Term
The Juxtaglomerular apparatus is made up of which 3 types of cells? What do they do? |
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Definition
1. renin granule containing cells of afferent arteriole - modified smooth muscle cells performing an endocrine function
2. Goormaghtigh cells - aka Lacis cells or extraglomerular mesangium; between afferent and efferent arterioles
3. macula densa - senses composition of fluid in tubule and communicates with Goormaghtigh cells and renin producing cells |
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Term
| function of proximal tubule |
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Definition
reabsorb 60-80% of total filtrate
regulate acid base balance via proton ATPases and Cl-HCO3 exchangers
(little glycolytic capacity and high rates of ATP turnover make them vulnerable to injury in conditions of ischemia and shock)
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Term
| function of thin limb of loop of henle |
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Definition
| countercurrent exchange of solutes and water in medulla - maintain concentration gradient |
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Term
| function of ascending thick limb of loop on henle |
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Definition
| high concentrations of Na pumps and Na/K/Cl cotransporters - hypertonic extrusion of salt - dilutes luminal fluid |
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Term
| function of distal convoluted tubule |
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Definition
| can remove more salt from luminal fluid and add or subtract acids/bases |
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Term
| function of collecting ducts |
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Definition
| control water reabsorption, acid base balance |
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Term
| 3 types of cells in the collecting ducts |
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Definition
1. principal - resopnd to ADH
2. intercalated A - basolateral ATPase, apical Cl/HCO3 exchanger
3. intercalated B - basolateral Cl/HCO3 exchanger, apical ATPase |
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Term
| many collecting ducts join together to form the... |
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Definition
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Term
| if specific gravity is not >1.022 (after a 12 hr period w/o food or water) it means that? |
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Definition
| renal concentrating ability is impaired |
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Term
| leukocyte esterase tests for? |
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Definition
| pyuria = infection in upper and lower urinary tract, glomerulonephritis, and acute tubulointerstitial nephritis (eosinophils) |
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Term
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Definition
| bacteria - especially gram negative rods like E.coli |
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Term
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Definition
| increased unconjugated bilirubin = hemolysis (liver and biliary systems are normal) |
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Term
| > 150mg/24 hr protein in the uring means... |
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Definition
| proteinuria - due to glomerular disease, tubular disease, or excess production (can be up to 300 in pregnancy) |
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Term
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Definition
| acetoacetic acid is only one measured; increased due to diabetic ketosis or calorie deprivation |
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Term
| conjugated bilirubin in urine |
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Definition
| present in cases of impaired liver function or biliary obstruction |
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Term
| hematuria seen in cases of |
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Definition
upper urinary tract diseases (glomerular injury, kidney trauma/malignancies, pyelonephrities), or lower urinary tract problems (stones, malignancies, infections);
*dysmorphic (spherical w/ blebs) - form only in the kidney; indicate glomerulonephritis |
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Term
| increased tubular epithelial cells seen in... |
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Definition
tubular necrosis or degeneration
when lipiduria occurs, TEC are stuffed w/ fat and called oval fat bodies, and show Maltese cross on polarized light |
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Term
Casts
formed where?
