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  • 1. Pathology of the kidney and itscollecting systemPr.Dr.Magdy Ismaeil Ahmed
  • 2. Anatomy of the Kidney
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.  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. 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. 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. Destruction of some GlCompansatory hypertrophy ofunaffected GlCapillary hypertensionSystemic hypertensionEpithelial &endothelialdamageLeakage of proteins intomesangiumFibrin deposition & proliferation ofmesangial cellsMore sclerosis
  • 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. 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. 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. 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. Lipiduria
  • 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. 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. 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. Acute GNAcute GN(post infectious GN)(post infectious GN)
  • 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. 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. 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. 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. 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. Crescent
  • 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. 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. 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. 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. Stage I Stage IIStage III Stage VISpike
  • 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. PLS & TOXINS+IgAC3B,D,Mg+C3bBb (alternate path.C3 convertase)ProperdinDegradeC3 C3bStabilizeFeed backC3 NefI.H
  • 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. 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. Protein
  • 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. 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. 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. 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. - Mild proteinuria- Crescent- Hypertension- Vascular sclerosis poor prognosis  passes to end stagerenal failure (40%) .Mesangial depositsIgA+C3 and properdin ,± IgG
  • 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. 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. Masson trichrome
  • 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. 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. 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. 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. 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. 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. Systemic lupus erythematosis kidneyThin arrow point to Wire-loop appearanceThick arrow point to hematoxyphil bodies in B.space
  • 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. 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. 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. Ischemia orToxinsDirect Gl damageV.CTubular damageTubularbackleakOliguriaObstructionby castsintratubularpressureGFRIschemia orToxinsV.C
  • 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. Acute tubular necrosis
  • 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. 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. 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. 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. Descendinginfection
  • 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. 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. 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. 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. 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.  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. 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. 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. 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. 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. 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. 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. Arteriolosclerosis Malignant hyprtension HypeplasticarteriolosclerosisGlomerulosclerosis Necrotizing arteriolitisHyaline arterioloscl.
  • 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. .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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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)
  • 100. Chromophobe renal cell carcinoma (5%) :-Chromophobe renal cell carcinoma (5%) :--Genetically multiple losses of chromosomes (hypodiploid tumor cells)-Genetically multiple losses of chromosomes (hypodiploid tumor cells)-It arises from intercalated cells of the renal cortex .-It arises from intercalated cells of the renal cortex .-Tumor cells are large ,round to polygonal with well defined cell borders and-Tumor cells are large ,round to polygonal with well defined cell borders andamphophilic to pale basophilic with perinuclear haloamphophilic to pale basophilic with perinuclear halo-It is of better prognosis.-It is of better prognosis.GradesGrades :- Four grades the 4:- Four grades the 4ththgrade showgrade show marked atypiamarked atypia withwith bizarre nucleibizarre nuclei andand giantgiantcellscellsClinical presentation :- (classic triad of hematuria,pain and mass)Clinical presentation :- (classic triad of hematuria,pain and mass)1-Dull ache pain in renal angle (41%)1-Dull ache pain in renal angle (41%)2-Hematuria :-Frank profuse ,painless ,total hematuria (59%)2-Hematuria :-Frank profuse ,painless ,total hematuria (59%)3-Mass in renal angle (45%) 4- Long fever,night sweats,malaise and weight loss3-Mass in renal angle (45%) 4- Long fever,night sweats,malaise and weight lossClinical courseClinical course:-Asymptomatic till reach a huge size.Symptomatic patients sufferes:-Asymptomatic till reach a huge size.Symptomatic patients sufferesfrom paraneoplastic syndrome ,or metastasis appears before local symptoms.Tr mayfrom paraneoplastic syndrome ,or metastasis appears before local symptoms.Tr mayregress.regress.Spread :- 1-DirectSpread :- 1-Direct :-:-Through the pelvis and ureters ,adrenal gland ,Perinephric fat .Through the pelvis and ureters ,adrenal gland ,Perinephric fat .B-ThroughB-Through the renal veinthe renal vein as a solid column of tumor growthas a solid column of tumor growthIVCIVCRt heartRt heartlungslungs2-Blood spread2-Blood spread:- to systemic organs :-Lungs,bone ,ect.:- to systemic organs :-Lungs,bone ,ect.3-Lymphatic spread3-Lymphatic spread :- Regional (lumbar) L.N,s.:- Regional (lumbar) L.N,s.
  • 101. 5 years survival : 45% and without metastasis 75%5 years survival : 45% and without metastasis 75%IHCIHC :- +ve for epithelial markers (CK,EMA and CEA).and vimentin ,:- +ve for epithelial markers (CK,EMA and CEA).and vimentin ,αα-1 antitrypsin-1 antitrypsinandand αα-1 antichemotrypsin and S100.-1 antichemotrypsin and S100.Diagnosis:-Diagnosis:-1-Cytology1-Cytology ::- Cytological examination of voided urine or bladder washing- Cytological examination of voided urine or bladder washing inefficientinefficient2-Retrograde brushing2-Retrograde brushing of pelvi-calyceal carcinoma give better resultsof pelvi-calyceal carcinoma give better results3-Percutaneous FNA3-Percutaneous FNA is safe and accurate ,it helps in D.D. of Renal cysts and RCC, Itis safe and accurate ,it helps in D.D. of Renal cysts and RCC, Itconfirms recurrence in renal fossa after nephrectomy.confirms recurrence in renal fossa after nephrectomy.Therapy :-Therapy :-1-Primary treatment1-Primary treatment Radical nephrectomyRadical nephrectomy (transabdominal or thoraco-abdominal(transabdominal or thoraco-abdominal((entire kidney ,surrounding fat ,Gerota`s fascia and adrenal glandentire kidney ,surrounding fat ,Gerota`s fascia and adrenal gland)+)+NodeNodedissectiondissection2-No benefits from conjunctive radiation therapy or chemotherapy .2-No benefits from conjunctive radiation therapy or chemotherapy .3-Bilateral RCC3-Bilateral RCC  Partial nephrectomyPartial nephrectomyPrognosis:-Prognosis:- 5 years survival 70%.It is related to some clinicopathological parameters5 years survival 70%.It is related to some clinicopathological parametersAs Sex&race,Age,staging,microscopic grade,invasion of renal vein &pelvis ,distantAs Sex&race,Age,staging,microscopic grade,invasion of renal vein &pelvis ,distantmetastasis ,oncocytic appearance (low grade),sarcomatoid appearance (poor prognosis)metastasis ,oncocytic appearance (low grade),sarcomatoid appearance (poor prognosis)
  • 102. Clear Vs granular cytoplasm (clearClear Vs granular cytoplasm (clear  less aggressive) and DNA poloidyless aggressive) and DNA poloidyStagingStaging:-IV stages (on the basis of of surgical findings):-IV stages (on the basis of of surgical findings)Microscopic gradingMicroscopic grading :-Nuclear grading .It ranged from G I-IV (G-IV marked nuclear:-Nuclear grading .It ranged from G I-IV (G-IV marked nuclearatypia ,Bizarre nuclei and giant cells .atypia ,Bizarre nuclei and giant cells .It depends upon nuclear size,shape,presence or absence of nucleoliIt depends upon nuclear size,shape,presence or absence of nucleoliNuclear size Nuclear shape nucleoli Others≤10um15um20um>20umRounded &uniformIrregularObivous irregularBizarre &multilobedIndistinctPresentLargeLargeX400X100X100Clumped chromatinSpindle cell.Stage UICC/AJCC/TNMStage 1Stage 2Stage3Stage 4≥7cm,organ confined<7cm,3a-Tr .extends into perinephric tissue within Gerota`s fascia3b-Tr in R.V or V.C below diaphragm3c-Tr in V.C above diaphragmTr beyond the Gerota`s fascia.
  • 103. CRCCPRCCSarcomatoidRCC
  • 104. OncocytomaSmall CCSq CC
  • 105. Nephroblastoma,Embryoma,Wilms ,carcino-sarcoma(Cong.Tr)Nephroblastoma,Embryoma,Wilms ,carcino-sarcoma(Cong.Tr)NatureNature :-:-Childhood tumor (2-4 Ys) derived fromChildhood tumor (2-4 Ys) derived from renal blastemarenal blastema ,A mixture of,A mixture ofPrimitive renal epithelium and stromal elements ,as well as, heterologus tissues.Primitive renal epithelium and stromal elements ,as well as, heterologus tissues.Genetic baseGenetic base :- Del ,11p:- Del ,11pSites :-Sites :- renal and extrarenal sites (retroperitoneal,sacrococcygeal region ,testisrenal and extrarenal sites (retroperitoneal,sacrococcygeal region ,testis,mediast-,mediast-inum and inguinal canal.inum and inguinal canal.Association :- V.R Hausen disease,G.U malformation ,Beck-Wiedemann synd.Association :- V.R Hausen disease,G.U malformation ,Beck-Wiedemann synd.(Omphalocele –macroglossia) and aniridia.Osteosarcoma ,B.rabdomyosarcoma(Omphalocele –macroglossia) and aniridia.Osteosarcoma ,B.rabdomyosarcoma,retinoblastoma.,retinoblastoma.Clinical presentationsClinical presentations :-1- Large abdominal mass can cross middle line:-1- Large abdominal mass can cross middle line2-Rare hematuria and abdominal pain 3-Hypertension 4-proteinuria 5- Intestinal2-Rare hematuria and abdominal pain 3-Hypertension 4-proteinuria 5- Intestinalobstruction .I.V. P :- Intra-renal mass distort the renal pelvis.obstruction .I.V. P :- Intra-renal mass distort the renal pelvis.Grossly :-Grossly :-1-Large ,expansile ,spherical non capsulated tumor mass that totally dwarf the kidney.1-Large ,expansile ,spherical non capsulated tumor mass that totally dwarf the kidney.2-Cut section is variegated reveals grayish white colour ,with soft or solid and myxo-2-Cut section is variegated reveals grayish white colour ,with soft or solid and myxo-matous areas (Fish-flesh appearance ) ,hyaline foci areas of cartilage or bone.matous areas (Fish-flesh appearance ) ,hyaline foci areas of cartilage or bone.3-Early capsular invasion3-Early capsular invasion early pain presentation ,late pelvis invasionearly pain presentation ,late pelvis invasion  late hema-late hema-
  • 106. Microscopic pictureMicroscopic picture :- Three elements are recognized :-:- Three elements are recognized :-1-Sarcomatous background1-Sarcomatous background :- consists of nests and sheets of sarcomatous spindle:- consists of nests and sheets of sarcomatous spindleshaped undifferentiated cells.The degree of anaplasia correlate with the prognosis.shaped undifferentiated cells.The degree of anaplasia correlate with the prognosis.2-Epithelial components in form of embryonic tubular and glomerular structures2-Epithelial components in form of embryonic tubular and glomerular structures3-Mesenchymal elements3-Mesenchymal elements .Like bone,cartilage,muscles (smooth and striated).Areas of.Like bone,cartilage,muscles (smooth and striated).Areas ofnecrosis and foci of lipid laden macrophages simulating teratoma (teratoid Wilms tr).necrosis and foci of lipid laden macrophages simulating teratoma (teratoid Wilms tr).I.H.CI.H.C :- Blastomatous elements:- Blastomatous elements  +ve vimentin+ve vimentinEpith.elementsEpith.elements  +ve keratin ,EMA ,various lectines+ve keratin ,EMA ,various lectinesMesenchymal components according :- Myoglobin & desmin ,NSE,GFAPMesenchymal components according :- Myoglobin & desmin ,NSE,GFAPS100S100Spread & metastasisSpread & metastasis :-:-1-Direct spread1-Direct spread:- Peri-renal tissue (liver, adrenal ,vertebrae , lately and rarely renal:- Peri-renal tissue (liver, adrenal ,vertebrae , lately and rarely renalpelvis & ureterpelvis & ureter2-Regional L.N,s2-Regional L.N,s :-15% of cases:-15% of cases3-Blood3-Blood :- Lungs ,liver and peritoneum.:- Lungs ,liver and peritoneum.A child with lung metastasis and R.peritoneum trA child with lung metastasis and R.peritoneum tr  suggests Wilms > neuroblastomasuggests Wilms > neuroblastomaPresence of bone metastasisPresence of bone metastasis  Exclude diagnosis or Wilm`s.Exclude diagnosis or Wilm`s.
