5. Pulmonary vascular diseases

Question 1

Types of pulmonary vascular diseases

Answer 1

1. Pulmonary edema
2. Pulmonary hypertension
3. Pulmonary embolism
4. Diffuse pulmonary haemorrhage syndromes

Question 2

Causes of pulmonary edema

Answer 2

1. Hemodynamic causes
   - Increased capillary hydrostatic pressure (left-sided heart failure, volume overload, pulmonary vein obstruction)
   - Decreased capillary oncotic pressure (hypoalbuminemia, nephrotic syndrome, liver disease, protein-losing enteropathies)
   - Lymphatic obstruction
2. Microvascular injury
   - Infections (pneumonia, septicaemia)
   - Inhaled toxic gases
   - Drugs & chemicals
   - Shock, trauma, radiation
3. Others (of unknown mechanisms)
   - High altitudes
   - Neurogenic (CNS trauma)

Question 3

Morphology of pulmonary edema

Answer 3

1. Interstitial edema
2. Edematous widening of alveolar septa
3. Accumulation of edema fluid in alveolar spaces
4. Hemosiderin-laden macrophages

Question 4

Causes of pulmonary hypertension

Answer 4

1. Primary idiopathic pulmonary hypertension
   - Most common in women, 20-40 years old
2. Left-sided heart disease
   - Left-sided heart failure, mitral stenosis
   - Results in chronic venous congestion and consequent increase in pulmonary arterial pressure
3. Congenital left-to-right shunts
   - Increase pulmonary blood flow increases shear stress on pulmonary vasculature, promoting endothelial dysfunction
4. Lung disease
   - Chronic obstructive lung disease (damaged vasculature, pulmonary hypoxia)
   - Lung fibrosis (damaged vasculature)
5. Recurrent pulmonary thromboembolism
   - Increase pulmonary vascular resistance over time
6. Pulmonary hypoxia
   - Causes hypoxic vasoconstriction of pulmonary vasculature, increasing vascular resistance
7. Connective tissue disease
   - Most notably systemic sclerosis
   - May involve pulmonary vasculature, leading to inflammation, intimal fibrosis and medial hypertrophy

Question 5

Pathogenesis of pulmonary hypertension

Answer 5

1. Process which initiates the disorder results in endothelial dysfunction which plays central role in the development of pulmonary hypertension in the following ways:
   - Decreased nitric oxide production & increased endothelin release → promote vasoconstriction
   - Decreased production of anti-thrombotic factors (e.g. prostacyclin) & endothelial activation → promote thrombosis
   - Production of cytokines & growth factors locally promote migration & proliferation of vascular smooth muscle cells & elaboration of extracellular matrix
2. Pulmonary vasospasm may also contribute in some cases
3. Ingestion of certain plant substances or medicines may also lead to pulmonary hypertension

Question 6

Morphology of pulmonary hypertension

Answer 6

1. Atherosclerosis (of pulmonary artery & its major branches)
2. Medial hypertrophy (increased thickness of smooth muscle & intimal proliferation)
3. Luminal occlusion (due to intimal fibrosis)
4. Plexiform lesions (nodular lesions of interlacing blood vessels, seen in small arteries of advanced pulmonary hypertension)
5. Fibrinoid necrosis
6. Hemorrhage (due to rupture of vessels)

Question 7

Pathological effects and complications of pulmonary hypertrophy

Answer 7

Cor pulmonale

Question 8

Causes of pulmonary embolism

Answer 8

1. Thrombus in the deep veins of the leg (95%)
2. Hypercoagulable states
3. Indwelling central venous lines

Question 9

Pathological effects & complications of pulmonary embolism

Answer 9

1. Respiratory compromise
   - Increased physiological dead space (areas of lung which are ventilated but not perfused)
2. Hemodynamic compromise
   - Pulmonary hypertension: multiple recurrent small
   emboli progressively increases pulmonary vascular resistance; may lead to the development of chronic cor pulmonale
   - Acute cor pulmonale: large embolus obstructing the main pulmonary artery; may lead to sudden death (saddle embolus = large embolus lodged at the bifurcation of pulmonary trunk)
   - Pulmonary infarct: rarely occurs as bronchial arterial supply is usually sufficient; appears as a wedge shape pale area with apex pointing towards hilum

Question 10

Definition of diffuse pulmonary haemorrhage syndrome

Answer 10

Hemorrhage from the lung as a dramatic complication of some interstitial lung disorders

Question 11

Types of diffuse pulmonary haemorrhage syndrome

Answer 11

1. Goodpasture syndrome

2. Pulmonary vasculitis

Question 12

Goodpasture syndrome

Answer 12

1. Type II hypersensitivity disorder caused by autoantibodies against the non-collagenous domain of the alpha3 chain of collagen IV (a constituent of alveolar & glomerular basement membranes)
2. Results in a necrotizing hemorrhagic interstitial pneumonitis
3. Also results in a proliferative & usually rapidly progressive glomerulonephritis

Question 13

Pulmonary vasculitis

Answer 13

Wegener granulomatosis, microscopic polyangiitis