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92 Cards in this Set
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So let's start with the broadest classifications of Glomerular Diseases?
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Those w/ Nephrotic Presentation
W/ Nephritic Presentation Systemic Diseases affecting kidney Chronic GN |
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Who are the guys presenting w/ Nephrotic Syndrome?
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Minimal Change
Focal Segmental Glomerulosclerosis Membranous Glomerulopathy Membranoproliferative GN |
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Kickers for Minimal Change?
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KIDS! (2-6 yo's)
minimal change on light microscopy Uniform and Diffuse foot process effacement on EM No deposits, no immunofluorescence |
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What is the most common cause of nephrotic syndrome in adults in the U.S.?
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FSGS
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Common Association for FSGS?
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Inherited forms
HIV heroin addiction Sickle Cell Big Fatties or it can be Secondary... |
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What's screwed up in inherited FSGS?
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nephrin
podocin alpha-actinin 4 |
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What's up when FSGS is a secondary process?
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Possibly Focal GN
Possibly adaptive response to renal tissue ablation in advanced disorders (reflux nephropathy, HTN nephropathy, or unilateral renal agenesis) |
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What about FSGS and Congenital Nephrotic Syndromes?
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CNS of Finnish Type = NPHS1 gene on 19
Steroid-Resistant Nephrotic Syndrome of Childhood Onset = NPHS2 gene on 1 |
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Morphology of FSGS?
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Focal and Segmental Sclerosis
Lipid Droplets and Foam Cells |
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Which type of FSGS is the worst?
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HIV variant
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FSGS Immunofluorescence?
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Focal Fibrin Deposits in areas of sclerosis
Focal IgM and C3 |
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FSGS on EM?
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Loss of foot processes
Epithelial Denudation Sclerosis Collapse of GBM |
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What can Membranous Glomerulopathy be secondary to?
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Drugs
Malignancies Lupus Infections (hep, syph, malaria, etc) |
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Morphology for Membranous Glomerulopathy?
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Uniform, Diffuse thickening of Glomerular Capillaries
No Prolif Irregular "spikes" on GBM |
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What do you have to do to see the GBM spikes in Membranous Glomerulopathy?
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Silver Stains
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IF and Membranous Glomerulopathy?
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Diffuse, finely granular deposits (lumpy bumpy) of:
C3 IgG +/- IgM and IgA on cap walls |
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EM and Membranous Glomerulopathy
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Subepithelial, electron-dense deposits
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Clinical Presentation of Membranoproliferative GN?
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Nephritic and/or Nephrotic
i.e. proteinuria +/- hematuria |
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Difference between nephritic and nephrotic?
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Nephritic = blood and protein (< 3)
Nephrotic = just lots of protein (> 3) |
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MPGN Type 1 vs 2?
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1: assoiated w/ cryoglobulinemia and hep C
2: Circulating Antibody C3 Nephrotic Factor which activates alt. C' cascade |
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Morphology for MPGN?
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Diffusely Enlarged, Hypercellular Glomeruli
Prolif of Mesangial Cells and Inc Matrix--> lobular appearance Thickened GBM --> Tram-Track Infiltration by leukocytes...occasionally crescent |
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MPGN Type 1 and IF?
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Granular C3
IgG and early C' components (C1q and C4) |
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EM and MPGN Type 1?
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Subendothelial electron-dense deposits
Occasionally Mesangial and Subepithelial deposits too |
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MPGN Type II and IF?
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Irregular granular or linear C3 in GBM and usually in mesangium too (mesangial rings)
IgG usually absent as are C1q and C4 |
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MPGN Type II and EM?
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Sausage Shaped/Ribbon-Like deposits in lamina densa of GBM
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OK...finally...on to Nephritic Syndromes...who presents this way?
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Acute Diffuse Proliferative GN
IgA Nephropathy Thin BM and Alport Syndrome |
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Causes of Acute Diffuse Proliferative GN
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Immune complexes to exogenous or endogenous Ag
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Prototype of Acute Diffuse Proliferative GN?
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Postinfectious GN after Group A Beta-hemolytic Streptococci Infection
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Presentation of Acute Diffuse Proliferative GN?
