The Kidney in Systemic Disease 1/2 Flashcards Preview

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Flashcards in The Kidney in Systemic Disease 1/2 Deck (59):
1

What are 4 vascular injury syndromes?

ANCA-assc glomerulonephritis
Thrombotic Microangiopathy
Lupus Nephritis
Scleroderma

2

What are the 2 pathogenesises of vascular disorder?

1. inflammation of blood vessels
2. Loss of thromboresistance (= loss of normal resistance to clot formation)

3

What are the differences between medium vessel disease and small vessel disease?

medium vessel disease:
-renal infarcts and distal glomerular ischemia
-decline in GFR **not assc with glomerular inflammation**
- NO RBC casts
-usually ANCA negative
-aka polyarteritis nodosa

small vessel disease:
- focal necrotizing lesions with crescent formation
- active urinary sediment
- rapid progression of kidney failure (decline in GFR)
- aka microscopic polyangiitis

4

What is pauci-immune glomerulonephritits? When is it usually seen?

negative immunefluoresence studies usually in the setting of crescentic glomerulonephritis

*often assc with ANCAs + extra renal findings (arthritis, athralgias, myalgias, fatigue) but not always and CRESCENTIC glomerulonephritis

5

What are ANCAs?

anti-neutrophil cytoplasmic Abs with 2 distinct patterns:
1. C-ANCA: anti-proteinase 3
2. P-ANCA: anti-lysosomal myeloperoxidase

6

What disease(s) are assc with positive C-ANCA Abs?

granulomatosis with polyangitis (Wegner's)

7

What disease(s) are assc with positive P-ANCA Abs?

-anti-GBM disease (~30% of pts)
-low titers seen in SLE
-sclerosing cholangitis, ulcerative colitis, and chron's disease

8

Describe the difference between C and P ANCAs with immunofluorescence?

C-ANCA: cytosplamic staining
P-ANCA: peri-nuclear staining

9

How are ANCAs pathogenic?

binding of ANCAs to neutrophils activates them -->
-inc contact and adhesions with endothelial cells/vascular structures by: B-2 integrin, Mac-1, Fc-gamma

--> endothelial cell injury (to glomeruli and blood vessels)
-inhibition of PR-3 inactivity
-EC activation
-ADCC
-complement activation via alt pathway
-monocyte activation/release of ROS and chemotactic molecules

10

_______ cells are the primary target in small vessel vasculitis.

endothelial cells

11

What is a specific and sensitive test for Wegner's Granulomatosis?

C-ANCA

12

What are signs and symptoms assc with granulomatosis with polyangitis (Wegner's)?

-Upper respiratory tract involvement with: rhinorrhea, sinusitism nasopharyngeal mucosal ulcerations
-Lower Respiratory Tract involvement with: cough, dyspnea, hemoptysis, transient pulmonary infiltrates on X-ray
-!0% have azotemia at presentation
-fever, weight loss, arthralgias/arthritis, mononeuritis multiplex, skin lesions

13

T or F: In most autoimmune mediated vascular necrosis, arteries and veins are involved

F: usually only arteries
**granulomatosis with polyangiitis/Weger's has BOTH a and v!!

14

Describe the shape/type of glomerulonephritis of granulomatosis with polyangiitis/Wegners.

crescentric

15

What is the treatment of granulomatosis with polyangiitis?

cyclophosphamide based with steroids, plasmapheresis

*80-90% mortality if left untreated

16

What are the 2 types of TMAs (thrombotic microangiopathies)?

TTP
HUS

17

How are TTP and HUS differentiated?

HUS:
-hemolytic anemia
-renal dysfunction
-thrombocytopenia

TTP:
-hemolytic anemia
-renal dysfunction
-thrombocytopenia
-fever
-neurologic dysfunction

18

Describe the appearence of vessels on biopsy that are assc with TMAs?

onion skin

19

What is the pathogenesis of TMAs?

-endothelial cell loses thromboresistance
-platelet activation
-fibrin clot formation in lumen of affected vessels
-endothelial cell injury

20

What are 3 causes of endothelial damage in HUS?

1. verotoxin producing E. coli that cause production of cytotoxic antiendothelial Abs
2. chemotherapeutic agents (cyclosporine, gemcitabine, bleomycin/cisplastinum)
3. radiation (BM transplant)

21

Familial TTP is seen with a genetic deficiency of ...

ADAMTS13 (vWF cleaving protease)

22

T or F: inc levels of vWF multimers may directly enhance platelet aggregation.

T

23

What are the differences between TMA and DIC?

PT and PTT are normal in TMA and prolonged in DIC

TMAs are assc with a thrombotic diathesis
DIC are assc with a bleeding diathesis

24

T or F: SLE is a systemic disease that spares no organ system

T

25

What is the ten year survival rate of SLE?

