1. Pathology of Kidney and Collecting System Assoc. Professor Jan Laco, MD, PhD

2. Congenital and developmental disorders 1. bilateral agenesis of kidneys – kidneys and ureters absent – + other disorders – oligohydramnion – Potter‘s syndrome (beak-like nose, low set ears, abnormally bent lower limbs) 2. unilateral agenesis – boys, compensatory hyperplasia 3. fixed dystopy – caudal position of kidney, short ureter, renal a. from iliac a. 4. ren migrans – normal development, secondary descent, long („folded“) ureter, renal a. in normal position 5. malformation: merge of poles – “horseshoe“ kidney

3. Renal cysts 1. simple cysts (solitary x multiple); indolent – cortex: mm to 5-10 cm, clear fluid, diff. dg. tumor – Micro: cuboidal or flat epithelium 2. autosomal recessive polycystic kidney disease – fibrocystin gene – G: large kidneys (bilateral) - multiple tiny cysts (1-2 mm) - huge abdomen, pulmonary hypoplasia, oligohydramnion = Potter‘s syndrome – Mi: elongated cysts from collecting tubuli – clinical course: stillborn or die very soon (pulmonary or renal failure) who survive infancy - impaired concentration ability, uremia, congenital hepatic fibrosis

4. Renal cysts 3. autosomal dominant polycystic kidney disease – PKD1 gene (chr. 16) for polycystin-1; 1: 800 – G: huge kidneys (1-3 kg), cysts up to 40 mm – Mi: cysts from all parts of nephron (flat epithelium), atrophy of residual renal parenchyma – clinical course: 4th decade, flank pain, hypertension, hematuria, renal failure (end stage kidney) intracystic bleeding, inflammation, tumor + liver & pancreatic cysts + aneurysms of cerebral aa. (10-30%)

5. Renal cysts 4. cystic dysplasia – developmental disorder, abnormal shape and structure - + urinary tract defects - uni- or bilateral, segmental, diff. dg. tumor - Mi: cysts and ducts with smooth muscle and fibrous tissue, cartilage 5. dialysis-associated acquired cysts – long term HD - cysts up to 1.5 - 2 cm 6. medullary cysts – in papillae („sponge kidney“) – cortico-medullary junction („juvenile familiary nephronophtisis“)

6. Glomerular diseases Normal glomerulus: - mesangium - basement membrane - podocytes - endotelial fenestrations - Bowman‘s capsule Light microscopy + IF + EM IF: Ig (IgG, IgM, IgA, …) + complement EM: localization: mesangial, subendothelial, subepithelial

7. Glomerular injury – terminology Diffuse – damage of > 80% glomeruli Focal – damage of some glomeruli (< 80 % G) Global – damage of whole glomerulus Segmental – damage of a part of glomerulus

8. Reaction of glomerulus to injury Proliferation: of cells (mesangial, endothelial, parietal) Exsudation: leukocytes, monocytes, fibrin (crescents) Thickening of BM: deposition of immune complexes, Sclerotization: deposition of homogenous material (mesangial matrix, basement membrane material) Hyalinization : advanced stage – homogenous substance (glycoproteins) !!! Glomerular diseases are always bilateral (both kidneys are affected) !!!

9. I. Immune glomerular injury 1. Circulating ImmC – viruses, streptococci, SLE, tumors – IF: granular positivity in G 2. In situ ImmC – Ag into G or Ag in G + subsequently Ab+Ag – IF: granular positivity in G 3. Heymann nephritis – experimental membranous GN 4. Ab × BM – IF: linear positivity in G 5. ANCA (anti neutrophil cytoplasmic antibodies) – pauciimmune

10. II. Non-immune damage of glomeruli 1. Loss of polyanion in BM 2. Hyperfiltration – decrease of number of G  increased flow in G  capillary hypertension  proliferation of mesangial cells and matrix  sclerosis 3. Hereditary defects of BM – Alport syndrome 4. Glomerular ischemia – collapse and glomerulosclerosis

