1. Pulmonary Embolism

1.1 Epidemiology

• Pulmonary embolism (PE) is the most common disorder affecting the pulmonary vasculature.
• Annual incidence: ~110 cases per 100,000 people (UK and USA); slightly lower in continental Europe.
• Autopsy studies suggest PE is often missed, and it is a major cause of sudden death.

1.2 Aetiology

• Most pulmonary emboli arise from thrombi in the deep veins of the lower limbs (e.g. femoral or popliteal veins).
• Emboli can also originate from:
  • Inferior vena cava
  • Right atrium or ventricle (especially if intravascular devices are present)
  • Upper limb veins
• Less common causes: Tumour, infected thrombus, fat (long-bone fractures), amniotic fluid (peri-delivery), or air.

Pathogenesis

• Emboli travel via the venous system to the right side of the heart, then lodge in the pulmonary arteries.
• Virchow’s triad explains predisposition to venous thrombosis:
  1. Blood composition changes (e.g. inherited thrombophilia, malignancy).
  2. Vascular endothelial injury.
  3. Altered blood flow (e.g. stasis from prolonged immobility).

1.3 Risk Factors

• Shared with deep vein thrombosis:
  • Recent surgery (especially pelvis or lower limb)
  • Prolonged immobilisation or bed rest
  • Malignancy
  • Pregnancy, postpartum
  • Oral contraceptive pill or hormone replacement therapy
  • Previous venous thromboembolism
  • Inherited or acquired thrombophilia (e.g. antiphospholipid syndrome)
  • Presence of indwelling intravenous lines (central lines, pacemakers)

1.4 Clinical Features

1.4.1 Acute Pulmonary Embolism

• Onset: Hours to days, or occasionally insidious over weeks.
• Symptoms:
  • Dyspnoea (often sudden)
  • Pleuritic chest pain
  • Cough ± haemoptysis
  • Syncope or dizziness (in massive PE)
• Signs:
  • Tachypnoea, tachycardia
  • Central cyanosis
  • A pleural rub or small effusion
  • Loud P2 on auscultation (pulmonary valve closure)
  • May be normal respiratory exam
  • Massive PE: Hypotension, raised jugular venous pressure (JVP), right ventricular (RV) gallop (S3), parasternal heave

1.4.2 Chronic Pulmonary Embolism

• Multiple small emboli cause progressive dyspnoea over weeks to months.
• May lead to pulmonary hypertension and right heart strain (raised JVP, peripheral oedema).
• Occasional episodes of chest pain or haemoptysis.
• Respiratory exam often unremarkable, though there may be signs of RV overload.

1.5 Diagnostic Approach

1.5.1 Clinical Assessment and Risk Stratification

• Clinical suspicion is paramount due to non-specific presentations.
• Modified Wells score helps estimate pre-test probability.

1.5.2 Investigations

1. Blood Tests
   • D-dimer: Elevated in >90% of acute PE but lacks specificity (also raised in malignancy, pregnancy, post-surgery, etc.). A normal D-dimer in a low-risk patient can help exclude PE.
   • Troponin T and BNP/NT-proBNP: May be elevated in massive or large PE, reflecting right ventricular strain.
   • Arterial blood gases (ABGs): Typically Type 1 respiratory failure and respiratory alkalosis.
2. Electrocardiogram (ECG)
   • Often non-specific changes: Sinus tachycardia, T-wave inversions in right-sided leads.
   • Classic findings (rare): S1Q3T3, right bundle branch block, right ventricular strain.
3. Chest X-ray
   • Often normal.
   • May show wedge-shaped peripheral opacities or small effusions (not sensitive or specific).
4. Definitive Imaging
   • CT Pulmonary Angiography (CTPA): First-line, high sensitivity and specificity; also identifies other lung pathologies.
   • Ventilation–Perfusion (VQ) Scan: For patients where CTPA is contraindicated (contrast allergy, severe renal impairment).
   • Pulmonary Angiography: The gold standard, but rarely used (invasive procedure).
5. Additional Tests
   • Venous Ultrasound (lower limbs) for DVT.
   • Echocardiography: May show right ventricular dilatation or dysfunction in massive/submassive PE.

