Renal: Glomerular Diseases Flashcards
nephrotic syndrome is characterized by:
heavy proteinuria (>3.5 mg/day)
- hypoalbuminemia (bc of heavy proteinuria)
- edema
- hyperlipidemia & lipiduria
- normal complement levels
why is there hypercoagulability in nephrotic syndrome?
loss of anti-thrombin III
ATIII breaks up thrombin and coagulation factors so that you cannot make thrombin; therefore loss of ATIII = increased coagulation risk
list the renal diseases associated with nephrotic syndrome based on immunoglobulin deposition
____ is the most common cause of nephrotic syndrome in children
minimal change disease is the most common cause of nephrotic syndrome in children
describe the EM image seen in the condition in the image
minimal change disease
PAS-stained image = normal
EM: arrow = effacement of foot processes and absence of deposits
the condition seen in the image is associated with ____ (another condition)
the condition seen in the image is associated with Hodgkin’s lymphoma
describe what is seen on physical exam in the condition seen in the image
normal BP, edema (periorbital and pedal)
>90% of children have complete remission proteinuria in the condition seen in the image within 8 weeks of ____ therapy
>90% of children have complete remission proteinuria in the condition seen in the image within 8 weeks of steroid therapy
in the condition seen in the, there is autoimmune destruction of ____ cells, facilitated by ____ cells
in the condition seen in the, there is autoimmune destruction of epithelial cells (podocytes), facilitated by T cells
in the condition seen in the image, there is diffuse effacement of ____
in the condition seen in the image, there is diffuse effacement of foot processes of podocytes
the injury in the condition seen in the image results in increased ____ and subsequent massive ____
the injury in the condition seen in the image results in increased permeability and subsequent massive proteinuria
what condition shows the following results:
minimal change disease
the condition seen in the image can be secondary to:
- secondary to:
- HIV
- morbid obesity
- chronic reflux nephropathy
- heroin use
- malignancies (lymphoma)
the prognosis of the condition in the image depends on ____
the prognosis of the condition in the image depends on the degree of proteinuria
if a patient has HIV or does heroin and then develops nephrotic syndrome, which disease is most likely?
FSGS
describe the pathogenesis of the condition seen in the image
decreased renal mass
↓
compensatory hyperfiltration
↓
intraglomerular HTN and hyperfiltration injury
↓
non-selective proteinuria
which condition shows the following lab results:
LM: segmental hyalinosis of some glomeruli
IF: negative (or non-specific IgM & C3)
EM: patchy fusion of the foot processes & effacement
FSGS
in minimal change disease, there is ___ fusion of the foot processes and effacement
whereas
in FSGS, there is ___ fusion of the foot processes and effacement
in minimal change disease, there is diffuse fusion of the foot processes and effacement
whereas
in FSGS, there is patchy fusion of the foot processes and effacement
describe presentation of the condition seen in the image
present with nephrotic syndrome
microscopic hematuria & HTN
the condition seen in the image does NOT respond to ___ and ultimately progresses to ____
the condition seen in the image does NOT respond to steroids and ultimately progresses to end-stage renal failure (ESRF)
describe what is seen in the EM image
membranous glomerulopathy
EM showing electron-dense deposits (arrow) along the epithelial side of the basement membrane (B); note the effacement of foot processes overlying deposits
the condition seen in the image is caused by ___ deposition in the ____ zone
the condition seen in the image is caused by immune-complex deposition in the subepithelial zone
describe the pathogenesis of the condition seen in the image
membranous glomerulopathy
in the 2 conditions with the word “membranous”, they are characterized by thickening of ____ due to ____ deposition
membranous nephropathy
membranoproliferative glomerulonephritis
in the 2 conditions with the word “membranous”, they are characterized by thickening of the membrane due to immune-complex deposition
if a patient has hepatitis B, which nephrotic syndrome are they at risk of developing?
membranous nephropathy
if a patient has SLE, which nephrotic syndrome are they at risk of developing?
