Pathology of Nephritic Syndrome Flashcards
Asymptomatic proteinuria/hematuria
1) symptoms
2) Urinalysis shows…
1) asymptomatic
2) proteinuria (> 150 mg/24 hr)
hematuria = dark or normal color urine + RBCs + red cell casts
Etiologies of asymptomatic proteinuria/hematuria
Proteinuria = leakage of protein thru glomerular basement membrane (glomerular disease) NOT TUBULAR
Hematuria = red cell casts = glomerular bleeding
Causes of leakage in basement membrane and what leaks thru
1) loss of electrostatic neg charge barrier so albumin leak thru
2) loss of size barrier so albumin, globulin and protein leak thru
Acute nephritic syndrome
1) signs and due to?
2) how does GFR change
3) effects of change in GFR
4) time frame
1) hematuria and proteinuria due to incr glomerular capillary permeability
2) decr GFR
3) Na+/H2O retention –> edema, CHF, HTN
azotemia (incr creatinine and BUN)
hyperkalemia
4) hours to days
Rapidly progressive nephritic syndrome
1) signs and due to?
2) how does GFR change
3) effects of change in GFR
4) time frame
1) hematuria and proteinuria due to incr glomerular capillary permeability
2) VERY DECR GFR
3) more fluid retention, more azotemia, oliguria
4) longer version of acute nephritic
Nephrotic syndrome
1) signs and due to?
2) effect on plasma oncotic pressure
3) effects of change in oncotic
1) massive proteinuria (> 3.5 g/24 hrs) not compensated by hepatic albumin syntheiss
2) decr plasma oncotic pressure
3) Na+ and H2O retention, edema, hypercholesterolemia
Chronic renal failure
1) due to
2) how does it affect GFR
3) assoc with
4) etiologies
1) nephron loss
2) decr GFR
3) uremia
4) glomerular disease, vascular disease/HTN (MOST COMMON), infection, drugs/toxins, UTI
Morphologic pattern of glomerular disease
1) mesangial, endocapillary, epithelial (podocyte) = crescent proliferation
2) leukocyte infiltration = PMN’s or leukocytes
3) basement membrane thickening/changes
4) sclerosis (segmental or global)
1) mesangial, endocapillary, epithelial (podocyte) = crescent proliferation
2) leukocyte infiltration = PMN’s or leukocytes
3) basement membrane thickening/changes
4) sclerosis (segmental or global)
indicative of…
glomerular disease
Distinguish between focal/diffuse sclerosis
Of all total glomeruli
focal = some normal, some abnormal
diffuse = affects all glomeruli
Distinguish between segmental/global sclerosis
within individual glomerulus
segmental = only portion of one
global = entire glomerulus
Things to identify on immunofluorescence
1) Ig’s/complement
2) distribution (mesangial/capillary)
3) pattern (linear/granular)
Things to identify on electron microscopy
1) deposits of Ag-Ab complexes
2) GBM changes
Things to identify on serum
1) complement levels (decr in some acute GN’s)
2) ANA- SLE
3) ASO (anti-strep O) = post-strep GN
4) ANCA = Wegener’s, PAN
IF you see ASO on serum what could that indicate?
If you see ANCA on serum what could that indicate?
1) post-strep GN
2) Wegener’s, PAN
Thin Basement Membrane Disease
1) also known as
2) prognosis
3) mutations in…
4) diagnsois based on …
1) benign familial hematuria
2) excellent
3) alpha chains of collagen IV (thin basement membrane)
4) electron microscopy)
Alport’s disease
1) triad of …
2) due to mutation in…
3) inheritance
4) can’t form …
5) definitive diagnosis based on what?
6) progress to…
1) nephritis, deafness, ocular lesions
2) alpha-5 chain of collagen IV
3) X-linked
4) normal basement membrane
5) basket-weave pattern on EM (abnormal lamina densa)
6) ESRD
Signs of non-inflamm pathogenesis DUE TO OXIDATIVE
1) mediated by…
2) immune complexes activ …
3) damages …
1) circulating factors or Ig’s that bind to membranes of glomerular epithelial cells
2) activ GEC to release reactive oxidants/proteases that damage diaphragms btwn podocytes
3) cause GEC to detach from basement membrane –> leak
Signs of non-inflamm pathogenesis DUE TO COMPLEMENT
1) mediated by…
2) antibodies bind…
3) damages …
1) complement-fixing anti-GEC antibodies
2) antibody bind GEC –> activ complement membrane attack complex
3) poke hole in glomerular basement membrane, incr permeability
Inflammatory pathogenesis of glomerular disease usually involves (4)
1) PMN’s
2) macrophages
3) mesangial cells
4) T cells
how are PMn’s involved in leading to inflamm pathogenesis
1) Ig antibody deposits within capillaries
2) activ complement
3) infiltrate of PMN’s
4) PMN’s burst –> release ROS –> damage glomerular basement membrane and endo cells
5) fibrin deposit in Bowman’s space –> form CRESCENTS
if crescents form what does that indicate
fibrin in bowman’s space –> severe inflammation
If Ig bind to endogenous antigens, what diseases
If Ig bind to EXOGENOUS antigen, what disease
1) SLE, good pasture’s
2) infection or toxin
macrophage role in inflamm disease
1) macrophage activ by cytokine
2) release oxidants and proteases that damage glomerular basement membrane
3) macrophage release cytokines that stim sclerosis
mesangial cell role in inflamm disease
1) immune complex, complement, cytokine activ mesangial cell
2) release oxidants, proteases, growth factors, ECM
T cell role in inflamm disease
1) T cells activate macrophage and mesangial cells
What is endocapillary hypercellualrity mean?