1.6 Immediate Management

1. Stabilisation
   • Oxygen if hypoxic
   • Analgesia (e.g. opioids)
   • IV fluids if hypotensive (massive PE)
2. High-Risk (Massive) PE
   • Urgent admission to intensive care.
   • Consider thrombolysis (e.g. alteplase) if severe shock or risk of cardiac arrest.
   • Embolectomy (surgical or catheter-directed) if thrombolysis is contraindicated or unsuccessful.
3. Empirical Anticoagulation
   • Low-molecular-weight heparin (LMWH) started before diagnostic confirmation if clinical suspicion is high and bleeding risk is acceptable.
   • Prevents clot extension and further emboli.

1.7 Long-Term Management

1. Anticoagulation
   • LMWH (or fondaparinux) for 5–7 days.
   • Transition to oral anticoagulant (e.g. warfarin with target INR 2.0–4.0) or a direct oral anticoagulant (DOAC), depending on protocol.
   • Duration:
     • 3 months for a transient/reversible risk factor (e.g. recent surgery).
     • Extended or lifelong if recurrent VTE or permanent risk factor (e.g. active cancer).
2. Vena Cava Filters
   • Prevent further emboli if anticoagulation fails or is contraindicated.
3. Outpatient Management
   • Patients with no significant comorbidities and stable vitals may be managed at home with LMWH until oral anticoagulation is therapeutic.
4. Prevention
   • Risk assessment for DVT in all hospital in-patients.
   • Thromboprophylaxis (e.g. LMWH, anti-embolism stockings) for at-risk individuals.

1.8 Prognosis and Complications

• Untreated PE has a mortality of ~30%, significantly reduced with appropriate treatment.
• Massive PE can have mortality up to 50% even with intervention.
• Factors linked to higher mortality: Advanced age, malignancy, right ventricular dysfunction (raised troponins, NT-proBNP).
• Chronic thromboembolic pulmonary hypertension (<5% of acute PE cases) can lead to progressive right heart strain.

2. Pulmonary Hypertension

2.1 Epidemiology

• Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) >25 mmHg at rest or >30 mmHg on exertion.
• Most cases are secondary to chronic hypoxic lung disease (e.g. COPD) or left-sided heart disease.
• Primary pulmonary hypertension (idiopathic or due to chronic pulmonary embolism) is rare, with an incidence of only 1–2 per million for idiopathic forms.

2.2 Aetiology

Pulmonary hypertension arises when processes increase pulmonary vascular resistance, pulmonary venous pressure, or pulmonary blood flow.

Broad categories:

1. Primary (Pulmonary Arterial) Hypertension
   • Directly affects pulmonary vessels (e.g. idiopathic PH, chronic pulmonary embolism).
2. Secondary Pulmonary Hypertension
   • Develops due to other chronic conditions:
     • Chronic hypoxic lung disease (e.g. COPD, interstitial lung disease, severe obesity hypoventilation syndrome)
     • Left-sided heart disease (e.g. congestive cardiac failure, valvular disease)
     • Loss or obstruction of pulmonary vessels (e.g. emphysema destroying alveolar walls, recurrent pulmonary emboli)
     • Increased pulmonary flow from left-to-right cardiac shunts

Cor Pulmonale

• Defined as right heart failure secondary to chronic hypoxic lung disease.
• Involves pulmonary hypertension, right ventricular hypertrophy (RVH), and dilatation leading to right-sided heart failure.
• Typical signs of cor pulmonale:
  • Central cyanosis
  • Ankle oedema
  • Raised jugular venous pressure
  • Loud P2 on auscultation
  • Tricuspid regurgitation murmur

2.3 Risk Factors

• Severe underlying lung diseases (COPD, interstitial lung disease, etc.)
• Recurrent or chronic pulmonary emboli
• Left-sided cardiac pathologies (valvular or myocardial dysfunction)
• High-altitude living (chronic hypoxia)
• Congenital heart disease (e.g. large left-to-right shunts)

2.4 Clinical Features

• Progressive dyspnoea on exertion and fatigue are common.
• Chest pain on exertion may occur due to right ventricular hypertrophy increasing oxygen demand.
• Exertional syncope occasionally, reflecting inability to increase cardiac output.
• In secondary PH, it can be difficult to distinguish symptoms from the underlying condition.

