Sách về các bệnh liên quan đến phổi

Một cuốn sách hay của tác giả Wright viết về các bệnh liên quan đến phổi. Sách gồm 30 chương từ giải phẩu phổi cho đến các bệnh liên quan đến lồng ngực, màng phổi, phổi, phế quản, khí quản ... Một cuốn sách gối đầu giường của các sinh viên khoa Y nước ngoài, đã xuất bản đến phiên bản lần thứ năm. Rất đáng tham khảo dành cho sinh viên Y Việt Nam

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Authors: Light, Richard W.

Title: Pleural Diseases, 5th Edition

> Front of Book > Authors

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> Front of Book > Dedication

Dedication

This book is dedicated to my many friends throughout the worldwho have collaborated with me in studying pleural disease

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> Front of Book > Preface

Preface

The first four editions of Pleural Diseases were well received.Since the fourth edition was published in 2001, there has been arapid advancement of knowledge concerning pleural diseases.Accordingly, the publishers have requested that I prepare a fifthedition

As I prepared the fifth edition, I was impressed with how muchnew information concerning pleural diseases has become knownduring the past 5 years New references have been added for

nearly every disease of the pleura discussed in the book

Highlights of the changes since the previous edition include thefollowing:

Three new chapters have been added to this edition First, there

is a chapter on the physiological effects of a pneumothorax or apleural effusion Included in this chapter are discussions of theeffects of pneumothorax or pleural effusion on pulmonary

function, blood gases, and exercise capacity The second newchapter is on animal models in pleural investigation This newchapter was included to aid the pleural researcher who is

interested in animal models to be used for research The cliniciancan also learn much from the information gleaned from animalmodels on pleural inflammation, pleurodesis, pleural infection,and pleural neoplasms The third new chapter is on cytokines andthe pleura Although measurement of pleural fluid levels of

cytokines has proved disappointing in the differential diagnosis of

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pleural effusions, cytokines are intimately involved in the variouspathologic processes that involve the pleura and their

involvement is discussed in this chapter

There are also significant updates in the diagnosis of pleural

effusions The use of the protein gradient (rather than the

albumin gradient) in identifying transudates that meet Light'sexudative criteria is discussed as is the use of pleural fluid levels

of brain natriuretic peptide in identifying pleural effusions due tocongestive heart failure The newly proposed serum tests for

mesothelioma (mesothelin family proteins and osteopontin) arediscussed as is the use of polymerase chain reaction (PCR) in thediagnosis of parapneumonic effusion The use of needle biopsy ofthe pleura has been de-emphasized whereas the use of

thoracoscopy has now assumed a larger role in the diagnosis ofpleural effusions

In the therapy of pleural effusions also there have been advances.For malignant pleural effusions, the use of indwelling pleural

catheters with the intermittent application of negative pressure isdiscussed in detail For mesothelioma, the advances in

chemotherapy with pemetrexed or raltitrexed are discussed withthe caveat that they are very expensive and do not prolong

survival for very long The use of fibrinolytics in the management

of parapneumonic effusions has a less prominent role

It is my hope that the fifth edition of this book will continue toprovide a practical, updated reference book for physicians whotake care of patients with pleural disease

Richard W Light MDNashville, Tennessee

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> Front of Book > Preface to the First Edition

Preface to the First Edition

Approximately one million patients develop a pleural effusion

each year Pleural effusions may occur with many different

infections or as a complication of pulmonary disease Additionally,pleural effusions frequently complicate malignant disease, heartdisease, liver disease, gastrointestinal disease, kidney disease,and collagen vascular disease Yet there are no recent books onpleural disease to guide the practicing physician in determiningthe origin of a pleural effusion or in managing a patient with

pleural disease Moreover, diseases of the pleura receive onlysuperficial treatment in books on pulmonary disease or internalmedicine

This book is intended primarily as a reference book for physicianswho take care of patients with pleural diseases Recent advances

in the knowledge of pleural disease make publication of this

volume timely In this one volume, the practicing physician willhave a comprehensive discussion of all aspects of pleural disease.The first three chapters discuss the anatomy, physiology, andradiology of the pleura The next chapter describes the clinicalmanifestations of pleural disease and discusses in depth the

various diagnostic tests that might be used to establish the

etiology of a pleural effusion In Chapter 5, I present my

recommended approach to the patient with an undiagnosed

pleural effusion The following 13 chapters contain discussions ofthe various disease states that can be associated with a pleural

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effusion For each disease, the pathophysiology, clinical

manifestations, diagnosis, and management of pleural effusionare outlined In Chapters 19 through 21, pneumothorax,

hemothorax, and chylothorax are presented, respectively Pleuralthickening not associated with pleural fluid is covered in Chapter

2 2 The next two chapters are devoted to those procedures usedmost often in managing patients with pleural disease, namely,diagnostic and therapeutic thoracentesis, pleural biopsy, and tubethoracostomy The final chapter includes a description of the

various drainage systems used with chest tubes

It is my hope that publication of this book will result in better andmore cost-effective management of patients with pleural disease

Richard W Light MD

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> Front of Book > Acknowledgments

