The structure of the parietal pleura and its relationship to pleural liquid dynamics in sheep

We studied the parietal pleura of six sheep to obtain information on pleura structure, blood supply, and lymphatic drainage. In the strict sense, the parietal pleura is composed of a single layer of mesothelial cells and a uniform layer of loose, irregular connective tissue (about 23 μm in width) subjacent to the mesothelial cells. The parietal pleural blood vessels are 10–15 μm from the pleural space. Tracer substances put in the pleural space are removed at specific locations. Colloidal carbon and chick red blood cells are cleared by teh parietal pleural lymphatics located over the intercostal spaces at the caudal end of the thoracic wall and over the lateral sides of the pericardial sac. In these areas the mesothelial cells have specialized openings, the stomata, that directly communicate with the underlying lymphatic lacunae. Cells and particulate matter in the pleural space are cleared only by the parietal pleural lymphatics. Compared to the visceral pleura, we believe the thinness of the parietal pleura, the closeness of its blood vessels to the pleural space, and its specialized lymphatic clearance pathways, together indicate that the parietal pleura plays a major role in pleural liquid and protein dynamics in sheep.     

Lymphatic drainage of the diaphragmatic pleura to the peritracheobronchial lymph nodes

Non-small cell lung cancer invading the visceral pleura is characterized by a particular richness of mediastinal lymph node (LN) metastases. This may be due to subpleural lymphatic drainage of tumor cells. The aim of this study was to determine mediastinal LN lymphatic drainage from the diaphragmatic pleura. Subpleural lymphatics of 30 adult cadavers and 12 fetuses were injected with a modified Gerota's medium to permit lymph vessels and nodes to be visualized and then dissected. Each stage of the dissection was described and photographed. In 32 cadavers mediastinal visceral LN chains were injected, of which 29 originated from the mediolateral portion of the diaphragm. On the right, injections (n=16) demonstrated lymph vessels (n=20) ascending directly along the inferior pulmonary ligaments (n=8) or after having encircled the inferior vena cava (n=8), and lymph vessels passing between the pulmonary veins (n=4); all these lymphatics were connected to the intertracheobronchial nodes and some ascended along the tracheobronchial LN chains in the upper mediastinum. On the left, injections (n=13) demonstrated lymph vessels (n=16) ascending along the inferior pulmonary ligament (n=5) or along the esophagus (n=11) and connecting to the intertracheobronchial nodes, some of which ascended further in the upper mediastinum (left paratracheobronchial LN chain). These mediastinal LN chains are the same as those that receive lymph from the pulmonary segments. Lymphatic drainage of the diaphragmatic pleura may add to that of the lung involved in cancer and potentially increases lymphatic spread of tumor cells.     

The yellow nail syndrome. Light and electron microscopic aspects of the pleura

The yellow nail syndrome is a rare cause of recurrent pleural effusions. We studied a case of this entity, placing special emphasis on the microscopic and ultrastructural aspects of the pleural lymphatics. The patient had the classic symptoms of recurrent bilateral pleural effusions, yellow, dystrophic fingernails and toenails, and lower-limb edema. To control the pleural effusions, a left parietal pleurectomy was performed. Histologic study showed both pleura to be thickened with fibrosis and chronic inflammatory infiltration. The lymphatic capillaries in the visceral pleura were dilated. Electron microscopy confirmed the lymphatic nature of these capillaries. We believe that these ectatic lymphatic capillaries suggest a downstream obstruction to the lymph drainage.     

Morphometric analysis of intralobular, interlobular and pleural lymphatics in normal human lung

