(Radiographics. 2000;20:491-524.)
© RSNA, 2000
From the Archives of the AFIP
Pulmonary Vasculature: Hypertension and Infarction1 (CME available in print version and on RSNA Link)
Aletta Ann Frazier, MD,
Jeffrey R. Galvin, MD ,
Teri J. Franks, MD and
Melissa L. Rosado-de-Christenson, Col, USAF, MC
1 From the Departments of Radiologic Pathology (A.A.F., J.R.G., M.L.R.) and Pulmonary and Mediastinal Pathology (T.J.F.), Armed Forces Institute of Pathology, 6825 16th St NW, Bldg 54, Room M-121, Washington, DC, 20306-6000; the Department of Radiology, University of Maryland Medical System, Baltimore (J.R.G.); and the Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD (M.L.R.). Received October 26, 1999; revisions requested November 24 and received December 28; accepted December 29. Address reprint requests to A.A.F. (e-mail: frazier@afip.osd.mil).
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Abstract
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Pulmonary hypertension is the hemodynamic consequence of vascular changes within the precapillary (arterial) or postcapillary (venous) pulmonary circulation. These changes may be idiopathic, as in primary pulmonary hypertension or pulmonary veno-occlusive disease, but more commonly they represent a secondary response to alterations in pulmonary blood flow. The pulmonary and systemic bronchial circulations form broad anastomoses that largely prevent infarction except in settings of markedly elevated pulmonary venous pressure, underlying malignancy, or excessive embolic burden. Causes of precapillary pulmonary hypertension include long-standing cardiac left-to-right shunt, chronic thromboembolic disease, and widespread pulmonary embolism arising from intravascular malignant cells, parasites, or foreign materials. The classic radiologic features of precapillary pulmonary hypertension are central arterial enlargement, sharply pruned peripheral vascularity, and right-sided heart hypertrophy and chamber dilatation. Postcapillary pulmonary hypertension may develop secondary to focal venous constriction or to compromised pulmonary venous drainage due to left atrial neoplasia, mitral stenosis, or left ventricular failure. Radiologic manifestations of postcapillary pulmonary hypertension include prominent septal lines, small pleural effusions, and occasionally air-space opacities. In addition, radiologic evaluation of postcapillary pulmonary hypertension may demonstrate evidence of pulmonary arterial hypertension, secondary to the retrograde transmission of elevated pulmonary venous pressure across the capillary bed.
Index Terms: Hypertension, pulmonary, 564.78, 565.78 • Pulmonary arteries, stenosis or obstruction, 564.78 • Pulmonary veins, stenosis or obstruction, 565.78
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Introduction
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The subject of pulmonary hypertension has undergone extensive investigation and reclassification by some of the most erudite pathologists of the 20th century. The radiology literature, however, rarely delves deeply into this complex topic and thus often limits radiologists' understanding of the causes, features, and distribution of hypertensive vascular changes within the pulmonary circulation. In accordance with the established approach of pathologists, pulmonary hypertension may be categorized as either precapillary (with changes limited to the arterial side of the pulmonary circulation) or postcapillary (with primary findings located within the pulmonary venous circulation, between the capillary bed and the left atrium). This article uses this simple framework to define and illustrate the underlying histopathologic characteristics, clinical features, and distinguishing radiologic manifestations of pre- and postcapillary pulmonary circulation.
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Anatomy of the Dual Pulmonary Circulation
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Two separate but vital vascular networks, often forming rich anastomoses, support the complex anatomy and physiology of the lung parenchyma. The primary pulmonary circulation comprises the entire venous return of the body, flowing forward from the main pulmonary artery, ramifying throughout the pulmonary interstitium and airways, and reconstituting itself into pulmonary veins before entering the left atrium. A second, "bronchial" circulation draws approximately 1% of the systemic cardiac output and transmits blood at six times the pressure of the pulmonary circulation (1). The pulmonary and bronchial circulations communicate with one another by several microvascular interconnections (2).