Acknowledgments

Many individuals contributed to this book I would like to

acknowledge my wife Judi Light who carefully read every chapterand constantly encouraged me to proceed with the book I wouldlike to acknowledge the many hours devoted to reviewing the

content of the book by Drs Huai Liao, KejingTang, Alaa Elgazzar,Mehran Zarifi, and Moon Jun Na and Mr Randal Barnette I wouldlike to acknowledge my administrative assistant Ms Bonnie

Cathey who spent hours gathering new references and AndrianaDevois who redrew the flow diagrams I would like to acknowledge

Dr Robert C Gilkeson who provided new radiographs for this

edition of the book Lastly, I thank Nancy Winter, Managing Editor

at Lippincott Williams & Wilkins and Jenny Koleth, Freelance

Editor at Cyrus-XP LLC, for their constant support while the bookwas being prepared

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Chapter 10 - Pleural Effusions Related to Metastatic Malignancies

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Chapter 20 - Pleural Disease in Obstetrics and Gynecology

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> Table of Contents > Chapter 1 - Anatomy of the Pleura

Chapter 1

Anatomy of the Pleura

The pleura is the serous membrane that covers the lung

parenchyma, the mediastinum, the diaphragm, and the rib cage.This structure is divided into the visceral pleura and the parietalpleura The visceral pleura covers the lung parenchyma, not only atits points of contact with the chest wall, diaphragm, and

mediastinum but also in the inter-lobar fissures The parietal pleuralines the inside of the thoracic cavities In accordance with the

intrathoracic surfaces that it lines, it is subdivided into the costal,mediastinal, and diaphragmatic parietal pleura The visceral and theparietal pleura meet at the lung root At the pulmonary hilus, themediastinal pleura is swept laterally onto the root of the lung

Posterior to the lung root, the pleura is carried downward as a thindouble fold called the pulmonary ligament.

A film of fluid (pleural fluid) is normally present between the

parietal and the visceral pleura This thin layer of fluid acts as alubricant and allows the visceral pleura covering the lung to slidealong the parietal pleura lining the thoracic cavity during respiratorymovements The space, or potential space, between the two layers

of pleura is designated as the pleural space The mediastinum

completely separates the right pleural space from the left in

humans As previously mentioned, only a thin layer of fluid is

normally present in this space, so it is a potential space rather than

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an actual one Many diseases are associated with increased amounts

of pleural fluid, however, and a large segment of this book is

directed toward an understanding of these diseases

Embryology of the Pleura and Pleural

S p a c e

The body cavity in the embryo, the coelomic cavity, is a U-shapedsystem with the thick bend cephalad The cephalad portion becomesthe pericardium and communicates bilaterally with the pleural

canals, which, in turn, communicate with the peritoneal canals Withdevelopment, the coelomic cavity becomes divided into the

pericardium, the pleural cavities, and the peritoneal cavity throughthe development of three sets of partitions: (a) the septum

transversum, which serves as an early, partial diaphragm; (b) thepleuropericardial membranes, which divide the pericardial and

pleural cavities; and (c) the pleuroperitoneal membranes, whichunite with the septum transversum to complete the partition

between each pleural cavity and the peritoneal cavity This newlyformed pleural cavity is fully lined by a mesothelial membrane, thepleura (1)

When the primordial bronchial buds first appear, they and the

trachea lie in a median mass of mesenchyme, cranial and dorsal tothe peritoneal cavity This mass of mesenchymal tissue is the futuremediastinum, and it separates the two pleural cavities In humans,

no communication normally exists between the two pleural cavities

As the growing primordial lung buds bulge into the right and leftpleural cavities, they carry with them a covering of the lining

mesothelium, which becomes the visceral pleura As the separatelobes evolve, they retain their mesothelial covering This coveringbecomes the visceral pleura in the fissures The lining mesothelium

of the pleural cavity becomes the parietal pleura (2)

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Histology of the Pleura

The parietal pleura over the ribs and intercostal spaces is composed

of loose, irregular connective tissue covered by a single layer of

mesothelial cells Within the pleura are blood vessels, mainly

capillaries, and lymphatic lacunas The lacunas are specialized initiallymphatics shaped like flat cisterns and are located over the

intercostal spaces, at least in sheep (3) The mean thickness of theparietal pleura in sheep is 20 to 25 Âµm, whereas the distance fromthe microvessels to the pleural space is 10 to 12 Âµm Deeper to theparietal pleura is the endothoracic fascia This continuous band ofdense irregular

thickness Dogs, cats, and monkeys have a thin visceral pleura,

whereas humans, sheep, cows, pigs, and horses have a thick visceralpleura (4) The distinction between lungs with a thick or thin

visceral pleura is important physiologically because the blood supply

is dependent on the thickness of the pleura In animals with a thickvisceral pleura, the predominant source of blood is the systemic

circulation; in those with a thin pleura, the predominant source ofblood is the pulmonary circulation (4)

Histologically, a thick visceral pleura is composed of two layers: themesothelium and connective tissue Blood, lymph vessels and nervesare located in the connective tissue Animals with a thick visceralpleura have a layer of dense connective tissue of varying thicknessinterposed between the mesothelium and the blood vessels (4) Insheep, the visceral pleura ranges in thickness from 25 to 83 Âµm

(as compared with 10â€“25 Âµm for the parietal pleura) and the

distance from the microvessels to the pleural space ranges from 18

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to 56 Âµm (as compared with 10â€“12 Âµm for the parietal space)(3)

