teaching
notes

12 PULMONARY VASCULAR DISEASE

Contents

12.1 Normal Anatomy and Physiology
12.2 Control of Normal Pulmonary Circulation
12.3 Secondary Pulmonary Vascular Disease

12.3.1 Pulmonary Thromboembolism
12.3.2 Pulmonary Hypertension Secondary to Chronic Obstructive Lung Disease
12.3.3 Pulmonary Hypertension Secondary to Fibrotic Lung Disease
12.3.4 Pulmonary Vascular Response to Mitral Stenosis

12.4 Primary Pulmonary Hypertension
12.5 Arteriovenous Fistulas
12.6 References

Two unique aspects of the pulmonary circulation predispose it to disease. Firstly, it receives the entire right cardiac output and acts as a sieve for all particulate matter from the systemic veins. Secondly, the pulmonary vasculature is intimately interwoven with lung structure and function and is thus very vulnerable to other lung disease.

Pulmonary vascular disease may be primary or secondary to other disorders of the lung or other organs. The secondary causes are more important and the most common entities are discussed below.

12.1 NORMAL ANATOMY AND PHYSIOLOGY
The pulmonary circulation conducts the entire cardiac output (CO) from the right to the left side of the heart. It is a low pressure system and this is reflected in the structure of the walls of the main pulmonary arteries compared with that of the aorta. The calibre of the pulmonary trunk is much the same as that of the aorta, but it is only 70% as thick and the elastic laminae are fragmented rather than continuous. During foetal and immediate postnatal life the pulmonary trunk is identical to that of the aorta, but the elastic tissue gradually diminishes and is replaced by collagen.

The pulmonary vascular tree is a rather irregular, dichotomous, branching system, down to small arterioles that supply the network of capillaries in the alveolar walls. These are very thin walled (approximately 1.8 microns) and form a convoluted sheet, the two walls of which are supported by 'posts', much like the structure of a car park. After traversing the channels, where gas exchange takes place with alveolar gas on the other side of the capillary wall, the blood flows into venules which are indistinguishable in structure from arterioles.

Normal pulmonary artery pressures are 25mmHg systolic and 10mmHg diastolic. Normal pulmonary vein pressure, as measured by a catheter wedged into a pulmonary vein, is approximately 9mmHg.

Pulmonary vasoconstriction:

• sympathetic neural stimuli
  
• alveolar hypoxia
  
• acidosis alpha
  
• adrenergic agonists
  
• histamine
  
• serotonin
  
• some leukotrienes
  
• prostaglandin F2alpha

Pulmonary vasodilators:

• ß adrenergic agonists
  
• prostaglandins E1 and E2
  
• theophylline
  
• acetylcholine
  
• nitrites
  
• calcium channel blockers
  
• oxygen

Alveolar hypoxia, causing pulmonary vasoconstriction, is the most important control mechanism. This diverts blood flow away from areas with a low V/Q ratio and hence helps to maintain arterial oxygen tension. However, this is at the expense of an increased pulmonary artery pressure and strain on the right heart. In chronic lung disease, such as chronic airflow limitation, this can lead to permanent pulmonary hypertension and right heart failure which may be partly relieved by oxygen or vasodilating drugs. Prolonged increase in pulmonary artery pressure leads to anatomic changes in the pulmonary arteries, causing a permanent increase in pressure and right heart strain.

12.3.1 Pulmonary thromboembolism
The most common and important pulmonary vascular disease. The embolus originates as a thrombus in the systemic veins and lodges in the pulmonary circulation producing sudden dyspnoea, chest pain and possibly serious cardiac compromise. Haemoptysis and a small pleural effusion may be present. Symptoms and signs vary from mild discomfort to sudden death if the embolus is massive and occludes the pulmonary outflow tract.

Peripheral vein thrombosis is most common in the deep veins of the legs and predisposed to by injury, venous stress, and hypercoagulable states (e.g. post surgery, malignancy, thrombophilias). Less than 50% of deep leg vein thromboses are detectable clinically; they are sensitively detected by X-ray contrast venography, impedance plethysmography, or venous duplex doppler ultrasound studies.

