L9- Nephritic Syndrome Flashcards
describe urine sediment in nephritic syndrome
- RBCs / RBC casts
- granular casts
- variable proteinuria
- possible WBCs
list the Nephritic syndromes based on complement levels
Normal: i) IgA nephropathy (Henoch-Schonlein Purpura), ii) Alport’s Syndrome (hereditary nephritis), iii) SLE (class I, II, V), iv) benign hematuria
Low: i) post-streptococcal glomerulnephritis, ii) membranoproliferative glomerulonephritis, iii) SLE (class III, IV), iv) bacterial endocarditis / infected ventriculoatrial shunt, v) cryoglobulinemia
Variable: rapidly progressive glomerulonephritis
the most common glomerulonephritis is (1) and is mostly seen in (2) age group and (3) ethnicities
1- IgA nephropathy
2- children, young adults
3- asians, whites
In IgA nephropathy, exposure to microbes or other Ags in the (1) leads to increased IgA synthesis. This allows for IC deposition in (2) where they will activate (3) and initiate (4).
1- GI, lungs
2- mesangium (+ its proliferation)
3- alternative complement pathway
4- glomerular injury
describe microscopic appearance of IgA nephropathy
LM- segmental areas with inc mesangial matrix + hypercellularity
IF- mesangial and subendothelial IgA, C3 deposits (C1q, IgG/IgM either absent or in very low levels)
EM- mesangial and subendothelial deposits
People with IgA nephropathy will present with episodes of (1) with (2) in between episodes and (3) is evident along with normal levels of (4).
(T/F) most people will progress to ESRD
(T/F) most cases are restricted to the kidney
1- gross hematuria 2- microscopic hematuria 3- proteinuria (<3.5g/day) 4- C3/C4 5- F, 20% progress to ESRD 6- T
list the 4 conditions commonly associated with IgA nephropathy
- hepatic cirrhosis
- gluten enteropathy
- HIV infection
- minimal change disease
In post-streptococcal glomerulonephritis, initially (1) forms and will make (2) deposits in the kidney. This will activate (3) resulting in influx of (4) and eventually decline in (5). Deposits will quickly (6), along with (7) symptoms.
1- Ab-Ag immune complex with streptococcal Ag 2- subendothelial 3- complement 4- inflammatory cells 5- GFR 6- clear (therefore not seen on biopsy) 7- hematuria, renal failure
After the clearance of IC in post-streptococcal nephritis, (1) is the main characteristic feature responsible for (2). (1) will be cleared slowly and therefore (3) symptoms and lesions will take (4) amount of time to resolve.
1- subepithelial ‘humps’ / ICs
2- epithelial damage –> proteinuria
3- proteinuria
4- 2 mos to start and up to 9 mos - years for complete resolution
Note- subendothelial ICs are cleared quickly b/c no GBM between it and blood like with the subepithelial ICs
describe the appearance of post-streptococcal glomerulonephritis on microscopy
LM: hypercellular glomeruli (neutrophils, monocytes), mesangial/epithelial/endothelial proliferation, diffuse (all glomeruli in all parts), closed capillary loops (due to cell infiltration and swelling)
IF: IgG, C3 granular deposits in mesangium + along capillary walls
EM: electron dense deposits in subepithelial space (‘humps’)
GN usually appears (1) after strep. pharyngitis or (2) after impetigo. It is common in (3) age group and has a (rapid/gradual) onset. It is defined by having (5) and (6) levels.
1- 10 days (throat) 2- 3 weeks (skin) 3- children (6-10 y/o) 4- rapid nephritic syndrome 5- proteinuria >2g/day 6- low complement levels
_________ are useful blood tests in diagnosing post-streptococcal GN
-elevated anti-streptolysin O Ab
-elevated anti-DNAase B
(+ low complement)
list the possible clinical outcomes of post-streptococcal GN
-children renal function recovers 99% of the time
- Long-term: some develop renal insufficiency 10-40 yrs after, due to the following:
i) irreversible glomerular damage during acute episode
ii) compensatory hyperfiltration by remaining glomeruli (maintain normal GFR)
iii) eventually => glomerulosclerosis
MPGN, aka (1), is characterized by the following: (2). It can be primary due to (3) or secondary due to (4).
1- membranoproliferative glomerularnephritis
2- GBM thickening, mesangial proliferation, inflammatory cell infiltration
3- idiopathic
4- underlying systemic disease
(3/4 have same histological findings)
describe the appearance of MPGN on LM
- all 3 types are identical on LM
- mesangial expansion
- hypercellularity
- peripheral capillary loop thickening double contour formation – GBM duplication (its split) ‘tram track’
describe the appearance of MPGN on EM
- Type I: subendothelial deposits (C3, IgG, C1q, C4)
- Type II: intramembranous (w/in GBM) deposits (C3 - NO IgG, C1q, C4)
- Type III: subendothelial, mesangial, subepithelial deposits (C3, IgG)
The most common MPGN is type (I/II/III) and due mostly to (primary/secondary), therefore there is usually an evaluation for the following, (3).
1- type I
2- secondary (primary / idiopathic is rare)
3- SLE, HepC, cryoglobulinemia, endocarditis, parasitic infection
MPGN type I activates (1) and type II activates (2). In both C4 levels are (high/low/normal) and C3 levels are (high/low/normal) because of (5).
