Transcript 慢性肾小球肾炎

The Kidney
Zhu keqing 竺可青
Pathology Department
Zhejiang University School of Medicine
2011-3
Glomerular Diseases
Primary Glomerulopathies 原发性
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Acute diffuse proliferative glomerulonephritis
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Poststreptococcal
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Non-poststreptococcal
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Rapidly progressive (crescentic) glomerulonephritis
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Membranous glomerulopathy
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Minimal change disease
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Focal segmental glomerulosclerosis
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Membranoproliferative glomerulonephritis
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IgA nephropathy
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Chronic glomerulonephritis
Systemic Diseases with Glomerular Involvement 继发性
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Systemic lupus erythematosus
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Diabetes mellitus
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Amyloidosis
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Goodpasture syndrome
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Microscopic polyarteritis/polyangiitis
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Wegener granulomatosis
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Henoch-Schönlein purpura
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Bacterial endocarditis
Hereditary Disorders
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Alport syndrome
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Thin basement membrane disease
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Fabry disease
肾小球组织学
• 肾小球由毛细血管丛及肾球囊构成，前者是毛细血管袢，后者壁薄衬
以单层扁平上皮（脏层与壁层上皮；二者间为腔。）
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肾小球的超微结构
肾小球囊的脏层存在肾小球滤过膜，有三层组织结构， 包含
内侧为连续性不强的内皮细胞层；
中间是基膜，是粘多糖形成的网架；
外侧为多数足突附着于基膜，其间见甚薄的空隙，称滤过隙。
• 足突是脏层上皮（足细胞）的最后胞突分枝。
• 血管袢的中央有系膜细胞及其基质。
Glomerular filter consisting, from bottom to top, of fenestrated endothelium,
basement membrane, and foot processes of epithelial cells.
Immune Mechanisms of Glomerular Injury
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In Situ Immune Complex Deposition
Fixed intrinsic tissue antigens
NC1 domain of collagen type IV antigen (anti-GBM nephritis)
Heymann antigen (membranous glomerulopathy)
Mesangial antigens
Planted antigens
Exogenous (infectious agents, drugs)
Endogenous (DNA, nuclear proteins, immunoglobulins, immune complexes,
IgA)
Circulating Immune Complex Deposition
Endogenous antigens (e.g., DNA, tumor antigens)
Exogenous antigens (e.g., infectious products)
Antibody-Mediated Injury
Cell-Mediated Immune Injury
Activation of Alternative Complement Pathway
病因
• 肾小球肾炎简称肾炎，是由于各种免疫复合物引起的两侧肾脏肾小球
弥漫性增生性炎，属Ⅲ型变态反应，即免疫复合物肾炎。
（一）抗原
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1．内源性抗原 包括肾小球性（肾小球基底膜抗原、足细胞的足突抗原、
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内皮细胞和系膜细胞的细胞膜抗原等）和非肾小球性（DNA、核抗原、免疫
球蛋白、肿瘤抗原等）。
2．外源性抗原 生物性病原体，最常见是链球菌感染后的产物，肝炎病毒、
疟疾以及药物、异种血清也可成为抗原。
（二）免疫复合物类型
– 肾小球原位免疫复合物 占10%。肾小球基膜内固有的或植入的抗原成分
与循环中的抗体结合，形成复合物。免疫荧光检查呈光滑线形荧光。
– 循环免疫复合物 占90%。由外源性抗原或非肾小球性内源性抗原和相应
的抗体结合，随血流经肾小球时沉积于局部。免疫荧光检查呈不连续的
颗粒状荧光。
发病机理
• 免疫复合物激活补体,进而激活白细胞,白细
胞释放氧自由基,蛋白酶及花生四烯酸等,引
起肾小球的损伤,导致增生性渗出性炎.
• 免疫复合物通过作用于血小板,系膜细胞及单
核细胞,使细胞因子产生增加, 损伤肾小球,导
致增生性渗出性炎.
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). D and E,
Two patterns of deposition of immune complexes as seen by immunofluorescence microscopy: granular, characteristic
of circulating and in situ immune complex nephritis (D) and linear, characteristic of classic anti-GBM disease (E).
Epithelial cell injury.
The postulated sequence is a consequence of antibodies against epithelial cell antigens, toxins,
cytokines, or other factors causing injury with foot process effacement and sometimes detachment of
epithelial cells and protein leakage through defective GBM and filtration slits.
Mediators of Glomerular Injury
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1 Neutrophils and monocytes infiltrate the glomerulus in certain types of glomerulonephritis,
largely owing to activation of complement, resulting in generation of chemotactic agents (mainly
C5a), but also by Fc-mediated adherence and activation. Neutrophils release proteases, which
cause GBM degradation; oxygen-derived free radicals, which cause cell damage; and arachidonic
acid metabolites, which contribute to the reductions in glomerular filtration rate (GFR).
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2 Macrophages, T lymphocytes, and natural killer (NK) cells, which infiltrate the glomerulus in
antibody- and cell- mediated reactions, when activated release a vast number of biologically
active molecules.
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3 Platelets aggregate in the glomerulus during immune-mediated injury. Their release of
eicosanoids and growth factors may contribute to the manifestations of glomerulonephritis.
Antiplatelet agents have beneficial effects in both human and experimental glomerulonephritis.
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4 Resident glomerular cells, particularly mesangial cells, can be stimulated to produce several
inflammatory mediators, including reactive oxygen species, cytokines, chemokines, growth factors,
eicosanoids, nitric oxide , and endothelin. In the absence of leukocytic infiltration, they may initiate
inflammatory responses in the glomerulus.
Soluble Mediators 可溶性介质
Virtually all the known inflammatory chemical mediators have been implicated in glomerular injury.
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The chemotactic complement components induce leukocyte influx (complement-neutrophildependent injury) and lead to formation of C5b-C9, the lytic component. C5b-C9 causes cell lysis
but, in addition, stimulates mesangial cells to produce oxidants, proteases, and other mediators.
Thus, even in the absence of neutrophils, C5b-C9 can cause proteinuria.
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Eicosanoids, nitric oxide , angiotensin, and endothelin are involved in the hemodynamic changes.
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Cytokines, particularly interleukin-1 and tumor necrosis factor, which may be produced by
infiltrating leukocytes and resident glomerular cells, induce leukocyte adhesion and a variety of
other effects.
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Chemokines such as monocyte chemoattractant protein 1 (MCP-1) and RANTES promote
monocyte and lymphocyte influx. Growth factors, such as platelet-derived growth factor, are
involved in mesangial cell proliferation. Transforming growth factor (TGF)-β and fibroblast growth
factor appear to be critical in the ECM deposition and hyalinization leading to glomerulosclerosis
in chronic injury.