The connective tissue layer in the visceral pleura has two importantfunctions: (a) it contributes to the elastic recoil of the lung, which isimportant in expelling air from the lung, and (b) it restricts the

volume to which the lung can be inflated, thereby protecting it (5)

In the visceral pleura, fibers of the elastic and collagenous systemsare clearly interdependent elements Collagenous fibers are

interwoven in a pleated structure that closely resembles the osiers

of a wicker basket, suggesting that collagen fibers allow the lungvolume to increase up to a point of maximal stretching of the

system (5) The pleural contribution to the elastic recoil pressure ofthe lung originates from the elastic network, which returns to itsresting position when inspiratory pressures are negligible (5)

Both the visceral and the parietal pleura are lined with a single layer

of flat mesothelial cells These mesothelial cells range in size from 6

to 12 Âµm in diameter (6) With scanning electron microscopy (7) ,the pleural surface is found to be either flattened or bumpy (F i g 1.1) The bumpy areas include most of the visceral pleura and

portions of the parietal pleura, including the subcostal regions andthe pleural recesses These areas appear to result from a lack ofrigidity of the underlying structures (6)

Scanning electron microscopy also demonstrates that microvilli arepresent diffusely over the entire pleural surface (Fig 1.1), but thedistribution of the microvilli is irregular The density of the microvilliranges from less than a few to more than 600/100 Âµm2, with a

mean of approximately 300 (1) The microvilli are most numerous onthe inferior parts of the visceral pleura and the anterior and inferiormediastinum on the parietal pleura (1) At corresponding regions inthe thoracic cavity, more microvilli are present on the visceral

pleura than on the parietal pleura The microvilli are approximately0.1 Âµm in diameter, and their length varies from 0.5 to 3.0 Âµm(1)

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The exact function of these numerous microvilli is yet to be defined.

At one time it was believed that their presence increased the

capacity of the visceral pleura to absorb pleural fluid This is

probably incorrect because recent observations have indicated thatthe visceral pleura plays a limited role in the absorption of pleuralfluid It is now thought that the most important function of the

microvilli is to enmesh glycoproteins that are rich in hyaluronic acid,especially in the lower thorax,

P.3

to lessen the friction between the lung and the chest wall (7)

Moreover, as mentioned earlier, a thin rim of fluid normally

separates the visceral and parietal pleura Impingement of the

microvilli from one pleural surface into the opposing pleural surfacecould possibly help maintain this thin rim of fluid (8), but this is

controversial (9)

FIGURE 1.1 â€¢ Scanning electron microscopic studies of the

pleura A : Bumpy pleural surface with cellular borders

irregularly depressed Note that the number of microvilli present

on each cell is variable (original magnification: 1,300Ã—) B:

Flattened pleural surface with indistinct cell boundaries and

sparse microvilli (original magnification: 1,250Ã—) (From

Wang NS The regional difference of pleural mesothelial cells in

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rabbits Am Rev Respir Dis 1974;110:623â€“633, with

permission

The mesothelial layer is very fragile At thoracotomy in patients

without clinical pleural disease, focal denudation of mesothelial cells

is common (1 0) When the normal layer of mesothelial cells liningthe pleura is disrupted, the defect is repaired through mitosis andmigration of the mesothelial cells (1 0,1 1) When irritated, they

retract but retain continuity with adjacent cells by projections called

cellular bridges Mesothelial cells are frequently dislodged from the

pleural surfaces and are thereby free in the pleural fluid When free

in the pleural space, the cells become round or oval (1 1) Their

cytoplasm is rich in organelles From this state, they may be

transformed into macrophages capable of phagocytosis and

erythrophagocytosis (1 1) Such transformed cells frequently havevacuoles in their cytoplasm Not all the macrophages in pleural fluidevolve from mesothelial cells; some definitely evolve from

peripheral blood mononuclear cells, and some may evolve from

alveolar macrophages (1 2) An immunologic role has been suggestedfor the macrophages derived from the mesothelial cells (1 2)

Mesothelial Cells

Mesothelial cells form a monolayer of specialized pavement-like cellsthat line the pleural surfaces The mesothelial cells are active cells,and they are sensitive and responsive to various stimuli The

mesothelial cells that line the pleural cavity and those that line theother body cavities have no recognizable cytologic difference (1 3) The cytoplasm always contains a moderate to abundant amount oforganelles, including mitochondria, rough and smooth endoplasmicreticulum, polyribosomes, intermediate fibrils, Golgi apparatus, andsome glycogen granules, suggesting that the mesothelial cell is ametabolically active cell (1 4)

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The mesothelium is now recognized as a dynamic cellular membranewith many important functions These include transport and

movement of fluid and particulate matter across the pleural

surfaces, leukocyte migration in response to inflammatory

mediators, synthesis of cytokines, growth factors and extracellularmatrix proteins, release of factors to promote both the depositionand clearance of fibrin, and antigen presentation (1 5) Mesothelialregeneration involves migration of cells from the wound edge andattachment and incorporation of free-floating mesothelial cells fromthe pleural fluid onto the denuded pleural surface (1 6) There isstrong evidence that mesothelial cells can convert to myofibroblasts.Yang et al (1 7) assessed the effects of incubating peritoneal

mesothelial cells with transforming growth factor beta (TGF-Î²) andreported that the mesothelial cells took on the characteristic

myofibroblastic phenotype We have observed that the incubation ofhuman mesothelial cells with TGF-Î² results in their morphologictransformation to cells that look like fibroblasts It has been shownthat the intrapleural administration of TGF-Î² results in an excellentpleurodesis (1 8) and the morphologic changes induced by TGF-Î²referred to here may be important in producing the pleurodesis

