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Pathology of Kidney and Collecting System

Pathology of Kidney and Collecting System. Assoc. Professor Jan Laco, MD, PhD. Congenital and developmental disorders. 1. bilateral agenesis of kidneys kidneys and ureters absent + other disorders – oligohydramnion

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Pathology of Kidney and Collecting System

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  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. Glomerular syndromes • 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

  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. Renal involvement in systemic disorders • 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

  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 + 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: ISCHEMICand 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 !!! - recoveryphase (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 • 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 urineor 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 !!!

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