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Chapter 10Chapter 10
Urinary Urinary SystemSystem
Tang Xiping
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ContentsContents
GlomerulonephritisGlomerulonephritis
PyelonephritisPyelonephritis
Tumors of the kidney and Tumors of the kidney and
bladderbladder
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QuestionsQuestions
How many patterns can How many patterns can inflammation be classified inflammation be classified into?into?
Which three patterns?Which three patterns? What kind of inflammations What kind of inflammations
are glomerulonephritis and are glomerulonephritis and
pyelonephrits?pyelonephrits?
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[[structure]structure]
kidney
ureter
bladder
urethra
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Nephron Nephron
Glomerulus
tubule
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Vascular pole
Urinary pole
Capillary loops
Renal saccule
Mesangium
Normal Structure of glomerulus
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正
常
肾
小
球
Bowman’s space
Capi. loops
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Podocytes
GBM
Fenestrated capillary
Glomerular filtering membrane
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[[Function]Function]
1. Form and discharge urine1. Form and discharge urine
Excretes the waste Excretes the waste
Regulates water and saltRegulates water and salt
Maintains acid balanceMaintains acid balance
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2. Excrete hormone :
Renin
—to regulate blood pressure
Erythropoietin
—to generate RBC
1,25-dihydroxycholecalciferol
—to absorb calcium
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Segment 1Segment 1
Glomerulonephritis (GN)Glomerulonephritis (GN)
All are proliferative and most are
immunologically mediated.
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Proliferation
of Epithelial cells
Mesangial cells
Endothelial cells
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Two
forms
Immune Complex Nephritis in situ
Circulating Immune Complex Nephritis
[Pathogenesis]
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1. Immune Complex Nephritis In Situ
1) Anti-GBM Nephritis
2) Heymann Nephritis
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11 ) ) Anti-GBM Nephritis
Fixed antigens in the glomerular Fixed antigens in the glomerular
basement membranebasement membrane Linear continuous pattern of Linear continuous pattern of
localization by immunofluorescene localization by immunofluorescene microscopy microscopy
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肾小球基底膜抗原 连续线形荧光连续线形荧光
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2 ) Heymann Nephritis
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“Planted” nonglomerular antigens
Granular pattern of localization
by immunofluorescene
microscopy
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植入性抗原 颗粒状荧光颗粒状荧光
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The glomerul is an innocent The glomerul is an innocent
“by stander”“by stander” 。。
The antigen is The antigen is
not of glomerular origin.not of glomerular origin.
2.Circulating Immune Complex Nephritis
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Endogenous
Exogenous
Unknown
The origin
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颗粒状荧光颗粒状荧光循环免疫复合物
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Three sites Of
Deposits
In the mesangium
Subendothelial
Subepithelial
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3. Cell-Mediated Immune Glomerulonephritis
Caused by sentisitized T cells.