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The coagulation system is also a mediator of glomerular damage. Fibrin is frequently present in
the glomeruli in glomerulonephritis, and fibrin may leak into Bowman space, serving as a stimulus
for parietal epithelial cell proliferation (crescent formation).
Mediators of immune glomerular injury including cells and soluble mediators
Mechanisms of chronic tubulointerstitial injury in glomerulonephritis.
Various components of the protein-rich filtrate and cytokines derived from leukocytes cause
tubular cell activation and secretion of cytokines, growth factors, and other mediators. These,
together with products of macrophages, incite interstitial inflammation and fibrosis. ET-1,
endothelin-1, PAI-1, plasminogen activator inhibitor-1; TIMP-1, tissue inhibitor of
metalloproteinases.
Various types of glomerulonephritis are characterized by one or more of four basic tissue reactions
基本病理变化
Hypercellularity. 增生性炎症
• Cellular proliferation of mesangial or endothelial cells
• Leukocytic infiltration, consisting of neutrophils, monocytes, and, in some
diseases, lymphocytes
• Formation of crescents.
Basement Membrane Thickening.
Hyalinization and Sclerosis.
Chronic renal failure progresses through four stages that merge into one another.
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In diminished renal reserve, the GFR is about 50% of normal. Serum BUN and
creatinine values are normal, and the patients are asymptomatic. However, they are
more susceptible to developing azotemia with an additional renal insult.
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In renal insufficiency, the GFR is 20% to 50% of normal. Azotemia appears, usually
associated with anemia and hypertension. Polyuria and nocturia can occur as a result
of decreased concentrating ability. Sudden stress (e.g., with nephrotoxins) may
precipitate uremia.
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In renal failure, the GFR is less than 20% to 25% of normal. The kidneys cannot
regulate volume and solute composition, and patients develop edema, metabolic
acidosis, and hypocalcemia. Overt uremia may ensue, with neurologic,
gastrointestinal, and cardiovascular complications.
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In end-stage renal disease, the GFR is less than 5% of normal; this is the terminal
stage of uremia.
Clinical syndrome
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Acute nephritic syndrome
Rapidly progressive nephritic syndrome
Nephrotic syndrome
Asymptomatic hematuria or proteinuria
Chronic nephritic syndrome
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Acute renal failure
Chronic renal failure
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Renal tubular defects
Urinary tract infection
Nephrolithiasis (renal stone)
Urinary tract obstruction and renal tumors
The Glomerular Syndromes
1. Acute nephritic Syndrome
Hematuria, azotemia, variable proteinuria, oliguria, edema, and hypertension
2. Rapidly progressive glomerulonephritis
Acute nephritis, proteinuria, and acute renal failure
3. Nephrotic syndrome
>3.5 gm proteinuria, hypoalbuminemia,hyperlipidemia, lipiduria
4. Chronic renal failure
Azotemia → uremia progressing foryears
5. Asymptomatic hematuria or proteinuria
Glomerular hematuria; subnephrotic proteinuria
1 Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis
Morphology.
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The classic diagnostic picture is one of enlarged, hypercellular glomeruli大红肾/蚤
咬肾. The hypercellularity is caused by
(1) infiltration by leukocytes, both neutrophils and monocytes;
(2) proliferation of endothelial and mesangial cells; and
(3) in severe cases by crescent formation.
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By immunofluorescence microscopy, there are granular deposits of IgG, IgM, and
C3 in the mesangium and along the basement membrane. Although almost
universally present, they are often focal and sparse.
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The characteristic electron microscopic findings are discrete, amorphous,
electron-dense deposits on the epithelial side of the membrane, often having the
appearance of "humps", presumably representing the antigen- antibody complexes at
the epithelial cell surface. Subendothelial and intramembranous deposits are also
commonly seen, and mesangial deposits may be present.
Acute proliferative glomerulonephritis.
A, Normal glomerulus.
B, Glomerular hypercellularity is due to intracapillary leukocytes and proliferation
of intrinsic glomerular cells.
C, Typical electron-dense subepithelial "hump" and a neutrophil in the lumen.
Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis
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More than 95% of affected children eventually recover totally with conservative
therapy aimed at maintaining sodium and water balance.
A small minority of children (perhaps less than 1%) do not improve, become severely
oliguric, and develop a rapidly progressive form of glomerulonephritis.
Some of the remaining patients may undergo slow progression to chronic
glomerulonephritis with or without recurrence of an active nephritic picture.
Prolonged and persistent heavy proteinuria and abnormal GFR mark patients with an
unfavorable prognosis.
In adults, the disease is less benign.
Although the overall prognosis in epidemics is good, in only about 60% of sporadic
cases do the patients recover promptly.
In the remainder, the glomerular lesions fail to resolve quickly, as manifested by
persistent proteinuria, hematuria, and hypertension. In some of these patients, the
lesions eventually clear totally, but others develop chronic glomerulonephritis. Some
patients will develop a syndrome of rapidly progressive glomerulonephritis.
急性弥漫性毛细血管内增生性肾小球肾炎（小结）
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Diffuse endocapillary proliferativeglomerulonephritis
简称急性肾炎，很常见，小儿多，病理属急性增生性炎症，属变态反应。大多数与溶血性链菌感染
有关，故又称链球菌感染后肾炎。
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1．病理变化
光镜：
增生性病变：双侧肾脏几乎全部肾小球的体积增大，细胞核数目增多（密集，深染）致使毛细血管
腔狭窄。
渗出性病变：有少许中性白细胞、少量纤维素渗出及红细胞（有时红细胞甚多）漏出到球囊腔内。
变质性病变：肾小管浊肿
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肉眼：大红肾，蚤咬肾。
电镜：见血管间质细胞及内皮细胞增生；足突下基膜上有散在的驼峰样免疫复合物沉积。
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2．临床病理联系
急性肾炎综合征
少尿、无尿
蛋白尿、管型尿、血尿
水肿
高血压
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3．结果
95%以上患者治愈，少数转为慢性，极少数发展为快速进行性肾炎。
2 RAPIDLY PROGRESSIVE (CRESCENTIC) GLOMERULONEPHRITIS
Rapidly progressive glomerulonephritis (RPGN) is a syndrome associated with
severe glomerular injury and does not denote a specific etiologic form of
glomerulonephritis.
It is characterized clinically by rapid and progressive loss of renal function associated
with severe oliguria and (if untreated) death from renal failure within weeks to months.
