14: Pulmonary hypertension

TABLE 14.1

Hemodynamic Subgroups of Pulmonary Hypertension

a1 Wood unit = 1 mm Hg/L/min.

bAlso called pulmonary capillary wedge pressure (PCWP) or pulmonary artery occlusion pressure (PAOP).

Because PH has many possible causes that presumably act by several different mechanisms, this chapter begins with a consideration of features relevant to PH in general, and follows with a discussion of some important specific causes of PH.

The current classification of PH is summarized in Table 14.2. The clarification of a few points is pertinent. First, the term pulmonary hypertension simply refers to elevated pulmonary arterial pressure, which may be due to a number of different mechanisms. The term pulmonary arterial hypertension (PAH) is reserved for specific types of PH—those categorized under Group 1 in the classification system in Table 14.2. The elevation of pulmonary arterial pressure may be acute or chronic and either reversible or irreversible, depending on the causative factors. In some cases, chronic PH is punctuated by further acute elevations in pressure, often as a result of exacerbations of underlying disease. Second, the development of right ventricular hypertrophy and eventual dysfunction is the consequence of chronic PH, whatever the primary cause of the latter. When PH is due to disorders of any part of the respiratory apparatus (airways, parenchyma and blood vessels, chest wall, respiratory musculature, or central nervous system controller), the term cor pulmonale is used to refer to the resulting alterations in the right ventricle. This term is not to be used to describe the right ventricular changes occurring as a consequence of primary cardiac disease or increased flow to the pulmonary vascular bed.

occlusion of a sufficient cross-sectional area of the pulmonary arteries by material (e.g., pulmonary emboli) within the vessels is an important factor (discussed in Chapter 13). In acute embolism where massive pulmonary emboli occlude more than approximately one-half to two-thirds of the vasculature, pulmonary arterial pressure is elevated. The right ventricle may dilate in response to its acutely increased workload because of insufficient time for hypertrophy to occur; consequently, in this acute circumstance, death may ensue prior to the right ventricle being able to generate adequately elevated PAPs to maintain cardiac output. In contrast, in chronic thromboembolic disease, multiple and recurrent pulmonary emboli may organize over a period sufficiently long for right ventricular hypertrophy to occur and markedly elevated pulmonary arterial pressures to result.

Second, remodeling of the pulmonary arterial walls causing diminution of the overall cross-sectional area of the pulmonary vascular bed is a potential factor causing PH. Disorders acting by this mechanism are characterized by intimal and medial changes (see Pathology) that lead to thickening of the arterial and arteriolar walls and narrowing or obliteration of the lumen. This group of disorders with pulmonary arterial pathology includes idiopathic pulmonary arterial hypertension (IPAH, formerly called primary PH). The familial form of this condition, called heritable pulmonary arterial hypertension, in most cases is related to mutations of the gene on chromosome 2 that encodes the bone morphogenetic protein receptor type 2 (BMPR2). Abnormalities in this receptor are believed to lead to the dysregulation of proliferative responses in the endothelium and pulmonary arterial smooth muscle cells, producing the well-described pathologic changes in small pulmonary arteries and arterioles (again, see Pathology). Lesions pathologically similar to those seen in IPAH are also observed in other conditions associated with PAH (e.g., scleroderma, portal hypertension, and human immunodeficiency virus [HIV] infection) or with exposure to drugs and toxins (e.g., cocaine, methamphetamine, and certain diet drugs). When compromise of the pulmonary vasculature and increased resistance to flow are sufficiently pronounced in these primary disorders of the vessel wall, the level of PH can be quite severe, both at rest and with exercise.

Factors contributing to pulmonary hypertension (PH):

1.Occlusion of vessels by emboli

2.Primary remodeling and thickening of arterial walls

3.Loss of vessels by scarring or destruction of alveolar walls

4.Pulmonary vasoconstriction

5.Increased pulmonary vascular flow (left-to-right shunt)

6.Elevated left atrial and pulmonary venous pressure

Third, the total cross-sectional area of the pulmonary vascular bed can be compromised by parenchymal lung disease, with loss of blood vessels from either a scarring or a destructive process affecting the alveolar walls. Interstitial lung disease and emphysema can affect the pulmonary vasculature via this mechanism, although the underlying disorder in the parenchyma is quite different. Because of the significant capacity of the normal pulmonary vascular bed to accept increased blood flow, a large amount of the pulmonary vascular bed must be lost before resulting in an elevation in pulmonary arterial pressure. With these diseases, pulmonary arterial pressure is often normal at rest, but becomes mildly to moderately elevated with exercise because of insufficient recruitment or distention of vessels to handle the increase in cardiac output.

A fourth mechanism of PH is vasoconstriction, which may be present in all forms of PH. It is most prominent in response to hypoxia and, to a lesser extent, to acidosis. The importance of this mechanism is