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4. Mediators of immune injury
Antibodies
Complements
Neutrophils
Monocytes
Macrophages
Platelets
Resident glomerular cellsFibrin related products
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Basic pathologic change
1. Hypercelullarity
2. Thickening of GBM
3. Inflammatary exudation and necrosis
4. Hyaline change and sclerosis
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Areas of lesions
Diffuse: affecting all or a majority of glomeruli
Focal: affecting a few or a part of glomeruli
Globic: involving the whole glomerulus
Segmental: involving only segments of each glomerulus
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弥漫性病变
球性病变
局灶性病变
节段性病变
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Clinical manifestationsClinical manifestations
Acute nephritic syndromeAcute nephritic syndrome
The The nephroticnephrotic syndrome syndrome
Asymptomatic hemauria or proteinuriaAsymptomatic hemauria or proteinuria
Rapidly progressive nephritic syndromeRapidly progressive nephritic syndrome
Chronic nephritic syndromeChronic nephritic syndrome
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Pathologic TypesPathologic Types
1.1. Acute diffuse proliferative GNAcute diffuse proliferative GN
2.2. Rapidly progressive GNRapidly progressive GN
3.3. Membranous GNMembranous GN
4.4. Membranoproliferative GNMembranoproliferative GN
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5.5. Focal segmental GNFocal segmental GN
6.6. Minimal GNMinimal GN
7.7. mesangial proliferative mesangial proliferative
GNGN
8.8. IgA nephropathyIgA nephropathy
9.9. Chronic GNChronic GN
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Acute Diffuse Proliferative Glomerulonephritis
(Endocapillary proliferative GN)
Location:
Diffuse, affecting almost all
glomeruli of two kidneys
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Pathogenesis
Post streptococcal GN( related to a group A streptococcal infection)
Typical immune complex disease:
Hypocomplementemia
Granular deposits of IgG
Complement on the GBM
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Morphology
Macropically:
Kidneys are enlarged and red 。
Sometimes with petechial hemorrhages
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大
红
肾
蚤
咬
肾
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LM:LM: 1. Proliferation and swelling of 1. Proliferation and swelling of endothelial and mesangial cellsendothelial and mesangial cells
PSGN
Normal
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2. 2. Neutrophilic infiltrateNeutrophilic infiltrate
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3. 3. Epithelial cell Epithelial cell renal tubules:renal tubules:
Cellular swellingCellular swelling
Fatty change Fatty change
Hyaline changeHyaline change
Urinary cylinder Urinary cylinder
in tubulesin tubules
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Electron microscopyElectron microscopy
The immune complex arrayed often The immune complex arrayed often
subepithelial “humps” nestled subepithelial “humps” nestled
against the GBMagainst the GBM
Sometimes subendothreial Sometimes subendothreial
or intramembranous or intramembranous
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Immune complex
EM :
Subepithelial
deposits
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ImmunofluorenscenceImmunofluorenscence
Granular pattern of localization on Granular pattern of localization on
the capillary wallthe capillary wall
IgG and complement within IgG and complement within
the depositsthe deposits
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Acute nephritic syndromeAcute nephritic syndrome:: Abrupt hematuria, proteinuria,Abrupt hematuria, proteinuria,
cylindruria, oliguria, , oliguria,
hypertension, edema.hypertension, edema.
[[Clinical course]Clinical course]
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PrognosisPrognosis
RecoveryRecovery
Rapidly progressive Rapidly progressive
glomerulonephritisglomerulonephritis
Chronic nephritisChronic nephritis
<1% renal failure, heart failure, <1% renal failure, heart failure,
hypertensive encephalopathy
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Rapidly progressive Rapidly progressive glomerulonephrits, RPGNglomerulonephrits, RPGN
( ( crecentic glomerulonephritis)crecentic glomerulonephritis)
The presence of crescents in
most of the glomeruli.
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Pathogenesis
1. TypeⅠ RPGN: Anti-GBM disease, linear deposits of IgG and C3 on the GBM
2. Type Ⅱ RPGN: Immune complex-mediated disorder
3. Type Ⅲ RPGN: Pauci-immune type
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Morphology
Macroscopically:
The kidneys are enlarged and pale.
Often with petechial hemorrhages
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Light microscopy
The formation of crescents:
Necrosis of capillary wall
The escape of abundant fibrinogen into Bowman’s space
Proliferation of
parietal epithelial cells
Crescents formed
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新月体性肾小球肾炎
新月体
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Early stageEarly stage :: Parietal epithelial cell + Parietal epithelial cell +
Monocytes Monocytes CCellular crescentsellular crescents
FibrocytesFibrocytes Fibrous - Fibrous - ccellular ellular crescentscrescents
Late stageLate stage :: FFibrous tissueibrous tissue ffibrous crescentsibrous crescents
TThe crescents obliterate he crescents obliterate Bowman’s space and compress Bowman’s space and compress the glomerulithe glomeruli
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细胞性新月体
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纤维性新月体
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Electron microscopeElectron microscope
Distinct ruptures in the GBM in all Distinct ruptures in the GBM in all cases, irregularly thickening of GBM cases, irregularly thickening of GBM
Subepithelial deposits in some Subepithelial deposits in some cases. cases.
