Nephrotic syndrome

Dr Rohan Gupta

NEPHRITIC

• Hematuria

• Proteinuria(nonselective)

• Oliguria

• Edema (salt and water

retention)

• Hypertension (mild)

NEPHROTIC

Proteinuria

(“nephrotic range”

>3.0g/24h)

Hypoalbumimenia

hypercoagulability

Hyperlipidemia

Lipiduria

edema

DISEASES ASSOCIATED WITH THE NEPHROTIC SYNDROME

PRIMARY RENAL DISEASE

Minimal-change disease (MCD )

Membranous glomerulonephritis (MGN)

Membranoproliferative glomerulonephritis (MPGN)

Focal segmental glomerulosclerosis (FGS)

Focal GN

Others: mesangial proliferate glomerulonephritis,

IgA nephropathy

SECONDARY DISEASE ASSOCIATED WITH THE NEPHROTIC SYNDROME

SECONDARY DISEASE

SYSTEMIC

DISEASE

Diabetes mellitus, amyloidosis ,SLE

MALIGNANCY Leukemia, lymphoma, myeloma, carcinoma, melanoma

HYPERSENSTIVITY

REACTION

DRUG - Gold, penicillamine, NSAIDs, lithium, penicillamine

ALLERGENIC Insect stings, snake venoms, antitoxins, ivy and oak

SYSTEMIC

INFECTION

Bacterial -. postinfective glomerulonephritis, vascular prosthetic nephritis, syphilis , leprosyViral - hepatitis B, Epstein-Barr, HCV , HIVProtozoal and parasite – malaria,Helminthic -

schistosomiasis, filariasis

MISCELLANEOUS - pregnancy, malignant hypertension

HEREDITARY ALPORT DISEASE ,FABRY’S DISEASE , NAIL – PATELLA SYNDROME 5

COMPONENT PHYSIOLOGIC

FUNCTION

CONSEQUENCES

OF

INJURY

RELATED

GLOMERU

LAR

INJURY

1. ENDOTHELIAL

CELLS

•MAINTAIN

GLOMERULAR

PERFUSION

•PREVENT PLATELET

AGGREGATION

• LEUCOCYTE

INFILTRATION

VASOCONSTRICT

ION

LEUCOCYTE

INFILTRATION

INTRAVASCULAR

MICROTHROMBI

ARF

FOCAL

/DIFFUSE

PROLIFER

ATIVE GN

THROMBO

TIC

MICROAN

GIOPATHIE

S

MESENGIAL

CELLS

CONTROL

GLOMERULAR

FILTRATION

PROLIFERATION

AND

INCREASED

MATRIX

MEMBRAN

O

PROLIFER

ATIVE GN

VISERAL

EPITHELIAL

PREVENT PLASMA

PROTEIN FILTRATION

PROTEINURIA MCD

FSGS

COMPONENT PHYSIOLOGIC

FUNCTION

CONSEQUENCES

OF

INJURY

RELATED

GLOMERULAR

INJURY

GBM PREVENT

PLASMA

PROTEIN

FILTRATION

PROTEINURIA MGN

PARIETAL

EPITHELIAL

CELLS

MAINTAIN

BOWMAN’S

SPACE

CRESENT

FORMATION

RPGN

MINIMAL CHANGE DISEASE

Is a nephrotic condition characterised by no

apparent change in glomeruli by ligth

microscopy .

Most common in children.

Insidious onset below 6 yr of age.

Other synonyms – MCD , LIPOID NEPHROSIS

, FOOT PROCESS

DISEASE .

ETIOPATHOGENESIS:

Idiopathic (majority of cases )

Cases associated with systemic disease

(hodking’s disease ,HIV infection and drug

therapy )

Pathological changes

Grossly - kidney are normal size and shape

By light microscope

• Glomeruli –

• no appaerent abnormality except increase in mesangial

matrix

•Tubule

•Lipid vacuolation and hyaline droplet in PCT cells .

•Interstitium

•Edema of interstium

•Vessels

•Donot show any changes

Electron microscopy

Diffuse flattening of foot process of visceral

epithelial cells.

No deposit seen

Immunofluroscence

no deposit of complement or

immunofluroscence seen

MEMBRANOUS

GLOMERULONEPHRITIS

MC GN in adult

Characterised by diffuse thickening of

glomerular capillary wall .

Etiopathogenesis :

Primary ( idiopathic ) MGN – Immune complex

Secondary – drug , tumour , infection

PATHOLOGICAL CHANGES

GROSSLY - Enlarged , pale and smooth

Light microscopy

•Glomeruli - diffuse thickening , duplicaton

of

GBM , Changes best appreciated by silver

impregnation stain .

• tubules – normal , lipid vacuolation of PCT

.

Interstitium :

fine fibrosis and scanty chronic inflammatory

infiltrate .

Vessels : hypertensive changes may occur later .

Electron microscopy

electron dense deposit at epithelial side of GBM

.

GBM material protudes bwt deposit – “spikes “

Immunoflorescence microscopy :

Deposit of immune complex consisting of IGg

associated with complement C3.

CLINICAL FEATURE

proteinuria (non selective ) along with hematuria

and hypertension.

