Renal pathology (dr magdy ismail) copy

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Renal pathology (dr magdy ismail) copy

  1. 1. Pathology of the kidney and itscollecting systemPr.Dr.Magdy Ismaeil Ahmed
  2. 2. Anatomy of the Kidney
  3. 3.  Normal structure of the kidneyNormal structure of the kidney :-:- Kidney consists of glomeruli ,tubules ,interstitium and bloodKidney consists of glomeruli ,tubules ,interstitium and bloodvessels .All are anatomically linked .Damage to one componentvessels .All are anatomically linked .Damage to one componentaffects the others . Whatever ,different renal diseases leading toaffects the others . Whatever ,different renal diseases leading todestruction all kidney componentsdestruction all kidney components  End stage kidney.End stage kidney. Normal kidney functionNormal kidney function :-:-1-Excretion of waste products1-Excretion of waste products2-Secretion of hormones ( renin ,eryropoietin )2-Secretion of hormones ( renin ,eryropoietin )3-Maintain acid-base balance3-Maintain acid-base balance4-Regulation of body salts and water.4-Regulation of body salts and water.
  4. 4. Congenital anomaliesCongenital anomalies10% of newborns develop significant malformation10% of newborns develop significant malformationMostly arises from maldevelopment rather than inherited genes.Mostly arises from maldevelopment rather than inherited genes.1-Renal agenesis1-Renal agenesis:-:- Failure of kidney developmentFailure of kidney developmenta-Bilaterala-Bilateral  incompatible with life .incompatible with life .b-Unilateralb-Unilateral Compensatory hypertrophy of the other kidneyCompensatory hypertrophy of the other kidney  ProgressiveProgressiveglomeruloscelrosis.glomeruloscelrosis.2-Hypoplasia :-2-Hypoplasia :- Incomplete development.Usually unilateral,and posses a reducedIncomplete development.Usually unilateral,and posses a reducednumber of renal lobes and pyramides (<6). D.D from atrophynumber of renal lobes and pyramides (<6). D.D from atrophy3-Ectopic kidney3-Ectopic kidney (out of place) ;-(out of place) ;- Presence of the kidney in an ectopic site (in pelvis orPresence of the kidney in an ectopic site (in pelvis orabove pelvic brim ).It complicated by kinking or tortuousity of uretersabove pelvic brim ).It complicated by kinking or tortuousity of ureters  UrinaryUrinaryretention and frequent infection.retention and frequent infection.4-Horse4-Horse ––shoe kidney:-shoe kidney:- Both kidneys are fused together :- Fusion of upper polesBoth kidneys are fused together :- Fusion of upper poles(10%) or lower poles (90%) in front the great vessels(10%) or lower poles (90%) in front the great vessels  may cause renal failure.may cause renal failure.5-Aberrant renal artery5-Aberrant renal artery ;-;- It passes in front renal pelvisIt passes in front renal pelvis  hydronephrosishydronephrosis6-Congenital double ureters and double pelvis6-Congenital double ureters and double pelvis7-Supernumerary kidney :-7-Supernumerary kidney :- More than 2 kidneys.More than 2 kidneys.
  5. 5. Cystic diseases of the kidneyCystic diseases of the kidney1-Simple cyst1-Simple cyst2-Cyst renal dysplasia2-Cyst renal dysplasia3-Polycystic kidney diseases3-Polycystic kidney diseases (adulthood)(A.D)(adulthood)(A.D)(PKD)(PKD) (childhood)(A.R)(childhood)(A.R)4-Medullary sponge kidney4-Medullary sponge kidney5-Nephronophthisis-uremic medullary cystic complex5-Nephronophthisis-uremic medullary cystic complex(UMCD)(UMCD)6-Acquired (dialysis-associated ) cystic disease.6-Acquired (dialysis-associated ) cystic disease.
  6. 6. 1-Simple cyst1-Simple cyst :-:--Non inherited-Non inherited-Single or multiple cysts-Single or multiple cysts-Cortical rarely medullary-Cortical rarely medullary-2-10 cm in diameter lined by low cubical epithelium ,filled with clear-2-10 cm in diameter lined by low cubical epithelium ,filled with clearserous fluidserous fluid-Complicated by hemorrhage-Complicated by hemorrhage flank painflank pain2-Cystic renal dysplasia:-2-Cystic renal dysplasia:--Sporadic (Non familial) either unilateral or bilateral-Sporadic (Non familial) either unilateral or bilateral-It results from abnormal metanephric differentiation-It results from abnormal metanephric differentiation-Associated with urinary tract obstruction-Associated with urinary tract obstructionGrosslyGrossly :- Affected kidney is multicystic:- Affected kidney is multicysticHistologyHistology :- immature ducts surrounded by undifferentiated mesenchyme:- immature ducts surrounded by undifferentiated mesenchyme+Focal cartilage formation+Focal cartilage formation
  7. 7. 3-Adult PKD (A.D.)3-Adult PKD (A.D.)-1/1000 persons-1/1000 persons-PKD gene is on-PKD gene is on Ch 16Ch 16-Always bilateral (arises in children till 50--Always bilateral (arises in children till 50-60 years of age.60 years of age.Clinical presentation :-Clinical presentation :-1-Abdominal pain and abdominal masses1-Abdominal pain and abdominal masses2-Hematuria and H.P2-Hematuria and H.P3-proteinuria3-proteinuria Renal failureRenal failureGrossly :-Grossly :- Massively enlarged kidneyMassively enlarged kidneyMultiple cysts (3-4 cm ) along nephronsMultiple cysts (3-4 cm ) along nephronsand compress renal parenchyma ,not conne-and compress renal parenchyma ,not conne-cted with renal pelvis (D.D hydronephrosis)cted with renal pelvis (D.D hydronephrosis)Microscopically :Microscopically :- variable sized cystic- variable sized cysticstructures lined by variable epitheliumstructures lined by variable epitheliumfilled by clear ,bloody or turbid fluid.filled by clear ,bloody or turbid fluid.Pathogenesis :-Pathogenesis :-1-Partial intratubular obstrction1-Partial intratubular obstrction3-Increased compliance of tubular B.M3-Increased compliance of tubular B.M3-Focal epithelial hyperplasia3-Focal epithelial hyperplasiaAssociations:-Associations:--40% of cases (polycystic liver disease)-40% of cases (polycystic liver disease)-10-30% (cerebral berry aneurysm)-10-30% (cerebral berry aneurysm)Cause of deathCause of death :- Brain hemorrhage,:- Brain hemorrhage,H.P or infection ,R.FH.P or infection ,R.FChildhood PKD (A.R)Childhood PKD (A.R)-Rarely bilateral anomaly-Rarely bilateral anomaly-Mostly at perinatal or neonatal or-Mostly at perinatal or neonatal orjuvenile periodsjuvenile periods Rapid R.FRapid R.FGrosslyGrossly :- Multicystic enlarged kidney:- Multicystic enlarged kidneyCylindrically dilated collecting tubulesCylindrically dilated collecting tubuleslie at right angles to the cortex fillinglie at right angles to the cortex fillingboth cortex and medullaboth cortex and medullaMicroscopic :Microscopic :- dilated collecting tubules- dilated collecting tubuleslined by uniform cubical cellslined by uniform cubical cellsAssociation :-Association :-1- Polycystic liver disease and prolifer-1- Polycystic liver disease and prolifer-ated bile ductsated bile ducts  Congenital hepaticCongenital hepaticfibrosisfibrosis2-In adults2-In adults  Hepatosplenomegaly andHepatosplenomegaly andPortal hypertensionPortal hypertension
  8. 8. Medullary cystic diseasesMedullary cystic diseases4-Medullary sponge kidney4-Medullary sponge kidney-Usually in adults-Usually in adults-Characterized by Multiple cystic-Characterized by Multiple cysticDilatation of the collecting ducts of theDilatation of the collecting ducts of theMedullaMedulla-It is discovered radiologically-It is discovered radiologically-It may predispose to renal infection or renal-It may predispose to renal infection or renalcalculi and hematuriacalculi and hematuria6-Acquired (dialysis associated) cystic6-Acquired (dialysis associated) cysticdiseasediseaseMultiple cortical and medullary cysts inMultiple cortical and medullary cysts inpatients with prolonged renal dialysis.patients with prolonged renal dialysis.The cysts are lined by atypical hyperplasticThe cysts are lined by atypical hyperplasticepitheliumepithelium  predisposes to adenoma orpredisposes to adenoma orcarcinoma .carcinoma .5-Nephronophisis-(UMCD) complex5-Nephronophisis-(UMCD) complex-A family of progressive renal disorders-A family of progressive renal disorders-It begins in childhood-It begins in childhood-It characterized by small cysts in the-It characterized by small cysts in themedulla (at cortico-medullary junction )medulla (at cortico-medullary junction )associated with cortical tubular atrophyassociated with cortical tubular atrophyand interstitial fibrosis.and interstitial fibrosis.4 variants:-4 variants:-1-sporadic (20%)1-sporadic (20%)2-Familial (A.R) juvnile nephronophisis2-Familial (A.R) juvnile nephronophisis(50%)(50%)3-Renal retinal (recessive) dysplasia (15%)3-Renal retinal (recessive) dysplasia (15%)4-Adult onset (dominant) MCD (15%)4-Adult onset (dominant) MCD (15%)Diagnosis :-Diagnosis :-1- in children or adolescent1- in children or adolescent  unexplainedunexplainedR.FR.F2-Positive family history +Chronic tubulo-2-Positive family history +Chronic tubulo-interstitial nephritis .interstitial nephritis .
  9. 9. RENAL PATHOLOGYRENAL PATHOLOGYDiseases can affect the following renal structures :-A- Glomeruli (often immunological) B- Tubules (toxic, infectious)C-Interstitium (toxic, infectious) D-Vascular (metabolic)GLOMERULIGLOMERULINetwork of capillariesa) lined by fenestrated endotheliumb) basement membranec) podocytes (“foot processes”)Glomerular capillary walla) lined with fenestrated endothelium ( 70-100 nm)b) glomerular basement membrane(GBM) consists of :-1-Collagen (type IV) forms network to which glycoproteins attach2-Heparan sulfate, laminin, glycoproteins.c) visceral epithelial cells (podocytes; “foot processes”) composed of :-i) Interdigitating foot processes embedded to basement membraneii) Foot processes are separated by 20-30 nm filtration slits bridged bythin diaphragm (nephrin)
  10. 10. D-Entire glomerulus is supported by mesangial cells, modified smoothmuscle cells and lying between capillaries ,they function as :-i-Phagocytic, contractile, supportive ,proliferative.ii-Can secrete biologically active mediators (hormones & collagen)Functions of glomeruliFunctions of glomerulia) very permeable to H2O and small solutesb) impermeable to large M.W proteins (~ 70 k.D or larger; i.e., albumin)c) “glomerular barrier function”i) Its selective permeability based on:-1-Size (M.W) :-large moleculescan`t cross GBM  Lead to no harm – 2-Charge: cationic (+) morepermeablesubepithelial deposits.Neutral mesangial deposits,while anionic (-)  subendothelial or do not deposits(no harm)ii) podocytes important in maintaining this “function”:-slit diaphragmmaintain size-selectivity by specific proteins
  11. 11. 1- NEPHRIN: extend towards each other from neighb-oring podocytes comprising the slit diaphragm2- PODOCIN: intracellular (podocyte) protein wherenephrin attaches - mutations in genes encodingthese proteins give rise to nephrotic syndrome(glomerular disease)
  12. 12. Clinical ManifestationsClinical ManifestationsTerminologyTerminologyA)-Azotemia: ↑ BUN and ↑ creatinine related to ↓ GFR due to :--Renal causes:- Parenchymal diseases-Pre-renal azotemia: ↓ RBF, hypoperfusion w/ou parenchymal damage- Postr-enal azotemia: obstruction of urine flow below level of kidneyb) Uremia :- Azotemia associated with clinical S & S .C-Asymptomatic hematuria and/or proteinuria:- Glomerular hematuria andsubnephrotic proteinuria ,due mild glomerular disease.D-Acute renal failure :- Oliguria or anuria and recent azotemiaE-Chronic renal failure :- Prolonged signs & symptoms of uremia
  13. 13. 5-Chronic renal failure: 4 stages1- ↓ Renal reserve:GFR 35-50% normal,Patient asymptomatic,More susceptible to develop azotemia2- Renal insufficiency:GFR 20-35% of normal,Azotemia, anemia, ↑ BP, polyuria/nocturia ( ↓ concentrating ability)3-Renal failure:GFR 5-20% of normalkidneys cannot regulate volume & ions: edema, hypocalcemia,metabolicacidosis, uremia with neurological, CV and GI complications4-End stage renal disease:GFR < 5% of normal, terminal stage of uremia
  14. 14. Glomerular DiseasesGlomerular DiseasesGlomerulonephr/ itisGlomerulonephr/ itisDefinitionDefinition :-:- Inflammation of the kidney glomeruli . It is a majorcause of renal diseases.Types :-Types :-1-Primary GNitis1-Primary GNitis :- The kidney is the principle organ involved.2-Secondary GNitis :-2-Secondary GNitis :--The kidney is one of many organs can damaged by systemic diseases.-It is the most common cause of CRF in humans.
