Path - Nephritic Syndrome Flashcards
Membranoproliferative glomerulonephritis is associated with immune complex deposition where?
Subendothelial
IgA nephropathy is associated with immune complex deposition where?
mesangium
6 symptoms of acute nephritic syndrome
Acute onset of:
- hematuria a) (microscopic or macroscopic) b) red blood cell casts
- HTN
- oliguria
- Edema - usually moderate
- mild to moderate proteinuria
- Azotemia
Describe what 1 - 4 are each indicated with
- late stage post infectious glomerulonephritis
- Membranous nephropathy
- Membranoproliferative glomerulonephritis (subendothelial deposits)
- IgA nephropathy (mesangial deposits)
What are the 3 common causes of endothelial cell injury?
- Deposition of immune complexes in the subendothelial space
- Thrombotic microangiopathies (HUS/TTP)
- Entrapment of paraproteins (B cell lymphoproliferative disorders, plasma cell dyscrasias, multiple myelomas)
2 types of thrombotic microangiopathies
HUS (Hemolytic uremic syndrome)
TTP (Thrombotic thrombocytopenic purpura)
3 main disorders associated with entrapment of paraproteins
B cell lymphoproliferative disorders
Plasma cell dyscrasias
Multiple myeloma
Describe mechanism of endothelial damage
- Cytokines and autocoids are released which (along with activated complement) upregulate adhesion molecules on endothelial and circulating immune cells
- RESULTS in enhancement of the local inflammatory response
- HEMATURIA seen clinically
Most common type of membranoproliferative glomerulonephritis?
Type 1 - 80% of cases
Buzzword for pathologic finding of membranoproliferative glomerulonephritis
“tram tracks”
Type 1 MPGN
Describe cellularity of glomerular tuft?
Hypercellular (hence the proliferative part)
Type 1 MPGN
Describe status of mononuclear cells (i.e. # and location)
Increased mononuclear cells within the expanded mesangium and within capillary lumens
Type 1 MPGN
What causes the tram track apperance?
Duplication of the basement membrane from endothelium displaced by immune deposits and infiltrating mesangial cells
There are multiple presentations in Type 1 MPGN. List as many as possible
Microscopic hematuria, Non-nephrotic range proteinuria, nephrotic syndrome, acute nephritic syndrome, rapidly progressive glomerulonephritis
Type 1 MPGN etiology (distinguish between children and adults)
Children - usually a primary disease
Adults - Idiopathic, but commonly secondary to Hepatitis C (occasionally hep B)
Type I MPGN associated with which type of complement pathway
Complement activation via classical pathway
Type 1 MPGN and complement relation?
Usually associated with low C3 levels
Treatment/Prognosis of MPGN type 1?
Poor response to steroids, spontaneous remission may occur rarely. USUALLY progresses to end stage renal disease
Geographically, where is Type 1 MPGN common?
South America, Africa, and Middle East
Another name for Type II MPGN
Dense deposit disease
What is the clinical presentation of type II MPGN. Complement status?
usually similar to type I MPGN, usually will have low C3 levels
Besides MPGN, what other renal disorder is associated with low C3 levels?
Post infectious glomerulonephritis
80% of Type II MPGN has what?
C3 nephritic factor
Type II MPGN associated with what type of complement pathway?
Complement activation via alternative pathway
What is C3 nephritic factor? What nephritic syndrome is it most common in?
Most common in Type II MPGN, C3 nephritic factor stabilizes C3 convertase, leading to overactivation of alternative complement system, inflammation, and low levels of circulating C3 (but normal levels of C4)
Immunofluoresence of Type II MPGN?
C3 deposition, but no immune complex deposition
Electron microscopy of Type II MPGN
Buzzword. Thick continuous ribbon
What type of renal disorder is shown here?
Type I MPGN, notice tram track appearance
Another name for IgA nephropathy?
Berger’s Disease
IgA is most common where (geographically)?
Most common worldwide…wide..wide (Prestige Worldwide)
-but also high incidence in Asia b/c they screen for it
IgA nephropathy is considered to be mesangioproliferative pattern of injury. What does this mean?
Indicates deposition of IgA containing immune complexes predominantly in the mesangium
Synpharyngitic means what? What disorder is it assocaited with?
IgA nephropathy, means you have nephritic sediment within 1 to 2 days of infection (as opposed to post infectious glomerulonephritis which could be up to weeks after. Know this difference)
IgA nephropathy can be triggered by what types of infection?
Infection involving mucousal tract (hence the IgA) as in upper respiratory infection or gastrointestinal tract
IgA nephropathy pathogenesis.
What happens to IgA to increase risk?
What 2 antibodies recognize this IgA?
Where does this process occur?
Where does it end up?
- Under-galactosylation of O-linked glycans in the hinge region of IgA 1 causes Galactose deficient IgA1.
- IgG or IgA1 antibodies recognize this galactose deficient IgA1
- forms immune complexes in circulation
- These immune complexes then get deposited in the mesangium
List some secondary causes of IgA nephropathy?
Henoch-Schoenlein purpura, Ankylosing spondylitis, dermatitis herpetiformis, celiac disease, IBS, cirrhosis, psoriasis
Presentation of IgA nephropathy is highly variable. List as many variations that present
Variable presentation:
asymptomatic
microscopic hematuria
intermittent gross hematuria
synpharyngitic hematuria
Nephrotic (15%) or non-nephrotic proteinuria
acute glomerulonephritis
rapidly progressive glomerulonephritis
IgA nephropathy - normal or elevated bp?