Changes are reversible , may find renal vein

thrombosis .

MEMBRANOPROLIFERATIVE GN

Characterised by : two histological feature

1. Increased cellularity of the mesengium with

lobulation of tuft

2. Alteration of GBM

ETIOPATHOGENESIS :

TYPE 1 or classic form – at subendothelial

position

TYPE 2 or dense deposit type(alternate pathway) –

at GBM

TYPE 3 - feature of type 1 with systemic disease

and drug

PATHOLOGICAL CHANGES :

GROSSLY : pale and firm in consistency

Light microscopy :

Glomeruli : accentuated lobular pattern and

mesengial proliferation – “tram –track “ or “ double

countor “

Tubule : vacuolation and hyaline droplet

Interstitium : ch inflammtory cell ,

Vessel : feature of hypertension

Electron microscopy and immunoflorescence:

Type 1 : electron dense deposit at subendothelial

deposit .

Type 2 : dense amorphous material at GBM and

mesengium .

TYPE 3 : elctron dense deposit within GBM and

subendothelial .

Focal Glomerulonephritis

pathological change Confined to one or two lobe of

glomeruli

Etiopathogenesis :

In systemic disease – SLE , H-S purpura , SABE .

As component of renal disease

Idiopathic

Pathological changes

By light microscopy :

Consist of focal and segmental cellular proliferation of mesengial cell and endothelial cell.

Immunofluorescence microscope :

deposit of immunoglobulin ( IgA with or without IgG)

Clinical feature

Hematuria is important feature

Focal segmental

glomerulosclerosis

Involve only segmental or focal .

Sclerosis and hyalinosis of glomeruli and

portion of tuft .

Etiopathogenesis : 3 group Idiopatheic : found in children and adult , steriod

resistant , progress to CRF .

With superimposed primary glomerular disease. –

MCD , IgA

Secondary - HIV , DM , Reflux nephropathy

Pathological changes

By light microscope :

sclerosis

Hyalinosis – refers to collection of eosinophilic ,

homogenous ,PAS

positive , hyaline material present on inner aspect of a

sclerotic peripheral capillary loop

HIV associates nephropathy in FSGS – shows

collapsed capillaries in the tuft.

Electron microscopy :

Diffuse loss of foot process and electron dense

deposit

Immunoflorescence microscopy :

deposit consist IgM and C3

IgA nephropathy

Characterised by aggregates of IgA , deposit

principally in their mesengium.

Etiopathogenesis :

Idiopathic most of cases

As a part of Henoch- scholein purpura

Associated with chronic inflammation – ch liver

disease , IBD , leprosy

PATHOGENESIS

Entrapment of IgA complex in the mesangium

Alternate complement pathway

Mucosal secretion of IgA

HLA- B35

PATHOLOGICAL CHANGES

By light microscopy :

pattern of involvment varies – FGN , FSGN , rarely

RPGN

By electron microscopy :

Electron dense deposit in the mesangium

By immunofluroscence :

Deposit of IgA with or without IgA usually C3

CHRONIC

GLOMERULONEPHRITIS

End – stage kidney

Final stage of variety of glomerular disease , result in

irreversible

imparement of renal function .

Pathological changes

Grossly :

small , contracted , with adhered capsule

MICROSCOPICALLY :

Glomeruli :

Reduced in number , completely hyalinised tuft ,

cellular eosinophilic masses – PAS positive

Tubules :

Many disappear , show hyaline-droplet degeneration

Interstitium :

Fibrosis of interstitial tissue and ch inflammatory

infiltrate .

Vessel :

Show hypertensive change – sclerosis

Secondary glomerular disease Lupus nephritis :

Renal manifestation of SLE .

Renal involvement incidence – 40-60 %

Two cardinal feature are :

Protienuria

Hematuria

along with red cell cast , fatty casts . And

hypertension .

Pathological changes

Diabetic nephropathy

Diabetic Nephropathy

Renal involvement is an important complication of

diabetes mellitus

End-stage kidney with renal failure accounts for deaths

in more than 10% of all diabetics.

Renal complications are more severe, develop early

and more frequently in type 1 (earlier called insulin-

dependent) diabetes mellitus (30-40% cases) than in

type 2 (earlier termed non-insulindependent) diabetics

(about 20% cases).

hyperglycaemia

glomerular hypertension

renal hyperperfusion

deposition of proteins in the mesangium

glomerulosclerosis

renal failure

Pathogenesis : Diabetic glomerulosclerosis

Diffuse glomerulosclerosis :

Mc changes

Consist of thickening of GBM and proliferation of

mesangial cells

Capsular drop – thickening of pariteal layer

Fibrin cap

Nodular glomerulosclerosis :

Kimmelstiel – wilson lesion (KW lesions )

Specific for juveline onset DM

Nodule are oval surrounded by capillary loop

Vascular lesion :

Atheroma

Hyaline arteriosclerosis

Diabetics pyelonephritis :

Susceptible to bacterial infection

Papillary necrosis is a important complication

Tubular lesion :

In untreated cases , epithelial cell of PCT develop

glycogen deposit appearing as vacuoles – Armanni-

Ebstein lesion.