1- classical complement pathway (type I)
2- alternative complement pathway (type II)
3- normal (C4)
4- low (C3)
5- C3 nephritic factor = IgG that binds and stabilizes C3bBb convertase => continuous C3 degradation
MPGN presents (before/after) 30 y/o in one of the following ways: (2). (T/F) most people will progress to ESRD.
1- before 2: -hematuria/proteinuria in UA -acute nephritic syndrome w/ hematuria -HTN, edema -recurrent episodes of gross hematuria -insidious onset of edema and nephrotic syndrome 3- T, in 10-15 yrs
RPGN, aka (1) or (2), is a group of disorders associated with (3) and if untreated it will result in (4). (5) is required for diagnosis.
1- rapidly progressive glomerulonephritis 2- crescentic glomerulonephritis 3- severe oliguria 4- renal failure (wks-mos) 5- renal biopsy, serological analysis
describe the appearance of RPGN on LM
- proliferative glomerulonephritis with prominent ‘crescent’ formation in 30-70% of glomeruli (proliferation in extracapillary space / Bowman’s space)
- w/ or w/o segmental necrosis
- crescents: cellular –> fibrocellular –> fibrous
- all three types present the same
RPGN:
(1) % type I
(2) IF staining
(3) alternate name
(4) causes
Type I RPGN 1- 20% 2- linear staining 3- anti-GBM disease 4- Goodpasture's syndrome, idiopathic
RPGN:
(1) % type II
(2) IF staining
(3) alternate name
(4) causes
Type II RPGN 1- 40% 2- granular staining 3- immune complex disease 4- SLE, post-infectious, IgA, Henoch-Schonlein, idiopathic
RPGN:
(1) % type III
(2) IF staining
(3) alternate name
(4) causes
Type III RPGN 1- 40% 2- no staining 3- pauci-immune glomerulonephritis 4- (vasculitis) Wegner's, Microscopic PA, Churg-Strauss, idiopathic
All types of RPGN have characteristic (1) evident by the following symptoms: (2). Prognosis is described by the following results, (3), where (4) have the best prognoses.
1- severe glomerular injury
2- proteinuria, hematuria, RBC casts, HTN, edema, varible oliguria
3- 75% die or on dialysis w/in 2 yrs of Dx
4- treatable underlying disorders (SLE) or ones with spontaneous remission (post-strep)
(1) % of SLE patients have renal disease at the onset
(2) % will develop renal disease
1- 25-50%
2- 60%
list the percentages that an organ will be involved in SLE (generally)
-joints 90%
-skin: 70% rashes, 30% discoid lesions, 40% alopecia
-pleura-pericardium 60%
-kidney 50%
(raynauds 20%, mucus membrane 15%, CNS 15%)
Lupus Nephritis results from the abnormal production of (1) against (2) causing (3) deposition in kidneys which will cause subsequent (4) events
1- Abs
2- nuclear Ags (dsDNA, ANA, Sm, RNA, Ro, La)
3- immune complex (anti-DNA)
4- complement activation –> inflammatory cell recruitment –> tissue destruction
list the 6 classifications of lupus nephritis
(based on histology, EM- all are IF positive for IgG, IgA, C3, C1q, IgM = full house // C1q is necessary for LN Dx) I- minimal mesangial II- mesangial proliferative III- focal segmental proliferative IV- diffuse proliferative V- membranous VI- advanced sclerosing lupus nephritis
describe the histological and clinical appearance of type I lupus nephritis
minimal mesangial LN
- LM: normal
- IF, EM: mesangial immune deposits
no clinical appearance
describe the histological and clinical appearance of type II lupus nephritis
mesangial proliferative LN
-mesangial immune deposit => expansion, hypercellularity
mild disease: microscopic hematuria, proteinuria, nephrotic syndrome (rarely renal insufficiency)
describe the histological and clinical appearance of type III lupus nephritis
focal segmental proliferative LN
-LM: <50% glomeruli affected with subendothelial, mesangial IC deposits –> complement activation, inflammatory cells
hematuria, nephrotic syndrome, HTN, renal failure
describe the histological and clinical appearance of type IV lupus nephritis
diffuse proliferative LN
-LM: >50% glomeruli affected with subendothelial, mesangial IC deposits + crescents/necrotizing lesions
(most common + most severe form)- hematuria, proteinuria, nephrotic syndrome, renal failure, low complement, high anti-DNA levels
describe the histological and clinical appearance of type V lupus nephritis
membranous LN
-LM: subepithelial IC deposits (‘full house’), GBM thickening
-nephrotic syndrome, ‘bland’ urinary sediment, mild renal insufficiency, normal C3/C4, negative anti-DNA
(ICs in BVs)
describe the histological and clinical appearance of type VI lupus nephritis
advanced sclerosing LN
-LM: global sclerosis, >90% glomeruli affected, advanced interstitial fibrosis and tubular atrophy
describe the general clinical course of lupus nephritis and how to monitor it
- remissions and exacerbation periods
- monitoring by measuring complement, anti-dsDNA Ab, ESR, CRP
IF stain of _____ is required for diagnosis of lupus nephritis
C1q
