2. • Glomerular
capillary wall,
• Its endothelium,
• GBM,
• Visceral epithelial
cells,
Which acts size and
charge barrier
through which
plasma filtrate
passes.
FILTRATION
3. Pathogenesis
• The primary disorder
of incresaed
glomerular
permeability to
plasma proteins.
• DUE TO
# Derangement in
capillary walls
# Change in GBM
construction
# Loss of negative
charge on GBM
4. Pathophysiology
NS is an accumulation of symptoms and
signs and is characterized by
• Proteinuria (>3.5g/day),
• hypoproteinemia,
• Hypoalbuminemia ( serum albumin < 2.5 gm/dL ),
• Hyperlipidemia,
• Thrombophilia and
• Generalized Edema (anasarca) – begins in the
face. Hypoproteinemia plasma oncotic pressure
so fluid goes to interstitial space.
5. • Puffiness around the eyes (Morning)
• Pitting edema over the legs.
• Pleural effusion and Pulmonary edema.
• Ascites,
• Hypertension,
• Anemia,
• Dyspnea,
• ESR >100mm/hr.
• Anorexia,
• Fatigue,
• Abdominal pain,
• Diarrhea
6. • Hyponatremia can also occur with a
low fractional sodium excretion.
• Muehrcke's nails – white lines (leukonychia)
that lie parallel to the lunula.
8. Epidemiology
• Nephrotic syndrome can affect any age,
Adults:Children = 26 : 1.
• 60% to 80% are primary,remainder are secondary.
• Men : Women = 2:1.
10. • CAUSES
-Prophylactic immunization,
-Corticosteroid and immunosupperssive therapy,
-Atopic disorders (eczema, rhinitis)
- Hodgkin's lymphoma,
-Allergy, Bee sting
PATHOGENESIS
uniform and diffuse effacement of the foot
processes of the podocytes
Minimal Change Disease
11. Minimal Change Disease
• Bening disorder, most frequent cause of children.
• Characterized by Diffuse Effacement of Foot
Process of Podocytes in Glomeruli that appear
normal by Light microscopy
12. • Electron microscopy shows uniform and diffuse
effacement of the foot processes of the podocytes.
13. Focal Segmental Glomerulosclerosis
• As the name implies, this lesion is charecterized by sclerosis
of some glomeruli (Focal); and in the affected glomeruli
only a portion of Capillary tuft is involved (segmental).
• CAUSES
Hypertensive nephrosclerosis
Idiopathic,
IgA nephropathy,
HIV,
Obesity,
Kidney loss,
Inherited.
14. PATHOGENESIS
• Charecteristic degeneration and focal disruption
of visceral epithelial cells.
– increased mesangial matrix,
– obliterated capillary lumens,
– deposition of hyaline masses and lipid droplets.
• On electron microscopy, podocytes exhibit
effacement of foot processes, as in MCD
16. • Immunofluorescence microscopy often reveals
nonspecific trapping of immunoglobulins, usually
IgM
• 50% of individuals with FSGS develop end-stage
renal failure within 10 years of diagnosis
17. Membranous Nephropathy
• Membranous Nephropathy is a common cause of
the nephrotic sydrome in adults ( age 30 to 50 ).
CAUSES
-Drugs (NSAID),
-Underlying malignant tumors,
-SLE,
-Infections (chronic hepatitis B,C and malaria),
-Autoimmune disorders,
-Diabetes mellitus,
-Sarcoidosis.
18. • Characterised by
Diffuse thickening
of glomerular
capillary wall due
to accumulation
of electron dense,
Ig containing
deposits along
subepithelial side
of basement
membarane.
("spike and dome"
pattern)
20. • In addition, the podocytes show effacement of
foot processes
• Later the incorporated deposits may be
catabolized and eventually disappear, leaving
cavities within the GBM.
• Further progression, the glomeruli can become
sclerosed
• Immunofluorescence microscopy shows typical
granular deposits of immunoglobulins and
complement along the GBM
21.
22. Membranoproliferative Glomerulonephritis
• Characterized histologically by alterations in the
glomerular basement membrane, proliferation
of glomerular cells, mesangial and endothelial
cells and leukocyte infiltration.
• Two major types (I and II).
• Type I is far more common.
• Types I & II have different
ultrastructural &
Immunofluorescence
and pathological features.
23. Type I MPGN
• It is characterized by discrete subendothelial
electron-dense deposits.
• By immunofluorescence microscopy,
C3 is deposited in an irregular
granular pattern.
• IgG and early complement
components (C1q and C4)
are often also present,
indicative of an immune
complex pathogenesis.
24. Type II MPGN
• The lamina densa and the subendothelial
space of the GBM are transformed into an
irregular, ribbon-like, extremely electron-dense
structure (dense-deposit disease).
• C3 is present in irregular chunky
and segmental linear foci in
basement membranes and in
mesangium in circular
aggregates (mesangial rings).
• IgG, C1q and C4 are usually absent.
25.
26. Diagnosis
• Urinalysis to test proteinuria
(>3.5 g per 1.73 m2 per 24 hours).
• Blood screen to look for hypoalbuminemia:
≤2.5 g/dL (normal=3.5-5 g/dL).
• Renal function Creatinine Clearance test to evaluate
renal function particularly the glomerular filtration
capacity.
• A lipid profile for hypercholesterolemia.
• A kidney biopsy may also be used.
• Further investigations include analysis of auto-
immune markers or ultrasound.
27. Treatment
• Symptomatic treatment for edema,
hypoalbuminemia, hyperlipidemia,
thrombophilia.
• Treatment of kidney damage:
#Corticosteroids (Prednisone)
#Frequent relapses treated
by: cyclophosphamide or nitrogen mustard or
cyclosporin or levamisole.
#Immunosupressors (cyclophosphamide)
28. COMPLICATIONS
• thromboembolic disorders
• Meningoencephalitis,
• Acute kidney failure due to hypovolemia,
• Hypothyroidism: thyroglobulin transport protein,
• hypochromic anaemia: ferritin loss(iron loss)
• Protein malnutrition,
• Pulmonary edema
• Growth retardation,
• Vitamin D deficiency. Vitamin D binding protein lost
• Cushing's Syndrome