7 types: |
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Definition
formed only in the kidney
1. hyalin - mucoprotein - post exercise, dehydration
2. RBC - nephritic syndrome (glomerulonephritis)
3. WBC - acute pyelonephritis or active inflammation
4. Tubular epithelial casts - tubular injury (acute tubular necrosis)
5. Fatty casts - libiduria - nephrotic syndrome
6. granular casts - renal disease (nonspecific)
7. Broad (waxy) - chronic renal failure |
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Term
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Definition
normal: calcium oxalate, triple phosphate, amorphous phosphates
abnormal: cystine crystals "benzene rings" - congenital cystenuria or severe liver disease |
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Term
| Nephrotic syndrome (definition) |
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Definition
1) heavy proteinuria (>3.5 gm/24hrs)
2) hypoalbuinemia (<3 gm/dl)
3) generalized edema
4) hyperlipidemia and lipiduria |
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Term
| Nephrotic syndrome (pathophysiology) |
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Definition
| increaed permeability of glomerular capillary wall to plasma proteins -> proteinuria -> depletion of serum albumin -> loss of colloid osmotic pressure -> edema and hypovolemia -> decreased GFR -> increased ADH -> Na and H2O retention -> increased edema |
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Term
| selective proteinuria (definition, occurs in?) |
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Definition
leak of low MW proteins in urine such as albumin, transferrin, and IgG
Occurs in minimal change disease |
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Term
| selective proteinuria (definition, occurs in?) |
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Definition
leak of low MW proteins in urine such as albumin, transferrin, and IgG
Occurs in minimal change disease |
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Term
| nonselective proteinuria (def, occurs in?) |
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Definition
leak of low and high MW proteins such as IgM and IgA in urine
occurs in diseases other than minimal change disease |
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Term
| hyperlipidemia and lipiduria (def, occurs?) |
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Definition
increased circulating cholesterol and triglycerides
due to:
1) hypoalbuminemia triggers increased synthesis by the liver
2) abnormal transport w/ decreased uptake into tissues
3) impaired breakdown of lipoproteins |
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Term
| Causes of nephrotic syndrme (10) |
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Definition
Minimal change disease
Focal segmental glomerulosclerosis
membranous glomerulonephritis
diabetes mellitus
amyloidosis
systemic lupus
drugs (NSAID)
Infection (Hep B, C, HIV)
Neoplasms |
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Term
Minimal change disease, aka nil disease or lipoid nephrosis
(most common cause in? sx?) |
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Definition
most common cause of nephrotic syndrom in children, peak 2-6 yrs
presents w/ edema, selective proteinuria, and normal renal function, usually no hypertension or hematuria |
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Term
| Minimal change disease (pathogenesis) |
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Definition
Abnormal immune function:
lymphokine toxic to glomerular visceral epithelial cells -> reversible cell injury, reduction in BM anion charge -> proteinuria
Non-immune:
mutation in Nephrine gene (NPHS1) -> congenital nephrotic syndrom of the Finnish type |
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Term
| Minimal change disease (pathology) |
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Definition
LM: normal glomeruli, tubules, interstitum and vessels
Immuno: negative
EM: normal, except for diffuse effacement of visceral epithelial cell foot processes; no immune complexes |
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Term
| Minimal change disease (clinical course) |
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Definition
| >90% children respond to corticosteriods; excellent prognosis; food process effacement is reversible with steriods; disease may recur and some pts become steroid dependent or resistent - use immunosuppresive agents |
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Term
| Focal segmental glomerulosclerosis (clinical) |
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Definition
primary FSGS is cause of nephrotic syndrome in 35% adults and 10% children; prevalent in hispanic and african american adults;
higher incidence of nonselective proteinuria, hematuria, hypertension |
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Term
| Focal segmental glomerulosclerosis (pathogenesis) |
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Definition
visceral epithelial cell degeneration and detachment of foot processes from basement membrane
causes: immune dysfunction (circulation 50kDa non-Ig factor); gene mutation encoding for slit diaphram proteins (podocin, alpha actinin 4, TRPC6) and adhesion molecules |
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Term
| Focal segmental glomerulosclerosis (pathology) |
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Definition
begins in juxtamedullary glomeruli; focal segmental
LM: sclerotic segments show wrinkling of BM, matrix expansion, hyaline deposition, adhesions to Bowman's capsule; uninvolved segments and glomeruli are normal. Interstitial fibrosis and tubular atrophy are usually present;
Immuno: segmental, nonspecific entrapment of IgM and C3 as course clumps (NOT immune complexes)
EM: diffuse effacement of foot processes + detachment of foot processes from basement membrane, wrinkling of BM, natrix expansion, hyalin.