11. Glomerular disorders „Primary glomerulonephritis and glomerulopathy“ – immune based nonpurulent inflammation of G with alteration, exsudation or proliferation Damage of G in systemic disorders – SLE, vasculitis, DM, amyloidosis, endocarditis

12. Glomerular syndromes 1. Nephrotic sy: – proteinuria > 3.5 g / 24 h, hypoalbuminemia, edema – hyperlipidemia, lipiduria 2. Nephritic sy: – acute onset – grossly visible hematuria – proteinuria (mild) – hypertension – oliguria, anuria – azotemia, mineral dysbalance

13. 3. Rapid progressive nephritic sy (RPGN): – hematuria, proteinuria + rapid progressive loss of renal functions (renal failure) 4. Recurrent and persistent hematuria: – long term macro- or microhematuria without proteinuria – no other symptoms of nephritic syndrome 5. Slowly developing uremia: – chronic G injury = sclerosis and hyalinization of G Glomerular syndromes

14. Nephrotic syndrome 1. Minimal change disease („lipoid nephrosis“) 2. Membranous GN 3. Focal segmental glomerulosclerosis 4. Membranoproliferative GN (type I-III) 5. Systemic disorders – DM, SLE, amyloidosis, drugs

15. 1. Minimal change disease in 75 % preschool children, 2nd – 4th Y selective albuminuria, edemas causes ? Mi: minimal G changes lipids in proximal tubules – reabsorption IF: negative EM: loss (effacement) of epithelial foot processes of podocytes therapy: corticosteroids - sensitive, dependent, resistant prognosis good, rarely sclerosis of G

16. 2. Membranous GN adults (30-50 Ys), non-selective albuminuria autoimmune ??? most common cause of nephrotic sy in adults 80% idiopatic x 20% (SLE, RA, drugs, hepatitis B, tumors) Mi: thickening BM (Jones spikes) IF: granular positivity in BM (IgG+C) EM: subepithelial deposits prognosis: in 40 % (G sclerosis) - end stage kidney

17. 3. Focal segmental glomerulosclerosis adults and children, NS + non-selective proteinuria cause ??? idiopathic (10%) x secondary (IgA, SLE, HIV, heroin,...) Mi: FSGs + hyalinosis IF: granular positivity (IgM + C) EM: effacement of the foot processes, podocyte detachment prognosis: bad - 50 % renal failure within 10 years

18. 4. Membranoproliferative GN (I-III) children + adults idiopathic x secondary (SLE, tumors, hepatitis B and C) MPGN I – Mi: lobular pattern of G, thickening of BM, mesangial proliferation – IF: granular positivity (IgG + C3) – EM: subendothelial deposits, interposition of mesangium into BM – prognosis bad MPGN II (dense deposit disease) – C3NeF in serum - autoAb × C3 convertase = activation of C by alternative pathway – EM: deposits of unknown composition in BM – prognosis bad (100% recurrence after tranplantation) MPGN III - deposits variably in BM

19. Acute nephritic syndrome 1. acute proliferative (postinfectious) GN 2. rapidly progressive GN 3. IgA nephropathy 4. Henoch-Schoenlein purpura

20. 1. Acute proliferative (postinfectious) GN 1-4 weeks after infection (ß-hemolytic STR, viruses, …) school children typical nephritic syndrome – macrohematuria, mild proteinuria, oliguria, azotemia, edema – ASLO , fatigue, fever, vomiting, hypertension G: large pale kidneys with punctuate bleeding Mi: large, hypercellular G (mesangium, endothelim, leuko) IF: granular positivity (IgG + C3 in mesangium and BM) EM: subepithelial deposits (“humps“) in BM prognosis: in children excellent, in adults relatively good