  15. 15. I-Pry glomerulonephritisI-Pry glomerulonephritis1-Acute diffuse proliferative GN1-Acute diffuse proliferative GN2-Rapidly progressive GN2-Rapidly progressive GN3-Membranous GN3-Membranous GN4-Membranoproliferative GN4-Membranoproliferative GN5-Lipoid nephrosis (minimal change5-Lipoid nephrosis (minimal changedisease)disease)6-Focal segmental glomerulosclerosis6-Focal segmental glomerulosclerosis7-IgA Nephropathy7-IgA Nephropathy8-Chronic GN8-Chronic GNII-2nd glomerulonephritisII-2nd glomerulonephritis1-SLE1-SLE2-D.M2-D.M3-Amyloidosis3-Amyloidosis4-Goodpasture’s syndrome4-Goodpasture’s syndrome5-Polyarteritis nodosa5-Polyarteritis nodosa6-Wagener’s granulomatosis6-Wagener’s granulomatosis7-Henoch-Schonlein purpura7-Henoch-Schonlein purpura8-Bacterial endocarditis8-Bacterial endocarditisHereditary disordersHereditary disorders-Alport`s syndrome-Alport`s syndrome-Fabry`s disease-Fabry`s disease
  16. 16. Glomerular diseases presented by :-Glomerular diseases presented by :-1-Nephritic syndrome1-Nephritic syndrome2-Nephrotic syndrome2-Nephrotic syndrome3-Mixture of both3-Mixture of bothGlomerular diseases should be studied in terms ofGlomerular diseases should be studied in terms of1-Pathogenesis 2-Morphology 3-Clinical presentation1-Pathogenesis 2-Morphology 3-Clinical presentationPathogenesis of Glomerular injuryPathogenesis of Glomerular injuryTwo basic mechanisms :-Two basic mechanisms :-1-Immune mechanisms ( pry or secondary ).1-Immune mechanisms ( pry or secondary ).2-Non -immune mechanisms .2-Non -immune mechanisms .I-The immune mechanismsI-The immune mechanismsThree mechanisms:-Three mechanisms:-1-Antibody mediated1-Antibody mediated2-Cell mediated2-Cell mediated3-Activation of alternate complement pathway3-Activation of alternate complement pathway
  17. 17. I-Anti-body mediated injuryI-Anti-body mediated injury1-In situ immune complex deposition :-1-In situ immune complex deposition :-Antibodies react directly with tissueAntibodies react directly with tissueantigenantigena-Fixed intrinsic tissue Ag (anti-tissue Aba-Fixed intrinsic tissue Ag (anti-tissue Ab ––mediated GN)mediated GN)i-Anti-GBM nephritis (e.g Good- pasture syndrome)i-Anti-GBM nephritis (e.g Good- pasture syndrome)ii-Heyman nephritis ( Heyman Ag of epithelial cells)ii-Heyman nephritis ( Heyman Ag of epithelial cells)iii-Idiopathic human membranous GNiii-Idiopathic human membranous GNb-Antibodies against Planted non-glomerular antigensb-Antibodies against Planted non-glomerular antigensi-Exogenous Ag (drugs &infectious agent)i-Exogenous Ag (drugs &infectious agent)ii-Endogenous (DNA,Igs, I.complexes)ii-Endogenous (DNA,Igs, I.complexes)2-Circulating I.C deposition (get trapped within glomeruli )(type III reaction)2-Circulating I.C deposition (get trapped within glomeruli )(type III reaction)i-Endogenous Ag (SLE )i-Endogenous Ag (SLE )ii-Exogenous Ag (infectious products )ii-Exogenous Ag (infectious products )
  18. 18.  II-Cell mediated injuryII-Cell mediated injury :-:- sensitized T cells can cause glomerularinjury, in absence of immune deposits . It may occur in some forms ofRP GNMediators of immune glomerular injury.Oxidants Proteases EicosanoidsCytokines Growth Factors Nitric OxideOthers
  19. 19. III-Activation of alternate complement pathway:-III-Activation of alternate complement pathway:- Circulating Ag-Circulating Ag-Abs complex trapped in glomeruliAbs complex trapped in glomeruli bind to and activate the complementbind to and activate the complement Releasing mediatorsReleasing mediators  glomerular injuryglomerular injuryI.F .microscopes :- It appears asI.F .microscopes :- It appears as aa linear pattern in anti-GBM nephritislinear pattern in anti-GBM nephritis or in aor in agranular patterngranular pattern in all other types.in all other types.Mediators of immune injuryMediators of immune injury :- Mediated either by antibodies:- Mediated either by antibodiesdeposition or T-cell immune reactiondeposition or T-cell immune reactionA-Antibody depositionA-Antibody deposition:-:- causes release ofcauses release of1-Neutrophils :1-Neutrophils :-- Release proteases (damage BM),archidonic acid metabolitesRelease proteases (damage BM),archidonic acid metabolites(decrease GFR) and oxygen free radicals (damage the cells)(decrease GFR) and oxygen free radicals (damage the cells)2-C5b-92-C5b-9 :-Terminal membrane attack complex:-Terminal membrane attack complex  cell lysis & stimulate mesangialcell lysis & stimulate mesangialcellscells  protease,oxygen free radicals ,IL-1 and PGprotease,oxygen free radicals ,IL-1 and PG3-Monocytes and macrophages3-Monocytes and macrophages :- Release cytokines ,and GFs:- Release cytokines ,and GFs4-Platelet4-Plateletss :-Release archidonic acid metabolites and GFs:-Release archidonic acid metabolites and GFs5-Coagulation proteins5-Coagulation proteins :-Fibrin:-Fibrin  stimulate cresentic GN.stimulate cresentic GN.B-T-cell reactionB-T-cell reaction :- stimulate:- stimulate macrophagesmacrophages && mesangial cellsmesangial cells GlomerularGlomerularinjuryinjury
  20. 20. Fate :-Fate :-1-One attack of streptococcal infection1-One attack of streptococcal infection  I.Cs ,degraded by mesangialI.Cs ,degraded by mesangialcellscells  ↓↓ inflammation and a limited courseinflammation and a limited course2-Showers of antigens (SLE or HBV)2-Showers of antigens (SLE or HBV) Repeated cycles of I.C,sRepeated cycles of I.C,sdepositiondeposition  Progressive glomerular injury.Progressive glomerular injury.II-Non immune mechanismsII-Non immune mechanisms1-Most of glomeruli1-Most of glomeruli destroyed by different renal diseasesdestroyed by different renal diseases ↓↓ GFR (30-GFR (30-50% )50% ) progressing to end stage glomerulosclerosis andprogressing to end stage glomerulosclerosis and RF.RF.2-Other glomeruli2-Other glomeruli hypertrophied to increase workloadhypertrophied to increase workload  glomerularglomerularcapillary hypertensioncapillary hypertension  systemic hypertensionsystemic hypertension  epithelial andepithelial andendoth . injuryendoth . injury  proteinuria .proteinuria .3-Mesangial response3-Mesangial response occurs in form of mesangial cell proliferationoccurs in form of mesangial cell proliferationand matrix deposition and Intra-glomerular coagulationand matrix deposition and Intra-glomerular coagulation  Glomerulo-Glomerulo-sclerosissclerosis further loss of renal function and vicious circle.further loss of renal function and vicious circle.
  21. 21. Destruction of some GlCompansatory hypertrophy ofunaffected GlCapillary hypertensionSystemic hypertensionEpithelial &endothelialdamageLeakage of proteins intomesangiumFibrin deposition & proliferation ofmesangial cellsMore sclerosis
  22. 22. Pathological features occur in GN.Pathological features occur in GN.a) Hypercellularitya) Hypercellularity:ii) Cell proliferation) Cell proliferation (endothelial ,epithelial and mesangial cells)(endothelial ,epithelial and mesangial cells)ii) Leukocytes infiltrationii) Leukocytes infiltration (neutrophils, monocytes and lymphocytes)(neutrophils, monocytes and lymphocytes)iii) Crescents formationiii) Crescents formation of glomeruli from proliferated parietal epithelial cell andof glomeruli from proliferated parietal epithelial cell andmonocytes (TNF, IL-1, IFN-monocytes (TNF, IL-1, IFN-γγ) as well as , fibrin .) as well as , fibrin .b) Basement membrane thickeningb) Basement membrane thickening:- Either due to :-i-Thickening of GBM proper as with diabetic glomerulosclerosis Orii-Deposition of immune complexes on subendothelial or subepithelial side of GBM orwithin GBM itself .c) Hyalinosis & sclerosisc) Hyalinosis & sclerosis :- Accumulation of plasma proteins Obliteratescapillary lumen of glomerulous (sclerotic feature) and increased mesangial matrix (hyalinosis) .d)-Others alterationsd)-Others alterations :- Thrombosis, fibrin deposition or lipid accumulationDifferent terminology of glomerlar affection1-Diffuse (all glomeruli are affected)2- Focal (Some glomeruli are affected )b) Global ( Entire glomerulus is affected )d) Segmental (Part or a segment of each glomerulous is affected )e) Mesangial (affecting mesangial region)
  23. 23. Proliferation of Gl cells + Leukocytic infiltrationSwollen endo.cells+Closed epith slitsDecrease GFROliguriaFluid retention HypertensionFocal damage of cells & BMEscape ofRBC,s ProteinsHematuria ProteinuriaNephritic syndrome :-*Definition : Acut clinical syndrome manifested by Oliguria, Hematuria (redcell casts) some Proteinuria ,little Edema ± HypertensionMechanism :-Diseases presenting with nephritic syndrome :- ADPGN,RPGN,G.P syndromeGN with vasculitis.
  24. 24. Nephrotic syndrome :-Nephrotic syndrome :-Definition ;Definition ;-- A clinical syndrome characterized by :-A clinical syndrome characterized by :-1-Heavy proteinuria >3.5 gm/day 2-Hypoalbuinemia1-Heavy proteinuria >3.5 gm/day 2-Hypoalbuinemia3-Massive edema(salt &water retention) 4-Hyperlipidemia &lipiduria3-Massive edema(salt &water retention) 4-Hyperlipidemia &lipiduria5-Increased liability to infection and thrombotic complications .5-Increased liability to infection and thrombotic complications .CausesCausesPry glomerular diseases1-Membranous GN (commonest inadults 30%)2-Membrano-proliferative GN3-Lipoid nephrosis (commonest inchildrens 65%)4-Focal segmental glomerulosclerosis5-IgA nephropathy & others2ndglomerular diseases (systemic)1-D.M 2-Amyloidosis 3-SLE4-Drugs (gold,pencillamine ,heroin)5-Infections (malaria ,syphilis,HBV,AIDS )6-Malignancy (melanoma ,carcinoma )7-Miscellanous ( bee sting allergy andhereditary nephritis )
  25. 25. Pathogenesis :-1-Initially GBM destroyed→  capillary permeability andprogressive loss of plasma proteins → hypoalbuminemia2-Hypoalbuminemia plasma colloid os.pr. → edema3-Edema → ↓plasma volume →↑ aldosterone↑ water and soluteretention by kidney → exacerbation of edema (anasarca; massiveamounts of edema fluid);4-Hypoalbuminemia → ↑ lipoprotein production by the liver Hyperlipidemia &lipiduriaEpidemiology :-In children < 15 yrs, nephrotic syndromeprimary renal disease(~ 98 %)In adults nephrotic syndrome associated with 2ndrenal disease
  26. 26. Lipiduria
  27. 27. Mixed nephritic & nephrotic syndromes :-MGN , IgA nephropathy, lupus nephritis, Henӧch - schonleinpurpura.1-Acute diffuse proliferative glomerulonephritisIt is common renal disease , mostly affect childrenCauses :- An immune complex disease ,the antigen either2-Exogenous antigen ( post-infection ) :-a- Bacterial group A β-hemolytic streptococci or S. pyogenesb- Viral (HBV, HCV,mumps) or parasitic (malaria ,toxoplasma)3-Endogenous antigen :- SLEPathogenesis:-*Post-streptococcal pharyngitis (1-4 weeks) anti-StreptococcalAbs raise .*The circulating Ag-Ab complex trapped within glomeruli activating, complement  glomerular injury .