membranous nephropathy
which condition shows the following lab results:
on EM of the condition seen in the image, there are subepithelial immune-complex deposits w/ alternating ___ and ____
on EM of the condition seen in the image, there are subepithelial immune-complex deposits w/ alternating spikes and domes
on immunofluorescence of the condition seen in the image, there are subepithelial deposits of ___ and ____
on immunofluorescence of the condition seen in the image, there are subepithelial deposits of IgG and C3
describe complications of the condition seen in the image
infections, hypercoagulability (ischemic heart disease), renal failure
what would indicate a poor prognosis of the condition seen in the image
males, >50 yrs old, >10 gm of proteinuria
what is the FIRST change seen in diabetic nephropathy?
high serum glucose leads to non-enzymatic glycosylation (NEG) of vascular basement membranes, resulting in hyaline arteriosclerosis
arteriosclerosis preferentially in efferent arterioles → increased backpressure in glomerulus →
in diabetic nephropathy, initially hyperglycemia leads to ____
in diabetic nephropathy, initially hyperglycemia leads to hyperfiltration
the earliest lesions seen in diabetic nephropathy is expansion of ____ and thickening of ____
the earliest lesions seen in diabetic nephropathy is expansion of mesangial matrix and thickening of GBM
later lesions seen in diabetic nephropathy is diffuse global ____ with:
diffuse increase in ____
and diffuse thickening of ____
later lesions seen in diabetic nephropathy is diffuse global glomerulosclerosis with:
diffuse increase in mesangial matrix
and diffuse thickening of GBM
in diabetic nephropathy, ____ nodules can be seen which contain ___ & ____
in diabetic nephropathy, Kimmelstiel-Wilson nodules can be seen which contain lipids & fibrin
amyloid fibrils are composed of various normal soluble proteins that have undergone a misfolding event resulting in formation of abnormal protein with ____ structures
amyloid fibrils are composed of various normal soluble proteins that have undergone a misfolding event resulting in formation of abnormal protein with B-pleated sheet structures
in amyloidosis, organ damage & dysfunction is due to ____ and replacement of normal organ architecture with consequent loss of cellularity
in amyloidosis, organ damage & dysfunction is due to infiltration by amyloid fibrils and replacement of normal organ architecture with consequent loss of cellularity
which condition shows the following lab results:
amyloidosis
describe what condition is seen in the images
describe what is seen in the urine in nephritic syndrome
- RBCs and/or RBC casts
- granular casts
- variable proteinuria
- possibly WBC
list the normal complement level nephritic disorders (4)
- IgA nephropathy/Henoch-Schonlein purpura
- Alport’s syndrome (hereditary nephritis)
- SLE (class I, II, V)
- benign hematuria
list the low complement level nephritic disorders (4)
- PSGN
- membranoproliferative glomerulonephritis
- SLE (class III, IV)
- bacterial endocarditis/infected ventriculoatrial shunt
- cryoglobulinemia
____ is the most common cause of nephritic syndrome
mesangioproliferative glomerulonephritis (IgA nephropathy/Berger’s disease) is the most common cause of nephritic syndrome
list the conditions associated with IgA nephropathy
- hepatic cirrhosis
- gluten enteropathy
- HIV infection
- minimal change disease
- others: membranous, Wegener’s, ankylosing spondylitis, small cell ca.
