徐芳英 ( xfy@zju )
DESCRIPTION
Diseases of the Kidney. 徐芳英 ( [email protected] ). Kidney Functions Excretion of the waste products of metabolism Regulation of body’s water and salt Maintenance of appropriate acid balance of plasma Secretion of a variety of hormones and autacoids: Erythropoietin Renin Prostaglandins. - PowerPoint PPT PresentationTRANSCRIPT
Kidney Functions
Excretion of the waste products of metabolism
Regulation of body’s water and salt
Maintenance of appropriate acid balance of plasma
Secretion of a variety of hormones and autacoids:
Erythropoietin
Renin
Prostaglandins
Nephron
Renal Corpuscle
Glomerulus
Renal Capsule (Bowman’s Capsule )
Bowman’s Space
Juxtaglomerular apparatus
Renal Tubule
Schematic representation of a glomerular lobe
Mesangium
A supporting structure in the center of the lobe
Consisting of mesangial cells & mesangial matrix
Functions:
Being contractile
Being phagocytic
Being capable of proliferation
Synthesize both matrix & collagen
Secreting a number of biologically active mediators
Filtering membrane consisting of
A thin layer of fenestrated endothelial cells
A glomerular basement membrane (GBM)
The visceral epithelial cells (podocyte) Filtering depended on Volume Charge
Bowman’s capsule & Bowman’s space
Bowman’s capsule:
Visceral epitheliumParietal epithelium
Bowman’s space (the urinary space)
A cavity in which plasma filtrate first collects
Disorders of the Kidney
Congenital– Malformations, ectopic, cysts,
dysplasia.
Acquired– Glomerular diseases
– Tubulointerstitial diseases
– Renal calculi
– Neoplasms – carcinoma
Glomerular Diseases(Glomerulonephritis,GN)
Primary Glomerular Diseases
Secondary to Systemic Diseases
Hereditary Disorders
Primary GNAcute diffuse proliferative glomerulonephritis
Rapidly progressive (crescentic) glomerulonephritis
Membranous glomerulopathy
Minimal change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
Mesangioproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis
Secondary GN
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
Hereditary Disorders
Alport syndrome
Thin basement membrane disease
Fabry disease
Immune Mechanisms
Antibody-Mediated Injury
In Situ Immune Complex
Circulating Immune Complex Deposition
Cell-mediated Immune Injury
Activation of Alternative Complement Pathway
Pathogenesis of Glomerular Injury
Antibody-mediated glomerular injury can result either from the deposition of circulating immune complexes (A) or, more commonly, from in situ formation of complexes exemplified by anti-GBM disease (B) or Heymann nephritis (C)
Two patterns of deposition of immune complexes as seen by immunofluorescence microscopy: granular, characteristic of circulating immune complex nephritis and linear, characteristic of in situ immune complex nephritis
肾小球损伤的机制
抗体介导的免疫损伤:主要通过补体和白细胞介导的途径发挥作用
大多数抗体介导的肾炎由循环免疫复合物沉积引起,免疫荧光呈颗粒状
抗 GBM 成分的自身抗体可引起抗 GBM 性肾炎,免疫荧光呈线性分布
抗体可与植入肾小球的抗原发生反应,形成原位免疫复合物,免疫荧光呈颗粒状
Basic Histologic Alteration
肾活检:
1. 光镜
特殊染色:
过碘酸 -Schiff ( PAS )染色:糖原和糖蛋白染成红色,可显示基膜和系膜基质
过碘酸六胺银( PASM) 染色:基膜、系膜基质及 IV 型胶原显黑色,可更好地显示基膜等结构
Masson 三色染色:基膜和胶原显蓝色或绿色,免疫复合物、血浆和纤维素显红色,可显示特殊蛋白性物质、胶原纤维等
Fibrin 染色:显示血栓和纤维素样坏死
2. 免疫荧光:显示免疫球蛋白和补体成分沉积
3. 透射电镜:超微结构改变和免疫复合物沉积状况及部位
Hypercellularity: 系膜细胞和内皮细胞、炎症细胞、壁层上皮细胞Basement Membrane Thickening and RuptureInflammatory Exudate and Necrosis :中性粒细胞和纤维素渗出,纤维素样坏死,血栓形成Hyalinization and Sclerosis : 玻璃样变:均质的嗜酸性物质沉积,成分为沉积的血浆蛋白、增厚的基膜和增多的系膜基质 硬化:系膜区和(或)毛细血管袢细胞外胶原数量增多肾小管和间质的改变: 肾小管上皮细胞变性,管腔内出现管型、萎缩和消失 间质充血、水肿和炎细胞浸润、纤维化
Basic Histologic Alteration
Syndromes
Nephritic syndrome
Rapid progressive nephritic syndrome
Chronic nephritic syndrome
Nephrotic syndrome
ProteinuriaHematuria Edema HypertensionAzotemia
Features
Hypoproteinemia
Hyperlipidemia
