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70 Cards in this Set
- Front
- Back
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What is MPGN?
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Membranoproliferative glomerulonephritis
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What are the 3 histologic characteristics of MPGN?
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-Alterations in the BM
-Proliferation of glomerular cells -WBC infiltration |
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Where is the proliferation predominant in MPGN?
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In the mesangium
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What type of clinical presentation is seen with MPGN?
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-May have only hematuria or proteinuria in non-nephrotic ranges
-May be combined nephritic and nephrotic picture |
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What % of nephrotic syndrome in children and young adults is due to MPGN?
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10-20%
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What are the 2 divisions of Primary MPGN (idiopathic), based on ultrastructure, IF, and pathologic findings?
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-Type I
-Type II |
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What is Type II MPGN called?
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Dense deposit disease
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What is the morphologic hallmark that particularly stands out by LM in MPGN?
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Lobular appearing glomeruli due to proliferating mesangial cells and increased mesangial matrix.
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What happens to the GBM in MPGN?
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It becomes focally THICKENED, primarily in peripheral capillary loops.
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What morphologic feature is often seen in the glomerular capillary wall in MPGN?
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A double-contour, tram-track appearance
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Why does the glomerular capillary wall take on a tram-track appearance in MPGN?
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Due to new BM synthesis and a 'duplication' of the Bm.
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What happens to the BM itself in MPGN?
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It becomes thicker and takes on a Split appearance due to cellular elements deposited within it
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How do MPGN types I and II differ?
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-Ultrastructurally
-Immunologically |
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What is the main ultrastructure feature seen on type I MPGN EM?
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Subendothelial deposits
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What is the main ultrastructure feature seen on type II MPGN EM?
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Intramembranous deposits (dense deposit disease) in the GBM
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What ultrastructural finding can be seen in both types of MPGN?
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Mesangial cell interposition in the GBM space so it looks like a split BM on light microscopy.
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Which type of MPGN are the majority of cases?
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Type I
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What IF findings are seen in Type I MPGN?
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-Granular C3 deposits
-IgG -C1q/C4 |
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What does the deposition of dense material in type II MPGN result in doing to the GBM?
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Transforms it into an irregular, ribbon-like structure that is extremely electron dense.
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What is the dense material in type II MPGN/dense deposit disease composed of?
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We don't know
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What IF findings are usually present/absent in type II MPGN?
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Present: C3 along the BM in granular/linear patterns but not in dense deposits; mesangial rings of C3 in mesangium also
Absent: IgG, C1q, and C4 |
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What is the most likely pathogenic process that occurs in MPGN type I?
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Immune complex deposition and activation of both C' pathways
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What do type II MPGN cases appear to have involved in their pathogenesis?
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Abnormal activated Alternative complement pathways
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Why do we think type II MPGN is associate with abnormal activity of the Alternative C' pathway?
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Because serum C3 levels are depleted, but not C1 or C4
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What antibody is present in 70% of patients with Type II MPGN?
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C3 nephritic factor
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What is C3NeF?
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An auto-Ab to the alternative pathway C3 convertase C3bBb
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How does C3NeF lead to MPGN?
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It stabilizes the convertase so that there is persistent C3 degradation
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What is the typical clinical presentation of MPGN?
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Nephrotic syndrome in older children or young adults, with a nephritic component too.
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What is the nephritic component typically seen in MPGN cases?
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Hematuria and mild proteinuria
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What is the typical nature of disease progression in primary MPGN cases?
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Slowly progressive
Unremitting |
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What % of MPGN cases develop into chronic renal failure within 10 yrs?
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50%
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What is interesting about the recurrence that often occurs in post-transplant patients with type II MPGN?
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The dense deposits recur in 90%, but renal failure is much less common.
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What form of MPGN is more common in adults?
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Secondary MPGN, type I
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So what causes secondary MPGN and where will deposits be seen?
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Immune complex deposits, subepithelial
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What is probably the most common type of glomerulonephritis worldwide?
