Lung and Upper Respiratory Tract PDF

CHAPTER 10 Lung and Upper Respiratory Tract 169 o a parcuar mucn,...

CHAPTER 10 Lung and Upper Respiratory Tract 169 o a parcuar mucn, MUC5B, or ave a germne muaon n a sur- Clncal Features. Idopac pumonary ibross s more common n acan gene. hese afeced genes are ony expressed n ung epea maes and s a dsease o agng, vruay never occurrng beore 50 years ces, mpcang epea abnormaes n e naon o e dsease o age. I presens w a nonproducve coug and progressve dyspnea. n a eas some paens. On pysca examnaon, caracersc “dry” or “Vecro-ke” crackes are eard durng nspraon. Cyanoss and cor pumonae may deveop n aer sages o e dsease. Anibroc erapes ave produced posve Morphology. e peura surace o e ung s “cobbesoned” due oucomes n cnca ras and are approved or use, bu e overa prog- o e reracon o scars, and e cu surace sows irm, r ubber y, noss s poor. Survva s ony 3 o 5 years ater dagnoss and ung rans- we areas o ibross. Mcroscopcay, ere s pacy nterstta panaon s e ony deinve reamen. Oer rare pumonary dseases ibross a vares n nensy. e eares esons demonsrae assocaed w ibross need o be consdered n e dferena dagnoss exuberan ibrobas proeraon, bu over me ese areas o dopac pumonary ibross. Reumaoogc dseases, suc as sysemc become more coagenous and ess ceuar (Suppemena eFg. sceross, reumaod arrs, and sysemc upus eryemaosus, may be 10.4). Usuay bo eary and ae esons are seen. e ibross compcaed by pumonary ibross and soud be excuded cncay. causes coapse o aveoar was and ormaon o c ysc spaces Pneumoconioses ned by yperpasc epeum (honeycomb ibross). S econdar y vascuar canges due o supermposed pumonar y yperenson Pneumoconiosis is a term coined to describe lung disorders caused are oten presen. Smar mor poogc eaures may be presen n by inhalation of mineral dusts, most commonly coal dust, silica, enes suc as asbesoss and reumaoogc dseases; ereore, and asbestos. dopac pumonar y ibross s a dagnoss o excuson. Tabe 10.3 ndcaes e paoogc condons assocaed w eac o ese mnera duss and e major ndusres n wc e dus expo- sure may occur. Environmental factors: Pathogeness. e reacon o e ung o mnera duss depends on e Smoking sze, sape, souby, and reacvy o e parces. Parces a are Occupational exposure 1 o 5 μm n dameer are mos dangerous because ey end o odge Other irritants, toxins a burcaons n dsa ar ways. Coa dus s reavey ner, and arge Viral infection At-risk epithelium: amouns mus be deposed beore cncay deecabe ung dsease s Age produced. Sca, asbesos, and ber yum are more reacve an coa Genetics: dus, resung n ibroc reacons a ower concenraons. Telomerase mutations e pumonary aveoar macropage s cenra o e naon and Surfactant mutations perpeuaon o nammaon, ung njury, and ibross. Foowng pago- MUC5B variant cyoss by macropages, e parces acvae e nammasome and Persistent epithelial Innate and adaptive nduce producon o cyoknes suc as IL-1, nang an nammaory injury/activation immune response response. In addon, parces may damage e membrane o pagoy- sosomes, eadng o ce njury a ampies e nammaory reacon. Cronc nammaon eads o nersa ibrobas proeraon and coagen deposon. Tobacco smokng exacerbaes e deeerous efecs Pro-fibrogenic factors o a naed mnera duss, more so w asbesos an oer parces. Coa worker’s pneumoconoss as decreased n ncdence as work n coa mnes as decned, bu scoss and asbesoss reman mpor- an ea probems and mer a bre menon. Abnormal intracellular signaling Silicosis Silico sis is curren tl y th e most p rev a l en t ch ro n ic o c c upa t i o n a l Proliferation, collagen production disease in the world. Pathogeness. Scoss s caused by e naaon o crysane sca, Fibrosis mosy n occupaona sengs (e.g., sandbasng and ard rock mnng). Ater naaon, sca parces are pagocyosed