泌尿系統(tǒng)疾病課件：泌尿系統(tǒng)病理學(xué)

1、Diseases of urinary system and male genital systemNephrologyUrologyOutlineGlomerulonephritis(GN)Tubulointerstitial nephritisUrinary outflow obstructionTumors of urinary systemProstate Disease, Testis and Penis TumorThe incidence rate of chronic kidney disease (CKD) is 9.4% to 11.8% in China, there i

2、s one patient for every ten peopleThe occurrence is occult, 20% of the patients at diagnosis are on late stageThe second Thursday of March is declared as the World Kidney Day (WKD). March 13, 2014 is the 9th WKD. The topic for WKD 2014 is “CKD in older people”CT scan12Gross viewFunctions of the kidn

3、eyExcretion metabolic waste productsRegulating fluid and electrolyte balanceInfluencing acid-base balanceSecreting hormones (renin, erythropoietin, et.al)Normal nephronFiltering membraneFiltering membraneA thin layer of fenestrated endothelial( Fenestra, 70 to 100 nm in diameter)The glomerular basem

4、ent membrane(GBM)The foot processes of visceral epithelial cell (slit diaphragm)Function of filtering membraneHigh permeability to water and small soluteGlomurular barrier function Size-dependent barrier function Charge-dependent barrier functionOutlineGlomerulonephritis(GN)Tubulointerstitial nephri

5、tisUrinary outflow obstructionTumors of urinary systemProstate Disease, Testis and Penis TumorEtiology of glomerular diseasesPrimary(majority): disease process appears to start within the glomerulusSecondary: disease process is secondary to systemic disease (SLE, vascular diseases, diabetes mellitus

6、, amyloidosis)Hereditary: congenital diseases ( Alport syndrome, Fabrys disease)Primary glomerulonephritiskidney is the only or predominant organ involvedEtiology and Pathogenesis Immune mechanisms underlie the majority of primary GN. The most common mechanism is antibody-medicated injury. Two basic

7、 forms of antibody-associated injury: Injury resulting from deposition of soluble circulating antigen-antibody complexes in the glomeruliInjury by antibodies reacting in situ within the glomeruliCirculating Immune Complex NephritisCaused by the trapping of circulating antigen-antibody complexes with

8、in glomeruliThe antibodies have no immunologic specificity for glomerular constituentsType hypersensitivity reactionThe antigens may be of endogenous or exogenous originsCirculating Immune Complex NephritisThe electron-dense deposits lie in the mesangium, between the endothelial cells and the GBM (s

9、ubendothelial deposits) or between the GBM and the podocytes (subepithelial deposits)The deposits may be degraded by monocytes and mesangial cellsIn Situ Immune Complex DepositionAntibodies react directly with intrinsic tissue antigen, or antigens “planted” in the glomeruli from the circulation.Auto

10、antibodies against components of the GBM are the cause of anti-GBMmediated disease, often associated with severe injury. The pattern of deposition is linear.Antibodies may also be formed against antigens that are planted in the GBM. The resultant in situ immune complexes may show a granular pattern

11、of deposition.Granular patternImmunofluorescence(IF) Linear patternImmunofluorescenceMechanism of glomerular injuryCirculating immune complex nephritisimmune complex nephritis in situCell-mediated immunity(sensitized T cells)Other mechanismsCell-Mediated Immunity in GNSensitized nephritogenic T cell

12、s, as a reflection of cell-mediated immune reaction, cause some forms of glomerular injury and are involved in the progression of many glomerulonephrities.Summary of pathogenesisAntibody-mediated immune injury is an important mechanism of glomerular damage, mainly via complement- and leukocyte-media

13、ted pathways. Antibodies may also be directly cytotoxic to cells in the glomerulus.The most common forms of antibody-mediated GN are caused by the deposition of circulating immune complexesSteps in diagnoses of glomerular lesionsClinical presentationRenal biopsy Light microscopic examination (HE，PAS

14、，MASSON，PASM stain) Immunofluorescence examination Electron microscopic examination Clinical manifestationsHematuria (red blood cells in urine)Proteinuria (protein lost in urine,3.5g/d) Oliguria (urine flow 400 ml/24 hours)Anuria ( urine flow 3.5g/d), hypoalbuminemia, severe edema, hyperlipidemia an

15、d lipiduriaChronic nephritic syndrome: slowly developing renal failure accompanied by proteinuria, hematuria ,hypertension and uremiaRenal failureTwo types ( acute and chronic renal failure)Two main syndromes of partial renal failure (nephritic syndrome and nephrotic syndrome)Chronic renal failure i

16、s irreversible, as it is caused by permanent destruction of nephronsAcute renal failure sometimes recovers when the damaging stimulus resolvesfocal 50%)The crescents lining Bowmans capsule are composed of a mixture of epithelial cells and macrophages proliferatingCresentic glomerulonephritisCresenti

