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75 Cards in this Set
- Front
- Back
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ways in which immune-mediated glomerular injury occurs
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antibodies against intrinsic glomerular antigens
extrinsic antigens planted in the basement membrane before antibody binding circulating antigen-antibody complexes filtered in glomerulus and activate complement ANCA related injury |
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what do ANCAs do
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bind to neutrophils directly and activate them to release proteolytic enzymes and proinflammatory cytokines most commonly targeting blood vessels
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what kind of antigen-antibody ratio leads to immune complexes disease causing glomerulonephritis
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equivalent or mild antigen excess
NOT modest excess is antigen or large excess of either antigen or antibody |
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normal charge of the BM
caused by what |
negative due to heparan sulfate
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what happens to large complexes
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picked up by mesangium or macrophages
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mechanisms of glomerular injury
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immune-mediated
loss of glomerular anion - leakage of anionic molecules (albumin) hyperfiltration - sclerosis ischemia |
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why does glomerular disease become progressive
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adaptive hemodynamics
increased intraglomerular capillary pressure chronic excessive protein load |
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what does chronic excessive protein load do
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stimulates inflammatory injury of the tubules along with progressive interstitial fibrosis
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two strategies for reducing progressive of renal disease
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ACE inhibitors - reduce intraglomerular pressure
restrict dietary protein |
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where do the parietal and visceral epithelial cells of Bowman's capsule line respectively
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parietal - line Bowman's capsule
visceral - line capillaries (contain foot processes) |
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stain that detects fibrosis and large immune deposits
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trichrome stain
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stain that delineates mesagium
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PAS stain
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stain that detail basement membranes
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Jones methenamine silver stain
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identifies, characterizes, and localizes immune deposits
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immunofluorescence microscopy
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immune-complex material between GBM and podocyte processes
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subepithelial
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antibodies that diffusely damage the GBM but do not form electron-dense deposits
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Anti-GBM antibodies
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immune-complex material between GBM and endothelial cytoplasm
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subendothelial
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what type of pattern is seen in immunoflurescence microscopy in anti-GBM antibody disease as opposed to normal immune complex deposition
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Anti-GBM disease - linear pattern
normally granular pattern of deposition |
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what parts of complement are seen if classical pathway is activated
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C3 and C1q
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what parts of complement are seen if alternate pathway of complement is activated
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C3 only, NOT C1q
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marked proteinuria
hypoalbuminemia edema hyperlipidemia No HTN present |
nephrotic syndrome
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associated with refractile oval fat bodies in the urine
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lipiduria in nephrotic syndrome
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most common cuase of nephrotic syndrome in children
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minimal change disease
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an inflammatory disease that leads to cellular proliferation of the glomerulus and impairs GFR resulting in secondary HTN, hematuria, and proteinuria
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Nephritic syndrome
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associated with crescent formation in bowmans' capsule and rapidly progressive renal failure
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rapidly progressive glomerulonephritis
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associated with secondary glomerular disease
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lupus
diabetes amyloidosis |
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most common abnormality of the urinary tract
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duplication or aberrent site of implantation of ureters
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glomerular disease related to immune-complex deposition or direct immunologic attach with secondary inflammation
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proliferative glomerular disease
*nephritic syndrome |
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Characteristics of post-infectious glomerulonephritis
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Ab-Ag complexes deposited in the subepithelial space where they activate both classical and alternative pathway resulting in chemotaxis and activation of neutrophils
Diffuse proliferation and exudative subepithelial humps seen on EM Granular IgG and C3 along GBM seen on IF |
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clinical presentation of post-infectious glomerulonephritis
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acute nephritis - hematuria with RBC casts, azotemia, mild HTN, and mild proteinuria
Elevated ASO titer Low complement levels |
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formation of autoantibodies against alpha-3 chain of type 4 collagen
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Anti-GBM disease
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Goodpasture's disease
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Anti-GBM along with reaction with lung alveolar basement membranes as well
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characteristics of Anti-GBM disease
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autoantibodies against alpha-3 chain of type IV collagen
Circulating antibodies attack GBM and evoke complement and neutrophil mediated injury GBM injury with no deposits diffuse crescentic GN linear staining for IgG along the GBM |
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Clinical presentation of Anti-GBM
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RPGN in young adult male with a flu-like illness
hemoptysis can be seen before signs and symptoms of renal disease in Goodpasture's results in end-stage renal failure |
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characteristics of Wegener's granulomatosis
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ANCA associated glomerulophritis
pulmonary disease necrotic lesions in nasal sinuses |
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makes up 75% of RPGN in patients over 60 and is associated with systemic small vessel vasculitis
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ANCA-associated GN
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anti-PR3 (proteinase 3)
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c-ANCA
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anti-MPO (myeloperoxidase)
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p-ANCA
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characteristics of ANCA-associated GN
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focal glomerular necrosis with crescents
IF is negative no immune-complex deposits *remember that ANCAs activate neutrophil attack, not immune complex associated |
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Diseases associated with RPGN
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Anti-GBM disease
ANCA-associated GN post-infectious RPGN lupus nephritis |
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most common form of GN world-wide
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IgA nephropathy (Berger's disease)
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characteristics of IgA nephropathy
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Mesangial deposition of IgA and C3 (but not C1q)
focal segmental GN |
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Clinical presentation of IgA nephropathy
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In children typically presents with hematuria following a viral infection
In adults, tends to be chronic a idiopathic |
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Systemic form of IgA disease
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Henoch-Schonlein Purpura
More acute IgA nephopathy with purpuric skin lesions |
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Characteristics of both membranoproliferative diseases
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mesangial and endothelail proliferation
double contouring of GBM |
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differentiate type 1 and type 2 membranoproliferative GN
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type 1 - immune complex deposition in the subendothelial and mesangium with activation of both classic and alternate complement, prominent granular C3, IgG, and C1q in capillary walls and mesagium see on IF.
