Nephrotic Syndrome

Question 1

What is the common pathogenesis in nephrotic syndrome?

Answer 1

Derangement in capillary wall of glomeruli, resulting in inc permeability to PPs leading proteinuria

Question 2

Describe mechanism of edema in nephrotic syndrome

Answer 2

Dec oncotic pressure due to proteins loss so fluid escapes from vascular tree into tissues, there is concomitant drop in plasma volume with diminished glomerular filtration volume. This leads to inc renin which promotes salt & water retention aggravating edema.

Question 3

What is the fause of hyperlipidemia in nephhrotic $

Answer 3

1. Hypoalbuminemia triggers inc synthesis of lipoproteins in the liver
2. Abnormal transport of circulating lipid particles
3. Impairment of peripheral breakdown of proteins

Question 4

List microscopic features of tubules & interstitial tissue in nephrotic sydrome

Answer 4

1. Hyaline droplet degeneration of the epithelium of the convoluted tubules due to resorption of protein from the urine
2. Vacuolar degeneration of the epithelium of the convoluted tubules due to resorption of lipids from urine
3. Protein casts within tubular lumen
   IT shows variable edema

Question 5

Common EM feature of nephrotic syndrome is……

Answer 5

Effacement of foot processes of the podocytes

Question 6

The most common cause of nephrotic syndrome is…….most common in age…….

Answer 6

Minimal change disease
1-7 yrs

Question 7

Describe pathogenesis of minimal change disease

Answer 7

Attributed to a circulating T-cell derived factor that causes podocyte damage and effacement of foot processes.

Question 8

Minimal change disease microscopic changes can only be seen by……

Answer 8

EM

Question 9

Describe C/P & prognosis of minimal change disease

Answer 9

Nephrotic syndrome with highly selective albuminuria
Good prognosis is good, particularly in children, with prolonged remission or even permenant cure occur spontaneously or in response to steroid therapy. Adults show more frequent relapses, only rare cases lead to chronic renal failure.

Question 10

Etiology of FSGS?

Answer 10

1. Primary (idiopathic)
2. 2ry to HIV infection, or to other causes of GN as IgA nephropathy or 2ry to hyperfiltration injury or due to maladaptation to nephron loss

Question 11

What is pathogenesis of FSGS?

Answer 11

It is unknown, injury to podocytes is thought to represent the initiating event of primary FSGS, in minimal change disease a circulating permeability inc factors produced by lymphocytes are suspected. The deposition of hyaline masses in the glomeruli represents the entrapment of PPs & lipids in foci of injury where sclerosis develops.

Question 12

Describe LM features of FSGS

Answer 12

1. Presence of sclerotic segments in a variable number of glomeruli
2. Affected glomeruli exhibit inc mesangial matrix, obliterated capillary lumina and deposition of hyaline & foamy macrophages
3. Tubules & interstitial tissue exhibit variable tubular atrophy & interstitial fibrosis

Question 13

Describe clinical course of FSGS

Answer 13

Nephrotic syndrome presentation or nephrotic/nephritic syndrome (HTN & hematuria), proteinuria is non-selective may be in subnephrotic range
It is resistant to steroid 50% or more develop end stage renal disease within 10 yrs of diagnosis

Question 14

Describe pathogenesis of membranous glomerulonephritis

Answer 14

1. It is a form of chronic immune complex GN induced by antibodies reacting in situ to fixed (1ry disaese, podocyte antigen phospholipase A2 receptor (PLA2R) or planted (2ry disease, endogenous or exogenous Ag
2. This activates MAC causing podocyte injury & proteinuria, also stimulates TGF receptor on Ep cells inc synthesis of GBM materal leading to thickening of GBMs

Question 15

Describe findings of EM & immunofluorescence in MGN

Answer 15

IFM: granular deposits of IgG & complement along the GBM
EM: reveals subepithelial electron dense deposits separated by outward projections of the GBM termed spikes. As the disease progresses the spikes incorporate into GBM (intramembranous), diffuse fusion of foot processes of podocytes, in more advanced stage there is actual thickening of GBM with disappearance of deposits.

Question 16

Describe clinical features & prognosis of MGN

Answer 16

Presents with isolated proteinuria or full blown nephrotic syndrome, unresponsive to CS, indolent course, proteinuria is non-selective & persists in greater than 60% of patients, about 40% suffer of progressive disease terminating in renal failure after 2 to 20 yrs, an additional 10% to 30% have a more benign course with partial or complete remission of proteinuria.