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ImmunofluorenscenceImmunofluorenscence
Linear patternLinear pattern
Granular patternGranular pattern
Lack of depositsLack of deposits
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Rapidly progressive nephritic Rapidly progressive nephritic syndrome:syndrome:
Abrupt hematuria, proteinuria, Abrupt hematuria, proteinuria,
anuria, oliguria, anaemia, anuria, oliguria, anaemia,
renal failurerenal failure
[[Clinical course]Clinical course]
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Goodpasture syndromeGoodpasture syndrome
Pulmonary hemorrhage & GNPulmonary hemorrhage & GN [Pathogenesis][Pathogenesis] Anti-GBM nephritis: Anti-GBM Anti-GBM nephritis: Anti-GBM
antibodies cross-act with basement antibodies cross-act with basement membranes of lung aveloli, resulting in lung membranes of lung aveloli, resulting in lung and kidney lesionsand kidney lesions
[Clinical][Clinical] Emptysis & Rapidly progress Emptysis & Rapidly progress renal failurerenal failure
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肺出血 &
肾小球肾炎
Goodpasture syndrome:
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Membranous GlomerulonephritsMembranous Glomerulonephrits
Basic change: Diffuse thickening Basic change: Diffuse thickening of the GBMof the GBM
Slowly progressive Slowly progressive disease, most common disease, most common between ages 30-50 years.between ages 30-50 years.
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MorphologyMorphology
Grossly: Grossly:
Kidneys enlarged and pale. Kidneys enlarged and pale.
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LMLM :: Thickening of the capillary wallThickening of the capillary wall
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膜性肾小球肾炎 (HE 染色 )
Cap. 壁增厚
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Electron microscopeElectron microscope
Subepithelial deposits that nestle Subepithelial deposits that nestle against the GBMagainst the GBM
Small, spikelike protrusions of Small, spikelike protrusions of GBM matrix (“spike and dome” GBM matrix (“spike and dome” pattern)pattern)
Later, the deposits are Later, the deposits are catabolized, leaving for a time catabolized, leaving for a time cavities within the GBMcavities within the GBM
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EM:
免疫复合物
钉突
虫蚀状
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膜性肾小球肾炎(嗜银染色)
钉突
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ImmunofluorescenceImmunofluorescence
Typical Typical granular deposition granular deposition of of
immunoglobulins (IgG) and immunoglobulins (IgG) and
complement( C3) along the complement( C3) along the
GBMGBM
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Nephrotic syndrome:Nephrotic syndrome:
1.1. Heavy ProteinuriaHeavy Proteinuria
2.2. Hyperlipedemia Hyperlipedemia
3.3. Severe edemaSevere edema
4.4. HypoalbuminemiaHypoalbuminemia
[[Clinical course]Clinical course]
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Membranoproliferative Membranoproliferative GlomerulonephritisGlomerulonephritis
[[Basic change]:Basic change]:
Alterations in the basement Alterations in the basement
membrane and mesangium membrane and mesangium
Proliferation of glomerular Proliferation of glomerular
cellscells
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MorphologyMorphology
Proliferation of mesangial cells as Proliferation of mesangial cells as
well as infiltrating leukocytes well as infiltrating leukocytes
extending into the peripheral extending into the peripheral
capillary loopscapillary loops..
