Robbins Essential Pathology Lung and Upper Respiratory Tract PDF
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This chapter from the book "Robbins Essential Pathology" focuses on the Lung and Upper Respiratory Tract, including pathogenesis, morphology, clinical features of malignant mesothelioma, and nasopharyngeal carcinoma. It provides detailed information on the diseases.
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CHAPTER 10 Lung and Upper Respiratory Tract 185 Pathogeness. Once nae...
CHAPTER 10 Lung and Upper Respiratory Tract 185 Pathogeness. Once naed, asbesos ibers reman n e body or e, Clncal Features. Magnan mesoeoma s a ea umor. e and e eme rsk ater exposure does no dmns over me. Asbes- medan sur vva s ess an 1 year n unreaed paens and ony os occurs n wo dsnc geomerc orms, ser pentne and ampboe sgy greaer n reaed paens. Because e umor encases e (needeke). Ampboes are more paogenc an serpenne orms, ung, surgca resecon requres remova o e enre ung and peura peraps because e srag ibers agn w e arsream and are (exrapeura pneumonecomy). Combnaon cemoerapy exends devered more deepy no e ungs. I s ypoeszed a asbesos e, bu ony by a maer o mons. ibers preerenay accumuae n aveo a e perper y, near e Nasopharyngeal Carcinoma mesoea ce ayer, were ey nduce e producon o reacve oxygen speces a cause DNA damage and muaons. Sequencng o Nasopar yngea carcnoma s a rare neopasm a mers a bre mesoeoma genomes as reveaed mupe drver muaons, many commen because o s srong assocaon w Epsen-Barr vrus o wc cuser n paways nvoved n DNA repar, ce cyce conro, (EBV) and s g requency among e Cnese, rasng e possby and grow acor sgnang. One o e mos commony muaed genes o vra oncogeness on a background o genec suscepby. e EBV n sporadc mesoeoma, BAP1, encodes a umor suppressor nvoved genome s ound n vruay a nasopar yngea carcnomas, ncudng n DNA repar a aso s afeced by germne muaons n ames ose a occur ousde e endemc areas n Asa. I s oug w a g ncdence o mesoeoma. a EBV necs e os by irs repcang n e nasopar yngea epeum, and n some ndvduas, s may ead o ransormaon o e epea ces. e umor ypcay s composed o arge epea Morphology. Magnan mesoeomas are oten preceded by ces w ndsnc ce borders and promnen nuceo (Suppemena peura ibross and paque formaton, bo ready seen on magng. eFg. 10.17). ere oten s a srkng nux o nraumora T ces, Once esabsed, e umor spreads aong e peura wdey, eer wc are beeved o be respondng o vra angens. by conguous grow or by e dfuse seedng o peura suraces. Nasopar yngea carcnomas nvade ocay, spread o cer vca A auopsy, e afeced ung ypcay s encased n a ayer o yeow- ymp nodes, and en measasze o dsan ses. ey end o be we, irm umor a oberaes e peura space (Fg. 10.22). radosensve, and 5-year sur vva raes o 50% are repored even or e neopasm may be ocay nvasve, bu dsan measases are paens w cancers a ave spread ocay. ey aso are gy uncommon. Norma mesoea ces are bpasc, gvng rse responsve o mmune ceckpon nbors, provdng a new er- o peura nng ces, as we as e underyng ibrous ssue. In apeuc sraeg y or umors a do no respond o convenona ne w s poena, mesoeomas conorm o one o ree erapy. morpoogc appearances: (1) epea; (2) sarcomaous, n wc Carcinoma of the Larynx spnded, occasonay ibrobasc-appearng ces grow n sees; and (3) bpasc, avng bo sarcomaous and epea areas. Nearly all cases of laryngeal carcinoma occur in smokers. Carcnoma o e ar ynx represens ony 2% o a cancers. I mos commony occurs ater 40 years o age and s more common n men an n women. In addon o smokng, acoo consumpon and asbesos exposure are assocaed w ncreased rsk. Human papo- mavrus (HPV) genomes are presen n abou 15% o umors, and ese umors ave a beer prognoss an ose a are HPV-negave. Mos ar yngea cancers are ypca squamous ce carcnomas. Carcnoma o e ar ynx maness cncay w perssen