102914 path of kidney Flashcards
systemic diseases associated with nephrotic syndrome
diabetic nephropathy
amyloidosis
light chain deposition disease
hereditary glomerular diseases
Alport syndrome
thin basement membrane disease
hyperfiltration in diabetes occurs when
early in diabetes
how does hyperfiltration in diabetes occur?
gluocse causes afferent arteriole dilation
angiotensin II causes efferent arteriole constriction
both lead to increased GFR and glomerular loss of proteins
pathogenesis of diabetic nephropathy
hyperfiltration
hypertrophy
widening of GBM and podocyte changes leading to proteinuria
fibrosis
hypertrophy in diabetic nephropathy
seen early
increase in number of mesangial cells and capillary loops, increasing filtration SA
size of kidney may increase
hallmarks of diabetic nephropathy
mesangial expansion mediated by glucose and glucose derived AGEs
nodular diabetic glomerulosclerosis (acellular Kimmelstiel Wilson lesion)
describe widening of GBM in diabetic nephropathy
accumulation of type IV collagen
net reduction in negatively charged heparin sulfate
tubulointerstitial fibrosis is seen when in diabetic nephropathy?
later
tubulointerstitial fibrosis
tubular cells change phenotype and become fibroblasts
stages of diabetic nephropathy
pre-DN: increase in GFR, renal hypertrophy
stage 3: mesangial expansion, GBM thickens. HTN. GFR not as high as before. start seeing protein in urine.
stage 4: overt DN. mesangial nodules and tubulointerstitial fibrosis. proteinuria, nephrotic syndrome, decreased GFR.
treatment for diabetic nephropathy
HTN therapy glucose control reduce proteinuria (with renin agiotensin aldosterone system blockade to decrease constric of efferent arteriole) lipid lowering therapy lifestyle change
amyloidosis
deposition in extracellular spaces of proteinaceous material
amyloidosis affecting the kidney can be described by
light chains secreted by single clone of B cells
manifestations in amyloidosis affecting the kidney
often enlarged kidney and HTN is absent even when renal fxn is impaired
proteinuria in absence of microscopic hematuria
tubular defects from amyloid deposits (renal tubular acidosis, polyuria polydipsia)
light microscopy of amyloidosis
light pink PAS as opposed to diabetes
what is another stain that can be done for amyloidosis
Congo red stain-apple green birefringence
light chain deposition disease
deposition of excess immunoglobulin light chains in kidney
usually kappa light chains
50% coexist with multiple myeloma
light microscopy for light chain deposition disease
see nodular glomerulosclerosis, like for diabetes and amyloidosis
wouldn’t be able to tell difference btwn it and amyloidosis unless tested positive for congo red for amyloidosis
extra renal manifestations of amyloidosis
AL amyloidosis can affect almost any organ other than brain
what you see hematuria independent of proteinuria, think about
changes in glomerular membrane
dysmorphic RBC in urine indicates
RBC had to have crossed the glomerular membrane
Alport syndrome
usually X linked recessive
mutation of COL4A5 gene which encodes alpha5 chain of type IV collagen (causes defect in basement membrane)
renal manifestations of Alport syndrome
hematuria
proteinuria (absent early but develops eventually)
HTN
ESRD in all affected males with XLAS
extrarenal manifestations of Alport syndrome
cochlear defects
ocular defects
leiomyomatosis (less common)
pathology of Alport syndrome
early in disease, glomeruli may be normal
later-global and segmental glomerulosclerosis, interstitial fibrosis
EM: variable thickening, thinning, basket weave, and lamellation of GBM
thin basement membrane disease (benign familial hematuria)
usually autosomal dominant
continuous/intermittent microhematuria, w or w/o gross hematuria. generally no renal insufficiency
extra renal symptoms are rare
small risk of progression to ESRD
pathology of thin basement membrane disease
LM: normal glomeruli
IF: negative
EM: thin GBM