  28. 28. Pathology :-Gross picture :-1-Bilateral renal affection .2-Enlarged kidneys with tense capsule and subcapsularsmall petechae.3-Cut section Goodly differentiated cortex and medullaMicroscopically :-A-Light microscopy ;-1-Glomeruli :- Enlarged & hypercellular (proliferated epithelial,endothelial and mesangial cells  obstructing capillary lumen+ fibrin deposition +PNL,s & monocytes infiltration of glomer.2-Tubules :- Red cell casts.3-Interstitial tissue ;-Edema +PNL,s infiltration4-Blood vessels :-Dilated & congestedB-Immunofluorescence:-Diffuse granular deposits of IgG , IgM& complement C3 along GBM
  29. 29. C-E/M :- Subepithelial electron dense deposits “humps” in case of post-streptococcal GN.*Clinically:- manifested as nephritic syndromei->95% recover in childrens :- (1%) proceed to RPGN or 1% chronic GNii-In adults 60% recovery rate , the rest proceed to RPGN or chronic renalfailure.Lab.findings :-Blood1-hypocomplementemia (C3) 2-increased ASOTUrine :- Proteinuria ,hyaline casts and red cell casts .
  30. 30. Acute GNAcute GN(post infectious GN)(post infectious GN)
  31. 31. Crescentic (rapidly progressive GN) (big white man)Crescentic (rapidly progressive GN) (big white man)DefinitionDefinition :-:-1-Clinico-pathologic syndrome1-Clinico-pathologic syndrome FormingForming crescentscrescents ( in most( in mostglomeruli).glomeruli).2-Accompanied by2-Accompanied by a rapid progressive loss of renal functiona rapid progressive loss of renal function3-Presenting with R.F3-Presenting with R.F  death (within weeks to months).death (within weeks to months).Etiology :-Etiology :-1-Primary (idiopathic)1-Primary (idiopathic) (RPGN)(RPGN)2-Secondary :-2-Secondary :-a-Post-infectiousa-Post-infectious (RPGN) complicating acute GN.(RPGN) complicating acute GN.b-Systemic diseasesb-Systemic diseases (SLE ,G.P, vasculitis ,W.G., H. Sch. Purpura ,(SLE ,G.P, vasculitis ,W.G., H. Sch. Purpura ,Essential cryoglobulinemia)Essential cryoglobulinemia)
  32. 32. type Example1-Type I (12%) ( Linear deposits (anti-GBM ab)2-Type II (44%) ( circulating I.C.)3-Type III (44%) (pauci-immune)- Idiopathic- G.P syndrome- Idiopathic- SLE,- Post-strept. Infection- H.Sc purpura- W.G or- Microscopic poly- angiitis.Types
  33. 33. Idiopathic RPGN (12%):-Idiopathic RPGN (12%):--No history of previous infection or systemic disease-No history of previous infection or systemic disease-About 1/3 of patients show linear fluorescence-About 1/3 of patients show linear fluorescence  denoting anti-GBMdenoting anti-GBMdiseasedisease-1/4 have granular I.F-1/4 have granular I.F denoting immunocomplex etiology.denoting immunocomplex etiology.-1/2 have no Igs and/or immuno-complement deposition.-1/2 have no Igs and/or immuno-complement deposition.PrognosisPrognosis :- Mostly going to:- Mostly going to CRFCRFTreatmentTreatment :-:-1-Plasma exchange Or1-Plasma exchange Or2-Corticosteroides if oligouria is less severe2-Corticosteroides if oligouria is less severe
  34. 34. Types:1-Type I – anti-GBM antibody disease :-Idiopathic or G.pasturesyndrome in which anti-GBM antibodies cross react with alveolar BM alveolar damage and presenting with pulmonary hemorrhageGood pasture`s syndromeood pasture`s syndrome-Autoimmune disease consists of-Autoimmune disease consists of pulmonary hemorrhage and RPGNpulmonary hemorrhage and RPGN..-It characterized by linear deposition of-It characterized by linear deposition of IgGIgG andand C3C3 on the GBMon the GBMMorphological features :-1-Most glomeruli show Crescent formation in Bowman’s space(proliferated parietal epithelial cells and monocytes ) Glom. damagehealed by scarring2-Fibrin in Bowman’s capsule  Crescent formation .(treated withanticoagulants3- Areas of segmental necrosis within glomeruli4-patients with substantial (~ 80%) crescents  Progress to R.F
  35. 35. Plasmapheresis :- is helpful to remove circulating anti-GBM Abs in this type ofRPGNPathologyPathologyGrosslyGrossly ;- Bilateral enlarged ,pale kidneys with surface petechae;- Bilateral enlarged ,pale kidneys with surface petechaeLight microscopicallyLight microscopically :-:-GlomeruliGlomeruli :-:- Involved glomeruliInvolved glomeruli :-show segmental necrosis , GBM breaks and:-show segmental necrosis , GBM breaks andCrescentsCrescents  compress glomerulicompress glomeruli..Uninvolved portionUninvolved portion of the glomerulousof the glomerulous No proliferationNo proliferationMechanism of crescents formation :-Mechanism of crescents formation :-1-Damaged capillaries1-Damaged capillaries  Leak fibrin +migrated mononuclear cells in Bowman`sLeak fibrin +migrated mononuclear cells in Bowman`sspacespace  stimulate proliferation of parietal epithelial cells .stimulate proliferation of parietal epithelial cells .2-Deposited fibrin and the Proliferated epithelial cells2-Deposited fibrin and the Proliferated epithelial cells  CrescentsCrescents3- Fibrosis follow later on .3- Fibrosis follow later on .E/ ME/ M :- Ruptured GBM ± sub-epithelial deposits.:- Ruptured GBM ± sub-epithelial deposits.I.F :I.F :- Linear staining of deposited- Linear staining of deposited IgGIgG andand C3C3 along GBM.along GBM.Lab findings :-Lab findings :- As nephritic syndromeAs nephritic syndrome OOligourialigouria andand azotemiaazotemia-Blood & urine :- As ADGN-Blood & urine :- As ADGNFateFate :- Fairly good prognosis , 50% recover . Renal dialysis or transplantation is a:- Fairly good prognosis , 50% recover . Renal dialysis or transplantation is a
  36. 36. Crescent
  37. 37. 2-Type II – immune-complex mediated disease:--Can be a complication of any of the immune -complex nephritidesSLE, post –streptococcal , IgA nephropathy,H.S PurpuraOr idiopathic-All these show immune- complex granular (lumpy-bumpy) pattern .-It show characteristic lesion of the underlying diseases (D.D. from type I)e.g.Diffuse proliferation and leukocytes infiltration  post-infection GN or SLEMesangial proliferation  IgA nepropathy and H.S purpura.plasmapheresis  ineffective ?3-Type III – pauci-immune type:- No anti-GBM Ab or immune- complexes .Patients do have ANCA (~90%) . Either c or p patterns , have a role in some vascul-itides (i.e.,Wegener Granulomatosis or microscopic poly- angiitis )Clinical:i) Hematuria Red cell casts in urineii) Transplant or chronic dialysis  Most patients
  38. 38. Glomeruli:-1-Segmental necrosis2-Focal GBM breaks3-Focal loss of epith. foot processes4-Subepithelial lumpy I.C deposits5-Crescents (prolif.parietal cells+fibrin(6-Mesangial cells hyperplasia
  39. 39. Membranous GNMembranous GN-The commonest cause of-The commonest cause of nephrotic syndrome in adultsnephrotic syndrome in adults ..-It characterized by-It characterized by diffuse thickening of G.B.M.diffuse thickening of G.B.M.-It is classified as non-inflammatory-It is classified as non-inflammatory  NO cellular proliferationNO cellular proliferationEtiology :-Etiology :-1-Idiopathic (85%):-1-Idiopathic (85%):-May be auto-immune disease ( imbalance between Th &Ts cells)May be auto-immune disease ( imbalance between Th &Ts cells)2- Secondary ,associated with :-2- Secondary ,associated with :--- CarcinomaCarcinoma !! (i.e., melanoma, carcinoma of lung and colon ) Or!! (i.e., melanoma, carcinoma of lung and colon ) Or--Systemic infectionsSystemic infections (HBV, malaria ,Bilh. ) Or(HBV, malaria ,Bilh. ) Or--DrugsDrugs (Gold , penicillamine , Hg , NSAID).(Gold , penicillamine , Hg , NSAID).Pathogenesis:-Pathogenesis:-1-Idiopathic MGN1-Idiopathic MGN :-Auto-immune disease ,the antibodies directed against renal auto-:-Auto-immune disease ,the antibodies directed against renal auto-antigen subepithelial siteantigen subepithelial site In situ immun-complex activate complementIn situ immun-complex activate complement ProteasesProteasesand oxidantsand oxidants Injury of capillary wallInjury of capillary wall  Leakage of proteinLeakage of protein2-Secondary MGN2-Secondary MGN :- Initiated through a circulating Ag-Ab complex:- Initiated through a circulating Ag-Ab complex
  40. 40. Morphology :-Morphology :-Grossly:-Grossly:- Both kidneys areBoth kidneys are enlarged and paleenlarged and paleA-Light microscopy :-A-Light microscopy :-1-Glomeruli :1-Glomeruli :- Early- Early lesionlesion  Normal glomeruli .Normal glomeruli . Later onLater on  diffusely thickened GBMdiffusely thickened GBM2-Tubules :-2-Tubules :- Hyaline droplets .Hyaline droplets .3-Interstitial tissue :-3-Interstitial tissue :- MNC,s infiltrationMNC,s infiltrationB-I.F:B-I.F:-- Diffuse granular deposits ofDiffuse granular deposits of IgsIgs andand complementcomplement Marked thickening of GBMMarked thickening of GBM obliteration of capillary lumen & mesangial sclerosis.obliteration of capillary lumen & mesangial sclerosis.C-E/M :C-E/M :- Irregular sub-epithelial deposits with loss of epithelial foot processes.- Irregular sub-epithelial deposits with loss of epithelial foot processes.Clinical :-Clinical :-a)-Presents mainly by nephrotic syndrome (non-selective proteinuria .No response to steroids) .b)- 15% Hematuria (Non-nephritic ) .c) 15-35% hematuria and hypertension .Fate :-Fate :- It persists in 60% of the cases May end by R.F or R. insufficiency.Progression of diseaseProgression of disease1- stage I: Subepithelial deposits (small and granular)2- stage II: “spikes” of BM protrude between deposits of electron dense material (e.g., IgG, C3)3-Stage III: Incorporated deposits into GBM .4-Stage IV : GBM very distorted and damaged
  41. 41. Stage I Stage IIStage III Stage VISpike
  42. 42. a) GBM thickening (i.e.,“membrano”) + Mesangial cell proliferation (“proliferative”) .It accounts 5-10% of Nephrotic Syndrome in children and adults.a) Sub-nephrotic stage :- Some patients have hematuria or proteinuria and othersdemonstrate a combined nephritic – nephrotic picture.Types .i-Type I: mainly idiopathic. Or chronic immune-complex reaction initiatedby ( HBV, HCV, SLE .bacterial endocarditis, Bilharziasis ,α -1 -ATD,strep.infections ).with granular deposits of Igs (IgG, IgM) and complement (C3 & C1q and C4), insubepithelial, sub-endothelial and mesangial positions .It occurs due to activation ofclassic complement pathway .ii) Type II & III) :- “Dense deposit disease”. GBM contain ribbon like depositsand sub-epithelial humps . Most patients of type II have C3 nephritic factor in theirsera  acts as properdin stabilize C3 convertase activity  It enhances C3breakdown and causes hypo-complementemia .pathologyGrossly :- Bilateral kidney enlargementL/M :- Glomeruli :-  Mesangial cells proliferation and accentuation of glomeularlobules .PAS stain show capillary wall doubling (double –contour or tram -trackappearance) due to interposition of the mesangial cell inside the capillary loopMembrano-proliferative GN:-Membrano-proliferative GN:- It characterized byIt characterized by:-:-
  43. 43. PLS & TOXINS+IgAC3B,D,Mg+C3bBb (alternate path.C3 convertase)ProperdinDegradeC3 C3bStabilizeFeed backC3 NefI.H
  44. 44. E/M &I.F.:- It categorized into two typesType1:- sub-endothelial deposits (complement &Igs)Type II (dense deposit disease) :- Dense deposits within lamina densa of BM(only C3 , no antibodies) It reflects alternate complement pathway.Clinical:i) It occurs primarily in older children and young adultsii) It manifested by nephritic or nephrotic syndromeiii) It reveals low levels of C3 (hypo-complementemia),due toincreased consumption of C3iv) Do not have post-infectious GNv) No systemic inflammatory conditionvi) Most progress to end-stage renal failure, regardless of treatment !!Within 10 YsPrognosis :- Type II has a worse prognosis ,being autoimmune in nature(the patient has nephritic factor in his serum) ,it recurs after transplan.
