Week 3: Nephritic Syndrome Flashcards Preview

Renal > Week 3: Nephritic Syndrome > Flashcards

Flashcards in Week 3: Nephritic Syndrome Deck (23):

Describe nephritic syndrome.

-acute onset
-hematuria: dysmorphic RBC and RBC casts
-acute renal failure
-complements may be low or normal
-LOW complement: post-infectious GN, lupus, membranoproliferative GN
-NORMAL complement: igA, anti-GBM (goodpastures)


Describe glomerulonephritis.

-inflammatory disorder involving primarily the glomerulus and affecting other renal structures
-due to deposition of circulating immune complexes or formation of in situ immune complexes in glomeruli-->glomerular damage by activating complement and enlisting inflammatory cells
-mesangium: monocytic cells phagocytose deposits-->mesangial cell proliferation, increased production of matrix
-subendothelium: deposits can extend to sub endothelium from mesangium because in continuity. Can attract inflammatory cells from blood
-subepithelial: antigens from epithelial cells (podocytes) trapped by anionic charge of lamina rare externa, circulating antibody complexes with it.
-deposition of antibody to antigen of BM (good pastures)


Define post-infectious Glomerulonephritis.

-diffuse proliferative GN occurring 1-2 weeks after infection
-children 3-14
-commonly due to Strep, but also other infections


Clinical presentation of post-infectious GN.

-abrupt onset
-hematuria: "tea colored" urine
-nephritic UA: red cells, red cell casts, leukocyte casts, protienuria
-serum complement is low (C3)
-elevated ASO
-great prognosis in children with full recovery of renal fxn, adults have worse prognosis, some get progressive disease


Pathological features of post-infectious GN.

-global mesangial and endocapillary proliferation with infiltrating PMNs
-EM: subepithelial humps along GBM, large dome electron dense deposits that protrude from outer surface of BM into urinary space
-less conspicuous mesangial and sub endothelial deposits
-the sub endothelial deposits are attractive to PMNs and drives inflammation
-immunofluorescence: IgG and C3 in granular (starry sky or lumpy bumpy) pattern
-later: C3 becomes dominant


pathogenesis of post infection GN

-bacterial antigens (mainly Strept pyrogenic exotoxin B SPEB) planted at sub epithelial and sub endothelial aspects of GBM, they activate complement directly
-SPEB reaches sub-epithlial aspect due to cationic charge
-circulating immune-complexes may be responsible for mesangial and sub endothelial deposits and activation of complement that drives influx of inflammatory cells


Clinical features of lupus nephritis.

-glomerulonephritis due to circulating (and planted) immune complexes occurring in the course of SLE
-typically present with acute renal failure, hematuria, and proteinuria
- +ANA and + DsDNA
-low complements
-symptoms of SLE
-requires steroids and cytotoxic agents
-1/3 progress to ESRD


Pathology of lupus nephritis.

-ranges based on class
-EM findings: electron dense deposits corresponding to immune complex deposits, may extend from mesangial regions to sub endothelial areas in more severe cases.
-Tubulo-reticular structures: TRS-proliferation of smooth ER in endothelial cells and lymphocytes, secondary to high interferon state
-fingerprints: organized electron-dense deposits or immune complex depotis, secondary to cryoprecipitable immune deposits
-immunofluorescence: granular immune deposits, full house of Igs (IgG, IgA, IgM), classical pathway of complement activation-early complement components present, including C3


Pathogenesis of lupus nephritis.

-large circulating immune-complexes easily penetrate the fenestrated endothelium but blocked in sub endothelium by lamina dense of BM
-shunt into mesangial matrix, which is in continuity with sub endothelial space
-mesangial hypercellularity due to influx of macrophages and proliferation of mesangial cells to phagocytose immune deposits
-phagocytic ability overwhelmed-->back up into sub endothelium
-subendothelial deposits attract neutrophils and macrophages-->GN


Clinical features of IgA Nephropathy (Berger's Disease)

-Definition: nephropathy characterized by mesangial/subendothelial localization of IgA, with less intense IgG and C3
-most common cause of recurrent hematuria world wide
-young men and adolescents
-may occur 1-3 days after viral like GI or URI illness
-mild proteinuria, rarely nephrotic syndrome
-IgA levels elevated in 50% patients
-chronic and variable progressive disease


Pathology of IgA Nephropathy

-circulating immune complexes of large size are deposited in the kidneys, mimicking spectrum of changes seen in lupus nephritis
-mesangial hypercellularity, focal GN, or diffuse GN all possible
-predominance of IgA and C3, with or without IgG or IgM
-immune deposits of IgA in dermal vessels-another site to biopsy
-variant: Henoch-Schonlein Purpura


Pathogenesis of IgA Nephropathy

-glomerular deposition of immune complexes containing IgA, IgG, C3-->mesangial hypercellularity-->subendotheilial regions when mesangial overwhelmed-->GN
-similar to lupus nephritis
-links with certain genetic markers on 6q 22-23 and 6p
-pts have heightened mucosal sensitivity to infectious pathogens or certain food antigens such as gluten and ovalbumin
-IgA itself may be abnormal -may trigger autoimmune reaction. Abnormal IgA1 may be more sticky and clump into aggregates


Clinical features of membranoproliferative GN TYPE 1.

