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CHAPTER 10 Lung and Upper Respiratory Tract 165 dsease...
CHAPTER 10 Lung and Upper Respiratory Tract 165 dsease (COPD). We w ins by dscussng asma, a reversbe orm ndvduas deveop empysema, wc occurs a an earer age and o obsrucve ar way dsease, and broncecass, an obsrucve dsor- s o greaer severy e ndvdua smokes. Sma ar ways are nor- der w dsncve cncopaoogc eaures. may ed open by e easc reco o e ung parencyma. e oss o easc ssue n e was o aveo a surround respra- Chronic Obstructive Pulmonary Disease or y broncoes reduces rada racon, eadng o coapse o e Chronic obstructive pulmonary disease is characterized by obstruc- respraor y broncoes durng expraon and uncona arow tive a irwa y a nd al v eo l a r a bn o rm al i t ies ca u s e d by inhalation of obsrucon. nox ious particles or g a s es , mo s t o ften d ue to smoking tobacco. Mcroba nfecton s oten presen bu as a secondar y roe, cey C ronc obs r uc ve pu monar y ds e as e (C OPD) a e c s more by mananng nammaon and exacerbang sympoms. an 5% o e adu s n e Un e d S aes, w ere s e rd e ad - ng c aus e o de a , exce e d e d on y by c ard ovas c u ar d s e as e and Mor phol og y. B o empys emaous and bronc c canges c ancer. Ar ow m a on s c aus e d by a comb na on o me can - are s e en n mos c as es. T e c ass c a on o e mpys emaous c a obs r uc on o a r w ays by mucous s e c re ons and bros s cange n C OPD and o er s e ng s s b as e d on e mac ros c op c (cronc bronct s) and unc ona obs r uc on due o p arency ma app e arance o e ung (Fg. 10.3). Te mos common p aer n des r uc on (empys ema), b o n resp ons e o cron c n am ma- n smokers s centr acnar empy s e ma , w c preeren a y on. C ronc bronc s s d e ne d by e pres enc e o a p e rs sen a e c s e er mna resp raor y bronc oe. Te es ons are pro duc ve coug or a e as 3 c ons e c u ve mon s n a e as 2 c on- more common and usu a y more s e ve re n e upp er ob es , s e c u ve ye ars. Empy s ema s d e ne d by e pres enc e o en arge d p ar c u ary n e ap c a s eg me n s. Hsoog c exam na on ar sp aces ds a o e er m na bronc oes and e de s r uc on o re ve a s des r uc on o a ve o ar w a s e ad ng o ar sp ac e a ve o ar wa s. en argemen, w ou over bross (Suppemen a eFg. 10. 1). Ter mna and resp raor y bronc oes a s o may be d eor me d Pathogeness. Inaed obacco smoke and oer noxous parces n- b e c aus e o e oss o s e p a a ep e er es e s r uc ure s ae severa processes a resu n parencyma desrucon (empy- n e p arency ma. Panac nar empys e ma s usu a y s e en n sema) and ar way dsease (broncos and cronc broncs). e s e ng o α1-an r ypsn de c enc y and re su s n g re aer Facors a nuence e deveopmen and severy o cronc bron- exp anson o ung voume an do es ce n r ac nar empys ema. cs and empysema ncude e oowng: Panacnar empys ema ends o o cc ur more c om mon y n e Inaaton of noxous partces. Tobacco smoke conans numerous ower zones and n e aner or marg ns o e ung; s usu a y oxc subsances and carcnogens a damage ces drecy and mos s e vere a e b as es. nduce deeerous reacve canges, suc as yperropy o mucous e broncc componen o COPD s marked by yperema gands n e racea and bronc and an ncrease n mucn-secre- o e bronca and racea mucosa and excessve mucnous or ng gobe ces n e epea suraces o smaer bronc and mucopuruen secreons. e mos caracersc mcroscopc broncoes. eaure s e enargemen o mucous-secreng gands (Sup- Inlammaton. C e njur y caused by oxc efecs o naed agens pemena eFg. 10.2). Varabe numbers o nammaor y ces, nduces e producon o nammaor y