Glomerular disease Flashcards
What is the broad definition of nephritic syndrome, conceptually?
Glomerular disorder characterized by inflammation and bleeding due to disruption of glomerular basement membrane.
What findings are associated with nephritic syndrome?
- Limited proteinuria (<3.5g/day)
- Oliguria
- Azotemia
- Salt retention with periorbital edema and HTN
- RBC casts and dysmorphic RBCs in urine
What are the subtypes of nephritic syndrome?
- Acute post-streptococcal glomerulonephritis
- IgA nephropathy (Berger disease)
- Rapidly progressive glomerulonephritis
- Diffuse proliferative glomerulonephritits
- Membranoproliferative glomerulonephritis
- Alport sydrome
What is the classic prelude to PSGN?
~2 weeks after group A streptococcal infection involving pharynx or impetigo. Due to nephritogenic strains that carry M protein.
What is the presentation of PSGN?
Hematuria (cola colored urine), oliguria, hypertension, and periorbital edema.
What kind of hypersensitivity reaction is PSGN?
Type III hypersensitivity, involving immune-complex (antibody+antigen).
What is the appearance of PSGN on light microscopy?
Hypercellular, enlarged glomeruli.
What is the appearance of PSGN on immunoflorescence? Why?
“Starry sky” granular appearance/lumpy-bumpy appearance. Due to immune complex deposition (IgM, IgG, C3) along GBM and mesangium.
What is the appearance of PSGN on electron microscopy?
Subepithelial immune complex humps –> get deposited and pile up.
What is the prognosis of PSGN?
Almost always resolves spontaneously in children– <1% children progress to renal failure.
25% of adults progress to renal failure.
What other lab findings are associated with PSGN?
Incr anti-DNAse B titers (antibodies to strep) and decreased complement levels (used up and deposited)
What is the classic prelude to IgA nephropathy?
2-3 days following mucosal infection (esp gastroenteritis/URI). Common in children, most common nephropathy worldwide.
What is the pathogenesis of IgA nephropathy?
IgA immune complex deposition in MESANGIUM of glomeruli.
What is the presentation of IgA nephropathy?
Episodic hematuria with RBC casts 2-3 days following mucosal infection - often gastroenteritis. May present as acute renal insufficiency.
What are the findings on light microscopy of IgA nephropathy?
Mesangial proliferation
What are the findings on immunoflorescence of IgA nephropathy?
IgA based IC deposits in mesangium
What are the findings on electron microscopy of IgA nephropathy?
Mesangial IC deposits.
What systemic syndrome can IgA nephropathy be involved in?
Henoch-Schonlein purpura.
What organ systems are involved in HSP?
- Skin - purpuric lesions on extensor surfaces
- GI - abdominal pain, vomiting, intestinal bleeding, intuss
- Renal - IgA nephropathy
What will biopsy of HSP purpura show on light microscopy?
Necrotizing vasculitis of small dermal vessels and subepidermal hemorrhage
What will biopsy of HSP purpura show on immunofluorscence?
IgA deposition in dermal capillaries
What is the prognosis of IgA nephropathy?
May slowly progress to renal failure.
What is the presentation of Rapidly progressive glomerulonephritis?
Very rapidly worsening nephritic syndrome that may progress to renal failure in weeks to months
What is the hallmark of RPGN on light microscopy and IF?
Crescents in bowman’s space.
What do the crescents of RPGN consist of?
Fibrin and macrophages, + plasma proteins (C3b), some glomerular cellls
What are three disease processes that may result in RPGN?
- Goodpasture syndrome
- Granulomatosis w/ polyangitis
- Microscopic polyangitis
What are the associated findings with goodpasture syndrome? (sx, hypersensitivity type, IF findings)
Hematuria and hemoptysis.
Type II hypersensitivity, with antibodies to GBM and alveolar basement membrane.
Linear IF.
What are the associated findings with Granulomatosis with polyangitis?
Hematuria/hemoptysis, with granulomatous inflammation.
c-ANCA.
Negative IF.
What are the associated findings with Microscopic polyangitis?
Necrosis on bx.
p-ANCA, MPO-ANCA.
Negative IF.
What is the presentation of Diffuse proliferative glomerulonephritis?
Often presents as nephritic and nephrotic syndromes concurrently
What disease process is diffuse proliferative glomerulonepthritis associated with?
SLE - most common cause of death in SLE
What are the findings on light microscopy of DPGN?
“wire looping” of capillaries
What are the findings on immunoflourscnece of DPGN?
granular appearance due to deposition
What are the findings on EM of DPGN?
subendothelial and sometimes intramembranous IgG-based immune complexes, often with C3 deposition.
What is the presentation of membranoproliferative glomerulonephritis?
Nephritic syndrome that often copresents with nephrotic syndrome.
What is “proliferative” about MPGN?
Cytoplasm of mesangial cells
What are the two types of MPGN? What is the difference between them?
Both are due to immune complex deposition with thick GBM membrane - difference is location of deposits.
- Subendothelial immune complex deposits
- Intramembranous immune complex deposits
What are the classic findings of Type I MPGN?