  45. 45. Minimal change disease (Lipoid nephrosis ,epithelial cell dise.)Minimal change disease (Lipoid nephrosis ,epithelial cell dise.)Most common cause of Nephrotic syndrome in children < 15 yrs (65%) peak 2-6Ys.Also in adults (~ 20 %). Associated with Hereditary disease . Or NSAIDsEtiology :-1-Idiopathic or2-Predisposed by R.T.I 25% or routine immunization 10% or atopyClinically :- 1-Presented mainly by selective proteinuria (albuminuria )2-Dramatically respond to corticosteroids with possible recurrence (steroidDependence or resistance . 3-High cure rate at puberty.Pathogenesis:-Immune dysfunction Elaboration of cytokine-like substances damaging visceral epithelial cells  Proteinuria.Morphology :-Grossly :- Within normal kidney appearanceLight microscopy :- Minimal change in glomeruli .The tubules show lipid ladenepithelial cells (lipoid -nephrosis)E/M :- Uniform diffuse effacement of “foot” processes of visceral epithelial cellsI/F:- No immune deposition .
  46. 46. Protein
  47. 47. Focal / segmental proliferative GNFocal / segmental proliferative GNa) Only some of the glomeruli and /or segments of individual glomeruli are involved.Others are normal .b) It differs from focal segmental glomerulosclerosis .It may be an immune-complexdisease rather than an inflammatory diseasec) Glomeruli are essentially normo-cellularPathogenesis:-Many conditions produce this defect:-1-Primary (idiopathic) renal disease.2-Secondary to a systemic disease :-As:- IgA nephropathy,H.Schönlein GNor W. granulomatosis. –PAN , SBE , Good-pasture`s syndromePathology :-L/M:- Focal & segmental endothelial cells & mesangial cells proliferationI.F.:-Mesangial deposits of IgA ± IgG & C3 and fibrin in most cases.Clinically :-1-Hematuria (Recurrent)2-Non nephrotic proteinuria  Nephrotic syndrome .
  48. 48. Focal segmental glomerulosclerosis (epithelial cell and B.M disease)Some glomeruli (focal) exhibit (segmental) areas of sclerosis whereas others arenormal (Focal segmental)Occurs in the following setting:1-Primary (idiopathic) disease (e.g., idiopathic focal segmental glomerulosclerosis)2-Secondary disease :- due to other conditions ( HIV, heroin addiction, sickle celldisease , morbid obesity and IgA nephropathy)3-Adaptive process :- due to nephrectomy or advanced stages of hypertension.FSGSclerosis differes from MCD by having :-FSGSclerosis differes from MCD by having :-1-↑ Incidence of hematuria and H.P2- Proteinuria (non- selective) and Steroids(poor or no response)3- 50% of Pts develop CRF (Within 10 years)5-IgM and C3 are present in selective area.
  49. 49. Pathogenesis :-Pathogenesis :-1-Idiopathic FSG1-Idiopathic FSG :- It is considered as an accentuation of MCD:- It is considered as an accentuation of MCD marketed bymarketed byepithelial damageepithelial damage Trapping of plasma proteins in hyperpermeabil fociTrapping of plasma proteins in hyperpermeabil foci HyalinosisHyalinosisAnd sclerosis and mesangial cell reaction to protein and fibrin.And sclerosis and mesangial cell reaction to protein and fibrin.2-Secondary FSG:-2-Secondary FSG:- It occurs as a complication of other diseases (heroin and AIDS)It occurs as a complication of other diseases (heroin and AIDS)  Renal functionRenal function Progressive glomerulosclrosis and R.FProgressive glomerulosclrosis and R.F.Presence of AIDS virus in epithelial cells.Presence of AIDS virus in epithelial cells  augment the epithelial damage .augment the epithelial damage .Pathology :-Pathology :-Light microscopyLight microscopy :- The lesion starts in glomeruli at J.G zone ,then spreads outward:- The lesion starts in glomeruli at J.G zone ,then spreads outwardEarlyEarly Focal segmental glomerulosclerosis .Focal segmental glomerulosclerosis .Later onLater on  Diffuse glomerulosclerolosis + tubular atrophy + Interstitial fibrosis.Diffuse glomerulosclerolosis + tubular atrophy + Interstitial fibrosis.E/ME/M :- Diffuse effacement of epithelial foot processes and detached cells .Denuded:- Diffuse effacement of epithelial foot processes and detached cells .DenudedBM . Hypertrophied mesangial cells .BM . Hypertrophied mesangial cells .I.FI.F.:- Deposition of.:- Deposition of IgMIgM andand C3C3 in hyaline massesin hyaline massesClinicallyClinically :- Nephrotic syndrome .Hematuria and:- Nephrotic syndrome .Hematuria and  GFR and H.P are commonGFR and H.P are commonfindings.findings.Fate :-Fate :- Progression to CRF in 50% of cases after (10 Ys).Progression to CRF in 50% of cases after (10 Ys).
  50. 50. IgA nephropathy (Berger`s Disease)- A major cause of recurrent hematuria .- It is associated with chronic liver disease (unable to remove circulating I.C )- IgA and fibronectin found in > 70 % of these patients.Pathogenesis :-Ab IgA :- Defective synthesis ,secretion or clearance  IgA nephropathy .Ag :- Either bacterial, viral or dietary .Hematuria following upper RTI,GIT or UTI due to increased surface secretion of IgA!!(surface epithelium)- C1q and C4 (classic pathway activation) are typically absent in serum- C3 and properdin and IgA are usually present in mesangium and absent in serum( indicate activation of alternate pathway)Lab findingsL/M :- It varies includes FPGN , FSGS , MPGN and rarely RPGNI.F :-Mesangial deposits of IgA+C3 and properdin ,± IgG .E/M:- Finely granular electron dense deposits in mesangium.clinical- Common in young men (15-30 Y)- Presents with recurrent attacks of hematuria post infections (respiratory,urinarytract or GIT)
  51. 51. - Mild proteinuria- Crescent- Hypertension- Vascular sclerosis poor prognosis  passes to end stagerenal failure (40%) .Mesangial depositsIgA+C3 and properdin ,± IgG
  52. 52. Chronic Diffuse Glomerulonephritis:-Chronic Diffuse Glomerulonephritis:-An end pool of many different renal diseasesAn end pool of many different renal diseases..Causes:-Causes:-A -Idiopathic (20%)A -Idiopathic (20%)B-Secondary to :B-Secondary to :1-Post-streptococcal GN (1-2%)1-Post-streptococcal GN (1-2%)2-RPGN (90%)2-RPGN (90%)3-Membranous GN (50%)3-Membranous GN (50%)4-Membrano-proliferative GN ( 50%)4-Membrano-proliferative GN ( 50%)5-Focal glomerulosclerosis (50%)5-Focal glomerulosclerosis (50%)6-IgA nephropathy ( 40%)6-IgA nephropathy ( 40%)Diagnosis :-Diagnosis :-1-In early lesions1-In early lesions :- The primary disease can be recognized:- The primary disease can be recognized2-In late lesions2-In late lesions :-:- GlomeruliGlomeruli :- hyalinosed .:- hyalinosed . TubulesTubules:-Atrophic .:-Atrophic .Bl.VsBl.Vs :- sclerosed:- sclerosedthat harden the recognition of the initiating diseasethat harden the recognition of the initiating disease
  53. 53. Pathology :-Pathology :-Grossly :-Grossly :--Small and contracted kidneys (< 50gm)-Small and contracted kidneys (< 50gm)-The capsule :- Thickened ,irregular and adherent to the cortex-The capsule :- Thickened ,irregular and adherent to the cortex-The cortical surface :- Is diffusely granular & increased peri-pelvic fat-The cortical surface :- Is diffusely granular & increased peri-pelvic fat-Cut section :- Cortex is thin and atrophic with unremarkable medulla.-Cut section :- Cortex is thin and atrophic with unremarkable medulla.Microscopically :-Microscopically :-1-Glomeruli1-Glomeruli :-:- At an early stage it reveals the primary disease ,later on the glomeruli becomeAt an early stage it reveals the primary disease ,later on the glomeruli becomefew in numbers , atrophic & acellular and hyalinized .few in numbers , atrophic & acellular and hyalinized .2-Tubules :2-Tubules :- Tubules related to atrophic glomeruli- Tubules related to atrophic glomeruli Small and atrophic .Degenerated tubularSmall and atrophic .Degenerated tubularcells with hyaline droplets .and containing eosinophilic casts.cells with hyaline droplets .and containing eosinophilic casts.3-Interstitium3-Interstitium :- Fibrosis and lymphocytic infiltration:- Fibrosis and lymphocytic infiltration4-Vessels :-4-Vessels :- arterial and arteriolosclerosis secondary to hypertension .arterial and arteriolosclerosis secondary to hypertension .5-Patient on5-Patient on long term dialysislong term dialysis show :- 1- Acquired cystic changes 2-Deposition of calciumshow :- 1- Acquired cystic changes 2-Deposition of calciumoxalate crystals in tubules 3-Calcification of tufts. 4-Adenoma or carcinoma of the kidneyoxalate crystals in tubules 3-Calcification of tufts. 4-Adenoma or carcinoma of the kidneyClinical courseClinical course :-:-1-Insidious course1-Insidious course2-Proteinuria , hypertension and azotemia2-Proteinuria , hypertension and azotemia3-Episodes of nephritic or nephrotic syndrome3-Episodes of nephritic or nephrotic syndrome
  54. 54. Masson trichrome
  55. 55. Glomerular lesions associated with systemic diseasesGlomerular lesions associated with systemic diseasesDiabetic glomerulo/sclerosisDiabetic glomerulo/sclerosis (Kimmelstiel-Wilson Disease)(Kimmelstiel-Wilson Disease)-It produces Nephrotic proteinuria (55% of JDM&30% of ADM , 12-22Y ofdiabetes )-It characterized by diabetic micro-angiopathy (small arteries,arterioles .capillaries)-Hyaline arteriosclerosis involves both afferent and efferent arterioles , which occur byprogressive accumulation of GBM material .-It depends upon severity and duration of hyperglycemia !! ??Etiology :- Origin proteinuria not known (non-nephrotic or nephrotic )1) EarlyThickening of GBM2) Lately :-Glomerular enlargement3) “Diffuse Glomerulosclerosis” refers to enlarged glomeruli with expandedMesangium and diffusely thickened GBM4- Nodular glomerulosclerosis (i.e.,Kimmelstiel-Wilson Disease) – highly specific fordiabetes5) one of leading causes  CRF in USA6) Two processes play role in diabetic glomerular lesions1- Metabolic defect (i.e glycosylation end products that ↑ GBM thickening and ↑mesangial matrix2-Hemodynamic effects: - glomerular hypertrophy  development of glomerulo-
  56. 56. Clinical features:-i) Usually mild proteinuria .ii) Nephrotic syndrome present → renal failure within 6 yrs. severe proteinuriausually associated with other signs of advanced diabetes (i.e.,retinopathy)
  57. 57. AmyloidosisAmyloidosis- Amyloid deposits in 1-B.M of glomerular capillaries 2- Walls of afferent andefferent arterioles 3-Basement membrane of the collecting tubules .- Either pry or 2ndforms- Congo red (amyloid ) deposits mainly in mesangium and capillariesClinicalClinicali) Proteinuria nephrotic syndromeii) progressive glomerular destruction death from uremia
  58. 58. Henoch-SchHenoch-Schöönlein Purpuranlein PurpuraUsually occurs in children 2-8 Y , and becomes severe in adults ,oftenly following RTI.Clinically :-1- Skin lesions :-Purpura on legs, arms and buttock (leukocyto-clastic vasculitis )2- Abdominal symptoms :-Pain, vomiting, intestinal bleeding and arthralagia3-Renal abnormalities:-hematuria , nephrotic syndrome (proteinuria ).Not all these S& S need to be present.Pathologically :-Glomerular lesion :-1-Focal mesangial proliferation 2-Crescentic GN 3- Alwaysassociated with IgA depositionCourse :--Resolution is the role (in children )-CRF  in cases of diffuse lesion orNephrotic Syndrome orcrescents.
