CIS complement pathology

Question 1

glomerular diseases are

Answer 1

immnunilogical in origin

Question 2

glomerular diseaes result from

Answer 2

either deposition of immune complexes or antibodoies directly binding to antigens in the kidneys

Question 3

Complement and the pathogenesis of Lupus Nephritis

Answer 3

1. formation of immune complexes
2. deposition of immune complexes in glomeruli
   2a. deposition of immune complexes and activation of complement
   2b. complement and Fc receptor-mediated activation of immune cells and chemotaxis
3. inflammation mediated by immune complexes and complement
   3a. production and relaese of proinflammatory mediators
4. lesion and tissue fibrosis

Question 4

vasculitis is

Answer 4

inflammation of the vellses which most commonly has an infectious or immune mediated causes

Question 5

immune-mediated vasculitis occurs due to

Answer 5

immune-complex deposition
direct antibody interaction

in many cases, the pathogenssis of vasculitis is unknown, but most likely it is an immune-mediated mechanism

Question 6

mechanism of immune mediated vasculitis

Answer 6

antibodies induce by the disease process bind antigens

this interactino forms an immune complex that deposits within the vessel wall

deposition of the ICs cases vasculitis through the classical pathway of complement activation

Question 7

diseases associated with IC deposition-mediated vasculitis

Answer 7

patients with hep B and C and SLE can develop an immune complex deposition-mediated vasculitis

drug induced vasculitis which often involves skin, is due to IC deposition

Question 8

hereditary angioedema

Answer 8

very rare and life threatening

sx include edema in the body, hands, face, feet, airway as well as abdominal pain, nausea and vomiting

can cause death

defect in gene tht controls for C1 inhibitor which causes imbalance and swelling

Question 9

C1 inhibitor (HAE) can

Answer 9

inactivate enzymes that are not part of the complement cascade

regulates different proteases (C1r, C1s, MASP-1 and 2)

pt’s with HAE have continuous activation of the plasma complement

also inactivates plasma kallikrein, which cleaves plamsa kininogen to bradykinin

bradykinin is the cause of swelling in HAE

Question 10

short term management of HAE

Answer 10

purified C1 inhibitor replacement therapy

sx resolve in 30-60 minutes

Question 11

short term prophylaxis

Answer 11

treated prophylactically with C1 inhibitor if in a situation that is likely to cause issue

Question 12

long term prophylaxis

Answer 12

for pts with HAE who have frequent/severe attacks, long term porphylaxis should be considered

androgens and anti-fibrinolytic drugs significnalty reduce the frequency of HAE attacks `

Question 13

paraoxysmal nocturan hemeglobinuria

Answer 13

failure to regualte formation of the MAC

somatic mutation causes def. in glycosylphosphatidylinositol

PNH cells lack proteins linked through GPI anchor to cell membrane

GPI anchors of importance are CD55 (DAF) and CD59 which are complementary regulatory proteins involved in protecting RBCs from complement

most likely cause of intravascular hemolysis in these ppl is increased susceptibility of RBCs to complement