glomerular

pathology
general concepts
deni&ons. :: glomerulopathy. any glom disease :: glomerulonephri&s. i mmunologically mediated glom disease ::primary vs. secondary. kidney-only disorder vs. complica8on of other disease. clinical eects. t wo most common features- :: hematuria. any upset of glom cap. o;en from acute/immunological diseases of glom, or other kidney/ lower UT injury. [clues that hematuria is related to kidney disease= proteinuria, dysmorphic RBCs a nd casts. ::proteinuria. any glom injury that i ncrases permeability of capillary wall. heavy proteinuria- usually glom problem categories of glom injury. :: immunological. glom--phri8s= GNs very common- primary and secondary :: metabolic. diabe8c glom--sclerosis common form of secondary chronic renal disease :: hereditary. abnormali8es of glom cap wall structure are common. :: other. hemodynamic stress, toxic injury, n eoplas8cd

normal

acute

histological ndings of glom disease

acute glom diseases. :: hypercellularity - prolifera8on of m esangial and endothelial cells, epithelial cells [crescents- lls b owmans s pace happens because of brin forming in urinary space as blood pours out the capillary. if majority of gloms have crescents= c rescen8c GN, usually cause of RPGN], and exuda8on= g lom inammatory cells :: necrosis, blood in bowmans space and tubules, glom cap thrombosis, loss of podocyte foot process architecture, tu; necrosis, red cell casts= red cells into tubules and become trapped in protein gel= good indica8on of glom injury. chronic glom diseases. :: sclerosis. scarring of glom= can be BM thickening, nodular g lomerulsclerosis, segmental GS, global GS :: brous crescents. when collagen replaces cellular crescents= permanent oblitera8on of bowmans space. :: tubulo-inters&&al s carring. tubular collapse+ brous growth of inters88al space. renal fxn + serum Cr can inform about this pathology. mechanisms of injury in GNs :: an&body mediated. + immune complex deposi&on. an8body and an8gen together- either xed- a n8gen is intrinsic to kidney 8ssue, ie autoimmunity [good pastures- an8gen in GMB, Heymanns- an8gen part of podocytes= membranous GN. planted- an8gen from outside kidney- collects in kidney and then an8body nds it there. an8gen exogeneous [ bugs and drugs] or endogenous [from pt own 8ssues- tumor or nucleic acid = lupus nephri8s] + circula&ng immune complexes. complex forms in circula8on and plants in kidney and circula8on. :: site of deposi&on depends on: site of an8gen, ra8o of an8gen to an8body. :: detect. using immunooresence against an8body + cytotoxic an&bodies. cause damage w/ out deposits. [see pauci] :: cell-mediated. cytokines from immune system cause g lom injury.

exuda8on crescents

prolif- endo + mesangial

chronic

sclerosis- BM m esangium sclerosis seen in DM brous crescent

immune complex deposi8on

glomerular pathology
glomerular diseases associated with hematuria and/or acute nephrI8c syndrome
IgA n ephropathy [Bergers] ::general. immune complexes of IgA a nd C3 deposit in mesangium = m esan8al e xpansion and prolifera8on +/- crescents. ::clinical. episodic hematuria [ mild proteinuria], o;en associated w / upper resp. infxn [increases IgA]. can be familial. progression to renal failure= 15-40%. systemic syndrome= henoch-schonlein purpura

glomerular diseases -associated with nephrO8c syndrome

minimal change disease. :: pathology. podocyte eacement= selec8ve proteinuria [mostly albunemia], cytokine mediated?. normal by LM, no immune complexes

focal segmental GS [FSGS] :: pathology. sclerosis of parts of some gloms. consolida8on of tu; incrased m atrix, accum of plasma proteins [hyaline] see C3 and IgM at sclerosis. no immune complexes, EM s houws podocyte e acement :: clincial. idiopathic, secondary to injury from other types of GN, obesity-associated hypertrohpy and hyperltra8on of gloms also from injury from HIV, pamidronate, parvovirus, most common in adults from n ephro8c syndrome. acute prolifera&ve GN/Post infec&ons GN :: general. streptococcal infxn immune complexes of IgG, IgM, C3= form sub-epithelial humps cause enlarged h ypercellular endothelial + normal mesangium/ glom cap loops lled w/ neutrophils and leukocy8c exudate= no space for RBCs to move through, +/- crescents. :: clinical. classic se\ng of acute nephri8c syndrome- hematuria, proteinuria [usually subnephro8c < 3], GFR w/ extracellular uid reten8on [oliguria, azotemia, HTN, edema] prognosis is good if no crescents. membranous GN :: path. capillary wall thickened see immune complexes -IgG and C3, granular subepi. spikes of BM between deposits. xed/intrinsic an8gen [PLA2R- not idio anymore] ::clinical. nephro8c range proteinuria. clinical course variable- resolu8on/renal i nsu/failure prolonged proteinuria = tubule injury cytokines promote inters88al brosis sCr increases/renal f xn decreases

diabe&c n ephroppathy ::general. m etabolic e8ology. no immune complexes, see : arteriolar hyaline, mesangial sclerosis [diuse and nodular - KW] micro aneurysms, and BM thickening [glom and tubular]

rapidly progressive GN
Crescen&c GN [RPGN] :: general. crescents = e xtracapillary [epithelial] prolifera8on. +/- tu; necrosis, +/- mesangial/endo prolifera8on :: clinical. highly destruc8ve w/ capillary necrosis, crescent forma8on and rapidly progressing renal failure. 3 major causes: an8-GBM an8bodies, pauci-immune GN, Crescen8c immune complex GN an&-GBM- autoan8bodies to g oodpasture a n8gen in GBM= destruc8on of cap. wall. will see linear distribu8on of I gG a n8body on cap wall. [cross rxn o f the an8body and pulmonary capillary BM = lung hemorrhage :: necro&zing and c rescen&c. a`ach = necrosis= crescent forma8on.

glomerular diseases to be seen in other lectures

amyloidosis. brillary deposts accumulate in gloms [made of light chain gamma-globulins-myeloma, amyloid, many other things. congo red posi8ve. seen in nephro8c syndrome. alport s yndrome. defect in collagen IV- component of GBM. isolated h ematuria. GBM thin and spli\ng also = nerve deafness/eye abnormali8es. progresses to G S. MPGN- membranoprolifera&ve. can be nephri8c or n ephro8c assoc. w/ Hep B and C tram track BM= duplica8on of BM. mesangial +endothelial prolifera8on