Nephropathology V. Žampachová I. PAÚ Anatomical remarks nVessels - 90% of blood flow through the cortex nAfferent arteriole → glomerular capillaries → efferent arteriole → peritubular capillary plexus (from superficial glomeruli) or vasa recta for medulla (from juxtamedullary glomeruli) nterminal arteries nglomerular damage commonly leads to damage of peritubular blood flow – risk of ischemia Possible clinical signs nWeight gain, edema – fluid retention nThirst – chronic renal failure, DM nFatigue – acute/chronic renal failure (RF) nFever – urinary tract infection (UTI) nHeadache – hypertension, RF nHematuria – UTI, glomerulonephritis, tumor, stone nPolyuria – DM, tubular disorders nRenal diseases commonly clinically silent! Clinical features nDiminished renal reserve – GFR ~ 50% of normal nRenal insufficiency - GFR 20-50% of normal nAzotemia – increase of blood urea and creatinine due to decreased glomerular filtration (20-30%), or extrarenal cause n Uraemia - azotemia together with several clinical and biochemical abnormities: metabolic, endocrine, … (uremic gastroenteritis, peripheral neuropathy, fibrinous pericarditis) nRenal failure - GFR less than 20-25%, oedema, uraemia; causes: prerenal, postrenal, renal (vascular, glomerular, tubulointerstitial); acute r.f. (oliguria→anuria) chronic r.f. nEnd-stage renal disease - GFR less than 5% of norm nAnuria <100ml/24hrs Clinical features nNephritic syndrome due to acute glomerular disease; hematuria + mild proteinuria + hypertension; oliguria + azotemia + mineral dysbalance nRapidly progressive glomerulonephritis – very rapid (days - a few weeks) nephritic syndrome nNephrotic syndrome: usually chronic gl. dis., severe proteinuria (>3,5 g/d) + hypoalbuminemia/oedema + hyperlipidemia + lipiduria; possible ↑ infections (IgG loss) n Clinical features nAsymptomatic hematuria and/or proteinuria – commonly mild glomerular lesion nPolyuria + nocturia + electrolyte disorders – renal tubular defects nBacteriuria + pyuria – urinary tract infection (UTI) nRenal colic + hematuria - nephrolithiasis Renal diseases n congenital anomalies n glomerular diseases n tubulointerstitial diseases n vascular diseases n tumors Congenital anomalies n10% of all people nhereditary or acquired developmental defect ndecreased volume of renal tissue (e.g. agenesis) ndisorders of differentiation (dysplasia) nanatomical abnormalities (ectopy) nmetabolic disorders (cystinuria) Agenesis nBilateral agenesis – incompatible with independent life, usually stillborn, accompanied by characteristic appearance (Potter‘s syndrome), commonly associated with other congenital defects nUnilateral agenesis – infrequent, the opposite kidney enlarged by compensatory hypertrophy n Oligohydramnion (Potter´s syndrome) ndecreased amount of amniotic fluid (placental abnormities, renal agenesis or malformation Potter copy Hypoplasia n n nAbnormally small kidneys (x atrophy) nreduced number of lobes and pyramids hypoplsieledviny Renal ectopy nAbnormal site, usually in pelvis, due to migration stop of the metanephros nA. renalis - from lower aorta or a. ilica communis nShort ureter Ren migrans, ren mobilis nNot a malformation, normal a. renalis nSecondary renal descensus, usually due to loss of adipous capsule nLong ureter, risk of obstruction and infection Horseshoe kidney nRenal pole fusion nUreteral obstruction podkovledv Cystic renal disease nHereditary, congenital nonhereditary, acquired nPathogenesis: primary defect of tubular epithelial cells and their growth, resulting in tubular dilatation nSecondary tubular obstruction (oxalate crystals etc.) nMultiple or solitary nAffects the whole kidney, or mostly cortex or medulla Cystic dysplasia nUni- or bilateral nEnlarged multicystic kidney nCysts mm-cm. nIslands of undifferentiated mesenchyme, immature tubules nCommonly cartilage nBilateral - renal insufficiency dysplasieledviny dysplasieledviny copy apckd Adult polycystic kidney disease (APKD) Autosomal-dominant, liver cysts, berry aneurysms. Pain, hematuria, UTI, stones, hypertension, chronic RF at 40-60 yrs. ↑risk of ca copy Polycystic kidney - autosomal recessive nChildhood nEnlarged kidney at birth, smooth surface nRadial elongated cysts and channels nCongenital hepatic fibrosis nRF in childhood dětskápolycystickanemoc copy Simple cyst nSingle or multiple nUp to 10 cm nHaemorrhage posible nDifferential diagnosis x cystic tumors n„Complicated“ cyst – with regressive changes, diff. dg. x ca Cystaprostá Renal biopsy imf2 Untitled1 ~LWF0002 Direct immunofluorescence Electron microscopy Normal glomerulus schemaglom copy Glomerular diseases nClassification by aetiology and mechanisms of injury (primary x secondary; immunological x non-immunological) nHistological classification (patterns of injury – proliferative, membranous change, membrano-proliferative, crescentic, hyalinosis + sclerosis) nOne disease may have variable morphology/pattern (SLE) nOne pattern may be seen in variable disorders n Glomerular diseases nNephritic syndrome, rapidly progressive GN: inflammation +/- endothelial damage; nImmune complex deposition (acute proliferative GN, SLE) nAntibodies x glomerular basement membrane (Goodpasture sy) nSystemic noninfectious vasculitis: autoantibodies p-ANCA, c-ANCA; (polyangiitis with granuloma) n Glomerular diseases nNephrotic syndrome: malfunction/leakage of barrier-filtration system - ↑ increased permeability nCapillary wall: thickening by in situ IC deposits (membranous glomerulopathy; primary, sec.), abnormal substances (DM, amyloid) nEpithelial cells: loss of normal structure (foot processes in minimal change disease; disruption in focal segmental glomerulosclerosis) n Patterns of glomerular injury nProliferative – increased glomerular cellularity, combination of endogenous proliferation and exogen. infiltration nMembranous change – thickening of loops due to BM expansion nMembrano-proliferative nCrescentic – florid prolif. of cells in Bowman‘s capsule + infiltration, later fibrotic changes nHyalinosis – extracellular/intramural amorphous material nSclerosis – extracellular collagenous matrix n Immune mechanisms of glomerular injury nAntibody-mediated injury nIn situ immune complex deposition (fixed intrinsic tissue antigens incl. GBM; planted antigens – exo- or endogenous nCirculating immune complex deposition nCytotoxic antibodies nCell-mediated immune injury nActivation of alternative complement pathway IMMUNOLOGIC PROCESSES in PATHOGENESIS n 1)Nephrotoxic antibodies against an antigen within the glomerular BM; Ag binds with Ab in situ n n Nephrotoxic anti-GBM antibodies react with Goodpasture antigen in GBM uncommon cause of GN scgemaantiGBM Anti-GBM glomerulonefritis copy Anti-GBM glomerulonefritis linimf Linear positivity of IgG along glomerular basal membranes IMMUNOLOGIC PROCESSES in PATHOGENESIS n n2) Antibodies reacting with epithelial Ag in situ. n subepithelial aspect of BM, membranous pattern – primary membranous GN – podocyte injury + loss of pedicles, but no inflammation (?complement) n schemaHeyman nAutoimmune membranous glomerulopathy copy Autoimmune membranous glomerulopathy mgm emmgn Subepithelial deposits ELMI Immunofluorescence – granular deposits copy IMMUNOLOGIC PROCESSES in PATHOGENESIS n n3) Antibodies reacting with implanted nonglomerular antigens in situ. n n 7emdeposita GranImF Immune deposits granular, similar to circulating immune complex nephritis Planted antigenes copy IMMUNOLOGIC PROCESSES in PATHOGENESIS n n4) Trapping or binding of circulating antigen-antibody immune complexes within glomeruli, Ag nonglomerular. n n imf1 imfmgn schemaik CIRCULATING IMMUNE COMPLEXES copy Variable deposition of IC in the glomerulus