Robbins Essential Pathology PDF, Chapter 10: Lung and Upper Respiratory Tract

CHAPTER 10 Lung and Upper Respiratory Tract 165 dsease...

CHAPTER 10 Lung and Upper Respiratory Tract 165 dsease (COPD). We w ins by dscussng asma, a reversbe orm ndvduas deveop empysema, wc occurs a an earer age and o obsrucve ar way dsease, and broncecass, an obsrucve dsor- s o greaer severy  e ndvdua smokes. Sma ar ways are nor- der w dsncve cncopaoogc eaures. may ed open by e easc reco o e ung parencyma. e oss o easc ssue n e was o aveo a surround respra- Chronic Obstructive Pulmonary Disease or y broncoes reduces rada racon, eadng o coapse o e Chronic obstructive pulmonary disease is characterized by obstruc- respraor y broncoes durng expraon and uncona arow 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 obsrucon. nox ious particles or g a s es , mo s t o ften d ue to smoking tobacco.    Mcroba nfecton s oten presen bu as a secondar y roe, cey C ronc obs r uc  ve pu monar y ds e as e (C OPD) a e c  s more by mananng nammaon and exacerbang sympoms.  an 5% o  e adu s n  e Un e d S aes, 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  empys emaous and bronc   c canges c ancer. Ar  ow m  a  on s c aus e d by a comb na  on o me can - are s e en n mos c as es. T e c ass    c a on o e mpys emaous c a  obs r uc  on o a r w ays by mucous s e c re  ons and  bros s cange n C OPD and o er s e  ng s s b as e d on  e mac ros c op c (cronc bronct s) and  unc  ona  obs r uc   on due o p arency ma  app e arance o  e ung (Fg. 10.3). Te mos common p aer n des r uc  on (empys ema), b o  n resp ons e o cron  c  n   am ma- n smokers s centr acnar empy s e ma , w c preeren  a  y  on. C ronc bronc s s d e  ne d by  e pres enc e o a p e rs sen a e c s  e er mna  resp raor y bronc oe. Te  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. Empy s ema s d e  ne d by  e pres enc e o en  arge d p ar  c u  ary n  e ap c a  s eg me n s. Hsoog c exam  na  on ar sp aces ds a  o  e er m na  bronc  oes 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 ar sp ac e a ve o ar wa  s. en  argemen, w  ou over   bross (Suppemen a  eFg. 10. 1). Ter mna  and resp raor y bronc oes a s o may be d eor me d Pathogeness. Inaed obacco smoke and oer noxous parces n- b e c aus e o  e oss o s e p a  a ep e er  es e s r uc ure s ae severa processes a resu n parencyma desrucon (empy- n  e p arency ma. Panac nar empys e ma s usu a  y s e en n sema) and ar way dsease (broncos and cronc broncs).  e s e ng o α1-an  r ypsn de c enc y and re su  s n g re aer Facors a nuence e deveopmen and severy o cronc bron- exp anson o ung voume  an do es ce n r  ac nar empys ema. cs and empysema ncude e oowng: Panacnar empys ema ends o o cc ur more c om mon y n  e    Inaaton of noxous partces. Tobacco smoke conans numerous ower zones and n  e aner  or marg  ns o  e ung;  s usu a  y oxc subsances and carcnogens a damage ces drecy and mos s e vere a  e b as es. nduce deeerous reacve canges, suc as yperropy o mucous e broncc componen o COPD s marked by yperema gands n e racea and bronc and an ncrease n mucn-secre- o e bronca and racea mucosa and excessve mucnous or ng gobe ces n e epea suraces o smaer bronc and mucopuruen secreons. e mos caracersc mcroscopc broncoes. eaure s e enargemen o mucous-secreng gands (Sup-    Inlammaton. C e njur y caused by oxc efecs o naed agens pemena eFg. 10.2). Varabe numbers o nammaor y ces, nduces e producon o nammaor y medaors (ncudng ncudng ympoc yes, macropages, and neurops, are seen eukorenes, nereukn-8 [IL-8], umor necross acor [TNF], n e bronca mucosa. and oers) a recru eukoc yes rom e crcuaon, amp-  yng e nammaor y process. e resung cronc nam- maon produces ibross o e broncoar wa and narrowng o bronca umens. In some paens, nammaon aso causes Clncal Features. Cnca eaures var y dependng on e reave yperresponsveness o e bronca smoo musce, eadng o severy o e empysemaous and broncc canges. Wen empy- broncospasm. sema s promnen, dyspnea s e irs sympom. I begns nsdousy    Proteases reeased rom neurops are oug o ave a cenra and s seady progressve. e cassc presenaon o empysemaous roe n e empysemaous canges a accompany COPD. s COPD s one n wc e paen s barre-cesed and dyspnec, w dea s based n par on e predsposon o paens w a genec obvousy proonged expraon, sng or ward n