1. Disease of the urinary system Tian Dong Ping （田东萍 教授 ) 汕头大学医学院病理学教研室 2003 年 5 月

2. Section 1 Introduction A. Anatomy of kidney Cut surface of kidney Cut surface of kidney Cortex Cortex Medullary Medullary Renal papilla Renal papilla Calyx Calyx Renal pelvis Renal pelvis

3. B. Histology of kidney Nephrons: include glomerulus and renal tubulus. Glomerulus: Bowman’s capsule and capillary tuft.

4. C. Ultrastructure of glomerulus 1. Glomerular filtration barrier: basement membrane (B. M) endothelial cell Visceral epithelial cell (podocyte), foot-process have plenty negative ion substances (heparan etc)

5. 2. Glomerular mesangium structure mesangial cell mesangial matrix mesangial matrix

8. D. Classification of urinary system disease 1. Glomerulonephritis 2. Pyelonephritis 3. Tumor of kidney 4. Tumor of bladder

9. Section 2 Glomerulonephritis (GN) A. A. Definition Glomerulonephritis is a hypersensitivity inflammatory diease. It cause by various immune complex and eppear diffuse glomeruli proliferative inflammation in bilateral kidney

10. B. Etiology and Pathogenesis 1. Antigen Endogenous antigen Endogenous antigen GBM, endothelial cell, mesangial cell GBM, endothelial cell, mesangial cell Exogenous antigen Exogenous antigen bacteric, virus, fungus, parasit, drug ect bacteric, virus, fungus, parasit, drug ect

11. 2. Immune complex (1) In site immune complex 10% Antibodies react directly with, intrinsic tissue antigen (GBM) or antigen planted planted (noglomerular antigen) Antibodies react directly with, intrinsic tissue antigen (GBM) or antigen planted planted (noglomerular antigen)

12. Immunofluorescent (IF) appear linear pattern or granular pattern. Immunofluorescent (IF) appear linear pattern or granular pattern.

13. (2) Circulating immune complex 90% The antigen and antibody have not immunologic specificity for glomerular constituents, antigen-antibody complex are formed in the circulation and then deposit in the glomeruli. IF appear granular pattern. The antigen and antibody have not immunologic specificity for glomerular constituents, antigen-antibody complex are formed in the circulation and then deposit in the glomeruli. IF appear granular pattern.

16. 3. Pathogenesis 免 疫 复 合 物 激活补体单核细胞激活血小板系膜细胞 细胞因子  细胞因子 C5-9 C5a 中性白细胞 肾 小 球 损 伤 释出蛋白酶 氧自由基 花生四烯酸 渗出性增生性炎

17. C. Classification and pathological-clinical character Ⅰ. Acute diffuse proliferative GN 急性弥漫性增生性肾小球肾炎 急性弥漫性增生性肾小球肾炎 （ endocapillary proliferative GN, poststreptococcus GN)

18. 1. Pathology Grossly: “big and red kidney” “flea- bitten kidney”Grossly: “big and red kidney” “flea- bitten kidney”

20. 1. Pathology LM: All the glomerule are enlarge, and filled with nuclei (endothelia and mesangial cell), capillary lumen narrowed. LM: All the glomerule are enlarge, and filled with nuclei (endothelia and mesangial cell), capillary lumen narrowed.

22. EM and IF: endothelial cell and mesangial cell proliferate, in the basement membrane and under the podocyte have hump-shaped deposite. IF appear granular pattern

23. 2. Clinical-pathological correlation Acute nephritis syndrome Oiguria or anuria Oiguria or anuria Proteinuria, cast (+) Proteinuria, cast (+) Hematuria Hematuria Edema EdemaHypertension Glomerulo filtration 

24. 3. Result : 95% would be cured, 5% might turn to chronic GN, and few cases develop rapidly progressive GN.

25. Ⅱ. rapidly progressive GN, crescentic GN 快速进行性肾小球肾炎（新月体性肾小球肾炎） Diffuse extracapillary proliferative GN 25% of this type be accompanied by acute nephritis and 25% of this type be accompanied by good pasture syndrome. 50% of this type the cause is unknown.

26. 1. Pathology (1) LM: Epithelia of parietal layer of Bowman’s capsule proliferates and monocytes, fibrin infiltrate into Bowman’s capsule. Forming “crescent” (cellular crescent). Them fibrosis and adhesion with the tuft. (fibrous crescent). The Bowman’s capsule cavity obstruct. The glomerulus develop hyalinigation rapidly progressively.