LM:LM:
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The capillary loops have The capillary loops have lobular appearancelobular appearance
The GBM is thickened , and The GBM is thickened , and shows a double contour or shows a double contour or “tramtruck” apperance“tramtruck” apperance
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双轨征
Cap.管壁增厚,管腔狭窄
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膜增生性肾小球肾炎(嗜银染色)
基底膜增厚呈车轨状
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膜增生性肾小球肾炎
( 染色)HE
Cap.Cap.丛呈丛呈分叶分叶
状状
Cap.Cap.丛呈丛呈分叶分叶
状状
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[Electron microscope]:
TypeⅠTypeⅠ :: Subendothelial electron-Subendothelial electron-dense deposits dense deposits
TypeⅡTypeⅡ :: The lamina densa and the The lamina densa and the subendothelial space of th GBM are subendothelial space of th GBM are transformed into an irregular, transformed into an irregular, ribbon-like, extremely electron-dense ribbon-like, extremely electron-dense structure — structure — dense deposit diseasedense deposit disease
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膜性增生性肾小球肾炎
右 Ⅱ型
左
Ⅰ型
免疫复合物
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Type : C3 deposited in a granular ⅠType : C3 deposited in a granular Ⅰpattern and IgG and early complement pattern and IgG and early complement components(C1q and C4) are often components(C1q and C4) are often presentpresent
Type : C3 is present in irregular ⅡType : C3 is present in irregular Ⅱgranular-linear foci in the GBM and granular-linear foci in the GBM and mesangium . IgG is usually absentmesangium . IgG is usually absent ,as ,as are are C1q and C4C1q and C4
Immunofluorescence
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Clinical course
The principle mode of presentation is the nephrotic syndrome
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Chronic GlomerulonephritisChronic Glomerulonephritis
((Diffuse Sclerosing Glomerulonephritis)Diffuse Sclerosing Glomerulonephritis)
Kidneys symmetrically contracted
Surface: red-brown and
diffusely granular
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大体: 大体:
颗颗粒粒性性固固缩缩肾肾
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颗 粒 性 固 缩 肾
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Light microscopeLight microscope
1.1. Advanced scarring of glomeruli Advanced scarring of glomeruli
and Bowman’s spaces. and Bowman’s spaces.
Sometimes complete replacement Sometimes complete replacement
and hylalinization.and hylalinization.
2.2. Compensatory hypertrophy of Compensatory hypertrophy of
remained nephrons remained nephrons
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3.3. Interstitial fibrosis, lymphocytic Interstitial fibrosis, lymphocytic
infiltrateinfiltrate
4.4. Small arteries thick-walled, with Small arteries thick-walled, with
narrowed luminanarrowed lumina
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慢性肾小球肾炎
慢性肾小球肾炎
玻璃样变
肾小球纤维化
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慢性肾小球肾炎
玻璃样变
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Chronic nephritic syndrome:Chronic nephritic syndrome:
1.1. Diuresis, nocturia, oliguria, auriaDiuresis, nocturia, oliguria, auria
2.2. Hypertensoin Hypertensoin
3.3. AnaemiaAnaemia
4.4. Azotemia – renal failureAzotemia – renal failure
[[Clinical course]Clinical course]
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Segment 2Segment 2PyelonephritisPyelonephritis
[location] : Interstitium , renal pelvis ,
tubules
[character]: Suppurative imflammation
[age]: any age . Female: Male = 10:1
[classification]: Acute and Chronic
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Tworoutes
Through the bloodstream
From the lowerUrinary tract
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上
行
性
感
染
肾
输尿管
膀胱
尿道
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Pathogenesis
Gram-negative bacteria , especially E. coli
Acute pyelonephritis: only one kind of bacteria
Chronic pyelonephritis: mixed infection
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Macroscopically:
Kidneys enlarged
Discrete, yellowish,
raised abscess on the
renal surface
Acute pyelonephritisAcute pyelonephritis
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急性肾盂肾炎:肾表面及切面多发散 在的小化脓灶(大体)
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[[Light microscope]Light microscope]
Suppurative inflammation involving Suppurative inflammation involving
renal pelvis, interstitium and tubules.renal pelvis, interstitium and tubules.