a unced-over deicency o α1-anr ypsn o deveop empysema. α1-anr ypsn poson. Hyper venaon manans adequae gas excange and bood s an nbor o proeases (e.g., easase, wc dgess easc ibers) gas vaues are reavey norma un ae n e course. In paens n a are secreed by neurops. Mos α1-anr ypsn–deicen wom cronc broncs w or wou broncospasm domnaes, 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 Pathogeness. Facors conrbung o e deveopmen o asma ncude a genec predsposon o ype I ypersensvy (aopy), acue Alveolus and cronc arway nammaon, and bronca yperresponsveness o a varey o smu. Asma may be subcassied as aopc (evdence o aergen senszaon) or nonaopc (no evdence o ype I ypersensv- NORMAL ACINUS y). In bo ypes, broncospasm may be rggered by dverse exposures, Respiratory ncudng aergens, respraor y necons (especay vra necons), Alveolar bronchiole duct arborne rrans (e.g., smoke, umes), cod ar, sress, and exercse. Aop 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  ae 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 ep e r T- c e  (T2) 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 T2 T c e s a c c ou n or mo s o  e e au re s : I L- 4 and I L- 1 3 s  mu  ae Ig E pro du c   on , I L- 5 a c  v ae s e o s  nop  s , and I L- 1 3 a s o s  mu  ae 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 one n s and s e c re e c y ok  ne s and Respiratory o e r me d  aors. Mas c e  – d e r ve d me d  aors pro du c e  wo w ave s Alveolar bronchiole o re a c   on : duct    e eary-pase reacton s domnaed by broncoconsrcon, mucous producon, and vasodaon. Broncoconsrcon s rg- gered by medaors reeased rom mas ces (samne, prosagan- C dns, and eukorenes) and aso by reex neura paways.    e ate-pase reacton s arbued o cemoknes (ncudng Panacinar emphysema B eoaxn, a poen cemoaracan and acvaor o eosnops) reeased by ces suc as epea ces a promoe e recru- Centriacinar emphysema men o 2 ces, eosnops, and oer eukocyes, ampyng an Fig. 10.3 Major patterns of emphysema. (A) Diagram of normal struc- nammaor y reacon a s naed by resden mmune ces. ture of the acinus, the fundamental unit of the lung. (B) Centriacinar Nonaopc asma s no assocaed w aergen senszaon; a pos- emphysema with dilation that initially affects the respiratory bronchi- ve amy sor y o asma s ess common. Respraor y necons 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 vruses (e.g., rnovrus, paranuenza vrus) and naed ar pou- extends to affect the respiratory bronchioles. ans (e.g., suur doxde, ozone, nrogen doxde) are common rggers, bu exposures o cod ar or exercse may aso rgger an aack. Aoug e mecansms o non-aopc asma are no we undersood, mas ce coug and weezng are common na compans. For uncear rea- acvaon s common o bo aopc and nonaopc varans. sons, dyspnea s ess promnen, and ese paens end o rean car- bon doxde, becomng ypoxc and oten cyanoc. In mos paens Morphology. Bronc and broncoes are occuded by ck, w COPD, sympoms a beween ese wo exremes. Pumonar y enacous mucus pugs conanng wors o sed epeum uncon ess revea reduced FEV , a norma or near-norma FVC, and 1 (Curscmann spras). Numerous eosnops and Carco-Leyden a reduced FEV -o-FVC rao 1 crysas (crysaods made o gaecn-10, a proen derved rom e erapeuc approac ncudes smokng cessaon programs eosnops) aso are presen. Oer caracersc morpoogc (o sow e decne n pumonar y uncon), vaccnaon agans canges, coecvey caed arway remodeng, ncude ckenng o nuenza and pneumococcus (o preven acue exacerbaons due o e arway wa, submucosa ibross, ncreased submucosa vascuary, necon), broncodaors (o couner nammaon-nduced bron- an ncrease n e sze o submucosa gands, gobe ce meapasa, and cospasm), and annammaor y agens suc as corcoserods. yperropy o bronca smoo musce (Suppemena eFg. 10.3) Hypoxa-nduced pumonar y vascuar spasm and oss o pumonar y capar y surace area  rom aveoar desrucon cause e gradua deveopmen o secondar y pumonar y yperenson, wc n 20% Clncal Features. An asma aack eads o severe dyspnea and o 30% o paens eads o rg-sded congesve ear aure (cor weezng due o broncoconsrcon and mucous puggng, produc- pumonae; see Caper 8). C ommon causes o dea n paens ng ar-rappng n dsa ar spaces and progressve ypernaon o w COPD ncude ear  aure, pneumona, and pumonar y e ungs. Aacks usuay as rom 1 our o severa ours and subsde romboembosm. sponaneousy or w erapy. Iner vas