17、c glomerulonephritisCrescentic glomerulonephritisCrescent Basement membrane destruction Cresentic glomerulonephritisAnti-GBM diseaseDamage to the pulmonary alveolar capillary basement membrane, producing the clinical features of pulmonary hemorrhages associated with renal failureAnti-GBM antibodies

18、in the serum (plasmapheresis is useful) Goodpasture syndromeGoodpasture syndromeClinical featuresRPGN is characterized by rapid and progressive loss of renal function associated with severe oliguria even anuriaPrognosis is poor Primary glomerulonephritisAcute diffuse proliferative glomerulonephritis

19、Crescentic glomerulonephritisMembranous glomerulonephritisMinimal change glomerulopathyFocal segmental glomerulosclerosis(FSGS)Membranoproliferative glomerulonephritisIgA nephropathyChronic glomerulonephritisMembranous glomerulopathyMajor cause of nephrotic syndrome in adults Characterized by electr

20、on-dense, immunoglobulin-containing deposits along the epithelial side of the BM. Diffuse thickening of the capillary wallMembranous glomerulopathyMembranous glomerulopathyMembranous glomerulopathyIgG Immunofluorescence Clinical ManifestationsThe condition usually starts as insidious onset of nephro

21、tic syndrome or sub-nephrotic-range proteinuria. Up to 40% of cases progress to renal insufficiency over an unpredictable time span of 2 to 20 years.Primary glomerulonephritisAcute diffuse proliferative glomerulonephritisCrescentic glomerulonephritisMembranous glomerulonephritisMinimal change glomer

22、ulopathyFocal segmental glomerulosclerosis(FSGS)Membranoproliferative glomerulonephritisIgA nephropathyChronic glomerulonephritisMajor cause of nephrotic syndrome in children Characterized by normal glomeruli on light microscopy but uniform and diffuse effacement of the foot processes of visceral ep

23、ithelial cells on EMImmunofluorescence shows no immune depositsMinimal change diseaseMinimal change diseaseClinical manifestationsProteinuria is usually selective The most characteristic feature of this condition is the dramatic response to corticosteroid therapyThe long-term prognosis is excellent

24、for children and adultsPrimary glomerulonephritisAcute diffuse proliferative glomerulonephritisCrescentic glomerulonephritisMembranous glomerulonephritisMinimal change glomerulopathyFocal segmental glomerulosclerosis(FSGS)Membranoproliferative glomerulonephritisIgA nephropathyChronic glomerulonephri

25、tisFocal segmental glomerulosclerosis(FSGS)Characterized by sclerosis of segment of the glomeruli, and only affected focal glomeruli (femalesPuberty to middle age: femalesmalesPost-40 years: malesfemalesThree age peaks Gender differencesRoutes of bacterial infectionAscending infection from the lower

26、 urinary tract(most common): enteric gram-negative rods ( Escherichia coli)Bloodstream spread in bacteremic or septicemic states: staphylococciRoute of infectionHematogenous infection(descending infection)Ascending infectionGross featureSuppurative inflammationCortical abscessesMedullary abscessesAc

27、ute pyelonephritisAcute pyelonephritisHistological feature Infiltration of tubules by neutrophilsAbscess formationInterstitial edemaAcute pyelonephritisClinical feature Sudden onsetPain in the backEvidence of systemic infection( chills, fever, malaise)Indications of bladder and urethral irritation(

28、dysuria, urgency, frequency of micturition)Urinary findingsPyuria ( white blood cells and pus cells in urine)Bacteriuria (bacteria in urine)Complications and sequelaeResolutionHealing with scarringChronicityPyonephrosisRenal papillary necrosisPerinephric abscessDeath in uremiaPapillary necrosisPyelo

29、nephritis Acute pyelonephritisChronic pyelonephritisChronic pyelonephritisChronic pyelonephritis is defined as a morphologic entity in which predominantly interstitial inflammation and scarring of the renal parenchyma is associated with grossly visible scarring and deformity of the pelvicalyceal sys

30、temAn cause of chronic renal failureChronic pyelonephritisChronic obstructive pyelonephritisChronic reflux-associated pyelonephritis (vesicoureteral reflux)Gross featureKidneys are not equally damagedIrregular areas of scarringMarked calyceal deformitiesGross featurenot equally damagedIrregular area

31、s of scarringMarked calyceal deformitiesChronic pyelonephritisChronic pyelonephritisnot equally damagedIrregular areas of scarringMarked calyceal deformitiesHistological featureChronic inflammatory cells infiltration, occasionally neutrophilsUneven interstitial fibrosisDilation or contraction of tub

32、ulesGlomeruli show periglomerular fibrosisChronic pyelonephritis“Thyroidization” Dilation of tubulesClinical featuresGradual onset of renal insufficiencyTubular dysfunction (polyuria, nocturia)Urinary tract infectionUremia Diagnosis Intravenous pyelogramUrine culture急性腎小管壞死(Acute tubular necrosis)急性