  59. 59. Bacterial endocarditisBacterial endocarditis :-:-Immune -complex mediated GN showing morphologic continuum fromImmune -complex mediated GN showing morphologic continuum from focalfocalNecrotizing GN to diffuse GNNecrotizing GN to diffuse GN , sometimes with crescents (not embolic as, sometimes with crescents (not embolic aspreviouslypreviouslythought)thought)SLE (lupus nephritis) :SLE (lupus nephritis) :The Kidneys are involved virtually in all cases of SLEThe Kidneys are involved virtually in all cases of SLE5 Patterns of lupus nephritis5 Patterns of lupus nephritisClassClass PathologyPathology ClinicalClinicalIIIIII(10%(10%((III(33%III(33%((NormalNormal By L/M , E/M and I.FBy L/M , E/M and I.F““Mesangial lupus nephritisMesangial lupus nephritis”” ,slight,slight  ininmesangial matrix &cells & mesangial Igsmesangial matrix &cells & mesangial Igs& complement deposits.& complement deposits.““Focal proliferative GNFocal proliferative GN”” Focal andFocal andsegmental glomerularsegmental glomerular swellingswelling withwithendothelial and mesangial proliferationendothelial and mesangial proliferation,PNL,s infiltration +fibrinoid deposits and,PNL,s infiltration +fibrinoid deposits andcapillar y thrombi +subendoth IC deposits.capillar y thrombi +subendoth IC deposits.10% of patients10% of patients minimalminimalhematuria or proteinuriahematuria or proteinuria1-Recurrent1-Recurrent hemturiahemturia2-Moderate2-Moderate proteinuriaproteinuria3-Mild3-Mild renal insufficiencyrenal insufficiency
  60. 60. ClassClass PathologyPathology ClinicalClinicalIVIV(50%)(50%)V(10%)V(10%)““Diffuse proliferative GNDiffuse proliferative GN””-Proliferated (endo. Mesa.epithel.)-Proliferated (endo. Mesa.epithel.)-Subendothelial deposits (wire--Subendothelial deposits (wire-looploop”” ..-Tubular changes ,BM and I.T ,I.C.-Tubular changes ,BM and I.T ,I.C.deposits .deposits .““Membranous GN”Membranous GN” diffuselydiffuselythickened capillay walls andthickened capillay walls andsubepithelial IC deposits.subepithelial IC deposits.-Either asymptomatic-Either asymptomatic-Hematuria ,proteinuria ,HP,-Hematuria ,proteinuria ,HP,-- GFRGFR--Most severe form with worstMost severe form with worstprognosis.prognosis.-Severe proteinuria-Severe proteinuria-Nephrotic syndrome-Nephrotic syndromeHereditary nephritis (Alport syndromeHereditary nephritis (Alport syndrome((A group of hereditary renal diseases causing primarily GNA group of hereditary renal diseases causing primarily GN..Clinically :-Clinically :- Commonly affecting males (40Y) .The patient is presented with :- 1-EarCommonly affecting males (40Y) .The patient is presented with :- 1-EarNerve deafness 2-EyeNerve deafness 2-Eye lens (dislocation ,cataract) & corneal dystrophy 3-lens (dislocation ,cataract) & corneal dystrophy 3-KidneyKidney hematuriahematuria..PathologicallyPathologically :- The GBM shows :-1-Irregular thickening:- The GBM shows :-1-Irregular thickening2-lamination and foci of rarefaction (defect in2-lamination and foci of rarefaction (defect in collagen type IVcollagen type IV necessary of BMnecessary of BM
  61. 61. Systemic lupus erythematosis kidneyThin arrow point to Wire-loop appearanceThick arrow point to hematoxyphil bodies in B.space
  62. 62. Acute renal failure (ARF) and acute tubular necrosis(ATN)Acute renal failure (ARF) and acute tubular necrosis(ATN)Acute tubular necrosis (ATN):-Acute tubular necrosis (ATN):- Major cause of ARF. It is reversible .Major cause of ARF. It is reversible .Acute renal failure:-Acute renal failure:- is a syndrome characterized by acute suppressionis a syndrome characterized by acute suppressionof renal function and presented byof renal function and presented by oliguria ,rarely anuria or polyuriaoliguria ,rarely anuria or polyuria..Causes of acute renal failure :-Causes of acute renal failure :-I-Pre-renal :-I-Pre-renal :-1-Shock1-Shock2-Vascular obstruction (thrombus ,embolism,atheroscl., PAN )2-Vascular obstruction (thrombus ,embolism,atheroscl., PAN )3-Hypertension3-HypertensionII-Renal :-II-Renal :-1-RPGN 2-Acute pyelonephritis 3-DIC with cortical necrosis 4-ATN1-RPGN 2-Acute pyelonephritis 3-DIC with cortical necrosis 4-ATN5-Papillary necrosis.5-Papillary necrosis.III-Post-renal :III-Post-renal :-- Obstructive uropathy.Obstructive uropathy.
  63. 63. Tubulo-interstitial diseases :-Most tubular diseases involve the interstitium1-Tubular diseases (ATN) :-2 distinct types of tubular diseases.-Ischemic - or nephrotoxic tubular injury :-ATN:- It is a clinical entity, characterized by destruction of tubular epithelial cellsand presented clinically by oliguria or anuria . It is caused by ischemia or toxins .Ischemic ATN :- After shock (sepsis,burns,crush imjury or acute pancreatitis).Uncommon after hemorrhagic shock “shock kidney”Nephrotoxic ATN :-1-It is caused by drugs (gentamycin,cephalosporine. contrast media, cyclosporine , Hg,lead, arsenic ,methyl alcohol) and certain toxins as (muschroome ,insecticides andherbiticides)2-Massive hemoglobinuria or myoglobinuria (hemolysis)3-Dehydration and hypoxiaPathologyGrossly :- Kidneys are enlarged with pale necrotic cortex and congested medulla
  64. 64. Ischemic ATNIschemic ATN :-:-1-Patchy tubular necrosis1-Patchy tubular necrosis in proximal & distal convoluted tubules and ascendingin proximal & distal convoluted tubules and ascendingLimbs of Henle`s with large skip areas in-betweenLimbs of Henle`s with large skip areas in-between2-Foci of ruptured BM2-Foci of ruptured BMNephrotoxic ATNNephrotoxic ATN :-:- Extensive tubular necrosisExtensive tubular necrosis in whole length of proximal CTin whole length of proximal CTwithwith preserved tubular basement membranepreserved tubular basement membrane .. In both types the distal tubules andIn both types the distal tubules andcollecting ducts containcollecting ducts contain castscasts. +interstitial edema and vascular infiltration by PNL,s. +interstitial edema and vascular infiltration by PNL,sThe recovery phase showThe recovery phase show epithelial regenerationepithelial regeneration (flat tubular cells and mitotic(flat tubular cells and mitoticFigures , except in areas with BM rupture .Figures , except in areas with BM rupture .Hg clHg cl  Acidophil inclusions in cellsAcidophil inclusions in cells Lately necrosis & calcification .Lately necrosis & calcification .CCl4CCl4Fatty changes + necrosis.Fatty changes + necrosis.Ethyl alcoholEthyl alcohol vacuolar degeneration + Ca oxalate crystals.vacuolar degeneration + Ca oxalate crystals.Mechanism of oliguria due to ATN:-Mechanism of oliguria due to ATN:- BothBoth ischemia and toxins causeischemia and toxins cause tubulartubularandand glomerularglomerular damagedamage1-Tubular damage1-Tubular damage :-:-a-Arterial V.Ca-Arterial V.C  RA systemRA system GFRGFROliguriaOliguriab-Cast formation +tubular obstruction and increase intra-tubular prb-Cast formation +tubular obstruction and increase intra-tubular prGFRGFROilguriaOilguriac-Back leak of tubular fluidsc-Back leak of tubular fluids  Press on glomeruli and tubulesPress on glomeruli and tubules  OliguriaOliguria2-Damaged glomeruli2-Damaged glomeruli  GFRGFR OliguriaOliguria
  65. 65. Ischemia orToxinsDirect Gl damageV.CTubular damageTubularbackleakOliguriaObstructionby castsintratubularpressureGFRIschemia orToxinsV.C
  66. 66. Treatment protocol1) Initial phase2) Maintenance phase3) Recovery phaseInitial phase :- About 36 hours. It incited by medical , surgical, obstetricevents and characterized by slight oliguria and azotemiaMaintenance phase:- 1-3 weeks and dominated by persistent R.F&hyperkalemia.It charcterized by :-a) Marked oliguria (50-400 ml/day)b) Edema, hyperkalemia and uremia- Treatment by dialysis ,the patient may die from poor managementRecovery phase :- It characterized by :--Polyuria (up to 3 L/day)-Electrolyte imbalances .-Increased infection-About 25% of patients die in this phaseFinally:- The patient recovers with some impairment of renal function
  67. 67. Acute tubular necrosis
  68. 68. Feature Ischemic ATN Nephrotoxic ATN1-Synonymus2-Frequency3-major causes3-Gross picture4-Microscopic5-PrognosisLower(distal)nephron nephrosis,anoxic nephrosis,shock kidneyMore common (80%)Shock,crush injures,mismatched bloodtransfusionEnlarged kidney,swollen ,cut sectionpale cortex ,dark medulla.1-Distal damage more prominent2-Focal tubular necrosis3-Regenerating epithelium4-casts,hayline,pigment,myoglobin5-BM disruptedWorseUpper( proximal) nephronnephrosis,toxic ATNLess commonPoisons ,heavy metals ,certaindrugsSimilar to ischemic ATN1-Proximal tubular damagemore prominent2-More diffuse necrosis3-Regenerating epithelium4-Luminal dystrophiccalcification5-BM intactGood
  69. 69. 2- Interstitial diseases (nephritis):-2- Interstitial diseases (nephritis):-A-Infective :-A-Infective :-1-Acute &chronic pyelonephritis1-Acute &chronic pyelonephritis2-T.B pyelonephritis2-T.B pyelonephritis3-Pyonephrosis3-Pyonephrosis4-Pyemic abscesses of the kidney4-Pyemic abscesses of the kidney5-Other infections (viruses,parasitic)5-Other infections (viruses,parasitic)B-Non-infective :-B-Non-infective :-1-Acute hypersensitivity interstitial nephritis1-Acute hypersensitivity interstitial nephritis2-Analgesic abuse (phenacetin) nephropathy2-Analgesic abuse (phenacetin) nephropathy3-Balkan nephropathy3-Balkan nephropathy4-Urate & gout nephropathy4-Urate & gout nephropathy5-Radiation nephritis5-Radiation nephritis6-Transplant rejection6-Transplant rejection7-Nephrocalcinosis7-Nephrocalcinosis8-Idiopathic interstitial nephritis .8-Idiopathic interstitial nephritis .
  70. 70. Urinary tract infection (UTI) and pyelonephritis(PN)Urinary tract infection (UTI) and pyelonephritis(PN)Definitions :-Definitions :-Cystitis :-Cystitis :- Inflammation of urinary bladderInflammation of urinary bladderPyelitisPyelitis :-Inflammation of renal pelvis:-Inflammation of renal pelvisNephritisNephritis :-Inflammation of interstitial tissue of the kidney:-Inflammation of interstitial tissue of the kidneyPyelonephritisPyelonephritis :- Inflammation of interstitial tissue of the kidney and renal pelvis:- Inflammation of interstitial tissue of the kidney and renal pelvisNephrosisNephrosis:- Renal tubules diseases .:- Renal tubules diseases .PyonephrosisPyonephrosis:-:- Severe suppurative inflammation of the kidney (sac of pus)Severe suppurative inflammation of the kidney (sac of pus)Predisposing factors of UTIPredisposing factors of UTI:-The normal kidney is resistant to organisms except under:-The normal kidney is resistant to organisms except undercertain pathological conditionscertain pathological conditions  Infection can occur.Infection can occur.1-Obstructive uropathy & Neurogenic bladder1-Obstructive uropathy & Neurogenic bladder2-Catheterization &instrumentations of the urinary tract.2-Catheterization &instrumentations of the urinary tract.3-Vesico-ureteral reflex3-Vesico-ureteral reflex4-Pregnancy4-Pregnancy5-Congenital anomalies of UT5-Congenital anomalies of UT6-D.M. & Immunosuppression6-D.M. & Immunosuppression7-It is common in females (15-45Ys)(short wide urethera , wetted perineum, absence of7-It is common in females (15-45Ys)(short wide urethera , wetted perineum, absence ofantibacterial prostatic secretion , hormonal effect of estrogen and pregnancy)antibacterial prostatic secretion , hormonal effect of estrogen and pregnancy)
  71. 71. Causative organisms :-Causative organisms :-1-Normal fecal flora (85%) of UTI1-Normal fecal flora (85%) of UTI2-E.coli , Proteus, Klebsiella , enterobacter , streptococcal fecalis , staphylococci.2-E.coli , Proteus, Klebsiella , enterobacter , streptococcal fecalis , staphylococci.Routes of infection :-Routes of infection :-1-Hematogenous spread1-Hematogenous spread :- S:- Septicemia &infective endocarditis (staph.&E.coliepticemia &infective endocarditis (staph.&E.coli.).) reachreachthe kidney by blood streamthe kidney by blood stream  infectioninfection2-Ascending infection2-Ascending infection :-:- Through urethera,bladder ,vesico-ureteral reflux or Intra-Through urethera,bladder ,vesico-ureteral reflux or Intra-renalrenalreflux (through blunted or concave renal papille) (E.coli , proteus or enterobacter),passreflux (through blunted or concave renal papille) (E.coli , proteus or enterobacter),passthrough patent renal tubules at the papillae (commonly at upper and lower poles of thethrough patent renal tubules at the papillae (commonly at upper and lower poles of thekidney)kidney)3-Descending infection3-Descending infection :-:-Through peri-ureteral lymphatic or through urineThrough peri-ureteral lymphatic or through urineManifestaions of UTI:-Manifestaions of UTI:-1-Asymptomatic bacteruria ( High bacterial count in urine )1-Asymptomatic bacteruria ( High bacterial count in urine )2-Urgency and frequency and dysuria2-Urgency and frequency and dysuria3-Flank pain ,fever and chills.3-Flank pain ,fever and chills.4-Pus casts in urine4-Pus casts in urine  pyelonephritispyelonephritis5-Number of bacteria > 103 to 105 indicate infection rather than contamination5-Number of bacteria > 103 to 105 indicate infection rather than contamination
  72. 72. Descendinginfection
  73. 73. Acute pyelonephritis :-Acute pyelonephritis :-Definition :-Definition :- Acute kidney infectionAcute kidney infectionwith patchy suppurative infl+tubularwith patchy suppurative infl+tubularnecrosis + pus castsnecrosis + pus castsGrosslyGrossly :- Either normal or enlarged:- Either normal or enlargedkidney.Small surface abscesseskidney.Small surface abscessesor large sized abscess .or large sized abscess .Microscopically ;Microscopically ;--1-Early1-Early:-Diffuse interstitial infiltration:-Diffuse interstitial infiltrationby PNL,sby PNL,s2-Later on2-Later on ,tubular infiltration by,tubular infiltration byPNL,s and formation of manyPNL,s and formation of manyabscesses ,extension of polymorphs toabscesses ,extension of polymorphs tocollecting tubules forming pus casts.collecting tubules forming pus casts.Glomeruli , resist this acute inflamma-Glomeruli , resist this acute inflamma-tion till a large area of necrosis ortion till a large area of necrosis orfungal infection can occurs.fungal infection can occurs.ClinicallyClinically :- As UTI:- As UTIChronic pyelonephritis and refluxChronic pyelonephritis and refluxnephropathynephropathy ..It is tubulo-interstitialIt is tubulo-interstitialinflammationinflammation  cortico-medullary scarscortico-medullary scarsoverlying dilated blunted and deformedoverlying dilated blunted and deformedcalyces.and CRF in 11-20% of casescalyces.and CRF in 11-20% of casesTwo forms :-Two forms :-1-Obstructive CPN (enteric bact.)1-Obstructive CPN (enteric bact.)Due to obstructive uropathyDue to obstructive uropathy  multiplemultiplerecurrences of infectionsrecurrences of infections CPNCPN2-Reflux nephropathy2-Reflux nephropathy :-:- caused bycaused bysuperadded infection over vesico-ureteralsuperadded infection over vesico-ureteralreflux and intra-renal refluxreflux and intra-renal refluxPyelography :- asymmetrical contractedPyelography :- asymmetrical contractedkidney with coarse scarkidney with coarse scarPathologyPathologyGrossly :-Grossly :-Visible scarring and deformity of the pelvi-Visible scarring and deformity of the pelvi-calyceal system.calyceal system.