Regardless of the cause, the classic histologic picture is characterized by the
presence of crescents in most of the glomeruli (crescentic glomerulonephritis).
These are produced in part by proliferation of the parietal epithelial cells lining
Bowman capsule and in part by infiltration of monocytes and macrophages.
Rapidly Progressive Glomerulonephritis (RPGN)
Type I RPGN (Anti-GBM Antibody)
• Idiopathic
• Goodpasture syndrome
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 nodosa/microscopic polyangiitis
Rapidly Progressive Glomerulonephritis (RPGN)
Morphology.
• The kidneys are enlarged and pale, often with petechial hemorrhages on
the cortical surfaces. 大白肾
• The histologic picture, however, is dominated by the formation of distinctive
crescents. Crescents are formed by proliferation of parietal cells and by
migration of monocytes and macrophages into the urinary space.
• The crescents eventually obliterate Bowman space and compress the
glomerular tuft. Fibrin strands are prominent between the cellular layers
in the crescents;
• Electron microscopy may, as expected, disclose subepithelial deposits in
some cases, but in many cases, it shows distinct ruptures in the GBM, the
severe injury that allows leukocytes, proteins, and inflammatory mediators
into the urinary space, where they trigger the crescent formation.
• By immunofluorescence microscopy, postinfectious cases exhibit granular
immune deposits; Goodpasture syndrome cases show linear fluorescence
for immunoglobulin and complement.
Crescentic glomerulonephritis (PAS stain).
Note the collapsed glomerular tufts and the crescent-shaped mass of
proliferating cells and leukocytes internal to Bowman capsule.
Clinical Course.
• In Goodpasture syndrome, the course may be dominated by recurrent
hemoptysis or even life-threatening pulmonary hemorrhage. Serum
analyses for anti-GBM antibodies, antinuclear antibodies, and ANCA are
helpful in the diagnosis of specific subtypes.
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Although milder forms of glomerular injury may subside, the renal
involvement is usually progressive over a matter of weeks and culminates in
severe oliguria.
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Recovery of renal function may follow early intensive plasmapheresis 血透
(plasma exchange) combined with steroids and cytotoxic agents in
Goodpasture syndrome.
This therapy appears to reverse both pulmonary hemorrhage and renal
failure.
Other forms of RPGN also respond well to steroids and cytotoxic agents.
Despite therapy, patients may eventually require chronic dialysis or
transplantation.
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Rapidly progressive glomerulonephritis.
Electron micrograph showing characteristic wrinkling of GBM with
focal disruptions in its continuity (arrows).
快速进行性肾小球肾炎（小结）
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又称弥漫性新月体性肾小球肾炎（diffuse crecsentic glomerulonephritis）。临床经过发展迅速，常
因少尿无尿、肾功能进行性障碍性在短期内（数周或数月）死亡。25%由急性肾炎转化而来，25%
合并抗基底膜肾炎，50%原因未明。
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1．病理变化
光镜：
肾小球囊壁层上皮增生，与与渗出的单核细胞形成新月体（细胞性新月体），随后纤维化并与毛细
血管袢粘连（纤维性新月体），致肾小球快速纤维化、玻璃样变。阻塞尿液出口。
肉眼：大白肾
电镜：一些病例有免疫复合物沉积，全部病例发现有基底膜局灶性破裂。
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2．临床联系
快速进行性肾炎综合征：
少尿、无尿。
血尿、蛋白尿严重。
快速进行性肾功能衰竭。
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3．结果
（1）预后极差，80%病例在半年内死亡。
预后取决新月体出现数量：50%新月体者预后较好；50-80%新月体者发展缓慢；80-90%新月体者
死亡。
（2）转为慢性硬化性肾小球肾炎
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3 The manifestations of the nephrotic syndrome include:
• Massive proteinuria, with the daily loss of 3.5 gm or more of protein
(less in children)
• Hypoalbuminemia, with plasma albumin levels less than 3 gm/dL
• Generalized edema
• Hyperlipidemia and lipiduria
Causes of Nephrotic Syndrome
Prevalence (%)
Children
Adults
Primary Glomerular Disease
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Membranous glomerulopathy
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30
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Minimal change disease
65
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Focal segmental glomerulosclerosis
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35
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Membranoproliferative glomerulonephritides
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Other proliferative glomerulonephritis
(focal,"pure mesangial," IgA nephropathy)
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Systemic Diseases
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Diabetes mellitus
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Amyloidosis
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Systemic lupus erythematosus
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Drugs (nonsteroidal anti-inflammatory, penicillamine , "street heroin")
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Infections (malaria, syphilis, hepatitis B and C, acquired immunodeficiency syndrome)
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Malignant disease (carcinoma, lymphoma)
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Miscellaneous (bee-sting allergy, hereditary nephritis)
1 MEMBRANOUS GLOMERULOPATHY (MEMBRANOUS NEPHROPATHY)
• Membranous glomerulopathy is the most common cause of the
nephrotic syndrome in adults.
• It is characterized by diffuse thickening of the glomerular capillary
wall and the accumulation of electron-dense, immunoglobulincontaining deposits along the subepithelial side of the basement
membrane.
Membranous glomerulopathy
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Membranous glomerulopathy occurring in association with other systemic diseases
and a variety of identifiable etiologic agents is referred to as secondary membranous
glomerulopathy. The most notable such associations are as follows:
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Drugs (penicillamine , captopril , gold, nonsteroidal anti-inflammatory drugs [NSAIDs]):
1% to 7% of patients with rheumatoid arthritis treated with penicillamine or gold
(drugs now used infrequently for this purpose) develop membranous glomerulopathy.
Underlying malignant tumors, particularly carcinoma of the lung and colon and
melanoma. According to some investigators, these are present in up to 5% to 10% of
adults with membranous glomerulopathy.
SLE. About 15% of glomerulonephritis in SLE is of the membranous type.
Infections (chronic hepatitis B, hepatitis C, syphilis, schistosomiasis, malaria)
Other autoimmune disorders, such as thyroiditis
In about 85% of patients, no associated condition can be uncovered, and the disease
is considered idiopathic.
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Membranous glomerulonephritis.
A, PAS stain. Note the marked diffuse thickening of the capillary wall without an increase
in the number of cells.
B, Electron micrograph showing electron-dense deposits (arrow) along the epithelial side
of the basement membrane (B). Note the obliteration of foot process overlying deposits.
CL, capillary lumen; End, endothelium; Ep, epithelium.
Membranous glomerulonephritis
C, Characteristic granular immunofluorescent deposits of IgG along GBM.
D, Diagrammatic representation of membranous glomerulonephritis.