beween aacks are carac- erscay asympomac, bu sube perssen deics can be deeced Asthma by pumonar y uncon ess. e usua erapeuc approac nvoves Asthma is a chronic inammatory disorder that causes episodic avodance o rrans and aergens and e use o annammaor y bronchospasm associated with airway obstruction. drugs (parcuary corcoserods) and broncodaors. Newer era- Asma s a common dsorder a as ncreased n ncdence n pes or aopc asma ncude an-IgE anbody and anbodes agans e Wesern word over e pas 4 decades. One proposed expanaon 2 cyoknes or er recepors. In mos cases, asma s dsabng bu or s rend s e ygene ypoess, accordng o wc a ack o no ea. However, occasonay a severe paroxysm occurs a does exposure o envronmena angens, parcuary mcroorgansms, n no respond o erapy and persss or days and even weeks (status eary cdood resus n deecs n mmune oerance and subsequen astmatcus), resung n ypercapna, acdoss, and severe ypoxa yperreacvy o mmune smu aer n e. a may prove aa.  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 Clncal Features. Broncecass s caracerzed by a severe coug Bronchiectasis and expecoraon o mucopuruen spuum, somemes assocaed Bronchiectasis is the permanent dilation of bronchi and bron- w dyspnea and emopyss. Sympoms oten are epsodc and may chioles caused by destruction of smooth muscle and supporting be precpaed by upper respraor y rac necons or supernecon elastic tissue; it typically results from or is associated with chronic by new paogenc agens. Severe dsease may ead o obsrucve ven- necrotizing infections. aor y deecs, ypoxema, ypercapna, pumonar y yperenson, and cor pumonae. Treamen ncudes e use o anbocs (o preven Pathogeness. Eer cronc obsrucon or cronc necon may and o rea dsease ares), mucoyc agens (o ep cear secreons), nae e deveopmen o broncecass. Obsrucon, wc may and surger y (or ocazed dsease). be due o umors, oregn bodes, or mucous mpacon (as n cysc ibross; see Caper 6), mpars e cearance o secreons, provdng a avorabe envronmen or supermposed necon. e resuan RESTRICTIVE LUNG DISEASES nammaor y damage o e bronca wa and e accumuang exu- Resrcve ung dseases are a eerogeneous group o dsorders car- dae urer dsend e ar ways, eadng o rreversbe daon. Con- acerzed by baera pumonar y ibross and var yng degrees o nam- versey, a perssen necrozng bacera necon n e bronc or maon. ey are subcassied based on cncopaoogc eaures broncoes may ead o poor cearance o secreons, obsrucon, and (Tabe 10.2), bu ere s consderabe overap among some o ese nammaon w perbronca ibross and racon on e bronc, condons. e amark o ese dsorders s reduced compance cumnang agan n broncecass. Suc necons are more com- (sf ungs), necessang an ncreased efor o breae (dyspnea), and mon n ose w mmunodeicency saes or rare nered dsorders damage o e aveoar epeum and nersa vascuaure, eadng (prmar y car y dysknesa, aso caed e mmoe ca syndrome) o an abnorma venaon–peruson rao and ypoxa. Forced va a mpar car y uncon and mucocar y cearance o e ar ways. capacy (FVC), wc s a reecon o oa ung voume, s decreased. Ces radograps sow sma nodues, rreguar nes, or “ground- Morphology. Broncecass usuay afecs e ower obes, parcuary gass sadows. ” W progresson, paens may deveop respraor y ar passages a are vercay agned. Wen caused by umors or aure, pumonar y yperenson, and cor pumonae (see Caper 8). oregn bodes,  may be ocazed o a snge ung segmen. Afeced A advanced sages, e eoog y o e underyng dsease may be d- arways are markedy daed (Fg. 10.5) and sow nense acue and icu o deermne because o dfuse scarrng and desrucon o e cronc nammaon n e was o e bronc and broncoes ung (end-sage or “oneycomb” ung) assocaed w desquamaon o e nng epeum and areas o uceraon. Many dferen bacera speces, ncudng aerobes and Fibrosing Diseases anaerobes, may be nvoved. In some nsances, e necross desroys Idiopathic Pulmonary Fibrosis e bronca or broncoar was, producng an abscess cavy. 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. Pathogeness. e nersa ibross s beeved o resu rom repeaed njury and deecve repar o aveoar epeum (Fg. 10.6). e cear- es eoogc cues come rom genec sudes. Germne oss-o-uncon muaons n eomerase are assocaed w ncreased rsk, suggesng a ceuar senescence conrbues o a proibroc penoype. Oer afeced ndvduas ave a genec varan a aers e producon 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.