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Nephritic Syndrome: hematuria, oliguria, mild to moderate HTN
1-4 weeks after strep infection of pharynx or skin Elevated titers of Ab's against strep Ag's Low Serum C' levels b/c of activation and consumption of cascade |
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Morphology of Acute Diffuse Proliferative GN?
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Diffusely, Enlarged Hypercellular Glomeruli
Infiltrated by leukocytes Prolif of endothelial, mesangial cells Occasional Crescents Obliterated Cap Lumens Edema and Infl of Interstitium Red Cell Casts geez |
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Acute Diffuse Proliferative GN and IF?
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Granular Deposits
IgG, IgM, C3 Mesangium and along BM |
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Acute Diffuse Proliferative GN and EM?
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Sub-epithelial deposits w/ HUMPS
Possibly Sub-endothelial deposits, intra-membranous, and mesangial deposits |
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Most common form of GN in the WORLD?
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IgA Nephropathy
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IgA Nephropathy: primary, secondary, ????
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Can just be Primary
or Component of Henoch-Schonlein Purpura Associated w/ liver disease (alcoholic), celiac's, IBD, Yersinia enterocolitis, psoriasis, HIV, etc |
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IgA Nephropathy Morphology
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DIFFERENT FORMS:
Mesangioproliferative Proliferative GN (focal/diffuse) Crescent Formation Sclerosis (focal/diffuse) |
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IgA Nephropathy and IF?
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Mesangial IgA deposits
C3, IgG, or IgM may be present in lesser amounts |
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IgA Nephropathy and EM?
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Deposits in the mesangium
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Types of Hereditary Nephritis?
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Alport's
Thin BM Disease |
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What is the most common cause of Benign Familial Hematuria?
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Thin BM Disease
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How does Alport's present?
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Nephritis
Nerve Deafness Various Eye Disorders (lens dislocation, post. cataracts, corneal dystrophy) |
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How is Alport's inherited?
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X-linked is most common
rarely Auto Rec or Auto Dom |
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Pathogenesis of Alport's?
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Defective GBM synthesis via abnormal Collagen Type IV synthesis
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Difference between pathogenesis of x-linked alport's and auto rec/dom alport's?
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X-linked: defect in alpha-5 chain of Type IV collagen
Auto Rec/Dom: defect in alpha 3 or 4 chain of Type IV collagen |
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Morphology of Alport's?
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Interstitial Foam Cells
FSGS, Global Glomerulosclerosis |
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Alports and EM?
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Diffuse GBM thinning
Splitting and lamination fo lamina densa (basket-weave) |
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Alports and IF?
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Missing alpha3, alpha4, and/or alpha5 collagen in glomerular and tubular BM's
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How does Thin BM Disease present?
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Usually asymptomatic
No hearing of visual abnormalities |
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Morphology of Thin BM Disease?
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Diffuse Thinning of GBM
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Pathogenesis of Thin BM Disease?
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Related to genes encoding alpha3 or alpha4 chains of Type IV Collagen
Most patients are heterozygous for the defective gene. Homozygotes can progress to RF |
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Moving on...Who are the systemic diseases who commonly cause glomerular diseases?
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Rapidly Progressive GN (crescentic)
Lupus Diabetes Amyloidosis |
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Classic picture of Rapidly Progressive GN?
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Crescents on Histo
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Progression of Rapidly Progressive GN?
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Can lead to Severe RF in weeks to months
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How are Crescents formed?
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proliferation of parietal cells and migration of inflammatory cells into urinary space
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Classification of Rapidly Progressive GN?
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Type 1: Anti-GBM Antibody
Type 2: Immune Complex Type 3: Pauci-Immune |
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Who are the Type 1 Rapidly Progressive GN?
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Idiopathic
Goodpasture's |
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Who are the Type 2 Rapidly Progressive GN?
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Idiopathic
Postinfection SLE Henoch-Schonlein Purpura Others |
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Who are the Type 3 Rapidly Progressive GN?
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Idiopathic
ANCA associated Wegener's Microscopic Polyarteritis Nodosa/Microscopic polyangitis |
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In Type 1 Rapidly Progressive GN, who are the antibodies directed against?