Immune complex GN nInjury by: complement activation, leukocytic infiltration, renal cells (mesangial, endothelial) activation + proliferation nDeposits localization according to size/charge of complexes, local changes: n subendothelial (SLE, membranoproliferative GN) n epimembranous (membranous GN) n subepithelial (acute proliferative GN) n mesangial (IgA nephropathy) IC localisation n n n n n n schemadepositglom Mesangial Subepithelial Subendothelial Epimembranous copy IC site → type of lesion nmesangial, subendothelial → contact with blood → complement activation + inflammatory/proliferative reaction → nephritis + hematuria (IgA disease, membrano-proliferative GN) nsubepithelial → no direct contact with blood → no inflammation → nephrotic sy (membranous glomerulopathy) n Cytotoxic antibodies nAB x mesangial cells → damage → repair by mesangial cell proliferation nAB x endothelial cells → e. injury → thrombosis Cell mediated damage nSensitized T lymphocytes release chemokines activating and attracting macrophages nMacrophages act as effector cells Progression in glomerular disease n↓ GFR (30-50% of normal) → independent progression to RF – ablation nephropathy nFocal segmental glomerulosclerosis – adaptation – compensatory glomerular hypertrophy (glomerular + systemic hypertension → proteinuria → mesangial proliferation + matrix accumulation → sclerosis) nTubulointerstitial fibrosis – proteinuria + ischemia → tubular damage + interstitial inflammation Glomerulopathy nAntigen-antibody deposition – general pathway of injury + local hemodynamics + structure/changes of glomerulus → n variable morphologic/functional alterations Glomerular injury distribution n nDiffuse – almost all glomeruli affected (> 50- 80%) nFocal – only some glomeruli nGlobal – affecting the whole glomerulus nSegmental – affecting only part of the glomerulus n Clinical presentations nAcute nephritic syndrome – rapid start, hematuria, hypertension; variable proteinuria, oliguria, azotemia nNephrotic syndrome - heavy proteinuria > 3,5 g, oedemas, hypoalbuminemia, hyperlipidemia, lipiduria nIsolated, sometimes asymptomatic hematuria or proteinuria nAcute renal failure – progressive oliguria to anuria, azotemia nChronic renal failure - prolongated symptoms of uremia, anemia, nausea GLOMERULAR DISEASES nPRIMARY GLOMERULAR DISEASE: kidney as a main affected organ, other clinical signs due to impaired renal function (i.e. minimal change disease) nSECONDARY GLOMERULAR DISEASE: renal injury only a part of systemic disease affecting multiple organs (lung, joints, skin), i.e. SLE NORMGLOMHE AKGNHE RPGNSRPKY IgAHEIMF fsgs2 ~AUT0001 mpgnhe FokGN 12slegnafog amyloid ChronsklerotisujíciGN chrongn chrongn Chronic sclerosing GN Normal kidney GN Glomerulopathy nOne histological type may have variable clinical presentation, i.e. membranoproliferative lesion may present as glomerulonephritis with nephritic sy, glomerulopathy with nephrotic sy, or isolated hematuria Glomerulopathy nAcute nephritic sy: nacute (diffuse endocapillary) proliferative GN nmembranoproliferative GN (C3, prim. IC), nmixed w. nephrotic nrapidly progressive GN (lupus) nIsolated or dominant hematuria nIgA nephropathy nPurpura Henoch-Schönlein nAlport sy /thin BM – collagen IV n Glomerulopathy nProteinuria or nephrotic sy nMinimal change disease nFocal segmental glomerulosclerosis nMembranous glomerulopathy nOther immune complex GN nAmyloidosis nDM nephropathy n Glomerulopathy nIn vascular disorders nsystemic vasculitis (ANCA+, microscopic polyangiitis, anti-GBM GN) nin hypertension nthrombotic microangiopathy (HUS, thrombotic thrompocytopenic purpura) nother vascular changes (infarction, renal artery stenosis) nSLE (variable changes) nChronic GN n Acute nephritis nPrimary: n diffuse proliferative (post-infectious) GN n rapidly progressive glomerulonephritis