Nephritic Syndrome

Question 1

Describe pathogenesis of nephritic syndrome

Answer 1

1. The lesions that cause nephritic syndrome have in common proliferation of cells within the glomeruli accompanied by leukocytic infiltrate.
2. The inflammatory reaction injures capillary walls allowing escape of RBCs to urine and hemodynamic changes that lead to dec GFR, manifested clinically as oliguria, reciprocal fluid retention and azotemia
3. HTN is probably a result of both fluid retention and some augmented renin release from ischemic kidneys

Question 2

Describe pathogenesis of acute postinfectious GN

Answer 2

1. It is an immune complex disease involving a microbial antigen
2. The antigen are most likely streptococcal proteins
3. It is not clear if they are formed in circulation or in situ
4. Tissue injury is mainly caused by complement activation by classic pathway,immune complexes fix complements and cause damage as C5a inc capillary permeability and attracts neutrophils and monocytes to glomeruli. They secrete proteases that cause damage of GBM, O2 & free radicals that injure cells and AA metabolites that dec GFR

Question 3

Describe LM features of postinfectious GN

Answer 3

All glomeruli are affected in diffuse manner, they are enlarged and hypercellular due to proliferation of endothelial and mesangial cells as well as infiltration by monocytes and neutrophils. There is obliteration of many capillary lumina by swollen and proliferated endothelial cells. Occasional crescents can develop in severely injured glomeruli. Tubules contain red cell casts. Blood vessels are unremarkable.

Question 4

Describe features of acute postinfect GN in:
1. Immunoflurescence
2. EM

Answer 4

1. Reveals granular fluorescence of GBM and mesangium for IgG and all complement components
2. Discrete subepithelial electron dense humps

Question 5

Mention causes of the following in acute postinfectious GN:
1. HTN
2. Periorbital and face edema
3. Inc BUN

Answer 5

1. Due to dec renal blood flow leading to release of renin from JGA
2. Due to salt and water retention
3. Due to dec GFR as a result of dec renal blood flow

Question 6

Describe course and prognosia of acute postinfect GN

Answer 6

In children over 95% completely recover. The remainder die during the attack by acute renal failure or complications of HTN get progressively worse and develop a rapidly progressive GN. Few cases progess to chronic
Adults: disease is less benign; only about 60% of cases completely recover.

Question 7

Berger’s disease is also knwon as …..

Answer 7

IgA nephropathy

Question 8

Describe pathogenesisbof IgA nephropathy

Answer 8

An abnormally glycosylated IgA1 elecits immune response and autoAbs may form large immune complexes with circulating IgA, these complexes deposit in mesangium. IgA aggregates in mesangium and activates alternative complement pathway leading to irritation of mesangial cells and inflammation of capillary walls.

Question 9

Describe role of genetics in IgA nephropathy

Answer 9

Genetic susceptiblity is suggesteb by running in families, respiratory or GI exposure to microbial Ag may lead to inc IgA production with abnormality in glycosylated of IgA leading to mesangial deposition.

Question 10

IgA nephropathyay be 2ry to…..

Answer 10

Liver diseses

Question 11

Describe LM features of Berger’s diseasr

Answer 11

Glomeruli may be:
1. Normal
2. Show mesangial widening and segmental inflammation (less tgan 50%, focal mesangioproliferative GN)
2. OR show diffuse mesangial proliferation involving more than 50% of glomeruli.
Rarely cescentic GN

Question 12

Describe features of Berger’s in:
1. Immunoflurescence
2. EM

Answer 12

1. Granular mesangial deposition of IgA,IgG, IgM and C3 with later conplement components
2. Electron dense deposits in mesangiym

Question 13

C/P of Berger’s disease

Answer 13

Children and young adults 10-29, usually male beguns with episode of gross hematuria occurs within 1-2 days of RTI. Lasts several days and subsides but recurs every few months.

Question 14

Describe course and prognosis of Berger’s disease

Answer 14

Good in most patients, the condition can sometimes lead to chronic GN
Poor prognostic features: cescents, prominent arteriolar hyalinization, older age, heavy proteinuria, HTN

Question 15

Write a short note on Henoch-Schönlein purpura

Answer 15

HPS is a systemic syndrome shwoing pirpuric rash, abdominal pain, arthritis and hematuria. Also shows deposition of IgA in mesnagium with similar morphological features to Berger’s.

Question 16

Manifestations of Alport syndrome include……..

Answer 16

Nephritis, sensorineural hearing loss, various eye disorders including lens dislocation, posterior cataract, corneal dystrophy.

Question 17

…….is the most common cause of benign familial hematuria with no systemic manifestation

Answer 17

Thin basement membrane disease

Question 18

Alport’s syndrome is chch by defect in…….

Answer 18

Heterodiers of a3, a4, a5 type IV collagen

Question 19

Mention mode of inheritance of hereditary nephritis

Answer 19

1. Alport’s syndrome is X-linked recessive in 85% of cases or AR is 15%
2. Thin basememt membrane disease carries same mutation but in heterozygous form thus is AD

Question 20

LM features of Alport’s include………

Answer 20

Glomerulosclerosis, tubular atrophy, interstitial fibrosis

Question 21

Describe EM picture of hereditary nephtitis

Answer 21

Alport’s shows alternating thinned out areas of GBM and thickened irregular areas with pronounced splitting and lamellation of lamina densa yielding a basket wave appearnce
Thin BM disease shows diffuse thinning of GBM

Question 22

C/P of hereditary nephritis

Answer 22

X-linked alport more common in male, presents age 5-20 with persistent gross or microscopic hematuria, proteinuria can be found.
Progress to overt renal failure by age 20-50 in Alport’s
Patients with thin BM disease present by microscopic hematuria and run a benign course.

Question 23

Describe the common pathogenesis of cresentric GM

Answer 23

Severe destruction of GBMs eith escape of fibrin into Bowman’s capsule and irritation of parietal epithelial cells leading to tgeir proliferation and crescent formation.

Question 24

List types of rapid progressive GN

Answer 24

1. Type I: Anti-GBM antibody-mediated crescentic GN, c
2. Type II: immune complex mediated complicating poststeprtococcal GN, SLE IgA nephropathy, HSP
3. Type III: Pauci-immune crescentic GN ANCA-associated with microscopic polyangitis and polyangitis with granulomatosis

Question 25

In LM Crescents may be………

Answer 25

Cellular, fibrocellular or fibrous

Question 26

With regards crescentric GN, Normocellular tufts are seen in……….

Answer 26

Anti-GBM disease & pauci-immune GN

Question 27

Necrotizing vacutitis is seen in…….

Answer 27

Pauci-immune GN

Question 28

Describe immunofluorescence findings in rapid progressive GN

Answer 28

Type 1: linear staining of capillary walls for IgG & C3
Type 2: granular staining of capillary walls for IgG & C3
Type 3: -ve immunofluorescence staining

Question 29

Describe EM picture of crescentric GN

Answer 29

1. Tuptures of GBM in Bowman’s capsule may be found in all types
2. Electron dense deposits in immune complex mediated crescentic GN

Question 30

What is the prognosis of rapid progressice GN

Answer 30

Fatal in few weeks to 2 yr unless dialysis or transplantation
Plasma exchange (plasmapharesis) may be of benefit in anti-GBM antibody GN