Physical Signs

• Loud P2 (forceful pulmonary valve closure)
• Raised jugular venous pressure with prominent V waves
• Right ventricular heave (parasternal heave) indicating RVH
• Third (S3) or fourth (S4) heart sound related to right ventricle dysfunction
• Eventually, right-sided heart failure: peripheral oedema, ascites, pleural effusions, tricuspid regurgitation murmur

2.5 Diagnostic Approach

1. Echocardiography
   • Key screening test: Estimates pulmonary artery pressures and detects RVH or tricuspid regurgitation.
   • Identifies left-sided heart disease (e.g. valvular lesions).
2. Chest X-ray
   • May be normal.
   • Possible enlarged central pulmonary arteries, reduced peripheral vasculature.
   • Right ventricular enlargement (widened cardiac silhouette).
3. Electrocardiography (ECG)
   • Signs of right ventricular hypertrophy: right axis deviation, tall R waves in V1, right bundle branch block, P pulmonale.
4. Pulmonary Function Tests
   • Transfer factor (DLCO) often decreased.
   • In cor pulmonale or severe lung disease, spirometry may show obstruction or restriction.
   • Six-minute walk test can assess functional impact.
5. Ventilation–Perfusion (VQ) Scan or CT Pulmonary Angiogram (CTPA)
   • Evaluates for chronic pulmonary emboli as a cause.
   • CTPA may reveal enlarged pulmonary arteries if significant PH.
6. Right Heart Catheterisation
   • Gold standard for accurate measurement of pulmonary artery pressure and wedge pressures.
   • Generally reserved for cases where advanced therapies (e.g. vasodilators) are considered or the aetiology is unclear.

2.6 Management

General Measures

• Diuretics to reduce fluid overload (oedema, ascites).
• Oxygen therapy (domiciliary) in chronic hypoxic lung disease to reduce hypoxic vasoconstriction.
• Anticoagulation if chronic thromboembolic disease or high risk of further emboli.
• Pulmonary rehabilitation to improve functional capacity.

Treating the Underlying Cause

• Optimise therapy for COPD, interstitial lung disease, or left-sided heart disease.
• Surgical correction of valvular disease or congenital defects if feasible.
• Thromboendarterectomy for chronic pulmonary emboli.

Specific Pulmonary Vasodilators

• Calcium channel blockers (only in proven vasoreactive cases, which are rare).
• Endothelin receptor antagonists (e.g. bosentan).
• Phosphodiesterase-5 inhibitors (e.g. sildenafil).
• Prostacyclin analogues (e.g. epoprostenol).
• Administered primarily in specialist centres due to complexity and side effects.

Surgical Options

• Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.
• Combined heart–lung transplantation in select younger patients with severe, refractory disease.

2.7 Prognosis / Complications

• Idiopathic or severe pulmonary hypertension has a poor prognosis, with many patients dying within 5 years of diagnosis.
• Cor pulmonale (right heart failure from lung disease) significantly worsens quality of life and increases mortality.
• Timely diagnosis and targeted therapies can improve symptoms and possibly extend survival.

3. Pulmonary Vasculitis

3.1 Epidemiology

• Pulmonary vasculitis is very rare.
• Primary importance is as a differential diagnosis for more common conditions such as tuberculosis, cavitating pneumonia, or lung cancer.

3.2 Aetiology

• Immune-mediated inflammation of blood vessel walls.
• Pathological features:
  • Inflammatory cell infiltration
  • Necrosis of vessel wall
  • Possible alveolar damage and haemorrhage
• Common immunopathological processes include:
  • Autoimmune attack on vessel tissue (autoantibodies such as anti-GBM or ANCA)
  • Immune complex deposition in vessel walls

Main Causes of Pulmonary Vasculitis

1. Granulomatosis with polyangiitis (GPA) (formerly Wegener’s granulomatosis)
2. Eosinophilic granulomatosis with polyangiitis (EGPA) (formerly Churg–Strauss syndrome)
3. Anti–glomerular basement membrane (GBM) antibody disease (formerly Goodpasture’s syndrome)

3.3 Clinical Features

• Marked systemic symptoms (e.g. fever, malaise, weight loss)
• Respiratory symptoms:
  • Cough (often with haemoptysis)
  • Dyspnoea
  • Alveolar haemorrhage in some cases (especially anti-GBM)
• GPA:
  • Lung nodules that may cavitate
  • Upper airway involvement (sinusitis, nasal or sinus destruction)
  • Rapidly progressive kidney damage in some cases
• EGPA:
  • Asthma (often adult-onset or severe)
  • Possible pulmonary infiltrates
  • Peripheral eosinophilia and involvement of nerves (mononeuritis multiplex)
• Anti-GBM disease:
  • Alveolar haemorrhage (haemoptysis)
  • Glomerulonephritis (haematuria, renal failure)