incl. anti-GBM disease n membrano-proliferative GN nSecondary: mostly in vasculitis – SLE, n polyarteritis n granulomatosis with polyangiitis (Wegener) n Henoch-Schönlein purpura n cryoglobulinemia n Diffuse proliferative GN npostinfectious (str., staph., viruses, protozoan - malaria, toxoplasmosis; schistosomiasis) nany age, children more commonly nacute nephritis (+ fever, nausea) nmay be partially crescentic (→ progressive) nprognosis – regeneration usual in children, in adults possible ↓ renal function Diffuse proliferative GN AKGNHE Diffuse proliferative GN subepithelial immune complex deposition, postinfective AKGNEMHUMPS akgnimf Elmi „humps“ Immunofluorescence copy granular deposits Crescentic GN nclinically rapidly progressive GN nvarious etiology (immune-complex mediated, pauci-immune + ANCA, anti-GMB) nprimary or secondary (small vessel vasculitis, SLE,…) nnecrotising GN – capillary rupture, exudation – extracapillary proliferation - crescentic nImmunosuppression in active lesion + plasma exchange in known circulating AB (anti-GBM) nNo direct therapy in fibrosing lesion n Rapidly progressive (crescentic) GN RPGNSRPKY Vasculitis nSmall vessel vasculitis (granulomatosis with polyangiitis – Wegener; ANCA+ vasculitis) nIncidence ↑ with age nRenal or multiorgan nRapidly progressive GN, hematuria, proteinuria, red cell casts Anti-GBM disease nuncommon nrapidly progressive renal failure +/- hemoptysis (Goodpasture sy) nlinear deposits of IgG Membranoproliferative GN npattern of variable diseases nmesangial + endothelial cells activation and proliferation (mesangiocapillary GN), mesangial matrix expansion, BM thickening – „duplication – tram-track“ nnephrotic syndrome or acute nephritis mpgnhe Membranoproliferative GN nsecondary to other diseases - IC: cryoglobulinemia (80% due to HCV); SLE, HIV; malignancy (CLL, ML), alpha1- AT deficiency), nprimary MPGN: young, poor progn., CHRI, recurrent in graft nnephrotic sy, mixed nephrotic + nephritic nC3 glomerulopathies – C3 activation control defect nmorphology nType I MPGN: subendothelial deposits n(Type II MPGN): dense deposit disease intramembranous nType III MPGN EM deposits subendothelial + subepithelial n Glomerulopathy with hematuria nPrimary: IgA nephropathy (Berger‘s disease) n Alport syndrome / thin basement mambranes sy nSecondary (systemic): SLE n Henoch-Schönlein purpura (+ skin rash, GIT hemorrhage, arthritis) n polyarteritis IgA nephropathy nRecurrent hematuria, children and young adults (male), after GIT, respitatory tract, urinary tract infections, may → RF; most common nIgA and C3 mesangial deposition, mesang. cells and matrix proliferation, segmental glomerulosclerosis nAbnormal increase/pathologic form of IgA production, AAxIgA – IC;↓ clearance of IC in cirrhosis IgAHEIMF copy Alport syndrome nPart of collagen IV glomerulopathies ngenetic disorder, 90% X-linked nabnormal basement membranes (lamina densa), later FSGS, tubular atrophy, interstitial fibrosis nmanifestation mostly in kidney (hematuria – nefritis, proteinuria) near – deafness neye – lens + cornea disorders, cataract n n Thin basement membrane nbenign familial hematuria ncommon inherited lesion nheterozygous carriers of collagen IV mutations nwithout other problems (ocular, …) ndifferential diagnosis Glomerulopathy with proteinuria / nephrotic sy nPrimary: minimal change disease n membranous glomerulopathy n membranoproliferative GN n focal segmental glomerulosclerosis nSecondary: SLE n diabetes mellitus n amyloidosis n … Minimal change disease nMost common cause of nephrotic sy in children nmostly in children ≤ 5 yrs nLight microscopy normal nGenetic predisposition + immunological basis (association with respiratory infection, atopy, Hodgkin lymphoma) nEpithelial cell injury – effaced foot processes nsteroid therapy, good prognosis in children Minimal