The large (500 to >1,000 µm in diameter) elastic pulmonary arteries travel along the lobar and segmental bronchi down to the subsegmental level and match the caliber of adjacent airways (Fig 1) (3–5). Their walls comprise multiple parallel elastic lamellae, smooth muscle cells, and collagen fibrils (6). Beyond the intrapulmonary cartilaginous bronchi, these vessels transition to muscular arteries (50–1,000 µm), which accompany subsegmental airways down to the level of the terminal bronchioles (Fig 1) (3,5,6). Medial smooth muscle fibers in the muscular arteries provide active vasodilation and constriction (4). As smooth muscularization progressively thins, these arteries become arterioles (15–150 µm), which proceed along the respiratory bronchioles and alveolar ducts to finally form a capillary network in the alveolar walls (Fig 1) (3–5). The venules accept flow from these capillary beds and unite to form pulmonary veins, which course within interlobular fibrous septa, apart from the airways (Fig 1). Two veins from each hilum drain into the left atrium (3–6).
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Figure 1. Cross-sectional drawings depict normal pulmonary vascular anatomy. Arterial vessels are located adjacent to a schematic airway (A). The walls of elastic arteries (a) contain multiple parallel elastic lamellae, smooth muscle cells, and collagen fibrils. The muscular arteries (b) contain a media of smooth muscle fibers, bordered by distinct internal and external elastic laminae. Arterioles (c) are distinguished by the absence of a distinct external elastic lamina. Veins (d) are identified by their septal location (S) and a media of loosely organized smooth muscle fibers.
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The bronchial circulation arises from the thoracic aorta or intercostal arteries to supply the esophagus, trachea, visceral pleura, lymph nodes, extra- and intrapulmonary airways, bronchovascular and neural bundles, and vasa vasora of the pulmonary circulation (Fig 2) (2,4). Each lung is typically supplied by two bronchial vessels that impart several branches to the extrapulmonary mediastinal structures en route to the pulmonary hila, where they enter the peribronchial sheath of each mainstem airway. The bronchial arteries then form a dual-layered adventitial and submucosal plexus along the airways that communicates freely across airway muscular walls and nourishes the bronchial tree down to the terminal bronchioles (2,4,6). Unlike the pulmonary arteries, bronchial arteries are notably smaller than their adjacent airways and follow more tortuous paths (4).
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Figure 2. Schematic illustrates how the bronchial arteries (ba) supply the visceral pleura, airways, vasa vasora of pulmonary arteries, lymph nodes, and bronchovascular and neural bundles. Extrapulmonary bronchial veins (ev) drain to the right side of the heart, and intrapulmonary veins (iv) anastomose with pulmonary arteries and return to the left side of the heart.
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Anastomoses between the bronchial and pulmonary arteries occur not only along the bronchioles but also beyond the pulmonary lobule, where the bronchial microvasculature broadly interconnects with the pulmonary arterial circulation via alveolar capillary beds (2). Anastomoses also exist between precapillary-sized bronchial arteries (in the pleura and bronchial walls) and pulmonary veins (2). In addition, the bronchial venous drainage located in the peripheral lung forms broad venous networks that communicate extensively with the pulmonary veins and ultimately drain into the left side of the heart, creating the so-called bronchial systemic-to-pulmonary flow (2,4). The bronchial circulation responds to decreased pulmonary flow and ischemia with enlargement, hypertrophy, and focal proliferation across these meshlike anastomotic channels (Fig 3) (2,7). Bronchial blood flow has been shown to increase by 300% in the weeks following pulmonary artery embolization (8).
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Figure 3. Contrast material-enhanced chest computed tomographic (CT) scan (mediastinal window) of a patient with corrected transposition demonstrates thrombosis of the right pulmonary artery (*) secondary to slow flow. There is compensatory enlargement and tortuosity of bronchial arteries within the mediastinum and along central airways (arrows).