In cell culture, mesothelial cells have been shown to produce type I,type II, and type IV collagens, elastin, fibronectin, and laminin, and

to express intermediate filaments typical of both epithelial cells andfibroblasts (1 9) Mesothelial cells also express procoagulant activitybecause of a tissue factor that binds factor VII at the cell surface(2 0) Mesothelial cells have also been demonstrated to produce

nitric oxide (2 1) and TGF-Î²1 as well as many other cytokines (seeChapter 5) (1 8)

Pleural Fluid

Major considerations in the understanding of pleural fluid are

volume, thickness, cellular components, and physicochemical

factors

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V o l u m e

Normally, a small amount of pleural fluid is present in the pleuralspace The mechanisms responsible for this small amount of residualfluid are discussed in Chapter 2 Noppen et al (2 2) have

demonstrated that the mean amount of fluid in the right pleural

space in normal individuals is 8.4 Â± 4.3 mL Normally, the volume

of fluid in the right and left pleural spaces is quite similar (2 2)

Expressed per kilogram of body mass, the total pleural fluid volume

in normal, nonsmoking humans is 0.26 Â± 0.1 mL/kg (2 2) The

mean total volume of pleural fluid in animal studies has been found

to vary from 0.04 to 0.2 mL/kg (2 3)

Thickness

The small amount of residual pleural fluid appears to be distributedrelatively evenly throughout the pleural space Therefore, the

pleural fluid behaves as a continuous system Albertine et al

studied the thickness of pleural fluid in rabbits by four different

methods (9) They found that the average arithmetic mean width ofthe pleural space was slightly more narrow near the top (18.5 Âµm)than at the bottom (20.3 Âµm) Pleural space width in the most

dependent recesses, such as the costodiaphragmatic recess, reached

1 to 2 mm They were unable to find any contacts between the

visceral and parietal pleura Because the microvilli of the

mesothelial cells in the visceral and parietal pleura do not

interdigitate, the frictional forces between the lungs and chest wallare low (9)

P.4

C e l l s

Noppen et al (2 2) analyzed the cellular contents of pleural fluid

from patients with normal pleura who were undergoing thoracoscopyfor hyperhidrosis They reported that the mean white blood cell

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count was 1,716 cells/mm3 and the mean red cell count was

approximately 700 cells/mm3 (2 2) These numbers are similar tothose recorded in animals Miserocchi and Agostoni reported thatpleural fluid in rabbits and dogs contains approximately 2,450 and2,200 white blood cells/mm3, respectively (2 4)

In humans, approximately 75% of the cells in the pleural fluid aremacrophages and 25% are lymphocytes, with mesothelial cells,

neutrophils, and eosinophils accounting for less than 2% each (2 2)

In the rabbit, 32% of the cells are mesothelial cells, whereas 61%are mononuclear cells and 7% are lymphocytes In the dog, 70% ofthe cells are mesothelial cells, 28% are mononuclear cells, and 2%are lymphocytes The variance in the differential count in these

series may be related to the stains used and the definition of

mesothelial cells and macrophages

Physicochemical Factors

A small amount of protein is normally present in the pleural fluid Inrabbits, the protein concentration averages 1.33 g/dL, whereas indogs, it averages 1.06 g/dL (2 4) The mean oncotic pressure in thepleural fluid is 4.8 cm H2O in rabbits and 3.2 cm H2O in dogs (2 4) Protein electrophoresis demonstrates that the electrophoretic

pattern for pleural fluid is similar to that of the corresponding

serum, except that low-molecular-weight proteins such as albuminare present in relatively greater quantities in the pleural fluid

Interestingly, the ionic concentrations in pleural fluid differ

significantly from those in serum The pleural fluid bicarbonate

concentration is increased by 20% to 25% relative to that in plasma,whereas the major cation (Na+) is reduced by 3% to 5%, and themajor anion (Cl-) is reduced by 6% to 9% The concentration of K+and glucose in the pleural fluid and plasma appears to be nearlyidentical (2 5) The gradient for bicarbonate persists when the

animals are given a carbonic anhydrase inhibitor When unilateralartificial pleural effusions of distilled water were produced in rats,

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electrolyte equilibrium between pleural fluid and venous plasma wasreached in approximately 40 minutes, but the foregoing gradientspersisted The pleural fluid PCO2 is approximately the same as theplasma PCO2 Accordingly, in view of the elevated pleural fluid

bicarbonate, the pleural fluid is alkaline with respect to the plasma

pH (2 5) These gradients for electrolytes suggest that an active

process is involved in pleural fluid formation The significance ofsuch an active process remains to be defined

