《病理學(xué)》英文課件：08 The disease of urinary system

1、Chapter IX The Diseases of Urinary System Xueguang Liu (劉學(xué)光) Room 204, #1 Building Tel: 54237533-2042 Email: , Kidney - producing urine - important functions Ureter, bladder, urethra - storing or eliminating urine,The Anatomy of the Urinary System,Which laboratory?,Four basic morphologic components,

2、Glomeruli: immunologically mediated Tubules Interstitium Blood vessels,toxic / infectious agents,Some agents affect more than one structure.,Main types of urinary diseases Inflammation - glomerulonephritis 腎小球腎炎 - pyelonephritis 腎盂腎炎 Stone urolithiasis - nephrolithiasis 腎結(jié)石 - hydronephrosis 腎盂積水 Tum

3、or - renal cell carcinoma - Wilms tumor - urothelial carcinoma ( transitional cell carcinoma),Important points,Normal structure of glomerulus,Glomerular Filtration,1. Glomerular filtrating membrane,Fenestrated endothelium - 70 100nm Glomerular basement membrane (GBM) - Negatively charged A meshwork

4、of fine fibrils (Col- IV, laminin) Embedded in an amorphous matrix (FN) Rich in heparan sulfate / glycosaminoglycan PAS / PASM staining (+),Visceral epithelium - Podocytes Slit diaphragm 20 30 nm Sieve pore 4 14 nm Cytoskeleton proteins (nephrin, podocin, etc.) A negatively-charged coat Glycocalyx,H

5、ighly selective albumin proteinuria,2. Mesangial region - axial area of glomerulus,Mesangial cells (MsC) Mesangial matrix, 4 MsC / mesangial area,Crescent,3. Bowmans capsule,How to affect renal functions?,I Glomerulonephritis GN,Primary GN - limited in kidney along Secondary GN - secondary to system

6、ic diseases,A group of hypersensitivity diseases two categories,Etiology and Pathogenesis Glomerular injury caused by immune complexes,Deposition of circulating immune complexes in glomeruli Antibodies reacting in situ within the glomerulus Intrinsic glomerular antigens (fixed) Molecules planted wit

7、hin the glomeruli,I. Circulating immune complex-mediated nephritis Antigens: (1) exogenous: bacteria (streptococci) , virus (HBV), Treponema pallidum(梅毒螺旋體), parasite, Plasmodium falciparum (惡性瘧原蟲), foreign serum, drug, toxin (2) endogenous: systemic lupus erythematousus (SLE, 系統(tǒng)性紅斑狼瘡), macroglobuli

8、n (巨球蛋白), thyroglobulin (甲狀腺球蛋白), carcinoembryonic antigen (CEA) In most cases, the inciting antigens are unkown.,“Innocent bystander”,Antigen-antibody complexes are formed in the circulation and then trapped in the glomeruli,Immunofluorescence staining(IF): Granular deposits,Ag,IF,Ab,EM: Electron d

9、ense deposits,Ag-Ab complexes formed,Trapped in glomeruli,Activation of complements,Recruitment of leukocytes,Injury,IF: complements deposition,IF: Ig deposition EM: electro-dense deposits,LM: inflammatory infiltration Intrinsic cells proliferation,II. In situ immune complexes-mediated nephritis int

10、rinsic tissue antigen “planted” antigens from the circulation,Caused by,1. Anti-Glomerular Basement Membrane (GBM) disease Antigen: NC1 of 3 of collagen IV (fixed) Self-Ab bind to GBM or LBM Goodpasture syndrome - simultaneous lung and kidney lesions 1% GN Crescentic GN Rapidly progressive GN,IF: li

11、near pattern,EM: No electron dense deposit,2. Heymann GN of rat Ag - proximal tubular brush border (megalin) Resembling human membranous GN IF: Granular pattern EM: Subepithelial electron dense deposit Other causes: DNA, bacteria products, virus protein - “planted antigens”,Antibody-mediated glomeru

12、lar injury,Basic pathological changes Extent of glomerular lesion Diffuse almost every glomeruli involved Focal partial (50%) glomeruli involved Global entire capillary loop Segmental partial capillary loop,Four essential pathological changes Hypercellularity - intrinsic glomerular cells (EnC, MsC,

13、EpC) inflammatory cells,Outcome: Reduction of GFR Oliguria / anuria 400ml 100ml 24 hr,Thickening of GBM Deposition of immune complexes and other proteins - May be accompanied with interposition of MsC and matrix Increased synthesis of GBM components,Outcome Negative-charged components GBM permeabili

14、ty Heavy proteinuria,(3) Necrosis and inflammatory exudation Fibroid necrosis of capillary loops Inflammatory exudation- protein, WBC, RBC,Outcome Hematuria Casturia,Hyalinosis, fibrosis and sclerosis Hyalinosis - plasma proteins insudated from the circulation (FSGS) Fibrosis - crescent, destruction

15、 of Bowmans capsule Sclerosis - increased matrix in mesangium thickening of GBM,Outcome: Glomerulosclerosis Uremia,Clinicopathologic correlations,The classification of GN,Histological classification Primary glomerulonephritis (GN) Diffuse proliferative GN Crescentic GN Membranous GN Lipoid nephrosis

16、 (minimal change disease) Focal segmental glomerulosclerosis Membranoproliferative GN IgA nephropathy Chronic GN,Secondary GN Systemic lupus erythematosus (SLE) Diabetes mellitus Amyloidosis Goodpasture syndrome Polyarteritis nodosa Wegener granulomatosis Henoch-Schonlein purpura Bacterial endocardi

17、tis Hereditary disorders ,Nephrotic syndrome,Derangement in capillary walls,Increased permeability of GBM,Heavy proteinuria (3.5g per day),Decreased serum albumin,hypoalbuminemia,Decreased plasma collid osmotic pressure,Retention of salt and water by the kidney,edema,Synthesis of lipoproteins by liver,Abnormal transport of circulating lipid particles,Impairment of lipoproteins breakdown,Hyperlipidemia,lipiduria,Plasma protein escape into ultrafiltrate,Nephrotic edema Pitting edema （凹陷性水腫）,Minimal-change disease (MCD, 微小病變病) Foot process disease （足突病）Lipoid nephrosis （脂性腎?。?Clinical features