糖尿病腎病的病理觀察 課件

1、糖尿病腎病的病理觀察NORMAL GLOMERULAR HISTOLOGYS3 - Normal glomerulusSl i de 3 N orm al gl om erul us: Hem atoxyl i n andeosi n st ai n of a norm al gl om erul us sect i onedt hrough the vascul ar pol e. N ot e the w i de-opencapi l l ary l um i na and the l arge percent age of thecross-secti onal area of the

2、 gl om erul us devot ed t ot he capi l l ary ci rcul at i on. The m esangi al cel l ul ari t yand m at ri x are norm al .NORMAL GLOMERULAR HISTOLOGYSl i de 5 N orm al gl om erul us: El ectronphotom i crograph i l l ustrati ng part of a norm al adul tgl om erul ar tuft w i th norm al gl om erul ar ba

3、sem entm em brane (w i dth 300-400 nm ), open capi l l aryl um i na, and del i cate m esangi al m atri x m ateri al .N ote erythrocytes w i thi n the capi l l ary l um en anddel i cate podocyti c foot processes of the vi scerall ayer of epi thel i al cel l s of Bow m an s capsul e.S5 - Normal glomer

4、ulusNORMAL GLOMERULAR HISTOLOGYSl i de 6 N orm al gl om erul us: El ect ronphot om i crograph show i ng a segm ent of acapi l l ary l oop w i t h endot hel i al cel l w i t hf enest rat i ons, l am i na rara i nt erna, m edi a andext erna of t he gl om erul ar basem ent m em brane,and epi t hel i al

5、 cel l f oot processes.S6 - Normal glomerulusNORMAL GLOMERULAR HISTOLOGYSl i de 1 N orm al gl om erul us: Schem at i zeddraw i ng of a norm al gl om erul us show i ng epi t hel i alcel l s i n green, endot hel i al cel l s i n yel l ow andm esangi al cel l s i n red. N ot e t hat t he gl om erul arb

6、asem ent m em branes (i n bl ack) do notcom pl et el y surround capi l l ary l oops, and t hatendot hel i al cel l s are i n di rect cont act w i t hm esangi al m at ri x (bl ue) at t he m esangi al pol esof capi l l ari es.NORMAL GLOMERULAR HISTOLOGYSl i de 2 N orm al gl om erul us: Schem ati zeddr

7、aw i ng of a si ngl e gl om erul ar capi l l ary l oop.N ote that the gl om erul ar basem ent m em branedoes not com pl etel y surround the capi l l ary,but spl ays out over the m esangi um as theparam esangi al basem ent m em brane.S2 - Normal glomerulus:DIABETIC NEPHROPATHYSl i de 165 Di abet i c

8、nephropat hy: Thi sschem at i zed draw i ng show s t he m arkedl yt hi ckened l am i na densa of t he GBM andi ncreased m esangi al m at ri x m at eri alw hi ch are t he si ne qua non of di abet i c renaldi sease. The subsequent sl i des (166-202)dem onst rat e t he spect rum of di abet i c renaldi

9、sease (st art i ng w i t h a revi ew of norm algl om erul ar hi st ol ogy), and i l l ust rat e di st i ngui shi ngpoi nt s bet w een ot her t ypes of gl om erul opat hi esw hi ch m ay m i m i c di abet i c nephropat hy.糖尿病腎?。耗I小球基底膜增厚伴系膜基質擴張DIABETIC NEPHROPATHYSl i de 166 Exam pl e of a norm al gl o

10、m erul ussect i oned t hrough t he vascul ar pol e (PAS). N ot et he w i de-open capi l l ary l um i na and t he l argepercent age of t he cross-sect i onal area of t hegl om erul us devot ed t o t he capi l l ary ci rcul at i on.The m esangi al cel l ul ari t y and m at ri x are norm al .S166 - Exa