oarseness. e ocaon o e umor wn e ar ynx as a sgni- can bearng on e prognoss. Goc umors are oten sympomac eary n er course due o efecs on speec, and spread beyond e ar ynx s uncommon. In conras, e supragoc ar ynx s rc n ympac spaces, and neary one rd o ese umors measasze o regona (cer vca) ymp nodes, and subgoc umors end o pro- duce sympoms ony ater ey ave spread. W surger y, radaon erapy, or combnaon reamen, many paens can be cured, bu abou one rd de o e dsease. e usua cause o dea s wde- spread measases and cacexa, somemes compcaed by pumo- nar y necon. Fig. 10.22 Malignant mesothelioma. Note the thick, firm, white pleural tumor that encases this bisected lung. CHAPTER 10 Lung and Upper Respiratory Tract 185.e1 Supplemental eFig. 10.17 Nasopharyngeal carcinoma, undifferenti- ated type. The syncytium-like clusters of epithelium are surrounded by lymphocytes. 11 Kidney O U T L I N E Overview of Renal Diseases, 186 Diseases of Tubules and Interstitium, 195 Diseases of Glomeruli, 187 Acute Pyelonephritis, 195 Mechanisms of Glomerular Injury, 187 Chronic Pyelonephritis, 196 Minimal Change Disease, 187 Drug-Induced Tubulointerstitial Nephritis, 197 Membranous Nephropathy, 187 Acute Tubular Injury, 197 Focal Segmental Glomerulosclerosis, 189 Cystic Diseases, 198 Membranoproliferative Glomerulonephritis, Diseases of Blood Vessels, 199 191 Nephrosclerosis, 199 C3 Glomerulopathies, 191 Malignant Hypertension, 199 Diabetic Nephropathy, 191 Thrombotic Microangiopathies, 199 Acute Poststreptococcal Glomerulonephritis, 192 Renal Stones (Urolithiasis), 201 Lupus Nephritis, 193 Hydronephrosis, 202 Rapidly Progressive Glomerulonephritis, 193 Tumors of the Kidney, 202 IgA Nephropathy, 194 Renal Cell Carcinoma, 202 Hereditary Nephritis, 194 Wilms Tumor, 203 Table 11.1 Glomerular Sy ndr ome s OVERVIEW OF RENAL DISEASES Syndrome Manifestations The majo r diseases of th e k i dn e y i n i ti a ll y involve o ne of the fo u r Nephritic syndrome Hematuria, azotemia, variable proteinuria, main structural ren a l co mp o n en ts , bu t in a ll d i s e a se s , a ll o th e r oliguria, edema, and hypertension components of the k i d n ey ma y be a ff e c t e d s e c o n da r i ly. Rapidly progressive Acute nephritis, proteinuria, and acute he our man srucura componens o e kdney are: glomerulonephritis renal failure Gomeru, uncona uns a er e bood, reanng macro- Nephrotic syndrome >3.5 gm/day proteinuria, hypoalbumin- moecues and ces and excreng soube maeras and lud (Sup- emia, hyperlipidemia, lipiduria pemena eFg. 11.1) Chronic renal failure Azotemia → uremia progressing for Tubues, wc conro e amoun o lud, ons, and sma moecues months to years a are excreed by reguang e reabsorpon o ese subsances he ntersttum, wc provdes e supporng scafod Isolated urinary Glomerular hematuria and/or subne- abnormalities phrotic proteinuria Bood vesses, wc dever arera bood o be ered and reurn venous bood o e crcuaon Acute kidney injury (not listed) is most often the result of diseases affecting tubules. R ena njur y c aus e d by d eren me cansms ends o preere n - a y a e c p ar c u ar s r u c u res ; or ex ampe, g omer u ar d s e as e s are o en mmunoog c a y me d ae d, w ere as ubu ar and ners - Rena faure s e oss o rena uncon. Acute rena faure s e cn- a ds orders are more key o be c aus e d by ox c or n e c ous ca sae a resus rom rapdy deveopng rena njury. I may pres- agens. We w ereore d s c uss ndv du a d s e as es by o c us ng on en w reduced or no urne oupu (ogura or anura, respecvey), e pr mar y se o rena nju r y, re c og n z ng a b e c aus e e com- yperenson, and oer sgns o rena dysuncon. Laboraory ess p onens o e k dne y are u nc ona y n ke d, as d s e as e adv anc e s revea an ncrease n bood urea nrogen (BUN) and serum creanne, a p ar s o e k dne y may be a e c