The nephrotic syndrome Def: It is a clinico -biochemical state of many causes Features 1-Heavy proteinuria. 2-Hypoproteinemia.( decrease protein in the blood) 3-Generalized oedema. 4-Hyperlipidemia and lipiduria
Causes Systemic Diseases Renal 1-SLE 1-Membranous GN 2-DM 3-Amyloidosis 4-Infections e.g.; malaria, HBV,B Syphilis 6-lymphoma 7-Drugs:gold salt and NSAI Renal 1-Membranous GN 2-membranoproliferative GN 3-Minimal change GN 4-Focal segmental GS 5-Focal GN.(Mesangial,IgA Nephropathy)
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) Patho: ICD Cause:- -Primary :Unknown (85%) -Secondary in course of infection like malaria syphilis, HBV, B, malignant tumors and gold salt therapy Patho: ICD
Microscopic Light: IF Thickening of the GBM Granular EM: flourescences to IgG and C3 EM: -Fusion of foot processes Of podocytes. -Subepithelial deposits
Thickened GBM IN MGN
Sikes formation in MGN. Silver stain
Spikes formation along GBM Silver 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
Prognosis: Remission and exacerbation, finally chronic renal failure. Clinical and laboratory findings Nephrotic syndrome Prognosis: Remission and exacerbation, finally chronic renal failure.
Minimal change GN Msc:1-Light Gross: as Nephrotic syndrome. Age: 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.
2-IF: Negative. 3-EM: Fusion of foot processes of podocytes 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.
Accentuated lobulation Patchy irregular thickening of GBM MSC;1-Light Hypercellularity Double contour of GBM Accentuated lobulation Patchy irregular thickening of GBM
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 findings Presentation Asymptomatic proteinuria Nephrotic syndome+ hypertension Nephritic syndrome 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
Focal glomerulonephritis Cause: -idiopathic -In association of SBE,SLE, Henoch-schonlein PAN, and Goodpasture’s syndrome Pathogenesis: -ICD -Activation of the alternative complement pathway by aggregation of IgA.(Berger’s disease)
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
LM EM IF MPGN Minimal change Focal and Seg.GS Focal GN Lupus Nephritis Disease LM EM IF Membranous GN MPGN Minimal change Focal and Seg.GS Focal GN Lupus Nephritis
Chronic GN Grossly:-Small contracted kidney. Def: 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. Tubules are atrophied and -Some are hypertrophied. Tubules are atrophied and dilated Interstitial fibrosis and chronic inflammatory cell infiltration Thick walle-blood vessels end arteritis obliterans
Chronic glomerulonephritis
Chronic GN Hyaline cast
Clinical and laboratory Findings: Prognosis: without Treatment is poor Urine changes -Polyuria. low Specific gra. -Mild albuminuria. -Hyaline and granular casts Marked hypertension Increase Bl. urea 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).
DM Effects of DM on the kidney: -Diabetic GS -Renal arteriolar sclerosis. -pyelonephritis. -papillary necrosis. Diabetic GS It leads to: a-Proteinuria. B-Nephrotic syndrome. C-CRF.
MSC: 1-Diffuse GS. -Diffuse increase in mesangial matrix -Thickening of GBM 2-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 Classification; 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 nephritis Flea-Bitten appearance
Class II: Mesangial GN
Focal and segmental necrosis of glomerulus 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