1. BY:
DR.LEENA HAFEEZ
GLOMERULAR DISEASES

2. 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

3. Three-dimensional schematic drawing of the glomerulus
Afferent arteriole
Efferent arteriole
Endothelial
cells
Capillary
loops
Mesangial matrix
and cell
Bowman’s Space

4. Light micrograph of glomerulus showing
Normal cellularity with patent capillary lumen

5. Electron micrograph
Podocytes
Glomerular
basement
membrane
Capillary Lumen
Endothelial cell
内皮细胞

6. GLOMERULAR DISEASES
PATHOGENESIS

7. WHAT CAUSES GLOMERULAR
DISEASES
Glomerular diseases results from:
• Immunological Injury(Glomerulonephritis)
• Inherited(Alport’s Syndrome)
• Metabolic stress(Diabetes mellitus)
• Deposition of extraneous materials(Amyloidosis)

8. 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

9. Activation of complements
cytokines
C5b-9 C5a,C3a
oxidative stress, protease, matrix accumulations
Glomerular Disease

10. GLOMERULAR DISEASES
CLASSIFICATION & CLINICAL FEATURES

11. 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

12. 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

13. 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

14. SPECTRUM OF GLOMERULAR
DISEASES

15. 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

16. Electron Microscopy: effacement and fusion of foot processes

17. 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

18. 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

19. IMMUNOFLUORESCENCE
IGG DEPOSITION ALONG GBM

20. ELECTRON MICROSCOPY
SUB EPI THELIAL ELECTRON DENSE MATERIAL

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

22. LIGHT MICROSCOPY
DIFFUSE MENINGEAL HYPER CELLULARITY

23. IMMUNOFLUORESCENCE
DIFFUSE MESANGIAL IGA

24. 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

25. POST STREPTOCOCCAL
GLOMERULONEPHRITIS
• Histology
• Diffuse endothelial and
mesengial cell
proliferation
• Neutrophils and
macrophage infiltration
• Sub endothelial
electron dense
deposits

26. 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

27. 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

28. 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

29. 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.

30. INHERITED GLOMERULAR
DISEASES
ALPORT’S SYNDROME

31. 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.

32. THANK YOU