In spite of their presumed relevance in maintaining interalveolar septal fluid homeostasis, the knowledge of the anatomy of human lung lymphatics is still incomplete. The recent discovery of reliable markers specific for lymphatic endothelium has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule in association with bronchioles, intralobular arterioles or small pulmonary veins. The aim of this study was to provide a morphometric characterization of lymphatic vessels in the periphery of the human lung. Human lung sections were immunolabelled with the lymphatic marker D2-40, followed by blood vessel staining with von Willebrand Factor. Lymphatic vessels were classified into: intralobular (including those associated with bronchovascular bundles, perivascular, peribronchiolar and interalveolar), pleural (in the connective tissue of the visceral pleura), and interlobular (in interlobular septa). The percentage area occupied by the lymphatic lumen was much greater in the interlobular septa and in the subpleural space than in the lobule. Most of the intralobular lymphatic vessels were in close contact with a blood vessel, either alone or within a bronchovascular bundle, whereas 7% were associated with a bronchiole and < 1% were not connected to blood vessels or bronchioles (interalveolar). Intralobular lymphatic size progressively decreased from bronchovascular through to peribronchiolar, perivascular and interalveolar lymphatics. Lymphatics associated with bronchovascular bundles had similar morphometric characteristics to pleural and interlobular lymphatics. Shape factors were similar across lymphatic populations, except that peribronchiolar lymphatics had a marginally increased roundness and circularity, suggesting a more regular shape due to increased filling, and interlobular lymphatics had greater elongation, due to a greater proportion of conducting lymphatics cut longitudinally. Unsupervised cluster analysis confirmed a marked heterogeneity of lymphatic vessels both within and between groups, with a cluster of smaller vessels specifically represented in perivascular and interalveolar lymphatics within the alveolar interstitium. Our data indicate that intralobular lymphatics are a heterogeneous population, including vessels surrounding the bronchovascular bundle analogous to the conducting vessels present in the pleural and interlobular septa, many small perivascular lymphatics responsible for maintaining fluid balance in the alveolar interstitium, and a minority of intermediate lymphatics draining the peripheral airways. These lymphatic populations could be differentially involved in the pathogenesis of diseases preferentially involving distinct lung compartments.     

Vagal nerve endings in visceral pleura and triangular ligaments of the rat lung

The inner thoracic cavity is lined by the parietal pleura, and the lung lobes are covered by the visceral pleura. The parietal and visceral plurae form the pleural cavity that has negative pressure within to enable normal respiration. The lung tissues are bilaterally innervated by vagal and spinal nerves, including sensory and motor components. This complicated innervation pattern has made it difficult to discern the vagal vs. spinal processes in the pulmonary visceral pleura. With and without vagotomy, we identified vagal nerve fibres and endings distributed extensively in the visceral pleura (‘P’‐type nerve endings) and triangular ligaments (‘L’‐type nerve endings) by injecting wheat germ agglutinin‐horseradish peroxidase as a tracer into the nucleus of solitary tract or nodose ganglion of male Sprague–Dawley rats. We found the hilar and non‐hilar vagal pulmonary pleural innervation pathways. In the hilar pathway, vagal sub‐branches enter the hilum and follow the pleural sheet to give off the terminal arborizations. In the non‐hilar pathway, vagal sub‐branches run caudally along the oesophagus and either directly enter the ventral‐middle‐mediastinal left lobe or follow the triangular ligaments to enter the left and inferior lobe. Both vagi innervate: (i) the superior, middle and accessory lobes on the ventral surfaces that face the heart; (ii) the dorsal‐rostral superior lobe; (iii) the dorsal‐caudal left lobe; and (iv) the left triangular ligament. Innervated only by the left vagus is: (i) the ventral‐rostral and dorsal‐rostral left lobe via the hilar pathway; (ii) the ventral‐middle‐mediastinal left lobe and the dorsal accessory lobe that face the left lobe via the non‐hilar pathway; and (iii) the ventral‐rostral inferior lobe that faces the heart. Innervated only by the right vagus, via the non‐hilar pathway, is: (i) the inferior (ventral and dorsal) and left (ventral only) lobe in the area near the triangular ligament; (ii) the dorsal‐middle‐mediastinal left lobe; and (iii) the right triangular ligament. Other regions innervated with unknown vagal pathways include: (i) the middle lobe that faces the superior and inferior lobe; (ii) the rostral‐mediastinal inferior lobe that faces the middle lobe; and (iii) the ventral accessory lobe that faces the diaphragm. Our study demonstrated that most areas that face the dorsal thoracic cavity have no vagal innervation, whereas the interlobar and heart‐facing areas are bilaterally or unilaterally innervated with a left‐rostral vs. right‐caudal lateralized innervation pattern. This innervation pattern may account for the fact that the respiratory regulation in rats has a lateralized right‐side dominant pattern.     

Ultrastructural study of pleural lymphatic drainage unit and effect of nitric oxide on the drainage capacity of pleural lymphatic stomata in the rat.

