Nephritic Syndrome Flashcards

1
Q

What are the three major symptoms of nephritis?

A

Renal failure

Hypertension

Hematuria: acute, chronic, or rapidly progressive
- deformed urine RBC, RBC casts

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2
Q

What makes the glomerulus susceptible to injury?

A

20-25% of cardiac output passes through

High glomerular capillary pressure

Fenestrated endothelium

Concentration (sieving effect)

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3
Q

What are the ways that you can get immunologic injury to glomerulus?

A

Glomerular deposition of Ag-Ab complexes

Binding of circulating Ab to fixed glomerular Ag

In situ immune complex formation

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4
Q

What are the consequences of glomerular immune complex deposition in acute glomerulonephritis?

A

Leukocytes come into capillary lumen

Releases proteases, elastase, ROS whcih digests GBM producing gas & rupturing it

These holes allow RBC to leak

It also damages the endothelium, causing activation of clotting system, fibrin can form

Also releas of interleukins & cytokines that activate platelets and mesangial cells leading to mesangial proliferation

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5
Q

What patterns of proliferation do you see in the glomerulus secondary to this inflammation?

A

Endocapillary

Extracapillary = Crescentic
(outside the confines of the glomerular capillaries)
Usually much more severe disease = rapidly progressing

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6
Q

Which patterns of glomerular disease can you get?

A

Focal v. diffuse: how many glomeruli

Global v. segmental: how much of the tuft

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7
Q

post-strep glomerulonephritis: patholophysiology

A

It’s an acute nephritic syndrome: decreased GFR: elevated BUN/creat, oliguria, edema, hypertension, urinary red cells & red cell casts

Latent period 10-14 days after strep infection, then glomerulonephritis, which is self-resolving

Diffuse & global endocapillary proliferation

Humps: electron dense deposits of ab-ag complexes, supepithelial: between epithelial cell & GBM, some in the mesangium too = in contact with circulating blood

Grossly: chronic: granular, leather grain appearance, kidney is contracted due to sclerosis of nephrons; atrophied, thin cortex

The antiobody is thought to be pyrogenic exotoxin B & the humps become more electron lucent and resolve within 6 weeks in most patients (rarely it can progress to end stage renal failure)

High complement, especially C3

IgG

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8
Q

Clinical presentation of post-strep glomerulonephritis?

A

More common in kids

10-14 days after infection

Nephritic picture common

Low serum complement and C3

Positive serological tests for recent strep infection

Prognosis is excellent in children, good in adults

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9
Q

Which glomerulonephritis do you get low serum complement levels? normal levels?

A

Low levels: acute post infection GN (including post strep)

Lupus nephritis

Idiopathic MPGN

Cyroglobulinemic GN

Normal levels: everything else

This is a good tests to do on a desert island, because there are only 4 with low serum complement!!

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10
Q

IgA Nephropathy

A

Most common glomerular disease seen worldwide

Diffuse mesangial proliferation, mesangial IgA aggregates in mesangium, RBC in urinary space

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11
Q

What’s the pathogenesis of IgA nephropathy?

A

4 options:

Defective hepatic clearance

Increased IgA production: most commonly; it’s associated with elevated serum IgA, onset may follow upper respiratory tract infection or gastroenteritis

Defect of antigen exclusion at the mucosal surface: URI or gastroenteritis, celiac dz/inflammatory bowel dz

Defective galactosylation of IgA hinge region of polymeric IgA1: hinge region can be immunogenic if it’s galactose deficient, & an autoimmune response drives the dz, may be resistant to clearance against mesangial cells which promotes their deposition

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12
Q

What is the systemic equivalent of IgA Nephropathy?

A

Henoch-Scholein Purpura

IgA-dominant immune deposits affecting small vessels –> vasculitis in capillaries, venules, arterioles

Typically involves skin, gut, glomeruli & is associated with arthralgias or arthritis

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13
Q

What is the clinical presentation of IgA Nephropathy?

A

Hematuria following upper resp tract infection or gastroenteritis or physical exercise – no lag time!!

Normal serum complements

Gross hematuria

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14
Q

Treatment of IgA nephropathy?

A

ACEI & ARB’s - slow the progression bc reduce intraglomeular pressure

Steroids: 6 month course - has long term effect on preventing ESRD even 10 years later

fish oil, mycophenolate

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15
Q

Systemic Lupus Nephritis: clinical features & pathological process

A

Systemic autoimmune disease

Reduced complement (it’s one of the 4 with reduced complement)

Nephritic features- decreased GFR (elevated creat), high blood pressure, RBC/casts in urine

Diffuse and global endocapillary proliferation with leukocyte infiltration

Full house immunofluorescence staining: IgG, IgM, IgA, C3, C1q

Wile loop deposits = subendothelial Ag-Ab deposits that lead to thickening of glomerular capillary wall

Hematoxyphil bodies = exposed nuclei (from leukocytes that have undergone cell death) complexed with ANA (antinuclear antibody): deposit in mesangium and subendothelial regions

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16
Q

Stages of lupus nephritis

A

Class I: minimal mesangial

II: mesangial proliferative

III: focal proliferative

IV: diffuse proliferative

V: membranous

VI: chronic sclerosing

17
Q

How do you treat lupus nephritis? by class

A

I: treat extrarenal lupus

II: treat extrarenal lupus

III: steroids, cytotoxics

IV: steroids, cytotoxics

V: steroid, cytotoxics

VI prepare for renal replacement

18
Q

What are the side effects of prednisone?

