Nephritic Syndrome Flashcards
What 2 types of Nephritic Syndrome Fall under the category of:
Visceral Epithelial Injury: Podocyte Disorder?
- Minimal Change Disease
* Focal Segmental Glomerulosclerosis
What 4 types of Nephritic Syndrome Fall under the category of:
Immune Complex Formation?
- Membranous Nephropathy (subepithelial) - really this is a nephrotic syndrome
- Post-infectious Glomerulonephritis (subepithelial)
- Membranoproliferative Glomerulonephritis (SubENDOthelial)
- IgA nephropathy (mesangial)
What 3 types of Nephritic Syndrome Fall under the category of:
Glomerular Basement Membrane Disease
- Anti-glomerular Basement Membrane Disease
- Alport’s Syndrome
- Thin Basement Membrane
What 2 types of Nephritic Syndrome Fall under the category of:
Vascular Injury Syndromes?
- ANCA-associated glomerulonephritis/pauci-immune glomerulonephritis
- Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenia Purpura (TTP)
What are some important Side Effects seen with most Nephritic Syndromes?
Hematuria
• microscopic or macroscopic
• Red Blood Cell Casts
HTN Oliguria Edema (moderate) Mild to moderate proteinuria Azotemia
Where are the immune deposits located in:
• Membranoproliferative GN
• IgA nephropathy
Membranoproliferative GN = SUBENDOTHELIAL
IgA Nephropathy = MESANGIAL
What are 4 diseases associated with SubENDOthelial and mesangial immune DEPOSITS?
• what particle/process is causing damage in these diseases?
- MEMBRANOPROLIFERATIVE GN
- IgA Nephropathy (mesangial)
- Lupus Nephritis
- Post-Infectious GN
*Diseases are associated with circulating immune complexes that deposit on the basis of size, charge, etc.
What are some diseases that cause actual ENDOTHELIAL CELL INJURY?
• how?
- Thombotic Microangiopathies
* Immune complexes/PARAproteins
What is the most common causes of Paraprotein entrapment that leads to Endothelial cell injury?
Multiple Myeloma
What causes endothelial damage nephritic syndrome?
INFLAMMATORY RESPONSE that results from…
CYTOKINES and Autacoids are released which UPREGULATE Adhesion Molecules on Endothelial and circulating immune cells
T or F: HEMATURIA is the clinical indication that nephritic syndrome is occuring.
True
What are the two forms of Membranoproliferative Glomerulonephritis?
• Prevalence
• Deposition location?
Type I: MOST COMMON
Type II: Dense Deposit Disease
Deposition Location: SubENDOthelial
Membranoproliferative Glomerulonephritis Type I
• light microscopic changes
• KEY thing to recognize visually
• Important Lab Value
Light Microscopic Changes:
• Hypercellularity of Glomerular Tuft
• Increased mononuclear cells within the expanded mesangium and in capillary lumens
KEY:
• Tram-Track Appearance
Lab Value:
• Reduced C3 levels
What is frequently the cause of Membranoproliferative Glomerulonephritis Type I in adults?
Hepatitis C
How do people of all ages typically present with MPGN (membranoproliferative glomerulonephritis) type I?
- Microscopic Hematuria
- Nephrotic range proteinuria and Nephrotic Syndrome is possible
- Acute Nephritic Syndrome
- Rapidy progressive glomerulonephritis (PRGN)
What is the typical prognosis of MPGN type I?
• treatment?
Px: USUALLY - slow progression to end stage renal disease; RARELY spontaneous remission may occur
Dense Deposit Disease (Membranoproliferative glomerulonephritis type II).
• KEY lab terms (pathophysiology)
• KEY TERM for histology
Key Lab Terms:
• LOW C3 is often present because 80% of ppl. ohave C3 NEPHRITIC FACTOR which binds and stabiliizes C3
Key Histo Terms:
• Dark SubENDOthelial ribbons on Electron Microscopy (aka electron dense deposits)
What causes Tram Track appearance?
• associated disease?
Tram Tracks:
• Splitting of the GBM is associated with Tram Track Appearace is due to MESANGIAL cells (which have macrophage-like function) PENETRATE the Basement Membrane in pursuit of Immune Complexes
What does the glomerulus look like in Membranoproliferative Glomerulonephritis and Dense Deposit Disease?
• Basement Membrane
• Cells
• Overall Appearance
Glomeruli = Large and Lobular
- All Cell Types have proliferated - Mesangial, Endothelial, and Leukocytes
- GBM has thickened
What differences exist between MPGN type I and II on immunofluorescence?
MPGN type I:
• Granular C3 positive Basement Membrane
Dense Deposit Disease:
• BRIGHT C3 DEPOSITS in MESANGIUM and some in the capillary wall
T or F: in some cases MPGN can be associated with MONOCLONAL GAMMOPATHIES
True
MPGN vs. DDD:
• Pathophysiology
MPGN:
Immune Complexes in GBM induced CLASSICAL COMPLEMENT PATHWAY*
Immune Complexes in GBM induce ALTERNATIVE COMPLEMENT PATHWAY
• this leads to damage endothelial cellls and basement membrane by leukocyte recruitment
What is the Most Common Primary GN worldwide?
• what are some secondary causes of this disease?
