05.15 - Kidney, Systemic 1 (Nichols) - PP + Handout Flashcards
What does factor H regulate
Complement
Demographic of SLE
Black Female of child-bearing age
Small vessel vasculitis causes
Focal necrotizing lesions with crescents, active urinary sediment, Rapid progression of kidney failure
AI necrotizing granulomatous vasculitis of respiratory tract and cause of crescentic GN associated with C-ANCA
Wegener’s
Small vessel vasculitis involving glomeruli usually causes
Pauci-immune Crescentic GN
Causes of Thrombotic Microangiopathy includes ___ in children and ___ in adults
Hemolytic Uremic Syndrome, TTP
Sudden onset of irritability, lethargy, weakness, pallor, and oliguria 5-10 days following gastroenteritis
HUS
Most common form of Lupus Nephritis
Diffuse Proliferative (Class IV) - Severe disease
Thrombotic Microangiopathy of Glomeruli in small children due to Shiga toxin from E Coli infection
Hemolytic Uremic Syndrome
Ab’s in Microscopic Polyangiitis
P-ANCA (anti-mpo)
What are Classes I, II, and III of Lupus Nephritis
Minimal Mesangial (rare), Mesangial Proliferative (15), Focal Proliferative (25)
Effect of Microscopic Polyangiitis on kidneys
Glomerulonephritis
First and second most common Classes/Patterns of GN
Diffuse Proliferative (50), then Focal Proliferative (25)
Typical patient with TTP
Older adult - Subacute onset of malaise, faitigue, petechiae, pallor, confusion, nausea, abdominal pain, weakness
Urine feature present in 100% of patients with SLE
Proteinuria
Manifestation of renal involvement of SS
Mild renal dysfunction, Proteinuria, HTN; or Scleroderma Renal Crisis
Which arteries show onion skinning in SS of kidneys
Interlobar arteries
Histological findings in kidney in scleroderma
Onion skinning, Intimal and Medial proliferation, Fibrinoud Necrosis
Which Class of Lupus Nephritis has significantly worse renal survivial rate
IV
Immediate consequence of PMN activation by ANCAs
Increased contact and adhesion with endothelial cells and vascular structures
Most forms of vasculitis involve on
Arteries
How do you differentiate between TMA and DIC
PT and PTT are normal in TMA, but prolonged in DIC
There are granular deposits of ___ in ___ locations in most cases of SLE
Ig and Complement, Subepithelial, Mesangial, and Subendothelial locations
Typical onset of HUS
Sudden irritability, lethargy, weakness, pallor, oliguria; 5-10 days following gastroenteritis
Vascular changes in Scleroderma Renal Crisis associated with poorer outcome
Mucoid Intimal thickening and thrombosis
Patients with Wegener’s develop necrotizing granulomatous inflammation in their ____, in addition to ____
Nose, Paranasal sinuses, and Lungs, in addition to Crescentic GN
What are Classes IV, V, and VI of Lupus Nephritis
Diffuse proliferative (50), Membranous (10), Advanced Sclerosing (?)
HUS + Fever and neurological dysfunction (seizures)
TTP
ANCA-associated GN is usually part of
syndrome with extra-renal signs and symptoms
For SLE, anti-dsDNA and anti-Sm Ab’s are less ___ than Anti-nuclear, but much more
Less sensitive, but more specific
T/F: Pauci-immune GN may be ANCA-negative and can occur w/out extra-renal disease
TRUE
Prevalance of anti-nuclear auto-ab’s in normal individuals
15%
90% of patients with ANCA-associated Crescentic GN have ___ before they develop symptoms of GN
Flu-like symptoms
PR3-ANCA =
Wegener’s
Factor H mutation
Uncontrolled activation of complement with intravascular thrombosis –> HUS
AI small vessel vasculitis cause of pauci-immune crescentic GN associated with P-ANCA
Microscopic Poly
Only approved tx of Lupus by FDA
Aspirin, Glucocorticoids, Hydroxychloroquine
Full House Immunofluorescence
In SLE, staining of deposits with antisera to all 3 Ig’s, C3, and Cr
When both P-ANCA and C-ANCA are present, call it
MPO-ANCA
Finding MHA and Thrombocytopenia with no other explananation besides TTP should prompt
Plasmapharesis
Clincially, patients with Thrombotic Microangiopathies have what 3 things
Microangiopathic Hemolytic Anemia, Thrombocytopenia, Often renal failure
Tx of HUS
Transfusions, Dialysis, Supportive measures
Mortality for HUS
4% if treated, poor if not
Which class of Lupus Nephritis is severe? Which is nephrotic?