Abscess formationAbscess formation Tubules are filled with pus cell Tubules are filled with pus cell
and and
bacteriabacteria
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急 性 肾 盂 肾 炎
肾间质化脓性炎
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急
性
肾
盂
肾
炎
急
性
肾
盂
肾
炎
肾小管内充满脓细胞
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1.1. Fever, chills, leucocytes ↑Fever, chills, leucocytes ↑
2.2. Flank pain , bladder irritation Flank pain , bladder irritation
(frequency, dysuria, urgency)(frequency, dysuria, urgency)
3.3. Pyuria, bacteriuria, hematuria, Pyuria, bacteriuria, hematuria,
cylinduria (white cell cast)cylinduria (white cell cast)
[[Clinical course]Clinical course]
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PrognosisPrognosisRecoveryRecovery
Improper therapy Chronic Improper therapy Chronic
pyelonephritispyelonephritis
ComplicationComplication :: 11 )) Necrosis of renal papillaeNecrosis of renal papillae 22 )) Pyonephrosis 33 )) Perinephric abscessPerinephric abscess
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肾
盂
积
脓
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Chronic PyelonephritisChronic Pyelonephritis
A chronic tubulointerstitial A chronic tubulointerstitial
inflammantioninflammantion
Renal scarringRenal scarring
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大体:瘢痕凹陷性固缩肾
瘢痕凹陷
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[[Light microscope]:Light microscope]:
Uneven interstitial fibrosis and an Uneven interstitial fibrosis and an
inflammatory inflitration of lymphocytes, inflammatory inflitration of lymphocytes,
plasma cells, and occasionally neutrophils.plasma cells, and occasionally neutrophils.
TubulesTubules show atrophy in some show atrophy in some
areas and hypertrophy in othersareas and hypertrophy in others
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Thyroidization (dilated tubules (dilated tubules
with colloid casts)with colloid casts)
Chronic inflammation infiltrate involving the
calyceal mucosa Some glomeruli may be involvedmay be involved
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慢
性
肾
盂
肾
炎
慢
性
肾
盂
肾
炎
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慢 性 肾 盂 肾 炎肾盂粘膜慢性炎性细胞浸润
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慢 性 肾 盂 肾 炎
肾小管管腔内蛋白
管型,
似甲状腺滤
泡
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慢 性 肾 盂 肾 炎慢 性 肾 盂 肾 炎
肾小球纤维
化玻璃样变
管型
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1.1. Dysuria,Dysuria, nocturia, nocturia, hypertensionhypertension
2.2. Azotemia, uraemiaAzotemia, uraemia
[[Clinical course]Clinical course]
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PrognosisPrognosis
Correct therapy: Incomplete Correct therapy: Incomplete
recoveryrecovery
Abroad lesions: Hypertension, Abroad lesions: Hypertension,
renal failurerenal failure
Unilateral serious disease: Unilateral serious disease:
NephrectomyNephrectomy
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Class is over
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Segment 3Segment 3
Tumors of the kidney and Tumors of the kidney and bladderbladder
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[[structure]structure]
kidney
ureter
bladder
urethra
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Renal cell carcinoma
Nephroblastoma
Transitional cell carcinoma of Transitional cell carcinoma of
the bladderthe bladder
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Renal cell carcinoma
Adenocarcinoma arising from the
renal tubular epithelium
Represents about 85% of all primary
malignant tumors of the kidney
Male : Female = 2 : 1
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肾癌 肾癌
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肾癌
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肾癌
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Grossly:
Most commonly at the upper pole
Usually spherical masses
Cut surface is colorful, yellow-
gray-white marked with areas
of hemorrhage and necrosis
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Histologically:
“Clear cells” type
“Granular cells” type
Intergradations
may be found
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Classification based on molecular origin:
1. Clear cell carcinoma
2. Papillary carcinoma
3. Chromophobe cell carcinoma
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肾透明细胞癌
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The most common type
Consists of “clear cells”
The tumor cells may cluster in nests , tubers or cords
1.Clear Cell Carcinoma
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2.Papillary Carcinoma2.Papillary Carcinoma
Tumor cells line like Tumor cells line like papillapapilla
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Obvious membraneObvious membrane Light basophilic cytoplasmLight basophilic cytoplasm
Have a comparatively Have a comparatively
good prognosisgood prognosis
3.Chromophobe carcinoma
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[Spread][Spread]1.Local invasion1.Local invasion
2.Metastasis2.Metastasis :: Hematogenous: early happened. Hematogenous: early happened.