Often associated with HTN
What percentage of IgA nephropathy patients have increased serum IgA levels?
50%
What risk factors are more associated with loss of renal function in IgA nephropathy?
HEAVY proteinuria
Decreased GFR at onset
Older age at onset
Uncontrolled HTN
Crescents and/or tubulointerstitial fibrosis/atrophy
Describe Light microscopy of IgA nephropathy
Highly variable
Describe immunofluorescence of IgA nephropathy
Immunofluorescence shows IgA deposition along with C3 in the mesangium
Describe electron microscopy of IgA nephropathy
D = IgA mesangial Deposits
MC = mesangial cell
Name the 2 glomerular basement diseases?
Anti-GBM disease
Alport Syndrome (aka hereditary nephritis)
What disease is associated with #5
Anti-GBM disease
Describe pathogenesis of Anti-GBM disease?
Formation of autoantibodies against non-collagenous portion of the alpha 3 subunit of type IV collagen
Buzzword for immunofluorescence description of anti-GBM disease
Linear appearance (not granular)
Relationship between anti-GBM titers and disease activity?
None. can have low anti-GBM titers but still have high disease activity, or vice versa
What exactly is the difference between anti-GBM and goodpasture syndrome?
anti-GBM = 1/2 of goodpasture syndrome, in that it only affects the kidneys, causing glomerulonephritis with hematuria
Good pasture will have pulmonary hemorrhage with hemoptysis in addition to kidney involvement
Prognosis of anti-GBM disease?
Horrible. Rapid development of kidney failure due to focal glomerular necrosis and crescent formation = rapidly progressive glomerulonephritis (RPGN)
Another name for goodpasture syndrome?
systemic anti-GBM disease (kidney + lungs)
Goodpasture syndrome epidemiology and etiology?
Epidemiology = Most common in young white males,
Etiology = usually due to smoking, viral infections, or exposure to volatile hydrocarbons
Prognosis of goodpasture syndrome?
Rapidly progressive renal failure with azotemia at presentation in about 50-70% of cases
List 3 other findings in patients with goodpasture syndrome?
Anemia is out of proportion to renal insufficiency
Arthritis/arthralgias common
HTN in only 20% of cases
Treatment for goodpasture’s syndrome?
Corticosteroids, plasmapheresis, and cytotoxic agents
Describe light microscopy of antiGBM/ Good pasture’s syndrome
Describe immunofluorescence
Light microscopy shows necrotizing crescentic glomerulonephritis with proliferating parietal epithelial cells and macrophages (also neutrophils, but less)
Immunofluorescence shows linear IgG deposits
Is necrotizing crescentic glomerulonephritis specific for antiGBM/goodpasture?
No, not specific (nichols smiled when he said this, like hes gonna put it on the test smile)
Crescents are considered to be an accumulation and proliferative of cells where? what does this result in?
Crescent = accumulation and proliferation of cells outside the glomerular tuft which can result in compression of the tuft with rapid progression to renal failure
What is this schematic showing? What does the black arrow represent? What disease is it associated with?
This is a schematic of rapidly progressive (crescentic) glomerulonephritis. The black arrow indicates rapidly proliferating parietal cells bulging into the bowman’s space. Also note the GBM has very broken up parts
Immunofluorescence of Type II crescentic glomerulonephritis?
Characteristic, but non-specific granular deposits (as opposed to linear in type 1)
Type III crescentic glomerulonephritis is also called? Immunofluorescence shows?
Pauci-immune glomerulonephritis (negative Immunofluoresence)
Pauci-immune glomerulonephritis (aka Type III) is associated with what disorders?
Wegner’s granulomatosis (cANCA)
microscopic polyangiitis, and churg-strauss syndrome (pANCA)
Is rapidly progressive glomerulonephritis a medical emergency?
No, but it requires prompt diagnosis and treatment to prevent severe permanent renal damage and failure
Alport Syndrome also called?
hereditary nephritis
Mode of inheritance of Alport syndrome?
X linked inheritance in 80% of cases, may be autosomal recessive
Pathogenesis of alport syndrome?
Defect in alpha-5 chain of Type IV collagen (COL4A5)
Heterozygous females in Alport syndrome have what 2 associated findings?
Hematuria and thin basement membrane
Affected males in Alport syndrome have what common findings?
persistent hematuria, progressive proteinuria, and ultimately end stage renal disease
Besides the signs and symptoms discussed with heterozygous females and males in Alport syndrome, what are some other findings you will see?
Associated with sensorineural hearing loss, lens abnormalities, and platelet defects; rarely esophageal leiomyomas
What buzzword do you think of when you see this? What disease is it associated with
Basketweave pattern basement membrane in alport (hereditary nephritis).
Thin basement membrane disease prognosis?
Usually benign as long as heterozygous (NOT homozygous or compound)
Pathogenesis of thin basement membrane disease?
Defect in alpha-3 or alpha-4 chain of Type IV collagen
Main difference in GBM between thin basement membrane and other disorders involving the GBM?
Thin basement membrane disease is associated with uniformly reduced thickness, about 1/2 normal thickness
Nichols tidbit. Describe charge of antibody in IgA nephropathy? What is the significance of it?
IgA nephropathy deals with neutral antibodies; therefore, they can freely move and will go into mesangium
Nichols tidbit. Describe charge of antibodies in post infectious glomerulonephritis? Significance of it?
Post infectious glomerulonephritis deals with cationic antibodies. Therefore, they will pass through the negative GBM and deposit subepithelial, giving them “subepithelial humps”