  74. 74. Fate :-Fate :-1-Renal abscess & Perinephric abscess1-Renal abscess & Perinephric abscess2-Pyonephrosis (if obstruction occurs)2-Pyonephrosis (if obstruction occurs)3-Renal scars and fibrosis.3-Renal scars and fibrosis.4-Chronic pyelonephritis4-Chronic pyelonephritis6-Necrotizing papillitis in diabetics6-Necrotizing papillitis in diabeticsSevere acute pyelonephritis +D.M.Severe acute pyelonephritis +D.M..Ischemic and supp.necrosis in tips of the.Ischemic and supp.necrosis in tips of therenal papillaerenal papillae papillay necrosispapillay necrosis(appears grayish white well demarcated(appears grayish white well demarcatednecrotic zones in form of coagulativenecrotic zones in form of coagulativenecrosis surrounded by PNL,s.necrosis surrounded by PNL,s.Bilateral renal affectionBilateral renal affection  unequalunequalcontraction .contraction .Diffuse or patchy fibrosis,scarring of theDiffuse or patchy fibrosis,scarring of thePelvicalcyseal systemPelvicalcyseal system  kidneykidneydeformity .Polar scar and blunt calyx indeformity .Polar scar and blunt calyx inchronic reflux diseasechronic reflux disease..Microscopically :-Microscopically :-1-Tubules :1-Tubules :-- Dilated with atrophic lining andDilated with atrophic lining andcontaining eosinophilic casts ( tubular thyr-containing eosinophilic casts ( tubular thyr-oidization)oidization)2-Interstitial tissue2-Interstitial tissue ;- fibrosis ,diffuse;- fibrosis ,diffuselymphocytic infiltrateslymphocytic infiltrates3-Glomeruli :3-Glomeruli :- First- First normal .Then withnormal .Then withincreased periglomerular fibrosisincreased periglomerular fibrosisFocalFocalsegmental glomerulosclerosissegmental glomerulosclerosisproteinuria.proteinuria.4-Blood vessels4-Blood vessels:- Arteriosclerotic changes due:- Arteriosclerotic changes dueto hypertension .to hypertension .
  75. 75. Non infectious – interstitial nephritisCaused by:i) Drugsii) Metabolic disorders (hypokalemia)iii) Radiation injuryiv) Immune reactionsAcute Drug –Induced (Hypersensitivity) Interstitial Nephritis :-It occurs 2-40 days after exposure to various drugs as (methicillin, ampicilline, rifam-picin ,furosemide thiazides various NSAID ,phenin ,cimitidine).Withdrwal of the drug recovery in most patients.C/P :-C/P :-1-Fever2-Transient eosinophilia3-Skin rashes4-Hematuria5-Mild proteinuria6-Sterile pyouria7-Azotemia & ARF
  76. 76. Mechanism :-Mechanism :- Presence of latent period ,IgG,IgE ,MNC,s ,granulomatous infiltratePresence of latent period ,IgG,IgE ,MNC,s ,granulomatous infiltrate,as well as,positive skin test denotes an immunological reaction .The drug acts as a,as well as,positive skin test denotes an immunological reaction .The drug acts as ahapten that react with the tubular cell cytoplasm causing its injury byhapten that react with the tubular cell cytoplasm causing its injury by type Itype I and typeand typeIV hypersensitivityIV hypersensitivity reaction .reaction .Analgesic NephropathyAnalgesic Nephropathylarge quantities of analgesics for long periodslarge quantities of analgesics for long periods  chronic tubulo-interstitial nephritis +chronic tubulo-interstitial nephritis +renal papillary necrosis . ( e.g aspirin, caffeine, acetaminophen , codeine, phenacetin)renal papillary necrosis . ( e.g aspirin, caffeine, acetaminophen , codeine, phenacetin)Mechanism :-Mechanism :-The drugs act together causing firstly papillary necrosis and secondary tubulointer-The drugs act together causing firstly papillary necrosis and secondary tubulointer-stitial nephritisstitial nephritisC/P:-C/P:-1-Polyuria 2-Headache 3-Anemia 4-GIT symptoms 5-Pyouria UTI 6-HP.1-Polyuria 2-Headache 3-Anemia 4-GIT symptoms 5-Pyouria UTI 6-HP.7-CRF7-CRFFate :-Fate :-Drug withdrawalDrug withdrawal stabilizes renalstabilizes renalfunction . Increased risk of TCCfunction . Increased risk of TCC
  77. 77. MorphologyMorphology :-:-GrosslyGrossly :-:-Normal or reduced kidney size with increased or decreasedNormal or reduced kidney size with increased or decreasedcortical thicknesscortical thickness..MicroscopicallyMicroscopically :-:- Patchy necrosis of papillaePatchy necrosis of papillae  become complete ,lately ghosts ofbecome complete ,lately ghosts oftubules and foci of dystrophic calcification with cortical atrophy of tubules and fibrosistubules and foci of dystrophic calcification with cortical atrophy of tubules and fibrosisMiscellanous tubulointerstitial diseasesMiscellanous tubulointerstitial diseases1-Urate nephropathy1-Urate nephropathy2-Hypercalcimia2-Hypercalcimia3-Multiple myeloma3-Multiple myeloma4-Radiation nephritis4-Radiation nephritisMultiple myeloma (myeloma nephrosis)Multiple myeloma (myeloma nephrosis)Multiple myelomaMultiple myeloma  myeloma nephrosis,with casts in DCT and collecting ducts .myeloma nephrosis,with casts in DCT and collecting ducts .Casts formed ofCasts formed of Bence-Jones proteinsBence-Jones proteins ,,Tamm-Horsfall poteinsTamm-Horsfall poteins andand albumin.albumin.Multinucleated giant cellsMultinucleated giant cells are found around the casts.The epithelial cells lining theare found around the casts.The epithelial cells lining thecast-filled tubules become necrotic or atrophic because of toxic action of the Bence-cast-filled tubules become necrotic or atrophic because of toxic action of the Bence-jones proteins .Metastatic calcification may be encountered . Nodular glomerular lesionjones proteins .Metastatic calcification may be encountered . Nodular glomerular lesionare present .are present .
  78. 78.  Pyelonephritis can also occur due to increased liability to infectionPyelonephritis can also occur due to increased liability to infection.Interstitial infiltration by abnormal plasma cells..Interstitial infiltration by abnormal plasma cells.
  79. 79. Diseases of blood vesselsDiseases of blood vesselsSystemic Hypertension :-Systemic Hypertension :- elevated systemic blood pressure above 140/90 mmHgelevated systemic blood pressure above 140/90 mmHgTypes of hypertensionTypes of hypertension :-:-Primary or idiopathicPrimary or idiopathic :- The commonest (90%):- The commonest (90%)Secondary hypertensionSecondary hypertension :-:- caused bycaused byRenal causesRenal causes EndocrineEndocrine vascularvascular NeurogenicNeurogenic1-Acute GN1-Acute GN2-CRF2-CRF3-R.A.stenosis3-R.A.stenosis4-Renal vasculitis4-Renal vasculitis5-Renin producing5-Renin producingTrTr1-Cushing`s syndrome1-Cushing`s syndrome2-Oral pills2-Oral pills3-Pheochromocytoma3-Pheochromocytoma4-Acromegaly4-Acromegaly5-Grave`s disease5-Grave`s disease1-Coarctation aorta1-Coarctation aorta2-A.S2-A.S3-PAN3-PAN11--PsychogenicPsychogenic22--I.C.PI.C.P33--PolyneuritisPolyneuritis..othersothersFactors involved in regulation of Bl.Pr.1- Vasoconstrictors :- Factors regulating peripheral resistance, includeangiotensin II , catecholamine, thromboxane, L.Ks and endothelin.
  80. 80. 2-Vasodilators2-Vasodilators :- Kinines ,PGs , lactic acid , H+ and adenosine.:- Kinines ,PGs , lactic acid , H+ and adenosine.3-Factors regulating C.O3-Factors regulating C.O. :- Blood volume ( which is regulated by Na. :- Blood volume ( which is regulated by Naload, mineralo-corticoids , natriuretic factors).Heart rate , strock volumeload, mineralo-corticoids , natriuretic factors).Heart rate , strock volumeand contractility.and contractility.4-Regional autoregulation4-Regional autoregulation :-:-blood volumeblood volume V.C and vice versa.V.C and vice versa.Mechanism of renal hypertensionMechanism of renal hypertensionThe kidney producesThe kidney produces reninrenin  angiotensin Iangiotensin Iangiotensin IIangiotensin II  on bl. Vson bl. VsV.CV.C and on adrenal cortex producingand on adrenal cortex producing aldosteronaldosteronsalt and water ret.salt and water ret.Causes of increased renin secretionCauses of increased renin secretion :-:-1-Unilateral renal artery stenosis (ischemia)1-Unilateral renal artery stenosis (ischemia)2-Malignant hypertension2-Malignant hypertension3-Vasculitis of renal blood vessels3-Vasculitis of renal blood vessels4-Some cases of unilateral PN.or CRF4-Some cases of unilateral PN.or CRF5-Renin secreting trs5-Renin secreting trs6-RCC or Wilm`s Tr6-RCC or Wilm`s Tr
  81. 81. Kidney has important role in sodium homeostasisKidney has important role in sodium homeostasis:-:---Via its response to aldosteron,GFR and nutriuretic factors . Failure of these systemVia its response to aldosteron,GFR and nutriuretic factors . Failure of these systemNa retentionNa retention  H.P (e.g CRFH.P (e.g CRF((--The loss of V.D substances of renal origin (PAF ,Kinins and PGI2)The loss of V.D substances of renal origin (PAF ,Kinins and PGI2)hypertensionhypertension(renoprival H.P(renoprival H.P((Mechanism of essential hypertensionMechanism of essential hypertensionNo obvious cause butNo obvious cause but:-:-11--Genetic predisposition and environmental factors are importantGenetic predisposition and environmental factors are important22--Behviour patterns ,stress , obesity,oral pillsBehviour patterns ,stress , obesity,oral pills increase riskincrease risk33--High sodium intake in genetically predisposed patientHigh sodium intake in genetically predisposed patient..
