Path - Kidney in Systemic Disease I Flashcards
Name the 4 vascular injury syndromes?
ANCA-associated glomerulonephritis
Thrombotic microangiopathy
Lupus nephritis
Scleroderma
What are the 2 forms of pathogenesis in vascular disorders?
- Inflammation of blood vessels (seen in vasculitides)
- Loss of thromboresistance (seen in thrombotic microangiopathies)
Most common medium vessel disease?
Polyarteritis nodosa
Name 3 most common small vessel diseases?
Microscopic polyangiitis, granulomatosis with polyangiitis (aka Wegeners), Churgg Stauss syndrome
Describe key difference between medium vessel disease and small vessel disease
Medium vessel
- causes distal glomerular ischemia leading to renal infarcts. It is NOT associated with glomerulonephritis
- Not associated with glomerular inflammation with RBC casts (usually ANCA negative)
Small vessel
- causes focal necrotizing lesions with crescent formation (aka glomerulonephritis)
- active urinary sediment and rapid progression of kidney failure (usually ANCA positive)
Medium vessel disease UA findings?
No RBC casts
Small vessel disease UA findings?
Active urinary sediment = hematuria (+ RBC casts)
3 disorders involving Hep B or C? (nephrotic or nephritic syndromes included)
Membranous - more commonly Hep B
MPGN - more commonly Hep C
Polyarteritis nodosa - more commonly Hep C
Polyarteritis nodosa affects what type of vessels?
Medium sized muscular arteries (does not affect veins)
Which type of vascular disorder is associated with ANCAs? (medium or small vessel)
Small vessel disorders
Polyarteritis nodosa epidemiology?
Most common in middle aged or older adults with peak incidence in sixth decade of life
Causes of PAN (polyarteritis nodosa)?
Idiopathic, also associated with Hep B or Hep C (more common than B), and hairy cell leukemia
Common presentation of PAN (polyarteritis nodosa)?
Fever, fatigue, rash, weight loss, arthralgia.
May see HTN, renal insufficiency, neurologic dysfunction, abdominal pain
Pathogenesis of PAN?
Unknown
Pathology of PAN (polyarteritis nodosa)
Buzzword. Segmental transmural necrotizing vasculitis
Early stage PAN - what pathologic finding?
Later stage PAN - what pathologic finding?
Early - lots of PMNs (neutrophils)
Later - fibrinoid necrosis
What disease process is shown in this kidney? Describe white arrows, black arrows, and red arrow
This is a kidney in polyarteritis nodosa
White arrows = renal cortical infarcts
Black arrows = aneurysms
Red arrow = ruptured aneurysm
In PAN, patient with ruptured aneurysm will present how? Significance of ruptured aneurysm in kidney?
Ruptured aneurysm causes painless hemorrhage shock (no nerve endings in retroperitoneum) - causing death if not treated immediately
- They will be hypotensive, syncopal, and have extremely low Hgb
Pauci immune means?
Negative immunofluoresence stains usually in setting of crescentic glomerulonephritis
Pauci-immune glomerulonephritis is often associated with what 2 findings?
ANCAs and extrarenal findings (arthritis, arthralgias, myalgias, fatigue)
2 Key points about pauci-immune glomerulonephritis and ANCAs
- ANCA titers may not always parallel disease activity
- Patient can be ANCA negative and without extrarenal findings, but still have pauci-immune glomerulonephritis
Another name for c-ANCA? Most commonly associated with?
anti-proteinase 3
seen in granulomatosis with polynagiitis (Wegeners)
Another name for p-ANCA? Commonly associated with?
anti-myeloperoxidase
seen in Microscopic polyangiitis or Churg-Strauss syndrome
Which ANCA has a greater specificity?
c-ANCA has a 95% specificty for Wegener’s. p-ANCA is not as specific
Are ANCAs diagnostic or pathogenic?
ANCAs are pathogenic, meaning they are not usually present.
Describe how ANCAs work? What 3 adhesion molecules are important?
ANCAs bind to neutrophils, activating them. This causes increased contact and adhesion with endotheilal cells and vascular structures.
The three main adhesion factors are Beta 2 integrin, Mac-1, and Fc gamma
What are the primary target cells in small vessel vasculitis?
Endothelial cells
What are the 2 common disorders affecting BOTH lungs and kidneys?
- Goodpasture syndrome
- Granulomatosis with polyangiitis
Wegener’s is considered what type of renal syndrome?
Sinopulmonary renal syndrome
3 sites involved in Wegener’s
Nasopharynx, Lungs, Kidney
Symptoms associated with Wegener’s
Rhinorrhea, sinusitis, nasopharyngeal mucosal ulcerations, dyspnea, hemopytis, transietn pulmonary infiltrates
fever, weight loss, arthralgias/arthritis, skin lesions
Main difference in renal function between Wegener’s and Goodpasture syndrome/Anti-GBM?
Wegener’s will not commonly have renal impairment at presentation (only 10% have azotemia) vs goodpasture that will commonly have renal impairment at presentation
Pathology of Wegener’s. What key feature is present (hence the granulomatosis)
Necrotizing granulomatous inflammation with multinucleated giant cells (red circles)
- can see vascular necrosis with thrombosis
- can see crescentic glomerulonephritis
Treatment for granulomatosis with polyangiitis
Cyclophosphamide, steroids, plasmapheresis
Prognosis of Wegener’s?
Mortality is 80-90% if untreated
Relapse in 25-50% of patients with 3-5 years of follow up
2 syndromes of thrombotic microangiopathies (TMA)
- Hemolytic uremic syndrome (HUS)
- Thrombotic thrombocytopenic purpura (TTP)
3 common findings of HUS?
