Clinical and pathologic features of nephritic syndrome Flashcards
1
Q
Overview of glomerulonephritis 1
A
- Inflammatory d/o involving the glom primarily and affecting other renal structures secondarily
- There are either circulating immune complexes or in situ immune complex formation/deposition
- Immune complexes cause glomerular damage mainly by activating complement and enlisting inflammatory cells
- Some nephritic syndromes do not activate complement and therefore have normal complement levels (not complement depleted)
2
Q
Overview of glomerulonephritis 2
A
- Normal complement nephritic syndromes: IgA, anti-GBM/goodpasture’s
- Low complement (depleted): post-infectious GN, SLE GN, membranoproliferative GN
- The mesangium attempt to eradicate the immune complexes by phagocytosing them, leading to mesangial cell hyperplasia and increased ECM
3
Q
Overview of glomerulonephritis 3
A
- The sub endothelial area (btwn endothelium and GBM, continuous w/ mesangium) begins to acquire deposits and extracts inflammatory cells from the blood
- The sub epithelial area sees accumulation of deposits since Ags released from epithelial cells (podocytes) are trapped by the GBM and held until circulating Abs complex with it
- Ags of LMW (and cationic) can also work their way thru the BM to be planted in the subepithelial area where circulating Abs complex with the Ags
4
Q
Findings in nephritic syndrome
A
- Pathognomonic findings: dysmorphic RBCs, RBC casts, hematuria
- Other findings: acute onset, poor renal function (AKI), proteinuria (may or may not be nephrotic range), HTN, complement may be low or normal
5
Q
Post-infectious glomerulonephritis clinical manifestations 1
A
- Most common in kids (5-15), usually due to URTI of strep (may be staph, other bacterial, viruses, parasites)
- Important to know onset of renal Sx after infection, b/c thats how to differentiate it from IgA
- Onset of renal Sx about 2 weeks after infection (IgA is a few days), Sx include hematuria, HTN, oliguria, edema
- Urine sediment shows RBCs, red cell casts, leukocyte casts, and proteinuria (usually <2g)
6
Q
Post-infectious glomerulonephritis clinical manifestations 2
A
- Serum complement (C3) is low, usually positive anti-step O (ASO)
- Sx usually self-limiting w/in a few weeks and usually no substantial sequelae in children
- In adults the progression is more variable and may continue to ESRD, particularly if there are abundant crescents (structures in bowman’s space due to break in GBM, glomerulus is done)
7
Q
Pathology and pathogenesis of PSGN 1
A
- Gloms show diffuse hypercellularity caused by influx of PMNs and macs into capillary lumens w/ swelling of endothelial cells
- Crescents may occur in Bowman’s space (worse prognosis)
- EM shows sub epithelial humps along GBM: dome-shaped e- dense deposits that protrude from the outer surface of the BM into the urinary space
- There are less conspicuous mesangial and sub endothelial deposits
- The deposits are positive for IgG and C3 and present a lumpy-bumpy or granular pattern (granular = immune complex deposits), later in the disease C3 is the dominant deposit
8
Q
Pathology and pathogenesis of PSGN 2
A
- PSGN is an immune-complex disease of bacterial Ags and host Abs complexes (both circulating and in situ- at both sub epithelial and sub endothelial levels) that activate complement
- The Strep Ag is usually an exotoxin (SPEB), which is cationic and can cross the GBM
- Important to note that it is the sub endothelial, not sub epithelial, complexes that stimulate the immune response (sub epithelial complexes are sequestered behind the GBM and thus do not attract inflammatory cells- as seen in MGN)
9
Q
Lupus nephritis (SLEN)
A
- Glomerular nephritis due to circulating (and some in situ) immune complexes secondary to SLE
- Pts often have concomitant SLE findings: malar rash, photosensitivity, arthralgias, serositis, chronic fatigue
- Other Sx include hematuria and/or proteinuria (often nephrotic range), pts may have elevated ANA and/or anti-dsDNA and show low complement levels
10
Q
Pathology and pathogenesis of SLEN 1
A
- Process of immune complex findings, first in mesangial cells then in sub endothelial area then in sub epithelial area (starts as focal- class 3- then progresses to diffuse- class 4)
- There are Igs of all types (IgG, IgA, IgM) and many complement components
- e- dense deposits spread out from mesangium to sub endo to sub epithelial
- Tubulo-reticular structures (TRS) can be seen, which represent proliferation of SER in endothelial cells and lymphocytes, secondary to a high interferon level
11
Q
Pathology and pathogenesis of SLEN 2
A
- The circulating immune complexes penetrate the fenestrated endothelium but cannot get past the GBM
- They are shunted to the periphery where mesangial cells phagocytose them (also other leukocytes that influx to the region) producing hypercellularity
- Once this system is overwhelmed the complexes are deposited in the sub endothelial area of the GBM and complement readily binds and attracts PMNs causing the GN (initially affects some glomeruli-focal- but eventually affects most glomeruli- diffuse)
12
Q
IgA nephropathy 1
A
- Glomerular staining of IgA in the absence of SLE
- Disease is similar to SLE in pathology by much more chronic and low-grade
- Onset is important, as the nephropathy is either syngenic w/ the URTI or just a few (2-3) days after the infection
- Males affected more than females
- Pt presents w/ hematuria and a URTI (or GI infection) still ongoing or recent
13
Q
IgA nephropathy 2
A
- There is often mild proteinuria (nephrotic syndrome uncommon), serum IgA elevated and IgA deposits can also be seen in dermal vessels
- Normal complement levels b/c the disease is so chronic and slow that complement is not depleted
- Progression is chronic and variable, and it infrequently causes loss of Tx kidney (takes too long for damage to occur)
- Associated w/ henoch-schonlein purpura
14
Q
Henoch-schonlein purpura and IgA nephropathy
A
- HSP is characterized by skin purpura (LE and butt), arthralgias, ab pain (vasculitis or GN)
- Is a more systemic and severe IgA disease
- Same lesions as IgAN but more severe GN
- Usually presents in young children and is often transient
15
Q
Pathology and pathogenesis of IgAN
A
- LM findings range from little change to mesangial matrix and cell expansion either diffusely or locally (similar to SLE)
- Predominant IgA (+/- IgM/IgG) and C3
- EM shows mesangial deposits w/ or w/o sub endothelial e- deposits (immune complexes)
- Progression of deposition: mesangial regions-> hypercellularity/matrix-> sub endothelial regions (focal-> diffuse)