change disease Loss of epithelial foot processes in elmi, fat in tubular epithelia („lipoid nephrosis“) n NORMGLOMHE MGZ copy Membranous glomerulopathy nidiopathic (85%) nsecondary – infections (HBV, HCV, syphilis, malaria) tumors (lung ca, colorectal ca, melanoma), drugs (NSAID), nautoimmune diseases (SLE, thyroiditis) nIC-mediated (incl. Ab x renal autoantigen), mostly older adults – most common nephrotic sy in this age group nproteinuria or nephrotic sy, variable course, 1/3 RI ndiffuse thickening of capillary wall, subepithelial IC deposits, „spikes“ - BM material in impregnation ~AUT0002 ~AUT0001 mgnimf Membranous glomerulopathy copy Focal segmental glomerulosclerosis nNephrotic sy, ↑ incidence nHematuria, ↓ GFR, proteinuria nProgression usual – 50% → RF in 7 years nPrimary – idiopathic, variable podocyte protein mutations, plasma factor ↑ permeability nSecondary: late part of adaptive response to preexisting renal disease (renal ablation - reflux nephropathy, hypertension, glomerulopathies – IgA, SLE,…) nAssociation with other diseases (HIV, obesity, toxins – heroin, drugs) n FSGS nepithelial damage nhyalinosis (plasma protein leakage), foamy macrophages nsegmental sclerosis (mesangial matrix production, capillary loops collapse) nNo immune deposits on IF nPodocyte injury on EM n n Focal segmental glomerulosclerosis fsgs2 SECONDARY glomerular diseases nSystemic lupus erythematosus nGoodpasture’s syndrome nHenoch-Schönlein purpura nMicroscopic form of polyarteritis nodosa nWegener’s granulomatosis nBacterial endocarditis nDiabetes mellitus nAmyloidosis Lupus nephritis 15sleimf 11slegnhe 12slegnafog Glomerular cells proliferation Immune deposit (red) Deposits in direct immnofluorescence Chronic glomerulonephritis nend stage of variable glomerular disease n different rate of progression in different diseases nFSGS 50-80% nRPGN, membranous, membranoproliferative ~ 50% npoststreptococcal 1-2% Chronic glomerulonephritis ngranular surface (!x chronic interstitial nephritis, nephrosclerosis, diabetic nephropathy,…) nthin cortex nobliterated glomeruli, arterio- and arteriolosclerosis (hypertension), tubular atrophy chrongn Chronic GN – end-stage kidney ChronsklerotisujíciGN Diabetic nephropathy nDiabetic microvascular disease nClinically: non-nephrotic proteinuria, nephrotic syndrome, chronic renal failure nMorphology: glomerulosclerosis (diffuse mesangial, nodular), hyalinizing arteriolar sclerosis, tubulointerstitial lesions (pyelonephritis, papillary necrosis) n n n Diabetes mellitus and kidneys nNonenzymatic glycosylation of proteins – accumulation of irreversible glycosylation products in BM of vessel walls, metabolic defect – increased collagen synthesis, hemodynamic changes nDiabetic microangiopathy in kidney (glomerulosclerosis) and retina (diabetic retinopathy). Diffuse thickening of capillary BM leads to ischemic changes, simultaneously increased plasmatic proteins permeability Diabetic glomerulosclerosis nDiffuse glomerulosclerosis – GBM thickening, increase in mesangial matrix nNodular glomerulosclerosis - (Kimmelstiel-Wilson) after 10-15 yrs; PAS+ nodular acellular material deposits at the tips of capillary loops; leads to chronic renal insufficiency Diabetic glomerulosclerosis Diabetic glomerulosclerosis Diabetic glomerulosclerosis nFurther renal complications in diabetics naccelerated arteriolosclerosis and arteriosclerosis, hypertension nPyelonephritis nRenal papillary necrosis in acute PN DiabetGS Diaibetes Diabetic glomerulosclerosis Renal amyloidosis nAmyloidosis – pathologic deposits of abnormal microfibrillary (8-10nm) proteinaceous acellular material nEosinophilic in HE, Kongo red +, green dichroism in polarised light nTough pale enlarged kidney in macroscopy Renal amyloidosis nAmyloid deposits in glomerular mesangial matrix and capillary walls; glomerular