What is the marker of mesangial hypercellularity
what are crescents a reaction to?
both mesangial and endothelial cells in vascular compartment
> 2-3 mesangial nuclei per island
severe injury to glomerular capillaries –> fibrosis in Bowman’s space
Describe cellularity, segmental vs.global, capillary loops
Hypercellular? yes, mesangial hypercellularity
Segmental or global? segmental
Capillary loops still open
Left = immune complexes deposited in mesangial region
podocytes intact
basement membrane intact
Right = IgA deposited in mesangial regions
IgA neuropathy
1) usually presents as …
2) often coincides with …
3) morphology on stain
4) on EM, on IF
5) therapy
6) prognosis
1) asymptoamtic hematuria
2) nephritic or nephrotic; with URI or GI infection, or liver disease
3) mesangial, focal (can be MPGN)
4)
EM = mesangial deposits
IF = mesangial IgA
5) ? steroids
6) ESRD
Henoch-Schonlein Purpura
1) also known as
2) due to …
3) may involve
4) renal biopsies look like …
5) patient population
1) systemic IgA vasculitis
2) systemic deposition of IgA immune complex
3) kidney, skin, joint, GI
4) IgA nephropathy but more endocapillary prolif or crescents
5) < 10 yrs post URI esp strep
Left = hypercellular, no open capillary, inflamm cells (PMN’s)
creatinine = 2.5, RBC and RBC casts in urine = nephritic
Right = diffuse global endocapillary proliferative GN
Subendothelial Hump-like depositis
left: red = humps
right = fenestrated endothelium too many cells inside
left = hypercellularity in capillary loop
subepithelial deposits
right = starry sky pattern = granular with IgG/C3 immune complexes
Postinfectious GN
1) usually due to
2) acute nephritic or nephrotic
3) morphology
4) on EM, IF, serology
5) therapy
6) __% of children recover, __ % OF ADULTS recover
1) post strep infection
2) acute nephritic
3) diffuse prolif, exudative GN
4) EM = subepithelial hump-like deposits
IF = granular GBM = starry sky
serology = elev ASO
5) supportive
6) 99, 60
left = necrotizing and crescent glomerulonephritis
karyolectic debris
right = proliferation = crescents in bowman’s space
left = ruptured capillary loop
Crescentic glomerulonephritis
1) crescents = sign of ___
2) caused by ___
3) present as ___
4) more crescents correl with ___
5) glomeruli will usually ___
1) severe acute glomerular disease
2) fibrinoid necrosis of capillaries
3) RPGN
4) serum creatinine levels and prognosis
5) heal with scar
FSGN and Crescentic glomerulonephritis
If you see linear staining on IF …
IF you see granular staining …
If you see no staining …
1) goodpasture’s, anti-GBM
2) IgA, SLE, endocarditis, Idiopathic
3) wegener’s, microscopic PAN, churg-strauss, idioapthic
left = linear staining for IgG
right = starry sky = postinfectious GN presents as rapidly prolif
FSGN, crescentic GN
Serum/blood studies
1) if you see anti-GBM antbodies…
2) ANA, anti-dsDNA, complement depletion (C3, C4)
3) ANCA (MPO- cationic protein fixing complement)
4) blood cultures
1) goodpasture
2) lupus
3) vasculitis
4) endocarditis
Anti-gbm disease
1) ___ IgG antibody
2) antibodies directed against ___
3) if renal limited, ___
4) if renal + lung, ___
5) classic presentation =
6) on IF?
1) nephrotoxic
2) alpha chain of collagen IV in basement membrane
3) anti-GBM
4) goodpasture
5) RPGN + hemoptysis
6) linear
Crescentic GN
1) usually __
2) therapy
3) prognosis
1) RPGN
2) steroids, cytotoxics, plasmaphoresis
3) poor
lupus nephritis
1) part of ___
2) IF shows…
3) present as …
4) prognosis
1) SLE
2) full house = granular with positive IgG, IgA, IgM, C1q, C3
3) nephritic syndrome, RPGN, nephrotic syndorme, or mixed nephritic-nephrotic
4) usually good with treatment
anti-gbm disease
left = diffuse glomerulonephritis, hypercelllular, endocapillary prolif, PMN’s thick peripheral capillary loop
right = wire loop lesions= very red and huge deposits
Normal glomerulus is 70% ___
Largely contains ___
Features of mesangial cells
1) space
2) largely mesangial cells
3) derived from monocytes; produce matrix that surrounds self and interdigitates with capillary loops; phagocytose; intravascular
what is the most selective barrier for filtration
made of?
what is the largest filterer of proteins
slit diaphragm = podocytes connected by thin line slits
made of nephrin (2 nephrins holding hands + adhesion molec holding podocytes to basement membrane
basement membrane = leaky so podocytes are most stringent
nephrotic syndrome
1) presents with ___
2) due to ___
3) leads to…
1) massive proteinuria (> 3.5 g/24 hr)
2) decr plasma oncotic pressure
3) severe edema, hypercholesterolemia, lipiduria
Hyperfiltration causing glomerular disease seen in ..
diabetics
segmental glomerulosclerosis
loss of glomerular polyanions
how cause glomerular disease
incr permeability of glomerular capillary wall –> lose albumin in urine –> decr plasma oncotic pressure –> fluid into extravascular