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Despite the protective effect of the bronchial circulation, pulmonary infarction does occur. It is less likely to develop in cases of central pulmonary arterial occlusion, in which massive bronchial collateral flow is easily accommodated by the pulmonary arterial circuit (2,9–11). The likelihood of infarction increases when a more distal medium- or small-sized (approximately 3 mm or less) artery is obstructed and the high-pressure collateral bronchial influx must be accommodated within a smaller intravascular volume (Fig 4). This reperfusion by the bronchial circulation, combined with locally increased vascular permeability due to tissue ischemia and capillary endothelial injury, causes the intraalveolar extravasation of blood cells. This creates a confined region of pulmonary hemorrhage (Fig 5a) (2,10–13). Within this area, the underlying tissue architecture is preserved and usually restored to a normal state once blood cells are resorbed (11). Nevertheless, localized pulmonary hemorrhage tends to progress to infarction in settings of underlying malignancy, high embolic burden, diminished bronchial flow (due to shock, hypotension, or impaired circulation in chronic disease), vasodilator use, or elevated pulmonary venous pressure, and interstitial edema (typically due to heart failure) (2,9–12,14). Heart failure is generally considered the single most important predisposing condition in the development of pulmonary infarction (10).
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Figure 4. Schematics show the anastomosis of a bronchial artery (b) and pulmonary arteriole (p) at an alveolar capillary loop (9). Normal (nl) antegrade flow in both vessels is shown in A. Occlusion of the pulmonary arteriole by thrombus, with recruitment of bronchial flow and consequent extravasation of blood cells into alveoli (arrows), is seen in B. Elevated postcapillary pulmonary pressure (P), combined with arterial occlusion, causes more significant intraalveolar hemorrhage (arrows), as illustrated in C. This higher degree of hemorrhage predisposes the patient to infarction.
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Figure 5a. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Figure 5b. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Figure 5c. Pulmonary hemorrhage and infarction. (a) Photograph of a gross specimen with pleural-based pulmonary hemorrhage shows thrombosis of the feeding vessel (arrow) and preservation of the underlying lung architecture. Scale is in millimeters. (b) Low-power photomicrograph (original magnification, x4; hematoxylin-eosin [H-E] stain) of a subpleural pulmonary infarct shows the triangular area of coagulation necrosis (*) surrounded by hemorrhage (arrows). (c) Photograph of a gross specimen with a wedge-shaped pulmonary infarct shows necrotic destruction of the affected parenchyma, surrounded by inflammatory infiltrates (solid arrows) and a rim of reactive hyperemia from bronchial arterial collateral flow (open arrows). (Fig 5a and 5c reprinted, with permission, from reference 13.)
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Once pulmonary hemorrhage evolves into infarction, the alveolar walls, bronchi, and vessels undergo ischemic coagulative necrosis (Fig 5b). Faint, ghostlike structures of lung tissue may remain evident at histologic examination (11,13). The outer perimeter of an infarct accumulates erythrocytes, neutrophils, and histiocytes deposited by the adjacent bronchial circulation (11,15). At gross inspection, a recent lung infarct consists of dark, necrotic material surrounded by a narrow rim of hyperemia and inflammation (Fig 5c). Septic emboli are associated with cavitation of an infarct, which may simulate or produce a lung abscess (7,11,15). Vascular fibrous tissue eventually replaces the infarction in ensuing weeks, folding into a collagenous platelike mass that produces pleural retraction (11,15).
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Pulmonary Hypertension: Definition and Causes
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Pulmonary hypertension is hemodynamically defined as a mean pulmonary artery pressure greater than 25 mm Hg at rest or greater than 30 mm Hg during exercise, with increased pulmonary vascular resistance (16). The diagnosis is made with clinical assessment of hemodynamic parameters, medical history, and histologic findings (3). Both precapillary (arterial) and postcapillary (venous) pulmonary hypertension are regarded as secondary when a cause is established (Fig 6). Causes of precapillary pulmonary hypertension include congenital cardiac left-to-right shunt; thromboembolic disease; tumor embolism; embolization of parasites, talc crystals, and other foreign materials; chronic alveolar hypoxia; and chronic interstitial lung disease (3,5,17). Primary pulmonary hypertension (PPH) is an idiopathic condition at the precapillary level that occurs in the absence of an embolic source or any other identifiable cause such as cardiac shunt, toxic insult, or interstitial lung disease (Fig 6) (16). Postcapillary lesions producing pulmonary venous hypertension include mediastinal fibrosis (which may also affect the precapillary vessels); an obstructive left atrial mass; mitral valve stenosis; left ventricular failure; and, rarely, invasive neoplasm, congenital venous stenosis, or anomalous pulmonary venous connections (3,17). The postcapillary counterpart to PPH is pulmonary veno-occlusive disease (PVOD), a rare idiopathic condition that diffusely affects the postcapillary pulmonary circulation (Fig 6) (16).