A

Weight gain

Stretch marks

19
Q

What are the side effects of cyclophosphamides?

A

Hypertension, ischemic heart dz, hyperlipidemia, valvular heart dz, avascular necrosis, osteoporosis, premature menopause, infections, herpes zoster infection

20
Q

What are alternative treatments to lupus nephritis instead of prednisone & IV cyclophsophamide?

A

MMF: mycophenolate

Cyclophosphamide (shorter course) followed by MMF

21
Q

What is rapidly progressive glomerulonephritis?

A

Rapidly progressive renal failure: days to weeks!

Crescentic GN

Pathogenesis can be due to: anti-GBM dz, immune complex GN, pauci-immune GN

22
Q

How is rapidly progressing glomerulonephritis rapid?

A

Progresses to renal failure in days to weeks rathern than months to years

23
Q

Wegener’s granulomatosis: what organs it affects and pathogenesis in the kidney

Also known as granulomatosis with polyangiitis

A

Sinusitis, cavitary lesion on chest xray, and nephritis

Rapidly progressing/crescent-shaped glomerulonephritis: proliferation of parietal epithelial cells = extracapillary inflammation

GBM rupture and fibrin extravasion

No immune type deposits: only fibrin is seen on immunofluorescence staining, in areas of necrosis & inflammation

No electron dense, immune deposits

You can also see:

  • necrotizing arteritis in interlobular artery of lung;
  • capillaritis and alveolitis (neutrophils marginated in the capillaries rupture and can go to alveolar spaces, leading to pulm hemorrhage)
  • granulomatous inflammation in the lungs, cartilage, and bone too!
24
Q

Wegener’s granulomatosis: which antigen?

A

ANCA: antineutrophil cytoplasmic antibody- 2 varieties

C-ANCA: cytoplasmic (in both alcohol and formalin fix)

P-ANCA: perinuclear (in alcohol fix)

It’s not just a serologic marker- it’s pathogenic!

ANKA Ab is normally sequestered in the neutrophil, until a priming event: i.e. upper resp tract infection –> neutrophil priming mobilizes ANKA to surface of the cell –> can compelx with ANKA Ag –> tell neutrophil to undergo activation & neutrophil degranulation –> NEUTROPHIL ACTIVATION is the mediator of the dz, not deposits of antigen-antibody complexes

25
Q

What are the forms of pulmonary-renal syndromes?

A

Pauci-immune: usually ANCA mediated, no immune deposits so paucity of immune staining
Wegener’s granulomatosis
Microscopic polyangiitis

  • *Immune Complex Deposits** = granular immunofluorescence pattern, leaves deposits in the lung and in the kidney
  • systemic lupus
  • cryoglobulinemic vasculitis
  • *Anti-glomerular basement membrane antibody deposits** (linear immunofluoresence pattern)
  • also known as Goodpasture’s Syndrome
26
Q

Anti-GBM nephritis

A

Difficult to distinguish from ANKA mediated disease because both can cause severe crescentic nephritis

Crescents contain fibrin from large ruptures in GBM

In fluoresence, you see linear staining (not paucity of immune staining like in ANKA dz)

You see the same type of linear staining in the lungs!!

Risk of life-threatening pulmonary hemorrhage!

The kidney on autoposy has areas of RBC cast formation due to the massive GBM rupture

27
Q

What is the antigen in anti-GBM nephritis?

A

Collagen 4, which is why the immuno staining is linear- because it’s binding to a local antigen of the GBM one-to-one

You get release of chemokines, attract neutrophils, which release their enzymes-proteases, ROS- on the GBM, which produces gaps, leads to activation of the clotting system, and fibrin comes out into the urinary spaces & stimulates the parietal epithelial cells to proliferate and gives rise to the crescent

Non-collagenous portion of alpha-3 collagen IV chain present in GBM and alveolar BM

The insult i.e. upper resp tract infection –> exposure of this part of the collagen 3 that’s not normally exposed –> antibody can form against it

28
Q

How do we rapidly progressive glomerulonephritis?

A

Depends on etiology and stage of dz

Anti-GBM dz: steroids, cytotoxics (to prevent production of cytokines), plasmapheresis (to remove the antibodies)

Immune-complex GN: treat underlying dz i.e. lupus

ANCA-associated/pauci-immune GN: cytotoxics (PO, IV) or plasmapheresis (to remove the ANCA) or rituximab

29
Q
A

ANCA (antibodies) is to rapidly progressive glomerulo-nephritis

just like

Anti-DNA is to systemic lupus erythematosus

High titer of these antibodies means that the are likely to have bad disease

High titer to anti-DNA means that they are likely to have glomerulonephritis in lupus