by macropages; s Fig. 10.6 Proposed pathogenic mechanisms in idiopathic pulmonary fibrosis. nduces e reease o IL-1 and oer nammaor y medaors. Table 10.3 Mineral Dust–Induced Lung Disease Agent Disease Exposure Coal dust Simple coal worker’s pneumoconiosis: macules and Coal mining nodules Complicated coal worker’s pneumoconiosis Silica Silicosis Sandblasting, quarrying, mining, stone cutting, foundry work, ceramics Asbestos Asbestosis, pleural effusions, pleural plaques, or diffuse Mining, milling, and fabrication of ores and materials; installation fibrosis; mesothelioma; carcinoma of the lung and larynx and removal of insulation  CHAPTER 10 Lung and Upper Respiratory Tract 169.e1 Supplemental eFig. 10.4 Usual interstitial pneumonia (idiopathic pul- monary fibrosis). Fibroblastic focus with collagen fibers running parallel to surface and bluish myxoid extracellular matrix (arrow). Honeycomb- ing is present on the left. 170 CHAPTER 10 Lung and Upper Respiratory Tract Fig. 10.7 Collagenous silicotic nodules. (Courtesy of Dr. John Godleski, Fig. 10.8 High-power detail of an asbestos body, revealing the typical Brigham and Women’s Hospital, Boston.) beading and knobbed ends (arrow). dyspnea appears 10 o 20 years ater exposure, usuay accompaned Morphology. Inammaon produced by sca resus n scoc by a coug and spuum producon. e nersa ung dsease may nodues, composed o concenrc wors o coagen ibers reman sac or progress o congesve ear aure, cor pumonae, surroundng an amorpous cener (Fg. 10.7). Examnaon o and dea. Peura paques are usuay asympomac and are deeced e nodues by poarzed mcroscopy reveas brerngen sca on radograps as crcumscrbed denses. e rsk or deveopng parces. As e dsease progresses, ndvdua nodues coaesce no ung carcnoma s ncreased abou 5-od or asbesos workers, wereas ard, coagenous scars, and w urer progresson a oneycomb e rsk or mesoeoma, normay a ver y rare umor, s more an paern o ibross may deveop. Fbroc esons aso may occur n 1000 mes greaer. Concoman cgaree smokng greay ncreases ar ymp nodes and e peura. e rsk or ung carcnoma bu no or mesoeoma. Clncal Features. Scoss usuay s deeced on roune ces rado- graps, wc sow a ine noduary n e upper ung zones. e ds- Granulomatous Diseases ease s sowy progressve, umaey mparng pumonar y uncon o Sarcoidosis suc a degree a pysca acvy s med. ere s an ncreased Sarcoidosis is a disease of unknown etiology characterized by non- suscepby o ubercuoss, possby because sca nereres w caseating granulomatous inammation in many tissues and organs. oca os deenses, and ere may be an ncreased rsk o ung cancer. Sarcodoss s dscussed ere because  may presen as a resrc- ve ung dsease. Baera ar ympadenopay assocaed w ung Asbestosis nvovemen s oten seen a presenaon. Eye and skn nvovemen Asbestos exposure is associated with interstitial and pleural pul- aso s common, and eer may occasonay be e presenng eaure. monary brosis and an increased risk of cancers of the lung and the pleura. Pathogeness. Sarcodoss occurs rougou e word, w a pred- econ or adus younger an 40 years o age. e ncdence s rea- Pathogeness. Asbesos s a amy o cr ysane ydraed scaes w a vey g n Dans and Sweds popuaons and n peope o Arcan ibrous geomer y. Exposure comes roug e workpace, bu ndvd- descen. A ger prevaence aso as been noed among nonsmokers. uas vng n e same ouseod aso may be exposed secondary. As e cause s unknown bu appears o nvove some exposure a produces w sca cr ysas, once pagocyosed by macropages, asbesos ibers a susaned CD4+ 1 T-ce response a ses o dsease, eadng o oca acvae e nammasome and damage pagoysosoma membranes, producon o nereron-γ, recrumen and acvaon o macropages, smuang e reease o pronammaor y and ibrogenc medaors. and ormaon o