The vascular changes of precapillary (arterial) pulmonary hypertension include intimal cellular proliferation and medial smooth muscle hypertrophy, chiefly in the walls of muscular arteries (Figs 7, 8a, 8b) (3,4,16). Necrotizing arteritis and plexiform lesions are additional histologic features that are exclusively found in PPH and in pulmonary hypertension caused by a congenital cardiac shunt (Figs 7, 8c, 8d) (3,16). A plexiform lesion is the hallmark of sustained and irreversible pulmonary arterial hypertension and is defined as focal disruption of the internal elastic lamina of a muscular pulmonary artery by a "glomeruloid" plexus of endothelial channels, which proceed to ramify into alveolar septal capillaries (3,6,16). The complications of sustained pulmonary hypertension include central arterial thrombosis, premature atherosclerosis of central elastic and muscular pulmonary arteries, aneurysmal dissection of pulmonary arteries, and hypertrophy and dilatation of the right side of the heart (Fig 9) (4,5,18–20).
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Figure 7. Schematics demonstrate the vascular changes of pulmonary arterial hypertension. In cross-section A, medial hypertrophy produces marked thickening of the medial smooth muscle in between internal and external elastic laminae. In cross-section B, intimal proliferation thickens the intima in concentric layers. In cross-section C, a plexiform lesion is characterized by intimal proliferation and interruption of the media by a "glomeruloid" proliferation of small vascular channels.
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Figure 8a. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8b. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8c. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 8d. Microscopic features of pulmonary arterial hypertension. (a) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows medial hypertrophy of the vessel wall (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a muscular artery shows intimal proliferation (arrow). (c) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) of a plexiform lesion in a muscular artery shows intimal proliferation with aneurysmal disruption of the wall (*) by proliferative vascular channels (arrows). (d) Medium-power photomicrograph (original magnification, x10; H-E stain) of a muscular artery shows a plexiform lesion, identified by the glomeruloid proliferation (curved arrow) and dilatation (straight arrows) of vascular channels.
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Figure 9a. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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Figure 9b. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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Figure 9c. Complications of pulmonary arterial hypertension. (a) Photograph of a sagittal cut section of the right pulmonary hilum shows golden atherosclerotic plaques (arrows) and thrombosis (*) within the central arteries. (b) Photograph of an opened central pulmonary artery reveals pale tan intimal atherosclerotic plaques (arrows). Scale is in centimeters. (c) Photograph of the heart (coronal cut section) shows marked right ventricular hypertrophy (arrow), in this case accompanied by left ventricular hypertrophy (*).
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The characteristic histologic changes of postcapillary (venous) pulmonary hypertension are venous medial hypertrophy and intimal proliferation, with marked prominence of the venous internal elastic lamina (Fig 10a). Secondary changes include capillary congestion, with adjacent vascular proliferation, and interlobular septal edema and fibrosis (Figs 10a, 10b) (3,21–23). Paraseptal venous infarcts may occur adjacent to complete venous occlusion, particularly when markedly elevated pulmonary venous pressure is present (Fig 10c) (22,24,25).
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Figure 10a. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Figure 10b. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Figure 10c. Microscopic features of pulmonary venous hypertension. (a) Low-power photomicrograph (original magnification, x4; H-E stain) shows a dilated vein (*) surrounded by a collar of fibrosis within a thickened interlobular septum (arrows). (b) Medium-power photomicrograph (original magnification, x20; Movat pentachrome elastic stain) demonstrates marked capillary congestion and proliferation (arrows). (c) Low-power photomicrograph (original magnification, x4; H-E stain) shows a venous infarct (*) within the interlobular septum, secondary to pulmonary venous obstruction.
