Pathophysiology of PAH

Pathophysiology of PAH

How does Pulmonary Arterial Hypertension (PAH) develop?

The exact causes behind the development of pulmonary arterial hypertension (PAH) remain unknown. However, research has led to a better understanding of the underlying pathological mechanisms.

What is PAH?

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The 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines classify pulmonary hypertension (PH) into five main groups, according to their similar clinical presentation, pathological findings, haemodynamic characteristics and treatment strategy. [1]

PAH-Explained-Pathophysiology - Classification of PAH

Adapted from Galiè et al. 2016[1]

These 5 PH groups are further subcategorised.[1]

1. PAH

1.1 Idiopathic
1.2 Heritable
1.2.1 Bone morphogenetic protein receptor type 2 (BMPR2) mutation
1.2.2 Other mutations
1.3 Drug- and toxin-induced
1.4 Associated with:
1.4.1 Connective tissue disease
1.4.2 Human immunodeficiency virus (HIV) infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis

1'. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis

1’.1 Idiopathic
1’.2 Heritable
1’.2.1 Eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutation
1’.2.2 Other mutations
1’.3 Drug-, toxin- and radiation-induced
1’.4 Associated with:
1’.4.1 Connective tissue disease
1’.4.2 HIV infection

1”. Persistent pulmonary hypertension of the newborn

2. PH due to left heart disease

2.1 Left ventricular systolic dysfunction
2.2 Left ventricular diastolic dysfunction
2.3 Valvular disease
2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
2.5 Congenital/acquired pulmonary veins stenosis

3. Pulmonary hypertension due to lung diseases and/or hypoxia

3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases

4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions

4.1 Chronic thromboembolic pulmonary hypertension
4.2 Other pulmonary artery obstructions
4.2.1 Angiosarcoma
4.2.2 Other intravascular tumours
4.2.3 Arteritis
4.2.4 Congenital pulmonary arteries stenoses
4.2.5 Parasites (hydatidosis)

5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

5.1 Haematological disorders: chronic haemolytic anaemia, myeloproliferative disorders, splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis, neurofibromatosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
5.4 Others: pulmonary tumoural thrombotic microangiopathy, fibrosing mediastinitis, chronic renal failure (with/without dialysis), segmental pulmonary hypertension

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Diagnosis of PAH

Clinical guidelines set out the diagnostic pathway so patients can be referred and treated as quickly as possible.

Treatment of PAH

Modern treatments can significantly improve patients’ symptoms and slow the rate of clinical deterioration.

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