Clinical Course of Membranous glomerulonephritis
• In a previously healthy individual, this disorder usually begins with
the insidious onset of the nephrotic syndrome or, in 15% of patients,
with non-nephrotic proteinuria. Hematuria and mild hypertension are
present in 15% to 35% of cases.
• It is necessary in any patient to first rule out the secondary causes
described earlier, since treatment of the underlying condition
(malignant neoplasm, infection, or SLE) or discontinuance of the
offending drug can reverse progression.
• The course of the disease is variable but generally indolent. In
contrast to minimal change disease, the proteinuria is nonselective
and does not usually respond well to corticosteroid therapy.
• Progression is associated with increasing sclerosis of glomeruli,
rising BUN reflecting renal insufficiency, and development of
hypertension.
• Although proteinuria persists in more than 60% of patients, only
about 10% die or progress to renal failure within 10 years, and no
more than 40% eventually develop renal insufficiency.
• Concurrent sclerosis of glomeruli in the renal biopsy at the time of
diagnosis is a predictor of worse prognosis.
弥漫性膜性肾小球肾炎（小结）
• 弥漫性膜性肾小球肾炎(diffuse membranous
glomerulonephritis)简称膜性肾炎，认为是早期性肾炎，进
展较慢。
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1.病理改变
光镜：弥漫性肾小球血管基底膜增厚（白金耳样）
肉眼：大白肾
电镜：“屋顶+大钉”，即大量屋顶形沉积物加上基膜物质
向外刺状增生。二者结合基膜因而增厚。晚期更厚，虫蚀样。
• 2.临床病理联系
• 典型肾病综合症：高度蛋白尿。高度水肿。高脂血症和脂尿。
低血浆白蛋白
• 3.结果 病程发展较慢，大多数病例晚期肾小球纤维化，
40%病例死于肾衰。一些病例可治愈。
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MINIMAL CHANGE DISEASE (LIPOID NEPHROSIS)
• This relatively benign disorder is the most frequent cause of
nephrotic syndrome in children, but it is less common in adults.
• It is characterized by diffuse effacement of foot processes of
epithelial cells in glomeruli that appear virtually normal by light
microscopy. 弥漫性上皮细胞足突消失
• The peak incidence is between 2 and 6 years of age. The disease
sometimes follows a respiratory infection or routine prophylactic 预
防immunization.
• Its most characteristic feature is its usually dramatic response to
corticosteroid therapy.
MINIMAL CHANGE DISEASE (LIPOID NEPHROSIS)
Etiology and Pathogenesis
• Several features of the disease point to an immunologic basis, including
• (1) the clinical association with respiratory infections and prophylactic
immunization;
• (2) the response to corticosteroids and/or other immunosuppressive therapy;
(3) the association with other atopic遗传过敏 disorders (e.g., eczema湿疹,
rhinitis鼻炎);
• (4) the increased prevalence of certain HLA haplotypes in patients with
minimal change disease associated with atopy (suggesting a genetic
predisposition);
• (5) the increased incidence of minimal change disease in patients with
Hodgkin disease, in whom defects in T cell-mediated immunity are well
recognized.
Morphology.
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The glomeruli are normal by light microscopy. By electron microscopy, the
basement membrane appears normal, and no electron-dense material is
deposited.
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The principal lesion is in the visceral epithelial cells, which show a
uniform and diffuse effacement of foot processes足突病。
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The visceral epithelial changes are completely reversible after corticosteroid
therapy, concomitant with remission免除 of the proteinuria.
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The cells of the proximal tubules are often laden with lipid and protein,
reflecting tubular reabsorption of lipoproteins passing through diseased
glomeruli (thus, the historical term lipoid nephrosis). 脂性肾病
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Immunofluorescence studies show no immunoglobulin or complement
deposits.
Minimal change disease
Minimal change disease
Clinical Course
• Despite massive proteinuria, renal function remains good, and there
is commonly no hypertension or hematuria. The proteinuria usually
is highly selective, most of the protein consisting of albumin.
• Most children (more than 90%) with minimal change disease
respond rapidly to corticosteroid therapy. However, the nephrotic
phase may recur, and some patients may become steroid
dependent or resistant.
• Nevertheless, the long-term prognosis for patients is excellent, and
even steroid-dependent disease resolves when children reach
puberty. 青春期
• Although adults are slower to respond, the long-term prognosis is
also excellent. 预后好
轻微病变性肾小球肾炎（小结）
• 轻微病变性肾小球肾炎（minimal change glomerulonephritis）又称
脂性肾病(lipoid nephrosis)。
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1．病理变化
肉眼：大白肾
光镜：肾小球无明显改变，肾小管脂肪变。
电镜：肾小球仅见足突融合，无沉积物或其它改变。
• 2．临床联系：
• 肾病综合症：高蛋白尿。高度水肿。高脂血症和脂尿。低血浆白蛋白
• 3．结果
• 本病多见小儿，用可的松治疗，90%患儿可被治愈。
3
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
•
As the name implies, this lesion is characterized by sclerosis of some, but
not all, glomeruli (thus, it is focal); and in the affected glomeruli, only a
portion of the capillary tuft is involved (thus, it is segmental).
•
Focal segmental glomerulosclerosis is frequently accompanied clinically by
the nephrotic syndrome or heavy proteinuria.
Classification and Types
Focal segmental glomerulosclerosis (FSGS) occurs in the following settings:
• In association with other known conditions, such as HIV infection (HIV
nephropathy), heroin addiction (heroin nephropathy), sickle cell disease, and
massive obesity.
•
As a secondary event, reflecting glomerular scarring, in cases of focal
glomerulonephritis (e.g., IgA nephropathy)
•
As a component of the adaptive response to loss of renal tissue (renal ablation) in
advanced stages of other renal disorders, such as reflux nephropathy, hypertensive
nephropathy, or with unilateral renal agenesis
•
In certain inherited forms of nephrotic syndrome where the disease, in some
pedigrees, has been linked to mutations in genes encoding nephrin, podocin, or αactinin 4.
•
As a primary disease (idiopathic focal segmental glomerulosclerosis)
FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Morphology
•
By light microscopy, the segmental lesions may involve only a minority of the
glomeruli and may be missed if the biopsy specimen contains an insufficient number
of glomeruli. Lipid droplets and foam cells are often present.
•
On electron microscopy, both sclerotic and nonsclerotic areas show the diffuse
effacement of foot processes characteristic of minimal change disease, but in addition,
there may be focal detachment of the epithelial cells with denudation剥脱 of the
underlying GBM.