28. (2) grossly: “big and white kidney” (3) EM and IF: EM disclose subepithelia deposites in some cases, but in all cases show focal ruptures in GBM. EM disclose subepithelia deposites in some cases, but in all cases show focal ruptures in GBM. IF exhibit granular immune deposites in acute nephritis. Linear fluorescence in goodpasture syndrome cases. IF exhibit granular immune deposites in acute nephritis. Linear fluorescence in goodpasture syndrome cases.

29. 2. Clinical-pathological correlation Rapidly progressive nephritis syndrome Hematuria Hematuria Proteinuria Proteinuria Oliguria and anuria Oliguria and anuria Rapidly progressing renal failure Rapidly progressing renal failure

30. 3. Result (1) It is very bad, the prognosis depend to the number of crescent: 50% crescent prognosis well 50% crescent prognosis well 50-80% crescent progress slowly 50-80% crescent progress slowly 80-90% death 80-90% death (2) Turn to chronic sclerosing GN

31. Ⅲ Diffuse membranous GN 弥漫性膜性肾小球肾炎 （ membranous nephritis) Early chronic nephritis, the duration is slow and prognosis is relatively good Early chronic nephritis, the duration is slow and prognosis is relatively good

32. 1. Pathology (1) LM: basement membrane diffusely thickened very much (platinic ring- like), but the capillary lumen is not obstructed usually. No cell proliferation.

33. Slide 21.26

34. (2) grossly: “big and white kidney”. (3) EM: There are “dome” and “spike”. Done is the deposit, spike is the proliferation of “basement membrane substance” so the BM becomes thickened and late stage BM becomes “moth-eaten” like.

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36. 2. Clinical-pathological correlation Typical nephrotic syndrome High proteinuria High edema High cholesterolemia and lipidemia Low blood albumin

37. 3. Result The duration is slow. Most of cases develop recurrent, in late stage a number of glomerulus develop fibrosis, some cases may be cure.

38. Ⅳ Diffuse membranous proliferative GN 弥漫性膜性增生性肾小球肾炎 （ mesangiocapillary GN) It is a chronic progressive nephritis it affect the mesaniun and capillary of glomerulus. It is more serious than membranous nephritis its prognosis is worse, easier to transit to atrophic kidney. It is a chronic progressive nephritis it affect the mesaniun and capillary of glomerulus. It is more serious than membranous nephritis its prognosis is worse, easier to transit to atrophic kidney.

39. 1. Pathology (1) LM: The glomerulus becomes lobulated, capillary wall thickened and lumen narrowed. Some hyaline glomeruli would be seen.

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41. (2) EM: (2) EM: Mesangial cell and mesangial matrix proliferate very much further more, they would insert into the capillary wall, the BM show splitting (two layer). Making the lumen seriouly narrow, the immune deposite can be seen elsewhere (mesangium and capillary wall).

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43. 2. Clinical-pathological correlation The early stage: proteinuria and hematuria is mild degree. The early stage: proteinuria and hematuria is mild degree. The disorder affect BM: nephrotic syndrome The disorder affect BM: nephrotic syndrome The late stage: hypertension and renal failure. The late stage: hypertension and renal failure.

44. 3. Result The prognosis is worse easier to transit to atrophic kidney, the 50% of cases develop chronic renal failure within 10 years. The prognosis is worse easier to transit to atrophic kidney, the 50% of cases develop chronic renal failure within 10 years.

45. Ⅴ. Minimal change glomerulonephritis 轻微病变性肾小球肾炎 （ Lipoid nephrosis) 1. Pathology: (1) Glossly: big and white kidney (2) LM: glomeruli no change at all; tubules: fatty degeneration. tubules: fatty degeneration. (3) EM: The unique change under EM is foot processes fusion. No deposit at all.

46. 图 脂性 肾病

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49. 2. Clinical-pathological correlation Nephrotic syndrome (1) High proteinuria (mainly is albumin) (2) Hypoalbuminemia (3) High edema (4) Hyperlipidemia and hypercholesterolemia

50. 3. Result The prognosis is good 90% of cases in children would be cure with cortisone The prognosis is good 90% of cases in children would be cure with cortisone

51. Ⅵ. Diffuse sclerosing GN 弥漫性硬化性肾小球肾炎 （ Chronic nephritis) This type is the final result of a lot of GN, its character is majority of glomeruli become hyaliniged, fibrosis, so renal failure, even uremia. This type is the final result of a lot of GN, its character is majority of glomeruli become hyaliniged, fibrosis, so renal failure, even uremia.

