Robbins Essential Pathology Kidney Chapter PDF

CHAPTER 11 Kidney 198.e1 ISCHEMIC TYPE...

CHAPTER 11 Kidney 198.e1 ISCHEMIC TYPE TOXIC TYPE DCT DCT PCT PCT CD PST CD PST HL HL Casts Necrosis Supplemental eFig. 11.4 Patterns of tubular damage in ischemic and toxic acute tubular injury. In the ischemic type, tubular necrosis is patchy, relatively short lengths of tubules are affected, and straight segments of proximal tubules (PST) and ascending limbs of Henle’s loop (HL) are most vulnerable. In toxic acute tubular injury, extensive necrosis is present along the proximal convoluted tubule segments (PCT) with many toxins (e.g., mercury), but necrosis of the distal tubule, particularly ascending HL, also occurs. In both types, lumens of the distal convoluted tubules (DCT) and collecting ducts (CD) contain casts.  CHAPTER 11 Kidney 199 Morphology. Te k dne ys are a rop c and  e su r ac e s   ney g ranu  ar, due o  ssue o ss (mo s y ubu  ar a ropy ) and ner- s   a   bross. Te y a  ne    cke n  ng o ar er  oes  e ads o nar- row ng o  er umen (Fg. 11.15). Clncal Features. Paens may deveop md azoema or proenura, bu e esons rarey produce rena aure. Malignant Hypertension This rare form of severe hypertension causes destructive lesions in renal arterioles and small arteries. Magnan yperenson, dened as a rapd ncrease n bood pres- sure o greaer an 200/120 mm Hg, occurs n ess an 5% o ndvd- uas w yperenson, bu oten causes acue rena aure. Pathogeness. Sma areres and areroes n e kdney sufer e major consequences o magnan yperenson. Endoea njur y and eakage o pasma proens no e vesse wa produce brnod necross, so named because  as e appearance o brn. Paees are acvaed and aggregae n e njured vesses, reeasng grow acors a smuae e proeraon o ces n e adjacen nma, eadng o umna narrowng. Vesse damage may be severe enoug o produce sma emorrages. I soud be noed a ere s consderabe cnca and morpoogc Fig. 11.13 Acute tubular injury. Necrotic tubular epithelial cells and cel- overap beween magnan yperenson and romboc mcroangopa- lular debris in tubular lumens. Congestion of peritubular capillaries is es. Abou 30% o cases o magnan yperenson ave mcroangopac prominent. (Courtesy ExpertPath, copyright Elsevier.) emoyc anema (dscussed beow) and conversey, severe yperenson can occur n prmary orms o emoyc uremc syndrome. Endoea suraces, and sow cyss n e medua, mos promneny a e cor- njury s a common paogenc acor n ese dsorders. comeduar y juncon. Mcroscopcay, ere s wdespread corca aropy and nersa bross. Morphology. here may be sma peeca emorrages on e Rena cysc dsease may aso arse n e seng o proonged day- surace o e cor ex, caused by e r upure o sma bood vesses, ss. Numerous meduar y and corca cyss are seen. ere s an amos gvng a “lea-ben” appearance. Ar eroes sow brnod necro- 30-od ncreased rsk o rena ce carcnoma, wc deveops n 7% o ss, and arger vesses sow proeraon o nma ces, produc- dayzed paens obser ved or 10 years. ng an “onon-skn” appearance (Fg. 11.16). Ar eroes and sma ar eres are severey narrowed. DISEASES OF BLOOD VESSELS Clncal Features. he cnca eaures o magnan yperenson Aoug a dseases o e kdney may secondary afec e rena ncude papedema (caused by lud eakage rom njured rena ves- vascuaure, ere are severa vascuar dseases n wc e rena bood ses), encepaopay (resung rom ncreased nracrana pressure), vesses are major arges. cardovascuar abnormaes (secondar y o e massve ncrease n bood pressure), and rena aure. Headace, nausea, vomng, and Nephrosclerosis vsua dsurbances are eary sympoms. he rena manesaons, Hypertension causes progressive narrowing of the small renal wc deveop soon ereater, sar w emaura and rapdy prog- arteries, resulting in chronic ischemia and damage to the renal ress o azoema. he syndrome s a medca emergency, requrng parenchyma. urgen reamen w anyperensve agens. Abou 50% o paens sur vve a eas 5 years; 90% o deas are caused