  • 107. Staging of Wilms tumorStaging of Wilms tumor :-:-1-Stage I1-Stage I :- Tumor:- Tumor limited tolimited to the kidney and completely excised.the kidney and completely excised.2-Stage II2-Stage II:- Tumor:- Tumor extends beyondextends beyond the kidney but is completely excisedthe kidney but is completely excised3-Stage III3-Stage III :- Residual non- hematogenous tumor confined to the abdomen.:- Residual non- hematogenous tumor confined to the abdomen.a- Hilar L.N,s are involveda- Hilar L.N,s are involvedb-Diffuse peritoneal contamination by the tumor spillageb-Diffuse peritoneal contamination by the tumor spillagec-Implants on peritoneal surface.c-Implants on peritoneal surface.d-Tumor extends beyond surgical marginsd-Tumor extends beyond surgical marginse-Local infiltration and the tr is not completely resected.e-Local infiltration and the tr is not completely resected.4-Stage IV4-Stage IV:_Hematogenous metastasis beyond stage III (lungs ,liver ,brain):_Hematogenous metastasis beyond stage III (lungs ,liver ,brain)5-Stage V5-Stage V :- Bilateral renal involvement at diagnosis.:- Bilateral renal involvement at diagnosis.TreatmentTreatment :- A combination of:- A combination of chemotherapy ,radiotherapy and surgerychemotherapy ,radiotherapy and surgery  dramaticdramaticresponse.response.Survival rateSurvival rate :- 90% in treated cases.:- 90% in treated cases.
  • 108. Other pediatric renal tumorsOther pediatric renal tumorsMesoblastic nephroma:-Mesoblastic nephroma:-Fetal,mesenchymal or leiomyomatous hamartomaFetal,mesenchymal or leiomyomatous hamartoma.A congenital neoplasm discovered before age of.A congenital neoplasm discovered before age of 66 monthsmonthsGrosslyGrossly :- Similar to:- Similar to uterine leiomyoma,uterine leiomyoma, maymay infiltrate the renal tissue with or withoutinfiltrate the renal tissue with or withoutcystic changes.cystic changes.MicroscopicallyMicroscopically :- Cellular growth of:- Cellular growth of spindle cellsspindle cells (fibroblasts or myofibroblasts or(fibroblasts or myofibroblasts orsmooth muscles) without formation of epithelial cells .Some tubules and glomeruli aresmooth muscles) without formation of epithelial cells .Some tubules and glomeruli aresurrounded by spindle cells.No capsule separate the tumor mass from the renal tissue.surrounded by spindle cells.No capsule separate the tumor mass from the renal tissue.Atypical mesoblastic nephromaAtypical mesoblastic nephroma :- Is very cellular and mitotically active can infiltrate:- Is very cellular and mitotically active can infiltratethe renal tissue with areas of hemorrhage and necrosis.the renal tissue with areas of hemorrhage and necrosis.BehaviorBehavior :- Benign .No need for radio-or chemotherapy.:- Benign .No need for radio-or chemotherapy.PrognosisPrognosis :- Age at time of diagnosis and adequacy of excision are important factors.:- Age at time of diagnosis and adequacy of excision are important factors.Multicystic nephroma:-Multicystic nephroma:-It may rises in infancy or at any age. Always unilateralIt may rises in infancy or at any age. Always unilateral.presented by renal mass or ureteral obstruction by one cyst..presented by renal mass or ureteral obstruction by one cyst.GrosslyGrossly :-sharply demarcated from adjacent renal tissue.usual size 5-15 cm.with:-sharply demarcated from adjacent renal tissue.usual size 5-15 cm.withnodular outer surface.Cut section multiloculr ,non communicated cysts varies in sizesnodular outer surface.Cut section multiloculr ,non communicated cysts varies in sizes(1mm-3cm),lined by thin wall,contain serous fluid ,having no papillae.(1mm-3cm),lined by thin wall,contain serous fluid ,having no papillae.Microscopically :-Microscopically :- Cyst lining ranged from flat to low columnar .intervening stroma isCyst lining ranged from flat to low columnar .intervening stroma isfibroblastic ,or muscles or cartilage.fibroblastic ,or muscles or cartilage.
  • 109. Absence of nephroblastomatous tissueAbsence of nephroblastomatous tissue  It is calledIt is called multilocular cyst.multilocular cyst.Presence of nephroblastomatous tissuePresence of nephroblastomatous tissue  Multicystic nephromaMulticystic nephromaBehviorBehvior :- Benign .:- Benign .TreatmentTreatment :- Cured by nephrectomy alone:- Cured by nephrectomy aloneNephroblastomatosis:-Nephroblastomatosis:- It is a congenital dysontogenetic rather than neoplasticIt is a congenital dysontogenetic rather than neoplasticdisorderdisorderVaritiesVarities :- Two:- Two 1-Perilobular form1-Perilobular form.. 2-Intralobular form2-Intralobular form :- In cortex or medulla:- In cortex or medullaassociated with Wilms tr. It presented by subcapsular aggregates ofassociated with Wilms tr. It presented by subcapsular aggregates of primitive Metane-primitive Metane-phric epitheliumphric epitheliumMicroscopic size of these aggregates are calledMicroscopic size of these aggregates are called persistent nodular renal blastemapersistent nodular renal blastema,metanephric hamartoma or,metanephric hamartoma or nephric restsnephric rests .When massive is called nephroblastomatosis.When massive is called nephroblastomatosisIt is found in 1% of neonatal kidney and in 30%of kidneys containing Wilms tr.It is found in 1% of neonatal kidney and in 30%of kidneys containing Wilms tr.GrosslyGrossly :- It similar to Wilms tr:- It similar to Wilms trMicroscopicallyMicroscopically :- Tightly backed primitive nephrogenic epithelial cells .Stroma is:- Tightly backed primitive nephrogenic epithelial cells .Stroma isscanty containing cartilage,striated cellsscanty containing cartilage,striated cellsTreatmentTreatment :- conservative therapeutic approach is indicated:- conservative therapeutic approach is indicatedIntrarenal neuroblastoma. NeuroblastomaIntrarenal neuroblastoma. Neuroblastoma can invade the kidney secondary fromcan invade the kidney secondary fromadrenal gland or retroperitoneal site. Or present as a primary intrarenal tumor.adrenal gland or retroperitoneal site. Or present as a primary intrarenal tumor.D.D Wilms tumor..D.D Wilms tumor..
  • 110. Clear cell sarcomaClear cell sarcoma :- A morphologic variant of Wilms tumor with bone:- A morphologic variant of Wilms tumor with bonemetastasis.metastasis.GrosslyGrossly ;-Infiltrative margin .Cut section homogenous tan or gray tan with cystic;-Infiltrative margin .Cut section homogenous tan or gray tan with cysticFormationFormationMicroscopicallyMicroscopically :-Diffuse growth of small cells with rounded normochromic nuclei and:-Diffuse growth of small cells with rounded normochromic nuclei andindistinct nucleoli ,vacuolated cytoplasm and indistinct borders.Connective tissueindistinct nucleoli ,vacuolated cytoplasm and indistinct borders.Connective tissuestroma arrange tumor cells in nests,cords ,palisade or trabeculae.Myxoid changestroma arrange tumor cells in nests,cords ,palisade or trabeculae.Myxoid change,hyalinosis and fibrosis may be present.The presence of distinctive arborizing vascular,hyalinosis and fibrosis may be present.The presence of distinctive arborizing vascularstroma is more reliable diagnostic feature than clear cells or sclerosis.stroma is more reliable diagnostic feature than clear cells or sclerosis.BehaviorBehavior:- very malignant tr with high tendency for relapse and skeletal metastasis:- very malignant tr with high tendency for relapse and skeletal metastasis(skull) .Mortality rate > 50%.Better results with chemotherapy by(skull) .Mortality rate > 50%.Better results with chemotherapy by adriamycinadriamycin..Rhabdoid tumorRhabdoid tumor :-A solid monophasic or rhabdomyosarcomatoid variant of:-A solid monophasic or rhabdomyosarcomatoid variant ofWilmsWilmsTumor, now it is considered as a separate tumor type.Median age 18Tumor, now it is considered as a separate tumor type.Median age 18months.Sometimesmonths.Sometimesassociated with hypercalcemiaassociated with hypercalcemiaGrosslyGrossly ;-it is solid ,soft with infiltrative features;-it is solid ,soft with infiltrative featuresMicrscopicallyMicrscopically :-Monomorphic neoplasm involves the medulla has a diffuse or:-Monomorphic neoplasm involves the medulla has a diffuse oralveolar or trabecular pattern of growth.Tumor ells are rounded or oval medium sizedalveolar or trabecular pattern of growth.Tumor ells are rounded or oval medium sizedOr spindle cells.The cells have intracytoplasmic eosinophilic hyaline globule displacesOr spindle cells.The cells have intracytoplasmic eosinophilic hyaline globule displaces
  • 111. IHC :_ strong +ve for vimentin and keratin –Ve desmin and myoglobinIHC :_ strong +ve for vimentin and keratin –Ve desmin and myoglobinHistogenesis:-Histogenesis:- From multipotential cells in medulla.From multipotential cells in medulla.BehaviorBehavior :- Exremely aggressive .Death rate >75%.High stage and male sex:- Exremely aggressive .Death rate >75%.High stage and male sexunfavorable signs.unfavorable signs.Other sarcomasOther sarcomas ;-;-
  • 112. Mesoblastic nephromaMulticystic nephromaNephroblastomatosisMalignant rhabdoid
  • 113. Clear cell sarcoma
  • 114. Lower urinary tractLower urinary tractLower urinary tract composed of urethra ,urinary bladder and ureters.Lower urinary tract composed of urethra ,urinary bladder and ureters.UretheraUrethera :-:-Diseases of the uretheraDiseases of the urethera :-:-InflammationInflammation :- Uretheritis ,consists of:- Uretheritis ,consists of1-Non-gonococcal uretheritis1-Non-gonococcal uretheritis :- very common ,occurs by many organisms comm-:- very common ,occurs by many organisms comm-only {E.coli , C. trachomatis mycoplasma (ureaplasma urealyticum )} It accompanyonly {E.coli , C. trachomatis mycoplasma (ureaplasma urealyticum )} It accompanyby cystitis in female and prostatitis in malesby cystitis in female and prostatitis in males2-Gonococcal uretheritis2-Gonococcal uretheritis :- Earliest manifestation of gonorrhea.:- Earliest manifestation of gonorrhea.UrethritiUrethritis in association withs in association with arthritisarthritis ,,conjunctivitisconjunctivitis are components ofare components of Reiter`sReiter`ssyndromesyndrome ..Clinical features of urethritisClinical features of urethritis :- Local pain ,itching and frequency.:- Local pain ,itching and frequency.PathologicallyPathologically :- as any local inflammation:- as any local inflammationTumors of the urethera :-Tumors of the urethera :-1-Benign tumors :-1-Benign tumors :- PapillomaPapilloma2-Malignant:-2-Malignant:- Sq.C.C or T.C.C or rarely adenocarcinoma (uncommon).It appears asSq.C.C or T.C.C or rarely adenocarcinoma (uncommon).It appears aswarty or papillary growth ,they ulcerate on progressionwarty or papillary growth ,they ulcerate on progression fungating ,ulceratingfungating ,ulceratinglesionlesion
  • 115. The urinary bladderThe urinary bladderNormal histologyNormal histologySuperficial zoneUmbrella cellsIntermediate zone4-5cell stretched6-8cells contractedBasal zone-singleCell either cubicalor flatBasal lamina
  • 116. Diseases of urinary bladderDiseases of urinary bladder1-Congenital anomalies1-Congenital anomalies:-:-a-Diverticulae b-Exstrophy c-Miscellanous anomalies (vesicoureteral reflux,a-Diverticulae b-Exstrophy c-Miscellanous anomalies (vesicoureteral reflux,persistent urachuspersistent urachus2-Inflammation2-Inflammation :- Cystitis (acute &chronic and special forms of cystitis):- Cystitis (acute &chronic and special forms of cystitis)3-Tumors3-Tumors :- Benign tumors (epithelial &mesenchymal ):- Benign tumors (epithelial &mesenchymal )Malignant tumors (primary &secondary)Malignant tumors (primary &secondary)1-Congenital anomalies1-Congenital anomaliesA-Diverticulum:-A-Diverticulum:-Definition :-Definition :- A localized out-pouching of bladder wall.A localized out-pouching of bladder wall.Types :-Types :-1-Congenital (true) diverticulum1-Congenital (true) diverticulum :- is a single diverticulum that involves all layers of:- is a single diverticulum that involves all layers ofbladder wall.It may arise from budlike outgrowth of the fetal bladder.bladder wall.It may arise from budlike outgrowth of the fetal bladder.2-Acquired (false) diverticulum2-Acquired (false) diverticulum :-May be multiple is formed of mucosal pouching:-May be multiple is formed of mucosal pouching,due to wall defect and increase intra-luminal pressure (bladder neck obstruction ),due to wall defect and increase intra-luminal pressure (bladder neck obstruction )Complications :Complications :--1-Secondary infection 2-Urinary stasis1-Secondary infection 2-Urinary stasis  stone formation .3-predisposes to vesico-stone formation .3-predisposes to vesico-Ureteral reflux 4- Rarely bladder carcinomaUreteral reflux 4- Rarely bladder carcinoma
  • 117. B-ExstrophyB-ExstrophyDefinitionDefinition :-:- Developmental failure in the anterior wall of abdomen and urinaryDevelopmental failure in the anterior wall of abdomen and urinarybladder.The bladder either communicate with the surface of abdomen or appears asbladder.The bladder either communicate with the surface of abdomen or appears asananopened sac.opened sac.ComplicationsComplications :-:-1-Infection of the exposed mucosa that may extends up.1-Infection of the exposed mucosa that may extends up.2-Squamous metaplasia2-Squamous metaplasia3-Adenocarcinoma may develop.3-Adenocarcinoma may develop.TreatmentTreatment :- Surgical correction:- Surgical correction Long term survival.Long term survival.C-Miscellanous anomaliesC-Miscellanous anomalies1-Vesicoureteral reflux :-1-Vesicoureteral reflux :- most common and seriousmost common and serious  renal infection and scaringrenal infection and scaring2-Absent or hypoplastic urinary bladder2-Absent or hypoplastic urinary bladder :- uncommon anomaly.:- uncommon anomaly.3-Transverse septum3-Transverse septum:-Hour-glass deformity:-Hour-glass deformity4-Fistula formation with4-Fistula formation with :- vagina,rectum or uterus:- vagina,rectum or uterus5-Persistent urachus or uracha cyst5-Persistent urachus or uracha cyst:-A patent urachus form a fistula with the:-A patent urachus form a fistula with theumbilicusumbilicusAdenocarcinoma may develops.Adenocarcinoma may develops.
