renal pathology 2

8/14/2019 Renal Pathology 2

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GLOMERULAR

DISEASES


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Glomerular Syndrome

1. Acute nephritic syndrome

2. Rapidly progressive glomerulonephritis

3. Chronic renal falure

4. Asymptomatic hematuria/proteinuria


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Nephrotic Syndrome

Manifestations Massive proteinuria

Hypoalbuminemia

Generalized edema

Hyperlipidemia and lipiduria


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Minimal Change Disease

Lipoid nephrosis, Nil disease, Idiopathicnephrotic syndrome

Most common cause of NS in children

Dramatic response to steroids Of unknown cause NSAID, allergic

reactions

May present with acute renal failure Differentiate from focal segmental

glomerulosclerosis


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Minimal Change Disease

LM: few, if any changes

IF: usually negative; may have mesangialIgM

EM: widespread effacement of podocytefoot processes Villous hypertrophy of podocytes

Absence of deposits


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Focal Segmental

Classifications In association with other known conditions

HIV, heroin, sickle cell disease, massive obesity

As a secondary event reflecting glomerularscarring

As an adaptive response

In certain inherited, congenital forms of NS As a primary disease --- idiopathic


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Failure to respond to steroidsMay have microscopic hematuria,hypertension or renal insufficiencySome develop ESRDRecurrence after transplantation


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Differ from minimal change disease

They have a higher incidence of hematuria,

reduced GFR and HPN

Their proteinuria is more often nonselective

They respond poorly to steroids

Many progress to CGN

IMF shows deposition of IgM and C3 in

sclerotic segment


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LM: some glomeruli with segmental sclerosis

(mesangial matrix material, collapse, BM-likematerial) +/- hyalinosis

Focal segmental consolidation of the tuft

with obliteration of the capillary, often withadhesions to Bowmans capsule

Hyalinosis

+/- podocyte hypertrophy


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IF: usually negative except IgM +/- C3 insclerotic segmentEM: widespread podocyte foot processeffacement

accumulation in collapsed loop of matrix-likematerial


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Membranous

Can be primary or secondary

Secondary causes Drugs Underlying malignant tumors

SLE

Infections Metabolic disorders


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Some have asymptomatic proteinuriaNephrotic syndromeSome --- remissionOthers --- ESRDDeposits may be formed by theinteraction of autoantibodies with

podocyte surface antigens


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LM: normal to extreme diffuse thickening of

the cap wall, foam cells in the interstitium

Spikes

IF: finely granular diffuse cap wall staining--- IgG +/- C3 and others

EM: numerous subepithelial deposits +/-

spikes of GBM betweenCourse: 1/3 progress, 1/3 remit, 1/3proteinuria only


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Membranoproliferative GN

Can be primary or secondary

Secondary causes Chronic immune-complex disorders

SLE, hepatitis B, hepatitis C, endocarditis, HIV,

schistosomiasis Partial lipoid dystrophy associated with C3NeF

Alpha-1 antitrypsin deficiency

Malignant diseases

CLL, lymphoma, melanoma Hereditary complement deficiency states


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MPGN types I, II and III

LM: proliferative, mesangial matrix increase,lobulation, tram-tracking, capillary wall thickening

IF: broad cap wall deposits and less often in themesangium --- C3 +/- others

EM:

Type I massive subendothelial deposits +/- mesangialdeposits

Type II large electron-dense deposits inintramembranous portion

Type III subepithelial deposits, segmental GBM

fragmentation


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Course: progressive (many to renal failure)

DX: low complement, nephrotic/nephritic


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IgA Nephropathy (Bergers

Frequent cause of recurrent gross ormicroscopic hematuria

+/- NS or RPGN

Initially considered to be benign

May lead to ESRD Reversible ARF from numerous tubular

casts and tubular injury


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LM: any glomerular patternIF: intense mesangial granular IgAEM: dense deposits in mesangial

paramesangial areas


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Pathogenesis: deposition in glomeruli ofabnormal forms of circulating IgAresulting from abnormal glycosylation

IgA binds to mesangial cells Role of alternative complement pathway

No diagnostic serologic test for IgAnephropathy


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PoststreptococcalGlomerulone hritis

1-4 weeks after a streptococcal infectionof the pharynx or skin

6-10 yo but may affect any age

Group A beta- hemolytic streptococcitypes 12, 4 and 1

Acute nephritis syndrome: gross

hematuria, edema and hypertension


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A minority --- severe renal insufficiencyLow C3Glomerular immune deposits represent

Ag-Ab complexes


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LM: proliferative, exudative (PMNs), +/-

crescentsIF: granular GBM --- IgG +/- C3

EM: subepithelial humps +/- small

subendothelial/mesangial deposits

Course: resolves in vast majority of cases

Dx: ASO up, complement down, nephriticsyndrome, HPN


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Nonstreptococcal acute GN

Bacterial, viral and parasitic infections


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Rapidly Progressive GN

Crescentic GN Rapid and progressive loss of renal function

associated with severe oliguria and (if

untreated) death from renal failure withinweeks to months


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LM: over 50% of glomeruli with crescents

IF:1/3 granular (immune complex GN, e.g. SLE, post-infectious GN)

1/3 linear (anti-GBM, e.g. Goodpastures disease)

1/3 no deposits (e.g. PAN, Wegeners, vasculitis)

EM: glomerular deposits anywhere

Course: terrible (progression to ESRD exceptpost-infectious)


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Anti-GBM Disease

Autoantibodies against the NC1 domain ofthe alpha 3 chain of type IV collagen(Goodpasture Ag)

Associated with pulmonary hemorrhage LM: crescentic

IF: strong linear staining along the GBM


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Hereditary Nephritis

Alport syndrome Nephritis accompanied by nerve deafness

and various eye disorders (lens dislocation,

post. Cataracts and corneal dystrophy) Males > females, hematuria

Defective form of BM due to mutations ingenes that encode components of type IV

collagen


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In 80% x-linked inherritanceIn 15% autosomal recessiveRarely autosomal dominantSkin biopsy (alpha 5)Anti-GBM disease after transplantation


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LM: segmental proliferation or sclerosis,fetal-like glomeruli, mesangial matrixincrease

EM: irregular foci of thickening or thinningwith splitting and lamination of laminadensa

- mainly thinning in female carriers


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Thin Basement Membrane

Benign familial hematuria

Diffuse thinning of the GBM to between150 and 225 nm (normal = 300 to 400 nm)


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Chronic GN

End-stage pool of glomerular diseases

A number of cases arise mysteriously

without antecedent history of any of thewell-recognized forms of early GN


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