Pulmonary Hypertension

• Pulmonary hypertension is when the mean pulmonary pressure reaches one four of the of systemic levels
• It is caused by increased pulmonary vascular resistance
• Most commonly it is secondary and due to;
  • Chronic obstructive or interstitial lung disease
    • Hypoxia as well as destruction of the lung parenchyma and reduced alveolar capillaries
    • This causes increased pulmonary arterial resistance and elevated pressure
  • Congenital or acquired lung disease with left sided heart failure
    • e.g. mitral stenosis
  • Recurrent thromboemboli
    • Due to a reduction in the functional cross sectional area of the pulmonary vascular bed
  • Autoimmune diseases
    • e.g. systemic sclerosis. Leads to inflammation, intimal fibrosis, medial hypertrophy and pulmonary hypertension
• Uncommonly all the causes of increased pulmonary pressure are excluded, this is referred to as idiopathic pulmonary hypertension. This is mostly sporadic, 6% is familial with autosomal dominant inheritance with variable penetrance.

 

Pathogenesis

• In the familial form, disease is caused by mutations in the BONE MORPHOGENETIC PROTEIN RECEPTOR TYPE 2 (BMPR2) signalling pathway
• In vascular smooth muscle cells, BMPR2 signalling is involved in apoptosis and the inhibition of  proliferation
• Not all patients with BMPR2 mutations get disease suggesting that there are other genes or environmental factors involved which may play a role in increasing vascular tone
• In the secondary forms of disease, endothelial cell dysfunction is produced resulting in persistent vasoconstriction with subsequent intimal and medial hypertrophy and increased vascular resistance
• Pulmonary hypertension has been reported after ingestion of certain plants or medicines including certain leguminous plants, olive oil and obesity drugs. The effect of these may be mediated via serotonin transporter expression or activity

 

Morphology

• Vascular lesions include;
  • Artheroma in large elastic arteries
  • Intimal fibrosis and medial hypertrophy in medium sized muscular arteries and arterioles
  • Plexogenic arteriopathy – tufts within capillary channels creating a vascular plexus of dilated, small thin walled arteries. This is seen in primary pulmonary hypertension and in some congenital cardiovascular anomalies
  • Numerous organised thrombi, suggest recurrent PE as an aetiology

 

Clinical

• Primary disease is most common in women aged 20 – 40
• Presenting features are dyspneoa, fatigue and possibly angina like chest pain
• Over time severe respiratory distress, cyanosis and right ventricular hypertrophy can occur
• Death is generally due to decompensated cor pulmonale often with superimposed PE and pneumonia
• Treatment is via vasodilators and anti-thrombotic therapy

 

Cor Pulmonale

 

• Right sided heart failure due to a disorder of the respiratory system most commonly pulmonary hypertension
• The right ventricle has a high pressure workload due to increased resistance of the pulmonary circulation
• This results in hypertrophy and dilation of the right ventricle and atrium

 

Causes include;

• Pulmonary vasoconstriction due to alveolar hypoxia or blood acidosis
• Anatomical compromise of the pulmonary vascular bed secondary to lung disorders e.g emphysema, PE, interstitial lung disease
• Increased blood viscosity secondary to blood disorders e.g. polycythaemia vera and sickle cell disease
• Idiopathic primary pulmonary hypertension

 

• Increased afterload of the RV results in its hypertrophy and dilation, eventually output is decreased resulting in decreased diastolic volume in the LV, resulting in reduced cardiac output
• Right ventrical overload can result in septal deviation which can also cause LV dysfunction

 

• Generally disease is chronic but there are two things that can cause acute cor pulmonale;
  • ARDS
  • Massive PE