  • 118. DiverticulumExostrophy
  • 119. Inflammation (cystitis)Inflammation (cystitis)Acute &chronic cystitis:-Acute &chronic cystitis:-Etiology of cystitis :-Etiology of cystitis :-1-Bacterial :-1-Bacterial :- E.coli,proteus ,klebsiella.E.coli,proteus ,klebsiella.Enterobacter,T.B bacilli.Enterobacter,T.B bacilli.2-Viral2-Viral :-Adenoviruses:-Adenoviruses3-Fungal3-Fungal :- Candida albicans (monilasis),:- Candida albicans (monilasis),Crypotococcal agentsCrypotococcal agents4-Parasitic4-Parasitic :- Bilharziasis:- Bilharziasis5-Clamydia &mycoplasma5-Clamydia &mycoplasma6-Cytotoxic antitumor drugs:6-Cytotoxic antitumor drugs:cyclophosphamide & busulfancyclophosphamide & busulfan7-Radiation cystitis7-Radiation cystitisMorphology :-Morphology :-1-Mucosal hyperemia with serous1-Mucosal hyperemia with serousexudateexudate2-Hemorrahgic cystitis2-Hemorrahgic cystitis  HemorrhageHemorrhage3-Suppurative cystitis3-Suppurative cystitis :- Exude pus:- Exude pus4-ulcerative cystitis4-ulcerative cystitis :- Wide mucosal:- Wide mucosal5-Polypoid cystitis5-Polypoid cystitis :-Chronic cystitis with:-Chronic cystitis withpolypoidal mucosal projectionspolypoidal mucosal projections6-Chronic non specific cystitis6-Chronic non specific cystitis :-Long:-Longterm cystitis ,bladder wall become thickterm cystitis ,bladder wall become thickand inelasticand inelastic7-Chronic specific7-Chronic specific :- T.B,Bilharziasis.:- T.B,Bilharziasis.8-Cystitis follicularis8-Cystitis follicularis :- Chronic cystitis:- Chronic cystitisWith lymphoid follicles .With lymphoid follicles .9-Emphysematous cystitis9-Emphysematous cystitis :- Caused by:- Caused bygas producing bacteriagas producing bacteria  SubmucosalSubmucosalbubbles surrounded by giant cellsbubbles surrounded by giant cells10-Cystitis cystica10-Cystitis cystica :- Small cystic mucosal:- Small cystic mucosalinclusions in long standing chronicinclusions in long standing chroniccystitiscystitis  Cystitis glandularisCystitis glandularis11-Eosinophilic cystitis11-Eosinophilic cystitis :-Chronic cystitis:-Chronic cystitiswith abundant S.M eosinophils+fibrosiswith abundant S.M eosinophils+fibrosisand giant cells(unknown etiology)and giant cells(unknown etiology)12-Malakoplakia12-Malakoplakia :-soft yellow raised:-soft yellow raised
  • 120. Bilh.cystitis Condyloma Eosinoph.cystitisHagic cystitisFollicular cystitisCystitis glandularisInterstitial cystitis polypoid cystitis Malakoplakia
  • 121. Is edematous ,hyperemic and inflamedIs edematous ,hyperemic and inflamedHistologyHistology :- Closely backed large,foamy macrophages(abundant granular cytoplasm):- Closely backed large,foamy macrophages(abundant granular cytoplasm)with occasional multinucleated giant cells,interspersed by lymphocytes. Laminatedwith occasional multinucleated giant cells,interspersed by lymphocytes. LaminatedMineralized concretions found between cells and within the macrophages (Mineralized concretions found between cells and within the macrophages (Michaelis-Michaelis-Gutmann bodies) .Gutmann bodies) .Pathogenesis of malakoplakiaPathogenesis of malakoplakia :-It may result from defects in the phagocytic process:-It may result from defects in the phagocytic processIn which the macrophages and giant phagosomes become overloaded by bacteria.In which the macrophages and giant phagosomes become overloaded by bacteria. GMGMbodies result from deposition of calcium phosphate and other minerals overbodies result from deposition of calcium phosphate and other minerals overdisintegrated phagosomes.disintegrated phagosomes.Tumors of urinary bladderTumors of urinary bladderClassification of tumorsClassification of tumorsTumor like conditions :-Tumor like conditions :-1-Granuloma1-Granuloma ::--Rheumatoid like -nodule ,can occurs after bladder surgery, as aRheumatoid like -nodule ,can occurs after bladder surgery, as areaction to necrosis or catheterization.reaction to necrosis or catheterization.2-Spindle ( pseudosarcmatous ) nodule :-2-Spindle ( pseudosarcmatous ) nodule :- Simulate leiomyosarcoma .few weeks afterSimulate leiomyosarcoma .few weeks afterTUR.Ulcerated fascicular pattern + Extravsated RBC,s,lack of significant atypia .TUR.Ulcerated fascicular pattern + Extravsated RBC,s,lack of significant atypia .3-Inflammatory pseudotumor3-Inflammatory pseudotumor4-Condyloma acuminatum:-4-Condyloma acuminatum:- associated with genital condylomaassociated with genital condyloma
  • 122. Bengin tumors :-Bengin tumors :-1-Transitional cell papilloma &inverted papilloma (Brunnian adenoma)1-Transitional cell papilloma &inverted papilloma (Brunnian adenoma)2-Adenomatoid tumor (nephrogenic adenoma ,mesonephric adenoma)2-Adenomatoid tumor (nephrogenic adenoma ,mesonephric adenoma)3-Paraganglioma3-Paraganglioma4-Other rare benign tumors (villous adenoma). leiomyoma (commonest), Fibroma,4-Other rare benign tumors (villous adenoma). leiomyoma (commonest), Fibroma,neurofibroma ,angioma,G.C myoblastomaneurofibroma ,angioma,G.C myoblastomaMalignant tumorsMalignant tumors:-:-1-TCC 2-Squamous cell carcinoma1-TCC 2-Squamous cell carcinoma ((verrucous carcinomaverrucous carcinoma ))3-Adenocarcinoma3-Adenocarcinoma(enteric type,Clear cell”mesonephric”type,signet ring cell type(enteric type,Clear cell”mesonephric”type,signet ring cell type )) 4-Small cell/ neuro –4-Small cell/ neuro –endocrine . 5-Sarcomatoidendocrine . 5-Sarcomatoid ““spindle cell”spindle cell”carcinomacarcinoma 6-Carcinosarcoma 7-Lympho-6-Carcinosarcoma 7-Lympho-epithelioma likeepithelioma like carcinomacarcinoma 8-Nested variant of urothelial carcinoma 9-Micro-8-Nested variant of urothelial carcinoma 9-Micro-papillary ca. 10-Microcysticpapillary ca. 10-MicrocysticPredisposing factors :-Predisposing factors :-1-Schistomiasis1-Schistomiasis:-can cause Sq.metaplasia:-can cause Sq.metaplasia  Cancer.Cancer.2-Local lesions2-Local lesions :- As exostrophied bladder ,diverticulum ,bladder calculi, leukoplakia:- As exostrophied bladder ,diverticulum ,bladder calculi, leukoplakiaof bladder mucosa and bladder diversionof bladder mucosa and bladder diversion  all cause sq.metaplasiaall cause sq.metaplasia CancerCancer3-Smoking3-Smoking :-Tobacco smoking leads to 2-3 folds increase of incidence of bladder:-Tobacco smoking leads to 2-3 folds increase of incidence of bladdercancer (chemical carcinogenes)cancer (chemical carcinogenes)
  • 123. Transitional cell papilloma Inverted papillomaInflam.pseudotumor Nephrogenic adenoma
  • 124. Papillary hyperplasiaUrothelial dysplasia
  • 125. 5-Aniline dyes5-Aniline dyes:-High incidence of cancer bladder:-High incidence of cancer bladderGross pathology :-Gross pathology :-Sites:-Sites:- lateral wall & ureteric orifices and trigone (75%) are common sites for cancerlateral wall & ureteric orifices and trigone (75%) are common sites for cancerbladder.bladder.Shape:-Shape:- Either fungating ,or infiltrative or papillary or ulceratedEither fungating ,or infiltrative or papillary or ulceratedBilharz.cancer mostly ulcerated while non-bilhraz.is papillary.Bilharz.cancer mostly ulcerated while non-bilhraz.is papillary.Papillary tumors 90% (invasive or non-invasive).Have floating fern-likePapillary tumors 90% (invasive or non-invasive).Have floating fern-likefrondsfrondswith broad base or narrow pedicle.with broad base or narrow pedicle.Non-papillary (flat) 10% (invasive or non-invasive) are bulkier with ulceratedNon-papillary (flat) 10% (invasive or non-invasive) are bulkier with ulceratedsurfacesurfaceNumbersNumbers :- Either single or multiple:- Either single or multipleMicroscopically :-Microscopically :-A-Transitional cell carcinoma :-A-Transitional cell carcinoma :- 90% of all epithelial bladder tumors.T.C.papilloma90% of all epithelial bladder tumors.T.C.papillomamust be distinguished from T.C.C G Imust be distinguished from T.C.C G IGrades :-T.C.C is divided according to Ash 1940 into three grades according to degreeGrades :-T.C.C is divided according to Ash 1940 into three grades according to degreeOf anaplasia and extent of invasion .Of anaplasia and extent of invasion .Anaplastic featuresAnaplastic features (increased cellularity,nuclear(increased cellularity,nuclearcrowding, loss of polarity , disorientation , pleomorphism,pleomorphic nuclei andcrowding, loss of polarity , disorientation , pleomorphism,pleomorphic nuclei and
  • 126. Grade IGrade I :- Regular frond like papillae ,composed of central fibro-vascular core covered:- Regular frond like papillae ,composed of central fibro-vascular core coveredby clearly transitional cells with increased number of layers.Larger and regularby clearly transitional cells with increased number of layers.Larger and regularcells with mild hyperchromatism .Mitosis is rare or absent.cells with mild hyperchromatism .Mitosis is rare or absent.Grade IIGrade II:-Still recognized transitional cells ,Increased layering and crowding of cells:-Still recognized transitional cells ,Increased layering and crowding of cellscells are larger and less regular . Increased nuclear hyperchromatism.increased mitosiscells are larger and less regular . Increased nuclear hyperchromatism.increased mitosisAnd loss of polarity.Tumor may or may not invasive.And loss of polarity.Tumor may or may not invasive.Grade IIIGrade III :- papillary areas still present but irregularly distributed ,tumor mass:- papillary areas still present but irregularly distributed ,tumor masscomposed of smaller groups of cells .Mitosis frequently found.Tumor invades thecomposed of smaller groups of cells .Mitosis frequently found.Tumor invades thebladder wall to a variable distance.bladder wall to a variable distance.Grade IV:-Grade IV:-Scanty or absence of papillary areas .Marked cellular atypia and pleomorph-Scanty or absence of papillary areas .Marked cellular atypia and pleomorph-ism.Transitional nature is obscure.Widely invasive tumor Grades III & IV show foci ofism.Transitional nature is obscure.Widely invasive tumor Grades III & IV show foci ofsquamous metaplasia.squamous metaplasia.N.B.:- A sharp distinction between benign and malignant tumors is difficult .to avoidN.B.:- A sharp distinction between benign and malignant tumors is difficult .to avoidthis a designation ofthis a designation of transitional cell tumortransitional cell tumor and grade from 0 - IV is usedand grade from 0 - IV is usedB-Transitional cell papilloma :-B-Transitional cell papilloma :- A small (2cm) single or multiple papillary withA small (2cm) single or multiple papillary withbranching pattern.composed of thin fibro-vascular cores covered bybranching pattern.composed of thin fibro-vascular cores covered by normal lookingnormal lookingurothelium (6-7 layers) in thickness. No mitosis,preserved polarity of the transitionalurothelium (6-7 layers) in thickness. No mitosis,preserved polarity of the transitionalcellscells .It may recur and behave in a malignant manner . Foci of squamous or.It may recur and behave in a malignant manner . Foci of squamous or