The objective of this study was twofold: first to investigate the ultrastructure of the lymphatic drainage unit on the costal pleura of rats by electron microscopy, and secondly to examine the effect of nitric oxide on the pleural lymphatic stomata and fluid absorption from the pleural cavity. The lymphatic drainage unit of the rat costal pleura is composed of three special components: the lymphatic stomata between the mesothelial cells, the initial part of the lymphatic vessels and the underlying connective tissue containing many foramina. The unit is the main passage to drainage fluid, particles and cells in the pleural space. To investigate the regulator of the lymph drainage, nitric oxide synthase inhibitor and nitric oxide donor were injected into the peritoneal cavity of the rats, respectively. Trypan blue was used as tracer. The ultrastructural changes of pleural lymphatic stomata were observed under scanning electron microscope and analyzed by a computer image processing system. It turned out that the area and density of the pleural lymphatic stomata were positively correlated with the nitric oxide quantity (p < 0.05). After the tracer was injected into the pleural cavity, the nitric oxide donor group exhibited a higher trypan blue concentration than the control group (p < 0.05). The ability of the pleura to absorb trypan blue was enhanced because of the larger opening of the lymphatic stomata (p < 0.05). It is suggested that nitric oxide can increase lymphatic absorption of the pleura by opening pleural lymphatic stomata.     

New method for evaluation of lung lymph flow rate with intact lymphatics in anaesthetized sheep

Aim: Lung lymph has commonly been studied using a lymph fistula created by tube cannulation into the efferent duct of the caudal mediastinal node in sheep. In this method, the tail region of the caudal mediastinal node is resected and the diaphragm is cauterized to exclude systemic lymph contamination, and cannulation is performed into one of the multiple efferent ducts originating from the caudal mediastinal node. Moreover, the pumping activity of lymphatics might be diminished by cannulation. Therefore, the purpose of the study was to evaluate the flow rate of lung lymph with maintenance of intact lymphatic networks around the caudal mediastinal node to the thoracic duct in sheep. Methods: An ultrasound transit‐time flow meter was used to measure lung lymph flow. The thoracic duct was clamped just above the diaphragm and the flow probe was attached to the thoracic duct just after the last junction with an efferent duct from the caudal mediastinal node. The lung lymph flow rate was measured at baseline and under conditions of lung‐oedema formation. Results: The baseline lung lymph flow rate in our model was three‐ to sixfold greater than values obtained with the cannulation method. With oedema‐formation, the lung lymph flow rate was the same as that measured using cannulation. Conclusion: The lung lymph flow was unexpectedly large under the conditions of the study, and our data suggest that the drainage effect of lymphatics is significant as a safety factor against pulmonary oedema formation.     

Pulmonary lymphatics are primary sites of Mycobacterium tuberculosis infection in guinea pigs infected by aerosol

Mycobacterium tuberculosis causes a lymphatic vasculitis in the lungs of guinea pigs infected by a low-dose aerosol. This observation suggests that in addition to being a direct conduit from the lungs to the regional lymph nodes, pulmonary lymphatics are themselves sites of infection and could be the site of latent infection.     

Forms of lung lymphatics: a scanning electron microscopic study of casts.

In a recent study, rats given monocrotaline underwent angiogenesis on their pleural surfaces. The rats also had novel structures in their bronchovascular bundles that were detected by scanning electron microscopy of vascular casts. These vessels could have been either new blood capillaries or dilated lymphatic capillaries. To determine if these structures were lymphatics or new blood vessels, specimens from animals that were undergoing angiogenesis were compared to those that were not. Finding similar structures in normal animals would imply that they were lymphatic. The second purpose of this work was to describe the three-dimensional anatomy of the lymphatics of the lung. Cast lymphatics were found in most lungs with edema or angiogenesis, but were rare in other conditions. The vascular structures in question were found in animals not undergoing angiogenesis and were, therefore, lymphatic. Additionally, scanning electron microscopy of casts showed several distinct forms of lymphatics in the lung. Prelymphatics are tissues planes beneath the pleura and around bronchovascular structures. They join reservoir, conduit or tubulo-saccular lymphatics. Reservoir lymphatics are broad ribbon-like structures with textured surfaces and small laterally branching pouches. They occur on the pleural surface, are closely linked with prelymphatics, and join conduit lymphatics. Conduit lymphatics are tubular structures that may contain valves, twist and go great distances without accepting tributaries. On the pleural surface, they may wind around blood vessels and vary greatly in diameter. Sacculo-tubular lymphatics surround arteries, veins and bronchioles. They have thin walls with wide saccular segments. They may be so dense that they form cylinders around the vessels or airways. Different forms of lung lymphatics suggest different function and potential.     