11、mple of a normal glomerulus DIABETIC NEPHROPATHYS167 - Moderate diffuse diabetic glomerulosclerosisSl i de 167 M oderat e di f f use di abet i cgl om erul oscl erosi s i n an i nsul i n-dependentdi abet i c (I DDM ) pat i ent w i t h 16 years durat i on.N ot e t he w i deni ng of t he gl om erul ar

12、m esangi um ,t he rest ri ct i on of t he gl om erul ar capi l l aryci rcul at i on, t he t hi ckeni ng of t he gl om erul arbasem ent m em brane com pared t o sl i de 1, and t hehyal i nosi s of t he art eri ol ar w al l at t he vascul arpol e (PAS).彌漫性輕度糖尿病腎小球硬化：系膜區(qū)基質擴張，GBM增厚，毛細血管腔受壓，血管極小動脈壁增厚。該患者

13、已經(jīng)有16年的1型糖尿病病史，DIABETIC NEPHROPATHYSl i de 168 M arked di f f use di abet i cgl om erul oscl erosi s. There i s ext rem e expansi onof t he m esangi um w i t h bot h m at ri x and cel l ul arm at eri al . The capi l l ary l um enal ci rcul at i on i sm arkedl y const ri ct ed (PAS). W hereas t hepat

14、 i ent i n sl i de 2 had norm al renal f unct i on, t hi spat i ent had overt nephropat hy w i t h prot ei nuri a,hypert ensi on, and a 50% reduct i on i n GFR.S168 - Marked diffuse diabetic glomerulosclerosis. 彌漫、嚴重糖尿病腎小球硬化：系膜區(qū)基質及細胞顯著增加，毛細血管腔嚴重受壓；該患者腎小球濾過率下降50%，伴顯著蛋白尿、嚴重高血壓。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小

15、球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYS lid e 1 7 1 N o d u la r d ia b e tic g lo m e ru lo scle ro sis(K im m e lstie l-W ilso n le sio n s) in a p a tie n t w itho ve rt d ia b e tic n e p h ro p a th y a n d p ro te in u ria ,h yp e rte n sio n , a n d re d u ce d G FR .

16、 N o te th ep a lisa d in g o f m e sa n g ia l n u cle i a ro u n d th ep e rip h e ry o f th e n o d u le a n d th e fib rilla r n a tu reo f th e n o d u la r m a trix m a te ria l. N o te a lso th ere strictio n o f g lo m e ru la r ca p illa ry lu m e n a l sp a ce(P A S ).S171 - Nodular diabet

17、ic glomerulosclerosis (Kimmelstiel-Wilson lesions)結節(jié)性腎小球硬化K-W結節(jié)：伴蛋白尿、高血壓及腎小球濾過率下降。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYS172 - End stage nodular diabetic Sl i de 172 End-st age nodul ar di abet i cgl om erul oscl erosi s wi t h al m ost com pl et e ca

18、pi l l arycl osure and repl acem ent of t he gl om erul us byf i brous m at eri al (PAS).終末期糖尿病結節(jié)性腎小球硬化，絕大數(shù)腎小球毛細血管閉塞。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 173 Gl om erul ar scarri ng consequent t onodul e f orm at i on i l l ust rat ed by t he

19、 green st ai ni ngof Ki m m el st i el -W i l son l esi ons (t ri chrom e).Thi s I DDM pat i ent had severe recurrence ofdi abet i c nephropat hy by 11 years af t er renalt ranspl ant at i on f or di abet i c nephropat hy, a rat herunusual out com e of t ranspl ant at i on.S173 - Glomerular scarring

20、 consequent to nodule formation結節(jié)性腎小球硬化引起的腎小球纖維化。該患者腎移植該患者腎移植11年后糖尿病腎病復發(fā)。年后糖尿病腎病復發(fā)。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 197 Thi s i s the sam e pati ent as i n sl i de 32.Thi s gl om erul us dem onstrates obvi ous nodul ardi abeti c gl om eru