Blood Supply to the Pleura

The parietal pleura receives its blood supply from the systemic

capillaries Small branches of the intercostal arteries supply thecostal pleura, whereas the mediastinal pleura is supplied principally

by the pericardiacophrenic artery The diaphragmatic pleura is

supplied by the superior phrenic and musculophrenic arteries Thevenous drainage of the parietal pleura is primarily by the intercostalveins, which empty into the inferior vena cava or the

brachiocephalic trunk The venous drainage of the diaphragm is

either caudally into the inferior vena cava through the inferior

phrenic veins, or cranially into the superior vena cava through thesuperior phrenic veins (1 4)

The blood supply to the visceral pleura is dependent on whether theanimal has a thick or thin pleura In general, the blood supply to thevisceral pleura in animals with a thin pleura originates from thepulmonary circulation, whereas the blood supply in animals with athick pleura originates from the systemic circulation through thebronchial arteries Albertine et al have demonstrated in sheep, ananimal with a thick pleura, that the bronchial artery supplies thevisceral pleura completely and exclusively (4) Humans have a thickvisceral pleura, which is probably why it is also supplied by the

bronchial artery, but there is still controversy (2 6) concerning thisstatement All investigators agree that the bronchial artery suppliesmost of the visceral pleura facing the mediastinum, the pleura

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covering the interlobular surfaces, and a part of the diaphragmaticsurface (1 4) The blood supply for the remaining portions of the

visceral pleura is less understood and is thought by some to be

through the pulmonary artery (1 4) The venous drainage of the

visceral pleura is through the pulmonary veins

Pleural Lymphatics

The lymphatic plexuses in the costal pleura are mainly confined tothe intercostal spaces and are absent or minimal over the ribs (1 4) The lymphatic vessels of the costal pleura drain ventrally toward

nodes along the internal thoracic artery and dorsally toward the

internal intercostal lymph nodes near the heads of the ribs The

lymphatic vessels of the mediastinal pleura pass to the

tracheobronchial and mediastinal nodes, whereas the lymphatic

vessels of the diaphragmatic pleura pass to the parasternal, middlephrenic, and posterior mediastinal nodes When quantum dots with adiameter of 15 Âµm are injected into the pleural space of pigs, theyare first visualized in the superior mediastinal nodes (2 7)

The lymphatic vessels in the parietal pleura are in communicationwith the pleural space by means of stomas that range in diameterfrom 2 to 6 Âµm (Fig 1.2) (2 8,2 9) When nitric oxide concentrationsare increased, the stomas enlarge (3 0) In one study in rabbits theaverage density of the stomas was

distribution of stomas is similar to the distribution of particulate

matter injected into the pleural space (see Chapter 2

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FIGURE 1.2 â€¢ Lymphatics of the parietal pleura A : Scanning

electron microscopic study of the parietal pleura in the rabbit,demonstrating a lymphatic stoma Microvilli and micropinocyticopenings on the mesothelial surface are both much smaller thanthe stoma (original magnification: 6,500Ã—) B: Toluidine blue

stain demonstrating a red blood cell at the stoma of a lacuna

(original magnification: 1,000Ã—) (From

Wang NS The preformed stomas connecting the pleural cavityand the lymphatics in the parietal pleura Am Rev Respir Dis

1975;111:12â€“20, with permission

)

The lymphatic vessels in the parietal pleura have many branches.Some submesothelial branches have dilated lymphatic spaces calledlacunas (Fig 1.2B) (2 8) Stomas are found only over the lacunas Atthe stoma, the mesothelial cells with their microvilli are in

continuity with the endothelial cells of the lymphatic vessels Whenred blood cells or carbon particles are injected into the pleural

space, they collect around the stomas and in the lacunas and

lymphatic vessels (Fig 1.2B) (3,2 8) Therefore, these stomas withtheir associated lacunas and lymphatic vessels are thought to be the

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main pathway for the elimination of particulate matter from the

pleural space (3,2 8) Occasionally macrophages can be visible

emerging from lymphatic stoma and entering the pleural cavity (2 9) The existence of such stomas has been difficult to demonstrate inhumans Gaudio et al (6) were unable to demonstrate any such

stomas in specimens from 30 patients undergoing thoracic surgicalprocedures Peng et al (1 0) were able to demonstrate stomas inonly two of their nine human specimens However, more recently Li(3 1) was able to demonstrate pleural stoma in the diaphragmaticpleura in human specimens The stoma were usually round or oval inshape and approximately 6.2 Âµm in diameter The stoma were notpresent in the visceral pleura or the parietal pleura on the chestwall Most stoma were quite deep, forming channels that seemed toconnect the pleural cavity with the underlying lymphatic lacunae.Interestingly, in the golden hamster, there are many stoma but none

in the diaphragmatic pleura (3 2)

The visceral pleura is abundantly endowed with lymphatic vessels.These lymphatics form a plexus of intercommunicating vessels thatrun over the surface of the lung toward the hilum and also penetratethe lung to join the bronchial lymph vessels by passing through theinterlobular septa Although lymph may flow in either direction, alllymph from the visceral pleura eventually reaches the lung root

either by penetrating the lung or by flowing on the surface of thelung The larger lymphatic vessels in the visceral pleura are

equipped with one-way valves directing flow toward the hilum of thelung (1 4) No stomas are seen in the visceral pleura, and the

lymphatic vessels of the visceral pleura are separated from the

mesothelial cells by a layer of connective tissue The lack of stomas

in the visceral pleura explains the observation that particulate

matter injected in the pleural space is removed through the parietalpleura (see Chapter 2) Fluid from the pleural space does not enterthe lymphatics in the visceral pleura in humans

