Classification
Although many conditions are associated with the development of PH, the PAH group is associated with the greatest elevation in PAP. Over the past 15 years a number of efforts have been made to classify conditions into groups according to common pathological and clinical features.5,6 These are outlined in Table 1.6
The PAH disorders are in group 1. At the present time, specific targeted therapy for PH is reserved for patients in groups 1 and 4. Group 1 patients share the 
histopathological entity known as PPA.7 In this condition, smooth muscle cells from the inner aspect of the media of muscularised pulmonary arterioles migrate though the intima into the lumen and proliferate. Once inside the lumen they differentiate into myofibroblasts, which are capable of laying down either fibrous tissue or smooth muscle tissue. The vascular proliferation develops in a concentric fashion so that on section the vessel has the appearance of an onion. Therefore, this type of proliferation is often referred to as onion skin proliferation. As the radius of the vessel gets less, the flow is reduced in proportion to the fourth power of the radius in accordance with Poiseuile’s Law. The pressure progressively rises and at points of proximal weakness where blood vessels branch, the wall gets progressively thinner and ultimately ruptures. Primitive blood vessels then grow into this area in a haphazard (plexiform) fashion giving rise to a plexiform lesion. The combination of concentric laminar (or onion skin) proliferation and plexiform lesions is known as PPA. Why this only occurs in those disorders listed in group 1 is far from clear although there are many theories relating to genetic predisposition, infection, autoimmunity and the role of pulmonary endocrine cells.1,4,7
Pulmonary thromboembolic disease can have many potential underlying causes including malignancy and thrombophillia abnormalities. Chronic thrombolembolic PH (CTEPH) is also an indication for advanced pulmonary vaso dilator therapy and for selected patients surgery in the form of pulmonary thromboendarterectomy may be an option.4
The pulmonary vasculature is normally a low-pressure low-resistance system with high distensibility as the resistance vessels normally possess only a small amount of smooth muscle relative to their systemic counterparts.7 This enables the right ventricle to deliver the same stroke volume as the left ventricle with 1/6 of the stroke work.8 However, as vascular remodelling occurs and vascular obstruction develops the resistance to flow increases.
The PVR is calculated by the following equation:
PVR = mPAP – mean pulmonary capillary wedge pressure (mPCWP) Cardiac output (CO)
As the PVR progressively increases in patients with PH, the right ventricle is susceptible to pressure overload and the response of the right ventricle to this increased after load determines the patient’s exercise capacity, symptoms and outcome.9,10 Ultimately patients die from right ventricular failure.
Over 90 % of patients do not fall within group 1 and left heart disease is one of the most common causes of PH in general.11,12
The functional class of patients can be determined using the New York Heart Association (NYHA) criteria and this can be used to help determine disease severity and prognosis.
Symptomatology
The diagnosis of PH is frequently missed. When it is associated with other comorbidities e.g. lung or heart diseases failure of the primary disease to respond to conventional therapies should lead one to suspect a possible association with PH in addition which warrants diagnosis, classification and potential therapeutic intervention.
For many patients symptoms develop late in the course of the disease and they are often non-specific. As a consequence, delay or failure of diagnosis is still far too common. Symptoms that are associated with PH include dyspnoea with exertion, which may progress and subsequently occur with minimal exertion, or may occur at rest as the PVR rises. Palpitations are often due to right atrial stretch and underlying atrial arrhythmias. Haemoptysis may reflect vessel rupture as elevation in PAP progresses or indeed can be associated with pulmonary thromboembolic disease. Pre-syncope and syncope are common as the PVR progressively rises. Certain conditions including hypoxia or general anaesthesia can lead to an acute elevation in PVR over a short period of time resulting in compromised left heart filling with low cardiac output and profound hypotension or even death. This is termed a PH crisis. Chest pain is often attributed to right ventricular angina as the right ventricle hypertrophies.
In addition to the NYHA classification of dyspnoea, an unencouraged 6-minute walk test is a useful benchmark and can be used to monitor a patient’s progression.
History and Examination
It is important to consider the diagnosis of PH and to take a careful history e.g. a familial background of PH, history of connective tissue disease or of thrombophilia abnormalities, alcohol consumption, etc. Physical examination may reveal evidence of other pathologies e.g. left heart failure, underlying lung disease, deep venous thrombosis, connective tissue disease or malignancy.
The clinical signs associated with PH include:
1.A prominent a wave reflecting high right ventricular filling pressures in the jugular venous pressure.
2.An accentuated V wave suggesting tricuspid regurgitation in the jugular venous pressure.
3.A loud pulmonary component of the second heart sound as a consequence of forceful valve closure from raised PAP.
4.A left parasternal lift as a consequence of right ventricular hypertrophy (a right ventricular heave).
5.A right ventricular gallop rhythm (third and or forth heart sound).
6.Signs of right ventricular failure.