21、l oscl erosi s (PAS). The poi nt i nthi s and the previ ous sl i de i s that di abeti c l esi onsm ay devel op i n absol ute cl i ni cal si l ence andpati ents w i th norm al al bum i nuri a, GFR and bl oodpressure m ay w el l have advanced renal structuralabnorm al i ti es.S197 - This is the same p

22、atient as in slide 32. 結節(jié)性糖尿病腎小球硬化：DIABETIC NEPHROPATHYSl i de 178 A capsul ar drop consi st i ng of hyal i nePAS posi t i ve m at eri al deposi t ed on t he pari et alsurf ace of Bowm ans m em brane (9 ocl ock).S178 - A capsular drop consisting of hyaline 帽狀滴：透明PAS陽性物質沉積于腎小球囊之內側壁。DIABETIC NEPHROPAT

23、HYS179 - Formation of a capsular drop by adhesionSl i de 179 Form at i on of a capsul ar drop byadhesi on of gl om erul ar capi l l ary l oops cont ai ni ngsubendot hel i al hyal i ne (t he so-cal l ed “ exudat i vel esi on” ) t o Bowm ans capsul e (9 ocl ock and11 ocl ock). I t i s l i kel y t hat

24、t he gl om erul ar capi l l aryl oops ret ract , deposi t i ng t he hyal i ne m at eri al al ongt he Bowm ans capsul ar wal l .帽狀滴之形成：腎小球毛細血管袢滲出性物質內皮細胞下透明樣物質附著與腎小球囊之內側壁，然后腎小球收縮。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 180 Ext

25、r em el y l ar ge capsul ar dr op i n agl om er ul us whi ch al so dem onst r at es ar t er i ol arhyal i nosi s ( PAS) .S180 - Extremely large capsular drop 帽狀滴、小動脈透明樣變性。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 174 Earl y gl

26、om erul ar art eri ol ar hyal i nosi si n an af f erent art eri ol e. Not e t he sm oot h, waxy,hom ogenous PAS posi t i ve m at eri al i n t hesubendot hel i al space. Thi s I DDM pat i ent hadnorm al renal f unct i on.S174 - Early glomerular arteriolar hyalinosis 入球小動脈透明樣變性早期改變：內皮細胞下非細胞均質成份沉積，腎功能尚

27、正常。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 175 Advanced arteri ol ar hyal i nosi s w i thvi rtual com pl ete repl acem ent of the vessel w al l byhyal i ne w axy m ateri al (PAS).S175 - Advanced arteriolar hyalinosis蠟樣物質填充于小動脈壁，引起血管腔幾乎完全閉塞。1型糖尿病

28、型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 176 Art eri ol ar hyal i nosi s i n bot h af f erent(l ow er l ef t si de) and ef f erent (l ow er ri ght si de)gl om erul ar art eri ol es (PAS). N ot e t he di f f use andnodul ar di abet i c gl om erul oscl

29、erosi s i n t hi s I DDMpat i ent w i t h earl y overt nephropat hy.S176 - Arteriolar hyalinosis in both afferent (lower left side)入球小動脈與出球小動脈壁透明樣變，彌漫性糖尿病結節(jié)性腎小球硬化：型糖尿病引起的臨床糖尿病腎病之早期。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYS181 - Mild expansion of the int

30、erstitial spaceS lid e 1 8 1 Mild e x p a n s io n o f th e in te rs titia ls p a c e a n d tu b u la r b a s e me n t me mb ra n eth ic k e n in g w ith o u t tu b u la r a tro p h y (P A S ).T h is ID D M p a tie n t h a d n o rma l re n a l fu n c tio n .T h is mild d e g re e o f in te rs titia

31、l e x p a n s io n isc o mmo n in d ia b e tic p a tie n ts , e v e n th o s e w h o s eg lo me ru la r a n d v a s c u la r d is e a s e d o n o t p ro g re s s .間質間隙輕度擴張，伴腎小管基膜增厚，腎小管不萎縮：1型糖尿病患者，腎功能正常。一些不伴腎小球或腎小管損傷的糖尿病患者也可發(fā)生這種小管間質改變。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變

