The nephrotic syndrome

Def: It is a clinico -biochemical state of many causes

Features1-Heavy proteinuria.2-Hypoproteinemia.( decrease protein in the blood)3-Generalized oedema.4-Hyperlipidemia and lipiduria

Causes

Renal1-Membranous GN2-membranoproliferative GN3-Minimal change GN4-Focal segmental GS5-Focal GN.(Mesangial,IgANephropathy)

Systemic Diseases1-SLE2-DM3-Amyloidosis4-Infections e.g.; malaria, HBV,BSyphilis6-lymphoma7-Drugs:gold salt and NSAI

Common features of nephrotic syndrome

Gross

-Enlarged pale kidney. -yellow ting due to fat resorption by tubular epithelium.

Microscopic

1-Glomeruli;• LM&IF: Features specific to the disease.• EM: Fusion of foot processes of podocytes.

2-Tubules• 1-Hyaline droplets. • 2-Vacuolar degeneration due to resorption of

fat • 3-Hyaline casts

3-Interstitial tissue

variable oedema

Hyaline casts

Membranous GN

Age: adults (30-50 ys)

Cause:--Primary :Unknown (85%)-Secondary in course of infection like malaria syphilis, HBV, B, malignant tumors and gold salt therapy

Patho: ICD

Light:Thickening of the GBM

IFGranular flourescences to IgG and C3

EM: -Fusion of foot processes Of podocytes.-Subepithelial deposits

Microscopic

Thickened GBM IN MGN

Sikes formation in MGN.Silver stain

Spikes formation along GBMSilver stain

Diffuse granular fluorescence of GBM

EM in MGN, the darker electron dense immune deposits are seen scattered within the thickened

basement membrane.

Membranous GN.EM

Subepithelial Deposits

Clinical and laboratory findings Nephrotic syndrome

Prognosis: Remission and exacerbation, finally chronic renal failure.

Minimal change GNAge: Commonest cause of nephrotic syndrome in children (1-4 ys )

Pathog: unknown or it is a disorder of T cells cytokines that cause loss of epithelial foot processes

Gross: as Nephrotic syndrome.

Msc:1-Light

Glomeruli ; no changes.

Tubules and interstitial tissues show changes of nephrotic syndrome

2-IF: Negative.3-EM: Fusion of foot processes of podocytes

Clinical and laboratory findings : as NS with selective proteinuria.

Prognosis: good response to steroid therapy

Membranoproliferative GN

Age; any age, mainly late childhood

Pathogenesis;

Type I; Common. It is ICD

Type II (Dense deposit disease) :rare mediated by activation of the alternative complement pathway.

Hypercellularity

Accentuated lobulation

Patchy irregular thickening of GBM

Double contour of

GBM

MSC;1-Light

MPGN, the glomerulus has increased overall

cellularity, mainly mesangial

MPGN.Lobulation. Patchy irregular Thickening of GBM

New matrix material is laid down resulting in replication of basement membrane material

Membranoproliferative GN type I

This silver stain demonstrates a double contour to many basement membranes, or the "tram-tracking" that is

characteristic of MPGN

2-IF; Type I: Gr.fluor.to Igs and C3

Bright deposits in type II MPGN To C3

TYPE II, intramembranous deposit

Clinical and laboratory findingsPresentation

Nephrotic syndome+ hypertension

Nephritic syndrome

Asymptomatic proteinuria

Prognosis : remission exacerbation and finally chronic renal failure

Focal segmental glomerulosclerosis

Microscopic: -Sclerotic segments in some gl. and Hyalinosis -tubular atrophy -interstitial fibrosis

IF: Granular fluorescence of the GBM for IgM andC3.EM:Fusion of foot processes and detachement of epithelial cells

Focal segmental GS

Clinically: Nephrotic syndrome, may be hypertension and microscopic hematuria.