Question 17

Describe pathogenesis of type I MPGN

Answer 17

Immune complex mediated GN
Caused by deposition of circulating immune complex or by in situ immune complex formation with a planted antigen. May be primary, the antigen involved is not known. Or 2ry associated with hepatitis C & B viral infection, also 2ry to SLE & chronic bacteral infections.

Question 18

Describe LM feature of MPGN (all types)

Answer 18

1. Hypercellularity due to proliferation of mesangial cells with/out infiltrating leukocytes.
2. Inc mesangial matrix with accentuated lobulation
3. Thickening of GBM often shows partial or circumferential double contours “Tram Track” appearance best seen in silver & PAS. (The subendothelial deposits and mesangial interposition along with mesangial matrix deposition cause thickening of GBMs & splitting creating a tram track appearance.

Question 19

Describe findings of EM & immunofluorescence in type I MPGN

Answer 19

IFM: Type I MPGN; IgG & C3 are deposited in granular pattern earlier complement components are present.
EM: subendotheial electron dense deposits and mesangial cell interposition

Question 20

Describe pathogenesis of C3 glomerulopathy

Answer 20

1. Complement dysregulation due to acquired or hereditary abnormalities in the alternative pathway of complement activation is underlying cause of C3GN
2. Some patients have an autoantibodies against C3 convertase, called C3 nephritic factor, that causes uncontrolled cleavage of C3 by the alternative pathway
3. In other patients, mutations in various complement regulatory proteins are the cause of unregulated activation of alternative pathway.

Question 21

Describe findings of EM & immunofluorescence in C3GN & DD

Answer 21

IFM: both show bright mesangial and capillary wall staining for C3 and IgG while early complement components (as C1q and C4) are usually absent.
EM: C3GN shows mesangial and subendothelial electron dense deposits and the mesangial cell interposition
DDD shows transformation of the lamina densa and the subendothelial space into an intramembranous irregular ribbon like extremely electron dense structure.

Question 22

Mention kidney lesions caused by diabetes

Answer 22

Diabetic glomerulosclerosis, renal arteriolar sclerosis, pyelonephritis, papillary necrosis

Question 23

Mention patterns of diabetic glomerulosclerosis

Answer 23

1. Diffuse GS: in which there is diffuse increase of mesangial matrix and thickening of GBM
2. Nodular GS (Kimmelsteil-Wilson lesion) in which one or more hyaline nodules are present in the mesangium, containing lipid & fibrin

Question 24

Describe microscopic findings of amyloid nephropathy

Answer 24

Chct by pale eosinophilic homogenous deposits in the glomeruli, tubular BMs, PTCs, & blood vessels detected by Congo Red with apple green birefringence under polarized light, Ab to AA and thioflavin T.

Question 25

Describe pathogenesis, IFM & EM features of lupus nephritis

Answer 25

P: due to deposition of DNA-anti-DNA complexes in glomeruli that may provoke proliferation of endothelial, mesangial, epithelial cells and may cause even necrosis
IF: reveals granular fluorescence of glomerular capillary walls and mesangium for most Igs and all complement components
EM: show large subendothelial and mesangial electron dense deposits, the former corresponding to the wire loops seen by LM

Question 26

List classes of lupus nephritis

Answer 26

Class I: minimal mesangial lupus nephritis
Class II: mesangial proliferative lupus nephritis
Class III: focal lupus nephritis (less than 50% of glomeruli)
Class IV: diffuse lupus nephritis (more than 50% of glomeruli)
Class V: membranous lupus nephritis
Class VI: advanced sclerosing lupus nephritis

Question 27

……..is the most common & serious type of lupus nephritis
Mention its features

Answer 27

Class IV
Involves more than 50% of glomeruli, they show global hypercellularity, capillary wall thickening with wire loop appearance, leukocytes & occasionally necrosis & crescents

Question 28

Describe microscopic features of CKD

Answer 28

1. Advanced scarring of glomeruli upto sclerosis
2. Marked interstitial chronic inflammatory infiltrate & fibrosis
3. Atrophy of many tubules in the cortex
4. The small and medium-sized arteries are thick-walled with narrowed lumina, 2ry to HTN
5. Such damaged kidneys are called end-stage kidneys