《病理学》教学课件：8 泌尿系统疾病

1、Chapter IX The Diseases of Urinary System Xueguang Liu (刘学光) Room 204, #1 Building Tel: 5423 7533-2042 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 Tubules Interstitium Blood vessels,toxic / infectious agents,Some agents affect more than one structure,immunologically mediated,Main types of urinary diseases Inflammation - glomerulonephritis 肾小球肾炎 - pyelonephritis 肾盂肾炎 Stone urolithiasis nephrolithiasis (肾结石) hydronephrosis (肾盂积水) Tumo

3、r - renal cell carcinoma - Wilms tumor - urothelial neoplasms,Important points,Normal structure of glomerulus,Glomerular Filtration,1. Glomerular filtrating membrane,Fenestrated endothelium - 70 100nm Glomerular basement membrane (GBM) - Negatively charged A meshwork of fine fibrils (Col IV, laminin

4、) 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,Highly selective albumin proteinur

5、ia,2. Mesangial region - axial area of glomerulus,Mesangial cells (MsC) Mesangial matrix, 4 MsC / mesangium,3. Bowmans capsule,Crescent,How to affect renal functions?,I Glomerulonephritis GN,Primary GN - limited in kidney along Secondary GN - secondary to systemic diseases,A group of hypersensitivit

6、y 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 within the glomeruli,I. Circulating immun

7、e complex-mediated nephritis Antigens: (1) exogenous: bacteria (streptococci) , virus (HBV), Treponema pallidum(梅毒螺旋体), parasite, Plasmodium falciparum (恶性疟原虫), foreign serum, drug, toxin (2) endogenous: systemic lupus erythematousus (SLE, 系统性红斑狼疮), macroglobulin (巨球蛋白), thyroglobulin (甲状腺球蛋白), carc

8、inoembryonic 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 dense deposits,Ag-Ab complexes formed,T

9、rapped 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 intrinsic tissue antigen “planted” antige

10、ns 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: linear pattern,EM: No electron dense dep

11、osit,2. Idiopathic membranous nephropathy Phospholipase A2 receptor (PLA2R) on podocytes cell membrane,3. Heymann GN of rat Ag - gp330, megalin present in proximal tubular brush border IF: C3 deposition ) EM: intramembranous deposits Type III - A “variant” of type I EM: subepithelial Glomeruli lesio

12、ns; Glomerular deposits of immunoglobulins, often with various components of complement,Clinical manifestations,Pyuria 脓尿 / bacteriuria; bladder and urethral irritation (dysuria, frequency and urgency) 尿路刺激征,hematuria, proteinuria, hypertention, azotemia, uremia,One or both affected; Tubules Suppura

13、tive inflammation,Different,2. Drug-induced interstitial nephritis,Acute & chronic Acute: associated most frequently with synthetic penicillins (methicillin, ampicillin), other synthetic antibiotics (rifampin), diuretics (thiazides), nonsteroidal anti-inflammatory agents, and numberous other drugs (

14、phenindione, cimetidine) hypersensitivity: latent peroid, eosinophilia, rash, serum IgE, joint pain, recurrence after reexposure to the same drug,LM: interstitial edema interstitial infiltration by mononulclear cells (lym & M), prominent eosinophils interstitial non-necrotizing granulomas,(2) Chroni

15、c Interstitial edema, mononuclear infiltration, fibrosis Lymphoid follicular like structure,Clinical course Begins about 15 days after exposure to the drug Clinically, fever, eosinophilia, a rash, renal abnormalities (hematuria, proteinuria, leukocyturia, SCrin 50% of cases) Withdraw of the drug is

16、followed by recovery,3. Acute Tubular Injury (ATI),A clinicopathologic entity Morphology: damaged tubular epithelial cells Clinical: acute decline of renal function Laboratory: granular casts and tubular cells in the urine Acute kidney injury (AKI): decreased GFR Causes: ischemia, toxins, drugs (gen

17、tamicin,etc.), radiographic contrast agents ATI is often reversible,(1) Ischemic ATI,Lesions in the straight portions of the proximal tubule and the ascending thick limbs A variety of tubular injuries: Attenuation of proximal tubular brush borders, blebbing and sloughing of brush borders, vacuolizat

18、ion of cells, detachment of tubular cells from their underlying basement membranes, proteinaceous casts in the distal tubules and collecting ducts, destruction of TBM,(2) Toxic ATI,Similar to ischemic ATI Overt necrosis is most prominent in the proximal tubules TBM generally are spared Inclusions,Tu

19、mors Renal cell carcinorma - Derived from renal tubular epithelium - Most common in old people, especially males - Increased 30-fold risk in persons who acquire polycystic disease as a complication of chronic dialysis. - Classification Morphology Morlecular origin,Morphology Gross: - located in cort

20、ex - cut surface is yellow to orange to gray-white with areas of cystic softening or hemorrhage,*,LM: 1. Clear cell carcinoma: Most common vacuolated 2. Papillary renal cell carcinoma: papilla formation 3. Chromophobe-type renal cell carcinoma: flocculent cytoplasm with distinct membranes Clinical c

21、ourse: “Painless hematuria”,Wilms tumor (nephroblastoma) - Children 10 years - Derived from the mesoderm - Tan to gray color and well circumscribed - Clinical: readily palpable abdominal mass less often, fever, pain, hematuria - Prognosis: very good nephrectomy & chemotherapy,Urothelial neoplasms (尿路上皮肿瘤) - Transitional epithelium - Bladder & ureter most affected - Pathogenesis: cigarette smoking, various occupational carcino