Nephritic Syndrome

Question 1

What disorder is caused by subendothelial immune complex deposits?

Answer 1

Membranoproliferative GN

Question 2

What disorder is caused by mesangial immune complex deposits?

Answer 2

IgA nephropathy

Question 3

Acute nephritic syndrome is characterized by the acute onset of: (6)

Answer 3

1. Hematuria (Microscopic or macroscopic, RBC casts)
2. Hypertension
3. Oliguria
4. Edema –usually moderate
5. Mild to moderate proteinuria
6. Azotemia

Question 4

Diseases due to immune deposition are associated with circulating immune complexes that are planted at sites according to their:

Answer 4

size
charge
(and other affinity characteristics)

Question 5

3 Causes of endothelial cell injury:

Answer 5

1. Deposition of immune complexes in the subendothelial space
2. Thrombotic microangiopathies
3. Entrapment of paraproteins (in B-cell lymphoproliferative disorders, Plasma cell dyscrasias, Multiple myeloma)

Question 6

Endothelial damage results in:

How does this manifest clinically?

Answer 6

a local inflammatory response

1. Cytokines + autacoids are released
2. Cytokines, autocoids + activated complement upregulate adhesion molecules on endothelial and circulating immune cells

Hematuria

Question 7

What pathophysiological findings are characteristic of Membranoproliferative glomerulonephritis type I?

Answer 7

1. Hypercellularity of the glomerular tuft
2. Increased mononuclear cells within expanded mesangium + capillary lumens
3. Double-contour/duplication of glomerular basement membrane (tram track)

Question 8

What causes duplication of the basement membrane?

Answer 8

endothelium displaced by

1) immune deposits
2) infiltrating mesangial cells

Question 9

What are possible presentations of MPGN type I? (5)

Answer 9

1. Microscopic hematuria
2. Non-nephrotic range proteinuria
3. Nephrotic syndrome
4. Acute nephritic syndrome
5. Rapidly progressive glomerulonephritis

Question 10

MPGN type 1 is often associated with what infection?

Answer 10

hepatitis C

Question 11

What lab value will be low in MPGN type 1 and 2?

Answer 11

C3

Question 12

MPGN type I progresses (slowly/rapidly) to end stage renal disease.

Answer 12

slowly

Question 13

What is present in 80% of patients with dense deposit disease (MPGN type 2)?

Answer 13

C3 nephritic factor

Question 14

What conditions may be associated with dense deposit disease (MPGN type 2)?

Answer 14

1. macular deposits in the eyes

2. acquired partial lipodystrophy (loss of subcut fat in upper 1/2 of body)

Question 15

In dense deposit disease (type II MPGN), what is seen on immunofluorescence? On Electron microscopy?

Answer 15

IF: C3, but no Ig
EM: characteristic electron-dense deposits in the GBM

Question 16

Describe the Pathophysiology of immune-complex-mediated membranoproliferative
glomerulonephritis.

Answer 16

1. complement activated via classical pathway
2. leukocytes recruited
3. leukocytes release proteases, etc, that damage endothelium/BMem/epithelium
4. repair leads to formation of new BMem that incorporates debris

Question 17

Describe the Pathophysiology of complement-mediated membranoproliferative
glomerulonephritis.

Answer 17

1. controls of complement activation are dysregulated
2. complement activated via alternative pathway
3. leukocytes recruited
4. leukocytes release proteases, etc, that damage endothelium/BMem/epithelium
5. repair leads to formation of new BMem that incorporates debris

Question 18

Most common primary glomerulonephritis worldwide:

Answer 18

IgA nephropathy (IgAN)

Question 19

What characterized IgA nephropathy (pathologically)?

Answer 19

deposition of IgA-containing immune complexes predominantly in the mesangium, which results in a mesangioproliferative pattern of injury

Question 20

IgA nephropathy may occur secondary to what conditions? (7)

Answer 20

Henoch-Schonlein Purpura
Ankylosing spondylitis
Dermatitis herpetiformis
Celiac disease 
Inflammatory bowel disease 
Cirrhosis 
Psoriasis

Question 21

What triggers IgA nephropathy, and how does this progress to the disease state (pathogenesis)?