53. (2) grossly: granular atrophy of kidney

56. 1. Pathology (1) LM: Most of glomeruli are partially or completely scarred and some converted to hyaline masses the nearby tubules are atrophy and fibrosis;Most of glomeruli are partially or completely scarred and some converted to hyaline masses the nearby tubules are atrophy and fibrosis; Fibrosis of interstitial tissue is prominent, and there is an inflammatory infiltration in stromaFibrosis of interstitial tissue is prominent, and there is an inflammatory infiltration in stroma Relatively normal glomeruli occur compensation glomeruli occur hypertrophy and tubules dilateRelatively normal glomeruli occur compensation glomeruli occur hypertrophy and tubules dilate

58. 2. Clinical-pathological correlation Chronic nephritis syndrome (1) Renal failure: azotemia  uremia (2) Hypertension (3) Proteinurea and edema are not severe (4) Polyuria and noturnuria

59. 3. Result Prognosis is very bad the death cause are: (1) uremia (2) Hypertensional heart disease and cerebral hemorrhage (3) Infection

60. The Kidney 15 IgA Nephropathy (Berger Disease): is the most common glomerular disease. Presence of prominent IgA deposits in the mesangial regions. Dx by immunocytochemical techniques. Frequent cause of recurrent gross or microscopic hematuria, nephrotic syndrome may be present. Affect children and young adults, variable courses. Associated with gluten enteropathy, liver disease.

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62. The Kidney 13 Focal Segmental Glomerulosclerosis (FSG): Sclerosis of some glomeruli; portions of capillary involved. Clinically show nephrotic syndrome or heavy proteinuria. Idiopathic responds poorly to steroids and progress to chronic renal failure. Causes: associated with HIV, drug abuse, sickle cell disease IgA nephropathy, certain inherited disease and as primary disease, idiopathic.

64. Section 3 Pyelonephritis A. Definition: Pyelonephritis is a suppurative inflammation of renal pelvis and renal stroma, it is caused by pyogenic bacteritic infection directly Pyelonephritis is a suppurative inflammation of renal pelvis and renal stroma, it is caused by pyogenic bacteritic infection directly

65. B. Etiology and pathogenesis Ⅰ. Etiology: colon bacilli (60-80%) proteus proteus staphylococci etc staphylococci etc

66. Ⅱ. Infective path 1. Ascending infection: Urethra  bladder  ureter  renal pelvis Organism: colon bacilli women affect more easily

67. 2. Descending infection: (hematogenous) Primary focus  blood stream  kidney  cortex  renal pelvis Primary focus  blood stream  kidney  cortex  renal pelvis Organism: staphylococci

68. Ⅲ The role of urinary tract obstruction gravidity uterus Urinary stone  urinary tract obstruction prostate hyperplasia  Defensive function of urinary tract  (IgA , WBC , clearance role of urine flow  )  bacteria grow in the urine (culture medium)

69. C. Pathological type Ⅰ. Acute pyelonephrity 1. LM: renal stroma and pelvis develop suppurative inflammation, forming abscess mainly. Ascending infection: pelvis and renal stroma predominance Ascending infection: pelvis and renal stroma predominance Descending infection: glomeruli and renal tubule around first affect Descending infection: glomeruli and renal tubule around first affect

70. 2. Grossly: The kidney is enlarge, surface show size and shape irregular abscesses, some abscesses are long shaped according to the “medulla radiate streak” structure, pelvis hyperemia and even purulent exudate covered.

71. 急性肾盂肾炎

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73. 3. Clinical-pathological correlation (1) Infective symptom (2) Bladder irritation (3) pyuria, proteinuria, casts in urine, hematuria

74. 4. Result : The most of cases would be cure, but when its treatment is uncomely, it may be recurrence and turn to chronic pyelonephritis. The most of cases would be cure, but when its treatment is uncomely, it may be recurrence and turn to chronic pyelonephritis.

75. Ⅱ Chronic pyelonephritis Acute pyelonephritis would transit to chronic the cause may be as follows: Acute pyelonephritis would transit to chronic the cause may be as follows: Treatment not thorough enoughTreatment not thorough enough Bacteria metamorphosis (become L- type )Bacteria metamorphosis (become L- type ) Urinary tract obstructionUrinary tract obstruction

76. 2. Grossly: Irregular scars scattered at the kidney cortex become thin, pelvis and calices are dilated, the mucosa is coarse “Large scar concave atrophy of the kidney”

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79. 1. LM: (1) Chronic purulent inflammation, fibrosis (2) Renal parenchyma destruction: hyalinized glomeruli and atrophic tubules are evident but some dilated tubules have big cast inside (thyroid tissue like )

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82. 3. Clinical-pathological correlation The symptoms are not marked (1) Urorrhagia (2) Neutrophils in urine will add (3) Urine culture bacteria will (+) (4) final, hypertension and renal failure

83. 4. Result: The prognosis is poor most of cases die dead cause: The prognosis is poor most of cases die dead cause: (1) Renal failure urinaemia (2) Hypertensive heart disease and hypertensive brain disease

