Pathology of Pulmonary Hypertension

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The secondary role of pathology in the present clinical management of pulmonary hypertension (PH) reflects to some extent the limitations of the current understanding of the disease. Ample room exists for the diagnostic translation of the pathobiologic studies, with the goal of improving the diagnostic and prognostic power of the pathologic assessment of pulmonary vascular remodeling. This article seeks to show the complementarities of the pathology and pathobiology of PH.

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Pathology

Intimal lesions account for most of the reduction of luminal area of small pulmonary arteries and potentially largely influence the overall pulmonary vascular resistance. Intimal lesions consist of eccentric intima thickening, and fibrotic, plexiform, concentric, and dilation or angiomatoid lesions (Fig. 1, Fig. 2, Fig. 3, Fig. 4; see Table 1). Focal eccentric lesions can be detected in normal lungs, but these lesions are more widespread and, to a larger extent, impinge on the vascular lumen in

Pathology

Medial smooth muscle cell hypertrophy is a characteristic pathologic feature of PH that involves muscularized arteries (between 70 and 500 μm in diameter) and precapillary vessels (less than 70 μm in diameter) (see Fig. 3). The medial smooth muscle cell layer represents approximately 10% to 15% of the outside diameter of normal muscularized pulmonary arteries, whereas it approaches 30% to 60% of the outside diameter in vessels of IPAH lungs [15], [39], [40], [41]. Although careful morphometric

Pathology

The adventitia is mostly composed of fibroblasts. Growing evidence shows that, rather than being just a structural support to pulmonary vessels, the adventitia may also play a role in regulating pulmonary vascular function from the “outside-in” [71]. The normal adventitia represents approximately 15% of the external diameter of pulmonary arteries larger than 50 μm in diameter. In IPAH arteries, the adventitial thickness increases to 28% of artery diameter, predominantly because of collagen

Pathology

The pulmonary veins are primarily involved in the pathogenesis of postcapillary PH, such as that caused by veno-occlusive disease, capillary hemangiomatosis, mitral valve and other forms of left heart dysfunction, and extrinsic main pulmonary vein obstructions. Veno-occlusive disease and pulmonary capillary hemangiomatosis are rare causes of idiopathic PH. Veno-occlusive disease is characterized by variable luminal obstruction by intraluminal bands or eccentrically placed fibrous tissue, which

Pathology

Perivascular cuffing of remodeled pulmonary arteries is present in IPAH lungs and severe PH associated with underlying conditions, such as HIV infection and CREST (see Fig. 5) [16], [73]. B cells, T cells, and macrophages infiltrate the vessel wall and are present within intimal lesions (Fig. 6) [16]. Both CD4 and CD8 cells are present, and many of these express the memory T-cell marker CD45RO, which might also indicate cell activation (see Fig. 6). Perivascular inflammation is more frequently

Summary

The secondary role taken by the pathology in the present clinical management of PH reflects to some extent the limitations of the current understanding of the disease. Ample room exists for the diagnostic translation of the pathobiologic studies, with the goal of improving the diagnostic and prognostic power of the pathologic assessment of pulmonary vascular remodeling. This article seeks to show the complementarities of the pathology and pathobiology of PH. The authors forecast that the

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    This work was supported by the grant P01HL66254 to RMT and grant R01 1HL083491 to SCF, from the National Institutes of Health.

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