Prognosis: unfavorable (ending in chronic renal failure

Cause: -idiopathic -In association of SBE,SLE, Henoch-schonlein PAN, and Goodpasture’s syndromePathogenesis: -ICD -Activation of the alternative complement pathway by aggregation of IgA.(Berger’s disease)

Focal glomerulonephritis

IgA Nephropathy (Berger’s Disease)

-Common in children and young adults- Recurrent hematuria-It follows infection of the respiratory,GI

and urinary tracts.-The IgA is deposited mainly in

mesangium, which then increases mesangial cellularity

MSC: Focal and segmental proliferation of mesangial cells+ necrosis and crescent formation

Clinically: Hematuria, proteinuria and may be nephrotic syndrome

Course: Subsides without residual renal impairment

Focal glomerulonephritis

IF:Granular

Focal GN

Necrosis

Amyloidosis

Amyloidosis of the kidney

Disease LM EM IFMembranous GN

MPGN

Minimal change

Focal and

Seg.GS

Focal GN

Lupus Nephritis

Chronic GNDef: it is end stage renal glomerular disease.

Grossly:-Small contracted kidney.-Granular outer surface.-Firmly adherent capsule.-Loss of differentiation bet. cortex and medulla.-Thick BVs at corticomedullary junction.

Chronic GN: Note contacted kidney& granular outer surface

Msc:

Glomeruli: -Hyalinised and sclerotic.-Some are hypertrophied.

Tubules are atrophied and

dilated

Interstitial fibrosis and

chronic inflammatory cell

infiltration

Thick walle-blood vessels end arteritis obliterans

Chronic glomerulonephritis

Hyaline cast

Chronic GN

Clinical and laboratory Findings:

Marked hypertension

IncreaseBl. urea

Urine changes-Polyuria.- low Specific gra.-Mild albuminuria.-Hyaline and -granular casts

Prognosis: without Treatment is poor

Small- Sized Kidney (contracted kidney)

1-Hypoplastic kidney.

2-Chronic GN

3-Chronic PN

4-Senile(atherosclerotic) kidney.

5-Kidney of benign hypertension (Benign nephrosclerosis).

DMEffects of DM on the kidney:-Diabetic GS-Renal arteriolar sclerosis.-pyelonephritis.-papillary necrosis.

Diabetic GSIt leads to:a-Proteinuria.B-Nephrotic syndrome.C-CRF.

MSC: 1-Diffuse GS.-Diffuse increase in mesangial matrix-Thickening of GBM2-Nodular GS. (kimmelsteil Wilson disease)Hyaline nodule is present in the mesangium,Containing fibrin and lipid.

3-Insudative lesion:-fibrin cap; eosinophilic focal Thickening of peripheral capillary loop.-Capsular drop: eosinophilic thickening of Bowman’s capsule

Diffuse glomeruosclerosis

Nodular GS

Nodular GS

Fibrin cap and Capsular drop

Lupus nephritis

Presentation: Recurrent hematuria,nephritic s,nephrotic s,hypertension,CRF.

Classification;-class I:Normal kidney.-Class II:Mesangial glomerular lesion.-Class III:Focal proliferaive GN.-Class IV:Diffuse Proliferative GN.-Class V:Membranous GN.-Class VI:Advancing sclerosing GN.

MSC of Class IV: Diffuse Proliferative GN

-Diffuse hypercellularity due to Proliferation of endothelial cells and mesangial cells -Irregular thickening of GBM - Wire loop appearance-Few epith.crescents-Hematoxylin bodies.

Proliferative lupus nephritisFlea-Bitten appearance

Class II: Mesangial GN

Class III: Focal GN

Focal and segmental necrosis of glomerulus

Class IV:Diffuse Proliferaive GN

Hematoxylin bodies Wire-Loop appearance

IF of Lupus Nephritis

EM of Lupus Nephritis

• IF: Granular fluorescence of capillary walls for Igs and comploments

• EM: Subendothelial and mesangial electron dense deposits