Flashcards in Module 4: Renal: Nephritic Disorders Deck (42):
This card deck will cover Nephritic Disorders. First which nephritic disorders have normal complement levels?
SLE (class I, II, V)
Which nephritic disorders have low complement levels?
SLE (class III and IV)
Bacterial endocarditis/ infected ventriculoatrial shunt
The first nephritic disorder to discuss is Mesangioproliferative Glomerulonephritis (IgA nephropathy/ Berger's Disease). What are some features?
Most common cause of nephritic syndrome in adults
--1 to 3 days following a resp or GI tract infection (making IgA)
--associated with liver cirrhosis, Celiac's Disease, HIV and minimal change disease
--most common in Asian and Caucasians in 2nd and 3rd decades
IgA nephropathy also presents in children. What syndrome is it apart of? What are features?
Henoch-Schonlein Purpura Nephritis
features of HSP:
--kidneys: IgA nephropathy
--skin: non blanching purpuric rash
---GI: mesenteric vasculitis: red infarct (Abd pain and bloody diarrhea)
What is the presentation for IgA nephropathy for both adults and children?
Episodic gross hematuria
Persistent microscopic hematuria (even though you dont see it the blood is there)
What is seen in the blood and urine for patients with IgA nephropathy?
Urine: protein less than 3.5 and RBC clasts
Blood: Elevated IgA, Azotemia, and Normal complement
What is seen on renal biopsy for IgA nephropathy?
LM: Diffuse proliferation of mesangial cells and deposits of mesangial matrix (thats why its pink in the pic)
--mesangial expansion and segmental hypercellularity
IF: Course granular deposits
--IgA and C3
--Mesangium and Subendothelium
EM: IgA and C3 deposits in the mesangium and subendothelium layer.
What are the complications seen with IgA nephropathy?
Usually self limiting in kids not adults
Iron Defiency Anemia: CHF
Switch to FSGS
--Nephritic to nephrotic
--look for frothy urine and periorbital to generalized edema
RPGN "Crescentic glomerulonephritis"
--2-3 weeks: oliguria to anuria; pericarditis, encephalopathy and ARDS
What is the pathogenesis for IgA nephropathy?
Mucosal Infections ---Excess IgA --- goes to the mesangial cells deposits there --- expansion of the mesangium -- hematuria which worsens during the period of infections
The next nephritic disorder is Post-Streptococcal Glomerulonephritis. What are the general features
Overall best outcome ( complete, spontaneous resolution)
--type III HSR to alpha 3 subunits of Type IV collagen in BM
What is the presentation for Post-Streptococcal Glomerulonephritis?
10 days after pharyngitis or 3 weeks after impetigo by Group A Beta-Hemolytic Streptococcus (S. pyogenes) b/c you need time to form immune complexes
--more common in children 6-10 years old
--dark, coke colored urine (Hematuria), periorbital edema and oliguria and HTN
What is seen in the urine and blood in patients with Post-Streptoococcal Glomerulonephritis?
Protein: less than 3.5g/day
RBCs: RBC casts
Blood: Low complement (hypocomplement), azotemia, elevated ASO titers/anti DNAase B titers
What is the pathogenesis for Post-Streptococcal Glomerulonephritis?
Initially: subendothelial IC deposits --- rapidly cleared --- resolution of hematuria
Later: Subepithelial humps --- account for slow rate of resolution of proteinuria
What is seen on LM, IF and EM in post Streptococcal Glomerulonephritis?
LM: Diffuse global hypercellularity with NO thickening of GBM (Excellent prognosis)
IF: coarse granular (lumpy bumpy, IgG and C3, everywhere)
EM: Subepithelial deposits only ones that do not get cleared
--subepithelial hump of IgG and C3
What are the complications of Post Streptococcal Glomerulonephritis?
Spontaneous resolution most common outcome (Even without treatment)
RPGN: type II in 2-3 weeks
--patient goes from oliguria to anuria
--azotemia to uremia
Uremia: encephalopathy, gastritis, ARDS (ground glass appearance), uremic bleeding
The next nephritic syndrome is Membranoproliferative Glomerulonephritis. What are some features?
Thickening of BM, mesangial Proliferation and infiltration of inflammatory cells
There are two types of Membranoproliferative Glomerulonephritis. What are the features of type I ?
Type I: Most common
Classical Complement Activation
Secondary forms are more common: hep C (give you cryoglobins so more likely to cause hemolysis in colder area of the body) , hep B and SLE
Subendothelial deposits on EM
--IgG and C3
What are features of type II Membranoproliferative Glomerulonephritis?
Type II: Dense deposit disease
--Alternate complement pathway
--Common in children
Idiopathic: worse prognosis b.c nothing to treat
--Intramembranous deposits on EM
What is the presentation for Membranoproliferative?
Nephritic or Nephrotic; presents in 1 of 4 ways
--Hematuria or proteinuria
---Acute nephritic syndrome with hematuria, HTN and edema
--Recurrent episodes of gross hematuria
--Insidious onset of edema and nephrotic syndrome
What are the complement levels for each type in Membranoproliferative?
Type I: low C1 and C4 in blood
--slighly low C3
Type II: normal C1 and C4
--C3 is extremely low
--C3 nephritic factor which stabilizes the C3 convertase so a continous activation of the alternate C3 pathway hence why C3 is extremely low.
What is the LM, IF and EM for membranoproliferative glomerulonephritis?
