徐芳英 (xfy@zju.edu.cn)

Diseases of the

Kidney

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

Thank You