Clues pointing to vasculitis:

• Kidney damage (proteinuria, haematuria, raised creatinine)
• Upper airway disease (GPA, EGPA)
• Peripheral neuropathy (GPA, EGPA)
• Skin nodules, cardiac involvement (EGPA)

3.4 Diagnostic Approach

1. Radiological Findings
   • Variable, can mimic cancer, TB, or pneumonia.
   • Cavitating nodules (GPA).
   • ‘Ground-glass’ alveolar infiltrates suggesting haemorrhage.
2. Autoantibodies
   • ANCA (antineutrophil cytoplasmic antibodies) often positive in GPA (c-ANCA) and sometimes in EGPA.
   • Anti-GBM antibodies in anti-GBM disease.
   • Eosinophilia in EGPA.
3. Renal Involvement
   • Haematuria, proteinuria (dipstick or microscopy).
   • Increased serum creatinine.
4. Histology (Biopsy)
   • Confirmatory test for definitive diagnosis.
   • Demonstrates vasculitis with necrotic changes in small-to-medium vessels.
   • Samples often taken from the lung or other affected organs.

3.5 Management

• Prognosis is poor without treatment; can be life-threatening.
• Intensive immunosuppression is the mainstay:
• Systemic corticosteroids (high-dose).
• Cyclophosphamide to induce remission (sometimes replaced or followed by other immunosuppressants).
• Plasma exchange (plasmapheresis) in severe cases or where rapid antibody removal is necessary (e.g. anti-GBM disease with alveolar haemorrhage).

4. Arterio-venous Malformation

4.1 Epidemiology

• Pulmonary arteriovenous malformations (AVMs) are relatively uncommon.
• They can occur idiopathically, be congenital, or develop in association with hereditary haemorrhagic telangiectasia (HHT) or liver cirrhosis.

4.2 Aetiology

• Arteriovenous malformation: an abnormal vascular connection directly linking a pulmonary artery to a pulmonary vein, resulting in right-to-left shunt.
• Possible underlying causes:
  • Congenital defects
  • Hereditary haemorrhagic telangiectasia (HHT)
  • Liver cirrhosis
  • Idiopathic (no identifiable trigger)

4.3 Risk Factors

• Family history of HHT (Osler–Weber–Rendu syndrome)
• Chronic liver disease or cirrhosis
• Existing congenital vascular anomalies

4.4 Clinical Features

• Often asymptomatic and found incidentally.
• Possible symptoms include:
  • Dyspnoea
  • Haemoptysis
  • Platypnoea (dyspnoea worsens when upright)
  • Hypoxia (due to right-to-left shunt)
• Paradoxical embolisation can lead to stroke or cerebral abscess.
• In HHT: telangiectasias on the tongue and lips; frequent epistaxis is also common
• Large AVMs can sometimes produce an audible bruit over the lung.

4.5 Diagnostic Approach

1. Imaging
   • Chest X-ray / CT scan: Often appear as well-demarcated nodules with a characteristic ‘feeding’ vessel and a ‘draining’ vein.
2. Clinical Clues
   • Family history or clinical signs of HHT.
   • Unexplained hypoxia, especially with a suspicious nodule on imaging.
3. Potential Complications to Consider
   • Paradoxical systemic embolisation (risk of stroke or abscess).

4.6 Immediate Management

• For acute complications (e.g. significant haemoptysis or hypoxia): provide supportive care with oxygen.
• Severe haemoptysis might occasionally require urgent intervention (e.g. bronchoscopic evaluation), though massive bleeding from an AVM is relatively rare.

4.7 Long-Term Management

• Definitive therapy: Embolisation of the feeding artery (usually with metallic coils) via pulmonary angiography.
  • Aims to close the abnormal connection and eliminate the right-to-left shunt.
• Follow-up imaging to ensure successful occlusion and monitor for recurrence.
• Genetic counselling or screening may be relevant if HHT is suspected.

4.8 Prognosis and Complications

• Generally good if the malformation is identified and embolised successfully.
• Potential for paradoxical emboli leading to stroke or brain abscess underscores the importance of timely intervention.
• Rarely, large untreated AVMs can cause chronic hypoxia or complications from haemoptysis.