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Noncollagenous Domain (NC1) of the alpha-3 chain of Type IV Collagen
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What else can the Type 1 Rapidly Progressive GN antibodies affect?
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Pulmonary Alveolar BM's--> Goodpastures
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Type 1 Rapidly Progressive GN and IF?
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Linear Deposits (along BM)
IgG and C3 |
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Type 1 Rapidly Progressive GN and EM?
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No deposits
GBM Disruptions Fibrin |
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Morphology of Type 2 Rapidly Progressive GN?
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Crescentic GN
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IF for Type 2 Rapidly Progressive GN?
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Granular Deposits according to underlying disorder
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EM for Type 2 Rapidly Progressive GN?
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deposits according to underlying disorder
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Type 3 Rapidly Progressive GN antibodies?
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cANCA in wegener's
pANCA in microscopic polyangiits |
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Type 3 Rapidly Progressive GN morphology?
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crescentic GN
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Type 3 Rapidly Progressive GN and IF?
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little or no deposition of immune complexes (pauci-immune)
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Type 3 Rapidly Progressive GN and EM?
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None or very few deposits
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What percent of lupus pts have renal involvment?
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50-80%
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Principle mechanism for renal involvement in SLE?
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Immune Complex deposition in renal structures
Also possible thrombotic process if pt has antiphospholipid antibodies |
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Five Patterns of Lupus Nephritis?
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Class 1: minimal or no detectable abnormalities
2: mesangial lupus GN 3: Focal Proliferative GN 4: Diffuse Proliferative GN 5: Membranous GN |
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Types of lesions in Lupus Nephritis?
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Active
Chronic |
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Types of Active Lesions in Lupus Nephritis?
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GLOMERULI:
hypercellularity fibrinoid necrosis crescents wire loops leukocyte infiltration more TUBULES/INTERSTITIUM mononuclear infiltration |
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Types of Chronic Lesions in Lupus Nephritis?
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Glomerulosclerosis
Fibrous Crescents Interstitial Fibrosis Tubular Atrophy |
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IF and Lupus Nephritis?
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FULL HOUSE
IgG, IgA, IgM C3, C1q*** Can be found in any location depending on pattern |
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EM and Lupus Nephritis?
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Deposits in mesangium, subepithelial, or subendothelial
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Usual Presentation of Diabetic Nephropathy?
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Non-Nephrotic Proteinuria
Nephrotic Syndrome CRF |
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difference between renal involvement in Type 1 and Type 2 Diabetes?
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changes are the same
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Three Main Morphological Changes in Diabetic Nephropathy?
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Capillary BM Thickening
Diffuse Mesangial Sclerosis Nodular Glomerulosclerosis (**kimmelsteil-Wilson nodules**) |
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Diabetic Nephropathy and IF?
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Linear IgG Deposits (not anti-GBM?)
Nodules may also show IgG |
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EM and Diabetic Nephropathy?
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BM Thickening
Diffuse Mesangial Expansion NO IMMUNE COMPLEX DEPOSITS |
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Most common renal amyloid?
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Light-Chain (AL)
or AA type |
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How do patients present with renal amyloidosis?
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Nephrotic Syndrome
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Kidney size in Amyloidosis?
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Normal or Enlarged b/c of deposits
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Morphology of Renal Amyloidosis?
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Hyaline substance deposits mainly in cap walls of glomeruli and blood vessels, mesangium, and interstitium
Later in progression may form nodules or obliterate glomerulus |
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Special stain for amyloid?
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Congo Red w/ apple green birefringence
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IF for Renal Amyloidosis?
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Deposits of Light Chain
Lambda Light Chain > Kappa |
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EM and Renal Amyloidosis?
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Randomly arranged fibrils, 10-12nm in diameter
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Who causes Chronic GN?
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All glomerulopathies can
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Morphology of Chronic GN?
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Small Kidneys w/ thin cortex
Diffuse, Global Glomerulosclerosis Arterial and arteriolar sclerosis Marked Tubular Atrophy Interstitial Fibrosis Lymphocytic Interstitial Infiltraiton |
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Chronic GN and IF?
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Findings according to underlying disease
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Chronic GN and EM?
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findings according to underlying disease
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