21. Rapidly progressive (crescentic) GN = syndrome; NOT specific etiologic form of GN common feature = crescents in most of G (at least 50%) rapid  renal functions (days, week), hematuria, proteinuria in 1-2 M – loss of all G ETI – 1. IgG × BM (+ lungs–Goodpasture sy): linear positivity IgG – 2. ImmC GN (SLE, Henoch-Schoenlein purpura...) – 3. ANCA associated vasculitides (microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss sy) Mi: severe injury of G (BM) - necrosis, perforation of capillaries  fibrin into urinary space (Bowmann capsule)  proliferation of parietal cells + migration of monocytes (cellular crescent)  later fibrosis and sclerosis of G prognosis ~ number of crescents, stage

22. 3. IgA nephropathy (Berger disease) most common G disease worldwide; Japan young adults, children macrohematuria 1-2 days after inflammation of respiratory tract Mi:  mesangial cells, later sclerosis of G IF: IgA in mesangium EM: deposits in mesangium prognosis: variable (20-40% in 20 years = renal failure) 4. Henoch-Schönlein purpura children, skin purpuric rash, arthritis, GIT, ± kidneys Mi: similar to IgA nephropathy

23. Hereditary nephropathies Alport‘s syndrome – mostly X-linked, mutations of colagen IV gene – boys, 50% deafness, 15% eye disorders (cataracta) – hematuria, later proteinuria – males affected more frequently and severely, RF between 25-50Ys – in females only mild persisting hematuria – Mi: slight mesangial proliferation, later glomerulosclerosis – EM: thick and thin BM, splitting of lamina densa of BM Benign familial hematuria (thin BM glomerulopathy) – EM: very thin BM – prognosis favorable

24. Renal involvement in systemic disorders Systemic lupus erythematodes – females, kidney – one of affected organs x critical !!! – autoAb × nuclear DNA – hematuria, proteinuria, nephrotic / nephritic syndrome – WHO - 6 types: I normal G II mesangial GN (  mesangial cells, deposits) – 20% III FSGN (proliferation, neurophiles, fibrin) – 25% IV diffuse lupus GN (proliferation, necroses, crescents, wire loops) – 50% –variable IF deposits, EM: subendothelial depositis,  prognosis V membranous GN – 15% VI sclerosing GN – terminal stage

25. GN in infective endocarditis – ImmC – focal GN with necrosis of parts of G Amyloidosis – in AA amyloidosis – kidney always involved, in AL in majority – Mi: amorphous material in G (mesangium ± BM) walls of arterioles / capillaries + peritubular stroma Congo red + polarized light, Sirius red, IHC – EM: fibrils in mesangium and in BM – clinically: proteinuria  nephrotic syndrome, renal failure Renal involvement in systemic disorders

26. Chronic sclerosing GN 30-50% patients requiring HD end stage of a variety entities – RPGN, FSGN, MGN, MPGN, IgA nephropathy, DM, SLE micro impossible to ascertain primary disease !!! G: small, contracted kidneys with granulated surface Mi: G sclerotic replaced by hyaline „targets“ fibrosis of interstitium + chronic inflammation atrophy of tubules („thyroid-like“) sclerosis of vessels (hypertension) clinical course: slowly progressive RF – HE + RX END STAGE KIDNEY

27. Diseases affecting tubules and interstitium Tubules and interstitium - „intimal relation“ = tubular injury can also involve the interstitium and vice versa Tubulointerstitial nephritis - bacterial TIN - pyelonephritis - non-infectious TIN metabolic diseases, drugs, immune, irradiation Acute tubular necrosis – ischemic and toxic

28. Acute pyelonephritis bacterial suppurative inflammation of the K and the pelvis important manifestation of UTI + infection of lower UT !!! etiology: E. coli, Proteus, Enterobacter, Klebsiella 2 routes of infection – ascending - from lower UT - most common – hematogenous - by bloodstream - rare Ascending route: rectum/perineum into urethra = urethritis (F:M = 10:1) after instrumentation (F : M = 1 : 1) Retention of urine = condition for  bacteria growth in UB cong. disorders, stones, gravidity, prostate, UB dysfunction, uterine prolapse, DM, tumors  urocystitis