•
By immunofluorescence microscopy, IgM and C3 may be present in the sclerotic
areas and/or in the mesangium. In time, this leads to total sclerosis of glomeruli, with
pronounced tubular atrophy and interstitial fibrosis.
Focal segmental glomerulosclerosis, PAS stain.
A, Low-power view showing segmental sclerosis in one of three glomeruli (at 3
o'clock).
B, High-power view showing hyaline insudation and lipid (small vacuoles) in
sclerotic area.
Clinical Course.
• There is little tendency for spontaneous remission in idiopathic focal
segmental glomerulosclerosis, and responses to corticosteroid therapy are
variable.
• In general, children have a better prognosis than adults do.
• Progression of renal failure occurs at variable rates. About 20% of patients
follow an unusually rapid course, with intractable难治 massive proteinuria
ending in renal failure within 2 years.
• Recurrences are seen in 25% to 50% of patients receiving allografts.
局灶性节段性肾小球硬化（小结）
（focal segmental glomeralosclerosis）
• 局灶性：仅累及少数或部分肾小球。
• 节段性：仅累及肾小球的部分血管丛。
• 病变特点：
• 早期仅少数肾小球或肾小球的部分毛细血管丛受
累（萎陷、系膜增宽、硬化、玻璃样变）。
• 病变继续发展，受累的肾小球逐渐增多。
• 有些肾小球毛细血管丛可全部纤维化、硬化，最
终可发展为终期肾。
4
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MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
Membranoproliferative glomerulonephritis (MPGN) is characterized histologically by
alterations in the basement membrane, proliferation of glomerular cells, and
leukocyte infiltration.
Because the proliferation is predominantly in the mesangium, a frequently used
synonym is mesangiocapillary glomerulonephritis. 系膜增生
•
MPGN accounts for 10% to 20% of cases of nephrotic syndrome in children and
young adults. Some patients present only with hematuria or proteinuria in the nonnephrotic range, and others have a combined nephrotic-nephritic picture.
•
Like many other glomerulonephritides, MPGN either can be associated with other
systemic disorders and known etiologic agents (secondary MPGN) or may be
idiopathic (primary MPGN).
Morphology
•
By light microscopy, the glomeruli are large and hypercellular. The hypercellularity is
produced both by proliferation of cells in the mesangium and so-called endocapillary
cell proliferation involving capillary endothelium and infiltrating leukocytes.系膜增生
•
The GBM is clearly thickened, often focally; this is most evident in the peripheral
capillary loops. The glomerular capillary wall often shows a “double-contour” or
“tram-track” appearance, especially evident in silver or PAS stains. This is caused by
“duplication” of the basement membrane, usually as the result of new basement
membrane synthesis. 双轨现象
•
Within the besement membrane there is inclusion or interposition of cellular elements,
which can be of mesangial, endothelial, or leukocytic origin. Such interposition gives
rise to the appearance of “split” basement membranes.系膜插入
Membranoproliferative glomerulonephritis,
showing mesangial cell proliferation, increased mesangial matrix (staining black with silver
stain), basement membrane thickening and focal splitting, accentuation of lobular architecture,
swelling of cells lining peripheral capillaries, and influx of leukocytes.
A, Membranoproliferative glomerulonephritis, type I. Note the large subendothelial deposit
(arrow) incorporated into mesangial matrix (M). E, endothelium; EP, epithelium; CL, capillary
lumen.
B, Type II membranoproliferative glomerulonephritis, dense-deposit disease. There are
markedly dense homogeneous deposits within the basement membrane proper. CL, capillary
lumen.
C, Schematic representation of patterns in the two types of membranoproliferative GN. In type I
there are subendothelial deposits; type II is characterized by intramembranous dense deposits
(dense-deposit disease). In both, mesangial interposition gives the appearance of split
basement membranes when viewed in the light microscope.
Clinical Course
•
•
•
•
The principal mode of presentation is the nephrotic syndrome occurring in
older children or young adults (idiopathic MPGN type I and cases of type II),
but usually with a nephritic component manifested by hematuria or, more
insidiously, as mild proteinuria.
Few remissions occur spontaneously in either type, and the disease follows
a slowly progressive but unremitting course. 预后较差
Some patients develop numerous crescents and a clinical picture of RPGN.
About 50% develop chronic renal failure within 10 years.
Treatments with steroids, immunosuppressive agents, and antiplatelet drugs
have not been proved to be materially effective. 疗效不佳
膜性增生性肾小球肾炎
（diffuse membranoproliferative glomerulonephritis）小结
•
膜性增生性肾小球肾炎认为是早期慢性肾炎，但预后差，较易进入固缩肾。
•
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1．病理变化：
光镜：肾小球呈分叶状，细胞增多，毛细管壁增厚，腔狭窄，也可见玻璃变
的肾小球。
电镜：主要是系膜细胞及其基质增生，并向基膜与内皮胞浆之间穿插，使毛
细管壁严重增厚，并见基膜分裂成“双轨状”。
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2．临床联系
早期：有轻度蛋白尿和血尿
病变侵犯基底膜：肾病综合征
晚期：高血压和肾功能衰竭。
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3．结果
预后较差，早期转为固缩肾。
5 IGA NEPHROPATHY (BERGER DISEASE)
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•
•
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This form of glomerulonephritis is characterized by the presence of
prominent IgA deposits in the mesangial regions, detected by
immunofluorescence microscopy.
The disease can be suspected by light microscopic examination, but
diagnosis is made only by immunocytochemical techniques.
IgA nephropathy is a frequent cause of recurrent gross or microscopic
hematuria and is probably the most common type of glomerulonephritis
worldwide.
Mild proteinuria is usually present, and the nephrotic syndrome may
occasionally develop. Rarely, patients may present with rapidly progressive
crescentic glomerulonephritis.
Morphology.
•
On histologic examination, the lesions vary considerably. The glomeruli may
be normal or may show mesangial widening and proliferation
(mesangioproliferative glomerulonephritis), segmental proliferation confined
to some glomeruli (focal proliferative glomerulonephritis), or rarely, overt
crescentic glomerulonephritis.
•
The presence of leukocytes within glomerular capillaries is a variable
feature. The mesangial widening may be the result of cell proliferation,
accumulation of matrix, or both.
•
The characteristic immunofluorescent picture is of mesangial deposition
of IgA, often with C3 and properdin and lesser amounts of IgG or IgM.
•
Electron microscopy confirms the presence of electron-dense deposits in
the mesangium.
IgA nephropathy.
A, Light microscopy showing mesangial proliferation and matrix increase.
