Glomerular Structure and Mechanisms of Disease (Nichols) Flashcards
9 places in a glomerulus that disease can be located
1 arterioles
2 capillaries (lumen & endothelial cells)
3 subendothelial (btwn capilary endothelial cells & GBM)
4 GBM
5 subepithelial (btwn GBM & epithelial cells)
6 in slit pore diaphragm
7 podocytes
8 bowman space and capsule
9 mesangium
8 most common primary glomerular diseases
1 minimal change disease 2 focal segmental glomerulosclerosis 3 membranous nephropathy 4 acute post-streptococcal glomerulonephritis 5 membranoproliferative glomerulonephritis 6 IgA nephropathy (Berger disease) 7 hereditary nephritis (Alport syndrome) 8 congenital nephrotic syndrome
5 most common secondary glomerular diseases
1 hypertensive nephropathy 2 diabetic nephropathy 3 lupus nephritis 4 amyloidosis 5 Goodpasture syndrome
3 most common types of glomerular disease in order of prevalence
1 hypertensive
2 diabetic
3 immune-mediated
pathophys of hypertensive glomerular disease
most common cause of glomerular disease
injury to endothelium -> thrombus
thrombotic microangiopathy
positive feedback loop
Malignant htn
black males ~40
intracranial pressure, headache, scotomas, vomiting
BP >200/120 mmHg
proteinuria, microscopic hematuria
fibrinoid necrosis of arterioles
proliferation of intimal cells in small arteries
hyperplastic arteriosclerosis
*onion-skin appearance*anti-GBM disease
More common in men as their GBM is thicker
associated with smoking
Tx by plasmapheresis
podocyte disease
??
crescentic nephritis
proliferative parietal epithelial cells, exudate, leaked plasma, visible crescent in BS
slit pore diaphragm disease
??
patterns and locations of immune complexes & diagnostic examples
mesangial - IgA nephropathy
subepithelial - post strep. glomerulonephritis
subendothelial - lupus
foot processes
part of pedicles - interdigitates with another
mesangium
mesanchymal cells
phagocytic
contractile
produce mesangial matrix
GBM
glomerular basement membrane
parlecan
basement membrane
highly charged w/heparan sulfate
entactin
basement membrane
Ca++ binding
fibronectin
basement membrane
high MW - binds collagen, heparan sulfate, integrins
laminin
basement membrane - binds type IV collagen, entactin, heparan sulfate, and cells
type IV collagen location & 2 types
basement membrane
alpha3, alpha4, alpha5 (IV)
alpha5, alpha5, alpha6 (IV)
noncollagenous domain of alpha3 (IV) chain
antiodies attack in Goodpasture’s
nephrin
transmembrane - major component of slit pore diaphragm. disulfide bridges
podocin
part of split pore diaphragm
metabolic (diabetic) nephropathy
hyperglycemia -> glycosylation of proteins
they get trapped in GBM, stim new GBM
GBM thickened
AGE & AOPP
diabetic protein glycosylation
non-enzymatic due to high glc
hemodynamic glomerular injury
pressure -> physical injury
diffuse vs focal glomerular disease
diffuse - most or all glomeruli
focal - few glomeruli
global vs segmental glomerular disease
global - the whole thing(s)
segmental - part of it (them)
proliferative glomerulonephritis
cells grow
membranous nephropathy
membrane thickening
membranoproliferative glomerulonephritis
both proliferative and membrane thickening
pauci-immune glomerulonephritis
no immunofluorescence
most patients have ANCA
pANCA
cANCA
glomerulosclerosis
fibrous replacement of the glomerulus
glomerular basement membrane layers
lamina lucida/rara (close to endothelial cells) lamina densa (double usual thickness) lamina rara externa (close to epithelial cells)
non-glomerular basement membrane layers
lamina rara (close to endothelial cells) lamina densa
Goodpasture syndrome
antibodies against alpha3 (IV) non-collagenous NC domain
antibodies to non-collagenous collagen
antibodies against alpha3 (IV) non-collagenous NC domain
how is African sleeping sickness circumvented?
Disease is caused by Trypanosoma brucei rhodesiense
variant apoL1 doesn’t bind trypanosomal protein, which would ordinarily lyse parasites.
Mutation associated with focal segmental glomerulosclerosis
foot process effacement
long segments of a capillary are covered by a single podocyte - no longer interigitating foot processes
nephrotic syndrome
severe loss of protein through slit pore diaphragms - shows effacement
FAT & cadherin function
binds adjacent pedicles
nephrin
transmembrane
filtration role in slit-pore diaphragm
disulfide bridges
IgA nephropathy
abnormal IgA - uncapped in hinge region
reduced negative charge allows filtration
binds IgA, fibronectin, CD89 (soluble IgA receptor), transferrin receptor (CD71) on mesangial cells
compliment activated 75% lectin, 25% alt.
anaphylotoxins, injury/inflammation
immune-mediated glomerular disease
fixed or planted antigens
directly toxic or (more likely) elicit leukocyte damage
platelets aggregate
IL-1 release, arachidonic acid metabolytes, NO, endothelin
large circulating immune complexes give this appearance microscopically
wire loops - can’t evenly distribute on basement membrane
streptococcal antigens appearance
planted - formed in place
subepithelial location
poststreptococcal eglomerulonephritis (abs against what?)
streptococcal exotoxin B
streptococcal GAPDH
endostroptosin
subepithelial humps inimmunofluorescence (suggest what?)
post-streptococcal glomerulonephritis
anti-GMB immunofluorescence pattern
linear pattern on GMB
4 stains and their uses in glomerulonephropathy
Hematoxylin & eosin (routine)
Jones methenamine silver (basement membranes)
periodic acid schiff (PAS) (cellular cytoplasmic inclusions)
trichrome (collagen)
pANCA
cANCA
(associations)
pANCA - microscopic polyangiitis or Churg-Strauss
cANCA - Wegener’s
AGE
advanced glycolation end-products
seen in diabetic/metabolic glomerular injury
leads to ROS, podocyte injury, apoptosis
AOPP
advanced oxidation protein products
seen in diabetic/metabolic glomerular injury
leads to ROS, podocyte injury, apoptosis
flea-bitten kidney
small vessel ruptures over kidney (htn)
scotomas
spots before eyes (htn)
% children’s glomerular disease primary
% adults’ glomerular disease primary
95% children
60% adults
onion-skin-like appearance
hyperplastic artherosclerosis
seen in malignant htn