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Kampmeier Foci

Kampmeier (3 3) in 1928 described small milky spots in the dorsaland caudal portions of the mediastinum in rats and humans

Microscopically, the foci are an aggregate of lymphocytes,

histiocytes, plasma cells, and other mononuclear cells around

central lymphatic or vascular vessels It has been suggested that theblack spots in patients with parietal anthracosis correspond to theKampmeier foci and that the distribution of asbestos fibers in thepleura is also concentrated in these foci (3 4) It has been

hypothesized that the high concentrations of asbestos in these

P.6

foci leads to the development of pleural plaques and mesothelioma(3 4) However, the occurrence of pleural plaques is not related tothe location of the black spots (3 5)

Innervation of the Pleura

Sensory nerve endings are present in the costal and diaphragmaticparietal pleura The intercostal nerves supply the costal pleura andthe peripheral part of the diaphragmatic pleura When either of

these areas is stimulated, pain is perceived in the adjacent chest

wall In contrast, the central portion of the diaphragm is innervated

by the phrenic nerve, and stimulation of this pleura causes the pain

to be perceived in the ipsilateral shoulder The visceral pleura

contains no pain fibers and may be manipulated without causing

unpleasant sensation Therefore, the presence of pleuritic chest painindicates inflammation or irritation of the parietal pleura

References

1 Wang NS Anatomy of the pleura Clin Chest Med

1998;19:229â€“240

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2 Gray SW, Skandalakis JE Development of the pleura In:

Chretien J, Bignon J, Hirsch A, eds The pleura in health and

disease Lung biology in health and disease, Vol 30 New York:Marcel Dekker Inc, 1985:319

3 Albertine KH, Wiener-Kronish JP, Staub NC The structure ofthe parietal pleura and its relationship to pleural liquid dynamics

in sheep Anat Rec 1984;208:401â€“409.

4 Albertine KH, Wiener-Kronish JP, Roos PJ, et al Structure,blood supply, and lymphatic vessels of the sheep visceral pleura

Am J Anat 1982;165:277â€“294.

5 Lemos M, Pozo RM, Montes GS, et al Organization of collagenand elastic fibers studied in stretch preparations of whole mounts

of human visceral pleura Anat Anz 1997;179:447â€“452.

6 Gaudio E, Rendina EA, Pannarale L, et al Surface morphology

of the human pleura: a scanning electron microscopic study

Chest 1988;92:149â€“153.

7 Wang NS The regional difference of pleural mesothelial cells

in rabbits Am Rev Respir Dis 1974;110:623â€“633.

8 Miserocchi G, Agostoni E Pleural liquid and surface pressures

at various lung volumes Respir Physiol 1980;39:315â€“326.

9 Albertine KH, Wiener-Kronish JP, Bastacky J, et al No

evidence for mesothelial cell contact across the costal pleuralspace of sheep J Appl Physiol 1991;70:123â€“143.

10 Peng M-J, Wang NS, Vargas FS, et al Subclinical surface

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alterations of human pleura Chest 1994;106:351â€“353.

11 Efrati P, Nir E Morphological and cytochemical investigation

of human mesothelial cells from pleural and peritoneal effusions

A light and electron microscopy study Isr J Med Sci

1976;12:662â€“673

12 Bakalos D, Constantakis N, Tsicricas T Distinction of

mononuclear macrophages from mesothelial cells in pleural andperitoneal effusions Acta Cytol 1974;18:20â€“22.

13 Jones JS The pleura in health and disease Lung

2001;179:397â€“413

14 Peng M-J, Wang N-S Embryology and gross structure In:Light RW, Lee YC, eds (Gary): Textbook of pleural diseases.Chapter 1 London: Arnold Publishers, 2003:3â€“16

15 Mutsaers SE Mesothelial cells: their structure, function androle in serosal repair Respirology 2002;7:171â€“191.

16 Mutsaers SE The mesothelial cell Int J Biochem Cell Biol

2004;36:9â€“16

17 Yang AH, Chen JY, Lin JK Myofibroblastic conversion of

mesothelial cells Kidney Int 2003;63:1530â€“1539.

18 Lee YC, Lane KB Cytokines in pleural diseases In: Light RW,Lee YC, eds (Gary): Textbook of pleural diseases Chapter 6.London: Arnold Publishers, 2003:63â€“89

19 Antony VB, Sahn SA, Mossman B, et al Pleural cell biology in

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health and disease Am Rev Respir Dis 1992;145:1236â€“1239.