B, Characteristic deposition of IgA, principally in mesangial regions, detected
by immunofluorescence.
Clinical Course.
•
The disease affects people of any age, but older children and young adults are most
commonly affected.
•
Many patients present with gross hematuria after an infection of the respiratory or,
less commonly, gastrointestinal or urinary tract.
•
30% to 40% have only microscopic hematuria, with or without proteinuria; and 5% to
10% develop a typical acute nephritic syndrome. The hematuria typically lasts for
several days and then subsides, only to return every few months.
•
Many patients maintain normal renal function for decades. Slow progression to
chronic renal failure occurs in 15% to 40% of cases over a period of 20 years.
•
Onset in old age, heavy proteinuria, hypertension, and the extent of
glomerulosclerosis on biopsy are clues to an increased risk of progression.
IgA肾病（IgA nephropathy） 小结
• 又称Berger病，是一种特殊类型的肾小球肾炎，特征性改
变是系膜区有IgA沉积。
• 病变特点：肾小球可正常或出现系膜增宽，也可表现为局
灶性节段性增生或弥漫性系膜增生，偶见新月体。
• 临床病理联系：多见于儿童和青少年，发病前常呼吸道感
染。复发性血尿，轻度蛋白尿，少数病人有肾病综合征。
• 预后：多数为良性经过，但可缓慢进展。
CHRONIC GLOMERULONEPHRITIS
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Primary glomerular diseases leading to chronic glomerulonephritis (GN).
•
The approximate proportion of patients in each group who progress to
chronic glomerulonephritis:
poststreptococcal (1% to 2%);
rapidly progressive (crescentic) (90%),
membranous (30% to 50%),
focal glomerulosclerosis (50% to 80%),
membranoproliferative glomerulonephritis (50%),
IgA nephropathy (30% to 50%).
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Primary glomerular diseases leading to chronic glomerulonephritis (GN)
Morphology.
•
The kidneys are symmetrically contracted and have diffusely granular, cortical
surfaces.
•
On section, the cortex is thinned, and there is an increase in peripelvic fat.
•
The glomerular histology depends on the stage of the disease. In early cases, the
glomeruli may still show evidence of the primary disease (e.g., membranous
glomerulopathy or MPGN).
•
However, there eventually ensues hyaline obliteration of glomeruli, transforming
them into acellular eosinophilic masses.
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The hyalin represents a combination of trapped plasma proteins, increased
mesangial matrix, basement membrane-like material, and collagen.
•
Because hypertension is an accompaniment of chronic glomerulonephritis, arterial
and arteriolar sclerosis may be conspicuous.
•
Marked atrophy of associated tubules, irregular interstitial fibrosis, and
mononuclear leukocytic infiltration of the interstitium also occur.
Clinical Course.
•
In most patients, chronic glomerulonephritis develops insidiously and slowly
progresses to renal insufficiency or death from uremia during a span of years or
possibly decades.
•
Not infrequently, patients present with such nonspecific complaints as loss of appetite,
anemia, vomiting, or weakness.
•
In some, the renal disease is suspected with the discovery of proteinuria,
hypertension, or azotemia on routine medical examination.
•
In others, the underlying renal disorder is discovered in the course of investigation of
edema.
•
Most patients are hypertensive, and sometimes the dominant clinical manifestations
are cerebral or cardiovascular.
•
If patients with chronic glomerulonephritis are not maintained with continued dialysis
or if they do not receive a renal transplant, the outcome is invariably death.
Chronic glomerulonephritis.
A Masson trichrome preparation shows complete replacement of
virtually all glomeruli by blue-staining collagen.
Diffuse and nodular diabetic glomerulosclerosis (PAS stain).
Note the diffuse increase in mesangial matrix and characteristic
acellular PAS-positive nodules.
慢性肾小球肾炎（小结）
•
又称弥漫性硬化性肾小球肾炎(diffuse sclerosing glomerulonephritis)，或终期肾。它是各种肾类的
最后结果，大量肾单位功能丧失肾小球玻变，纤维化，临床上为慢性肾功能不全和高血压，预后甚
差。
•
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1．病理变化
肉眼：为颗粒性固缩肾。双侧肾脏明显缩小，重量减轻，质地变硬，表面布满较均匀的细颗粒状结
节；颗粒之间为凹陷。切面皮质变薄，皮髓质界限不清晰，小血管断面呈哆开状。
光镜：相当于凹陷部份见大量集中的“玻璃球”（萎缩纤维化及玻变的肾小球），周围肾小管高度
萎缩，其间纤维增生，并有少许淋巴细胞浸润。细动脉和小动脉有硬化。相当于颗粒的部份可见代
偿肥大的肾小球和扩张的肾小管，肾小管内有管型。
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2．临床病理联系
(1)肾功能不全较严重，因有功能的肾单位数目大大减少
(2)高血压较严重，常引起心力衰竭，其机制是肾缺血而产生肾素，促使血管紧张素激活。
(3)蛋白尿，管型尿较轻。
(4)多尿，夜尿，低比重尿，是因少量尚好的肾单位“努力”代偿，日夜工作，因而使肾小管内液流
速过快，来不及重吸收之故。
(5)贫血 肾组织大量破坏，促红细胞生成素减少以及自身中毒抑制造血功能。
3．结果
慢性肾炎病情进展的速度有很大差异，但预后均极差，病人常因尿毒症、高血压引起的心力衰竭
和脑出血而死亡。有效的治疗方法是长期的血液透析或肾移植。
Causes of Tubulointerstitial Nephritis
Infections
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Acute bacterial pyelonephritis
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Chronic pyelonephritis (including reflux nephropathy)
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Other infections (e.g., viruses, parasites)
Toxins
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Drugs
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Acute hypersensitivity interstitial nephritis
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Analgesic nephropathy
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Heavy metals
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Lead, cadmium
Metabolic Diseases
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Urate nephropathy
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Nephrocalcinosis (hypercalcemic nephropathy)
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Hypokalemic nephropathy
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Oxalate nephropathy
Physical Factors
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Chronic urinary tract obstruction
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Radiation nephropathy
Neoplasms
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Multiple myeloma (cast nephropathy)
Immunologic Reactions
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Transplant rejection
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Sjögren syndrome
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Sarcoidosis
Vascular DiseasesMiscellaneous
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Balkan nephropathy
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Nephronophthisis-medullary cystic disease complex
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"Idiopathic" interstitial nephritis
Acute tubular necrosis.
Some of the tubular epithelial cells in the tubules are necrotic, and many have become
detached (from their basement membranes) and been sloughed into the tubular lumina,
whereas others are swollen, vacuolated, and regenerating.