  • 127. G IG IIIG IIG IV
  • 128. C-Carcinoma in situ (considered as G 0 carcinoma )C-Carcinoma in situ (considered as G 0 carcinoma ) :-:- Invasive and non invasiveInvasive and non invasivecancer having foci of hyperplasia, dysplasia and carcinoma in situ.Similar foci may becancer having foci of hyperplasia, dysplasia and carcinoma in situ.Similar foci may bepresent in the ureters and renal pelvis.The malignant epithelial cells occupy the fullpresent in the ureters and renal pelvis.The malignant epithelial cells occupy the fullthickeness of mucosa without invasion of the B.M.thickeness of mucosa without invasion of the B.M.D-Squamous cell carcinomaD-Squamous cell carcinoma :-:- Most squamous cell carcinoma of the bladder inMost squamous cell carcinoma of the bladder incontrast to papillary carcinoma are sessile,nodular infiltrative and ulcerating .Thecontrast to papillary carcinoma are sessile,nodular infiltrative and ulcerating .Thecarcinoma may be differentiated with keratin pearls or anaplastic.carcinoma may be differentiated with keratin pearls or anaplastic.E-AdenocarcinomaE-Adenocarcinoma :-:- It is rare and may arise on top of exostrophy with glandularIt is rare and may arise on top of exostrophy with glandularmetaplasia ,or arise from urachal rests ,periuretheral and periprostatic glands or frommetaplasia ,or arise from urachal rests ,periuretheral and periprostatic glands or fromcystitis cystica .Tumor composed of glandular and tubular pattern with or withoutcystitis cystica .Tumor composed of glandular and tubular pattern with or withoutmucus secretion.mucus secretion.Staging of bladder cancerStaging of bladder cancer :-:-1-Stage 01-Stage 0 :- Tumor confined to mucosa:- Tumor confined to mucosa2-Stage A2-Stage A :-Invade lamina propria ,not Ms.:-Invade lamina propria ,not Ms.Stage B1Stage B1 :-Carcinoma invades superficial Ms.:-Carcinoma invades superficial Ms.B2B2 :-Carcinoma invade deep Ms.:-Carcinoma invade deep Ms.Stage CStage C:- Carcinoma invades perivesical tissue:- Carcinoma invades perivesical tissueStage D1Stage D1:- carcinoma show regional metastasis.:- carcinoma show regional metastasis.
  • 129. Jewett-Marshall Depth of invasion AJCC0AB1B2CD1D2Non invasive (in situ(Lamina propriaSuperficial musclesDeep musclesPerivesical tissueRegional metastasisDistant metastasisPa,Pi (Ti)P1 (T1(P2a (T2a(P2b (T2b(P3 (T3(P4a (T4a(P4b (T4b(Pathologic staging of bladder cancer
  • 130. Staging of bladder cancer according to Jewett :-Staging of bladder cancer according to Jewett :-1-Non –infiltrative1-Non –infiltrative  mucosal tumormucosal tumor2-Infiltrative2-Infiltrative superficialsuperficial SubmucosaSubmucosa AAsuperficial Mssuperficial MsB1B1DeepDeep  deep Msdeep Ms B2B2PerivesicalPerivesical  CCRhabdomyosarcomaRhabdomyosarcoma :- Is the most frequent malignant mesenchymal tumor .2 forms :-:- Is the most frequent malignant mesenchymal tumor .2 forms :-Adult formAdult form :-in patients aged >40Ys as ordinary rhabdomyosarcoma:-in patients aged >40Ys as ordinary rhabdomyosarcomaChildhood formChildhood form :- sarcoma butryoides (embryonal rhabdomyosarcoma).:- sarcoma butryoides (embryonal rhabdomyosarcoma).Local spread & metastasisLocal spread & metastasis1-Direct :-1-Direct :- to ureters, neck of bladder ,urethera ,prostatic ducts and seminal vesicleto ureters, neck of bladder ,urethera ,prostatic ducts and seminal vesicle2-Lymphatic spread2-Lymphatic spread :- Pelvic chains in 25% of invasive tumors:- Pelvic chains in 25% of invasive tumors3-Blood spread3-Blood spread :- Lungs ,liver and bones .:- Lungs ,liver and bones .Clinical course :-Clinical course :-1-Painless hematuria (1-Painless hematuria ( only clinical manifestationonly clinical manifestation),necroturia,pneumaturia),necroturia,pneumaturia2-Frequency ,urgency and dysuria2-Frequency ,urgency and dysuria accompany hematuria.accompany hematuria.3-Pyelonephritis or hydronephrosis3-Pyelonephritis or hydronephrosis may develop.may develop.4-Recurrences4-Recurrences :- G I (>60-80% ) recur.80-90% of G III recur.:- G I (>60-80% ) recur.80-90% of G III recur.
  • 131. The pathology report should include:-The pathology report should include:-1-1-ConfigurationConfiguration 2- Tumor2- Tumor stage ( ±stage ( ± muscles &Depth of penetration )muscles &Depth of penetration ) 3-Tr grade3-Tr grade4- Vascular invasion (Bl.Vs or Lymphatics)4- Vascular invasion (Bl.Vs or Lymphatics) 5-5-Mucosal changesMucosal changesTreatment :-Treatment :-1-Carcinoma in situ1-Carcinoma in situ :-:- Total cystectomyTotal cystectomy ,except small localized lesion,except small localized lesion intravesicalintravesicalchemotherapychemotherapy (recurrence in 40-70% within 6-12 months.)(recurrence in 40-70% within 6-12 months.)2-Grade I & II (without muscle invasion)2-Grade I & II (without muscle invasion) :-:-transuretheral resectiontransuretheral resection ++Intravesical chem-Intravesical chem-otherapy or radiation therapyotherapy or radiation therapy especially in multiple or recurrent tumors.especially in multiple or recurrent tumors.3-Grade III & IV (with muscle invasion irrespecive of grade):-Radical cystectomy3-Grade III & IV (with muscle invasion irrespecive of grade):-Radical cystectomy ±±preoperative radiotherapy or chemotherapy.Or radiation alonepreoperative radiotherapy or chemotherapy.Or radiation alone (it obliterate superficial(it obliterate superficialpapillary components but not invasive components ,also increase nuclear pleomorphi –papillary components but not invasive components ,also increase nuclear pleomorphi –sm and produce tumor squamous metaplasia.sm and produce tumor squamous metaplasia.A-Radical cystectomA-Radical cystectomyy includes :-includes :-A-In males :- Bladder,prostate,seminal vesicle +adjacent perivesical tissueA-In males :- Bladder,prostate,seminal vesicle +adjacent perivesical tissueB-In females :- Bladder ,urethera,anterior vagina ,uterus ,tubes and ovaries.B-In females :- Bladder ,urethera,anterior vagina ,uterus ,tubes and ovaries.B-Partial cystectomyB-Partial cystectomy :- disfavored:- disfavored  High recurrence rate in residual bladder.High recurrence rate in residual bladder.C-Intravesical immunotherapyC-Intravesical immunotherapy with Calmette Guerine Bacillus (BCG) reduce recur-with Calmette Guerine Bacillus (BCG) reduce recur-rence rate.It producerence rate.It produce superficial mucosal erosion ,submucosal T.B. granuloma andsuperficial mucosal erosion ,submucosal T.B. granuloma andUreteraldiversion
  • 132. PrognosisPrognosis :- Depends on the patient age ,the histologic pattern ,grade ,clinical stage:- Depends on the patient age ,the histologic pattern ,grade ,clinical stage(extent of invasion),Lymph node involvement ,abnormalities in the remaining bladder(extent of invasion),Lymph node involvement ,abnormalities in the remaining bladdermucosa , Status of blood group antigens,ABH and Lewis Ag.(absent in high grade tr)mucosa , Status of blood group antigens,ABH and Lewis Ag.(absent in high grade tr). abnormal karyotyping,mutated oncogenes ,polyoidy. abnormal karyotyping,mutated oncogenes ,polyoidy
  • 133. Reactive dysplasia Flat “in situ” carcinomaSq.C.C.Sq.metaplasia
  • 134. Metaplastic carcinoma Small cell carcinomaPoorly diff .Tr. C.CInfiltrative .Tr. C.C
  • 135. Verrucous carcinomaSpindle cellcarcinomaTr .C.C with glandulardifferentiation
  • 136. Nested variant ofTr.C.CMicropapillary Tr.C.CIn situ papillary Tr.C.CSarcomatoid Tr.C.C
  • 137. Sarcomatoid “spindle cell”carcinoma
  • 138. Histocompatibility antigens (HLA complexHistocompatibility antigens (HLA complex((Definition:- The genes that evokerejection of transplanted organs .Theydisplayed on the cell surfaces of thedonor organ. They clustered on asmall segment of ch 6.They stand forHuman Leukocytes Antigens (HLA(Functions :-1-They regulate immune responses2-They resists or assists acquiring of diseasesClassifications :- The genes products are classified according to:-Chemical structure,tissue distribution and function into three categories.1-Class I antigenes :- Are called HLA- A,B,C ,are found in all nucleated cells andplatelets.They evokes the formation of humoral antibodies in genetically non-identicalindividuals.2-Class II antigens:- They code for D region with subregions DP,DQ,DR.They arefound in antigen presenting cells(monocytes ,macrophages and dendritic cells),B cellsand some activated T cells and they expressed by γ interferon on endothelial cells,fibroblasts and renal tubular epithelial cells.