  82. 82. Defect in renal Sodexcretion+Excess salt intakeInadequate sod excretionSalt &H2O retentionplasma &ECF vol.C.O autoregulationHypertensionNeurohormonal release+Excess salt intakevascular reactivity Naturitic hormoneTotal P.R
  83. 83. Diseases of renal blood vesselsDiseases of renal blood vessels :-:-Types:-Types:-1-Atherosclerotic kidney 2-Arteriolosclerotic kidney 3-Polyarteritis nodosa1-Atherosclerotic kidney 2-Arteriolosclerotic kidney 3-Polyarteritis nodosa4-Infarction kidney 5-Bilateral cortical necrosis 6-Necrosis of the renal papillae.4-Infarction kidney 5-Bilateral cortical necrosis 6-Necrosis of the renal papillae.1-Atherosclerotic (senile) kidney :-1-Atherosclerotic (senile) kidney :-This caused by atheroma of the renal arteryThis caused by atheroma of the renal artery Infarction ,ischemic atrophy and fibrosisInfarction ,ischemic atrophy and fibrosisThe kidney is contracted with an irregular outer surface due to depressed scars over theThe kidney is contracted with an irregular outer surface due to depressed scars over theareas of healed infarction .areas of healed infarction .2-Arteriolosclerotic kidney:-2-Arteriolosclerotic kidney:-A-Benign nephrosclerosis:-A-Benign nephrosclerosis:- It refers to renal changes in cases of benign hypertensionIt refers to renal changes in cases of benign hypertensionGrossly :-Grossly :- Bilateral uniformly atrophic kidneys with finely granular outer surfacesBilateral uniformly atrophic kidneys with finely granular outer surfacesMicroscopically :-Microscopically :-11--Hyaline arteriolosclerosisHyaline arteriolosclerosis :-Hyaline thickening of arteriolar walls with obliterated:-Hyaline thickening of arteriolar walls with obliteratedlumenslumens2-All kidney structures undergo2-All kidney structures undergo ischemic atrophyischemic atrophy :-:-a-Tubular atrophic changes b-Diffuse glomerulosclerosis followed by hyalinosis ofa-Tubular atrophic changes b-Diffuse glomerulosclerosis followed by hyalinosis ofthe tuft c-Interstitial tissue fibrosis and lymphocytic infiltratethe tuft c-Interstitial tissue fibrosis and lymphocytic infiltrate
  84. 84. Clinical picture :-a) Mild oliguriab) Slight loss of concentrating mechanism and  GFRc) Mild degree of proteinuria is a constant findingd)These patients usually die from hypertensive heart disease or cerebrovasculardisease rather than from renal diseaseB-Malignant nephrosclerosis:-Causes:-1-Chronic benign hypertension  arteriolar wall injury 2-Arteritis .In both conditions :-A-Increased vascular permeability to fibrinogen along with endothelial injury andplatelets deposition fibrinoid necrosis.B-Thrombosis with intimal hyperplasia narrowing of vascular lumensC-Narrowed afferent vessels stimulate R-A system  More elevated blood pressure.Grossly :- Kidney size either normal or slightly shrunken with surface hemorrhagicpetechiae (flea-bitten appearance)Microscopically :-:- Necrotizing arteriolitisNecrotizing arteriolitis (arteriolar fibrinoid necrosis and infiltration(arteriolar fibrinoid necrosis and infiltrationby PNL,s .large arterioles show hyperplastic arteriolosclerosis (onion- skin).by PNL,s .large arterioles show hyperplastic arteriolosclerosis (onion- skin).
  85. 85. Arteriolosclerosis Malignant hyprtension HypeplasticarteriolosclerosisGlomerulosclerosis Necrotizing arteriolitisHyaline arterioloscl.
  86. 86. Clinical picture (Diastolic bl. pressure > 130 mmHg,):-1-Early symptoms due to ↑ I.C.P .Headache, nausea, vomiting and visual impairments2-Hypertensive crisis(loss of consciousness, convulsions proteinuria and hematuria(micro- or macro-)3- Papilledema , encephalopathy, CV disorders, renal .F.Fate :-90% deaths due to uremia10% deaths due to CV or cerebral hemorrhage
  87. 87. .Renal Artery StenosisRenal Artery Stenosis:-(Common in females 20-30Ys):-(Common in females 20-30Ys)Causes:-Causes:-1- ~ 70 % due to atheromatous plaque at origin of renal artery2-Second leading cause is fibromuscular dysplasia of renal artery (hyperplasia of alllayers)- Unilateral RAS is uncommon cause of hypertension (2-4% of renal hypertension )Surgical treatment:- Cure rate :-Surgical treatment:- Cure rate :-1-90% in fibromuscular dysplasia1-90% in fibromuscular dysplasia2-60-75% in atherosclerotic stenosis.2-60-75% in atherosclerotic stenosis.Renal cortical necrosisRenal cortical necrosis:-:-CausesCauses:-It occurs due to thrombosis of small renal arteries &arterioles due to:-:-It occurs due to thrombosis of small renal arteries &arterioles due to:-1-Toxemia of pregnancy1-Toxemia of pregnancy2-Infections e.g pneumonia ,diphtheria ,scarlet fever2-Infections e.g pneumonia ,diphtheria ,scarlet feverMorphologyMorphology :-Complete coagulative necrosis of the cortex of both kidneys.:-Complete coagulative necrosis of the cortex of both kidneys.ClinicallyClinically :- Oliguria ,anuria:- Oliguria ,anuria  Acute renal failure.Acute renal failure.
  88. 88. Renal diseases associated with micro-angiopathic hemolytic anemiaRenal diseases associated with micro-angiopathic hemolytic anemiaA group of diseases with overlapping clinical manifestation :-A group of diseases with overlapping clinical manifestation :-1-Microangiopathic hemolytic anemia1-Microangiopathic hemolytic anemia2-Thrombocytopenia2-Thrombocytopenia3-Renal failure3-Renal failure4-Manifestations of DIC4-Manifestations of DIC  all are characterized by thrombosis of the interlobularall are characterized by thrombosis of the interlobulararteries ,afferent arterioles and glomeruli , with necrosis and thickening of the vesselarteries ,afferent arterioles and glomeruli , with necrosis and thickening of the vesselwalls .The morphologic changes are similar to those of malignant hypertensionwalls .The morphologic changes are similar to those of malignant hypertension,either preceds it or not associated with.,either preceds it or not associated with.These diseases include :-These diseases include :-1-Childhood and adulthood hemolytic uremic syndromes1-Childhood and adulthood hemolytic uremic syndromes2-Thrombotic thrombocytopenic purpura.2-Thrombotic thrombocytopenic purpura.3-Scleroderma3-Scleroderma..All these diseases are caused by endothelial cell injury or intravascular coagulationAll these diseases are caused by endothelial cell injury or intravascular coagulation
  89. 89. Childhood hemolytic uremic sy.Childhood hemolytic uremic sy.It produces ARF after GIT trouble & inf-It produces ARF after GIT trouble & inf-Luenza .Up to 75% of patients are infectedLuenza .Up to 75% of patients are infectedwith verocytotoxin producing E.coli.with verocytotoxin producing E.coli.UndercookedUndercooked humburgerhumburgerManifestaionsManifestaions :-:-Sudden oliguria,hematuria,microagiop-Sudden oliguria,hematuria,microagiop-athic hemolytic anemia and sometimesathic hemolytic anemia and sometimesneurological signs.H.Pneurological signs.H.PPathogenesis:-Pathogenesis:-Shigella toxins affects endotheliumShigella toxins affects endothelium↑↑ adhesion of leukocytes.adhesion of leukocytes.↑↑ endothelinendothelinandand ↓↓ NO. Endothelial lysis (in presenceNO. Endothelial lysis (in presenceof cytokines such as TNF).These changesof cytokines such as TNF).These changesfavour thrombosis and V.Cfavour thrombosis and V.C. verocytotoxin can directly bind to Platletes. verocytotoxin can directly bind to Platletesand cause activationand cause activationMorphology :-Morphology :--Renal cortical necrosis.-Renal cortical necrosis.-Gl.capillary wall thickening-Gl.capillary wall thickening(deposition of fibrin)(deposition of fibrin)-Arteriolar fibrinoid necrosis, intimal Hyper--Arteriolar fibrinoid necrosis, intimal Hyper-plasia and thrombi. most patients recover inplasia and thrombi. most patients recover infew weeks, with proper care (i.e., dialysis,few weeks, with proper care (i.e., dialysis,etc); < 5% lethalityetc); < 5% lethalityAdulthood HUSAdulthood HUSSimilar to that of children andSimilar to that of children andarises in these sittingsarises in these sittings1-In women with complicated pregnancy1-In women with complicated pregnancy(retained placenta)(retained placenta)2-In postpartum women(P.P RF)2-In postpartum women(P.P RF)1-3 months after labour1-3 months after labour3-As a complication of oral pills.3-As a complication of oral pills.4-in Association with typhoid fever,E.coli4-in Association with typhoid fever,E.coli,septicemia ,viral infection and,septicemia ,viral infection andshigellosisshigellosis..Familial HUSFamilial HUSrecurrent thromboses (~ 50%lethality)recurrent thromboses (~ 50%lethality)deficiency of complement regulatorydeficiency of complement regulatoryprotein e.g Factor Hprotein e.g Factor H
  90. 90. Idiopathic Thrombotic thrombocytopenic purpura.Idiopathic Thrombotic thrombocytopenic purpura.It differes from HUS by itsIt differes from HUS by its CNS involvemenCNS involvement.Renal involvement in only 50% of casest.Renal involvement in only 50% of cases.There is biochemical evidence of I.V coagulation . Exchange transfusion and steroid.There is biochemical evidence of I.V coagulation . Exchange transfusion and steroidTxTx →→ mortality rate to < 50%mortality rate to < 50%Atheroembolic renal disease:-Atheroembolic renal disease:-Emboli of cholesterol crystals embolizes from aortic aneurysm or during cannulaizationEmboli of cholesterol crystals embolizes from aortic aneurysm or during cannulaization.They lodge in intra-renal vessels.They lodge in intra-renal vessels arterial narrowing and ischemic injury .arterial narrowing and ischemic injury .Renal infarctRenal infarct :-:-Kidney receive about 25% of C.OKidney receive about 25% of C.OCauses of kidney infarctionCauses of kidney infarction1-Atrial fibrillation1-Atrial fibrillation2-Myocardial infarction complicated by mural thrombosis.2-Myocardial infarction complicated by mural thrombosis.Manifestaions :-Manifestaions :-1-Asymptomatic1-Asymptomatic2-Pain &hematuria2-Pain &hematuria3-Hypertension.3-Hypertension.