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Precapillary Pulmonary Hypertension
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Primary Pulmonary Hypertension
Clinical Characteristics, Histopathologic Features, and Treatment.—The first English description of PPH appears in the medical literature of 1909, when Sanders reported the perplexing autopsy findings of a previously healthy young man with "enormous hypertrophy and dilatation of the right ventricle" accompanied by "primary pulmonary arteriosclerosis" in the "smaller and middle-sized branches" of the lung vasculature (26). PPH remains an enigmatic condition that creates a hemodynamic pattern of elevated right atrial and mean pulmonary arterial pressures, normal pulmonary-capillary wedge pressures, and decreased cardiac output (27).
Patients with PPH present with progressive dyspnea (60% of cases), fatigue, angina, syncope, cor pulmonale, and Raynaud phenomenon (27,28). Women are affected three times as often as men, and onset is typically in youth or middle age (29). Patients with portal hypertension (with or without liver disease), collagen vascular disease, human immunodeficiency virus infection, or a history of aminorex fumarate (an appetite suppressant) ingestion have an increased risk of developing PPH, although no direct causal link has been established (3,16,22,27). Pregnant or postpartum patients and those using oral contraceptives may also be at increased risk (3). The majority of patients succumb 2–5 years following diagnosis, but prolonged survivals of up to 18 years may occur (3,27,30,31). Therapeutic agents include vasodilators, calcium channel blockers, anticoagulants, and diuretics to counteract the unfavorable hemodynamics (27,32,33). Lung or combined heartlung transplantation may be performed according to organ availability and the patient's clinical status (27).
Scientific evidence supports endothelial injury and vasoconstriction of small pulmonary arteries and arterioles as the inciting mechanisms of PPH. A relentless proliferative and obliterative response ensues throughout the pulmonary vascular bed (16,34). Humoral, genetic, exogenous toxic, and autoimmune factors have all been implicated in this fatal cascade (16). The histologic features of PPH include medial hypertrophy and intimal proliferation of small precapillary pulmonary vessels, necrotizing arteritis with segmental destruction of arterial walls, and plexiform lesions (3). Although plexiform lesions are found in approximately 75% of all cases of PPH, it is interesting to note that the simple quantitation of plexiform lesions does not directly correlate with patient survival or pulmonary artery pressures (3,16).
Acute and organizing thrombi are noted in over 50% of cases of PPH, and the role of thrombosis in both primary and secondary pulmonary arterial hypertension remains controversial (3,33). Organizing thrombi often demonstrate histologic features similar to those of plexiform lesions, but thrombi are distinguished by the presence of an intact intima and elastic laminae (3,16). When in situ recanalized thrombi of the smaller, more peripheral pulmonary arteries are identified in PPH (without coexistent plexiform lesions), the term thrombotic PPH is applied by some authors (3,16). Both clinically and histologically, it may be difficult to distinguish between secondary and in situ thrombosis of peripheral vessels in PPH, and the thromboembolic forms of secondary pulmonary hypertension discussed below (3,11,19,32).
Radiologic Features.—The definitive diagnosis of PPH is often delayed because of its insidious clinical onset and minimal early radiographic findings (Fig 11a). Advanced disease produces prominent central pulmonary arteries, sharply tapering peripheral vessels, and right ventricular enlargement (Figs 11b, 12a, 12b) (28,31). Several patterns of pulmonary vascularity are recognized in both primary and secondary pulmonary arterial hypertension, although affected vessels may be beyond radiographic resolution (31). There may be oligemia and rapidly tapering vessels or overcirculation and vascular distension (31,35,36). In patients with PPH, the right descending pulmonary artery has a mean width of 25 mm at chest radiography (37).
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Figure 11a. Progression of PPH. (a) Frontal chest radiograph of a 34-year-old man who presented with mild symptoms of dyspnea and fatigue shows minimal prominence of the main pulmonary artery. (b) On a chest radiograph obtained 10 years later, when the patient returned with severe dyspnea and elevated right ventricular pressure (120 mm Hg), marked enlargement of the main pulmonary artery and hilar vessels is seen.