progress to diffuse global glomerulosclerosis and increased interstitial fibrosis and tubular atrophy |
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Term
| Focal segmental glomerulosclerosis (clinical course) |
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Definition
poor response to steroids alone, may respond to long course of sterouds + cyclosporine/cyclophysphamide; prognosis better in children than adult
50% progress to ESRD in 10 yrs
recurs in 25-50% of transplants |
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Term
| Secondary focal segmental glomerulosclerosis (etiology) |
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Definition
| HIV, heroin addiction, massive obesity, focal glomerulonephritis |
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Term
| ablation focal segmental glomerulonephritis |
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Definition
| loss of nephrons -> glomerular hyperfiltration & HTN and hypertrophy and systemic HTN -> epithelial/endothelial injury and leakage of plasma proteins into mesangium that organize to form hyaline, matrix expands -> FSGS -> further loss of nephrons |
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Term
| HIV associated nephropathy (HIVAN) |
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Definition
high incidence in african americans and IV drug users
LM: glomerular tuft is collapsed; rpliferation and hypertrophy of visceral epithelial cells, contain hyalin droplets, interstitial fibrosis, severe tubular injury, cystic dilation
EM: numerous tubuloreticular structures in endothelial cells
Collapsing varient has poor prognosis, resistant to steroids, progress to ESRD in 1 yr |
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Term
| membranous nephropathy, aka membranous glomerulonephrities, MGN (clinical) |
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Definition
mostly idiopathic; most common cause of nephrotic syndrome in adults
presents w/ nonselective proteinuria, hematuria, mild hypertension can occur |
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Term
| membranous nephropathy (pathogenesis) |
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Definition
autoimmune: autoantibody to nephritogenic antigen (megalin-like complex), phospholipase A2 receptor) located on basal surface of visceral epithelial cells
antigen-antibody immune complexes form in situ on epithelial cells -> activate comoplement and MAC -> glomerular cells release proteases/oxidants -> capillary wall injury and protein leakage -> ag-ab complexes shed from epithelial surface onto subepithelial side of GBM
in secondary MGN, inciting agent may be identified in immune complex (ex hep B) |
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Term
| membranous nephropathy (pathology) |
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Definition
LM: diffuse uniform thickening of GBM of all glomeruli w/o significan cellular proliferation (idiopathic); increased meangial cells (secondary)
Immuno: uniform granular deposits stain w/ IgG and C3 long GBM "capillary loop", mesangial staining is negative in idiopathic but positive in secondary.
EM: early cases show numerous osmophilic electron dense deposits (ag-ab immune complexes) in subepithelial location
Later - GBM material accumulates btwn deposits forming spikes which eventually in advanced cases surround the deposits; foot processes are effaced; mesangial deposits are absent in idiopathic but present in secondary |
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Term
| membranous nephropathy (clinical course) |
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Definition
| indolent and unpredictable, 30% spontaneous remission; 10% progress to ESRD in 10 yrs; 40% eventually ESRD; response to steroid therapy is poor; cyclosporine may induce remissions in proteinuria and progressive renal dysfunction |
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Term
| secondary membranous glomerulonephritis (etiology & tx) |
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Definition
Etiology: lupus, tumors (lung, colon, melanoma), drugs (penicillamine, gold, NSAID), infection (hep B & C, syphilis, malaria), metabolic disorders (diabetes, thyroiditis)
treatment of underlying condition may eradicate lesion and nephrotic syndrome |
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Term
| Nephritic Syndrom (definition) |
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Definition
1) hematuria w/ dysmorphic RBC and RBC casts
2) azotemia (increased BUN and creatinine)
3) oliguria (<400ml urine/24hr)
4) hypertension
5) mild edema and proteinuria ( |
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Term
| Nephritic syndrome (pathophysiology) |
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Definition
inflammatory cells in glomerulus injure capillary wall -> hematuria
inflammation -> hemodynamic changes, decreased perfusion and GFR -> oliguria and azotemia -> Na/H2O retention
hemodynamic changes -> increase renin/aldosterone -> exacerbate Na/H2O retention
do NOT have hypoalbumenemia, so Na/H2O retained in vascular tree -> increae plasma volume -> hypertension and mile edema |