肾盂肾炎Pyelonephritis and Urinary Tract Infection
•
Pyelonephritis is a renal disorder affecting the tubules, interstitium, and renal pelvis
and is one of the most common diseases of the kidney.
•
•
It occurs in two forms.
Acute pyelonephritis is caused by bacterial infection and is the renal lesion
associated with urinary tract infection.
Chronic pyelonephritis is a more complex disorder: bacterial infection plays a
dominant role, but other factors (vesicoureteral reflux, obstruction) are involved in its
pathogenesis.
•
•
Bacterial infection of the lower urinary tract may be completely asymptomatic
(asymptomatic bacteriuria) and most often remains localized to the bladder without
the development of renal infection. However, lower urinary tract infection always
carries the potential of spread to the kidney.
Schematic representation of pathways of renal infection.
1 hematogenous or descending infection
2 ascending infection p329
Vesicoureteral reflux demonstrated by a voiding cystourethrogram
The vesicoureteral junction. In normal individuals (A), the intravesical portion of
the ureter is oblique倾斜, such that the ureter is closed by muscle contraction
during micturition. The most common cause of reflux is congenital complete or
partial absence of the intravesical ureter (B).
• 肾盂肾炎是由化脓菌直接感染引起肾盂、肾间质和肾小管
为主的化脓性炎。
• （一）病因
• 大肠杆菌最常见（占60-80%），其次变形杆菌、产气杆
菌、肠杆菌以及葡萄球菌等。
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•
•
•
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（二）感染途径
1．上行性感染
尿道→膀胱→输尿管→肾盂
病原体：大肠杆菌
2．下行性感染
原发性化脓灶→败血症→肾及肾盂
病原体：金黄色葡萄菌多见
• （三）尿路阻塞和膀胱输尿管尿液返流在肾盂肾炎发生的
作用。
Acute Pyelonephritis
Morphology.
•
The hallmarks of acute pyelonephritis are patchy interstitial suppurative
inflammation, intratubular aggregates of neutrophils, and tubular necrosis.
•
In the early stages, the neutrophilic infiltration is limited to the interstitial tissue. Soon,
however, the reaction involves tubules and produces a characteristic abscess with the
destruction of the engulfed tubules.
•
Since the tubular lumens present a ready pathway for the extension of the infection,
large masses of intraluminal neutrophils frequently extend along the involved nephron
into the collecting tubules.
•
Characteristically, the glomeruli appear to be resistant to the infection. Large areas of
severe necrosis, however, eventually destroy the glomeruli, and fungal pyelonephritis
(e.g., Candida) often affects glomeruli.
•
Three complications of acute pyelonephritis p330
•
Papillary necrosis is seen mainly in diabetics and in those with urinary
tract obstruction. One or all of the pyramids of the affected kidney may be
involved. On cut section, the tips or distal two-thirds of the pyramids have
areas of gray-white to yellow necrosis. On microscopic examination, the
necrotic tissue shows characteristic coagulative necrosis, with preservation
of outlines of tubules.
•
Pyonephrosis肾盂积脓 is seen when there is total or almost complete
obstruction, particularly when it is high in the urinary tract. The suppurative
exudate is unable to drain and thus fills the renal pelvis, calyces, and ureter,
producing pyonephrosis.
•
Perinephric abscess 肾周围脓肿 implies extension of suppurative
inflammation through the renal capsule into the perinephric tissue.
Acute pyelonephritis.
Cortical surface exhibits grayish white areas of inflammation and
abscess formation.
Acute pyelonephritis marked by an acute neutrophilic exudate
within tubules and the renal substance
Papillary necrosis
Clinical Course. 肾盂肾炎原因
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•
•
•
•
•
•
•
Urinary tract obstruction, either congenital or acquired
Instrumentation of the urinary tract, most commonly catheterization
Vesicoureteral reflux
Pregnancy. Four percent to 6% of pregnant women develop bacteriuria
sometime during pregnancy, and 20% to 40% of these eventually develop
symptomatic urinary infection if not treated.
Patient's sex and age. After the first year of life (when congenital anomalies
in males commonly become evident) and up to around age 40 years,
infections are much more frequent in females. With increasing age, the
incidence in males rises owing to the development of prostatic hypertrophy
and frequent instrumentation.
Preexisting renal lesions, causing intrarenal scarring and obstruction
Diabetes mellitus, in which acute pyelonephritis is caused by more frequent
instrumentation, the general susceptibility to infection, and the neurogenic
bladder dysfunction exhibited by patients
Immunosuppression and immunodeficiency
急性肾盂肾炎 (acute pyelonephritis)小结
• 病理变化
• 光镜：肾盂和肾间质化脓性炎、形成脓肿。上行性，肾盂
和肾间质首先累及。下行性，肾皮质肾小球首先累及。
• 肉眼：肾脏表面和切面有大小不等、形状不规则肿脓灶。
髓质内可见黄色条纹状病变。肾盂粘膜有脓性分泌物或积
脓。
• 临床联系：感染症状;尿急尿频尿痛等膀胱刺激症状;脓尿、
蛋白尿、管型尿、血尿、菌尿。
• 结果:绝大多数治愈。如治疗不彻底，反复发作，可转为
慢性肾盂肾炎。
Chronic pyelonephritis
is a chronic tubulointerstitial renal disorder in which chronic tubulointerstitial
inflammation and renal scarring are associated with pathologic involvement of
the calyces and pelvis.
从发生机制可分两种类型
• Reflux Nephropathy
• Chronic Obstructive Pyelonephritis
Morphology
• The characteristic changes of chronic pyelonephritis are seen on
gross examination. The kidneys usually are irregularly scarred; if
bilateral, the involvement is asymmetric.This contrasts with chronic
glomerulonephritis, in which the kidneys are diffusely and
symmetrically scarred.
• The hallmark of chronic pyelonephritis is the coarse, discrete,
corticomedullary scar overlying a dilated, blunted, or deformed calyx.
• The scars can vary from one to several in number and may affect
one or both kidneys. Most are in the upper and lower poles,
consistent with the frequency of reflux in these sites.
•
1 The microscopic changes involve predominantly tubules and interstitium.
•
2 The tubules show atrophy in some areas and hypertrophy or dilation in others.
Dilated tubules with flattened epithelium may be filled with colloid casts
(thyroidization).
•
3 There are varying degrees of chronic interstitial inflammation and fibrosis in the
cortex and medulla. In the presence of active infection, there may be neutrophils in
the interstitium and pus casts in the tubules.