medaors (ncudng ncudng ympoc yes, macropages, and neurops, are seen eukorenes, nereukn-8 [IL-8], umor necross acor [TNF], n e bronca mucosa. and oers) a recru eukoc yes rom e crcuaon, amp- yng e nammaor y process. e resung cronc nam- maon produces ibross o e broncoar wa and narrowng o bronca umens. In some paens, nammaon aso causes Clncal Features. Cnca eaures var y dependng on e reave yperresponsveness o e bronca smoo musce, eadng o severy o e empysemaous and broncc canges. Wen empy- broncospasm. sema s promnen, dyspnea s e irs sympom. I begns nsdousy Proteases reeased rom neurops are oug o ave a cenra and s seady progressve. e cassc presenaon o empysemaous roe n e empysemaous canges a accompany COPD. s COPD s one n wc e paen s barre-cesed and dyspnec, w dea s based n par on e predsposon o paens w a genec obvousy proonged expraon, sng or ward n a unced-over deicency o α1-anr ypsn o deveop empysema. α1-anr ypsn poson. Hyper venaon manans adequae gas excange and bood s an nbor o proeases (e.g., easase, wc dgess easc ibers) gas vaues are reavey norma un ae n e course. In paens n a are secreed by neurops. Mos α1-anr ypsn–deicen wom cronc broncs w or wou broncospasm domnaes, Table 10.1 Disorders Associated with Airflow Obstruction: The Spectrum of Chronic Obstructive Pulmonary Disease Clinical Entity Anatomic Site Major Pathologic Changes Etiology Signs/Symptoms Chronic bronchitis Bronchus Mucous gland hypertrophy and hyperpla- Tobacco smoke, air pollutants Cough, sputum pro- sia, hypersecretion duction Emphysema Acinus Air space enlargement, wall destruction Tobacco smoke Dyspnea Asthma Bronchus Smooth muscle hypertrophy and hyper- Immunologic or undefined Episodic wheezing, plasia, excessive mucus, inflammation causes cough, dyspnea Bronchiectasis Bronchus Airway dilation and scarring Persistent or severe infections Cough, purulent spu- tum, fever CHAPTER 10 Lung and Upper Respiratory Tract 165.e1 Supplemental eFig. 10.1 Pulmonary emphysema. There is marked enlargement of the air spaces, with destruction of alveolar septa but without fibrosis. Note the presence of black anthracotic pigment. Supplemental eFig. 10.2 Chronic bronchitis. The lumen of the bron- chus is at the top. Note the marked thickening of the mucous gland layer (approximately twice-normal) and squamous metaplasia of lung epithelium. (From the Teaching Collection of the Department of Pathol- ogy, University of Texas, Southwestern Medical School, Dallas.) 166 CHAPTER 10 Lung and Upper Respiratory Tract Pathogeness. Facors conrbung o e deveopmen o asma ncude a genec predsposon o ype I ypersensvy (aopy), acue Alveolus and cronc arway nammaon, and bronca yperresponsveness o a varey o smu. Asma may be subcassied as aopc (evdence o aergen senszaon) or nonaopc (no evdence o ype I ypersensv- NORMAL ACINUS y). In bo ypes, broncospasm may be rggered by dverse exposures, Respiratory ncudng aergens, respraor y necons (especay vra necons), Alveolar bronchiole duct arborne rrans (e.g., smoke, umes), cod ar, sress, and exercse. Aop c as ma s e mo s c om mon yp e and s an e x amp e o an Ig E - me d ae d yp e I y p e rs e ns v y re a c on (F g. 10.4). I usu - a y b e g ns n c d o o d. A e c e d c d re n d e ve op yp e 2 ep e r T- c e (T2) re sp ons e s o v ar ous a e rge ns pre s e n n dus , p o e n , an ma d and e r, or o o d. Cy ok ne s pro du c e d by T2 T c e s a c c ou n or mo s o e e au re s : I L- 4 and I L- 1 3 s mu ae Ig E pro du c on , I L- 5 a c v ae s e o s nop s , and I L- 1 3 a s o s mu ae s mu c ous pro- du