Nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It is caused by increased permeability of the glomerular capillary wall due to damage or abnormalities of the glomerular basement membrane or podocytes. There are several histological types including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and membranoproliferative glomerulonephritis. Treatment involves controlling symptoms through dietary changes and medications, with corticosteroids often used to treat the underlying condition.

1. NEPHROTIC SYNDROME
Munivenkatesh
Paramasivam
Group: 02

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.

7. Classification
• Minimal change disease (Lipoid Nephrosis)
• Focal segmental glomerulosclerosis
• Membranous nephropathy (Membranous
glomerulonephritis)
• Membranoproliferative Glomerulonephritis

8. Epidemiology
• Nephrotic syndrome can affect any age,
Adults:Children = 26 : 1.
• 60% to 80% are primary,remainder are secondary.
• Men : Women = 2:1.

9. CAUSES-SECONDARY
• Focal segmental glomerulosclerosis
– Hypertensive nephrosclerosis
– HIV, Obesity, Kidney loss.
• Membranous nephropathy (MN):
– Systemic lupus erythematosus (SLE)
– Diabetes mellitus, Sarcoidosis, Cancer
– Drugs (such as corticosteroids, gold, heroin)
– Bacterial infections, e.g. leprosy & syphilis.

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

15. Typical Lesions

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)

19. THICKENED BASEMENT MEMBRANE

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

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.

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