Oliguria Anuria
Polyuria Nocturia Isosthenuria
Clinical Manifestations
Asymptomatic hematuria or proteinuria
Azotemia Renal function failure
HypertensionAnemia Azotemia Uremia
Proteinuria Edema
Major Primary GN
Acute proliferative GN
Rapidly Progressive GN
Membranous Nephropathy
Minimal-change GN
Membranoproliferative GN
IgA Nephropathy
Chronic GN
Acute Proliferative GN
Acute Proliferative GN
Postinfectious GN : Poststreptococcal GN
Nonstreptococcal GN
Appears usually 1-4 weeks after a group A β-hemolytic streptococcal pha
ryngeal or skin infection
Occurs most frequently in children 6-10 years old
Characterized histologically by diffuse proliferation of glomerular cells (e
ndothelial cells and Mesangial cells) with infiltration of leukocytes
Caused by deposition of immune complexes:Inciting Ag may be exogenous or endogenous
Morphology
大红肾 蚤咬肾
Enlarged kidneys slightly with scattered petechial hemorrhages
Hypercellularity: proliferation of Mesangial cells Endothelial cells Enlarged glomeruli-diffuseInfiltrated by WBC’s (neutrophils and monocytes)Compression of glomerular capillary lumina
Granular deposits of IgG, IgM & C3 in the mesangium & along the GBM
Electron dense deposits –subepithelial “humps”
Clinical Manifestation
Acute Nephritic Syndrome
血尿: 30% 肉眼血尿,红细胞管型 水肿:肾小球滤过率降低,水、钠潴留 高血压:轻 - 中度,水、钠潴留,血容量增加 > 95% of children completely recover
30-50% of adults suffer progressive renal disease
Rapidly Progressive GN
Crescentic GN
Characterized clinically by rapid & progressive loss of renal function with severe oliguria
Death from renal failure within weeks to months if untreated
Is a syndrome associated with severe glomerular injury and does not denote a specific etiologic form of glomerulonephritis
Type I RPGN (Anti-GBM Antibody) Idiopathic Goodpasture syndrome ( 肺出血 - 肾炎综合征)
Type II RPGN (Immune Complex) Idiopathic Postinfectious Systemic lupus erythematosus Henoch-Schönlein purpura (IgA) Others
Type III RPGN (Pauci-Immune) ANCA associated Idiopathic Wegener granulomatosis Microscopic polyarteritis
Morphology
The kidneys are enlarged and pale, often with petechial hemorrhages on the cortical surfaces
Morphology
Crescent formation by proliferation of
parietal cells and infiltration of WBC’s &
fibrin
deposition in Bowman’s space
EM reveals focal disruptions in the GBM
fibrinoid necrosis in the wall of capillary
cellular crescent
fibrous crescent
Clinical Manifestation
acute nephritic syndrome occasionally, nephrotic Syndrome
ANCA, anti-GBM & antinuclear Ab’s are helpful in diagnosis
Poor prognosis steroids, cytotoxic drugs & longterm d
ialysis or renal transplantation
肾病综合征相关肾炎肾小球毛细血管壁损伤
蛋白尿(≥ 3.5 g/day )
选择性蛋白尿(主要为低分子量的白蛋白和转铁蛋白)
非选择性蛋白尿(严重时大分子量蛋白也滤过)
低蛋白血症( < 3 g/dl )
血浆胶体渗透压降低
血容量下降,醛固酮和抗利尿激素分泌增加,水钠潴留
水肿
刺激肝脏合成脂蛋白
脂质颗粒运送障碍
外周脂蛋白分解障碍
高脂血症
脂尿
Membranous Nephropathy
Membranous Nephropathy
Main cause of nephrotic syndrome in adults
Characterized by diffuse thickening of the GBM & the accumulation of electron-dense immunoglobulin-containing deposits
Primary membranous GN (85% of cases)
Secondary membranous GN
Drugs (e.g., penicillamine, NSAIDs)
Malignancies (esp. carcinoma of lung & colon,
melanoma)
SLE
Infections (e.g. hepatitis B & C, syphilis)
Hashimoto thyroiditis
Primary membranous GN is caused by autoantibodies directed against an Ag on the visceral epithelial cells
Secondary membranous GN is caused by deposition of immune complexes
大白肾
Diffuse thickening of glomerular capillary wall
Spikes can be seen by silver stains
Granular deposits of Ig’s & complements
Subepithelial deposits
Important to rule out secondary ca
uses proteinuria is nonselective &
does not usually respond well to co
rticosteroids
Course is variable but generally ind