Embolism to the lung may cause symptoms (above) and lead to ECG (S1,Q3,T3 pattern) and chest X-ray (small effusion) changes. A sensitive (but not very specific) method of detection in individuals with normal lungs and a clear chest x-ray is the ventilation-perfusion lung scan. While the 'gold standard' for diagnosis remains pulmonary angiography. Spiral CT angiograms are now recognised as sensitive investigation for identifying pulmonary emboli in major pulmonary arteries and segmented branches of the pulmonary arterial system. This technique has particular application in people with abnormal chest x-rays and in patients with severe airways disease in whom ventilation/perfusion abnormalities due to the underlying illness make interpretation of V/Q scans very difficult.

Therapy of pulmonary embolus involves adequate anticoagulation with heparin (fractionated or low molecular weight) followed by longer term therapy with oral anticoagulants (warfarin) in many patients. Thrombolytic therapy or surgical interruption of the inferior vena cava are sometimes used.

12.3.2 Pulmonary hypertension secondary to chronic obstructive lung disease
Pulmonary hypertension and right heart failure are quite common complications of long standing chronic airway obstruction. The causes are a combination of hypoxic pulmonary vasoconstriction, hypoxia induced polycythaemia causing an increased blood viscosity and blood volume, alveolar hypercapnia and local acidosis and raised intra-alveolar pressure during expiration. The degree of mechanical destruction of the pulmonary capillary bed in emphysema does not appear to be related to pulmonary hypertension. This hypertension may be partly, but not completely, relieved by chronic oxygen administration. The role of vasodilator drugs such as calcium channel blockers is being assessed.

12.3.3 Pulmonary hypertension secondary to fibrotic lung disease
Idiopathic pulmonary fibrosis or fibrotic complications of the pneumoconiosis will produce intravascular thrombosis and fibrosis of the vessels. Interestingly, these patients do not tend to develop pulmonary hypertension as only a small part of the pulmonary arterial tree is involved until very late in the disease process. Scleroderma (progressive systemic sclerosis) may cause pulmonary hypertension disproportionate to the lung disease. Bronchopulmonary anastomoses between bronchial and pulmonary arteries occur in the normal lung but may become larger around bronchiectatic areas and in congenital heart disease.

12.3.4 Pulmonary vascular response to mitral stenosis
Mitral stenosis and other left heart valvular lesions that lead to passive pulmonary venous hypertension, cause a transmitted capillary and arterial hypertension, which then leads to an active constriction of pulmonary arterioles and muscular arteries leading to further increase in pulmonary vascular resistance. The mechanism of this may be alpha-adrenergic neural activity and intrinsic myogenic vasoconstriction. This is reversible following correction of the valvular lesion.

Congenital heart disease:
Such disease that causes a volume load (e.g. ventricular septal defect) or pressure load (e.g. congenital mitral stenosis) may lead to reactive pulmonary hypertension.

Symptoms of dyspnoea on exertion and exercise syncope develop in children or young adults although no age range is exempt. Boys and girls are equally affected before puberty but thereafter females are predominant. The cause is unknown, although one outbreak of the condition in Europe in 1967 was attributed to an appetite suppressant, aminorex.

There is no known effective treatment. Mean survival time is 2-3 years after onset of symptoms but, rarely, spontaneous regression of the hypertension has been reported.

It is important to exclude recurrent pulmonary emboli (by pulmonary angiography and/or lung biopsy) as a cause of pulmonary hypertension.

Presenting symptoms are asymptomatic pulmonary masses on chest x-ray, haemoptysis or cyanosis from extensive shunting of blood through the fistula. About 60% of patients have the Osler-Rendu-Weber syndrome with telangiectasia elsewhere. There are congenital fistulas but they may develop as acquired lesions in patients with liver cirrhosis. Complications are cyanosis, rupture or cerebral abscess. Surgical removal or local occlusion with artificial emboli via pulmonary artery catheters may be considered options for treatment.

There are other very rare primary vascular tumours of the lung such as chemodectomas and hemangiopericytomas.

Moser KM. "Venous Thromboembolism." Am Rev Respir Dis. 1990. 141:235-249.

Goldhaber SZ. "Pulmonary Embolism." NEJM. 1998. 339:93-104.

Tapson VF. "Pulmonary Embolism - new diagnostic approaches." NEJM. 1997. 336:1449-1451.

Teaching Notes 13 - Pleural, Mediastinal, Chest Wall & Rare Lung Disease