e d. I s a s o mp or an o appre - coecvey ermed azotema. hese canges are caused by a reduced c ae a e k dne y as a arge u nc ona res er ve; us , e ary sg ns gomeruar raon rae (GFR), wc may resu rom nrnsc ds- o k dne y ds e as e are o en mss e d, and sub s an a d amage may eases o e kdney (e.g., gomeruar or ubuar dseases) or exrarena o cc ur b eore rena dy s unc on b e come s c n c a y app aren. causes (e.g., severe yperenson or emoyc-uremc syndrome). he Renal diseases manifest with different clinical syndromes (Table 11-1). causave abnormaes ousde e kdney may be prerena (reduced he naure o e syndrome oten provdes vauabe cues abou e lud voume and, ereore, reduced gomeruar peruson) or pos- underyng dagnoss and, ereore, e mos efecve erapy. he rena (obsrucon o e oulow rac). Wen e azoema s severe major rena syndromes a no severa broad caegores. enoug o cause cnca sgns and sympoms, e erm urema s used. 186 GLOMERULUS Capillary Urinary space loops Mesangium Mesangial cell Mesangial matrix Red cell Parietal epithelium Fenestrae in Proximal endothelium tubule Urinary space Capillary lumen Parietal epithelium Basement membrane Visceral epithelium Endothelium Foot processes Basement membrane Red blood cell B Foot processes Supplemental eFig. 11.1 Schematic representation of a lobe of a glomerulus. 186.e1 CHAPTER 11 Kidney 187 oer nsances, dependng on e makeup and anaomc ocaon Acute kdney njur y reers o abrup onse o azoema w o e deposs, ey may nsead dsrup e gomeruar permea- ogura or anura. I s mos oten caused by severe ubuar by barrer wou causng nlammaon (neproc syndrome). njur y (prevousy caed acute tubuar necross, or ATN), bu D eposton of ant-GBM antbody. Less requeny, anbodes bnd aso may resu rom acue, usuay severe, njur y o gomeru, o angens a are eveny dsrbued aong e GBM, resung n vesses, or e nersum. a near paern o mmunoluorescen sanng (e.g., Goodpasure Rapdy progressve gomeruoneprts (RPGN) s a dsnc syndrome). he subsequen njur y s caused by nlammaon rg- eny a aso can cause acue rena aure. gered by compemen and Fc recepor–dependen mecansms, as Neprotc syndrome as dverse causes a sare a common pao- n mmune compex dseases. pysoogy : a derangemen n e capary was o e gomeru a Oter mecansms of gomeruar njur y. Some dseases are caused resus n ncreased permeaby o pasma proens and proenura by deecve reguaon o compemen acvaon, resung n (urnary proen oss >3.5g/24 ours). he proen oss eads o ypo- unconroed deposon o pronlammaor y compemen producs abumnema, wc reduces e pasma cood osmoc pressure, n e gomeruus. In oer cases, epea ces (podocyes) a and e resung ransudaon o lud across sma bood vesses pro- ne e gomeruar capar y wa may be njured (e.g., by oxns or duces generazed edema. Hyperpdema s aso oten seen. here s unknown causes), or abnorma gomeruar permeaby may be e requeny reenon o sa and waer, wc exacerbaes e edema. resu o muaons n genes encodng proens o e s dapragm Neprtc syndrome s caused by nlammaory esons o e gomeru- (e raon membrane o e oo processes o e podocyes). us (ence e erm neprts), caracerzed by emaura, azoema, Podocyes are nmaey nvoved n mananng e barrer unc- and yperenson. I s seen n dseases n wc gomeruar nlamma- on o e GBM, and podocye abnormaes are a vruay unver- on s promnen. Proenura, presen, s modes. sa eaure o dseases assocaed w neproc syndrome. Cronc kdney dsease s caused by progressve scarrng o e kd- neys and oss o rena parencyma, evenuay resung n eecro- Minimal Change Disease ye and meaboc abnormaes. I s oten asympomac or a ong Minimal change disease is the most common cause of nephrotic me, un urema deveops, bu can be preceded by one o severa syndrome in children; its unique feature is the absence of glomer- cnca syndromes menoned above. I cumnaes n end-stage rena ular pathology by light microscopic evaluation. dsease, wc