  91. 91. Urinary tract obstruction (Obstructive uropathy)Urinary tract obstruction (Obstructive uropathy)Causes :-Causes :-1-Urethral causes1-Urethral causes:-(congenital anomalies,phimosis,U.valve stricture,uretheritis and:-(congenital anomalies,phimosis,U.valve stricture,uretheritis andrarely uretheral tumor )rarely uretheral tumor )2-Prostatic causes2-Prostatic causes:- BPH,prostatic tumor,prostatitis:- BPH,prostatic tumor,prostatitis3-U.bladder3-U.bladder:- bladder neck obstruction. bilharz. ,stone ,tumor, neurogenic bladder,:- bladder neck obstruction. bilharz. ,stone ,tumor, neurogenic bladder,4-Ureters4-Ureters :- Ureteral stenosis ,stone ,sloughed papillae,clots , tumor,ureteritis.Kinking.:- Ureteral stenosis ,stone ,sloughed papillae,clots , tumor,ureteritis.Kinking.5-Kidney5-Kidney :- Stone,tumor,abbarant renal artery,cong.stenosis.uretropelvic stricture:- Stone,tumor,abbarant renal artery,cong.stenosis.uretropelvic stricture6-pressure by pregnant uterus ,retropreitoneal fibrosis6-pressure by pregnant uterus ,retropreitoneal fibrosisEffects:-Effects:-ObstructionObstruction Infection and stone formation .Long term unrelievedInfection and stone formation .Long term unrelievedobstructionobstruction HydronephrosisHydronephrosispyonephrosis and renal atrophypyonephrosis and renal atrophyHydronephrosis:-Hydronephrosis:- It is marked distension of the pelvi-calyceal system with urineIt is marked distension of the pelvi-calyceal system with urinecaused by partial and intermittent obstruction of the urinary tract ,followed by renalcaused by partial and intermittent obstruction of the urinary tract ,followed by renaltissue atrophy .Unilateral ( partial or complete obstruction)tissue atrophy .Unilateral ( partial or complete obstruction) remain silent for longremain silent for longperiod .Bilateral partial obstructionperiod .Bilateral partial obstruction  Polyuria, acquired distal tubular acidosisPolyuria, acquired distal tubular acidosis+salt wasting +renal calculi +Tubulo-interstitial nephritis +atrophy and HP.+salt wasting +renal calculi +Tubulo-interstitial nephritis +atrophy and HP.Morphology :-Morphology :-1-Hydronephrosis either unilateral or bilateral depending on the site of obstruction1-Hydronephrosis either unilateral or bilateral depending on the site of obstruction
  92. 92. 2-Either intrarenal or extrarenal according to position of the renal pelvis2-Either intrarenal or extrarenal according to position of the renal pelvis3-Above the site of obstruction the urinary tract is distended by urine3-Above the site of obstruction the urinary tract is distended by urine4-When pelvis and calyces are distended ,pressure atrophy is exerted upon pyramids4-When pelvis and calyces are distended ,pressure atrophy is exerted upon pyramidsFlattened pyramids with progressive renal atrophy.Flattened pyramids with progressive renal atrophy.Grossly :-Grossly :-A-Enlarged kidney with a nodular surfaceA-Enlarged kidney with a nodular surfaceB-Cut sectionB-Cut section  multilocular sacs filled with urine,connected with each others and withmultilocular sacs filled with urine,connected with each others and withPelvi-calcyceal system (D.D polycystic kidney)Pelvi-calcyceal system (D.D polycystic kidney)C-Thin and atrophic intervening renal tissueC-Thin and atrophic intervening renal tissueMicroscopically :-Microscopically :-1-Glomeruli :- Firstly spared ,later they undergo atrophy as well.1-Glomeruli :- Firstly spared ,later they undergo atrophy as well.2-Tubules :- Early tubular dilatation ,followed by atrophy and replaced by fibrosis.2-Tubules :- Early tubular dilatation ,followed by atrophy and replaced by fibrosis.3-Interstitial tissue :- Fibrosis with compression and obliterated blood vessels.3-Interstitial tissue :- Fibrosis with compression and obliterated blood vessels.Clinical course :-Clinical course :-1-Dull ache1-Dull ache painpain and sensation of heaviness in renal angleand sensation of heaviness in renal angle2-Obstruction2-Obstruction  stasis and infectionstasis and infection  stonestone formationformation3-Urinary tract infection3-Urinary tract infection pyonephrosis or pyelonephritispyonephrosis or pyelonephritis ..4-Renal atrophy4-Renal atrophy  renal ischemiarenal ischemia  HypertensionHypertension ..5-Bilateral hydronephrosis5-Bilateral hydronephrosisUremiaUremia6-Obstruction below level of U.B.6-Obstruction below level of U.B. trabeculation of bladder wall and diverticulaetrabeculation of bladder wall and diverticulae
  93. 93. PyonephrosisPyonephrosisDefinitionDefinition :-:- Distended pelvis and calyces by pus (kidneyDistended pelvis and calyces by pus (kidney  as a bag of pus) followedas a bag of pus) followedby pressure atrophy and fibrosis of renal tissueby pressure atrophy and fibrosis of renal tissue..Etiology :-Etiology :-1-Primary :- It starts de novo1-Primary :- It starts de novo2-Secondary to chronic obstructive pyelonephritis or infected hydronephrosis2-Secondary to chronic obstructive pyelonephritis or infected hydronephrosis..Morphology :-Morphology :-The kidney is enlarged with bossy outer surface .Pelvi-calyceal system is dilated as aThe kidney is enlarged with bossy outer surface .Pelvi-calyceal system is dilated as amultilocular cysts filled with pus.Intervening renal tissue is atrophic and fibrosed .multilocular cysts filled with pus.Intervening renal tissue is atrophic and fibrosed .
  94. 94. Renal stones(urolithiasis)renal calculiUrolithiasis: Calculus formation at any level in the urinary tract , most often arisein renal pelvis or urinary bladder due to precipitation of crystalloids.Causes:- Dysbalance between solvents and solutesA-abnormal composition of urine1-Increased concentration of urine2-Increased urinary crystalloids (exceed solubility) e.g Ca ,oxalates ,urates &uric acidand cysteineB-Urinary stasis (obstruction)1-Urinary obstruction  stasis and infection  creating a nidus for stone formation2-Urinary obstruction  stasis and precipitation of crysalloids.C-Urinary tract infection :-1-Necrotic epithelial cells ,RBC,s,Bilh.ova and pus cells act as nuclei for stoneformation2-Infection  a change of urinary pH  deposition of crystalloids (Acidic pHformed by E.coli infection  forms oxalate and urates stones.Alkaline pH formedby pyogenic infection  forms triple phosphate stone.)D-Absence of solvents :- As absence of gylocoprotein (nephrocalcin) and some muco-polysaccharides..
  95. 95. Type of stone % pH CharacterPrimary stones1-Oxalate stones2-Uric acid &urates stones3-Cystine stoneSecondary stonesTriple phosphate (Magammonium phosphate)stones60%8%2%30%AcidicAcidicAcidicAlkalineHard,dark,spinyHard,yellowish brown ,smoothSoft,yellowish ,granularSingle,large white ,friable,smooth surface (stag –hornstones) –Large branching stonetaking shape of pelvi-calcyealsystem.Clinical presentation and complications:-1-Migration of stones  Renal colic2-Obstruction ,causes:-a-Hydroureter &hydronephrosisb-Stones formationc-Infection:cystitis ,pyelonephritisand pyonephrosis3-Injury of bladder wall causes:-Hematuria &squamous metaplasia
  96. 96. Tumors of the kidneyTumors of the kidney1-Tumors of the renal pelvis :-1-Tumors of the renal pelvis :-A-Benign tumorsA-Benign tumors :-T.C.(Villous) papilloma &hemangioma:-T.C.(Villous) papilloma &hemangiomaB-Malignant tumorsB-Malignant tumors :-:-1-Primary tumors :-TCC and Sq.C.C1-Primary tumors :-TCC and Sq.C.C2-Secondary:- Tumors from renal tissue directly infiltrate renal pelvis .2-Secondary:- Tumors from renal tissue directly infiltrate renal pelvis .2-Tumors of the renal cells :-2-Tumors of the renal cells :-A-Benign tumorsA-Benign tumors :- Oncocytoma ,papillary(chromophil)adenoma ,Metanephric:- Oncocytoma ,papillary(chromophil)adenoma ,Metanephric(embryonal ) adenoma,nephrogenic adenofibroma.Medullary fibroma(embryonal ) adenoma,nephrogenic adenofibroma.Medullary fibromaMalignant tumorsMalignant tumors :-:-1-Conventional (clear cell) carcinoma,1-Conventional (clear cell) carcinoma,2-papillary(chromophil)carcinoma ,2-papillary(chromophil)carcinoma ,3-chromophobe carcinoma ,3-chromophobe carcinoma ,4-collecting duct carcinoma ,4-collecting duct carcinoma ,5-medullary carcinoma ,5-medullary carcinoma ,6-renal cell carcinoma .6-renal cell carcinoma .
  97. 97. R.C.adenoma :-R.C.adenoma :-The cells are regular ,cuboidal or polygonal with regular central nucleiThe cells are regular ,cuboidal or polygonal with regular central nucleiand cytoplasm containing lipid vacuoles .and cytoplasm containing lipid vacuoles .D.D.:- from renal cell carcinoma by the tumor size (tumor size >3cm in diameter areD.D.:- from renal cell carcinoma by the tumor size (tumor size >3cm in diameter arelikely to metastasize.Tumor size(2-3 cm border line tumor is treated as an early cancer)likely to metastasize.Tumor size(2-3 cm border line tumor is treated as an early cancer)Medullary fibromaMedullary fibroma :-:-A tiny nodule in medulla composed ofA tiny nodule in medulla composed of fibroblast –like cellsfibroblast –like cells inin hyalinized stromahyalinized stroma ..Juxtaglomerular tumor(reninoma):-Juxtaglomerular tumor(reninoma):-A tumor of renal cortex consists of sheets of epithelioid cells with many small sizedA tumor of renal cortex consists of sheets of epithelioid cells with many small sizedblood vesselsblood vessels  produce excessive amounts of reninproduce excessive amounts of renin HypertensionHypertensionMalignant tumors :-Malignant tumors :-1-Renal cell carcinoma (hypernephroma ,adenocarcinoma of kidney or Grawitz1-Renal cell carcinoma (hypernephroma ,adenocarcinoma of kidney or Grawitztumor)tumor)NatureNature :- Adenocarcinoma originating from:- Adenocarcinoma originating from tubular epithelial cellstubular epithelial cellsIt is common in old man (6It is common in old man (6thth-7-7ththdecades).It sought to arise from adrenal rests (cleardecades).It sought to arise from adrenal rests (clearcells) so called hypernephromacells) so called hypernephromaPredisposing factors :-Predisposing factors :-1-Environmental factors :- Carcinogens(chemical or viruses),Smoking .1-Environmental factors :- Carcinogens(chemical or viruses),Smoking .3-Genetic factors (Von-Hipple lindau ) ot tr ch 3-8 and 3-11(familial) .3-Genetic factors (Von-Hipple lindau ) ot tr ch 3-8 and 3-11(familial) .
  98. 98. Three types of renal cell carcinoma are found:-Three types of renal cell carcinoma are found:-11-Conventional (Clear cell ) carcinoma (60%):--Conventional (Clear cell ) carcinoma (60%):--Either sporadic or familial-Either sporadic or familial-Del .of 3p .Common in males>females (34-90Y)-Del .of 3p .Common in males>females (34-90Y)Gross picture :-Gross picture :-ShapeShape:-:- a large well circumscribed mass with projecting processes or satellite nodulesa large well circumscribed mass with projecting processes or satellite nodulesSite of originSite of origin ;-Upper pole of kidney cortex.;-Upper pole of kidney cortex.SizeSize :- mean size about 8 Cm:- mean size about 8 CmCut sectionCut section :-variegated ,golden yellow with areas of hemorrhage and necrosis.:-variegated ,golden yellow with areas of hemorrhage and necrosis.The massThe mass early fungates through the renal pelvis and ureterearly fungates through the renal pelvis and ureter  painless hematuriapainless hematuria.Capsular invasion occurs lately.Capsular invasion occurs lately  Late painLate painMicroscopically :-Microscopically :-1-Pattern of growth1-Pattern of growth :-Either solid sheets of tumor cells separated by delicate richly:-Either solid sheets of tumor cells separated by delicate richlyvascularized fibrous stroma or well developed acinar growth pattern .Cystic,papillaryvascularized fibrous stroma or well developed acinar growth pattern .Cystic,papillary/pseudopapillary ,tubular and sarcomatoid patterns are also seen .A rich vascular/pseudopapillary ,tubular and sarcomatoid patterns are also seen .A rich vascularnetwork is prominent in all .Others change as fibrosis ,hyalinosis , necrosis andnetwork is prominent in all .Others change as fibrosis ,hyalinosis , necrosis andhemorrhages are common but desmoplasia is absent or minimalhemorrhages are common but desmoplasia is absent or minimal2-Cell morphology2-Cell morphology :-the tumor cells are polygonal or cuboidal in shape or spindle cells:-the tumor cells are polygonal or cuboidal in shape or spindle cellsThe tumor cells are clear cells (vegetable cells ) or granular cells or sarcomatoid orThe tumor cells are clear cells (vegetable cells ) or granular cells or sarcomatoid or
  99. 99. anaplastic with excessive mitosis and giant cells . The cell shape and cytoplasmicanaplastic with excessive mitosis and giant cells . The cell shape and cytoplasmiccontent correlate with the grade ( spindle cellcontent correlate with the grade ( spindle cell  high grade, also clear cellhigh grade, also clear cell  gradegrade1)1)2-Papillary (chromophil) renal cell carcinoma2-Papillary (chromophil) renal cell carcinoma :- It is a minority of RCC .:- It is a minority of RCC . FamilialFamilial(trisomy of ch 7) and sporadic (trisomy 7,16,17) as well as loss of ch Y .(trisomy of ch 7) and sporadic (trisomy 7,16,17) as well as loss of ch Y .ClinicallyClinically :- It represents 7-14% of epithelial renal neoplasms . Common in males at:- It represents 7-14% of epithelial renal neoplasms . Common in males at6-76-7ththdecades of life .decades of life .Gross pictureGross picture :-:-SiteSite :At renal cortex .:At renal cortex .SizeSize Mean size 6.4 cm .Mean size 6.4 cm . CapsuleCapsule :- May be:- May be..NumberNumber :- May be multifocal.:- May be multifocal.ConsistencyConsistency :- Varigated appearance with hemorrhage:- Varigated appearance with hemorrhageand necrosis.and necrosis.MicroscopicallyMicroscopically :- It may be papillary (the cores contain foamy macrophages and:- It may be papillary (the cores contain foamy macrophages andhemosiderin laden macrophages . , papillary –trabecular (the papillae are compressedhemosiderin laden macrophages . , papillary –trabecular (the papillae are compressedforming trabecular growth pattern. and papillary –solidforming trabecular growth pattern. and papillary –solidOutcomeOutcome :- It is more favourable than conventional type:- It is more favourable than conventional typeD.D. :- CRRC with papillary or pseudopapillary growth patterns.D.D. :- CRRC with papillary or pseudopapillary growth patterns.Papillary (chromophil )adenomaPapillary (chromophil )adenoma :- Is restricted to a papillary tumor that measure 1:- Is restricted to a papillary tumor that measure 1cm or less and contain small ,regular nuclei( G I)cm or less and contain small ,regular nuclei( G I)

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