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Term
| Nephritic syndrom (causes - general & 3 primary & 6 secondary) |
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Definition
inflammatory lesions of the glomeruli -> hypercellular due to proliferation of mesangial, endothelial and epithelial cells & inflitration by inflamitory cells
Primary: acute postinfectious glomerulonephritis, IgA nephropathy, Rapidly progressive (crescentric) glomerulonephritis
Systemic: cryoglobulinemic glomerulonephritis, Henoch-Schonlein purpura, Goodpasture syndrome, microscopic polyangitis, Wegener granulomatosis, Lupus glomerulonephritis |
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Term
| Acute Poststreptococcal Glomerulonephritis (clinical) |
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Definition
step is mcc of acute postinfectious glomerulonephritis; most common in kids 6-10yr
occurs 1-4 wks after group A beta hemolytic strep of pharynx or skin
abrupt onset of nephritic syndrome w/ increased ASO titer and decreased serum complement |
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Term
| acute postinfectious (poststreptococcal) glomerulonephritis (pathogenesis) |
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Definition
types 1, 4, 12 of GABHS
antigen-antibody immune complex mediated
glomerular injury due to planted antigens -> in situ formation of immune complexes OR entrapment of preformed circulating ag-ab immune complexes |
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Term
| acute postinfectious glomerulonephritis (pathology) |
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Definition
LM: diffuse proliferative glomerulonephritis - hypercellular due to proliferation of endothelial and mesangial cells & neutrophils - obliterate capillar lumina; mesangial matrix is expanded, GBM NOT thickened; occassional crescents; tubules contain RBCs
Immuno: IgG and C3 positive in granular lumpy bumpy deposits along GBM and in mesangium
EM: numerous large subepithelial electron dense deposits (humps) along GBM and some deposits in mesangium, subendothelial deposits may also be seen |
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Term
| Acute postinfectious glomerulonephritis (clinical course) |
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Definition
| good prognosis, >95% children recover, less favorable for adults; therapy is supportive, NO steroids/ immunosuppression; 1% rapidly progressive; 1-2% chronic glomerulonephritis |
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Term
| Membranoproliferative Glomerulonephritis (clinical - classification) |
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Definition
either primary (idiopathic - type I or II) or secondary
Type I idiopathic - more frequent than type II, most common in older children/ young adults
most cases present w/ nephrotic syndrome, usually w/ nephritic comoponent and serum hypocomplementemia.
secondary - usually type I, may be associated w/ lupus, infected AV shunts, bacterial endocarditis, hep B/C |
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Term
| Membranoproliferative Glomerulonephritis Type I (pathogenesis) |
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Definition
immune complex mediated - both classic and alternative complement pathways
antigen unknown (maybe Hep B/C)
glomerular injury due to planted antigens -> in situ formation of immune complexes OR entrapment of preformed circulating ag-ab complexes |
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Term
| Membranoproliferative Glomerulonephritis Type II (pathogenesis) |
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Definition
complement activation through alternative pathway
circulating IgG autoantibody = C3 nephritic factor (C3NeF) binds to and stabilizes C3 convertase C3bBb of alternative pathway -> persistent C3 degradation and hypocomplementemia
frequent recurrence in renal transplant |
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Term
| Membranoproliferative Glomerulonephritis (pathology) |
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Definition
LM: diffuse global hypercellularity w/ accentuation of lobular architecture "cauliflowers" due to endocapillary proliferation and influx of inflammatory cells; Mesangial matrix expanded; GBM thickened; silver stain shows duplication of GBM "tram-track"; some cases show crescents
Immuno:
Type I - granular C3 deposits and lesser IgG and C1q both in mesangium and along GBM "broken curvilinear" = "egg-shell";
Type II - C3 deposition as irregular granular foci along GBM (on either side but not w/in the dense deposits) and as "rings" in mesangium; IgG and C1q are usually negative
EM:
Type I - duplication of BM, extension of mesangial cells and matrix into subendothelial space (mesangial cell interpositioning), presense of immune complexes in subendothelial location and mesangium;
Type II - intramembranous electron dense ribbon like material of unknown composition and same dense material in mesangium |
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Term
| Membranoproliferative Glomerulonephritis (clinical course) |
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Definition