70%

26

What are the 11 criteria for SLE?

mala rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, immunologic disorder, antinuclear Abs

27

What are the stages of lupus nephritis?

I: minimak mesangial
II: mesangial proliferative
III: focal proliferative
IV: diffuse proliferative
V: Membranous
VI: Advanced sclerosing

28

What is the most common stage of lupus nephritis?

IV: diffuse proliferative

29

Class __ is mild, class ___ is moderate, and class ___ is severe.

II, III, IV

30

What pathologies can be seen in a biopsy of a class IV (diffuse proliferative) lupus nephritis?

wireloop lesions
hyaline thrombus (immune complex)
crescent formation
excess cells

31

What can be seen in EM with a pt with lupus nephritis?

subendothelial and mesengial depositis

32

Describe immunofluroesence pattern that is consistant with a diagnosis of lupus nephritis.

"full house immunofluoresence" = all 3 Ig present (IgG, IgM, and IgA) as well as C3 and C4

33

What is the treatment for SLE?

Glucocorticoids, aspirin, and hydroxychloroquine (TLR inhibitor) are FDA approved for the treatment of lupus

*immunosuppresants can also be used (class 4 = cyclophosphamide and class 5 = mycophenolate mofetil)

34

What class of lupus nephritis is assc with poor renal survival?

IV

35

What is scleroderma?

disease that involves connective tissue and the microvasculature with fibrosis and vascualr occlusion

36

What are the 2 subsets of scleroderma? What are they based on?

limited and diffuse cutaneous based on pattern of skin involvement

37

What is the epidemiology of scleroderma?

femal predominance
more frequent in AA
1 in 4000 US adults affected

38

How is renal involvement of scleroderma characterized? Renal crisis?

proteinuria
HYP
(mild renal dysfuction)

Renal crisis: new onset of accelerated arterial HYP and/or rapidly progressive oliguric renal failure

39

How is scleroderma renal crisis treated?

ACE inhibitors

40

What are the risk factors for scleroderma renal crisis?

-early diffuse systemic sclerosis (subtype)
-rapidly progressive skin disease
-anti-RNA pol Abs
-corticosteriod therapy

41

What happens to the arcuate arteries with scleroderma?

intimal and medial proliferation with luminal narrowing
*fibrinoid necrosis and thrombus is common

42

Describe the histology of interlobar arteries with scleroderma.

concentric sclerosing intimal thickening --> resembles onion skin

43

What disease from this lecture is sinopulmonay?

Wegner's

44

What disease from this lecture is assc with puci-immune glomerulonephritis?

Wegner's

45

What is scleroderma renal crisis?

new onset of accelerated arterial HYP and/or rapidly progressive oliguric renal failure

46

What is the difference between microscopic polyangiitis and polyarteritis nodosa?

microscopic polyangiitis: small vessel disease (focal necrotizing lesions with crecentric formation) that causes glomerulonephritis (usually pauci-immune crescentric)

polyarteritis nodosa: medium vessel disease that causes macroscopic areas of ischemia and infarction --> kidney damage/dec GFR

47

What is the pathogenesis of HUS?

Shiga toxin in circulation causes widespread endothelial injury:
-shiga toxin binds receptor on endothelial cell
-inc endothelin production
-dec NO production
- TNF released
- toxin internalized (10% of time) --> apoptosis
-pro-coag state--> thrombus formation

48

What is the classical presentation of HUS?

sudden onset of irritability, lethargy, weakness, pallor, and oliguira in a SMALL CHILD, 5 - 10 days following gastroenteritis

49

TTP treatment

plasmaphoresis

50

What is the characteristic feature of lupus nephritis? (occurs in 100% of pts)

proteinuria
*nephrotic syndrome in 65%
*microscopic hematuria in 80%

51

Glossary of terms to know:

inflammation of blood vessels, usually autoimmune

vasculitis

52

autoimmune ANCA-negative medium vessel arteritis

Polyarteritis nodosa

53

antibodies against proteinase 3 or myeloperoxidase associated with specific autoimmune diseases

ANCA

54

autoimmune small vessel vasculitis cause of pauci-immune crescentic glomerulonephritis associated with P-ANCA

Microscopic polyangiitis

55

autoimmune necrotizing granulomatous vasculitis of respiratory tract and cause of crescentic glomerulonephritis associated with C-ANCA

5. Granulomatosis with polyangiitis (Wegener’s

56

thrombotic microangiopathy of glomeruli in small children due to Shiga toxin from diarrheal E. coli H7:O157 infection

HUS

57

thrombotic microangiopathy due to von Willebrand factor multimers from ADAMTS13 deficiency

TTP

58

immune complex-mediated glomerulonephritis of systemic lupus erythematosus (the prototype multi-system autoimmune disease)

Lupus nephritis

59

rapidly progressive renal failure of systemic sclerosis

scleroderma renal crisis