5. Causes of nephritic syndrome
Primary glomerulonephritis
– Acute GN
• Post streptoccocal
• Non streptococal
Rappidly progressive GN
Membranoproliferative GN
Focal GN
IgA nephropathy GN
7. Classification of glomerular disease
Primary glomerulonephritis
– Acute GN
• Post streptoccocal
• Non streptococal
Rappidly progressive GN
Minimal change GN
Membranous GN
Membranoproliferative GN
Focal GN
IgA nephropathy GN
Chronic GN
10. Nephritis Caused by Circulating
immune Complexes
With
circulating
immune
complexmediated disease,
the gromerulus is considered “innocent
bystander” because it does not incite the
reaction.
The antigen is not of glomerular origin.
It may be endogenous, as in the GN
associated with SLE, or
it may be exogenous, as is probable in the
GN that follows certain bacterial, viral,
parasitic and spirochetal infections.
Often the inciting antigen is unknown, as
in most cases of membranous nephropathy.
11.
Whatever the antigen may be,
antigen-antibody complexes are formed
in situ or in the circulation and are then
trapped in the glomeruli,
where they produce injury, in large
part
through
the
activation
of
complement and the recruitment of
leukocytes.
Regardless of the mechanism, the
glomerular lesions usually consist of
leukocytic infiltration into glomeruli and
variable proliferation of endothelial,
mesangial, and parietal epithelial cells.
12. Electron microscopy reveals the immune
complexes as electron-dense deposits
or clumps that lie at one of three sites:
in the mesangium,
between the endothelial cells and the
GBM, or
between the outer surface of the GBM
and the podocytes.
Seen in most cases of poststreptococcal
or acute infection-related GN.
13. Nephritis Caused by in Situ Immune
Complexes
Anti-Glomerular Basement
Membrance (GBM) Antibody
Glomerulonephritis.
In this type of injury, antibodies
are directed against fixed antigens
in the GBM.
14. Cell-Mediated Immune
Glomerulonephritis
It has often been suggested that
sensitized T cells, formed during the
course of a cell-mediated immune
reaction, can cause glomerular injury.
In some forms of experimental GN
in rodents, the disease can be
induced by transfer of sensitized T
cells.
15. T cell-mediated injury may account for
the instances of GN in which either
there are no deposits of antibodies or
immune complexes or the deposits do
not correlate with the severity of
damage.
16. Mediators of Immune Injury
Glomerular damage, reflected
by loss of glomerular barrier
function,
is
manifested
by
proteinuria and, in some instances,
by reduction in GFR.
A major pathway of antibody –
initiated injury is complementleukocyte-mediated
17.
Activation of complemnt leads to the
generation of chemo tactic agents and
the recruitment of neutrophils and
monocytes.
Neutrophils release proteases, which
cause GBM degradation; oxygen-derived
free radicals, which cause cell damage;
and arachidonic acid metabolites, which
contribute to reduction in GFR.
This mechanism applies only to some
types of GN.
18.
Some models suggest complementdependent but not neutrophil-dependent
injury, due to an effect of the C5 lytic
component of complement,
which
causes
epithelial
cell
detachment and stimulates mesangial
and epithelial cells to secrete various
mediators of cell injury.
Thus giving rise to altered GBM
composition and thickening.
19. Other mediators of glomerular
damage include
(1)monocytes and macrophages,
which infiltrate the glomerulus in
antibodyand
cell-mediated
reactions and, when activated,
release
a
vast
number
of
biologically active molecules;
(2) platelets, which aggregate in the
glomerulus
during
immunemediated
injury
and
release
prostaglandins and growth factors;
20. (3) Resident glomerular cells, which
can be stimulated to secrete
mediators such as cytokines
arachidonic
acid
metabolites,
growth factors, nitric oxide, and
endothelin; and
(4) fibrin-related products, which
cause leukocyte infiltration and
glomerular cell proliferation as a
consequence of intraglomerular
thrombosis.
21. Other Mechanisms of Glomerular Injury
Two that deserve special mention are
podocyte injury and injury secondary to
nephron loss.
Podocyte Injury:
This can be induced by antibodies to
visceral epithelial cell antigens; by
toxins, certain cytokines; or by still
poorly characterized factors, as in some
cases of focal and segmental
glomerulosclerosis.
22.
23. Such injury is reflected by
morphologic
changes
in
the
podocytes,
which
include
effacement of foot processes,
vascularization, and retraction and
detachment of cells from the GBM,
and functionally by proteinuria.
In most forms of glomerular
injury,
loss
of
normal
slit
diaphrangms is key in the
development of proteinuria.
24. Nephron Loss.
Once
any
renal
disease,
glomerular or otherwise, destroys
sufficient functioning nephrons to
reduce the GFR to 30% to 50% of
normal progression to end-stage
renal
failure
often
proceeds.
develop proteinuria, and their
kidneys
show
widespread
glomerulosclerosis.
25. These remaining glomeruli undergo
hypertrophy to maintain renal function.
This is associated with hemodynamic
changes, including increases in single
nephron, GFR, blood flow, and
transcapillary pressure.
These adaptations in the intact
glomeruli are ultimately maladaptive
and lead to further endothelial and
epithelial cell injury, increased
glomerular permeability to proteins,
and accumulation of proteins and lipids
in the mesangial matrix.