84. Section 4 Renal carcinoma (renal cell carcinoma, clear cell carcinoma ) A. Definition: Renal carcinoma is a malignant tumor, it is originate from renal tubule epithelium Renal carcinoma is a malignant tumor, it is originate from renal tubule epithelium

85. B. Pathology Ⅰ. Grossly: Nodular, might have a pseudo capsula, usually on the upper pole of the kidney; yellow colored, hemorrhagic and necrotic Nodular, might have a pseudo capsula, usually on the upper pole of the kidney; yellow colored, hemorrhagic and necrotic

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88. Ⅱ. LM: The cancer cells are clear (lipid and glycogen deposition), nuclei not big, nucleus-cytoplasm ratio not large. Cancer cells arrange nest-like or gland-like. Stroma is scanty. The cancer cells are clear (lipid and glycogen deposition), nuclei not big, nucleus-cytoplasm ratio not large. Cancer cells arrange nest-like or gland-like. Stroma is scanty.

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90. C. Spread of tumor and clinical features Ⅰ. Hematogenic metastasis: early stage, lung, bone, liver, adrenal gland, brain. early stage, lung, bone, liver, adrenal gland, brain. Peculiar site: nose, mouth, throat, vagina, eye Peculiar site: nose, mouth, throat, vagina, eye Retrograde metastasis: left kidney tumor  left renal vein  left spermatocord vein  left epididymis Retrograde metastasis: left kidney tumor  left renal vein  left spermatocord vein  left epididymis

91. Ⅱ. Hematurine without pain Ⅲ. Atopic endocrine syndrome (para- tumor syndrome) 甲状旁腺样激素、 肾素、促性腺激素、肾上腺皮质激 素、红细胞生成素等

92. D. Result The prognosis is poor No operation: die within 1 year Operation: 2 years survival 67% 5 years survival 50% 5 years survival 50% 10 years survival 34% 10 years survival 34%

93. Section 5 Nephroblastoma (embryonal adenosarcoma, wilm’s tumor) A. Definition : Nephroblastoma is a malignant tumor, it originate from embryonal cell (Nephroblast). Usually is seen in the children, very common. Nephroblastoma is a malignant tumor, it originate from embryonal cell (Nephroblast). Usually is seen in the children, very common.

94. B. Pathology Ⅰ. Grossly: a large clear-border, nodular, grey color tumor arisen from the kidney. Which is replaced by the tumor. The pelvis and calices are pressured distorted.

95. Ⅱ. LM: Two components: adenocarcinoma fibrosarcoma fibrosarcoma Sometime tumor cell would form glomerulus-like or tubule-like structures. Sometime tumor cell would form glomerulus-like or tubule-like structures. Sometime having some well differentiated cartilage Sometime having some well differentiated cartilage

96. C. Result The prognosis is more better. Recently record: using the operative treatment, chemotherapy and radiothrapy, 89% of cases may be cure. Recently record: using the operative treatment, chemotherapy and radiothrapy, 89% of cases may be cure.

97. Section 6 carcinoma of bladder Transitional cell carcinoma of bladder A. Definition Transitional cell carcinoma of bladder is a malignant tumor. It originate from transitional cell of bladder. It occupy 90% of cases in carcinoma of bladder. Transitional cell carcinoma of bladder is a malignant tumor. It originate from transitional cell of bladder. It occupy 90% of cases in carcinoma of bladder.

98. B. Pathology Ⅰ. Grossly: Usually it is a papillary tumor with slender or broad pedicle, sometime it show cauliflower-like or polypous, sometime it is flat.

100. The key is to decide whether the tumor has invaded the underline tissue or not and how deep is it. The key is to decide whether the tumor has invaded the underline tissue or not and how deep is it.

101. Ⅱ. LM: It may be divided three grade: 1. grade Ⅰ : Low malignancy, the papilla is covered by orderly transitional epithelium. (5~10 layer).

103. 2. Grade Ⅱ : The papilla epithelium having atypia with evident multilayer and solid focus appear also.

105. 3. Grad Ⅲ : high malignancy, the tumor cell show anaplastic and often deeply infiltrated without papilloma pattern.

107. C. Clinical feature Ⅰ. Hematurine without pain Ⅱ. Bladder irritation Ⅲ. Urinary tract obstruction

108. D. Result It is depend to the defferentiation and infiltration of the tumor. It is depend to the defferentiation and infiltration of the tumor. Grade Ⅰ : postoperation 5 years survival 90% Grade Ⅱ, : recurrence 60~90% Grade Ⅱ, Ⅲ : recurrence 60~90%

109. Thanks!