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IgA Nephropathy
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What is the hallmark feature of IgA Nephropathy?
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IgA deposits in mesangial regions
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How are the IgA deposits detected?
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By IF microscopy
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What is the most common clinical presentation of IgA Nephropathy?
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-Gross or microscopic hematuria
-Mild proteinuria |
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What other systemic disorder shows IgA deposits?
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Henoch-Schonlein purpura in children
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In what 2 conditions does secondary IgA nephropathy often occur?
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Liver disease
Intestinal disease |
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Where is IgA normally found, and what is its norm serum conc.?
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-Main mucosal immunoglobulin
-Normal conc in serum is low, and predominantly monomeric |
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What happens to serum IgA levels in patients with IgA nephropathy?
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-Polymeric forms become elevated
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What does the prominent mesangial deposition of IgA suggest?
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That glomerular damage is caused by entrapment of IgA Immune complexes in the mesangium
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What immune components can be seen on FM in IgA nephropathy?
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C3 only - no C1q/C4
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What does the presence of only C3 in mesangial deposits in IgA nephropathy suggest?
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That only the alternative complement pathway is activated
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What is thought to be the cause of increased mucosal IgA synthesis in IgA nephropathy?
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Genetic or acquired abnormality of immune regulation, eg a response to exposure to an Ag.
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What patients have increased frequency of IgA Nephropathy?
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-Gluten enteropathy patients
-Liver disease patients |
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What are the glomerular lesions in IgA nephropathy like?
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Considerably variable
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What is the characteristic immunofluorescent picture of IgA nephropathy?
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Mesangial deposition of IgA
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What age of patients are more commonly affected by IgA nephropathy?
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Older children/young adults
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What is the typical clinical presentation of IgA Nephropathy?
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Gross hematuria following a respiratory, GI, or UTI
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What happens after the acute onset of hematuria?
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It lasts for several days, subsides, then returns every few months.
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So the general course of IgA nephropathy is?
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Indolent and variable
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What are the 2 most important hereditary syndromes of isolated hematuria?
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-Alport syndrome
-Thin basement membrane disease |
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Which hereditary syndrome is the more common cause of benign familial hematuria?
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Thin BM disease
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What are the 3 hallmark components of Alport syndrome?
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-Nephritis progressing to CRF
-Nerve deafness -Eye disorders |
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What 3 eye disorders can be manifested in Alport syndrome?
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-Lens dislocation
-Posterior cataracts -Corneal dystrophy |
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What is the genetic inheritance pattern of most Alport syndrome cases?
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X-linked
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What will be seen on EM in fully developed alport syndrome cases?
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Alternating thickening/thinning of the GBM
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What is the pronounced splitting and lamination of the lamina dense in Alport syndrome called?
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Basket weave appearance
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What is the reason for the renal lesions in alport syndrome?
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Defective GBM synthesis due to production of abnormal type IV collagen
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What FM features of Alport syndrome are helpful in diagnosis?
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Absent a3, a4, and a5 collagen staining
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What is the most common presenting sign of Alport syndrome?
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Gross or microscopic hematuria
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What is the main manifestation of Thin BM disease?
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Asymptomatic hematuria that is familial
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What is the prognosis for most cases of thin BM disease?
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Excellent
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How is Thin BM disease differentiated from Alport and IgA nephropathy?
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-No hearing loss, cataracts, or family history of renal failure
-Skin biopsy specimens show presence of a5 type IV collagen |
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What is the abnormality that causes thinning of the GBM in Thin BM disease?
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Absence of a3 or a4 type IV collagen
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What is the pool of end-stage glomerular disease that is fed by a number of streams of specific types of GN called?
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Chronic glomerulonephritis
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What is a rare cause of chronic GN? What is more common?
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Rare = post strep GN
More common = RPGN |
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Do all cases of chronic GN arise from a specific glomerulonephritis?
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No, some arise mysteriously
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