Haemodynamic pulmonary oedema
Increased hydrostatic presusre.
Fluid accumulates initially in the basal regions of the lower lobes because the pressure is greater. Alveolar capillaries are engorged. Alveolar micro haemorrhages and haemosiderin laden macrophages may be seen. In longer standing cases brown induration may be seen.
Pulmonary oedema by microvascular injury
Injury to the microvascular endothelium or alveolar epithelial cells - when diffuse known as ARDS.
Undetermined pulmonary oedema
High altitude, neurogenic
Acute respiratory distress syndrome is characterised by abrupt onset of hydpnoea, hypoxaemia and diffuse pulmonary infiltrates.
ARDS is caused by severe acute lung injury (ALI).
Histological identification of ARDS
Histologically, ARDS is identified as diffuse alveolar damage (DAD).
Causes of diffuse alveolar damage
DAD can be a complication of numerous and diverse conditions including:
- Gastic aspiraion
- Infection (sepsis, diffuse pulmonary infections)
- Toxins (inhaled/drug)
- Hypersensitivity reactions
Acute interstitial pnumonia
In the absence of an underlying aetiology DAD is called acute interstitial pneumonia.
Pathogenesis of DAD
Central to the causation is damage to the alveolar capillary walls and/or the alveolar epithelium, resulting in increased vasuclar permeability. The lung injury is mediated by acute inflammatory response. IL-8, IL-1 and TNF leads to endothelial activation, pulmonary microvascular sequestrationo f neutrophils that contribute ot the acute lung injury.
Loss of diffusion capacity and widespread surfactant loss is caused by damage to type II pneumocytes (that produce surfactant). The exudate and diffuse tissue destruction generally result in organisation with scarring, producing chronic disease.
Macroscopic appearance of ARDs
Acute congestion, interstitial and intra-alveolar oedema, inflammation and fibrin deposition.
Microscopic features of ARDs
Alveolar walls become lined with waxy hyaline membranes. membranes consist of fibrin-rich oedema fluid mixed with cytoplasmic and lipid remnants of necrotic epithelial cells.
Organisation stage: epithelial cells undergo proliferation to regenerate the alveolar lining. Resolution is unusual, organisation of the fibrin exudate usually results in intra-alveolar fibrosis. Marked thickening of the alveolar septa ensues caused by proliferation of interstitial cells and deposition of collagen.
Clinical course of ARDs
Hospitalised with associated condition. Profound tachypnoea and dyspnea, cyanosis, hypoxia, and respiratory failure, diffuse bilateral infiltrates. Focal stiffness of lungs and difficulty in ventilation. Mortality may be around 40-60%.
Acute interstitial pneumonia
Similar clinical course to ARDS but no known associated cause. Occurs in those around 50, patient present with acute respiratory fialure following an illness of less than three weeks. Pathological features are very similar to DAD> 50% die within 2 months. Those that survive may have recurrences and develop chronic interstitial disease.
Pulmonary HTN classification
1. Primary (idiopathic pulmonary HTN)
Primary pulmonary HTN
Unknown cause, most sporadic, 6% familial. Associated with mutations int he bone morphogenic protein receptor type-2 (BMPR2). Normal function of BMPR2 is the inhibition of proliferation and favours apoptosis in vascular smooth muscle cells. Mutation results in vascular thickening and occlusion. Not everyong with a mutation gets it so there is a suspected environmental trigger.
Secondary pulmonary HTN
- Increased pulmonary blood flow
- Left heart disease
- Associated with lung disease and/or hypoxia
- Chronic thrombotic and/or embolic disease; and
- Ingestion of certain plants, appetite suppressants (fenfluramine)
Aetiology of primary pulmonary HTN
- Chronic obstructive or interstitial lung diseases (hypoxia and destruction of lung parenchyma - fewer alveolar capillaries)
- Congenital (increased pulmonary blood flow in left to right shunts) or acquired heart disease (eg left valvular heart disease)
- Recurrent thromboemboli (reduction in vascular bed due to obstruction emboli)
- Autoimmune disorders (scleroderma in particular - results in intimal fibrosis, medial hypertrophy) and obstructive sleep apnoea.
Aetiology of secondary pulmonary HTN
Endothelial dysfunction results in platelet activaion, thrombus formation and the release of growth factors and cytokines that induce the migration and replication of vascular smooth muscle cells and elaboration of extracellular matrix.
Microscopic appearance of pulmonary HTN
Pattern depends on the aetiology. Arterioles and small arteries affected with medial hypertrophy and intimal fibrosis, often severely narrowing the lumina. Increased pressure can make the pulmonary arteries susceptible to atherosclerosis.
Clinical course of primary pulmonary HTN
Most common in women who are 20-40 in age occasionally young children. Presents with dyspnoea and fatigue, some may have chest pain of the anginal type. Eventually severe respiratory distress, cyanosis, right ventricular hypertrophy and death from cor pulmonale often with associated thromboembolism and pneumonia - 2-5 years in 80% of patients.
Pulmonary HTN treatment
Vasodilators, antithrombotic agents, lung transplant.