• IgA Nephropathy - Berger Disease
Secondary Causes: • Henoch - Schoenlein Purpura • Ankylosing Spondylitis • Dermatitis Herpetiformis • Celiac Disease • Inflammatory Bowel Disease • Cirrhosis • Psoriasis
What is the location of Immune Deposits in IgA nephropathy?
• aka what is the pattern of Injury
IgA containing Immune complexes are found mostly in the MESANGIUM
Pattern of Injury:
• Mesangioproliferative Pattern of Injury
What is Classically the trigger of IgA nephropathy?
IgA nephropathy:
• Often Triggered by Upper Respiratory Tract infection
IMPORTANT: sediment forms in a SYNPHARYNGITIC manner i.e. within 1 to 2 days of infection (not after infection)*
What is the problem with the IgA formed in IgA nephropathy (Berger’s disease)?
• Where do these immune complexes form?
• why do they form?
GALACTOSE DEFICIENT IgA1 circulating immune complexes deposit in the MESANGIUM***
WHY:
• underglycosylation of O-linked glycans that terminate with N-acetylgalactosamine instead of galactose
• OTHER IgG or IgA antibodies recognize this unglycosylated region and form IMMUNE COMPLEX
How does IgA nephropathy present?
SUPER VARIABLE:
- Asymptomatic
- Microscopic Hematuria
- Intermittent Gross Hematuria
- Synpharyngitic Hematuria
- Nephrotic (15%) or non-nephrotic proteinuria
- Acute Glomerulonephritis
- Rapidly Progressive Glomerulonephritis
T or F: patients must have elevated to serum IgA levels to have IgA nephropathy.
FALSE, only ~50% of patients with this have increased serum IgA levels
What are some Poor Prognostic Indicators of IgA nephropaty?
- Heavy Proteinuria
- Decreased GFR at onset of disease
- Older age at Onset
- Uncontrolled HTN
- Cresents and/or tubulointerstitial fibrosis/atrophy
T or F: immune deposits are found in the subendothelium in IgA glomerulonephropathy
FALSE, IgA nephropathy has Immune Deposits in the MESANGIUM
What two diseases involve the basement membrane?
- Anti-GBM disease
* Hereditary Nephritis
What causes anti-GBM disease?
• what is another name for this disease?
• Disease progression?
Anti-GBM
Cause:
• IgG Autoantibodies against a noncollagenous portion of the ALPHA-3 SUBUNIT of type IV collagen
Development:
• Disease is rapidly progressing!!! - days to weeks until these people develop renal failure
What is the appearance of anti-GBM antibodies in immunofluorescence?
• Appearance on H and E?
• correlation between concentration of anti-GBM in the membrane and disease activity.
Appearance:
• LINEAR pattern on Immunofluorescence - PATHOpneumonic for Goodpasture’s
• H and E = CRESCENT formation (focal or diffuse); Glomerulonephritis
Anti-GBM conc.:
• NO correlation between anti-GBM titers and disease activity
What other antibody besides Anti-alpha-3 collagen antibodies are present in Goodpastures?
MPO-ANCA
What besides renal dysfunction, what are some other symptoms/problems associated with Goodpastures?
Pulmonary Problems:
• Cough, dyspnea, crackles, hemoptysis (may precede or coincide with renal dysfunction)
• Smoking makes this worse
Blood Problems:
• Anemia out of proportion to renal insufficiency
• NORMOTENSIVE with decreased renal function (late complication)
Bone/joint Problems:
• Arthritis/Arthralgias
What is the treatment for Goodpasture’s (anti-GBM) disease?
- Corticosteroids
- Plasmapheresis
- Cytotoxic Agents
What happens to the glomerulus in light of the formation of crescents in Goodpasture’s syndrome?
• Glomerular Tuft is compressed by PROLIFERATING EPITHELIAL CELLS in the crescent
What is the progression of disease severity in crescent formation?
• when can you classify a disease as a crescentric glomerulonephritis?
Segmental Proliferative and Necrotizing Lesions => Cellular Crescents => Fibrocellular Crescents => Fibrous Crescents
Classification:
• Referred to as a diffuse crescentric glomerulonephritis if greater then 50% glomeruli are involved under light microscopy
What is the etiology of crescent formation in the kidney?
• May be due to severe damage ot capillary walls that tear and necrose the GBM
Result:
• RBCs, WBCs, fibrinogen, and plasma constituents enter Bowman’s space and cause proliferation of mononuclear cells and parietal epithelial cells
In Rapidly progressive glomerulonephritis what is seen on Immunofluorescence?
- FIBRINOGEN stains into GREEN CRESCENTS
Alport Syndrome
•Cause?
• Who is most often affected?
• Associated Symptoms?
Cause:
•X-linked (most often) defects in ALPHA-5 COLLAGEN TYPE IV
Who is affected:
• Because its X-linked MALES are most often affected
Associated symptoms:
• Sensorineural Hearing Loss
• Lens abnormalities, Platelet Defects
• Esophageal Leiomyomas
Alport Syndrome
• Key terms
• microscopy used in dx?
BASKET WEAVE APPEARANCE
EM is where you see basket weave appearance, but early in the disease you don’t see anything
Thin Basement membrane Disease
• cause
• severity of Disease
• appearance
Cause:
• Defects in ALPHA-3 or ALPHA-4 collagen type IV
Severity:
• Heterozygotes = Benign
• Homozygotes/Compound Heterozygotes = Affected
Appearance:
• GBM appears at 1/2 thickness