Lymphatic drainage of heart and lungs comparison between pig and man

In its anatomy and physiology the pig is comparable with humans and its organs can be considered for xenotransplantation. We have studied the lymphatic drainage of the heart and lungs in 15 pigs. A coloured mass was injected into the myocardium and/or beneath the visceral pleura. The first nodes coloured were directly injected again. No lymph node was observed inside the heart and lungs. The first lymph nodes coloured were the peritracheobronchial nodes. There was no node in front of the thoracic trachea (Barety’s compartment in man). Left suprabronchial nodes were connected with the thoracic duct in the mediastinum. The lymphatics of the heart and lungs in the pig are similar to those of human. Phylogenesis explains “skipping” metastases and the significance of N1 disease in lung cancer, as well as chylothorax occurring after heart and lung surgery.     

Na+-glucose cotransporter is also expressed in mesothelium of species with thick visceral pleura

Molecular evidence for Na+-glucose cotransporter (SGLT1) in rabbit pleural mesothelium has been recently provided, confirming earlier functional findings on solute-coupled liquid absorption from rabbit pleural space. In this research we checked whether SGLT1 is also expressed in pleural mesothelium of species with thick visceral pleura, which receives blood from systemic circulation, but drains it into pulmonary veins. To this end immunoblot assays were performed on total protein extract of scraped visceral and parietal mesothelium of lambs and adult sheep, and of a human mesothelial cell line. All of them showed SGLT1 specific bands. Moreover, confocal immunofluorescence images of lamb pleural mesothelium showed that SGLT1 is located in apical membrane. Therefore, a solute-coupled liquid absorption should also occur from pleural space of species with thick visceral pleura. Because of this protein-free liquid entering interstitium between visceral mesothelium and capillaries, inherent Starling forces should be different than hitherto considered, and visceral pleura capillaries could absorb liquid even in these species.     

Regional lymph drainage routes from the diaphragm in the rat

Absorption from the peritoneal cavity by lymphatics of the diaphragm is of considerable surgical importance. The pattern of lymphatic drainage from the diaphragm of the rat, used as an experimental model, was studied following intraperitoneal injection of diluted India ink. Peritoneal absorption of ink was remarkably rapid. Within 1 minute, subperitoneal lymphatic lacunae filled with ink. The lacunae ran radially between muscular fibers of the diaphragm and were confined only to the muscular part of the diaphragm. The regional lymph drainage from the diaphragm was predominantly to the mediastinal lymph nodes (parathymic and posterior mediastinal nodes) by way of the retrosternal and intercosto-paravertebral lymph trunks, and also to retroperitoneal lymph nodes (cisternal and renal nodes) by the retroperitoneal lymphatic trunks. These data indicate that the cranial drainage of lymph from the peritoneal cavity, mainly by way of the retrosternal lymphatic trunks, predominates over the caudal drainage route and thoracic duct; the intercosto-paravertebral, mediastinal, and retroperitoneal lymphatic channels are only secondary pathways. Knowledge of these lymphatic routes may prove valuable clinically in peritoneal dialysis and in the prediction of the spread of the animal's own cells (e.g., lymphocytes and macrophages), of tumor cells and of bacteria from the peritoneal cavity. © 1994 Wiley-Liss, Inc.     

Pleural liquid and its exchanges

After an account on morphological features of visceral and parietal pleura, mechanical coupling between lung and chest wall is outlined. Volume of pleural liquid is considered along with its thickness in various regions, and its composition. Pleural liquid pressure (P_liq) and pressure exerted by lung recoil in various species and postures are then compared, and the vertical gradient of P_liq considered. Implications of lower P_liq in the lung zone than in the costo-phrenic sinus at iso-height are pointed out. Mesothelial permeability to H₂O, Cl⁻, Na⁺, mannitol, sucrose, inulin, albumin, and various size dextrans is provided, along with paracellular “pore” radius of mesothelium. Pleural liquid is produced by filtration from parietal pleura capillaries according to Starling forces. It is removed by absorption in visceral pleura capillaries according to Starling forces (at least in some species), lymphatic drainage through stomata of parietal mesothelium (essential to remove cells, particles, and large macromolecules), solute-coupled liquid absorption, and transcytosis through mesothelium.     