c on. Ig E b nds o submu c o s a mas c e s , w c on e x p o su re o A Alveolus a e rge ns re e as e e r g r anu e c one n s and s e c re e c y ok ne s and Respiratory o e r me d aors. Mas c e – d e r ve d me d aors pro du c e wo w ave s Alveolar bronchiole o re a c on : duct e eary-pase reacton s domnaed by broncoconsrcon, mucous producon, and vasodaon. Broncoconsrcon s rg- gered by medaors reeased rom mas ces (samne, prosagan- C dns, and eukorenes) and aso by reex neura paways. e ate-pase reacton s arbued o cemoknes (ncudng Panacinar emphysema B eoaxn, a poen cemoaracan and acvaor o eosnops) reeased by ces suc as epea ces a promoe e recru- Centriacinar emphysema men o 2 ces, eosnops, and oer eukocyes, ampyng an Fig. 10.3 Major patterns of emphysema. (A) Diagram of normal struc- nammaor y reacon a s naed by resden mmune ces. ture of the acinus, the fundamental unit of the lung. (B) Centriacinar Nonaopc asma s no assocaed w aergen senszaon; a pos- emphysema with dilation that initially affects the respiratory bronchi- ve amy sor y o asma s ess common. Respraor y necons due oles. (C) Panacinar emphysema with initial distention of all the periph- eral structures (i.e., the alveolus and alveolar duct); the disease later o vruses (e.g., rnovrus, paranuenza vrus) and naed ar pou- extends to affect the respiratory bronchioles. ans (e.g., suur doxde, ozone, nrogen doxde) are common rggers, bu exposures o cod ar or exercse may aso rgger an aack. Aoug e mecansms o non-aopc asma are no we undersood, mas ce coug and weezng are common na compans. For uncear rea- acvaon s common o bo aopc and nonaopc varans. sons, dyspnea s ess promnen, and ese paens end o rean car- bon doxde, becomng ypoxc and oten cyanoc. In mos paens Morphology. Bronc and broncoes are occuded by ck, w COPD, sympoms a beween ese wo exremes. Pumonar y enacous mucus pugs conanng wors o sed epeum uncon ess revea reduced FEV , a norma or near-norma FVC, and 1 (Curscmann spras). Numerous eosnops and Carco-Leyden a reduced FEV -o-FVC rao 1 crysas (crysaods made o gaecn-10, a proen derved rom e erapeuc approac ncudes smokng cessaon programs eosnops) aso are presen. Oer caracersc morpoogc (o sow e decne n pumonar y uncon), vaccnaon agans canges, coecvey caed arway remodeng, ncude ckenng o nuenza and pneumococcus (o preven acue exacerbaons due o e arway wa, submucosa ibross, ncreased submucosa vascuary, necon), broncodaors (o couner nammaon-nduced bron- an ncrease n e sze o submucosa gands, gobe ce meapasa, and cospasm), and annammaor y agens suc as corcoserods. yperropy o bronca smoo musce (Suppemena eFg. 10.3) Hypoxa-nduced pumonar y vascuar spasm and oss o pumonar y capar y surace area rom aveoar desrucon cause e gradua deveopmen o secondar y pumonar y yperenson, wc n 20% Clncal Features. An asma aack eads o severe dyspnea and o 30% o paens eads o rg-sded congesve ear aure (cor weezng due o broncoconsrcon and mucous puggng, produc- pumonae; see Caper 8). C ommon causes o dea n paens ng ar-rappng n dsa ar spaces and progressve ypernaon o w COPD ncude ear aure, pneumona, and pumonar y e ungs. Aacks usuay as rom 1 our o severa ours and subsde romboembosm. sponaneousy or w erapy. Iner vas beween aacks are carac- erscay asympomac, bu sube perssen deics can be deeced Asthma by pumonar y uncon ess. e usua erapeuc approac nvoves Asthma is a chronic inammatory disorder that causes episodic avodance o rrans and aergens and e use o annammaor y bronchospasm associated with airway obstruction. drugs (parcuary corcoserods) and