EM: Subendothelial IC deposits
IF: granular
Light microscopy: tram track apperance due to GBM splitting caused by mesangial proliferation
What are associated diseases with Type I MPGN?
HBV and HCV.
What are the classic findings of Type II MPGN?
Intramembranous “dense deposits” associated with C3 nephritic factor.
What is C3 nephritic factor?
Stabilizes C3 convertase, leading to decrease serum C3 levels, overactivation of complement and inflammation.
What is the prognosis of MPGN?
Tends to have a poor response to steroids, progresses to chronic renal failure.
What is the pathogensis of Alport syndrome?
X-linked mutation in Type IV collagen –> thinning and splitting of glomerular basement membrane.
What is the presentation of Alport syndrome?
Isolated hematuria, sensorineural hearing loss, and ocular disturbances (retinopathy, lens dislocation)
What is the electron microscopy finding of Alport syndrome?
Basket-weave appearance.
What is the basic principle behind nephrotic syndrome?
Charge barrier (basement membrane) disruption: massive proteinuria.
What are the resulting sx of nephrotic syndrome?
Hypoalbuminemia - pitting edema
Hypogammaglobulinema - increased risk of infection
Hypercoaguable state - loss of antithrombin III
Hyperlipidemia and hypercholesterolemia - may result in fatty casts
What are the types of nephrotic syndromes?
Podocyte: Minimal Change and FSGS
Membrane: Membranous nephropathy and membranoproliferative
Mesangium: DM, amyloidosis
In what populations is minimal change disease most commonly seen?
Children - most common cause of nephrotic syndrome
What are the causes of minimal change disease?
Most often idiopathic
Can be triggered by recent infection/immunization
Rarely can be secondary to hodgkin’s lymphoma
What are the findings of minimal change disease on light microscopy?
normal glomeruli
What are the findings of minimal change disease on IF?
No findings
What are the findings of minimal change disease on EM?
Effacement (fusion) of podocyte foot processes.
What is the prognosis of minimal change disease?
Very good. Usually responds v well to steroids.
What is causing the damage in minimal change disease?
Cytokine-mediated damage (from T cells)
In what populations is focal segmental glomerulosclerosis most commonly seen?
Most common cause of nephrotic syndrome in Hispanics and African Americans.
What are the causes of FSGS?
Most commonly idiopathic, or secondary to:
HIV, Heroin use,
Sickle Cell Dz, massive obesity,
Interferon treatment, CKD due to congenital malformations
What are the findings of FSGS on light microscopy?
segmental sclerosis and hyalinosis
What are the findings of FSGS on immunoflorescence?
non-specific IF
What are the findings of FSGS on electron microscopy?
effacement of podocytes
What does the variant of FSGS associated with HIV consistent of?
Collapsing glomerulonephropathy - collapse and sclerosis of whole glomerular tuft, glom epithelial cell proliferation and hypertrophy, with marked tubular injury w/ accompanying microcyst formation
What is the prognosis of FSGS?
poor response to steroids, progresses to chronic renal failure.
What population is membranous nephropathy associated with?
Most common cause of nephrotic syndrome in white people
What can membranous nephropathy be assocaited with?
Most common nephrotic presentation of SLE
Usually idiopathic, may be associated with:
solid tumors
HBV/HCV
drugs (NSAIDs/ penicillamine)
Antibodies to phospholipase A2 receptor.
What are the findings of membranous nephropathy on light microscopy?
diffiuse capillary and GBM thickening.
What are the findings of membranous nephropathy on IF?
Granular due to immune complex deposition
What are the findings of membranous nephropathy on EM?
Spike and dome appearance with subepithelial deposits –> podocytes are trying to lay down addtiional membrane to sit on, dome forms over the deposits.
What is the prognosis of membranous nephropathy?
Poor response to steroids, progresses to chronic renal failure.
Membranous Nephropathy and Membranoproliferative nephropathy both involve immune complex deposition in the GBM membrane. What differentiates them?
Membranous: Subepithelial deposits (above membrane - between epithelial cells and basement membrane)
MPN Type 2: Intramembranous.
MPN Type 1: Subendothelial deposits (below the membrane - this is where mesangial proliferation cuts them in half).
What is the pathogenesis of renal dysfunction in DM?
High serum glucose leads to non-enzymation glycosylation of the vascular basement membrane –> this leads to hyaline arteriosclerosis.
Non-enzymation glycosylation of efferent arterioles preferentially –> Increases GFR, leads to mesangial expansion and sclerosis
How does DM cause microalbuminuria?
Sclerosis of efferent arteriole increases GFR
Hyperfiltration injury leads to microalbuminuria
What is the classic finding of DM nephropathy?
Sclerosis of the mesangium; Kimmelsteil-Wilson nodules (eosinophilic nodular glomerular sclerosis).
What is the most commonly involved organ in systemic amyloidosis?
Kidney.
How does amyloidosis cause nephrotic syndrome?
Deposits in the mesangium
What is the typical finding of amyloidosis?
apple-green bireferingence under polarized light after staining w/ congo red.