Unusual organs are involved, such Unusual organs are involved, such as mouth, larynx, eyepit, vagina. as mouth, larynx, eyepit, vagina. LymphaticLymphatic :: renal hilum, renal hilum,
paraaorta lymph nodesparaaorta lymph nodes
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1.1. Hematuria ,flank pain and palpable mass Hematuria ,flank pain and palpable mass
2.2. Fever, malaise, lose weightFever, malaise, lose weight
3.3. Some tumors produce a variety of Some tumors produce a variety of hormone-like substance: hormone-like substance:
Renin hypertension
Hemopoietin polycythemia
Parathormone analog hypercalcemiaParathormone analog hypercalcemia
[Clinical course][Clinical course]
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肾透明细胞癌
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Nephroblastoma ( Nephroblastoma ( Wilms’ tumor)Wilms’ tumor)
The third most common organ The third most common organ malignant tumor in children under malignant tumor in children under the age of 10 years, and the most the age of 10 years, and the most common in kidneys .common in kidneys .
Peak incidence is 2-4 years Peak incidence is 2-4 years Rare cases occur in adultsRare cases occur in adults
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[Grossly][Grossly] Usually unilateral( about 90%) Usually unilateral( about 90%) Generally large ,spherical masses Generally large ,spherical masses with clear boundarywith clear boundary Cut surface: Cut surface:
Soft; fish-flesh areas; Gray, hyaline cartilaginous tis
sue;;Areas of hemorragic necrosis are common.
MorphologyMorphology
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肾 母 细 胞 瘤
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肾母细胞
瘤
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Three basesThree bases Nests and sheets of Nests and sheets of primitive blastemaprimitive blastema
Abortive tubules and Abortive tubules and abortive glomeruli consists abortive glomeruli consists of primitive epithelial cellsof primitive epithelial cells
MesenchymaMesenchyma ;; Spindle Spindle cellscells
Histologically:
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肾 母 细 胞 瘤
原始肾小
管
原始肾小球
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Transitional Cell Carcinoma Transitional Cell Carcinoma (TCC) of the Bladder(TCC) of the Bladder
[Age][Age] Peak incidence is 50-70 yearsPeak incidence is 50-70 years
[Position] [Position] vesical triangle and vesical triangle and
lateral wall of the bladderlateral wall of the bladder
The most common malignant tumor in the urinary system
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MorphologyMorphology
Range from papillary to flat, Range from papillary to flat,
noninvasive to invasive, and from noninvasive to invasive, and from
extremely well –differentiated extremely well –differentiated
(grade )to highly anaplastic Ⅰ(grade )to highly anaplastic Ⅰ
aggressive (grade ) Ⅲaggressive (grade ) Ⅲ
cancerscancers . .
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膀胱癌
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LM : TCCⅠ Papillary tumors with slightly atypical appearing transitional epithelium.
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TCCⅡ have irregular papillary component, obvious atypia
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TCC Ⅲ irregular nests, extremely obvious atypia, pathologic numerous mitoses are often seen, invade deep to muscular layer
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AtypiaAtypiaHyper-Hyper-plasiaplasia PolarityPolarity MitosesMitoses
TCC TCC Ⅰ SlightSlight >7>7
Slightly Slightly abnormabnorm
alalRareRare
TCCⅡ
ObvioObviousus >10>10 AbnormAbnorm
alalCommoCommo
nn
TCC Ⅲ
ExtreExtremely mely
obviouobviouss
ProminProminentent AbsentAbsent ProminPromin
entent
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[Metastasis][Metastasis] Lymphatic spreadLymphatic spread :: Local lymph Local lymph
nodesnodes Hematogenous spread: occurs laterHematogenous spread: occurs later
[Clinical course ][Clinical course ]
Painless hematuriaPainless hematuria
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Class is over