the condition seen in the image in children is part of ____
the condition seen in the image in children is part of Henoch-Schonlein Purpura Nephritis
- kidneys = IgA nephropathy
- skin = non-blanching purpuric rash
- GI = mesenteric vasculitis → red infarct
- joints = arthralgia
the condition seen in the image presents in adults 1-3 days after ____
the condition seen in the image presents in adults 1-3 days after respiratory (or GI) infection
resp. + GI are lined by mucous membranes and therefore secrete IgA
the condition seen in the image is associated with ____
the condition seen in the image is associated with liver cirrhosis, Celiac’s disease, HIV and minimal change disease
describe the presentation of the condition seen in the image
episodic gross hematuria w/ a background of persistent hematuria, oliguria
describe what is seen on microscopy of the urine in the condition seen in the image
RBC casts
blood investigations in the condition seen in the image would show normal ____ levels, elevated ____ levels and _____
blood investigations in the condition seen in the image would show normal complement levels, elevated IgA levels and azotemia
describe what is seen on LM in the condition seen in the image
segmental areas of increased mesangial matrix & hypercellularity
describe what is seen on IF in the condition seen in the image
coarse granular (lumpy-bumpy) with mesangial & subendothelial IgA and C3
describe what is seen on EM in the condition seen in the image
mesangial and subendothelial IgA & C3
describe the complication of the condition seen in the image
can progress to Type II RPGN
the condition seen in the image can occur 10 days after ____ or 3 weeks after ____
the condition seen in the image can occur 10 days after pharyngitis or 3 weeks after impetigo
diagnosis of the condition seen in the image is with elevated titers of ___ or ____ in association with low ____
diagnosis of the condition seen in the image is with elevated titers of anti-streptolysin O Ab or anti-DNAse B in association with low complement levels
in the condition seen in the image, initially, there are ____ deposits which then become ____ which is responsible for ___
in the condition seen in the image, initially, there are subendothelial deposits which then become subepithelial humps which is responsible for epithelial cell damage & proteinuria
on LM of the condition seen in the image, what is seen?
- hypercellular glomeruli: neutrophils + monocytes
- proliferation of: mesangial, endothelial, epithelial cells
- process is diffuse (entire lobules of all glomeruli)
- closure of capillary loops due to proliferation & swelling of endothelial cells & leukocytes infiltration
in the condition seen in the image, there is closure of ____
in the condition seen in the image, there is closure of capillary loops due to proliferation & swelling of endothelial cells & leukocytes infiltration
describe what is seen on IF in the condition seen in the image
coarse, granular, (lumpy bumpy) deposits of IgG & C3 in mesangium & along capillary walls
in the EM of the condition seen in the image, there are ___
in the EM of the condition seen in the image, there are electron-dense deposits in subepithelial space; humps
a complication of the condition in the image is that it can progress to ____
a complication of the condition in the image is that it can progress to type II RPGN
the outcome of most cases of the condition seen in the image is ____
the outcome of most cases of the condition seen in the image is complete resolution
on LM of the condition seen in the image, there is ___ expansion and ____
on LM of the condition seen in the image, there is mesangial expansion and hypercellularity
what is a characteristic finding in the condition seen in the image?
duplication of the GBM = “tram-track” appearance
describe what is seen on EM in type I of the condition seen in the image
type I = subendothelial deposits (C3, +/- IgG, C1q, C4)
describe what is seen on EM in type II of the condition seen in the image
deposition of dense material along GBM (complement deposition, no immune complexes)
describe what is seen on EM in type III of the condition seen in the image
subendothelial, mesangial, subepithelial deposits (C3 +/- IgG)
describe what is seen in the image
MPGN: type I
note the discrete, electron-dense deposits (arrows) incorporated into the glomerular capillary wall between duplicated (split) BMs (double arrows)
describe what is seen in the image
MPGN: type II
dense-deposit disease (type II MPGN)
there are dense homogenous deposits within the BM
in type I of the condition seen in the image, there is ___ activation via the ___ pathway
in type I of the condition seen in the image, there is complement activation via the classical pathway
in type II of the condition seen in the image, there is activation of the ___ pathway which leads to depressed ____ levels
in type II of the condition seen in the image, there is activation of the alternate pathway which leads to depressed C3 levels
list the 4 ways the condition seen in the image can present
- hematuria or proteinuria discovered on urinalysis
- acute nephritic syndrome with hematuria, HTN and edema
- recurrent episodes of gross hematuria
- insidious onset of edema and nephrotic syndrome
on LM of the condition seen in the image, there is proliferative GN with prominent ____ formation +/- segmental ____
on LM of the condition seen in the image, there is proliferative GN with prominent crescent formation +/- segmental necrosis
describe type I of the condition seen in the image; what kind of staining is seen on IF?