remissions are rare; disease is slowly progressive
50% develop chronic renal failure in 10 yrs
crescents -> rapid deteriorating renal fxn
tx w/ corticosteriods/ immunosuppressents not effective
high incidence of recurrence in transplants - 90% in type II |
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Term
| Cryoglobulinemic Glomerulonephritis (definiction & classification) |
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Definition
immunoglobins that precipitatin in the cold (4C) and dissolve when heated (37C)
Type I: single monoclonal immunoglobulin (associated w/ myeloma and lymphomas)
Type II - polyclonal IgG Monoclonal IgMK complexes
Type III - Polyglonal IgG polyclonal IgM complexes
II and III are "mixed" and are most common in connective tissue diseases (lupus, rheumatoid arthritis) and Hep C |
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Term
| Cryoglobulinemic Glomerulonephritis (clinical) |
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Definition
systemic small vessel vasculitis involving arterioles, capillaries, and venules
cryoglobulins precipitate in vessels -> thrombi in all organs and systemic vasculitis
skin purpura, arthralgias, underlying disease (lupus or hep C) and low serum complement; skin biopsy of purpura is diagnostic for leukocytoclastic vasculitis
25% pts w/ cryogobulinemia develop renal disease
cryoglobulinemic GN is most common in cases w/ type II cryoglobulins - proteinuria, hematuria, nephritic or nephrotic syndrome or rapidly progressive course |
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Term
| Cryoglobulinemic Glomerulonephritis (pathology) |
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Definition
LM: membranoproliferative type I pattern of glomerular injury due to subendothelial and mesangial cryoglobulin deposition; cryoglobulin thrombi often in capillary lumens
Immuno:
Type I - monoclonal immunoglobulin deposition (IgGK in myeloma) as granular deposits in mesangium and along GBM and thrombi
Type II - associated w/ Hep C - IgG, IgM, C3, C1q, kappa, lambda in same locations as type I
EM: identical in all types of CGN, diagnostic - subendothelial and mesangial deposits that show microtubular structures, "thumbprint" |
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Term
| Cryoglobulinemic Glomerulonephritis (clinical course) |
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Definition
| indolent w/ remission/recurrences, only 10% -> ESRD; tx w/ corticosteroids and cytoxan; plasmapheresis for actue flares |
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Term
| Immune complex glomerulopathies associated w/ recurrent hematuria |
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Definition
1) IgA nephropathy (Berger's Disease)
2) Henoch Schonlein Purpura |
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Term
| IgA Nephropathy (clinical) |
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Definition
most common type of glomerulonephritis worldwide
most common in older children and young adults
recurrent self-liviting episodes of gross or microscopic hematuria, often following RTIs
mild proteinuria and normal renal function in most cases, may have nephritic syndrome
minority have nephrotic syndrome or crescentic RPGN |
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Term
| Primary IgA Nephropathy (pathogenesis) |
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Definition
idiopathic: familial - abnormal regulation of IgA production OR acquired mucosal immune dysfunction
mucosal exposure to antigen -> increase synthesis of abnormal polymeric IgA1 -> deposits in mesangium or forms immune complexes -> activate alternative complement pathway (C3) -> glomerular injury |
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Term
| Secondary IgA Nephropathy (pathogenesis) |
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Definition
| associated w/ chronic inflammatory lesions of IgA containing mucosal surfaces (celiac, chronic liver diseases) -> impaired ability to clear immune complexes from blood |
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Term
| IgA Nephropathy (pathology) |
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Definition
LM: spectrum - normal glomeruli, mesangioproliferative, focal or diffuse, or crescentric (diffuse) proliferative IgA nephropathy
Immuno: diagnosis depends on IgA as dominant immunoglobulin; all glomeruli show strong staining w/ IgA and C3 as granular deposits in mesangium and occasionally in the subendothelial region, C1q is negative
EM: electron dense deposits predominantly in mesangium, occasionally in subendothelium |
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Term
| IgA Nephropathy (clinical course) |
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Definition
most maintain normal renal fxn for decades
slow progression to chronic renal failure in 15-40% over 20 yrs
steriods may reduce proteinuria; if have crescents need immunosuppression, nutritional (fish oil) can help
disease recurs in 20-60% transplants |
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Term
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Definition
most comon form of childhood systemic small vessel vasculitis, 3-8 yo