29. from UB into ureter - vesicoureteral reflux – children - congenital incompetence - short intravesical portion – adults – acquired - after inflammation, stone passage, flaccid UB infected urine  ureter (ureteritis)  pelvis (pyelitis)  renal parenchyma through collecting ducts (intrarenal reflux) or by ruptured calyces into interstitium (pyelonephritis) Hematogenous : by bloodstream from heart (endocarditis) G (ascending): unilateral x bilateral K (edema), raised long cortical and medullar yellow abscesses, reddish pelvis G (hematogenous): bilateral, small cortical abscesses

30. Mi (asc.): WBC in interstitium and in tubules = tubules melted by inflammation - abscesses Mi (hemat): bacteria in G and arteries - abscesses in interstitium Complications: - necrotizing papillitis (DM) - pyonephros – pelvis + calyces filled by pus - perinephritic abscess (subcapsular) - paranephritic abscess (pus in perinephric fat tissue) - urosepticemia (renal failure + septicemia) Clinical course: sudden onset, costovertebral angle pain, fever, chills, dysuria, bacteriuria, pyuria

31. Chronic pyelonephritis and reflux nephropathy interstitial inflammation + scarring of renal parenchyma interstitial inflammation + scarring of renal parenchyma + scarring and deformity of pelvicalyceal system + scarring and deformity of pelvicalyceal system chronic obstructive – reccurent acute inflammations – stones, ureteral obstruction, prostate hyperplasia, obstruction of urethra chronic reflux-associated – vesicoureteral reflux - infection ? G: unilateral x bilateral /// diffusely x in patches diffusely = small, contracted K in patches = cortical flat scars + blunted calyces - scarring of the pelvicalyceal system = deformation obstructive = whole K reflux = polar scarring Mikro: atrofie kanálků („tyreoidizace“), fibróza intersticia, chronický zánět, periglomerulární fibróza, skleróza cév Klinicky: pomalý rozvoj poklesu ren funkcí, snížená koncentrační schopnost, hypertenze. Někdy se zjistí až v terminálním stádiu -častá příčina CHRI

32. Micro: - uneven interstitial fibrosis + inflammation - tubular dilation, epithelial atrophy (thyreoidisation) - arteriosclerosis (hypertension) - inflammation and fibrosis of calyceal mucosa and wall - periglomerular fibrosis, glomerulosclerosis clinically: - progressive deterioration of renal functions - loss of concentrating ability - arterial hypertension !!! chronic pyelonephritis is important cause of chronic renal failure !!!

33. Non-infectious TIN graft rejection /see later/ acute drug-induced (alergic) TIN – drugs (ATB, PNC, diuretics, sulphonamides, NSAID...) - haptens – 2 weeks after exposure = hematuria, fever, eosinophilia, rash – Mi: interstitial edema, lymphocytes, eosinophils, leukocytes, tubular changes, rarely granulomas – complete remission in months

34. Analgesic nephropathy – a few years lasting abusus of analgesics (phenacetin, aspirin) – metabolits are inhibitors of vasodilation = papillary ischemia – chronic TIN + papillary necrosis – G: contracted kidneys with yellowish brown necrotic papillae (into the pelvis = hydronephrosis) – Mi: necrotic papillae without leukocytic reaction, interstitial scarring, tubular atrophy, inflammation, analgesic microangiopathy (BM thickening) – clinicalally: chronic renal failure, hypertension, increased incidence of urothelial carcinoma (pelvis + UB)

35. Non- infectious TIN Hypokalemic nephrosis – loss of K+ (diarrhoea) - vacuoles in cells of distal tubules Osmotic nephrosis – hypertonic solutions (infusions) - fine vacuolization within proximal tubules Hepatorenal syndrome – renal failure in liver disorder (bile in tubules) Myeloma cast nephropathy – Bence-Jones protein casts in the tubular system Radiation nephropathy – after ionizing radiation for malignancy of the retroperitoneum – tubular atrophy, interstitial fibrosis

