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