broncodaors. Newer era- Asma s a common dsorder a as ncreased n ncdence n pes or aopc asma ncude an-IgE anbody and anbodes agans e Wesern word over e pas 4 decades. One proposed expanaon 2 cyoknes or er recepors. In mos cases, asma s dsabng bu or s rend s e ygene ypoess, accordng o wc a ack o no ea. However, occasonay a severe paroxysm occurs a does exposure o envronmena angens, parcuary mcroorgansms, n no respond o erapy and persss or days and even weeks (status eary cdood resus n deecs n mmune oerance and subsequen astmatcus), resung n ypercapna, acdoss, and severe ypoxa yperreacvy o mmune smu aer n e. a may prove aa. CHAPTER 10 Lung and Upper Respiratory Tract 166.e1 Supplemental eFig. 10.3 Bronchus from an asthmatic patient showing goblet cell hyperplasia (green arrow), subbasement membrane fibrosis (white arrow), eosinophilic inflammation (yellow arrow), and muscle hyper- trophy (blue arrow). CHAPTER 10 Lung and Upper Respiratory Tract 167 A NORMAL AIRWAY C TRIGGERING OF ASTHMA Mucus Goblet cell T cell T 2 Pollen h Epithelium receptor cell Basement T 2 H membrane IgE Lamina IL-4 B cell propria Antigen Smooth (allergen) B muscle Dendritic IL-5 Glands cell Cartilage IgE antibody Eotaxin Mucosal IgE Fc lining receptor Eosinophil recruitment Goblet cell Mast cell Activation Release of granules and mediators Antigen Mucosal lining Mucus Mucus B AIRWAY IN ASTHMA Mucus Goblet cell Eosinophil Basement membrane Major basic Vagal afferent nerve protein Macro- Eosinophil phage Mast cell T 2 h cationic protein Smooth muscle Glands T 2 h Eosinophil Increased vascular permeability Basophil Eosinophil and edema T 2 h Mast cell Eosinophil Neutrophil Lymphocyte Smooth Vagal efferent nerve Neutrophil muscle D IMMEDIATE PHASE (MINUTES) E LATE PHASE (HOURS) Fig. 10.4 (A and B) Comparison of a normal airway and an airway involved by asthma. The asthmatic airway is marked by accumulation of mucus in the bronchial lumen secondary to an increase in the number of mucous-secreting goblet cells in the mucosa and hypertrophy of submucosal glands; chronic inflammation marked by the presence of eosinophils, macrophages, and other inflammatory cells; a thickened basement membrane; and hypertrophy and hyperplasia of smooth muscle cells. (C) In the atopic form, inhaled aller- gens elicit a Th2-dominated response favoring IgE production and eosinophil recruitment. (D) On reexposure to antigen, the binding of antigen to IgE on Fc receptors triggers mast cell activation. Mast cells release preformed mediators that directly and via neuronal reflexes induce bronchospasm and increase vascular permeability, mucous production, and recruitment of leukocytes. (E) Recruited leukocytes release additional mediators that initiate the late phase of an asthma “attack.” Factor released from eosinophils also causes damage to the epithelium. 168 CHAPTER 10 Lung and Upper Respiratory Tract Clncal Features. Broncecass s caracerzed by a severe coug Bronchiectasis and expecoraon o mucopuruen spuum, somemes assocaed Bronchiectasis is the permanent dilation of bronchi and bron- w dyspnea and emopyss. Sympoms oten are epsodc and may chioles caused by destruction of smooth muscle and supporting be precpaed by upper respraor y rac necons or supernecon elastic tissue; it typically results from or is associated with chronic by new paogenc agens. Severe dsease may ead o obsrucve ven- necrotizing infections. aor y deecs, ypoxema, ypercapna, pumonar y yperenson, and cor pumonae. Treamen ncudes e use o anbocs (o preven