chapter 10 urinary system tang xiping contents glomerulonephritis glomerulonephritis pyelonephritis...

Chapter 10Chapter 10

Urinary Urinary SystemSystem

Tang Xiping

ContentsContents

GlomerulonephritisGlomerulonephritis

PyelonephritisPyelonephritis

Tumors of the kidney and Tumors of the kidney and

bladderbladder

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?

[[structure]structure]

kidney

ureter

bladder

urethra

Nephron Nephron

Glomerulus

tubule

Vascular pole

Urinary pole

Capillary loops

Renal saccule

Mesangium

Normal Structure of glomerulus

正

常

肾

小

球

Bowman’s space

Capi. loops

Podocytes

GBM

Fenestrated capillary

Glomerular filtering membrane

[[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

2. Excrete hormone ：

Renin

—to regulate blood pressure

Erythropoietin

—to generate RBC

1,25-dihydroxycholecalciferol

—to absorb calcium

Segment 1Segment 1

Glomerulonephritis (GN)Glomerulonephritis (GN)

All are proliferative and most are

immunologically mediated.

Proliferation

of Epithelial cells

Mesangial cells

Endothelial cells

Two

forms

Immune Complex Nephritis in situ

Circulating Immune Complex Nephritis

[Pathogenesis]

1. Immune Complex Nephritis In Situ

1) Anti-GBM Nephritis

2) Heymann Nephritis

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

肾小球基底膜抗原 连续线形荧光连续线形荧光

2 ） Heymann Nephritis

“Planted” nonglomerular antigens

Granular pattern of localization

by immunofluorescene

microscopy

植入性抗原 颗粒状荧光颗粒状荧光

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

Endogenous

Exogenous

Unknown

The origin

颗粒状荧光颗粒状荧光循环免疫复合物

Three sites Of

Deposits

In the mesangium

Subendothelial

Subepithelial

3. Cell-Mediated Immune Glomerulonephritis

Caused by sentisitized T cells.

4. Mediators of immune injury

Antibodies

Complements

Neutrophils

Monocytes

Macrophages

Platelets

Resident glomerular cellsFibrin related products

Basic pathologic change

1. Hypercelullarity

2. Thickening of GBM

3. Inflammatary exudation and necrosis

4. Hyaline change and sclerosis

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

弥漫性病变

球性病变

局灶性病变

节段性病变

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

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

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

Acute Diffuse Proliferative Glomerulonephritis

(Endocapillary proliferative GN)

Location:

Diffuse, affecting almost all

glomeruli of two kidneys

Pathogenesis

Post streptococcal GN( related to a group A streptococcal infection)

Typical immune complex disease:

Hypocomplementemia

Granular deposits of IgG

Complement on the GBM

Morphology

Macropically:

Kidneys are enlarged and red 。

Sometimes with petechial hemorrhages

大

红

肾

蚤

咬

肾

LM:LM: 1. Proliferation and swelling of 1. Proliferation and swelling of endothelial and mesangial cellsendothelial and mesangial cells

PSGN

Normal

2. 2. Neutrophilic infiltrateNeutrophilic infiltrate

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

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

Immune complex

EM ：

Subepithelial

deposits

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

Acute nephritic syndromeAcute nephritic syndrome:: Abrupt hematuria, proteinuria,Abrupt hematuria, proteinuria,

cylindruria, oliguria, , oliguria,

hypertension, edema.hypertension, edema.

[[Clinical course]Clinical course]

PrognosisPrognosis

RecoveryRecovery

Rapidly progressive Rapidly progressive

glomerulonephritisglomerulonephritis

Chronic nephritisChronic nephritis

<1% renal failure, heart failure, <1% renal failure, heart failure,

hypertensive encephalopathy

Rapidly progressive Rapidly progressive glomerulonephrits, RPGNglomerulonephrits, RPGN

( ( crecentic glomerulonephritis)crecentic glomerulonephritis)

The presence of crescents in

most of the glomeruli.

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

Morphology

Macroscopically:

The kidneys are enlarged and pale.

Often with petechial hemorrhages

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

新月体性肾小球肾炎

新月体

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

细胞性新月体

纤维性新月体

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.

ImmunofluorenscenceImmunofluorenscence

Linear patternLinear pattern

Granular patternGranular pattern

Lack of depositsLack of deposits

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]

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

肺出血 &

肾小球肾炎

Goodpasture syndrome:

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.

MorphologyMorphology

Grossly: Grossly:

Kidneys enlarged and pale. Kidneys enlarged and pale.

LMLM ：： Thickening of the capillary wallThickening of the capillary wall

膜性肾小球肾炎 (HE 染色 )

Cap. 壁增厚

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

EM:

免疫复合物

钉突

虫蚀状

膜性肾小球肾炎（嗜银染色）

钉突

ImmunofluorescenceImmunofluorescence

Typical Typical granular deposition granular deposition of of

immunoglobulins (IgG) and immunoglobulins (IgG) and

complement( C3) along the complement( C3) along the

GBMGBM

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]

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

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:

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

双轨征

Cap.管壁增厚，管腔狭窄

膜增生性肾小球肾炎（嗜银染色）

基底膜增厚呈车轨状

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

[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

膜性增生性肾小球肾炎

右 Ⅱ型

左

Ⅰ型

免疫复合物

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

Clinical course

The principle mode of presentation is the nephrotic syndrome

Chronic GlomerulonephritisChronic Glomerulonephritis

((Diffuse Sclerosing Glomerulonephritis)Diffuse Sclerosing Glomerulonephritis)