33、腎小管壞死過(guò)敏性間質(zhì)性腎炎過(guò)敏性間質(zhì)性腎炎OutlineGlomerulonephritis(GN)Tubulointerstitial nephritisUrinary outflow obstructionTumors of urinary systemProstate Disease, Testis and Penis TumorUrinary outflow obstructionRenal stonesHydronephrosis Renal stonesUrolithiasis is calculus formation at any level in the urinary co

34、llecting system most common sites: pelvicalyceal system and bladderMain predisposing factors Increased concentration of solute in urine Reduced solubility of solute in urine Etiology Acquired Inherited Renal calculusRenal staghorn calculusSFluoroscopy Ureteral calculusClinical featureWithout symptom

35、sRenal colic with nausea , vomiting and hematuriaDual ache in the loinsRecurrent urinary tract infectionUrinary outflow obstructionRenal stonesHydronephrosis Hydronephrosis Hydronephrosis refers to dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstr

36、uction to the outflow of urine Renal pelvisPelviureteric junctionUreterBladderUrethraHydronephrosisObstruction of the levelsMorphologyUnilateral :caused by obstruction at the level of the ureter , pelviureteric junction or renal pelvis Bilateral: caused by obstruction of the level of the bladder or

37、urethra Hydronephrosis Normal urinary tractIntravenous pyelogram (IVP)Hydronephrosis Intravenous pyelogram (IVP) Hydronephrosis ( cut surface)Clinical featureClinical features depend on the cause and site of the lesionEffects of hydronephrosisObstruction is removed: renal function returns to normalP

38、ersistence of obstruction: atrophy of renal tubules with glomerular hyalinization and fibrosisStaghorn calculusHydronephrosis Abscess OutlineGlomerulonephritis(GN)Tubulointerstitial nephritisUrinary outflow obstructionTumors of urinary systemProstate Disease, Testis and Penis TumorTumors of urinary

39、systemTumors of the kidneyTumors of the bladderTumors of the ureterTumors of the urethraKey factsrenal cell carcinoma80%-85% of all primary renal malignant tumor, 2%-3% of all adult cancersMale: female incidence is 3:1Incidence is greatest in those over 50 years, and increases with ageRisk factors:

40、smokers , exposure to cadmium, genetic factors(VHL gene, TFE3 fusion gene)CTRenal cell carcinomaRenal cell carcinomaRenal cell carcinoma invade into the renal vein Renal cell carcinoma (clear cell type)Renal cell carcinoma (clear cell type)Papillary renal cell carcinomachromophobe renal cell carcino

41、maKey factsrenal cell carcinomaCommon presenting symptoms include painless hematuria, loin pain, loin massOccasional presenting symptoms include bone metastasis, pulmonary metastasis, brain metastasis, paraneoplastic syndrome (hypercalcemia , hypertension , Cushing syndrome)Key factsrenal cell carci

42、nomaLocal spread through renal capsule into perinephritic fat tissueLymphatic spread to para-aortic and other nodesBlood stream spread to lungs, bone, brain, liverPrognosis depends on stage at presentationWilms tumor (Nephroblastoma)Common malignant tumors of childhood Abdominal enlargementGenetic d

43、efects on chromosome 11Wilms tumorAngiomyolipoma Angiomyolipoma Metastatic carcinoma of the kidneyQuestions List five kinds of diseases of unilateral enlargement of the kidney.What are the causes of urinary tract obstruction?Tumors of the lower urinary tract Most tumors of the lower urinary tract ar

44、ise from transitional-cell epithelium （urothelium)Urothelial carcinoma of the bladderUrothelial carcinoma of the ureterIntravenous pyelogram (IVP) Carcinoma of the bladderCarcinoma of renal pelvisUrothelial carcinoma of pelvisKey factsWHO classification:Urothelial papilloma urothelial neoplasm of lo

45、w malignant potentialpapillary urothelial carcinoma, low gradepapillary urothelial carcinoma, high gradeinvasive urothelial carcinoma, low gradeinvasive urothelial carcinoma, high gradeKey factsCommon presenting symptoms is painless hematuriaIndications of bladder and urethral irritation( dysuria, u

46、rgency, frequency of micturition)Outflow obstructionPrognosis depends on stage at presentation, recur is commonCase studyA 57-year-old man who presents to his family doctor complaining of a dragging sensation in his left loin. On questioning, he admits to having had intermittent painless hematuria f

47、or three weeks. Following referral to a urological surgeon, investigation reveals a large mass replacing the left kidney. He undergoes a left nephroectomy from which he makes a good recovery. Questions What is the most likely diagnosis?The most likely diagnosis is renal cell carcinomaQuestions What

48、is the most common histological pattern of this lesion and what causes this appearance?The most common pattern is clear cell type of RCC. The cause is of lipid and glycogen within the cytoplasm of neoplastic cellsQuestions What factors in the pathologists report would have a particular bearing on the prognosis for this patient?The size of the tumor, the perinephrotic infiltration, the involvement of lymph node and the involvement of vessels. If the tumor is confined within the renal capsule, there is a 70% 10-year surviv