IV is severe, 5 is nephrotic
What is Onion Skinning? (in context of kidney in SS)
Concentric Sclerosing Intimal thickening of interlobar arteries
Which is ANCA+: PAN or Microscopic Polyangiitis
Microscopic Polyangiitis
A ____ event is likely necessary for endothelial injury with ANCA-associated vasculitis
Synergistic pro-inflammatory event (like exposure to TNF-alpha)
HUS is usually a complication of
intestinal infection of Shiga-toxin producing E Coli
New onset of accelerated arterial HTN and/or rapidly progressive oliguric renal failure
Scleroderma Renal Crisis
3 general locations affected by Wegener’s
URT, LRT, Kidney
Cause of TTP
Deficiency of ADAMTS13 - Cleaving protease of vWF
Demographic of SS
Black women in their 50s
Tx of TTP
Plasmapharesis
Medium vessel arteritis (eg classic PAN) causes
renal infarcts and distal glomerular ischemia
Most common and characteristic forms of lupus nephritis involve
the glomeruli
Negative Ab (pauci-immune) is usually in the setting of
Crescentic GN
T/F: Pauci-immune means no Ab’s
False, can still have ANCA’s
T/F: Patients with Wegener’s can also have P-ANCA
True, or be ANCA negative
Which is usually ANCA positive: Medium or Small vessel vasculitis
Small
Tx of SLE
Steroids, Immunosuppressants: Mycophenolate, Cyclo, MTX, Azathioprine
2 main types of Thrombotic Microangiopathies
HUS, TTP
Vasculitis in SLE
Acute necrotizing vasculitis of small arteries and arterioles with fibrinoid deposits
Extra-renal signs and symptoms in ANCA-associated GN
Athralgias, Arthritis, Myalgias, Fatigue
Fundamental pathogenesis of Thrombotic Microangiopathy
Loss of Thromboresistance by endothelial cells
Type of vasculitis caused by Wegener’s
Necrotizing
Tx of Wegener’s
Cyclophosphamide, Steroids, sometimes plasmapharesis
What are Hyaline thrombi
Misnomer of wire loop deposits that protrude into lumen
Microscopic Polyangiitis vs PAN effects on Kidney
MP causes GN, whereas PAN causes macroscopic ishcemia and infarction (thrombosis, aneurysm)
Tx of Scleroderma Renal Crisis
ACEi
Scleroderma Renal Crisis
New onset of accelerated HTN and/or rapidly progressive oliguric renal failure
Hemolytic Uremic Syndrome is triad of
Microangiopathic Hemolytic Anemia, Thrombocytopenia, AKI
Eculizamab is used for
Block complement activation (HUS subtype)
Systemic Sclerosis is characterized by
Fibrosis of CT and Vascular Occlusive Disease
Wegener’s causes rapidly progressive
Crescentic GN
Microangiopathic Hemolytic Anemia, Thrombocytopenia, AKI
Hemolytic Uremic Syndrome is triad of
3 significant causes of endothelial damage
E Coli toxin (auto-Ab’s), Chemo, Radiation
Fibrinoid Necrosis and Thrombosis in Scleroderma
Common
What has prolonged PT and PTT: TMA or DIC
DIC - Consumptive coagulopathy
2 features shared between TMA and DIC
Thrombocytopenia and Microangiopathic Hemolytic Anemia
PR3-ANCA is specific for Granulomatosis w Polyangiitis
True, 95%
Primary target in small vessel vasculitis
Endothelial cells
Effect of PAN on kidneys
Not GN - Macroscopic ischemia and infarction
Which arteries are affected by intimal and medial proliferatioin scleroderma renal crisis
Arcuate
Who is usually affected by HUS
Small children under 5 years
4 most common inflammatory manifestations of SLE
Non-erosive Synovitis (90), Skin lesions (85), Nephritis (50), Cerebritis (50)
2 major features of TTP
MHA, Thrombocytopenia
Thrombotic Microangiopathy must be differentiated from
DIC
Wire loop lesions are inidicative of
Active disease
What do ANCA’s do to their targets in granulocytes
Activate neutrophils, which then adhere to endothelial cells; Also prevent inactivation of the targeted granulocyte componens (PR3, MPO, etc)
Which part of glomerulus is affected in SLE
All 3 locations
ANCA cause
Endothelial Cell injury in Glomeruli and Blood Vessels
Segmental Transmural Necrotizing Vasculitis
PAN
In about 10% of cases, HUS in children is due to
Inherited mutation that inactivates Factor H
P-ANCA may be positive in up to ___% of patients with Anti-GBM disease
30%
5 features of TTP
2 major: MHA, Thrombocytopenia; Others: Neurologic dysfunction, renal dysfunction, fever
What causes wire loops in SLE
Confluent circumferential Subendothelial deposits cause the glomerular capillary walls to be thickened
