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BY: DR.LEENA HAFEEZ GLOMERULAR DISEASES

Glomerular diseases

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BY:DR.LEENA HAFEEZ

GLOMERULAR DISEASES

ANATOMY AND FUNCTION

• A renal corpuscle consists of:

• Glomerulus – tuft of fenestrated capillaries

• Glomerular (Bowman’s) capsule• Parietal layer – simple squamous epithelium• Visceral layer – consists of podocytes

• Blood travels from efferent arteriole to peritubular capillaries

• Blood leaves the nephron via the efferent arteriole

Three-dimensional schematic drawing of the glomerulus

Afferent arteriole

Efferent arteriole

Endothelial cells

Capillary loops

Mesangial matrix and cell

Bowman’s Space

Light micrograph of glomerulus showing

Normal cellularity with patent capillary lumen

Electron micrograph

Podocytes

Glomerularbasementmembrane

Capillary Lumen

Endothelial cell内皮细胞

GLOMERULAR DISEASESPATHOGENESIS

WHAT CAUSES GLOMERULAR DISEASES

Glomerular diseases results from:

• Immunological Injury(Glomerulonephritis)• Inherited(Alport’s Syndrome)• Metabolic stress(Diabetes mellitus)• Deposition of extraneous

materials(Amyloidosis)

MECHANISM OF IMMUNOLOGICAL INJURY

• Most types of glomerulonephritis are immune mediated and respond to immunosuppressive drugs

• Mechanisms of immune mediated injury involve• circulating immune complexes• In-situ immune complexes

• Circulating immune complexes and in situ immune deposits lead to the activation of complement complexes which result in glomerular injury,as shown

Activation of complements

cytokinesC5b-9 C5a,C3a

oxidative stress, protease, matrix accumulations

Glomerular Disease

GLOMERULAR DISEASESCLASSIFICATION & CLINICAL

FEATURES

CLASSIFICATION & CLINICAL FEATURES

Clinically, a glomerular disease can be classified as being in one of two spectra—either in the nephritic spectrum or the nephrotic spectrum

NEPHROTIC SPECTRUM

• The nephrotic spectrum comprises diseases that present with

• Proteinuria• Hypoalbuminuria• Edema• Hyperlipidemia• Diseases falling in nephritic spectrum include:• Minimal change disease• FSGS• Membranous nephropathy• Focal segmental glomerulosclerosis• Diabetic Nephropathy

NEPHRITIC SPECTRUM

• Nephritic spectrum glomerular diseases presents with

• Hematuria• Proteinuria (0.3–3 g/d)• Hypertension • Edema, if present, in dependent (e.g., periorbital or

scrotal) areas• Diseases falling in nephritic spectrum include:• Post streptococcal glomerulonephritis• IgA nephropathy• Sle

SPECTRUM OF GLOMERULAR DISEASES

MINIMAL CHANGE DISEASE

• Occurs as sudden onset nephrotic syndrome in children

• Electron microscopy shows fusion of podocyte foot processes• Good response to steroids(Prednisolone

1mg/Kg for 6 weeks)• Does not progress to CKD

Electron Microscopy: effacement and fusion of foot processes

FOCAL SEGMENTAL GLOMERULOSECLEROSIS

• Focal process• Primary FSGS• Presents with idiopathic nephrotic syndrome• Poor response to steroids• Progresses to CKD• Recurs after transplant• Secondary FSGS • Variable presentation and outcome• Histology: Segmental scars in glomeruli• Associations: Local glomerular Injury• ,HIV infection, Heroin misuse, Morbid obesity

MEMBRANOUS NEPHROPATHY

• Common in Adults• Nephrotic presentation• Histology:Thickening of GBM,progressing to matrix

deposition and glomerulosclerosis with granular sub epithelial IgG deposits

• Pathogenesis:Antibodies to podocyte surface antigens with complement dependent podocyte injury

• Course:• 1/3 remits spontaneously• 1/3 remains in nephrotic state• 1/3 progressive loss of renal function

IMMUNOFLUORESCENCE

IGG DEPOSITION ALONG GBM

ELECTRON MICROSCOPY SUB EP ITHEL IAL ELECTRON DENSE MATERIAL

IGA NEPHROPATHY

• Presents with Hematuria, Proteinuria HTN• Leads to ESRD• Histology:Increased mesengial matrix and cellsMesengial IgA deposits• Poor response to immunosuppressive

therapy

LIGHT MICROSCOPY

D I F F U S E ME N I N G E A L H Y P E R CE L L U L A RI T Y

IMMUNOFLUORESCENCE

DIFFUSE MESANGIAL IGA

POST STREPTOCOCCAL GLOMERULONEPHRITIS

• More common in children• Follows streptococcal throat or skin infection

• Presentation:• Acute nephritic syndrome of varying severity• Hematuria• Characteristic “smoky/red urine”• Hypertension• Edema• Decreased GFR

POST STREPTOCOCCAL GLOMERULONEPHRITIS

• Histology

• Diffuse endothelial and mesengial cell proliferation• Neutrophils and

macrophage infiltration• Sub endothelial

electron dense deposits

POST STREPTOCOCCAL GLOMERULONEPHRITIS

Lumpy-bumpy deposits of immunoglobulin G and

complement C3 along the capillary loops and within the mesangium

Immunofluorescence

•Sub epithelial electron-dense deposits or “humps”

Electron microscope

POST STREPTOCOCCAL GLOMERULONEPHRITIS

• Laboratory findings:• Low serum complements levels of C3 and C4• Aso titre raised• Positive culture of throat swab

Treatment:• Fluid and sodium restriction• Diuretics• Control of HTN

• Resolves Completely

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

• Presents with Rapid deterioration of renal function• Oliguria and obvious

macroscopic hematuria• Crescent

formation>50% often associated with necrotizing lesions within glomerulus

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

• Seen in Good pasture’s disease, SLE and Small vessel vasculitides

• Need aggressive therapy with large dose steroids

• Prognosis: poor, most require dialysis.

INHERITED GLOMERULAR DISEASES

ALPORT’S SYNDROME

ALPORT ‘S SYNDROME

• X-linked recessive disorder characterized by• hematuria progressing to ESRD• Sensorineural hearing loss• Caused by mutation of COL4A5 gene on X

chromosome which encodes type IV collagen• Abnormal collagen results in degradation on GBM

and ocular abnormalities.• Female carriers presents with hematuria and does

not progress to ESRD• No definitive treatment available.

THANK YOU