LM: both types
--diffuse global thickening of BM and hypercellularity
--silver stain: double contour (Splitting of the BM via the Mesangial cells) = tram track
Type I: subendothelial deposits of IgG and C3
Type 2: Intramembranous deposits of C3
--ribbon like deposits
Next topic is not really a syndrome more like a complication. Called Rapidly Progressive Glomerulonephritis / Crescentic Glomerulonephritis. What is the pathogenesis of this?
Proliferation of parietal epithelial cells and infiltration of macrophages and fibrin -- severe glomerular BM injury
What is RPGN?
Is a group of disorders associated with a rapid decline in renal function with associated severe oliguria and if untreated death from renal failure within weeks to months. Classified into 3 types
What is the first type of RPGN?
Type I: Anti-Glomerular BM Antibody-Mediated Crescentic Glomerulonephritis.
--type II HSR
--characterized by linear deposits of IgG and C3 in the GBM
--patients are said to have Goodpasture syndrome or anti-GBM disease
What is the second type of RPGN?
Immune Complex-Mediated Crescentic Glomerulonephritis
--characterized by any cause of granular (lumpy bumpy) pattern of GBM including Post-Streptococcal GN, SLE, IgA nephropathy, and Henoch-Schonlein Purpura
What is the third type of RPGN?
Type III: Pauci-Immune Crescentic Glomerulonephritis
---characterized by a lack of anti-GBM antibodies or a significant immune complex deposition detectable by IF and EM
--ANCA is typically found in the serum, therefore has a role in Wegener's (necrotizing pneumonia that does not respond to abx - CNCA) ; Churg-Strauss (bronchial asthma and peripheral eosinophilla PNCA) and Microscopic Polyangitis (PNCA)
What is the presentation for RPGN?
1.Oliguria --- anuria and azotemia -- uremia in 2-3 weeks due to blocking of Bowman's Space -- no filtration
2. Initially crescents are cellular --- fibrocellular -- fibrous
3. In type I it is important to distinguish the cause as either Good Pasture or Anti-GBM disease
--in Good Pasture: both pulmonary hemorrhage and renal involvement (hematuria and hemoptysis)
What are the complications associated with RPGN?
Rapid Progression to renal failure and death within weeks to months
--progression is worse, increased proteinuria, number of crescents and more fibrosis (more collagen and less cells)
Best prognosis: if underlying disorder is treatable
What do you see on LM, IF and EM for RPGN?
LM: Crescents made up of -- Fibrin + macrophages + proliferating parietal cells (mass of proliferating cells and leukocytes filling the urinary space)
IF: type I: linear deposits of IgG and C3 (Seen on the slide)
Type II: coarse granular deposits of IgG and C3 or IgA and C3 in IgA neuropathy
Type III: Pauci-immune (aka see nothing)
EM: Disruption of the GBM
The next nephritic syndrome is Alport Syndrome. What are some features?
X-linked: so males (5-20 y.o)
--defect in alpha 3,4, and 5 subunit of the Type IV collagen
What is presentation for Alport Syndrome?
Glomerulonephritis: Hematuria, Oliguria, Periorbital edema, and HTN
What is seen in the blood and urine in a patient with Alport Syndrome?
Urine: protein less than 3.5 grams and RBC casts
Blood: Normal complement and azotemia
What is seen on LM, IF, and EM for Alport Syndrome?
LM: initially normal then as the syndrome progressed FSFS later
EM: splitting and lamination of the lamina dense of the GVM
What are the complications of Alport Syndrome?
--so look for oval fat bodies since now its nephrotic as well as anasarca and greater than 3.5 grams of protein
--leads to ESRD (this is the major cause of death)
Lupus nephritis is the last nephritic disease to be discussed in this section. What is the pathogenesis?
Immune complex (anti-DNA) deposited in the kidney --- complement activation --- recruitment of inflammatory cells and tissue destruction
There are 6 classes of lupus nephritis based on immune deposits on histology. Each card will go through one. Class I --
Class I: Minimal mesangial lupus nephritis
--LM: normal; IF and EM: mesangial immune deposits
Class II lupus features
Class II: Mesangial Proliferative Lupus Nephritis
--mesangial immune deposits -- lead to expansion and hypercellularity
--mild; microscopic hematuria, proteinuria, nephrotic syndrome, renal insufficiency is RARE
Class III lupus features ?
Class III: Focal Segmental Proliferative lupus nephritis
-LM: less than 50% glomeruli are affected
-Subendothelial and mesangial IC deposits; complement activation, influx of inflammatory cells
--hematuria, nephrotic syndrome, HTN and renal failure
Class IV lupus features?
Class IV: Diffuse Proliferative Lupus Nephritis
--LM: greater than 50% glomeruli are affected
-marked deposition of IC in subendothelium and mesangium; crescents and necrotizing lesions
--Most common and most severe form; hematuria, proteinuria, nephrotic syndrome, renal failure, low complement, high anti-DNA levels
Class V lupus features?
Class V: Membranous Lupus Nephritis
--subepithelial immune complexes; IC deposits in blood vessels; diffuse thickening of GBM
--Same clinical presentation as idiopathic membranous: nephrotic syndrome, bland urine sediment, mild renal insufficiency, normal C3/4 and negative anti- DNA
Class VI lupus features?
Class VI: Advanced Sclerosing Lupus Nephritis
--global sclerosis of over 90% glomeruli; advanced interstitial fibrosis and tubular atrophy
--represents healing of prior inflammatory injury, advanced stages of chronic Class III, IV and V.