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Figure 11b. Progression of PPH. (a) Frontal chest radiograph of a 34-year-old man who presented with mild symptoms of dyspnea and fatigue shows minimal prominence of the main pulmonary artery. (b) On a chest radiograph obtained 10 years later, when the patient returned with severe dyspnea and elevated right ventricular pressure (120 mm Hg), marked enlargement of the main pulmonary artery and hilar vessels is seen.
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Figure 12a. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12b. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12c. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12d. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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Figure 12e. PPH in a young adult woman. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show an enlarged pulmonary trunk and right ventricular dilatation. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates a widened pulmonary trunk. (d) Contrast-enhanced chest CT scan (mediastinal window) obtained at a lower level shows right ventricular dilatation and thickening of the free right ventricular wall (arrow). (e) Chest CT scan (lung window) shows large-caliber central pulmonary arteries (arrows) with abrupt tapering of the peripheral vessels (arrowheads).
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CT demonstrates the vascular and cardiac changes of both primary and secondary pulmonary hypertension, including right ventricular hypertrophy, enlargement of central pulmonary arteries, and abruptly diminished caliber of peripheral pulmonary vessels (Figs 12c–12e). The CT-determined diameter of the main pulmonary artery is measured in the scan plane of the bifurcation, at a right angle to its long axis and just lateral to the ascending aorta (38). A CT-determined mean pulmonary artery diameter of greater than or equal to 29 mm demonstrates 87% sensitivity and 89% specificity for predicting pulmonary hypertension. Specificity climbs to 100% when a mean pulmonary artery diameter of greater than or equal to 29 mm is accompanied by findings of a segmental artery-to-bronchus ratio greater than 1:1 in three of four pulmonary lobes (39). When the ratio of CT-determined pulmonary artery diameter to aortic diameter is greater than one (rPA > 1), a strong correlation with elevated mean pulmonary artery pressure has been shown, particularly in patients less than 50 years of age (40). On high-resolution CT scans, both primary and secondary forms of pulmonary hypertension may produce a mosaic pattern of lung attenuation, a finding suggestive of regional variations in parenchymal perfusion (41,42). A vascular cause for the mosaic pattern is suggested when areas of high attenuation contain larger caliber vessels and areas of low attenuation contain vessels of diminished size (42–45).
Radionuclide ventilation-perfusion scans in PPH are typically read as normal or low probability for pulmonary embolism (Fig 13) (43,46–48). Many secondary causes of pulmonary arterial hypertension may produce similar scintigraphic findings. One notable exception is acute or chronic thromboembolic disease, which typically produces a high-probability lung (46). Arteriography in PPH demonstrates symmetrically enlarged central arteries, a diffuse pattern of abruptly tapering and pruned subsegmental vessels, filamentous or "corkscrew" peripheral arteries, and occasionally subpleural collateral vessels (Figs 14, 15) (31,49,50).
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Figure 13. PPH in a young adult man. Lung perfusion scans (anterior view, left; posterior view, right) demonstrate multiple, bilateral subsegmental perfusion defects. Such a nonspecific pattern is also seen with many secondary causes of precapillary pulmonary hypertension.
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In general, magnetic resonance (MR) imaging of patients with pulmonary hypertension shows the characteristic anatomic changes of right ventricular hypertrophy, reversal of septal curvature, and dilatation of pulmonary arteries (51). A direct relationship between MR imaging–determined pulmonary artery diameter and the hemodynamic measure of pulmonary artery pressure has not been established. However, there is a direct linear correlation between mean pulmonary arterial pressure (PAP) and the ratio of mean pulmonary artery (MPA) caliber to descending aorta (AO) caliber (ie, MPA/AO) when measured on electrocardiographically gated spin-echo MR images (37,39,52,53). Further observations include abnormal intravascular signal corresponding to slow pulmonary arterial blood flow on gated spin-echo MR images in 92% of all cases of pulmonary arterial hypertension, notably with a direct relationship to elevated pulmonary vascular resistance (51).