36. Transplantation nephropathology Hyperacute rejection – minutes/hours after transplantation – ready antibodies against graft – G: graft cyanosis – Mi: necrotizing vasculitis, thrombi in capillaries Acute rejection – days, weeks, months – impairment of renal functions, azotemia – T lymphocytes + antibodies – Mi.: lymph. in intersticium, tubulitis, endotelialitis, edema Chronic rejection – months, years – G: shrunken kidney – Mi.: thickened arterial intima  ischemia, fibrosis,  G

37. Acute tubular necrosis (ATN) destruction of tubular cells = ARF + oliguria < 400 ml 2 causes: ISCHEMIC and TOXIC ischemic – hypoperfusion (shock), septicemia, pancreatitis, trauma – crush syndrome (myoglobinuria), mismatched transfusion Toxic: – heavy metals (Hg), ethylenglycol, herbicids, solvents, ATB (gentamicin) patogenesis: tubular necrosis = oliguria - blockage by necrotic debris, vasoconstriction (RAA, endothelin), tubular fluid leakage into interstitium - edema = tubular collapse, inflammation (leukocytes)

38. G: pale cortex + dark medulla Micro: ischemic ATN – necrosis of segments of proximal and distal tubules – rupture of tubular BM = tubulorrhexis – necrotic material (myoglobin, Hb) + TH protein = casts in distal and collecting tubuli – interstitial edema, inflammation (lymphocytes) toxic ATN – similar necrosis of proximal tubules – tubular BM are spared !!! – sometimes calcification of necrotic cells

39. after a week = regeneration of tubular cells – tubules with undestroyed BM - complete regeneration possible clinical course: 3 stages - initiating phase (lasting 36 hours) decline in urine output, azotemia - maintenance phase (2nd-6th day, lasting up to 3 weeks) urine 50-400 ml/24 hrs. = uremia !, water overload DIALYSIS !!! - recovery phase (regeneration) urine volume 3 litres /24 hrs. threat of dehydratation, mineral dysbalance, infection GF normalize in 2-3 months concentrating ability in 6 months survival 90-95 %

40. Rare types of tubular necrosis Hypochloremic „nephrosis“ – repeated vomiting and diarrhoea (children) = dehydratation shock with tubular necrosis Massive cortical necrosis – long term shock or DIC – G: bilateral damage, yellow necrotic cortex – Mi: arteriolar thromboses - massive necrosis – clinical course: ATN - like (anuria), adverse prognosis

41. Diabetic nephropathy Diabetic nephropathy G: slightly enlarged, yellow, granulated kidneys Vessels: – accelerated ARTS (plaques reach aa. arcuatae) – hyalinne arteriolosclerosis of vas afferens et efferens Glomerular lesion: thickened BM – diffuse glomerulosclerosis (thickened BM + inc. mesang. matrix) – nodular Gsclerosis (Kimmelstiel-Wilson lesion) - ball-like nodules of laminated matrix within mesangium – clinically - proteinuria, nephrotic syndrome, later renal failure glomerulosclerosis = ischemia =scaring=cortex granulation Tubulointerstitial lesion: – increased risk for repeated pyelonephritis + necrosis of papillae – storage of glykogen in proximal tubules - Armani cells

42. Diseases involving blood vessels 1. renal artery stenosis – elderly (ARTS) x younger patients - fibromuscular hyperplasia (dysplasia) = hypertension – long term stenosis = atrophy 2. kidney infarction – trombembolism from heart, atheroembolism from aorta – trombosis (ATS, PAN) 3. arteriosclerotic nefrosclerosis – ARTS aorta = branches ren. artery in parenchyma = „V shaped“ scars 4. benign nefrosclerosis: benign hypertension – G: symmetrical atrophy, finely granulated surface – Mi: hyalinne thickening of small arteries and arterioles

43. = hyalinne arteriolosclerosis (insudation of plasma proteins into the wall = production of hyalinne matrix) thickening = stenosis = ischemia = atrophy (collapse and obliteration G) = granulated surface, tubular atrophy, intersticial fibrosis clinical course: slight functional impairment, NO uremia 5. Malignant nefrosclerosis: malignant BP (dia 120) – fibrinogen into wall = endothelial injury = fibrinoid necrosis – intimal hyperplasia (hyperplastic arteriolosclerosis) = stenosis (ischemia) – ischemia (renin-ang.-aldos) = elev BP = malignant hypertension – G: petechial hemorrhages, granulated K, shrunken K – Mi: larger aa - concentric proliferation of intimal smooth m. cells („onion skin“ appearance) arterioles - fibrinoid necrosis (inflammation = arteriolitis) glomeruli - segmental necrosis, crescents