type 2 - membranous dense deposits, alternate pathway activation by C3 nephritic factor, only C3 seen on IF with no Ig or C1q present. |
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circulating IgG autoantibody that protects C3 degredation
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C3 nephritic factor
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five classes of SLE nephritis
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I - normal glomeruli with mild hematuria/proteinuria
II - mesangial lupus nephritis with slight hematuria/proteinuria and normal GFR III - focal proliferative GN with < 50% of glomeruli involved having subendothelial and mesangial deposits IV - diffuse proliferative GN with >50% glomeruli involved, hyalin thickening of capillary walls (wire looping), and patients having nephritic symptoms V - diffuse membranous glomerulonephopathy, diffuse GBM thickening and typically presents as nephrotic syndrome |
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morphologic features of all classes of lupus nephritis
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deposits typically not retricted to a single location (except class I and II)
staining of IgA, IgG, IgM, C3, and C1q are all present fingerprint deposits with lamellar substructure |
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characteristics of chronic glomerulonephritis
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can develop from chronic glomerular disease or non-glomerular disease (ischemia)
kidneys shrunken and granular sclerosis and masses of collagen renal insufficiency with anemia (EPO) and HTN (GFR) proteinuria typically decreases as disease progresses |
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glomerular disease with isolated hematuria or proteinuria
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non-proliferative glomerular disease
*nephrotic syndrome |
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differentiate selective and nonselective proteinuria
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selective - leakage of only small molecules (albumin)
nonselective - leakage of larger proteins as well |
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complications of nephrotic syndrome
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wasting - decreased protein
infection - decreased protein hypercoagulability - loss of AT III in urine (nonselective proteinuria) |
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primary glomerular disease causes of nephrotic syndrome
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minimal change disease - children
focal segmental glomerular sclerosis - most common in adults membranous glomerulopathy |
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systemic disease causes of nephrotic syndrome
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DM
amyloidosis SLE type V |
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Cause of nephrotic syndrome by loss of podocyte foot processes (lack of significant glomerular abnormalities by LM) and selective proteinuria
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Minimal change nephropathy
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Nephrotic syndrome caused by segmental consolidation of some but no all glomeruli, not an immune complex disease
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focal segmental glomerulosclerosis
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Clinical presentation of focal segmental glomerulosclerosis
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nephrotic syndrome
non-selective proteinuria - decreased AT III leads to increased risk of renal vein thrombosis poor response to corticostoid therapy |
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why does nonselective proteinuria leads to hypercoagulability and potential renal vein thrombosis
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lose AT III in the urine leading to a hypercoagulable state
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why could you confuse focal segmental glomerulsclerosis and minimal change disease
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because the normal appearance of uninvolved glomeruli in focal segmental GS may result in confusion with minimal change disease if the segmentally sclerotic glomeruli are missed on biopsy
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frequent cause of adult nephrotic syndrome characterized by numerous subepithelial immune-complex deposits with no evidence of inflammation or proliferation
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membranous glomerulopathy
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Causes of membranous glomerulopathy
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**Most common is idiopathic
SLE syphilis hep B and C Lung carcioma/melanoma penicillamine gold |
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characteristics of membranous glomerulopathy
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thickening of GBM with spike formation
granular positivity for IgG and C3 in subepithelial space |
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single most common cause for renal failure in U.S.
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diabetic glomerulosclerosis
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Pathogenesis of diabetic glomerulosclerosis
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microangiopathy of arterioles and sclerosis, both of which are caused by glycosylation due to hyperglycemia
sclerosis due to: increased synthesis of type IV collagen accumulation of other mesangial matrix and BM components |
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two different forms of diabetic glomerulsclerosis
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diffuse glomerular sclerosis - uniform increase in mesangial matrix and thickened capillary walls
nodular glomerular sclerosis (Kimmelstiel-Wilson nodules) - nodular expansion of mesangium with small amounts of fibrin, lipid, and other debris |
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clinical presentation of diabetic glomerulosclerosis
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occurs in about 50% of juvenile-onset diabetes
presents as proteinuria typically 10-20 years after onset of diabetes unlike to have diabetic nephropathy if no evidence of retinoapathy |
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differentiate primary and secondary amyloidosis
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primary - proliferation of plasma cells producing monoclonal antibodies
secondary - chronic elevation of immunoglobulins secondary to: myeloma, chronic infections (TB), chronic inflammatory process (RA) |
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amyloid staining
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congo-red stain with apple-green birefringence under polarized light
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two diseases associated with activation of alternate complement pathway
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IgA nephropathy
dense deposit disease |
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classic examples of exogenous antigens causing nephritis
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Group A Streptococcus
bacterial endocarditis hepatitis B |
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which cell proliferate giving the crescent formation in Bowman's space and ultimately scarring
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parietal epithelium
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causes of nephritic syndrome
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IgA nephropathy
membranoproliferative gromerulonephritis SLE nephritis class IV |
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disorder that can present as nephritic or nephrotic syndrome
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membranoproliferative glomerulonephritis
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associated with C3 nephritic factor
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dense deposit disease - type 2 membranoproliferative GN
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