Pathogeness. Eer cronc obsrucon or cronc necon may and o rea dsease ares), mucoyc agens (o ep cear secreons), nae e deveopmen o broncecass. Obsrucon, wc may and surger y (or ocazed dsease). be due o umors, oregn bodes, or mucous mpacon (as n cysc ibross; see Caper 6), mpars e cearance o secreons, provdng a avorabe envronmen or supermposed necon. e resuan RESTRICTIVE LUNG DISEASES nammaor y damage o e bronca wa and e accumuang exu- Resrcve ung dseases are a eerogeneous group o dsorders car- dae urer dsend e ar ways, eadng o rreversbe daon. Con- acerzed by baera pumonar y ibross and var yng degrees o nam- versey, a perssen necrozng bacera necon n e bronc or maon. ey are subcassied based on cncopaoogc eaures broncoes may ead o poor cearance o secreons, obsrucon, and (Tabe 10.2), bu ere s consderabe overap among some o ese nammaon w perbronca ibross and racon on e bronc, condons. e amark o ese dsorders s reduced compance cumnang agan n broncecass. Suc necons are more com- (sf ungs), necessang an ncreased efor o breae (dyspnea), and mon n ose w mmunodeicency saes or rare nered dsorders damage o e aveoar epeum and nersa vascuaure, eadng (prmar y car y dysknesa, aso caed e mmoe ca syndrome) o an abnorma venaon–peruson rao and ypoxa. Forced va a mpar car y uncon and mucocar y cearance o e ar ways. capacy (FVC), wc s a reecon o oa ung voume, s decreased. Ces radograps sow sma nodues, rreguar nes, or “ground- Morphology. Broncecass usuay afecs e ower obes, parcuary gass sadows. ” W progresson, paens may deveop respraor y ar passages a are vercay agned. Wen caused by umors or aure, pumonar y yperenson, and cor pumonae (see Caper 8). oregn bodes, may be ocazed o a snge ung segmen. Afeced A advanced sages, e eoog y o e underyng dsease may be d- arways are markedy daed (Fg. 10.5) and sow nense acue and icu o deermne because o dfuse scarrng and desrucon o e cronc nammaon n e was o e bronc and broncoes ung (end-sage or “oneycomb” ung) assocaed w desquamaon o e nng epeum and areas o uceraon. Many dferen bacera speces, ncudng aerobes and Fibrosing Diseases anaerobes, may be nvoved. In some nsances, e necross desroys Idiopathic Pulmonary Fibrosis e bronca or broncoar was, producng an abscess cavy. Idiopathic pulmonary brosis is a progressive disorder of unknown etiology characterized by patchy, progressive bilateral interstitial brosis that usually leads to “end-stage” lung and respiratory failure. Pathogeness. e nersa ibross s beeved o resu rom repeaed njury and deecve repar o aveoar epeum (Fg. 10.6). e cear- es eoogc cues come rom genec sudes. Germne oss-o-uncon muaons n eomerase are assocaed w ncreased rsk, suggesng a ceuar senescence conrbues o a proibroc penoype. Oer afeced ndvduas ave a genec varan a aers e producon Table 10.2 Categories of Chronic Interstitial Lung Disease Fibrosing Diseases Usual interstitial pneumonia (idiopathic pulmonary fibrosis) Nonspecific interstitial pneumonia Cryptogenic organizing pneumonia Collagen vascular disease–associated Pneumoconiosis Therapy-associated (drugs, radiation) Granulomatous Diseases Sarcoidosis Hypersensitivity pneumonia Eosinophilic Diseases Loeffler syndrome Drug allergy–related Idiopathic chronic eosinophilic pneumonia Fig. 10.5 Bronchiectasis in a patient with cystic fibrosis who under- Smoking-Related Diseases went lung resection for transplantation. The cut surface of the lung Desquamative interstitial pneumonia shows markedly dilated bronchi filled with purulent mucus that extend Respiratory bronchiolitis to subpleural regions.