by urema, and e Pathogeness. he paogeness o yperenson s dscussed n Cap- oer 10% are caused by cerebra emorrage or cardac aure. er 7. In e kdney, e common (bengn) orm o yperenson causes endoea dysuncon and emodynamc sress, resung n brous Thrombotic Microangiopathies nma and meda ckenng o was, prmary n sma areres. In areroes, pasma proens eak no e vesse wa and, ogeer These diverse diseases are characterized by microvascular w ncreased syness o e basemen membrane, produce pnk thrombi, microangiopathic hemolytic anemia, platelet consump- yane maera. he nma and meda are ckened w ncreased tion, and, occasionally, renal failure. coagen-ke brous maera. hese vascuar esons are caed ya- Severa orms o ese dseases are prmar y and are dscussed ne arteroosceross, sceross reerrng o e scar-ke ckenng o ere (Tabe 11.3). Secondar y orms o romboc mcroangopaes e vesse was. he resung narrowng o e sma vesses causes (TMAs) are ose assocaed w severe yperenson, sysemc sce- scema, wc no ony damages rena ssues bu aso acvaes e ross, and oer condons. Two orms o prmar y TMA a nvove renn–angoensn sysem, ereby ncreasng e bood pressure. hus, e kdney are caed emoytc-uremc syndrome (HUS) and trombotc e cyce o yperenson and vascuar narrowng becomes muuay trombocytopena pur pura (TTP). renorcng. hese esons are ess severe and dfer rom ose n mag- Pathogeness. he varous orms o TMA ave dferen paogenc nan yperenson (descrbed aer), so s yperenson-reaed kd- mecansms. ney dsease s aso commony known as bengn neprosceross. 200 CHAPTER 11 Kidney A B Fig. 11.14 Autosomal dominant adult polycystic kidney, viewed from the external surface (A) and bisected (B). The kidney is markedly enlarged, with numerous dilated cysts. B A Fig. 11.15 Benign nephrosclerosis. (A) The external surface is finely granular because of scarring, and the cut surface shows cortical atrophy. (B) Tubular atrophy resulting from vascular narrowing, and interstitial fibrosis. The biopsy is stained with the trichrome stain, which stains collagen blue. (C) Two arterioles with hyaline deposition, marked thickening of the walls, and a narrowed lumen. (B, Courtesy Dr. Vighnesh Wala- valkar, Department of Pathology, University of California San Francisco; C, Courtesy Dr. M. A. Venkatachalam, Department of Pathology, University of Texas Health Sciences Center, San Antonio, Texas.)  CHAPTER 11 Kidney 201 A B Fig. 11.16 Malignant hypertension. (A) Fibrinoid necrosis of afferent arteriole, typically an acute lesion. (B) Hyperplastic arteriolosclerosis (onion-skin lesion, more often seen in cases with long-standing hypertension. PAS stain. (Courtesy ExpertPath, copyright Elsevier.) anema. Sga oxn–assocaed HUS s a major cause o acue rena a-    Sga toxn–assocated HUS s caused by necons by bacera (E. ure n cdren. I e acue kdney njury s managed w dayss, mos co, Sgea) a produce a oxn a damages endoea ces, paens recover wn weeks; e ong-erm prognoss (over 15 o 25 especay n rena gomeru, resung n romboss. years), owever, s no unormy avorabe, as abou 25% o afeced c-    Atypca (or compement-medated) HUS s caused by nered or dren evenuay deveop rena nsuicency. Aypca HUS as a poorer acqured abnormaes eadng o excessve compemen acvaon. prognoss; ony 60% o 70% o paens recover rena uncon, and abou Precsey wy s eads o mcrovascuar romboss s no known. 