32、化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 182 M ore advanced t ubul ar i nt erst i t i aldi sease w i t h t ubul ar at rophy and i nt erst i t i alf i brosi s i ndi cat ed by t he green col or on t het ri chrom e st ai ni ng. Thi s I DDM pat i ent had m i l ddi f f use di abet i c gl om erul

33、oscl erosi s andm i croal bum i nuri a.S182 - More advanced tubular interstitial disease腎小管萎縮伴間質纖維化： 1型糖尿病伴輕度彌漫性腎小球硬化及微量白蛋白尿。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 196 Art eri ol ar hyal i nosi s, di f f use di abet i cgl om

34、 erul oscl erosi s, and earl y nodul argl om erul oscl erosi s i n an I DDM pat i ent w i t hnorm al renal f unct i on. Thi s pat i ent had norm aluri nary al bum i n excret i on, GFR, and bl oodpressure (PAS).S196 - Arteriolar hyalinosis, diffuse diabetic 小動脈透明樣變性、彌漫性糖尿病腎小球硬化、早期結節(jié)性腎小球硬化：1型糖尿病、血肌酐正常

35、、尿檢正常、GFR正常、血壓正常。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSlide 1 9 9 T his NIDDM pa t ie nt ha smic r oa lbuminur ia a nd mor e t y pic a l le s ions ofdia be t ic ne phr opa t hy inc luding dif f us e dia be t icglome r ulos c le r

36、os is , a r t e r iola r hy a linos is , a ndt ubuloint e r s t it ia l dis e a s e oc c ur r ing r oughly inpr opor t ion t o e a c h ot he r ( PAS) . Suc h pa t ie nt s wit hdia be t ic r e na l le s ions t y pic a l of t hos e s e e n inIDDM us ua lly ha v e r e t inopa t hy whic h, of t e n, iss

37、 e v e r e .S199 - This NIDDM patient has microalbuminuria 2型糖尿病患者型糖尿病患者，伴微量白蛋白尿及典型的糖尿病腎病病理改變：彌漫性糖尿病腎小球硬化、動脈透明樣變性、小管間質病變。糖尿病視網(wǎng)膜病變嚴重。2型糖尿病型糖尿病微量白蛋白尿伴顯微量白蛋白尿伴顯著腎臟病理改變。著腎臟病理改變。DIABETIC NEPHROPATHYSl i de 200 Thi s and t he subsequent t w o sl i desi l l ust rat e t he at ypi cal l esi ons com m onl y s

38、een i nm i croal bum i nuri c N I DDM pat i ent s. Som e of t hesepat i ent s, as i l l ust rat ed i n t hi s PAS sl i de, haveest abl i shed art eri ol ar hyal i nosi s l esi ons w i t h l i t t l eor no gl om erul ar or t ubul oi nt erst i t i al i nj ury.S200 - This and the subsequent two slides

39、2型糖尿病伴微量白蛋白尿：不典型腎臟改變不典型腎臟改變小動脈顯著透明樣變性，而腎小球以及腎間質改變不明顯。2型糖尿病型糖尿病微量白蛋白尿伴顯著腎微量白蛋白尿伴顯著腎臟病理改變。臟病理改變。小動脈小動脈-腎小球腎小球-小管間質小管間質病理改變不平行。病理改變不平行。DIABETIC NEPHROPATHYS lid e 2 0 2 T h is N ID D M p a tie n t w ithm ic ro a lb u m in u ria a n d h yp e rte n sio n sh o w s a re a so f a d va n c e d tu b u lo in t

40、e rstitia l in ju ry w ith o u tsig n ific a n t g lo m e ru lo p a th y o r va sc u lo p a th y. T h isa n d th e p re c e d in g tw o slid e s illu stra te th a tm ic ro a lb u m in u ric N ID D M p a tie n ts m a y h a ve re n a lle sio n s w h ic h a re n o t typ ic a l o f th o se se e n inID D