Forms of lung lymphatics: A scanning electron microscopic study of casts

In a recent study, rats given monocrotaline underwent angiogenesis on their pleural surfaces. The rats also had novel structures in their bronchovascular bundles that were detected by scanning electron microscopy of vascular casts. These vessels could have been either new blood capillaries or dilated lymphatic capillaries. To determine if these structures were lymphatics or new blood vessels, specimens from animals that were undergoing angiogenesis were compared to those that were not. Finding similar structures in normal animals would imply that they were lymphatic. The second purpose of this work was to describe the three-dimensional anatomy of the lymphatics of the lung. Cast lymphatics were found in most lungs with edema or angiogenesis, but were rare in other conditions. The vascular structures in question were found in animals not undergoing angiogenesis and were, therefore, lymphatic. Additionally, scanning electron angiogenesis and were, therefore, lymphatic. Additionally, scanning electron microscopy of casts showed several distinct forms of lymphatics in the lung. Prelymphatics are tissues planes beneath the pleura and around bronchovascular structures. They join reservoir, conduit or tubulo-saccular lymphatics. Reservoir lymphatics are broad ribbon-like structures with textured surfaces and small laterally branching pouches. They occur on the pleural surface, are closely linked with prelymphatics, and join conduit lymphatics. Conduit lymphatics are tubular structures that may contain valves, twist and go great distances without accepting tributaries. On the pleural surface, they may wind around blood vessels and vary greatly in diamater. Sacculo-tubular lymphatics surround arteries, veins and bronchioles. They have thin walls with wide saccular segments. They may be so dense that they form cylinders around the vessels or airways. Different forms of lung lymphatics suggest different function and potential. © 1992 Wiley-Liss, Inc.     

狗腹腔器官淋巴系的研究

用１０％普鲁士蓝溶液做淋巴管间接注射法，观察了１６只成狗腹腔器官的淋巴系。结果表明；肝淋巴管全由肝门走出，注入肝总淋巴结，少部分注入肝右淋巴结或胰十二指肠淋巴结。     

Blood supply of the caudal mediastinal lymph node in sheep

We investigated the arterial supply to, and the venous drainage from, the caudal mediastinal lymph node (CMN) in 18 anesthetized and exsanguinated sheep. The purpose of this gross anatomic investigation was to determine the CMN's blood supply so that a structural base can be used to interpret studies of the bronchial circulation's role in the pathogenesis of pulmonary edema. In ten sheep, we cannulated the bronchoesophageal artery at its origin from the aorta and injected Microfil. This artery, which branches into cranial and caudal divisions 2-4 mm distal to its origin, supplied the esophagus, trachea, bronchi, and visceral pleura. The CMN is supplied by the caudal division, as it courses between the CMN and aorta. Microfil injected through the thoracic aorta did not enter the CMN when the bronchoesophageal artery was ligated at its origin. These results indicate that only the bronchoesophageal artery supplies the CMN. In eight sheep we cannulated the vein at the head of the CMN (dorsal mediastinal vein) and injected Microfil, both peripherally and centrally. Peripherally, injected veins reached the CMN and esophagus. The dorsal mediastinal vein extended posteriorly to the CMN in three of the eight sheep, eventually emptying into the left azygos vein near the diaphragm. Centrally, the dorsal mediastinal vein joined the left azygos vein near the heart in six of the eight sheep, including the three in which the dorsal mediastinal vein extended posteriorly to the CMN. In the remaining two sheep the dorsal mediastinal vein drained centrally into the right azygos vein. We conclude that the bronchoesophageal artery supplies the CMN and that either the left or right azygos vein drains it.     

Imaging the hepatic lymphatics: experimental studies in swine.