noncaseang granuomas. ere s a ama and raca e oncogenc efecs o asbesos may be medaed by reacve ree rad- cuserng o cases, suggesng e nvovemen o genec acors. cas generaed by asbesos ibers, wc preerenay ocaze n e dsa ung cose o e mesoea ayer. Carcnogens a are adsorbed Morphology. e cardna sopaoogc eaure s e ono e asbesos ibers aso may conrbue o e paogency o e nonnecrotzng granuoma, a dscree, compac coecon o ibers. e adsorpon o carcnogens n obacco smoke ono asbesos epeod macropages admxed w munuceaed gan ces ibers may expan e remarkabe synerg y beween obacco smokng a are rmmed by a zone rc n CD4+ T ces (Suppemena and e deveopmen o ung carcnoma n asbesos workers. eFg. 10.6). Newy ormed granuomas are surrounded by a rng o ibrobass; over me, ese proerae and ay down coagen a Morphology. e pumonar y nersa ibross s assocaed w repaces e granuoma w a yanzed scar. ese granuomas asbestos bodes: goden brown, beaded rods w a ransucen are seen n e ung, ar ymp nodes, skn, eye, acrma gands, cener conssng o asbesos ibers coaed w ron-conanng and oer ses o acve dsease. proenaceous maera (Fg. 10.8). Fbross aso deveops n e vscera peura, causng adesons beween e ungs and e ces Clncal Features. In many ndvduas, e dsease s asympom- wa, oten n e orm o we-crcumscrbed paques o dense ac and s dscovered ncdenay on roune ces ims. In oers, coagen (Suppemena eFg. 10.5). perpera ympadenopay, cuaneous esons, eye nvovemen, spenomegay, or epaomegay are e presenng manesaons. Clncal Features. e cnca indngs are ndsngusabe rom ose In abou wo rds o sympomac cases, ere s a gradua appear- o oer cronc nersa ung dseases. Progressvey worsenng ance o respraor y sympoms or consuona sgns and sympoms  CHAPTER 10 Lung and Upper Respiratory Tract 170.e1 Supplemental eFig. 10.5 Asbestos-related pleural plaques. Large, dis- crete, fibrocalcific plaques are seen on the pleural surface of the dia- phragm. (Courtesy Dr. John Godleski, Brigham and Women’s Hospital, Boston.) Supplemental eFig. 10.6 Bronchus with characteristic noncaseating sarcoidal granulomas (asterisks), with many multinucleated giant cells (arrowheads). Note subepithelial location of granulomas.  CHAPTER 10 Lung and Upper Respiratory Tract 171 (ever, ague, weg oss, anorexa, ng sweas). A deinve dag- nosc es does no exs, and esabsng e dagnoss requres e presence o cnca and radoogc indngs a are conssen w e dsease, e excuson o oer dsorders w smar presena- ons, and e denicaon o noncaseang granuomas n nvoved ssues. In parcuar, ubercuoss mus be excuded. Sarcodoss s unpredcabe: I may be cronc and progressve or ave perods o acvy nerspersed w remssons. O vera, 65% o 70% o afeced ndvduas recover w mnma or no resdua manesaons. Anoer 20% deveop permanen ung dysuncon or vsua mpar- men. In e remanng 10% o 15%, re racor y dsease may ead o aa pumonar y ibross and cor pumonae. Hypersensitivity Pneumonitis Hypersensitivity pneumonitis is an immunologically mediated inammatory lung disease that primarily affects the alveoli and is therefore often called allergic alveolitis. Hypersensvy pneumons s usuay an occupaona dsease resung rom egened sensvy o ceran naed angens (Tabe 10.4). I maness predomnany as a resrcve ung dsease. e responsbe occupaona and ouseod exposures are dverse, bu e assocaed syndromes are smar and probaby ave a com- mon paopysoogc bass. e os response o angens usuay Fig. 10.9 Large saddle embolus from the femoral vein lying astride the nvoves bo B ces and T ces, and “oose, ” poory ormed granuo- main left and right pulmonary arteries. (Courtesy of Dr. Linda Margraf, mas are ound n e ungs o wo rds o afeced paens (Suppe- Department of Pathology, University of Texas Southwestern Medical mena eFg. 10.7). In cronc cases, baera upper-obe–domnan