obliteration nPeritubular and blood vessel walls nProteinuria nNephrotic syndrome nCHRI amyloid Tubulo-interstitial disorders nConcurrent damage to the tubular epithelium and interstitium nUsually no glomerular damage, or only secondary (e.g. glomerulosclerosis) n Tubulo-interstitial disorders - groups nTUBULOINTERSTITIAL NEPHRITIS (TIN) n Acute pyelonephritis n Chronic pyelonephritis, reflux nephropathy n Abacterial interstitial nephritis (drugs, etc.) nISCHAEMIC AND TOXIC INJURY n Acute tubular necrosis nOTHERS (e.g. obstructive uropathy, tbc, myeloma, urate nephropathy) Acute tubular necrosis (ATN) nDestruction/injury of tubular epithelium, leading to acute diminution or loss of renal function nIschemic ATN – due to decreased or interrupted blood flow, e.g. in shock, trauma, acute pancreatitis, polyarteritis nodosa, haemoglobinuria (haemolysis), myoglobinuria (crush), etc. nNephrotoxic ATN – direct toxic injury to the tubules by drugs, heavy metals (mercury), organic solvents (carbon tetrachloride), ethylene glycol Acute tubular necrosis (ATN) nMorphology: ischemic ATN with loss of proximal epithelial brush border, cell flattening, focal tubular epithelial necrosis along the whole nephron, BM rupture, occlusion by casts; interstitial oedema, inflammatory infiltrate nLater epithelial regeneration starting from uninjured parts nToxic ATN: extensive tubular necrosis/cytotoxic changes along the proximal tubules Acute tubular necrosis (ATN) ATNmikro ATNmikro2 Acute pyelonephritis nCommon purulent renal inflammation, bacterial infection by Escherichia coli, Proteus, Klebsiella, Enterobakter nAscending infection by urine reflux in urinary tract inflammation nDescending (haematogenous) infection in septicaemia, rare Acute pyelonephritis nFacilitated by DM, gout, all causes of obstructive uropathy (e.g. nephrolithiasis, tumors, urinary tract anomalies incl. vesicoureteric and intrarenal reflux) nInstrumental interventions (cathetrization, cystoscopy) nMACRO: enlarged kidney, cortical and medullary abscessses nMICRO: purulent neutrophilic exudate in tubules and interstitium, oedema Acute pyelonephritis schemapyelonefritidy copy Acute pyelonephritis n pyelonefritida pyelonephr2 pyememboli Pyelonefritisasvrstela pyelonphr Acute pyelonephritis n nPyonephrosis nPapillary necrosis in diabetics nPeri- and paranephritic abscess nekrpapil Papillary necrosis Chronic pyelonephritis nUni- or bilateral chron. tubulo- interstitial renal inflammation with scarring n10-20% end-stage kidney nObstructive PN - repeated infections nReflux nephropathy –vesicoureteric and/or pelveorenal reflux (from lower and upper pole calyces into renal parenchyme) Vesicoureteric reflux n refluxrtg reflux cystoureterogram Vesicoureteric junction chgronpyel2 reflux2 reflux3 Chronic pyelonephritis Reflux Chronic pyelonephritis chronpyel Obstructive Xanthogranulomatous pyelonephritis nUncommon form of chronic pyelonephritis with accumulation of foamy macrophages in interstitium nYellowish focal lesions in macroscopy, diff. dg. x renal carcinoma xantoranulomatosnípyelonefritis Tubulointerstitial nephritis induced by drugs and toxins (hypersensitivity nephritis) nSulfonamids, synthetic penicilins, some diuretics, NSAIDs n7-15 days after exposure fever, eosinophilia, rash, hematuria, proteinuria, leukocyturia, cca 50% acute renal failure with oliguria nLate-phase reaction of an IgE-mediated hypersensitivity (type I) nOedema and mononuclear interstitial infiltration, commonly with eosinophils, giant cell granulomas may be present. Tubulitis and tubular regressive changes. Analgesic nephropathy nChronic renal disease due to excessive use of analgesic mixtures nForm of chronic tubulointerstitial nephritis with renal papillary necrosis nCombination effects of aspirin (papillary ischaemia), phenacetin (toxic metabolites) Renal TBC nPart