linear staining on IF
Anti-GBM disease, such as Goodpasture’s syndrome
describe type II of the condition seen in the image; what kind of staining is seen on IF?
granular staining on IF
immune-complex disease; found in SLE, post-infectious, IgA, Henoch-Schonlein Purpura
describe type III of the condition seen in the image; what kind of staining is seen on IF?
no staining on IF; pauci-immune GN
Wegener’s (c-ANCA)
microscopic polyangitis (p-ANCA)
Churg-Strauss (p-ANCA)
what are the crescents in the image composed of?
crescents = fibrin + macrophages + proliferating parietal cells
the best prognosis of the condition seen in the image is with patients with ___
the best prognosis of the condition seen in the image is with patients with treatable underlying disorders (such as SLE) or one that spontaneously remits (such as post-strep)
describe what is seen in the image
type I RPGN; anti-BM disease, such as Goodpasture’s
on IF examination of lupus nephritis, it is positive for ____ which is also called a ____
on IF examination of lupus nephritis, it is positive for IgG, IgA, C3, IgM which is also called a full house
describe class I of lupus nephritis
minimal mesangial lupus nephritis
- LM = normal
- IF & EM = mesangial immune deposits
describe class II lupus nephritis
mesangial proliferative lupus nephritis
- mesangial immune deposits resulting in expansion & hypercellularity
- clinical: mild disease, microscopic hematuria, proteinuria, nephrotic syndrome
describe class III lupus nephritis
focal segmental proliferative lupus nephritis
- <50% glomeruli affected on LM
- subendothelial & mesangial IC deposits; complement activation, influx of inflam. cells
- clinical: hematuria, nephrotic syndrome, HTN, renal failure
describe class IV of lupus nephritis
diffuse proliferative lupus nephritis
- >50% glomeruli affected on LM
- marked deposition of IC in subendothelial and mesangium
- crescents and necrotizing lesions
- clinical: most common and severe form; hematuria, proteinuria, nephrotic syndrome, renal failure, low complements, high anti-DNA levels
describe class V lupus nephritis
membranous lupus nephritis
- subepithelial immune complex deposits
- diffuse thickening of GBM
- clinical: same as idiopathic membranous; nephrotic syndrome, normal C3/C4, negative anti-DNA
- IC deposits in blood vessels
describe class VI lupus nephritis
advanced sclerosing lupus nephritis
- global sclerosis of >90% of glomeruli
- advanced interstitial fibrosis and tubular atrophy
- represents healing of prior inflammatory injury, advanced stages of chronic class III, IV, V lupus nephritis
disease activity of lupus nephritis can be monitored by serial measurements of ____ (4 things)
disease activity of lupus nephritis can be monitored by serial measurements of:
- complements
- anti-dsDNA Ab
- ESR
- CRP
the condition seen in the image is also called _____
the condition seen in the image is also called inherited nephritic syndrome
the condition seen in the image has a defect in ____
the condition seen in the image has a defect in α-5 subunit of type IV collagen
the genes associated with the condition seen in the image are….
COL4A3, COL4A4, COL4A5
COL4 = collagen 4
describe the presentation of the condition seen in the image
- hematuria, periorbital edema, oligura
- cataracts
- sensorineural deafness
describe the blood levels of the condition seen in the image
NORMAL complements levels, azotemia (increased BUN + increased creatinine without uremic symptoms)
describe what is seen on LM in the condition in the image
initially normal → hyperfiltration → FSGS
describe what is seen on EM in the condition in the image
basket-weave appearance due to alternating thickening and thinning of lamina densa in BM
list complications of the condition seen in the image
- can progress to nephrotic FSGS → anasarca & 3.5g of protein & fatty casts
- deafness, blindness