School, Dallas.) nersa ibross occurs. Hypersensvy pneumons may manes as an acue reacon, (2) surgery (especay oropedc surgery on e knee or p); w coug, dyspnea, and consuona sgns and sympoms appearng (3) severe rauma (ncudng burns or mupe racures); (4) congesve 4 o 8 ours ater exposure, or as a cronc dsease caracerzed by an ear aure; (5) n women, e perod around paruron or e use o nsdous onse o coug, dyspnea, maase, and weg oss. I angenc ora conracepve ps w g esrogen conen; (6) dssemnaed can- exposure ceases ater an acue aack, e pumonary sympoms resove cer; and (7) prmary dsorders o ypercoaguaby (e.g., acor V Leden). wn days. Faure o remove e ncng agen rom e envronmen e consequences o pumonary romboembosm depend on e may resu n cronc nersa pumonary dsease. sze o e occuded pumonary arery and e cardopumonary sa- us o e paen. Pumonary arera occuson mmedaey ncreases e pumonary arery pressure, pary rom e bockage o ow and PULMONARY DISEASES OF VASCULAR ORIGIN possby aso rom vasospasm caused by neurogenc mecansms, and Pulmonary Embolism, Hemorrhage, and Infarction nduces scema o e downsream pumonary parencyma. Large, Pulmonary thromb o emb o l is m mo s t o ft e n ori g in a t e s f ro m abrup ncreases n pumonary arery pressure may produce acue rg- thrombi in deep l eg v ei n s and u su a ll y c om p l i c a t e s the co u r s e sded ear aure (acute cor pumonae) and, somemes, sudden dea. of other diseases. Hypoxema aso deveops as a resu o mupe mecansms, ncudng I s esmaed a pumonar y embosm causes abou 50,000 venaon–peruson msmac; wdenng o e dference n arer- deas per year n e Uned Saes, bu e rue ncdence s unknown: a-venous oxygen sauraon, due o decreased cardac oupu; and rg- Even among ospazed paens no more an one rd are dag- o-et sunng, wc occurs n ndvduas w a paen oramen ovae. nosed beore dea. Auopsy daa on e ncdence var y rom 1% n Because e ungs are oxygenaed by bronca areres and drecy e genera ospazed popuaon o 30% n ndvduas dyng ater rom ar n e aveo, scemc necross (narcon) s e excepon burns, rauma, or racures. raer an e rue. I occurs ony  ere s cardac dysuncon or e bronca crcuaon s compromsed, or  e ung a rsk s under- Pathogeness. Bood cos a occude arge pumonary areres usuay venaed due o underyng pumonar y dsease. orgnae rom romb nvovng e popea ven o e eg or e arger vens above . As dscussed n Caper 3, e oowng rsk acors are Morphology. A arge embous may obsruc e man pumonary paramoun: (1) proonged bed res (parcuary w eg mmobzaon); arery or s major brances or odge asrde e burcaon as a sadde embous (Fg. 10.9). Dea may oow so suddeny a morpoogc Table 10.4 Sources of Antigens Causing Hypersensitivity aeraons n e ung are absen. Smaer embo odge n medum- Pneumonitis szed and sma-szed pumonary areres. W adequae crcuaon and bronca arera ow, e nvoved ung remans vabe, bu Source of Antigen Types of Exposures aveoar emorrage may occur as a resu o scemc damage o Bacteria Dairy barns (farmer’s lung) endoea ces. W a compromsed cardovascuar saus (e.g., Mycobacteria Metal-working fluids, sauna, hot tub congesve ear aure), narcon resus, parcuary  e occuson Birds Pigeons, dove feathers, ducks, parakeets occurs n e perpery o e ung. Caracerscay, acue narcs Chemicals Isocyanates (auto painters), zinc, dyes are rased, wedge-saped, emorragc, red-bue areas (Suppemena eFg. 10.8). W me, ibrous repacemen evenuay convers e Fungi, yeasts Contaminated wood, humidifiers, central hot air heating ducts, peat moss plants narc no a we-gray scar.  CHAPTER 10 Lung and Upper Respiratory Tract 171.e1 Supplemental eFig. 10.7 Hypersensitivity pneumonitis. Loosely formed interstitial granulomas and chronic inflammation are characteristic. Supplemental eFig. 10.8 Acute hemorrhagic pulmonary infarct.