  • 139. Transplant rejectionTransplant rejectionMany organs can be transplanted (skin, liver, lung, heart ,pancreas,B.M.kidney others )Many organs can be transplanted (skin, liver, lung, heart ,pancreas,B.M.kidney others )The goal is successful transplantation of these organs with immunologicalThe goal is successful transplantation of these organs with immunologicalreactions .reactions .Graft rejectionGraft rejection :- depends on recognition by the host of the grafted tissue as foreign:- depends on recognition by the host of the grafted tissue as foreign.Antigens responsible for such rejection in humans are those of the major (.Antigens responsible for such rejection in humans are those of the major (HLAHLA))system.system.RejectionRejection :-Is a complex process in which both:-Is a complex process in which both cell mediated immunitycell mediated immunity andandcirculating antibodiescirculating antibodies play a role .play a role .-T-cell mediated reactions :--T-cell mediated reactions :- It is initiated by recognition of the recipient`sIt is initiated by recognition of the recipient`slymphocytes to the donorlymphocytes to the donor HLA class IHLA class I on the surface of the antigen presenting cell oron the surface of the antigen presenting cell orwithin grafted tissuewithin grafted tissue differentiated into mature CTLsdifferentiated into mature CTLsThey lyse the grafted tissue .They lyse the grafted tissue .-Antibody –mediated reaction:--Antibody –mediated reaction:- The humoral response is important in two types ofThe humoral response is important in two types ofrejection in human kidney transplant recipient.rejection in human kidney transplant recipient.1-Preformed circulating antibodies1-Preformed circulating antibodies :- It occurs due to previous sensitization of the:- It occurs due to previous sensitization of therecipient by the donor`s antigen before transplantation ( blood transfusion ).Therecipient by the donor`s antigen before transplantation ( blood transfusion ).Thecirculating anti-donor antibodies rapidly fix the graft vascular bedcirculating anti-donor antibodies rapidly fix the graft vascular bed  Hyper-acuteHyper-acuterejection .rejection .2-The recipient not previously sensitized to transplantation antigens2-The recipient not previously sensitized to transplantation antigens.The formed.The formed
  • 140. MechanismsMechanisms:-:-aa-Complement dependent cytotoxicity-Complement dependent cytotoxicityb-Antibody dependent cell mediated cytotoxicityb-Antibody dependent cell mediated cytotoxicity3-deposition of Ag-Ab complexes3-deposition of Ag-Ab complexes.The target for these antibodies is the graft.The target for these antibodies is the graftvasculature (vasculature (rejection vasculitisrejection vasculitis).The complement cause tissue injury causing).The complement cause tissue injury causingplatelets aggregations ,leakage of neutrophils lysosomes ,coagulation ,fibrinolysisplatelets aggregations ,leakage of neutrophils lysosomes ,coagulation ,fibrinolysisand activation of kinin cascades.and activation of kinin cascades.Morpholoy of rejection reactions:-Morpholoy of rejection reactions:- Rejection reactions are classified intoRejection reactions are classified into hype-hype-racute , acuteracute , acute andand chronicchronic according toaccording to timing ,morphologytiming ,morphology andand the mechanism.the mechanism.1-Hyperacute rejection1-Hyperacute rejection :-:-TimeTime :- within minutes after transplantation .Or (delayed to hours – two days:- within minutes after transplantation .Or (delayed to hours – two daysaccordingaccordingto titer of circulating cytotoxic antibodies)to titer of circulating cytotoxic antibodies)MechanismMechanism :- It is caused by the preformed:- It is caused by the preformed anti-donor antibodiesanti-donor antibodies against the graftagainst the graftAgAgMorphologyMorphology :-:-GrosslyGrossly:- The hyper-acute rejecting , kidney rapidly become:- The hyper-acute rejecting , kidney rapidly become cyanotic ,mottled , flaccidcyanotic ,mottled , flaccidand excretes few drops of bloody urine .and excretes few drops of bloody urine .MicroscopicallyMicroscopically :-:-ClassicClassic arthus reactionarthus reaction :-:-1-In 11-In 1ststhh neutrophilsneutrophils accumulation on arteriolar endothelium & glomerular andaccumulation on arteriolar endothelium & glomerular and
  • 141. 2-Igs and complement aredeposited in vessel wall3-E/M  Early endothelialinjury ,fibrin -platelets thrombi
  • 142. A-The early lesions indicates Ag-Ab reaction at the level of vascular endothelium .A-The early lesions indicates Ag-Ab reaction at the level of vascular endothelium .B-Then the changes become diffuse and intense whereB-Then the changes become diffuse and intense where the glomerular capillariesthe glomerular capillariesbecome thrombotic andbecome thrombotic and the arterial wallsthe arterial walls show fibrinoid necrosis.The kidneyshow fibrinoid necrosis.The kidney cortexcortexbecomes necrotic (infarcted )becomes necrotic (infarcted ) The kidney is removed.The kidney is removed.To overcome this prior to transplantation ,To overcome this prior to transplantation , cross matching of the donor`s lymphocytescross matching of the donor`s lymphocyteswith the recipient`s serumwith the recipient`s serum2-Acute rejection :-2-Acute rejection :-TimeTime :-:- May appear withinMay appear within daysdays of transplantation in untreated recipient (or delayed toof transplantation in untreated recipient (or delayed toappear suddenly inappear suddenly in months or even yearsmonths or even years later,when the used immunosuppression islater,when the used immunosuppression isterminated)terminated)MechanismMechanism :-Both:-Both humoralhumoral andand cellular reactionscellular reactions are blamed ,any one mayare blamed ,any one maypredominate.predominate.MorphologyMorphology :-:- HumoralHumoral rejection is dominated byrejection is dominated by vasculitisvasculitis ,while,while cellularcellular rejectionrejectionshow interstitialshow interstitial mononuclear cellular infiltratesmononuclear cellular infiltrates(CD4 &CD8) edema and(CD4 &CD8) edema andhemorrhage . .IL2 receptors on lymphocytes and plasma cells can be found also.Thehemorrhage . .IL2 receptors on lymphocytes and plasma cells can be found also.Thecapillaries (glomerular & peritubular) are invaded by mononuclear cells and becomecapillaries (glomerular & peritubular) are invaded by mononuclear cells and becomenecrotic .necrotic .ClinicallyClinically :- Acute rejection occurs in initial months after transplantation and appear by:- Acute rejection occurs in initial months after transplantation and appear bysigns ofsigns of R.F.R.F. Diagnosis of cellular rejection is important ,because it responds goodDiagnosis of cellular rejection is important ,because it responds goodwithwith immunosuppressionimmunosuppression in absence of vasculitis .in absence of vasculitis .
  • 143. A-Acute rejection vasculitisA-Acute rejection vasculitis:-:- Humoral rejectionHumoral rejection commonly occurs in first fewcommonly occurs in first fewmonths after transplantation or when immunosuppression is stopped.It is followedmonths after transplantation or when immunosuppression is stopped.It is followedby poor function of the graft and dose not respond to high doses of immunosuppre-by poor function of the graft and dose not respond to high doses of immunosuppre-ssion .ssion . MorphologyMorphology :- 1-Necrotizing vasculitis (endothelial cell injury) 2-Neutrophilic:- 1-Necrotizing vasculitis (endothelial cell injury) 2-Neutrophilicinfiltration .3-deposition of Igs ,complement and fibrin & thrombosis.infiltration .3-deposition of Igs ,complement and fibrin & thrombosis.Glomerular necrosis and cortical arteriolar thrombosis.Glomerular necrosis and cortical arteriolar thrombosis.Cortical infarction .It mayCortical infarction .It maybe associat-ed with cellular rejection .be associat-ed with cellular rejection .B-Subacute vasculitisB-Subacute vasculitis :-It occurs in first months after transplantation .:-It occurs in first months after transplantation . MorphologyMorphology :-:- Intimal lesionIntimal lesion  Markedly thickened by proliferated fibroblastsMarkedly thickened by proliferated fibroblasts,myocytes and foamy macrophages,myocytes and foamy macrophages  luminal narrowing or obliteration .Theluminal narrowing or obliteration .Thethickened intima infiltrated by neutrophils and mononuclear cells with deposition ofthickened intima infiltrated by neutrophils and mononuclear cells with deposition ofIgs and complement.Igs and complement.3-Chronic rejection :-3-Chronic rejection :-Mechanism ;Mechanism ;- It is caused by- It is caused by ischemic damageischemic damage to renal parenchymato renal parenchymaMorphologyMorphology :- The vascular changes are:- The vascular changes are dense intimal fibrosisdense intimal fibrosis in cortical arteries .(endin cortical arteries .(endstage of acute and subacute vasculitis)stage of acute and subacute vasculitis) renal ischemiarenal ischemia glomerular atrophyglomerular atrophy,interstitial fibrosis , tubular atrophy and shrinkage of renal tissue. Acute arteritis,interstitial fibrosis , tubular atrophy and shrinkage of renal tissue. Acute arteritismay supervenes the chronic state (may supervenes the chronic state (humoral rejection crisishumoral rejection crisis).The rejecting kidney).The rejecting kidneyinfiltrated by lymphocytes ,plasma cells and eosinophilsinfiltrated by lymphocytes ,plasma cells and eosinophils
  • 144. Acute cellular rejection:-Glomeruli :- Shrunken with swollenendothelial cellsTubules :- atrophic with degeneratedepithelial cellsInterstitium :- Edema and peritubularlymphocytic infiltrateAcute vascular and cellularrejection:-Tubules :- extensively necrotic withluminal eosinophilic fluid or bloodInterstitium :- extensive hemorrhage&MNC infiltratesThe arteries show severe rejectiondamageLumen :-ObliteratedIntima :-Proliferated endothelium+lymphocytes
  • 145. Clinically :-Clinically :- manifested by progressive rise in serum creatinine level over 4-6 monthsmanifested by progressive rise in serum creatinine level over 4-6 monthsSevere chronic vascular rejection:-One glomerulus:-One glomerulus:- is atrophic ,othersis atrophic ,othersshow epithelial and mesangial prolifshow epithelial and mesangial prolif--Tubules at left bottom :-Tubules at left bottom :- are atrophicare atrophicInterstitium :-Interstitium :- Fibrotic with MNC,sFibrotic with MNC,sinfiltratesinfiltratesthe glomerulus:-the glomerulus:- endothelial swelling andendothelial swelling andcollapse of capillary loopcollapse of capillary loopTubules :-Tubules :- are atrophic (arroware atrophic (arrow((Small arteries :-Small arteries :- thick intima ,narrowthick intima ,narrowlumenslumens
  • 146. .. Methods of increasing graft survivalMethods of increasing graft survival1-Minimization of the1-Minimization of the HLAHLA disparity between the donor and recipient.disparity between the donor and recipient.2-Immunosuppressive therapy2-Immunosuppressive therapy (drugs as azathioprine, steroides, cyclo-(drugs as azathioprine, steroides, cyclo-sporine ,and antilymphocytes antibodies are used).These drugssporine ,and antilymphocytes antibodies are used).These drugsincrease susceptibility to opportunistic infections and cyclosporine isincrease susceptibility to opportunistic infections and cyclosporine isnephrotoxic.nephrotoxic.3-Previous blood transfusion is beneficial in allowing greater survival of3-Previous blood transfusion is beneficial in allowing greater survival oftransplanted kidney,especially in cadaver renal transplants.Unknown.transplanted kidney,especially in cadaver renal transplants.Unknown.