olent
Only ~ 10% die or progress to CRF
within 10 years
IgA Nephropathy
Berger Disease
Characterized by presence of prominent de
posits of IgA in the mesangium
Most common type of GN worldwide
Affects children & young adults
Present with hematuria often after a respirat
ory infection
Abnormality of immune regulation ⇒ mucosal IgA synthesis in response to respiratory or GI exposure to environmental antigens
IgA & IgA immune complexes are entrapped in the mesangium ⇒ activation of alternative complement pathway ⇒ glomerular injury
Considerable variation on LM: glomeruli may appear normal, may exhibit mesangioproliferative GN, focal proliferative GN or rarely crescentic GN
Mesangial cellularity and matrix increased, and there was a thickening of the glomerular basement membrane
Mesangial deposition of IgA, often with C3 & properdin
Affects children & young adults
Slow progression to CRF in 15-40%
of cases in 20 years
IgA deposits recur in 20-60% of allo
grafts
Chronic GN
Chronic sclerosing glomerulonephritis
The result of a number of specific types of glom
erulonephritis
Certain types of glomerulonephritis are more lik
ely to progress to chronic GN than others
Some cases of chronic GN arise mysteriously wi
th no antecedent history of any of the well-recog
nized forms of glomerulonephritis End-stage renal disease
30%
50-80%
50%
Nephropathy
1-2%
90%
50%
Granular Contracted Kidney
The kidneys are symmetrically small The outer surface is diffusely granular On section, the cortex is thin and there is in
crease in peripelvic fat
Hyalinization and fibrosis of the most of the glomeruli Compensatory hypertrophy & tubular dilatation of the
remained glomeruli Arterial & arteriolar sclerosis Interstitial chronic inflammation and fibrosis
肾小球、小动脉玻璃样变
临床病理联系
早期:食欲差、贫血、呕吐、乏力等 多尿、夜尿和低比重尿:残留肾单位滤过
增加但重吸收有限 高血压:肾素分泌增多 贫血:促红细胞生成素分泌减少 氮质血症和尿毒症:心外膜炎、胃肠炎
Tubulointerstitial Nephritis
肾小管 - 间质性肾炎
Characterized by histologic and functional alterati
ons that involve predominantly the tubules and int
erstitium
Primary: Infections, Toxins, et al.
Secondary: Disease of glomerulus, Metabolic Dise
ases, Vascular Diseases, et al.
急性:间质水肿、间质和肾小管内中性粒细胞等炎症细胞浸润,常伴局灶性肾小管坏死
慢性:淋巴细胞、单核细胞浸润,肾间质纤维化和肾小管萎缩
Pyelonephritis
Inflammation in renal pelvis, interstitium, and tubules
Acute: Bacterial infections
Ascending infection
Chronic: Bacterial infections,
Vesicoureteral reflux
Urinary obstruction
G¯ bacilli (E coli ) Pathways: Ascending infection: Hematoge
nous infection
易发生于上极和下极:此处肾乳头为扁平凹面状,中部乳头开口为凸面状
Predisposing Factors Systemic Defense mechnisms Local : Urinary tract obstruction Urinary tract mucosa injury Vesicoureteral reflux
Acute Pyelonephritis
Acute Suppurative Inflammation
Patchy interstitial suppurative inflammation
Intratubular aggregates of neutrophils Tubular necrosis
Acute pyelonephritis marked by an acute neutrophilicexudate within tubules and the renal substance
并发症 肾乳头坏死( papillary necrosis) 可发生急性肾衰
Papillary necrosis. Areas of pale gray necrosis arelimited to the papillae( 常见于伴有糖尿病或尿路阻塞患者)
Perinephric abscesses
Pyonephrosis
临床病理联系
起病急 发热、寒战、白细胞增多腰部酸痛、肾区叩击痛 尿道刺激症:尿频、尿急和尿痛 尿检:脓尿、蛋白尿、管型尿和菌尿、 可有血尿、白细胞管型一般无高血压、氮质血症和肾功能障碍
Chronic Pyelonephritis
肾小管 - 间质慢性炎症慢性间质性炎症、纤维化和瘢痕形成常伴肾盂和肾盏的纤维化和变形是慢性肾衰的常见原因之一
发病机制
反流性肾病( reflux nephropathy ) chronic reflux-associated pyelonephritis 多于儿童期发病,单侧或双侧 膀胱输尿管反流或肾内反流慢性阻塞性肾盂肾炎( chronic obstructive
pyelonephritis ) 双侧或单侧 尿液潴留使反复发作,形成大量瘢痕
病理变化
一侧或双侧肾体积缩小,出现不规则瘢痕 切面皮髓质分界不清,肾乳头萎缩,肾盏肾盂变形,黏膜粗糙
肾小管和肾间质的慢性非特异性炎 局灶淋巴细胞、浆细胞浸润,间质纤维化 肾小管萎缩 /扩张,可出现胶样管型 肾内细动脉因高血压玻璃样变、硬化 后期肾小球可纤维化、玻璃样变,肾球囊周纤维化
临床病理联系
常缓慢起病,可反复急性发作 多尿和夜尿:肾小管尿浓缩功能下降和丧失 低钠、低钾、代谢性酸中毒 :钠、钾和重碳酸盐丧失 高血压:肾素分泌增加 氮质血症、尿毒症:晚期
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