Answer 21

1. URI or GI tract infection
2. IgA are produced that are under galactosylated at O-linked glycans in the hinge region of IgA1
3. IgG or IgA1 antibodies recognize these O-linked glycans terminating with N-acetylgalactosamine instead of galactose
4. Circulating immune complexes (CICs) deposit in the mesangium
   * may result in a proliferative and occasionally necrotizing glomerulitis

Question 22

________ nephritic sediment occurs within 1-2 days of infection.

Answer 22

synpharyngitic

Question 23

Possible presentations of IgA nephropathy:

*highly variable

Answer 23

1. Asymptomatic
2. Microscopic hematuria
3. Intermittent gross hematuria
4. Synpharyngitic hematuria
5. Proteinuria – nephrotic or non-nephrotic
6. Acute glomerulonephritis
7. Rapidly progressive glomerulonephritis

Question 24

How does IgA nephropathy present clinically?

Answer 24

hypertension (often)
50% have increased serum IgA levels
increased risk for loss of renal function

Question 25

Risk factors for IgA nephropathy-associated loss of renal function:

Answer 25

``` Heavy proteinuria Decreased GFR at onset Older age at onset Uncontrolled hypertension Crescents and/or tubulointerstitial fibrosis/atrophy Familial forms ```

Question 26

What is the pathophysiology of anti-GBM disease?

Answer 26

1. autoantibodies form against a noncollagenous portion of the α-3 subunit of type IV collagen 2. antibodies (usually IgG) bind to the GBM in a linear + uniform manner 3. Rapidly progressive glomerulonephritis develops, leading to kidney failure rapidly develops (due to focal glomerular necrosis and crescent formation)

Question 27

What symptoms may precede or coincide with onset of renal dysfunction in Goodpasture's disease?

Answer 27

Cough dyspnea crackles hemoptysis

Question 28

In Goodpasture's disease, what may exacerbate pulmonary hemorrhage?

Answer 28

tobacco smoke influenza volatile hydrocarbons

Question 29

How does Goodpasture's disease present?

Answer 29

Rapidly progressive renal failure with azotemia (50-70%) Anemia out of proportion to renal insufficiency Arthritis/arthralgias common Hypertension (~20%)

Question 30

How is Goodpasture's disease treated?

Answer 30

corticosteroids, plasmapheresis, and cytotoxic agents

Question 31

What are "crescents", and what do they result in?

Answer 31

accumulation and proliferation of cells outside the glomerular tuft result in compression of the tuft with rapid progression to renal failure

Question 32

____ crescentic glomerulonephritis is a condition characterized by >50% glomeruli affected (under light microscopy).

Answer 32

diffuse

Question 33

What are the 4 progressive/worsening crescent appearances? | *sorry, couldn't figure out how to word this

Answer 33

1. segmental proliferative and necrotizing lesions 2. cellular crescents 3. fibrocellular crescents 4. fibrous crescents

Question 34

Pathogenesis of crescents:

Answer 34

1. severe damage to capillary walls 2. damage causes tears and necrosis to GBM 3. RBC, WBC, fibrinogen and plasma constituents enter Bowman’s space 4. mononuclear cells and parietal epithelial cells proliferate (antibody and cell-mediated processes may be involved)

Question 35

Type II Crescentic Glomerulonephritis is associated with what pattern of immune deposits?

Answer 35

granular

Question 36

Rapidly progressive glomerulonephritis (is/isn't) a medical emergency.

Answer 36

"not"-- | but requires prompt dx and trx to prevent severe permanent renal damage/failure

Question 37

How is Alport syndrome inherited, and what is defective?

Answer 37

defects in α-5 collagen type IV (COL4A5) X-linked (but may be AR)

Question 38

How do heterozygous females present with Alport syndrome? Heterozygous males?

Answer 38

females: hematuria + thin basement membranes males: persistent hematuria, progressive proteinuria, ultimately ESRD (heterozygous=affected) Both: sensorineural hearing loss, lens abnormalities, platelet defects, (rarely) esophageal leiomyomas

Question 39

What would you see in a kidney biopsy from a patient with Alport syndrome?

Answer 39

abnormally thin basement membranes | splintering of lamina densa, “basket weave appearance”

Question 40

What protein abnormality causes thin basement membrane disease, and how severe is it?

Answer 40

defects in α-3 or α-4 collagen type IV, which results in GBM that is uniformly reduced by half Usually benign if heterozygous