44. clinical course: - diastolic BP greater than 120 mm - papilledema (visual impairment) - encephalopathy (headaches, nausea, vomiting) - renal failure + proteinuria + hematuria

45. Systemic vasculitides 1. Polyarteritis nodosa – aa interlobulares, aa. arcuatae – fibrinoid necrosis, inflammation, trombosis = infarctions – G are not affected 2. Polyangiitis microscopica (pANCA+) – interlobular aa., vas afferens, G capillaries – focal segmental necrotizing glomerulonephritis with crescents 3. Wegener granulomatosis (cANCA+) – morfology - see above – + periglomerular granulomas 4. Alergic granulomatosis (Churg-Strauss syndrome) – focal segmental necrotizing GN + eosinophils

46. Thrombotic microangiopathies thrombosis in microcirculation clinically: hemolytic anemia, thrombocytopenia, renal failure Hemolytic - uremic syndrome children, E. coli infection (verocytotoxin) = endothelial injury bleeding (hematemesis, melena) + hematuria + TMA one of the main causes of acute renal failure in children !!! 25% children develop renal failure within 15-25 years Thrombotic thrombocytopenic purpura adult females + neurologic symptoms autoAB x enzyme cleaving von Willebrand factor multimers

47. Renal stones urolithiasis: nephro-, uretero-, urocysto-litiasis 75 % calcium oxalate / phosphate - hard, dark 15 % magnesium ammonium phosphate - white 10 % uric acid or cystine - round, smooth-surfaced, brown causes: often unclear 1. hypersaturation of urine by stone´s constituents - idiopatic hypercalciuria, hypercalcemia 2. persistent alkaline urine due to UTI (Proteus vulgaris) - - magnesium ammonium phosphate stones 3. high uric acid level in urine or acid urine (pH < 5.5) - uric acid stones; gout, cell break down 4. defective renal transport of cystine - cystine stones

48. Renal stones predisposition dehydratation, bacteria colonies, epithelial desquamation, calcification = nidi for stones formation morphology: - 80 % unilateral - 20 % bilateral number, shape and size vary (solitary x multiple), mm - cm, smooth, jagged, „staghorn“ clinical course - large stones often asymptomatic or dysuria - small stones into ureter = hydronephrosis (+ infection) = renal colic = hematuria

49. Hydronephrosis = dilation of renal pelvis and calyces + atrophy of renal parenchyma due to obstruction of outflow of urine insidious x sudden, complete x incomplete obstruction at any level of UT (renal pelvis - urethra) - below pelvis = hydroureter congenital – atresia of uretra, valve formations in urethra – valve formation in ureter, aberrant renal a. compressing ureter acquired – „foreign bodies“ (stones, necrotic papillae, blood clotts) – tumors (prostate, UB, ureter, cervix, retroperitoneum, rectum) – inflammations (prostate, retroperitoneal fibrosis, postinflammatory stricture of ureter) – neurogenic dysfunction of UB, pregnancy

50. bilateral HN (obstruction below level of ureters) unilateral HN (obstruction at ureter or above) G: long term obstruction = dilation of pelvis + (ureter), flat papilae, atrophied K parenchyma Mi: tubular dilation, interstitial edema, later atrophy of tubular epithelia, interstitial fibrosis, glomerulosclerosis clinically: - sudden bilateral = ARF without dilation - rapid unilateral = GF declined in affected K, normal function (2. kidney) - long term unilateral = clinically silent dilation !!! HN  disposition to pyelonephritis !!!