1/3 pts have history of atopy, follows URI, rapidly progressive
presents w/ purpuric skin rash, abdominal pain, melena, vomiting, arthralgia
renal involvement in 10-25% = hematuria, proteinuria
skin bipsy diagnostic for leukocytoclastic vasculitis and IgA in vessels
renal biopsy = IgA nephropathy
prognosis in children is self limited and good
less favorable prognosis w/ adults w/ crescents
tx supportive (don't use corticosteroids or immunosuppression) |
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Term
| Hereditary syndromes of isolated hematuria |
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Definition
Alport's syndrome
Thin Basement Membrane Disease (TBMD) aka Benign Familial Hematuria |
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Term
| Alport's Syndrome (clinical) |
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Definition
x-linked: sx @ 5-20 yo, hematuria, proteinuria w/ progressive renal disease, nerve deafness and eye disorders; progress to end stage @ 20-50 yo
females are carriers, may have hematuria |
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Term
| Alport's Syndrome (pathogenesis) |
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Definition
X-linked: mutation in alpha 5 chain of collagen type IV -> altered alpha 5 and decrease synthesis of alpha 3 & 4 -> interferes w/ assembly of collagen type IV -> altered structure and fxn of GBM
AR: mutation in alpha 3 or 4 of collagen type IV
alpha 3 chain includes anti-GBM (Goodpasture) antigen |
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Term
| Alport's Syndrome (pathology) |
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Definition
LM: spectrum of lesions w/ most cases progressing to focal segmental and global glomerulosclerosis
Immuno: negative
EM: GBM is irregularly thickened and thinned and shows splitting -> "basket-woven"; no immune complex |
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Term
| Thin Basement Membrane Disease, aka Benign Familial Hematuria (clinical) |
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Definition
familial or sporadic
presents w/ asymptomatic microscopic hematuria +/- mild proteinuria
renal fxn usually normal; excellent prognosis |
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Term
| Thin Basement Membrane Disease, aka Benign Familial Hematuria (pathogenesis) |
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Definition
AD: heterozygous for mutations in genes encoding alpha 3 or 4 chains of collagen type IV
Alports and TBMD = continuum |
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Term
| Thin Basement Membrane Disease, aka Benign Familial Hematuria (pathology) |
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Definition
LM: normal glomeruli
Immuno: negative
EM: diffuse thinning of GBM, no immune complex |
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Term
| Rapidly Progressive (Crescentric) Glomerulonephritis (clinical) |
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Definition
| clinical syndrome associated w/ severe glomerular injury and rapid decline - not a specific form of glomerulonephritis; diagnostic = crescents in most glomeruli |
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Term
| Rapidly Progressive (crescentric) Glomerulonephritis (clinical) |
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Definition
| rapid and progressive loss of renal fxn over days-wks; severe oliguria and signs of nephritic syndrome; if untreated -> death in wks-months |
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Term
| Rapidly Progressive (crescentric) Glomerulonephritis (3 types) |
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Definition
I. Anti-GBM Antibody: idiopathic, Goodpasture
II. Immune Complex: Idiopathic, Postinfectious Glomerulonephritis, Diffuse Lupus Glomerulonephritis Class V, Diffuse IgA Nephropaty/Henoch Schonlein; Membranoproliferative Glomerulonephritis
III. Pauci-Immune (most common): Idiopathic, Microscopic Polyangitis, Wegener's Granulomatosis, Churg-Strauss |
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Term
| Type I RPGN = Anti-GBM Disease (classification and clinical) |
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Definition
Idiopathic = kidney only OR Goodpasture = kidney + lung
Goodpasture's - young adult male w/ renal sx, hemoptysis, pulmonary infiltrates and hemorrhage |
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Term
| Type I RPGN = Anti-GBM Disease (pathogenesis) |
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Definition
autoimmune dysfunction -> increase production of circulating IgG autoantibody against GBM
Anti-GBM antibody binds to noncollagenous domain of alpha 3 chain of collagen type IV along entier GBM (= linear staining) -> inflammatory reaction -> crescentric glomerulonephritis
In Goodpasture's, pulmonary hemorrhage occurs as a result of cross-reactivity of anti-GBM antibody w/ alveolar capillary BM |
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Term
| Crescent formation pathology |
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Definition