Congenital Heart Disease
Clinical Characteristics, Histopathologic Features, and Treatment.—Precapillary pulmonary hypertension may develop from a sustained congenital left-to-right cardiac shunt (4). Patients with transposition of the great vessels are also predisposed to early onset of pulmonary arterial hypertension (4,5). Although some authors have contended that the severity of pulmonary hypertension varies according to patient age and location of the intracardiac defect, a recent large study based on data gathered at the National Institutes of Health has shown that pulmonary vascular changes secondary to congenital heart disease correspond only to the level of pulmonary arterial pressure (4,6). The pulmonary circulation in adult patients with congenital heart disease and secondary pulmonary hypertension has shown adaptive anastomotic pathways that connect pulmonary arterial vessels (containing plexiform lesions) to the bronchial arteries located within terminal bronchioles and the vasa vasora of pulmonary arteries (54).
In the current era of medical care, congenital cardiac lesions that may eventually cause pulmonary hypertension are now often detected and repaired at an early age, before marked vascular changes ensue (Burke AP, written communication, December 1999). In unusual cases in which severe pulmonary hypertension is suspected on the basis of clinical and hemodynamic findings, lung biopsy may be performed to determine operability and prognosis by assessing the potential reversibility of pulmonary hypertension after corrective surgery (3,15). The pathologic findings are graded on a spectrum of severity according to the Heath and Edwards system (22). Grades I and II represent mild, potentially reversible disease and are characterized by medial hypertrophy, intimal proliferation, and the abnormal muscularization of the pulmonary arterioles (5,22). The presence of intimal laminar fibrosis and progressive vessel obliteration represents grade III disease, which is considered borderline for reversibility. The more severe grades IV, V, and VI are largely irreversible and are characterized by plexiform lesions, aneurysmal muscular arteries ("dilatation lesions"), and sites of necrotizing arteritis (3,5,22).
Radiologic Features.—The radiographic features of pulmonary hypertension caused by a chronic shunt physiology include the familiar complex of a prominent pulmonary trunk and central pulmonary arteries in concert with sharply diminished peripheral pulmonary vascularity (Fig 16a, 16b) (6,55). Although the right ventricle and atrium typically enlarge in proportion to the volume overload, a normal-sized cardiac silhouette may actually reflect diminished intracardiac shunting due to a markedly elevated pulmonary vascular resistance (55). Linear calcification and thrombus may be evident in the central pulmonary arteries at CT (Fig 16c–16e) (6,55). In cases of a patent ductus arteriosus, mural calcification or aneurysmal dilatation of the ductus may be identified (6). In some cases, significant cardiac volume overload may eventually produce superimposed findings of secondary pulmonary venous hypertension (55). MR imaging may reveal enlargement of the main pulmonary artery, cardiac chamber dilatation, septal defects, right ventricular hypertrophy, and abnormal intravascular signal in the central pulmonary arteries (Fig 17) (51).
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Figure 16a. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16b. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16c. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16d. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 16e. Pulmonary arterial hypertension in a 39-year-old woman with atrial septal defect. (a, b) Posteroanterior (a) and lateral (b) radiographs of the chest show enlargement of the pulmonary trunk and hilar vessels and a prominent right ventricle. (c) Contrast-enhanced chest CT scan (mediastinal window) demonstrates marked enlargement of the central pulmonary arteries, which contain extensive thrombus and calcified atherosclerotic plaques. (d) Radiograph of the right lung specimen reveals linear calcific deposits compatible with advanced atherosclerosis of the central pulmonary arteries. (e) Low-power photomicrograph (original magnification, x4; Movat pentachrome elastic stain) of a large elastic pulmonary artery shows organizing intraluminal thrombus (*).
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Figure 17a. Pulmonary arterial hypertension secondary to long-standing ventricular septal defect (VSD). (a) Axial spin-echo T1-weighted MR image (cardiac gated) demonstrates a large VSD (*) and biventricular hypertrophy (arrows). (b) Axial spin-echo T1-weighted MR image (cardiac gated) shows dilatation of the main pulmonary artery (*) and mixed signal intensity within the bifurcation compatible with flow-related artifact (arrow).
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Figure 17b. Pulmonary arterial hypertension secondary to long-standing ventricular septal defect (VSD). (a) Axial spin-echo T1-weighted MR image (cardiac gated) demonstrates a large VSD (*) and biventricular hypertrophy (arrows). (b) Axial spin-echo T1-weighted MR image (cardiac gated) shows dilatation of the main pulmonary artery (*) and mixed signal intensity within the bifurcation compatible with flow-related artifact (arrow).