can be reaed ony by dayss or ranspanaon. Oter cnca manfestatons o kdney dsease ncude asympom- Pathogeness. here are no deposs o anbodes or mmune com- ac emaura. pexes n e gomeruus, and no nlammaon. B ecause o e eak- ness o e GBM o abumn, a permeaby-nducng crcuang acor s suspeced, bu aemps o deny s eusve cupr ave aed, DISEASES OF GLOMERULI and e paogeness o e dsease remans unknown. Saen eaures o e mos common prmar y gomeruar dseases are Morphology. he gomeru appear norma by g mcroscopy. summarzed n Tabe 11.2. Here we dscuss rs e genera meca- Eecron mcroscopc evauaon reveas dfuse efacemen o nsms o gomeruar njur y and en dseases a are requeny podocye oo processes (Fg. 11.2); s no known s s e encounered cncay or a usrae mporan prncpes o pao- cause or consequence o proenura. geness. As we sa see n s dscusson, paoogc anayss o rena bopses s oten e mansay o dagnoss. Clncal Features. he dsease ypcay presens w neproc syn- Mechanisms of Glomerular Injury drome n a prevousy eay cd, mos commony beween e ages Most glomerular diseases are immunological in origin, caused by o 1 and 7 years. Casscay, e proen oss s seecve, prmary o deposition of immune complexes or antibodies in the glomerular ow-moecuar-weg proens suc as abumn. he majory o paens capillary wall (Fig. 11.1). respond we o corcoserod erapy, bu proenura recurs n 60% o Immune compex deposton. Compexes o angen and anbody na responders, many o wom become serod dependen. In adus are usuay ormed n e crcuaon and are prone o depos n e response o serods s sower and reapses are more common. gomeru because o e g vascuar pressure a drves e - Membranous Nephropathy raon o pasma o orm urne, as we as e negave carge and permeaby caracerscs o e gomeruar basemen membrane Membranous nephropathy is caused by immune complex deposition (GBM), wc promoe e sabe aacmen o anbodes. Two in the glomerular capillary wall, resulting in the nephrotic syndrome. nonexcusve mecansms o anbody deposon n e gomer- uus ave been esabsed: (1) deposon o crcuang angen– Pathogeness. In e majory o cases, mmune compexes are ormed n anbody compexes n e gomeruar capar y wa or mesangum stu by auoanbodes bndng o endogenous podocye angens (e.g., pos- (e.g., n sysemc upus er yemaosus [SLE]), and (2) anbodes popase A2 recepor) or paned angens. hus, membranous neprop- reacng n su wn e gomeruus, eer w xed (nrnsc) ay s an auommune dsease, and, ke mos dseases n s group, s gomeruar angens or w exrnsc moecues a are paned eoogy s unknown. In up o 80% o cases, membranous nepropay s n e gomeruus. Wen anbody bndng s pacy (resembng prmary w no assocaed dsease; ess commony, s seen n assocaon deposon o crcuang compexes) s caed n stu mmune w oer we-dened auommune dseases, suc as SLE. I may aso be compex ormaon. Immune compex deposs are seen as granu- secondary o necons (e.g., maara, syps, and epas B) or umors ar areas conanng mmunogobun or compemen producs by (e.g., meanoma and carcnomas o e ung and coon), or may occur n mmunoluorescen sanng or as eecron-dense “umpy bumpy” paens akng erapeuc drugs (e.g., pencamne, capopr, nonsero- deposs on e GBM by eecron mcroscopy. Once mmune com- da annlammaory agens); a o ese condons may ec anbodes pexes are ormed n e gomeruus, ey may acvae e com- a may bnd o angens a are paned n e GBM. he ormaon o pemen sysem and recru eukocyes va compemen producs, subepea mmune deposs eads o compemen acvaon on e sur- as we as by Fc recepor bndng (see Caper 4), resung n oca ace o podocyes and generaes e membrane aack compex (C5 o C9). nlammaon (gomeruoneprs w neprc syndrome). In hs n urn causes podocye and GBM njury and proenura. 