  • 147. Male genital systemMale genital systemPenisPenis :-:-A-Congenital anomaliesA-Congenital anomalies :-:-1-Hypospadias &Epispadias1-Hypospadias &Epispadias:- Malformed uretheral groove and uretheral canal with an:- Malformed uretheral groove and uretheral canal with anabnormal opening on ventral surface of the penisabnormal opening on ventral surface of the penis Hypospadias.Or on dorsal surfaceHypospadias.Or on dorsal surface Epispadias.Epispadias.ComplicationsComplications :”-:”-1-Associated with failure of normal descent of the testes and malformed U.T .1-Associated with failure of normal descent of the testes and malformed U.T .2-Associated with UT.infection2-Associated with UT.infection3-failure of ejaculation and erection3-failure of ejaculation and erectionsterilitysterility2-Phimosis:-2-Phimosis:-Too small prepuce to permit its normal retractionToo small prepuce to permit its normal retraction ..It may be congenital orIt may be congenital oracquired due to fibrosis .Failure of retracted prepuce to returnacquired due to fibrosis .Failure of retracted prepuce to return  marked constrictionmarked constrictionand swelling of the glansand swelling of the glans  paraphimosis.paraphimosis.Complication :-Complication :-1-Predisposes to infection1-Predisposes to infection  may be carcinomamay be carcinoma2-Extreme pain2-Extreme pain3-Potential uretheral consriction3-Potential uretheral consriction  Acute urinary retention .Acute urinary retention .
  • 148. 3-Inflammtion :-3-Inflammtion :- Of glans and prepuce.Of glans and prepuce.1-Specific infection:-Syphilis ,gonorrhea ,chancroid granuloma inguinale or genital1-Specific infection:-Syphilis ,gonorrhea ,chancroid granuloma inguinale or genitalherpes.herpes.2-Non specific :- Nonspecific infection of glans and prepuce2-Non specific :- Nonspecific infection of glans and prepuce BalanoposthitisBalanoposthitisEtiologyEtiology :- It usually occur by strept.,staphy.coliform bacilli and lessely by gonococci.It:- It usually occur by strept.,staphy.coliform bacilli and lessely by gonococci.Itoccurs in patients with phimosis or redundant prepuceoccurs in patients with phimosis or redundant prepuce infection of accumulatedinfection of accumulatedsmegmasmegmaB-TumorsB-Tumors1-Benign tumors :-1-Benign tumors :-i-Condyloma acuminatum :-i-Condyloma acuminatum :-Sexually transmitted disease caused by HPV(types 6 &11)Sexually transmitted disease caused by HPV(types 6 &11)in both sexesin both sexesGrossly :-Grossly :-The lesion is found on external genitalia or perineal areas.On the penis itThe lesion is found on external genitalia or perineal areas.On the penis itoccurs about coronal sulcus and inner surface of the prepuce.Either single or multipleoccurs about coronal sulcus and inner surface of the prepuce.Either single or multiple,sessile or pedunclated red papillary projections (several mm).,sessile or pedunclated red papillary projections (several mm).MicroscopicallyMicroscopically:-A branched villous papillary connective tissue stroma covered by:-A branched villous papillary connective tissue stroma covered byhyperplastic epithelium wih (hyperkeratosis,acanthosis ,koilocytosis) and intact B.M.hyperplastic epithelium wih (hyperkeratosis,acanthosis ,koilocytosis) and intact B.M.ii-Giant condyloma (Buschke-Lowenstein tr,Verrucous carcinoma ) :-ii-Giant condyloma (Buschke-Lowenstein tr,Verrucous carcinoma ) :- Is larger thanIs larger thancondyloma acuminatum.it occurs as solitary lesion that cover and destroy much of thecondyloma acuminatum.it occurs as solitary lesion that cover and destroy much of the
  • 149. It lies in intermediate position between condyloma and squamous cell carcinoma.It lies in intermediate position between condyloma and squamous cell carcinoma.MicroscopicallyMicroscopically :- It has exophytic and endophytic components .Exophytic one like:- It has exophytic and endophytic components .Exophytic one likecondyloma acuminatum with (koilocytosis) but the endophytic part has broad frontscondyloma acuminatum with (koilocytosis) but the endophytic part has broad frontscomposed of well differentiated squamous epithelium with no cellular atypia.composed of well differentiated squamous epithelium with no cellular atypia.2-Malignant tumors ;-2-Malignant tumors ;-A-Carcinoma in situ :-A-Carcinoma in situ :-A precancerous condition characterized by intraepithelialA precancerous condition characterized by intraepithelialneoplasia without invasion or metastasis.Three lesions in male genitalia having theneoplasia without invasion or metastasis.Three lesions in male genitalia having thehistologic features of carcinoma in situ.histologic features of carcinoma in situ.1-Bowen`s disease:-1-Bowen`s disease:- In genital regions of both sexes (>35Y).In males it involves shaftIn genital regions of both sexes (>35Y).In males it involves shaftof penis and scrotum.of penis and scrotum.GrosslyGrossly :- Solitary ,thickened grayish -white opaque area with shallow ulceration and:- Solitary ,thickened grayish -white opaque area with shallow ulceration andCrusting.Crusting.MicroscopicallyMicroscopically ;- Carcinoma in situ with many mitosis and some atypia.Bowen`s dise.;- Carcinoma in situ with many mitosis and some atypia.Bowen`s dise.Associated with visceral malignancy.Associated with visceral malignancy.2-Bowenoid papulosis.:-2-Bowenoid papulosis.:- It affects external genitalia of sexually active adults . ItIt affects external genitalia of sexually active adults . Itaffects younger patients and it is multiple ,pigmented (reddish brown)papular lesions.Itaffects younger patients and it is multiple ,pigmented (reddish brown)papular lesions.ItMay by verrucoid .HPV 16 may be the cause that leads to carcinoma in female genitalMay by verrucoid .HPV 16 may be the cause that leads to carcinoma in female genitaltract.tract.
  • 150. MicroscopicallyMicroscopically :- Like Bowen`s disease.No association with visceral malignancy.:- Like Bowen`s disease.No association with visceral malignancy.B-Carcinoma (epidermoid):-B-Carcinoma (epidermoid):-Its distribution throughout the world is different depending on circumcision ( it lowIts distribution throughout the world is different depending on circumcision ( it lowamong moslems and Jewish),where circumcision protect against accumulation ofamong moslems and Jewish),where circumcision protect against accumulation ofSmegma (harboring HPV 16&18).Commonest age 40-70 Y).Smegma (harboring HPV 16&18).Commonest age 40-70 Y).GrosslyGrossly :-It occurs on the glans or inner surface of the prepuce near coronal sulcus.1:-It occurs on the glans or inner surface of the prepuce near coronal sulcus.1ststEpithelial thickening ,graying and fissuring of the mucosal surface.Then leukoplakicEpithelial thickening ,graying and fissuring of the mucosal surface.Then leukoplakicpapulepapule  malignant ulcer.It may destroy the entire tip of the penis or large area of themalignant ulcer.It may destroy the entire tip of the penis or large area of theShaft.Another pattern is papillary growthShaft.Another pattern is papillary growth  cauliflower –like ,ulcerated ,fungatingcauliflower –like ,ulcerated ,fungatingmass.mass.MicroscopicallyMicroscopically :- As squamous cell carcinoma elswhere or spindle cell or adenoid:- As squamous cell carcinoma elswhere or spindle cell or adenoidpatterns.patterns.Clinical courseClinical course :-the lesion is asymptomatic till ulceration and secondary infection:-the lesion is asymptomatic till ulceration and secondary infectionoccur. Early stage show metastasis to inguinal and iliac L.N,s.Prognosis depends onoccur. Early stage show metastasis to inguinal and iliac L.N,s.Prognosis depends onstage of advancement of the tumor.stage of advancement of the tumor.Three years survival in tr not involve penile shaftThree years survival in tr not involve penile shaft 95-100%.It reaches 30-50% in tr95-100%.It reaches 30-50% in trinvolves the penile shaft .involves the penile shaft .
  • 151. Condyloma accuminatumBowen`s diseaseErythroplasia of quarate
  • 152. Spindle cell ca.Verrucous ca.Sq.C.C.
  • 153. Testis &Epididymis :-Testis &Epididymis :-A-Congenital anomalies :-A-Congenital anomalies :-1-Cryptorchidism1-Cryptorchidism :-:-DefinitionDefinition :-:- Incomplete descent of the testes into scrotal sac .It is found in 0.3-Incomplete descent of the testes into scrotal sac .It is found in 0.3-0.8% of adult males.0.8% of adult males.PathogenesisPathogenesis :- The testes arises within celeomic cavity ,they come from the caudalend:- The testes arises within celeomic cavity ,they come from the caudalendOf the urogenital ridge to lie within lower abdomen or at pelvic brimOf the urogenital ridge to lie within lower abdomen or at pelvic brim External desce-External desce-nt. The testes pass through inguinal canal to reside in scrotal sac.The tetes may bent. The testes pass through inguinal canal to reside in scrotal sac.The tetes may befoundfoundat any point in this pathway of descentat any point in this pathway of descentCauses :-Causes :-1-Idiopathic1-Idiopathic2-Mechanical :-due to short spermatic cord or narrow inguinal canal.2-Mechanical :-due to short spermatic cord or narrow inguinal canal.3-Genetic :- in associatin with Down`s syndrome.3-Genetic :- in associatin with Down`s syndrome.4-Hormonal :- Deficiency of LH-R hormone4-Hormonal :- Deficiency of LH-R hormoneGrosslyGrossly :-Usually unilateral ,25% bilateral.The testis is small in size and firm (fibrosis):-Usually unilateral ,25% bilateral.The testis is small in size and firm (fibrosis)MicroscopicallyMicroscopically :- The changes appears after 2 years of age in form of arrest of:- The changes appears after 2 years of age in form of arrest ofsperma-sperma-
  • 154. Complications :-Complications :-1-Exposure to trauma and crushing1-Exposure to trauma and crushing2-Concomitant inguinal hernia2-Concomitant inguinal hernia3-Sterility3-Sterility4-Increased risk of malignancy (10-40 folds)4-Increased risk of malignancy (10-40 folds)TreatmentTreatment :-Orchiopexy:-Orchiopexy2-Congenitl absence of one or both tetes2-Congenitl absence of one or both tetes..3-Synorchism:-3-Synorchism:-Fusion of both testes.Fusion of both testes.4-Bifid testes4-Bifid testes ..5-Insignificant cysts within tesis5-Insignificant cysts within tesis..B-Regressive changes (atrophy)B-Regressive changes (atrophy)Causes:Causes:--1-Progressive atherosclerosis of blood supply in old age. 2-End stage of orchitis of1-Progressive atherosclerosis of blood supply in old age. 2-End stage of orchitis ofdifferent etiology .3-Cryptorchidism 4-Hypopitutarism 5-Generalized malnutritiondifferent etiology .3-Cryptorchidism 4-Hypopitutarism 5-Generalized malnutrition6-Obstruction of outflow of semen 7-Irradiation 8-prolonged taking of sex hormones6-Obstruction of outflow of semen 7-Irradiation 8-prolonged taking of sex hormones(cancer prostate) 9-Exhaustion atrophy ( high level of FSH)(cancer prostate) 9-Exhaustion atrophy ( high level of FSH)C-Inflammation :-C-Inflammation :-1-Non-specific epididymitis &orchitis1-Non-specific epididymitis &orchitis
  • 155. Etiology :-Etiology :--Epididymo-orchitis can occur secondary to cystitis ,urethritis or prostatitis .Infection-Epididymo-orchitis can occur secondary to cystitis ,urethritis or prostatitis .Infectionreach them through vas deferens or lymphatics of spermatic cord.reach them through vas deferens or lymphatics of spermatic cord.-epididymitis in childhood is associated with genitourinary abnormality(G-ve rods)-epididymitis in childhood is associated with genitourinary abnormality(G-ve rods)-In sexually active men (<35Y) ,infection occur by Chlamydia trachomatis or Neisseria-In sexually active men (<35Y) ,infection occur by Chlamydia trachomatis or NeisseriaGonorrhea .In male >35 E.coli and pseudomonas are blamedGonorrhea .In male >35 E.coli and pseudomonas are blamedMicroscopic :- Tissue infiltration by PNL,s,macrophages and lymphocytes ,Microscopic :- Tissue infiltration by PNL,s,macrophages and lymphocytes , supp-supp-urative inflammation and abscess formationurative inflammation and abscess formation followed by fibrous scarring and sterilityfollowed by fibrous scarring and sterilityGranulomatous (auto-immune) orchitisGranulomatous (auto-immune) orchitis :- Nontuberculous granulomatous ,unilateral:- Nontuberculous granulomatous ,unilateralenlargement ,commonly occur in middle aged men.Usually presented by moderatelyenlargement ,commonly occur in middle aged men.Usually presented by moderatelytender testicular mass and fevertender testicular mass and feverCauseCause :- Unknown:- UnknownMicroscopicallyMicroscopically:- Granuloma formation in tubules or interstitial connective tissue co:- Granuloma formation in tubules or interstitial connective tissue composed of lymphocytes ,plasma cells ,PNL,s and surrounded by fibroblasts.mposed of lymphocytes ,plasma cells ,PNL,s and surrounded by fibroblasts.2-Specific inflammation:-Caused by gonorrhea,mumps,syphilis ,T.B. and others2-Specific inflammation:-Caused by gonorrhea,mumps,syphilis ,T.B. and others1-Gonorrhea:-1-Gonorrhea:-Extension of infection from posterior uretheraExtension of infection from posterior urethera  prostateprostateSeminalSeminalvesiclevesicleEpididymsEpididymsEpididymitis and epididymal abscess.In neglected casesEpididymitis and epididymal abscess.In neglected cases extension of infection to testesextension of infection to testes Suppurative orchitis.Suppurative orchitis.