Kidneys symmetrically contracted

Surface: red-brown and

diffusely granular

大体： 大体：

颗颗粒粒性性固固缩缩肾肾

颗 粒 性 固 缩 肾

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

3.3. Interstitial fibrosis, lymphocytic Interstitial fibrosis, lymphocytic

infiltrateinfiltrate

4.4. Small arteries thick-walled, with Small arteries thick-walled, with

narrowed luminanarrowed lumina

慢性肾小球肾炎

慢性肾小球肾炎

玻璃样变

肾小球纤维化

慢性肾小球肾炎

玻璃样变

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]

Segment 2Segment 2PyelonephritisPyelonephritis

[location] : Interstitium , renal pelvis ,

tubules

[character]: Suppurative imflammation

[age]: any age . Female: Male = 10:1

[classification]: Acute and Chronic

Tworoutes

Through the bloodstream

From the lowerUrinary tract

上

行

性

感

染

肾

输尿管

膀胱

尿道

Pathogenesis

Gram-negative bacteria , especially E. coli

Acute pyelonephritis: only one kind of bacteria

Chronic pyelonephritis: mixed infection

Macroscopically:

Kidneys enlarged

Discrete, yellowish,

raised abscess on the

renal surface

Acute pyelonephritisAcute pyelonephritis

急性肾盂肾炎：肾表面及切面多发散 在的小化脓灶（大体）

[[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

急 性 肾 盂 肾 炎

肾间质化脓性炎

急

性

肾

盂

肾

炎

急

性

肾

盂

肾

炎

肾小管内充满脓细胞

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]

PrognosisPrognosisRecoveryRecovery

Improper therapy Chronic Improper therapy Chronic

pyelonephritispyelonephritis

ComplicationComplication ：： 11 ）） Necrosis of renal papillaeNecrosis of renal papillae 22 ）） Pyonephrosis 33 ）） Perinephric abscessPerinephric abscess

肾

盂

积

脓

Chronic PyelonephritisChronic Pyelonephritis

A chronic tubulointerstitial A chronic tubulointerstitial

inflammantioninflammantion

Renal scarringRenal scarring

大体：瘢痕凹陷性固缩肾

瘢痕凹陷

[[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

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

慢

性

肾

盂

肾

炎

慢

性

肾

盂

肾

炎

慢 性 肾 盂 肾 炎肾盂粘膜慢性炎性细胞浸润

慢 性 肾 盂 肾 炎

肾小管管腔内蛋白

管型,

似甲状腺滤

泡

慢 性 肾 盂 肾 炎慢 性 肾 盂 肾 炎

肾小球纤维

化玻璃样变

管型

1.1. Dysuria,Dysuria, nocturia, nocturia, hypertensionhypertension

2.2. Azotemia, uraemiaAzotemia, uraemia

[[Clinical course]Clinical course]

PrognosisPrognosis

Correct therapy: Incomplete Correct therapy: Incomplete

recoveryrecovery

Abroad lesions: Hypertension, Abroad lesions: Hypertension,

renal failurerenal failure

Unilateral serious disease: Unilateral serious disease:

NephrectomyNephrectomy

Class is over

Segment 3Segment 3

Tumors of the kidney and Tumors of the kidney and bladderbladder

[[structure]structure]

kidney

ureter

bladder

urethra

Renal cell carcinoma

Nephroblastoma

Transitional cell carcinoma of Transitional cell carcinoma of

the bladderthe bladder

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

肾癌 肾癌

肾癌

肾癌

Grossly:

Most commonly at the upper pole

Usually spherical masses

Cut surface is colorful, yellow-

gray-white marked with areas

of hemorrhage and necrosis

Histologically:

“Clear cells” type

“Granular cells” type

Intergradations

may be found

Classification based on molecular origin:

1. Clear cell carcinoma

2. Papillary carcinoma

3. Chromophobe cell carcinoma

肾透明细胞癌

The most common type

Consists of “clear cells”

The tumor cells may cluster in nests , tubers or cords

1.Clear Cell Carcinoma

2.Papillary Carcinoma2.Papillary Carcinoma

Tumor cells line like Tumor cells line like papillapapilla

Obvious membraneObvious membrane Light basophilic cytoplasmLight basophilic cytoplasm

Have a comparatively Have a comparatively

good prognosisgood prognosis

3.Chromophobe carcinoma

[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

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]

肾透明细胞癌

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

[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

肾 母 细 胞 瘤

肾母细胞

瘤

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:

肾 母 细 胞 瘤

原始肾小

管

原始肾小球

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

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 . .

膀胱癌

LM ： TCCⅠ Papillary tumors with slightly atypical appearing transitional epithelium.

TCCⅡ have irregular papillary component, obvious atypia

TCC Ⅲ irregular nests, extremely obvious atypia, pathologic numerous mitoses are often seen, invade deep to muscular layer

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

[Metastasis][Metastasis] Lymphatic spreadLymphatic spread ：： Local lymph Local lymph

nodesnodes Hematogenous spread: occurs laterHematogenous spread: occurs later

[Clinical course ][Clinical course ]

Painless hematuriaPainless hematuria

Class is over