- Hemolytic anemia (schistocytes on blood smear)
- Renal dysfunction
- Thrombocytopenia (due to platelet consumption)
5 common findings of TTP?
- Fever
- Hemolytic anemia
- Thrombocytopenia
- Renal dysfunction
- Neurologic dysfunction
Note: Now patients are being diagnosed even in the absence of 1 or more findings
Pathogenesis of thrombotic microangiopathies?
Loss of thromboresistance by the endothelial cell, leads to platelet activation and deposition (along with fibrin) in lumen of affected vessels
2 main deposits in thrombotic microangiopathies?
Platelet and fibrin deposition in affected vessels
Buzzword for thrombotic angiopathies?
Onionskin apperance, however this is not specific for thrombotic microangiopathies
Onionskinning is common in what other syndromes besides thrombotic microangiopathies
Common in:
HTN, Scleroderma, sometimes Lupus
In what vessels does onionskinning occur? Why?
Occurs in arterioles due to thrombosis of capillaries (leading to increased back pressure)
Endothelial damage in thrombotic microangiopathies are commonly caused by what 3 mechanisms?
- E. coli H7:0157 (in HUS)
- Chemotherapeutic agents (cyclosporine, gemcitabine, bleomycin/cisplatinum)
- Radiation (bone marrow transplant)
Hemolytic uremic syndrome commonly caused by? Mechanism?
E.Coli H7:O157 verotoxin, causes production of cytotoxic anti-endothelial Ab’s
Increased levels of von Willebrand factor causes what?
Enhanced platelet aggregation
Familial TTP mechanism? What percentage of TTP patients are familial TTP?
genetic deficiency of vWF cleaving protease (Low ADAMTS13 activity)
10% of TTP
Autoimmune TTP mechanism?
autoantibody to vWF cleaving protease develops (ADAMTS13 autoantibodies)
Buzzword. Schistocytes?
HUS, TTP
Treatment for TTP?
Plasmaphoresis
2 Key differences between thrombotic microangiopathies and DIC?
- PT, PTT, INR:
TMA - PT, PTT, and INR are normal
DIC - PT, PTT, INR are prolonged (think, prolonged DIC(k)!)
- Diathesis (tendency to suffer from medical condition)
TMA - associated with thrombotic diathesis
DIC - associated with bleeding diathesis
Lupus epidemiology?
Black women, but can be present in almost all races/ages
Lupus antibodies most common?
ANA - antinuclear antibody
anti-dsDNA antibody
anti-smith antibody
Last 2 are specific for Lupus
What test is commonly done to screen for syphilis? What is the relation to lupus?
If patient has +RPR test (which is used to screen for syphilis) you must follow up with anti-smith and anti-dsDNA antibody screening to r/o lupus
BRS version:
+RPR, - antismith, - dsDNA = possible Syphilis
+RPR, +antismith, + dsDNA = Lupus
How many classes of Lupus nephritis are there? What are they? Which is most common?
6 classes
Class I = Minimal mesangial, rare
Class II = Mesangial proliferative, 15%, mild
Class III = Focal proliferative, 25%, moderate
Class IV = Diffuse proliferative, 50%, severe
Class V = Membranous, 10%, nephrotic
Class VI = Advanced sclerosing, ? %
Class II Lupus nephritis = ?
%?
Severity?
Class II = Mesangial proliferative
15%
Mild severity
Class III Lupus Nephritis = ?
%?
Severity?
Class III = Focal Proliferative
25%
Moderate severity
Class IV Lupus Nephritis = ?
%?
Prognosis?
Class IV = Diffuse proliferative
50%
SEVERE
Class V Lupus Nephritis = ?
%?
Description?
Class V = Membranous
10%
Nephrotic
Type IV Lupus nephritis = ?
What 3 types of proliferative cells are present
Class IV = Diffuse proliferative lupus nephritis = most common
Lots of excess cells (inflammatory cells, mesangial cells, capillary endothelial cells)
Class IV Lupus Nephritis is associated with what buzzword pathology?
Wireloop lesions
Crescent formation is possible in what class of Lupus nephritis?
Class IV (diffuse proliferative). If in doubt, pick Class IV, its the most talked about in lecture
Immunofluorescence of Lupus Nephritis? What is present?
FULL HOUSE immunofluoresence
IgG, IgA, IgM, C3, and C4
Which class is associated with poor renal survivial?
Class IV (both global and segmental) has poor prognosis. Will need to put on dialysis
Treatment for SLE?
Aspirin
Glucocorticoids,
Immunosuppressants:Cyclophosphamide (IV only), Mycophenolate mofetil,
TLR inhibitors: Hydroxychloroquine
Bold = preferential therapy
Another name for scleroderma?
Systemic sclerosis
Scleroderma MOA?
Involves CT and microvasculature with fibrosis and vascular occlusion, causing onion skin sclerotic thickening of interlobar arteries (larger arteries)
Scleroderma epidemiology?
Black females (1/4000 adults in US)
2 subtypes of scleroderma? Mechanism of differentiation?
Limited cutaneous
Diffuse cutaneous
Separated based on pattern of skin involvement
Which subtype of Scleroderma is more likely to have renal involvement?
Diffuse scleroderma
What is scleroderma renal crisis?
New onset of accelerated arterial HTN and/or rapidly progressive oliguric renal failure
How do you treat scleroderma renal crisis?
Treat with ACE-I. This is the one time where you give ACE-I to patient with poor renal function.
What drug can cause scleroderma?
Corticosteroid therapy can increase risk for scleroderma
