Ckd Pathophysiology Flashcards
Is the cause known in most cases
No. Only those who see a kidney specialist which is mainly on those on dialysis
What is the major cause in ckd
Diabetes
Intervention to reduce glycemia reduced what sign of ckd
Albuminuria
What accumulates I’m gbm which alters it’s ionic charge due to hyperglycaemia
Advanced glycosylated ends AGE
Which kinase activated in hyperglycaemia
Pkc
What does it activate which can cause hyperfiltration and damage
Angiotensin II
How can pkc stimulate renal fibrosis
Through tgfb
What gf is increased in podocytes during hyperglycaemia which causes vascular permeability in nephrons = hyperfiltration
Vegf
On avg how much GFR lost every year over 40
1ml
Is there a genetic risk
Yes eg African apoL1 most predominant here
Give 3 factors likely to cause progression to esrd
Underlying diabetes, hypertension and high proteinuria
What 2 types of fibrosis can occur which also increases risk of esrd
Tubulointerstitial fibrosis
And glomerulosclerosis
What happens in tubulointerstitial
Myofibroblasts accumulate and deposition of matrix in the interstitial, which widens it and separates nephron cells
Harder to get blood and nutrients from peritubular capillaries and cells become nephrotic
Which types of immune cells involved in scarring/fibrosis after multiple injury and inflammation
M2 and th2
How do th2 modulate m2
Via il4 and 13
How are m2 profibrogenic
Release tgfb
What is mmt
Transition of Mac to myofibroblasts from tgfb1 inducrion
What attracts macrophages
Glomerular cytokines, proteinuria, angiontensin II, injury to cells
Why is th1 not important
Balances timpnwith mmp but th2 increases collagen
Other than stimulate m2 tgfb release what do il13 do indirectly to increase fibroblast lay down
Cleave LAP from tgfb releasing active tgfb to bind fibroblast receptors
Why does nephron integrity decline with age
Cellular senescence, ros, deceased tubular proliferation
How can mmp2 induced by tgfb cause more fibrosis than degrade ecm
It degrades the bm of tubular cells allowing for EMT
How does angiotensin II cause release of chemokines like mcp1 from epi cells attracting macrophages to kidney
Nfkb activation
What can complement be activated by
Proteinuria which activates cells to activate complement