20 Idell S, Zwieb C, Kumar A, et al Pathways of fibrin turnover

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by rat pleural mesothelial cells: induction by growth factors and

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22 Noppen M, De Waele M, Li R, et al Volume and cellular

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> Table of Contents > Chapter 2 - Physiology of the Pleural

Space

Chapter 2

Physiology of the Pleural Space

The pleural space is the coupling system between the lung and

the chest wall, and, accordingly, it is a crucial feature of the

breathing apparatus The pressure within the pleural space (thepleural pressure) is important in cardiopulmonary physiology,because it is the pressure at the outer surface of the lung and theheart and the inner surface of the thoracic cavity Because thelung, the heart, and the thoracic cavity are all distensible, andbecause the volume of a distensible object depends on the

pressure difference between the inside and the outside of the

object and its compliance, pleural pressure plays an importantrole in determining the volume of these three important

structures

Pleural Pressure

If the thorax is opened to atmospheric pressure, the lungs

decrease in volume because of their elastic recoil, while at thesame time, the thorax enlarges With the thorax open, the volume

of the thoracic cavity is approximately 55% of the vital capacity,whereas the volume of the lung is below its residual volume Withthe chest closed and the patient relaxed, the respiratory system is

at its functional residual capacity (FRC), which is approximately

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35% of the total lung capacity (1) Thus, at FRC, the opposingelastic forces of the chest wall and lung produce a negative

pressure between the visceral and the parietal pleura, which iscalled the pleural pressure This pressure surrounds the lung and

is the primary determinant of the volume of the lung The pleuralpressure represents the balance between the outward pull of thethoracic cavity and the inward pull of the lung (1)

Pleural Liquid Pressure versus Pleural Surface Pressure

There has been a controversy for many years as to whether thereare two pleural pressures or one (2) The two different pressureshad been proposed to explain a discrepancy obtained when thepleural pressure was measured in two different ways If the

pressure was measured using fluid-filled catheters, the verticalgradient obtained was approximately 1.0 cm H2O/cm vertical

height This pressure was designated the pleural liquid pressure

and was believed to represent the pressure that influenced theabsorption of fluid If the pressure was measured using surfaceballoons or suction cups, then a gradient of 0.3 cm H2O/cm

vertical height was obtained This pressure was designated the

pleural surface pressure and represented the balance between the

outward pull of the thoracic cavity and the inward pull of the

lung It now appears that there is only one pressure and that thediscrepancies in the pressures arose because of the distortionfrom the catheters (3) It should be noted, however, that there isstill a school of researchers who believe in the presence of twodifferent pressures (4,5)

Measurement

Pleural pressure can be measured directly by inserting needles,trocars, catheters, or balloons into the pleural space Direct

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measurement of the pleural pressure is not usually made because

of the danger of producing a pneumothorax or of introducing

infection into the pleural space Rather, the pleural pressure is

measured indirectly by a balloon positioned in the esophagus (6) Because the esophagus is a compliant structure situated betweenthe two pleural spaces, esophageal pressure measurements

provide a close approximation of the pleural pressure at the level

of the balloon in the thorax (7) Estimation of pleural pressure bymeans of an esophageal balloon is not without difficulties (7) Thevolume of air within the balloon must be small, so that the

balloon is not stretched and the esophageal walls are not

displaced; otherwise, pleural pressure estimates are falsely

elevated Moreover, the balloon must be short and must be placed

in the lower part of the esophagus

P.8

It has been demonstrated that reliable measurements of

esophageal pressures can be made with micromanometers (8)

The use of the micromanometer should circumvent some of the

problems associated with esophageal balloons

Gradients

Only one value for the pleural pressure is obtained when it is

estimated by an esophageal catheter or balloon It should be

emphasized, however, that the pleural pressure is not uniform

throughout the pleural space A gradient in pleural pressure is

seen between the superior and the inferior portions of the lung,

with the pleural pressure being lowest or most negative in the

superior portion and highest or least negative in the inferior

portion (3) The main factors responsible for this pleural pressuregradient are probably gravity, mismatching of the shapes of the

chest wall and lung, and the weight of the lungs and other

intrathoracic structures (1)

The magnitude of the pleural pressure gradient appears to be

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approximately 0.30 cm H2O/cm vertical distance (3) It should benoted that over the last 30 years, there have been many studiesdirected at measuring the pleural pressure gradient and the

resulting values have ranged from 0.20 to 0.93 cm H2O/cm

vertical distance (3) The results have been largely dependent onthe method used (3) It appears that the higher values were

obtained with catheters that were large relative to the narrowpleural space, and accordingly produced distortion of the pleurawith subsequent alterations in the measured pressures (3)

In the upright position, the difference in the pleural pressurebetween the apex and the base of the lungs may be 8 cm H2O ormore Because the alveolar pressure is constant throughout thelungs, the end result of the gradient in the pleural pressure isthat different parts of the lungs have different distending

pressures The pressureâ€“volume curve is thought to be thesame for all regions of the lungs; therefore, the pleural pressuregradient causes the alveoli in the superior parts of the lung to belarger than those in the inferior parts The higher pressure

gradient at the apex of the lung is thought to be responsible forthe formation of pleural blebs almost exclusively at the apex ofthe lung The pleural pressure gradients also account for the

unevenness in the distribution of ventilation

Pleural Fluid Formation

Fluid that enters the pleural space can originate in the pleuralcapillaries, the interstitial spaces of the lung, the intrathoraciclymphatics, the intrathoracic blood vessels, or the peritonealcavity

Pleural Capillaries

The movement of fluid between the pleural capillaries and thepleural space is believed to be governed by Starling's law of