20% de. In TTP, e domnan sympoms more oten are reaed o I s noabe a e esons are dferen rom ose n C3 gomer- nvovemen o organs oer an e kdney, suc as e bran. Wou uopaes, dscussed earer, mpyng a e paogenc abnor- erapy, TTP ypcay oows a rapdy aa course, w survva raes o maes are aso dsnc. approxmaey 10%. Forunaey, mey reamen greay owers e rsk    hromboc rombocyopenc pur pura (TTP), anoer orm o sys- o dea and ncudes repacng e mssng ADAMTS13 enzyme and/ emc TMA, s caused by decency o a proease caed ADAMTS13 or removng e paogenc auoanbody, ypcay by pasma excange. a ceaves and ereby ms e sze o mumers o von W- ebrand acor. he abnormay arge mumers resung rom ADAMTS13 decency cause paee acvaon and aggregaon RENAL STONES (UROLITHIASIS) and e deposon o romb n mupe organs, ncudng e kd- neys. ADAMTS13 decency may resu rom muaons n e gene Renal stones (calculi) can produce local symptoms and obstruct (nered orm) or auoanbodes agans e proen (acqured). urine outow. In bo HUS and T TP, e romb are “paee-rc” and ere s a Pathoge ne s s. Sones or m n  e rena  c a yc e s and p ev s w en  e decency o crcuang paees (rombocyopena) due o er concen ra on o  e sone’s c ons uens n  e u r  ne e xc e e ds  e r consumpon, somemes assocaed w emorrages (purpura). s oub  y, e adng o sup ers aura  on and pre c p a on o  e cem- Morphology. A orms o TMA sow romb mosy n gomeruar c a . Te mos common sones (⁓80%) conss o calcum ox alae, capares and areroes (Suppemena eFg. 11.5). In severe cases, w   or w  ou ad m xe d c a  c um pospae. Mos p a  en s w   s may produce scemc necross o e rena corex. he nar-  s  yp e o sone excree g   e ves o c a c u m n  e u r  ne, w   c rowng caused by romb n sma vesses creaes seer orces a may be s e cond ar y o unex p a ne d, exc essve ab s or p  on o c a c u m sred red ces, eadng o emoyss and e appearance o red ce  rom  e gu. On y a m nor  y o p a  e ns w   c a c u m sone s as ragmens (scsocyes) n perpera bood smears (see Caper 9). ee vae d bo o d c a  cum. L ess common  an c a c u m sones are mag nesum-conanng sones  a  ypc a  y ar s e n  e s e ng o Clncal Features. Paens usuay presen w e sudden onse o o- a  ka ne ur ne, mos o en s e cond ar y o b ac e r  a   n e c   ons o  e gura, emaura, beedng probems, and mcroangopac emoyc ur nar y  rac  by organ s ms suc as Proeu s v ulgar  s, w c ncre as e Table 11.3 Primary Thrombotic Microangiopathies Forms Etiology and Pathogenesis Shiga toxin–mediated HUS Acquired Shiga toxin–producing E. coli Shigella dysenteriae serotype 1 Complement-mediated HUS Inherited Complement dysregulation due to genetic abnormalities (relatively common) Acquired Acquired complement dysregulation due to autoantibodies (rare) TTP Inherited Genetic ADAMTS13 deficiency (rare) Acquired ADAMTS13 deficiency due to autoantibodies (relatively common) ADAMTS13, von Willebrand factor cleaving protease; HUS, hemolytic-uremic syndrome; TTP, thrombotic thrombocytopenic purpura. 202 CHAPTER 11 Kidney Morphology. he pevs and cayces are daed, and e kdney parencyma s compressed and becomes aropc (Fg. 11.17). he eares mcroscopc esons are ubuar daon, oowed by aropy and nersa bross; gomeru become aropc  e obsrucon s severe and proonged. Clncal Features. Anura resus  e obsrucon s baera and com- pee, bu s s rarey e case. Paradoxcay, ncompee baera obsruc- on causes poyura raer an ogura as a resu o deecs n ubuar concenrang mecansms, and s may obscure e rue naure o e eson. Hydronepross s ypcay dagnosed by magng, eer ncden- ay or as par o e evauaon o e underyng cause o e obsrucon. TUMORS OF THE KIDNEY he mos mporan and common umor o e kdney s rena ce carc- noma, represenng 2% o 3% o cancers n adus and 80% o 85% o pr- mary rena umors. Wms umor s e commones rena umor o cdren. Fig. 11.17 Hydronephrosis, showing marked dilation of the pelvis and Renal Cell Carcinoma calyces and thinning of renal parenchyma. This malignant tumor of the tubular epithelium is strongly associated with acquired mutations that mimic adaptive responses to hypoxia and has a striking propensity to metastasize through blood vessels.  e ur ne pH by sp  ng ure a. G ou and o er cond ons n w  c bo o d ur c acd e ves are e e v ae d are ass o c  ae d w   ur c acd Pathogeness. he mos common soogc orm o e umor s cear ce stones. Ab ou 50% o ndv  du a s w   ur  c ac d sones , owe ver, carcnoma. hs umor s usuay sporadc, bu ere s aso a rare ama ave ne er yp er u r  cem a nor  ncre as e d u r  ne u rae, bu  nse ad orm a occurs a g requency n assocaon w von Hppe-Lndau demons rae an unexp a ne d ende nc y o e xc ree a p ers se n y (VHL) dsease. hs assocaon as ed o e dscovery a e mos re- acdc ur ne (pH < 5. 