51. Renal failure / uremia azotemia: elevation of blood nitrogen (urea, creatinine) - metabolits do not get into kidneys (prerenal failure) - kidneys can not clear them (renal and postrenal failure) causes – prerenal (hypoperfusion - shock) – renal (parenchymal disorders) – postrenal (obstruction of urine flow below level of kidneys) azotemia + clinical symptoms + biochemical abnormalities = uremia (uremic syndrome)

52. Manifestations of the uremia - hyperkalemia = arrhythmia - fibrinous pericarditis - fibrinous pleuritis (incr. permeability of vessels) - gastroenteritis - hemorhagic gastritis, Treitz‘s pseudomembranous colitis - lung edema / uremic lung with features of DAD - brain edema / uremic encephalopathy - apatia, somnolence, convulsions - face edema (retention of Na+ and water) - peripheral neuropathy (disordered tendon reflexes) - anemia (hypoproduction of erytropoetin)

53. - gray skin (anemia, deposition of urine pigment) - renal tubules (deposition of the oxalate crystals) - renal osteopathy - impaired metabolism of vitamin D - hyperphosphatemia, hypocalcemia = sec. hyperparathyreoidism = demineralisation and resorption of bone tissue - increased disposition to bleeding - fragility of capillaries - metabolic acidosis - decreased excrecion of H+, decreased resorbtion of bicarbonate - pancreatitis - uremic dehydratation and inspissation of secretion

54. Tumors BENIGN – adenoma - in cortex, white nodules, solitary or multiple, mm, tubular, papilar – angiomyolipoma - tuberous sclerosis (fat, vessels, smooth muscle) – oncocytoma - elderly, centimeters, brown, central scar MALIGNANT: carcinoma (85% of malignat tumors of K) – clear cell carcinoma 70-80% of Cas kidney, 5.-7. Decade cortex, spheric, sometimes huge (> 10 cm), yellow, regressive ch., cystic invasion of perirenal tissues, adrenal glands, pelvis and renal vein - vena cava - right heart („tumor thrombus“)

55. Mi: from prox. tubules, clear cells (lipids, glycogen) metastases: lung, brain, bone, LN, thyroid gland, skin, SG clinicaly: symptoms vary - small tumors often incidentally (ultrasound, CT) - large tumors: hematuria, flank pain, fever - paraneoplastic syndrome: Cushing syndrome, polycytemia, hypercalcemia metastasis is sometimes first manifestation of tumor ! prognosis: stage, nuclear grade, generally unfavourable papillary carcinoma (10-15%) - better prognosis chromophobe carcinoma (5%) - favourable prognosis

56. Wilms tumor (nephroblastoma) children, 2.- 4. year, from embryonal tissues G: gray white, necroses, pseudocysts Mi: triphasic - nefrogenic blastema + epithelial structures + stromal structures (cartilage, muscle) 5% foci of anaplasia (pleomorphic nuclei, atypical mitoses) clinically: pain, hematuria, palpable abdominal mass very good prognosis ( 90 %); anaplasia - metastases (lung) transitional carcinoma of renal pelvis carcinoma 5-10 % kidney malignancies G: flat - invasive exophytic – invasive / non-invasive (obstruction = HN) Mi: papillocarcinoma clinically: painless hematuria, metastases to LN

57. Tumors of the ureter and urinary bladder urothelial (transitional) carcinomas like in pelvis ureter = hematuria, obstruction (HN) Bladder 6.-7. decades risk = beta-naphtylamine, smoking, chronic cystitis… G: flat or papillary(exophytic growth), later invasion into wall of bladder clinically: hematuria, later obstruction of the ureters metastases in LN p rognosis depends on histologic grade and depth of invasion !!!

58. Other disorders of the urinary bladder, renal pelvis and ureter developmental disorders – pelvis renalis duplex + ureter duplex), ureter fissus – exstrophy of UB – epispadias, hypospadias inflammations – pyelitis, ureteritis, urocystitis, urethritis – causes: bacteria, instruments, cystoscopy, iradiation, drugs, … – types: catarrhal, catarrhal-purulent, pseudomembranous, hemorrhagic, …