•
4 Arcuate and interlobular vessels demonstrate obliterative intimal sclerosis in the
scarred areas; and in the presence of hypertension, hyaline arteriosclerosis is seen in
the entire kidney.
•
5 There is often fibrosis around the calyceal epithelium as well as a marked chronic
inflammatory infiltrate.
•
6 Glomeruli may appear normal except for periglomerular fibrosis, but a variety of
glomerular changes may be present, including ischemic fibrous obliteration as well as
secondary changes related to hypertension.
Typical coarse scars of chronic pyelonephritis associated with vesicoureteral reflux
A, Chronic pyelonephritis. The surface (left) is irregularly scarred. The cut section (right) reveals
characteristic dilation and blunting of calyces. The ureter输尿管 is dilated and thickened, a finding that
is consistent with chronic vesicoureteral reflux.
B, Low-power view showing a corticomedullary renal scar with an underlying dilated deformed calyx.
Note the thyroidization of tubules in the cortex.
Clinical Course.
•
Chronic obstructive pyelonephritis may be insidious in onset or may present with
clinical manifestations of acute recurrent pyelonephritis with back pain, fever, frequent
pyuria, and bacteriuria.
•
Chronic pyelonephritis associated with reflux may have a silent onset. These patients
come to medical attention relatively late in the course of their disease because of the
gradual onset of renal insufficiency and hypertension or because of the discovery of
pyuria or bacteriuria on routine examination.
•
Reflux nephropathy is often discovered when the etiology of hypertension in children
is investigated. Loss of tubular function-in particular of concentrating ability-gives rise
to polyuria and nocturia.
•
Radiographic studies show asymmetrically contracted kidneys with characteristic
coarse scars and blunting and deformity of the calyceal system.
•
Significant bacteriuria may be present, but it is often absent in the late stages.
慢性肾盂肾炎 (chronic pyelonephritis)小结
• 急性肾盂肾炎转为慢性肾盂肾炎的机理，可能是：治疗不完全彻底，
细菌变异成为原生质型、尿路阻塞或尿液返流。
• 病理变化
• 光镜：肾间质慢性化脓性炎症病变，纤维化。肾实质部分破坏，肾小
球玻璃样变和肾小管萎缩。但部分肾小管扩张、腔内有管型，似甲状
腺滤泡。
• 肉眼：大疤痕凹陷性固缩肾、肾盂粘膜粗糙增厚。
• 临床联系:多尿夜尿;尿液中性白细胞数增多;尿液培养菌（+）;血压和
肾衰
• 结果
• 预后较差，常反复发作，如能及时治疗，消除诱发因素，病情可得到
控制变严重且广泛，则可因尿毒症和高血压而死亡。
Drug-induced interstitial nephritis
Analgesic nephropathy
• 慢性肾小管间质炎+肾乳头坏死
Close-up of the gross appearance of the cortical surface in benign nephrosclerosis 肾硬化
illustrating the fine, leathery granularity of the surface
Hyaline arteriolosclerosis
Malignant hypertension
Diffuse cortical necrosis
Urinary tract obstraction
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Congenital anomalies: posterior urethral valves and urethral
strictures, meatal stenosis, bladder neck obstruction; ureteropelvic
junction narrowing or obstruction; severe vesicoureteral reflux
Urinary calculi
Benign prostatic hypertrophy
Tumors: carcinoma of the prostate, bladder tumors, contiguous
malignant disease (retroperitoneal lymphoma), carcinoma of the
cervix or uterus
Inflammation: prostatitis, ureteritis, urethritis, retroperitoneal
fibrosis
Sloughed papillae or blood clots
Normal pregnancy
Uterine prolapse and cystocele
Functional disorders: neurogenic (spinal cord damage or diabetic
nephropathy) and other functional abnormalities of the ureter or
bladder (often termed dysfunctional obstruction)
Obstructive lesions of the urinary tract
Hydronephrosis of the kidney, with marked dilation of the pelvis and
calyces and thinning of the renal parenchyma.
Nephrolithiasis 肾结石
Renal cell carcinoma
Renal cell carcinoma.源于肾小管上皮细胞/肾腺癌 A, Clear cell type, B, Papillary type.
Note the papillae and foamy macrophages in the stalk. C, Chromophobe type.
Urothelial carcinoma of the renal pelvis
• 肾细胞癌，肾腺癌。本癌不太多见，男性中年较多，临床较隐蔽，难
早期发现。
• 肉眼：结节状，可有假包膜，在肾上极较多，色带土黄，易出血坏死
• 镜检：由含类脂及糖原的透明细胞构成，核不大，核浆比例小。腺体
样结构（现认为其来自肾小管），亦可呈巢状；间质较少。
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肾癌临床病理特点：
(1)无痛性血尿；但常为隐匿性；
(2)血道转移；
(3)常有意外的远隔转移（如转至鼻尖）；
(4)逆行转移：男性左肾癌可侵入左肾静脉→左精索内静脉→逆行引起
左附睾发生转移。（右侧精索内静脉直接流入下腔V，故无此现象）；
• (5)异位内分泌现象较其它癌为多。
肾母细胞瘤Nephroblastoma
• 亦名：肾胚胎性腺肉瘤，Wilm氏瘤
• 来源：胚胎性肾母细胞，可分化为腺体及纤维、软骨等间
叶组织；细胞分化差。其发生与抑癌基因WT1异常有关。
一般见于3岁左右儿童。
• 肉眼：大结节状，境界清楚，灰白，肾组织受压萎缩，肾
盂肾盏变形。
• 镜检：有腺癌和纤维肉瘤两种成份，二者均有恶性特征，
有时移行。瘤细胞有时可分化成类似肾小球或肾小管的结
构，有时见分化较好的软骨。
膀胱癌Carcinoma of bladder
• 膀胱移行细胞癌比较常见，临床上发生无痛性血尿。
• 肉眼：多呈乳头状突出表面。检查标本时需特别注意乳头
基底宽或细，切面有无向下浸润。由于乳头很脆，常折断
脱落，尿沉淀涂片镜检可查出癌细胞。
• 镜检：移行上皮癌，可分Ⅰ～Ⅲ级。Ⅰ级为低度恶性，Ⅱ
级细胞层次明显增多，有一定异型性。Ⅲ级可不形成乳头，
而是癌巢。移行上皮乳头状瘤，细胞几乎无异型性，但一
般认为其极易恶变，须按癌处理。
• 临床特点：无痛性血尿;膀胱刺激症状;尿路阻塞。
• 肾母细胞瘤/Wilms’s tumor 7岁以下
• 膀胱移行细胞癌 0-3级