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Pulmonary Embolism
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Clinical Characteristics, Histopathologic Features, and Treatment.—Pulmonary embolism may be a complication of deep venous or pelvic vein thrombosis, right atrial neoplasia or thrombus, thrombogenic intravenous catheters, or endocarditis of the tricuspid or pulmonic valves (4,5,11,56–59). Pulmonary emboli are often multiple, bilateral, and more numerous in the right lung (11). Although acute pulmonary embolism may produce a temporary mild elevation of pulmonary arterial pressure (in 70%–80% of cases), verifiably sustained thromboembolic pulmonary hypertension is attributed to chronic, recurrent major vessel pulmonary thromboembolism (4,60). An estimated 1%–5% of patients with acute pulmonary thromboembolism go on to develop chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary infarction is a well-documented complication (61,62). CTEPH may mimic PPH clinically, making precise diagnosis difficult (35,63,64).
Patients with CTEPH may be asymptomatic for several years (the "honeymoon period") before they present with recurrent acute or progressive exertional dyspnea, chronic nonproductive cough, atypical chest pain, tachycardia, syncope, and even cor pulmonale (3–5,60–62,65). In these patients, pulmonary arterial pressure is elevated (range, 36–78 mm Hg in one series), right atrial pressures are high, cardiac output is reduced, and pulmonary capillary wedge pressures are normal (60,65). Women are affected more frequently than men, and patients with underlying malignant, cardiovascular, or pulmonary disease are at increased risk of developing this condition (3–5,60). In 11%–24% of patients, a lupus anticoagulant is present (66). One series has shown that a mean pulmonary artery pressure of 30 mm Hg corresponds to 5-year survival in only 30% of patients with CTEPH (60).
The treatment of choice is surgical thromboendarterectomy (operative mortality, 7%–40%) (3, 60,61). Surgical accessibility must be established preoperatively to ensure that the organized thrombi are not located beyond the margin of a safe dissection plane for endarterectomy, namely distal to the lobar arteries or to the origin of the segmental vessels (66). Radiologic imaging, most often conventional pulmonary angiography ("the gold standard"), is used to assess the presence and extent of disease (66,67). Contrast-enhanced helical CT is an excellent, noninvasive modality with which to demonstrate emboli in the central pulmonary vessels and segmental arterial branches (see discussion below) (67). Nevertheless, in cases in which imaging is limited, direct inspection of vessels may be achieved with a fiberoptic angioscope to visualize the intimal surface configuration of pulmonary arteries (66,67). Operative risk assessment for pulmonary thromboendarterectomy also weighs comorbid conditions (such as coronary artery disease and parenchymal lung disease) and the patient's status of cardiac, hemodynamic, and ventilatory compromise (66). Supplemental warfarin anticoagulation therapy is also indicated, in some cases combined with vasodilators, to treat the more peripheral thrombotic occlusions that are beyond the segmental arteries and not amenable to surgical resection (60,61).
At gross inspection, the main pulmonary arteries and their branches contain fibrous webs and bands corresponding to organized thromboemboli, often with overlying recent thrombosis (4,5). Marked right ventricular hypertrophy is typical (4). At histologic examination, various stages of organized and recanalized thromboemboli in both the elastic and muscular arteries are confirmed (Fig 18) (3–5). "Organization" of a thrombus implies its transition to a vascularized lesion of connective tissue that adheres to the vessel wall (11). The "recanalization" of an organized clot implies the presence of a vascular channel network that may reduce the "organized" portion to septations of collagen and elastic fibers, often lined by endothelium (4,11). In response to elevations in pulmonary pressure produced by CTEPH, the patent pulmonary arterial vessels develop medial hypertrophy, intimal thickening, and atherosclerotic plaques compatible with hypertensive changes (4,60). In accordance with our understanding of the bronchial circulation, the bronchial arteries in CTEPH may dilate and form extensive collateral pathways to minimize a
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Abstract
Introduction