Magnetic resonance (MR) imaging augmented with 3-D MR reconstruction provides an excellent display of the soft tissues and surface anatomy of the human body. The excellent anatomical detail of MR images makes this radiographic modality an ideal tool to teach anatomy to all health-care professionals. Previous studies of the lung and liver in swine revealed that the hepatic lymphatics communicated with the visceral pleural lymphatics via the so-called pulmonary ligament, which appears as a sheet of visceral pleura containing lymphatics and small blood vessels in the swine model. A review of the surgical operative reports at the UCLA School of Medicine revealed that the hepatic lymphatics are not connected or even ligated during hepatic resections and transplantations. Therefore, the authors hypothesized that the unattached lymphatics may be a cause of postoperative complications and that interruption of these important lymphatic pathways may specifically result in immediate ascites and right pleural effusions. Cannulation of the hepatic lymphatics is proposed as a method to reduce postoperative complications. The purpose of this research is to demonstrate the visual and radiographic display of the hepatic lymphatics in a swine model and to provide a means to teach anatomical-pathological correlation.     

Structure and distribution of the lymphatic vessels in the parietal pleura of the monkey as studied by enzyme-histochemistry and by light and electron microscopy.

The entire distribution of lymphatics in whole mount preparations of the Japanese monkey was studied using the enzyme-histochemical technique reported by KATO et al. (1990, 1991). In this staining, the lymphatic endothelium was colored dark brown by its positive 5'-nucleotidase activity, while most blood vessels (especially arterioles) were colored blue due to their positive alkaline phosphatase reaction. The whole mount preparations of the pleura treated enzyme-histochemically clearly indicated the distribution, branching patterns and running courses of lymphatic vessels. They revealed numerous short blind-ending knobs which represented the initial portions of lymphatics. These knobs were seen near the surface of the parietal pleura along its entire extent. In the costal and diaphragmatic pleura, the lymphatics ran parallel to the intercostal muscle fibers, but perpendicular to the tendinous and muscular fibers of the diaphragm; they formed ladders, independent of the courses of blood vessels. In the mediastinal pleura, lymphatic vessels showed a tree-like branching accompanying blood vessels. Under the light microscope, toluidine-blue stained semithin sections revealed the initial part of lymphatics as a small irregularly outlined cavity (7-10 microns in diameter) surrounded by a dense connective tissue. This lymphatic dilation was sometimes located close to a thin mesothelial layer. Such a structure suggesting a "stoma" was seen near the attachment of the muscular diaphragm to the sternum and along the borders of the ribs. Transmission electron microscopy revealed an occasional interruption in the mesothelium. This stoma continued to a submesothelial cavity whose base comprised an attenuated endothelium of an extended lymphatic vessel.     

Visceral pleural lipoma: description of a autopsy case]

Pleural lipomas are rare tumours, usually arising from the parietal pleura, which are often asymptomatic and observed incidentally. We describe the clinicopathological features of a case of lipoma arising from the visceral pleura, accidentally discovered in a 69-year-old ma, at autopsy. A review of the literature concerning pleural lipomas is also presented.     

Pulmonary lymphatic filling is increased in spontaneously hypertensive rats

Extravascular lung liquid must rely on tissue-space pressure gradients to drive it into the lymphatics because the fluid is outside the lymphatic contractile pumping and valve control. Focal tissue pressure changes could result from muscular contraction in the blood vessel walls. Perivascular lymphatics usually lie within the adventitia of pulmonary blood vessels, and are generally more noticeable in veins than arteries. Spontaneously hypertensive rats have exaggerated focal pulmonary venous muscle (venous sphincters). These muscular tufts are often near initial lymphatics; if their contraction was important for lymph transport, spontaneously hypertensive rats could have more lymphatic filling in the areas of the pulmonary venous sphincters than normotensive rats. Because the focal muscularity is found in pulmonary veins more than arteries, veins may have more focal lymphatic filling than arteries. To test these hypotheses, lung histology and vascular and lymphatic casts of spontaneously hypertensive and normotensive rats were examined. Contracted venous sphincters were found on 108 of 127 veins with lymphatics in the spontaneously hypertensive rats and 5 of 41 in the normotensive rats P<0.01). The spontaneously hypertensive rats had deeper venous contractions and more lymphatic filling around both arteries and veins (P<0.01). In the hypertensive rats, the venous was greater than the arterial lymphatic filling (P<0.01). On the pleural surface, hypertensive rats also had greater lymphatic filling than controls (P<0.01). This anatomic evidence suggests that pulmonary venous sphincters are associated with focal lymphatic filling, and perivascular muscle action might be a component of the pulmonary lymphatic system.