41、 M w h e re th e g lo m e ru la r, a rte rio la r,g lo m e ru lo sc le ro tic , a n d tu b u lo in te rstitia l le sio n ste n d to a d va n c e in p a ra lle l.P a tie n ts w ith th e p a tte rn s sh o w n in th e la st th re eslid e s te n d n o t to h a ve p ro life ra tive re tin o p a th ya n d

42、 , g e n e ra lly, a re m o re o b e se th a n N ID D Mp a tie n ts w ith typ ic a l d ia b e tic n e p h ro p a th y.H o w e ve r, p a tie n ts w ith th e se a typ ic a l p a tte rn s a lsoh a ve h ig h e r le ve ls o f h e m o g lo b in A 1 c th a nN ID D M p a tie n ts w ith o u t re n a l in ju

43、ry, su g g e stin gth a t th e se “ a typ ic a l” fo rm s o f in ju ry m a y a lso b ein flu e n c e d b y th e d ia b e tic sta te .S202 - This NIDDM patient with microalbuminuria 2型糖尿病伴微量白蛋白尿、高血壓：不典型腎臟改變不典型腎臟改變腎小球以及腎血管改變不明顯 ，腎間質改變顯著。2型糖尿病型糖尿病微量白蛋白尿伴顯著腎微量白蛋白尿伴顯著腎臟病理改變。臟病理改變。小動脈小動脈-腎小球腎小球-小管間質小管間質病理

44、改變不平行。病理改變不平行。DIABETIC NEPHROPATHYSl i de 185 El ectron photom i crograph i l l ustrati nga norm al gl om erul ar basem ent m em brane w i dth(bottom panel ) and di ffuse thi ckeni ng of thegl om erul ar basem ent m em brane consequent todi abetes (upper panel ). The basem ent m em branew i dth of t

45、he di abeti c pati ent show n here i s m orethan tw i ce norm al thi ckness.S185 - Electron photomicrograph illustrating 透射電子顯微鏡：正常/糖尿病引起的GBM增厚DIABETIC NEPHROPATHYS186 - Electron photomicrograph of an IDDM Sl i de 186 El ect ron phot om i crograph of an I DDMpat i ent w i t h est abl i shed renal l

46、esi ons. Despi t e t hei ncreased GBM w i dt h and m esangi al expansi on,especi al l y w i t h i ncreased m esangi al m at ri xm at eri al , t hi s pat i ent had norm al renal f unct i on,i ncl udi ng norm al uri nary al bum i n excret i on rat es.透射電子顯微鏡：1型糖尿病引起腎病GBM增厚、系膜區(qū)基質增多，腎功能正常、無微量白蛋白尿。DIABET

47、IC NEPHROPATHYSl i de 187 El ect ron phot om i crographdem onst rat i ng advanced di abet i c nephropat hyw i t h m arked t hi ckeni ng of t he GBM , great l yi ncreased m esangi al m at ri x m at eri al , andconst ri ct i on of t he capi l l ary l um i na. Thi s I DDMpat i ent had overt di abet i c

48、 nephropat hy.S187 - Electron photomicrograph 透射電子顯微鏡：1型糖尿病引起腎病GBM增厚、系膜區(qū)基質增多、毛細血管腔塌陷，腎功能下降、臨床蛋白尿。1型糖尿病型糖尿病血管、腎小球及小管間血管、腎小球及小管間質病變程度一致質病變程度一致病程與腎臟改變相一致病程與腎臟改變相一致病理變化與臨床表現(xiàn)相病理變化與臨床表現(xiàn)相一致一致DIABETIC NEPHROPATHYSl i de 188 I m m unofl uorescent m i croscopy l i neari m m unofl uorescent stai ni ng for al bum i n al ong thegl om erul ar capi l l ary basem ent m em brane,Bow m an s capsul e, and tubul ar basem entm em brane i n an I D D M pati ent.S188 - Immunofluorescent microscopy linear 1型糖尿病患者、免疫熒光：白蛋白線樣沉積于腎小球毛細血管基底膜、腎