  • 156. 2-Mumps:2-Mumps:- 20-30% of cases occurs in childrens <10 Ys.20% of cases develops- 20-30% of cases occurs in childrens <10 Ys.20% of cases developsorchitisorchitisAcute interstitial orchitis develops one week following onset of parotid swelling.Acute interstitial orchitis develops one week following onset of parotid swelling.GrosslyGrossly :- Unilateral,patchy orchitis in 70% of cases:- Unilateral,patchy orchitis in 70% of casesMicroscopicallyMicroscopically :-Intense interstitial edema and mononuclear iniltration (lymphocytes:-Intense interstitial edema and mononuclear iniltration (lymphocytes,plasma cells and macrophages ) .PNL,s usually less prominent,become more in intense,plasma cells and macrophages ) .PNL,s usually less prominent,become more in intenseinflammationinflammation tubulr lumina filled by suppuration.tubulr lumina filled by suppuration.3-T.B3-T.B. :-It begins in epididymis and spread to testis.It reflects T.B.elsewhere in the. :-It begins in epididymis and spread to testis.It reflects T.B.elsewhere in thebody(lungs or kidney).T.B. epididymitis occurs due to blood spread or secondarybody(lungs or kidney).T.B. epididymitis occurs due to blood spread or secondaryinvolvement from T.B. prostatitis or seminal vesiculitis.involvement from T.B. prostatitis or seminal vesiculitis.PathologicallyPathologically :- Classic T.B. granuloma with caseation:- Classic T.B. granuloma with caseation posterior sinus .It mayposterior sinus .It mayextends to the testisextends to the testis  Healing by scarring and calcification.Healing by scarring and calcification.3-Syphilis3-Syphilis :- The testis and epididymis are affected in both acquired and congenital:- The testis and epididymis are affected in both acquired and congenitalsyphilis .The testis is affected firstly but with or without epididymitissyphilis .The testis is affected firstly but with or without epididymitischancre.chancre.PathologyPathology :- It may be gumma or diffuse syphilitic reaction (mainly plasma cells):- It may be gumma or diffuse syphilitic reaction (mainly plasma cells)diffuse scarringdiffuse scarring  testicular atrophy and sterility.testicular atrophy and sterility.4-Others infections4-Others infections :- As brucella ,typhoid ,leprosy,meningococcal and riketsial:- As brucella ,typhoid ,leprosy,meningococcal and riketsialinfections.infections.
  • 157. Vascular disturbancesVascular disturbancesTorsion :-Torsion :- Twisted spermatic cordTwisted spermatic cord Obstruct venous drainage and cut arterialObstruct venous drainage and cut arterialSupply to testesSupply to testes InfarctionInfarctionEtiology :-Etiology :-1-Violent movement or physical trauma1-Violent movement or physical trauma2-Or predisposed by :-2-Or predisposed by :-a-Incomplete descent of the testisa-Incomplete descent of the testisb-Absence of scrotal ligamentb-Absence of scrotal ligamentc-Small atrophic testisc-Small atrophic testis  freely mobile within tunica.freely mobile within tunica.d-Abnormal attachment of the testis to the epididymis or other abnormalitiesd-Abnormal attachment of the testis to the epididymis or other abnormalitiesPathologyPathology:-The morphological changes depends on the duration and severity of the:-The morphological changes depends on the duration and severity of theprocess . In extreme cases hemorrhagic infarction of the testis occursprocess . In extreme cases hemorrhagic infarction of the testis occursGrosslyGrossly :- Lately the testis is markedly enlarged and is converted into sac of soft:- Lately the testis is markedly enlarged and is converted into sac of softnecrotic and hemorrhagic tissue.necrotic and hemorrhagic tissue.MicroscopicallyMicroscopically :-It ranged from intense congestion to wide spread extravasation of:-It ranged from intense congestion to wide spread extravasation ofblood into interstitial tissue of the testis with variable PNL,s infiltration .blood into interstitial tissue of the testis with variable PNL,s infiltration .
  • 158. Cryptorchidism SyphiliticorchitisTorsionGranulomatousOrchitis
  • 159. Testicular tumorsTesticular tumorsOrigin of testicular tumorsOrigin of testicular tumors :-:-1-Germ cells tumors (95%):-1-Germ cells tumors (95%):-Highly aggressive cancers with rapid and wide dissmin-Highly aggressive cancers with rapid and wide dissmin-ation .ation .2-Non germinal tumors (sex cord stromal tumors) 5%:-2-Non germinal tumors (sex cord stromal tumors) 5%:-Generally benignGenerally benign prod-prod-ucing hormonesucing hormonesendocine syndromes.endocine syndromes.Mostofi or WHO classificationMostofi or WHO classification :-:-
  • 160. 1-Germ cell tumors (95%):-1-Germ cell tumors (95%):-Tumors of one histologic patternTumors of one histologic pattern:-:-{Seminoma ,spermatocytic seminoma ,embryonal carcinoma ,yolk sac tumor(infantile{Seminoma ,spermatocytic seminoma ,embryonal carcinoma ,yolk sac tumor(infantileE.C), polyembryoma ,choriocarcinoma ,teratoma (mature ,immature ,teratoma withE.C), polyembryoma ,choriocarcinoma ,teratoma (mature ,immature ,teratoma withmalignant trnasformation )}malignant trnasformation )}Tumors showing more than one histologic pattern:-Tumors showing more than one histologic pattern:--Embryonal carcinoma +teratoma (teratocarcinoma-Embryonal carcinoma +teratoma (teratocarcinoma-Choriocarcinoma and any other types-Choriocarcinoma and any other types-Other combinations-Other combinations2-Sex cord stromal tumors (5%):-2-Sex cord stromal tumors (5%):-Well differentiated forms :- (Well differentiated forms :- (Leydig`s cell tr ,Sertoli cell tr ,granulosa cell tr)Leydig`s cell tr ,Sertoli cell tr ,granulosa cell tr)Mixed formsMixed formsIncompleely differentiated forms.Incompleely differentiated forms.Germ cell tumorsGerm cell tumorsIncidence :-Incidence :- 2/100.000 males2/100.000 malesAge :-Age :- 15-35 Ys15-35 YsPathogenesis:-Pathogenesis:-Unclear ,important predisposing factorsUnclear ,important predisposing factors
  • 161. 1-Cryptorchidism ;-in 10% of testicularneoplasm.Contralateral undescended tetis oreven orchiopexed testis are also at risk ofmalignancy.2-Genetic factors :-Lower incidence inAfrican blacks3-Testicular dysgenesis:- Occurs in 25% ofdysgenetic gonads.4-Other factors :- Environmental,endocrine abnormalities  remainuncertainSEMINOMA:- It accounts for 30% of all testicular tumors.Its peak in 4thdecade.Variants;-1-Classic seminoma (85%(2-Anaplastic seminoma (5-10%(3-Spermatocytic seminoma (4-6%(Morphology:-Grossly :- A homogenous ,lobulated ,gray white mass without hemorrhage ornecrosisWith intact tunical albuginea .Sometimes entire testis is repalced,it extends to epidid.Microscopically:- Large polyhedral”seminoma cells” with abundant clearcytoplasm ,large nuclei and prominent nucleoli .A fibrous stroma of variable density
  • 162. Syncytial cells (+vge HCG) ,infequent mitosis .and elevated serum level of HCG.Syncytial cells (+vge HCG) ,infequent mitosis .and elevated serum level of HCG.Anaplastic seminomaAnaplastic seminoma :-Differes from classic seminoma by greater nuclear atypia:-Differes from classic seminoma by greater nuclear atypiaMany giant cells and high mitotic rate > 3/HPFMany giant cells and high mitotic rate > 3/HPFSpermatocytic seminomaSpermatocytic seminoma :-Occurs in patients > 65 years ,slowly growing with no:-Occurs in patients > 65 years ,slowly growing with notendency to metastasize .tendency to metastasize .Gross pictureGross picture :- Larger than those of classic seminoma with pale gray,soft friable cut:- Larger than those of classic seminoma with pale gray,soft friable cutsection .section .MicroscopicMicroscopic :-It composed of mixed population of cells including :-:-It composed of mixed population of cells including :-1-Medium sized cells1-Medium sized cells ,with rounded nuclei and eosinophilic cytoplasm.,with rounded nuclei and eosinophilic cytoplasm.2-Smaller cells2-Smaller cells with small rim of eosinophilic cytoplasm like secondary spermatocyteswith small rim of eosinophilic cytoplasm like secondary spermatocytes(spermatocytic designation) .(spermatocytic designation) .3-Uninucleated or multinucleated giant cells3-Uninucleated or multinucleated giant cells..Unlike classic seminoma, no lymphocytic infiltration ,mitoses is commonUnlike classic seminoma, no lymphocytic infiltration ,mitoses is commonEmbryonal carcinomaEmbryonal carcinomaAge of onset :-Age of onset :-20-30 Ys.More aggressive than seminoma.20-30 Ys.More aggressive than seminoma.GrosslyGrossly :- Poorly demarcated small sized testicular masses punctated by hemorrhagic:- Poorly demarcated small sized testicular masses punctated by hemorrhagicand necrotic foci.It may extends to tunica albuginea ,epididymis and spermatic cord.and necrotic foci.It may extends to tunica albuginea ,epididymis and spermatic cord.Microscopically :-Primitive epithelial cells with indistinct cell borders (angry lookingMicroscopically :-Primitive epithelial cells with indistinct cell borders (angry looking
  • 163. Mitoses and giant cells are common.Syncytial cells containing HCG±cells containingMitoses and giant cells are common.Syncytial cells containing HCG±cells containingAFP(indicate germ cell tumors)AFP(indicate germ cell tumors)Seminoma Embryonal carcinoma30% of germ cell tumorsAge (5-65Y)Slowly growingLarge sized tumor massNo hemorrhage or necrosisTunical is intactDifferentiated seminomatous cellsInfequent mitosisLess aggressiveIHC +Ve HCG-Ve keratin3% of germ cell tumorsAge 20-30Rapid growthSmall tumor massesPunctated by hemorrhagic &necrotic fociTunica involvedPrimitive cells with angry looking nucleiProminent nucleoli Frequent mitosisAggressive (lethal)IHC :- +ve HCG & AFP+Ve keratinYolk sac tumors (infantile E.C. &endodermal sinus tr):--most common testicular trin infants and childrens.In adults it is frequently found in combination with E.C.Grossly :- Infiltartive ,homogenous ,yellow white mucinous lesion.Microscopically :- Sheets & cords or paillary structures of primitive neoplastic cellswith vacuolated cytoplasm .Sometimes line irregular cystic spaces with centralcapillar ,similar to primitive glomeruli(endodermal sinuses)(Schiller –Duval bodies(I.H.C :- +ve AFP, keratin and alpha1-antitrypsin.