5). Cystne stones are a mos nvar  aby ass o c - quen drver muaon n bo e ama and sporadc orms s oss or ae d w   a gene c d ee c  n re na   ransp or  o c e r  a n am no ac  ds, nacvaon o e VHL gene. As dscussed n Caper 5, VHL reguaes ncudng c ys ne. adapve responses o ypoxa, and n s absence ere s overexpresson o vascuar endoea grow acor (VEGF), a key reguaor o angogen- Morphology. Sones are usuay unaera and sma (2 o 3 mm); ess. he uncommon papary ype o rena ce carcnoma s assocaed ey are mos commony presen n e rena pevs and cayces and w acvang muaons n e oncogene MET (aso muaed n papary e badder (Suppemena eFg. 11.6). Large sones odged n e yrod cancer), wc encodes a recepor yrosne knase a smuaes rena pevs may cause sgncan rena damage. paways eadng o ncreased ce grow and survva. Clncal Features. Sma sones a pass roug e ureer can cause severe paroxysms o lank pan radang oward e gron (rena coc), Morphology. Grossy, e cear ce ype o rena ce carcnoma s oten assocaed w gross emaura. B ecause ey obsruc e low usuay soary, as areas o necross and emorrage, and exbs a o urne, sones o a ypes predspose o bacera necons. In mos propensy o nvade no rena vens. Mcroscopcay, e ces con- cases, e dagnoss s ready made radoogcay. an abundan pd and gycogen, accounng or e cear appear- ance o e ces ater ssue processng (Fg. 11.18). Because o er orgn rom ubues, ey can arse anywere n e corex. Papary Hydronephrosis umors, as e name mpes, ave papae w brovascuar cores. Urinary outow obstruction causes dilation of the renal pelvis and ey end o be baera and mupe (Suppemena eFg. 11.7). calyces, called hydronephrosis. Pathogeness. Oulow obsrucons eadng o ydronepross may be Clncal Features. Carcnomas o e kdney are mos common rom e resu o congena srucura anomaes or acqured cacu, bengn e sx o seven decades, and men are afeced abou wce as oten prosac yperpasa, umors a compress e ureers, pregnancy, or as women. he rsk s ger n smokers, yperensve and obese parayss o e badder (e.g., ater spna cord njury). Reroperonea paens, and ose wo ave ad occupaona exposure o cadmum. bross, wc s a manesaon o IgG4 reaed dsease, causes baera he rsk or deveopng rena ce cancer s ncreased 30-od n ndvd- ydronepross. Fraon connues, causng daon o e afeced cay- uas w acqured poycysc dsease as a compcaon o cronc da- ces and pevs. Unusuay g pressure generaed n e rena pevs and yss. In more an 50% o cases, ese umors presen w emaura. ransmed back roug e coecng ducs resus n compresson o e In oer cases, ey presen as papabe masses causng lank pan, or are rena vascuaure, eadng o arera nsuicency and venous sass. he deeced ncdenay durng magng or oer condons. Uncommon na uncona dsurbances are argey ubuar, manesed prmary by manesaons ncude ever, poycyema (reaed o er yropoen an mpared concenrang aby. Daon o e rena pevs and cayces producon by e umor ces), and varous paraneopasc syndromes s ready deecabe by radoogc magng, and  unaera, kdney unc- (ypercacema, yperenson, Cusng syndrome, or emnzaon or on s usuay mananed un ae n e course. W compee baera mascunzaon) because o aberran ormone producon. Measa- obsrucon, rreversbe rena njury occurs n as e as 3 weeks. ses, especay o e ungs and bones, are requen.  CHAPTER 11 Kidney 202.e1 Supplemental eFig. 11.5 Fibrin stain showing platelet-fibrin thrombi (red) in the glomerular capillaries, characteristic of thrombotic microan- giopathic disorders. Supplemental eFig. 11.6 Nephrolithiasis. A large stone impacted in the renal pelvis. (Courtesy Dr. E. Mosher, Brigham and Women’s Hos- pital, Boston, Mass.) Supplemental eFig. 11.7 Renal cell carcinoma, papillary type. Note the papillae and foamy macrophages in the stalk. (Courtesy Dr. A. Renshaw, Baptist Hospital, Miami.)