26. TYPES OF GLOMERULONEPHRITIS:There are different types of GN
It may involve either the nephrotic
syndrome or nephritic syndrome
Diagnosis made by C/F or by renal
biopsy
27. Types of glomerulonephritis (ACUTE NON
STREPTOCOCAL)
Minimal change disease
Is a benign disorder
Frequent cause of nephrotic
syndrome in children
Here the glomeruli shows a diffuse
effacement of podocyte foot
process.
28. 1. MINIMAL CHANGE DISEASE
(LIPOID NEPHPOSIS)
It is a begin disorder.
Frequence cause of nephrotic
syndrome.
Different affacement of
pocodeyti foot processes (they
appear flattened
29. CAUSES
Idiopathic
Systemic disease (hodgkins disease, HIV
infection) & drug therapy (NSAID)
PATHOGONESIS:
Protenuria has been attributed to T cell
derived factor that cause podoeyte
enjury & affacement.
C/F:- Protein Loss
Prognosis – good, Rx is corticosteroids
30. Focal & segmental to slecrosis :
Characterized by sclerosis
affecting some but not all the
glomeruli
CAUSES
Associated with HIV infection
IgA nephropathy
Maladaptation after nephron loss
Congenital malformation in
podocytes
31. PATHOGENS:
Unknown
Investigators have said that FSGS
and MCD are continuous – MCD
may transform into PSGS
C/F:
Variable protunuria
Not responding to corticosteroids
Prognosis:
Poor
Recurs after transplantation
32. 3. MEMBRANOUS NEPHROPATHY
(MENBRANEOUS GN)
Occurs between 30 & 50 years.
Subepithelial deposits
Causing thickening of the capillary wall.
Causes:
idiopathic secondary to
Infections (chronic hepatitis, syphillis,
malaria)
Malignant tumors of lung & colon
SLE & other auto immune disorders
Drugs (NSAID’S)
33. C/F
Heavy protenuria
Does not respond to
cortecosteroids
They may respond to prednisolone.
PROGNOSIS :Variable
30% may have spontaneous
remission
34. Menbranoproliferative FN:Alteration in the GBM &
mesangium
Proliferation of glomerular cell
TYPES:
Mesengial cells are found between
the endothelium & GBM
Immune deposits are found in
subendotheal region
(SLE)
(bacterial endocardites, HIV,
hepatitis
35. TYPE II
Is autoimmune disease called
IgG autoantibodies called c3
nephretic factor
Causing lipodystrophy loss of
subcutaneous fat from the upper
half of the body.
36. IGA NEPHROPATHY :
Affects children
Associated with gross hematuria
Associated with loin pain
Here there is deposition of IgA is
mesangium (due to IgA production
& clearance abnormal)
It is due to some infection is to
respiratory or GI tract.
These activates the alternative
complement pathway
Glomerular injury
39. PATHOPHYSIOLOGY:
Antigen (group A seta – hemolylic
streptococcus
Antigen – antibody products
Deposition of antigen – antibody
complexes in glomerulers
Increase production of epithelial
cells lining the glonerulus
42. Elderly patient may experience
circulattory ocurroal, with dyspnea,
engorged nec ceeins, cardionegely
and pulmonary edema.
Hypoalbuninenia and
hyperlipedemia.
43. DIAGNOSTIC STUDIES: History and physical examination
Urinalysis
CBC
BUN, seum creatinine and albunmin
Complement levels and ASO titre
Renal biopsy.
Signs of overload
Periorbital edema
Edema and hypertension due to overload
Crackles
Elevated jugular venous pressure
Rashes
Pallor
45. Lab studies:
Urine analysis
Complement levels
Twenty-four hours urine test for
total protein
Anti sterptolysin O titre
Dipstick test
Imaging studies
Renal biopsy: cellular infiltration,
granular deposits of
immunoglobulin.
46. Treatment:
Antimicrobial therapy:
Penicillin 500000 IU q6 q8 hourly
Loop diuretics:
Frusemide:
Edema: 40-80mg to 20- 40mg 6th
hourly.
Hypertension: 20- 40mg bid PO bid
Vasodilators:
Sodium nitroprusside
0.5-8mcg/kg/mim IV infusion
47. Diet:
Sodium and fluid restriction
Protein restriction 0.6 – 0.75g/kg/wt
Water restriction to 600ml plus the
previous days urine output.
Sodium restriction; 2 to 4g
depending on the degree of edema.
Avoid high sodium food.
49. Pathophysiology:
Acute GN (repeated episodes)
Cause hardening of renal arteries
Reducing the size
Scar tissue formation (numerous
glomerulus and branches of renal
arteries are thickened)
Severe glomerular damage
End stage renal failure
58. NEPHTOTIC SYNDROME
Nephrotic syndrome is a cluster of
clinical findings, including
Marked increase in protein
(particularly albumin) in the urine
(protienuria)
Decreased in albumin in the blood
(hypoalbuminenia)
Edema, hypercholesterolemia &
normal renal function.
59. The causes can be classified also
Primary glomerulonephrills
Minimal change disease
Membranous GN
Menbranoproliferative GN
Focal segmental
glomerulosclerosis
Focal GN
IgA nephropathy
64. Pathophysiology:
Damage to the glomerular capillary
membrane
Loss of plasma protein
Stimulate synthesis
of liporotiens
hypoalbuminimea
Hyperlipidemia
decreased oncotic press
generalized edema
renin angeotensin
edema