of miliary spread nSolitary postprimary tbc lesion nGross: caseous-cavernous mass with fibrous capsule (closed tbc) or rupture and drain into pelvis (open tbc), possible infection of urinary tract. Renal TBC tbcledv Caseation kittniere copy Urate nephropathy nHyperuricemic disorders (urate crystals formation) may lead to 3 forms of injury: nAcute urate nephropathy in patients with haematologic malignancies, commonly during chemotherapy (extensive cell breakdown – release of nucleic acids – urate crystals in tubules – acute renal failure nChronic urate nephropathy – in gout. Urate crystals surrounded by foreign body giant cells, tubulo-interstitial nephritis nUrate stones Multiple myeloma nAmyloidosis nMyeloma nephrosis: tubular casts formed by precipitated Bence-Jones protein, giant cell reaction myelomováledvina nBlood vessels na. renalis na. segmentalis na. interlobaris na.arcuata na. interlobularis nafferent arteriole schemacévledviny Renal infarction nCauses: thrombosis due to AS; n polyarteritis nodosa; n thrombembolia; n aneurysm of abdominal aorta; n n inarktledv inarktnarezu2 Benign nephrosclerosis arteriolosclerotic arteriolohylinosa DSCN1577 koradenomyacystygranpovrch Benign nephrosclerosis – hypertensive nephropathy na. renalis stenosis, renal atrophy and hypertension (Goldblatt) asledvarterie Benign nephrosclerosis nefrosklerosa Nephrosclerosis arterioarteriolo granulations and post-infarct scars arteriepřimalignínefrosklerose maligníhypertense Onion-skin formations – hyperplastic arteriolosclerosis +/- arteriolonecrosis; hyaline arteriolosclerosis hypertension Fibrinoid necrosis Thrombotic microangiopathy nEndothelial damage → microthrombi → damage of erythocytes + platelets → hemolytic anaemia nHemolytic-uremic sy (typical – epidemic – Shiga toxin; atypical – antiphospholipid antibodies, malignant hypertension, pregnancy, drugs, irradiation, …) nThrombotic thrombocytopenic purpura (deficiency in von Willebrand-cleaving factor) n n Hemolytic-uremic syndrome 1)Ischemic cortical changes with tubular dilatation 2)Disperse focal hemoragies, necroses 3)Diffuse cortical necrosis Acute nephropathy + haemolysis thrombocytopenia diarrhea E.coli verotoxin, other toxins, AI krovéhemoragiešoknekrosa korovánekrosa Hemolytic-uremic syndrome nMicrotrombi in glomerular capillaries (endothelial injury + platelet activation) nThickening of capillary walls nNecrosis and intimal hyperplasia of small arteries xxxxx Renal tumors n Benign renal tumors nCortical papillary adenoma n n nSmall tumors (1-5 mm), nMay be multiple nPapillary structure koradenomyacystygranpovrch Benign renal tumors nAngiomyolipoma (PEComa) angiomylipom Benign renal tumors nOncocytoma onkocytom onkocytom2 onkocytom3 Renal cell carcinoma nAdenocarcinoma from tubular epithelium (clear cell - Grawitz ) n85% of renal malignancies caledviny RCC nClear cell (conventional) RCC (80%) nChromophobe RCC nPapillary RCC n nRisk f.: smoking, obesity, familiar factors, industrial pollution nIncidental finding, hematuria, metastasis Renal cell carcinoma n caledvinyX Renal cell carcinoma n caledvinyY Renal cell carcinoma n caledvinyQ Renal cell carcinoma caledvinyZ Renal cell carcinoma caledvinyhistol Monosomia chromosom 1 (FISH) in chromophobe ca copy Transitional cell ca of the renal pelvis n capanvicky Transitional cell ca of the renal pelvis n capanvicky2 capanvicky3 Wilms’ tumor - nephroblastoma nMalignant embryonal tu metanefrogennous blastema nPeak incidence 1-4 yrs nSupresoric gen WT1 (11p13), WT2 (11p15) nMACRO: large, soft nMICRO blastic cells, immature epithelial, mesenchymal differentiation wilmshistol tuledv wilms Secondary tumors nLocal spread (adrenals, pancreas, liver) nLung carcinoma nMalignant lymphoma nOthers rejekceschema Normal Hyperacute - preformed antibodies Acute cellular Chronic Type of graft rejec-tion n