| necrosis of glomerular segments -> breaks in GBM (seen on silver stain and EM) -> fibrinogen, leukocytes, plasma proteins and inflammatory mediators escape into Bowman's space -> stimulate proliferation of parietal epithelial cells to form crescent (extracapillary proliferation) |
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Term
| Type I RPGN = Anti-GBM Disease (pathology) |
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Definition
LM: early - focal segmental necrosis of glomeruli; later - global glomerular necrosis & extensive crescent formation; non-necrotic segments are normal w/o endocapillary proliferation
Immuno: strong linear staining w/ IgG and C3 along GBM
EM: breaks in GBM, inflammatory cells and fibrin in areas of necrosis, NO immune complexes |
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Term
| Type I RPGN = Anti-GBM Disease (clinical course) |
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Definition
circulating anti-GBM abs used to follow disease
tx w/ immunosuppression and plasmapheresis - prevent crescent formation, preserve renal fxn, reverse pulmonary hemorrhage
in advanced disease, necrotic glomeruli and crescents may undergo sclerosis and progress to chronic renal failure |
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Term
| Type II RPGN = Immune Complex (classification and clinical) |
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Definition
idiopathic or secondary
most frequent in young pts w/ postinfectious GN, lupus GN type IV, diffuse IgA nephropathy, Henoch-Schonlein purpura and MPGN
Renal sx similar to type I except proteinuria is mild to nephrotic
prognosis varies |
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Term
| Type II RPGN = Immune Complex (pathology) |
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Definition
LM: crescents, HYPERCELLULAR, expanded matrix
Immuno: granular staining in mesangium and along GBM (IgA and C3 for IgA nephropathy; full house for lupus)
EM: immune complex deposits in mesangium and along BM |
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Term
| Type III RPGN = Pauci-Immune (classification and clinical) |
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Definition
NO antibodies or immune complexes
idiopathic OR systemic vasculitis (microscopic polyangitis, wegener granulomatosis, or churg-strauss)
90% have circulating antineutrophil cytoplasmic autoantibody (ANCA)
P-ANCA (perinuclear) - microscopic polyangitis
C-ANCA (cytoplasmic) - Wegener's |
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Term
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Definition
Myeloperoxidase (MPO) - P-ANCA -> microscopic polyangitis
Proteinase 3 (PR3) - C-ANCA -> Wegener's |
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Term
| Type III RPGN = Pauci-Immune (pathogenesis) |
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Definition
| cytokines activate neutrophils and monocytes -> ANCA antigens migrate to cell surface and are released from cell -> antigens, neutrophils, monocytes bind to endothelial cells -> ANCA antibody binds to MPO or PR3 on endothelial cells and leukocytes -> complement activation -> endothelial damage -> neutrophils/monocytes release toxic O2 metabolites and injure endothelial cells |
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Term
| Microscopic Polyangitis/Polyarteritis |
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Definition
necrotizing vasculitis
P-ANCA + in 70% pts
crescentic GN same in idiopathic and systemic
Idiopathic - present w/ nephritic syndrome
Systemic: crescentic GN, nephritic syndrome, skin purpura, hemoptysis, arthralgias, abdominal pain
skin biopsy is diagnostic - necrotizing (leukocytoclastic) vasculitis
pulmonary capillaries accounts for hemoptysis |
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Term
| Wegener Granulomatosis (triad) |
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Definition
1) necrotizing granulomas of lung, upper respiratory tract, or both
2) necrotizing or granulomatous vasculitis affecting small to medium size vessels in lung and other sites
3) focal necrotizing or crescentic GN
C-ANCA + in 95% pts
Usually male in 5th decade
present w/ nephritic syndrome, pneumonitis w/ bilateral nodular and cavitary infiltrates and chronic or recurrent sinusitis |
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Term
| Type III RPGN = Pauci-Immune (pathology) |
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Definition
LM: early - focal segmental necrosis of glomeruli; later - global necrosis of glomeruli and extensive crescents; non-necrotic segments and glomeruli are normal w/o endocapillary proliferation; small vessels show segmental necrotizing vasculitis w/ fibroid necrosis of muscle wall and inflammation +/- thrombosis
Immuno: negative
EM: breaks in GBM, inflammatory cells, firin, NO immune complexes |
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Term
| Type III RPGN = Pauci Immune (clinical course) |
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Definition
ANCA titers correlate w/ disease activity - use to monitor relapse/remission
if detected early, tx w/ corticosteriods and other immunosuppressives may lead to remission
many pts progress to chronic renal failure/ESRD |
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