  • 164. PolyembryomaPolyembryoma:-:-Extremely rare tumor in its pure form.it form a component of E.C or teratomaExtremely rare tumor in its pure form.it form a component of E.C or teratomaCharacterized by presence ofCharacterized by presence of Embryoid bodiesEmbryoid bodies :-:-1-Discs :- like embryonic discs ,made up of undifferentiated large epithelial cells1-Discs :- like embryonic discs ,made up of undifferentiated large epithelial cells2-The cavity :- represents amniotic space is lined by flat epithelial cells .These2-The cavity :- represents amniotic space is lined by flat epithelial cells .TheseEmbryoid structures are surrounded by loose mesenchyme in which trophoblasticEmbryoid structures are surrounded by loose mesenchyme in which trophoblasticelements may be present.elements may be present.ChoriocarcinomaChoriocarcinoma :-1% of germ cell tumors in ages between 20-30 Ys:-1% of germ cell tumors in ages between 20-30 YsIn its pure form it is rare testicular tumor .It is found as foci in mixed tumorsIn its pure form it is rare testicular tumor .It is found as foci in mixed tumorsThis highly malignant tumor can also found in placental site,ovary,rests of totipotentThis highly malignant tumor can also found in placental site,ovary,rests of totipotentcells in mediastinum ,or abdomen.cells in mediastinum ,or abdomen.GrosslyGrossly :- Pure choriocarcinoma is usually:- Pure choriocarcinoma is usually small sized testicular nodulesmall sized testicular nodule causes nocauses notesticular enlargement.Its size ranged from bulky hemorrhagic mass with tiny pits oftesticular enlargement.Its size ranged from bulky hemorrhagic mass with tiny pits ofgray tumor to small fibrotic mass.gray tumor to small fibrotic mass.MicroscopicallyMicroscopically :- The tumor composed of two cells :-:- The tumor composed of two cells :-1-Syncytiotrophoblastic cells1-Syncytiotrophoblastic cells :-Giant cells with irregular or lobulated hyperchromatic:-Giant cells with irregular or lobulated hyperchromaticnuclei and abundant eosinophilic vacuolated cytoplasm (+ve HCG)nuclei and abundant eosinophilic vacuolated cytoplasm (+ve HCG)2-Cytotrophoblasts2-Cytotrophoblasts:-More regular polygonal cells with distinct cell borders and clear:-More regular polygonal cells with distinct cell borders and clear
  • 165. Cytoplasm forming group cords or masses,with single uniform nuclei .No well devel-Cytoplasm forming group cords or masses,with single uniform nuclei .No well devel-oped chorionic villi found in choriocarcinoma .Presence of only syncytiotrophoblastsoped chorionic villi found in choriocarcinoma .Presence of only syncytiotrophoblastsasasevidenced by hCG,is sufficient for diagnosis of choriocarcinoma .These cells areevidenced by hCG,is sufficient for diagnosis of choriocarcinoma .These cells arefoundfoundscattered among large hemorrhagic ± necrotic areas.scattered among large hemorrhagic ± necrotic areas.TeratomaTeratoma :-:-A group of neoplasms exhibiting differentiation along endodermal,mesodermal andA group of neoplasms exhibiting differentiation along endodermal,mesodermal andectodermal lines.They may occur at any age.ectodermal lines.They may occur at any age.VariantsVariants :-:-1-Mature teratoma1-Mature teratoma :-Composed of haphazard arranged differentiated:-Composed of haphazard arranged differentiated mesodermalmesodermal (Ms(MsCartilages &adipose),Cartilages &adipose),ectodermalectodermal (skin &neural tissues) and(skin &neural tissues) and endodermalendodermal (gut&respira-(gut&respira-Tory)elements .More common in infants and childrens.Tory)elements .More common in infants and childrens.2-Immature teratoma2-Immature teratoma :- Elements of the three layers are found in incomplete stages of:- Elements of the three layers are found in incomplete stages ofDifferentiation (malignant).Cytologic features of malignancy indistinct.Differentiation (malignant).Cytologic features of malignancy indistinct.3-Teratoma with malignant transformation :-3-Teratoma with malignant transformation :- Presence of carcinoma (SCC or adenocar-Presence of carcinoma (SCC or adenocar-cinoma),developed within mature teratoma .2&3 are found in adults.cinoma),developed within mature teratoma .2&3 are found in adults.Mixed tumorsMixed tumors :-60% of germ cell neoplasm.With variable histologic patterns .:-60% of germ cell neoplasm.With variable histologic patterns .
  • 166. Classic seminoma Anaplastic seminomaSpermatocytic seminoma
  • 167. Embryonic carcinomaYolk sac tumor
  • 168. Mature teratomaMature teratomaimmature teratomaTeratoma with malignantTransformation
  • 169. Choriocarcinoma
  • 170. Clinical features of germ cell neoplasmsClinical features of germ cell neoplasms:-:-1-Most cases presents with1-Most cases presents with painless enlarged testispainless enlarged testis2-Lymphatic metastases :- Common in retroperitoneal2-Lymphatic metastases :- Common in retroperitoneal para-aortic nodespara-aortic nodesmediastinalmediastinalandand supraclavicular nodes.supraclavicular nodes.BloodBlood spread commonly occur in lungs,followed by liver,spread commonly occur in lungs,followed by liver,brain and bones.Metastatic tr may be identical to the primary or contain other germ cellbrain and bones.Metastatic tr may be identical to the primary or contain other germ cellelements {teratomatous metastases in patient with E.C.(forward differentiation )}elements {teratomatous metastases in patient with E.C.(forward differentiation )}3-The biologic behavior of3-The biologic behavior of non-seminomatous trs is more aggressivenon-seminomatous trs is more aggressive than that ofthan that ofsemin-semin-omatous .70% of seminomas present with clinical stage (I).60% of non -seminomatousomatous .70% of seminomas present with clinical stage (I).60% of non -seminomatousPresents with advanced stages (II or III).Small sized choriocarcinomaPresents with advanced stages (II or III).Small sized choriocarcinoma  extensiveextensivemetastasismetastasis4-Clinical staging :- is evaluated by physical examin.X-ray findings of retroperiton and4-Clinical staging :- is evaluated by physical examin.X-ray findings of retroperiton andchest .as well as tumor markerschest .as well as tumor markersClinical staging include :-Clinical staging include :-Stage IStage I:- Tr confined to testis:- Tr confined to testisStage IIStage II:- Metastases limited to retroperitoneal nodes below diaphragm:- Metastases limited to retroperitoneal nodes below diaphragmStage IIIStage III:-Metastases outside retroperitoneal nodes or above diaphragm:-Metastases outside retroperitoneal nodes or above diaphragmAlpha-fetoprotein and hCG are of value in :-Alpha-fetoprotein and hCG are of value in :-
  • 171. TreatmentTreatment :-radiation and chemotherapy according to histologic type and stage:-radiation and chemotherapy according to histologic type and stage.Chemotherapy dramatically improve the prognosis of patients with NSGCT. Semin-.Chemotherapy dramatically improve the prognosis of patients with NSGCT. Semin-oma is dramatically radisensitive .oma is dramatically radisensitive .Tumors of sex- cord –gonadal stroma ;-Tumors of sex- cord –gonadal stroma ;-ClassificationClassification :- according to differentaition into Leydig or Sertoli cells:- according to differentaition into Leydig or Sertoli cellsLeydig (interstitial) cell tumors :-Leydig (interstitial) cell tumors :-Relatively uncommon (2%) of all testicular neoplasms.Between ages 20-60Ys,or atRelatively uncommon (2%) of all testicular neoplasms.Between ages 20-60Ys,or atanyanyage.May produce hormones as androgen,estrogen and corticosteroidsage.May produce hormones as androgen,estrogen and corticosteroidsClinicallyClinically:-presented by testicular mass or produce hormonal abnormalities (gynecom.:-presented by testicular mass or produce hormonal abnormalities (gynecom.or prepubertal males)or prepubertal males)GrosslyGrossly :-Size ranged from <1-10 cm .Bulky masses with yellow -brown color .:-Size ranged from <1-10 cm .Bulky masses with yellow -brown color .MicroscopicallyMicroscopically :- Polygonal cells with abundant granular eosinophilic cytoplasm and:- Polygonal cells with abundant granular eosinophilic cytoplasm andindistinct cell borders.Lipochrome pigment ,lipid droplets and eosinophilic Reink cryst-indistinct cell borders.Lipochrome pigment ,lipid droplets and eosinophilic Reink cryst-Alloids.10% turn malignant and metastasize.Alloids.10% turn malignant and metastasize.Sertoli cell tumors (gonadoblastoma)Sertoli cell tumors (gonadoblastoma) :-:-Uncommon neoplasm .Composed of Sertoli cells or admixed with garnulosa cells .mayUncommon neoplasm .Composed of Sertoli cells or admixed with garnulosa cells .mayproduce androgen or estrogensproduce androgen or estrogensfeminization or gynecomastia.feminization or gynecomastia.
  • 172. MicroscopicallyMicroscopically :- Tall columnar cells forming cords similar to seminiferous tubules:- Tall columnar cells forming cords similar to seminiferous tubules.Mostly benign .10% invades or metastsize..Mostly benign .10% invades or metastsize.Other testicular tumorsOther testicular tumors :-:-Testicular lymphoma :-Testicular lymphoma :-5% of all testicular neoplasms ,in patients > 60Y.Most are5% of all testicular neoplasms ,in patients > 60Y.Most arediffuse large cell (high grade NHL).Disseminate widelydiffuse large cell (high grade NHL).Disseminate widely  poor prognosis.D.D.poor prognosis.D.D.Spermatocytic seminomaSpermatocytic seminomaAdenomatoid tumors:-Adenomatoid tumors:-Benign slowly growing nodules arising in epididymis (believed to be mesothelialBenign slowly growing nodules arising in epididymis (believed to be mesothelialelement).Composed of abundant fibrous tissue stroma and benign epithelial cells liningelement).Composed of abundant fibrous tissue stroma and benign epithelial cells liningirregular cystic channels or forming tubules and cords.irregular cystic channels or forming tubules and cords.
  • 173. Leydig `s cell hyperplasiaLeydig `s cell tumorSertoli cell hyperplasia Sertoli cell tumor
  • 174. Sertoli cell tumorSertoli cell tumorAdenomatoid tumor Adenomatoid tumor
  • 175. Juvenile granulosacell tumorGonadoblastoma
  • 176. Miscellaneous lesions of tunica vaginalis and spermatic cordMiscellaneous lesions of tunica vaginalis and spermatic cord..1-Hydrocele1-Hydrocele :-:-DefinitionDefinition:-:-Accumulation of serous fluid within tunia vaginalis.Accumulation of serous fluid within tunia vaginalis.CausesCauses :- 1-incomplete closure of tunica vaginalis:- 1-incomplete closure of tunica vaginalis2-As a part of generalized edema2-As a part of generalized edemaComplicationComplication:- Secondary infection:- Secondary infection pyocelepyocele2-Hematocele:-2-Hematocele:-DefinitionDefinition :-:- Accumulation of blood in tunica vaginalisAccumulation of blood in tunica vaginalisCausesCauses:-1- Secondary to trauma ,torsion and hemorrhage:-1- Secondary to trauma ,torsion and hemorrhage2-Generalized bleeding diathesis2-Generalized bleeding diathesis3-Invasion of tunica by neoplasm3-Invasion of tunica by neoplasm3-Chylocele :3-Chylocele :--DefinitionDefinition :- Accumulation of lymphatic fluid within tunica.:- Accumulation of lymphatic fluid within tunica.CausesCauses:-Lymphatic obstruction secondary to elephantiasis.:-Lymphatic obstruction secondary to elephantiasis.4-Spermatocele4-Spermatocele :-:-DefinitionDefinition :-Accumulation of semen in spermatic cord.:-Accumulation of semen in spermatic cord.CauseCause :- Generally within dilated duct in the head of epididymis.:- Generally within dilated duct in the head of epididymis.5-Varicocele5-Varicocele :-Dilated tortuous veins in spermatic cord:-Dilated tortuous veins in spermatic cord

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