-diffuse form of GN where almost all or all glomeruli have mesangial cell proliferation with mesangial cell processes extending peripherally into capillaries. Thickened and reduplicated BM
-idiopathic form affects children and young adults
-secondary forms associated with chronic immune complex diseases: Hep C
Nephrotic syndrome in 50% cases, hematuria common, 20% present with nephritic and nephrotic syndrome
-disease usually preceded by URI
-50% have decreased C3 levels and C4


Clinical features of MPGN Type 2-dense deposit disease

-capillary thickening and mesangial cell proliferation associated with dense deposits within lamina dense of BM
-rare in comparison to type I
-older children and young adults with proteinuria or nephrotic syndrome, hematuria, HTN
-persistent or constant hypocomplemntemia
-alternative pathway activation


Pathology of Type 1 MPGN.

-thickened capillary walls with hyper cellular glomeruli
-proliferated mesangial cells
-peripheral extension of mesangial cell cytoplasm with interposition of cytoplasm internal to BM
-new BM made internal to original BM
-double counter or tram track appearance in silver stain
-immunofluorescence: C3 and IgG (+/- IgM and IgA) in granular pattern
-hyperlobar appearance


Pathogenesis of MPGN Type 1

-antigenic stimulus-->formation of immune complexes
-stimulus is unknown, autoimmune disease and chronic infection are known to cause secondary forms of MPGN type 1
-many patients have onset of disease or flares after infection


Pathology of MPGN type 2

-capillary wall thickening and mesangial cell proliferation associated with presence of ribbon like dense deposits within lamina dense of GBN by EM
-pathognomonic: elongated sausage like electron dense deposits within lamina dens of GBM and BM of bowman's capsule and tubules
-immunofluorescence: intense isolated linear staining for C3 in GBMs


Pathogenesis of MPGN Type II

-composition of glomerular deposits: C3,5,6,7,8,9
-dysregulation of alternative complement pathway-->persistent activation and glomerular deposition of C3
-mutations in factor H and I-regulators of alternative pathway that promote decay of active C3 convertase
-C3NeF is autoantibody that stabilizes C3 convertase and protects it from factor H and I. detectable in DDD
-associated with acquired partial lipodystrophy
-MGUS in patients >49


Clinical features of Goodpasture's disease.

-60-80% men
-crescentic GN and pulmonary hemorrhage (it is anti-GBM if no pulmonary involvement)
-young men or older men and women 50-60 yrs
-crescentic GN: majority of glomeruli contain accumulation of cells within Bowman's space, fibrin in bowman's space, rapid progression to renal failure


Which are crescentic GN associated diseases?

-post infectious GN
-goodpasture's disease or anti-GBM disease


Pathology of Goodpasture's disease

-crescentic glomerulonephritis seen in most patients
-crescents: macrophages derived from blood and proliferated visceral epithelial cells within Bowman's space
-rupture of GBMs seen in silver and PAS stains
-Crescent preceded by physical breaks in GBM
-extravasated RBCs and fibrin in Bowman's space
-linear deposition of IgG along GBM
-fibrinogen in Bowman's space
-no electron dense deposits-small number of IgG
-lung shows pulmonary hemorrhage and focal linear IgG in alveolar septa


Pathogenesis of Goodpasture's Disease.

-autoimmune disease-antibody to BM collagen a-3-chain of type 4 collagen--binds to glomerular and alveolar septal BM, fixes complement and causes inflammatory reaction
-genetic predisposition (HLA DR and DQ antigens) in 85% patients
-triggers: hydrocarbons, cigarette smoking, respiratory viral infections.


Nephrotic and nephritic syndromes based on deposit location

1. Subepithelial
-membranous nephropathy (spike and dome)
-post-infectious GN (humps)
2. Subendothelial
-Lupus nephritis
-MPGN Type 1
3. BM
-MPGN Type 2: worm like deposits
4. Mesangial area
-lupus-->goes to subendo
-IgA nephropathy