188 CHAPTER 11 Kidney Table 11.2 Summary of Major Primary Glomerular Diseases Glomerular Pathology Most Frequent Fluorescence Disease Clinical Presentation Pathogenesis Light Microscopy Microscopy Electron Microscopy Minimal change Nephrotic syndrome Unknown; permeability- Normal Negative Loss of foot processes; disease inducing factor? no deposits Membranous Nephrotic syndrome Deposition of immune Diffuse GBM thick- Granular deposits of IgG Subepithelial deposits nephropathy complexes; in most cases ening and C3; diffuse with interspersed of primary disease the spikes of GBM antigen is unknown material; loss of foot processes Diabetic Nephrotic syndrome Unclear; may include GBM thicken- Nonspecific GBM thickening nephropathy increased synthesis of ing, mesangial GBM material stimulated by sclerosis, nodular growth factors; glomerular deposits of matrix hyperfiltration because of material microvascular disease Focal segmen- Nephrotic syndrome, Unknown; podocyte injury, Focal and segmen- Focal IgM + C3 in some Effacement of podo- tal glomer- sometimes with glomerular hyperfiltration? tal sclerosis and cases, reflecting non- cyte foot processes ulosclerosis microscopic accumulation of specific trapping (FSGS) hematuria and matrix material hypertension (“hyaline”) Membranopro- Nephrotic/nephritic Immune complex deposition Proliferation of Granular deposits of IgG Subendothelial depos- liferative glo- syndrome mesangial and and C3 its merulonephri- epithelial cells; tis (MPGN GBM thickening; type I) splitting Dense deposit Nephrotic/nephritic Unregulated activation of Mesangial prolifer- C3; no IgG or C1q Ribbon-like elec- disease syndrome alternative pathway of ative or mem- tron-dense deposits complement because of branoproliferative in GBM autoantibody that binds to patterns of prolifer- and stabilizes C3 conver- ation; GBM thick- tase ening; splitting C3 glomerulo- Nephrotic/nephrotic Same as dense deposit Mesangial prolifer- C3; no IgG or C1q Mesangial and sub- nephritis syndrome disease ative or mem- endothelial elec- branoproliferative tron-dense “waxy” patterns of deposits proliferation Acute post- Nephritic syndrome Immune-complex mediated; Diffuse proliferation Granular deposits of IgG Primarily subepithelial streptococcal circulating or planted of endothelial and and C3 in GBM and humps; subendothe- glomerulone- antigen other glomerular mesangium lial deposits in early phritis cells; leukocytic disease stages infiltration Lupus nephritis Nephrotic or Immune-complex mediated, Variable; diffuse Granular deposits of IgG Subendothelial, subep- nephritic syn- circulating self-antigens proliferative GN and C3 in GBM and ithelial, or mesangial drome (mainly nuclear antigens) or primarily mem- mesangium deposits branous pattern Rapidly Nephritic syndrome, Anti-GBM antibodies Extracapillary prolif- Linear IgG and C3, Typically no deposits; progressive renal failure (Goodpasture syndrome), eration with cres- immune complexes, GBM disruptions; glomeru- immune complexes, (in cents; necrosis or negative in differ- fibrin lonephritis association with other dis- ent forms; fibrin in (RPGN) ease such as SLE) or “pau- crescents ci-immune” (sometimes with ANCA vasculitis) IgA nephrop- Recurrent hematuria Unknown Focal mesangial IgA ± IgG, IgM, and C3 Mesangial and athy or proteinuria proliferative in mesangium paramesangial dense glomerulonephri- deposits tis; mesangial widening Hereditary Proteinuria, hema- Mutation of the genes encod- Glomerulosclerosis No deposits Thinning and lamina- nephritis turia ing the α3, α4, or α5 chain tion of the basement of type IV collagen (Alport membrane syndrome) Diabetic nephropathy is discussed in Chapter 16. FSGS and membranous nephropathy are the most common causes of idiopathic nephrotic syndrome in adults. Their relative incidence varies in different population groups. ANCA, Antineutrophil cytoplasmic antibodies; GN, glomerulonephritis; GBM, glomerular basement membrane.
