteral virus acquired by ingestion or respiratory droplet.

pathophysiology of poliomyelitis.

After 1–3 weeks, virus invades intestinal blood supply → circulates → invades CNS → neural damage and inflammation → respiratory muscle nerve involvement → paralysis.

poliomyelitis- clinical manifestations

Tremors, muscle weakness, respiratory paralysis

Duchenne muscular dystrophy

X-linked recessive, passed from mothers to sons

Duchenne muscular dystrophy- Pathophysiology

Progressive lower-limb weakness initially, respiratory muscles become involved → skeletal deformities, hypoxia, and hypercapnia; increased risk of respiratory tract infections

Guillain-Barre syndrome

Acute idiopathic polyneuropathy thought to be an autoimmune disease triggered by viral infection or vaccination.

Guillain-Barre Syndrome- Pathophysiology

Peripheral nerves are affected → neural inflammation, demyelination, and axon destruction.

Guillain-Barre Syndrome- Clinical Manifestations

• Progressive ascending weakness and motor loss from feet upward

• sensory loss

• loss of respiratory muscle control → respiratory failure

• tachycardia, dysrhythmias, hypo/hypertension

• inability to sweat

Path of Deoxygenated blood through pulmonary circulation

Vena cava → right atrium → right ventricle → pulmonary artery → lungs (gas exchange) → pulmonary veins (now oxygenated) → left atrium → left ventricle → systemic circulation.

Function of Pulmonary Circulation

To carry deoxygenated blood from the right heart to the lungs for gas exchange, then return oxygenated blood to the left heart for systemic distribution.

Pulmonary Hypertension (PH)

A haemodynamic disorder defined as a mean pulmonary artery pressure (mPAP) >20 mmHg at rest, with multiple possible causes. Confirmed via right heart catheterisation.

• Right heart catheterisation- measures pulmonary artery pressure (PAP)

WHO Classification of Pulmonary Hypertension (group 1-5)

Group 1: Pulmonary Arterial Hypertension (PAH) (idiopathic, heritable, drug-induced, connective tissue disease, HIV, congenital heart disease).

Group 2: PH due to Left heart disease.

Group 3: PH due to Chronic lung disease/hypoxia.

Group 4: PH due to Chronic thromboembolic pulmonary hypertension (CTEPH)

Group 5: PH due to multifactorial/unclear mechanisms.

Aetiology- Primary PH

Unknown

Aetiology- Secondary PH

Results from a known disease process e.g. COPD

Pathogenesis of Pulmonary hypertension

Morphologic changes within the arterial lumen.

• Internal layer of the pulmonary artery wall becomes fibrotic

• Pulmonary atherosclerosis is present in major pulmonary vessels.

• Formation of network of blood vessel lesions.

• Tissue necrosis and hemorrhage

pathophysiological consequences of pulmonary hypertension

Increased pulmonary vascular resistance (PVR) and right ventricular strain and failure

Clinical manifestations of Pulmonary Hypertension

Exertional dyspnoea and fatigue, cehst pain and syncope, peripheral oedema, ascites, right heart failure

Pulmonary hypertension- Diagnosis tools

Pulmonary artery catheter (gold standard — PAP measurement), chest X-ray, ECG, and echocardiogram.

Pulmonary embolism

Obstruction of the pulmonary arteries, most commonly by a thromboembolism originating from a deep vein thrombosis (DVT).

PE- Aetiology

thrombotic, fat, amniotic fluid, air, tumor, foreign material, septic, parasitic

PE- Pathogenesis

Thrombi travel to the pulmonary vasculature. Impact depends on size and cross-sectional area of circulatory impairment — can cause right-sided heart failure, hypotension, and decreased CO.

PE- Pathophysiological consequences

Mechanical obstruction, Acute RV strain in severe cases, V/Q mismatch and hypoxaemia, Pulmonary infarction

PE- Clinical Manifestations

Acute dyspnoea, pleuritic chest pain, tachypnoea and tachycardia, hypoxaemia, and syncope

pulmonary embolism- diagnosis tools

• V/Q scan, ABG, ECG, CXR

• CTPA (CT pulmonary angiography — gold standard for imaging)

• Blood tests and Wells rules