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transcapillary exchange (9) When this law is applied to the

pleura as indicated in Equation 2.1 here,

where [Q with dot above]f is the liquid movement; Lp is the

filtration coefficient/unit area or the hydraulic water conductivity

of the membrane; A is the surface area of the membrane; P andÏ€ are the hydrostatic and oncotic pressures, respectively, of thecapillary (cap) and pleural (pl) space; and Ïƒd is the solute

reflection coefficient for protein, a measure of the membrane'sability to restrict the passage of large molecules (3) Widely

varying values for Ïƒd have been reported For example, the Ïƒd ofthe canine visceral pleura combined with the endothelium hasbeen reported to exceed 0.80 (3), indicating a marked restriction

in the movement of large molecules such as albumin In contrast,the Ïƒd of the mediastinal pleura in the pig was reported to bebetween 0.02 and 0.05, indicating little restriction in the

movement of large molecules (3) It appears that the restriction

of protein by the pleural capillary endothelialâ€“interstitial barrier

is largely associated with the endothelium (3)

Estimates for the magnitude of the pressures affecting fluid

movement from the capillaries to the pleural space in humans areshown in Fig 2.1 In the parietal pleura, a gradient for fluid

formation is normally present The hydrostatic pressure in theparietal pleura is approximately 30 cm H2O, whereas the pleuralpressure is approximately -5 cm H2O The net hydrostatic

pressure is therefore 30 - (-5) = 35 cm H2O and this favors themovement of fluid from the capillaries in the parietal pleura tothe pleural space Opposing this hydrostatic pressure gradient isthe oncotic pressure gradient The oncotic pressure in the plasma

is approximately 34 cm H2O Normally, the small amount of

pleural fluid contains a small amount of protein and has an

oncotic pressure of approximately 5 cm H2O (1 0), yielding a netoncotic pressure gradient of 34 - 5 = 29 cm H2O Thus, the net

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gradient is 35 - 29 = 6 cm H2O, favoring the movement of fluid

from the capillaries in the parietal pleura to the pleural space

The net gradient for fluid movement across the visceral pleura in

humans is probably close to zero, but this has not been

demonstrated (Fig 2.1) The pressure in the visceral pleural

capillaries is approximately 6 cm H2O less than that in the

parietal pleural capillaries because the visceral pleural capillariesdrain into the pulmonary veins Because this is the only pressure

that differs from those affecting fluid movement across the

parietal pleura and because the net gradient for the parietal

pleura is 6 cm H2O, it follows that the net gradient for fluid

movement across the visceral pleura is approximately zero It is

also likely that the filtration coefficient (Lp) for the visceral pleura

is substantially less than that for the parietal pleura because the

capillaries in the visceral pleura are much farther from the pleuralspace than those in the parietal pleura (1 1)

P.9

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FIGURE 2.1 â€¢ Various pressures that normally influence

the movement of fluid in and out of the pleural space in

species with a thick visceral pleura, such as humans

The movement of pleural fluid is not the same across all theparietal pleura Wang and Lai-Fook (1 2) used Evans blueâ€“dyedalbumin to study regional pleural filtration of prone anesthetizedrabbits They reported that there appeared to be more fluid

formation across the parietal pleura over the ribs compared withthe intercostal spaces In contrast, pleural liquid absorption wasprimarily in the parietal pleura adjacent to the intercostal spacerather than in the parietal pleura overlying the ribs There wasalso more fluid formation over the caudal ribs than over thecranial ribs (1 2) If the breathing frequency was increased, morefluid was formed (1 2)

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The transpleural exchange of fluid is species dependent Humansand sheep have a thick visceral pleura and its blood supply isfrom the bronchial artery rather than from the pulmonary artery(1 3) However, many species, such as the rabbit and the dog,have a thin visceral pleura that receives its blood supply from thepulmonary circulation In such a situation, as shown in Fig 2.2,the net gradients favor pleural fluid formation across the parietalpleura and pleural fluid absorption through the visceral pleura.

Interstitial Origin

In recent years, it has been demonstrated that the origin of much

of the fluid that enters the pleural space, especially in diseasestates, is the interstitial spaces of the lungs Either high-pressure

or high-permeability pulmonary edema can lead to the

accumulation of pleural fluid When sheep are volume overloaded

to produce high-pressure pulmonary edema, approximately 25%

of all the fluid that enters the interstitial spaces of the lungs iscleared from the lung through the pleural space (1 4) Within 2hours of starting the volume overloading, the amount of fluidentering the pleural space increases, and within 3 hours, the

protein concentration in the pleural fluid is the same as that inthe interstitial spaces of the lungs (1 4) The amount of pleuralfluid formed is directly related to the elevation in the wedge

pressure Increases in pleural fluid accumulation occur only afterthe development of pulmonary edema (1 5)

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FIGURE 2.2 â€¢ Various pressures that normally influence

the movement of fluid in and out of the pleural space in

species with a thin visceral pleura, such as the dog See textfor explanation

The pulmonary interstitial space is probably the origin of the

pleural fluid in patients with congestive heart failure The

likelihood of a pleural effusion increases as the severity of

pulmonary edema increases (1 6) In addition, the presence ofpleural effusions is more closely correlated with the pulmonaryvenous pressure than with the systemic venous pressure (1 6) The amount of fluid that enters the pleural space is also increasedwhen there is increased interstitial fluid due to high-permeabilitypulmonary edema When increased-permeability edema was

induced in sheep by the infusion of oleic acid, again, pleural fluid

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